A growing body of evidence suggests that cognitive impairment is a significant contributing factor in the increased incidence of falls among older adults. With that said, the exact neural systems within the brain that underlie an increased risk of falling remain unclear. Recently, it has been suggested that medial-frontal cortex, a region of the brain typically associated with cognitive control, plays an important role in evaluating the success or failure of movement. Therefore, one might assume that the ability of the medial-frontal system to evaluate motor output might be impaired with aging. Functional deficits within the medial-frontal system brought about by aging may result in a reduced ability to evaluate stride and/or balance, and subsequently contribute to the increased incidence of falls observed in older adults. Dr. Olave Krigolson’s current research utilizes neuroimaging techniques to assess the effectiveness of the medial-frontal system in evaluating motor output in two groups of older adults; a group of older adults prone to falling and a group not prone to falling. Dr. Krigolson is testing the hypothesis that evaluation capabilities of the medial-frontal cortex will be diminished in older adults prone to falling compared to the control group. The findings from Dr. Krigolson’s study will improve our understanding of the mechanisms that contribute to the increased propensity for falling evident with increasing age, and will also potentially provide a basis for the development of assessment techniques and interventions to decrease the occurrence of falls in older adults.
Research Location: University of British Columbia - Vancouver Campus
The role of leptin in the regulation of glucagon release from pancreatic alpha-cells.
The prevalence of diabetes is increasing worldwide due to population growth, aging and increasing frequency of obesity and physical inactivity. Diabetes mellitus is caused by a relative or absolute deficiency of the hormone insulin, which results in the characteristic feature of high blood sugar levels that play a key role in diabetes-associated complications. Inappropriately high levels of the sugar-raising hormone glucagon further aggravate the disease. Therefore, diabetes may be treated by increasing insulin levels and/or action, or inhibiting glucagon production and/or action. In an effort to identify the causes of diabetes, most studies have focused on better understanding the physiology of insulin-secreting beta-cells: despite the importance of glucagon, the counter-regulatory hormone to insulin, little is known about the physiology of pancreatic alpha-cells. Recently, Ms. Eva Tuduri and colleagues established that the hormone leptin controls both the secretion of insulin and glucagon, and thereby regulates blood sugar levels. Leptin is produced by fat cells and the levels of leptin in the blood typically correlate to the total content of fat in the body. Leptin is best known for its effects on feeding centers in the brain, where it regulates both food intake and energy expenditure. Ms. Tuduri’s current research project is focusing on understanding the role of leptin in regulating levels of glucagon, independent of leptin actions on body weight. An inhibitory effect of leptin on the function of alpha-cells could be considered as a potential therapeutic strategy to regulate glucagon levels and to normalize sugar levels in diabetic patients.
Bayesian Adjustment for Unmeasured Environmental Confounding
Studies in environmental epidemiology are often concerned with understanding the health effects of environmental exposure in various forms. Because these studies are, by nature, observational, it is often difficult to make valid statistical conclusions. Additional complications arise from the presence of confounding variables, which relate to both the exposure and health effect, and hence complicate the relationship. Traditionally these confounders are controlled for by including them as explanatory variables in a statistical model. Bias-free conclusions become much more difficult, however, when some confounders are unmeasured or inadequately measured. A wide variety of environmental epidemiology studies have suffered from this problem, including, for instance, estimating the association between air pollution and mortality, between magnesium levels in drinking water and mortality from acute myocardial infarction, and between ethnicity, income and limiting long-term illness. The focus of Luke Bornn’s research is the development of a coherent, unified framework for modeling environmental risk exposure in the presence of unmeasured confounding. His model will account for spatial dependencies between adjacent geographical groups as well as other factors that are important for these studies, such as ecological bias and pure specification bias. His hypothesis is that by accounting for spatial dependence and unmeasured confounding under a comprehensive and unified framework, the risk estimates will more accurately estimate the true exposure risk and provide more appropriate estimates of the corresponding uncertainty. By developing a model through simulations, analytic results and application to real data sets, Mr. Bornn’s research will create a model that is both practical and useable for environmental epidemiology practitioners.
Automated Malaria Diagnostic Test via Microfluidic Separation of Infected Red Blood Cells
Every year, 350 to 500 million cases of malaria occur worldwide, resulting in over a million deaths. The majority of these cases occur in sub-Saharan Africa and are responsible for 25 percent of pediatric fatalities under the age of five. In terms of the financial burden, estimates suggest that malaria costs Africa more than $12 billion annually. The global campaign to control and eradicate malaria requires accurate, rapid and cost-effective diagnostic tools. Inaccurate diagnosis results in patients failing to receive needed treatment as well as an overuse of malaria drugs which could contribute to the emergence of drug resistant strains. Currently, the most accurate diagnostic approach requires a trained technician to count the infected cells in a blood sample under a microscope, which is impractical for low-resource regions. Microfluidic devices have shown great potential for cell sorting applications. Such devices can have high selectivity and sensitivity while still being relatively inexpensive to produce. Ms. Sarah Mcfaul is utilizing microfluidics to construct an automated malaria diagnostic test that will be available as a small portable device, requiring no special training to use. Ideally, this automated diagnostic tool will provide sensitivity and quantitative results equal to microscopy, and will also be inexpensively manufactured in order to be accessible to low-resource regions where malaria is a serious threat. Not only will such a device aid in diagnosing malaria, but it will also track the effectiveness of malaria treatments over time in individual patients, enabling clinics can make the best use of their anti-malarial drugs. This in turn will help to lower the number of deaths from malaria and slow the emergence of drug-resistant strains of this deadly parasite.
Promoting beta-cell function and survival in rodent models of diabetes with an analogue of the incretin hormone, GIP
Diabetes mellitus is a chronic, debilitating disease in which the body is unable to adequately dispose of circulating glucose. As a result, diabetes mellitus causes damage to the eyes, kidneys, peripheral nerves and cardiovascular system. Type 2 diabetes accounts for about 90 percent of diabetes cases and is typically caused by the development of obesity with its associated resistance to the glucose-lowering actions of insulin, compounded by decreased circulating levels of insulin. Insufficient insulin levels in Type 2 diabetes are caused by the diminished function and increased death of the important insulin-secreting beta-cells located in the pancreas. Therefore, therapeutic interventions that improve the function and survival of beta-cells would clearly benefit patients with Type 2 diabetes. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are insulin secreting (incretin) hormones that do just that. As a result, drugs have been developed that enhance the activity of these hormones and they have demonstrated powerful anti-diabetic actions in patients with Type 2 diabetes. Scott Widenmaier’s current research project is building on his earlier work involving the development of a long-acting GIP analogue that has demonstrated potent effects on cultured beta-cells, and triggered acute increases in insulin levels during single dose treatments of diabetic rodents. More recently it has shown potential to decrease fat levels in obese rodents. Mr. Widenmaier’s current project will evaluate the ability of long-term administration of this same GIP analogue to improve the function and survival of beta cells, and decrease circulating glucose levels and obesity in rodent models of Type 2 diabetes. Ultimately, the information resulting from these studies could contribute to a better understanding of the underlying basis for the beneficial effects of incretin therapy, and potentially lead to the development of next generation therapeutics.