Children with attention-deficit/hyperactivity disorder (ADHD) have trouble sustaining attention and may also display excessive hyperactivity and impulsivity. A major day-to-day impairment for children with ADHD is in their social relationships with peers. In this area, children with ADHD frequently struggle, and have trouble making and keeping friends as a result. It is important to address these issues early, as social problems increase children’s risk for many negative outcomes including academic failure, aggression and delinquency, substance abuse, and depression and suicide.
Research suggests that difficulties with executive functions (e.g., attention, self-control, working memory, organization and planning) are a key part of ADHD. However, it is not yet clear how executive functioning difficulties may affect the problems children with ADHD face in their daily life, such as peer relationships.
Dr. Hudec will explore how executive functions relate to social skills and the ability to make and keep friends in children with ADHD. This will lead to a better understanding of the social problems affecting children with ADHD.
Importantly, symptoms of ADHD frequently occur within families, so parents of children with ADHD are more likely to experience ADHD themselves, and to be at risk for poor executive functioning themselves. Dr. Hudec will also examine how parental executive functioning may affect parents’ ability to implement behavioural interventions.
Understanding how executive functioning in both children and adults affects children’s social problems may help improve available clinical treatments for children with ADHD and will guide development of therapeutic activities that can be adapted to parents’ strengths and weaknesses. Dr. Hudec’s findings will be shared through family-based interventions and community-based education sessions, as well as professional presentations and publications that will inform practice by researchers and clinicians.
Spinal cord injury (SCI) resulting from traumatic accidents is one of the most debilitating chronic conditions. In addition to the toll on quality of life, lifetime health care expenditures for these patients are among the most expensive of any medical condition, since many injuries occur in young patients who live with SCI for decades. SCI also comes with steep indirect costs, including morbidity due to chronic complications.
In individuals with SCI, bladder dysfunction and episodes of high blood pressure are two chronic conditions that present as significant clinical problems. Bladder dysfunction is commonly associated with a sudden, life threatening increase in blood pressure known as autonomic dysreflexia (AD). This episodic hypertension cannot be addressed with typical treatments, and if misdiagnosed or poorly managed can lead to myocardial infarction, stroke, and even death. Bladder dysfunctions and irritation such as a urinary tract infection are leading triggers for AD.
It is suspected that chronic exposure to AD episodes results in cerebrovascular damage in those with SCI. Chronically elevated blood pressure negatively impacts the brain and is specifically associated with cerebrovascular decline, altered brain morphology, cognitive dysfunctions and stroke in able-bodied individuals. However, identical pathologies are present in those with SCI.
Dr. Walter will investigate whether treating bladder dysfunction in patients with SCI will decrease possible triggers for episodes of AD, ameliorate its symptoms and consequently reduce chronic cardiovascular complications. Reducing the chronic cardio- and cerebrovascular complications of SCI would dramatically improve the health and wellbeing of patients with SCI and positively impact health care costs.
Heart failure (HF) is a progressive condition wherein the heart is unable to fill its chambers and/or pump sufficient blood into the arteries. While there are many causes of HF, it usually presents in two major forms: HF with preserved ejection fraction (HFpEF; ‘stiff’ heart), and HF with reduced ejection fraction (HFrEF; ‘baggy’ or ‘weak’ heart).
A key challenge in HF diagnosis is that, while the causes of HFpEF and HFrEF differ, their clinical presentation is often the same. As a routine echocardiogram in HFpEF can appear normal, the diagnosis can be overlooked and delayed. In clinical practice, the diagnosis of HF is often made late, at which time evidence-based treatments or other lifestyle strategies may have less benefit for those with HFrEF. At the same time, many HFpEF patients are being treated with drugs that provide no proven benefit.
Dr. Singh will investigate novel, non-invasive diagnostic approaches that can identify patients with HFpEF versus HFrEF at an early stage of disease. The results of this research will include innovative methods for data integration and biomarker discovery, which will improve biological insights into the mechanisms of HF. Identifying the form of HF earlier on will allow clinicians to develop and tailor diagnostic and therapeutic approaches, and use a firm diagnosis as a tool to encourage lifestyle changes.
Diagnosis of HFpEF versus HFrEF will ensure that the most appropriate additional tests and treatments can be provided for each patient in a timely fashion, improving disease management and patient quality of life.
Type 2 diabetes (T2D) is a chronic disease with serious health implications (e.g., cardiovascular disease) that can be prevented with lifestyle changes. Lifestyle-based interventions are particularly needed in the community to help reduce the incidence of chronic disease in Canadian adults, and are critical for preventing T2D.
For example, the Diabetes Prevention Program (DPP) is a lifestyle change program that promotes healthy eating and physical activity. This program translates to a 58% risk reduction for developing T2D for individuals who maintain 150 min/week of moderate physical activity and lose 7% of their body weight. However, the DPP is less sustainable in community settings because it is costly and lengthy (~12 months long). Diabetes prevention programs are needed that can be implemented and scaled up in the community for adults at high risk of developing T2D.
Towards the pursuit of preventing T2D with brief-behavioural interventions, the Health and Exercise Psychology Laboratory at UBC Okanagan developed a diabetes prevention program called Small Steps for Big Changes, which has proven effective in enhancing health outcomes of low-active adults at risk for diabetes and, excitingly, demonstrates long-term physical activity adherence.
Given the promising findings, knowledge translation research is needed to ensure successful research uptake of Small Steps for Big Changes into the community. The aim of Dr. Ivanova’s research will be to translate this evidence-based exercise intervention for use in the community with adults who are at risk for T2D.
Small Steps for Big Changes will be implemented in a YMCA centre (Kelowna, BC) to ensure that this evidence-based program is integrated in a sustainable manner and that it adequately serves the community. The Knowledge-to-Action (KtA) framework will be used to guide this knowledge translation effort, and the results of this research will be the development of knowledge products, namely manuals for Small Steps for Big Changes, a two-day train-the-trainer workshop, and audiovisual training materials that will be used to train the knowledge users how to deliver Small Steps for Big Changes.
Dr. Ivanova will co-lead the sharing of these results, alongside research end users, guiding the path for sustained use of Small Steps for Big Changes at the YMCA and for feasible continued scale-up.
Dr. Vila-Rodriguez's research will work towards improving diagnostic accuracy and treatment outcomes in persons suffering treatment-resistant depression (TRD). By incorporating neurophysiological-based biomarkers (NPBs) into clinical practice, treatment response can be more easily predicted, preventing relapse in patients with major depressive disorder. This program of research focuses on the use of repetitive transcranial magnetic stimulation (rTMS), a non-invasive neurostimulation therapy recommended by the Canadian Network for Mood and Anxiety Treatments (CANMAT) as a first-line treatment option for TRD.
This research encompasses the Canadian rTMS Treatment and Biomarker Network in Depression (CARTBIND) trial, an ongoing randomized clinical trial that aims to identify relevant NPBs and uses rTMS to treat TRD. Participants in this trial undergo resting-state electroencephalographic and resting-state functional magnetic resonance imaging before and after rTMS treatment to ascertain which neurophysiological features are good predictors of treatment response. Based on this data Dr. Vila-Rodriguez will develop and test a treatment response classifier and relapse prediction classifier.
The aim of this research is to transform how clinicians prescribe rTMS and how they monitor the treatment course and maintenance by incorporating reliable and robust biomarkers. This approach will optimize treatment efficiency by increasing the response rates for TRD and reducing treatment failure, thereby improving the health of British Columbians who struggle with depression and decreasing costs to the health care system.
Dr. Vila-Rodriguez's knowledge translation model involves the regular use of both the lab website as well as the Twitter account to engage his research audience in research activities to keep them up-to-date on new findings, as well as to facilitate self-learning via educational materials.
The rising incidence of type 2 diabetes (T2D) puts financial stress on health care systems in British Columbia and across the world. Lifestyle interventions can improve cardiometabolic health to prevent or treat T2D, but optimal lifestyle strategies (e.g. exercise intensity, type, timing; diet composition) are not well-defined and adherence is notoriously poor.
The goals of Dr. Little's research are to optimize lifestyle interventions for improving cardiometabolic outcomes and uncover potential mechanisms underlying these health benefits. The research program aims to improve cardiometabolic health and reduce inflammation via a series of translational studies to define the optimal exercise and diet strategies and uncover cellular mechanisms underlying the benefits. To translate findings for true health impact, YMCA has partnered to implement an HIIT walking intervention in the community. In addition, a randomized controlled trial will be implemented to evaluate the effectiveness of a pharmacist-led intervention, implemented through a network of 13 BC pharmacies, to teach patients with T2D how to follow a low-carb, high-fat (LCHF) diet while also reducing their medications. This has tremendous potential to change diabetes management in BC through an innovative pharmacist-led therapeutic nutrition program using LCHF diets.
The long-term goals of this research will be to develop optimal evidence-based exercise and diet interventions that improve patient health and inform clinical practice guidelines for the prevention and treatment of T2D. Elucidation of the cellular and molecular mechanisms underlying the anti-inflammatory effects of exercise and diet approaches will also be used to define the best anti-inflammatory lifestyle interventions, and identify potential therapeutic targets for prevention and treatment of T2D.
Previous research by Dr. Foster has illustrated that angiotensin receptor blockade can abolish the blood pressure response to intermittent hypoxia (IH), reduce oxidative stress and increase nitric oxide bioavailability. In addition, recent work suggests heightened peripheral neurovascular transduction in response to baroreflex activation.
Building on this work, over the next 5 years Dr. Foster will focus on the cardiovascular consequences of IH associated with obstructive sleep apnea (OSA). Since OSA and IH directly contribute to the morbidity and mortality of hypertension, myocardial infarction and stroke, there is an urgent need to establish a treatment capable of protecting OSA patients from IH-induced cardiovascular disease (CVD).
Dr. Foster's research will elucidate the mechanisms by which AT1R antagonists or statins could protect OSA patients from IH-induced CVD. By breaking the link between CVD and OSA, and capitalizing on the pleiotropic properties of angiotensin receptor blockers and statins, this research is ultimately intended to generate a novel treatment. This knowledge will provide the necessary proof of concept for large-scale clinical trials, and will help reduce stress on health care infrastructure and improve the health, quality of life and longevity of Canadians.
Cardiovascular disease (CVD) is the leading cause of death of Canadians, and is strongly influenced by genetic factors. Integrating basic biomedical research into how specific gene variants influence the function of cardiac cells, with clinical research of patients and families with early onset CVD, will lead to important advances in translating the results of genetics research to improved care for patients and families with CVD.
Empty Nose Syndrome (ENS) is thought to be an unusual outcome of sinus surgery due to excessive loss of nasal tissues, particularly from a pair of structures called the inferior turbinates. Turbinates usually function to warm and humidify air flowing into the nose. Patients with ENS often have severe nasal symptoms and develop very poor quality of life as well as mental health problems. As a result of these mixed symptoms, ENS patients are often misdiagnosed, mismanaged, and left to their own devices.
Our research has shown that ENS patients can be identified based on specific clinical symptoms and imaging of the sinuses. We have also found that by rebuilding structures within the nasal cavity known as inferior turbinate augmentation (ITA) we can greatly improve nasal function. However, little is known about the specific changes in nasal function with ENS, how mental health problems develop, or how to best treat these patients.
Our objectives are three-fold: 1) to measure the patterns of nasal airflow and sense of smell present in ENS patients by using computer analysis and smell testing; 2) to understand how ITA might improve function in ENS patients by measuring nasal airflow and sense of smell before and after surgery; and 3) to study the impact of ENS on mental health using depression and anxiety survey scores, and then measure the change in these scores after ITA to study the relationship between the nasal and mental health problems in ENS. By studying the relationship between nasal and psychiatric symptoms in ENS we will both improve our understanding of how this syndrome develops and improve our understanding of how surgical interventions might help mend these symptoms.
Patients with human immunodeficiency virus (HIV) are now living to older ages thanks to effective anti-HIV medicines. Despite these gains, many of them suffer from chronic lung disease that greatly impacts their ability to carry out their daily activities and impairs their quality of life. The type of lung disease they face is similar to what longtime smokers develop, a progressive narrowing of the airways and destruction of the lung. However, in HIV, the process appears to be accelerated and more severe. It’s not unusual, for instance, to see patients in their 30s and 40s develop this lung disease (which is approximately 30-40 years earlier than expected). Also, it’s not unusual for HIV patients who have never smoked before to develop this kind of disease. Unfortunately, the traditional medications we use to treat lung disease often interact with anti-HIV medicines, causing severe side effects. Management of breathing symptoms in HIV patients is therefore difficult and it is imperative that we find better agents to combat lung disease in this population. Only by understanding what causes and drives this lung injury process can this goal be achieved, though.
Multiple studies have now shown that smoking alone cannot explain the lung disease phenomenon in HIV. I believe that HIV injures the lung in a two phase process. First, the virus directly breaks down the protective layer of the airway known as the epithelium. Second, over time, as patients develop repeated lung infections due to their weakened immune systems, the bacterial community of the lung or microbiome shifts. I believe that this community disruption results in molecular changes that age the lung faster. My approach is to perform an in-depth investigation into the epithelium of the airway using two innovative methods. To explore the injury that HIV inflicts on the airway, I have created a novel model of the HIV airway using HIV-infected cells co-cultured on a cell culture model of the airway epithelium. We will use this model to see how HIV-infected cells break down the protective barrier of the lung. To explore the shifts in the microbiome, I have collected airway cells from HIV-infected and uninfected patients to not just describe what bacteria exist in the airway but also to determine what effect the community differences between the two groups have on the function of genes in the cells. We will measure how ‘old’ these cells are and compare these findings to uninfected patients.
End of Award Update: December 2022
Most exciting outputs
The work of my laboratory was the first to detect accelerated epigenetic aging and methylation disruptions in the HIV airway epithelium, work that has now been published in the American Journal of Respiratory and Critical Care Medicine, and eBioMedicine.
Impacts so far
These insights into accelerated aging in the HIV airway epithelium provide clues into why people living with HIV may be prone to developing chronic lung diseases such as Chronic Obstructive Pulmonary Disease or COPD.
Potential future influence
Our work highlights the importance of accelerated aging in HIV, even in patients with well controlled infection. Reversing these aging mechanisms may be critical in the prevention or attenuation of airflow obstruction in this population.
Next steps
We are continuing to explore mechanisms of early aging in the HIV airway using novel technologies such as magnetic resonance imaging, optical coherence tomography, and single cell sequencing.
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