In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver

Background: Maternal smoking is one of the most important modifiable risk factors for low birthweight, which is strongly associated with increased cardiometabolic disease risk in adulthood. Maternal smoking reduces the levels of the methyl donor vitamin B12 and is associated with altered DNA methylation at birth. Altered DNA methylation may be an important mechanism underlying increased disease susceptibility; however, the extent to which this can be induced in the developing fetus is unknown. Methods: In this retrospective study, we measured concentrations of cobalt, vitamin B12, and mRNA transcripts encoding key enzymes in the 1-carbon cycle in 55 fetal human livers obtained from 11 to 21 weeks of gestation elective terminations and matched for gestation and maternal smoking. DNA methylation was measured at critical regions known to be susceptible to the in utero environment. Homocysteine concentrations were analyzed in plasma from 60 fetuses. Results: In addition to identifying baseline sex differences, we found that maternal smoking was associated with sex-specific alterations of fetal liver vitamin B12, plasma homocysteine and expression of enzymes in the 1-carbon cycle in fetal liver. In the majority of the measured parameters which showed a sex difference, maternal smoking reduced the magnitude of that difference. Maternal smoking also altered DNA methylation at the imprinted gene IGF2 and the glucocorticoid receptor (GR/NR3C1). Conclusions: Our unique data strengthen studies linking in utero exposures to altered DNA methylation by showing, for the first time, that such changes are present in fetal life and in a key metabolic target tissue, human fetal liver. Furthermore, these data propose a novel mechanism by which such changes are induced, namely through alterations in methyl donor availability and changes in 1-carbon metabolism

Put It in Your Shoe It Will Make You Limp: British Men’s Online Responses to a Male Pill

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.This article analyzes online interactions between British men and other online readers’ comments in response to two news articles focused on a male contraceptive pill. The aim of the study was to explore how British men’s online accounts construct a male pill as a potential contraceptive option for family planning. The two online articles reported the scientific innovations, as well as the production and marketing, of a nonhormonal, plant-based pill for men. Discourse analysis was used to analyze the online comments, from which two discourses emerged: (a) “Men as responsible health consumers” and (b) “‘Killing sperm’ and other side effects on semen.” When provided with the opportunity to take future responsibility for family planning, male readers were found to be unlikely to use a contraceptive pill. The men expressed the need for new options of contraception but, overall, felt a male pill was not the solution

The Extent of Diffuse Intravascular Coagulation and Fibrinolysis in Patients with Liver Cirrhosis

Peer Reviewe

The association between fibrinogen, von Willebrand Factor, antithrombin III, and D-dimer levels and survival outcome by 36 months from ovarian cancer

10.1177/107602960601200102Clinical and Applied Thrombosis/Hemostasis1213-

Fundamentos epistemológicos da teoria modular da mente de Jerry A. Fodor Epistemological fundaments of Jerry A. Fodor's modular theory of mind

Este artigo é uma apresentação dos fundamentos da teoria modular desenvolvida por Jerry A. Fodor e uma reflexão sobre seus principais desafios. A noção de modularidade da mente de Fodor, por um lado, procura superar as insuficiências metodológicas e epistemológicas do associacionismo e do localizacionismo a respeito das explicações da estrutura e do funcionamento mental; por outro lado, é uma oposição à postura culturalista de Vygotsky, para o qual as funções superiores da mente, como a cognição, são produtos artificiais, culturais. A psicologia cognitiva de Chomsky converteu esse produto "artificial" em "natural", postulando a existência de módulos inatos para desempenhar funções cognitivas específicos. Com base nessa ideia de Chomsky, Fodor procura explicar a mente como um conjunto de módulos. No entanto, sua principal contribuição para as ciências cognitivas é a apresentação da arquitetura mental em dois níveis e a afirmação da existência de módulos centrais responsáveis pelas atividades cognitivas superiores, como criatividade, reflexão ou imaginação.<br>The aim of this paper is to present the basic elements regarding the modular theory developed by Jerry A. Fodor and some considerations about its main challenges. Fodor's notion of mind modularity, on the one hand, aims at overcoming the methodological and epistemological gaps of associationism and localizationism concerning the explanations of the structure and functioning of the mind; on the other hand, Fodor's notion stands as an opposition to Vygotsky's culturalist posture, since for the latter the higher functions of the mind, such as cognition, are artificial and cultural products. Chomsky's cognitive psychology has converted this "artificial" product into a "natural" one, postulating the existence of innate modules to perform specific cognitive functions. Based on Chomsky's idea, Fodor describes the mind as a group of modules. However, his main contribution to the cognitive sciences is the presentation of the mental architecture in two levels and the affirmation of the existence of central modules that are responsible for the higher cognitive activities such as creativity, reflection or imagination

Seminal tissue factor revisited

Studies of seminal tissue factor (TF) are few and mostly based on small numbers. Due to the reported lack of factor (F) X in semen, it has been suggested that TF may not have a role in seminal coagulum formation. However, recent identification of a number of haemostatic factors in semen justifies a re-evaluation of its occurrence. Semen specimens were collected from sub-fertile (n = 19), normally fertile (n = 33), semen donors (n = 30) and vasectomized subjects (n = 62), some fractionated into sperm, a prostasome-rich fraction and seminal plasma. Functional and antigenic TF levels were measured and related to conventional fertility parameters. Semen contains high concentration of functional and antigenic TF. Most TF was found in seminal plasma prepared by low-speed centrifugation. When further fractionated by ultracentrifugation much of this may reside in the pellet (prostasomal fraction). It was also detectable on sperm. TF antigen levels were higher in vasectomized subjects than sub-fertile, normally fertile, donor (p = 0.02) and a 'pooled normal semen parameters' (PNSP) stratification (derived from a combination of measurements) (p = 0.06). The sub-fertile group showed a wider variation than normal, donor or the PNSP subjects. Seminal TF antigen levels correlated significantly with sperm agglutination (p = 0.03) and abnormal sperm morphology (p = 0.04). Subjects with anti-sperm antibodies also showed high TF antigen levels. In conclusion, semen contains functional and antigenic TF at high concentrations. A full complement of clotting factors probably exists in semen, so some pro-coagulant role for TF should not be excluded. Decreased seminal TF levels appear to be associated with seminal parameters that are known to favour male fertility