Exploring the efficacy of Transcutaneous Auricular Vagus nerve stimulation (taVNS) in modulating local and systemic inflammation in experimental models of colitis.

Background: Current inflammatory bowel disease (IBD) treatments often fail to achieve lasting remission and have adverse effects. Vagus nerve stimulation (VNS) offers a promising therapy due to its anti-inflammatory effects. Its invasive nature, however, has led to the development of non-invasive methods like transcutaneous auricular VNS (taVNS).

Crosstalk Between Microbiota, Microbial Metabolites, and Interferons in the Inflammatory Bowel Disease Gut.

With the prevalence of inflammatory bowel diseases (IBD) continuing to rise in Canada and globally, developing improved therapeutics that successfully treat greater percentages of patients with reduced complications is paramount. A better understanding of pertinent immune pathways in IBD will improve our ability to both successfully dampen inflammation and promote gut healing, beyond just inhibiting specific immune proteins; success of combination therapies supports this approach. Interferons (IFNs) are key cytokines that protect mucosal barrier surfaces, and their roles in regulating gut homeostasis and inflammation differ between the three IFN families (type I, II, and III).

Integration of hospital with congregate care homes in response to the COVID-19 pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to improve the safety of the environments where we care for older adults in Canada. After providing assistance during the first wave, many Ontario hospitals formally partnered with local congregate care homes in a "hub and spoke" model during second pandemic wave onward. The objective of this article is to describe the implementation and longitudinal outcomes of residents in one hub and spoke model composed of a hospital partnered with 18 congregate care homes including four long-term care and 14 retirement or other congregate care homes.

Omics approaches for the assessment of biological responses to nanoparticles.

Nanotechnology has enabled the development of innovative therapeutics, diagnostics, and drug delivery systems. Nanoparticles (NPs) can influence gene expression, protein synthesis, cell cycle, metabolism, and other subcellular processes. While conventional methods have limitations in characterizing responses to NPs, omics approaches can analyze complete sets of molecular entities that change upon exposure to NPs.

Virtual Fracture Care in Long-Term Care Homes Avoiding Emergency Department Visits.

Long-term care residents with suspected fractures as a result of a fall typically transfer to the emergency department (ED) for diagnostic imaging and care. During the COVID-19 pandemic, transfer to the hospital increased the risk of COVID-19 exposure and resulted in extended isolation days for the resident. A fracture care pathway was developed and implemented to provide rapid diagnostic imaging results and stabilization in the care home, reducing transportation and exposure risk to COVID-19.

Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer.

Our previous studies demonstrated that the FOXM1 pathway is upregulated and the PPARA pathway downregulated in breast cancer (BC), and especially in the triple negative breast cancer (TNBC) subtype. Targeting the two pathways may offer potential therapeutic strategies to treat BC, especially TNBC which has the fewest effective therapies available among all BC subtypes. In this study we identified small molecule compounds that could modulate the PPARA and FOXM1 pathways in BC using two methods.

Evaluation of factors that influenced the length of hospital stay using data mining techniques.

Background: length of stay (LOS) is the time between hospital admission and discharge. LOS has an impact on hospital management and hospital care functions.

Methods: A descriptive, retrospective study was designed on about 27,500 inpatients between March 2019 and 2020.

The maternal-fetal transfer of passive immunity as a mechanism of transplacental nanoparticle drug delivery for prenatal therapies.

Nanoparticles administered into the maternal circulation and across the placenta are a potential clinical therapy to treat congenital diseases. The mechanism by which nanoparticles can safely cross the placenta for targeted drug delivery to the fetus remains poorly understood. We demonstrate that the maternal-fetal transfer of passive immunity through the neonatal Fc Receptor (FcRn) can induce the transplacental transfer of chitosan nanoparticles modifed with IgG antibodies (414 ± 27 nm).

The Rural Opioid Initiative Consortium description: providing evidence to Understand the Fourth Wave of the Opioid Crisis.

Objective: To characterize and address the opioid crisis disproportionately impacting rural U.S. regions.

Individual and poly-substance use and condomless sex among HIV-uninfected adults reporting heterosexual sex in a multi-site cohort.

Background: We analyzed the association between substance use (SU) and condomless sex (CS) among HIV-negative adults reporting heterosexual sex in the Seek, Test, Treat, and Retain (STTR) consortium. We describe the impact of SU as well as person/partner and context-related factors on CS, identifying combinations of factors that indicate the highest likelihood of CS.

Methods: We analyzed data from four US-based STTR studies to examine the effect of SU on CS using two SU exposures: 1) recent SU (within 3 months) and 2) SU before/during sex.

Patient values and preferences on polypharmacy and deprescribing: a scoping review.

Background Understanding how patient values and preferences towards polypharmacy and deprescribing have been studied is important to gain insight on current knowledge in this area and to identify knowledge gaps. Aim To describe methods and outcomes for studying patient values and preferences towards polypharmacy and deprescribing, and to identify gaps in the existing literature. Method A scoping review was conducted on English-language studies that examined patient preferences and values related to polypharmacy and/or deprescribing among community-dwelling adults.

Predicting breast cancer drug response using a multiple-layer cell line drug response network model.

Background: Predicting patient drug response based on a patient's molecular profile is one of the key goals of precision medicine in breast cancer (BC). Multiple drug response prediction models have been developed to address this problem. However, most of them were developed to make sensitivity predictions for multiple single drugs within cell lines from various cancer types instead of a single cancer type, do not take into account drug properties, and have not been validated in cancer patient-derived data.

The role of pharmacists in opioid stewardship: Protocol.

Background: The opioid crisis is a worldwide public health concern. In North America, evidence suggests that the increase in opioid prescriptions correlates with the observed increase in opioid-related mortality and morbidity. Pharmacists are in a strategic position to promote effective opioid stewardship as they have a central role on healthcare teams.

ECHO Care of the Elderly: Innovative Learning to Build Capacity in Long-term Care.

Background: Older adults are entering long-term care (LTC) homes with more complex care needs than in previous decades, resulting in demands on point-of-care staff to provide additional and specialty services. This study evaluated whether Project ECHO (Extension for Community Healthcare Outcomes) Care of the Elderly Long-Term Care (COE-LTC)-a case-based online education program-is an effective capacity-building program among interprofessional health-care teams caring for LTC residents.

Methods: A mixed-method, pre-and-post study comprised of satisfaction, knowledge, and self-efficacy surveys and exploration of experience via semi-structured interviews.

Outpatient oral anticancer agent utilization and costs in Manitoba from 2003 to 2016: a population-based study.

Intervention: In April 2012, the Manitoba Home Cancer Drug Program (HCDP) was introduced to allow 100% coverage for eligible oral anticancer agents (OAA) and supportive medications for Manitobans with cancer requiring these therapies.

Research Questions: What is the extent of use and cost of OAAs among outpatients in Manitoba from 2003/04 to 2015/16? Did the HCDP change OAA user and prescription patterns?

Methods: This was a retrospective, population-based study using administrative data to measure the prevalence of drug utilization over time and the impact of HCDP on OAA use and prescriptions using generalized linear models. Manitobans with cancer who filled an OAA or supportive medication covered by HCDP from 2003/04 to 2015/16 were included.

Building Long-Term Care Staff Capacity During COVID-19 Through Just-in-Time Learning: Evaluation of a Modified ECHO Model.

Objectives: The onset of the COVID-19 pandemic significantly challenged the capacity of long-term care (LTC) homes in Canada, resulting in new, pressing priorities for leaders and health care providers (HCPs) in the care and safety of LTC residents. This study aimed to determine whether Project ECHO (Extension for Community Healthcare Outcomes) Care of the Elderly Long-Term Care (COE-LTC): COVID-19, a virtual education program, was effective at delivering just-in-time learning and best practices to support LTC teams and residents during the pandemic.

Design: Mixed methods evaluation.

NK cells modulate T cell responses via interaction with dendritic cells in Chlamydophila pneumoniae infection.

Protective immune response to chlamydial infection is largely dependent on cell-mediated immune responses with IFN-γ production. Recent studies have shown the critical role of NK cells in bridging innate and adaptive immune responses. In this study, we investigated the effect of NK cells on T cell responses during Chlamydophila pneumoniae (Cpn) lung infection.

A QSAR study that compares the ability of bisdioxopiperazine analogs of the doxorubicin cardioprotective agent dexrazoxane (ICRF-187) to protect myocytes with DNA topoisomerase II inhibition.

The cardiotoxicity caused by doxorubicin and extravasation injury caused by anthracyclines is reduced by the clinically approved bisdioxopiperazine drug dexrazoxane. Dexrazoxane is a rings-closed analog of EDTA and is hydrolyzed in vivo to a form that strongly binds iron. Its protective effects were originally thought to be due to the ability of its metabolite to remove iron from the iron-doxorubicin complex, thereby preventing oxygen radical damage to cellular components.

Mechanisms of the Cardiac Myocyte-Damaging Effects of Dasatinib.

The anticancer drug dasatinib (Sprycel) is a BCR-ABL1-targeted tyrosine kinase inhibitor used in treating chronic myelogenous leukemia that has been shown in clinical trials to display cardiovascular toxicities. While dasatinib potently inhibits BCR-ABL1, it is not a highly selective kinase inhibitor and may have off-target effects. A neonatal rat cardiac myocyte model was used to investigate potential mechanisms by which dasatinib damaged myocytes.

Time to benefit and the long-term persistence of new users of oral bisphosphonates.

Introduction: This study aimed to examine long-term persistence in new users of oral bisphosphonates in a population-wide cohort in Manitoba, Canada.

Materials And Methods: A longitudinal observational study was conducted using administrative health data characterizing long-term bisphosphonate persistence in those who started treatment between 1997 and 2018. Treatment discontinuation was evaluated using Kaplan-Meier methods.

A New Microfluidic Platform for Studying Natural Killer Cell and Dendritic Cell Interactions.

The importance of the bi-directional natural killer-dendritic cell crosstalk in coordinating anti-tumour and anti-microbial responses in vivo has been well established. However, physical parameters associated with natural killer-dendritic cell interactions have not been fully elucidated. We have previously used a simple "Y" shaped microfluidic device to study natural killer cell-migratory responses toward chemical gradients from a conditioned medium of dendritic cells.

The Role of Topoisomerase IIβ in the Mechanisms of Action of the Doxorubicin Cardioprotective Agent Dexrazoxane.

Dexrazoxane is clinically used to reduce doxorubicin cardiotoxicity and anthracycline-induced extravasation injury. Dexrazoxane is a strong catalytic inhibitor of topoisomerase II. It can also undergo metabolism to form an iron-binding analog of EDTA.

Isolation and characterization of a new basal-like luminal progenitor in human breast tissue.

Background: Adult stem cells and progenitors are responsible for breast tissue regeneration. Human breast epithelial progenitors are organized in a lineage hierarchy consisting of bipotent progenitors (BPs), myoepithelial- and luminal-restricted progenitors (LRPs) where the LRP differentiation into mature luminal cells requires estrogen receptor (ER) signaling. However, the experimental evidence exploring the relationship between the BPs and LRPs has remained elusive.

Leukocyte Tracking Database, a collection of immune cell tracks from intravital 2-photon microscopy videos.

Recent advances in intravital video microscopy have allowed the visualization of leukocyte behavior in vivo, revealing unprecedented spatiotemporal dynamics of immune cell interaction. However, state-of-the-art software and methods for automatically measuring cell migration exhibit limitations in tracking the position of leukocytes over time. Challenges arise both from the complex migration patterns of these cells and from the experimental artifacts introduced during image acquisition.