Cláudia Maria Dornelles da Silva

High proportion of hepatitis C virus genotypes 1 and 3 in a large cohort of patients from Southern Brazil

Hepatitis C virus (HCV) isolates have been divided into six genotypes (1 to 6). The duration of hepatitis C standard treatment is 48 weeks for patients infected with HCV genotype 1 vs 24 weeks for those infected with genotypes 2 and 3. A total of 1544 HCV isolates from chronic patients living in the southern Brazilian states of Rio Grande do Sul (RS, n=627) and Santa Catarina (SC, n=917) were genotyped by restriction fragment length polymorphism (RFLP) of polymerase chain reaction (PCR) products. In RS, 338 (53.9%; 95% CI 50.0-57.8%), 34 (5.4%; 95% CI 3.8-7.4%) and, 255 (40.7%; 95% CI 36.9-44.6%) samples were from genotypes 1, 2, and 3, respectively. In SC, 468 (51%; 95% CI 47.8-54.2%), 26 (2.9%; 95% CI 1.9-4.1%) and, 423 (46.1%; 95% CI 42.9-49.3%) samples were from genotypes 1, 2, and 3, respectively. Genotyping results were confirmed by direct nucleotide sequencing of PCR products derived from 68 samples, without any discrepancy between PCR-RFLP and nucleotide sequencing methods. In conclusion, almost half of the hepatitis C patients from South of Brazil are infected by genotypes 2 and 3 and, these results have important consequential therapeutic implications as they can be treated for only 24 weeks, not 48.

Allele frequencies of 15 STRs in a representative sample of the Brazilian population

Allele frequencies for 15 short tandem repeat (STR) loci were obtained from a sample of 12,030 individuals undergoing paternity testing. This sample includes individuals from all States in Brazil, combined according to the current country division into five regions (North, Northeast, Central West, Southeast, and South). The most polymorphic loci were D2S1338 and D18S51. All the analysed loci meet Hardy-Weinberg equilibrium expectations. Combined power of discrimination and combined power of exclusion for the 15 tested STR loci were 0.999999999999990 and 0.9999992, respectively. Comparative analysis between populations from different Brazilian macroregions as well as between Brazil and other relevant populations are presented.

Mutation rate estimates for 13 STR loci in a large population from Rio Grande do Sul, Southern Brazil

Short tandem repeat (STR) polymorphisms have been extensively used in forensic genetics analysis. Knowledge about the locus-specific mutation rates of STRs improves forensic probability calculations and interpretations of diversity data. To incorporate single-locus diversity information into autosomal STR mutation rate estimations, 13 STR loci were studied during 2007–2009 in 10,959 paternity investigation cases from Rio Grande do Sul, the southernmost state of Brazil, covering an overall number of 284,934 allelic transfers. A total of 355 mutations were identified; 348 repeats were gains or losses of one step, three were gains or losses of two steps, and four were gains or losses of not stepwise mutation. The mutation rates ranged from 4.6u2009×u200910−5 to 2.3u2009×u200910−3, and the overall mutation rate estimate was 1.2u2009×u200910−3. The average of the paternal mutation rate (1.8u2009×u200910−3) was five times higher than the maternal rate (0.36u2009×u200910−3). The observed mutational features for STRs have important consequences for forensic applications, including the definition of criteria for exclusion in paternity testing and the interpretation of DNA profiles in identification analysis.

Population genetic analyses of the AmpFlSTR ® NGM™ in Brazil

Population data of 15 short tandem repeat loci of the AmpFlSTR® next generation multiplex (NGM)™ were obtained from a sample of 835 individuals. The loci are the ten short tandem repeats (STRs) in the SGM Plus® Kit plus the EDNAP- and ENSFI-recommended STRs D10S1248, D22S1045, D2S441, D1S1656, and D12S391. Allele frequency and other forensically relevant statistics data were generated for the NGM loci into five current country macroregions of Brazil (North, Northeast, Central West, Southeast, and South). All the analyzed loci meet Hardy–Weinberg equilibrium expectations and no linkage disequilibrium in all pairs of loci. The observed and expected heterozygosity, power of discrimination, polymorphic information content, and the other population–genetic indices were calculated. The overall power of discrimination was greater than 0.99999999999999999996 and the combined power of exclusion was greater than 0.9999998 in all Brazilian populations. Comparative analysis between populations from different Brazilian macroregions as well as between Brazil and Caucasian, African Americans, and Hispanic US populations are presented.

15 STR loci frequencies with mutation rates in the population from Rio Grande do Sul, Southern Brazil

Allele frequencies for 15 short tandem repeats (STR) loci were obtained from a sample of 2038 individuals undergoing paternity testing. The population is from Rio Grande do Sul, Brazil. The loci are the most commonly used in forensic and paternity testing, being analysed by the AmpFlSTR Identifiler (Applied Biosystems) commercial kit. The most polymorphic locus was D2S1338. Mutation rates were ascertained from this population sample. All the loci analysed reached the Hardy-Weinberg equilibrium. The results of genetic distance are consistent with the European-derived origins of Rio Grande do Sul population.

Response to treatment in Brazilian patients with chronic hepatitis C is associated with a single-nucleotide polymorphism near the interleukin-28B gene

A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

A pessoa com úlcera de perna, intervenção estruturada dos cuidados de enfermagem: revisão sistemática da literatura

The objective of this study is to identify the nursing interventions for people with venous, arterial or mixed leg ulcers. This study was performed using the EBSCO search engine: CINAHL and MEDLINE yielded results, based on full-text articles published between 2000 and 2010, using the following descriptors: Leg* Ulcer* AND Nurs* AND Intervention*, filtered using a starting question using PICO. At the same time, a search was performed on the National Guideline Clearinghouse, using the same search guidelines. A person-centered intervention increased positive health outcomes, with a range of direct wound care in agreement with the etiology. The following interventions associated with the healing of leg ulcers of any etiology were highlighted: nurse/client treatment relationship, individualization of care and pain monitoring.The objective of this study is to identify the nursing interventions for people with venous, arterial or mixed leg ulcers. This study was performed using the EBSCO search engine: CINAHL and MEDLINE yielded results, based on full-text articles published between 2000 and 2010, using the following descriptors: Leg* Ulcer* AND Nurs* AND Intervention*, filtered using a starting question using PICO. At the same time, a search was performed on the National Guideline Clearinghouse, using the same search guidelines. A person-centered intervention increased positive health outcomes, with a range of direct wound care in agreement with the etiology. The following interventions associated with the healing of leg ulcers of any etiology were highlighted: nurse/client treatment relationship, individualization of care and pain monitoring.

Association between cervical lesion grade and micronucleus frequency in the Papanicolaou test.

The aim of this study was to evaluate the association between the frequency of micronuclei (MN) and the cellular changes detected in the conventional Papanicolaou test. One hundred and seventy-four Papanicolaou test smears with cellular changes were examined. MN screening was done in cytopathological smears by counting 1,000 cervical cells in a light microscope. MN frequencies were significantly higher in the group with cellular changes compared to the control group (p < 0.001). The mean MN frequencies were 0.95 ± 1.12 (mean ± SD) in the control group (n = 223), 2.98 ± 1.20 in individuals with atypical squamous cells of undetermined significance (ASC-US) (n = 50), 4.04 ± 1.45 in cervical intraepithelial neoplasia (CIN) I (n = 52), 5.97 ± 1.83 in CIN II (n = 30), 7.29 ± 1.55 in CIN III (n = 17) and 8.64 ± 1.55 in invasive cancer (n = 25). These findings suggest that MN monitoring should be included as an additional criterion for the early detection of cytogenetic damage in routine examinations. This monitoring should be done in the same smear as used for cytopathological examination. More specific and systematic studies are necessary to confirm this proposal.

15 STR loci frequencies in the population from Santa Catarina, Southern Brazil.

Allele frequencies for 15 short tandem repeats (STR) loci were determined with a sample of 3000 unrelated individuals from the population of Santa Catarina, Southern Brazil. The loci are most commonly used in forensic and paternity testing, being analyzed by the Powerplex 16 (Promega) commercial kit. The data shows that most polymorphic loci were Penta E and FGA. The distributions of the genotypes in the evaluated loci are in Hardy-Weinberg equilibrium. Comparative analyses between our population data and other Brazilian populations are presented. The calculated forensic parameters showed that the loci are useful for the solution of forensic problems in Brazilian Southern region.

Association of CYP7A1 -278A>C polymorphism and the response of plasma triglyceride after dietary intervention in dyslipidemic patients

We investigated the effect of the -278A>C polymorphism in the CYP7A1 gene on the response of plasma lipids to a reduced-fat diet for 6 to 8 weeks in a group of 82 dyslipidemic males with a mean age of 46.0 +/- 11.7 years. Individuals who presented at least one high alteration in total cholesterol, low-density lipoprotein cholesterol or triglyceride values were considered to be dyslipidemic. Exclusion criteria were secondary dyslipidemia due to diabetes mellitus, renal, liver, or thyroid disease. None of the subjects were using lipid-lowering medication. Baseline and follow-up lipid concentrations were measured. The genotypes were determined by the digestion of PCR products with the BsaI restriction endonuclease. There were statistically significant reductions in plasma total cholesterol, low-density lipoprotein cholesterol and triglyceride concentrations after dietary intervention. The minor allele C has a frequency of 43%. Carriers of the C allele had significantly lower triglyceride concentrations (P = 0.02) than AA homozygotes. After adjustment of covariates, subjects with the AC and CC genotypes showed a greater reduction in triglyceride concentrations compared to subjects with the AA genotype. Multiple linear regression analyses showed that the AC and CC CYP7A1 genotypes accounted for 5.2 and 6.2% of triglyceride concentration during follow-up and adjusted percent of change of triglyceride concentration, respectively. The present study provides evidence that -278A>C polymorphism in the CYP7A1 gene can modify triglyceride concentrations in response to a reduced fat diet in a dyslipidemic male population. This gene represents a potential locus for a nutrigenetic directed approach.