Expanding the Utilization of Formalin-Fixed, Paraffin-Embedded Archives : Feasibility of miR-Seq for Disease Exploration and Biomarker Development from Biopsies with Clear Cell Renal Cell Carcinoma

Novel predictive tools for clear cell renal cell carcinoma (ccRCC) are urgently needed. MicroRNAs (miRNAs) have been increasingly investigated for their predictive value, and formalin-fixed paraffin-embedded biopsy archives may potentially be a valuable source of miRNA sequencing material, as they remain an underused resource. Core biopsies of both cancerous and adjacent normal tissues were obtained from patients (n = 12) undergoing nephrectomy. After small RNA-seq, several analyses were performed, including classifier evaluation, obesity-related inquiries, survival analysis using publicly available datasets, comparisons to the current literature and ingenuity pathway analyses. In a comparison of tumour vs. normal, 182 miRNAs were found with significant differential expression; miR-155 was of particular interest as it classified all ccRCC samples correctly and correlated well with tumour size (R-2 = 0.83); miR-155 also predicted poor survival with hazard ratios of 2.58 and 1.81 in two different TCGA (The Cancer Genome Atlas) datasets in a univariate model. However, in a multivariate Cox regression analysis including age, sex, cancer stage and histological grade, miR-155 was not a statistically significant survival predictor. In conclusion, formalin-fixed paraffin-embedded biopsy tissues are a viable source of miRNA-sequencing material. Our results further support a role for miR-155 as a promising cancer classifier and potentially as a therapeutic target in ccRCC that merits further investigation.Peer reviewe

Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.publishedVersio

Tutors Matter: The Relationship between Medical Students’ Satisfaction from Their Tutor and Their Overall Satisfaction from Clinical Rotations

Background and Aim: Medical students are required to complete a number of clinical rotations in hospital departments, affiliated with the Azrieli Faculty of Medicine, under the supervision of a department tutor. Our experience shows that departments receiving good scores typically also receive good feedback for their tutor. Accordingly, our aim was to assess the tutor contribution to students’ overall satisfaction from clinical rotations in hospital departments across northern Israel. Methods: Here, we recorded the students’ reported satisfaction with tutors as well as the satisfaction with clinical rotations in different departments of Galilee Medical Center (GMC) in Naharia, and Baruch Padeh Medical Center in Poria. The students’ reported satisfaction was assessed numerically and verbally using questionnaires over a period of three years. Results: We find that the students reported satisfaction with a clinical rotation is positively and significantly correlated with the student satisfaction with the tutor, and less with other factors such as hospital organization and department facilities, geographical distance from home, working hours, etc. Conclusion: Our findings suggest that medical schools can increase students’ satisfaction through investment in good tutors