The profile of Rafsanjan Cohort Study.

Owning the largest human-made jungle of pistachio, the second largest copper mine, and being located on the trade route of opium transit, distinguish Rafsanjan from many other cities in Iran. The environmental exposures and lifestyle factors associated with these characteristics of Rafsanjan, have raised concern about possible health outcomes for individuals living in and around this city. Thus, local health authorities initiated the Rafsanjan Cohort Study (RCS), as part of the prospective epidemiological research studies in IrAN (PERSIAN). RCS is a population-based prospective cohort of men and women aged 35-70 years, launched in August 2015. Individuals from diverse socioeconomic levels and lifestyles were recruited from four urban and suburban areas of Rafsanjan (participation rate 67.42%). Questionnaire-based interviews regarding demographics, dietary and environmental exposures, medical and occupational history, as well as anthropometric measurements were completed for all participants. Additionally, bio-specimens (blood, urine, hair, and nail) were collected, and dental and eye examinations were performed. The enrollment phase ended in December 2017, and a 15-year follow-up is planned. A total of 9990 individuals were enrolled in RCS (53.41% females). About 26% of men are pistachio farmers. The baseline prevalence of major non-communicable disease (NCD) risk factors such as cigarette smoking, alcohol consumption and opium use were 25.45%, 10.02%, and 23.81%, respectively. The mean ± SD of other common risk factors are as follows: body mass index (27.83 ± 4.89 mm Hg), systolic blood pressure (107.18 ± 17.56 mm Hg) diastolic blood pressure (71.13 ± 10.83), fasting blood sugar (113.27 ± 39.11 mg/dL) and plasma cholesterol (198.78 ± 41.89 mg/dL). These results indicate a concerning prevalence of NCD risk factors in Rafsanjan city, warranting further detailed investigations, particularly regarding the association of NDC with agricultural/industrial pollutants and drug abuse.

Early assessment of proarrhythmic risk of drugs using the in vitro data and single-cell-based in silico models: proof of concept.

BACKGROUND AND PURPOSE: To determine the predictive performance of in silico models using drug-specific preclinical cardiac electrophysiology data to investigate drug-induced arrhythmia risk (e.g. Torsade de pointes (TdP)) in virtual human subjects. EXPERIMENTAL APPROACH: To assess drug proarrhythmic risk, we used a set of in vitro electrophysiological measurements describing ion channel inhibition triggered by the investigated drugs. The Cardiac Safety Simulator version 2.0 (CSS; Simcyp, Sheffield, UK) platform was used to simulate human left ventricular cardiac myocyte action potential models. RESULTS: This study shows the impact of drug concentration changes on particular ionic currents by using available experimental data. The simulation results display safety threshold according to drug concentration threshold and log (threshold concentration/ effective therapeutic plasma concentration (ETPC)). CONCLUSION AND IMPLICATIONS: We reproduced the underlying biophysical characteristics of cardiac cells resulted in effects of drugs associated with cardiac arrhythmias (action potential duration (APD) and QT prolongation and TdP) which were observed in published 3D simulations, yet with much less computational burden.