Clinical and Investigative Medicine最新文献

The 2022 Annual Joint Meeting (AJM) and Young Investigators' Forum of the Canadian Society for Clinical Investigation / Société Canadienne de recherches clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) was held in Montréal, November 13-14, 2022. The theme of this year's AJM was "Strength in Perseverance" and focused on highlighting clinician-investigator trainee achievements and resilience in research engagement through recent challenging and unprecedented times. The opening remarks were given by Nicola Jones (president of CSCI/SCRC) and Heather Whittaker (past president of CITAC/ACCFC). The keynote speaker was Dr. Michael Strong, who delivered the presentation "The Future of Clinician Scientists in Canada." Dr. Caroline Quach (Université de Montréal) received the CSCI Distinguished Scientist Award and Dr. Amy Metcalfe (University of Calgary) received the CSCI Joe Doupe Young Investigator Award. Each of the clinician-scientists delivered presentations on their award-winning research. The four interactive workshops included "Social Media in Science and Medicine," "Diversity in Science and Medicine," "Running a Successful Research Program," and "Mentorship in Action." The AJM also included presentations from clinician investigator trainees from across the country. Over 90 abstracts were showcased at this year's meeting, most of which are summarized in this review. Six outstanding abstracts were selected for oral presentations during the President's Forum.

Background: Stroke is a major contributor to disability and death worldwide. Studies have demonstrated that inflammasome/pyroptosis and its mediated inflammatory response are important factors aggravating brain injury after stroke. We aimed to investigate and map the knowledge structure and global trends on inflam- masome/pyroptosis in stroke.

Methods: All relevant documents were obtained from the Web of Science on 5 June 2023. Bibliometric visualization diagrams were created using VOSviewer and CiteSpace. Excel was used for statistical analysis and drawing graphs.

Results: A total of 1106 publications were included, with more articles published each year, especially since 2014. China (740 papers), Zhejiang University (57 papers), Wang J (25 papers), and the Journal of Neuroinflammation (45 papers) were the most productive countries, institutions, authors, and journals, respectively. The United States was the country with highest centrality (0.56) and total link strength (171), and all of the top 10 institutions were in China. China and the U.S. cooperated closely. The centralities of the top 10 authors were all lower than 0.01; no leader has yet emerged in this field. "NLRP3 inflammasome" ranked first with 447 occurrences among 2136 keywords, of which 56 terms appeared more than 10 times when categorized into four clusters: cluster 1 (inflammation), cluster 2 (pyroptosis), cluster 3 (NLRP3 inflammasome), and cluster 4 (neuroinflammation). The studies focused on the mechanisms of inflammasome/pyroptosis in stroke were mainly limited to cell and animal experiments.

Conclusion: Interest in inflammasome/pyroptosis in stroke is progressively increasing. The NLRP3 inflammasome is the most extensively studied and has been a research hotspot. The mechanisms of cell death in stroke are complex and future studies are needed to strengthen the clinical research on the relationship between pyroptosis-related processes and stroke, determine at which stage NLRP3 inflammasome activation, and clarify the detailed mechanism of NLRP3 in stroke.

Background: H19 is the first long noncoding RNA (lncRNA) found to be associated with gene imprinting. It is highly expressed in the embryonic stage and may have important regulatory effects on human embryonic development. We investigated the differences between the levels of H19 promoter DNA methylation in the chorionic villi of patients who experienced spontaneous abortion (SA) following in vitro fertilization embryo transfer (IVF-ET) and those of patients with a normal early pregnancy (NEP). We also analyzed the associated DNA methyltransferase (DNMT) activity.

Methods: Chorionic villus tissue from patients with SA and NEP were collected. The DNA methylation levels of two CpG islands in the promoter region of the H19 gene in the two groups were detected by bisulfite sequencing, and the mRNA expression of DNMTs was analyzed by real-time polymerase chain reaction.

Results: The sample size of each group was 32, and there were no significant differences in baseline data, including age, parity, and body mass index, between the two groups. Among the 7 CpG islands measured, the methylation rates of 3 CpG islands (CpG 1, 6, and 7) were significantly lower in the SA group than in the NEP group (P < 0.01). The methylation levels of the other 4 CpG islands were not significantly different between the two groups. There were no differences in the expression of DNMT1 between the two groups (P > 0.05), but DNMT3a and DNMT3b RNA levels were significantly lower in SA group than in the NEP group (P < 0.01).

Conclusions: The lower H19 promoter DNA methylation levels found in the chorionic villi of patients with SA patients following IVF-ET may be explained by decreased expression of DNMT3a and DNMT3b.

This has been a great first half of the year for CITAC-ACCFC (Clinician Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada)! We are looking forward to our new members joining us in the fall and welcoming back our previous members after the summer.

Purpose: The hyperinflammatory response is one of the main complications associated with novel coronavirus disease 2019 (COVID-19), and there is no effective treatment for cytokine storm. Therefore, it is important to investigate the key genes associated with severity of the disease.

Methods: In this study, we used a microarray data set to analyze the key genes associated with severe illness in patients with COVID-19. The proportion of immune cells was determined using the CIBERSORT algorithm. The key genes were further verified by detecting the levels of cytokines and chemokines in the serum of patients. Additionally, macrophages were stimulated with SARS-CoV-2 spike protein and chemokine ligand (CCL) 2. The expression of cytokines, ERK1/2, and NF-κB in macrophages was detected.

Results: Four hub genes were identified. Among them, C-C motif chemokine receptor 2 (CCR2) was an upregulated hub gene, while killer cell lectin-like receptor subfamily K member 1 (KLRK1), macrophage colony-stimulating factor receptor (CSF1R), and CD3D human recombinant protein (CD3D) were downregulated genes. Immune cell type identification found that the proportion of monocytes was higher in patients with severe COVID-19 than that in controls. Moreover, levels of CCL2 were significantly higher in patients with COVID-19. When stimulated with SARS-CoV-2 S protein and CCL2, macrophages secreted more inflammatory cytokines. The expression level of ERK1/2 was elevated.

Conclusions: These results suggested that S protein and CCL2 may mediate macrophage inflammatory responses through the ERK1/2 signaling pathway. This study provides a basis for clinical treatment and improves the prognosis of critically ill patients with COVID-19.

Dr. Caroline Quach-Thanh is a Professor in the Departments of Microbiology, Infectious Diseases and Immunology and of Pediatrics at University of Montreal. She is in charge of Infection Prevention and Control at CHU Sainte-Justine where she works as a pediatric infectious diseases specialist and medical microbiologist. Dr. Quach is a clinician-scientist and the Canada Research Chair, Tier 1 in Infection Prevention and Control. In 2022, Dr. Quach-Thanh received the Distinguished Scientist Award 2022 from the Canadian Society for Clinical Investigation. In the same year, she received a Women of Distinction Award-for public service-from the Women's Y Foundation. Dr. Quach-Thanh is the former president from the Association for Medical Microbiology and Infectious Diseases Canada (AMMI), a past Chair of the National Advisory Committee on Immunization (NACI) and is the current chair of the Quebec Immunization Committee. She was named Fellow of the Canadian Academy of Health Sciences and of the Society for Healthcare Epidemiology of America. Dr. QuachThanh was selected as one of the 2019 most Powerful Women in Canada. In 2021, she received the Order of Merit from Université de Montréal and was made Officière de l'Ordre national du Québec in 2022.

Purpose: This research investigated the utility of a QR code-based video pharmaceutical education program to guide the proper use of the inhalation device in elderly chronic obstructive pulmonary disease (COPD) patients.

Methods: The patients were recruited for this prospective study during a COPD hospitalization, with 96 patients in the control group (CG) receiving conventional hospital care and 93 patients in the intervention group (IG) receiving QR code-based video pharmaceutical education from hospitalization to six months after discharge to improve proper utilization of inhalation technology The outcome measures used to assess the effectiveness of the education program were the COPD Assessment Test (CAT), inhaler use accuracy, inhaler technique score, Beliefs about Medicines Questionnaire (BMQ) score and patient satisfaction.

Results: Compared with CG, inhaler use accuracy and inhaler use scores improved in the IG group, while BMQ-Concern and CAT scores were significantly lower (P<0.05). Improvements in patient quality-of-life and satisfaction were reported.

Conclusions: This study revealed that the QR code-based video pharmaceutical education program can improve the quality of life and satisfaction of elderly COPD patients.

Purpose: To compare uric acid levels in children with Henoch-Schonlein purpura (HSP)without nephritis and with renal damage, and at different pathological grades.

Methods: A total of 451 children were enrolled in this study, including 64 with HSP without nephritis and 387 HSP with kidney damage. Age, gender, uric acid, urea, creatinine and cystatin C levels were reviewed. Pathological findings of those with renal impairment were also reviewed.

Results: Among the HSP children with renal damage, 44 were grade I, 167 were grade II and 176 were grade III. There were significant differences in age, uric acid, urea, creatinine and cystatin C levels between the two groups (p<0.05, all). Correlation analysis showed that uric acid levels in children with HSP without nephritis were positively correlated with urea and creatinine levels (p<0.05). Uric acid levels in HSP children with renal damage was positively correlated with age, urea, creatinine and cystatin C levels (p<0.05, all). Regression analysis found that, without adding any correction factors, there were significant differences in uric acid levels between the two groups; however, after adjusting for pathological grade, there was no longer a significant difference.

Conclusions: There were significant differences of uric acid levels in children with HSP without nephritis and with renal impairment. Uric acid levels in the renal impairment group were significantly higher than that in the HSP without nephritis group. Uric acid levels were related to only the presence or absence of renal damage, not to the pathological grade.

Dr. Amy Metcalfe is an Associate Professor in the Departments of Obstetrics and Gynecology, Medicine, and Community Health Sciences at the University of Calgary. She is also the Maternal and Child Health Program Director with the Alberta Children's Hospital Research Institute. Dr. Metcalfe's training is a perinatal epidemiologist whose research broadly focuses on the management of chronic illness during pregnancy, and how events in pregnancy impact women's health and wellbeing throughout the life course. Current major projects include co-leading the P3 Cohort study (https://p3cohort.ca), a longitudinal pregnancy cohort study, and the GROWW (Guiding interdisciplinary Research On Women's and girls' health and Wellbeing) Training Program (https://www.growwprogram.com).

Purpose: Women have traditionally been underrepresented in MD and MD-PhD training programs. Here, we describe the changing demographics of an MD-PhD Program over three distinct time intervals.

Methods: We designed a 64-question survey and sent it to 47 graduates of the McGill University MD-PhD program in Montréal, Québec, Canada, since its inception in 1985. We also sent a 23-question survey to the 24 students of the program in 2021. The surveys included questions related to demographics, physician-scientist training, research metrics, as well as academic and personal considerations.

Results: We collected responses from August 2020 to August 2021 and grouped them into three intervals based on respondent graduation year: 1995-2005 (n = 17), 2006-2020 (n = 23) and current students (n = 24). Total response rate was 90.1% (n = 64/71). We found that there are more women currently in the program compared to the 1995-2005 cohort (41.7% increase, p<0.01). In addition, women self-reported as physician-scientists less frequently than men and reported less protected research time.

Conclusions: Overall, recent MD-PhD alumni represent a more diverse population compared with their earlier counterparts. Identifying barriers to training remains an important step in ensuring MD-PhD trainees become successful physician-scientists.