Secondary Leukemia in a Patient With EBV-HLH Carrying Heterozygous STXBP2 Variant.

Hemophagocytic lymphohistiocytosis (HLH) is a symptom with severe systemic hyperinflammation. A 26-month-old male presented with Epstein-Barr virus associated HLH with a heterozygous variant of syntaxin-binding protein-2 (STXBP2). Complete remission was achieved with the HLH-2004 protocol, but the disease soon relapsed. Four weeks after re-installing HLH-2004 protocol, HLH was resolved. The cumulative dosage of etoposide was 2100 mg/m2. He developed acute promyelocytic leukemia 17 months later. The patient underwent standard chemotherapy and since remained in complete remission. In conclusion, a regular screening of malignance might be in necessity for the patients harboring gene variants associated with familial HLH.

Conditioned generalisation in generalised anxiety disorder: the role of concurrent perceptual and conceptual cues.

Previous research in extinction indicates no difference in US expectancies for aversive and non-aversive unconditioned stimuli (USs). In this study, we bridged these topics by examining how concurrent perceptual and conceptual cues influence conditioned generalisation of generalised anxiety disorder (GAD) patients by using non-aversive USs. The study included two consecutive phases: acquisition and generalisation. In the acquisition phase, we used blue and purple images as the perceptually conditioned stimuli, images of animals and household items as the conceptually conditioned stimuli, and non-aversive images as unconditioned stimuli (US). In the generalisation phase, we used images containing both conceptual and perceptual cues (e.g. blue animals) as the generalisation stimuli. Participants rated the US expectancy for all images. We found that compared with the control group, the patients exhibited generalisation in response to stimuli that included conditional conceptual cues. These results reveal novel evidence of generalisation in GAD and may have implications for considering the concept-based information in extinction treatment.

Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

BACKGROUND: Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. METHODS: We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. RESULTS: EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to ß-adrenergic stimulation mediated via canonical ß1- and ß2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. CONCLUSIONS: We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions.

Sensing Cardiac Electrical Activity With a Cardiac Myocyte--Targeted Optogenetic Voltage Indicator.

RATIONALE: Monitoring and controlling cardiac myocyte activity with optogenetic tools offer exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac excitation from the cellular to the whole heart level. OBJECTIVE: To test the hypothesis that cardiac myocyte-targeted voltage-sensitive fluorescence protein 2.3 (VSFP2.3) can be exploited as optogenetic tool for the monitoring of electric activity in isolated cardiac myocytes and the whole heart as well as function and maturity in induced pluripotent stem cell-derived cardiac myocytes. METHODS AND RESULTS: We first generated mice with cardiac myocyte-restricted expression of VSFP2.3 and demonstrated distinct localization of VSFP2.3 at the t-tubulus/junctional sarcoplasmic reticulum microdomain without any signs for associated pathologies (assessed by echocardiography, RNA-sequencing, and patch clamping). Optically recorded VSFP2.3 signals correlated well with membrane voltage measured simultaneously by patch clamping. The use of VSFP2.3 for human action potential recordings was confirmed by simulation of immature and mature action potentials in murine VSFP2.3 cardiac myocytes. Optical cardiograms could be monitored in whole hearts ex vivo and minimally invasively in vivo via fiber optics at physiological heart rate (10 Hz) and under pacing-induced arrhythmia. Finally, we reprogrammed tail-tip fibroblasts from transgenic mice and used the VSFP2.3 sensor for benchmarking functional and structural maturation in induced pluripotent stem cell-derived cardiac myocytes. CONCLUSIONS: We introduce a novel transgenic voltage-sensor model as a new method in cardiovascular research and provide proof of concept for its use in optogenetic sensing of physiological and pathological excitation in mature and immature cardiac myocytes in vitro and in vivo.

Chinese college students' PGD symptoms and their relationship to cognitive variables: a latent profile analysis.

Bereavement is a commonly experienced grief event; however, bereavement can also trigger a number of psychological consequences, such as prolonged grief disorder (PGD). At present, the differences in prolonged grief disorder symptoms (PGD symptoms) among various individuals and how those symptoms relate to cognitive variables are unclear. In the present study, 817 Chinese college students with bereavement experience were selected as participants. Based on the evaluation results of their irrational beliefs, bereavement-related irrational beliefs, basic world assumptions, and PGD symptoms, an individual-centered latent profile analysis was used to divide a group with PGD symptoms into several subgroups and comprehensively examine the relationships between these subgroups and cognitive variables. (1) The severity of PGD symptoms among Chinese college students can be categorized into three subgroups: mild, moderate, and severe. (2) Cognitive variables such as irrational beliefs and basic world assumptions were all found to correlate with the severity of PGD symptoms; bereavement-related irrational beliefs was the variable with the largest correlation. However, for the first time, this study found that different dimensions of basic world assumptions had different directions of correlation, based on the severity of the PGD symptoms. Justice, control, randomness, and self-control had significantly positive correlations. Conversely, benevolence of the world, benevolence of people, and worthiness of the self had significantly negative correlations. These results have important reference value for cognitive behavioral therapy (CBT) treatment and interventions for PGD issues in Chinese college students.

Memristive competitive hopfield neural network for image segmentation application.

Image segmentation implementation provides simplified and effective feature information of image. Neural network algorithms have made significant progress in the application of image segmentation task. However, few studies focus on the implementation of hardware circuits with high-efficiency analog calculations and parallel operations for image segmentation problem. In this paper, a memristor-based competitive Hopfield neural network circuit is proposed to deal with the image segmentation problem. In this circuit, the memristive cross array is applied to store synaptic weights and perform matrix operations. The competition module based on the Winner-take-all mechanism is composed of the competition neurons and the competition control circuit, which simplifies the energy function of the Hopfield neural network and realizes the output function. Operational amplifiers and ABM modules are used to integrate operations and process external input information, respectively. Based on these designs, the circuit can automatically implement iteration and update of data. A series of PSPICE simulations are designed to verify the image segmentation capability of this circuit. Comparative experimental results and analysis show that this circuit has effective improvements both in processing speed and segmentation accuracy compared with other methods. Moreover, the proposed circuit shows good robustness to noise and memristive variation.

Non-suicidal self-injury and suicidal ideation among adolescents: the chain-mediating role of rumination and decentering.

Objective: To explore the relationship between non-suicidal self-injury and suicidal ideation in adolescents and examine the roles of rumination and decentering in that relationship. Method: By means of a questionnaire, 175 adolescent patients in a psychiatric hospital in Fujian Province were given the Functional Assessment of Self-Mutilation: Chinese Version, Positive and Negative Suicide Ideation, Ruminative Response Scale: Chinese Version, and Experiences Questionnaire: Decentering Scale. Results: (1) Adolescent non-suicidal self-injury was significantly positively related to suicidal ideation and rumination and significantly negatively related to decentering. Suicidal ideation was significantly positively related to rumination and significantly negatively related to decentering. Rumination was significantly negatively related to decentering. (2) Rumination and decentering played a complete chain-mediating role between non-suicidal self-injury and suicidal ideation. Non-suicidal self-injury was found to indirectly affect suicidal ideation along three pathways: the independent mediating role of rumination (the mediating effect accounted for 40.166%), independent mediating role of decentering (the mediating effect accounted for 41.274%), and chain-mediating role of rumination and decentering (the mediating effect accounted for 14.958%). Conclusion: Adolescent non-suicidal self-injury can indirectly affect suicidal ideation through rumination and decentering. In the future, mindfulness and other methods should be used to improve individuals' levels of decentering and cultivate emotional regulation abilities, so as to reduce the incidence of non-suicidal self-injury and suicide in adolescents.

Distinct Classes of Statistical Anxiety: Latent Profile and Network Psychometrics Analysis of University Students.

Purpose: Many university students will experience statistical anxiety. Consequentially, the relationship between such anxiety and learning performance has been of concern to various educational researchers. To date, however, there has been no consistent resolution to this problem. Because previous studies have mainly used the perspective of variant-centered analysis rather than taking into account individual differences, this study argues that the different classes of statistical anxiety among university students may be an important influencing factor. Participants and Methods: In this study, 1607 Chinese university students who had just completed a statistics course were assessed using the Statistical Anxiety Scale, Statistics Learning Self-Efficacy Scale, and Learning Engagement Scale, and an exploratory study was conducted to determine whether university students' statistical anxiety could be divided into different classes. Latent profile and network psychometrics analyses were then used to analyze the data. Results: (1) The latent profile analysis found that university students' statistical anxiety could be divided into three different latent classes: mild test anxiety, moderate text anxiety, and severe statistical anxiety. (2) The correlation analysis showed that the relationships among the three latent classes of statistical anxiety and learning performance were not entirely consistent, indicating that there was heterogeneity in the statistical anxiety of these university students. (3) Further network psychometrics analysis showed that the statistical anxiety network structure of the three latent classes has different core nodes that reflected the most important symptoms of statistical anxiety. Conclusion: There is heterogeneity in university students' statistical anxiety that can be divided into three latent classes. These core nodes in the statistical anxiety networks of the three latent classes were different, helping statistics instructors to better understand the nature of these latent classes, take different intervention measures for different latent classes of university students.

Predictive model for early death risk in pediatric hemophagocytic lymphohistiocytosis patients based on machine learning.

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening disease in children, with a high early mortality rate. This study aimed to construct machine learning model to predict the risk of early death using clinical indicators at the time of HLH diagnosis. Methods: This observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data was collected from pediatric HLH patients diagnosed by the HLH-2004 protocol between January 2006 and December 2022. Six machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction. Results: The study included 587 pediatric HLH patients, and the early mortality rate was 28.45 %. The logistic and XGBoost model with the best performance after feature screening were selected to predict early death of HLH patients. The logistic model had an AUC of 0.915 and an accuracy of 0.863, while the XGBoost model had an AUC of 0.889 and an accuracy of 0.829. The risk factors most associated with early death were the absence of immunochemotherapy, decreased TC levels, increased BUN and total bilirubin, and prolonged TT. We developed an online calculator tool for predicting the probability of early death in children with HLH. Conclusions: We developed the first web-based early mortality prediction tool for pediatric HLH to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200061315).

The relationship between social class and subjective well-being: A serial mediation model.

Despite recent research associating social class with subjective well-being (SWB), the relationship between the two, manifested through victim justice sensitivity and envy, has not been properly investigated. Guided by social comparison and social cognitive tendency theories, we explored the direct and indirect relationships between social class and SWB among Chinese undergraduate students. This study employed a cross-sectional, questionnaire-based research design. 1,405 undergraduate students completed questionnaires regarding subjective social class, victim justice sensitivity, envy, and SWB. The results showed that social class was positively related to SWB and negatively associated with victim justice sensitivity and envy. Victim justice sensitivity was negatively related to SWB, victim justice sensitivity was positively related to envy, and envy was negatively associated with SWB. Social class correlated with SWB through three paths: the mediating role of victim justice sensitivity, the mediating role of envy, and the serial mediating roles of victim justice sensitivity and envy. The results indicate that social class could contribute to college students' SWB through the mechanisms of victim justice sensitivity and envy. This study advances the understanding of how the relationship between social class and college students' SWB operates. Furthermore, the findings will facilitate the promotion of college students' SWB.

3-(4-Bromo-phen-yl)-4-[2-(4-nitro-phen-yl)hydrazin-yl]furan-2(5H)-one.

In the title compound, C(16)H(12)BrN(3)O(4), the furan-2(5H)-one ring forms a dihedral angle of 33.19 (9)° with the 4-bromo-benzene unit and is nearly perpendicular to the 4-nitro-benzene segment, making a dihedral angle of 89.93 (10)°. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules, generating an infinite chain along [010]. The chains are linked into a three-dimensional network by C-H⋯O, C-H⋯π and π-π contacts [centroid-centroid separation = 3.805 (2) Å].

Novel Porous Nitrogen Doped Graphene/Carbon Black Composites as Efficient Oxygen Reduction Reaction Electrocatalyst for Power Generation in Microbial Fuel Cell.

To improve the power generation of a microbial fuel cell (MFC), a porous nitrogen-doped graphene/carbon black (NG/CB) composite as efficient oxygen reduction reaction (ORR) electrocatalyst was successfully synthesized by pyrolyzing graphene oxide (GO) encapsulated CB with cetyltrimethyl ammonium bromide as a bridge. This concept-to-proof synthesis can be considered as a template-like method. Based on this method, one composite named as NG/CB-10 was acquired using the optimized GO-to-CB mass ratio of 10:1. Electrochemical tests demonstrate that NG/CB-10 can catalyze ORR in neutral-pH medium through a four-electron pathway with positively shifted the onset potential, the enhanced current density and reduced charge transfer resistance. CB addition also prolongs the stability of NG/CB-10. The enhancement in electrochemical performance of NG/CB-10 was attributed to the enlarged surface area, abundant mesopores and high content of pyridinic nitrogen. The maximum power density of MFC equipping NG/CB-10 as cathode electrocatalyst reached 936 mW·m-2, which was 26% higher than that of NG and equal to that of platinum/carbon. The cost of NG/CB-10 was reduced by 25% compared with that of NG. This work provides a novel method to synthesize promising ORR electrocatalyst for MFC in the future.

Detection of common diarrhea-causing pathogens in Northern Taiwan by multiplex polymerase chain reaction.

Conventional methods for identifying gastroenteritis pathogens are time consuming, more likely to result in a false-negative, rely on personnel with diagnostic expertise, and are dependent on the specimen status. Alternatively, molecular diagnostic methods permit the rapid, simultaneous detection of multiple pathogens with high sensitivity and specificity. The present study compared conventional methods with the Luminex xTAG Gastrointestinal Pathogen Panel (xTAG GPP) for the diagnosis of infectious gastroenteritis in northern Taiwan. From July 2015 to April 2016, 217 clinical fecal samples were collected from patients with suspected infectious gastroenteritis. All specimens were tested using conventional diagnostic techniques following physicians' orders as well as with the xTAG GPP. The multiplex polymerase chain reaction (PCR) approach detected significantly more positive samples with bacterial, viral, and/or parasitic infections as compared to conventional analysis (55.8% vs 40.1%, respectively; P < .001). Moreover, multiplex PCR could detect Escherichia coli O157, enterotoxigenic E coli, Shiga-like toxin-producing E coli, Cryptosporidium, and Giardia, which were undetectable by conventional methods. Furthermore, 48 pathogens in 23 patients (10.6%) with coinfections were identified only using the multiplex PCR approach. Of which, 82.6% were from pediatric patients. Because the detection rates using multiplex PCR are higher than conventional methods, and some pediatric pathogens could only be detected by multiplex PCR, this approach may be useful in rapidly diagnosing diarrheal disease in children and facilitating treatment initiation. Further studies are necessary to determine if multiplex PCR improves patient outcomes and reduces costs.

Antihyperglycemic effect of oolong tea in type 2 diabetes.

OBJECTIVE: To determine the efficacy of oolong tea for lowering plasma glucose in type 2 diabetic patients in Miaoli, Taiwan. RESEARCH DESIGN AND METHODS: A total of 20 free-living subjects who had type 2 diabetes and took hyperglycemic drugs as prescribed were enrolled in the present study. Subjects consumed oolong tea (1,500 ml) or water for 30 days each in a randomized crossover design. Tea was not consumed for 14 days prior to treatments. RESULTS: Relative to initial concentrations, oolong tea markedly lowered concentrations of plasma glucose (from 229 +/- 53.9 to 162.2 +/- 29.7 mg/dl, P < 0.001) and fructosamine (from 409.9 +/- 96.1 to 323.3 +/- 56.4 micromol/l, P < 0.01), whereas the water control group had not changed (208.7 +/- 61.0 vs. 232.3 +/- 63.1 mg/dl for glucose and from 368.4 +/- 85.0 to 340.0 +/- 76.1 micromol/l for fructosamine). CONCLUSIONS: Oolong tea may be an effective adjunct to oral hypoglycemic agents in the treatment of type 2 diabetes.

[Detection of circulating lung cancer cells with cytokeratin and 2F7/S5A monoclonal antibody in patients with lung cancer].

BACKGROUND: To investigate the clinical possibility of detection of lung cancer cells in the peripheral blood with cytokeratin and 2F7/S5A monoclonal antibody by flow cytometry (FCM) in patients with lung cancer. METHODS: Five mililiter peripheral blood was collected. The mononuclear cells were isolated by Ficoll-Hypaquegradient centrifugation. Then the cells were labeled with lung specific antibody (2F7/S5A) and antibodies against CD45, cytokeratin (CK). The quantitation of CD45 -CK +2F7/S5A + cells were performed by FCM. RESULTS: A total of 151 people were studied, including 20 healthy controls, 116 patients with lung cancer and 15 patients with benign pulmonary diseases. The phenotype of monocytes of peripheral blood was CD45 +CK -2F7/S5A -, while the phenotype of lung cancer cells was CD45 -CK +2F7/S5A +. No cancer cell was found in peripheral blood of all the healthy controls. One out of 15 cases of benign pulmonary diseases was found to have CD45 +CK -2F7/S5A - cells in peripheral blood. And 39 out of 116 patients with lung cancer were found to have circulating lung cancer cells. The sensitivity, specificity, positive predictive value and negative predictive value of detection was 33.62% , 93.33%, 97.50% and 15.38%, respectively. The average quantitation of circulating cancer cell detected was 0.12×106/L. CONCLUSIONS: There is high specificity and positive predictive value of the examination of circulating cancer cells in patients with lung cancer by FCM, which could detect trace cancer cell in peripheral blood of lung cancer. It may be valuable in diagnosis and treatment of lung cancer.

Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats.

BACKGROUND: Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood. METHODS: In this study, we prepared levodopa methyl ester (LDME)/benserazide-loaded nanoparticles, which can release LDME and benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus benserazide or the same dose of LDME/benserazide-loaded nanoparticles. Apomorphine- induced rotations and abnormal involuntary movements (AIMs) were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate- regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay. RESULTS: Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus benserazide or LDME/benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO) AIMs of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20, respectively, which were significantly reduced compared with dyskinetic rats treated with LDME plus benserazide (25 ± 3.7, 27 ± 3.8, and 25 ± 3.5, respectively). The locomotive AIMs of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 2.3 ± 0.42, 1.7 ± 0.35, and 1.6 ± 0.37 on treatment days 10, 15, and 20, respectively, which were also reduced compared with dyskinetic rats treated with LDME plus benserazide (4.4 ± 0.85, 4.7 ± 0.95 and 4.8 ± 0.37, respectively). Western blot showed that the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, tau, and ΔfosB in dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 134.6 ± 14.1, 174.9 ± 15.1, 134.2 ± 19.3, and 320.5 ± 32.8, respectively, which were significantly reduced compared with those of dyskinetic rats treated with LDME plus benserazide (210.3 ± 19.7, 320.8 ± 21.9, 340.4 ± 27.1, and 620.7 ± 48.3, respectively). Immunohistochemistry indicated that the level of phosphorylated tau was (7.2 ± 1.1) × 10(4) in dyskinetic rats treated with LDME/benserazide-loaded nanoparticles. However, the tau level was only (14.6 ± 2.3) × 10(4) in LDME plus benserazide-treated dyskinetic rats. There was a significant difference between the two groups. Enzyme-linked immunosorbent assay showed that dynorphin levels in the striatum and cortex of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 5.7 ± 1.2 and 4.8 ± 0.87, respectively, which were significantly reduced compared with LDME plus benserazide-treated dyskinetic rats (13.3 ± 2.1 and 8.1 ± 1.1 for the striatum and cortex, respectively). CONCLUSION: Results suggest that LDME/benserazide-loaded nanoparticles can be used to reduce the expression of dyskinesia in dyskinetic rats.

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone.

BACKGROUND: Silicone oil, as a major component in conditioner, is beneficial in the moisture preservation and lubrication of hair. However, it is difficult for silicone oil to directly absorb on the hair surface because of its hydrophobicity. Stable nanoemulsions containing silicone oil may present as a potential solution to this problem. METHODS: Silicone oil nanoemulsions were prepared using the oil-in-water method with nonionic surfactants. Emulsion particle size and distribution were characterized by scanning electron microscopy. The kinetic stability of this nanoemulsion system was investigated under accelerated stability tests and long-term storage. The effect of silicone oil deposition on hair was examined by analyzing the element of hair after treatment of silicone oil nanoemulsions. RESULTS: Nonionic surfactants such as Span 80 and Tween 80 are suitable emulsifiers to prepare oil-in-water nanoemulsions that are both thermodynamically stable and can enhance the absorption of silicone oil on hair surface. CONCLUSION: The silicone oil-in-water nanoemulsions containing nonionic surfactants present as a promising solution to improve the silicone oil deposition on the hair surface for hair care applications.

Optical mapping of ventricular arrhythmias in LQTS mice with SCN5A mutation N1325S.

Transgenic expression of SCN5A mutation N1325S creates a mouse model for type-3 long QT syndrome (LQT3), TG-NS/LQT3. Optical mapping is a high temporal and spatial resolution fluorescence mapping system that records 256 action potentials simultaneously in a Langendorff-perfused heart. Here for the first-time, we provide a spatial view of VT in a genetic LQT3 model using optical mapping. Spontaneous VT was detected in TG-NS/LQT3 hearts, but not in littermate control hearts. VT was initiated primarily by activation of a new firing focus as well as functional conduction block of new activation waves. New firing was initiated at many different Loci in the heart, suggesting that "increased automaticity" is a key mechanism for initiation of VT. The sustained VT was maintained by a reentry mechanism. Nifedipine, an L-type calcium channel blocker, decreased the frequency of VT, indicating the involvement of abnormalities of the calcium homeostasis in the genesis of VT in TG-NS/LQT3 mice.