2 resultados para Uniformly Gateaux Smooth Norms

em QSpace: Queen's University - Canada


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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.

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Vascular smooth muscle cell (VSMC) behaviour and phenotypic modulation is critical to vessel repair following damage, and the progression of various cardiovascular diseases. The second messenger cyclic adenosine monophosphosphate (cAMP) plays a key role in VSMC function under the synthetic/activated phenotype, which is typically associated with unhealthy cell behaviour. Consequently, cAMP signaling is often targeted in attempts to impact several pathological diseases, including atherosclerosis, restenosis, and pulmonary arterial hypertension (PAH). The cyclic nucleotide phosphodiesterases (PDEs) catalyze hydrolysis of cAMP to an inactive form, and therefore directly regulate cAMP signaling. The PDE4D family dominates in synthetic VSMCs, and there is considerable interest in determining how distinct PDE4D isoforms affect cell function. Specifically, we are interested in the potential link between short isoforms of PDE4D and VSMC desensitization to pharmacological agents that impact cardiovascular disease via cAMP signaling. This study extends on previous work that assessed the expression of PDE4D splice variants in rat aortic VSMCs following prolonged challenge with cAMP-elevating agents. It was determined that PDE4D1 and PDE4D2 were uniquely expressed in synthetic VSMCs incubated with these agents, and that this upregulation impacted PDE activity and cAMP accumulation in these cells. Here, we report that PDE4D1 and PDE4D2 are markedly upregulated in synthetic human aortic smooth muscle cells (HASMCs) following prolonged challenge with cAMP-elevating agents. Using a combination of RNAi-based and pharmacological approaches, we establish that this upregulation is reflected in levels of cAMP PDE activity, and restricted to the cytosolic sub-cellular compartment. Our results suggest a role for localized PDE4D1 and PDE4D2 activity in regulating cAMP-mediated desensitization in HASMCs, and highlight their therapeutic potential in treating various cardiovascular diseases.