METHODS: This is a prospective cohort study, where cognitive assessments were done 1-day before surgery, at discharge, and during 6 weeks of follow-up. Sample size calculation, accounting for an estimated 20% dropout rate, determined a minimum of 170 subjects were required for the study. Reduction of MMSE score of more than 2.5 was considered as having POCD. Score differences between groups were analysed using T-test and analysis of variance (ANOVA), while consistency between tools was analysed using correlation and regression.
RESULTS: A total of 188 patients completed the study, with a POCD prevalence of 20.2% and 6.9% at discharge and at the 6 week follow up, respectively. All cognitive tools show a significant difference between preoperative and postoperative scores. All tests show a significant moderate correlation with MMSE.
CONCLUSIONS: In conclusion, it is imperative to employ a battery of cognitive assessments to evaluate cognitive changes comprehensively.
METHODS: Electronic health records were linked to echocardiography data between 2015 and 2021 from patients in Tayside, Scotland (population~450 000). Incident HF diagnosis was classified into inpatient or outpatient and stratified by ejection fraction (EF). A non-HF comparator group with normal left ventricular function was also defined. The primary outcome was time to cardiovascular death or hHF within 12 months of diagnosis.
RESULTS: In total, 5223 individuals were identified, 4231 with HF (1115 heart failure with reduced ejection fraction (HFrEF), 666 heart failure with mildly reduced ejection fraction, 1402 heart failure with preserved ejection fraction and 1048 HF with unknown EF) and 992 with non-HF comparators. Of the 4231 HF patients, 2169 (51.3%) were diagnosed as inpatients. The primary outcome was observed in 1193 individuals with HF (28.1%) and 32 (3.2%) non-HF comparators and was significantly more likely to occur in individuals diagnosed as inpatients than outpatients (809 vs 384 events; adjusted HR: 1.62 (1.39-1.89), p<0.001), and this was consistent regardless of EF. For HFrEF patients first diagnosed as inpatients, those discharged on ≥2 GDMT had a reduced incidence of the primary outcome compared with those discharged on <2 GDMT (303 vs 175 events; adjusted HR: 0.72 (0.55-0.94), p=0.016).
CONCLUSIONS: Individuals whose first presentation was a HF hospitalisation had a significantly worse outcome than those who were diagnosed in the community. Among hospitalised individuals, higher use of GDMT was associated with improved outcomes. Our results highlight the importance of improving diagnostic pathways to allow for earlier identification and treatment of HF.
RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells. By culturing rat pancreatic β-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic β-cells. We postulate that miR-15a, produced in pancreatic β-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic β-cell-specific miR-15a-/- mice.
INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications.
CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.
OBJECTIVE: The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.
METHODOLOGY: Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.
RESULTS: In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50 was predicted as 6.025 nM.
CONCLUSION: Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.