Global pharmacogenomics: Impact of population diversity on the distribution of polymorphisms in the CYP2C cluster among Brazilians

The impact of biogeographical ancestry, self-reported 'race/color' and geographical origin on the frequency distribution of 10 CYP2C functional polymorphisms (CYP2C8*2, *3, *4, CYP2C9*2, *3, *5, *11, CYP2C19*2, *3 and *17) and their haplotypes was assessed in a representative cohort of the Brazilian population (n = 1034). TaqMan assays were used for allele discrimination at each CYP2C locus investigated. Individual proportions of European, African and Amerindian biogeographical ancestry were estimated using a panel of insertion-deletion polymorphisms. Multinomial log-linear models were applied to infer the statistical association between the CYP2C alleles and haplotypes (response variables), and biogeographical ancestry, self-reported Color and geographical origin (explanatory variables). The results showed that CYP2C19*3, CYP2C9*5 and CYP2C9*11 were rare alleles (<1%), the frequency of other variants ranged from 3.4% (CYP2C8*4) to 17.3% (CYP2C19*17). Two distinct haplotype blocks were identified: block 1 consists of three single nucleotide polymorphisms (SNPs) (CYP2C19*17, CYP2C19*2 and CYP2C9*2) and block 2 of six SNPs (CYP2C9*11, CYP2C9*3, CYP2C9*5, CYP2C8*2, CYP2C8*4 and CYP2C8*3). Diplotype analysis generated 41 haplotypes, of which eight had frequencies greater than 1% and together accounted for 96.4% of the overall genetic diversity. The distribution of CYP2C8 and CYP2C9 (but not CYP2C19) alleles, and of CYP2C haplotypes was significantly associated with self-reported Color and with the individual proportions of European and African genetic ancestry, irrespective of Color self-identification. The individual odds of having alleles CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3, and haplotypes including these alleles, varied continuously as the proportion of European ancestry increased. Collectively, these data strongly suggest that the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of pharmacogenomic studies of the CYP2C cluster in order to avoid spurious conclusions based on improper matching of study cohorts. This conclusion extends to other polymorphic pharmacogenes among Brazilians, and most likely to other admixed populations of the Americas. The Pharmacogenomics Journal (2012) 12, 267-276; doi: 10.1038/tpj.2010.89; published online 21 December 2010

SPATIAL VARIABILITY OF THE RAINFALL EROSIVE POTENTIAL IN THE STATE OF MATO GROSSO DO SUL, BRAZIL

Information about rainfall erosivity is important during soil and water conservation planning. Thus, the spatial variability of rainfall erosivity of the state Mato Grosso do Sul was analyzed using ordinary kriging interpolation. For this, three pluviograph stations were used to obtain the regression equations between the erosivity index and the rainfall coefficient EI30. The equations obtained were applied to 109 pluviometric stations, resulting in EI30 values. These values were analyzed from geostatistical technique, which can be divided into: descriptive statistics, adjust to semivariogram, cross-validation process and implementation of ordinary kriging to generate the erosivity map. Highest erosivity values were found in central and northeast regions of the State, while the lowest values were observed in the southern region. In addition, high annual precipitation values not necessarily produce higher erosivity values.

The viewpoint of health professionals on the role of basic units in the healthcare network of the Brazilian Unified Health System

In the process of creation of the Unified Health System (SUS) as a universal policy seeking to ensure comprehensive care, unscheduled assistance in primary healthcare units (UBS) is an unresolved challenge. The scope of this paper is to analyze the viewpoint of health professionals on the role of primary healthcare units in meeting this demand. It is a transversal study of qualitative data obtained through questionnaires and interviews with 106 medical practitioners from 6 emergency medical services and 190 professionals from 30 units. They explained why people seek emergency care for occurrences pertaining to primary care. The content analysis technique with thematic categories was used for data analysis. Lack of resources and problems with primary health unit work processes (50.8%) were the reasons most frequently cited by emergency care physicians to explain this inadequate demand. Only 33.3% of the health unit professionals agreed that these occurrences should be attended in the primary healthcare services. The limited viewpoint of the role of health services on the unscheduled care, particularly among primary care professionals, possibly leads to restrictive practices for access by the population.

Influence of Genomic Ancestry on the Distribution of SLCO1B1, SLCO1B3 and ABCB1 Gene Polymorphisms among Brazilians

The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of this study was to evaluate the influence of self-reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the north, north-east, south-east and south of Brazil were recruited for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T>G (rs4149117) and c.699G>A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'-nuclease assays. The ABCB1 c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) polymorphisms were genotyped using a previously described single-base extension/termination method. The results showed that genotype and haplotype distributions are highly variable among populations of the same self-reported colour and geographical region. However, genomic ancestry showed that these associations are better explained by a continuous variable. The influence of ancestry on the distribution of alleles and haplotype frequencies was more evident in variants with large differences in allele frequencies between European and African populations. Design and interpretation of pharmacogenetic studies using these transporter genes should include genomic controls to avoid spurious conclusions based on improper matching of study cohorts from Brazilian populations and other highly admixed populations.

Selenate and selenite on yield and agronomic biofortification with selenium in rice

The objective of this work was to evaluate the effect of doses of selenate and selenite on rice (Oryza sativa) biofortification with Se, as well the influence of these forms of Se in the levels of P, S, Fe, and Zn in grains. The experiment was conducted in a greenhouse, in pots with 4 dm(3) of a sandy clay loam Latosol, with medium texture, in a 5x2 factorial arrangement with five doses of Se (0, 0.75, 1.50, 3.0, and 6.0 mg dm(-3)) and two forms of Se (selenate and selenite). Selenate provided greater efficiency of root uptake of Se, plant-use efficiency, translocation from roots to shoots, and content of this element in rice grains. The application of Se during fertilization influences the levels of P, S, and Zn, but does not affect those of Fe in rice grains.

Niobium Effects on the Recrystallization Behavior on a Full Austenitic 15Cr-15Ni Stainless Steel Investigated Using Adaptive Neural Networks (ANN)

A new series of austenitic stainless steels-Nb stabilized, without Mo additions, non-susceptible to delta ferrite formation and devoid of intemetallic phases (sigma and chi), without deformation induced martensite is being developed, aiming at high temperature applications as well as for corrosive environments. The base steel composition is a 15Cr-15Ni with normal additions of Nb of 0.5, 1.0 and 2 wt%. Mechanical properties, oxidation and corrosion resistance already have been invetigated in previous papers. In this paper, the effects of Nb on the SFE, strain hardening and recrystallization resistance are evaluated with the help of Adaptive Neural Networks (ANN).

String Quartet n degrees 02 by Villa-Lobos: a dialogue with the cyclic form of Franck, Debussy and Ravel

This article investigates Villa-Lobos's String Quartet n degrees 02, an early work by this composer, written according cyclic sonata principles, as developed by Cesar Franck and systematized by Vincent d'Indy. Another important source are the string quartets composed by Franck (1889), Debussy (1893) and Ravel (1903), which possibly served as compositional models to Villa-Lobos. In this light, the themes of the Exposition in the first movement were analyzed and this procedure reveals some harmonic and rhythmic aspects throughout all the other movements.

Multi-criteria analysis in the strategic environmental assessment of the sugar and alcohol sector

The Strategic Environmental Assessment (SEA) of the sugar and alcohol sector guides a territorial and sectoral planning that benefits most of the local society and supports this economic activity in all its stages. In this way, the present work aims to determine an index of aggregation of the indicators generated in the baseline of the SEA process, called Index of Sustainability of Expansion of the Sugar and Alcohol Sector (IScana). For this, it was used the normalization of the indicators of each city by the fuzzy logic and attribution of weights by the Analytic Hierarchy Process (AHP). Then, the IScana values had been spatialized in the region of 'Grande Dourados'-Mato Grosso do Sul State. The northern portion concentrated the highest values of IScana, 0.48 and 0.55, referring to the cities of Nova Alvorada do Sul and Rio Brilhante, while, in the central portion, the city of Dourados presented the lowest value, 0.10. The selection of the set of indicators forming the IScana, and their relative importance, was satisfactory for the application of fuzzy logic and AHP techniques. The IScana index supplies objective information regarding the diagnosis of the region for the application of SEA.

Management of diabetes mellitus and associated cardiovascular risk factors in Brazil – the Brazilian study on the practice of diabetes care

Abstract Background The Brazilian Study on the Practice of Diabetes Care main objective was to provide an epidemiological profile of individuals with type 1 and 2 diabetes mellitus (DM) in Brazil, concerning therapy and adherence to international guidelines in the medical practice. Methods This observational, cross-sectional, multicenter study collected and analyzed data from individuals with type 1 and 2 DM attending public or private clinics in Brazil. Each investigator included the first 10 patients with type 2 DM who visited his/her office, and the first 5 patients with type 1 DM. Results A total of 1,358 patients were analyzed; 375 (27.6%) had type 1 and 983 (72.4%) had type 2 DM. Most individuals were women, Caucasian, and private health care users. High prevalence rates of hypertension, dyslipidemia and central obesity were observed, particularly in type 2 DM. Only 7.3% and 5.1% of the individuals with types 1 and 2 DM, respectively, had optimal control of blood pressure, plasma glucose and lipids. The absence of hypertension and female sex were associated with better control of type 1 DM and other cardiovascular risk factors. In type 2 DM, older age was also associated with better control. Conclusions Female sex, older age, and absence of hypertension were associated with better metabolic control. An optimal control of plasma glucose and other cardiovascular risk factors are obtained only in a minority of individuals with diabetes. Local numbers, compared to those from other countries are worse.

Associação entre doenças imunológicas e suas manifestações clínicas semelhantes

Trata-se de um caso de uma paciente de 30 anos do sexo feminino, com prótese biológica valvar mitral em razão de estenose mitral sintomática e antecedentes de infarto agudo do miocárdio, episódios de convulsões tônico-clônicas generalizadas, alucinações visuais, eventos tromboembólicos cerebrais, apresentando no momento coreia e cardite aguda. Foram diagnosticados na paciente febre reumática em atividade, lúpus eritematoso sistêmico e síndrome do anticorpo antifosfolipídeo. A combinação de três diagnósticos incomuns em um mesmo paciente torna esse caso único, modificando o tratamento e seu prognóstico.

Estudo da anatomia do nervo tibial e seus ramos ao nível do terço distal da perna

OBJETIVO: Determinar, através de dissecção em cadáveres frescos, a anatomia topográfica do nervo tibial e seus ramos ao nível do tornozelo, em relação ao túnel do tarso. MÉTODOS: Foram realizadas dissecções bilaterais em 26 cadáveres frescos e as localizações da bifurcação do nervo tibial e seus ramos aferidas em milímetros, com relação ao eixo maleolar-calcaneal (EMC). Para os ramos calcâneos, a quantidade e seus respectivos nervos de origens também foram analisados. RESULTADOS: A bifurcação do nervo tibial ocorreu sob o túnel em 88% dos casos e proximalmente em 12%. Quanto aos ramos calcâneos, o medial apresentou-se com um (58%), dois (34%) e três (8%) ramos, com a origem mais comum do nervo tibial (90%) e o inferior com ramo único por perna, tendo o nervo plantar lateral como origem mais comum (70%). Nivel de Evidência V, Opinião de especialista.

Haydn, segundo Villa-Lobos: uma análise do 1º movimento do Quarteto de cordas nº 7 de Villa-Lobos

Este estudo analisa o 1º movimento do Quarteto de Cordas nº 7 de Villa-Lobos e investiga possíveis referências aos quartetos de cordas compostos por Franz Haydn, como Villa-Lobos sugeriu a Arnaldo Estrella.

Estresse oxidativo no plasma sanguíneo de indivíduos submetidos ao esforço físico agudo seguido de crioimersão corporal

O objetivo deste estudo foi analisar a influência da crioimersão corporal (CIC) imediata ao esforço físico agudo no estresse oxidativo (EOx) no plasma sanguíneo. Participaram do presente estudo 12 homens, com idade média de 22±1 anos, submetidos ao teste de esforço físico intenso em esteira, seguido de CIC em um tanque com água a 10ºC durante 10 minutos contínuos. Do repouso ao final da CIC, os indivíduos foram monitorados através de alguns parâmetros como: o índice de percepção subjetiva do esforço (IPE) expresso conforme escala de Borg, frequência cardíaca (FC), pressão arterial (PA) e temperatura corporal (TC) através da temperatura timpânica. A análise morfológica do EOx plasmático foi realizada de acordo com o método denominado Morfologia Óptica do Estresse Oxidativo no Plasma (MEOP), utilizando-se gotas de sangue capilar. Observou-se uma significativa elevação (p<0,01) no grau do estresse oxidativo plasmático após a realização do esforço físico, em relação ao respectivo grau em repouso. Porém, esta elevação no grau do EOx foi significativamente reduzida (p<0,001) em função da CIC. Embora sejam necessários mais estudos científicos com o MEOP, concluiu-se que, para o presente estudo, este teste mostrou-se viável. Os dados encontrados no presente estudo sugerem que a CIC em água a 10ºC por 10 minutos imediatos ao esforço físico agudo com intensidade alta, apresenta-se como uma importante conduta fisioterapêutica para a normalização do EOx pós-esforço.

Crônica dos Potenciais Vetor e Quântico.

Neste artigo, vamos apresentar o desenvolvimento histórico dos conceitos dos potenciais vetor e quântico formulados, respectivamente, por Maxwell e Bohm. Em suas concepções iniciais, eles foram considerados apenas como um artifício matemático. Contudo, enquanto o potencial vetor já apresenta uma grande evidência experimental (efeito Aharonov-Bohm) sobre a sua interpretação física, o potencial quântico ainda aguarda a sua, muito embora esse efeito e alguns resultados teóricos sinalizem a sua existência física. Este artigo já foi publicado na revista MensAgitat vol.1(2),pp.93- 108(2006) da Academia Roraimense e Paraense de Ciências. Está sendo publicado novamente como e-print no IFUSP para que ele tenha uma divulgação mais ampla e mais ágil pela internet.