Preeclampsia is the most common dangerous complication of pregnancy, affecting the health of both mother and fetus. While high blood pressure in the mother and the excretion of protein in her urine are the most visible symptoms of the disease, preeclampsia also causes systemic inflammation and organ damage. When this disorder occurs early in pregnancy, it is particularly dangerous and increases a woman’s later cardiovascular risk. Normally during pregnancy, the immune system changes and women become more susceptible to infectious agents. Two infectious agents in particular, Chlamydia pneumoniae (a bacteria) and cytomegalovirus (a virus), are thought to trigger early onset preeclampsia. These agents have already been linked to the development of cardiovascular disease later in life. However, it is still unclear what role they play in the onset and development of preeclampsia and its long term cardiovascular effects. Fang Xie is investigating the mechanisms between infection, innate immune response and the development of preeclampsia. Focusing on Chlamydia pneumoniae and cytomegalovirus, she will determine how pregnant women are affected by these two infectious agents and how immune system receptors respond to the infection, including possible gene mutations and inflammatory changes associated with these two types of agents. She will also determine whether infection results in changes to blood clotting mechanisms during pregnancy. A greater understanding of the role of infectious agents in preeclampsia will help in developing targeted treatments to prevent and cure this disease, leading to improved health care for both mother and fetus.
Research Pillar: Clinical
Neuroimaging and quality of life of children with developmental coordination disorder
Developmental coordination disorder (DCD) affects six to 15 per cent of children aged five to 11. In BC, up to 48,000 of children may meet the diagnostic criteria for DCD. Children with DCD have significant motor coordination difficulties that interfere with their academic achievement and/or activities of daily living. While it was once believed that children with DCD would outgrow their motor difficulties, research suggests that these difficulties persist into adolescence and adulthood. Individuals with DCD tend to avoid social and physical activities, are at higher risk for obesity and coronary vascular disease, and experience social and emotional difficulties. There is some suggestion that DCD is related to differences in brain development, but this has yet to be confirmed. No studies have been conducted to determine how the brains of children with DCD differ from those of typically developing children, and few studies have explored the quality of life of children with this disorder. Jill Zwicker is exploring the neurobiological explanations for children with DCD, and studying how DCD impacts their quality of life. She is examining patterns of brain activation of children with and without DCD using neuroimaging techniques to determine differences in brain anatomy and activation during a fine-motor task. Zwicker will also be interviewing school-age children with DCD to determine how the disorder affects their quality of life. Zwicker’s findings will be used to educate physicians and therapists in BC and beyond regarding DCD. In the longer term, these efforts will lead to the development of scientifically grounded rehabilitation approaches specifically targeted towards enhancing brain activity, function and quality of life for children with DCD.
IL-13 and the Glycomics of Airway Epithelial Repair
Asthma is the most common chronic disease in childhood and continues to increase in prevalence in adults. Every day, lung airways are subjected to challenges that damage their lining, known as the epithelium. The accumulation of damaged epithelium is a common and consistent feature in those with asthma, suggesting that asthmatics are more susceptible to damage, or are less able to repair the epithelium, than people without asthma. While the epithelium normally protects the underlying tissue from noxious particles, epithelial damage may account for airway hyper-reactivity in asthma, and the chronic nature of the disease. Previously supported by an MSFHR Scholar award, Dr. Delbert Dorscheid is researching the role of glycosylated proteins – proteins that have a sugar or sugar chain added to them – in epithelial repair. These proteins appear on the surface of cells that mediate repair, and their formation heralds the start of cell repair. Dorscheid has identified a specific protein that’s linked to the beginning of this process. His goal is to observe any changes in the modification and regulation of this receptor in asthmatic airways and healthy airways, and determine how this may influence injury and repair of the airway. The overall objective is to better understand the differences in asthmatic airways to develop new treatment strategies to improve the quality of life of those who suffer from this disease.
Causal Attributions and Self-Conscious Emotions in Coping with Alcoholism
Although there are large individual differences in recovery rates from alcoholism, little is known about the emotional factors that underlie these differences. Studies suggest that shame and guilt, two negative self-conscious emotions (emotions that require self-evaluations), may have divergent effects on a range of health outcomes. Specifically, shame promotes a range of negative outcomes, such as depression, whereas guilt has more positive effects, including empathy and high self-esteem. In addition, two distinct kinds of pride — “authentic” and “hubristic” — may also have divergent effects. Dr. Jessica Tracy is researching the influence of these four emotions on recovery from alcohol addiction. She is testing whether newly-sober members of Alcoholics Anonymous (AA) who experience guilt and authentic pride, rather than shame and hubristic pride, enjoy greater health and recovery benefits over time. Tracy is also testing whether the thought processes that promote these emotions contribute to health outcomes, and if so, whether specific self-conscious emotions account for these effects. This research is unique in its emphasis on self-conscious emotions, which may play an important role in addiction. The findings could lead to new treatment methods for clinicians, such as targeting these important emotions.
Stimulation of Brain Activity and Recovery of Function after Stroke
Stroke is the third leading cause of death and the most common cause of adult disability in Canada and worldwide. Nearly half of all people with stroke do not have full use of their arms for daily tasks and seek rehabilitation to help restore their function. Recent discoveries have targeted effective treatments for individuals who are still able to move their wrist and fingers after stroke, but there are currently few therapies for individuals with poorer hand movement ability.
Dr. Lara Boyd is exploring whether learning and recovery of function can be enhanced by pairing direct stimulation of the brain with practice of a new motor task. Her research focuses on two areas: testing whether exciting the brain using transcranial magnetic stimulation (TMS) before practicing a new motor skill will promote faster learning and recovery of former motor function; and determining the effect of stroke severity on motor learning. Boyd expects that pairing brain stimulation and practice will help people with stroke learn new motor skills faster and more effectively than when brain stimulation is not delivered. This research may lead to new therapies to help people with stroke return to their regular activities of daily life. Brain stimulation using TMS may specifically offer an effective treatment for people with poor hand and arm function after stroke.
Role of the startle reflex and cervical multifidus in whiplash injury
Low-speed rear-end collisions can generate whiplash injuries, especially when the victim is unprepared for the collision. Neck pain is the most frequent symptom experienced by victims of a car collision, and up to 30% of people injured in a car collision will develop chronic symptoms. In fact 6% of people who develop chronic whiplash from a collision have not returned to work 12 months after the injury. The precise cause of whiplash is not known, but an overreaction in unprepared individuals — known as a startle response — along with the sudden recoil movement of the head, is thought to damage the joints and muscles of the neck.
As an MSFHR-funded post doctoral fellow, Dr. Jean-Sébastien Blouin conducted research that suggested the presence of a startle response when people are exposed to low-speed rear-end collision. Now he is investigating whether the startle response is linked to stimulation of the deep neck muscles, and if activation of these muscles during a collision may increase the risk of injury. With volunteers acting as “crash test dummies,” Blouin is simulating very low speed (1.8 km/hour) collisions to observe their startle response and measure the corresponding muscle activity. He’s investigating the link between a strong startle response during a low speed collision and the development of whiplash symptoms. He’s also exploring if stimuli delivered immediately prior to the collision can inhibit the startle response, possibly providing protection against injury. Findings could contribute to development of a warning device in cars that will help prevent whiplash injuries.
Cognitive decline through normal aging to dementia and death: Identifying early risk factors and targeting effective interventions
The number of Canadians older than 65 is steadily increasing, a trend that will continue over the next few decades. The prevalence of age-related disorders such as dementia is also increasing, along with the related need for personal care and treatment. Cognitive impairment adversely affects quality of life in late adulthood, limiting independence and survival. To examine these important health issues, Dr. Stuart MacDonald is studying factors related to age-related declines in cognitive performance. Part of his research employs existing data from a Swedish study (the Kungsholmen Project; http://www.kungsholmenproject.se/) to examine patterns and identify early predictors of cognitive decline. As the average age of the Swedish population far exceeds that of Canada, research on the Kungsholmen data may provide important insights that can help inform Canadian healthcare policy and prevention strategies.
Dr. MacDonald is also researching how performance for select measures of memory and intelligence is influenced by cognitive training across a period of weeks, as well as regular aerobic exercise (walking three times per week for 30 minutes) over a period of months. Dr. MacDonald's goal is to clearly demarcate the stages and transitions of cognitive decline from mild age-related impairment to more severe dementia deficits. This will help identify early warning signs of cognitive impairment from a broad range of predictors. The findings could lead to more effective prevention based on knowledge of these risk factors, including campaigns to promote health-smart behavior.
Translating gene expression into clinical care for sarcomas and breast cancer
Cancer is one of the leading causes of death in Canada. As a pathologist, Dr. Torsten Nielsen’s job is to accurately diagnose cancer and determine its type from more than 200 possibilities. For more than 50 years, these diagnoses have been made using a light microscope to examine tissue biopsies. However, this can be subjective, requiring the pathologist to make a judgment call in certain cases. Recent new technologies help determine the genetic profile of each type of cancer. This profile can be used to distinguish between cancers that otherwise appear almost identical under the microscope. The ability to detect subtle differences among cancers can be enormously important because the exact diagnosis determines what combination of surgery, radiation, hormone treatment or chemotherapy is the best treatment plan.
Using advanced genetic tools, Dr. Nielsen aims to develop clinical tests that more accurately identify difficult subtypes of cancer, and to then determine which treatments will work best for each subtype. Previously supported by an MSFHR Scholar award, he works with two cancer types in particular: breast cancer and sarcomas (tumours of muscle and bone). With breast cancer, he is working to develop inexpensive and easy-to-conduct clinical tests that accurately diagnose four types not easily distinguished under the microscope. With sarcomas, he is using new molecular tools to develop diagnostic tests and treatments that target specific molecular changes, to see if new drugs can cure these cancers with minimal side effects. His research could lead to simple, effective, and widely available diagnostic tools and personalized treatment strategies that will improve survival for cancer patients.
Preventing falls and disability in older adults after hip fracture
Every year, more than 20,000 people in Canada sustain a hip fracture. Of these, up to 20% die within 12 months and 50% do not return to their pre-fracture level of mobility. People who have a hip fracture have a higher risk of falling and an increased risk of a subsequent hip fracture compared with those of the same age who have never had a hip fracture. After a hip fracture, relative immobility initiates a vicious cycle where deteriorating balance and muscle weakness increases risk of falls and diminished bone health contributes to fracture risk. Although exercise is key to reversing this pattern, there have been relatively few clinical trials aimed at improving muscle strength, balance and enhancing bone health following hip fracture.
Dr. Maureen Ashe is conducting a randomized controlled trial to evaluate the impact of a targeted exercise program on the rate of falls, functional mobility and bone micro-architecture among older adults who have sustained a hip fracture. If successful, this intervention will result in fewer falls and improved bone health in a vulnerable senior population. Data from the research will inform recommendations for rehabilitation and contribute to the knowledge base for health-professionals, both in hospital and in the community, who manage care after hip fracture.
Trajectories towards self-harm, suicide, and other maladaptive coping behaviours
Borderline personality disorder is a serious mental health problem characterized by heightened emotional vulnerability and difficulty modulating emotional responses. Individuals with BPD have high rates of health risk behaviours, such as suicide attempts (75 per cent), self-harm (69-80 per cent), and substance abuse (60 per cent). Despite frequent intense emotional reactions to stressful events, people with BPD lack the skills to reduce their distress through adaptive coping methods. In an effort to reduce these unpleasant emotions and feel better, persons with BPD features often resort to maladaptive coping strategies that are quick and easy to execute (e.g., self-harm, substance abuse) but have negative long-term consequences. However, not everyone with BPD engages in these risky behaviours in response to every stressor, and the specific triggers for these behaviours are largely unknown. Certain types of emotional states (e.g., shame) and life stressors (e.g., being rejected) may be particularly linked with self-destructive coping behaviours. Kristy Walters is examining the specific negative emotions or particular stressful triggers that may be strongly associated with maladaptive behaviours such as self-harm, substance abuse, or suicide. This research will also examine whether or not these relationships among emotions, stressors, and maladaptive behaviours is unique among individuals with borderline personality disorder (BPD). A better understanding of which specific emotions constitute cause for concern, or which types of negative events are more likely to result in self-destructive behaviour, will considerably improve clinicians’ ability to evaluate their client’s level of risk and better identify those clients who are in urgent need of life-saving interventions.