(MIS)PERCEIVED DRINKING NORMS AND HAZARDOUS DRINKING BEHAVIOURS IN UNIVERSITY FIRST-YEAR UNDERGRADUATE STUDENTS AND THE EFFECTS OF GENDER

Purpose: Across Canada, undergraduate university students are one of the highest alcohol-consuming populations. Many students engage in hazardous drinking and are at risk for negative health and social consequences. Social Norms Theory suggests that students’ overestimation of drinking norms can result in an increase in their drinking behaviour. As of yet, none of the literature addresses the possible link between drinking norm (mis)perception and hazardous drinking in a Canadian undergraduate context. This is the first Canadian study to examine this potential association in first-year undergraduate students across multiple universities using gender as an effect modifier. Methods: Using data collected by the Caring Campus Project, for 2347 first-year students from three Canadian universities, I evaluated the prevalence of drinking norm misperceptions by site and gender. Using multiple-logistic regression models, I analyzed the relationship between misperceived drinking norms and hazardous drinking behaviours (assessed via AUDIT-C). Results: The proportion of students who overestimated drinking and binge drinking frequency norms varied by site and gender. There was a positive relationship between overestimated drinking/ binge drinking frequency norms and hazardous drinking, modified by gender. Controlling for living arrangement and site, the odds of female students being hazardous drinkers increased by a factor of 2.27 (CI: 1.73-2.99) when the drinking frequency norm was overestimated. A non-significant association was found for male students. Among female students, when living arrangement and site were controlled, the odds of being a hazardous drinker were 1.83 (0.84-3.95) and 2.69 (1.24-5.83) times greater when the drinking frequency norm was perceived at “2-4 times per month” and “2 or more times per week”, respectively. Among male students, when living arrangement, previous residence and site were controlled, the odds of being a hazardous drinker were 4.03 (2.62-6.19) and 8.54 (5.41-13.49) times greater when the binge drinking frequency norm was perceived at “2-4 times per month” and “2 or more times per week”, respectively. Conclusion: This novel study enhances the understanding of the association between (mis)perceived drinking norms and drinking behaviours in Canadian undergraduate students. The demonstrated importance of gender and site provides a strong impetus for Canadian universities to develop targeted alcohol reduction interventions.

IMPACT OF RNA VIRUSES ON THE REGULATION OF IL-23 IN MOUSE AND HUMAN MODELS OF INFECTION.

Interluekin-23 (IL-23) is a pro-inflammatory cytokine critical to the regulation of innate and adaptive immune responses. The main role for this cytokine is in the proliferation and differentiation of the IL-17 producing CD4 T helper cell, Th17. Virus infection deregulates IL-23 expression and function, but little is known about the mechanism behind this phenomena. Here, I demonstrate a reduction of Toll like receptor (TLR) ligand-induced IL-23 expression in lymphocytic choriomeningitis virus (LCMV)-infected bone marrow-derived dendritic cells (BMDCs), indicating that a function of these cells is disrupted during virus infection. I propose a mechanism of TLR ligand-induced IL-23 expression inhibition upon LCMV infection via the deactivation of p38, AP-1, and NF-κB. Further analysis revealed a direct relationship between LCMV infection with the IL-10 and SOCS3 expression. To understand IL-23 function, I characterized IL-23-induced JAK/STAT signalling pathway and IL-23 receptor expression on human CD4 T cells. My results demonstrate that IL-23 induces activation of p-JAK2, p-Tyk2, p-STAT1, p-STAT3, and p-STAT4 in CD4 T cells. For the first time I show that IL-23 alone induces the expression of its own receptor components, IL-12Rβ1 and IL-23Rα, in CD4 T cells. Blocking JAK2, STAT1, and STAT3 activation with specific inhibitors detrimentally effected expression of IL-23 receptor demonstrating that activation of JAK/STAT signalling is important for IL-23 receptor expression. I also addressed the effect of viral infection on IL-23 function and receptor expression in CD4 T cells using cells isolated from HIV positive individuals. These studies were based on earlier reports that the expression of IL-23 and the IL-23 receptor are impaired during HIV infection. I demonstrate that the phosphorylation of JAK2, STAT1, and STAT3 induced by IL-23, as well as IL-23 receptor expression are deregulated in CD4 T cells isolated from HIV positive individuals. This study has furthered the understanding of how the expression and function of IL-23 is regulated during viral infections.