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1.
Inquiry ; 61: 469580241239143, 2024.
Article in English | MEDLINE | ID: mdl-38506439

ABSTRACT

A good death is a human right. Unfortunately, patients with chronic heart failure (CHF) in the terminal stage still receive inappropriate life-sustaining treatment before death. There is limited understanding of the status of intensive care unit (ICU) admission, mechanical ventilation (MV), cardiopulmonary resuscitation (CPR), and even extracorporeal membrane oxygenation (ECMO) for patients with CHF before death, as well as their use of hospice-related services. This study investigated the trends and trend changes in intensive procedures and hospice-related services for patients with CHF in the last month of life. This population-based retrospective observational study included 25 375 patients with CHF from the National Health Insurance research database in Taiwan and collected information on their intensive treatments during the last month of life. We computed intensive treatment utilization rates and analyzed the trends and trend changes via joinpoint regression. The average percentage of patients with CHF admitted to ICUs was 53.27% (n = 13 516). A total of 327 (1.29%) patients with CHF received ECMO. The percentages of patients receiving MV (54.3%'41.5%) and CPR (41.5%'17%) decreased over time. Conversely, the percentage of ECMO use (0.52%'1.78%) increased. However, only 222 (0.87%) patients with CHF received hospice care in the last month of life between 2001 and 2013. The rates of ICU admission and life-sustaining treatment among patients with CHF in the month before death remain high, and hospice-related services remain inadequate. This study highlights the need for research and training in providing palliative and hospice care for patients with CHF.


Subject(s)
Heart Failure , Hospice Care , Humans , Hospitalization , Retrospective Studies , Chronic Disease , Critical Care , Intensive Care Units , Heart Failure/therapy
2.
Kaohsiung J Med Sci ; 40(4): 384-394, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38332510

ABSTRACT

Transcatheter aortic valve replacement (TAVR) is a well-established procedure using a catheter-introduced valve prosthesis for patients with severe aortic stenosis (AS). This retrospective study investigated sex-related differences in pre- and post-TAVR clinical and hemodynamic outcomes and analyzed data of the first 100 cases at Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) between December 2013 and December 2021. Baseline characteristics, procedural outcomes, mortality rates, and echocardiographic parameters were analyzed and compared between sexes. Among the 100 patients, male (46%) and female (54%) were of similar age (mean age, male 86.0 years vs. female 84.5 years) and of the same severity of AS (mean pressure gradient, male 47.5 mmHg vs. female 45.7 mmHg) at the time receiving the TAVR procedure. Women had smaller aortic valve areas calculated by continuity equation (0.8 ± 0.3 cm2 vs. 0.7 ± 0.2 cm2, p < 0.001). In addition, women had better left ventricle ejection fraction (59.6 ± 14.0% vs. men 54.7 ± 17.2%, p < 0.01). In the post-TAVR follow-up, regression of left ventricle mass and dimension was better in women than in men. None of the patient died within 30 days after the procedure, and women tended to have a more favorable survival than men (2-year mortality and overall mortality rate in 8.3 year, women 9.1% and 22.2% vs. men 22.2% and 34.8%; p = 0.6385 and 0.1277, respectively). In conclusion, the sex-based difference in post-TAVR regression of LV remodeling suggests a need for sex-based evaluation for patients with severe AS and their post TAVR follow-up.


Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Male , Female , Aged, 80 and over , Transcatheter Aortic Valve Replacement/methods , Follow-Up Studies , Retrospective Studies , Aortic Valve Stenosis/surgery , Heart Ventricles/diagnostic imaging , Treatment Outcome , Hypertrophy/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Severity of Illness Index
3.
Antioxidants (Basel) ; 12(5)2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37237867

ABSTRACT

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.

4.
Sci Rep ; 13(1): 6575, 2023 04 21.
Article in English | MEDLINE | ID: mdl-37085694

ABSTRACT

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.


Subject(s)
Atrial Remodeling , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Metabolic Syndrome , Humans , Lipoproteins, VLDL , Phosphatidylethanolamines , Triglycerides , Fatty Acids, Unsaturated
6.
Int J Rheum Dis ; 26(8): 1608-1611, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36938829

ABSTRACT

Non-radiographic axial spondyloarthropathy (nr-axSpA) is a clinical diagnosis of symptoms matching inflammatory back pain criteria without radiological lesions at the sacroiliac joint. The frequency of an early nr-axSpA-like presentation in lymphoma patients has not been clarified. Here we report a woman in her 20s with a fever and musculoskeletal discomfort. Detailed investigations revealed that she was suffering from Burkitt lymphoma in which nr-axSpA-like symptoms were a musculoskeletal manifestation of the disease, irrelevant to the anti-neoplastic treatment.


Subject(s)
Burkitt Lymphoma , Endocarditis , Non-Radiographic Axial Spondyloarthritis , Spondylarthritis , Spondylarthropathies , Spondylitis, Ankylosing , Humans , Female , Burkitt Lymphoma/complications , Burkitt Lymphoma/diagnosis , Burkitt Lymphoma/drug therapy , Spondylarthritis/diagnosis , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/pathology , Endocarditis/pathology , Spondylitis, Ankylosing/diagnosis
7.
J Chin Med Assoc ; 86(5): 472-478, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36800262

ABSTRACT

BACKGROUND: Propafenone is a class IC antiarrhythmic agent that is commonly used as the first-line therapy for patients with paroxysmal atrial fibrillation (AF) in Taiwan. This study compared the efficacy and safety of generic (Rhynorm) and brand name (Rytmonorm) propafenone for rhythm control of paroxysmal AF in Taiwan. METHODS: This was an open-label randomized multicenter noninferior study conducted in Taiwan. We enrolled 76 patients with AF. To investigate the efficacy of propafenone, we used a wearable electrocardiogram (ECG) event recorder to evaluate the daily burden of AF episodes in patients for 24 weeks. The primary efficacy endpoint was the frequency of AF with clinical significance, which was indicated by AF duration ≥30 seconds. The safety endpoints included proarrhythmic or hemodynamic adverse events. RESULT: To analyze the efficacy and safety of these agents, 71 patients (five patients with screen failure) were randomized to two groups, specifically a Rhynorm group (n = 37) and a Rytmonorm group (n = 34), for 24 weeks of the treatment period. The baseline patient characteristics were comparable between the groups. However, the Rhynorm group was older (65.4 ± 8.40 vs 59.8 ± 10.8 years; p = 0.02). The primary efficacy endpoint at week 24 decreased by 4.76% ± 18.5% (from 24.3% ± 33.9% to 19.0% ± 28.7%; p = 0.13) in the Rhynorm group and by 3.27% ± 15.2% (from 16.9% ± 26.4% to 13.6% ± 19.2%; p = 0.22) in the Rytmonorm group, with an intergroup difference of 1.5% ± 17.0%; p = 0.71. This finding indicates that Rhynorm is not inferior to Rytmonorm ( p = 0.023 for noninferiority). The safety profile of the agents was comparable between the two groups. CONCLUSION: Our results verified that Rhynorm was noninferior to Rytmonorm in terms of efficacy and safety for treating paroxysmal AF in Taiwan ( ClinicalTrials.gov Identifier: NCT03674658).


Subject(s)
Atrial Fibrillation , Propafenone , Humans , Propafenone/therapeutic use , Anti-Arrhythmia Agents/adverse effects , Electrocardiography , Taiwan , Treatment Outcome
8.
Europace ; 26(1)2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38195705

ABSTRACT

AIMS: Metabolic syndrome (MetS) is associated with arrhythmias and cardiovascular mortality. Arrhythmogenesis in MetS results from atrial structural and electrical remodelling. The small-conductance Ca2+-activated K+ (SK) currents modulate atrial repolarization and may influence atrial arrhythmogenicity. This study investigated the regulation of SK current perturbed by a high-fat diet (HFD) to mimic MetS. METHODS AND RESULTS: Thirty mice were divided into two groups that were fed with normal chow (CTL) and HFD for 4 months. Electrocardiography and echocardiography were used to detect cardiac electrical and structure remodelling. Atrial action potential duration (APD) and calcium transient duration (CaTD) were measured by optical mapping of Langendorff-perfused mice hearts. Atrial fibrillation (AF) inducibility and duration were assessed by burst pacing. Whole-cell patch clamp was performed in primarily isolated atrial myocytes for SK current density. The SK current density is higher in atrial myocytes from HFD than in CTL mice (P ≤ 0.037). The RNA and protein expression of SK channels are increased in HFD mice (P ≤ 0.041 and P ≤ 0.011, respectively). Action potential duration is shortened in HFD compared with CTL (P ≤ 0.015). The shortening of the atrial APD in HFD is reversed by the application of 100 nM apamin (P ≤ 0.043). Compared with CTL, CaTD is greater in HFD atria (P ≤ 0.029). Calcium transient decay (Tau) is significantly higher in HFD than in CTL (P = 0.001). Both APD and CaTD alternans thresholds were higher in HFD (P ≤ 0.043), along with higher inducibility and longer duration of AF in HFD (P ≤ 0.023). CONCLUSION: Up-regulation of apamin-sensitive SK currents plays a partial role in the atrial arrhythmogenicity of HFD mice.


Subject(s)
Atrial Fibrillation , Calcium , Mice , Animals , Calcium/metabolism , Potassium/metabolism , Apamin/metabolism , Small-Conductance Calcium-Activated Potassium Channels/genetics , Action Potentials/physiology , Myocytes, Cardiac/metabolism
9.
Front Cardiovasc Med ; 9: 993633, 2022.
Article in English | MEDLINE | ID: mdl-36267630

ABSTRACT

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.

10.
Int J Gen Med ; 15: 6189-6198, 2022.
Article in English | MEDLINE | ID: mdl-35874912

ABSTRACT

Purpose: 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.

11.
Arch Toxicol ; 96(10): 2731-2737, 2022 10.
Article in English | MEDLINE | ID: mdl-35876889

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Heart Diseases , Heart Failure , Anthracyclines/toxicity , Antibiotics, Antineoplastic/toxicity , Artificial Intelligence , Breast Neoplasms/chemically induced , Breast Neoplasms/drug therapy , Cardiotoxicity , Female , Heart Diseases/chemically induced , Heart Failure/chemically induced , Heart Failure/drug therapy , Humans , Prospective Studies , Stroke Volume
12.
Heart Rhythm ; 19(10): 1613-1619, 2022 10.
Article in English | MEDLINE | ID: mdl-35525422

ABSTRACT

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.


Subject(s)
Acute Coronary Syndrome , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnosis , Arrhythmias, Cardiac , Electrocardiography/methods , Female , Humans , Male , Norepinephrine , Sympathetic Nervous System
13.
Comput Biol Med ; 146: 105584, 2022 07.
Article in English | MEDLINE | ID: mdl-35551013

ABSTRACT

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.


Subject(s)
Atrial Fibrillation , Deep Learning , Algorithms , Atrial Fibrillation/diagnosis , Early Diagnosis , Electrocardiography/methods , Humans , Neural Networks, Computer
14.
BMC Med Educ ; 22(1): 318, 2022 Apr 26.
Article in English | MEDLINE | ID: mdl-35473710

ABSTRACT

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 < .001) and Self-Perceived Communication Competence Scale (r = .45, p < .001), indicating excellent evidence of the relationships to other variables with other self-report assessments of communication. 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.


Subject(s)
Students, Nursing , Communication , Factor Analysis, Statistical , Humans , Learning , Self-Assessment
15.
Int J Mol Sci ; 23(8)2022 Apr 13.
Article in English | MEDLINE | ID: mdl-35457118

ABSTRACT

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.


Subject(s)
Lipoproteins, VLDL , Metabolic Syndrome , Apolipoproteins B/metabolism , Heart Atria/metabolism , Humans , Lipoproteins, VLDL/metabolism , Liver/metabolism , Metabolic Syndrome/metabolism , Triglycerides/metabolism
16.
Cells ; 11(2)2022 01 15.
Article in English | MEDLINE | ID: mdl-35053411

ABSTRACT

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.


Subject(s)
Aging/pathology , Brain/pathology , Diet, High-Fat , Feeding Behavior , Neuroglia/pathology , Neurons/pathology , Tyrosine 3-Monooxygenase/metabolism , Animals , Astrocytes/pathology , Cognition , Dopaminergic Neurons/pathology , Glial Fibrillary Acidic Protein/metabolism , Hippocampus/pathology , Locus Coeruleus/metabolism , Microglia/pathology , Motor Activity , Norepinephrine/metabolism , Pyramidal Cells/pathology , Rats, Inbred WKY , Time Factors
17.
J Pers Med ; 11(11)2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34834405

ABSTRACT

(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 < 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.

18.
Nurse Educ Pract ; 56: 103219, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34628178

ABSTRACT

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 < .001), health-promoting behaviors (Wald χ2 = 34.89, p < .001), depressive symptoms (Wald χ2 = 46.75, p < .001) and resilience (Wald χ2 = 21.54, p < .001). Spiritual health, health-promoting behaviors were positively correlated with resilience (p < .001); depressive symptoms were negatively correlated (p < .001). Controlling for the effect of time, resilience of novice nurses was positively associated with nursing school practicum grade, spiritual health and health-promoting behaviors (ß = 10.30, p < .001; ß = 12.14, p < .001; and ß = 14.62, p < .001, respectively) and negatively associated with depressive symptoms (ß = - 0.53, p < .001). 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.


Subject(s)
Nurses , Students, Nursing , Depression , Humans , Longitudinal Studies , Spirituality , Surveys and Questionnaires , Workplace
19.
Sci Rep ; 11(1): 6013, 2021 03 16.
Article in English | MEDLINE | ID: mdl-33727609

ABSTRACT

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 Aß-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, Aß-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.


Subject(s)
CA3 Region, Hippocampal , Cognitive Dysfunction , Lipoproteins, VLDL/toxicity , Prefrontal Cortex , Animals , CA3 Region, Hippocampal/metabolism , CA3 Region, Hippocampal/pathology , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/pathology , Dyslipidemias/metabolism , Humans , Inflammation/chemically induced , Inflammation/metabolism , Inflammation/pathology , Lipoproteins, VLDL/metabolism , Male , Metabolic Syndrome/metabolism , Mice , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology
20.
Int J Mol Sci ; 22(4)2021 Feb 22.
Article in English | MEDLINE | ID: mdl-33671654

ABSTRACT

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.


Subject(s)
Calcium/metabolism , Chromaffin Cells/metabolism , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/metabolism , Lysophospholipids/metabolism , Sphingosine/analogs & derivatives , Animals , Cattle , Cell-Free System , Chromaffin Cells/drug effects , Dose-Response Relationship, Drug , Electrophysiology/methods , Lysophospholipids/administration & dosage , Lysophospholipids/pharmacology , PC12 Cells , Rats , Sphingosine/administration & dosage , Sphingosine/metabolism , Sphingosine/pharmacology
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