Beware of atrial pacing-induced ventricular depolarization: A case of lead malfunction.

Although ventricular capture during the atrial threshold test is possible, there are rare reports on the insulation defect and inactive leads thereof. In this case, we present a pacemaker-dependent patient with a history of pacemaker generator replacements. The patient experienced ventricular capture induced by atrial pacing due to adhesion of the atrial and ventricular leads with an insulation defect. The atrial lead was abandoned and a new lead was implanted. However, there was a significant decrease in ventricular impedance detected shortly after the new lead was implanted. When observing the phenomenon of atrial pacing-induced ventricular depolarization, one uncommon reason to consider is lead adhesive wear. It is important to pay attention to the contact and bending sites of the leads.

Non-coding genome in small cell lung cancer between theoretical view and clinical applications.

Small cell lung cancer (SCLC) is a highly aggressive cancer of the neuroendocrine system, characterized by poor differentiation, rapid growth, and poor overall survival (OS) of patients. Despite the recent advances in the treatment of SCLC recently, the 2-year survival rate of patients with the cancer is only 14-15%, occasioned by the acquired resistance to drugs and serious off-target effects. In humans, the coding region is only 2% of the total genome, and 20% of that is associated with human diseases. Beyond the coding genome are RNAs, promoters, enhancers, and other intricate elements. The non-coding regulatory regions, mainly the non-coding RNAs (ncRNAs), regulate numerous biological activities including cell proliferation, metastasis, and drug resistance. As such, they are potential diagnostic or prognostic biomarkers, and also potential therapeutic targets for SCLC. Therefore, understanding how non-coding elements regulate SCLC development and progression holds significant clinical implications. Herein, we summarized the recent discoveries on the relationship between the non-coding elements including long non-coding RNAs (lncRNA), microRNAs (miRNAs), circular RNA (circRNA), enhancers as well as promotors, and the pathogenesis of SCLC and their potential clinical applications.

Artificial intelligence-based prediction of clinical outcome in immunotherapy and targeted therapy of lung cancer.

Lung cancer accounts for the main proportion of malignancy-related deaths and most patients are diagnosed at an advanced stage. Immunotherapy and targeted therapy have great advances in application in clinics to treat lung cancer patients, yet the efficacy is unstable. The response rate of these therapies varies among patients. Some biomarkers have been proposed to predict the outcomes of immunotherapy and targeted therapy, including programmed cell death-ligand 1 (PD-L1) expression and oncogene mutations. Nevertheless, the detection tests are invasive, time-consuming, and have high demands on tumor tissue. The predictive performance of conventional biomarkers is also unsatisfactory. Therefore, novel biomarkers are needed to effectively predict the outcomes of immunotherapy and targeted therapy. The application of artificial intelligence (AI) can be a possible solution, as it has several advantages. AI can help identify features that are unable to be used by humans and perform repetitive tasks. By combining AI methods with radiomics, pathology, genomics, transcriptomics, proteomics, and clinical data, the integrated model has shown predictive value in immunotherapy and targeted therapy, which significantly improves the precision treatment of lung cancer patients. Herein, we reviewed the application of AI in predicting the outcomes of immunotherapy and targeted therapy in lung cancer patients, and discussed the challenges and future directions in this field.

Small cell lung cancer transformation: From pathogenesis to treatment.

Small cell lung cancer (SCLC) is a type of neuroendocrine tumor with high malignancy and poor prognosis. Besides the de novo SCLC, there is transformed SCLC, which has similar characteristics of pathological morphology, molecular characteristics, clinical manifestations and drug sensitivity. However, de novo SCLC and transformed SCLC have different pathogenesis and tumor microenvironment. SCLC transformation is one of the mechanisms of resistance to chemotherapy, immunotherapy, and targeted therapy in NSCLC. Two hypotheses have been used to explain the pathogenesis of SCLC transformation. Although SCLC transformation is not common in clinical practice, it has been repeatedly identified in many small patient series and case reports. It usually occurs in epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma after treatment with tyrosine kinase inhibitors (TKIs). SCLC transformation can also occur in anaplastic lymphoma kinase (ALK)-positive lung cancer after treatment with ALK inhibitors and in wild-type EGFR or ALK NSCLC treated with immunotherapy. Chemotherapy was previously used to treat transformed SCLC, yet it is associated with an unsatisfactory prognosis. We comprehensively review the advancements in transformed SCLC, including clinical and pathological characteristics, and the potential effective treatment after SCLC transformation, aiming to give a better understanding of transformed SCLC and provide support for clinical uses.

Catheter ablation of atrial fibrillation using FireMagic TrueForce ablation catheter: The TRUEFORCE trial.

BACKGROUND: The use of contact force (CF) sensing catheters has provided a revolutionary improvement in catheter ablation (CA) of atrial fibrillation (AF) in the past decade. However, the success rate of CA for AF remains limited, and some complications still occur. METHODS: The TRUEFORCE trial (Catheter Ablation of Atrial Fibrillation using FireMagic TrueForce Ablation Catheter) is a multicenter, prospective, single-arm objective performance criteria study of AF patients who underwent their first CA procedure using FireMagic TrueForce ablation catheter. RESULTS: A total of 120 patients (118 with paroxysmal AF) were included in this study, and 112 patients included in the per-protocol analysis. Pulmonary vein isolation (PVI) was achieved in 100% of the patients, with procedure and fluoroscopy time of 146.63 ± 40.51 min and 12.89 ± 5.59 min, respectively. Freedom from recurrent atrial arrhythmia after ablation was present 81.25% (95% confidence interval [CI]: 72.78%-88.00%) of patients. No severe adverse events (death, stroke/transient ischemic attack [TIA], esophageal fistula, myocardial infarction, thromboembolism, or pulmonary vein stenosis) were detected during the follow-up. Four (4/115, 3.33%) adverse events were documented, including one abdominal discomfort, one femoral artery hematoma, one coughing up blood, and one postoperative palpitation and insomnia. CONCLUSIONS: This study demonstrated the clinical feasibility of FireMagic force-sensing ablation catheter in CA of AF, with a satisfactory short- and long-term efficacy and safety.

Changes in Heart Rate after Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation and Sinus Bradycardia.

This study aimed to evaluate the effect of circumferential pulmonary vein isolation (CPVI) on autonomic nervous function and prognosis in patients with paroxysmal atrial fibrillation (AF) with or without sinus bradycardia.A total of 66 patients with paroxysmal AF accompanied by sinus bradycardia and who underwent CPVI were recruited as the sinus bradycardia group. A total of 91 patients with paroxysmal AF but without sinus bradycardia and who underwent catheter ablation were selected as the control group. After surgical contraindications were eliminated, CPVI was performed by three-dimensional mapping system. 24-hour dynamic electrocardiogram was used to observe the changes of heart rate before and 2 days after surgery.A total of 45 (68%) and 51 (56%) patients in the sinus bradycardia and control groups, respectively, maintained sinus rhythm. There was an increase in heart rate after CPVI in both groups. The standard deviation of normal-to-normal (NN) intervals (SDNN), standard deviation of the average NN intervals (SDANN), low frequency (LF), and LF/high frequency (HF) in the sinus bradycardia and control groups decreased after CPVI (P < 0.01). Moreover, SDANN was higher in patients with sinus bradycardia treated by successful ablation than in those with recurrence (P < 0.01), while SDNN, a standard statistical measure of heart rate variability (rMSSD), LF, and HF were significantly lower in patients with sinus bradycardia (P < 0.05).CPVI was able to produce a significant reduction effect on vagal nerve and sympathetic activity regardless of whether patients with paroxysmal AF had sinus bradycardia. Moreover, CPVI exerted a certain influence on the success rate of AF catheter ablation.

Gold Nanoparticle-Bridge Array to Improve DNA Hybridization Efficiency of SERS Sensors.

The interfacial mass transfer rate of a target has a significant impact on the sensing performance. The surface reaction forms a concentration gradient perpendicular to the surface, wherein a slow mass transfer process decreases the interfacial reaction rate. In this work, we self-assembled gold nanoparticles (AuNPs) in the gap of a SiO2 opal array to form a AuNP-bridge array. The diffusion paths of vertical permeability and a microvortex effect provided by the AuNP-bridge array synergistically improved the target mass transfer efficiency. As a proof of concept, we used DNA hybridization efficiency as a research model, and the surface-enhanced Raman spectroscopy (SERS) signal acted as a readout index. The experimental verification and theoretical simulation show that the AuNP-bridge array exhibited rapid mass transfer and high sensitivity. The DNA hybridization efficiency of the AuNP-bridge array was 15-fold higher than that of the AuNP-planar array. We believe that AuNP-bridge arrays can be potentially applied for screening drug candidates, genetic variations, and disease biomarkers.

Self-Assembled Supercrystals Enhance the Photothermal Conversion for Solar Evaporation and Water Purification.

Photothermal materials can convert renewable solar energy into thermal energy and have great potential for solar water evaporation. Copper sulfide (Cu2- x S) is an easily available and inexpensive plasmonic material with a high photothermal conversion efficiency and can be applied to solar evaporation and water purification. Monodispersed Cu7 S4 nanoparticles (NPs) and supercrystalline self-assembled superparticles are obtained via wet chemical synthesis and micelle self-assembly. The photothermal properties of the superstructures are investigated using the finite difference time domain method and laser radiation photothermography. The results show that the electromagnetic field intensity and photothermal efficiency of the self-assembly are significantly higher than those of isolated NPs, which is due to the plasmonic coupling of the NPs. The evaporation efficiency of the superstructure is significantly higher than that of isolated NPs, the metal salt ion and total organic carbon concentrations in the waterbody significantly decrease after evaporation, and the water polluted by high salt and organic dye concentrations is purified. The water quality significantly improves after the lake water from Fuxian Lake in the Yunnan-Guizhou Plateau of China is used for solar evaporation. The color changes from pale yellow to colorless and the ion and total organic carbon contents significantly decrease.

TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

Impact of baseline impedance of pulmonary vein antrum on success of catheter ablation for paroxysmal atrial fibrillation guided by ablation index.

OBJECTIVE: Ablation index (AI) is an effective ablation quality marker. Impedance is also an important factor for lesion formation. The present study evaluated the influence of the baseline impedance in the effect of ablation for atrial fibrillation (AF) guided by AI. METHODS: This was a retrospective study. 101 patients with paroxysmal AF (PAF) were enrolled. All patients underwent radiofrequency ablation guided by the same AI strategy. The ablation strategy was pulmonary vein (PV) isolation with non-PV triggers ablation. The baseline impedance of the ablation points was recorded. The patients were followed up every 3 months or so. RESULTS: During a median follow-up of 12 (4-14) months, freedom from AF/atrial tachycardia recurrence were 82.2%. No difference existed in baseline characteristics between the success group and the recurrence group. The average baseline impedance was 124.3 ± 9.7 Ω. The baseline impedance of the ablation points in success group was lower compared to the recurrence group (122.9 ± 9.4 vs. 130.5 ± 8.8 Ω, P < 0.01). The ratio of impedance drop in the success group was higher than the recurrence group ([8.8 ± 1.4]% vs. [8.1 ± 1.2]%, P = 0.03). Multivariate analysis revealed that baseline impedance, PAF duration and AI were the independent predictors of AF recurrence. The cumulative free of recurrence rate of low-impedance group (≤ 124 Ω, n = 54) was higher than that of high-impedance group. CONCLUSION: Baseline impedance correlates with clinical outcome of radiofrequency ablation for PAF guided by AI. Higher impedance in the same AI strategy may result in an ineffective lesion which probably causes recurrence.

Influencing factors of treatment and prognosis perceptions among advanced cancer patients: a cross-sectional study.

PURPOSE: The present study aimed to investigate the status and significantly influencing factors of treatment and prognosis perceptions among advanced cancer patients based on patient-reported outcome. METHODS: A cross-sectional study was conducted at two tertiary A general hospitals. From June to September 2019, 300 patients were invited and 292 of them participated in this study. Except for 9 invalid questionnaires, 283 pen-paper questionnaires including sociodemographic and clinical characteristics, Chinese Version of Prognosis and Treatment Perception Questionnaire, Herth Hope Index, and Hospital Anxiety and Depression Scale were well completed. Descriptive analysis, Pearson's correlation test, logistic regression analysis, and multiple linear regression analysis were applied for analysis. RESULTS: One hundred seventy-five (61.8%) advanced cancer patients reported inaccurate treatment perception. Prognosis perception scored 87.9 ± 13.72 indicating a middle level of prognosis perception. Fourteen (4.9%), 138 (48.8%), and 131 (46.3%) patients presented low, middle, and high prognosis perception levels, respectively. In patients, without spouse and religion beliefs, received chemoradiotherapy, diagnosed as cancer equal to or less than 1 year, and higher hope level were inaccurate treatment perception's risk factors. Younger age, longer diagnosis time, higher educational level, less support for medical expenses payment, receiving chemoradiotherapy, and lower hope level but more anxiety and depression symptoms were positive predictors of prognosis perception. CONCLUSIONS: A majority of advanced cancer patients in this study reported inaccurate treatment and middle level of prognosis perception influencing by objective and subjective factors. Clinical interventions could be developed referring these impacting factors originating from patient-reported outcome.

Electrocatalytic CO2 Reduction and H2 Evolution by a Copper (II) Complex with Redox-Active Ligand.

The process of electrocatalytic CO2 reduction and H2 evolution from water, regarding renewable energy, has become one of the global solutions to problems related to energy consumption and environmental degradation. In order to promote the electrocatalytic reactivity, the study of the role of ligands in catalysis has attracted more and more attention. Herein, we have developed a copper (II) complex with redox-active ligand [Cu(L1)2NO3]NO3 (1, L1 = 2-(6-methoxypyridin-2-yl)-6-nitro-1h-benzo [D] imidazole). X-ray crystallography reveals that the Cu ion in cation of complex 1 is coordinated by two redox ligands L1 and one labile nitrate ligand, which could assist the metal center for catalysis. The longer Cu-O bond between the metal center and the labile nitrate ligand would break to provide an open coordination site for the binding of the substrate during the catalytic process. The electrocatalytic investigation combined with DFT calculations demonstrate that the copper (II) complex could homogeneously catalyze CO2 reduction towards CO and H2 evolution, and this could occur with great performance due to the cooperative effect between the central Cu (II) ion and the redox- active ligand L1. Further, we discovered that the added proton source H2O and TsOH·H2O (p-Toluenesulfonic acid) could greatly enhance its electrocatalytic activity for CO2 reduction and H2 evolution, respectively.

Appropriate intraprocedural initial heparin dosing in patients undergoing catheter ablation for atrial fibrillation receiving uninterrupted non-vitamin-K antagonist oral anticoagulant treatment.

BACKGROUND: To clarify the appropriate initial dosage of heparin during radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) receiving uninterrupted nonvitamin K antagonist oral anticoagulant (NOAC) treatment. METHODS: A total of 187 consecutive AF patients who underwent their first RFCA in our center were included. In the warfarin group (WG), an initial heparin dose of 100 U/kg was administered (control group: n = 38). The patients who were on NOACs were randomly divided into 3 NOAC groups (NG: n = 149), NG110, NG120, and NG130, and were administered initial heparin doses of 110 U/kg, 120 U/kg, and 130 U/kg, respectively. During RFCA, the activated clotting time (ACT) was measured every 15 min, and the target ACT was maintained at 250-350 s by intermittent heparin infusion. The baseline ACT and ACTs at each 15-min interval, the average percentage of measurements at the target ACT, and the incidence of periprocedural bleeding and thromboembolic complications were recorded and analyzed. RESULTS: There was no significant difference in sex, age, weight, or baseline ACT among the four groups. The 15 min-ACT, 30 min-ACT, and 45 min-ACT were significantly longer in the WG than in NG110 and NG120. However, no significant difference in 60 min-ACT or 75 min-ACT was detected. The average percentages of measurements at the target ACT in NG120 (82.2 ± 23.6%) and NG130 (84.8 ± 23.7%) were remarkably higher than those in the WG (63.4 ± 36.2%, p = 0.007, 0.003, respectively). These differences were independent of the type of NOAC. The proportion of ACTs in 300-350 s in NG130 was higher than in WG (32.4 ± 31.8 vs. 34.7 ± 30.6, p = 0.735). Severe periprocedural thromboembolic and bleeding complications were not observed. CONCLUSIONS: For patients with AF receiving uninterrupted NOAC treatment who underwent RFCA, an initial heparin dosage of 120 U/kg or 130 U/kg can provide an adequate intraprocedural anticoagulant effect, and 130 U/kg allowed ACT to reach the target earlier. TRIAL REGISTRATION: Registration number: ChiCTR1800016491, First Registration Date: 04/06/2018 (Chinese Clinical Trial Registry http://www.chictr.org.cn/index.aspx ).

Brady-arrhythmias in patients with atrial fibrillation and heart failure of reduced ejection fraction: is his-bundle pacing superior to biventricular pacing？.

OBJECTIVE: To investigate the efficacy and safety of His-bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady-arrhythmias, who suffer from permanent atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). METHODS: All patients with brady-arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end-diastolic diameter (LVEDD), and left atrial size were compared. RESULTS: A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow-up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his-bundle and the threshold of the left ventricular lead remained stable during follow-up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow-up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP. CONCLUSION: HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady-arrhythmias, permanent AF and HFrEF compared with BVP.

Nurses' behaviours towards physical restraint use in the ICU: A descriptive qualitative study.

AIMS AND OBJECTIVES: The study aims to explore and describe nurses' behaviours towards physical restraint (PR) use in intensive care units (ICUs) and identify key characteristics of these experiences. BACKGROUND: Patients within the ICU are always vulnerable, which requires a thoughtful deliberation when employing PR in ethically laden situations. Considering that the qualitative study on nurses' behaviours towards PR use in ICUs is limited, a deep understanding of how nurses reason and restrict patients is necessary before developing a minimizing programme in hospitals. METHODS: A descriptive qualitative study was conducted in this paper. Data were collected by 24 semistructured, in-depth and individual interviews about PR, where 24 nurses were drawn from six ICUs of four hospital settings from a comprehensive tertiary care hospital in Qingdao. The QSR NVivo 11.0 software program was used to manage the interview data, and data analysis was guided by the Qualitative Analysis Guide of Leuven. The checklist of Consolidated Criteria for Reporting Qualitative Studies was followed as a guideline in reporting the study. RESULTS: Regarding PR, nurses' behaviours start with a hazard perception, followed by hesitation about whether to restrict the patient. They would usually decide to apply PR when they think that no other choice to control the situation is available. Then, they would reflect on and rationalize their behaviours. Nurses, intensivists, patients and their families participate in and affect this process directly or indirectly. CONCLUSIONS: Nurses' behaviours towards PR use comprise a series of complex processes centred on safety. Nurses' decision making should be performed with the participation of intensivists, patients and family caregivers.

Familial paroxysmal kinesigenic dyskinesia is associated with mutations in the KCNA1 gene.

Paroxysmal kinesigenic dyskinesia (PKD) is a heterogeneous movement disorder characterized by recurrent dyskinesia attacks triggered by sudden movement. PRRT2 has been identified as the first causative gene of PKD. However, it is only responsible for approximately half of affected individuals, indicating that other loci are most likely involved in the etiology of this disorder. To explore the underlying causative gene of PRRT2-negative PKD, we used a combination strategy including linkage analysis, whole-exome sequencing and copy number variations analysis to detect the genetic variants within a family with PKD. We identified a linkage locus on chromosome 12 (12p13.32-12p12.3) and detected a novel heterozygous mutation c.956 T>G (p.319 L>R) in the potassium voltage-gated channel subfamily A member 1, KCNA1. Whole-exome sequencing in another 58 Chinese patients with PKD who lacked mutations in PRRT2 revealed another novel mutation in the KCNA1 gene [c.765 C>A (p.255 N>K)] within another family. Biochemical analysis revealed that the L319R mutant accelerated protein degradation via the proteasome pathway and disrupted membrane expression of the Kv1.1 channel. Electrophysiological examinations in transfected HEK293 cells showed that both the L319R and N255K mutants resulted in reduced potassium currents and respective altered gating properties, with a dominant negative effect on the Kv1.1 wild-type channel. Our study suggests that these mutations in KCNA1 cause the Kv1.1 channel dysfunction, which leads to familial PKD. The current study further extended the genotypic spectrum of this disorder, indicating that Kv1.1 channel dysfunction maybe one of the underlying defects in PKD.

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

EEF1A2 mutations in epileptic encephalopathy/intellectual disability: Understanding the potential mechanism of phenotypic variation.

EEF1A2 encodes protein elongation factor 1-alpha 2, which is involved in Guanosine triphosphate (GTP)-dependent binding of aminoacyl-transfer RNA (tRNA) to the A-site of ribosomes during protein biosynthesis and is highly expressed in the central nervous system. De novo mutations in EEF1A2 have been identified in patients with extensive neurological deficits, including intractable epilepsy, globe developmental delay, and severe intellectual disability. However, the mechanism underlying phenotype variation is unknown. Using next-generation sequencing, we identified a novel and a recurrent de novo mutation, c.294C>A; p.(Phe98Leu) and c.208G>A; p.(Gly70Ser), in patients with Lennox-Gastaut syndrome. The further systematic analysis revealed that all EEF1A2 mutations were associated with epilepsy and intellectual disability, suggesting its critical role in neurodevelopment. Missense mutations with severe molecular alteration in the t-RNA binding sites or GTP hydrolysis domain were associated with early-onset severe epilepsy, indicating that the clinical expression was potentially determined by the location of mutations and alteration of molecular effects. This study highlights the potential genotype-phenotype relationship in EEF1A2 and facilitates the evaluation of the pathogenicity of EEF1A2 mutations in clinical practice.

High efficiency and workflow of His bundle pacing and atrioventricular node ablation guided by three-dimensional mapping system.

BACKGROUND: Atrioventricular node (AVN) ablation combined with His bundle pacing is an effective strategy for permanent atrial fibrillation (AF) with rapid ventricular rate refractory to pharmacological therapy. We aimed to access the feasibility and efficiency of His bundle pacing and AVN ablation guided by three-dimensional (3-D) mapping system throughout the procedure. METHODS: Eighteen patients with permanent AF with refractory rate and symptoms were referred for His bundle pacing and AVN ablation guided by 3-D mapping (CARTO3). Electroanatomic 3-D mapping of the right atrium and right ventricle was performed by the ablation catheter with CARTO 3 system, followed by the visualization of the leads for implantation and AVN ablation. RESULTS: Implantation of His bundle and ventricular leads and AVN ablation were achieved successfully with the help of 3-D mapping in 17 patients. Selective His bundle pacing was achieved in five patients (29.4%), and the other (70.6%) were nonselective His bundle pacing. The mean procedure duration was 99.4 ± 16.4 minutes. The mean fluoroscopy time was 7.0 ± 2.6 minutes. The time spent on His lead implantation was 6.1 ± 3.2 minutes. One patient experienced AVN ablation from left side under aortic valves due to no effect of ablation in right atrium. CONCLUSION: His bundle pacing and AVN ablation guided by throughout real-time 3-D mapping system are of high-efficiency and feasibility.

Long-read sequencing identified intronic repeat expansions in SAMD12 from Chinese pedigrees affected with familial cortical myoclonic tremor with epilepsy.

BACKGROUND: The locus for familial cortical myoclonic tremor with epilepsy (FCMTE) has long been mapped to 8q24 in linkage studies, but the causative mutations remain unclear. Recently, expansions of intronic TTTCA and TTTTA repeat motifs within SAMD12 were found to be involved in the pathogenesis of FCMTE in Japanese pedigrees. We aim to identify the causative mutations of FCMTE in Chinese pedigrees. METHODS: We performed genetic linkage analysis by microsatellite markers in a five-generation Chinese pedigree with 55 members. We also used array-comparative genomic hybridisation (CGH) and next-generation sequencing (NGS) technologies (whole-exome sequencing, capture region deep sequencing and whole-genome sequencing) to identify the causative mutations in the disease locus. Recently, we used low-coverage (~10×) long-read genome sequencing (LRS) on the PacBio Sequel and Oxford Nanopore platforms to identify the causative mutations, and used repeat-primed PCR for validation of the repeat expansions. RESULTS: Linkage analysis mapped the disease locus to 8q23.3-24.23. Array-CGH and NGS failed to identify causative mutations in this locus. LRS identified the intronic TTTCA and TTTTA repeat expansions in SAMD12 as the causative mutations, thus corroborating the recently published results in Japanese pedigrees. CONCLUSIONS: We identified the pentanucleotide repeat expansion in SAMD12 as the causative mutation in Chinese FCMTE pedigrees. Our study also suggested that LRS is an effective tool for molecular diagnosis of genetic disorders, especially for neurological diseases that cannot be positively diagnosed by conventional clinical microarray and NGS technologies.