Clinical and Investigative Medicine最新文献

The 2024 Annual Joint Meeting (AJM) and Young Investigators' Forum of the Canadian Society for Clinical Investigation (CSCI) and Clinician Investigator Trainee Association of Canada (CITAC) was held on April 11, 2024, in Vancouver, British Columbia. Hosted in collaboration with the University of British Columbia (UBC) and the International Congress on Academic Medicine (ICAM), this meeting marked a significant opportunity for clinician investigator trainees to present their research and connect with national and international peers. The event included 70 trainees, consisting of 58 MD+ (MD/PhD, MD and PhD, MD-MSc, MD and MSc) and 12 Clinician Investigator Program and/or Surgeon-Scientist Training Program trainees. The keynote speaker, Dr. Marco Marra, delivered a presentation titled "From C. elegans Genetics to Precision Cancer Genomic Medicine, via the Human Genome Project: Reflections on a Collaborative Scientific Journey." Dr. Kenneth Rockwood (Dalhousie University) received the CSCI Distinguished Scientist Award, and Dr. Bertrand Routy (Université de Montréal) received the CSCI Joe Doupe Young Investigator Award. Over 60 abstracts were showcased, most of which are summarized in this review, and six were selected for oral presentations. Following the AJM, trainees participated in ICAM's three-day health research program, where three AJM attendees were recognized among the top four presenters and were invited to the 2024 Canada Gairdner Awards Gala, with one of our AJM attendees winning the competition and being named the next Lindau Nobel Laurate Meetings Nominee.

Introduction: Ischemic stroke (IS) is a global health concern, often tied to dyslipidemia and vascular endothelial dysfunction. MicroRNA-34a (miR-34a) was reported to be up-regulated in the blood samples of patients with IS, but the specific role of miR-34a and methylenetetrahydrofolate reductase (MTHFR) in IS remains to be elucidated.

Methods: We studied 143 subjects: 71 IS patients, and 72 healthy controls. Human umbilical vein endothelial cells (HUVECs) were cultured and transfected with a miR-34a mimic, inhibitor, or negative control. The miR-34a expression in serum and HUVECs was quantified via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Viability and apoptosis of HUVECs were assessed using CCK-8 assay and flow cytometry. The expression levels of bcl-2, bax, cyt-c, cleaved caspase 3, MTHFR, and homocysteine were measured by Western blot or enzyme-linked immunosorbent assay (ELISA). The relationship between miR-34a and MTHFR was verified by luciferase reporter assay. The levels of MTHFR and homocysteine in serum were examined by ELISA.

Results: MiR-34a expression was increased in IS patients and inhibited viability of HUVECs while promoting their apoptosis. Overexpression of miR-34a up-regulated pro-apoptotic proteins (bax, cyt-c and cleaved caspase 3) and down-regulated anti-apoptotic protein bcl-2 in HUVECs. MTHFR was identified as the downstream target of miR-34a and its expression was reduced by miR-34a overexpression, while homocysteine levels increased. Consistently, MTHFR levels were lower and homocysteine levels were higher in IS patients compared with controls.

Discussion: Our results suggest that up-regulated miR-34a plays a role in the pathogenesis of IS, potentially through inhibiting MTHFR expression and increasing homocysteine in endothelial cells. Therefore, miR-34a might be a therapeutic target for IS.

Purpose: This study aimed to establish a CT imaging grading system and explore its value in evaluating upper urinary tract calculi associated with kidney infections.

Methods: CT images of 126 patients with kidney infections caused by upper urinary tract calculi were retrospectively analyzed. The CT grading system was developed based on CT images. CT images were classified into 4 grades. General information, symptoms, and clinical findings of patients in different CT grades were analyzed. With the occurrence of systemic inflammatory response syndrome (SIRS) as the endpoint, univariate and multivariate analysis was conducted to analyze the risk factors of SIRS.

Results: Patients with fever or diabetes had higher CT grades, and the following examination data revealed significant differences across the various CT grades (P < 0.05): the white blood cell count, urine leucocytes count, CT1, CT2, maximum body temperature, duration of disease, the proportion of blood neutrophils, the size of stones, and levels of the C-reactive protein and procalcitonin. Only CT grading was statistically significant after multivariate analysis. According to the values of the partial regression coefficient (B), the higher the CT grade, the greater the risk of SIRS. The risk of SIRS was 4.472 times higher with each increment of the CT grade.

Conclusions: The CT grade is directly associated with clinical symptoms and the risk of SIRS.

[Figure: see text] Dr. Kenneth Rockwood is a Professor of Medicine in the Division of Geriatric Medicine and Neurology and Clinical Research Professor of Frailty and Aging at Dalhousie University, as well as an actively practising geriatric physician. Dr. Rockwood has made significant contributions to geriatric medicine and research, including his involvement in developing the Clinical Frailty Scale. He has been recognized with countless prestigious awards, the most recent being the Distinguished Scientist Award from the Canadian Society for Clinical Investigation.

Purpose: Over the past 20 years, much of the research on diabetes has focused on pancreatic beta cells. In the last 10 years, interest in the important role of pancreatic alpha cells in the pathogenesis of diabetes, which had previously received little attention, has grown. We aimed to summarize and visualize the hotspot and development trends of pancreatic alpha cells through bibliometric analysis and to provide research direction and future ideas for the treatment of diabetes and other islet-related diseases.

Methods: We used two scientometric software packages (CiteSpace 6.1.R6 and VOSviewer1.6.18) to visualize the information and connection of countries, institutions, authors, and keywords in this field.

Results: A total of 532 publications, published in 752 institutions in 46 countries and regions, were included in this analysis. The United States showed the highest output, accounting for 39.3% of the total number of published papers. The most active institution was Vanderbilt University, and the authors with highest productivity came from Ulster University. In recent years, research hotspots have concentrated on transdifferentiation, gene expression, and GLP-1 regulatory function. Visualization analysis shows that research hotspots mainly focus on clinical diseases as well as physiological and pathological mechanisms and related biochemical indicators.

Conclusions: This study provides a review and summary of the literature on pancreatic alpha cells through bibliometric and visual methods and shows research hotspot and development trends, which can guide future directions for research.

Purpose: The COVID-19 pandemic has resulted in a significant diagnostic, screening, and procedure backlog in Ontario. Engagement of key stakeholders in healthcare leadership positions is urgently needed to inform a comprehensive provincial recovery strategy.

Methods: A list of 20 policy recommendations addressing the diagnostic, screening and procedure backlog in Ontario were transformed into a national online survey. Policy recommendations were rated on a 7-point Likert scale (strongly agree to strongly disagree) and organized into those retained (≥75% strongly agree to somewhat agree), discarded (≥80% somewhat disagree to strongly disagree), and no consensus reached. Survey participants included a diverse sample of healthcare leaders with the potential to impact policy reform.

Results: Of 56 healthcare leaders invited to participate, there were 34 unique responses (61% response rate). Participants were from diverse clinical backgrounds, including surgical subspecialties, medicine, nursing, and healthcare administration and held institutional or provincial leadership positions. A total of 11 of 20 policy recommendations reached the threshold for consensus agreement with the remaining 9 having no consensus reached.

Conclusion: Consensus agreement was reached among Canadian healthcare leaders on 11 policy recommendations to address the diagnostic, screening, and procedure backlog in Ontario. Recommendations included strategies to address patient information needs on expected wait times, expand health and human resource capacity, and streamline efficiencies to increase operating room output. No consensus was reached on the optimal funding strategy within the public system in Ontario or the appropriateness of implementing private funding models.