{"title":"Genetic and Inflammatory Predictors of Asthma: The Role of VDR and CaSR Genotypes in Risk Assessment and Management","authors":"Jie Li, Aiguo Dai, Ruicheng Hu, Chuangyu Huang","doi":"10.3138/cim-2024-2605","DOIUrl":"https://doi.org/10.3138/cim-2024-2605","url":null,"abstract":"Objective: This study investigates the predictive value and risk factors associated with different vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) genotypes in asthma. Methods: From December 2020 to February 2023, we studied 86 asthma patients and 70 healthy controls, analyzing VDR single nucleotide polymorphisms (SNPs) (rs1544410 and rs731236) and CaSR SNPs (rs1801726 and rs1042636) using DNA extracted from whole blood. We compared genotype distributions, demographic data, lung function parameters, vitamin D levels, and immune and inflammatory markers between the two groups. Results: The study group exhibited higher frequencies of VDR rs1544410 genotype TT and allele T, and CaSR rs1801726 genotype GG and allele G, but lower frequencies of CaSR rs1042636 genotype GG and allele G compared with controls ( p < 0.05). Additionally, patients in the study group showed elevated rates of family history/genetic predisposition, allergy history, smoking, and higher levels of neutrophils, interleukin (IL)-4, IL-6, IL-8, IL-10, IL-17, and interferon-gamma (IFN-γ). They also demonstrated lower levels of FEV1, FVC, PEFR, and 25-(OH)-D (P < 0.05). Logistic regression identified several factors, including specific genotypes, family history, and biomarker levels, as significant asthma risk factors. Conclusion: VDR rs1544410 and CaSR rs1801726 and rs1042636 may serve as potential diagnostic markers for asthma, highlighting their role in assessing genetic predisposition and disease severity.","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 3","pages":"18-26"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147897191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lina Liang, Xueli Yi, Chunfang Wang, Li Su, Guijiang Wei
{"title":"The Impact of miR-34a on Endothelial Cell Viability and Apoptosis in Ischemic Stroke: Unraveling the <i>MTHFR</i>-Homocysteine Pathway.","authors":"Lina Liang, Xueli Yi, Chunfang Wang, Li Su, Guijiang Wei","doi":"10.3138/cim-2024-2711","DOIUrl":"10.3138/cim-2024-2711","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p>","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 3","pages":"27-37"},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MohdWessam Al Jawhri, Salonee V Patel, Teija Bily, Yujin Suk, Robert X Lao
{"title":"Newsletter Fall 2024: Clinician Investigator Trainee Association of Canada (CITAC).","authors":"MohdWessam Al Jawhri, Salonee V Patel, Teija Bily, Yujin Suk, Robert X Lao","doi":"10.3138/cim-47-3-news","DOIUrl":"https://doi.org/10.3138/cim-47-3-news","url":null,"abstract":"","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 3","pages":"1-4"},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Application of CT Imaging Grading System in Upper Urinary Tract Calculi with Kidney Infection.","authors":"Jianping Zhang, Lingfeng Zhu, Xiaoxia Wu, Haiying Chen, Runyang Pan, Zihuang Hong, Rongkai Lin","doi":"10.3138/cim-2024-0107","DOIUrl":"10.3138/cim-2024-0107","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to establish a CT imaging grading system and explore its value in evaluating upper urinary tract calculi associated with kidney infections.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Patients with fever or diabetes had higher CT grades, and the following examination data revealed significant differences across the various CT grades (<i>P</i> < 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.</p><p><strong>Conclusions: </strong>The CT grade is directly associated with clinical symptoms and the risk of SIRS.</p>","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 3","pages":"7-17"},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Young Investigator Interview with CSCI Awardee, Dr. Kenneth Rockwood.","authors":"Salonee V Patel, Kenneth Rockwood","doi":"10.3138/cim-47-3-award","DOIUrl":"10.3138/cim-47-3-award","url":null,"abstract":"<p><p>[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.</p>","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 3","pages":"5-6"},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142331753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Teng Guo, Haoling Zhang, Yunpeng Luo, Xi Yang, Lidan Wang, Guangde Zhang
{"title":"Global Trends and Frontier in Research on Pancreatic Alpha Cells: A Bibliometric Analysis from 2013 to 2023.","authors":"Teng Guo, Haoling Zhang, Yunpeng Luo, Xi Yang, Lidan Wang, Guangde Zhang","doi":"10.3138/cim-2024-2744","DOIUrl":"10.3138/cim-2024-2744","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 2","pages":"23-39"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MohdWessam Al Jawhri, Salonee V Patel, Robert X Lao
{"title":"Spring 2024: Clinician Investigator Trainee Association of Canada (CITAC).","authors":"MohdWessam Al Jawhri, Salonee V Patel, Robert X Lao","doi":"10.3138/cim-2024-2740","DOIUrl":"https://doi.org/10.3138/cim-2024-2740","url":null,"abstract":"","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 2","pages":"1-3"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Teagan T Telesnicki, Andrea N Simpson, Charles de Mestral, Nancy N Baxter, David R Urbach, David Gomez
{"title":"Recommendations for Recovery of the COVID-19 Pandemic-related Diagnostic, Screening, and Procedure Backlog in Ontario: A Survey of Healthcare Leaders.","authors":"Teagan T Telesnicki, Andrea N Simpson, Charles de Mestral, Nancy N Baxter, David R Urbach, David Gomez","doi":"10.3138/cim-2024-2655","DOIUrl":"10.3138/cim-2024-2655","url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 2","pages":"4-11"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mimosa Luigi, Charles Yin, Ehsan Misaghi, Robert X Lao, Bryce J M Bogie, Jillian Macklin, Andy Zeng, Nicola Jones
{"title":"Training Outcomes and Satisfaction in Canadian MD/PhD and MD/MSc Programs: Findings from a National Survey.","authors":"Mimosa Luigi, Charles Yin, Ehsan Misaghi, Robert X Lao, Bryce J M Bogie, Jillian Macklin, Andy Zeng, Nicola Jones","doi":"10.3138/cim-2024-2714","DOIUrl":"10.3138/cim-2024-2714","url":null,"abstract":"<p><strong>Purpose: </strong>Despite the impact of physician-scientists on scientific discovery and translational medicine, several reports have signalled their declining workforce, reduced funding, and insufficient protected research time. Given the paucity of outcome data on Canadian MD/PhD programs, this study presents a national portrait of the sociodemographic characteristics, training trajectories, productivity, and satisfaction in trainees and alumni from Canadian MD/PhD and MD/MSc programs.</p><p><strong>Methods: </strong>Quantitative data were collected in a national survey launched in 2021. Respondents included 74 MD/PhD alumni and 121 trainees across 12 Canadian MD/PhD and MD/MSc programs.</p><p><strong>Results: </strong>Among MD/PhD alumni, 51% were independent practitioners/researchers while others underwent residency training. Most trainees (88%) were in MD/PhD programs. Significantly more alumni identified as men than did trainees. Significantly more alumni conducted clinical and health services research, while more trainees conducted basic science research. Average time to MD/PhD completion was 8 years, with no correlation to subsequent research outcomes. Self-reported research productivity was highest during MD/PhD training. Concerning training trajectories, most alumni completed residency, pursued additional training, and practised in Canada. Finally, regression models showed that trainees and alumni were satisfied with programs, with significant moderators in trainee models.</p><p><strong>Conclusion: </strong>Survey findings showed Canadian MD/PhD and MD/MSc programs recruit more diverse cohorts of trainees than before, provide productive research years, and graduate alumni who pursue training and academic employment in Canada. Both alumni and trainees are largely satisfied with these training programs. The need to collect in-depth longitudinal data on Canadian MD/PhD graduates to monitor diversity and success metrics is discussed.</p>","PeriodicalId":50683,"journal":{"name":"Clinical and Investigative Medicine","volume":"47 2","pages":"12-22"},"PeriodicalIF":1.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}