Genomics and epidemiology for gastric adenocarcinomas (GE4GAC): a Brazilian initiative to study gastric cancer

Gastric cancer (GC) is the fifth most common type of cancer worldwide with high incidences in Asia, Central, and South American countries. This patchy distribution means that GC studies are neglected by large research centers from developed countries. The need for further understanding of this complex disease, including the local importance of epidemiological factors and the rich ancestral admixture found in Brazil, stimulated the implementation of the GE4GAC project. GE4GAC aims to embrace epidemiological, clinical, molecular and microbiological data from Brazilian controls and patients with malignant and pre-malignant gastric disease. In this letter, we summarize the main goals of the project, including subject and sample accrual and current findings

Ansiedade na performance musical: tradução, adaptação e validação do Kenny Music Performance Anxiety Inventory (K-MPAI) para a língua portuguesa / Music performance anxiety: translation, adaptation and validation of the Kenny Music Performance Anxiety Inventory (K-MPAI) to the Portuguese language

CONTEXTO: A performance musical requer alto nível de habilidade em diversos parâmetros, como coordenação motora, atenção e memória, o que a torna particularmente suscetível aos estados de ansiedade. Pesquisas nessa área têm avançado com a introdução de instrumentos específicos para abordar a ansiedade na performance musical, como é o caso da Kenny Music Performance Anxiety Inventory (K-MPAI). OBJETIVOS: O presente estudo teve como objetivo traduzir, adaptar e validar a K-MPAI para a língua portuguesa. MÉTODOS: Após autorização da autora, a escala K-MPAI foi traduzida e validada. A escala em língua portuguesa foi aplicada a 218 músicos de ambos os sexos, amadores e profissionais. Para a validação concorrente, foi utilizado o Inventário de Ansiedade Traço-Estado (IDATE), versão validada na língua portuguesa da State Trait Anxiety Inventory (STAI). RESULTADOS: A análise da consistência interna apresentou alfa de Cronbach = 0,957 com p < 0,001, reprodutibilidade com p = 0,378 e validação concorrente com a IDATE com alfa de Cronbach = 0,642 e p < 0,001. CONCLUSÃO: O estudo permite considerar a amostra com graus de confiabilidade e reprodutibilidade elevados, o que traduz este estudo como provindo de uma amostra não tendenciada e replicável a outras populações. A validação concorrente entre a K-MPAI e a IDATE permite inferir que ambas as escalas são comparáveis na capacidade de medir os níveis de ansiedade em musicistas.

BACKGROUND: Musical performance demands high-leveled coordination, concentration, motor- and memory-skills, making it particularly susceptible to anxiety states. Researches in this field have advanced significantly with the development of specific instruments to evaluate music performance anxiety, such as the Kenny Music Performance Anxiety Inventory (K-MPAI). OBJECTIVES: The present study has the objective of translating, adapting and validating the K-MPAI to the Portuguese language. METHODS: After the written consent given by the author of the original K-MPAI scale, the K-MPAI scale was translated and validated for Portuguese idiom. The Portuguese-version of K-MPAI was then applied to 218 amateur and professional musicians of both genders. For the concurrent validation, the validated Portuguese-version of the State Trait Anxiety Inventory (STAI) was used. RESULTS: Analysis of the internal consistency demonstrated a Cronbach's alpha = 0.957, with p < 0.001, replicated with p = 0.378 and the concurrent validation with the State Trait Anxiety Inventory, demonstrated a Cronbach's alpha = 0.642 and p < 0.001. DISCUSSION: The study allows evaluating data samples with high levels of reliability and replicability, which translates this study based on an unbiased sample and replicable to other populations. The concurrent validation between K-MPAI and IDATE, allows inferring that the scales are comparable in their capability of measuring anxiety levels in musicians.

O genoma humano e as perspectivas para o estudo da esquizofrenia / Human genome and the perspectives for schizophrenia

O seqüenciamento de nosso genoma representa um passo essencial no entendimento da biologia humana e no planejamento racional de pesquisas biomédicas. Contudo, é importante notar que o seqüenciamento de um dado genoma é apenas uma parte de um complexo quebra-cabeças. A informação genética deve ser usada como um mapa, a partir do qual começamos a compreender a base das doenças e a importância da variação genética através da análise da complexidade e do comportamento das regiões reguladoras, genes e proteínas, funções gênicas e sistemas celulares. Apesar dos enormes esforços para identificar genes de susceptibilidade, os resultados de estudos de genética molecular de esquizofrenia até o momento têm sido modestos. O uso apropriado da genômica poderá ajudar imensamente na elucidação das causas da esquizofrenia, permitindo avaliar o papel de novos genes, das variações genéticas, das formas de splicing alternativo, das variações de expressão gênica e de vias metabólicas de interesse. A convergência de dados bioquímicos, de imagem, de neuroanatomia, farmacológicos, clínicos e genéticos permite prever que estamos muito próximos de uma melhor compreensão das bases biológicas da esquizofrenia. A disponibilidade desses avanços terá um enorme impacto na pesquisa desta doença.

Alterações genéticas na doença de Alzheimer / Genetic Alterations in Alzheimer's disease

Com o aumento da expectativa de vida, visto hoje em todo o planeta, um maior número de indivíduos alcança uma idade avançada em que a manifestação de doenças neurodegenerativas é mais freqüente. Entre essas, a doença de Alzheimer (DA) é a causa mais freqüente de demência. Os achados mais marcantes na DA, em cérebros de pacientes acometidos pela doença, são as placas senis, os emaranhados neurofibrilares e a extensa perda neuronal. No entanto, existe uma carência generalizada de marcadores biológicos preditivos ou com valor diagnóstico para a DA. Estudos de genética molecular permitiram identificar quatro genes consistentemente associados com o maior risco de desenvolvimento da doença: APP, apoE, PSEN1 e PSEN2. No entanto, inúmeros estudos apontam para papel importante de outros genes, fortalecendo a hipótese de uma doença poligênica e multifatorial. Neste sentido, novas abordagens de estudo têm um futuro promissor, podendo indicar uma vasta população de genes ou alterações moleculares que possam explicar o surgimento da doença, vindo a fornecer as bases para a compreensão da DA e também para o delineamento de novas e mais eficazes abordagens de tratamento ou prevenção da doença.

Apolipoproteína E e a doença de Alzheimer / Apolipoprotein E and Alzheimer's disease

Sabemos hoje que os polimorfismos no gene da apolipoproteína E (apoE) são importantes fatores de risco para o desenvolvimento da doença de Alzheimer (DA). O gene apoE humano, mapeado no braço longo do cromossomo 19 (19q13.2), codifica uma glicoproteína com 317 aminoácidos, a qual desempenha um papel fundamental para o catabolismo de componentes ricos em triglicérides no corpo humano. Em humanos, existem três alelos principais do gene apoE, decorrentes de apenas duas alterações no DNA, chamados de Upsilon2, Upsilon3 e Upsilon4. A identificação da variante Upsilon4 do gene apoE como o fator genético de risco mais comum para a DA de início tardio sugere que o colesterol deva ter um papel direto na patogênese da doença. Contudo, a simples presença do alelo apoE Upsilon4 não é necessária nem suficiente para causar DA; este alelo apenas aumenta o risco de o indivíduo vir a desenvolver a doença, indicando que existem outros fatores ambientais e genéticos importantes no desenvolvimento da mesma.

Recent advances in the diagnosis of Schistosoma infection: the detection of parasite DNA

As Schistosoma sp. control programs are chiefly based on treatment of infected population, adequate case finding has a crucial role. The available diagnostic methods are far from ideal, since the search for eggs in stools and the detection of circulating antigens lack sensitivity in low prevalence and post-treatment situations and antibody detection lacks specificity. In most endemic foci, repeated treatment of infected people leaves a number of non-diagnosed and consequently non-treated persons, enough to maintain a persistent residue of 5 to 10 percent prevalence. In an attempt to surpass these diagnostic limitations we have developed a polymerase chain reaction (PCR) for the detection of Schistosoma sp. in feces that, in a first population study, has shown to be more sensitive than three-repeated stool Kato-Katz examination. The PCR may constitute a valuable tool for the diagnosis of the Schistosoma sp. infection in special situations, when high sensitivity and specificity are required and infrastructure is available

Genetic variability and identification of the intermediate snail hosts of Schistosoma mansoni

Studies based on shell or reproductive organ morphology and genetic considerations suggest extensive intraspecific variation in Biomphalaria snails. The high variability at the morphological and genetic levels, as well as the small size of some specimens and similarities between species complicate the correct identification of these snails. Here we review our work using methods based on polymerase chain reaction (PCR) amplification for analysis of genetic variation and identification of Biomphalaria snails from Brazil, Argentina, Uruguay and Paraguay. Arbitrarily primed-PCR revealed that the genome of B. glabrata exhibits a remarkable degree of intraspecific polymorphism. Low stringency-PCR using primers for 18S rRNA permited the identification of B. glabrata, B. tenagophila and B. occidentalis. The study of individuals obtained from geographically distinct populations exhibits significant intraspecific DNA polymorphism, however specimens from the same species, exhibit some species specific LSPs. We also showed that PCR-restriction fragment of length polymorphism of the internal transcribed spacer region of Biomphlaria rDNA, using Ddel permits the differentiation of the three intermediate hosts of Schistosoma mansoni. The molecular biological techniques used in our studies are very useful for the generation of new knowledge concerning the systematics and population genetics of Biomphalaria snails.

A low stringency polymerase chain reaction approach to the identification of Biomphalaria glabrata and B. tenagophila, intermediate snail hosts of Schistosoma mansoni in Brazil

The low stringency polymerase chain reaction (LS-PCR) with a pair of specific primers for the amplification of the 18S rRNA gene was evaluted as a means of differentiating between the two Schistosoma mansoni intermediate host species in Brazil: Biomphalaria glabrata and B. tenagophila. Individual snails obtained from different states of Brazil were used and the amplification patterns obtained showed a high degree of gentic variability in these species. Nevertheless, 4 and 3 clearly defined specific diagnostic bands was observed in individuals from B. glabrata and B. tenagophila respectively. The detection of snail specific diagnostic bands suggests the possibility of reliable species differentiation at DNA level using LS-PCR.

Suscetibilidade aos agentes quimioterápicos de isolados de Schistosoma mansoni oriundos de pacientes tratados com oxamniquine e praziquantel e näo curados / Susceptibility to the chemotherapeutical compounds of Schistosoma mansoni from patients treated with oxamniquine and praziquantel and not cured ones

Ten inhabitants of Itaquara, Bahia, Brazil treated with oxamniquine and subsequently praziquantel were not cured. Schistosoma mansoni isolates derived from these patients were studied. Snails were infected with miracidia derived from the feces of these patients and the cercariae produced used to infect albino mice. The animals were then treated with a single oral dose of oxamniquine (25, 50 and 100mg/kg) or praziquantel (100, 200 and 400 mg/kg). The response to chemotherapy was significantly different in some of the isolates although it was not possible to characterize any of them as resistant. In addition, DNA analysis of the isolates by means of ®Random Amplified Polymorphic DNA® indicated a low degree of variability as compared with a laboratory strain, LE. Thus, it was not possible to characterize these organisms at a genetic level as a distinct strain.

DNA polymorphism of schistosomes and their snail hosts

Analysis of the genomes of schistosomes and one of their intermediate hosts, Biomphalaria glabrata, using Random Amplified Polymorphic DNA (RAPD) demonstrated that intraspecific genetic polymorphism in the parasite is limited but in the snail is highly pronounced. This suggests an important role for the snail in the determination of the epidemiology of the disease. In addition to their intraspecific stability, schistosome derived RAPDs exhibit a high level of interspecific polymorphism and are thus ideal for the construction of phylogenetic trees. For the detection of intraspecific polymorphisms extensive variation in the mitochondrial DNA is being exploited for the development of a PCR based test for Schistosoma mansoni. Gene level polymorphisms are being analyzed by Low Stringency Single Specific Primer PCR.

Dot-dye-immunoassay for the diagnosis of schistosomiasis mansoni

A new serological assay dot-dye-immunoassay (dot-DIA) was evaluated for the diagnosis of schistosomiasis mansoni. This method consist of four steps: (a) biding of antigens to a nitrocellulose membrane (NC); (b) blocking of free sites of the NC; (c) incubation in specific primary antibody; (d) detection of primary antibody reactivity by color development using second antibody coupled to textile dyes. Sera from 82 individuals, 61 with Schistosoma mansoni eggs in the stool and 21 stool negative were tested by ELISA, dot-ELISA, and dotDIA. A high level of agreement between the methods tested was observed for all sera tested: ELISA x dot-ELISA: 95.1%, ELISA x dot-DIA: 92.7% and dot-ELISA x dot-DIA: 97.6%. In this study, dot-DIA proved to be a feasible, sensitive, rapid and practical test for the diagnosis of shcistosomiasis