Assessing the implementation of evidence-based alcohol policies on Atlantic Canadian post-secondary campuses: A comparative analysis.

Objective: This study assessed the quality of campus alcohol policies against best practice to assist campus decision-makers in strengthening their campus alcohol policies and reducing student alcohol use and harm.

Methods: Drawing on empirical literature and expert opinion, we developed an evidence-based scoring rubric to assess the quality of campus alcohol policies across 10 alcohol policy domains. Campus alcohol policy data were collected from 12 Atlantic Canadian universities.

Nonclassical Zwitterions as a Design Principle to Reduce Lipophilicity without Impacting Permeability.

The ionization of bioactive molecules impacts many ADME-relevant physicochemical properties, in particular, solubility, lipophilicity, and permeability. Ampholytes contain both acidic and basic groups and are distinguished as ordinary ampholytes and zwitterions. An influential review states that zwitterions only exist if the acidic p is significantly lower than the basic p.

Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers.

The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens. Despite advances in treatment with immune checkpoint inhibitors, there is an unmet need in the treatment of MSI cancers. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy.

Fasting as a precursor to high-fat diet enhances mitochondrial resilience in Drosophila melanogaster.

Changes in diet type and nutrient availability can impose significant environmental stress on organisms, potentially compromising physiological functions and reproductive success. In nature, dramatic fluctuations in dietary resources are often observed and adjustments to restore cellular homeostasis are crucial to survive this type of stress. In this study, we exposed male Drosophila melanogaster to two modulated dietary treatments: one without a fasting period before exposure to a high-fat diet and the other with a 24-h fasting period.

Health Care Providers' Perspectives on Promoting Physical Activity and Exercise in Health Care.

Health care providers (HCPs) are entrusted with providing credible health-related information to their patients/clients. Patients/clients who receive physical activity and exercise (PAE) advice from an HCP typically increase their PAE level. However, most HCPs infrequently discuss PAE or prescribe PAE, due to the many challenges (e.

Systemic and mitochondrial effects of metabolic inflexibility induced by high fat diet in Drosophila melanogaster.

Metabolic inflexibility is a condition that occurs following a nutritional stress which causes blunted fuel switching at the mitochondrial level in response to hormonal and cellular signalling. Linked to obesity and obesity related disorders, chronic exposure to a high-fat diet (HFD) in animal models has been extensively used to induce metabolic inflexibility and investigate the development of various metabolic diseases. However, many questions concerning the systemic and mitochondrial responses to metabolic inflexibility remain.

Structure-Based and Property-Driven Optimization of -Aryl Imidazoles toward Potent and Selective Oral RORγt Inhibitors.

Retinoic acid receptor-related orphan receptor gamma-t (RORγt) is considered to be the master transcription factor for the development of Th17 cells that produce proinflammatory cytokines such as IL-17A. Overproportionate Th17 cell abundance is associated with the pathogenesis of many inflammatory conditions including psoriasis. In a high-throughput fluorescence resonance energy transfer (FRET) screen, we identified compound 1 as a hit with promising lipophilic efficiency (LipE).

Discovery of CDZ173 (Leniolisib), Representing a Structurally Novel Class of PI3K Delta-Selective Inhibitors.

The predominant expression of phosphoinositide 3-kinase δ (PI3Kδ) in leukocytes and its critical role in B and T cell functions led to the hypothesis that selective inhibitors of this isoform would have potential as therapeutics for the treatment of allergic and inflammatory disease. Targeting specifically PI3Kδ should avoid potential side effects associated with the ubiquitously expressed PI3Kα and β isoforms. We disclose how morphing the heterocyclic core of previously discovered 4,6-diaryl quinazolines to a significantly less lipophilic 5,6,7,8-tetrahydropyrido[4,3-]pyrimidine, followed by replacement of one of the phenyl groups with a pyrrolidine-3-amine, led to a compound series with an optimal on-target profile and good ADME properties.

Molecular hybridization yields triazole bronchodilators for the treatment of COPD.

A 1,2,4-triazole motif was employed as a bioisostere for the ester commonly used in muscarinic antagonists, and subsequent integrative conjugation to a β2 agonist quinolinone furnished a new class of bifunctional MABAs for the treatment of COPD. Medicinal chemistry optimization using the principles of 'inhalation by design' furnished a clinical candidate with desirable pharmacological, pharmacokinetic and biopharmaceutical properties.

Orally bioavailable Syk inhibitors with activity in a rat PK/PD model.

Design and optimization of benzo- and pyrido-thiazoles/isothiazoles are reported leading to the discovery of the potent, orally bioavailable Syk inhibitor 5, which was found to be active in a rat PK/PD model. Compound 5 showed acceptable overall kinase selectivity. However, in addition to Syk it also inhibited Aurora kinase in enzymatic and cellular settings leading to findings in the micronucleus assay.

Is there a relation between shoulder dysfunction and core instability?

Background: Overhead athletes often suffer injury to the glenohumeral joint secondary to inherent instability. However, little is known about the relationship between core stability and shoulder dysfunction among athletes.

Purpose: The purpose of this study was to analyze the difference between healthy athletes and those with shoulder dysfunction in regard to core stability measures.

Immunization completeness of children under two years of age in Nova Scotia, Canada.

Objectives: Canada's progress in establishing a national immunization registry and coordinated immunization schedule across provinces has been slow. The absence of a centralized registry means there are only limited data available on childhood immunization coverage in Canada. The aim of this study was to estimate the completeness and timeliness of immunization for two year-old children in Nova Scotia.

Improving community health and safety in Canada through evidence-based policies on illegal drugs.

Illegal drug use remains a serious threat to community health in Canada, yet there has been a remarkable discordance between scientific evidence and policy in this area, with most resources going to drug use prevention and drug law enforcement activities that have proven ineffective. Conversely, evidence-based drug treatment programs have been chronically underfunded, despite their cost-effectiveness. Similarly, various harm reduction strategies, such as needle exchange, supervised injecting programs and opioid substitution therapy, have also proven effective at reducing drug-related harm but receive limited government support.

Canadian initiatives to prevent hypertension by reducing dietary sodium.

Hypertension is the leading risk for premature death in the world. High dietary sodium is an important contributor to increased blood pressure and is strongly associated with other important diseases (e.g.

Inhalation by design: novel tertiary amine muscarinic M₃ receptor antagonists with slow off-rate binding kinetics for inhaled once-daily treatment of chronic obstructive pulmonary disease.

A novel tertiary amine series of potent muscarinic M(3) receptor antagonists are described that exhibit potential as inhaled long-acting bronchodilators for the treatment of chronic obstructive pulmonary disease. Geminal dimethyl functionality present in this series of compounds confers very long dissociative half-life (slow off-rate) from the M(3) receptor that mediates very long-lasting smooth muscle relaxation in guinea pig tracheal strips. Optimization of pharmacokinetic properties was achieved by combining rapid oxidative clearance with targeted introduction of a phenolic moiety to secure rapid glucuronidation.

Synthesis and evaluation of heteroarylalanine diacids as potent and selective neutral endopeptidase inhibitors.

Heteroarylalanine derivatives 4 were designed as potential inhibitors of neutral endopeptidase (NEP EC 3.4.24.