Significance of topoisomerase III beta expression in breast ductal carcinomas: strong associations with disease-specific survival and metastasis

Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase III beta, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase III beta in breast cancer and its relationships with clinicopathologic features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase III beta, estrogen receptor, progesterone receptor, HER-2, BRCA-1, p53, and Ki67. Immunostaining for topoisomerase III beta was found in 33.9% of breast carcinomas, and immunopositivity was correlated with distant metastasis (P = .036) and death (P = .006). Decreased expression of topoisomerase III beta correlated with low expression of Ki67 (P < .001) and negativity for HER-2 (P < .001), BRCA-1 (P = .001), and p53 (P < .001). In the multivariate analysis, topoisomerase Hip expression was a significant predictor of survival (hazard ratio, 3.006 [95% confidence interval, 1.582-5.715]; P = .001). In conclusion, topoisomerase III beta expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival. (C) 2010 Elsevier Inc. All rights reserved.

Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (NOS3) polymorphisms are associated with high relapse risk in childhood acute lymphoblastic leukemia (ALL)

Background: Angiogenesis has been shown as an important process in hematological malignancies. It consists in endothelial proliferation, migration, and tube formation following pro-angiogenic factors releasing, specially the vascular endothelial growth factor (VEGF), which angiogenic effect seems to be dependent on nitric oxide (NO). We examined the association among functional polymorphism in these two angiogenesis related genes: VEGF (-2578C>A, -1154G>A, and -634G>C) and NOS3 (-786T>C, intron 4 b>a, and Glu298Asp) with prognosis of childhood acute lymphoblastic leukemia (ALL). Methods: The genotypes were determined and haplotypes estimated in 105 ALL patients that were divided in 2 groups: high risk (HR) and low risk of relapse (LR) patients. In addition, event-free survival curves according to genotypes were assessed. Results: The group HR compared to the LR showed a higher frequency of the alleles -2578C and -634C and the haplotype CGC for VEGF (0.72 vs. 0.51, p<0.008; 0.47 vs. 0.26, p<0.008; and 42.1 vs. 14.5, p<0.006; respectively) and a lower frequency of the haplotype CbGlu (0.4 vs. 8.8, p<0.006), for NOS3. Conclusion: Polymorphisms of VEGF and NOS3 genes are associated with high risk of relapse, therefore may have a prognostic impact in childhood ALL. (C) 2010 Elsevier B.V. All rights reserved.

Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome in childhood acute lymphoblastic leukemia

The interindividual variation in the activity of xenobiotic metabolizing enzymes and DNA repair genes could modify an individual`s risk of recurrent malignancy and response to therapy. We investigated whether ALL outcome was related to polymorphisms in genes CYP2D6. MPO, EPHX1, NQO1, TS, XPD and XRCC1 in 95 consecutive ALL children by PCR or PCR-FRLP techniques. Polymorphisms in genes NQO1 and TS were associated with a significantly slow response to induction chemotherapy and NQO1 was also associated with a lower five-year event-free survival. This study suggests that polymorphisms of NQO1 and TS could be important for patient response to induction therapy and for treatment outcome. (C) 2009 Elsevier Ltd. All rights reserved.

Transcriptional profiling reveals genes in the human pathogen Trichophyton rubrum that are expressed in response to pH signaling

Trichophyton rubrum is a dermatophyte that infects human skin and nails. Its growth on keratin as its carbon source shifts the ambient pH from acidic to alkaline, which may be an efficient strategy for its successful infection and maintenance in the host. In this study, we used suppression subtractive hybridization to identify genes preferentially expressed in T rubrum incubated at either pH 5.0 or pH 8.0. The functional grouping of the 341 overexpressed unigenes indicated proteins putatively involved in diverse cellular processes, such as membrane remodeling, cellular transport, metabolism, cellular protection, fungal pathogenesis, gene regulation, interaction with the environment, and iron uptake. Although the basic metabolic machinery identified under both growth conditions seems to be functionally similar, distinct genes are upregulated at acidic or alkaline pHs. We also isolated a large number of genes of unknown function, probably unique to T rubrum or dermatophytes. Interestingly, the transcriptional profiling of several genes in a pacC mutant suggests that, in T rubrum, the transcription factor PacC has a diversity of metabolic functions, in response to either acidic or alkaline ambient pH. (C) 2009 Elsevier Ltd. All rights reserved.

Qualitative analysis of hippocampal plastic changes in rats with epilepsy supplemented with oral omega-3 fatty acids

Studies have provided evidence of the important effects of omega-3 fatty acid on the brain in neurological conditions, including epilepsy. Previous data have indicated that omega-3 fatty acids lead to prevention of status epilepticus-associated neuropathological changes in the hippocampal formation of rats with epilepsy. Omega-3 fatty acid supplementation has resulted in extensive preservation of GABAergic cells in animals with epilepsy. This study investigated the interplay of these effects with neurogenesis and brain-derived neurotrophic factor (BDNF). The results clearly showed a positive effect of long-term omega-3 fatty acid supplementation on brain plasticity in animals with epilepsy. Enhanced hippocampal neurogenesis and BDNF levels and preservation of interneurons expressing parvalbumin were observed. Parvalbumin-positive cells were identified as surviving instead of newly formed cells. Additional investigations are needed to determine the electrophysiological properties of the newly formed cells and to clarify whether the effects of omega-3 fatty acids on brain plasticity are accompanied by functional gain in animals with epilepsy. (C) 2009 Elsevier Inc. All rights reserved.

Identification of T cell epitopes on the 33-kDa fragment of Plasmodium yoelii merozoite surface protein 1 and their antibody-independent protective role in immunity to blood stage malarial

Merozoite surface protein 1 (MSP1) of malaria parasites undergoes proteolytic processing at least twice before invasion into a new RBC. The 42-kDa fragment, a product of primary processing, is cleaved by proteolytic enzymes giving rise to MSP1(33), which is shed from the merozoite surface, and MSP1(19), which is the only fragment carried into a new RBC. In this study, we have identified T cell epitopes on MSP1(33) of Plasmodium yoelii and have examined their function in immunity to blood stage malaria. Peptides 20 aa in length, spanning the length of MSP1(33) and overlapping each other by 10 aa, were analyzed for their ability to induce T cell proliferation in immunized BALB/c and C57BL/6 mice. Multiple epitopes were recognized by these two strains of mice. Effector functions of the dominant epitopes were then investigated. Peptides Cm15 and Cm21 were of particular interest as they were able to induce effector T cells capable of delaying growth of lethal P. yoelii YM following adoptive transfer into immuno-deficient mice without inducing detectable Ab responses. Homologs of these epitopes could be candidates for inclusion in a subunit vaccine.

Texto para discuss??o 33: a iman??ncia do planejamento e da gest??o: a experi??ncia de Curitiba

O prop??sito deste artigo ?? fazer uma reflex??o em torno da iman??ncia do planejamento com a gest??o, da inseparabilidade dessas duas pr??ticas sociais. Trata-se, aqui, de uma explora????o e reflex??o sobre o tema a partir da experi??ncia concreta que est?? sendo conduzida pela Prefeitura Municipal de Curitiba, desde janeiro de 1997

Interação mãe-bebê e uso de chupeta no contexto do nascimento pré-termo : cultura, representações sociais e processos proximais

Objetivo: Investigar a avaliação de mães de recém-nascidos pré-termo (RNPT) egressos de unidades de terapia intensiva neonatal (UTIN) quanto à interação mãe-bebê e uso de chupeta nos primeiros dois anos. Método: O planejamento do estudo longitudinal foi baseado na Teoria Bioecológica do Desenvolvimento Humano, com foco nos processos proximais (PP), utilizando entrevistas gravadas com 62 mães de RNPT no contexto da UTIN e 33 aos seis, 12, 18 e 24 meses de idade do bebê, considerando Grupo-A (chupeta) e Grupo-B (não usou chupeta). Resultados: A vivência em UTIN foi considerada evento impactante na vida das mães, mas expectativas futuras para a relação mãe-bebê foram positivas. A tentativa de oferta da chupeta foi 96,2% e seu uso aos seis meses foi 50% (n=52), significativamente associado com prematuridade pela relação peso/idade-gestacional (p-valor=0,044), dificuldades para estabelecer aleitamento materno exclusivo (AME) (p=0,012) e primiparidade (p=0,02). Apresentaram relação com menor frequência de chupeta: AME ≥3 meses (p=0,026) e tempo de aleitamento materno ≥6 meses. A chupeta configurou-se como uma das representações sociais sobre objetos de bebê, elaboradas pelas participantes aos 12 meses de idade do bebê. Características de temperamento calmo/tranquilo da mãe foram mais frequentes no Grupo-A e o temperamento nervoso/agitado/irritado no Grupo-B (p-valor=0,041). No Grupo-A predominou o temperamento do bebê calmo/fácil-de-cuidar/independente, enquanto no Grupo-B as características de temperamento agitado/bagunceiro/teimoso/agressivo (p-valor=0,026), associado também à necessidade de várias tentativas de oferta da chupeta (p-valor=0,006). No Grupo-A, o número de pessoas para apoio social foi uma ou duas (77,8%), enquanto no Grupo-B foram três a sete (66,7%), p-valor=0,001. A contribuição da chupeta como auxiliar nos PP foi indiferente para mães que controlavam o hábito, enquanto o uso irrestrito facilitava a resolução do choro, liberando a mãe para outras tarefas, atuando como limitador dos PP. A análise da evolução e complexidade dos PP demonstrou não haver interferência pelo uso da chupeta, tendo sido mais efetivos quando as mães tinham maior escolaridade e nas classes econômicas A e B. Conclusão: Aspectos culturais influenciaram na oferta da chupeta, mas sua aceitação ocorreu principalmente em RNPT pequeno para idade gestacional, diante das dificuldades para AME, menor extensão do apoio social e temperamento do bebê calmo/fácil-de-cuidar/independente, também associado à aceitação mais fácil da chupeta. O uso irrestrito da chupeta demonstrou atuar como limitador dos processos proximais.

Avaliação crítica de 33 pacientes com bócio mergulhante tratados cirurgicamente por cervicotomia

A possibilidade de ser necessário um acesso combinado, com uma incisão cervical e outra torácica, torna o tratamento do bócio mergulhante um desafio tanto no pré quanto no intra-operatório. Discutimos uma padronização da técnica cirúrgica para minimizar a necessidade da abordagem torácica, tornando o bócio mergulhante uma patologia tratável cirurgicamente, por uma única incisão cervical, e com baixos índices de complicações. OBJETIVO: Avaliar a abordagem cirúrgica do bócio mergulhante por cervicotomia e analisar as complicações cirúrgicas. MATERIAL E MÉTODOS: Foi realizada uma coorte histórica com corte transversal por análise retrospectiva dos prontuários de pacientes submetidos à tireoidectomia no período de maio de 2002 a julho de 2007. Um total de 316 pacientes foi submetido à tireoidectomia sendo 33 (10,4%) por bócio mergulhante. RESULTADOS: Todos os 33 pacientes foram tratados cirurgicamente por via cervical sem necessidade de esternotomia. Não foram observadas lesões definitivas de nervo laríngeo inferior ou hipoparatireoidismo definitivo. Apenas 2 pacientes apresentaram paresia de nervo recorrente e 2 pacientes foram reabordados por hematoma cervical. CONCLUSÃO: Pacientes com bócio mergulhante podem ser tratados cirurgicamente por uma única incisão cervical com segurança e baixos índices de complicação.

Estudo das diferenças de género nas cognições antecipatórias, estratégias de coping e depressão em adultos

RESUMO: A presente dissertação tem o objectivo de estudar a relação das diferenças de género nas cognições antecipatórias, estratégias de coping e depressão. Para o efeito, constituiu-se duas amostras, uma de indivíduos do género feminino (n=224) de 57,9% (com uma média de idades de 36,2 e um DP=10,5), e outra por indivíduos do género masculino (n=163), perfazendo uma percentagem de 42,1% (com uma média de idades de 41,1 e um DP=12,5). Foi elaborado um protocolo de investigação composto por: Questionário de dados sócio-demográficos, Questionário de Cognições Antecipatórias (QCA), de Figueira & Ramos, 1995, o Questionário de Modos de Lidar com os Acontecimentos (QMLA), de J. Pais Ribeiro, C. Santos, 2001 e o Inventário de Avaliação Clínica da Depressão (IACLIDE), de A, Vaz Serra, 1995. Os resultados demonstraram que não existem diferenças estatisticamente significativas entre géneros nas cognições antecipatórias (p=0,594). Em relação às estratégias de coping, os resultados foram estatisticamente significativos, com as mulheres a recorrerem mais à procura de suporte social (p=0,042) e à fuga-evitamento (p=0,006). O índice de depressão mostra, de forma estatisticamente significativa, que o género feminino apresenta valores mais elevados (p=0,038). A escala de depressão permitiu ainda verificar de forma estatisticamente significativa que as mulheres revelam mais dificuldades no desempenho das tarefas associadas a queixas biológicas e cognitivas (p=0,003), tal como nas dimensões biológica (p=0,002) e de desempenho da tarefa (p=0,007). A relação entre as três variáveis, permite concluir que o índice global da escala de depressão está relacionado positivamente com as Cognições Antecipatórias (p=,000), e nas estratégias de coping, as dimensões fuga-evitamento (p=,002), resolução planeada do problema (p=,000) e a reavaliação positiva (p=,034) também estão relacionadas com esta escala da depressão de forma estatisticamente significativa. ABSTRACT: This dissertation aims to study the relationship of gender differences in anticipatory cognitions, coping strategies and depression. For this purpose, it was constituted two samples, one for female gender (n = 224) 57.9% (with a mean age of 36.2 and a SD=10.5), and other of male gender (n = 163), giving a percentage of 42.1% (with an average age of 41.1 and a SD=12.5). It was prepared a research protocol composed of data questionnaire included social-demographic, Anticipatory Cognitions Questionnaire (QCA), Figueira & Ramos, 1995, the Ways of Coping Questionnaire (WCQ), J. Pais Ribeiro, C. Santos, 2001, and the Inventory and Evaluation of Clinical Depression (IACLIDE) A, Vaz Serra, 1995. The results have shown no statistically significant differences between genders in anticipatory cognitions (p= 0.594). In the coping strategies, the results were statistically significant, with women looking to take more advantage of social support (p= 0.042) and escape-avoidance (p= 0.006). The rate of depression shows a statistically significant with females having higher values (p=0.038). The depression scale allowed us to verify statistically significant that women shows more difficulty in performing tasks associated with biological and cognitive complaints (p=0,003), as in the biological (p=0,002) and task performance (p=0,007). The relationship between the three variables, shows that the overall rate of depression scale is positively related to the Anticipatory Cognitions (p =, 000), and strategies for coping, escape-avoidance dimensions (p =, 002), resolution of the planned problem (p =, 000) and positive reappraisal (p =, 034) are also related to the scale of depression and were also statistically significant.

Norma internacional de contabilidade [NIC 33]: resultados por acção

Revista Fiscal, Março 2008

Fatores associados à preferência por cesareana

OBJETIVO: Estudar os fatores relacionados à preferência por cesariana, em gestantes sem intercorrências. MÉTODOS: Estudo transversal com 156 gestantes, de clínica privada na cidade de Osasco, Estado de São Paulo, no período de outubro de 2000 a dezembro de 2001. As gestantes estavam em idade gestacional de 28 semanas ou mais, sem contra-indicação formal para parto vaginal, no momento da entrevista. Foi aplicado questionário sobre informações sociodemográficas, história obstétrica passada e atual. Perguntou-se à gestante questão específica sobre preferência para o parto. Realizou-se teste do qui-quadrado de Pearson e regressão logística para análise multivariada, com nível de significância de 5%. RESULTADOS: Sessenta e sete (42,9%) gestantes se diziam pouco motivadas para parto vaginal. Na análise multivariada foram estatisticamente significativas as seguintes variáveis: parto vaginal prévio (p<0,001; ORaj=0,04; IC 95%=0,01-0,12); a renda do marido superior a 750 Reais mensais (p=0,006; ORaj=3,44; IC 95%=1,38-8,33). As mulheres com parto vaginal prévio apresentaram chance 25 vezes menor de optarem por cesariana. O fato de a gestante não ter considerado satisfatória a experiência do parto prévio esteve marginalmente associado ao desfecho (p=0,06; ORaj=0,42; IC 95%=0,16-1,05). CONCLUSÕES: A motivação para parto cesariano está associada a influências como tipo e grau de satisfação com o parto prévio e renda.

Unesp Informa, 2012, número 33

Boletim elaborado pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Nutritional status and overhydration: can bioimpedance spectroscopy be useful in haemodialysis patients?

Background: Protein-energy wasting (PEW), associated with inflammation and overhydration, is common in haemodialysis (HD) patients and is associated with high morbidity and mortality. Objective: Assess the relationship between nutritional status, markers of inflammation and body composition through bioimpedance spectroscopy (BIS) in HD patients. Methods: This observational, cross-sectional, single centre study, carried out in an HD centre in Forte da Casa (Portugal), involved 75 patients on an HD programme. In all participating patients, the following laboratory tests were conducted: haemoglobin, albumin, C-reactive protein (CRP) and 25-hydroxyvitamin D3 [25(OH)D3]. The body mass index of all patients was calculated and a modified version of subjective global assessment (SGA) was produced for patients on dialysis. Intracellular water (ICW) and extracellular water (ECW) were measured by BIS (Body Composition Monitor®, Fresenius Medical Care®) after the HD session. In statistical analysis, Spearman’s correlation was used for the univariate analysis and linear regression for the multivariate analysis (SPSS 14.0). A P value of <.05 was considered statistically significant. Results: PEW, inversely assessed through the ICW/body weight (BW) ratio, was positively related to age (P<.001), presence of diabetes (P=.004), BMI (P=.01) and CRP (P=.008) and negatively related to albumin (p=.006) and 25(OH)D3 (P=.007). Overhydration, assessed directly through the ECW/BW ratio, was positively related with CRP (P=.009) and SGA (P=.03), and negatively with 25(OH)D3 (P=.006) and BMI (P=.01). In multivariate analysis, PEW was associated with older age (P<.001), the presence of diabetes (P=.003), lower 25(OH)D3 (P=.008), higher CRP (P=.001) and lower albumin levels (P=.004). Over-hydration was associated with higher CRP (P=.001) and lower levels of 25(OH)D3 (P=.003). Conclusions: Taking these results into account, the ICW/BW and ECW/BW ratios, assessed with BIS, have proven to be good markers of the nutritional and inflammatory status of HD patients. BIS may be a useful tool for regularly assessing the nutritional and hydration status in these patients and may allow nutritional advice to be improved and adjusted.

A comprehensive approach to evaluate nutritional status in Crohn's patients in the era of biologic therapy: a case-control study

Objectives - Evaluate the nutritional status of patients with inactive or mildly active Crohn's disease (CD), and identify possible causes for potential deficiencies. Methods - A total of 78 CD patients and 80 healthy controls were evaluated in respect of nutritional status, dietary intake, and life styles factors. Results - These 73/78 CD patients were on immunomodulating therapies. Mean body mass index (BMI) was lower in patients as compared to controls (P= 0.006) but 32% of CD patients and 33.8% of controls had a BMI > 25, whereas 8% and 23.8% in each group, respectively, were obese (BMI > 30Kg/m(2)). Fat free mass was significantly decreased in both genders (P < 0.05) whereas fat mass was decreased only in males (P= 0.01). Energy intake was significantly lower in CD patients (P < 0.0001) and we observed significantly lower adjusted mean daily intakes of carbohydrates, monounsaturated fat, fiber, calcium, and vitamins C, D, E, and K (P < 0.05). 29% of patients had excluded grains from their usual diet, 28% milk, 18% vegetables, and 11% fruits. Milk exclusion resulted in a significantly lower consumption of calcium and vitamin K (P < 0.001) and the exclusion of vegetables was associated to a lower consumption of vitamins C and E (P < 0.05). Physical activity was significantly lower in CD patients (P= 0.01) and this lack of physical activity was inversely correlated with increased fat mass percentage (r=-0.315, P= 0.001). Conclusions - Results showed that the most prevalent form of malnutrition in CD patients was an excess of body weight, which was concomitant with an inadequate dietary intake, namely micronutrients, clearly related to dietary exclusion of certain foods.