Surpass Evolve Flow Diverter for the Treatment of Intracranial Aneurysm: A Systematic Review.

PURPOSE: This systematic review aims to summarize the evidence investigating the effectiveness and safety of the Surpass Evolve-Flow Diverter (SE-FD) to treat brain aneurysms. METHOD: We searched MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane Library from January 2019 to 29 March 2022. Terms related to the "intracranial aneurysm" and "surpass evolve flow diverter" concepts were used to search the databases; Medical Subject Headings (MeSH) and reference hand search were also utilized. RESULTS: The searches primarily identified 1586 documents. A total of five studies (four case series and one cohort) were included in this review. In the included studies, 192 (74 male and 118 females) patients with 198 aneurysms were involved. In total, 153 SE-FDs were used to treat 145 aneurysms. Complete occlusion was achieved in 69/145 (48%) cases and near-complete occlusion in 24/145 (17%) cases from aneurysms treated with SE-FD. Reported postoperative complications included stent thrombosis (n = 4 patients), hemorrhage (n = 5 patients), ischemia (n = 9 patients), and neurological complications (n = 12 patients). In total, four deaths were reported with only one related to the SE-FD procedure. CONCLUSION: The results of this review are based on observational data, due to the absence of clinical trials. The findings of the included studies suggest that the effectiveness of the SE-FD procedure is lower than previous FDs but the safety is similar. The included studies also suggested that SE-FD has navigability and resistance to twisting, which makes the procedure an easier method to treat aneurysms that are proximal and distal to the circle of Willis deployment. This review highlights the urgency to conduct clinical trials to confirm these suggestions.

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis.

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.

Genetic Studies of Metabolic Syndrome in Arab Populations: A Systematic Review and Meta-Analysis.

Background: The metabolic syndrome (MetS) is prevalent in Arabian populations. Several small-scale studies have been performed to investigate the genetic basis of MetS. This systematic review and meta-analysis aimed to examine whether candidate gene polymorphisms are associated with MetS susceptibility among ethnic groups of the Arabian world and to suggest possible directions for future research regarding genetic markers and MetS. Methods: A search was conducted for peer-reviewed articles that examined the genetic association of MetS in Arabian populations in the following databases: Medline, Embase, Scopus, Direct Science, Web of Science, ProQuest, and Google Scholar until March 31, 2021. Articles were eligible if they were case-control studies, which investigated MetS as a dichotomous outcome (MetS vs no MetS). To assess the quality of the studies, the Q-Genie tool (Quality of Genetic Association Studies) was used. A non-central chi2 (random-effect) distribution was used to determine the heterogeneity (H) of Q and I (Galassi et al., The American journal of medicine, 2006, 119, 812-819) statistics. Results: Our search strategy identified 36 studies that met our inclusion criteria. In most cases, studies were excluded due to a lack of statistical information such as odds ratios, confidence intervals, and p-values. According to the Q-Genie tool, 12 studies scored poorly (a score of≤35), 13 studies scored moderately ( >35 and≤45), and 12 studies had good quality ( >45 or higher). The most frequently studied genes were FTO and VDR (both included in four studies). Three SNPs indicated increased risk for MetS after calculating the pooled odds ratios: FTO-rs9939609 (odds ratio 1.49, 95% CI: 0.96-2.32); LEP-rs7799039 (odds ratio 1.85, 95% CI: 1.37-2.5); and SERPINA12-rs2236242 (odds ratio 1.65, 95% CI: 1.21-2.24). Meta-analysis studies showed no significant heterogeneity. Conclusion: There were many sources of heterogeneity in the study settings. Most of the studies had low to moderate quality because of sample size and power issues, not considering all potential sources of bias, and not providing details about genotyping methods and results. As most studies were small-scale, aimed to replicate findings from other populations, we did not find any unique genetic association between MetS and Arabian populations.

Heart Rate Variability Indices as Possible Biomarkers for the Severity of Post-traumatic Stress Disorder Following Pregnancy Loss.

Background: Psychological distress, such as posttraumatic stress disorder (PTSD), is commonly evaluated using subjective questionnaires, a method prone to self-report bias. The study's working hypothesis was that levels of autonomic dysfunction determined by heart rate variability (HRV) measures are associated with the severity of PTSD in women following pregnancy loss. Methods: This was an observational prospective cohort study with 53 patients enrolled. The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) PTSD scale (PCL-5) was used to assess the severity of PTSD in women after pregnancy loss. The cardiac autonomic function was assessed using HRV measurements during a deep breathing test using an HRV scanner system with wireless ECG enabling real-time data analysis and visualization. HRV measures were: standard deviation (SD) of normal R-R wave intervals [SDNN, ms], square root of the mean of the sum of the squares of differences between adjacent normal R wave intervals [RMSSD, ms], and the number of all R-R intervals in which the change in consecutive normal sinus intervals exceeds 50 milliseconds divided by the total number of R-R intervals measured [pNN50 = (NN50/n-1)*100%] [pNN50%]. Results: The PCL-5 scores had a statistically significant association with HRV indices (SDNN; RMSSD, and pNN50%). Patients with PTSD had similar mean heart rate values as compared to patients without PTSD (PCL-5), but significantly higher SDNN [median[IQR, interquartile range]: 90.1 (69.1-112.1) vs. 52.5 (36.8-65.6)], RMSSD [59.4 (37.5-74.9) vs. 31.9 (19.3 - 44.0)], and PNN50% values [25.7 (16.4-37.7) vs. 10.6 (1.5-21.9)]. The SDNN of the deep breathing test HRV was effective at distinguishing between patients with PTSD and those without, with an AUC = 0.83 +/- 0.06 (95 % CI 0.94, p = 0.0001) of the ROC model. Conclusions: In this study, HRV indices as biomarkers of cardiac dysautonomia were found to be significantly related to the severity of PTSD symptoms in women after pregnancy loss.

Structural insights into the polypharmacological activity of quercetin on serine/threonine kinases.

Polypharmacology, the discovery or design of drug molecules that can simultaneously interact with multiple targets, is gaining interest in contemporary drug discovery. Serine/threonine kinases are attractive targets for therapeutic intervention in oncology due to their role in cellular phosphorylation and altered expression in cancer. Quercetin, a naturally occurring flavonoid, inhibits multiple cancer cell lines and is used as an anticancer drug in Phase I clinical trial. Quercetin glycosides have also received some attention due to their high bioavailability and activity against various diseases including cancer. However, these have been studied to a lesser extent. In this study, the structural basis of the multitarget inhibitory activity of quercetin and isoquercitrin, a glycoside derivative, on serine/threonine kinases using molecular modeling was explored. Structural analysis showed that both quercetin and isoquercitrin exhibited good binding energies and interacted with aspartate in the highly conserved Asp-Phe-Gly motif. The results indicate that isoquercitrin could be a more potent inhibitor of several members of the serine/threonine kinase family. In summary, the current structural evaluation highlights the multitarget inhibitory property of quercetin and its potential to be a chemical platform for oncological polypharmacology.