Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting anticancer T-cell immunity. We show that Smac-mimetic compound and oncolytic virus therapies synergize in driving CD8+ T-cell responses toward tumors through distinct activities. Smac-mimetic compound treatment with LCL161 reinvigorates exhausted CD8+ T cells within immunosuppressed tumors by targeting tumor-associated macrophages for M1-like polarization. Oncolytic virus treatment with vesicular stomatitis virus (VSVΔM51) promotes CD8+ T-cell accumulation within tumors and CD8+ T-cell activation within the tumor-draining lymph node. When combined, LCL161 and VSVΔM51 therapy engenders CD8+ T-cell-mediated tumor control in several aggressive mouse models of cancer. Smac-mimetic compound and oncolytic virus therapies are both in clinical development and their combination therapy represents a promising approach for promoting anticancer T-cell immunity.
Essential workers, those who work in a variety of sectors that are critical to sustain the societal infrastructure, were affected both physically and mentally by the COVID-19 pandemic. While the most studied group of this population were healthcare workers, other essential non-health workers such as those working in the law enforcement sector, grocery services, food services, delivery services, and other sectors were studied less commonly. We explored both the academic (using MEDLINE, PsycInfo, CINAHL, Sociological Abstracts, and Web of Science databases) and grey literature (using Google Scholar) to identify studies on the mental health effects of the six pandemics in the last 20 years (2000–2020). We identified a total of 32 articles; all of them pertained to COVID-19 except for one about Ebola. We found there was an increase in depression, anxiety, stress, and other mental health issues among non-health essential workers. They were more worried about passing the infection on to their loved ones and often did not have adequate training, supply of personal protective equipment, and support to cope with the effects. Generally, women, people having lower education, and younger people were more likely to be affected by a pandemic. Exploring occupation-specific coping strategies of those whose mental health was affected during a pandemic using more robust methodologies such as longitudinal studies and in-depth qualitative exploration would help facilitate appropriate responses for their recovery.
Objectives Canadian regulations have made it challenging for the international medical graduates (IMGs) to get jobs in their original profession as physicians. Consequently, alternative careers are gaining interest among IMGs to avoid underemployment or unemployment. We conducted research to identify the factors that IMGs consider for taking up an alternative career in Canada. Based on those understandings, we aimed to create a database where information about health-related alternative jobs is presented in a searchable way, which can aid IMGs’ strategic job search. Data description We first determined job searching preferences and constraints for IMGs regarding alternative career through focus groups. We used their preferred and constraining factors for collecting job-specific information through systematically reviewing job advertisements. Using this information, we created a database that contains available alternative career pathways for IMGs living in Canada. In total, we have identified 1374 job titles under 192 unique job categories comprising 47 National Occupational Classification (NOC) codes that could be suitable for IMGs seeking an alternative career based on their own short, intermediate, and long-term career goals. We expect that this database will help IMGs in deciding on alternative careers.
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