The effects of height and BMI on prostate cancer incidence and mortality: A Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Background Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality. Methods We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies. Results The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03). Conclusions We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication.

Sapientia, 2003, Vol. LVIII, nº 213-214 (número completo)

Contenido: Das wahrheits-thema in der resten epoche der philosophie / Heribert Boeder – El prólogo del comentario de Santo Tomás de Aquino al Evangelio de San Juan / Nicolás Baisi – La pobreza como forma de marginalidad en la historia de la Orden Franciscana / Amelia Urrutibeheity de Di Pietro – El procedimiento per imaginationem en la física de Guillermo de Ockham / Olga L. Larre – El conocimiento divino del ente futuro contingente (2ª parte) / Gabriel Delgado – Sentido escatológico de la libertad: Santo Tomás de Aquino / Ciro E. Schmidt Andrade – El sentido ilativo en la obra del Cardenal Newman: un intento de superación del racionalismo inglés / Santiago Tomás Bellomo – La racionalidad moderna y la fenomenología de Husserl / Francisco Leocata – Valor, razón y subjetividad en Joseph De Finance / Juan Carlos Pablo Ballesteros – El bien en “Una teoría de la justicia” de J. Rawls – Notas y comentarios

Medida provisória nº 214, de 2004

Consultoria Legislativa - Área XII - Recursos Minerais, Hídricos e Energéticos.

Diário da Constituinte [gravação de vídeo] : [programa n. 214]

O Relator Bernardo Cabral começa a analisar as emendas ao substitutivo. Três blocos de emendas foram apresentados pelo Grupo do Consenso e pelo Grupo dos 32 (Trinta e dois). A Assembleia Nacional Constituinte (ANC) discute a reforma tributária e a repartição de receitas entre a União, os Estados e os Municípios. O Deputado Mello Reis (PDS-MG) defende o fortalecimento do município brasileiro como a melhor forma de gerir os recursos públicos. O Deputado Mauro Campos (PMDB-MG) diz que é aspiração da sociedade quebrar o controle econômico do poder central. Os Deputados Waldeck Ornellas (PFL-BA) e Jutahy Magalhães (PMDB-BA) querem mais recursos para o Nordeste. O substitutivo do Relator Bernardo Cabral avançou na questão da redistribuição das receitas. O Deputado Ronaldo Carvalho (PMDB-MG) e o Senador João Lobo (PFL-PI) são contra a nova proposta. O Deputado Nion Albernaz (PMDB-GO) declara que para o governo federal melhorar a receita, deve melhorar a máquina arrecadadora.

miR-7 and miR-214 are specifically expressed during neuroblastoma differentiation, cortical development and embryonic stem cells differentiation, and control neurite outgrowth in vitro

The mammalian nervous system exerts essential control on many physiological processes in the organism and is itself controlled extensively by a variety of genetic regulatory mechanisms. microRNA (miR), an abundant class of small non-coding RNA, are emerging as important post-transcriptional regulators of gene expression in the brain. Increasing evidence indicates that miR regulate both the development and function of the nervous system. Moreover, deficiency in miR function has also been implicated in a number of neurological disorders. Expression profile analysis of miR is necessary to understand their complex role in the regulation of gene expression during the development and differentiation of cells. Here we present a comparative study of miR expression profiles in neuroblastoma, in cortical development, and in neuronal differentiation of embryonic stem (ES) cells. By microarray profiling in combination with real time PCR we show that miR-7 and miR-214 are modulated in neuronal differentiation (as compared to miR-1, -16 and -133a), and control neurite outgrowth in vitro. These findings provide an important step toward further elucidation of miR function and miR-related gene regulatory networks in the mammalian central nervous system. (C) 2010 Elsevier Inc. All rights reserved.

MEF2C-MYOCD and leiomodin1 suppression by miRNA-214 promotes smooth muscle cell phenotype switching in pulmonary arterial hypertension

Background Vascular hyperproliferative disorders are characterized by excessive smooth muscle cell (SMC) proliferation leading to vessel remodeling and occlusion. In pulmonary arterial hypertension (PAH), SMC phenotype switching from a terminally differentiated contractile to synthetic state is gaining traction as our understanding of the disease progression improves. While maintenance of SMC contractile phenotype is reportedly orchestrated by a MEF2C-myocardin (MYOCD) interplay, little is known regarding molecular control at this nexus. Moreover, the burgeoning interest in microRNAs (miRs) provides the basis for exploring their modulation of MEF2C-MYOCD signaling, and in turn, a pro-proliferative, synthetic SMC phenotype. We hypothesized that suppression of SMC contractile phenotype in pulmonary hypertension is mediated by miR-214 via repression of the MEF2C-MYOCD-leiomodin1 (LMOD1) signaling axis. Methods and Results In SMCs isolated from a PAH patient cohort and commercially obtained hPASMCs exposed to hypoxia, miR-214 expression was monitored by qRT-PCR. miR-214 was upregulated in PAH- vs. control subject hPASMCs as well as in commercially obtained hPASMCs exposed to hypoxia. These increases in miR-214 were paralleled by MEF2C, MYOCD and SMC contractile protein downregulation. Of these, LMOD1 and MEF2C were directly targeted by the miR. Mir-214 overexpression mimicked the PAH profile, downregulating MEF2C and LMOD1. AntagomiR-214 abrogated hypoxia-induced suppression of the contractile phenotype and its attendant proliferation. Anti-miR-214 also restored PAH-PASMCs to a contractile phenotype seen during vascular homeostasis. Conclusions Our findings illustrate a key role for miR-214 in modulation of MEF2C-MYOCD-LMOD1 signaling and suggest that an antagonist of miR-214 could mitigate SMC phenotype changes and proliferation in vascular hyperproliferative disorders including PAH.

Radon and progeny (Pb-214 and Bi-214) in urban water-supply systems of São Paulo State, Brazil

Many water-supply systems in South America utilize the waters of the Guarani aquifer at least as part of their networks. However, there is little present knowledge in Brazil of the factors affecting Rn presence in the water supplied for end-users, despite the economic importance of Guarani aquifer. Rn-222 analyzes of 162 water samples were performed at 8 municipalities in São Paulo State, Brazil, with the aim of investigating the major factors affecting its presence in solution. The Rn-222 activity concentration ranged from 0.04 up to 204.9 Bq/L, with three samples exceeding the World Health Organization maximum limit of 100Bq/L. Aeration was confirmed as the most important factor for Rn release, as expected due to its gaseous nature. Accumulation in pipes and stratification in the water column were other significant factors explaining the data obtained in some circumstances. The Rn daughters Ph-214 and Bi-214 were also determined in a set of selected samples and their presence was directly related to the occurrence of Rn dissolved in water. (c) 2008 Elsevier Ltd. All rights reserved.

The Itinerant, or Wesleyan Methodist Visiter - Accession 214 - M95 (121)

The Itinerant, or Wesleyan Methodist Visiter is a newspaper of the Methodist Church that was published every two weeks in Baltimore, MD. The bound issues in the collection extend from November 10, 1830 to October 12, 1831.

Epidemiological survey of 214 families with bladder exstrophy-epispadias complex

PURPOSE: We sought to identify causative nongenetic and genetic risk factors for the bladder exstrophy-epispadias complex. MATERIALS AND METHODS: A total of 237 families with the bladder exstrophy-epispadias complex were invited to participate in the study, and information was obtained from 214 families, mainly from European countries. RESULTS: Two families showed familial occurrence. Male predominance was found among all subgroups comprising epispadias, classic bladder exstrophy and cloacal exstrophy, with male-to-female ratios of 1.4:1, 2.8:1 and 2.0:1, respectively (p = 0.001). No association with parental age, maternal reproductive history or periconceptional maternal exposure to alcohol, drugs, chemical noxae, radiation or infections was found. However, periconceptional maternal exposure to smoking was significantly more common in patients with cloacal exstrophy than in the combined group of patients with epispadias/classic bladder exstrophy (p = 0.009). Only 16.8% of mothers followed the current recommendations of periconceptional folic acid supplementation, and 17.6% had started supplementation before 10 weeks of gestation. Interestingly, in the latter group mothers of patients with cloacal exstrophy were more compliant with folic acid supplementation than were mothers of the combined group of patients with epispadias/classic bladder exstrophy (p = 0.037). Furthermore, mothers of children with cloacal exstrophy knew significantly more often prenatally that their child would have a congenital malformation than did mothers of children with epispadias/classic bladder exstrophy (p <0.0001). CONCLUSIONS: Our study corroborates the hypothesis that epispadias, classic bladder exstrophy and cloacal exstrophy are causally related, representing a spectrum of the same developmental defect, with a small risk of recurrence within families. Embryonic exposure to maternal smoking appears to enforce the severity, whereas periconceptional folic acid supplementation does not seem to alleviate it. There is a disproportional prenatal ultrasound detection rate between severe and mild phenotypes, possibly due to the neglect of imaging of full bladders with a focus on neural tube defects.