Regioselective iodination of aryl amines using 1,4-dibenzyl-1,4-diazoniabicyclo [2.2.2] octane dichloroiodate in solution and under solvent-free conditions

1,4-Dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate is an efficient and regioselective reagent for iodination of aryl amines. A wide variety of aryl amines in reaction with this reagent afforded regioselectively iodinated products. The iodination reaction can be carried out in solution or under solvent-free condition at room temperature. KEY WORDS:  Regioselective iodination, Aryl amines, 1,4-Dibenzyl-1,4-diazoniabicyclo [2.2.2] octane dichloroiodate,  Solvent-free conditions Bull. Chem. Soc. Ethiop. 2015, 29(1), 157-162DOI: http://dx.doi.org/10.4314/bcse.v29i1.1

Systolic blood pressure, chronic obstructive pulmonary disease and cardiovascular risk

\ua9 2023 Author(s) (or their employer(s)). Objective: In individuals with complex underlying health problems, the association between systolic blood pressure (SBP) and cardiovascular disease is less well recognised. The association between SBP and risk of cardiovascular events in patients with chronic obstructive pulmonary disease (COPD) was investigated. Methods: and analysis In this cohort study, 39 602 individuals with a diagnosis of COPD aged 55-90 years between 1990 and 2009 were identified from validated electronic health records (EHR) in the UK. The association between SBP and risk of cardiovascular end points (composite of ischaemic heart disease, heart failure, stroke and cardiovascular death) was analysed using a deep learning approach. Results: In the selected cohort (46.5% women, median age 69 years), 10 987 cardiovascular events were observed over a median follow-up period of 3.9 years. The association between SBP and risk of cardiovascular end points was found to be monotonic; the lowest SBP exposure group of <120 mm Hg presented nadir of risk. With respect to reference SBP (between 120 and 129 mm Hg), adjusted risk ratios for the primary outcome were 0.99 (95% CI 0.93 to 1.05) for SBP of <120 mm Hg, 1.02 (0.97 to 1.07) for SBP between 130 and 139 mm Hg, 1.07 (1.01 to 1.12) for SBP between 140 and 149 mm Hg, 1.11 (1.05 to 1.17) for SBP between 150 and 159 mm Hg and 1.16 (1.10 to 1.22) for SBP ≥160 mm Hg. Conclusion: Using deep learning for modelling EHR, we identified a monotonic association between SBP and risk of cardiovascular events in patients with COPD

Smoking status in Iranian male adolescents: A cross-sectional study and a meta-analysis

The present study aimed to estimate the prevalence of smoking status and its associated factors in Iranian adolescents and a meta-analysis of recent cross-sectional studies in order to estimate the corresponding prevalence for all Iranian adolescents. In a cross-sectional study, 1064 male high school students in Zanjan city (northwest of Iran) were recruited. A self-administered questionnaire was used for smoking status and associated factors. Through the meta-analysis, all relevant published studies were reviewed. Almost one-third of adolescents (34.2, n =354) have experienced smoking either experimentally (23.4, n=242), or regularly (10.8, n=112). Multivariate analysis showed that older age (OR = 1.20; 95 CI: 1.05-1.37), risky behaviors (OR=1.83; 1.25-2.68), Tramadol medication (OR = 2.19; 1.54-3.11), low self-esteem (OR 1.07; 1.03-1.11), positive attitude toward smoking (OR= 1.15; 1.09-1.21), positive thinking about smoking (OR= 1.07; 1.01-1.14) and having smoker friends (OR= 1.94; 1.36-2.77) were significantly associated with cigarette smoking in adolescents. Meta-analysis results showed that 7 of Iranian adolescents are regular smokers and 27 are experimenters. Increasing prevalence of smoking in Iranian adolescents is a major concern for public health. Controlling risky behaviors and increasing health education are recommended. (C) 2013 Elsevier Ltd. All rights reserved

The effect of immunomodulatory drugs on aortic stenosis: a Mendelian randomisation analysis

There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1β inhibitor) and colchicine (β-tubulin inhibitor) through a Mendelian randomisation (MR) approach. Genetic proxies for these drugs were identified as single nucleotide polymorphisms (SNPs) in the gene, enhancer or promoter regions of IL6R, IL1β or β-tubulin gene isoforms, respectively, that were significantly associated with serum C-reactive protein (CRP) in a large European genome-wide association study (GWAS; 575,531 participants). These were paired with summary statistics from a large GWAS of AS in European patients (653,867 participants) to then perform primary inverse-variance weighted random effect and sensitivity MR analyses for each exposure. This analysis showed that genetically proxied tocilizumab was associated with reduced risk of AS (OR 0.56, 95% CI 0.45–0.70 per unit decrease in genetically predicted log-transformed CRP). Genetically proxied canakinumab was not associated with risk of AS (OR 0.80, 95% CI 0.51–1.26), and only one suitable SNP was identified to proxy the effect of colchicine (OR 34.37, 95% CI 1.99–592.89). The finding that genetically proxied tocilizumab was associated with reduced risk of AS is concordant with an inflammatory hypothesis of AS pathogenesis. Inhibition of IL6R may be a promising therapeutic target for AS management

Prevalence of Cannabis Lifetime Use in Iranian High School and College Students: A Systematic Review, Meta-Analyses,and Meta-Regression

Cannabis is the most widely used substance in the world. This study aimed to estimate the prevalence of cannabis lifetime use (CLU) in high school and college students of Iran and also to determine factors related to changes in prevalence. A systematic review of literature on cannabis use in Iran was conducted according to MOOSE guideline. Domestic scientific databases, PubMed/Medline, ISI Web of Knowledge, and Google Scholar, relevant reference lists, and relevant journals were searched up to April, 2014. Prevalences were calculated using the variance stabilizing double arcsine transformation and confidence intervals (CIs) estimated using the Wilson method. Heterogeneity was assessed by Cochran's Q statistic and I-2 index and causes of heterogeneity were evaluated using meta-regression model. In electronic database search, 4,000 citations were retrieved, producing a total of 33 studies. CLU was reported with a random effects pooled prevalence of 4.0 (95 CI = 3.0 to 5.0). In subgroups of high school and college students, prevalences were 5.0 (95 CI = 3.0 to -7.0) and 2.0 (95 CI = 2.0 to -3.0), respectively. Meta-regression model indicated that prevalence is higher in college students (beta = 0.089, p < .001), male gender (beta = 0.017, p < .001), and is lower in studies with sampling versus census studies (beta = -0.096, p < .001). This study reported that prevalence of CLU in Iranian students are lower than industrialized countries. In addition, gender, level of education, and methods of sampling are highly associated with changes in the prevalence of CLU across provinces

Systolic Blood Pressure and Cardiovascular Risk in Patients with Diabetes: A Prospective Cohort Study

\ua9 2023 Lippincott Williams and Wilkins. All rights reserved. Background: Whether the association between systolic blood pressure (SBP) and risk of cardiovascular disease is monotonic or whether there is a nadir of optimal blood pressure remains controversial. We investigated the association between SBP and cardiovascular events in patients with diabetes across the full spectrum of SBP. Methods: A cohort of 49 000 individuals with diabetes aged 50 to 90 years between 1990 and 2005 was identified from linked electronic health records in the United Kingdom. Associations between SBP and cardiovascular outcomes (ischemic heart disease, heart failure, stroke, and cardiovascular death) were analyzed using a deep learning approach. Results: Over a median follow-up of 7.3 years, 16 378 cardiovascular events were observed. The relationship between SBP and cardiovascular events followed a monotonic pattern, with the group with the lowest baseline SBP of &lt;120 mm Hg exhibiting the lowest risk of cardiovascular events. In comparison to the reference group with the lowest SBP (&lt;120 mm Hg), the adjusted risk ratio for cardiovascular disease was 1.03 (95% CI, 0.97-1.10) for SBP between 120 and 129 mm Hg, 1.05 (0.99-1.11) for SBP between 130 and 139 mm Hg, 1.08 (1.01-1.15) for SBP between 140 and 149 mm Hg, 1.12 (1.03-1.20) for SBP between 150 and 159 mm Hg, and 1.19 (1.09-1.28) for SBP ≥160 mm Hg. Conclusions: Using deep learning modeling, we found a monotonic relationship between SBP and risk of cardiovascular outcomes in patients with diabetes, without evidence of a J-shaped relationship

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

Background Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased and Aims blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Methods Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. Results A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. Conclusions This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.BACKGROUND AND AIMS: Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. METHODS: Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non-sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. RESULTS: A total of 460 980 and 14 462 patients were identified for the non-sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference -0.04 mmHg (95% confidence interval -0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. CONCLUSIONS: This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice

The association between dietary glycemic and insulin indices with incidence of cardiovascular disease: Tehran lipid and glucose study

Background: The present study was conducted to investigate the association of dietary insulin index(II), insulin load(IL), glycemic index(GI), and glycemic load(GL) with the risk of cardiovascular disease(CVD). Methods: This cohort study was conducted within the framework of the Tehran Lipid and Glucose Study on 2198 subjects, aged�19 years old, who were followed-up for a median (IQR) 6.7 (6.1-7.1) years. Dietary GI, GL, II, and IL were calculated using a food frequency questionnaire at the baseline. Multivariate Cox proportional hazard regression models were used to estimate the risk of CVD across quartiles of dietary insulin and glycemic indices. Results: Mean ± SD age of the subjects(44.9 men) was 38.3 ± 13.4 years. During a mean of 2406 ± 417 person-years of follow-up, 76(3.5) new cases of the CVD were ascertained. The mean ± SD of II, IL, GI, and GL of participants were 51.7 ± 6.5, 235.8 ± 90.2, 61.9 ± 7.8, and 202.2 ± 78.1, respectively. After adjusting for the variables of age, sex, smoking, physical activity, daily energy intake, body mass index, diabetes, and hypertension, the hazard ratio (HR) of the highest quartile of dietary GL was 2.77(95CI:1.00-7.69,P for trend:0.033) compared to the lowest one. Also, each one SD increase in the GL score was associated with a higher risk of CVD(RR:1.46;CI:1.00-2.16),P-value = 0.047. However, there was no significant association between the dietary GI, II, and IL and risk for CVD incidence. Conclusions: Our results suggested that a high GL diet can increase the incidence of CVD, whereas high dietary II and IL were not associated with the risk of CVD among adults. © 2020 The Author(s)

Genetic susceptibility, elevated blood pressure, and risk of atrial fibrillation: a Mendelian randomization study

BACKGROUND: Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual’s genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. METHODS: First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a population of one million Europeans in total. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. RESULTS: The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mmHg [OR] 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers, and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease. CONCLUSIONS: The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF