Genomic view of heavy-ion-induced deletions associated with distribution of essential genes in Arabidopsis thaliana.

Heavy-ion beam, a type of ionizing radiation, has been applied to plant breeding as a powerful mutagen and is a promising tool to induce large deletions and chromosomal rearrangements. The effectiveness of heavy-ion irradiation can be explained by linear energy transfer (LET; keV µm-1). Heavy-ion beams with different LET values induce different types and sizes of mutations. It has been suggested that deletion size increases with increasing LET value, and complex chromosomal rearrangements are induced in higher LET radiations. In this study, we mapped heavy-ion beam-induced deletions detected in Arabidopsis mutants to its genome. We revealed that deletion sizes were similar between different LETs (100 to 290 keV µm-1), that their upper limit was affected by the distribution of essential genes, and that the detected chromosomal rearrangements avoid disrupting the essential genes. We also focused on tandemly arrayed genes (TAGs), where two or more homologous genes are adjacent to one another in the genome. Our results suggested that 100 keV µm-1 of LET is enough to disrupt TAGs and that the distribution of essential genes strongly affects the heritability of mutations overlapping them. Our results provide a genomic view of large deletion inductions in the Arabidopsis genome.

Wnt/ß­catenin signaling is a novel therapeutic target for tumor suppressor CYLD­silenced glioblastoma cells.

Tumor suppressor cylindromatosis (CYLD) dysfunction by its downregulation is significantly associated with poor prognosis in patients with glioblastoma (GBM), the most aggressive and malignant type of glioma. However, no effective treatment is currently available for patients with CYLD­downregulated GBM. The aim of the present study was to identify the crucial cell signaling pathways and novel therapeutic targets for CYLD downregulation in GBM cells. CYLD knockdown in GBM cells induced GBM malignant characteristics, such as proliferation, metastasis, and GBM stem­like cell (GSC) formation. Comprehensive proteomic analysis and RNA sequencing data from the tissues of patients with GBM revealed that Wnt/ß­catenin signaling was significantly activated by CYLD knockdown in patients with GBM. Furthermore, a Wnt/ß­catenin signaling inhibitor suppressed all CYLD knockdown­induced malignant characteristics of GBM. Taken together, the results of the present study revealed that Wnt/ß­catenin signaling is responsible for CYLD silencing­induced GBM malignancy; therefore, targeting Wnt/ß­catenin may be effective for the treatment of CYLD­negative patients with GBM with poor prognosis.

Atrial late potentials are associated with atrial fibrillation recurrence after catheter ablation.

Background: Previous studies have identified noninvasive methods for predicting atrial fibrillation (AF) recurrence after catheter ablation (CA). We assessed the association between AF recurrence and atrial late potentials (ALPs), which were measured using P-wave signal-averaged electrocardiography (P-SAECG). Methods: Consecutive patients with paroxysmal AF who underwent their first CA at our institution between August 2015 and August 2019 were enrolled. P-SAECG was performed before CA. Two ALP parameters were evaluated: the root-mean-square voltage during the terminal 20 ms (RMS20) and the P-wave duration (PWD). Positive ALPs were defined as an RMS20 <2.2 µV and/or a PWD >115 ms. Patients were allocated to either the recurrence or nonrecurrence group based on the presence of AF recurrence at the 1-year follow-up post-CA. Results: Of the 190 patients (age: 65 ± 11 years, 37% women) enrolled in this study, 21 (11%) had AF recurrence. The positive ALP rate was significantly higher in the recurrence group than in the nonrecurrence group (86% vs. 64%, p = .04), despite the absence of differences in other baseline characteristics between the two groups. In the multivariate analysis, positive ALP was an independent predictor of AF recurrence (odds ratio: 3.83, 95% confidence interval: 1.05-14.1, p = .04). Conclusions: Positive ALP on pre-CA P-SAECG is associated with AF recurrence after CA.

Humanized anti-IL-26 monoclonal antibody as a novel targeted therapy for chronic graft-versus-host disease.

IL-26 is a Th17 cytokine, with its gene being absent in rodents. To characterize the in vivo immunological effects of IL-26 in chronic systemic inflammation, we used human IL26 transgenic (hIL-26Tg) mice and human umbilical cord blood mononuclear cells (hCBMC) in mouse allogeneic-graft-versus-host disease (GVHD) and chronic xenogeneic-GVHD model, respectively. Transfer of bone marrow and spleen T cells from hIL-26Tg mice into B10.BR mice resulted in GVHD progression, with clinical signs of tissue damage in multiple organs. IL-26 markedly increased neutrophil levels both in the GVHD-target tissues and peripheral blood. Expression levels of Th17 cytokines in hIL-26Tg mice-derived donor CD4 T cells were significantly increased, whereas IL-26 did not affect cytotoxic function of donor CD8 T cells. In addition, granulocyte-colony stimulating factor, IL-1ß, and IL-6 levels were particularly enhanced in hIL-26Tg mice. We also developed a humanized neutralizing anti-IL-26 monoclonal antibody (mAb) for therapeutic use, and its administration after onset of chronic xenogeneic-GVHD mitigated weight loss and prolonged survival, with preservation of graft-versus-leukemia effect. Taken together, our data elucidate the in vivo immunological effects of IL-26 in chronic GVHD models and suggest that a humanized anti-IL-26 mAb may be a potential therapeutic agent for the treatment of chronic GVHD.

Ribosomal proteins induce stem cell-like characteristics in glioma cells as an "extra-ribosomal function".

The characteristic features of plasticity and heterogeneity in glioblastoma (GB) cells cause therapeutic difficulties. GB cells are exposed to various stimuli from the tumor microenvironment and acquire the potential to resist chemoradiotherapy. To investigate how GB cells acquire stem cell-like phenotypes, we focused on ribosomal proteins, because ribosome incorporation has been reported to induce stem cell-like phenotypes in somatic cells. Furthermore, dysregulation of ribosome biogenesis has been reported in several types of cancer. We focused on ribosomal protein S6, which promotes sphere-forming ability and stem cell marker expression in GB cells. We expect that investigation of dysregulation of ribosome biogenesis and extra-ribosomal function in GB will provide new insights about the plasticity, heterogeneity, and therapeutic resistance of GB cells, which can potentially lead to revolutionary therapeutic strategies.

Atrial flutter with an epicardial and endocardial breakthrough in the cavotricuspid isthmus.

We performed cavotricuspid isthmus (CTI) linear ablation for atrial flutter; however, the tachycardia cycle length was not changed at all. In such cases, repeated or broad line ablation is usually performed. We presented that high-density three-dimensional mapping after the first CTI linear ablation, which revealed the complex tachycardia circuit with the epicardial and endocardial breakthrough.

Reduced atrial conduction velocity is associated with the recurrence of atrial fibrillation after catheter ablation.

The recurrence of atrial fibrillation (AF) after catheter ablation (CA) is still an unsolved issue. Although structural remodeling is relatively well defined, the method to assess electrical remodeling of the atrium is not well established. In this study, we evaluated the relationship between atrial conduction properties and recurrence after CA for AF. One hundred six consecutive patients (66 ± 11 years old, male: 68%) who underwent CA for AF with a CARTO system from July 2016 to July 2019 were enrolled in this study. An activation map of both atria was constructed to precisely evaluate the total conduction time, distance, and conduction velocity between the earliest and latest activation sites during sinus rhythm. All parameters were compared between the patients with or without AF recurrence. Of the patients, 27 had an AF recurrence (Rec group). The left atrial (LA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (101.2 ± 17.9 vs. 116.9 ± 18.0 cm/s, P < 0.01). Likewise, the right atrial (RA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (81.1 ± 17.5 vs. 103.6 ± 25.4 cm/s, P < 0.01). A multivariate logistic analysis demonstrated that the LA and RA conduction velocities were independent predictors of AF recurrence, with adjusted odds ratios of 0.95 (95% confidential interval: 0.91-0.98, P < 0.01) and 0.94 (0.89-0.98, P < 0.01), respectively. In conclusion, slower conduction velocity of the atrium was associated with AF recurrence after pulmonary vein isolation.

Glioma Cells Acquire Stem-like Characters by Extrinsic Ribosome Stimuli.

Although glioblastoma (GBM) stem-like cells (GSCs), which retain chemo-radio resistance and recurrence, are key prognostic factors in GBM patients, the molecular mechanisms of GSC development are largely unknown. Recently, several studies revealed that extrinsic ribosome incorporation into somatic cells resulted in stem cell properties and served as a key trigger and factor for the cell reprogramming process. In this study, we aimed to investigate the mechanisms underlying GSCs development by focusing on extrinsic ribosome incorporation into GBM cells. Ribosome-induced cancer cell spheroid (RICCS) formation was significantly upregulated by ribosome incorporation. RICCS showed the stem-like cell characters (number of cell spheroid, stem cell markers, and ability for trans differentiation towards adipocytes and osteocytes). In RICCS, the phosphorylation and protein expression of ribosomal protein S6 (RPS6), an intrinsic ribosomal protein, and STAT3 phosphorylation were upregulated, and involved in the regulation of cell spheroid formation. Consistent with those results, glioma-derived extrinsic ribosome also promoted GBM-RICCS formation through intrinsic RPS6 phosphorylation. Moreover, in glioma patients, RPS6 phosphorylation was dominantly observed in high-grade glioma tissues, and predominantly upregulated in GSCs niches, such as the perinecrosis niche and perivascular niche. Those results indicate the potential biological and clinical significance of extrinsic ribosomal proteins in GSC development.

Novel Predictor for New-Onset Atrial High-Rate Episode in Patients With a Dual-Chamber Pacemaker.

Background: The incidence of new-onset atrial high-rate episode (AHRE) is higher among patients with cardiac implantable electronic devices (CIEDs) than in the general population. We sought to elucidate the clinical factors associated with AHRE in CIED patients, including P-wave dispersion (PWD) in sinus rhythm. Methods and Results: In all, 101 patients with CIEDs newly implanted between 2010 and 2014 were included in the study. PWD was measured at the time of device implantation via a body-surface electrocardiogram. AHRE was defined as any episode of sustained atrial tachyarrhythmia (>170 beats/min) recorded in the device's memory. Patients were divided into an AHRE (n=34) and non-AHRE (n=67) group based on the presence or absence of AHRE within 1 year of device implantation and compared. Mean (±SD) patient age was 75±11 years. A greater incidence of sick sinus syndrome (P=0.05) and longer PWD (62.6±13.1 vs. 38.2±13.9 ms; P<0.0001) were apparent in the AHRE than non-AHRE group. Multivariate analysis revealed that PWD was an independent predictor of new-onset AHRE (odds ratio 1.11; 95% confidence interval 1.06-1.17; P<0.0001). In logistic regression analysis, receiver-operating characteristic curve analysis (area under the curve 0.90; P<0.001) suggested the best cut-off value for PWD was 48 mm (sensitivity 73.8%, specificity 77.9%). Conclusions: PWD is a simple but feasible predictor of new-onset AHRE in patients with CIEDs.

Optimized lesion size index (o-LSI): A novel predictor for sufficient ablation of pulmonary vein isolation.

BACKGROUND: Although the lesion size index (LSI) has been well established, it is sometimes difficult to achieve first-pass pulmonary vein isolation (PVI) and to avoid acute pulmonary vein reconnections, even with LSI-guided procedures. The purpose of this study was to assess the predictive accuracy of a novel parameter, the optimized lesion size index (o-LSI), to perform PVI. METHODS: The voltage maps created by the Advisor™ high-density (HD) grid catheter before PVI in 35 atrial fibrillation (AF) patients were examined for an association between the voltage amplitude and insufficient ablation sites (IAS), which were defined as either (i) spontaneous reconnection sites, (ii) dormant PV conduction sites unmasked with 20 mg of adenosine triphosphate disodium hydrate (ATP) injection, or (iii) PV-LA gap sites after the initial PVI. RESULTS: IAS was observed in 25/1417 of the total ablation sites. IAS was significantly associated with higher bipolar voltage areas (4.20 ± 2.68 vs 2.43 ± 1.93 mV, P < .0001) but not with LSI. A novel index, o-LSI (defined as LSI/bipolar voltage), was significantly lower in IAS than in others (1.14 [0.82, 1.81] vs 2.35 [1.31, 4.80] LSI/mV). By receiver operating characteristic analysis, an o-LSI of 2.04 was the best cutoff value for the prediction of IAS (88% sensitivity and 55% specificity, P < .0001, areas under the curve: 0.742). CONCLUSION: Low o-LSI was strongly associated with IAS, potentially providing a novel index to improve first-pass PV isolation.

IL-26 mediates epidermal growth factor receptor-tyrosine kinase inhibitor resistance through endoplasmic reticulum stress signaling pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. Although epidermal growth factor receptor (EGFR) is overexpressed in TNBC, clinical trials with EGFR inhibitors including tyrosine kinase inhibitors (EGFR-TKI) in TNBC have heretofore been unsuccessful. To develop effective EGFR-targeted therapy for TNBC, the precise mechanisms of EGFR-TKI resistance in TNBC need to be elucidated. In this study, to understand the molecular mechanisms involved in the differences in EGFR-TKI efficacy on TNBC between human and mouse, we focused on the effect of IL-26, which is absent in mice. In vitro analysis showed that IL-26 activated AKT and JNK signaling of bypass pathway of EGFR-TKI in both murine and human TNBC cells. We next investigated the mechanisms involved in IL-26-mediated EGFR-TKI resistance in TNBC. We identified EphA3 as a novel functional receptor for IL-26 in TNBC. IL-26 induced dephosphorylation and downmodulation of EphA3 in TNBC, which resulted in increased phosphorylation of AKT and JNK against EGFR-TKI-induced endoplasmic reticulum (ER) stress, leading to tumor growth. Meanwhile, the blockade of IL-26 overcame EGFR-TKI resistance in TNBC. Since the gene encoding IL-26 is absent in mice, we utilized human IL-26 transgenic (hIL-26Tg) mice as a tumor-bearing murine model to characterize the role of IL-26 in the differential effect of EGFR-TKI in human and mice and to confirm our in vitro findings. Our findings indicate that IL-26 activates the bypass pathway of EGFR-TKI, while blockade of IL-26 overcomes EGFR-TKI resistance in TNBC via enhancement of ER stress signaling. Our work provides novel insights into the mechanisms of EGFR-TKI resistance in TNBC via interaction of IL-26 with its newly identified receptor EphA3, while also suggesting IL-26 as a possible therapeutic target in TNBC.

Energy loss by right ventricular pacing: Patients with versus without hypertrophic cardiomyopathy.

BACKGROUND: Right ventricular (RV) pacing causes left ventricular (LV) dyssynchrony sometimes resulting in pacing-induced cardiomyopathy. However, RV pacing for hypertrophic obstructive cardiomyopathy is one of the treatment options. LV flow energy loss (EL) using vector flow mapping (VFM) is a novel hemodynamic index for assessing cardiac function. Our study aimed to elucidate the impact of RV pacing on EL in normal LV function and hypertrophic cardiomyopathy (HCM) patients. METHODS: A total of 36 patients with dual-chamber pacemakers for sick sinus syndrome or implantable cardioverter defibrillators for fatal ventricular tachyarrhythmias were enrolled. All patients were divided into two groups: 16 patients with HCM (HCM group) and others (non-HCM group). The absolute changes in EL under AAI (without RV pacing) and DDD (with RV pacing) modes were assessed using VFM on color Doppler echocardiography. RESULTS: In the non-HCM group, the mean systolic EL significantly increased from the AAI to DDD modes (14.0 ± 7.7 to 17.0 ± 8.6 mW/m, P = .003), whereas the mean diastolic EL did not change (19.0 ± 12.3 to 17.0 ± 14.8 mW/m, P = .231). In the HCM group, the mean systolic EL significantly decreased from the AAI to DDD modes (26.7 ± 14.2 to 21.6 ± 11.9 mW/m, P < .001), whereas the mean diastolic EL did not change (28.7 ± 16.4 to 23.9 ± 19.7 mW/m, P = .130). CONCLUSIONS: RV pacing increased the mean systolic EL in patients without HCM. Conversely, RV pacing decreased the mean systolic EL in patients with HCM.

Canagliflozin Suppresses Atrial Remodeling in a Canine Atrial Fibrillation Model.

Background Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium-glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate. Methods and Results The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model. The study included 12 beagle dogs, with 10 receiving continuous rapid atrial pacing and 2 acting as the nonpacing group. The 10 dogs that received continuous rapid atrial pacing for 3 weeks were subdivided as follows: pacing control group (n=5) and pacing+CAN (3 mg/kg per day) group (n=5). The atrial effective refractory period, conduction velocity, and AF inducibility were evaluated weekly through atrial epicardial wires. After the protocol, atrial tissues were sampled for histological examination. The degree of reactive oxygen species expression was evaluated by dihydroethidium staining. The atrial effective refractory period reduction was smaller (P=0.06) and the degree of conduction velocity decrease was smaller in the pacing+CAN group compared with the pacing control group (P=0.009). The AF inducibility gradually increased in the pacing control group, but such an increase was suppressed in the pacing+CAN group (P=0.011). The pacing control group exhibited interstitial fibrosis and enhanced oxidative stress, which were suppressed in the pacing+CAN group. Conclusions CAN and possibly other SGLT2 inhibitors might be useful for preventing AF and suppressing the promotion of atrial remodeling as an AF substrate.

Optimal interlesion distance in ablation index-guided pulmonary vein isolation for atrial fibrillation.

PURPOSE: Ablation index (AI) is a useful tool of the CARTO® system to make effective lesions during pulmonary vein isolation (PVI) for atrial fibrillation (AF). However, the optimal distance between neighboring ablation points (interlesion distance (ILD)) is still unclear. Here, we evaluated the optimal ILDs in the AI-guided PVI. METHODS: Forty-nine AF patients who underwent AI-guided PVI in our institute from July 2018 to March 2019 were retrospectively enrolled in this study. Target AI was set at 500 and 400 for anterior and posterior walls, respectively, and we compared the ILDs with and without electrical gaps after a first encircling PVI. RESULTS: In both PV, the ILDs with electrical gaps were longer than those without electrical gaps. The best cutoff values of ILD to detect the electrical gaps using the ROC curve were 5.4 mm for the RPV anterior wall (AUC, 0.67; sensitivity, 0.42; specificity, 0.84, P < 0.01) and 4.4 mm for the RPV posterior wall (AUC, 0.68; sensitivity, 0.91; specificity, 0.39, P < 0.01). Similarly, the best cutoff values of ILD were 5.5 mm for the LPV anterior wall (AUC, 0.74; sensitivity, 0.65; specificity, 0.82, P < 0.01) and 5.1 mm for the LPV posterior wall (AUC, 0.67; sensitivity, 0.79; specificity, 0.53, P =0.03). CONCLUSION: The optimal interlesion distances for PVI were different in each PV segment. To achieve the first-pass isolation, less than 5.4/4.4 mm for the RPV anterior/posterior and 5.5/5.1 mm for the LPV anterior/posterior walls of interlesion distances were the best cutoff values in the patients with AF.

Additional posterior wall isolation is associated with gastric hypomotility in catheter ablation of atrial fibrillation.

BACKGROUND: Gastric hypomotility (GH) is a possible complication of catheter ablation (CA) for atrial fibrillation (AF). However, it is unclear which factors are associated with GH. We sought to elucidate the relationship between the CA procedure and GH. METHODS: The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 119 patients were enrolled and divided into two groups: with or without GH (GH or non-GH groups). To evaluate the association with GH, the clinical backgrounds and procedure characteristics of the radiofrequency CA (RFCA) were compared between the two groups. RESULTS: The median age was 69 years old with 34% of female. GH were observed in 27.7% of patients who underwent RFCA, which was significantly higher than that in the cohort of patients who underwent esophago-gastro-duodenoscopy during the same time period (1.9%: 151 in 8063 patients, p < 0.0001). According to the detailed RFCA procedure, additional posterior wall isolation with pulmonary vein isolation (PVI) had a higher prevalence of GH than that with only PVI (54.8% vs. 18.2%; odds ratio 5.46, 95%CI 2.24-13.32, p = 0.0002). After an adjustment using a multivariate logistic analysis, a posterior wall isolation with the PVI was identified as the only independent predictor for GH (odds ratio 5.01, 95%CI 1.94-13.43, p = 0.0009). CONCLUSIONS: Additional posterior wall isolation with PVI was associated with gastric hypomotility.

Visually cued fear conditioning test for memory impairment related to cortical function.

AIM: Fear conditioning tests are intended to elucidate a subject's ability to associate a conditioned stimulus with an aversive, unconditioned stimulus, such as footshock. Among these tests, a paradigm related to precise cortical functions would be increasingly important in drug screening for disorders such as schizophrenia and dementia. Therefore, we established a new fear conditioning paradigm using a visual cue in mice. In addition, the validity of the test was evaluated using a genetically engineered mouse, heterozygous deficient in Mdga1 (Mdga1+/-), which is related to schizophrenia. RESULTS: Mice were given footshocks associated with a visual cue of moving gratings at training in 25-minute sessions. The mice showed the conditioned response of freezing behavior to the visual stimulus at testing 24 hours after the footshocks. In the test for validation, the Mdga1+/- deficient mice showed significantly less freezing than wild-type mice. CONCLUSION: The visually cued fear conditioning paradigm with moving gratings has been established, which is experimentally useful to evaluate animal cortical functions. The validity of the test was confirmed for Mdga1-deficient mice with possible deficiency in cortical functions.

Prediction of Lethal Arrhythmic Events Through Remote Monitoring Using Heart Rate Variability Analysis in Patients with an Implantable Cardioverter Defibrillator.

We prospectively collected device and heart rate data through remote monitoring (RM) of patients with an implantable cardioverter defibrillator (ICD). The objective was to identify the predictors of lethal arrhythmic events (VT/VF).Thirty-three patients (mean age: 50 years) with ICDs [with functionality of heart rate variability (HRV) analysis] were divided into two groups [VT/VF (+), VT/VF (-) ]. Clinical, device (ventricular lead impedance; amplitude of ventricular electrogram), and HRV data were compared between the two groups. The NN interval-index (SDNNi) was calculated for every 5 minutes, and the mean, maximum, minimum, and standard deviation of SDNNi during the 24-hour period were used.During the observation period of 13 ± 10 months, 10 patients experienced VT/VF events. Total mean, max, and min SDNNi were higher in the VT/VF (+) than the VT/VF (-) group (132.9 ± 9.3 versus 93.5 ± 6.1, P = 0.0013; 214.6 ± 10.6 versus 167.0 ± 7.0, P = 0.0007; 71.2 ± 7.5 versus 43.9 ± 4.9, P = 0.0047). On logistic regression analysis, a total mean SDNNi of 100.1, max SDNNi of 185.0 and min SDNNi of 52.0 as cut-off values for prediction of a VT/VF event demonstrated significant receiver operating characteristic (ROC) curves (AUC = 0.86, P = 0.0007; AUC = 0.84, P = 0.0005; AUC = 0.78, P = 0.0030). The max ΔSDNNi, i.e., difference from baseline SDNNi, and min ΔSDNNi in 7 and 28 days preceding VT/VF events were significant predictors of VT/VF events.Time-domain HRV analysis through a RM system may help identify patients at high risk of lethal arrhythmic events; in addition, it may help predict the occurrence of lethal arrhythmic events in specific cases.

Precise Signals with a High-Density Grid Mapping Catheter Are Useful for an Entrainment Study.

Complex atrial tachycardias (ATs) after catheter ablation or a MAZE procedure is sometimes difficult to determine the circuits of the tachycardia. A high-density, grid-shapes mapping catheter has been launched, which can be useful for detecting the detail circuits of tachycardias on three-dimensional mapping systems. The signal quality is also important for performing electrophysiological studies (EPSs), such as entrainment mapping, to identify the circuit. This unique mapping catheter has 1 mm electrodes on 2.5 Fr shafts, which improve the signal quality. The high-quality intracardiac electrograms facilitate differentiating small critical potentials, which allows us to perform detailed entrainment mapping in targeted narrow areas. Here, we describe a patient with a perimetral AT with epi-endocardium breakthrough after a MAZE surgery and catheter ablation, which was treated successfully along with detailed entrainment mapping using the HD Grid. This catheter with high-quality signals could be a significant diagnostic tool for a classic EPS as well as for the construction of 3D mapping.

Severe hypoperistalsis caused by a 3-min single shot cryoballoon ablation for paroxysmal atrial fibrillation: A case report.

A 61-year-old male was referred to our hospital to receive catheter ablation of paroxysmal atrial fibrillation. Since no anatomical abnormalities were detected by preoperative computed tomography of left atrium and pulmonary veins (PVs), he underwent a cryoballoon ablation for a PV isolation. We performed single, 3-min freeze applications to all four PVs while monitoring the esophageal temperature. Immediately after the procedure, he complained of nausea, followed by a body weight loss of 9 kg over 2 months. Since no structural abnormalities were detected even through careful evaluation, he was diagnosed with hypoperistalsis caused by the cryoballoon ablation. Although his symptoms partially improved, they persisted over a year. The cryoballoon procedure is believed to be relatively safe, but even just a simple 3-min freeze application caused severe hypoperistalsis in the present case. Operators should recognize the risk of such complications. .

Ribosomal protein S6 promotes stem-like characters in glioma cells.

Glioblastoma multiforme (GBM), a lethal brain tumor developing in the white matter of the adult brain, contains a small population of GBM stem cells (GSCs), which potentially cause chemotherapeutic resistance and tumor recurrence. However, the mechanisms underlying the pathogenesis and maintenance of GSCs remain largely unknown. A recent study reported that incorporation of ribosomes and ribosomal proteins into somatic cells promoted lineage trans-differentiation toward multipotency. This study aimed to investigate the mechanism underlying stemness acquisition in GBM cells by focusing on 40S ribosomal protein S6 (RPS6). RPS6 was significantly upregulated in high-grade glioma and localized at perivascular, perinecrotic, and border niches in GBM tissues. siRNA-mediated RPS6 knock-down significantly suppressed the characteristics of GSCs, including their tumorsphere potential and GSC marker expression; STAT3 was downregulated in GBM cells. RPS6 overexpression enhanced the tumorsphere potential of GSCs and these effects were attenuated by STAT3 inhibitor (AG490). Moreover, RPS6 expression was significantly correlated with SOX2 expression in different glioma grades. Immunohistochemistry data herein indicated that RPS6 was predominant in GSC niches, concurrent with the data from IVY GAP databases. Furthermore, RPS6 and other ribosomal proteins were upregulated in GSC-predominant areas in this database. The present results indicate that, in GSC niches, ribosomal proteins play crucial roles in the development and maintenance of GSCs and are clinically associated with chemoradioresistance and GBM recurrence.