G1P[8] Rotavirus in children with severe diarrhea in the post-vaccine introduction era in Brazil: Evidence of reassortments and structural modifications of the antigenic VP7 and VP4 regions.

Worldwide rotaviruses A (RVA) are responsible for approximately 215,000 deaths annually among children aged <5 years. RVA G1P[8] remains associated with >50% of gastroenteritis cases in this age group. The aim of this study was to assess the genetic variability of G1P[8] strains detected in children with severe diarrhea in Belém, Pará, Brazil, during the post-rotavirus vaccine introduction era. Phylogenetic analysis clustered the VP4 and VP7 genes of 40 samples selected between 2009 and 2011 into lineages found to be different from the Rotarix® vaccine strain. A detailed investigation of their complete genotype constellations identified 2 reassortant viruses (5%), resulting from reassortments between the genogroups Wa-like and DS-1-like (G1-P[8]-I1-R2-C1-M1-A1-N1-T2-E1-H1) and Wa-like and AU-1-like (G1-P[8]-I1-R3-C1-M1-A1-N1-T1-E1-H1) genotype constellations. A comparison of the amino acid residues presents in the antigenic epitopes of VP7 and VP4, showed differences in the electrostatic charges distribution, between wild type Brazilian strains and the Rotarix® and RotaTeq® vaccine strains. These findings reflect the structural analyses of the antigenic regions of VP7 and VP4 of the RVA G1P[8] in children with gastroenteritis in Northern Brazil raising the hypothesis that structural modifications at these sites over time may account for the emergence of new strains that could possibly pose a challenge to current vaccines.

Prevalence of Parkinson's disease: a population-based study in Portugal.

BACKGROUND AND PURPOSE: Portugal has been identified as one of the countries with a high prevalence of LRRK2-G2019S, considered to be the most frequent known cause of familial and sporadic Parkinson's disease (PD). The aim of this study was to evaluate the prevalence of PD in Portugal using a door-to-door methodology. METHODS: A cross-sectional study was conducted in the Portuguese community-dwelling population; that is, elderly people living in the community on their own, aged ≥50 years and resident in mainland Portugal, in two phases: (i) a questionnaire was applied to screen potential cases of PD; and (ii) screened cases were evaluated by an expert in PD to confirm diagnosis. RESULTS: The adjusted prevalence of PD for the Portuguese community-dwelling population aged ≥50 years was 0.24%. The estimated total number of cases of PD for the Portuguese population is 180/100 000 inhabitants. CONCLUSIONS: The results of this study show that a geographical region with a high frequency of a causal mutation for PD does not automatically imply a high prevalence of patients with PD.

Timing of adjuvant chemotherapy in colorectal cancer.

AIM: Delay in commencing adjuvant therapy for colorectal cancer seems to impair survival in some retrospective studies. This study was planned to evaluate its impact on survival. METHODS: This was a retrospective study enrolling patients registered from 2000 to 2012 in two large cancer-dedicated institutions in Brazil. The primary outcome was overall survival according to early vs late chemotherapy initiation. The interval between the primary surgery and the start of adjuvant chemotherapy was calculated. Survival was estimated using the Kaplan-Meier method and the impact of multiple prognostic factors on survival by Cox regression analysis. RESULTS: By the end of 2012, a total of 1963 Stage II and III colorectal patients were identified and 1318 patients received adjuvant chemotherapy, with 22% and 46% of those starting adjuvant chemotherapy within 6 weeks and 8 weeks of surgery. The median period of follow-up was 41 months. Patients starting chemotherapy within 6-8 weeks of surgery had longer overall survival compared with those who started after (6 weeks vs later, hazard ratio 0.76, 95% CI 0.57-0.99, P = 0.046; 8 weeks vs later, hazard ratio 0.74, 95% CI 0.59-0.93, P = 0.011). In the multivariate analysis, age, stage, histological grade, angiolymphatic invasion, emergency surgery and preoperative therapy were independent prognostic factors, but the interval between surgery and start of adjuvant therapy was not. CONCLUSION: In this large retrospective study, the standard prognostic factors impacted on survival whereas the timing of adjuvant therapy did not. Patients with delayed adjuvant chemotherapy may have worse prognostic factors which could play a major role in their poor outcome.

Effect of particle polydispersity on the irreversible adsorption of fine particles on patterned substrates.

We performed extensive Monte Carlo simulations of the irreversible adsorption of polydispersed disks inside the cells of a patterned substrate. The model captures relevant features of the irreversible adsorption of spherical colloidal particles on patterned substrates. The pattern consists of (equal) square cells, where adsorption can take place, centered at the vertices of a square lattice. Two independent, dimensionless parameters are required to control the geometry of the pattern, namely, the cell size and cell-cell distance, measured in terms of the average particle diameter. However, to describe the phase diagram, two additional dimensionless parameters, i.e., the minimum and maximum particle radii, are also required. We find that the transition between any two adjacent regions of the phase diagram solely depends on the largest and smallest particle sizes, but not on the shape of the distribution function of the radii. We consider size dispersions up to 20% of the average radius using a physically motivated, truncated, Gaussian-size distribution, and focus on the regime where adsorbing particles do not interact with those previously adsorbed on neighboring cells to characterize the jammed state structure. The study generalizes previous exact relations on monodisperse particles to account for size dispersion. Due to the presence of the pattern, the coverage shows a nonmonotonic dependence on the cell size. The pattern also affects the radius of adsorbed particles, where one observes preferential adsorption of smaller radii, particularly at high polydispersity.

Genetic diversity in local and commercial dry bean (Phaseolus vulgaris) accessions based on microsatellite markers.

Dry beans are considered to be a crop of great socio-economic importance, because they are an inexpensive source of nutrients and because their cultivation requires considerable manual labor. Studies of genetic diversity have been very important for genetic improvement programs, because they give parameters for the identification of genitors that can provide large heterosis effects and improved segregation in recombinants, increasing the probability of obtaining superior genotypes in the progeny. We evaluated the genetic diversity of 57 dry bean accessions, including 31 local accessions, propagated by small-scale farmers, 20 accessions supplied by the Brazilian Agricultural Research Agency, and six commercial accessions, using 16 microsatellite primers. Among these primers, 13 were found to be polymorphic, giving 29 polymorphic alleles. The largest number of alleles per locus was observed for primer BM141, which had four alleles. The polymorphic information content varied from 0.11 to 0.51, observed for loci BM212 and BM141, respectively. The lowest degree of dissimilarity (0.0) was found between the accession Iapar 81 and the accessions E03, E04, E09, and E13 and between the accession pairs E08 with E16 and Iapar 31 with E06. The highest degree of dissimilarity was found between the accessions Carioca and E22 (1.0). Grouping analysis revealed four groups, according to the place of origin. This tendency was also found in the principal coordinate analysis. The local genotypes were found to have relatively high genetic diversity, while the EMBRAPA and commercial cultivars had a relatively narrow genetic basis.

Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension.

Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05). Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA), C344T (TC/TT) and A4582C (AC/CC). Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05). These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.

Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension

Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05). Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA), C344T (TC/TT) and A4582C (AC/CC). Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05). These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.

Personalized diagnosis by cached solutions with hypertension as a study model.

Statistical modeling of links between genetic profiles with environmental and clinical data to aid in medical diagnosis is a challenge. Here, we present a computational approach for rapidly selecting important clinical data to assist in medical decisions based on personalized genetic profiles. What could take hours or days of computing is available on-the-fly, making this strategy feasible to implement as a routine without demanding great computing power. The key to rapidly obtaining an optimal/nearly optimal mathematical function that can evaluate the "disease stage" by combining information of genetic profiles with personal clinical data is done by querying a precomputed solution database. The database is previously generated by a new hybrid feature selection method that makes use of support vector machines, recursive feature elimination and random sub-space search. Here, to evaluate the method, data from polymorphisms in the renin-angiotensin-aldosterone system genes together with clinical data were obtained from patients with hypertension and control subjects. The disease "risk" was determined by classifying the patients' data with a support vector machine model based on the optimized feature; then measuring the Euclidean distance to the hyperplane decision function. Our results showed the association of renin-angiotensin-aldosterone system gene haplotypes with hypertension. The association of polymorphism patterns with different ethnic groups was also tracked by the feature selection process. A demonstration of this method is also available online on the project's web site.

Personalized diagnosis by cached solutions with hypertension as a study model

Statistical modeling of links between genetic profiles with environmental and clinical data to aid in medical diagnosis is a challenge. Here, we present a computational approach for rapidly selecting important clinical data to assist in medical decisions based on personalized genetic profiles. What could take hours or days of computing is available on-the-fly, making this strategy feasible to implement as a routine without demanding great computing power. The key to rapidly obtaining an optimal/nearly optimal mathematical function that can evaluate the [quot ]disease stage[quot ] by combining information of genetic profiles with personal clinical data is done by querying a precomputed solution database. The database is previously generated by a new hybrid feature selection method that makes use of support vector machines, recursive feature elimination and random sub-space search. Here, to evaluate the method, data from polymorphisms in the renin-angiotensin-aldosterone system genes together with clinical data were obtained from patients with hypertension and control subjects. The disease [quot ]risk[quot ] was determined by classifying the patients' data with a support vector machine model based on the optimized feature; then measuring the Euclidean distance to the hyperplane decision function. Our results showed the association of renin-angiotensin-aldosterone system gene haplotypes with hypertension. The association of polymorphism patterns with different ethnic groups was also tracked by the feature selection process. A demonstration of this method is also available online on the project's web site.

Energy cost and intracyclic variation of the velocity of the centre of mass in butterfly stroke.

The purpose of this study was to examine the relationship between the intra-cycle variation of the horizontal velocity of displacement (dV) and the energy cost (EC) in butterfly stroke. Five Portuguese national level swimmers performed one maximal and two sub-maximal 200-m butterfly swims. The oxygen consumption was measured breath-by-breath by portable metabolic cart. A respiratory snorkel and valve system with low hydrodynamic resistance was used to measure pulmonary ventilation and to collect breathing air samples. Blood samples from the ear lobe were collected before and after each swim to analyse blood lactate concentration. Total energy expenditure ( E (tot)) and EC were calculated for each swim. The swims were videotaped in the sagittal plane with a set of two cameras providing dual projection from both underwater and above the water surface. The APAS system was used to analyse dV for the centre of mass. The E (tot) increased linearly with the increasing V, presenting a significant correlation coefficient between these parameters ( r =0.827, P <0.001). The increase in EC was significantly associated with the increase in the dV ( r =0.807, P <0.001). All data were presented as the mean value and the standard deviation. It is concluded that high intra-cycle variation of the velocity of the centre of mass was related to less efficient swimming and vice versa for the butterfly stroke.

Proposta de um método alternativo para a determinação da concentração de hemoglobina / Proposed an alternative method to determinate the hemoglobin concentration

A hemoglobina (Hb), principal componente das células vermelhas sanguíneas, é um conjugado de proteínas que serve como transporte de O2 e CO2, sendo assim, indispensável à manutenção da vida dos mamíferos. A quantidade de hemoglobina por 100 mL de sangue pode ser utilizada como índice da capacidade de transporte de oxigênio. O teor total de hemoglobina no sangue depende principalmente do número de eritrócitos e, em menor grau, da quantidade de hemoglobina existente em cada eritrócito. Dependendo do método utilizado e dos cuidados com os quais o laboratório afere seus instrumentos, os métodos para a determinação da hemoglobina que utilizam o espectrofotômetro e contadores automáticos, apresentam uma precisão de 4 a 5% e 2 a 3% respectivamente. Como alguns métodos para dosagem da hemoglobina baseiam-se na medida do índice de hemólise, introduzimos no presente trabalho uma técnica na qual foi utilizada apenas água deionizada como diluente, que, seguramente também provoca tal fenômeno. O método proposto tem como objetivo investigar a compatibilidade entre os resultados obtidos com os que fazem uso do ferricianeto de potássio e hidróxido de amônia. A concentração de hemoglobina foi determinada em 30 amostras de sangue recentemente colhidas com EDTA em tubo a vácuo. Para efeito comparativo, foram utilizados dois tipos de padrão: o que acompanha o kit e uma amostra de sangue devidamente padronizada pelo laboratório (LACT). Os resultados obtidos demonstram diferenças significativas entre os métodos realizados com o padrão do fabricante, enquanto que, com o padrão de referência do laboratório, foi verificada uma significativa compatibilidade. Portanto, os dados indicam que o método proposto poderá ser útil na determinação da concentração de hemoglobina no laboratório clínico, não esquecendo o fato de que, além de outras vantagens, a toxicidade causada pelo ferricianeto é totalmente eliminada.