A Novel KCNH2 S981fs Mutation Identified by Whole-Exome Sequencing Is Associated with Type 2 Long QT Syndrome.

KCNH2 loss-of-function mutations cause long QT syndrome type 2 (LQT2), an inherited cardiac disorder associated with life-threatening ventricular arrhythmia. Through whole-exome sequencing, we discovered a novel AGCGACAC deletion (S981fs) in the hERG gene of an LQT2 patient. Using a heterologous expression system and patch clamping, we found that the mutant K channel had reduced cell surface expression and lower current amplitude compared to the wild type. However, functional expression was restored by lowering temperature and using potassium channel inhibitors or openers (E4031, cisapride, nicorandil). Co-immunoprecipitation experiments confirmed the assembly of mutant proteins with wild-type hERG. Confocal imaging showed decreased hERG distribution on the cell membrane in cells expressing S981fs. Notably, treatment with G418 significantly increased hERG current in wild-type/S981fs heterozygotes. In conclusion, our study identifies a novel hERG mutation leading to impaired Kv11.1 function due to trafficking and nonsense-mediated RNA decay defects. These findings shed light on the mechanisms underlying LQT2 and offer potential therapeutic avenues.

Arrhythmia Detection is Improved by 14-Day Continuous Electrocardiography Patch Monitoring and CHA2DS2-VASc Score.

BACKGROUND: Arrhythmias are not always easy to capture because they are often paroxysmal or asymptomatic. METHODS: Using the CHA2DS2-VASc score for arrhythmia risk assessment, a 14-day electrocardiography monitor patch was used to evaluate patients with no documented history of arrhythmia. RESULTS: Ninety-three patients (mean age 59.8 ± 12.0 years, 46.2% female) received 14-day electrocardiography telemonitoring, and 14 patients (15%) were diagnosed with arrhythmias during a follow-up of 1004.4 person-days (mean recorded days 10.8 ± 4.1). The patients who were detected to have arrhythmias were older and had a higher prevalence of heart failure and chronic kidney disease. The result showed that arrhythmias were more likely to develop during a 14-day monitoring period in the patients with a CHA2DS2-VASc score of ≥ 3 or ≥ 4. Atrioventricular block was more likely to be detected in the patients with a CHA2DS2-VASc score of ≥ 3 or ≥ 4 during 7-day or 14-day monitoring periods. Ventricular tachycardia was also more likely to be detected in the patients with a CHA2DS2-VASc score of ≥ 4 or ≥ 5 during a 14-day monitoring period. When evaluating the risk of arrhythmia, a CHA2DS2-VASc score of ≥ 3 or ≥ 4 was associated with a higher risk of any arrhythmias during a 14-day monitoring period, while a CHA2DS2-VASc score of ≥ 4 was associated with a higher risk of any arrhythmias during a 7-day monitoring period. CONCLUSIONS: The results may suggest that a 14-day monitoring period is more favorable to detect arrhythmias. Atrioventricular block and ventricular tachycardia were more likely to develop in the patients with a higher CHA2DS2-VASc score.

Beneficial Effects of Fixed-Dose Combination of Amlodipine and Atorvastatin in Patients with Concomitant Hypertension and Hypercholesterolemia: A Multi-Institutional Cohort Study.

Background: Blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) are important risk factors for cardiovascular (CV) diseases. Although treating these factors simultaneously is recommended by current guidelines, only short-term clinical results are available. Objectives: To examine the longer-term efficacy and safety of fixed-dose combination (FDC) versus free combination of amlodipine and atorvastatin in patients with concomitant hypertension and hypercholesterolemia. Methods: Patients with hypertension and hypercholesterolemia were stratified into three groups [FDC of amlodipine 5 mg/atorvastatin 10 mg (Fixed 5/10), FDC of amlodipine 5 mg/atorvastatin 20 mg (Fixed 5/20), and free combination of amlodipine 5 mg/atorvastatin 10 mg (Free 5/10)]. After inverse probability of treatment weighting, the composite CV outcome, liver function, BP, LDL-C and glycated hemoglobin (HbA1c) changes were compared. Results: A total of 1,788 patients were eligible for analysis, and the mean follow-up period was 1.7 year. There was no significant difference in the composite CV outcome among the three groups (Fixed 5/10 6.1%, Fixed 5/20 6.3% and Free 5/10 6.0%). The LDL-C level was significantly reduced in the Fixed 5/20 group (-35.7 mg/dL) compared to the Fixed 5/10 (-23.6 mg/dL) and Free 5/10 (-10.3 mg/dL) groups (p = 0.001 and < 0.001, respectively). The changes in HbA1c were similar among the three groups. Conclusions: FDC of amlodipine and atorvastatin, especially the regimen with a higher dosage of statins, significantly reduced the mid-term LDL-C level compared to a free combination in patients with concomitant hypertension and hypercholesterolemia. Blood sugar level was not significantly changed by this aggressive treatment strategy.

Benzodiazepines in Patients with Heart Failure and Reduced Ejection Fraction.

Background: In patients with heart failure (HF), anxiety or insomnia is prevalent and associated with poor clinical outcomes. Benzodiazepines (BZDs) are one of the most commonly prescribed medications for anxiety or insomnia in Taiwan. Evidence regarding the effects of BZDs on patients with heart failure and reduced ejection fraction (HFrEF) is inconclusive. Objectives: To evaluate whether BZDs can mitigate the adverse effects of anxiety or insomnia on the prognosis of patients with HFrEF. Methods: Patients with HFrEF were identified from the Chang Gung Research Database between January 1, 2007 and December 31, 2018. Those who received BZD prescriptions were defined as the BZD group; patients in the BZD group were then paired with those who had never been prescribed BZDs after matching for age, sex, and baseline left ventricular ejection fraction, defined as the no-BZD group. Propensity score matching was used to balance baseline characteristics. Cox proportional hazards model and the Fine-Gray subdistribution hazard model were used to examine the association between BZD prescription and the risks of adverse cardiovascular outcomes. Results: After propensity score matching, there were 1,941 patients in both BZD and no-BZD groups. The composite of cardiovascular (CV) death or HF hospitalization (HFH) occurred in 64.4% and 54.4% of the patients in the BZD and no-BZD groups, respectively [hazard ratio (HR): 1.44; 95% confidence interval (CI): 1.32-1.56], which was mainly driven by HFH (HR: 1.52; 95% CI: 1.39-1.67). Conclusions: In the patients with HFrEF, those who received BZD were at a higher overall risk of CV death and HFH.

Resuscitation outcomes of a wireless ECG telemonitoring system for cardiovascular ward patients experiencing in-hospital cardiac arrest.

BACKGROUND/PURPOSE: In-hospital cardiac arrest is a serious issue for hospitalized patients. The documented initial rhythm and detected medical events have been reported to influence the survival of cardiopulmonary resuscitation. This study aimed to identify the effect of continuous real-time electrocardiogram (ECG) monitoring on the prognosis of resuscitated patients in a general cardiac ward. METHODS: We conducted this retrospective study using medical records of hospitalized patients in a cardiovascular ward who experienced an in-hospital cardiac arrest and received cardiopulmonary resuscitation from February 2015 to December 2018. The patients who were considered to be at high risk of cardiac events such as ventricular arrhythmia would receive continuous ECG monitoring. A wireless ECG telemonitoring system was introduced to replace traditional bedside ECG monitors. The outcome measures were the initial success of resuscitation, 24-h survival after resuscitation, and survival to discharge. RESULTS: We enrolled 115 patients with a cardiac arrest during hospitalization, of whom 73 (63%) patients received wireless ECG telemonitoring. Patients receiving continuous ECG monitoring were associated with higher opportunities of initial success of resuscitation and 24-h survival after resuscitation (67.1% vs. 40.5%, p = 0.005; and 49.3% vs. 26.2%, p = 0.015, respectively) when comparing to the non-monitoring group; but no significant difference in survival to discharge (21.9% vs. 16.7%, p = 0.498) was observed. With adjustment of the covariates, the monitoring group was associated with a higher likelihood to reach the initial success of resuscitation (odds ratios [ORs], 3.21; 95% confidence interval [CI], 1.03-9.98). However, the effect of monitoring on 24-h survival and survival to discharge was close to null after adjusting for covariates. CONCLUSION: A wireless ECG telemonitoring system were beneficial to the initial success of resuscitation for patients at high risk of cardiovascular events suffering an in-hospital cardiac arrest; but had less impact on 24-h survival and survival to discharge.

Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis.

BACKGROUND: Whether four direct oral anticoagulants (DOACs) are superior to warfarin among Asians with non-valvular atrial fibrillation (NVAF) remains unclear in the real-world setting. METHODS: We searched PubMed and Medline + Journals@Ovid + EMBASE from September 17, 2009 to May 4, 2019 to perform a systematic review and meta-analysis of all observational real-world studies comparing four DOACs with warfarin specifically focused on Asian patients with NVAF. RESULTS: From the original 212 results retrieved, 18 studies were included in the meta-analysis. Overall, DOACs were associated with lower risks of thromboembolism (hazard ratio; [95% confidence interval], 0.70; [0.63-0.78]), acute myocardial infarction (0.67; [0.57-0.79]), all-cause mortality (0.62; [0.56-0.69]), major bleeding (0.59; [0.50-0.69]), intracranial hemorrhage (0.50; [0.40-0.62]), gastrointestinal bleeding (0.66; [0.46-0.95]), and any bleeding (0.82; [0.73-0.92]) than warfarin. There was statistic heterogeneity between DOACs for the risks of thromboembolism (P interaction = 0.03) and acute myocardial infarction (P interaction = 0.007) when compared to warfarin. However, all DOACs showed lower risks of thromboembolism and acute myocardial infarction than warfarin when pooling studies that compared individual DOAC with warfarin. With regard to the other outcomes when compared to warfarin, there was no statistical heterogeneity between DOACs. In addition, the effectiveness and safety of four DOACs versus warfarin persisted in the subgroups of either standard-dose or low-dose DOACs. CONCLUSIONS: The meta-analysis shows that the DOACs had greater effectiveness and safety compared to warfarin in real-world practice for stroke prevention, among Asian patients with NVAF.

Fibroblast inward-rectifier potassium current upregulation in profibrillatory atrial remodeling.

RATIONALE: Fibroblasts are involved in cardiac arrhythmogenesis and contribute to the atrial fibrillation substrate in congestive heart failure (CHF) by generating tissue fibrosis. Fibroblasts display robust ion currents, but their functional importance is poorly understood. OBJECTIVE: To characterize atrial fibroblast inward-rectifier K(+) current (IK1) remodeling in CHF and its effects on fibroblast properties. METHODS AND RESULTS: Freshly isolated left atrial fibroblasts were obtained from controls and dogs with CHF (ventricular tachypacing). Patch clamp was used to record resting membrane potential (RMP) and IK1. RMP was significantly increased by CHF (from -43.2±0.8 mV, control, to -55.5±0.9 mV). CHF upregulated IK1 (eg, at -90 mV from -1.1±0.2 to -2.7±0.5 pA/pF) and increased the expression of KCNJ2 mRNA (by 52%) and protein (by 80%). Ba(2+) (300 µmol/L) decreased the RMP and suppressed the RMP difference between controls and dogs with CHF. Store-operated Ca(2+) entry (Fura-2-acetoxymethyl ester) and fibroblast proliferation (flow cytometry) were enhanced by CHF. Lentivirus-mediated overexpression of KCNJ2 enhanced IK1 and hyperpolarized fibroblasts. Functional KCNJ2 suppression by lentivirus-mediated expression of a dominant negative KCNJ2 construct suppressed IK1 and depolarized RMP. Overexpression of KCNJ2 increased Ca(2+) entry and fibroblast proliferation, whereas the dominant negative KCNJ2 construct had opposite effects. Fibroblast hyperpolarization to mimic CHF effects on RMP enhanced the Ca(2+) entry. MicroRNA-26a, which targets KCNJ2, was downregulated in CHF fibroblasts. Knockdown of endogenous microRNA-26 to mimic CHF effects unregulated IK1. CONCLUSIONS: CHF upregulates fibroblast KCNJ2 expression and currents, thereby hyperpolarizing RMP, increasing Ca(2+) entry, and enhancing atrial fibroblast proliferation. These effects are likely mediated by microRNA-26a downregulation. Remodeling-induced fibroblast KCNJ2 expression changes may play a role in atrial fibrillation promoting fibroblast remodeling and structural/arrhythmic consequences.

Activation of histone deacetylase-6 induces contractile dysfunction through derailment of α-tubulin proteostasis in experimental and human atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is characterized by structural remodeling, contractile dysfunction, and AF progression. Histone deacetylases (HDACs) influence acetylation of both histones and cytosolic proteins, thereby mediating epigenetic regulation and influencing cell proteostasis. Because the exact function of HDACs in AF is unknown, we investigated their role in experimental and clinical AF models. METHODS AND RESULTS: Tachypacing of HL-1 atrial cardiomyocytes and Drosophila pupae hearts significantly impaired contractile function (amplitude of Ca(2+) transients and heart wall contractions). This dysfunction was prevented by inhibition of HDAC6 (tubacin) and sirtuins (nicotinamide). Tachypacing induced specific activation of HDAC6, resulting in α-tubulin deacetylation, depolymerization, and degradation by calpain. Tachypacing-induced contractile dysfunction was completely rescued by dominant-negative HDAC6 mutants with loss of deacetylase activity in the second catalytic domain, which bears α-tubulin deacetylase activity. Furthermore, in vivo treatment with the HDAC6 inhibitor tubastatin A protected atrial tachypaced dogs from electric remodeling (action potential duration shortening, L-type Ca(2+) current reduction, AF promotion) and cellular Ca(2+)-handling/contractile dysfunction (loss of Ca(2+) transient amplitude, sarcomere contractility). Finally, atrial tissue from patients with AF also showed a significant increase in HDAC6 activity and reduction in the expression of both acetylated and total α-tubulin. CONCLUSIONS: AF induces remodeling and loss of contractile function, at least in part through HDAC6 activation and subsequent derailment of α-tubulin proteostasis and disruption of the cardiomyocyte microtubule structure. In vivo inhibition of HDAC6 protects against AF-related atrial remodeling, disclosing the potential of HDAC6 as a therapeutic target in clinical AF.

Role of small-conductance calcium-activated potassium channels in atrial electrophysiology and fibrillation in the dog.

BACKGROUND: Recent evidence points to functional Ca²âº-dependent K⁺ (SK) channels in the heart that may govern atrial fibrillation (AF) risk, but the underlying mechanisms are unclear. This study addressed the role of SK channels in atrial repolarization and AF persistence in a canine AF model. METHODS AND RESULTS: Electrophysiological variables were assessed in dogs subjected to atrial remodeling by 7-day atrial tachypacing (AT-P), as well as controls. Ionic currents and single-channel properties were measured in isolated canine atrial cardiomyocytes by patch clamp. NS8593, a putative selective SK blocker, suppressed SK current with an IC50 of ≈5 µmol/L, without affecting Na⁺, Ca²âº, or other K⁺ currents. Whole-cell SK current sensitive to NS8593 was significantly larger in pulmonary vein (PV) versus left atrial (LA) cells, without a difference in SK single-channel open probability (P(o)), whereas AT-P enhanced both whole-cell SK currents and single-channel P(o). SK-current block increased action potential duration in both PV and LA cells after AT-P; but only in PV cells in absence of AT-P. SK2 expression was more abundant at both mRNA and protein levels for PV versus LA in control dogs, in both control and AT-P; AT-P upregulated only SK1 at the protein level. Intravenous administration of NS8593 (5 mg/kg) significantly prolonged atrial refractoriness and reduced AF duration without affecting the Wenckebach cycle length, left ventricular refractoriness, or blood pressure. CONCLUSIONS: SK currents play a role in canine atrial repolarization, are larger in PVs than LA, are enhanced by atrial-tachycardia remodeling, and appear to participate in promoting AF maintenance. These results are relevant to the potential mechanisms underlying the association between SK single-nucleotide polymorphisms and AF and suggest SK blockers as potentially interesting anti-AF drugs.

Effects of Door-to-Balloon Times on Outcomes in Taiwanese Patients Receiving Primary Percutaneous Coronary Intervention: A Report of Taiwan Acute Coronary Syndrome Full Spectrum Registry.

PURPOSE: The impact of door-to-balloon (DTB) time on patient outcomes is unclear in a Taiwanese population receiving primary percutaneous coronary intervention (PCI). The study aimed to investigate the relationship between stratified DTB times and outcomes through analysis of the database from the Taiwan acute coronary syndrome full spectrum registry. METHODS: Relevant data were collected from case report forms of patients receiving primary PCI who were categorized as group 1, 2, 3, and 4 according to the DTB time < 45, 45-90, 91-135, and > 135 minutes, respectively. The differences were analyzed by using ANOVA and Kaplan-Meier analyses. RESULTS: There were significant variations in DTB times at baseline, which included patients salvaged at centers, patients with prior cardiovascular disease, and those patients with different coronary artery flows (p < 0.01) separated into 4 groups (n = 189, 443, 299, and 401, respectively). The in-hospital adverse event rates were identical among the 4 groups except for a higher rate of acute renal failure and a longer hospital stay observed in group 4 (p < 0.01). The results showed no decrease in the incidences of repeated revascularization, major adverse cardiac event, or cardiovascular composite at 1 year in group 1. CONCLUSIONS: This study suggested that the DTB time is not a good determinant for outcomes in Taiwanese patients receiving primary PCI. KEY WORDS: Acute myocardial infarction; Cardiovascular outcome; Door-to-balloon time; Myocardial ischemia; Percutaneous coronary intervention.

Detailed characterization of microRNA changes in a canine heart failure model: Relationship to arrhythmogenic structural remodeling.

Heart failure (HF) causes left-atrial (LA) and left-ventricular (LV) remodeling, with particularly-prominent changes in LA that create a substrate for atrial fibrillation (AF). MicroRNAs (miRs) are potential regulators in cardiac remodeling. This study evaluated time-dependent miR expression-changes in LA and LV tissue, fibroblasts and cardiomyocytes in experimental HF. HF was induced in dogs by ventricular tachypacing (varying periods, up to 2weeks). Following screening-microarray, 15 miRs were selected for detailed real-time qPCR assay. Extracellular matrix mRNA-expression was assessed by qPCR. Tachypacing time-dependently reduced LV ejection-fraction, increased LV-volume and AF-duration, and caused tissue-fibrosis with LA changes greater than LV. Tissue miR-expression significantly changed in LA for 10 miRs; in LV for none. Cell-selective analysis showed significant time-dependent changes in LA-fibroblasts for 10/15 miRs, LV-fibroblasts 8/15, LA-cardiomyocytes in 6/15 and LV-cardiomyocytes 3/15. Cell-expression specificity did not predict cell-specificity of VTP-induced expression-changes, e.g. 4/6 cardiomyocyte-selective miRs changed almost exclusively in fibroblasts (miR-1, miR-208b, miR133a/b). Thirteen miRs directly implicated in fibrosis/extracellular-matrix regulation were prominently changed: 9/13 showed fibroblast-selective alterations and 5/13 LA-selective. Multiple miRs changed in relation to associated extracellular-matrix targets. Experimental HF causes tissue and cell-type selective, time-dependent changes in cardiac miR-expression. Expression-changes are greater in LA versus LV, and greater in fibroblasts than cardiomyocytes, even for most cardiomyocyte-enriched miRs. This study, the first to examine time, chamber and cell-type selective changes in an experimental model of HF, suggests that multiple miR-changes underlie the atrial-selective fibrotic response and emphasize the importance of considering cell-specificity of miR expression-changes in cardiac remodeling paradigms.

Wearable mobile health device for monitoring postoperative ambulation among patients with colorectal cancer undergoing minimally invasive surgery: A prospective comparison study.

BACKGROUND: This study aimed to evaluate the feasibility of using mHealth devices for monitoring postoperative ambulation among patients with colorectal cancer undergoing minimally invasive surgery (MIS). METHODS: Patients with colorectal cancer undergoing MIS were prospectively recruited to wear mHealth devices for recording postoperative ambulation between October 2018 and January 2021. The primary outcome was the compliance by evaluating the weekly submission rate of step counts. The secondary outcome was the association of weekly step counts and postoperative length of stay. RESULTS: Of 107 eligible patients, 53 patients wore mHealth devices, whereas 54 patients did not. The average weekly submission rate was 72.6% for the first month after surgery. The total step counts <4000 or >10 000 in the postoperative week one were negatively associated with postoperative length of stay (ß = -2.874, p = 0.038). CONCLUSIONS: mHealth devices provide an objective assessment of postoperative ambulation among patients with colorectal cancer undergoing MIS. CLINICAL TRIAL REGISTRATION: NCT03277235.

Clinical significance of regional constructive and wasted work in patients receiving cardiac resynchronization therapy.

Background: Previous studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT. Methods: We performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months. Results: At six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700-0.866) and 0.737 (95% CI: 0.644-0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755-0.908). Both LW CW ≤878 mmHg% (HR 2.01; 95% CI: 1.07-3.79) and septal WW ≤181 mmHg% (HR 2.60; 95% CI: 1.38-4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up. Conclusion: LW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.

Clinical Assessment and Implication of Left Ventricular Mechanical Dyssynchrony in Patients with Heart Failure.

UNLABELLED: There have been numerous studies focusing on the assessment of left ventricular mechanical dyssynchrony. These studies are diverse in their purposes, which include more effectively predicting the response to cardiac resynchronization therapy, improving the guidance of the left ventricular lead position, and better prediction of outcome in patients with heart failure. This article reviews the current assessment methods, clinical applications and limitations of left ventricular dyssynchrony indices derived from echocardiography, magnetic resonance imaging and radionuclide imaging in patients with heart failure. KEY WORDS: Cardiac resynchronization therapy; Dyssynchrony; Echocardiography; Heart failure.

Factors affecting the intensity of chronic musculoskeletal pain in patients with cardiovascular disease and evaluation of the efficacy of magnesium emulsion cream for muscle cramps.

Chronic musculoskeletal pain (CMP) is associated with an increased risk of cardiovascular disease (CVD). This study aimed to determine the factors associated with the intensity of CMP in patients with underlying CVD and to evaluate the efficacy of Ice Power Magnesium In Strong Cream in patients with muscle cramps. We investigated 396 patients with or without CMP who visited an outpatient cardiology clinic and analyzed the features of CMP and factors associated with pain intensity and specific types of CVD in study 1. We also analyzed 73 patients who had muscle cramps in the lower extremities in study 2 to evaluate the efficacy of Ice Power Magnesium In Strong Cream in reducing pain intensity. In study 1, multivariable linear regression analysis showed that older age (regression coefficient [B] = 0.66, 95% confidence interval [CI], 0.07-1.24), female sex (B = 1.18, 95% CI, 0.59-1.76), presence of hypertension (B = 0.69, 95% CI, 0.05-1.33), and use of calcium supplements (B = 1.27, 95% CI, 0.31-2.24) were significantly associated with a higher intensity of CMP. In study 2, the mean pain scores at baseline, week 2 and week 4 after treatment were 5.99 ± 2.12, 2.92 ± 2.63, and 1.90 ± 2.41, respectively, and the reductions were significant at both week 2 and week 4 after treatment (P < .05). Older age, female sex, hypertension, and use of calcium supplements were associated with an increased intensity of CMP. Ice Power Magnesium In Strong Cream was effective in reducing the pain intensity of muscle cramps in the lower extremities.

Prevention of Glutamate-Induced Neurodegeneration by Piceatannol via Mitochondrial Rescue In Vitro and In Vivo.

SCOPE: Parkinson's disease is one of the neurodegenerative diseases that have no cure. Excitotoxicity induced by excess glutamate is known to be a hallmark of these diseases. Therefore, this study aims to evaluate the preventive effect of piceatannol on glutamate-induced neurodegeneration via mitochondrial rescue. METHODS AND RESULTS: The PC12 cell line and three Caenorhabditis elegans (C. elegans) strains are employed to achieve the aim. In the in vitro study, the results show that piceatannol can prevent glutamate-induced apoptosis. Piceatannol also reduces mitochondrial reactive oxygen species (ROS) accumulation by activating the antioxidant system. Moreover, piceatannol can also promote mitochondrial biogenesis and induced mitochondrial fusion-related genes to preserve mitochondrial functionality. In the C. elegans model, piceatannol can prevent mitochondrial fragmentation induced by glutamate. More importantly, piceatannol effectively protects dopaminergic neurons from degradation and preserves the responses controlled by these neurons. CONCLUSION: The findings suggest that piceatannol can be a more effective and potent candidate for the treatment of neurodegenerative diseases, such as Parkinson's disease, compared to resveratrol. It is capable of preventing neurodegeneration induced by excess glutamate, possibly via mitochondrial rescue. It is recommended that piceatannol be developed into a neuroprotective agent.

Acute Fulminant Myocarditis After ChAdOx1 nCoV-19 Vaccine: A Case Report and Literature Review.

According to recent literatures, myocarditis is an uncommon side effect of mRNA vaccines against COVID-19. On the other hand, myocarditis after adenovirus based vaccine is rarely reported. Here we report a middle-aged healthy female who had acute fulminant perimyocarditis onset 2 days after the first dose of ChAdOx1 vaccine (AstraZeneca) without any other identified etiology. Detailed clinical presentation, serial ECGs, cardiac MRI, and laboratory data were included in the report. Possible mechanisms of acute myocarditis after adenoviral vaccine was reviewed and discussed. To our knowledge, a few cases of myocarditis after Ad26.COV2.S vaccine were reported, and this is the first case report after ChAdOx1 vaccine.

Dietary Methylglyoxal Exposure Induces Alzheimer's Disease by Promoting Amyloid ß Accumulation and Disrupting Autophagy in Caenorhabditis elegans.

Methylglyoxal (MG) is a precursor of advanced glycation end products usually generated during cooking. The high level of MG in the brain is correlated to the pathogenesis of Alzheimer's disease (AD). However, it is not clear if MG consumed through the diet can cause AD-related toxicity. Herein, the Caenorhabditis elegans (C. elegans) AD model was used to investigate the neurotoxicity after long-term MG exposure at dietary levels. The results showed that C. elegans locomotive behaviors were significantly decreased after 0.1, 0.5, and 1 mM MG exposure (p < 0.001). In amyloid ß (Aß)-expressing transgenic C. elegans strains, 0.5 mM MG significantly promoted Aß accumulation by around 50% in day-8 CL2006 (p < 0.001), enhanced paralysis in CL4176 (p < 0.001) and CL2006 (p < 0.01), and made CL2355 around 17% more vulnerable to 5-HT, indicating impaired serotonin reuptake (p < 0.05). Additionally, 0.5 mM MG significantly increased the reactive oxygen species level (p < 0.001) by inhibiting the expression of stress-response genes including sod-3, gst-4, and hsp-16.2 in day-8 aged worms. Moreover, the autophagic pathway was disrupted through lgg-1, vps-34, and bec-1 expression after MG exposure and Aß accumulation. Treatment with the citrus flavonoid nobiletin reduced the MG-induced toxicity (p < 0.001). Overall, these findings imply that it is possible to exacerbate AD pathogenesis by MG exposure through the diet.

Panic Attack Prediction Using Wearable Devices and Machine Learning: Development and Cohort Study.

BACKGROUND: A panic attack (PA) is an intense form of anxiety accompanied by multiple somatic presentations, leading to frequent emergency department visits and impairing the quality of life. A prediction model for PAs could help clinicians and patients monitor, control, and carry out early intervention for recurrent PAs, enabling more personalized treatment for panic disorder (PD). OBJECTIVE: This study aims to provide a 7-day PA prediction model and determine the relationship between a future PA and various features, including physiological factors, anxiety and depressive factors, and the air quality index (AQI). METHODS: We enrolled 59 participants with PD (Diagnostic and Statistical Manual of Mental Disorders, 5th edition, and the Mini International Neuropsychiatric Interview). Participants used smartwatches (Garmin Vívosmart 4) and mobile apps to collect their sleep, heart rate (HR), activity level, anxiety, and depression scores (Beck Depression Inventory [BDI], Beck Anxiety Inventory [BAI], State-Trait Anxiety Inventory state anxiety [STAI-S], State-Trait Anxiety Inventory trait anxiety [STAI-T], and Panic Disorder Severity Scale Self-Report) in their real life for a duration of 1 year. We also included AQIs from open data. To analyze these data, our team used 6 machine learning methods: random forests, decision trees, linear discriminant analysis, adaptive boosting, extreme gradient boosting, and regularized greedy forests. RESULTS: For 7-day PA predictions, the random forest produced the best prediction rate. Overall, the accuracy of the test set was 67.4%-81.3% for different machine learning algorithms. The most critical variables in the model were questionnaire and physiological features, such as the BAI, BDI, STAI, MINI, average HR, resting HR, and deep sleep duration. CONCLUSIONS: It is possible to predict PAs using a combination of data from questionnaires and physiological and environmental data.