Identification of protein expression signatures in gastric carcinomas using clustering analysis

Background and Aim: The identification of gastric carcinomas (GC) has traditionally been based on histomorphology. Recently, DNA microarrays have successfully been used to identify tumors through clustering of the expression profiles. Random forest clustering is widely used for tissue microarrays and other immunohistochemical data, because it handles highly-skewed tumor marker expressions well, and weighs the contribution of each marker according to its relatedness with other tumor markers. In the present study, we e identified biologically- and clinically-meaningful groups of GC by hierarchical clustering analysis of immunohistochemical protein expression. Methods: We selected 28 proteins (p16, p27, p21, cyclin D1, cyclin A, cyclin B1, pRb, p53, c-met, c-erbB-2, vascular endothelial growth factor, transforming growth factor [TGF]-beta I, TGF-beta II, MutS homolog-2, bcl-2, bax, bak, bcl-x, adenomatous polyposis coli, clathrin, E-cadherin, beta-catenin, mucin (MUC) 1, MUC2, MUC5AC, MUC6, matrix metalloproteinase [ MMP]-2, and MMP-9) to be investigated by immunohistochemistry in 482 GC. The analyses of the data were done using a random forest-clustering method. Results: Proteins related to cell cycle, growth factor, cell motility, cell adhesion, apoptosis, and matrix remodeling were highly expressed in GC. We identified protein expressions associated with poor survival in diffuse-type GC. Conclusions: Based on the expression analysis of 28 proteins, we identified two groups of GC that could not be explained by any clinicopathological variables, and a subgroup of long-surviving diffuse-type GC patients with a distinct molecular profile. These results provide not only a new molecular basis for understanding the biological properties of GC, but also better prediction of survival than the classic pathological grouping.

Time constraints on magmatism along the Major Gercino Shear Zone, southern Brazil: Implications for West Gondwana reconstruction

The Dom Feliciano Belt, situated in southernmost Brazil and Uruguay, contains a large mass of granite-gneissic rocks (also known as Florianopolis/Pelotas Batholith) formed during the pre-, syn- and post-orogenic phases of the Brasiliano/Pan-African cycle. In the NE extreme of this granitic mass, pre-, syn- and post-tectonic granites associated with the Major Gercino Shear Zone (MGSZ) are exposed. The granitic manifestation along the MGSZ can be divided into pre-kinematic tonalitic gneisses, peraluminous high-K calcalkaline early kinematic shoshonitic, and metaluminous post-kinematic granites. U-Pb zircon data suggest an age of 649 +/- 10 Ma for the pre-tectonic gneisses, and a time span from 623 +/- 6 Ma to 588 +/- 3 Ma for the early to post-tectonic magmatism. Negative epsilon Hf (t) values ranging from -4.6 to -14.6 and Hf model ages ranging from 1.64 to 2.39 Ga for magmatic zircons coupled with whole rock Nd model ages ranging from 1.24 to 2.05 Ga and epsilon Nd (t) values ranging from -3.84 to -7.50, point to a crustal derivation for the granitic magmatism. The geochemical and isotope data support a continental magmatic arc generated from melting of dominant Paleoproterozoic crust, and a similar evolution for the granitic batholiths of the eastern Dom Feliciano Belt and western Kaoko Belt. (C) 2011 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

CD44(+)/CD24(-) cells and lymph node metastasis in stage I and II invasive ductal carcinoma of the breast

The presence of tumor-initiating cells (CD44(+)/CD24(-)) in solid tumors has been reported as a possible cause of cancer metastasis and treatment failure. Nevertheless, little is know about the presence of CD44(+)/CD24(-) cells within the primary tumor and metastasis. The proportion of CD44(+)/CD24(-) cells was analyzed in 40 samples and in 10 lymph node metastases using flow cytometry phenotyping. Anti-human CD326 (EpCam; FITC), antihuman CD227 (MUC-1; FITC), anti-human CD44 (APC), and anti-human CD24 (PE), anti-ABCG2 (PE), and anti-CXCR4 (PeCy7) were used for phenotype analysis. The mean patient age was 60.5 years (range, 33-87 years); mean primary tumor size (pT) was 1.8 cm (0.5-3.5 cm). The Wilcoxon or Kruskal-Wallis test was used for univariate analyses. Logistic regression was used for multivariate analysis. The median percentage of CD44(+)/CD24(-) cells within primary invasive ductal carcinomas (IDC) was 2.7% (range, 0.2-71.2). In lymph node metastases, we observed a mean of 6.1% (range, 0.07-53.7). The percentage of CD44(+)/CD24(-) cells in IDCs was not associated with age, pT, tumor grade and HER2. We observed a significantly enrichment of CD44(+)/CD24(-) and ABCG2(+) cells in ESA(+) cell population in patients with positive lymph nodes (P = 0.02 and P = 0.04, respectively). Our data suggest that metastatic dissemination is associated with an increase in tumorinitiating cells in stage I and II breast cancer.

In vivo study of laser irradiation of fractionated drug administration based mechanism for effective photodynamic therapy in rat liver

Up-regulation of stress-activated proteins in cancer cells plays a protective role against photodynamic induced apoptosis. Post photodynamic therapy extracted normal rat liver tissue usually shows a fraction of surviving cells, the photodynamic resistant cells, residing in the necrotic region. To treat these photo-dynamic resistant cells a technique has been proposed based on fractionated drug administration of diluted photosensitizer, keeping the net concentration (5 mg/kg) constant, and subsequently varying drug light interval (DLI). Flourescence measurements were made for the presence of photosensitizer in a tissue. For qualitative analysis both histological and morphological studies were made. Although preliminary aim of this approach was not achieved but there were some interesting observation made i.e. for higher dilution of photosensitizer there was a sharp boundary between necrotic and normal portion of tissue. An increase in the absorption coefficient (alpha) from 2.7 -> 2.9 was observed as photosensitizer was diluted while the corresponding threshold dose (D (th)) persistently decreases from (0.10 -> 0.02) J/cm(2) when irradiated with a 635 nm laser fluence of 150 J/cm(2).

The erosion and abrasion-inhibiting effect of TiF4 and NaF varnishes and solutions on enamel in vitro

Objective. Previous in vitro study has shown that TiF(4) varnish might reduce enamel erosion. No data regarding the effect of this experimental varnish on enamel erosion plus abrasion, however, are available so far. Thus, this in vitro study aimed to analyse the effect of TiF4 compared with NaF varnishes and solutions, to protect against enamel erosion with or without abrasion. Methods. Enamel specimens were pre-treated with experimental-TiF4 (2.45% F), experimentalNaF (2.45% F), NaF-Duraphat (2.26% F), and placebo varnishes; NaF (2.26% F) and TiF4 (2.45% F) solutions. Controls remained untreated. The erosive challenge was performed using a soft drink (pH 2.6) 4 u 90 s / day (ERO) and the toothbrushing abrasion (ERO+ ABR) 2 u 10 s / day, for 5 days. Between the challenges, the specimens were exposed to artificial saliva. Enamel loss was measured profilometrically (lm). Results. Kruskal-Wallis / Dunn tests showed that all fluoridated varnishes (TiF4-ERO: 0.53 +/- 0.20, ERO+ ABR: 0.65 +/- 0.19/ NaF-ERO: 0.94 +/- 0.18, ERO+ ABR: 1.74 +/- 0.37 / Duraphat-ERO: 1.00 +/- 0.37, ERO+ ABR: 1.72 +/- 0.58) were able to significantly reduce enamel loss when compared with placebo varnish (ERO: 3.45 +/- 0.41 / ERO+ ABR: 3.20 +/- 0.66) (P < 0.0001). Placebo varnish, control (ERO: 2.68 +/- 0.53 / ERO+ ABR: 3.01 +/- 0.34), and fluoridated (NaF-ERO: 2.84 +/- 0.09 / ERO+ ABR: 2.40 +/- 0.21 / TiF4-ERO: 3.55 +/- 0.59 / ERO+ ABR: 4.10 +/- 0.38) solutions did not significantly differ from each other. Conclusion. Based on the results, it can be concluded that the TiF4 varnish seems to be a promising treatment to reduce enamel loss under mild erosive and abrasive conditions in vitro.

Low cost ion implantation technique

We describe an approach to ion implantation in which the plasma and its electronics are held at ground potential and the ion beam is formed and injected energetically into a space held at high negative potential. The technique allows considerable savings both economically and technologically, rendering feasible ion implantation applications that might otherwise not be possible for many researchers and laboratories. Here, we describe the device and the results of tests demonstrating Nb implantation at 90 keV ion energy and dose about 2 x 10(16) cm(-2). (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4768699]

Photoisomerization for a model protonated Schiff base in solution: Sloped/peaked conical intersection perspective

The topographical character of conical intersections (CIs)-either sloped or peaked-has played a fundamental and important role in the discussion of the efficiency of CIs as photochemical "funnels." Here this perspective is employed in connection with a recent study of a model protonated Schiff base (PSB) cis to trans photoisomerization in solution [Malhado et al., J. Phys. Chem. A 115, 3720 (2011)]. In that study, the calculated reduced photochemical quantum yield for the successful production of trans product versus cis reactant in acetonitrile solvent compared to water was interpreted in terms of a dynamical solvent effect related to the dominance, for the acetonitrile case, of S-1 to S-0 nonadiabatic transitions prior to the reaching the seam of CIs. The solvent influence on the quantum yield is here re-examined in the sloped/peaked CI topographical perspective via conversion of the model's two PSB internal coordinates and a nonequilibrium solvent coordinate into an effective branching space description, which is then used to re-analyze the generalized Langevin equation/surface hopping results. The present study supports the original interpretation and enriches it in terms of topographical detail. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4754505]

A feature selection approach for identification of signature genes from SAGE data

Abstract Background One goal of gene expression profiling is to identify signature genes that robustly distinguish different types or grades of tumors. Several tumor classifiers based on expression profiling have been proposed using microarray technique. Due to important differences in the probabilistic models of microarray and SAGE technologies, it is important to develop suitable techniques to select specific genes from SAGE measurements. Results A new framework to select specific genes that distinguish different biological states based on the analysis of SAGE data is proposed. The new framework applies the bolstered error for the identification of strong genes that separate the biological states in a feature space defined by the gene expression of a training set. Credibility intervals defined from a probabilistic model of SAGE measurements are used to identify the genes that distinguish the different states with more reliability among all gene groups selected by the strong genes method. A score taking into account the credibility and the bolstered error values in order to rank the groups of considered genes is proposed. Results obtained using SAGE data from gliomas are presented, thus corroborating the introduced methodology. Conclusion The model representing counting data, such as SAGE, provides additional statistical information that allows a more robust analysis. The additional statistical information provided by the probabilistic model is incorporated in the methodology described in the paper. The introduced method is suitable to identify signature genes that lead to a good separation of the biological states using SAGE and may be adapted for other counting methods such as Massive Parallel Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS) technique. Some of such genes identified by the proposed method may be useful to generate classifiers.

Awareness and knowledge of HPV, cervical cancer, and vaccines in young women after first delivery in São Paulo, Brazil - a cross-sectional study

Abstract Background The success of HPV vaccination programs will require awareness regarding HPV associated diseases and the benefits of HPV vaccination for the general population. The aim of this study was to assess the level of awareness and knowledge of human papillomavirus (HPV) infection, cervical cancer prevention, vaccines, and factors associated with HPV awareness among young women after birth of the first child. Methods This analysis is part of a cross-sectional study carried out at Hospital Maternidade Leonor Mendes de Barros, a large public maternity hospital in Sao Paulo. Primiparous women (15-24 years) who gave birth in that maternity hospital were included. A questionnaire that included questions concerning knowledge of HPV, cervical cancer, and vaccines was applied. To estimate the association of HPV awareness with selected factors, prevalence ratios (PR) were estimated using a generalized linear model (GLM). Results Three hundred and one primiparous women were included; 37% of them reported that they "had ever heard about HPV", but only 19% and 7%, respectively, knew that HPV is a sexually transmitted infection (STI) and that it can cause cervical cancer. Seventy-four percent of interviewees mentioned the preventive character of vaccines and all participants affirmed that they would accept HPV vaccination after delivery. In the multivariate analysis, only increasing age (P for trend = 0.021) and previous STI (P < 0.001) were factors independently associated with HPV awareness ("had ever heard about HPV"). Conclusions This survey indicated that knowledge about the association between HPV and cervical cancer among primiparous young women is low. Therefore, these young low-income primiparous women could benefit greatly from educational interventions to encourage primary and secondary cervical cancer prevention programs.

Diagnosis and biomarkers of predementia in Alzheimer's disease

In view of the growing prevalence of Alzheimer's disease (AD) worldwide, there is an urgent need for the development of better diagnostic tools and more effective therapeutic interventions. At the earliest stages of AD, no significant cognitive or functional impairment is detected by conventional clinical methods. However, new technologies based on structural and functional neuroimaging, and on the biochemical analysis of cerebrospinal fluid (CSF) may reveal correlates of intracerebral pathology in individuals with mild, predementia symptoms. These putative correlates are commonly referred to as AD-related biomarkers. The relevance of the early diagnosis of AD relies on the hypothesis that pharmacological interventions with disease-modifying compounds are likely to produce clinically relevant benefits if started early enough in the continuum towards dementia. Here we review the clinical characteristics of the prodromal and transitional states from normal cognitive ageing to dementia in AD. We further address recent developments in biomarker research to support the early diagnosis and prediction of dementia, and point out the challenges and perspectives for the translation of research data into clinical practice.

Assessing malaria transmission in a low endemicity area of north-western Peru

Background Where malaria endemicity is low, control programmes need increasingly sensitive tools for monitoring malaria transmission intensity (MTI) and to better define health priorities. A cross-sectional survey was conducted in a low endemicity area of the Peruvian north-western coast to assess the MTI using both molecular and serological tools. Methods Epidemiological, parasitological and serological data were collected from 2,667 individuals in three settlements of Bellavista district, in May 2010. Parasite infection was detected using microscopy and polymerase chain reaction (PCR). Antibodies to Plasmodium vivax merozoite surface protein-119 (PvMSP119) and to Plasmodium falciparum glutamate-rich protein (PfGLURP) were detected by ELISA. Risk factors for exposure to malaria (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific antibody prevalence of both P. falciparum and P. vivax were analysed using a previously published catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR). Results The overall parasite prevalence by microscopy and PCR were extremely low: 0.3 and 0.9%, respectively for P. vivax, and 0 and 0.04%, respectively for P. falciparum, while seroprevalence was much higher, 13.6% for P. vivax and 9.8% for P. falciparum. Settlement, age and occupation as moto-taxi driver during previous year were significantly associated with P. falciparum exposure, while age and distance to the water drain were associated with P. vivax exposure. Likelihood ratio tests supported age seroprevalence curves with two SCR for both P. vivax and P. falciparum indicating significant changes in the MTI over time. The SCR for PfGLURP was 19-fold lower after 2002 as compared to before (λ1 = 0.022 versus λ2 = 0.431), and the SCR for PvMSP119 was four-fold higher after 2006 as compared to before (λ1 = 0.024 versus λ2 = 0.006). Conclusion Combining molecular and serological tools considerably enhanced the capacity of detecting current and past exposure to malaria infections and related risks factors in this very low endemicity area. This allowed for an improved characterization of the current human reservoir of infections, largely hidden and heterogeneous, as well as providing insights into recent changes in species specific MTIs. This approach will be of key importance for evaluating and monitoring future malaria elimination strategies.

Phylogeography of the neotropical Anopheles triannulatus complex (Diptera: Culicidae) supports deep structure and complex patterns

Abstract Background The molecular phylogenetic relationships and population structure of the species of the Anopheles triannulatus complex: Anopheles triannulatus s.s., Anopheles halophylus and the putative species Anopheles triannulatus C were investigated. Methods The mitochondrial COI gene, the nuclear white gene and rDNA ITS2 of samples that include the known geographic distribution of these taxa were analyzed. Phylogenetic analyses were performed using Bayesian inference, Maximum parsimony and Maximum likelihood approaches. Results Each data set analyzed septely yielded a different topology but none provided evidence for the seption of An. halophylus and An. triannulatus C, consistent with the hypothesis that the two are undergoing incipient speciation. The phylogenetic analyses of the white gene found three main clades, whereas the statistical parsimony network detected only a single metapopulation of Anopheles triannulatus s.l. Seven COI lineages were detected by phylogenetic and network analysis. In contrast, the network, but not the phylogenetic analyses, strongly supported three ITS2 groups. Combined data analyses provided the best resolution of the trees, with two major clades, Amazonian (clade I) and trans-Andean + Amazon Delta (clade II). Clade I consists of multiple subclades: An. halophylus + An. triannulatus C; trans-Andean Venezuela; central Amazonia + central Bolivia; Atlantic coastal lowland; and Amazon delta. Clade II includes three subclades: Panama; cis-Andean Colombia; and cis-Venezuela. The Amazon delta specimens are in both clades, likely indicating local sympatry. Spatial and molecular variance analyses detected nine groups, corroborating some of subclades obtained in the combined data analysis. Conclusion Combination of the three molecular markers provided the best resolution for differentiation within An. triannulatus s.s. and An. halophylus and C. The latest two species seem to be very closely related and the analyses performed were not conclusive regarding species differentiation. Further studies including new molecular markers would be desirable to solve this species status question. Besides, results of the study indicate a trans-Andean origin for An. triannulatus s.l. The potential implications for malaria epidemiology remain to be investigated.

Prevalência de asma e fatores associados: estudo de base populacional em São Paulo, SP, 2008-2009

OBJETIVO: Estimar a prevalência de asma em crianças e adolescentes e identificar fatores associados. MÉTODOS: Estudo transversal de base populacional com 1.185 crianças e adolescentes de ambos os sexos de São Paulo, SP, de 2008 a 2009. As informações foram coletadas por meio de entrevistas domiciliares e os participantes foram selecionados a partir de amostragem probabilística, estratificada por sexo e idade, e por conglomerados em dois estágios (setores censitários e domicílios). Foi realizada regressão múltipla de Poisson na análise ajustada entre o desfecho e variáveis sociodemográficas, econômicas, estilo de vida e condições de saúde. RESULTADOS: Dos entrevistados, 9,1% (IC95% 7,0;11,7) referiram asma. Após análise ajustada, identificaram-se os seguintes fatores independentemente associados ao agravo: idade (zero a quatro anos/15 a 19) RP = 3,18 (IC95% 1,20;8,42), idade (cinco a nove anos/15 a 19) RP = 6,37 (IC95% 2,64;15,39), idade (10 a 14 anos/15 a 19) RP = 4,51 (IC95% 1,95;10,40), alergia (sim/não) RP = 2,22 (IC95% 1,24;4,00), rinite (sim/não) RP = 2,13 (IC95% 1,22;3,73), problemas de saúde nos 15 dias prévios à entrevista (sim/não) RP = 1,96 (IC95% 1,23;3,11), número de cômodos no domicílio (1 a 3/4 e mais) RP = 1,67 (IC95% 1,05;2,66), e cor da pele (preta e parda/branca) RP = 2,00 (IC95% 1,14;3,49). CONCLUSÕES: Os achados do presente estudo apontam a importância da asma associada à presença de rinite e alergia, idade entre cinco e nove anos, cor da pele preta e parda e moradia com menor número de cômodos. Os frequentes problemas de saúde podem ser considerados consequência dessa doença.

In vitro schistosomicidal effects of the essential oil of Tagetes erecta

The in vitro schistosomicidal effects of the essential oil obtained from Tagetes erecta L. Asteraceae, leaves (TE-EO) collected in Brazil against Schistosoma mansoni worms are reported in this paper. The oil caused a significant decrease in the motor activity at 50 µg/mL as minimal concentration after 24 h. This oil also caused death of all the parasites and the separation of coupled pairs into individual male and female at 100 µg/mL after 24 h. The viability of adult worm groups treated with the TE-EO at 100 µg/mL was similar to that of groups treated with praziquantel (positive control). In addition, the oil promoted the inhibition of eggs development at all the tested concentrations. These data indicate that the TE-EO could be considered as a promising source for the development of new schistosomicidal agents.

Fatores de influência no preço do milho no Brasil

Compreender a dinâmica de funcionamento do mercado de milho brasileiro, procedendo a uma investigação dos fatores que afetam as quantidades e preços nesse mercado, é o objetivo deste trabalho. Os testes de raiz unitária foram feitos utilizando-se a metodologia DF-GLS - Dickey Fuller Generalized Least Square - e os de cointegração de Johansen (1988). O modelo estimado, de ajuste pelo preço, foi um Modelo de Autorregressão Vetorial com Correção de Erros - VEC, sendo a identificação feita pelo procedimento de Sims-Bernanke. O estudo permite afirmar que existe forte interação entre os mercados de milho e de soja, mostrando uma relação de complementaridade na oferta e substitutibilidade na demanda, e que fatores macroeconômicos como renda e juros são importantes na determinação dos preços do milho ao produtor e no atacado. Vale ressaltar que os preços externos do milho mostraram relativa importância no processo de formação do preço doméstico do grão.