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The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS. This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections. Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for β-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD. These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under β-blockers. This may inform secondary prevention strategies and trial design for CeAD. [Display omitted] [ABSTRACT FROM AUTHOR]

Machine learning that is the vital part of modern artificial intelligence was used to classify the potential effects of two drugs on induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM). Peak data were detected from calcium transient signals of cycling iPSC-CMs first at baseline, second exposed to adrenaline and third exposed with one of the drugs either flecainide or carvedilol. Various machine learning classification tests were executed to evaluate whether a drug did or did not affect signal shape after exposing adrenaline or the drugs. According to our classification results, machine learning can be applied to analyze possible effects of drugs on induced pluripotent stem cell-derived cardiomyocytes derived from the catecholaminergic polymorphic ventricular tachycardia patients’ cell samples.

Background: Alzheimer’s disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer’s properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet’s test, p

This is the cardiodynamic evaluation of a single ascending dose study in healthy participants with the primary objective of assessing the effect of ANAVEX3‐71, formerly AF710B, on ECG parameters. Twelve‐lead ECGs were obtained at 3 time points within 1 hour prior to dosing to establish a baseline and then serially postdose. Concentration–QTc analysis of plasma concentrations of ANAVEX3‐71 and metabolite M8 was conducted. ANAVEX3‐71 at the studied doses did not have a clinically relevant effect on heart rate or on the PR and QRS intervals. ANAVEX3‐71 alone was retained in the primary model due to small fit differences between models which included the metabolite M8. The estimated population slope of the concentration–QTcF relationship was small and slightly negative: −0.017 ms per µg/L, with a small treatment effect‐specific intercept of −0.49 ms. An effect on the placebo‐corrected, change‐from‐baseline QTc exceeding 10 ms can be excluded within the full observed ranges of plasma concentrations of ANAVEX3‐71 and M8 up to ∼996 and ∼58 µg/L, respectively. The results from this cardiodynamic evaluation demonstrated that ANAVEX3‐71 at single ascending doses of 5‐200 mg had no clinically relevant effects on any of the studied ECG parameters. [ABSTRACT FROM AUTHOR]