In 2000/01, approximately 264 000 Canadians required a wheelchair for mobility. Independence with mobility is important for day-to-day living, social activities, and overall quality of life. However, although wheelchair skills training has become much more prevalent in the past decade, more than half of Canadians using a wheelchair are not independent and require assistance with their mobility. One factor that has not yet been explored by research is the impact of confidence on a personâs mobility and independence. Confidence contributes to the acquisition of knowledge and refinement of new abilities. It also influences an individualâs choice of activities, motivational level, effort, resilience, life choices, and perseverance in the face of difficulties. Preliminary research suggests that confidence may affect wheelchair mobility, but there is currently no tool to assess or address this important factor. Paula Rushton is developing and validating an assessment tool to measure wheelchair skills confidence. The creation of this tool involves input from occupational therapists, physical therapists and physicians, as well as wheelchair users in the community. The second phase of her project will involve testing the tool with one hundred community dwelling wheelchair users. The creation and validation of this tool is an important first step in developing treatment strategies that could address low confidence with wheelchair mobility. Ultimately, this work could result in better mobility and independence for people who use wheelchairs, and a decreased burden on the health care system and on caregivers.
Research Location: Vancouver Coastal Health Research Institute
Effect of cam-type deformity associated with femoroacetabular impingement on hip mechanics
Hip osteoarthritis (OA) is a painful condition affecting 4.4 per cent of the population aged 55 and older. Currently, there are very limited treatment options and no known cure for OA. Improving prevention and treatment of early hip OA requires a thorough understanding of the joint mechanics and how these mechanics affect the initiation and progression of the disease. Hip OA can either be primary (occurs with no previously known cause) or it can be secondary to a known deformity. It has recently been hypothesized that most “”primary”” cases are actually caused by small deformities in the joint that were previously unnoticed. One deformity that has been found to have a strong correlation with hip OA is called a cam deformity, which can cause pain and decreased range of motion in the hip. Cam deformities occur on the upper femur (thigh bone) and cause increased contact between the femur and the acetabulum (hip socket). Joint contact pressure is thought to play a role in accelerating the onset of OA. To determine the association between cam deformity and the onset of hip OA, Laura Given is studying how the joint mechanics change depending on the degree of cam deformity. She will track how the joint translations and rotations are affected throughout the range of motion of the hip and determine how the range of motion is affected by simulated cam deformity. By describing how the size of cam deformity affects joint mechanics, Givenâs research will help surgeons understand how to effectively correct the deformity in an effort to slow or even stop the osteoarthritic disease progression. It could also lead to preliminary guidelines in arthritis screening programs. This could reduce the number of cases of hip OA seen in the future.
Protein tyrosine phosphatase A (PtpA) dependent mycobacterial manipulation of host response to infection
Tuberculosis (TB) is currently the worldâs leading cause of mortality due to a single infectious agent. It has been estimated that approximately one-third of the worldâs population is infected with Mycobacterium tuberculosis, the bacteria that causes TB. Approximately two million people die of TB annually, and about eight million new cases arise each year. In addition to the emergence of multi-drug resistant strains of the disease, TB develops much more readily in people with HIV infection, and is a leading cause of AIDS-related death. There is an urgent need for novel therapeutics and drug targets in order to control the global spread of TB. In order to evade attack by the host immune system, M. tuberculosis secretes a protein called Protein tyrosine phosphatase A (PtpA). PtpA interacts with multiple proteins in the host that are normally essential for the destruction of bacterial pathogens. However, the exact role of these interactions in relation to the survival of M. tuberculosis within cells is not yet completely understood. Dennis Wong is defining the role of TB-Host interactions and identifying the molecular events that are disrupted by PtpA to promote TB infection. Understanding the mechanisms by which PtpA promotes the survival of M. tuberculosis will provide important insights regarding the pathogenesis of TB and the response of the host immune system to infections. As PtpA is a potential drug target, the new knowledge may contribute to the development of novel therapeutics against one of the deadliest diseases in the world.
The role of SHIP's C2 and PH domains in regulating hematopoietic cell growth and function
Various cancers and inflammatory diseases occur as a result of inappropriate activation of the bodyâs blood-forming hematopoietic cells. Normally, cellular activation, growth and survival in hematopoietic cells are regulated by the phosphoinositide 3-kinase (PI3K) pathway, which drives a wide range of cellular processes. Keeping tight control on this pathway is SHIP (SH2 domain-containing inositol 5′ phosphatase), a counteracting enzyme that inhibits PI3K action. SHIP is found only in blood and immune system cells and is the major restraining mechanism in these cell types. Loss or impaired activity of SHIP â in effect, removing the brakes on the PI3K pathway â has been implicated in certain leukemias and in inflammatory disease. Recently, researchers discovered small molecules that are capable of enhancing SHIP activity, resulting in both the inhibition of immune cell activation and the death of hematopoietic cancer cells. This represents a previously unknown mode of regulating SHIP enzyme activity. Andrew Ming-Lum is determining the significance of this novel type of regulation of SHIP function. Using cell lines and mouse models, he is focusing on a previously unrecognized domain on the enzyme, upon which the small molecules are believed to act. These studies will provide greater insight into how this mechanism affects the function, growth and survival of hematopoietic cells. It will also provide insight into the dysregulation that occurs in certain cancers and inflammatory diseases.
Translational TB Research: Identification of Novel Drug Targets and Development of Protective Vaccines
A recent report from the World Health Organization revealed that about 1.5 million people died from TB in 2006. In addition, another 200,000 people with HIV died from HIV-associated TB. Current strategies aim to reduce the annual death toll from TB to less than 1 million worldwide by 2015, as set out in the United Nations Millennium Development Goals. Infection by the Mycobacterium tuberculosis microorganism causes TB. The current global strategy for TB control is based on reducing the spread of infection through massive vaccination campaigns with the BCG (bacille Calmette-Guérin) vaccine, and treatment of individuals with active disease using multi-drug combinations. However, there are challenges to this approach, including inefficiency of the BCG vaccine, the emergence of drug resistant strains of Mycobacterium tuberculosis (Mtb) and the difficulty in delivering a treatment that requires multiple drugs over periods of six months or more.
Until recently, little was known about how Mtb alters the host immune system to cause infection. Through Dr. Zakaria Hmama’s work as an MSFHR Scholar over the past six years, important new knowledge has been developed regarding the sub-cellular and molecular mechanisms of host/pathogen interactions. His research over the next five years will focus on gene manipulation technologies to upgrade the current BCG vaccine with recent immunological concepts to maximize its protective properties. Hmama is also investigating an important virulence factor identified by his lab as a potential drug target for TB treatment.
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.
The characterization of KiSS1 and GPR54 in breast cancer and other hormonally responsive cancers
Cancers whose growth is influenced by sex hormones, such as estrogen and testosterone, form the largest group of cancers that affect Canadian men and women. Breast cancer remains the second most common cause of cancer death among women in North America, and prostate cancer rates third for men. While there have been advances in treatment, many of these patients will succumb to their disease when tumors metastasize (spread to other organs or tissues in the body). The KiSS1 and GPR54 genes have demonstrated the ability to prevent metastases from developing. While the importance of KiSS1 and GPR54 are being studied in other cancers, little has been done to investigate the involvement of these two genes in clinical breast and ovarian cancers, and no studies have been conducted in prostate cancer. Building on her MSFHR-funded Masterâs research, Leah Prentice is investigating whether KiSS1 and GPR54 have dual roles as both tumor promoters, via their involvement in hormonal processes, and also as suppressors of metastasis. By understanding the anti-metastatic mechanism of these two genes, Prentice hopes to contribute to the development of more targeted therapies and diagnostic tests that would allow for earlier detection of these potentially life-threatening cancers.
Action Schools! BC: The effect of a school based physical activity model on risk factors for cardiovascular disease in Aboriginal children
Cardiovascular disease (CVD) is a chronic condition that can lead to heart attack and stroke. CVD costs the BC health care system approximately $2.5 billion a year. Sadly, the onset of cardiovascular disease often starts in childhood. About 50 per cent of North American children exhibit one or more risk factors for CVD and many children and adolescents exhibit multiple risk factors. These statistics are worrisome because the severity of CVD increases with the number of risk factors, and risks during childhood tend to track into adulthood. As a result, these children are susceptible to developing cardiovascular disease as adults. Previous research has linked higher levels of physical activity during childhood to a lower risk for CVD as adults. Lindsay Nettlefold is examining the prevalence of CVD risk factors in children and whether differences exist between girls and boys and between children of different ethnicity. She is also studying whether a school-based physical activity program can reduce the level of risk factors for cardiovascular disease in children. The goal to develop an effective program that could be used to improve cardiovascular health in children will prove beneficial in helping to prevent the development of disease later in life.
Links between Patellofemoral Biomechanics and Osteoarthritis
One in ten Canadians suffers from osteoarthritis, an incurable disease that causes pain and limits motion in joints. It occurs most often in the knee joint; the patellofemoral joint, which is located at the juncture of the kneecap and thigh bone, is involved in half of these cases. Emily McWalterâs research is focused on improving the diagnosis and treatment of patellofemoral osteoarthritis. It is widely believed that biomechanical factors, such as abnormal joint motion and excessive force exerted on bone and cartilage are related to the onset and progression of osteoarthritis. While treatment focuses on correcting abnormal joints through surgery or physiotherapy, these treatments do little to slow progression of the disease. Thatâs likely because the procedures do not correct all of the biomechanical factors contributing to the damage. With recent advances in MRI imaging, itâs now possible to study biomechanical factors and cartilage degeneration simultaneously. Emily McWalterâs research is focused on developing better methods of detecting and identifying the causes of cartilage degeneration earlier. She is currently working to develop and validate a tool that can estimate the pressure that develops on the surface of cartilage, with a view to using this information to determine if areas under abnormal levels of pressure are at greater risk for degeneration. If successful, this tool will be a valuable asset in understanding the onset and development of patellofemoral osteoarthritis and in assessing the effectiveness of surgeries and other biomechanics-based treatment strategies.