A model based on electronic health records to predict transfusion events in on-pump cardiac surgery.

Perioperative blood transfusion is costly and raises safety concerns. We developed and validated a model for predicting minor, moderate, or major transfusion given to patients during on-pump cardiac procedures based on two centers' database. Model performance incorporating 7 variables on the development set had an AUC of 0.803 [95% CI, 0.790-0.815] for minor transfusion; moderate transfusion, giving an AUC of 0.822 (95% CI, 0.803-0.841); and major transfusion, giving an AUC of 0.813 (95% CI, 0.759-0.866). Model performance on the validation set had an AUC of 0.739 (95% CI 0.714-0.765), 0.730 (95% CI 0.702-0.758), and 0.713 (95% CI 0.677-0.749), respectively. A model based entirely on readily available electronic health records can accurately predict intraoperative minor, moderate, or major transfusion and provide individualized transfusion risk profiles before surgery among those on-pump cardiac surgical patients, and may help guide patient management.

Palmitic acid methyl ester induces cardiac hypertrophy through activating the GPR receptor-mediated changes of intracellular calcium concentrations and mitochondrial functions.

Myocardial hypertrophy is associated with a significant increase in intracellular Ca2+ , which can be induced by long-chain fatty acid. Palmitic acid methyl ester (PAME), a fatty acid ester released from adipose tissue, superior cervical ganglion, and retina, has been found to have anti-inflammation, antifibrosis, and peripheral vasodilation effects. However, the effects of PAME on cardiomyocytes are still unclear. The aim of this study was to determine whether PAME could disrupt the intracellular Ca2+ balance, leading to cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were treated with various concentrations (10-100 µM) of PAME for 1-4 days. Cytosolic Ca2+ and mitochondrial Ca2+ concentrations were examined using Fura-2 AM and Rhod-2, respectively. After treatment with PAME for 4 days, mitochondrial Ca2+ , an indicator of the state of mitochondrial permeability transition pore (MPTP), and cell death were monitored by flow cytometric analysis. ATP levels were detected using the ATP assay kit. Cardiomyocyte hypertrophy was analyzed by measuring the cardiac hypertrophy biomarker and cell area using quantitative real time-polymerase chain reaction, Western Blot analysis and immunofluorescence analysis. Our results show that PAME concentration- and time-dependently increased cytosolic and mitochondria Ca2+ through the mitochondrial calcium uniporter. Moreover, treatment with PAME for 4 days caused MPTP opening, thereby reducing ATP production and enhancing reactive oxygen species (ROS) generation, and finally led to cardiomyocyte hypertrophy. These effects caused by PAME treatment were attenuated by the G-protein coupled receptor 40 (GPR40) inhibitor. In conclusion, PAME impaired mitochondrial function, which in turn led to cardiomyocyte hypertrophy through increasing the mitochondrial Ca2+ levels mediated by activating the GPR40 signaling pathway.

Prediction of the severity of acute kidney injury after on-pump cardiac surgery.

STUDY OBJECTIVE: On-pump cardiac surgery is associated with a high risk of acute kidney injury (AKI), which can substantially affect risk of mortality and morbidity depending on its severity. Current methods are limited in predicting AKI severity. This study aimed to develop and validate a model to predict AKI severity after on-pump cardiac surgery. DESIGN: Observational retrospective cohort study. SETTING: Two tertiary general hospitals in China. PATIENTS: The sample in this study came from two hospitals: 6919 patients who underwent on-pump cardiac surgery between January 1, 2011 and June 30, 2017 at West China Hospital of Sichuan University, and 1575 patients who underwent on-pump cardiac surgery between September 1, 2013 and June 30, 2017 at the Second Affiliated Hospital of Zhejiang University. MEASUREMENTS: Data from West China Hospital was used to develop an individualized prediction for AKI severity. The model was internally validated, and a cohort from the Second Affiliated Hospital of Zhejiang University was used for external validation. MAIN RESULTS: AKI incidence was 14.7% in the development cohort and 42.3% in the external validation cohort. Ten predictors of AKI severity were identified: age; sex; preoperative levels of serum creatinine, serum cystatin C, and blood urea nitrogen; preoperative red blood cell count; hypertension; cardiopulmonary bypass time; operation time; and red blood cell transfusion. The model incorporating these variables showed a concordance index of 0.730 (95% CI 0.713, 0.747) for predicting stage I AKI, 0.772 (95% CI 0.738, 0.806) for predicting stage II, and 0.770 (95% CI 0.712, 0.828) for predicting stage III in the development cohort. The corresponding indices for the external validation cohort were 0.676 (95% CI 0.650, 0.703), 0.730 (95% CI 0.691, 0.769), and 0.795 (95% CI 0.737, 0.852). CONCLUSIONS: The prediction model incorporating 10 predictors may be useful for predicting severity of AKI after on-pump cardiac surgery.

Xanthohumol Protects the Rat Myocardium against Ischemia/Reperfusion Injury-Induced Ferroptosis.

Ferroptosis is an iron-dependent form of cell death caused by the inactivation of glutathione peroxidase 4 (GPX4) and accumulation of lipid peroxides. Ferroptosis has been found to participate in the ischemia-reperfusion (I/R) injury, leading to heart dysfunction and myocardial cell death. Xanthohumol (XN), a prenylated flavonoid isolated from Humulus lupulus, has multiple pharmacological activities, such as anti-inflammatory and antioxidant. This study is aimed at investigating whether XN could attenuate the I/R-induced ferroptosis in cardiomyocytes and the underlying mechanisms. Cardiomyocytes were treated with Fe-SP and RSL3, and the rat hearts were treated with I/R. The results from the present study show that XN was able to protect cardiomyocytes against Fe-SP- and RSL3-induced ferroptotic cell death by decreasing the production of lipid peroxidation and ROS, chelating iron, reducing the NRF2 protein level, and modulating the protein levels of GPX4. Moreover, XN significantly decreased the mRNA levels of ferroptosis markers, Ptgs2 and Acsl4, and the protein levels of ACSL4 and NRF2 and modulated the protein levels of GPX4 in I/R-treated hearts. The findings from the present study suggest that XN might have the therapeutic potential for the I/R-induced ferroptosis injury.

Gossypol Acetic Acid Attenuates Cardiac Ischemia/Reperfusion Injury in Rats via an Antiferroptotic Mechanism.

Myocardial ischemia/reperfusion (I/R) injury has been associated with ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxide to lethal levels. Gossypol acetic acid (GAA), a natural product taken from the seeds of cotton plants, prevents oxidative stress. However, the effects of GAA on myocardial I/R-induced ferroptosis remain unclear. This study investigated the ability of GAA to attenuate I/R-induced ferroptosis in cardiomyocytes along with the underlying mechanisms in a well-established rat model of myocardial I/R and isolated neonatal rat cardiomyocytes. H9c2 cells and cardiomyocytes were treated with the ferroptosis inducers erastin, RSL3, and Fe-SP. GAA could protect H9c2 cells against ferroptotic cell death caused by these ferroptosis inducers by decreasing the production of malondialdehyde and reactive oxygen species, chelating iron content, and downregulating mRNA levels of Ptgs2. GAA could prevent oxygen-glucose deprivation/reperfusion-induced cell death and lipid peroxidation in the cardiomyocytes. Moreover, GAA significantly attenuated myocardial infarct size, reduced lipid peroxidation, decreased the mRNA levels of the ferroptosis markers Ptgs2 and Acsl4, decreased the protein levels of ACSL4 and NRF2, and increased the protein levels of GPX4 in I/R-induced ex vivo rat hearts. Thus, GAA may play a cytoprotectant role in ferroptosis-induced cardiomyocyte death and myocardial I/R-induced ferroptotic cell death.

Genetics of the glutamate-mediated methylamine utilization pathway in the facultative methylotrophic beta-proteobacterium Methyloversatilis universalis FAM5.

The ability of some microbial species to oxidize monomethylamine via glutamate-mediated pathways was proposed in the 1960s; however, genetic determinants of the pathways have never been described. In the present study we describe a gene cluster essential for operation of the N-methylglutamate pathway in the methylotrophic beta-proteobacterium Methyloversatilis universalis FAM5. Four major polypeptides from protein fractions displaying high activities of N-methylglutamate synthetase, N-methylglutamate dehydrogenase and gamma-glutamylmethylamide synthetase were selected for mass spectrometry-based identification. The activities of enzymes were associated with the presence of peptides identified as ferredoxin-dependent glutamate synthase (GltB2), large subunit of putative heterotetrameric sarcosine oxidase (SoxA) and glutamine synthetase type III (GSIII) respectively. A gene cluster (8.3 kb) harbouring gltB2, soxA and gsIII-like genes was amplified from M. universalis FAM5, sequenced and assembled. Two partial and six complete open reading frames arranged in the order soxBDAG-gsIII-gltB132 were identified and subjected to mutational analysis, functional and metabolic profiling. We demonstrated that gltB-like and sox-like genes play a key role in methylamine utilization and encode N-methylglutamate synthetase and N-methylglutamate dehydrogenase respectively. Metabolic, enzymatic and mutational analyses showed that the gsIII-like gene encodes gamma-glutamylmethylamide synthetase; however, this enzyme is not essential for oxidation of methylamine.

Understanding individual adoption of mobile booking service: an empirical investigation.

Based on information systems acceptance literature, this study develops an integrated model to predict and explain behavioral intention to use mobile booking (m-booking). Data collected from 201 users in Taiwan are tested against the research model, using the structural equation modeling approach. The proposed model is mostly supported by the empirical data. The findings of this study provide several crucial implications for m-booking service practitioners and researchers.

Developing and validating an instrument for measuring mobile computing self-efficacy.

IT-related self-efficacy has been found to have a critical influence on system use. However, traditional measures of computer self-efficacy and Internet-related self-efficacy are perceived to be inapplicable in the context of mobile computing and commerce because they are targeted primarily at either desktop computer or wire-based technology contexts. Based on previous research, this study develops and validates a multidimensional instrument for measuring mobile computing self-efficacy (MCSE). This empirically validated instrument will be useful to researchers in developing and testing the theories of mobile user behavior, and to practitioners in assessing the mobile computing self-efficacy of users and promoting the use of mobile commerce systems.