STRATEGIES FOR PREVENTION AND TREATMENT OF HEPATITIS C VIRUS INFECTION

Hepatitis C virus (HCV) is the causative agent of Hepatitis C, a serious global health problem which results in liver cirrhosis and hepatocellular carcinoma. Currently there is no effective treatment or vaccine against the virus. Therefore, development of a therapeutic vaccine is of paramount importance. In this project, three alternative approaches were used to control HCV including a DNA vaccine, a recombinant viral vaccine and RNA interference. The first approach was to test the effect of different promoters on the efficacy of a DNA vaccine against HCV. Plasmids encoding HCV-NS3 and E1 antigens were designed under three different promoters, adenoviral E1A, MLP, and CMV ie. The promoter effect on the antigen expression in 293 cells, as well as on the antibody level in immunized BALB/c mice, was evaluated. The results showed that the antigens were successfully expressed from all vectors. The CMV ie promoter induced the highest antigen expression and the highest antibody level. Second, the efficiency of a recombinant adenovirus vaccine encoding HCV-NS3 was compared to that of a HCV-NS3 plasmid vaccine. The results showed that the recombinant adenovirus vaccine induced higher antibody levels as compared to the plasmid vaccine. The relationship between the immune response and miRNA was also evaluated. The levels of mir-181, mir-155, mir-21 and mir-296 were quantified in the sera of immunized animals. mir-181 and mir-21 were found to be upregulated in animals injected with adenoviral vectors. Third, two recombinant adenoviruses encoding siRNAs targeting both the helicase and protease parts of the NS3 region were tested for their ability to inhibit NS3 expression. The results showed that the siRNA against protease was more effective in silencing the HCV-NS3 gene in a HCV replicon cell line. This result confirmed the efficiency of adenovirus for siRNA delivery. These results confirmed that CMV ie is optimum promoter for immune response induction. Adenovirus was shown to be an effective delivery vector for antigens or siRNAs. In addition, miRNAs were proved to be involved in the regulation of immune response.

Analysis of the feeding behaviour of the mosquito Culex pipiens L. (Diptera: Culicidae) in relation to West Nile virus

The goal ofthis literature review is to inform the reader on several aspects of West Nile Virus (WNV) transmission by its mosquito vector, Culex pipiens and to elucidate how Cx. pipiens and WNV are intertwined. The first few sections of the literature review describe the life cycle and blood feeding behaviours ofmosquitoes so that baseline data ofmosquito biology are established. In addition to explaining how and why a mosquito blood feeds, the section on "Blood Meal Analysis" describes the different methods for determining the vertebrate source of mosquito blood meals and a brief history of these testing methods. Since this thesis looks at the feeding behaviour of Cx. pipiens, it is important to know how to determine what they are feeding upon. Discussion on other mosquito-borne diseases related to WNV gives a broader perspective to the thesis, and examines other diseases that have occurred in Ontario in the past. This is followed by background information on WNV and theories on how this virus came to North America and how it relates to Cx. pipiens. The final sections discuss Cx. pipiens and give background information to how this species of mosquito exists and behaves within North America.

Comprehensive school health, the social determinants of health, and the health status of children

As children are becoming increasingly inactive and obese, there is an urgent need for effective early prevention and intervention programs. One solution is a comprehensive school health (CSH) program, a health promotion initiative aimed at educating students about healthy behaviours and lifestyles, which also provides a link between the school, students, families, and the surrounding community. The purpose of this study was to explore the relationship between different components of CSH programs, as well as three determinants of health (gender, social support, socio-economic status), and physical activity, on the aerobic fitness and body mass index (BMI) of children. A newly developed and pilot-tested survey derived from Health Canada's fourpart CSH model (instruction, social support, support services, and a healthy physical environment) was sent to elementary school principals. Data on the gender, physical activity, parental education, and social support levels of students from these schools were gathered from a previous study. Multiple regression procedures were conducted to estimate the relationships between CSH components, the social determinants of health, physical activity, and BMI and aerobic fitness. Results showed that three CSH components were significantly associated with both BMI and aerobic fitness values in children, but accounted for less than 5% of the variance in both variables. Physical activity partially mediated the relationship between the significant CSH components, BMI, and particularly aerobic fitness. Furthermore, the social determinant and physical activity variables played independent roles in aerobic fitness values. No moderating effects of the social determinants were discovered.

Patterns and correlates of tobacco use among young adults at college and university

This thesis describes college and university students' smoking behaviours and examines whether socioenvironmental and personal characteristics experienced during adolescence are differentially associated with their smoking participation. Results show more college students than university students currently smoke (37% and 21 % respectively) and more began smoking prior to post-secondary school (93% and 84% respectively). Early age of onset of alcohol use increased the odds of current smoking (main effect model, OR = 8.56 CI = 6.47, 11.33), especially for university students (interaction effect model, b = 2.35 CI = 7.50, 14.64). Lower levels of high school connectedness were associated with increased odds of current smoking but for university students only (interaction effect model, b = -0.15 CI = 0.84, 0.88). While limitations associated with convenience sampling and low response rate exist, this is the first Canadian study to examine college and university students separately. I t reveals that tobacco control programming needs to differ for college and university students, and early alcohol prevention and school engagement programs for adolescents may influence tobacco use. Given that both educational pathway and use of tobacco are associated with SES, future research may consider examining in more detail, SES-related socioenvironmental variables.

Inhibition of human lung cancer cell proliferation and survival by wine

Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events.

Conduct Disorder: A Handbook for Elementary School Educators

This research project examined the behavioural, social, and emotional issues affecting children and youth with conduct disorder. Based on the literature review, the deconstruction of theoretical and empirical studies, and findings from the needs assessment, Conduct Disorder: A Handbook for Elementary School Educators was created. This handbook was developed based on the evidence that conduct problems can most effectively be improved when multiple systems are included in the prevention and intervention of the disorder. Educators, related service providers, and the child all play an important role in designing and implementing effective interventions. Therefore, it is imperative to provide educators with the information necessary to begin this emerging collaborative process. The handbook was created as a tool for educators intending to enhance their knowledge when working with students with conduct disorder. A Needs Assessment was conducted to determine what educators wanted the handbook to contain to assist them in working with students displaying conduct problems. The educators evaluated the handbook, providing constructive feedback and confirming the potential value and practicality of this handbook for elementary school educators. The educators reported an increase in their understanding of conduct disorder, as well as a heightened awareness of the causal factors that contribute to the disorder. The list of community resources and agencies was thought to be a good starting point for educators looking for supplementary aids. The educators indicated that the handbook is a good reference tool to use when teaching students with conduct problems. The educators concluded with the hope that this handbook will be shared with others.

Inhibition of human lung cancer cell proliferation and survival by wine

Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events.