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

Latin American immigrants in Indianapolis: Perceptions of prejudice and discrimination

The article focuses on immigrants’ interactions with the Indiana natives, with emphasis in the city of Indianapolis and its suburbs. More specifically, this study aims at providing an understanding of the experiences of Latin American immigrants with special attention to perceptions of prejudice and discrimination and to feelings of social exclusion. A substantial proportion of Latin American immigrants interviewed indicated that they considered Indiana natives to be prejudiced and that they had personally experienced discrimination. The study reveals specific examples of discrimination experienced by the immigrants at the work place, in housing, in stores, restaurants and by various service providers. The results of the study demonstrate the relevance of the normative and power resource theories to explain prejudice and discrimination

Genome-wide RNA-Sequencing analysis reveals a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery

Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues

Importance of Academic Legacy on Student Success in First- and Second-Semester General Chemistry

This investigation sought to elucidate the influence of students' academic legacy on their prior knowledge and course outcomes providing crucial insights for educators who teach general chemistry. This six-semester analysis involved 6,914 students enrolled in classes across nine Texas universities. Explored were personal circumstances associated with students' successes and failures that influenced performance in on- and off-sequence, first- and second-semester general chemistry (Chem 1 and Chem 2). Students' academic legacy based on their categorization as first generation (neither grandparent nor parent/guardian with a 4-year bachelor's degree), second generation (at least one grandparent or parent/guardian with a bachelor's degree), or third generation (at least one grandparent and at least one parent/guardian hold a bachelor's degree) was investigated. Of the students in the dataset 33.8% (n = 2,340) self-identified as Hispanic. Results for Hispanic and non-Hispanic students indicated that first-generation students struggled more with Chem 1 and Chem 2 than students in the other two legacy groups. As students' academic legacy extended, they were more apt to succeed in general chemistry. Second- and third-generation students demonstrated stronger prior high-school chemistry backgrounds and were enrolled in more advanced mathematics courses. As expected, students with stronger academic backgrounds in chemistry and mathematics scored higher on the diagnostic MUST (Math-Up Skills Test), had greater self-efficacy relative to their preparation to succeed, and reported fewer paid work hours. First-generation students on the average entered with lower diagnostic MUST scores, felt less prepared to succeed, and disclosed a greater need to be employed

A codex of care: assessing the Liverpool hospital admission and discharge protocol for homeless people

There has recently been an upsurge of interest in the relationship between homelessness and hospital discharge policies and processes in England. In this paper, we investigate the significance of these developments by assessing the Liverpool Hospital Admission and Discharge Protocol for Homeless People. Drawing on in-depth qualitative interviews with hospital-based clinicians and community-based health and social care practitioners, we identify four central features of the Liverpool protocol: (1) local prioritisation, (2) good systems of communication, (3) partnership working and (4) access to appropriate post-discharge care and support. Overall, we contribute to the literature of care coordination by filling a gap in the knowledge base in relation to the multiple and complex needs of homeless people, while delivering important insights into the delivery of integrated care

MUST-Know Pilot—Math Preparation Study from Texas

Since 2007, the reported SAT (reading + math) scores for the state of Texas have steadily fallen from a high of 999 to an all-time low of 944. Solving this problem requires a multifaceted approach. For our part as instructors of a known gateway course, general chemistry, we chose to focus on the most fundamental crosscutting topic in STEM: arithmetic. Hence, the MUST Know (Mathematics: Underlying Skills and Thinking) study was conceived and implemented. General chemistry is widely considered a gateway course because students\u27 success in general chemistry provides entry into several STEM and some non-STEM careers. Failure to succeed in general chemistry has been linked to students\u27 mathematics fluency that other researchers have attributed to poor algebra skills. However, is it possible that this relationship should really be attributed to students\u27 lack of must-know arithmetic skills? In Fall 2016-Spring 2017, a team of 11 chemical educators investigated the relationships between solving simple arithmetic problems and course grades for 2,127 students (60.3% female) enrolled in general chemistry I and II at six post-secondary institutions (3, large public research universities; 2 Hispanic Serving Institutions; and 1, 4-year private university) from varied geographic locations in the heart of the state of Texas overlaying 32,000 square miles. The arithmetic concepts evaluated for this study are introduced to most Texas students starting at the 4th-grade level. The selected concepts include multiplication, division, fractions, scientific notation, exponential notation, logarithms, square roots and balancing chemical equations. Results support that students, without the aid of a calculator, succeeded at the 40%-correct level (Chem I) and 60%-correct level (Chem II). Students\u27 algebra skills might be a better predictor of overall success, but the initiator of the problem we posit starts with lack of automaticity and fluency with basic arithmetic skills. Correlations between final course grades and mathematics fluency ranged from 0.2-0.5 with the Hispanic-serving classes being among the weakest correlations and the research universities exhibiting the strongest. Building a strong profile of a successful general chemistry student is beginning to form from this continuing investigation. Future plans include implementation of High-Impact Practices (HIPs) to increase numeracy followed by dissemination of outcomes and expansion of the study to include other needed success-producing skills like logical thinking, spatial ability, and quantitative reasoning ability

Is the STEM Gender Gap Closing?

The Networking for Science Advancement (NSA) team's institutions consist of nine universities located in one large southwestern US state. This study evaluated students enrolled from Spring 2017 to Fall 2019 in firstand second-semester general chemistry. Over 90% of the students (n = 6,694) have been exposed to a secondary school isomorphic curriculum. The population studied, Chem I (n = 4,619) and Chem II (n = 2,075), met entry-level criteria and are therefore expected to succeed (i.e., earn grades of A, B or C). This study's focus is to disaggregate data based on binary gender (M/F) in hopes of revealing patterns that might remain hidden when studying an undivided population. In Chem I, the female population was 59.6% and increased to 64.5% for Chem II. The 15- min., diagnostic Math-Up Skills Test’s (MUST) scores identified about half of all students who were unsuccessful (grades of D and F). Results from the study support that males enter Chem I and II with better automaticity skills (what can be done without using a calculator) than females. However, females outperformed males on course averages in Chem I but not Chem II. Our data provide supporting evidence that the gender gap may be closing