A familial form of Amyotrophic lateral sclerosis (ALS8) is caused by a point mutation (P56S) in the vesicle-associated membrane protein associated protein B (VapB). Human VapB and Drosophila Vap-33-1 (Vap) are homologous type II transmembrane proteins that are localized to the ER. However, the precise consequences of the defects associated with the P56S mutation in the endoplasmic reticulum (ER) and its role in the pathology of ALS are not well understood. Here we show that Vap is required for ER protein quality control (ERQC). Loss of Vap in flies shows various ERQC associated defects, including protein accumulation, ER expansion, and ER stress. We also show that wild type Vap, but not the ALS8 mutant Vap, interacts with a lipid-binding protein, Oxysterol binding protein (Osbp), and that Vap is required for the proper localization of Osbp to the ER. Restoring the expression of Osbp in the ER suppresses the defects associated with loss of Vap and the ALS8 mutant Vap. Hence, we propose that the ALS8 mutation impairs the interaction of Vap with Osbp, resulting in hypomorphic defects that might contribute to the pathology of ALS8.

British Columbia’s (BC) Take-Home Naloxone (THN) program provides naloxone to bystanders for use in cases of suspected opioid overdose. This study seeks to provide trends and analysis from the provincial BC THN program since inception in 2012 to the end of 2018. BC THN shipment and distribution records from 2012–2018 were retrieved. Frequency distributions were used to describe characteristics of individuals accessing the program. To evaluate correlates of distribution after the addition of hundreds of pharmacy distribution sites, an analytic sample was limited to records from 2018, and multivariate logistic regression was used to evaluate correlates of collecting naloxone at a pharmacy site. Since program inception to the end of 2018, there were 398,167 naloxone kits shipped to distribution sites, 149,999 kits reported distributed, and 40,903 kits reported used to reverse an overdose in BC. There was a significant increasing trend in the number of naloxone kits used to reverse an overdose over time (p<0.01), and more than 90% of kits that were reported used were distributed to persons at risk of an overdose. Individuals not personally at risk of overdose had higher odds of collecting naloxone at a pharmacy site, compared to other community sites (including harm reduction supply distribution sites, peer led organizations, drop-in centers, and supportive housing sites) (Adjusted Odds Ratio (AOR): 2.69; 95% CI: 2.50–2.90). This study documents thousands of opioid overdose reversals facilitated through the BC THN program. While those at highest risk of overdose may preferentially access naloxone through community sites, naloxone distribution through pharmacies has allowed the BC THN program to expand dramatically, increasing naloxone availability through longer opening hours on evenings and weekends. and in rural and remote regions. A diversity of naloxone distribution sites and strategies is crucial to prevent rising opioid overdose deaths.

Introduction: The literature suggests that differential colorectal cancer (CRC) screening adherence exists between Canada’s immigrant and nonimmigrant populations. This study explores the impact of Ontario’s population screening program, ColonCancerCheck, on CRC screening uptake in immigrant and nonimmigrant population groups.Methods: Data from 2005, 2007‐2008, and 2011‐2012 was obtained from the Canadian Community Health Survey, to represent the intervention periods (the time periods before, during, and after implementation of the ColonCancerCheck intervention). Multivariable logistic regression was used to examine the effect of immigration status on the risk of nonadherence to guideline‐recommended CRC screening, and an interaction analysis was performed to determine whether the screening differential between immigrant and nonimmigrant populations changed upon introduction of the ColonCancerCheck program.Results: Recent and long‐term immigrants were both at increased risk of CRC screening nonadherence compared to the Canadian‐born population (OR 3.73 (CI 2.25‐6.18) and OR 1.24 (CI 1.13‐1.36), respectively). While not statistically significant, there was an attenuation of the risk of nonadherence to screening for recent immigrants compared with Canadian‐born individuals after the implementation of the ColonCancerCheck program.Conclusions: This study provides evidence of a screening differential between immigrants and nonimmigrants, and suggests that the implementation of the ColonCancerCheck screening program in Ontario may have increased colon screening uptake amongst recent immigrants. Further studies are needed to address the factors leading to inequities in immigrant CRC screening adherence.

The rapidly increasing skin cancer rates in Canada are alarming, with current data estimating that 1/3 of Canadians will be affected in their lifetime. Thus, deeper understanding of high-risk sun exposure behaviors is needed to help counter this trend. Only limited action has been taken by federal/provincial governments to reduce skin cancer incidence. A cross-sectional survey study was conducted in Manitoba, with frequency counts, means, and percentages used to encapsulate responses. Age- and gender-adjusted odds ratios were calculated using logistic regression analyses. Our study identified worrying inadequacies in sun protective behaviors and attitudes, with the threat of such high-risk behaviors amplified by a lack of skin cancer awareness. Alarming elements were noted in participants’ sun exposure history (>65% reported a history of sunburns, >50% previously used a tanning bed, and >75% recently tanned for pleasure), beliefs and attitudes (>50% believe that they look better/healthier with a tan, and >40% believe that having a base tan is protective against further sun damage), and sun protection efforts (sun protective clothing was used <60% of the time, sunscreen was used by <50%, and there was a lack of knowledge about sunscreen characteristics in ~30% of respondents), in addition to significant differences being established between demographic subgroups (based on gender, age, skin phototype, income, and education attained). This study provides worrisome insight onto the grim landscape of sun protective behaviors and attitudes in Manitoba, which will inevitably translate into higher skin cancer rates and should serve as a call to action to promote targeted public health messaging in this jurisdiction and beyond.

Cutaneous melanoma (CM) is a significant contributor to skin cancer-related mortality globally and in Canada. Despite the well-established link between ultraviolet (UV) radiation exposure and skin cancer risk, there remains a gap in population-level interventions and persistent misconceptions about sun exposure and impact of environment on individual behavior. The current study provides an ecological analysis using latest available data (2011-2017) to define geographic/environmental contributors to the CM landscape in Canada. Utilizing Canadian Cancer Registry and Canadian Urban Environmental Health Research Consortium data, we analyzed 39,605 CM cases occurring in Canada from 2011 to 2017. Environmental data, including UV radiation, greenspace (normalized difference vegetation index), temperature, heat events, and precipitation was used to evaluate the effect of environment on CM incidence rates across Forward Sortation Area postal codes. Forward Sortation Areas with increased CM incidence were associated with higher annual average temperature, snowfall, heat events, normalized difference vegetation index, and vitamin D-weighted UV exposure. Conversely, factors associated with decreased incidence included an increased annual highest temperature, rain precipitation, and a longer duration of heat events. This study is subject to ecological bias and findings should be interpreted with caution. This study further substantiates associations between specific environmental factors and CM incidence.

Introduction: The mortality-to-incidence ratio (MIR) can be used to approximate healthcare inequities and is helpful to understand/compare cancer survival between geographic regions/jurisdictions. We investigated cutaneous melanoma (CM) outcomes through MIR analysis in Canadian jurisdictions and census divisions (CDs) between 1992 and 2016. Methods: Data were obtained from the national databases from 1992 to 2016 for all Canadian jurisdictions, except Quebec. Age-standardized overall and median MIRs were calculated per province per year, while crude MIRs were calculated for CDs. Generalized linear regression models were conducted to study the effect of province and year on MIR, while a mixed effect regression model was used to determine how healthcare and socioeconomic factors affect MIR, while accounting for possible clustering effects (eg, year and province). Results: We identified 106,015 CM cases and 20,570 CM deaths between 1992 and 2016. National MIR from 1992 to 2016 demonstrated a significant linear decrease ( P value < .0001). The national median MIR was 15.4 (ie, 0.154 × 100), whereby Manitoba (19.9), Ontario (19.5), Saskatchewan (18.5), British Columbia (16.1), and Newfoundland and Labrador (15.9) demonstrated higher MIRs than the Canadian average. CDs with the highest MIRs were commonly identified in the southern regions of provinces. No healthcare or socioeconomic factors were found to be significantly associated with higher MIR at the provincial level. Conclusion: MIRs have decreased at the national and provincial levels in recent decades, which is reassuring. Higher MIRs were noted in select rural CDs and in the Canadian territories, reinforcing the importance of proper dermatological care in all parts of the country.