Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

<p>Abstract</p> <p>Background</p> <p>Activation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We <it>hypothesized </it>that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knockout (KO) mice would be more susceptible to mammary carcinogenesis.</p> <p>Methods</p> <p>Premalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT) and KO mice were fed either control diet or diets containing auraptene (500 ppm). A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34). Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test.</p> <p>Results</p> <p>All mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice.</p> <p>Conclusions</p> <p>We report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary carcinoma progression.</p

Human resources: the Cinderella of health sector reform in Latin America

Human resources are the most important assets of any health system, and health workforce problems have for decades limited the efficiency and quality of Latin America health systems. World Bank-led reforms aimed at increasing equity, efficiency, quality of care and user satisfaction did not attempt to resolve the human resources problems that had been identified in multiple health sector assessments. However, the two most important reform policies – decentralization and privatization – have had a negative impact on the conditions of employment and prompted opposition from organized professionals and unions. In several countries of the region, the workforce became the most important obstacle to successful reform. This article is based on fieldwork and a review of the literature. It discusses the reasons that led health workers to oppose reform; the institutional and legal constraints to implementing reform as originally designed; the mismatch between the types of personnel needed for reform and the availability of professionals; the deficiencies of the reform implementation process; and the regulatory weaknesses of the region. The discussion presents workforce strategies that the reforms could have included to achieve the intended goals, and the need to take into account the values and political realities of the countries. The authors suggest that autochthonous solutions are more likely to succeed than solutions imported from the outside

Border Theory: A New Point of Access into Literature. A border-theoretical reading of China Miéville’s Un Lun Dun, The City and the City and Embassytown

“Border Theory: A New Point of Access into Literature” seeks to explore the use of a border-theoretical approach to literature. Border theories by Johan Schimanski, Stephen Wolfe, David Newman, Homi Bhabha, and a set of different border planes – the symbolic, epistemological, topographic, temporal and textual border plane – provide the scholarly framework for this thesis. Border theory studies the notion of hybridity, diversity and doubling, discusses the border and the change between the visible and invisibility, reviews binary oppositions and goes on to explore how borders can move beyond binaries and create a new space – a third space. The thesis uses three novels by China Miéville to examine border theory: Un Lun Dun (2007), The City and the City (2009) and Embassytown (2011). Miéville is a science fiction writer that introduces the genre of weird fiction. The main idea is that border theory, as its own theoretical point of access into the field of literary studies, can contribute with a new aspect of literary analysis, and that China Miéville’s contemporary weird fiction invites and benefits from a border-theoretical analysis. Border theory creates a new access-point into the theoretical analysis of novels, and further explores and shows how borders are represented in literature. Un Lun Dun presents the reader with a city and its abcity where the border between the two is not easy to see and understand. In addition, the abcity UnLondon is filled with strange spaces and extraordinary characters that give no shortage of borders to explore. The City and the City is a detective story that crosses the border between two sister cities – Besźel and Ul Qoma – with an invisible law enforcement agency operating within the invisible border between the two cities. Embassytown uses language as a barrier and a border between species. Set in the far future, the novel describes and explores complex relations and divisions of space, time and people – and the complications surrounding the inability to communicate. These novels have been chosen because of their borders-inquisitive qualities, and together they can each be read as a piece of the puzzle to a more complex understanding of borders and border crossings – both in literature and in real life. “Border Theory: A New Point of Access into Literature – A border-theoretical reading of China Miéville’s Un Lun Dun, The City and the City and Embassytown” is a thesis with a theoretical approach to contemporary literature – exploring the literary field of border theory