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Although anti-cancer therapy-induced cardiotoxicity is known, until now it lacks a reliable risk predictive model of the subsequent cardiotoxicity in breast cancer patients receiving anthracycline therapy. An artificial intelligence (AI) with a machine learning approach has yet to be applied in cardio-oncology. Herein, we aimed to establish a predictive model for differentiating patients at a high risk of developing cardiotoxicity, including cancer therapy-related cardiac dysfunction (CTRCD) and symptomatic heart failure with reduced ejection fraction. This prospective single-center study enrolled patients with newly diagnosed breast cancer who were preparing for anthracycline therapy from 2014 to 2018. We randomized the patients into a 70%/30% split group for ML model training and testing. We used 15 variables, including clinical, chemotherapy, and echocardiographic parameters, to construct a random forest model to predict CTRCD and heart failure with a reduced ejection fraction (HFrEF) during the 3-year follow-up period (median, 30 months). Comparisons of the predictive accuracies among the random forest, logistic regression, support-vector clustering (SVC), LightGBM, K-nearest neighbor (KNN), and multilayer perceptron (MLP) models were also performed. Notably, predicting CTRCD using the MLP model showed the best accuracy compared with the logistic regression, random forest, SVC, LightGBM, and KNN models. The areas under the curves (AUC) of MLP achieved 0.66 with the sensitivity and specificity as 0.86 and 0.53, respectively. Notably, among the features, the use of trastuzumab, hypertension, and anthracycline dose were the major determinants for the development of CTRCD in the logistic regression. Similarly, MLP, logistic regression, and SVM also showed higher AUCs for predicting the development of HFrEF. We also validated the AI prediction model with an additional set of patients developing HFrEF, and MLP presented an AUC of 0.81. Collectively, an AI prediction model is promising for facilitating physicians to predict CTRCD and HFrEF in breast cancer patients receiving anthracycline therapy. Further studies are warranted to evaluate its impact in clinical practice.

Ming-Chuan Lee,1 Yu-Tsang Wang,2 Yu-Ju Li,1 Ching-Yi Tsai,1 Su-Te Chen,1 Wun-Jyun Jhuang,1,3 Meng-Chi Chang,1 Mei-Yu Chien,1 Hsiang-Chun Lee1,3– 5 1Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 2Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 3Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 4Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan; 5Institute/Center of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 804, TaiwanCorrespondence: Hsiang-Chun Lee, Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan, Tel +886-7-3121101#2293, Fax +886-7-3234845, Email hclee@kmu.edu.twPurpose: Manifestations of metabolic syndrome (MetS) carry risks for atrial fibrillation (AF). The study determined whether any electrocardiographic parameter can reflect increased AF risk in individuals with MetS.Patients and Methods: From our University Hospital database, we examined the presence of AF and its correlation with MetS manifestations, renal function, lipid profiles, and electrocardiographic parameters (P wave duration, PR interval, QRS width, and QTc intervals). Between January 2008 and December 2015, data from 4479 adults (women 41.6% vs men 58.4%) were identified.Results: The overall prevalence of AF was 12.4%, without sex differences (women, 12.8% vs men, 12.1%). Patients with AF were older (age 73.9 ± 11.8 vs non-AF 67 ± 13.5 years), with lower lipid levels (TG, total cholesterol, and LDL-cholesterol, all p < 0.0001), and at lower eGFR level (64.1 ± 30.9 vs non-AF 68.8 ± 41.4 mL/min/1.73m2, p < 0.0001). Besides, sex differences were present in all electrocardiographic parameters (all p < 0.05). Hypertension had the highest odds ratio (1.33; p = 0.026) for AF. Comparing AF to non-AF, the QTc of quartiles was significantly different (p < 0.0089). The shortest and longest QTc quartiles had an increased incidence of AF.Conclusion: AF risk in patients with MetS phenotypes can be reflected by QTc quartiles.Keywords: atrial fibrillation, electrocardiography, metabolic syndrome, lipid, QTc interval

Subjects with metabolic syndrome (MetS) commonly have atrial remodeling, which indicates a risk for atrial fibrillation. This study determined MetS-related changes in lipid components in very-low-density lipoprotein (VLDL), which has been shown to cause atrial remodeling, the effect of statins on these changes, and the correlation between atrial remodeling and VLDL lipid compositions. Blood samples were collected from 12 non-MetS and 27 sex- and age-matched MetS subjects. Fourteen patients with MetS (MetS-off statin) discontinued statin therapy 14 days before the study, while the remaining 13 remained on it (MetS-on statin). The VLDLs were isolated and processed for mass-based lipid profiling. Lipidomic analyses were performed and associated with atrial remodeling markers measured using standard echocardiography and electrocardiography. Compared with the VLDL components of the non-MetS group, glucosyl/galactosyl ceramide, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were enriched in the MetS-off statin group. Statin therapy attenuated all abnormally abundant lipid classes in MetS, except for triglycerides. In addition, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were significantly correlated with atrial dilatation, and the latter two were also correlated with the PR interval. Enrichment of double bonds, which indicate unsaturated fatty acids, was also significantly correlated with atrial remodeling and P-wave duration. This study suggests that the pathological lipid payload of MetS-VLDL may contribute to atrial remodeling in patients.

Very-low-density lipoprotein (VLDL) is the only lipoprotein containing apolipoprotein B that is secreted from the liver, where VLDL is assembled from apolipoproteins, cholesterol, and triglycerides. The primary function of VLDL is to transport cholesterol and other lipids to organs and cells for utilization. Apart from its role in normal biologic processes, VLDL is also known to contribute to the development of atherosclerotic cardiovascular disease. Large VLDL particles, which are subclassified according to their size by nuclear magnetic resonance spectrometry, are significantly correlated not only with atherosclerosis, but also with insulin resistance and diabetes incidence. VLDL can also be subclassified according to surface electrical charge by using anion-exchange chromatography. The most electronegative VLDL subclass is highly cytotoxic to endothelial cells and may contribute to coronary heart disease. In addition, electronegative VLDL contributes to the development of atrial remodeling, especially in patients with metabolic syndrome, which is an established risk factor for atrial fibrillation. In this review, we focus on the VLDL subclasses that are associated with apolipoprotein alterations and are involved in cardiometabolic disease. The postprandial enhancement of VLDL’s pathogenicity is a critical medical issue, especially in patients with metabolic syndrome. Therefore, the significance of the postprandial modification of VLDL’s chemical and functional properties is extensively discussed.

Background: Subjects with metabolic syndrome (MetS) commonly have atrial remodeling, which indicates a risk for atrial fibrillation. Objective: This study determined MetS-related changes in lipid components in very-low-density lipoprotein (VLDL), which has been shown causing atrial remodeling, and the effect of statins on these changes, and the correlation between atrial remodeling and VLDL lipid compositions. Methods: Blood samples were collected from 12 non-MetS and 27 sex- and age-matched MetS subjects. Fourteen patients with MetS (MetS­–off statin) discontinued statin therapy 14 days before the study, while the remaining 13 remained on it (MetS–on statin). The VLDLs were isolated and processed for mass-based lipid profiling. Lipidomic analyses were performed and associated with atrial remodeling markers measured using standard echocardiography and electrocardiography. Results: Compared with the VLDL components of the non-MetS group, glucosyl/galactosyl ceramide, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were enriched in the MetS–off statin group. The statin therapy attenuated all abnormally abundant lipid classes in MetS, except for triglycerides. In addition, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were significantly correlated with atrial dilatation, and the latter two were also correlated with the PR interval. Enrichment of double bonds, which indicates unsaturated fatty acids, was also significantly correlated with atrial remodeling, and P-wave duration. Conclusion: This study suggests that the pathological lipid payload of MetS-VLDL may contribute to atrial remodeling in patients.

Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of cognitive dysfunction. We previously showed that patients with metabolic syndrome (MetS) had significantly higher plasma levels of electronegative very-low-density lipoprotein (VLDL) than did healthy controls. However, the effects of electronegative-VLDL on the brain and cognitive function remain unclear. In this study, VLDL isolated from healthy volunteers (nVLDL) or patients with MetS (metVLDL) was administered to mice by means of tail vein injection. Cognitive function was assessed by using the Y maze test, and plasma and brain tissues were analyzed. We found that mice injected with metVLDL but not nVLDL exhibited significant hippocampus CA3 neuronal cell loss and cognitive dysfunction. In mice injected with nVLDL, we observed mild glial cell activation in the medial prefrontal cortex (mPFC) and hippocampus CA3. However, in mice injected with metVLDL, plasma and brain TNF-α and Aβ-42 levels and glial cell activation in the mPFC and whole hippocampus were higher than those in control mice. In conclusion, long-term exposure to metVLDL induced levels of TNF-α, Aβ-42, and glial cells in the brain, contributing to the progression of cognitive dysfunction. Our findings suggest that electronegative-VLDL levels may represent a new therapeutic target for cognitive dysfunction.

Mitochondrial oxidative stress has been implicated in aging and several cardiovascular diseases, including heart failure and cardiomyopathy, ventricular tachycardia, and atrial fibrillation. The role of mitochondrial oxidative stress in bradyarrhythmia is less clear. Mice with a germline deletion of Ndufs4 subunit respiratory complex I develop severe mitochondrial encephalomyopathy resembling Leigh Syndrome (LS). Several types of cardiac bradyarrhythmia are present in LS mice, including a frequent sinus node dysfunction and episodic atrioventricular (AV) block. Treatment with the mitochondrial antioxidant Mitotempo or mitochondrial protective peptide SS31 significantly ameliorated the bradyarrhythmia and extended the lifespan of LS mice. Using an ex vivo Langendorff perfused heart with live confocal imaging of mitochondrial and total cellular reactive oxygen species (ROS), we showed increased ROS in the LS heart, which was potentiated by ischemia-reperfusion. A simultaneous ECG recording showed a sinus node dysfunction and AV block concurrent with the severity of the oxidative stress. Treatment with Mitotempo abolished ROS and restored the sinus rhythm. Our study reveals robust evidence of the direct mechanistic roles of mitochondrial and total ROS in bradyarrhythmia in the setting of LS mitochondrial cardiomyopathy. Our study also supports the potential clinical application of mitochondrial-targeted antioxidants or SS31 for the treatment of LS patients.

Embraced with apolipoproteins (Apo) B and Apo E, triglyceride-enriched very-low-density lipoprotein (VLDL) is secreted by the liver into circulation, mainly during post-meal hours. Here, we present a brief review of the physiological role of VLDL and a systemic review of the emerging evidence supporting its pathological roles. VLDL promotes atherosclerosis in metabolic syndrome (MetS). VLDL isolated from subjects with MetS exhibits cytotoxicity to atrial myocytes, induces atrial myopathy, and promotes vulnerability to atrial fibrillation. VLDL levels are affected by a number of endocrinological disorders and can be increased by therapeutic supplementation with cortisol, growth hormone, progesterone, and estrogen. VLDL promotes aldosterone secretion, which contributes to hypertension. VLDL induces neuroinflammation, leading to cognitive dysfunction. VLDL levels are also correlated with chronic kidney disease, autoimmune disorders, and some dermatological diseases. The extra-hepatic secretion of VLDL derived from intestinal dysbiosis is suggested to be harmful. Emerging evidence suggests disturbed VLDL metabolism in sleep disorders and in cancer development and progression. In addition to VLDL, the VLDL receptor (VLDLR) may affect both VLDL metabolism and carcinogenesis. Overall, emerging evidence supports the pathological roles of VLDL in multi-organ diseases. To better understand the fundamental mechanisms of how VLDL promotes disease development, elucidation of the quality control of VLDL and of the regulation and signaling of VLDLR should be indispensable. With this, successful VLDL-targeted therapies can be discovered in the future.

Hepatitis C virus (HCV) eradication deteriorates lipid profiles. Although HCV eradication may reduce the risk of vascular events as a whole, whether deteriorated lipid profiles increases the risk of cardio‐cerebral disease in certain patients is elusive. Serial lipid profiles were measured before, during, at and 3 months after the end of direct‐acting antivirals (DAAs) therapy, and annually thereafter in chronic hepatitis C patients who achieved a sustained virological response (SVR, undetectable HCV RNA at posttreatment week 12). The primary end‐point was the occurrence of the events. A total of 617 patients were included, with a mean follow‐up period of 26.8 months (range: 1‐65 months). The total cholesterol and low‐density lipoprotein cholesterol (LDL‐C) levels increased significantly from treatment week 4 to 2 years after treatment. Logistic regression analysis revealed that the factors independently associated with a significant cholesterol increase included age (odds ratio [OR]/95% confidence intervals [CIs]:1.02/1.006‐1.039, P = .007) and smoking (OR/CI:3.21/1.14‐9.02, P = .027). Five patients developed cardio‐cerebral diseases during 1376 person‐years follow‐up period. Compared to patients without vascular events, a significantly higher proportion of those with vascular events experienced an LDL‐C surge >40% (80% vs 19.9%, P = .001). Cox‐regression analysis revealed that an LDL‐C surge >40% was the only factor predictive of vascular events (HR/CI: 15.44/1.73‐138.20, P = .014). Dyslipidemia occurred after HCV eradication, and it was associated with the risk of cardio‐cerebrovascular diseases. Attention should also be paid to the extrahepatic consequence beyond liver‐related complications in the post‐SVR era.

Acute coronary syndrome (ACS) is major cause of ventricular arrhythmias (VAs) and sudden death. neuECG is a noninvasive method to simultaneously record skin sympathetic nerve activity (SKNA) and electrocardiogram.The purpose of this study was to test the hypotheses that (1) ACS increases average SKNA (aSKNA), (2) the magnitude of aSKNA elevation is associated with VAs during ACS, and (3) there is a gender difference in aSKNA between patients without and with ACS.We prospectively studied 128 ACS and 165 control participants. The neuECG was recorded with electrodes at Lead I configuration at baseline, during mental math stress, and during recovery (5 minutes for each phase). All recordings were done in the morning.In the control group, women have higher aSKNA than do men at baseline (0.82 ± 0.25 μV vs 0.73 ± 0.20 μV; P = .009) but not during mental stress (1.21 ± 0.36 μV vs 1.16 ± 0.36 μV; P = .394), suggesting women had lower sympathetic reserve. In comparison, ACS is associated with equally elevated aSKNA in women vs men at baseline (1.14 ± 0.33 μV vs 1.04 ± 0.35 μV; P = .531), during mental stress (1.46 ± 0.32 μV vs 1.33 ± 0.37 μV; P = .113), and during recovery (1.30 ± 0.33 μV vs 1.11 ± 0.30 μV; P = .075). After adjusting for age and gender, the adjusted odds ratio for VAs including ventricular tachycardia and ventricular fibrillation is 1.23 (95% confidence interval 1.05-1.44) for each 0.1 μV aSKNA elevation. aSKNA is positively correlated with plasma norepinephrine level.ACS is associated with elevated aSKNA, and the magnitude of aSKNA elevation is associated with the occurrence of VAs. Women have higher aSKNA and lower SKNA reserve than do men among controls but not among patients with ACS.

(1) Background: The autonomic imbalance plays a role in vasovagal syncope (VVS) diagnosed by head-up tilting test (HUT). neuECG is a new method of recording skin electrical signals to simultaneously analyze skin sympathetic nerve activity (SKNA) and electrocardiogram. We hypothesize that SKNA is higher in subjects with tilt-positive than tilt-negative and the SKNA surges before syncope. (2) Methods: We recorded neuECG in 41 subjects who received HUT (according to the “Italian protocol”), including rest, tilt-up, provocation and recovery phases. Data were analyzed to determine the average SKNA (aSKNA, μV) per digitized sample. Electrocardiogram was used to calculate standard deviation of normal-to-normal beat intervals (SDNN). The “SKNA-SDNN index” was calculated by rest aSKNA multiplied by the ratio of tilt-up to rest SDNN. (3) Results: 16 of 41 (39%) subjects developed syncope. The aSKNA at rest phase is significantly higher in the tilt-positive (1.21 ± 0.27 µV) than tilt-negative subjects (1.02 ± 0.29 µV) (p = 0.034). There are significant surges and withdraw of aSKNA 30 s before and after syncope (both p ≤ 0.006). SKNA-SDNN index is able to predict syncope (p &lt, 0.001). (4) Conclusion: Higher SKNA at rest phase is associated with positive HUT. The SKNA-SDNN index is a novel marker to predict syncope during HUT.

Epidemiological studies have reported that elderly patients with metabolic syndrome (MetS) are significantly more likely to develop neuronal degenerative diseases than those without MetS. Our previous study showed that patients with MetS had significantly higher levels of negatively charged very low density lipoproteins (VLDLs) in the plasma than healthy controls. Highly electronegative VLDL is a key risk factor for endothelial dysfunction and atrial fibrillation. However, the impact of negatively charged VLDL in brain immunity remains unclear. In this study, VLDLs were isolated from normal healthy (nVLDL) individuals or patients with MetS (metVLDL). Primary astroglia and microglia mixed cell cultures as well as microglial-enriched cultures were used to test the effects of VLDLs. Microglia/astroglia activation as evidenced by their morphological changes and production of pro-inflammatory factors, such as tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2), were assessed by immunofluorescence staining and ELISA, respectively. Our results showed that metVLDLs mainly act on the microglia, and not the astroglia, with low concentration (0.05–0.5 μg/mL) inducing cell morphological changes and decreased cellular processes in the microglia. However, nVLDL treatment at these concentrations had no effects on microglia and astroglia. Most importantly, TNF-α and PGE2 levels significantly increased in the microglia treated with metVLDL via a dose-dependent manner. Together, our data indicate that metVLDLs can contribute to MetS-associated brain disorders through microglia activation and neuroinflammation.

Young-onset hypertensives (YOHs) with resistant hypertension (RH) have a greater long-term cardiovascular risk. The present study examined whether a functional adiponectin T94G polymorphism (rs2241766) is associated with RH in YOHs. We analyzed data from the Academia Sinica Collaborative Study on Hypertension Genetics in Taiwanese subjects to compare rs2241766 between YOHs with and without RH (≤50 years of age). RH was defined as the need for at least 3 drugs, including a diuretic to control blood pressure. Genotyping of rs2241766 was performed using TaqMan allelic discrimination. A total of 861 YOHs were enrolled and 54 had RH in enrolled population. For the rs2241766 in the allelic model, the odds ratio (OR) of RH allele frequency was 2.45 (p = 0.008), and there was a linear relationship between allele numbers and the presence of RH (p = 0.005). In multivariate analysis, the rs2241766 (OR = 2.766, p = 0.002), age (OR = 1.103, p = 0.001), uric acid (OR = 1.322, p = 0.001), high-sensitivity C-reactive protein (OR = 2.769, p = 0.001) and aldosterone (OR = 1.004, p = 0.001) were independently associated with the presence of RH. In the Taiwanese population, the adiponectin T94G polymorphism (rs2241766) is associated with RH in YOHs.

Atrial fibrillation (AF) is the most common type of sustained arrhythmia. It results from abnormal irregularities in the electrical performance of the atria, and may cause heart thrombosis, stroke, arterial disease, thromboembolism, and heart failure. Prior to the onset of atrial fibrillation, most people experience atrial cardiomyopathy which, if effectively managed, can be prevented from progressing to atrial fibrillation. Electrocardiogram (ECG) can show changes in the heartbeats, and is a common and painless tool to detect heart problems. P-waves in exercise ECGs change more drastically than those in regular ECG, and are more effective in the detection of atrial myocardial diseases. In this paper, we propose a deep learning system to help clinicians to early detect if a patient has atrial enlargement or fibrillation. Firstly, a Convolutional Recurrent Neural Network is employed to locate the P-waves in the patient's exercise ECGs taken in the exercise ECG test process. Relevant parameters are then calculated from the located P-waves. Then a Parallel Bi-directional Long Short-Term Memory Network is applied to analyze the obtained parameters and make a diagnosis for the patient. With our proposed deep learning system, the changes of P-waves collected in different phases in the exercise ECG test can be analyzed simultaneously to get more stable and accurate results. The system can take data of different length as input, and is also applicable to any number of ECG collections. We conduct various experiments to show the effectiveness of our proposed system. We also show that the more ECG data collected in the exercise phase are involved, the more effective our system is in diagnosis of the diseases.

Background: Oral presentations are an important educational component for nursing students. However, there are no reliable tools for objective evaluations of presentations. We aimed to develop a measurement scale for nursing students’ oral presentations and evaluate its reliability and validity. Methods: A literature review and face-to-face interviews with university tutors in oral presentations and students generated 28 scale items. The validity and reliability of the scale was evaluated with exploratory and confirmatory factor analysis, criterion-related validity, internal consistency, and test-retest reliability. Results: Nursing students provided data for exploratory factor analysis (n = 325), which resulted in 20 items. Three factors explained 64.75% of the total variance: accuracy of content, effective communication, and clarity of speech. The Cronbach's α value was .94 for the total scale and the three factors ranged from .84 to .93. Construct validity was examined with confirmatory factor analysis using data from another 325 students. Five items were deleted, and fit indices of the model were acceptable, with the exception of the adjusted goodness of fit index, which was below the minimum criteria. The final 15-item oral presentation scale (OPS) was significantly correlated with the Personal Report of Communication Apprehension scale (r = -.51, p < .001) and Self-Perceived Communication Competence Scale (r = .45, p < .001) indicating excellent criterion-related validity. The intra-class correlation coefficient for a 3-week test-retest (r = .681, p < .001) indicated the OPS was stable over time. Conclusions: The OPS could be adopted to help nursing programs prepare for and improve students’ oral presentations.

Background Oral presentations are an important educational component for nursing students and nursing educators need to provide students with an assessment of presentations as feedback for improving this skill. However, there are no reliable validated tools available for objective evaluations of presentations. We aimed to develop and validate an oral presentation evaluation scale (OPES) for nursing students when learning effective oral presentations skills and could be used by students to self-rate their own performance, and potentially in the future for educators to assess student presentations. Methods The self-report OPES was developed using 28 items generated from a review of the literature about oral presentations and with qualitative face-to-face interviews with university oral presentation tutors and nursing students. Evidence for the internal structure of the 28-item scale was conducted with exploratory and confirmatory factor analysis (EFA and CFA, respectively), and internal consistency. Relationships with Personal Report of Communication Apprehension and Self-Perceived Communication Competence to conduct the relationships with other variables evidence. Results Nursing students’ (n = 325) responses to the scale provided the data for the EFA, which resulted in three factors: accuracy of content, effective communication, and clarity of speech. These factors explained 64.75% of the total variance. Eight items were dropped from the original item pool. The Cronbach’s α value was .94 for the total scale and ranged from .84 to .93 for the three factors. The internal structure evidence was examined with CFA using data from a second group of 325 students, and an additional five items were deleted. Except for the adjusted goodness of fit, fit indices of the model were acceptable, which was below the minimum criteria. The final 15-item OPES was significantly correlated with the students’ scores for the Personal Report of Communication Apprehension scale (r = −.51, p r = .45, p Conclusions The OPES could be adopted as a self-assessment instrument for nursing students when learning oral presentation skills. Further studies are needed to determine if the OPES is a valid instrument for nursing educators’ objective evaluations of student presentations across nursing programs.

Sphingosine-1-phosphate (S1P), is a signaling sphingolipid which acts as a bioactive lipid mediator. We assessed whether S1P had multiplex effects in regulating the large-conductance Ca2+-activated K+ channel (BKCa) in catecholamine-secreting chromaffin cells. Using multiple patch-clamp modes, Ca2+ imaging, and computational modeling, we evaluated the effects of S1P on the Ca2+-activated K+ currents (IK(Ca)) in bovine adrenal chromaffin cells and in a pheochromocytoma cell line (PC12). In outside-out patches, the open probability of BKCa channel was reduced with a mean-closed time increment, but without a conductance change in response to a low-concentration S1P (1 µM). The intracellular Ca2+ concentration (Cai) was elevated in response to a high-dose (10 µM) but not low-dose of S1P. The single-channel activity of BKCa was also enhanced by S1P (10 µM) in the cell-attached recording of chromaffin cells. In the whole-cell voltage-clamp, a low-dose S1P (1 µM) suppressed IK(Ca), whereas a high-dose S1P (10 µM) produced a biphasic response in the amplitude of IK(Ca), i.e., an initial decrease followed by a sustained increase. The S1P-induced IK(Ca) enhancement was abolished by BAPTA. Current-clamp studies showed that S1P (1 µM) increased the action potential (AP) firing. Simulation data revealed that the decreased BKCa conductance leads to increased AP firings in a modeling chromaffin cell. Over a similar dosage range, S1P (1 µM) inhibited IK(Ca) and the permissive role of S1P on the BKCa activity was also effectively observed in the PC12 cell system. The S1P-mediated IK(Ca) stimulation may result from the elevated Cai, whereas the inhibition of BKCa activity by S1P appears to be direct. By the differentiated tailoring BKCa channel function, S1P can modulate stimulus-secretion coupling in chromaffin cells.

Background Negatively charged very-low-density lipoprotein (VLDL-χ) in metabolic syndrome (MetS) patients exerts cytotoxic effects on endothelial cells and atrial myocytes. Atrial cardiomyopathy, manifested by atrial remodeling with a dilated diameter, contributes to atrial fibrillation pathogenesis and predicts atrial fibrillation development. The correlation of VLDL-χ with atrial remodeling is unknown. This study investigated the association between VLDL-χ and remodeling of left atrium. Methods Consecutively, 87 MetS and 80 non-MetS individuals between 23 and 74 years old (50.6% men) without overt cardiovascular diseases were included in the prospective cohort study. Blood samples were collected while fasting and postprandially (at 0.5, 1, 2, and 4 h after a unified meal). VLDL was isolated by ultracentrifugation; the percentile concentration of VLDL-χ (%) was determined by ultra-performance liquid chromatography. The correlations of left atrium diameter (LAD) with variables including VLDL-χ, LDL-C, HDL-C, triglycerides, glucose, and blood pressure, were analyzed by multiple linear regression models. A hierarchical linear model was conducted to test the independencies of each variable’s correlation with LAD. Results The mean LAD was 3.4 ± 0.5 cm in non-MetS subjects and 3.9 ± 0.5 cm in MetS patients (P P Conclusions Postprandial VLDL-χ is associated with atrial remodeling particularly in the MetS group. VLDL-χ is a novel biomarker and may be a therapeutic target for atrial cardiomyopathy in MetS patients. Trial registration ISRCTN 69295295. Retrospectively registered 9 June 2020.

Background: Negatively charged very-low-density lipoprotein (VLDL-χ) in metabolic syndrome (MetS) patients exerts cytotoxic effects on endothelial cells and atrial myocytes. Atrial cardiomyopathy, manifested by atrial remodeling with a dilated diameter, contributes to atrial fibrillation pathogenesis and predicts atrial fibrillation development. The correlation of VLDL-χ with atrial remodeling is unknown. This study investigated the association between VLDL-χ and left atrial dilatation. Methods: Consecutively, 87 MetS and 80 non-MetS individuals between 23 and 74 years old (50.6% men) without overt cardiovascular diseases were included in the prospective cohort study. Blood samples were collected while fasting and postprandially (at 0.5, 1, 2, and 4 hours after a unified meal). VLDL was isolated by ultracentrifugation; the percentile concentration of VLDL-χ (%) was determined by ultra-performance liquid chromatography. The correlations of left atrial diameter (LAD) with variables including VLDL-χ, LDL-C, HDL-C, triglycerides, glucose, and blood pressure, were analyzed by multiple linear regression models. A hierarchical linear model was conducted to test the independencies of each variable’s correlation with LAD. Results: The mean LAD was 3.4 ± 0.5 cm in non-MetS subjects and 3.9 ± 0.5 cm in MetS patients (P< 0.01). None of the fasting lipid profiles were associated with LAD. VLDL-χ, BMI, waist circumference, hip circumference, and blood pressure were positively correlated with LAD (all PConclusions: Postprandial VLDL-χ is associated with atrial remodeling. VLDL-χ is a novel biomarker and may be a therapeutic target for atrial cardiomyopathy in MetS patients. Trial registration: ISRCTN 69295295. Retrospectively registered 9 June 2020.

Background:Negatively charged very-low-density lipoprotein (VLDL-χ) in metabolic syndrome (MetS) patients exerts cytotoxic effects on endothelial cells and atrial myocytes. Atrial cardiomyopathy, manifested by atrial remodeling with a dilated diameter, contributes to atrial fibrillation pathogenesis and predicts atrial fibrillation development. The correlation of VLDL-χ with atrial remodeling is unknown. This study investigated the association between VLDL-χ and left atrial dilatation. Methods: We evaluated 87 MetS and 80 non-MetS individuals between 23 and 74 years old (50.6% men) without overt cardiovascular diseases. Blood samples were collected while fasting and postprandially (at 0.5, 1, 2, and 4 hours after a unified meal). VLDL was isolated by ultracentrifugation; the percentile concentration of VLDL-χ (%) was determined by ultra-performance liquid chromatography. The correlations of left atrial diameter (LAD) with variables including VLDL-χ, LDL-C, HDL-C, triglycerides, glucose, and blood pressure, were analyzed by multiple linear regression models. A hierarchical linear model was conducted to test the independencies of each variable’s correlation with LAD. Results: The mean LAD was 3.4 ± 0.5 cm in non-MetS subjects and 3.9 ± 0.5 cm in MetS patients (P< 0.01). None of the fasting lipid profiles were associated with LAD. VLDL-χ, BMI, waist circumference, hip circumference, and blood pressure were positively correlated with LAD (all PConclusions: Postprandial VLDL-χ is associated with atrial remodeling. VLDL-χ is a novel biomarker for atrial cardiomyopathy in MetS patients and may be a therapeutic target. Trial registration: ISRCTN 69295295. Retrospectively registered 9 June 2020.

Background: Negatively charged very-low-density lipoprotein (VLDL-χ) in metabolic syndrome (MetS) patients exerts cytotoxic effects on endothelial cells and atrial myocytes. Atrial cardiomyopathy, manifested by atrial remodeling with a dilated diameter, contributes to atrial fibrillation pathogenesis and predicts atrial fibrillation development. The correlation of VLDL-χ with atrial remodeling is unknown. This study investigated the association between VLDL-χ and left atrial dilatation. Methods: We evaluated 87 MetS and 80 non-MetS individuals between 23 and 74 years old (50.6% men) without overt cardiovascular diseases. Blood samples were collected while fasting and postprandially (at 0.5, 1, 2, and 4 hours after a unified meal). VLDL was isolated by ultracentrifugation; the percentile concentration of VLDL-χ (%) was determined by ultra-performance liquid chromatography. The correlations of left atrial diameter (LAD) with variables including VLDL-χ, LDL-C, HDL-C, triglycerides, glucose, and blood pressure, were analyzed by multiple linear regression models. A hierarchical linear model was conducted to test the independencies of each variable’s correlation with LAD. Results: The mean LAD was 3.4 ± 0.5 cm in non-MetS subjects and 3.9 ± 0.5 cm in MetS patients (P< 0.01). None of the fasting lipid profiles were associated with LAD. VLDL-χ, BMI, waist circumference, hip circumference, and blood pressure were positively correlated with LAD (all P Conclusion: Postprandial VLDL-χ is associated with atrial remodeling. VLDL-χ is a novel biomarker for atrial cardiomyopathy in MetS patients and may be a therapeutic target. Trial registration: ISRCTN 69295295. Registered 9 June 2020.

Mesenchymal stem cells (MSCs) have two characteristics of interest for this paper: the ability to self-renew, and the potential for multiple-lineage differentiation into various cells. MSCs have been used in cardiac tissue regeneration for over a decade. Adult cardiac tissue regeneration ability is quite low; it cannot repair itself after injury, as the heart cells are replaced by fibroblasts and lose function. It is therefore important to search for a feasible way to repair and restore heart function through stem cell therapy. Stem cells can differentiate and provide a source of progenitor cells for cardiomyocytes, endothelial cells, and supporting cells. Studies have shown that the concentrations of blood lipids and lipoproteins affect cardiovascular diseases, such as atherosclerosis, hypertension, and obesity. Furthermore, the MSC lipid profiles, such as the triglyceride and cholesterol content, have been revealed by lipidomics, as well as their correlation with MSC differentiation. Abnormal blood lipids can cause serious damage to internal organs, especially heart tissue. In the past decade, the accumulated literature has indicated that lipids/lipoproteins affect stem cell behavior and biological functions, including their multiple lineage capability, and in turn affect the outcome of regenerative medicine. This review will focus on the effect of lipids/lipoproteins on MSC cardiac regenerative medicine, as well as the effect of lipid-lowering drugs in promoting cardiomyogenesis-associated MSC differentiation.

Atrial fibrillation (AF) is the most common persistent arrhythmia, and can lead to systemic thromboembolism and heart failure. Aging and metabolic syndrome (MetS) are major risks for AF. One of the most important manifestations of MetS is dyslipidemia, but its correlation with AF is ambiguous in clinical observational studies. Although there is a paradoxical relationship between fasting cholesterol and AF incidence, the beneficial benefit from lipid lowering therapy in reduction of AF is significant. Here, we reviewed the health burden from AF and MetS, the association between two disease entities, and the metabolism of triglyceride, which is elevated in MetS. We also reviewed scientific evidence for the mechanistic links between very low density lipoproteins (VLDL), which primarily carry circulatory triglyceride, to atrial cardiomyopathy and development of AF. The effects of VLDL to atria suggesting pathogenic to atrial cardiomyopathy and AF include excess lipid accumulation, direct cytotoxicity, abbreviated action potentials, disturbed calcium regulation, delayed conduction velocities, modulated gap junctions, and sarcomere protein derangements. The electrical remodeling and structural changes in concert promote development of atrial cardiomyopathy in MetS and ultimately lead to vulnerability to AF. As VLDL plays a major role in lipid metabolism after meals (rather than fasting state), further human studies that focus on the effects/correlation of postprandial lipids to atrial remodeling are required to determine whether VLDL-targeted therapy can reduce MetS-related AF. On the basis of our scientific evidence, we propose a pivotal role of VLDL in MetS-related atrial cardiomyopathy and vulnerability to AF.

Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of neuronal degeneration. However, the effects of chronic dyslipidemia on brain function, especially in older individuals, remain unclear. In this study, middle-aged 37-week-old male Wistar-Kyoto rats were fed a normal diet (ND) or a 45% high-fat diet (HFD) for 30 weeks (i.e., until 67 weeks of age). To study the effects of chronic dyslipidemia on the brain, we analyzed spontaneous locomotor activity, cognitive function, and brain tissues in both groups of rats after 30 weeks. Compared with age-matched rats fed a ND, Wistar-Kyoto rats fed a HFD had dyslipidemia and showed decreased movement but normal recognition of a novel object. In our brain analyses, we observed a significant decrease in astrocytes and tyrosine hydroxylase–containing neurons in the substantia nigra and locus coeruleus of rats fed a HFD compared with rats fed a ND. However, hippocampal pyramidal neurons were not affected. Our findings indicate that the long-term consumption of a HFD may cause lipid metabolism overload in the brain and damage to glial cells. The decrease in astrocytes may lead to reduced protection of the brain and affect the survival of tyrosine hydroxylase–containing neurons but not pyramidal neurons of the hippocampus.

Electronegative L5 low-density lipoprotein (LDL) level may be a useful biomarker for predicting cardiovascular disease. We determined the range of plasma L5 levels in healthy adults (n = 35) and examined the power of L5 levels to differentiate patients with coronary artery disease (CAD; n = 40) or patients with hyperlipidemia (HLP) without evidence of CAD (n = 35) from healthy adults. The percent L5 in total LDL (L5%) was quantified by using fast-protein liquid chromatography with an anion-exchange column. Receiver operating characteristic curve analysis was performed to determine cut-off values for L5 levels. The mean L5% and plasma concentration of L5 (ie, [L5]) were significantly higher in patients with HLP or CAD than in healthy adults (P 1.6%, the odds ratio was 9.636 for HLP or CAD. In individuals with [L5] >1.7 mg/dL, the odds ratio was 17.684 for HLP or CAD. The power of L5% or [L5] to differentiate patients with HLP or CAD from healthy adults was superior to that of the LDL/high-density lipoprotein ratio. The ranges of L5% and [L5] in healthy adults determined here may be clinically useful in preventing and treating cardiovascular disease.

Background/Purpose: Left ventricular hypertrophy is a major cause of heart failure in aging population. This study is to determine whether an excess dietary fat is lipotoxic or lipoprotein to the hypertrophic aging heart. Methods: At 44-week-old, a normal chow (12% fat) was replaced a high-fat diet (HFD; 45% fat) for randomly selective spontaneously hypertensive rats (SHR + HFD, n = 6) and Wistar-Kyoto rats (WKY + HFD, n = 6, normotensive control). Others (SHR, n = 11; WKY, n = 10) were continuously fed with normal diets. After 27 weeks, electrocardiogram, echocardiography, and femoral arterial catheterization were performed before rats being sacrificed for molecular biology analyses. Results: HFD aggravated cardiac atrial, ventricular dilation and hypertrophy in SHR (LV mass: SHR + HFD 2026.0 ± 424.9 vs SHR 1449 ± 461.1 mg, unpaired t test P

Aim To determine if levels of spiritual health, health-promoting behaviors, depressive symptoms and resilience change over time and determine if any variables have an impact on resilience among new nurses. Background Nurses provide patients with medical care and emotional support in high-stress environments. Resilience is a characteristic that allows one to adjust to these adverse situations. Resilience can help new nurses withstand the emotional stress of the workplace and improve nurse retention. Method The study was conducted from 2017 to 2019 with a convenience sample of nursing students (N = 195). Data were collected at four timepoints with self-report questionnaires on spiritual health, health-promoting behaviors, resilience and the Beck Depression Inventory-II from 2017 to 2019. Three timepoints were collected during the fourth year of the student stage: fall semester (T1), spring semester (T2) and just prior to graduation (T3); the fourth timepoint was the novice stage (T4), after at least 3 months as a registered nurse. General estimating equations determined predictors of resilience. Results A total of 124 new nurses completed all questionnaires (63% response rate). Although mean scores fluctuated slightly during the student stage, the scores at T4 were significantly worse for spiritual health (Wald χ2 = 30.23, p Conclusions Scores for all variables were similar over the three timepoints of the student stage. However, the significant changes at T4 compared with the student stage suggest the novice stage of nursing was challenging. Increasing resilience could reduce the challenges of transitioning to a hospital environment. Nursing educators and administrators could increase nursing students’ resilience by restructuring the educational curricula. This could include helping nurses increase their spirituality and health-related behaviors and providing psychological support to reduce depressive symptoms. Increasing levels of resilience could reduce nurses’ emotional stress and improve retention of new nurses.

Context Electronegative low-density lipoprotein (LDL) L5 is a naturally occurring, atherogenic entity found at elevated levels in the plasma of patients with metabolic syndrome (MetS) in the absence of elevated plasma LDL levels. Objective To investigate the role of L5 in the mechanism of adipose tissue inflammation associated with MetS. Patients/Setting Plasma LDL isolated from patients with MetS (n = 29) and controls (n = 29) with similar plasma LDL levels was separated into five subfractions, L1 to L5, with increasing electronegativity. Design We examined the invivo effects of L5 on adipose tissue in mice and the in vitro effects of L5 on adipocytokine signaling and monocytes. Results Tail-vein injection of human L5 but not L1 into C57BL/6 mice induced the accumulation of F4/80+ and CD11c+ M1 macrophages. The effects of L5 were attenuated in mice deficient for L5's receptor, lectin-like oxidized LDL receptor 1 (LOX-1). L5 but not L1 induced human adipocytes to release inflammatory adipocytokines. Incubating human THP-1 monocytes with LDL-free culture media from L5-treated adipocytes enhanced the migration of monocytes by 300-fold (P < 0.001 vs L1-treated adipocyte media)-effects that were attenuated by LOX-1 neutralizing antibody. Migrated cells were positive for mature macrophage marker PM-2K, indicating the transformation of monocytes into macrophages. The infiltration of M1 macrophages in adipose tissue was also observed in a previously established hamster model of endogenously elevated L5. Conclusions L5 induces adipose inflammation through LOX-1 by promoting macrophage maturation and infiltration into adipose tissue. Elevated plasma L5 levels may be a novel etiology of adipose tissue inflammation in patients with MetS.

Gain-of-function mutations in the pore-forming subunit of IKs channels, KCNQ1, lead to short QT syndrome (SQTS) and lethal arrhythmias. However, how mutant IKs channels cause SQTS and the possibility of IKs-specific pharmacological treatment remain unclear. V141M KCNQ1 is a SQTS associated mutation. We studied its effect on IKs gating properties and changes in the action potentials (AP) of human ventricular myocytes. Xenopus oocytes were used to study the gating mechanisms of expressed V141M KCNQ1/KCNE1 channels. Computational models were used to simulate human APs in endocardial, mid-myocardial, and epicardial ventricular myocytes with and without β-adrenergic stimulation. V141M KCNQ1 caused a gain-of-function in IKs characterized by increased current density, faster activation, and slower deactivation leading to IKs accumulation. V141M KCNQ1 also caused a leftward shift of the conductance-voltage curve compared to wild type (WT) IKs (V1/2 = 33.6 ± 4.0 mV for WT, and 24.0 ± 1.3 mV for heterozygous V141M). A Markov model of heterozygous V141M mutant IKs was developed and incorporated into the O’Hara–Rudy model. Compared to the WT, AP simulations demonstrated marked rate-dependent shortening of AP duration (APD) for V141M, predicting a SQTS phenotype. Transmural electrical heterogeneity was enhanced in heterozygous V141M AP simulations, especially under β-adrenergic stimulation. Computational simulations identified specific IK1 blockade as a beneficial pharmacologic target for reducing the transmural APD heterogeneity associated with V141M KCNQ1 mutation. V141M KCNQ1 mutation shortens ventricular APs and enhances transmural APD heterogeneity under β-adrenergic stimulation. Computational simulations identified IK1 blockers as a potential antiarrhythmic drug of choice for SQTS.

BACKGROUND Religion is an important cultural asset that is known to affect the thoughts, behaviors, and lifestyles of individuals. However, the impact of religious affiliation, religious activities, and religious beliefs on the attitudes of nurses toward providing spiritual care to their patients is an issue that has been inadequately explored. PURPOSES The aim of this study was to explore the relationship between religion (including religious affiliation, religious activities, and religious beliefs) and attitude toward spiritual care in clinical nurses. METHODS This study used a cross-sectional correlation study design. Six hundred nineteen nurses were included as participants. The measurements used included a questionnaire on religious affiliation, religious activities, and religious beliefs; the Spiritual Health Scale-Short Form; the Spiritual Care Attitude Scale; and a sociodemographic datasheet. The study employed hierarchical regression modeling to establish the relationships between the aspects and degrees of religious belief and practice as well as the attitudes of participants toward spiritual care. RESULTS Most of the participants participated infrequently in religious activities. After controlling for demographic variables and spiritual health, religious belief was found to be an important factor impacting participants' attitudes toward providing spiritual care. CONCLUSIONS/IMPLICATIONS FOR PRACTICE The findings indicate that religious belief is an important factor impacting the attitudes of nurses toward providing spiritual care and that the religious/spiritual beliefs of nurses may impact on their fitness to provide spiritual care to patients. Education on religion may be needed to improve the attitude of nurses toward providing spiritual care.

OBJECTIVE Patients with systemic lupus erythematosus (SLE) often have atherosclerotic complications at a young age but normal low-density lipoprotein (LDL) levels. This study was undertaken to investigate the role of LDL composition in promoting early vascular aging in SLE patients. METHODS Plasma LDL from 45 SLE patients (SLE-LDL) and from 37 normal healthy controls (N-LDL) was chromatographically divided into 5 subfractions (L1-L5), and the subfraction composition was analyzed. Correlations between subfraction levels and signs of early vascular aging were assessed. Mechanisms of lipid-mediated endothelial dysfunction were explored using in vitro assays and experiments in apoE-/- mice. RESULTS The L5 percentage was increased 3.4 times in the plasma of SLE patients compared with normal controls. This increased percentage of SLE-L5 was positively correlated with the mean blood pressure (r = 0.27, P = 0.04), carotid intima-media thickness (IMT) (right carotid IMT, r = 0.4, P = 0.004; left carotid IMT, r = 0.36, P = 0.01), pulse wave velocity (r = 0.29, P = 0.04), and blood levels of CD16+ monocytes (r = 0.35, P = 0.004) and CX3CL1 cytokines (r = 0.43, P < 0.001) in SLE patients. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis revealed that plasma levels of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF) were increased in SLE-LDL and in the SLE-L5 plasma subfraction. Injecting SLE-LDL, SLE-L5, or LPC into young, male apoE-/- mice caused increases in plasma CX3CL1 levels, aortic fatty-streak areas, aortic vascular aging, and macrophage infiltration into the aortic wall, whereas injection of N-LDL or SLE-L1 had negligible effects (n = 3-8 mice per group). In vitro, SLE-L5 lipid extracts induced increases in CX3CR1 and CD16 expression in human monocytes; synthetic PAF and LPC had similar effects. Furthermore, lipid extracts of SLE-LDL and SLE-L5 induced the expression of CX3CL1 and enhanced monocyte-endothelial cell adhesion in assays with bovine aortic endothelial cells. CONCLUSION An increase in plasma L5 levels, not total LDL concentration, may promote early vascular aging in SLE patients, leading to premature atherosclerosis.

Background Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. Methods and results The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. Conclusions Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.

For studies related to cardiovascular physiology or pathophysiology, blood pressure (BP) and electrocardiography are basic observational parameters. Research focusing on cardiovascular disease models, potential cardiovascular therapeutic targets or pharmaceutical agents requires assessment of systemic arterial pressure and heart rhythm changes. In situations where radio telemetry systems are not available or affordable, the technique of femoral artery cannulation is an alternative way to obtain intra-arterial pressure waveform recordings and systemic BP measurements. This technique is economical and can be performed with standard equipment in animal facilities. However, invasive arterial pressure recording requires cannulation of small arteries, which can be a challenging surgical skill. Here, we present step-by-step protocols for femoral artery cannulation procedures. Key procedures include the calibration of the data acquisition system, tissue dissection and femoral artery cannulation, and setup of the arterial cannulation system for pressure recording. Surface electrocardiography recording procedures are also included. We also present examples of BP recordings from normotensive and hypertensive rats. This protocol allows reliable direct recordings of systemic BP with simultaneous electrocardiography.

The study aimed to determine the impact of an elective spiritual education course for nursing students on spiritual competencies. A convenience sample of nursing students (N = 92) was recruited from a baccalaureate school of nursing between February and July 2016. The intervention group (n = 45) was comprised of students enrolled in the elective spiritual education course which integrated non-Christian Eastern cultural beliefs; the control group was comprised of students not enrolled in the elective (n = 47). A quasi-experimental design examined pretest, posttest, and follow-up data from students' self-administered questionnaires. The intervention effect of the course was analyzed using generalized estimation equation. The results indicated posttest scores among nursing students in the intervention group were significantly better than the comparison group for spiritual health. Practicum stress and professional commitment were significantly better at follow-up. Spiritual care attitudes, caring behavior, and religious belief were significantly improved from pretest to posttest, and at follow-up for the intervention group compared with the control group. In conclusion, a spiritual education course should be considered as a regular course in the nursing curriculum, which could improve students’ spiritual competencies, individual spiritual growth, and the ability to care for patients.

Aims To: (a) explore the prevalence of the symptoms perceived by patients with childhood-onset systemic lupus erythematosus; (b) identify the symptom clusters occurring in patients with childhood-onset Systemic lupus erythematosus; and (c) examine the association of the burden of each symptom cluster with sleep quality and depression. Background Systemic lupus erythematosus is an inflammatory autoimmune disease that may result in patients' perception of various symptoms, with possible negative effects on their quality of life. Understanding the prevalence of symptoms perceived by childhood-onset Systemic lupus erythematosus patients and the disease's symptom clusters may be helpful in managing such burdensome symptoms. Design A correlational study design was used for this study in 2016. Methods Self-reported data from the Systemic lupus erythematosus symptom checklist were used to assess the symptoms perceived by patients. Symptom clusters were analysed using cluster analysis. Results Seventy-five patients were included in this study. The most prevalent and burdensome symptom perceived by patients was fatigue. Five clusters were derived, including symptoms related to pain and itching; bruises and stomach complaints; weight gain; body image and circulatory problems; and fatigue. A poor sleeper may perceive a greater symptom burden in all five of the symptom clusters, except for cluster #3, which refers to symptoms related to weight gain. Conclusion Five symptom clusters were identified. It is hoped that this study will give useful knowledge for understanding the symptom clusters for patients with Systemic lupus erythematosus and for improving nursing care quality.

The ankle-brachial index (ABI) is a reliable diagnostic examination for peripheral arterial occlusive disease (PAOD). We previously reported CHADS2 score was significantly correlated with PAOD. However, the association between CHA2DS2-VASc score and ABI 2DS2-VASc score has a strong association with PAOD. We enrolled 1482 patients in this study. PAOD was defined as ABI 2DS2-VASc score was modified as vascular disease except PAOD. Of the 1482 subjects, the prevalence of ABI 2DS2-VASc score (OR, 1.764; p 2DS2-VASc score of 0, 1, and 2DS2-VASc score was significantly associated with ABI 2DS2-VASc score might be useful in identifying patients with PAOD and in stratifying the risk of PAOD in non-AF patients.

Background: Nurses account for a significant percentage of staff in the healthcare system. The religious beliefs of nurses may affect their competence to provide spiritual care to patients. No reliable and valid instruments are currently available to measure the religious beliefs of nurses in Taiwan. Purposes: The aims of this study were to develop a religious belief scale (RBS) for Taiwanese nurses and to evaluate the psychometric properties of this scale. Methods: A cross-sectional study design was used, and 24 RBS items were generated from in-depth interviews, a literature review, and expert recommendations. The RBS self-administered questionnaire was provided to 619 clinical nurses, who were recruited from two medical centers and one local hospital in Taiwan during 2011-2012. A calibration sample was used to explore the factor structure, whereas a validation sample was used to validate the factor structure that was constructed by the calibration sample. Known-group validity and criterion-related validity were also assessed. Results: An exploratory factor analysis resulted in an 18-item RBS with four factors, including ＂religious effects,＂ ＂divine,＂ ＂religious query,＂ and ＂religious stress.＂ A confirmatory factor analysis recommended the deletion of one item, resulting in a final RBS of 17 items. The convergent validity and discriminate validity of the RBS were acceptable. The RBS correlated positively with spiritual health and supported concurrent validity. The known-group validity was supported by showing that the mean RBS between nurses with or without religious affiliation was significant. Conclusions/Implications for Practice: The 17-item RBS developed in this study is a reliable, valid, and useful scale for measuring the religious beliefs of nurses in Taiwan. This scale may help measure the religious beliefs of nurses and elicit the relationship between these beliefs and spirituality.

Very-low-density lipoproteins (VLDL) is a hallmark of metabolic syndrome (MetS) and each manifestation of MetS is related to atrial fibrillation (AF) risks. Slowed atrial conduction is a mechanism of AF in MetS. We hypothesized that VLDL can modulate and reduce atrial gap junctions. VLDLs were separated from normal (Normal-VLDL) and MetS (MetS-VLDL) individuals. VLDLs (15 µg/g) and equivalent volumes of saline (CTL) were injected respectively to C57BL/6 mice for 6 weeks. Electrocardiograms demonstrated that MetS-VLDL induced prolongation of P wave (P = 0.041), PR intervals (P = 0.014), QRS duration and QTc interval (both P = 0.003), but Normal-VLDL did not. Optical mapping of perfused hearts confirmed slowed conduction on atria and ventricles of MetS-VLDL mice. Slowed cardiac conduction was associated with significant atrial and ventricular remodeling, along with systolic dysfunction and comparable intra-cardiac fibrosis. MetS-VLDL induced downregulation of Cx40 and Cx43 at transcriptional, translational and tissue levels, and it also enhanced O-GlcNAcylation of Cx40 and Cx43. Protein structure analyses predicted O-GlcNAcylation at serine 18 of Cx40 and Cx43 which may impair stability of gap junctions. In conclusion, MetS-VLDL modulates gap junctions and delays both atrial and ventricular conduction. VLDL may contribute to the pathophysiology of atrial fibrillation and ventricular arrhythmias in MetS.

The ankle-brachial index (ABI) is a reliable diagnostic examination for peripheral arterial occlusive disease (PAOD). We previously reported CHADS2 score was significantly correlated with PAOD. However, the association between CHA2DS2-VASc score and ABI

Hyperglycemia-associated glucotoxicity induces β-cell dysfunction and a reduction in insulin secretion. Voltage-dependent K+ (Kv) channels in pancreatic β-cells play a key role in glucose-dependent insulin secretion. KMUP-1, a xanthine derivative, has been demonstrated to modulate Kv channel activity in smooth muscles; however, the role of KMUP-1 in glucotoxicity-activated Kv channels in pancreatic β-cells remains unclear. In this study we examined the mechanisms by which KMUP-1 could inhibit high glucose (25 mM) activated Kv currents (IKv) in pancreatic β-cells. Pancreatic β-cells were isolated from Wistar rats and IKv was monitored by perforated patch-clamp recording. The peak IKv in high glucose-treated β-cells was ∼1.4-fold greater than for normal glucose (5.6 mM). KMUP-1 (1, 10, 30 μM) prevented high glucose-stimulated IKv in a concentration-dependent manner. Reduction of high glucose-activated IKv was also found for protein kinase A (PKA) activator 8-Br-cAMP (100 μM). Additionally, KMUP-1 (30 μM) current inhibition was reversed by the PKA inhibitor H-89 (1 μM). Otherwise, pretreatment with the PKC activator or inhibitor had no effect on IKv in high glucose exposure. In conclusion, glucotoxicity-diminished insulin secretion was due to IKv activation. KMUP-1 attenuated high glucose-stimulated IKv via the PKA but not the PKC signaling pathway. This finding provides evidence that KMUP-1 might be a promising agent for treating hyperglycemia-induced insulin resistance.

Background: The most electronegative subfraction of low-density lipoprotein (LDL), L5, is atherogenic in vitro and in vivo, and its plasma levels are elevated in patients with high cardiovascular disease risk and ischemic stroke (Blood 2016;127:1336-45). Because L5 LDL may be a useful biomarker for predicting cardiovascular disease, we defined a reference range for L5 plasma levels in healthy adults and examined the power of L5 levels to differentiate patients with hyperlipidemia (HLP) or coronary artery disease (CAD) from healthy individuals. Methods: We enrolled 35 healthy individuals, 40 patients with stable CAD, and 35 patients with HLP without evidence of CAD. Plasma LDL was isolated from each individual, and the percentage of L5 in total LDL (L5%) was quantified by using fast-protein liquid chromatography with an anion-exchange column. Results: Plasma L5% and L5 concentration (ie, [L5]) were significantly higher in patients with HLP or CAD than in healthy controls (P Conclusions: The power of L5% and [L5] in predicting cardiovascular risk is superior to that of other markers currently in use. Therefore, the reference ranges of L5% and [L5] identified in this study may be clinically useful in the prevention and treatment of cardiovascular disease. As previously reported, elevated plasma L5 levels may promote or aggravate ischemic stroke by enhancing platelet aggregation and platelet-endothelium interactions.

Significantly higher cytotoxic and thrombogenic human electronegative low-density lipoprotein (LDL), or L5, has been found in patients with stable coronary artery disease and acute coronary syndrome. We hypothesized that the statin-benefit groups (SBGs) defined by the new cholesterol guideline were of higher electronegative L5.In total, 62 hyperlipidemia patients (mean age 59.4 ± 10.5, M/F 40/22) were retrospectively divided into SBGs (n = 44) and N-SBGs (n = 18). The levels of complete basic lipid panel, biochemical profile and electronegative L5 of each individual were obtained before and after rosuvastatin 10 mg/day for 3 months.After 3 months' statin therapy, significant reduction of total cholesterol, LDL-C and triglyceride were demonstrated (all p-values0.05), with 38.4% LDL-C reduction. The percentage of L5 was significantly reduced by 40.9% (from 4.4% to 2.6%) after statin therapy (p = 0.001). Regarding absolute L5 concentration, derived from L5% multiplied by LDL-C, there was approximate 63.8% reduction (from 6.3 mg/dL to 2.3 mg/dL) of absolute L5 (p0.001) after statin treatment. Notably, while plasma LDL-C levels were similar between SBGs and N-SBGs (152.8 ± 48.6 vs. 146.9 ± 35.0 mg/dL), the SBGs had significantly elevated L5% (5.2 ± 7.4% vs. 2.6 ± 1.9%, p = 0.031) and higher absolute L5 concentration (7.4 ± 10.4 vs. 3.7 ± 3.1 mg/dL, p = 0.036). Linear regression showed the significantly positive correlation between the plasma L5 concentration and the 10-year cardiovascular risk by pooled cohort equation (r = 0.297, p0.05).The four SBGs defined by the 2013 ACC/AHA new cholesterol guideline tend to have increased atherogenic electronegative L5. Statin therapy can effectively reduce the electronegative L5 of these four major SBGs.