Effects of Hepatocyte CD14 Upregulation during Cholestasis on Endotoxin Sensitivity

Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS) may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro. To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL) or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats

Adolescent pregnancies in the Amazon Basin of Ecuador: a rights and gender approach to adolescents' sexual and reproductive health

In the Andean region of Latin America over one million adolescent girls get pregnant every year. Adolescent pregnancy (AP) has been associated with adverse health and social outcomes, but it has also been favorably viewed as a pathway to adulthood. AP can also be conceptualized as a marker of inequity, since it disproportionately affects girls from the poorest households and those who have not been able to attend school

Incrementally Closing Octagons

The octagon abstract domain is a widely used numeric abstract domain expressing relational information between variables whilst being both computationally efficient and simple to implement. Each element of the domain is a system of constraints where each constraint takes the restricted form ±xi±xj≤c. A key family of operations for the octagon domain are closure algorithms, which check satisfiability and provide a normal form for octagonal constraint systems. We present new quadratic incremental algorithms for closure, strong closure and integer closure and proofs of their correctness. We highlight the benefits and measure the performance of these new algorithms

Adolescent pregnancies and girls' sexual and reproductive rights in the amazon basin of Ecuador: an analysis of providers' and policy makers' discourses

<p>Abstract</p> <p>Background</p> <p>Adolescent pregnancies are a common phenomenon that can have both positive and negative consequences. The rights framework allows us to explore adolescent pregnancies not just as isolated events, but in relation to girls' sexual and reproductive freedom and their entitlement to a system of health protection that includes both health services and the so called social determinants of health. The aim of this study was to explore policy makers' and service providers' discourses concerning adolescent pregnancies, and discuss the consequences that those discourses have for the exercise of girls' sexual and reproductive rights' in the province of Orellana, located in the amazon basin of Ecuador.</p> <p>Methods</p> <p>We held six focus-group discussions and eleven in-depth interviews with 41 Orellana's service providers and policy makers. Interviews were transcribed and analyzed using discourse analysis, specifically looking for interpretative repertoires.</p> <p>Results</p> <p>Four interpretative repertoires emerged from the interviews. The first repertoire identified was "sex is not for fun" and reflected a moralistic construction of girls' sexual and reproductive health that emphasized abstinence, and sent contradictory messages regarding contraceptive use. The second repertoire -"gendered sexuality and parenthood"-constructed women as sexually uninterested and responsible mothers, while men were constructed as sexually driven and unreliable. The third repertoire was "professionalizing adolescent pregnancies" and lead to patronizing attitudes towards adolescents and disregard of the importance of non-medical expertise. The final repertoire -"idealization of traditional family"-constructed family as the proper space for the raising of adolescents while at the same time acknowledging that sexual abuse and violence within families was common.</p> <p>Conclusions</p> <p>Providers' and policy makers' repertoires determined the areas that the array of sexual and reproductive health services should include, leaving out the ones more prone to cause conflict and opposition, such as gender equality, abortion provision and welfare services for pregnant adolescents. Moralistic attitudes and sexism were present - even if divergences were also found-, limiting services' capability to promote girls' sexual and reproductive health and rights.</p

Meat and Nicotinamide:A Causal Role in Human Evolution, History, and Demographics

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B 3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital

Does organ donation legislation affect individuals' willingness to donate their own or their relative's organs?: evidence from European Union survey data

Background Maintaining adequately high organ donation rates proves essential to offering patients all appropriate and available treatment options. However, the act of donation is in itself an individual decision that requires a depth of understanding that interacts with the social setting and the institutional framework into which an individual is embedded. This study contributes to understanding factors driving organ donation rates by examining how country regulation, individuals' awareness of regulatory setting, social interactions and socio-demographic determinants influence individuals' willingness to donate their own organs or those of a relative. Methods We draw representative data from the Eurobarometer survey 58.2 undertaken in 2002 with respondents throughout the European Union to capture heterogeneity in institutional setting. We use logistic regression techniques to estimate the determinants of willingness to donate one's own organs and those of a deceased relative. We employ interaction terms to examine the relationship between institutional setting and respondent's awareness of organ donation legislation in their country. Results Our findings indicate that individuals are more likely to donate their organs than to consent to the donation of a relative's organs. Both decisions are affected by regulation (presumed consent), awareness of regulation and social interactions such as the ability to count on others in case of a serious problem (reciprocity). Furthermore, education (more educated), age (younger), expressing some sort of political affiliation determine willingness to donate one's own organs and consent to the donation of those of a relative. Conclusion This study confirms and develops further previous research findings that presumed consent organ donation policy positively affects the willingness of individuals to donate their own organs and those of relative by highlighting the importance of awareness of this regulation and an individual's level of social interactions in making choices about donation. Results found using interaction terms underline the importance of population awareness of organ donation legislation as well as the legislation type itself. Findings also point to the role of social interactions in influencing individuals' willingness to donate their organs or those of a relative