Antioxidant Activity of Uruguayan Propolis. In Vitro and Cellular Assays

The antioxidant capacity of propolis from the southern region of Uruguay was evaluated using in vitro as well as cellular assays. Free radical scavenging capacity was assessed by ORAC, obtaining values significantly higher than those of other natural products (8000 mu mol Trolox equiv/g propolis). ORAC values correlated well with total polyphenol content (determined by Folin-Ciocalteu method) and UV absorption. Total polyphenol content (150 mg gallic acid equiv/g propolis) and flavonoids (45 mg quercetin equiv/g propolis) were similar to values reported for southern Brazilian (group 3) and Argentinean propolis. Flavonoid composition determined by RP-HPLC indicates a strong poplar-tree origin. Samples high in polyphenols efficiently inhibit low-density lipoprotein lipoperoxidation and tyrosine nitration. In addition, Uruguayan propolis was found to induce the expression of endothelial nitric oxide synthase and inhibit endothelial NADPH oxidase, suggesting a potential cardiovascular benefit by increasing nitric oxide bioavailability in the endothelium.

Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas

Context Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. Objectives To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. Design, Setting, and Participants We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. Main Outcome Measures The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. Results We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P=2.7 x 10(-4)) and/or with familial disease (5 of 20 samples; P=.005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P=.54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Conclusions Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occured in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein. JAMA. 2010;304(23):2611-2619 www.jama.com

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Methods We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < 18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI > 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >= 30 kg/m(2) (0.43, 0.33-0.57), compared with BMI > 18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < 18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

Interaction between Tobacco and Alcohol Use and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Background: The magnitude of risk conferred by the interaction between tobacco and alcohol use on the risk of head and neck cancers is not clear because studies have used various methods to quantify the excess head and neck cancer burden. Methods: We analyzed individual-level pooled data from 17 European and American case-control studies (11,221 cases and 16,168 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We estimated the multiplicative interaction parameter (psi) and population attributable risks (PAR). Results: A greater than multiplicative joint effect between ever tobacco and alcohol use was observed for head and neck cancer risk (psi = 2.15; 95% confidence interval, 1.53-3.04). The PAR for tobacco or alcohol was 72% (95% confidence interval, 61-79%) for head and neck cancer, of which 4% was due to alcohol alone, 33% was due to tobacco alone, and 35% was due to tobacco and alcohol combined. The total PAR differed by subsite (64% for oral cavity cancer, 72% for pharyngeal cancer, 89% for laryngeal cancer), by sex (74% for men, 57% for women), by age (33% for cases < 45 years, 73% for cases > 60 years), and by region (84% in Europe, 51% in North America, 83% in Latin America). Conclusions: Our results confirm that the joint effect between tobacco and alcohol use is greater than multiplicative on head and neck cancer risk. However, a substantial proportion of head and neck cancers cannot be attributed to tobacco or alcohol use, particularly for oral cavity cancer and for head and neck cancer among women and among young-onset cases. (Cancer Epidemiol Biomarkers Prev 2009;18(2):541-50)

Type of Alcoholic Beverage and Risk of Head and Neck Cancer-025EFA Pooled Analysis Within the INHANCE Consortium

The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for <= 5, 6-15, 16-30, and > 30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.

Early onset of primary hypogonadism revealed by serum anti-Mullerian hormone determination during infancy and childhood in trisomy 21

Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2 months-20 year). To compare with an adequate control population, we established reference levels for serum anti-Mullerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6 months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6 months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy.

Genomic deletions at 1p and 14q are associated with an abnormal cDNA microarray gene expression pattern in meningiomas but not in schwannomas

The molecular pathology of meningiomas and shwannomas involve the inactivation of the NF2 gene to generate grade I tumors. Genomic losses at 1p and 14q are observed in both neoplasms, although more frequently in meningiomas. The inactivation of unidentified genes located in these regions appears associated with tumor progression in meningiomas, but no clues to its molecular/clinical meaning are available in schwannomas. Recent microarray gene expression studies have demonstrated the existence of molecular subgroups in both entities. In the present study, we correlated the presence of genomic deletions at 1p, 14q, and 22q with the expression patterns of 96 tumor-related genes obtained by cDNA low-density microarrays in a series of 65 tumors including 42 meningiomas and 23 schwannomas. Two expression pattern groups were identified by cDNA mycroarray analysis when compared to the expression pattern in normal control RNA in both meningiomas and schwannomas, each one with patterns similar and different from the normal control. Meningioma and schwannoma subgroups differed in the expression of 38 and 16 genes, respectively. Using MLPA and microsatellites, we identified genomic losses at 1p, 14q, and 22q at nonrandom frequencies (12.5-69%) in meningiomas and schwannomas. Losses at 22q were almost equally frequent in both molecular expression subgroups in both neoplasms. However, deletions at 1p and 14q accumulated in meningiomas with a gene expression pattern different from the normal pattern, whereas the inverse situation occurred in schwannomas. Those anomalies characterized the schwannomas with expression pattern similar to the normal control. These findings suggest that deletions at 1p and 14q enhance the development of an abnormal tumor-related gene expression pattern in meningiomas, but this fact is not corroborated in schwannomas. (C) 2010 Elsevier Inc. All rights reserved.

Allelic status of 1p and 19q in oligodendrogliomas and glioblastomas: multiplex ligation-dependent probe amplification versus loss of heterozygosity

Identification of the 1p/19q allelic status in gliomas, primarily those with a major oligodendroglial component, has become an excellent molecular complement to tumor histology in order to identify those cases sensitive to chemotherapy. In addition to loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH), or comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA) has been shown to be an alternative methodology to identify deletions of those chromosome arms. We used MLPA to explore the 1p and 19q glioblastomas, and a series of 76 gliomas: 41 tumors with a major oligodendroglial component, 34 glioblastomas, and one low-grade astrocytoma. We compared the MLPA findings of the oligodendroglial cases with those previously obtained using LOH in the same samples. Thirty-eight of 41 oligodendrogliomas displayed identical findings by both LOH and MLPA, and losses at either 1p and/or 19q were identified in 12 of 35 (34%) astrocytic tumors. These findings agree with data previously reported comparing MLPA versus FISH or CGH in gliomas and suggest that MLPA can be used in the identification 1p/19q allelic deletions on these brain neoplams. (c) 2009 Elsevier Inc. All rights reserved. reserved.

Meningiomas and schwannomas: Molecular subgroup classification found by expression arrays

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.

Sistematiza????o normativa e tipologia preliminar de organiza????es federais

O segundo volume da s??rie Inova????o na Gest??o P??blica trata de estudo realizado pela consultora Suely Komatsu sobre estruturas organizacionais do Governo Federal. O trabalho foi realizado em agosto de 2009 e, portanto, traz um retrato das estruturas ?? ??poca da pesquisa. Apesar do lapso temporal de tr??s anos, o estudo permanece relevante e atual. A publica????o ?? composta por tr??s cap??tulos. O Cap??tulo 1 traz a consolida????o e an??lise da evolu????o das reformas administrativas que orientamos arranjos institucionais e organizacionais no pa??s. O Cap??tulo 2, por sua vez, apresenta o levantamento e a sistematiza????o de marcos legais e orienta????es normativas relevantes para defini????o de estruturas organizacionais nas ??reas meio e final??stica. Por fim, o Cap??tulo 3 identifica par??metros comuns e compar??veis nos arranjos organizacionais, com a proposi????o de uma tipologia inicial de estruturas organizacionais da esfera federal tendo como base as seguintes vari??veis: ???concentra????o das atribui????es principais???, ???natureza jur??dico- -institucional???, ???grau de descentraliza????o das principais atividades???, ???n??mero de subunidades em cada n??vel hier??rquico??? e ???amplitude de comando???

Resenha de estudos sobre o executivo

Este artigo ?? uma resenha da literatura sobre o Executivo que discute o impacto dos sistemas parlamentarista e presidencialista na capacidade governamental de formular e implementar pol??ticas p??blicas. Ao longo do texto, busca-se identificar fatores que permitem ou bloqueiam o exerc??cio de uma fun????o coordenadora e unificadora de a????es, analisando a rela????o entre os poderes Executivo e Legislativo, a estrutura do poder Executivo e as rela????es entre o Executivo pol??tico e a burocracia. Os estudos sobre parlamentarismo enfocam: import??ncia dos partidos, papel dos ministros, extens??o do poder do primeiro ministro e papel coletivo do gabinete. J?? os trabalhos sobre presidencialismo v??o de pesquisas sobre o Congresso norte-americano, envolvendo infer??ncias estat??sticas e an??lises baseadas na teoria institucional a estudos de caso sobre a American Politics (presid??ncia e lideran??a). Apesar das diferen??as entre parlamentarismo e presidencialismo, a literatura indica que mecanismos institucionais de controle de agenda produzem os mesmos efeitos nos dois sistemas.

Machado de Assis funcion??rio p??blico

Joaquim Maria Machado de Assis, uma das maiores figuras do mundo liter??rio brasileiro do s??culo passado e do in??cio deste s??culo, teve duas carreiras paralelas, a de homem de letras e a de burocrata. Na primeira iniciou-se mais cedo, quando, apenas um adolescente de pouco mais de 15 anos, publicou um soneto ??? por sinal bem ruinzinho ??? no Peri??dico dos Pobres, a 3 de outubro de 1854. Nascido no morro do Livramento, perto da Gamboa e do Saco do Alferes, a 21 de junho de 1839, deu mostras de impressionante precocidade, ao assinar um Soneto, no mesmo jornalzinho. Nota-se que, nessa ??poca, o Rio de Janeiro ainda n??o tinha sequer ilumina????o a g??s ??? s?? contratada pelo governo imperial em 1859 ??? nem sabia ainda o que fossem estradas de ferro. Seu ingresso no servi??o p??blico s?? se daria quase treze anos depois dessa estreia liter??ria, que em nada fazia prever o grande escritor que viria a ser. E isto se deu a 8 de abril de 1867, com a sua nomea????o para ???ajudante do diretor de publica????o do Di??rio Oficial???, ent??o subordinado ao Minist??rio da Fazenda, durante o 22?? gabinete ministerial da monarquia, chefiado pelo ent??o deputado-geral Zacarias de G??is e Vasconcelos.

Educa????o a dist??ncia: o estado da arte e o futuro necess??rio

Este artigo analisa alguns desafios que cercam a ado????o da Educa????o a Dist??ncia por institui????es de ensino, unidades de forma????o e qualifica????o profissional e de educa????o corporativa. Al??m disto, ?? sugerida uma agenda de pesquisa sobre EAD. O artigo trata do papel da EAD na educa????o continuada de adultos e na amplia????o do acesso ?? aprendizagem, em fun????o da possibilidade de intera????es ass??ncronas, mediadas por tecnologias da informa????o e comunica????o. Uma an??lise da situa????o EAD no Brasil mostra um grande crescimento da modalidade. Observa-se que ainda s??o raras as pesquisas sobre EAD no servi??o p??blico. H?? informa????es sugerindo que, em ??rg??os p??blicos com pr??ticas institucionalizadas de EAD, a modalidade representa uma valiosa e eficaz estrat??gia de inclus??o de pessoas em atividades de ensino-aprendizagem. S??o analisados alguns importantes desafios ligados ?? implementa????o e ao desenho de cursos a dist??ncia, e, al??m disto, ?? apresentada uma agenda de pesquisas para a ??rea.

Burocracia profissional e a livre nomea????o para cargos de confian??a no Brasil e nos EUA

A problem??tica do emprego de cargos de livre nomea????o e exonera????o para assegurar o comando pol??tico e administrativo na m??quina p??blica tem sido objeto, tanto no Brasil quanto nos EUA, de diversos questionamentos. Este artigo debate a situa????o em ambos os pa??ses, com base em alguns dados esclarecedores obtidos pela compara????o entre as estruturas de cargos comissionados e suas quantidades e formas de provimento existentes, no n??vel do governo federal, relativos ?? quantidade, tipos e emprego dos cargos em comiss??o, destacando-se a diferencia????o no que se refere ao uso desses cargos, assim como promove, a partir da literatura da ??rea, um exame da influ??ncia da utiliza????o dos cargos de livre provimento sob o aspecto do conflito entre compet??ncia ???neutra??? e ???compet??ncia responsiva???. A partir dos avan??os alcan??ados desde 1998 no Brasil, conclui-se pela necessidade do aprofundamento da profissionaliza????o das estruturas de comissionamento, tendo em vista a possibilidade de que uma estrutura menos vulner??vel ??s injun????es da pol??tica clientelista possa melhor atender aos princ??pios da efici??ncia e da transpar??ncia.

Evas??o em cursos de educa????o continuada a dist??ncia: um estudo na Escola Nacional de Administra????o P??blica

A an??lise da literatura brasileira sobre educa????o a dist??ncia ?? ainda limitada no que diz respeito a estudos que investiguem o fen??meno da evas??o, em especial, em contextos de escolas de governo. Este artigo procura identificar e analisar os fatores que contribuem para a evas??o de participantes nos cursos de educa????o continuada a dist??ncia em uma organiza????o governamental respons??vel pela capacita????o dos servidores da administra????o p??blica federal. A ??nfase das investiga????es encontra-se nas vari??veis referentes ??s dificuldades pessoais, profissionais e tecnol??gicas, ??s peculiaridades do curso e caracter??sticas da clientela, contrastadas com as vari??veis demogr??ficas referentes ?? evas??o em cursos a dist??ncia mediados por tecnologias da informa????o e da comunica????o. O trabalho ?? embasado em metodologia quantitativa, por meio de pesquisa descritiva de campo junto aos participantes, valendo-se do uso de question??rio eletr??nico. Procura contribuir para investiga????es sobre o tema, em especial no que se refere aos servidores p??blicos.