Acne is the most common skin disorder worldwide, affecting approximately 80 per cent of individuals at some point in their lives. How the skin develops this inflammatory condition is not entirely understood, nor is there a cure for severe, persistent cases of acne that often result in permanent scarring. Antibiotics are often prescribed as a first-line treatment, but the most effective antibiotic (Accutane) is known to have serious side effects, including birth defects and depression. In addition, antibiotic resistance is a growing problem. Propionibacterium acnes is present on most people’s skin and is the principal microorganism associated with acne. It can behave as an opportunistic pathogen under certain circumstances, expressing genes that lead to symptoms of acne. The genome of the bacterium has been sequenced and research has shown several genes that can generate enzymes for degrading skin, and proteins that may activate the immune system, leading to the initiation of acne, its development into inflammatory lesions and scarring. Angel Yu is focusing on O-sialoglycoprotein endopeptidase, a skin tissue-degrading enzyme. In order to understand how this protease works and how it recognizes its protein targets, she is growing crystals of the enzyme and using X-ray crystallography to study its structure at the atomic level. She will conduct studies that confirm the enzyme’s biological function and identify associated amino acid residues. Ultimately, Yu hopes her findings will provide insight into the molecular mechanism of this inflammatory skin disorder and identify new leads for the treatment of acne.
Program: Trainee
The development of the corticospinal tract in premature newborns: impact of early brain injury and relationship with motor abilities
Approximately eight per cent of babies in British Columbia are born prematurely (less than 37 weeks after conception), and survival rates have improved dramatically for these infants. Motor and cognitive impairments are common among children born prematurely: five to 10 per cent will exhibit motor deficits such as cerebral palsy, and up to half will experience problems with brain functions (such as learning to speak). At school age, these delays in development can become greater concerns as they may interfere with learning and social interaction. Recent studies suggest that the developmental impairment observed may be associated with abnormal development of the brain regions responsible for motor and brain functioning. Early brain abnormalities, such as white matter injury (WMI), may underlie maturational impairments of these regions. A key brain pathway of interest is the corticospinal tract, which carries voluntary motor information from the control centre of the brain (the cortex) to muscles of the body. Elysia Adams is determining whether brain abnormalities, such as WMI, in premature newborns in their early life will affect their motor and brain function. Using advanced imaging techniques with magnetic resonance imaging (MRI), she is comparing corticospinal tract development among premature babies with and without these brain abnormalities,. This will allow her to determine whether WMI affects the development of the corticospinal tract and to establish whether later motor function can be predicted by assessing the tract’s development. Ultimately, this research could lead to ways to predict brain outcome among babies born prematurely. This would allow doctors to identify motor problems earlier and provide appropriate treatments, such as physiotherapy, to improve outcomes or prevent the long-term consequences of these developmental delays.
Video games can be good for you: an investigation of why games can be good and how to enhance their health benefits
In addition to video games being an enjoyable pastime for many people, research is increasingly indicating the beneficial effects of video game use on various cognitive abilities. Studies have demonstrated that in comparison to people who don’t play video games, “gamers” are typically better at focusing their attention and multi-tasking, and they demonstrate superior spatial processing and faster reaction times. A growing amount of anecdotal evidence suggests that video games could have health benefits, such as the use of video games as rehabilitation for stroke patients, or for improving the speed and accuracy of surgeons performing laparoscopic surgery. Although previous work has identified that video game use can lead to enhancements in attentional processing in the brain, research to date has been limited to studying how the brain orients its attention to tasks without considering the role of eye movements in this process. Joseph Chisholm is using video games to investigate the attentional differences between game players and non-game players. He is focusing on the use of “distractors” – objects or events that attempt to capture an individual’s attention and distract from the task at hand. He will compare the ability of game players and non-game players to control what they pay attention to by measuring reaction times and eye movements. In identifying the mechanisms underlying how gaming enhances attentional control, this research could yield potentially novel and specialized treatment options for individuals with deficiencies in attentional processing, such as stroke patients.
Spatial modulation of vestibular reflexes by the cerebellum characterized in healthy volunteers and spinocerebellar ataxia patients
While maintaining balance appears effortless and relatively simple, it depends on a complex integration of sensory and motor signals that originate from a variety of sources in the body. When you turn your head, even though the vestibular organs of the inner ear change their orientation relative to the body, they still provide information which can be used to aid balance. This response relies on information received from vestibular organs (which measure linear and angular acceleration of the head) and sensory information from the neck (which conveys the head’s position). These two signals are then integrated to provide contextually specific directional information to the brain. As such, patients with damage to their vestibular organs tend to be posturally unstable. The cerebellum has emerged as a potential contributor to the convergence and interpretation of vestibular and somatosensory information in the brain. Patients with cerebellar dysfunction often exhibit similar abnormal balance behaviour to those with vestibular damage. Christopher Dakin is investigating the cerebellum’s role in the vestibular systems influence on balance. He is comparing postural responses associated with vestibular activation among two groups: healthy people, whose cerebellar function is temporarily inhibited by a technique called Transcranial magnetic stimulation; and individuals with spinocerebellar ataxia, a neurological disease marked by atrophy (wasting) of the cerebellum. By increasing our understanding of the human nervous system as it relates to cerebellar processing of vestibular information, Dakin’s research will contribute to more accurate balance disorder diagnoses and treatments. Ultimately, his work could lead to improved therapeutic and rehabilitative techniques directed towards patients with vestibulo-cerebellar dysfunction.
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, Given’s 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.
The reliability and validity of the External Hostile Attributions Scale (EHAS) in a sample of civil psychiatric patients and criminal offenders
Violence, victimization, and suicide-related behaviours have many negative consequences on society and are viewed as critical public health issues. It is estimated that 2,000,000 violent crimes are committed each year in Canada, and that costs to victims, such as health services, approximate $47 billion annually (Statistics Canada, 2003). In addition to the important costs to the healthcare system, these violent outcomes greatly affect individuals’ quality of life as well as mental and physical health. Melissa Hendry’s research aims to reduce the risk of these negative behaviours by investigating risk factors for such behaviours; specifically, she is interested in hostile attributions, which is the attribution of malevolent intent to others, which she will study in a sample of civil psychiatric patients and criminal offenders. This research will assess participants’ level of hostile attributions using a new measure of hostile attributions, as well as other variables such as psychiatric symptoms, substance use, and criminal attitudes, to see how these relate to one another. Another purpose of her project is to look at the association between hostile attributions and behaviours such as violence, victimization, self-harm, and suicidal ideation and attempts. Exploring this research area to a greater degree could have far-reaching consequences in terms of decreasing the incidence of violence-related adverse outcomes in civil psychiatric patients and criminal offenders, thereby enhancing overall population health and reducing health care system costs. The results of Melissa’s research are expected to raise implications for reducing the risk of harmful behaviours in these individuals in terms of implementing new treatment and intervention programs.
Can intrapulmonary arteriovenous shunting explain exercise-induced arterial hypoxemia in women?
The cardio-respiratory system (heart and lungs) is efficient in maintaining oxygen and carbon dioxide levels in the blood most of the time. However, during very strenuous exercise, the cardio-respiratory system may become less efficient in maintaining equilibrium of these gases. Known as exercise-induced arterial hypoxemia (EIAH), this condition is characterized by a reduction in oxygen levels in the arterial blood, starving muscles of oxygen and impairing exercise capacity. In men, EIAH has been found to be prevalent mainly in highly-trained endurance athletes at near maximal exercise intensities. However, research has demonstrated that women who are not highly trained may experience EIAH, and at lower exercise intensities. This may be due to anatomical differences: women have smaller lungs, airways, and surface areas for gas exchange relative to men. One potential explanation for the EIAH phenomenon is through intrapulmonary arteriovenous shunting, where instead of taking its normal route through the lungs to gain oxygen, deoxygenated blood from the veins is diverted directly back into the heart. This results in lower oxygen levels in the arterial blood and less oxygen available for the working muscles. Research suggests that intrapulmonary arteriovenous shunting exists in healthy, exercising humans. Jill Kennedy is conducting the first systematic study of whether intrapulmonary arteriovenous shunting accounts for EIAH observed in women during exercise. She will also explore whether this relationship is influenced by fitness. Kennedy’s research will shed new light on female physiological responses to dynamic exercise with respect to the pulmonary system. Ultimately, this knowledge could lead to the establishment of scientifically-based, gender-specific exercise prescription guidelines for women throughout their life span.
BPD as a disorder of intersubjectivity: identity disturbances in borderline personality disorder
Borderline Personality Disorder (BPD) is a psychiatric condition marked by instability in interpersonal relationships, behaviour, mood and self-image. BPD is associated with high rates of suicide, self-harm, substance abuse and hospitalization, and comes at a significant cost to both individuals and society. One symptom of BPD is an inability to maintain a stable sense of identity, which is associated with distress and health risk behaviours. However, the specific types of identity problems, the factors that contribute to identity problems, and the effects of identity disturbance in BPD are unclear. In recent decades, it has been proposed that personal identity is related to life narratives, where a cohesive life story helps a person to maintain a stable sense of identity. Nathalie Lovasz is clarifying the specific identity problems experienced by persons with BPD. Using measures of identity disturbance, she is comparing people with and without BPD. She is also examining potential contributors to identity disturbance in BPD, focusing in particular on whether narrative coherence mediates or accounts for identity disturbance, and the relationship between identity disturbances and emotional states. This research could help clinicians zero in on the specific types of identity problems faced by people with BPD. This research could also lead to improved diagnosis, identifying components of the symptom that are most unique and important to BPD.
Neural connectivity and memory in schizophrenia patients and healthy controls
Schizophrenia is a brain disease that affects one per cent of Canadians — more than 300,000 people — causing hallucinations, disordered thought and memory dysfunction. Two specific types of memory are known to be affected in schizophrenia: working memory, or the ability to temporarily store and manipulate information (e.g. remembering a phone number until you can write it down); and source memory – the ability to recall where a memory, idea or piece of information came from (e.g. remembering that it was your sister who told you that Oslo is the capital of Norway). Paul Metzak is measuring brain activity during these two types of memory in both healthy volunteers and schizophrenia patients. His goal is to see how differences in activity in various areas of the brain can lead to selective memory impairments. He is using newly-developed statistical tools to look at how networks of brain areas interact to give rise to successful remembering. These tools also enable him to determine how the different components of successful remembering are affected in the schizophrenic brain – whether memory impairment arises from a failure in storing the memory properly, or from an inability to retrieve the correct item once it has already been stored. By identifying the dysfunctional components of brain activity that give rise to memory disorders in schizophrenia, Metzak’s research provides a vital first step on the road to improving memory problems. This work could lead to the development of strategies, therapies, and techniques that can minimize the impact of memory deficiencies in the day-to-day life of patients suffering from these impairments.
Temporal processing deficits in developmental dyslexia – a functional MRI study
Developmental dyslexia is defined as the difficulty in learning to read, and affects between 5 and 17.5 per cent of school-age children. The cause of dyslexia is unknown, but there may be a neurobiological basis. Current diagnostic tests for dyslexia are typically conducted by grade two or three, however by this time, the child already displays significant reading difficulties and may never catch up to their peers. Developing diagnostic tests to assess or predict reading difficulties at an earlier age could allow for earlier intervention and prevention of academic and social difficulties associated with dyslexia. For many children, the main problem in dyslexia involves sound (phonological) processing. For instance, the child may not be able to link sounds to letters, or break words up into their individual sounds. Also, people with dyslexia may show deficits in visual and auditory temporal processing, which is the perception and integration of rapidly presented stimuli. For example, the child may have difficulty with determining the direction of motion or sound. It is unknown whether there is a link between reading and temporal processing skills. Marita Partanen is examining whether reading and temporal processing use overlapping brain networks, and whether these brain areas are affected in children with dyslexia. She is using functional magnetic resonance imaging (fMRI) to track brain activation in children as they complete simple tasks. If a link between reading ability and temporal processing can be established, there is potential for simpler and earlier diagnostic tests for dyslexia that assess temporal processing. Ultimately, the ability to diagnose dyslexia at a younger age may lead to new programs that can improve academic and social outcomes for people with dyslexia.