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A Physical Interaction between the Dopamine Transporter and DJ-1 Facilitates Increased Dopamine Reuptake

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2015
Abstract: 

The regulation of the dopamine transporter (DAT) impacts extracellular dopamine levels after release from dopaminergic neurons. Furthermore, a variety of protein partners have been identified that can interact with and modulate DAT function. In this study we show that DJ-1 can potentially modulate DAT function. Co-expression of DAT and DJ-1 in HEK-293T cells leads to an increase in [3H] dopamine uptake that does not appear to be mediated by increased total DAT expression but rather through an increase in DAT cell surface localization. In addition, through a series of GST affinity purifications and co-immunoprecipitations, we provide evidence that the DAT can be found in a complex with DJ-1, which involve distinct regions within both DAT and DJ-1. Using in vitro binding experiments we also show that this complex can be formed in part by a direct interaction between DAT and DJ-1. Co-expression of a mini-gene that can disrupt the DAT/DJ-1 complex appears to block the increase in [3H] dopamine uptake by DJ-1. Mutations in DJ-1 have been linked to familial forms of Parkinson’s disease, yet the normal physiological function of DJ-1 remains unclear. Our study suggests that DJ-1 may also play a role in regulating dopamine levels by modifying DAT activity.

Document type: 
Article
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Randomized Controlled Trials in Environmental Health Research: Unethical or Underutilized?

Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2015
Document type: 
Article
File(s): 

Probing Mechanical Properties of Jurkat Cells under the Effect of ART Using Oscillating Optical Tweezers

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2015
Abstract: 

Acute lymphoid leukemia is a common type of blood cancer and chemotherapy is the initial treatment of choice. Quantifying the effect of a chemotherapeutic drug at the cellular level plays an important role in the process of the treatment. In this study, an oscillating optical tweezer was employed to characterize the frequency-dependent mechanical properties of Jurkat cells exposed to the chemotherapeutic agent, artesunate (ART). A motion equation for a bead bound to a cell was applied to describe the mechanical characteristics of the cell cytoskeleton. By comparing between the modeling results and experimental results from the optical tweezer, the stiffness and viscosity of the Jurkat cells before and after the ART treatment were obtained. The results demonstrate a weak power-law dependency of cell stiffness with frequency. Furthermore, the stiffness and viscosity were increased after the treatment. Therefore, the cytoskeleton cell stiffness as the well as power-law coefficient can provide a useful insight into the chemo-mechanical relationship of drug treated cancer cells and may serve as another tool for evaluating therapeutic performance quantitatively.

Document type: 
Article
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Gaps in the Hepatitis C Continuum of Care among Sex Workers in Vancouver, British Columbia: Implications for Voluntary Hepatitis C Virus Testing, Treatment and Care

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2015
Abstract: 

BACKGROUND: Hepatitis C virus (HCV) eradication leads to reduced morbidity, mortality and transmission. Despite the disproportionate burden of HCV among sex workers, data regarding the HCV care continuum in this population remain negligible. METHODS: Using baseline data from an ongoing cohort of women sex workers in Vancouver (An Evaluation of Sex Workers’ Health Access, January 2010 to August 2013), the authors assessed HCV prevalence and engagement in the HCV care continuum within the past year. Multivariable logistic regression analyses were used to evaluate associations with recent (ie, in the past year) HCV testing. RESULTS: Among 705 sex workers, 302 (42.8%) were HCV seropositive. Of these, 22.5% were previously unaware of their HCV status, 41.7% had accessed HCV-related care, 13.9% were offered treatment and only 1.0% received treatment. Among 552 HCV-seronegative sex workers, only one-half (52.9%) reported a recent HCV test. In multivariable analysis, women who self-identified as a sexual/gender minority (adjusted OR [aOR] 1.89 [95% CI 1.11 to 3.24]), resided in the inner city drug use epicentre (aOR 3.19 [95%CI 1.78 to 5.73]) and used injection (aOR 2.00 [95% CI 1.19 to 3.34]) or noninjection drugs (aOR 1.95 [95% CI 1.00 to 3.78]) had increased odds of undergoing a recent HCV test, while immigrant participants (aOR 0.24 [95% CI 0.12 to 0.48]) had decreased odds. CONCLUSIONS: Despite a high burden of HCV among sex workers, large gaps in the HCV care continuum remain. Particularly concerning are the low access to HCV testing, with one-fifth of women living with HCV being previously unaware of their status, and the exceptionally low prevalence of HCV treatment. There is a critical need for further research to better understand and address barriers to engage in the HCV continuum for sex workers.

Document type: 
Article
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Knowledge and Perceptions of Latent Tuberculosis Infection among Chinese Immigrants in a Canadian Urban Centre

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2015
Abstract: 

Background. Since most tuberculosis (TB) cases in immigrants to British Columbia (BC), Canada, develop from latent TB infection (LTBI), treating immigrants for LTBI can contribute to the eradication of TB. However, adherence to LTBI treatment is a challenge that is influenced by knowledge and perceptions. This research explores Chinese immigrants' knowledge and perceptions towards LTBI in Greater Vancouver. Methods. This mixed methods study included a cross-sectional patient survey at BC's Provincial TB clinics and two focus group discussions (FGDs) with Chinese immigrants. Data from FGDs were coded and analyzed in Simplified Chinese. Codes, themes, and selected quotes were then translated into English. Results. The survey identified a mean basic knowledge score: 40.0% (95% CI: 38.3%, 41.7%). FGDs confirmed that Chinese immigrants' knowledge of LTBI was low, and they confused it with TB disease to the extent of experiencing LTBI associated stigma. Participants also expressed difficulties navigating the health system which impeded testing and treatment of LTBI. Online videos were the preferred format for receiving health information. Conclusion. We identified striking gaps in knowledge surrounding an LTBI diagnosis. Concerns of stigma may influence acceptance and adherence of LTBI treatment in Chinese immigrants. Integrating these findings into routine health care is recommended.

Document type: 
Article
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Climate Change and the New Normal for Cardiorespiratory Disease

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2015
Abstract: 

Climate change is already affecting the cardiorespiratory health of populations around the world, and these impacts are expected to increase. The present overview serves as a primer for respirologists who are concerned about how these profound environmental changes may affect their patients. The authors consider recent peer-reviewed literature with a focus on climate interactions with air pollution. They do not discuss in detail cardiorespiratory health effects for which the potential link to climate change is poorly understood. For example, pneumonia and influenza, which affect >500 million people per year, are not addressed, although clear seasonal variation suggests climate-related effects. Additionally, large global health impacts in low-resource countries, including migration precipitated by environmental change, are omitted. The major cardiorespiratory health impacts addressed are due to heat, air pollution and wildfires, shifts in allergens and infectious diseases along with respiratory impacts from flooding. Personal and societal choices about carbon use and fossil energy infrastructure should be informed by their impacts on health, and respirologists can play an important role in this discussion.

Document type: 
Article
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Prelude to a Systematic Review of Activity-based Funding of Hospitals: Potential Effects on Cost, Quality, Access, Efficiency, and Equity

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2013-10
Abstract: 

Until recently, hospital funding in Canada has been based predominantly on global budgets, but health care system decision-makers throughout the country are now seriously considering an alternative funding model referred to as activity-based funding (ABF). Under this system, hospital services are classified prospectively into clinically meaningful "bundles" of care that use similar levels of resources. Opinion is divided as to whether ABF would help the Canadian health care system to achieve any of the putative benefits originally achieved by ABF in other countries, or whether the risks would outweigh the benefits. As yet, there has been no systematic review of the evidence. In March 2012 our research team launched a systematic review to inform Canadian policy-makers about how this funding model affects health care systems around the world. Of the more than 16 000 potentially eligible titles and abstracts screened, 261 studies, representing 64 countries (either singly or in aggregate), provide data on at least one of the cost, quality, access, efficiency, and equity outcomes of interest to our research team. We are now in the process of analyzing data from the eligible studies most germane to the Canadian context. This commentary is intended to alert decision-makers to the upcoming release of a series of papers based on our systematic review of ABF, in the hope that our synthesis will soon provide a more robust evidence base to better inform decision-makers.

Document type: 
Article
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High Levels of Heterogeneity in the HIV Cascade of Care across Different Population Subgroups in British Columbia, Canada

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-12-26
Abstract: 

Background

The HIV cascade of care (cascade) is a comprehensive tool which identifies attrition along the HIV care continuum. We executed analyses to explicate heterogeneity in the cascade across key strata, as well as identify predictors of attrition across stages of the cascade.

Methods

Using linked individual-level data for the population of HIV-positive individuals in BC, we considered the 2011 calendar year, including individuals diagnosed at least 6 months prior, and excluding individuals that died or were lost to follow-up before January 1st, 2011. We defined five stages in the cascade framework: HIV ‘diagnosed’, ‘linked’ to care, ‘retained’ in care, ‘on HAART’ and virologically ‘suppressed’. We stratified the cascade by sex, age, risk category, and regional health authority. Finally, multiple logistic regression models were built to predict attrition across each stage of the cascade, adjusting for stratification variables.

Results

We identified 7621 HIV diagnosed individuals during the study period; 80% were male and 5% were <30, 17% 30–39, 37% 40–49 and 40% were ≥50 years. Of these, 32% were MSM, 28% IDU, 8% MSM/IDU, 12% heterosexual, and 20% other. Overall, 85% of individuals ‘on HAART’ were ‘suppressed’; however, this proportion ranged from 60%–93% in our various stratifications. Most individuals, in all subgroups, were lost between the stages: ‘linked’ to ‘retained’ and ‘on HAART’ to ‘suppressed’. Subgroups with the highest attrition between these stages included females and individuals <30 years (regardless of transmission risk group). IDUs experienced the greatest attrition of all subgroups. Logistic regression results found extensive statistically significant heterogeneity in attrition across the cascade between subgroups and regional health authorities.

Conclusions

We found that extensive heterogeneity in attrition existed across subgroups and regional health authorities along the HIV cascade of care in B.C., Canada. Our results provide critical information to optimize engagement in care and health service delivery.

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Article
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The Role of Hormones in the Differences in the Incidence of Breast Cancer between Mongolia and the United Kingdom

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-12-23
Abstract: 

Background

There are striking differences in breast cancer incidence between Asian and western women. Rates vary substantially within Asia also, with Mongolia's even lower than China's. These profound differences have been speculated to be due in part to diet, mediated by circulating hormone concentrations.

Methods

Sex steroid hormone concentrations were measured in women living in Ulaanbaatar, Mongolia and the United Kingdom (U.K.). Diet was obtained by interview and national survey data. Mean hormone differences were compared by country, and systematic variation by number of days since last menstrual period was modeled and adjusted for age and parity; difference in overall area under the curves was assessed.

Findings

The diet in Mongolia was higher in meat and dairy than in the U.K. Mean testosterone concentrations were 18.5% lower (p<0.0001) while estradiol concentrations were 19.1% higher (p = 0.02) in Mongolian than British women, adjusted for age and parity. Progesterone was almost 50% higher in Mongolian women (p = 0.04), particularly during the follicular phase and early luteal surge. Hormone concentrations generally were similar in Mongolian women born in Ulaanbaatar compared with those born in rural areas, although there was a decreasing progesterone trend by degree of westernization (rural Mongolia; urban Mongolia; U.K.). Mean hormone differences were similar when restricted to parous women, and with further adjustment for body mass index, height, and smoking status.

Interpretation

These data augment accumulating evidence that circulating estrogens are unlikely to explain reduced breast cancer rates in Asia compared with the west, and suggest casting a wider net with respect to biomarkers. Lower testosterone and higher progesterone in Mongolian women raise the possibility that these hormones may be important to consider. In addition, the almost exclusive dietary reliance of Mongolians on meat and dairy argues against beneficial effects of a low-fat diet on circulating hormones explaining international breast cancer differences.

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Article
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A Novel Method to Evaluate the Community Built Environment Using Photographs – Environmental Profile of a Community Health (EPOCH) Photo Neighbourhood Evaluation Tool

Peer reviewed: 
Yes, item is peer reviewed.
Date created: 
2014-11-04
Abstract: 

Background

Previous research has shown that environments with features that encourage walking are associated with increased physical activity. Existing methods to assess the built environment using geographical information systems (GIS) data, direct audit or large surveys of the residents face constraints, such as data availability and comparability, when used to study communities in countries in diverse parts of the world. The aim of this study was to develop a method to evaluate features of the built environment of communities using a standard set of photos. In this report we describe the method of photo collection, photo analysis instrument development and inter-rater reliability of the instrument.

Methods/Principal Findings

A minimum of 5 photos were taken per community in 86 communities in 5 countries according to a standard set of instructions from a designated central point of each community by researchers at each site. A standard pro forma derived from reviewing existing instruments to assess the built environment was developed and used to score the characteristics of each community. Photo sets from each community were assessed independently by three observers in the central research office according to the pro forma and the inter-rater reliability was compared by intra-class correlation (ICC). Overall 87% (53 of 60) items had an ICC of ≥0.70, 7% (4 of 60) had an ICC between 0.60 and 0.70 and 5% (3 of 60) items had an ICC ≤0.50.

Conclusions/Significance

Analysis of photos using a standardized protocol as described in this study offers a means to obtain reliable and reproducible information on the built environment in communities in very diverse locations around the world. The collection of the photographic data required minimal training and the analysis demonstrated high reliability for the majority of items of interest.

Document type: 
Article
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