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Aim: The purpose of this study was to establish a mode of action for diosgenin against breast cancer employing a range of system biology tools and to corroborate its results with experimental facts.Methodology: The diosgenin-regulated domains implicated in breast cancer were enriched in the Kyoto Encyclopedia of Genes and Genomes database to establish diosgenin-protein(s)-pathway(s) associations. Later, molecular docking and the lead complexes were considered for molecular dynamics simulations, MMPBSA, principal component, and dynamics cross-correlation matrix analysis using GROMACS v2021. Furthermore, survival analysis was carried out for the diosgenin-regulated proteins that were anticipated to be involved in breast cancer. For gene expression analyses, the top three targets with the highest binding affinity for diosgenin and tumor expression were examined. Furthermore, the effect of diosgenin on cell proliferation, cytotoxicity, and the partial Warburg effect was tested to validate the computational findings using functional outputs of the lead targets.Results: The protein-protein interaction had 57 edges, an average node degree of 5.43, and a p-value of 3.83e-14. Furthermore, enrichment analysis showed 36 KEGG pathways, 12 cellular components, 27 molecular functions, and 307 biological processes. In network analysis, three hub proteins were notably modulated: IGF1R, MDM2, and SRC, diosgenin with the highest binding affinity with IGF1R (binding energy −8.6 kcal/mol). Furthermore, during the 150 ns molecular dynamics (MD) projection run, diosgenin exhibited robust intermolecular interactions and had the least free binding energy with IGF1R (−35.143 kcal/mol) compared to MDM2 (−34.619 kcal/mol), and SRC (-17.944 kcal/mol). Diosgenin exhibited the highest cytotoxicity against MCF7 cell lines (IC50 12.05 ± 1.33) µg/ml. Furthermore, in H2O2-induced oxidative stress, the inhibitory constant (IC50 7.68 ± 0.51) µg/ml of diosgenin was lowest in MCF7 cell lines. However, the reversal of the Warburg effect by diosgenin seemed to be maximum in non-cancer Vero cell lines (EC50 15.27 ± 0.95) µg/ml compared to the rest. Furthermore, diosgenin inhibited cell proliferation in SKBR3 cell lines more though.Conclusion: The current study demonstrated that diosgenin impacts a series of signaling pathways, involved in the advancement of breast cancer, including FoxO, PI3K-Akt, p53, Ras, and MAPK signaling. Additionally, diosgenin established a persistent diosgenin-protein complex and had a significant binding affinity towards IGF1R, MDM2, and SRC. It is possible that this slowed down cell growth, countered the Warburg phenomenon, and showed the cytotoxicity towards breast cancer cells.

Objectives: Objective of the present study was to translate and validate the Kidney Disease Quality of Life-Short form 1.2 (KDQOL-SF TM 1.2) questionnaire in Hindi language for use in Indian Hindi speaking patients with kidney stone. MethOds: Forward and backward translations were performed. Intermediate version of Hindi questionnaire was developed and was used for pilot study (n= 20). Modified final version after pilot study was used for validation study. Results: Questionnaire was administered to patients (n= 99) with kidney stone twice with an interval of four weeks. Cronbach alpha for total score was 0.71. For individual domains i.e. for the domain symptoms and kidney disease alpha value of 0.99 was gained, for the domain burden of kidney disease it was 0.79, for the domain effect of kidney disease on daily life it was 0.82, for the domain pain it was 0.99, for the domain physical functioning it was 0.91 and for the domain sexual function it was 0.99. No significant (p< 0.05) difference was observed in total score in test-retest analysis. cOnclusiOns: Translated Hindi Version of KDQOL-SF TM 1.2 showed good internal consistancy, test-retest reliability and linguistic validity. an outcome measure in interventional studies. Psychological distress is a subset of HRQoL that specifically evaluates the impact on mental health. In addition, social support and patients' perception of illness have been shown to predict all-cause mortality in ESRD patients. However, local data comparing PRO and social support in hemodialysis (HD) vs. peritoneal dialysis (PD) patients are lacking. Hence, the objective of this cross-sectional, observational study was to evaluate and compare patient-reported and laboratory outcomes in our multi-ethnic HD and PD patients. MethOds: Eligible chronic dialysis patients from National University Hospital were recruited. PRO measures include Kidney Disease Quality of Life-Short Form, EuroQoL-5 Dimensions and Kessler Psychological Distress Scale. Social support was assessed using Family Functioning Measure. Relevant sociodemographic information and medication list/laboratory parameters were captured using a pretested health services utilization questionnaire, and clinic notes/electronic medical records respectively. All data were analysed and compared between HD and PD patients using Stata version 10. Results: A total of 113 patients were recruited (HD: n= 81, PD: n= 32). There were no significant differences in HRQoL, social support, level of distress and most laboratory parameters between HD and PD patients. However, HD patients had significantly higher serum albumin levels (38.2±3.6 g/L vs. 32.5±4.5 g/L, p< 0.001) while PD patients had significantly higher serum corrected calcium levels (2.41±0.2 mmol/L vs. 2.27±0.2 mmol/L, p= 0.004) and number of medications (10.1±3.1 vs. 8.8±2.9, p= 0.039). cOnclusiOns: Barring cost and patient-specific factors, HD and PD are likely equivalent therapeutic options for ESRD patients in Singapore. However, the findings need to be confirmed in a larger study.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040 . 1