Addressing HIV/AIDS, sexual health, and substance use among gay and other men who have sex with men

New HIV diagnoses are 71 times higher among gay, bisexual and other men who have sex with men (GBM) than other men in Canada. Since 2010, BC has adopted Treatment as Prevention (TasP) as a policy to increase HIV testing and engage more HIV-positive individuals in effective treatment to reduce transmission at a population level. However, the number of new diagnoses among GBM in BC has remained largely unchanged. Further, surveillance shows an increase of HIV diagnoses among the youngest birth cohorts of GBM. HIV pre-exposure prophylaxis (PrEP) is a new preventive tool for HIV-negative GBM, but inaccurate information, sub-optimal adherence or risk-compensation could result in a false sense of security, paradoxically leading to increased HIV transmission. In addition to HIV, infectious syphilis is now epidemic among GBM in BC.

This research program will address the HIV and sexually transmitted infection (STI) epidemics among GBM in Metro Vancouver and BC. Dr. Lachowsky will measure HIV risk behaviour over time, determine how PrEP affects bacterial STI incidence, and analyze shifting attitudes about HIV, challenges with HIV prevention and treatment, and changes in sexual negotiation and practices. Results will directly inform population-specific, age-relevant public health policy, programming, and interventions to reduce the burden of HIV for GBM, especially young GBM.

Dr. Lachowsky will employ a bidirectional, integrated knowledge translation approach, with a Community Engagement Committee and key academic, public health, and community partners. An interactive Web 2.0 hub will allow for knowledge dissemination and generation with community and service providers, and will be complemented with more traditional presentations, workshops, and publications.This single research project is part of a larger program of research examining health disparities amongst GBM in BC and Canada using interdisciplinary, community-based approaches.

The Effect of Psychosocial Stressors on Health Behaviours and Indicators of Cardiometabolic Risk in the Transition to Young Adulthood

Adolescence and young adulthood are critical periods for health promotion and disease prevention. Cardiometabolic risk (CMR) refers to a set of indicators that increase an individual’s risk for diabetes, heart disease or stroke. These indicators start to show predictive variability in adolescence and identification and implementation of early strategies for risk management can have significant long-term health benefits. Much of what we know about CMR comes from studies of adults; therefore, research focusing on earlier age groups is needed.

The first objective of the proposed research is to describe the frequencies of select, non-invasive CMR indicators, including body mass index (BMI), systolic and diastolic blood pressure (BP), and waist circumference in young adulthood (ages 22-29). Research in psychoneuroimmunology documents the deleterious effects of stress on physical health; however, less attention has been given to adolescents and young adults.

The second objective is to examine how psychosocial stressors that become salient in adolescence (e.g. internalizing symptoms and interpersonal stress) predict CMR.

The third objective is to examine how these stressors compromise the enactment of key health behaviours (e.g. physical activity, eating habits, sleep duration) leading to increased CMR.

The project will use six waves of the Victoria Healthy Youth Survey (V-HYS), a 10-year longitudinal study that surveyed youth (N = 662) biannually from 2003 (T1; ages 12-18) to 2014 (T6; ages 22-29). In-person measurements of CMR (BMI, systolic and diastolic BP, waist circumference) were collected at T6. Measurements of internalizing symptoms, interpersonal stress (e.g. peer victimization), and health behaviours were collected at each wave.

Findings will highlight the variability in CMR in young adulthood and increase knowledge on the effects of two salient stressors on CMR from adolescence to young adulthood, providing new information about targets for prevention and interventions. The results will also inform guidelines for early identification and preventative healthcare.

Knowledge translation efforts will include 1) peer-reviewed publications, conference presentations, media reports, and policy formats; 2) creating an infographic about CMR in young adulthood to release to the media; and 3) developing a training tool to educate healthcare professionals about the relations between stress and CMR in these young age groups.

Improving health equity through cross-cultural collaboration: Learning from Indigenous-developed programs to strengthen public health systems in preventing the harms of substance use in BC

A function of public health systems and services is to reduce health inequities. The harms of substance use impact British Columbians differently based on their social position and access to resources. Over the last decade, BC has had renewed interest in health equity as demonstrated by several key policy documents. Initial research findings however, have demonstrated that the application of a health equity lens is a challenge for public health decision makers and practitioners. However, for many public health service providers, First Nations and Aboriginal health organizations and service providers are seen as leaders in the understanding and application of health equity principles.

Accordingly, there is an immense opportunity in BC for collaboration and learning with First Nations and Aboriginal health partners to optimize health equity for all British Columbians. Despite these opportunities, little is known about the synergies between Indigenous knowledge and health equity strategies related to the reduction of harms of substance use in BC. In particular, more research is needed to understand if Indigenous approaches to health and wellness can be imported into the current BC public health system and to  explore how Indigenous-developed programs and services can inform health equity strategies related to reducing the harms of substance use in BC public health systems and services.

This research project will be one of the first to systematically examine how health equity strategies in the BC public health system could benefit from Indigenous knowledge and worldviews. This project has the potential to impact the health of all British Columbians by informing the development of more equitable health programs and services. In addition, by prioritizing Indigenous ontologies and processes, this project also has implications for how Aboriginal communities in BC are perceived and esteemed, thereby having the potential also to specifically improve the well-being of those communities. In addition, this prioritization has the potential to mitigate epistemological colonialism and shift power relations which are integral in promoting health equity for Indigenous peoples.

Dr. Shahram received a 2017 Health Policy Fellowship to promote Indigenous health in BC’s southern interior by integrating cultural safety and health equity assessments into the fabric of the Interior Health. Her 2016 Trainee Award will placed on hold during her health policy fellowship assignment.

Unique contributors to caregiver well-being across neurodegenerative diseases that present with dementia

Five million new cases of dementia are diagnosed every year worldwide. These diagnoses disrupt home environment patterns and relationships and cause  repercussions on families. Accordingly, dementia caregivers experience higher stress than other groups and face diverse care demands. Existing literature suggests dementia presentation may impart different caregiver challenges: cognition in Alzheimer’s disease (AD); delusions in Dementia with Lewy Body (DLB); and neuropsychiatry in Parkinson’s disease associated dementia (PDD). Inconsistencies in studies comparing dementia caregivers make it difficult to draw clear conclusions. First, caregiver definitions are inconsistent. Second, caregiver well-being is under-represented. Third, disease pathology and associated-dependencies place differential demands on caregivers, which has yet to be examined in a comparative framework.  

The proposed research will address this gap by comparing dementia-related symptoms that contribute to caregiver well-being[LL1] . The aim is to determine the unique profile of contributors to caregiver well-being in neurodegenerative diseases (i.e. AD, DLB, PDD) present with dementia[LL2] .

It is expected dementia presentations and associated factors will differentially impact caregiver well-being. Dr. Roland will administer questionnaires to evaluate well-being (life-satisfaction, depression), burden and coping in caregivers. Focus groups will bring together a range of dementia caregivers from three groups (AD, DLB, PDD) to explore group norms and diverse experiences. Subsequent interviews will further explore the issues pertinent to caregiver well-being. This novel research will identify the unique profile of caregiving factors within a comparative framework. This is important since different presentations of dementia have discrete long-term implications for caregiver psychosocial outcomes.

Relevant knowledge gained from Dr. Roland’s research will inform resources targeted to reduce stressors and support care needs

Mechanisms of impaired functional recovery in diabetic mice following stroke

Diabetics are two to four times more likely than non-diabetics to suffer a stroke during their lifetime, and their prognosis for recovery from stroke is poor. Diabetes is known to negatively affect blood vessels throughout the body, including the eye, heart, kidney, and limbs, leading to a heightened risk of stroke in diabetics. Poor circulation and peripheral nerve damage can lead to blindness, hearing loss, foot injury and amputation. High blood pressure is common in diabetics and increases the risk of heart disease and stroke. However, little is known about how the vascular changes associated with diabetes affect the brain and contribute to poorer recovery of function following stroke.

Dr. Kelly Tennant's research will determine why diabetics suffer from greater impairments following strokes. She will monitor changes in neurons and blood vessels over time following a stroke in diabetic mice and assess the relationship between these changes and recovered use of the forelimb. Dr. Tennant will employ cutting edge in vivo imaging technologies such as intrinsic optical signal, two-photon, and voltage sensitive dye imaging, combined with behavioural testing of forelimb function.

These experiments will shed light on how neurons and blood vessels of diabetics respond differently to ischemic stroke and how these differences contribute to poor behavioural recovery in diabetic stroke survivors. This research will aid understanding of the greater impairment caused by stroke in diabetic patients and lead towards development of treatments that ameliorate the negative effects of diabetes on the brain.

Mitigation of hippocampal dysfunction and cognitive deficits in early-symptomatic YAC128 transgenic mice for Huntington’s disease

Huntington's disease is a devastating neurodegenerative disorder affecting between three and 10 individuals per 100,000 in the Western world. It is caused by a mutation in the huntingtin gene, which results in the accumulation of mutated huntingtin protein in the brain and the eventual degeneration of certain types of brain cells. The disease is primarily characterized by the onset of motor deficits; this develops when the striatum region deep within the brain begins to degenerate. However, Huntington’s disease patients commonly show cognitive impairments decades before the onset of the motor symptoms. The hippocampus is a brain region known to be involved both in cognitive (i.e. learning and memory) and emotional (i.e. depression) processes.

Dr. Joana Gil-Mohapel is investigating whether the hippocampus is involved in the early cognitive impairments in Huntington’s disease. She is working with a mouse model of Huntington’s disease, which closely mimics the human condition. These mice demonstrate profound structural and functional deficits in this region; significantly, as seen in Huntington’s disease patients, these deficits can be detected when the animals are still in an early-symptomatic stage, before the onset of motor symptoms. Therefore, the goal of the present research is to gain a better understanding of how this structure is affected in this mouse model.

Dr. Gil-Mohapel will investigate whether relevant cellular pathways are altered in this brain region and whether therapies aimed at promoting hippocampal function can reverse these deficits and be of therapeutic value for Huntington’s disease. She hopes her research will help elucidate novel targets for the mitigation of the cognitive deficits characteristic of early-stage Huntington’s disease patients.

Structures, catalytic mechanisms, and contribution to pathogenesis of polysaccharide lyases from Streptococcus pneumoniae

Beyond playing an important role in nutrition, carbohydrate building blocks and their biochemistry have been described as the "last frontier of cell and molecular biology." It is easy to see why their study has remained a great challenge: even a simple chain with only six sugar links has over a trillion possible arrangements. This vast structural diversity is reflected in the role of polysaccharides (sugar chains) as the "language of the cell," in that specific arrangements of carbohydrate messages act like dual receivers and transmitters of cell-signaling events. These signals may contribute to friendly cell-cell interactions, lead immune responses, or help to disguise human pathogens from immune detection. Because of the central importance of polysaccharides in signaling events, characterizing the cellular mechanisms responsible for the synthesis, breakdown, and recognition of cell-surface polysaccharides are of vast importance in understanding how the cell works.

Dr. Michael Suits is working to understand how infection by Streptococcus pneumoniae, a human pathogen that is one of the world's leading causes of death, causes infection by recognizing and manipulating the carbohydrate building blocks present on many of our cell surfaces. Certain strains of S. pneumoniae have evolved resistance to antibiotics, are not recognized by human immune defenses even following vaccination, and have the capacity to act in lethal synergy with the Influenza virus. As part of a concerted attack, S. pneumoniae releases proteins, which help the microbe to attach to host cells and short circuit the carbohydrate messages being transmitted. Dr. Suits is directing his research attention towards a pair of carbohydrate-modifying enzymes produced by S. pneumoniae.

Using powerful X-rays to investigate these key enzymes in very precise detail, Dr. Suits hopes to determine how these enzymes interact with an important type of carbohydrate found on the surface of human cells. Additionally, he will use molecular biology tools to "knock out" S. pneumoniae genes encoding important carbohydrate modifying enzymes and then examine how this influences bacterial growth and the ability to cause infection. These research results will help identify potential targets for therapeutic intervention, and provide a platform to develop compounds to inhibit carbohydrate-modifying enzymes.

Understanding the mechanisms of experience and injury based cortical plasticity

Strokes are caused by the interruption of blood flow or the rupture of blood vessels to the brain. This sudden loss of brain function can damage the brain centers that sense or move parts our body, profoundly impacting both physical and mental functions. As a result, stroke is the number one cause of acquired disability in adults around the world. Some stroke survivors are able to recover more quickly and more completely than others. Although recovery is influenced by the location of damage in the brain and the extent of the damage, recovery is also influenced by the brain's innate ability to initiate repair and re-wire damaged blood vessels and neuronal circuits in surviving regions. At the present time, we do not yet know why this re-wiring takes place in some patients but not others, nor do we know how to manipulate this process. What we do know is that this repair process can vary between patients and that some patients, such as diabetics, have a poorer prognosis following stroke.

Dr. Craig Brown's lab will use advanced imaging technologies to assess brain structure and function to understand how the brain is able to repair itself following a stroke and to understand why this is such a variable process between different patients. His research program is focused on three distinct yet complimentary lines of research, including: 1) understanding the impact of diabetes on recovery from stroke; 2) using electrical nerve stimulation to improve stroke recovery; and 3) elucidating the cellular/molecular mechanisms of learning or experience-based brain "plasticity".

As a result of this innovative research, Dr. Brown hopes to better understand the brain's plasticity associated with normal (learning/memory) and pathological (diabetes/stroke) brain states. His intent is that this work will stimulate new therapies for improving brain function both in normal situations and after stroke, particularly in patients who have previously had a poor prognosis.

Treatment of drug-resistant influenza: Rationally designed inhibitors of viral neuraminidase

Each year the influenza virus infects approximately 10% of the human population, resulting in hundreds of thousands of deaths. Even in North America, nearly 40,000 annual “excess deaths” are attributed to influenza or to secondary bacterial infections. Despite a World Health Organization-monitored vaccine program, the disease remains a significant global health issue, requiring the use of antiviral drugs like oseltamivir (Tamiflu). A significant problem in controlling the spread of influenza is the emergence of oseltamivir-resistant strains.

To address this problem, Dr. Jeremy Wulff is taking a collaborative approach to develop potent new influenza virus inhibitors. With Professor Martin Boulanger's group at the University of Victoria Department of Biochemistry, Dr. Wulff has developed a new class of antiviral agents that function by a similar mechanism to oseltamivir. His research group is working to further improve the efficacy of these agents through structural and kinetic means. Finally, Dr. Wulff will test the potency of the new anti-influenza compounds in collaboration with Dr. Terrence Tumpey, from the U.S. Centers for Disease Control in Atlanta.

Identifying and developing new drugs to fight oseltamivir-resistant influenza is anticipated to have wide-reaching impacts on global health. In addition to creation of new influenza drugs, Dr. Wulff’s research interests include the development of novel methodologies for the synthesis of complex molecules, and the invention of new kinds of inhibitors that specifically block interactions between certain proteins involved in pancreatic cancer and HIV.

Fostering cultural safety in nursing practice with people experiencing problematic substance use

The purpose of this project is to generate new knowledge that will foster understanding of what constitutes safe nursing care in acute care settings for people who are experiencing problematic substance use and social disadvantage. The target audience will be practicing nurses who provide care to people experiencing substance use, as well as health care administrators, nursing leaders and policy makers. The key research question is: What is culturally safe care from the perspective of patients and nurses in acute care settings and what supports the delivery of culturally safe care?

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