Molecular dissection of the Campylobacter jejuni regulatory system CprRS and its control of key aspects of pathogenesis and biofilm formation

Campylobacter jejuni is the leading cause of bacterial food poisoning in the developed world. Infection with C. jejuni typically presents as severe gastroenteritis, termed campylobacteriosis, and presents as intense, often bloody, diarrhea, vomiting, fever and stomach cramps. Prior infection correlates strongly with autoimmune disorders such as irritable bowel syndrome, reactive arthritis and alarmingly, Guillain-Barré syndrome. Furthermore, antibiotic resistance is skyrocketing in C. jejuni isolates, and an effective human vaccine is not presently available. Currently, very little is known about the virulence mechanisms of C. jejuni. Even less is understood about how this fastidious organism survives and thrives in hostile environments, including those associated with environmental transmission and in vivo stresses such as acid, bile and the immune system. In her research, Sarah Svensson is characterizing the CprRS (Campylobacter planktonic growth regulation) two-component regulatory system (TCRS). TCRS represents ideal targets for antibiotic treatment due to their omnipresence in bacteria (and not humans) and control of phenomena related to virulence. By determining 1) genes that comprise the CprRS regulon; 2) how information is relayed from the environment through CprRS and connected regulatory proteins to elicit the appropriate physiological response; and 3) how survival strategies such as biofilm formation are controlled by CprRS, will contribute to our understanding of what makes apparently fragile bacterial pathogens such as C. jejuni so prevalent. As a result, this work will also provide a framework for design of novel infection control antimicrobial treatment, and vaccine strategies for an underappreciated bacterial pathogen.

The influence of technology on pedestrian safety behaviour

The use of personal electronic devices, such as cell phones and Pods, in everyday situations is a growing safety concern, and there is a common belief that all personal electronic devices threaten pedestrian safety in the same way, that is via distraction. However, recent data indicate that cell phones and iPods influence pedestrian safety behaviours (e.g. looking both ways before crossing a street), in qualitatively different ways, and that cell phones and iPods have different effects on an individual’s behaviour in naturalistic contexts. Building on her earlier research in this area, Sophie Lanthier’s current project will test the hypothesis that cell phone and iPod users are affected differently by these devices: specifically, that cell phone users’ conversations absorb general-purpose attentional resources (i.e. they are distracted from their environment), which increases their likelihood of being in an accident, whereas iPod listeners are not distracted by their music, but rather the music limits auditory input from the environment, rendering them unable to hear unexpected events that could occur after they begin to cross the street. This inability to adapt to a potentially important change in the environment (i.e. a car that has just turned onto the street), could increase an iPod user’s likelihood of being in an accident. This study will help to identify what cues individuals rely on to monitor changes in their environment and how personal electronic devices influence one’s ability to use these cues. With this information firmly in hand, methods to reduce risk in pedestrian behaviours can be undertaken.

The Positive Illusory Bias (PIB) in parents with and without Attention-Deficit/Hyperactivity Disorder (ADHD)

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common psychological conditions in childhood. This disorder is characterized by inattentiveness and/or hyperactivity or impulsivity. Children with ADHD can have major difficulties in important areas of their life, such as in relationships, in their family, and at school. In addition, although treatments are available for this disorder, none of the treatments are without problems and they are of limited long-term effectiveness. Recent studies show that adults can also have ADHD. These adults are at risk for conduct problems, substance abuse, relationship difficulties, driving impairments, employment issues, academic deficits, and poor parenting. Thus, ADHD has negative consequences for both the individual and society. However, as with children, much remains to be done to improve the success of treatments for adults with ADHD. Children with ADHD overestimate their abilities in areas in which they are actually deficient. This is called a Positive Illusory Bias. It is well-known that children are typically optimistic, but the bias of children with ADHD is different from this normal optimism in three major ways. First of all, children with ADHD have a greater absolute positive bias than children without ADHD in that their self-perceptions are even more positive than the self-perceptions of children without ADHD. Secondly, in contrast to those without ADHD, the positive illusions of children with ADHD do not serve to enhance the children’s motivation, endurance, or performance. Finally, children with ADHD maintain their positive illusions even in the face of clear contradictory evidence while the positive illusions of those without ADHD move closer to reality after receiving feedback. Clearly, the Positive Illusory Bias found in children with ADHD is qualitatively different than the self-enhancing optimism generally found in children, and it may have detrimental consequences for the performance of these children and for their motivation to engage in treatment. To date, no research explores the existence of the Positive Illusory Bias in adults with ADHD. In particular, no studies have tested whether the Positive Illusory Bias found in children with ADHD also exists in parents with ADHD. Given research showing that children with ADHD are likely to have parents with ADHD, it seems crucial to examine this question. If a Positive Illusory Bias does indeed exist in parents with ADHD, then these adults may have less motivation to seek or maintain treatment for managing both themselves and their children. For instance, if adults with ADHD hold overly positive views of their parenting, they will be less likely to use parenting programs and services. This could have a negative effect on the outcome of their children. My research will test whether parents with ADHD have a Positive Illusory Bias in the areas of work, relationships, intelligence, and parenting. Female participants who are mothers will be recruited into two groups: a group of mothers with ADHD, and a control group of mothers without ADHD. The diagnosis of ADHD will be determined by information provided by the participant and by someone who knows the participant well (e.g. a spouse). All mothers will complete a self-perception questionnaire that inquires about the four previously-mentioned domains of functioning. The other informants (those who know the mother well) will complete the same questionnaire, answering the questions in reference to the mother. The ratings of the other informants will then be compared to the self-ratings of the mothers. It is predicted that differences in discrepancies between self and other ratings will be larger in the ADHD group than the control group. I will also assess whether the mother is depressed, whether her child has ADHD, and whether the mother has a tendency to respond in a socially desirable manner, so that these variables can be controlled for in analyses of the discrepancy scores. Knowing whether a Positive Illusory Bias exists in adults and more specifically, parents with ADHD can lead to improvements in relevant treatments. For instance, this Positive Illusory Bias may contribute to treatment resistance, whether the treatment is ultimately for the adult or for their child, and it may be possible to develop and utilize specialized techniques to bring the positive self-perceptions of parents with ADHD more in line with reality before beginning treatment. Moreover, consideration of the Positive Illusory Bias as a predictor of treatment response will allow for more informed problem-solving on the part of the clinician in response to resistance to treatment from the client. As such, although there are a number of ways in which the Positive Illusory Bias in parents with ADHD may contribute to improved treatment for this disorder, it is necessary to first answer the question of this study, which is whether or not this bias exists in parents with ADHD.

Exposure assessment for women’s occupational exposure to carcinogens and other hazardous substances

Studies that have evaluated workplace exposure to hazardous chemicals and associated health outcomes have traditionally focused on men in male dominated jobs such as manufacturing and other heavy industries. Consequently, women weren’t generally included in the earlier studies and the industries in which they worked weren’t regarded as important. This, in turn, negatively affected women’s access to workers’ compensation compared with men, especially with respect to injuries, stress and lung diseases from asbestos. However, the research focus has recently shifted to include the changing role of women in the workplace and subsequent hazardous materials exposure that might adversely affect their health. The CAREX study, currently underway in Canada, is a national surveillance project aimed at estimating the number of Canadians exposed to environmental and workplace carcinogens. Cheryl Peter’s research will augment the CAREX project by looking at how these types of exposures differ between men and women. Her study identifies research gaps in women’s occupational health in general, and industries or jobs where women are more susceptible to exposures or adverse health outcomes specifically. The results of this study will help improve the health of female workers by identifying women at higher risk of exposure to hazardous chemicals, and may also help to prevent future health problems, including cancer. Further, Ms. Peter’s data will inform researchers with respect to improved research methods and recommendations on improvements for future studies, accounting for differences in exposures on the job between men and women.

Measuring equity in the use and financing of prescription medicines

The use of prescription drugs outside of hospitals is not addressed in the Canada Health Act or by any legislation that would ensure national standards for accessibility. As a result, public pharmaceutical insurance programs designed to provide access to prescription medicines outside of hospitals have evolved independently in each province and territory. In May 2003, BC instituted Fair PharmaCare, an income-based catastrophic drug coverage program which links individuals’ private financial contributions to the costs of their medicines (either out-of-pocket or through their private insurance), with their household income. Current research suggests that the implementation of income-based drug coverage has shifted the financial burden away from public sources toward private ones, which raises several important questions regarding equity. Using data from three comprehensive, population-level health care databases, namely: 1) the BC PharmaNet; 2) the British Columbia Linked Health Database (BCLHD); and 3) Fair Pharmacare registration files, Ms. Hanley is investigating the degree of income-related inequity in medicine use before and after the BC policy change in the general population, and in specific subpopulations (e.g., drug use after myocardial infarction). The analysis of specific subpopulations will allow for evaluation of the use of essential medicines and of medications known to be safe and effective. Further, it will enable greater needs standardization. Additionally, she is evaluating the redistributive effect of the policy change on income distribution in BC, specifically focusing on determining inequity in pharmaceutical financing among individuals of equivalent incomes. Taken overall, the results of the project will provide timely and relevant evidence to federal and provincial policy makers, as well as all Canadians, when Pharmacare reform is increasingly on the policy agenda.

Mind Wandering in Individuals with Schizotypal Personality Traits

Disruption of attention is a hallmark symptom of schizophrenia, and it has been shown that people with schizophrenia exhibit reduced levels of sensitivity in processing external stimuli. However, it has also been suggested that healthy individuals do not process external stimuli when they are ‘mind wandering’ to the extent that they normally would when they are paying attention to the task-at hand. That schizophrenia and mind wandering both involve reduced sensitivity to ongoing events in the external world suggests they may be closely related. Therefore, it is possible that the processing deficits associated with schizophrenia are related to levels of mind wandering. Julia Kam is investigating mind wandering states in healthy individuals who may be vulnerable to developing schizophrenia with the purpose of determining whether abnormal levels of mind wandering are consistently evident across the entire spectrum of disorders in which schizophrenia is present. A key implication of this study is that varying levels of mind wandering and the brain wave counterparts observed in the general population may be considered as indicators for the potential development of schizophrenia. Given that schizophrenia has a strong genetic component, these ‘indicators’ may serve to identify healthy individuals, especially relatives of patients with schizophrenia, who are themselves at higher risk for developing the disorder. This is an important first step in implementing preventive interventions for such high-risk individuals. Once identified, persons considered at-risk may then benefit substantially from programs that highlight protective factors and increase awareness of risk factors, all of which are intended to prevent the development of schizophrenia.

Sensory contributions to motor deficits after stroke: What is the role of the unaffected cortex in motor recovery?

Sensorimotor deficits after stroke are commonly associated with increased activation in a number of cortical areas in the non-affected hemisphere, including primary motor and sensory cortex. Constraining the unaffected arm in individuals with stroke stimulates recovery in the use of the stroke affected arm, perhaps by reestablishing the balance of excitability between affected and non-affected cortices controlling each arm. However, the specific physiological mechanisms that follow decreasing unaffected arm use are not completely understood. Immobilization of the unaffected limb in stroke patients, by ischemia or anesthetic numbing, results in transient increases in motor function of the hemiparetic upper limb. The benefit of peripheral numbing may work through decreased proprioceptive and tactile inputs to sensory cortex which in turn diminish the overall excitability of the contralesional motor areas; the net result is a reduction in transcallosal inhibition on the affected cortex. However, beyond these preliminary findings, the role of the unaffected sensory cortex in movement deficits after stroke remains largely uncharacterized. Dr. Sean Meehan is investigating whether reducing the efficacy of proprioceptive and tactile inputs from the non-affected hand at the level of sensory cortex using continuous theta burst (cTBS), a variant of transcranial magnetic stimulation (TMS), can result not only in transient improvements in motor performance in the hemiparetic arm but also longer lasting functional changes associated with motor learning. The results of Dr. Meehan’s research may encourage rehabilitative strategies that target both the sensory and motor causes of movement deficits. The addition of sensory specific rehabilitative techniques may allow for even greater increases in function than are currently possible in individuals in the chronic phase of stroke. This line of research offers a promising new avenue for advances in the conceptualization of stroke rehabilitation.

An Innovative Approach to Providing Patient Care: Examining the Role of the Nurse Practitioner in Primary Care Group Medical Visits

As the Canadian population ages, primary health care has increased its focus on the prevention and management of chronic disease in the elderly. However, access to primary care providers such as family doctors has become more difficult in recent years. Consequently, nurse practitioners (NPs) are increasingly delivering primary health services for people with chronic disease through what’s called the group medical visit (GMV). GMVs are a model of care delivery in which primary care is offered in a group format, instead of single patient/provider format. GMVs are being implemented across BC as part of the practice support program aimed at improving the primary health care system in the province. Past work indicates that patients and providers of GMVs are satisfied with GMVs. However, research on their effectiveness is limited. Laura Housden is examining the role of NPs in providing GMVs in BC and whether or not the GMV format is associated with quality patient care, such as patient self management of disease and chronic disease health indicators. To that end, she is conducting in-depth interviews with NPs currently providing GMVs. Direct observation of GMVs will be undertaken to better understand the process of the visit and context of the appointments. Chart audits will also be done to determine quality of care. The results of Ms. Housden’s research will provide a greater understanding of the role of NPs in providing GMVs, as well as the effectiveness of this care model in reaching and caring for people with chronic illnesses. Ultimately, this information could help to inform public health policy in BC.

Seasonal plasticity in brain estrogen signaling mechanisms regulating aggression

While estradiol, a kind of estrogen, is often considered a “”female”” hormone, it is fundamentally important for both female and male brain function. It is a hormone with a wide range of effects on the brain and human behaviour. In early life, estradiol plays an important role in the growth of brain cells and in the establishment of differences between male and female brains. In adulthood, estradiol activates both male and female reproductive behaviour. Studies also implicate estradiol in the regulation of aggression, learning and memory, muscle control and the perception of pain. Furthermore, estradiol has been shown to influence depression, recovery from stroke and brain injury, Parkinson’s disease and Alzheimer’s disease. Because estradiol is involved in a vast array of brain functions, many of which are critical to human health, it is important to understand how estradiol affects brain cells. Dr. Sarah Heimovics’ research explores the degree to which there is plasticity in how estradiol affects the brain and behaviour. Specifically, she is investigating the effect of environmental factors, such as photoperiod, on estradiol signalling mechanisms the brain. Traditionally, estradiol has been understood to influence brain and behaviour genomically, via changes in gene expression over a relatively long timescale (days to weeks). However, a growing body of research suggestes that estradiol also has rapid (within 30 minutes), non-genomic effects. Dr. Heimovics will compare the role of genomic and non-genomic estradiol signalling mechanisms in the neural regulation of aggressive behaviour on short and long photoperiods. She is testing the hypothesis that non-genomic estradiol signalling is more pronounced on short photoperiod (as during the winter in BC), which may have implications relative to depression. The results of this research will contribute to the greater understanding of how estradiol acts on the brain, which is a critical issue for the health of British Columbians.

The role of microbiota in susceptibility to inflammatory bowel disease.

The cause of inflammatory bowel disease (IBD), including intestinal disorders characterized by chronic inflammation such as Crohn’s disease and ulcerative colitis, remains unclear. However, changes in the microbiota have been linked to IBD, including Crohn's disease and ulcerative colitis, as significant differences exist between the microbiota of IBD patients and healthy individuals. As western societies have developed, improvements in health and hygiene have altered human-microbe interactions through increased sanitation, antibiotic usage and vaccination. Concordantly, epidemiological studies have shown an alarming increase in the occurrence of immune mediated disorders, such as IBD. However, whether a change in microbiota composition precedes and contributes to onset of IBD or is a result of IBD remains to be determined. Marta Wlodarska and colleagues have previously shown that clinical levels of antibiotics will cause a shift in, but not complete ablation of the microbiota which results in a differential disease outcome by Salmonella Typhimurium infection. Her current research project expands on this work by investigating how antibiotic-induced fluctuations of the microbiota disrupt the homeostatic state of the intestinal immune system, potentially leading to increased susceptibility to IBD. Specifically, she is using clinical levels of antibiotics to shift the composition of the microbiota and evaluate how that affects the outcome and severity of C.rodentium-induced colitis. Additionally, her research should also provide an understanding of how changes in microbiota composition affect the homeostatic state of the mucosal immune system through intestinal epithelial cell-mediated cytokine secretion. Collectively, her work will increase the understanding of the interplay between the microbiota and immune responses as well as any associated impact on colitis. These issues are central to increasing our understanding of IBD in general, and may lead to the development of new diagnostic and therapeutic tools.