Grant Recipients » 2012
The Manitoba Medical Service Foundation has been awarding Research Grants to researchers and students since 1971, and over $18 million has been donated to furthering this cause.
We only keep the last five consecutive years of Grant Recipients online. Contact the Administrative Assistant for information on prior years.
Please Note: Institutional Costs are not eligible expenses for MMSF Grants and Awards funding.
Diagnostic and Prognostic Significance of Colour Contrast Sensitivity Testing in Patients with Clinically Isolated Syndrome, Multiple Sclerosis Compared to Normal Population
Dr. N. Anssari
$12,000
Multiple sclerosis (MS) is a common disease that can cause permanent disability in young adults. The prevalence of MS in Manitoba is among the highest in the world. Currently, magnetic resonance imaging (MRI) is used for diagnosis of MS. However, it is not readily available in all health centres and it is not helpful in determining the future progression of the disease.
Optic neuritis (ON), inflammation of the optic nerve, is the presenting manifestation of multiple sclerosis (MS) in 20% of the patients. ON will show itself in overt attacks with painful progressive visual loss in one eye. Visual recovery can be complete or partial after the attack, but even patients with complete recovery of eyesight report that colours may appear washed out or desaturated.
Given the provided background, it is possible that determining the green-red colour vision testing in apparently healthy eyes of MS patients (that have never suffered from ON), might help with early diagnosis and also have predictive significance.
This study is proposed to test the hypothesis that colour contrast sensitivity is impaired in eyes of MS patients who are not clinically affected by ON. It can be the initial step to discover a novel tool for early diagnosis of MS and future prognostication.
Targeting Nicotinamide Adeninde Dinucleotide (NAD) in Chronic Lymphocytic Leukemia (CLL)
Dr. V. Banerji
$20,000
Chronic lymphocytic leukemia (CLL) is an incurable disease with the exception of bone marrow transplantation. Most patients requiring treatment do not meet the criteria for transplantation.
To date, conventional modalities used in CLL therapy include nucleoside analogues and alkylating agents and are therefore rather non-specific. Although monoclonal antibodies are currently being used, patients continue to relapse with treatment.
Hence, the development of novel-targeted therapeutic approaches remains a critical goal of CLL research. A novel approach targeting the metabolic enzyme, nicotinamide-phosphoribosyl-transferase (NAPRT), which impedes nicotinamide adenine dinucleotide(NAD) synthesis, may serve as an alternative to conventional therapy in isolation or in combination in the context of CLL.
Novel Strategy Improving the Proportion of Inactive Older Adults who Reach the Canadian Physical Activity Guidelines to Improve Health and Physical Capacity
Dr. D. Bouchard
$10,000
$10,000 (WF)
Physical inactivity is a leading cause of mortality in the world, and has a significant impact on overall health. Although many older adults are aware of the health benefits related to physical activity, they still fail to exercise regularly. The Canadian Physical Activity Guidelines (CPAG) recommends a minimum of 150 minutes of accumulated aerobic activity per week at a moderate to vigorous intensity. The duration of these guidelines is simple, but when it comes to identifying what moderate to vigorous intensity is even regular exercisers struggle.
The main objective of this study is to determine if learning how to use a pedometer to monitor walking intensity can improve the ability of older adults to identify what is considered moderate to vigorous intensity, and therefore increase the number of older adults that reach the CPAG. Fifty inactive adults 65 years and older will be recruited for this study. Health and functional outcomes, like changes in vital signs and physical capacity, will also be measured.
If our hypotheses are confirmed, this simple intervention could immediately be used on a community level to help older adults reach the CPAG. At a broader level, the information gathered in this study can be used to form strategies that will increase the number of Canadians reaching the CPAG.
Stance and Stand-training for Therapeutic Benefit and Functional Recovery After Spinal Cord Injury
Dr. K. Cowley
$20,000
Traumatic spinal cord injury is a life-altering event for over 1,700 persons per year in Canada. In the absence of successful regeneration strategies, research is needed to prevent or minimize the development of secondary complications of living with spinal cord injury, including osteoporosis and the increased risk of leg and hip bone breakage, that are largely thought to be due to the absence of normal weight-bearing activities.
Our lab is interested in investigating the neural basis, and therapeutic benefit of, stance and balance. Keeping those with spinal cord injury above the ‘fracture threshold’ for bone breakage would represent a significant improvement in quality of life, and would also translate into reduced health care and social costs.
This project will develop an adult animal model for stance and stand training after spinal cord injury, and find out whether matched doses of body-weight-supported standing have similar protective effects on bone mineral density and muscle mass as body-weight-supported stepping. This new knowledge can be used to inform rehabilitation strategies during the early stages of spinal injury. Information gathered from this project will also provide the basis for future research to find better ways to maintain stance and preserve musculoskeletal health after spinal cord injury.
Process Measures during Direct Laryngoscopy and Orotracheal Intubation: Validation of Applied Forces and Torques - Part II
Dr. P. Dawe
$9,000
Endotracheal intubation is an intricate and critically important clinical skill that medical professionals, respiratory therapists and emergency medical technicians must learn to master. Despite its importance, the assessment of technical skill in performing this procedure is largely informal and non-standardized. The lack of well-developed, reliable and valid measures of technical skill may compromise the ability of clinicians and medical educators to set standards, follow trainee’s progress, and provide functional feedback. Moreover, without reliable and valid measures, it is difficult for educators to assess the effects of any teaching interventions. This project aims to develop feasible, objective and valid measures of laryngoscopy and intubation skill.
In order to meet this aim, we have developed a laryngoscope handle equipped with a 6-directional force-torque sensor that will be used to capture forces and torques applied during repeated attempts of laryngoscopy and endotracheal intubation by participants on an airway simulator. By comparing the data from junior participants to more experienced participants, we hope to observe statistically significant differences that may serve as valid measures of skill.
How Often Are Antibiotics Prescriptions Filled After Children Are Discharged From Hospital?
Dr. C. Daymont
$10,000
$10,000 (MICH)
Bacterial infections like pneumonia, urinary tract infections, and skin infections are a common reason children are admitted to the hospital. Most children admitted with one of these infections stay for only a couple of days. They usually receive antibiotics through an intravenous line (IV) and are then prescribed antibiotics to take orally at home. We know that many people do not take, or give to children, all of the medication prescribed. We therefore plan to look at how often antibiotic prescriptions are filled after children are discharged from hospital with a bacterial infection.
This study may impact care in a couple of ways. If we find out that some children are not receiving antibiotics after discharge, we can try to find ways to improve our discharge instructions explaining why it is important for them to continue to receive antibiotics at home. If we identify certain groups of children who are less likely to get antibiotics after discharge, we may be able to focus our efforts on making sure we help them get their prescriptions filled before discharge. Filling a prescription is only the first step in taking all the prescribed medication. In the future, we hope to do more studies to look at how much medicine children get after their prescriptions are filled.
The Transcriptional Regulation of Human Endogenous Retrovirus-K in Neurodegenerative Disease
Dr. R. Douville
$20,000
Integrated into human DNA resides thousands of retrovirus-like sequences which comprise nearly 8% of the human genome. Not all human endogenous retroviruses (HERVs) remain silent passengers within our genomes; re-activation of HERVs is associated with many inflammatory diseases. Our research initially highlighted that there is active HERV-K in neurons of patients with amyotrophic lateral sclerosis (ALS). As retroviruses can cause central nervous system damage before the onset of diagnosable symptoms, it is important to understand what cell signals can turn HERVs on and off. Human cells can actively counteract retrovirus replication when aided by inflammatory transcription factors, proteins that are up-regulated by the innate immune response.
We plan to evaluate whether inflammatory transcription factors drive or repress HERV-K levels in human cortical neurons and cell lines chronically expressing the virus. We will also determine whether these inflammatory transcription factors are over-expressed in the HERV-K positive cortical neurons of patients with ALS using advanced tissue imaging techniques. Our findings will provide insight into therapeutic antiviral regimens which could prevent the onset of central nervous system damage and symptoms triggered by endogenous retrovirus activity in ALS.
Role of Cateslytin in the Context of Inflammatory Bowel Disease
Dr. J. Ghia
$20,000
Inflammatory bowel diseases (IBD) are chronic, recurrent intestinal disorders, which include Crohn’s disease and ulcerative colitis. The estimated prevalence in Canada is around 500/100,000 persons. These diseases often present in adolescence or young adulthood resulting in a long burden of disease with significant psychosocial, physical and economic impacts. In Canada, IBD represents a public health issue with an estimated cost of $1.7 billion.
The etiopathogenesis of IBD is multifactorial, involving an aberrant immune response in genetically predisposed individuals. However, some patients are resistant to current drugs and all of these agents have adverse side effects, so new agents are in need.
Changes in a protein called chromogranin-A (CgA) are observed in patients with IBD. Due to the strategic location of CgA, that protein may play an important role in immune activation in relation to IBD. This study aims to elucidate a new immunoendocrine pathway, which could ultimately serve as a safe therapeutic target. Our studies will use physiological and molecular tools to identify CgA changes as well as changes in macrophages, a type of immune cell present in the colon that has an important role in inflammation. In summary, we will explore new pathways implicating the CgA during intestinal inflammation that will provide a basis for possible new treatments of IBD.
Molecular Regulation of Insulin Sensitivity During Skeletal Muscle Differentiation
Dr. J. Gordon
$10,000
$10,000 (MICH)
During skeletal muscle development, precursor cells called myoblasts fuse to form multi-nucleated myotubes while simultaneously increasing the expression of muscle-specific genes. This process of specialization is largely regulated by the myocyte enhancer factor-2 (MEF2) and serum response factor (SRF) families of transcription factors. Although much has been learned regarding the role of MEF2 and SRF in regulating the expression of muscle contractile genes, the role of MEF2 and SRF proteins in the regulation of muscle insulin sensitivity during development and in post-natal life remains unknown. However, this particular aspect of embryonic and post-natal muscle development may be a critical factor in determining the risk of type II diabetes.
Therefore, the objective of this proposal is to test the central hypothesis that MEF2 and SRF regulate skeletal muscle insulin sensitivity during development and that this molecular pathway becomes dysregulated during states of insulin resistance and type II diabetes. Completion of these studies will uncover new molecular insights into the regulation of insulin-regulated glucose uptake and the dysregulation of these molecular pathways during states of obesity and type II diabetes. Successful completion of these objectives will bring us closer to identifying molecular targets for small molecule drug discovery aimed at treating or preventing type II diabetes.
Investigation of the Impact of Low-Abundance Drug Resistant HIV-1 Variants on Antiretroviral Therapy Outcome by Tagged Pooled Pyrosequencing in HIV-1 Infected Children
Dr. B. Liang
$20,000
Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has claimed more than 30 million lives and another 33 million are living with the virus. Since 1996, the use of antiretroviral therapy (ART) has resulted in a dramatic reduction in AIDS-related sicknesses and deaths. However, the emergence and spread of drug resistant HIV viruses to people who have not been exposed to ART treatments threatens to reverse the gains so far made in controlling the epidemic.
In an effort to increase treatment success in the presence of transmitted drug resistance, national guidelines now recommend drug resistance testing for HIV-infected individuals before commencing therapy. However, current major drug resistance testing techniques, Sanger sequencing, cannot consistently detect transmitted drug resistant viruses comprising greater than 20% of the viral population. Advance of more sensitive assays makes it possible to detect low abundance HIV drug resistant viruses. Nevertheless, the role of these variants on ART failure is largely unknown.
We propose to carry out a preliminary investigation using a new sensitive technique, called ultra deep pyrosequencing, on blood samples from 40 HIV infected patients who have developed HIV drug resistance to determine if low abundance HIV drug resistant viruses are correlated to ART treatment failure.
The Role of NIMA-Related Kinase Nek9 in Cancer, Cell Cycle Regulation and Control of Cellular Differentiation
Dr. P. Pelka
$20,000
Cancer is the leading cause of death among the Canadian population accounting for 30% of all deaths. Viruses are thought to cause approximately 15% of human cancers so they are useful tools to study cancer development in that they allow those molecular pathways deregulated during cancer formation to be uniquely identified.
We have recently identified Nek9 as a cellular target of the adenoviral oncoprotein E1A. E1A is the immediate early gene expressed following viral infection and its primary role is to activate the expression of other viral genes as well as to initiate the cell growth and division of the infected cell for viral replication to occur.
We hypothesize that Nek9 is important for the regulation of cellular differentiation and E1A interferes with this function of the kinase. The goal of this project is to understand how an oncogene (E1A) modulates the function of the cellular kinase Nek9 and how this relates to cancer and cellular transformation.
The anticipated results will shed an important light on our understanding of how Nek9 and E1A are involved in regulation and deregulation of the cell cycle and cellular differentiation. Because Nek9 is a kinase, it also represents a very attractive therapeutic target and could be an important treatment option for people with a variety of cancers.
Effects of Innovative, Technology-Assisted Circuit Training for Dynamic Balance and Mobility; A Community-Based Group Training Program as an Alternate to Out-Patient Rehabilitation Post Stroke: Phase 2 Randomized Controlled Trial
Dr. S. Pooyania
$12,000
With the aging of the population and the significant decline in mortality and morbidity post-stroke, the absolute number of stroke survivors living in the community will increase in the next 20-30 years. It is therefore reasonable to assume there will be a corresponding increase in the need for various forms of rehabilitation and health care. The activity with the greatest impact on daily living independency is walking, a skill initially lost by as many as 70% of stroke survivors. Stroke patients clearly benefit from intensive and coordinated rehabilitation programs. Adequate well-resourced out-patient therapy, which is relatively inexpensive, is essential to ensure rapid and timely discharge from costly inpatient programs.
This is a proof-of-principle pilot RCT to test the efficiency and effectiveness of treating adults who have suffered a single stroke using the following essential treatment components: community setting, group activity program, flexible, task-specific, interactive computer-based exercise regime. A control group will receive conventional out-patient rehabilitation.
If effective, this will help in making better choices for maximizing restorative therapies, development of cost-effective community resources, secondary prevention, and lifestyle decisions. Clients would be encouraged and motivated to take an active role in their personal health management, which is a cost-effective way of providing rehabilitation services to the growing number of people with chronic disabilities.
Role of Oxidized Phospholipids in Myocardial Ischemia and Reperfusion Injury
Dr. A. Ravandi
$20,000
A heart attack occurs when there is sudden blockage to one of the arteries that feeds the heart. We have had great advancements in health care that allow for therapies that can rapidly open the artery. Even with the flow of blood restored to the heart, muscle damage continues to occur due to a powerful tissue reaction. We call this phenomenon ischemia-reperfusion injury and it is thought to involve novel lipid molecules that are released from the heart cells. It has been very difficult in the past to identify these molecules in heart muscles since they are present in very small amounts. We have now developed sophisticated technology that allows us to identify and measure these compounds in a very sensitive way.
We propose a study that will identify and quantify new oxidized lipids in an animal model of ischemia-reperfusion injury. To show the mechanism of heart damage, we will study how these novel molecules trigger healthy heart cells to die and how we can inhibit that process. By inhibiting the action of compounds that lead to cell death, we can improve the function of the heart and improve quality of life after a heart attack. Our findings can be used as a novel therapy in preventing heart damage.
The Efficacy of rTMS in Treatment of Obsessive Compulsive Disorder, a Double Blind Randomized Clinical Trial
Dr. A. Saligheh
$20,000
Despite the disabling nature and burden of obsessive compulsive disorder (OCD), only one third of OCD patients show complete remission of their symptoms with conventional interventions. A new non-invasive method called repetitive transcranial magnetic stimulation (rTMS) has been used for investigation of brain functions. rTMS allows easy and painless central nervous system (CNS) stimulation by inducing magnetic pulses to the brain.
In a preliminary pilot study, we tested the efficacy of rTMS in symptom profiles of OCD patients. All participants were evaluated with Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The average improvement in the Y-BOCS score was 44%. In the current proposal, through a randomized clinical trial, we aim to further evaluate the efficacy of rTMS in OCD in a larger sample for a longer period. In our pilot study, we applied rTMS for two weeks. We hypothesize that longer duration of rTMS treatment will have greater benefit in OCD symptom reduction.
By replicating the results of our pilot study within a double blind controlled design, we will have taken another step forward towards improving the quality of life of OCD patients. To our knowledge, we are the first group who found a promising improvement in OCD symptoms using rTMS.
A Multilevel Analysis of Risk and Protective Factors for Youth Homicide and Severe Intentional Injury in Winnipeg
Dr. C. Snider
$10,000
$10,000 (WF)
Youth violent injuries are a source of personal, social, and health care costs. Understanding the risk and protective factors amongst the violent injury patient population is vital to developing health system and social policy interventions aimed at reducing and preventing violent injuries. Canadian studies on youth homicide and violence are far fewer than the United States and no one in North America has used population-based data to study this problem. The Manitoba Centre for Health Policy (MCHP) houses the Population Health Research Data Repository, which can link health care data with a multitude of social databases such as education, child welfare, housing, justice, and registries like vital statistics. This provides the opportunity to use a population-based data approach and determine risk and protective factors that have not yet been examined.
The objective of this study is to determine the individual and community-level risk and protective factors for homicide and violent injury hospitalization amongst youth in Winnipeg, with an emphasis on socio-economic status. This will enable evidence-based emergency department care for the prevention of youth violence in Winnipeg, supporting a future clinical intervention program. Moreover, the results will support future policy recommendations targeting both individual and social risk factors to reduce the burden of youth violent injury and homicide in Winnipeg.
Applying the Kidney Failure Risk Equation in Manitoba
Dr. N. Tangri
$20,000
Chronic kidney disease (CKD) is a major public health problem. Manitoba's aboriginal population suffers from high rates of CKD and also has the highest rates of kidney failure (KF) requiring dialysis in Canada.
We have previously developed a risk equation (Kidney Failure Risk Equation- KFRE) that predicts the risk of KF in patients with CKD. The KFRE was developed in CKD patients from Ontario, and has proven to be accurate in patients from British Columbia. However, the accuracy of the KFRE in Manitoba's aboriginal CKD population remains unknown.
In this study, we will test the performance of the KFRE in predicting the need for dialysis in Manitoba's aboriginal population. If the equation is proven accurate, we can then use it in our clinics and help optimize the treatment of patients with CKD.
Prospective Study of Metabolic Syndrome and Liver Disease in a Healthy Male Cohort: The Manitoba Follow-up Study
Dr. J. Uhanova
$20,000
The aim of this study is to establish a lifetime incidence of various forms of liver disease in originally healthy men and to determine the association between metabolic syndrome and non-alcoholic fatty liver disease (NAFLD).
The Manitoba Follow-up Study (MFUS) is a truly unique resource, consisting of prospectively collected health data on 3,983 air force men followed for the duration of their lifetime. This data is well-suited to determine the lifetime risk of NAFLD and other liver diseases, liver disease-related mortality, prevalence of various clinical features of metabolic syndrome, and the relationship to hepatic diseases.
The evaluation of these findings together with clinical features (morbidity, related conditions and complications) is essential for designing specific public health programs, which is particularly important now as population obesity reaches epidemic proportions.
Identification of Biomarkers From Blood Samples of Patients With Acute Stroke
Dr. K. I. Vadakkan
$20,000
Strokes result from the sudden stoppage of blood supply to a brain region, resulting in the death of neurons and other cells. When patients arrive to the hospital with symptoms of a stroke, they undergo computerized axial tomography scanning (CAT scan). In many cases, it is not possible to view changes in the brain from the stroke. This makes it difficult to differentiate a stroke from conditions that can cause similar symptoms. As a result, clinicians often make a reasonable assumption that a stroke has taken place and begin treatment. The identification of a stroke marker from blood samples could complement appropriate management of these patients. Moreover, identification of a blood test would enable us to study the progression of the stroke-induced changes in the brain tissue over time.
A molecular marker has been identified from blood samples of stroke patients at both the Health Sciences Centre and St. Boniface Hospital. Tests were developed to report the results within 15 minutes of blood collection. The next step is to optimize these test protocols using small volumes of blood in automatic machines (auto-analyzers) close to the emergency department. The results from nearly 100 stroke and the same number of control patients will be analyzed to further verify the practical use of the test.
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