Clinical and Investigative Medicine最新文献

Background: MD-PhD programs play a critical role in training the next generation of clinician-scientists in Canada. However, since 2015, these programs have faced increasing financial pressures. This review examines the impact of cost-cutting measures on Canadian MD-PhD programs and their implications for equity, diversity, and inclusion initiatives in the Canadian context.

Methods: Using a mixed-methods approach, we analyzed funding structures across all 11 Canadian MD-PhD programs and compared them with 120 U.S. MD-PhD programs using publicly available data.

Results: Eighteen percent of Canadian MD-PhD programs (2 of 11) offer full funding, compared to 43% (52 of 120) of U.S. programs. Canadian MD-PhD applicants from two provinces (British Columbia and Ontario) have access to fully funded in-catchment programs (49% of Canada's population). By contrast, U.S. MD-PhD applicants from 31 states have access to fully funded in-catchment programs through Medical Scientist Training Programs (MSTPs) (85% of the U.S. population). Canadian MD-PhD programs have a more uneven geographical distribution and funding landscape than those in the United States, limiting accessibility for Canadian students from underrepresented and lower socioeconomic backgrounds.

Conclusions: Despite recent increases in diversity among MD-PhD trainees, financial constraints threaten to reverse these gains, reducing opportunities for historically marginalized groups. This review highlights the need for renewed provincial and federal investment in MD-PhD training. Without targeted policy and funding supports, the sustainability of Canadian MD-PhD programs-and the future of Canada's clinician-scientist training pipeline-remains uncertain. Addressing these challenges is essential to maintaining Canada's global competitiveness in medical and scientific innovation and ensuring that clinician-scientist leadership reflects the diversity of the patient populations they serve.

Objective: This study investigates the protective effects of AU-rich element RNA-binding protein 1 (AUF1) on retinal ganglion cells (RGCs) in a model of retinal injury, focusing on its interaction with the nuclear factor erythroid 2-related factor 2 / heme oxygenase-1 (Nrf2/HO-1) signalling pathway.

Methods: Using a combination of histological, molecular, and flow cytometry analyses, we evaluated retinal thickness, apoptosis, and gene/protein expression in four experimental groups: one control, one model, and 2 intervention groups-AUF1 and AUF1+Nrf2/HO-1 inhibitor.

Results: The results revealed that compared to the control group, the model group and the AUF1+Nrf2/HO-1 inhibitor group exhibited significant retinal damage, characterized by reduced retinal thickness and increased RGC apoptosis. Notably, the AUF1 intervention group showed a marked increase in retinal thickness and a significant reduction in RGC apoptosis, indicating that AUF1 overexpression protects RGCs from ischemic injury. Further analysis through Western blotting and quantitative real-time reverse transcription polymerase chain reaction demonstrated that AUF1 overexpression led to increased expression of Nrf2 and HO-1 proteins and mRNA, while inhibition of the Nrf2/HO-1 pathway reversed these effects.

Conclusion: These findings suggest that AUF1 mediates its protective effects through activation of the Nrf2/HO-1 pathway, offering a potential therapeutic target for retinal diseases involving RGC apoptosis. This study provides novel insights into the molecular mechanisms by which AUF1 regulates retinal cell survival and highlights the importance of the Nrf2/HO-1 signalling axis in retinal protection.

Background: Kawasaki disease (KD) is an acute vasculitis in children, and the resultant inflammatory process can lead to coronary artery aneurysms. The study aimed to investigate the role of 25-hydroxyvitamin D₃ (25-OH-D₃), a stable circulating form of vitamin D₃, in KD mouse models.

Methods: The KD mouse model was established through intraperitoneal injection of 500 μg Lactobacillus casei cell wall extract (LCWE). 25-OH-D₃ was intraperitoneally injected to mice before and after LCWE injection. The mice were euthanized 7, 14, or 28 days after LCWE injection. Hematoxylin-eosin staining was performed to observe inflammation in mouse coronary artery tissues. ELISA was conducted to assess serum levels of inflammatory cytokines (tumour necrosis factor α and interleukin-1 beta ). Aorta areas and maximal aorta diameters were measured. Western blotting was performed to measure factors involved in JAK1/STAT3 and TLR4 signalling pathways.

Results: LCWE caused inflammatory cell infiltration in mouse coronary arteries, leading to high heart vessel inflammation scores, coronary artery lesion scores, and inflammatory cytokine levels within 28 days. In addition, LCWE induced the development of abdominal aorta aneurysms and dilatations. 25-OH-D₃ exerted a protective role in the KD mouse model by inhibiting coronary artery lesions and inflammation. Moreover, 25-OH-D₃ suppressed LCWE-induced activation of the JAK1/STAT3 and TLR4 pathways in coronary artery tissues.

Conclusion: 25-OH-D₃ ameliorates LCWE-induced coronary artery lesions and inflammation in mice by inhibiting the JAK1/STAT3 and TLR4 pathways.

The 16th annual Leaders in Medicine (LIM) Research Symposium was held in person at the Health Sciences Centre in Calgary on November 15, 2024. The event featured a keynote address by Dr. Bryan Yipp, titled "Medically Trained Scientists: Fueling Healthcare Revolutions." Dr. Yipp is a clinician-scientist and a graduate of the LIM program. A workshop on "Integrating Anti-Racism, Equity, Diversity, and Inclusion into Health Research and Practise" was presented by Dr. Bukola Salami, Vice President of the Canadian Nurses Association and a board member of the Black Opportunity Fund. Dr. Salami is a Full Professor in the Department of Community Health Sciences at the University of Calgary. Over eighty 80 students presented their research in the poster and oral presentation sessions. Abstracts included represented an incredible diversity of research areas, including biochemistry and molecular biology, biomedical technology and precision health, community health sciences and health services, medical sciences, and neurosciences. The symposium highlighted the incredible remarkable research accomplishments of LIM students and medical students at the University of Calgary.

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Objective: To investigate the value of serum ferritin (SF) in conjunction with glycated hemoglobin (HbA_1c) for the early prediction of gestational diabetes mellitus (GDM) and to provide insights that could enhance health care standards for women and newborns.

Methods: A retrospective cohort study was conducted involving 650 pregnant women who received regular prenatal check-ups at our institution from January 2019 to April 2024. Participants were categorized into four groups based on their SF concentration quartiles during the 11th to 13th weeks of gestation. Logistic regression analyses were conducted to assess the predictive value of early GDM risk factors, with the lowest quartile group serving as a reference.

Results: The incidence rate of GDM rose progressively with increasing SF concentrations at 11-13 weeks of gestation, with rates of 18.79%, 21.25%, 24.38%, and 25.45% respectively. Notably, the incidence rate in the highest quartile group (quartile 4) was significantly higher compared to the lowest (quartile 1), with an odds ratio of 1.48 and a 95% confidence interval of 1.12 to 1.93. Additionally, the predictive model incorporating both SF concentration and HbA_1c (Model 2) outperformed the model with SF alone (Model 1), indicating a heightened predictive accuracy for GDM when these two biomarkers are used in combination.

Conclusion: The findings of this study highlight the potential utility of SF and HbA_1c as early predictors of GDM risk, especially when employed in combination.

Purpose: Cardiac hypertrophy is a critical contributor to heart failure. Therapies that effectively manage cardiac hypertrophy are still inadequate. Crocin is a natural component of saffron, and its beneficial properties have been previously documented. This study aimed to investigate the role of crocin in cardiac hypertrophy and apoptosis and its related mechanisms.

Methods: Sprague-Dawley rats were infused with angiotensin II (Ang II; 520 ng/kg/min) or normal saline and then intraperitoneally injected with crocin (40 mg/kg) or dimethyl sulfoxide for 4 weeks. Systolic and diastolic blood pressure were recorded. Cardiac hypertrophy was evaluated by echocardiography, heart weight, hematoxylin-eosin staining, TUNEL assay, and gene expression. For in vitro studies, H9C2 cells were treated with Ang II (1 μM) for 48 hours to induce cardiac hypertrophy-like conditions. An immunofluorescence assay was used for [Formula: see text]-actinin staining. reverse transcription quantitative real-time polymerase chain reaction was performed to measure the expression of hypertrophic markers, and western blotting was used to detect apoptosis and underlying mechanisms.

Results: Our findings revealed that crocin attenuated diastolic dysfunction, cardiac hypertrophy, and apoptosis caused by Ang II in vivo. Additionally, crocin prevented Ang II-stimulated cardiomyocyte enlargement and apoptosis in vitro. Mechanistically, crocin induced AMP-activated protein kinase (AMPK)[Formula: see text] activation and mTOR/p70S6K inhibition in cellular and animal models of cardiac hypertrophy. Moreover, AMPK inhibition abolished the anti-hypertrophic effect of crocin in vitro, while mTOR inhibition enhanced the protective effect of crocin against Ang II-induced cardiomyocyte hypertrophy.

Conclusion: This study demonstrates that crocin can ameliorate Ang II-stimulated cardiac hypertrophy in vivo and in vitro by regulating AMPK[Formula: see text]/mTOR/ p70S6K signalling.