Alcohol consumption and mortality among Canadian drinkers: A national population-based survival analysis (2000-2017).

Introduction: Alcohol contributes significantly global disease burden. Over 50 countries, including Canada, have established low-risk drinking guidelines to reduce alcohol-related harm. Canada's Guidance on Alcohol and Health (CGAH) was released in 2023.

BD SurePath Direct to Slide (DTS) cervical cytology: Migrating the benefits of liquid-based cytology to low-resource settings.

Objectives: The benefits of liquid-based cytology (LBC) in routine cervical cancer screening are often associated with the availability of instrumented platforms and economic considerations. A low-cost alternative to LBC in low-volume settings remains an unmet need.

Methods: A multisite evaluation of the BD SurePath (SurePath) LBC Direct to Slide (DTS) method was conducted.

Community pharmacists' awareness, identification, and management of prescribing cascades: A cross-sectional survey.

Background: Prescribing cascades can lead to unnecessary medication use, healthcare costs, and patient harm. Pharmacists oversee prescriptions from multiple prescribers and are well positioned to identify such cascades, making pharmacists key stakeholders to address them.

Objectives: To evaluate community pharmacists' awareness, identification, and management of prescribing cascades and to assess behavioural determinants that may be targeted in future strategies to minimise inappropriate prescribing cascades.

Gut bacteria-derived serotonin promotes immune tolerance in early life.

The gut microbiota promotes immune system development in early life, but the interactions between the gut metabolome and immune cells in the neonatal gut remain largely undefined. Here, we demonstrate that the neonatal gut is uniquely enriched with neurotransmitters, including serotonin, and that specific gut bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit serotonin breakdown. We found that serotonin directly signals to T cells to increase intracellular indole-3-acetaldehdye and inhibit mTOR activation, thereby promoting the differentiation of regulatory T cells, both ex vivo and in vivo in the neonatal intestine.

Ultra-low content physio-chemically crosslinked gelatin hydrogel improves encapsulated 3D cell culture.

Gelatin-based hydrogels are extensively used for 3D cell culture, bioprinting, and tissue engineering due to their cell-adhesive nature and tunable physio-chemical properties. Gelatin hydrogels for 3D cell culture are often developed using high-gelatin content (frequently 10-15 % w/v) to ensure fast gelation and improved stability. While highly stable, such matrices restrict the growth of encapsulated cells due to creating a dense, restrictive environment around the encapsulated cells.

Canada's cannabis legalization and adult crime patterns, 2015-2021: A time series study.

Background And Aim: A central goal of the Cannabis Act (October 17, 2018) - Canada's national cannabis legalization framework - aimed to reduce cannabis-related criminalization and consequent impact on the Canadian criminal justice system. We assessed whether Canada's cannabis legalization was associated with changes in adult police-reported cannabis-related, property, or violent criminal incidents.

Design: Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models evaluated relations between legalization and adult cannabis-related, property, and violent crimes, using criminal incident data from the Canadian Uniform Crime Reporting Survey (UCR-2; January 1, 2015-December 31, 2021).

Biochemical interactions between the Atm1-like transporter from Novosphingobium aromaticivorans and heavy metals.

Novosphingobium aromaticivorans has the ability to survive in harsh environments by virtue of its suite of iron-containing oxygenases that biodegrade an astonishing array of aromatic compounds. It is also resistant to heavy metals through Atm1, an ATP-binding cassette protein that mediates active efflux of heavy metals conjugated to glutathione. However, Atm1 orthologues in higher organisms have been implicated in the intracellular transport of organic iron complexes.

Canada's cannabis legalization and police-reported cannabis-related criminal incidents among youth, 2015-2021.

Background: We previously reported that the 2018 Canadian Cannabis Act, allowing youth to possess up to 5 g dried cannabis or equivalent for personal use/sharing, was associated with short-term (76 days) post-legalization reduction in police-reported cannabis-related crimes among youth. To establish whether the change might be sustained, we now estimate this association during a much longer time period by including an additional three years of post-legalization data.

Methods: Using national daily police-reported criminal incident data from January 1, 2015-December 31, 2021 from the Canadian Uniform Crime Reporting Survey (UCR-2), the study employed Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models to assess the associations between legalization and youth (12-17 years) cannabis-related offenses (male, n = 34,508; female, n = 9529).

Impact of Canada's cannabis legalisation on youth emergency department visits for cannabis-related disorders and poisoning in Ontario and Alberta, 2015-2019.

Introduction: Although there is momentum towards legalising adult recreational cannabis use worldwide, the extent of youth cannabis-related harm associated with legalisation is still uncertain. The current study aimed to assess whether the initial implementation of Canada's cannabis legalisation (via the Cannabis Act) on 17 October 2018 might be associated with youth harm, as assessed by emergency department visits for cannabis-related disorders/poisoning.

Methods: We used Ontario and Alberta, Canada emergency department data from 1 April 2015 to 31 December 2019.

Temporal Diffusion Ratio (TDR) for imaging restricted diffusion: Optimisation and pre-clinical demonstration.

Temporal Diffusion Ratio (TDR) is a recently proposed dMRI technique (Dell'Acqua et al., proc. ISMRM 2019) which provides contrast between areas with restricted diffusion and areas either without restricted diffusion or with length scales too small for characterisation.

Regulation of P-Glycoprotein in the Brain.

Maintenance of the tightly regulated homeostatic environment of the brain is facilitated by the blood-brain barrier (BBB). P-glycoprotein (P-gp), an ATP-binding cassette transporter, is expressed on the luminal surface of the endothelial cells in the BBB, and actively exports a wide variety of substrates to limit exposure of the vulnerable brain environment to waste buildup and neurotoxic compounds. Downregulation of P-gp expression and activity at the BBB have been reported with ageing and in neurodegenerative diseases.

Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer.

Inflammatory bowel disease (IBD) is a chronic life-long inflammatory disease affecting almost 2 million Americans. Although new biologic therapies have been developed, the standard medical treatment fails to selectively control the dysregulated immune pathways involved in chronic colonic inflammation. Further, IBD patients with uncontrolled colonic inflammation are at a higher risk for developing colorectal cancer (CRC).

Using enaction to evolve from pre-Covid to post-Covid pedagogy: a case study with South African mathematics teachers.

The Covid-19 pandemic and subsequent national lockdown in South Africa induced a rapid, albeit challenging, implementation of blended learning (with a strong online focus) at all educational levels. During this time, a group of teachers were involved in a specialised computer integrated education course, preparing them for the design and implementation of technologically enhanced modes of teaching. In this research we considered the positive impact of the situation during the pandemic on these mathematics teachers' practice, as well as their conceptualisation of the way forward for technology enhanced mathematics education.

Population-based comparison of cancer survival outcomes in patients with and without psychiatric disorders.

Background: Individuals with psychiatric disorders (PD) have a high prevalence of tobacco use. Patients with PD also potentially receive substandard care in comparison to the general population. Previous research has shown that individuals with PD have a decreased risk of receiving a tobacco related (TR) cancer diagnosis.

Vinca alkaloid binding to P-glycoprotein occurs in a processive manner.

A mechanistic understanding of how P-glycoprotein (Pgp) is able to bind and transport its astonishing range of substrates remains elusive. Pharmacological data demonstrated the presence of at least four distinct binding sites, but their locations have not been fully elucidated. The combination of biochemical and structural data suggests that initial binding may occur in the central cavity or at the lipid-protein interface.

UCP2 - Taking the heat out of P-glycoprotein?

Cancer cells are highly proliferative, invasive, metastatic and initiate angiogenesis. These activities demand plentiful energy and bountiful stores of anabolic precursors, a situation that puts significant strain on metabolic pathways and necessitates juggling of finite resources. However, the location and erratic structural organisation of tumours means they reside in a nutrient-poor environment.

The Ubiquitin E3 Ligase Nedd4 Regulates the Expression and Amyloid-β Peptide Export Activity of P-Glycoprotein.

The ATP-binding cassette transporter, P-glycoprotein (P-gp), has been demonstrated to facilitate the clearance of amyloid-beta (Aβ) peptides, exporting the neurotoxic entity out of neurons and out of the brain via the blood-brain barrier. However, its expression and function diminish with age and in Alzheimer's disease. P-gp is known to undergo ubiquitination, a post-translational modification that results in internalisation and/or degradation of the protein.

Associations Between Canada's Cannabis Legalization and Emergency Department Presentations for Transient Cannabis-Induced Psychosis and Schizophrenia Conditions: Ontario and Alberta, 2015-2019.

Objective: Cannabis legalization in many jurisdictions worldwide has raised concerns that such legislation might increase the burden of transient and persistent psychotic illnesses in society. Our study aimed to address this issue.

Methods: Drawing upon emergency department (ED) presentations aggregated across Alberta and Ontario, Canada records (April 1, 2015-December 31, 2019), we employed Seasonal Autoregressive Integrated Moving Average (SARIMA) models to assess associations between Canada's cannabis legalization (via the implemented on October 17, 2018) and weekly ED presentation counts of the following ICD-10-CA-defined target series of cannabis-induced psychosis (F12.

Identification of Tobacco-Related Cancer Diagnoses among Individuals with Psychiatric Disorders: A Population-Based Matched Cohort Study Using a Competing Risks Approach from British Columbia.

Background: Individuals with psychiatric disorders (PD) have a high prevalence of tobacco use. Therefore, we assessed the hazard of receiving a tobacco-related (TR) cancer diagnosis among individuals with PD.

Methods: Several population-based provincial databases were used to identify individuals in BC diagnosed with depression, schizophrenia, bipolar disorder, anxiety disorders, or multiple PD between 1990 and 2013.

Canada's cannabis legalization and drivers' traffic-injury presentations to emergency departments in Ontario and Alberta, 2015-2019.

Background: Worldwide momentum toward legalization of recreational cannabis use has raised a common concern that such policies might increase cannabis-impaired driving and consequent traffic-related harms, especially among youth. The current study evaluated this issue in Canada.

Methods: Utilizing provincial emergency department (ED) records (April 1, 2015-December 31, 2019) from Alberta and Ontario, Canada, we employed Seasonal Autoregressive Integrated Moving Average (SARIMA) models to assess associations between Canada's cannabis legalization (via the Cannabis Act implemented on October 17, 2018) and weekly provincial counts of ICD-10-CA-defined traffic-injury ED presentations.

Comparative analysis of signal models for microscopic fractional anisotropy estimation using q-space trajectory encoding.

Microscopic diffusion anisotropy imaging using diffusion-weighted MRI and multidimensional diffusion encoding is a promising method for quantifying clinically and scientifically relevant microstructural properties of neural tissue. Several methods for estimating microscopic fractional anisotropy (µFA), a normalized measure of microscopic diffusion anisotropy, have been introduced but the differences between the methods have received little attention thus far. In this study, the accuracy and precision of µFA estimation using q-space trajectory encoding and different signal models were assessed using imaging experiments and simulations.

"If I knew I could get that every hour instead of alcohol, I would take the cannabis": need and feasibility of cannabis substitution implementation in Canadian managed alcohol programs.

Background: While there is robust evidence for strategies to reduce harms of illicit drug use, less attention has been paid to alcohol harm reduction for people experiencing severe alcohol use disorder (AUD), homelessness, and street-based illicit drinking. Managed Alcohol Programs (MAPs) provide safer and regulated sources of alcohol and other supports within a harm reduction framework. To reduce the impacts of heavy long-term alcohol use among MAP participants, cannabis substitution has been identified as a potential therapeutic tool.