FANCF methylation contributes to chemoselectivity in ovarian cancer

AbstractA new model of ovarian cancer tumor progression implicates aberrant FANCF promoter methylation that is associated with gene silencing and disruption of the Fanconi-anemia-BRCA pathway. Disruption of the pathway occurs de novo in ovarian cancers and may contribute to selective sensitivity to platinum salts

The association between alcohol consumption and high risk sexual behaviour in the South African adult population.

MMed, Epidemiology and Biostatistics,University of the Witwatersrand, 2009Background: South Africa is one of the countries with the highest Human Immunodeficiency Virus (HIV) prevalence in the world. The main mode of transmission in South Africa is via heterosexual intercourse. Thus there is the need to identify factors associated with HIV high risk sexual behaviour to inform future intervention programmes. Objective: To determine the association between alcohol consumption and high risk sexual behaviour in South African adults in 2006. Methods: Secondary data analysis of cross sectional study involving 1544 adult males and females, between 16-65 years interviewed in the Soul City National Survey. A multi-stage, stratified and clustered probability sampling technique was used. Univariate and multivariate analysis was done using student t test, chi square test and logistic regression models. Results: The prevalence of alcohol consumption in the week prior to the survey was 24.4% (95%CI: 22.2-26.6). The prevalence of heavy episodic drinking in last one month was 17.5% (95%CI: 15.5-19.4). There was an association between broad socioeconomic conditions and sexual behaviour particularly age, sex and race (P<0.05). The mean age at sexual debut was 17.13 (SD 2.61) years in the males and 17.91 (2.45 SD) years in females (P<0.001). Of the sexually active respondents, 12.7% and 4.2% of the men and women respectively had multiple partners currently (P<0.001). Generally consistent condom use was more in men although, only 10.3% of the men and 5.6% of the women used the condoms consistently with their casual partners (P=0.28). Multivariate regression showed that alcohol use predicted having multiple partners (AOR 2.37; 95%CI 1.19-4.69 and AOR 4.15; 95%CI 1.37-11.97) for moderate and problem drinkers respectively. Also, heavy episodic drinking predicted having multiple partners by three times (AOR 3.21; 95%CI 1.69-6.39). There was a significant dose response relationship for having multiple partners (P<0.05). As regards unprotected sexual intercourse, although not significant, female drinkers were found to be protected from inconsistent condom use with a casual partner. Male drinkers on the other hand, were found to be at a higher risk of having unprotected sex with casual partners. Perceptions of susceptibility to HIV (AOR 0.31; 95%CI 0.17-0.56), and alcohol related harm (AOR 0.17; 95%CI; 0.22-0.71) influenced consistent condom use with casual partners. Also regards gender differences, women who drank alcohol (AOR 9.68; 95%CI 1.31-17.45 vs. 1.17; 0.28-4.89) or were heavy episodic drinkers (AOR 4.45; 95%CI 1.46-3.55 vs. 2.43; 1.03-5.92) had a higher probability of having multiple partners than men. Conclusion: There is a strong association between risky alcohol use and high risk sexual behaviours. HIV prevention programmes need to address reduction in alcohol intake and changes in drinking pattern. Further research to disentangle the relationship between condom use and alcohol use is needed

Experience of gender-based violence to students in public and private secondary schools in Ilorin, Nigeria

Objective: To determine and compare prevalence of Gender based Violence (GBV) in public and private secondary schools students and to identify factors associated with experience of GBV by the students.Design: Comparative cross-sectional survey of using a 60 item self-administered questionnaire.Setting: Ten public and private secondary schools in Ilorin South Local Government area of Kwara State.Participants: 640 students, (320 each) from public and private schools.Main outcome variable: Prevalence and factors influencing experience of physical, sexual and psychological violenceResults: At least one form of GBV was experienced by 89.1% of public and 84.8% private schools students(p=0.32). Psychological violence was commonest type of GBV experienced (Public -72.5% vs. Private - 69.2%;p=0.37), while sexual violence was least (Public -41.4% vs. Private - 37.4%; p=0.3). Females were less likely toexperience physical violence (OR 0.3; 95% CI 0.2-0.4) and psychological violence (aOR 0.6; 95%CI 0.4-0.8). Studentswho were in a relationship and who had history of parental violence were more likely to experience sexual(aOR 1.7; 95%CI 1.2-2.4) and aOR 1.5; 95%CI 1.2-2.2) and psychological (aOR 1.3; 95%CI 1.1-1.5 and aOR 1.3;95%CI respectively) violence.Conclusions: GBV was a common experience of students in both groups of schools. Multi-disciplinary interventionsemphasising ending physical and psychological violence among private school students and sexual violence in public school are recommended. Interventions that involve the parents, school authorities and students on nonviolence conflict resolution are urgently required. Parents and students who perpetrate violence should be referred for counselling.Funding: Author fundedKeywords: Violence, Gender based violence, Violence exposure, Secondary School, Student

Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.

Epidermal growth factor receptor (EGFR) inhibitors have demonstrated efficacy in squamous cell carcinoma of the head and neck (SCCHN). In addition to EGFR, other ErbB family members are expressed and activated in SCCHN. Afatinib is an ErbB family blocker that has been approved for treating patients with EGFR-mutated nonsmall cell lung cancer. We sought to determine the efficacy of afatinib in preclinical models and compare this to other EGFR-targeted agents. Afatinib efficacy was characterized in a panel of ten SCCHN cell lines and found to be most effective against cell lines amplified for EGFR. Afatinib had lower IC(50) values than did gefitinib against the same panel. Two EGFR-amplified cell lines that are resistant to gefitinib are sensitive to afatinib. Cetuximab was not found to have a synergistic effect with afatinib either in vitro or in vivo. Both afatinib and cetuximab were effective in tumor xenograft model. Afatinib is an effective agent in SCCHN especially in models with EGFR amplification

β-Catenin is required for the tumorigenic behavior of triple-negative breast cancer cells

Our previous data illustrated that activation of the canonical Wnt signaling pathway was enriched in triple-negative breast cancer and associated with reduced overall survival in all patients. To determine whether Wnt signaling may be a promising therapeutic target for triple-negative breast cancer, we investigated whether β-catenin was necessary for tumorigenic behaviors in vivo and in vitro. β-catenin expression level was significantly reduced in two human triple-negative breast cancer cell lines, MDA-MB-231 and HCC38, using lentiviral delivery of β-catenin-specific small hairpin RNAs (shRNAs). Upon implantation of the cells in the mammary fat pad of immunocompromised mice, we found that β-catenin shRNA HCC38 cells formed markedly smaller tumors than control cells and grew much more slowly. In in vitro assays, β-catenin silencing significantly reduced the percentage of Aldefluor-positive cells, a read-out of the stem-like cell population, as well as the expression of stem cell-related target genes including Bmi-1 and c-Myc. β-catenin-knockdown cells were also significantly impaired in their ability to migrate in wound-filling assays and form anchorage-independent colonies in soft agar. β-catenin-knockdown cells were more sensitive to chemotherapeutic agents doxorubicin and cisplatin. Collectively, these data suggest that β-catenin is required for triple-negative breast cancer development by controlling numerous tumor-associated properties, such as migration, stemness, anchorage-independent growth and chemosensitivity

An Overview of the Design Principles of Drinking Water Chlorination

The goal of drinking water chlorination is the inactivation of pathogenic organisms in water. It offers the advantage of producing residuals useful for the preservation of water quality in a distribution system. Basic key chlorination concepts include chlorine demand/decay, chlorine residuals, and CT disinfection. The application of these concepts required a good understanding of the hydraulic condition of the system. Important consideration is the determination of initial required chlorine dose. A demonstration model using a public school water supply scheme with an overhead tank is done. This incorporates the kinematic of Contact Time (CT) disinfection, and the application of a demand model for the determination of initial chlorine concentration/dose required. Optimal application of chlorine will prevent incidences of either an over-dose or under-doze which highlight the importance of this study. Keywords— chlorine demand, CT Disinfection, initial chlorine concentration,  log removal value,  residual concentration

Preparing medical students to recognize and respond to gender based violence in Nigeria

Background: Medical practitioners are ideally positioned to mitigate the impact of gender based violence (GBV) on the health of victims.  However, there is a lack of information on students’ ability and willingness to do so. Objective:  To identify factors which impact on students’ attainment of the knowledge and perceived ability to manage victims. Methods: A cross-sectional survey was conducted on 388 (91.5%) final year medical students from three medical schools in South West, Nigeria.   Results: Students were knowledgeable on sexual (63.7%) and physical (54.6%) forms of GBV and unfamiliar with other forms. The mean scores for knowledge (7.1 ± 2.5 out of 11); attitude (52.6 ± 10.3 out of 80); personal comfort (44.1 ± 10.0 out of 65) and skills (3.1 ± 2.6 out of 7) were calculated.  Younger respondents, females and married students reported less skill to manage victims.  The location of school, previous training and personal comfort remained significant determinants of students’ self reported skills on GBV. Respondents with prior training on GBV and comfortable with managing patients, were four times more likely to perceive they were more skilled than their peers [AOR = 4.33, 95% CI: 2.37 – 7.90 and AOR 3.53; 95% CI 2.16- 5.78 respectively]. Conclusion: Formalised skills training on GBV is a necessity, especially for young, female students and training cannot be left to serendipity. The medical curriculum should be reviewed.Keywords: Undergraduate medical curriculum, gender based violence, violence against women, medical student perceptions, teaching and training undergraduate

Gender Equity as a Quest for Social Peace in Nigeria

Women today appear to be more hopeful, energetic and optimistic than ever before in our time. Though, this is not to say that women are totally exempted from experiencing stressful or traumatic events based on gender-related issues, which persist for women as threats to their health, economic and social equities. This paper is thus designed to look at the concept of gender equity as a quest for national peace. Gender equity could be seen as providing equal opportunities for all, regardless of their sex, in accessing and understanding cultural and social events in the pursuance of peaceful co-existence in their respective environments in Nigeria, as a nation. In place of discrimination, gender equity makes it possible for the two sexes to find strength in their diversity, sharing between them those things that make them unique entities. The benefits of gender equity in attending to corroborative role performance of every individual in the maintenance of peace across the social diversity in Nigeria cannot be over emphasized. Based on the discussion, conclusions were drawn and recommendations made

Regulation of Tcf7l1 DNA Binding and Protein Stability as Principal Mechanisms of Wnt/β-Catenin Signaling

SummaryWnt/β-catenin signal transduction requires direct binding of β-catenin to Tcf/Lef proteins, an event that is classically associated with stimulating transcription by recruiting coactivators. This molecular cascade plays critical roles throughout embryonic development and normal postnatal life by affecting stem cell characteristics and tumor formation. Here, we show that this pathway utilizes a fundamentally different mechanism to regulate Tcf7l1 (formerly named Tcf3) activity. β-catenin inactivates Tcf7l1 without a switch to a coactivator complex by removing it from DNA, which leads to Tcf7l1 protein degradation. Mouse genetic experiments demonstrate that Tcf7l1 inactivation is the only required effect of the Tcf7l1-β-catenin interaction. Given the expression of Tcf7l1 in pluripotent embryonic and adult stem cells, as well as in poorly differentiated breast cancer, these findings provide mechanistic insights into the regulation of pluripotency and the role of Wnt/β-catenin in breast cancer