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Background: A public health initiative that is common across jurisdictions is provision of advice to people to limit the frequency, amount of time and amount of money spent gambling in order to reduce the risk of gambling-related harm. The purpose of this study is to use consistent methodology with existing population-based prevalence surveys of gambling and related harms from different countries to identify quantitative limits for lower and higher risk gambling. Risk limits from different countries and for men and women are compared. Methods: Risk curve analyses were conducted with eleven high quality data sets from eight Western countries to identify optimal limits for predicting increased risk of gambling-related harms. Gambling indicators were monthly expenditure, percentage of income spent on gambling, monthly frequency, duration of gambling sessions, and number of different types of gambling. Harm indicators included financial, emotional, health, and relationship impacts. Findings: The limit ranges were remarkably consistent across harm indicators, cross nationally and between men and women. Reliable results were obtained for all gambling indicators except gambling session duration. Risk of gambling-related harm is likely to increase if an individual gambles at these levels of greater: $60 to $120 CAD per month, five to eight times per month, spends more than 1 to 3% of gross monthly income or plays three to four different gambling types. Interpretation: This study provides evidence that lower-risk gambling guidelines can be based upon empirically derived lower-risk limits, which are relatively consistent across Western countries. Funding Statement: La Fondation Mise sur Toi Declaration of Interests: DH, MA, RB, NB, JMC, MD, SK, DOUR, AS, RV, LN, and SC report receiving personal fees from the Canadian Centre for Substance Use and Addiction during this project. MY, CP, and MCFP have no conflicts to report.

Background: Changes in the use of alcohol and other substances during COVID-19 is of considerable public health interest. This study examined changes in per capita alcohol, cannabis and other essential retail sales across Canada during the early phase of COVID-19, and associations between these changes and different jurisdictional approaches to drug control. Methods: A time series analysis was used to examine trends in monthly per capita alcohol, cannabis, and essential and non-essential retail sales before and during the first three months of COVID-19 for 12 jurisdictions across Canada. We compared observed sales during the first three months of COVID-19 to predicted sales based on model outputs using pre-COVID-19 trends. Next, we used difference in difference models to estimate the associations between different models of alcohol and cannabis retail systems and changes in retail sales during COVID-19. Findings: In Canada, observed per capita sales were significantly greater than predicted for alcohol (+9.6%) and cannabis (+14.1%) during March 2020, and consistent with predicted sales in April and May 2020. Essential retail sales were significantly less than predicted during March to May 2020 (average of -7.4%). During COVID-19, per capita alcohol sales in jurisdictions with a private retail system increased significantly (+$8.5 on average, 95%CIs; 2.1,15.6) after accounting for changes over time. In contrast, the relative change in per capita alcohol sales in jurisdictions with a public retail model prior to and during COVID-19 was, on average, $13.3 lower (95% CIs; -22.6,-4.0) compared to the changes in jurisdictions with a private retail model. Similar trends were observed for cannabis sales with respect to retail model. Interpretation: There was a modest increase in alcohol and cannabis purchasing during the first three months of COVID-19. Changes in sales were influenced by pre-existing policies, and jurisdictions with a private retail model had greater than expected alcohol and cannabis sales compared to jurisdictions with a public model. This study adds to the body of research showing that government-run retail models for alcohol and cannabis provide protection for public health. Funding Statement: There is no funding to disclose for this project. Declaration of Interests: The authors have all completed ICMJE conflict of interest forms. The authors have no conflicts of interest to declare. Ethics Approval Statement: This project was approved by the Public Health Ontario Ethics Review Board file number 2020-038.01.

Alcohol labels are one strategy for raising consumer awareness about the negative consequences of alcohol, but evidence to inform labels is limited. This quasi-experimental study sought to test the real-world impact of strengthening health messages on alcohol container labels on consumer attention, message processing (reading, thinking, and talking with others about labels), and self-reported drinking. Alcohol labels with a cancer warning, national drinking guidelines, and standard drink information were implemented in the intervention site, and usual labelling practices continued in the comparison site. Changes in key indicators of label effectiveness were assessed among a cohort of adult drinkers in both the intervention and comparison sites using three waves of surveys conducted before and at two time-points after the alcohol label intervention. Generalized Estimating Equations with difference-in-difference terms were used to examine the impact of the label intervention on changes in outcomes. Strengthening health messages on alcohol container labels significantly increased consumer attention to [Adjusted Odds Ratio (AOR)=17.2, 95%CI:8.2,36.2] and processing of labels (e.g., reading labels: AOR=2.6, 95%CI:1.8,3.7), and consumer reports of drinking less due to the labels (AOR=3.7, 95%CI: 2.0,7.0). Strengthening health messages on alcohol containers can achieve their goal of attracting attention, deepening engagement, and enhancing motivation to reduce alcohol use. Strengthening alcohol labelling policies should be a priority for alcohol control globally.

This study tests the hypothesis that the relationship between parenthood and heavy drinking is mediated by drinking locations. The analysis is based on a random sample of 4180 female and 3630 male Canadian drinkers aged between 18 and 55 years old. A multiple mediator model is tested. Results show that the parental role may be associated with variation in where people drink, and where people drink may be associated with variation in heavy drinking. For women, parenthood is related to a reduction in heavy drinking associated with a reduction of drinking occasions that occur at bars, offset to some extent by the fact that drinking in restaurants is also less common among mothers than non-mothers. For men, parenthood is related to a reduction in heavy drinking partly because fathers more often drink at friends' homes and the proportion of drinking occasions that occur at bars is smaller among fathers than non-fathers. The results of this study correspond with a refined version of the opportunity perspective. Given the nature of the processes by which parenthood is related to heavy drinking, alcohol consumption needs to be understood through a perspective that includes both individual and contextual factors.

The pharmacophoric space of streptococcal MurF was explored using a set of 39 known inhibitors. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and physicochemical descriptors that access self-consistent quantitative structure–activity relationship (QSAR) ( r 2 = 0.93 ,F = 56.9 , r LOO 2 = 0.91 , r PRESS 2 against eight external test inhibitors = 0.75). Two orthogonal pharmacophores (of cross-correlation r 2 = 0.26) emerged in the QSAR equation suggesting the existence of at least two distinct binding modes accessible to ligands within MurF binding pocket. The validity of the QSAR equation and the associated pharmacophore models was experimentally established by the identification of three promising new MurF inhibitors retrieved from the NCI database. Docking studies conducted on active hits supported the binding modes suggested by the pharmacophore/QSAR analysis.

As a model system for designing new inhibitors of bacterial cell division, we studied the essential and highly conserved FtsZ GTPase from Pseudomonas aeruginosa. A collection of GTP analogues were prepared using the solid-phase parallel synthesis approach. The synthesized GTP analogues inhibited the GTPase activity of FtsZ with IC50 values between 450 μM and 2.6 mM, and 5 compounds inhibited Staphylococcus aureus growth in a biological assay. The FtsZ spectrophotometric assay developed for screening of synthesized compounds is the first step in identification of antibacterials targeting the bacterial cell division essential proteins.

The purified Pseudomonas aeruginosa cell wall biosynthesis MurD amide ligase enzyme was used to screen C-7-C and 12 mers peptides from phage display libraries using competitive biopanning approaches with the specific substrates D-glutamate and ATP. From the 60 phage-encoded peptides identified, DNA was sequenced, deduced amino acid sequences aligned and two peptides were synthesized from consensus sequences identified. The UDP-N-acetylmuramyl-L-alanine MurD substrate was synthesized, purified and used to develop a spectrophotometric assay. One peptide synthesized was found to specifically inhibit ATPase activity of MurD. The IC50 value was estimated at 4 microM for the C-7-C MurDp1 peptide. The loop conformation of MurDp1 was shown to be important for the inhibition of the UDP-N-acetylmuramyl-L-alanine:D-glutamate MurD ligase. The linear 12 mers MurD2 peptide has an IC50 value of 15 mM. A conserved amino acid motif was found between MurDp2 and the bacterial glyceraldehyde 3-phosphate dehydrogenase indicating that MurDp2 binds at a protein-protein interacting site. The approach proposed and results obtained suggest that efficient peptide inhibitors as well as protein-protein interaction domains can be identified by phage display.