Since both myocardium and vasculature in the heart are excessively damaged following myocardial infarction (MI), therapeutic strategies for treating MI hearts should concurrently target both so as to achieve true cardiac repair. Here we demonstrate a concomitant method that exploits the advantages of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) and human mesenchymal stem cell-loaded patch (hMSC-PA) to amplify cardiac repair in a rat MI model. Epicardially implanted hMSC-PA provide a complimentary microenvironment which enhances vascular regeneration through prolonged secretion of paracrine factors, but more importantly it significantly improves the retention and engraftment of intramyocardially injected hiPSC-CMs which ultimately restore the cardiac function. Notably, the majority of injected hiPSC-CMs display adult CMs like morphology suggesting that the secretomic milieu of hMSC-PA constitutes pleiotropic effects in vivo. We provide compelling evidence that this dual approach can be a promising means to enhance cardiac repair on MI hearts.
This study adds substantial evidence that hearing loss acts as a risk for agricultural injuries. Prevention of hearing loss and noise exposure may be important in reducing the burden of agricultural injuries.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is considered as the most significant global public health crisis of the century. Several drug candidates have been suggested as potential therapeutic options for COVID-19, including remdesivir, currently the only authorized drug for use under an Emergency Use Authorization. However, there is only limited information regarding the safety profiles of the proposed drugs, in particular drug-induced cardiotoxicity. Here, we evaluated the antiviral efficacy and cardiotoxicity of remdesivir using cardiomyocytes-derived from human pluripotent stem cells (hPSC-CMs) as an alternative source of human primary cardiomyocytes (CMs). In this study, remdesivir exhibited up to 60-fold higher antiviral activity in hPSC-CMs compared to Vero E6 cells; however, it also induced moderate cardiotoxicity in these cells. To gain further insight into the drug-induced arrhythmogenic risk, we assessed QT interval prolongation and automaticity of remdesivir-treated hPSC-CMs using a multielectrode array (MEA). As a result, the data indicated a potential risk of QT prolongation when remdesivir is used at concentrations higher than the estimated peak plasma concentration. Therefore, we conclude that close monitoring of the electrocardiographic/QT interval should be advised in SARS-CoV-2-infected patients under remdesivir medication, in particular individuals with pre-existing heart conditions.
Objective: This study aimed to describe the health behaviors of cancer survivors in the Republic of Korea and to compare them with the health behaviors of two control groups: (i) individuals with no history of cancer but with other chronic diseases and (ii) individuals with no history of cancer or other chronic diseases. Methods: This is a cross-sectional study of 17 311 adults at least 19 years of age who participated in the Fourth Korea National Health and Nutrition Examination Survey (2007-09). Smoking, alcohol drinking, physical activity and cancer screening behaviors of cancer survivors were assessed and compared with those of the two control groups. x 2 tests and multiple logistic regression analyses were performed to determine the likelihood and predictors of health behaviors. Results: The proportion of cancer survivors who were current smokers, heavy drinkers and engaged in physical activity were 9.6, 6.6 and 26.0%, respectively. Cancer screening rates reported among survivors were 44.2, 17.0, 49.8 and 47.7% for stomach, colorectal, breast and cervical cancers, respectively. Cancer survivors showed lower smoking and alcohol drinking rates compared with both control groups after adjusting for sex, age, marital status, education, household income and health insurance. Cancer survivors also showed stomach, breast and cervical cancer screening rates that differed from both control groups. However, in multiple analyses, these differences were not significant. Conclusions: Cancer survivors are more likely to adopt good health behaviors than individuals without a history of cancer. Further study is needed to determine the factors that lead to continued unhealthy behaviors after cancer diagnosis.
The effects of remote ischemic preconditioning (RIPC) in cardiac surgery have been inconsistent. We investigated whether anesthesia or beta-blockers interfere with RIPC cardioprotection. Fifty patients undergoing cardiac surgery were randomized to receive limb RIPC (four cycles of 5-min of upper arm cuff inflation/deflation) in the awake state (no-anesthesia; n = 17), or under sevoflurane (n = 17) or propofol (n = 16) anesthesia. In a separate crossover study, 11 healthy volunteers received either carvedilol or no medication prior to RIPC. Plasma dialysates were obtained and perfused through an isolated male Sprague–Dawley rat heart subjected to 30-min ischemia/60-min reperfusion, following which myocardial infarct (MI) size was determined. In the cardiac surgery study, pre-RIPC MI sizes were similar among the groups (39.7 ± 4.5% no-anesthesia, 38.9 ± 5.3% sevoflurane, and 38.6 ± 3.6% propofol). However, post-RIPC MI size was reduced in the no-anesthesia group (27.5 ± 8.0%; p < 0.001), but not in the anesthesia groups (35.7 ± 6.9% sevoflurane and 35.8 ± 5.8% propofol). In the healthy volunteer study, there was a reduction in MI size with RIPC in the no-carvedilol group (41.7 ± 4.3% to 30.6 ± 8.5%; p < 0.0001), but not in the carvedilol group (41.0 ± 4.0% to 39.6 ± 5.6%; p = 0.452). We found that the cardioprotective effects of limb RIPC were abolished under propofol or sevoflurane anesthesia and in the presence of carvedilol therapy.
On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID‐19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV‐ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC‐CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug‐induced CV‐ADRs from COVID‐19 effects, we restricted analyses to patients with COVID‐19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC‐CMs in time‐ and dose‐dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.
Background/AimsAlthough notably common, irritable bowel syndrome (IBS) has no specific cure. Lifestyle modification may be as important as medication; however, few studies support the effectiveness of such modifications. We performed this observational study of IBS patients to explore further the role of lifestyle changes in treatment.MethodsThis study included 831 men who enlisted in 2010 as armed surgeon cadets and 85 women who concurrently entered the Armed Forces Nursing Academy. Of these 916 participants, 89 were diagnosed with IBS using the Rome III criteria. Subjective changes in bowel habits, quality of life, pain, stress, stool frequency and stool consistency were surveyed before and after 9 weeks of army training. We evaluated the lifestyle risk factors that impacted improvement in IBS symptoms by comparing those who responded to lifestyle modification (the responding group) to those who did not respond (the nonresponding group).ResultsMore than half of the participants (63%) reported that their symptoms improved after training. The quality of life and levels of pain and stress significantly improved after military training. Initial stress levels before military training and smoking history affected IBS symptom improvement.ConclusionsLifestyle modification may be effective in managing IBS patients.
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