1.
Sex, Age, and BMI Modulate the Association of Physical Examinations and Blood Biochemistry Parameters and NAFLD: A Retrospective Study on 1994 Cases Observed at Shuguang Hospital, China.
Tang, Z, Pham, M, Hao, Y, Wang, F, Patel, D, Jean-Baptiste, L, Fan, L, Wang, W, Wang, Y, Cheng, F
BioMed research international. 2019;:1246518
Abstract
OBJECTIVE Previous studies have shown that some metabolic risk factors are related to nonalcoholic fatty liver disease (NAFLD). This retrospective study was performed to investigate the associations between physical examinations and blood biochemistry parameters and NAFLD status and to identify possible risk factors of NAFLD. METHODS Study participants underwent general physical examinations, blood biochemistry, and abdominal ultrasound evaluations. In addition, data regarding sex, age, ethnicity, medical history, and alcohol consumption of participants were recorded. Among the study participants (N=1994), 57.8% were male, 41.2% over the age of 50, and 52.6% with BMI≥24. 986 patients had NAFLD and 1008 had no NAFLD. We used effect size analysis and logistic regression to determine which physical examinations and blood biochemistry parameters were significant for the association between these parameters and NAFLD status. RESULTS Both the effect size and logistic regression indicated that BMI, diastolic blood pressure (DBP), triglycerides (TG), and serum uric acid (SUA) show a significant association with NAFLD. Females are overall at a higher risk of NAFLD, but factors such as high BMI, DBP, TG, and SUA increase the associated risk for both sexes. Compared with males, females have a higher risk of NAFLD given that they are over 50, overweight and obese (BMI at or over 24), or have high SUA. In terms of age, people older than 50 with high SUA, and people younger than 50 with high DBP and low-density lipoprotein cholesterol (LDL-C) all increase the risk of NAFLD. For BMI, high DBP and low high-density lipoprotein cholesterol (HDL-C) are risk factors for NAFLD in overweight and obese people (BMI at or over 24), whereas in normal weight and underweight people (BMI under 24), elevated LDL-C increases the risk of NAFLD. CONCLUSIONS Our results revealed sex, age, and BMI modulate the association of physical examinations and blood biochemistry parameters and NAFLD, which may facilitate the development of personalized early warning and prevention strategies of NAFLD for at-risk populations.
2.
Clinical Trial in a Dish: Personalized Stem Cell-Derived Cardiomyocyte Assay Compared With Clinical Trial Results for Two QT-Prolonging Drugs.
Blinova, K, Schocken, D, Patel, D, Daluwatte, C, Vicente, J, Wu, JC, Strauss, DG
Clinical and translational science. 2019;(6):687-697
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Abstract
Induced pluripotent stem cells (iPSCs) have shown promise in investigating donor-specific phenotypes and pathologies. The iPSC-derived cardiomyocytes (iPSC-CMs) could potentially be utilized in personalized cardiotoxicity studies, assessing individual proarrhythmic risk. However, it is unclear how closely iPSC-CMs derived from healthy subjects can recapitulate a range of responses to drugs. It is well known that QT-prolonging drugs induce subject-specific clinical response and that all healthy subjects do not necessarily develop arrhythmias or exhibit similar amounts of QT prolongation. We previously reported this variability in a study of four human ether-a-go-go-related gene (hERG) potassium channel-blocking drugs in which each subject underwent intensive pharmacokinetic and pharmacodynamic sampling such that subjects had 15 time-matched plasma drug concentration and electrocardiogram measurements throughout 24 hours after dosing in a phase I clinical research unit. In this study, iPSC-CMs were generated from those subjects. Their drug-concentration-dependent QT prolongation response from the clinic was compared with in vitro drug-concentration-dependent action potential duration (APD) prolongation response to the same two hERG-blocking drugs, dofetilide and moxifloxacin. Comparative results showed no significant correlation between the subject-specific APD response slopes and clinical QT response slopes to either moxifloxacin (P = 0.75) or dofetilide (P = 0.69). Similarly, no significant correlation was found between baseline QT and baseline APD measurements (P = 0.93). This result advances our current understanding of subject-specific iPSC-CMs and facilitates discussion into factors obscuring correlation and considerations for future studies of subject-specific phenotypes in iPSC-CMs.