Experiences and Perspectives of Transgender Individuals Accessing Gender-Affirming Care in Manitoba, Canada.

As the number of trans people seeking gender-affirming care (GAC) continues to increase globally, it is increasingly important to understand the experiences of this patient population to improve healthcare delivery and ensure identified needs are being met. This qualitative descriptive study describes the experiences and perspectives of trans people (age 18-34) accessing GAC in Manitoba, Canada based on data obtained from semi-structured focus groups and individual interviews ( = 10). Three major themes were identified to capture key elements of seeking GAC: (1) the transition decision, (2) the transition process, and (3) barriers to receiving desired care.

Together, alone: Personal experiences of virtual funeral attendance during the COVID-19 global pandemic.

The COVID-19 pandemic caused profound distortions in how deaths were marked by those left to mourn their passing. Public health restrictions prohibited gatherings of friends and families for traditional funerals, causing an upsurge in reliance on virtual alternatives. The aim of this study was to explore the experiences of individuals attending virtual funerals following a death of any cause, including reasons for choosing virtual attendance, perceived differences relative to in person attendance, and the extent to which mourning practices were accommodated.

Expansion of tumor-infiltrating and marrow-infiltrating lymphocytes from pediatric malignant solid tumors.

Introduction: The expansion of tumor-infiltrating lymphocytes (TIL) for adoptive cellular therapy is under investigation in many solid tumors of adulthood. Marrow-infiltrating lymphocytes (MIL) have demonstrated antitumor reactivity preclinically. Successful expansion of TIL/MIL has not been reported across pediatric solid tumor histologies.

Development of an engineered extracellular vesicles-based vaccine platform for combined delivery of mRNA and protein to induce functional immunity.

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EV vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EV vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors.

Endothelial Immunosuppression in Atherosclerosis : Translational Control by Elavl1/HuR.

Atherosclerotic plaques are defined by the accumulation of lipids and immune cells beneath the endothelium of the arterial intima. CD8 T cells are among the most abundant immune cell types in plaque, and conditions linked to their activation correlate with increased levels of cardiovascular disease. As lethal effectors of the immune response, CD8 T cell activation is suppressed at multiple levels.

Evaluating the impact of COVID-19 on medication adherence and health care utilization among individuals with psychotic disorders who are prescribed long-acting injectables (LAIs) or clozapine: A population-based study in Manitoba, Canada.

Background: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization.

Methods: A retrospective population-wide study was conducted for adults in Manitoba, Canada.

The first casualty of COVID-19 for patients nearing death was human dignity: Understanding the experience of palliative care patients during the COVID-19 pandemic.

The COVID-19 pandemic changed the way people lived, but also the way they died. It accentuated the physical, psychological, social, and spiritual vulnerabilities of patients approaching death. This study explored the lived experience of palliative inpatients during the pandemic.

When "virtual" works and when it doesn't: A survey of physician and patient experiences with virtual care during the COVID-19 pandemic.

Objective: To assess the experience of virtual care among both patients and physicians across a range of clinical scenarios during the COVID-19 pandemic.

Methods: A web-based survey was disseminated to patients and physicians through a variety of media and healthcare communications from May 2020 to July 2021. Demographic details and attitudes across a range of virtual care domains were collected.

"It took so much of the humanness away": Health care professional experiences providing care to dying patients during COVID-19.

COVID-19 has affected healthcare in profound and unprecedented ways, distorting the experiences of patients and healthcare professionals (HCPs) alike. One area that has received little attention is how COVID-19 affected HCPs caring for dying patients. The goal of this study was to examine the experiences of HCPs working with dying patients during the COVID-19 pandemic.

Exosomes modified with anti-MEK1 siRNA lead to an effective silencing of triple negative breast cancer cells.

Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered.

SARS-CoV-2 antibody response duration and neutralization following natural infection.

Background: The role of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody response from natural infection and vaccination, and the potential determinants of this response are poorly understood. Characterizing this antibody response and the factors associated with neutralization can help inform future prevention efforts and improve clinical outcomes in those infected.

Objectives: The goals of this study were to prospectively evaluate SARS-CoV-2 antibody levels and the neutralizing antibody responses among naturally infected adults and to determine demographic and behavioral factors independently associated with these responses.

Protective Effects of Polyphenol-Rich Extracts against Neurotoxicity Elicited by Paraquat or Rotenone in Cellular Models of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model.

Engineered exosomes targeting MYC reverse the proneural-mesenchymal transition and extend survival of glioblastoma.

Dysregulated Myc signaling is a key oncogenic pathway in glioblastoma multiforme (GBM). Yet, effective therapeutic targeting of Myc continues to be challenging. Here, we demonstrate that exosomes generated from human bone marrow mesenchymal stem cells (MSCs) engineered to encapsulate siRNAs targeting Myc (iExo-Myc) localize to orthotopic GBM tumors in mice.

Psychiatric consultation: Characteristics, satisfaction, and perceived opportunities among referrers to a 1-time service.

Objective: To further understand and optimize primary care provider (PCP) referrals to a 1-time psychiatric consultation service by developing profiles of PCP referrers, assessing PCP satisfaction with the service, and determining intervention opportunities.

Design: Secondary analysis of a referral database and subsequent cross-sectional survey of referrers.

Setting: Winnipeg, Man.

Increasing access to specialist care with group medical visits: summary of a pilot in a post-crisis psychiatric clinic.

Background: Group medical visits (GMVs) have strong evidence of acceptability and effectiveness in the management of chronic medical diseases. Adaptation of GMVs for psychiatric care has potential to increase access, decrease stigma and save costs. Despite promise, this model has not been widely adopted.

Providing crisis care in a pandemic: a virtual based crisis stabilization unit.

Background: Winnipeg, Canada operates a 16-bed subacute unit, the Crisis Stabilization Unit (CSU), for voluntary patients in crisis not requiring hospital admission. The virtual CSU (vCSU) launched in March 2020 as an adjunct to the in-person CSU during the COVID-19 pandemic, providing the same resources virtually, allowing patients to remain at home.

Methods: Program data were collected for vCSU admissions between April 1, 2020 and April 7, 2021 ( = 266) to examine patient characteristics and discharge outcomes.

Physician benzodiazepine self-use prior to and during the COVID-19 pandemic in Ontario, Canada: a population-level cohort study.

Objectives: The aim of this study was to investigate physician benzodiazepine (BZD) self-use pre-COVID-19 pandemic and to examine changes in BZD self-use during the first year of the pandemic.

Design: Population-based retrospective cohort study using linked routinely collected administrative health data comparing the first year of the pandemic to the period before the pandemic.

Setting: Province of Ontario, Canada between March 2016 and March 2021.

Mental health and addiction health service use by physicians compared to non-physicians before and during the COVID-19 pandemic: A population-based cohort study in Ontario, Canada.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has exacerbated mental health challenges among physicians and non-physicians. However, it is unclear if the worsening mental health among physicians is due to specific occupational stressors, reflective of general societal stressors during the pandemic, or a combination. We evaluated the difference in mental health and addictions health service use between physicians and non-physicians, before and during the COVID-19 pandemic.

Virtual Acute Psychiatric Ward: Evaluation of Outcomes and Cost Savings.

Objective: The COVID-19 pandemic motivated rapid expansion of virtual care. In Winnipeg, Canada, the authors launched a virtual psychiatric acute care ward (vWARD) to divert patients from hospitalization through daily remote treatment by a psychiatry team using telephone or videoconferencing. This study examined vWARD patient characteristics, predictors of transfer to a hospital, use of acute care postdischarge, and costs of the vWARD compared with in-person hospitalization.

Early Learning From a Low-Resource COVID-Response Virtual Mental Health Crisis Ward: Mixed Methods Study.

Background: The COVID-19 pandemic was accompanied by the accelerated uptake of virtual care, leading to a proliferation of virtual ward models as alternatives to facility-based care. Early in the pandemic, our program implemented a virtual mental health crisis ward (vWard) to provide options for individuals requiring intense psychiatric and/or crisis support but who preferred to remain in the community and were deemed safe to do so.

Objective: The aim of this study was to identify early learnings from the vWard, which was implemented rapidly in a resource-constrained environment, to inform the future state should it be sustained beyond the pandemic.

Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy.

Background: Molecular detection of lymph node (LN) micrometastases by analyzing mRNA expression of epithelial markers in prostate cancer (PC) patients provides higher sensitivity than histopathological examination.

Objective: To investigate which type of marker to use and whether molecular detection of micrometastases in LNs was predictive of biochemical recurrence.

Design Setting And Participants: LN samples from PC patients undergoing radical prostatectomy with extended LN dissection between 2009 and 2011 were examined for the presence of micrometastases by both routine histopathology and molecular analyses.

Needs Assessment of Clients Accessing a Community Mental Health Crisis Stabilization Unit.

This study aimed to examine the needs of clients accessing a community mental health crisis stabilization unit (CSU) in Winnipeg, Canada. Sociodemographics, service connections, and need were assessed among CSU clients. The Camberwell Assessment of Need Short Appraisal Schedule - Patient (CANSAS-P) was administered to differentiate need domains that were met and unmet.

Systemic Checkpoint Blockade by PD-L1 Single-Chain Antibody Confers Potent Antitumor Immunity and Long-term Survival.

Immune checkpoint inhibitors (ICI) are promising in adjuvant settings for solid tumors and hematologic malignancies. They are currently used in the treatment as mAbs in high concentrations, raising concerns of toxicity and adverse side effects. Among various checkpoint molecules, targeting the programmed cell death protein-1 (PD-1)-programmed death-ligand 1 (PD-L1) axis has garnered more clinical utility than others have.

Analysis of the uptake and associated factors for virtual crisis care during the pandemic at a 24-h mental health crisis centre in Manitoba, Canada.

Background: The coronavirus pandemic necessitated the rapid transition to virtual care. At a 24-h walk-in mental health Crisis Response Centre (CRC) in Winnipeg, Canada we adapted crisis mental health assessments to be offered virtually while the crisis centre also remained open to in person visits. Little is known about the sustainability of virtual visits in the presence of comparable in person care, and which visits are more likely to be done virtually, particularly in the crisis setting.

Adoptive Cellular Therapy for Pediatric Solid Tumors: Beyond Chimeric Antigen Receptor-T Cell Therapy.

Children and adolescents with high-risk (metastatic and relapsed) solid tumors have poor outcomes despite intensive multimodal therapy, and there is a pressing need for novel therapeutic strategies. Adoptive cellular therapy (ACT) has demonstrated activity in multiple adult cancer types, and opportunity exists to expand the use of this therapy in children. Employment of immunotherapy in the pediatric population has realized only modest overall clinical trial results, with success thus far restricted mainly to antibody-based therapies and chimeric antigen receptor T-cell therapies for lymphoid malignancy.