Zero-fluoroscopy ablation in patients with cardiac electronic implantable devices.

INTRODUCTION: Utilizing a three-dimensional (3-D) mapping system and intracardiac echocardiography (ICE) has allowed ablation procedures with less or without fluoroscopy; however, there is limited data for patients with cardiac electronic implantable device (CIED) leads regarding the suspected risk of lead injury. Therefore, we sought to explore technics to perform safe trans-septal approach and catheter manipulation technique in patients with CIED leads. METHODS AND RESULTS: This study comprised 49 consecutive patients (59% males, median 73 years old) with CIED who underwent catheter ablation for supraventricular tachycardia requiring the trans-septal approach, 15 without fluoroscopy (zero-fluoro group), and 34 with fluoroscopy (conventional-fluoro group), between July 2019 and April 2021. All procedures were performed under a 3-D mapping system and ICE guidance. We compared the differences in treatment and development of complications between the two groups. The procedures were for atrial fibrillation (82%) and atrial tachycardia (76%). Coronary sinus catheter insertion and the trans-septal procedure were successfully performed in all patients. The median time from venipuncture to trans-septal procedure (zero-fluoro vs. conventional-fluoro group: 28 [18-37] min vs. 24 [21-31] min, p = .70), total procedure time (231 [142-274] min vs. 175 [163-225] min, p = .63), and the acute procedural success rate (100% vs. 97%, p = 1.00) did not differ between both groups. No patient showed lead-related complications in both groups. CONCLUSION: This is the first study to show zero-fluoro ablation for supraventricular arrhythmia using 3-D mapping and ICE in patients with CIED leads was feasible under careful catheter manipulation.

Single-Session, Internet-Based Cognitive Behavioral Therapy to Improve Parenting Skills to Help Children Cope With Anxiety During the COVID-19 Pandemic: Feasibility Study.

BACKGROUND: The COVID-19 pandemic has had a major impact on families' daily routines and psychosocial well-being, and technology has played a key role in providing socially distanced health care services. OBJECTIVE: The first objective of this paper was to describe the content and delivery of a single-session, internet-based cognitive behavioral therapy (iCBT) intervention, which has been developed to help parents cope with children's anxiety and manage daily situations with their children. The second objective was to report user adherence and satisfaction among the first participants who completed the intervention. METHODS: The Let's Cope Together intervention has been developed by our research group. It combines evidence-based CBT elements, such as psychoeducation and skills to manage anxiety, with parent training programs that strengthen how parents interact with their child and handle daily situations. A pre-post design was used to examine user satisfaction and the skills the parents learned. Participants were recruited using advertisements, media activity, day care centers, and schools and asked about background characteristics, emotional symptoms, and parenting practices before they underwent the iCBT. After they completed the 7 themes, they were asked what new parenting skills they had learned from the iCBT and how satisfied they were with the program. RESULTS: Of the 602 participants who filled in the baseline survey, 196 (32.6%) completed the program's 7 themes, and 189 (31.4%) completed the postintervention survey. Most (138/189, 73.0%) of the participants who completed the postintervention survey were satisfied with the program and had learned skills that eased both their anxiety (141/189, 74.6%) and their children's anxiety (157/189, 83.1%). The majority (157/189, 83.1%) reported that they learned how to organize their daily routines better, and just over one-half (100/189, 53.0%) reported that the program improved how they planned each day with their children. CONCLUSIONS: The single-session iCBT helped parents to face the psychological demands of the COVID-19 pandemic. Future studies should determine how the participation rate and adherence can be optimized in digital, universal interventions. This will help to determine what kinds of programs should be developed, including their content and delivery.

A Comparison of the Required Bronchial Cuff Volume Obtained by 2 Cuff Inflation Methods, Capnogram Waveform-Guided Versus Pressure-Guided: A Prospective Randomized Controlled Study.

BACKGROUND: Double-lumen endobronchial tubes (DLTs) are used for one-lung ventilation (OLV) during thoracic surgery. Overinflation into the bronchial cuff causes damage to the tracheobronchial mucosa, whereas underinflation leads to an incomplete collapse of the nonventilated lung or incomplete ventilation of the ventilated lung. However, how to determine the appropriate bronchial cuff volume and pressure during OLV is unclear. The objective of this study is to compare the required bronchial cuff volume for lung separation obtained by 2 different cuff inflation methods under closed- and open-chest conditions. METHODS: A total of 64 patients scheduled to undergo elective thoracic surgery requiring OLV were recruited. Left DLTs were used for both right- and left-sided surgery. The patients were randomly assigned to 1 of 2 inflation-type groups to estimate the bronchial cuff volume. In the capnogram waveform-guided bronchial cuff inflation group (capno group, n = 27), the bronchial cuff was inflated until a capnometer sampling gas containing CO2 from the nonventilated lung displayed a flat line. The corresponding bronchial cuff volume and pressure were then recorded. In the pressure-guided bronchial cuff inflation group (pressure group, n = 29), the bronchial cuff was inflated by a cuff inflator to a pressure of 20 cm H2O. Lung separation was confirmed when a flat line of a capnometer was observed after gas sampling from the nonventilated lung. RESULTS: Under closed-chest conditions, the bronchial cuff sealing volume for the capno group was significantly lower than that for the pressure group (mean [standard deviation {SD}], 1.00 [0.65] mL vs 1.44 [0.59] mL, mean difference, -0.44; 97.5% confidence interval [CI], -0.78 to -0.11; P = .010). Under open-chest conditions, the bronchial cuff sealing volume for the capno group was also significantly lower than that for the pressure group (mean [SD], 0.65 [0.66] mL vs 1.22 [0.45] mL, mean difference, -0.58; 97.5% CI, -0.88 to -0.27; P < .001). CONCLUSIONS: The lowest cuff volume providing an air-tight bronchial seal was obtained by the capnogram waveform-guided bronchial cuff inflation method. Since the cuff volume required to achieve an air-tight seal decreases after opening the chest, readjustment of the bronchial cuff volume to prevent bronchial cuff damage to the tracheobronchial mucosa after opening the chest may be advisable.

Determination of Absolute Purities of Hygroscopic Substances by Quantitative NMR Analysis for the Standardization of Quantitative Reagents in the Japanese Pharmacopoeia (Part 2).

As a new absolute quantitation method for low-molecular compounds, quantitative NMR (qNMR) has emerged. In the Japanese Pharmacopoeia (JP), 15 compounds evaluated by qNMR are listed as reagents used as the HPLC reference standards in the assay of crude drug section of the JP. In a previous study, we revealed that humidity affects purity values of hygroscopic reagents and that (i) humidity control before and during weighing is important for a reproducible preparation and (ii) indication of the absolute amount (not purity value), which is not affected by water content, is important for hygroscopic products determined by qNMR. In this study, typical and optimal conditions that affect the determination of the purity of ginsenoside Rb1 (GRB1), saikosaponin a (SSA), and barbaloin (BB) (i.e., hygroscopic reagents) by qNMR were examined. First, the effect of humidity before and during weighing on the purity of commercial GRB1, with a purity value determined by qNMR, was examined. The results showed the importance afore-mentioned. The results of SSA, which is relatively unstable in the dissolved state, suggested that the standardization of humidity control before and during weighing for a specific time provides a practical approach for hygroscopic products. In regard to BB, its humidity control for a specific time, only before weighing, is enough for a reproducible purity determination.

Absolute Purity Determination of a Hygroscopic Substance, Indocyanine Green, Using Quantitative NMR (qNMR).

Quantitative NMR (qNMR) is applied to determine the absolute quantitative value of analytical standards for HPLC-based quantification. We have previously reported the optimal and reproducible sample preparation method for qNMR of hygroscopic reagents, such as saikosaponin a, which is used as an analytical standard in the assay of crude drug section of Japanese Pharmacopoeia (JP). In this study, we examined the absolute purity determination of a hygroscopic substance, indocyanine green (ICG), listed in the Japanese Pharmaceutical Codex 2002, using qNMR for standardization by focusing on the adaptation of ICG to JP. The purity of ICG, as an official non-Pharmacopoeial reference standard (non-PRS), had high variation (86.12 ± 2.70%) when preparing qNMR samples under non-controlled humidity (a conventional method). Additionally, residual ethanol (0.26 ± 0.11%) was observed in the non-PRS ICG. Next, the purity of non-PRS ICG was determined via qNMR when preparing samples under controlled humidity using a saturated sodium bromide solution. The purity was 84.19 ± 0.47% with a lower variation than that under non-controlled humidity. Moreover, ethanol signal almost disappeared. We estimated that residual ethanol in non-PRS ICG was replaced with water under controlled humidity. Subsequently, qNMR analysis was performed when preparing samples under controlled humidity in a constant temperature and humidity box. It showed excellent results with the lowest variation (82.26 ± 0.19%). As the use of a constant temperature and humidity box resulted in the lowest variability, it is recommended to use the control box if the reference ICG standard is needed for JP assays.

Flexibility of small molecular CD4 mimics as HIV entry inhibitors.

CD4 mimics such as YIR-821 and its derivatives are small molecules which inhibit the interaction between the Phe43 cavity of HIV-1 gp120 with host CD4, an interaction that is involved in the entry of HIV to cells. Known CD4 mimics generally possess three structural features, an aromatic ring, an oxalamide linker and a piperidine moiety. We have shown previously that introduction of a cyclohexyl group and a guanidine group into the piperidine moiety and a fluorine atom at the meta-position of the aromatic ring leads to a significant increase in the anti-HIV activity. In the current study, the effects of conformational flexibility were investigated by introduction of an indole-type group in the junction between the oxalamide linker and the aromatic moiety or by replacement of the oxalamide linker with a glycine linker. This led to the development of compounds with high anti-HIV activity, showing the importance of the junction region for the expression of high anti-HIV activity. The present data are expected to be useful in the future design of novel CD4 mimic molecules.

Effectiveness and safety of sulcus fixation of Baerveldt glaucoma implants in glaucomatous eyes in patients who underwent multiple intraocular surgeries.

PURPOSE: The purpose of this study was to evaluate the surgical success of sulcus fixation of Baerveldt glaucoma implant (BGIs) in special reference to corneal damage. METHODS: This observational prospective cohort study included 24 patients who underwent a median of 3.0 previous intraocular surgeries and sulcus fixation of BGIs for the first time. The intraocular pressure (IOP), the number of ocular hypotensives used, corneal endothelial cell density (ECD), and logMAR-converted best-corrected visual acuity (VA) of each patient were measured preoperatively and postoperatively until 12 months after surgery. Surgical success was evaluated after 12 months based on the reduction of IOP (5-21 mmHg and > 20% reduction), corneal damage (postoperative development of decompensation, unmeasurable ECD, or ECD reduction of > 20%), loss of light perception, and need for additional surgeries. RESULTS: Surgical success was noted in 16 (66.7%) patients when corneal damage was included as a failure criterion, whereas surgery was successful in 21 (87.5%) patients when solely judged using IOP control similarly as previous clinical trials. The median IOP decreased from 27.5 mmHg preoperatively to 14.5 mmHg postoperatively (P < 0.0001). The number of ocular hypotensives was significantly reduced postoperatively (P < 0.0001). The median postoperative ECD reduction was only 0.15%, although ECD could not be measured during follow-up or it was significantly reduced by > 20% in six patients. VA was not significantly reduced after surgery. Adverse effects were observed in 15 patients (62.5 cumulative %). CONCLUSION: Sulcus fixation of BGIs may be effective and safe in patients with glaucomatous eyes who underwent multiple prior intraocular surgeries.

Foveal Depression and Related Factors in Patients with a History of Retinopathy of Prematurity.

PURPOSE: This study evaluates optical coherence tomography (OCT) findings of the macula in patients with a history of retinopathy of prematurity (ROP). METHODS: We enrolled 112 patients (age: 6-15 years) and categorized them into 3 groups: gestational age (GA) < 36 weeks with or without a history of ROP (ROP group, preterm group) and GA ≥37 weeks. We included 1 eye of each patient and measured the retinal thickness of the macula by OCT. RESULTS: The ROP group demonstrated the worst VA and the shallowest foveal depression. Furthermore, foveal depression significantly correlated with birth weight, GA, ganglion cell layer/inner plexiform layer (GCL-IPL) thickness, and a history of ROP. CONCLUSIONS: This study established a correlation of fovea formation with premature birth, damage of GCL-IPL, and a history of ROP. The retention of the inner retina possibly contributes to abnormal foveal morphology in patients with a history of ROP.

Anti-Ro52 antibody level is an important marker of fetal congenital heart block risk in anti-Ro/SSA antibody positive pregnancy.

OBJECTIVE: The aims of this study are to determine the incidence of congenital heart block (CHB) in the Japanese population and identify maternal factors predicting fetal CHB in anti-Ro/SSA antibody positive pregnancy. METHODS: A retrospective study was performed using 52,147 clinical records of pregnancies followed in a single center. For 183 anti-Ro/SSA antibody-positive women, anti-Ro52 and Ro60 antibodies were measured, and the odds of CHB in relation to maternal clinical features were calculated by multivariate analysis. The receiver-operating characteristic (ROC) curves for predicting CHB were constructed for the titers of anti-Ro/SSA, anti-Ro52 and anti-Ro60 antibodies. RESULTS: Fetal CHB occurred in two pregnancies among those without known risks such as positive anti-Ro/SSA antibody or previous CHB-affected pregnancy, suggesting an incidence similar to that in Caucasian populations. As for the anti-Ro/SSA antibody positive pregnancies, the titers of anti-Ro/SSA, anti-Ro52 and anti-Ro60 antibodies were independent risk factors for fetal CHB and the use of corticosteroids before 18 gestational weeks was an independent protective factor. The area under the ROC was 0.84, 0.73 and 0.74 for anti-Ro52, anti-Ro60 and anti-Ro/SSA antibodies, respectively. CONCLUSION: CHB occurred in two among approximately 50,000 pregnancies without known risks such as positive anti-Ro/SSA antibody or previous delivery of CHB-affected babies. Measurement of anti-Ro52 antibody levels may be helpful in extracting a risk group of delivering CHB infants in the anti-Ro/SSA antibody positive pregnancy.

Home Monitoring of Intraocular Pressure and it's Diurnal Patterns Using Icare® HOME.

Purpose: To evaluate Icare® HOME for home monitoring of intraocular pressure (IOP) and to observe diurnal IOP patterns for a short term. Patients and methods: Twenty six eyes of 16 patients with open angle glaucoma were included. After instruction and practice in using Icare® HOME, patients were asked to measure their IOP by themselves at home or in a sick room. Patients measured their IOP four times a day with a four hour interval between each measurement for three days. Patients repeated measurements until three successful measurements were obtained at each time. Intra-rater reliability was assessed calculating intraclass correlation coefficient (ICC) of the three measurements. Diurnal IOP patterns were assessed for three days. Results: No adverse events occurred. ICC of three measurements was 0.76 (95% confidence coefficient; 0.71 to 0.81). The median of the difference between the highest and the lowest IOP during a day was 4.26 mmHg (95% CI; 4.06 to 4.67). Repeatable patterns were not found in diurnal IOP for three days. Three out of ten patients who answered the questionnaire after measurements found difficulties in handling the device. Conclusions: Although Icare® HOME is safe and could be used for home monitoring of IOP, some patients had difficulties in using the instrument. Diurnal IOP patterns did not show repeatability during a short term.

[Plain X-ray or Computed Tomography Image of Epidural Catheters with Various Materials].

BACKGROUND: Although breakage of the epidural catheter inside patients is a rare complication, plain X-ray or computed tomography (CT) image is useful for diagnosis of catheter remnant However, it is not well known whether the catheter materials are visible in these images. METHODS: We examined 3 types of X-ray permeabil- ity catheters and 6 types of X-ray impermeability cath- eters available in Japan. We obtained plain X-ray images of catheters alone, plain X-ray images of cathe- ters with bone dummy and CT images of catheters in the model of epidural space. RESULTS: On plain X-ray images of catheters alone, we could confirm all 6 types of X-ray impermeability catheters. However, on plain X-ray images of catheters with bone dummy, we could confirm only 3 types of catheters among 6 X-ray impermeability catheters. On CT images, we could confirm all 6 types of X-ray impermeability catheters, but not X-ray permeability catheters. CONCLUSIONS: Plain X-ray image can not provide the detection for some X-ray impermeability catheters. CT image is useful- for diagnosis of X-ray impermeability catheters.

Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice.

Myocardin-related transcription factor (MRTF)-A is a Rho signalling-responsive co-activator of serum response factor (SRF). Here, we show that induction of MRTF-A expression is key to pathological vascular remodelling. MRTF-A expression was significantly higher in the wire-injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE(-/-) mice than in healthy control tissues, whereas myocardin expression was significantly lower. Both neointima formation in wire-injured femoral arteries in MRTF-A knockout (Mkl1(-/-)) mice and atherosclerotic lesions in Mkl1(-/-); ApoE(-/-) mice were significantly attenuated. Expression of vinculin, matrix metallopeptidase 9 (MMP-9) and integrin ß1, three SRF targets and key regulators of cell migration, in injured arteries was significantly weaker in Mkl1(-/-) mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs was the downregulation of microRNA-1. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. MRTF-A could thus be a novel therapeutic target for the treatment of vascular diseases.

A minimally cytotoxic CD4 mimic as an HIV entry inhibitor.

Several CD4 mimics have been reported as HIV-1 entry inhibitors which can block the interaction between the viral envelope glycoprotein gp120 and the cell surface protein CD4. We previously found a lead compound 2 (YYA-021) with high anti-HIV activity and low cytotoxicity. Pharmacokinetic analysis however showed compound 2 to have wide tissue distribution and relatively high distribution volumes in rats and rhesus macaques. In the present study we searched for more hydrophilic CD4 mimics with a view to reducing tissue distribution. A new compound (5) with a 1,3-benzodioxolyl moiety was found to have relatively high anti-HIV activity and no significant cytotoxicity. Compound 5 is more hydrophilic than compound 2 and the pharmacokinetics of the intravenous administration of compound 5 in a rhesus macaque showed that compound 5 has lower tissue distribution than compound 2, suggesting that compound 5 possesses a better profile.

Trabeculotomy with Schlemm's Canal Endothelium Removal and Deep Sclerectomy.

Purpose: To evaluate the effects of trabeculotomy (TLO) combined with Schlemm's canal endothelium removal (SER) and deep sclerectomy (DS). Method: This retrospective study involved 131 adults eyes, diagnosed with glaucoma that were enrolled with at least 1 year follow-up after TLO. Fifty three eyes received TLO+SER+DS and 78 eyes underwent TLO+DS without SER. SER was performed as peeling of Schlemm's canal endothelium opening under the scleral flap. Surgical success was defined by the need for additional glaucoma surgery, or intraocular pressure (IOP) ≤20 mmHg (criterion A) and ≤16 mmHg (criterion B). Results: The occurrence rate of transient ocular hypertension (≥30 mmHg) was significantly less (p<0.001) in SER (3.8%) compared with Non-SER (21.8%). SER decreased IOP at 3 years without significant efficacy in terms of lowered IOP compared with Non-SER. At 3 years, Kaplan-Meier survival analysis revealed that the success rate of SER was higher than Non-SER for criterion A (p=0.008), but comparable for criterion B (p=0.06). Conclusions: SER was effective for reducing the rate of transient ocular hypertension in TLO and controlling IOP≤20 mmHg in adult eyes.

Clinical and Pathological Impact of Tissue Fibrosis on Lethal Arrhythmic Events in Hypertrophic Cardiomyopathy Patients With Impaired Systolic Function.

BACKGROUND: The natural history of hypertrophic cardiomyopathy (HCM) varies from an asymptomatic benign course to a poor prognosis. Myocardial fibrosis may play a critical role in ventricular tachyarrhythmias (VT/VF); however, the clinical significance of tissue fibrosis by right ventricular (RV) biopsy in the long-term prognosis of HCM patients remains unclear. METHODS AND RESULTS: We enrolled 185 HCM patients (mean age, 57±14 years). The amount of fibrosis (%area) was quantified using a digital microscope. Hemodynamic, echocardiographic, and electrophysiologic parameters were also evaluated. Patients with severe fibrosis had longer QRS duration and positive late potential (LP) on signal-averaged ECG, resulting in a higher incidence of VT/VF. At the 5±4 year follow-up, VT/VF occurred in 31 (17%) patients. Multivariate Cox regression analysis revealed that tissue fibrosis (hazard ratio (HR): 1.65; P=0.003 per 10% increase), lower left ventricular ejection fraction (HR: 0.64; P=0.001 per 10% increase), and positive SAECG (HR: 3.14; P=0.04) led to a greater risk of VT/VF. The combination of tissue fibrosis severity and lower left ventricular ejection fraction could be used to stratify the risk of lethal arrhythmic events in HCM patients. CONCLUSIONS: Myocardial fibrosis in RV biopsy samples may contribute to abnormal conduction delay and spontaneous VT/VF, leading to a poor prognosis in HCM patients.

Clinical impact of mapping strategies for treatment of ventricular tachycardias in patients with structural heart disease.

BACKGROUND: Substrate-based catheter ablation (CA) can be applied to more complicated cases such as hemodynamically unstable ventricular tachycardia (VT). We aimed to compare the efficacy between substrate-based and activation/entrainment-based ablation. METHODS: We investigated 85 consecutive patients (62 male, 53 ± 16 years) who underwent CA of VT to analyze the relationship between the ablation strategy and clinical outcome. The patients included 34 individuals with arrhythmogenic right ventricular cardiomyopathy, 16 with ischemic heart disease, 14 with dilated cardiomyopathy, 11 with sarcoidosis, and 10 with other heart diseases. The primary strategy was activation/entrainment mapping (Group-AE, N = 35); otherwise, substrate-based strategy was adopted (Group-S, N = 50) because of non-inducibility of VT or hemodynamic instability. Successful CA was defined as the non-inducibility of any VT at the end of the procedure in those with inducible clinical VT before ablation, and substrate elimination in those without. RESULTS: There were no significant differences in the left ventricular function, percentage of implantable cardioverter-defibrillator implantations, results of CA, and number of radiofrequency applications between Group-S and Group-AE. During 5 years of follow-up, there were no significant differences in sustained VT recurrences (15/50 vs. 15/35, P = 0.22), and cardiac death (2/50 vs. 3/35, P = 0.38). In patients with inducible VT before ablation, the elimination of the VT inducibility was associated with a lower recurrence rate (12/47 vs. 16/26, P = 0.003). CONCLUSIONS: The substrate-based strategy adopted as an alternative option when the activation/entrainment-based strategy was unable to be performed resulted in a comparable VT recurrence rate. The extinction of VT inducibility achieved a favorable prognosis in structural heart disease patients.

Clinicopathological analysis of thymic malignancies with a consistent retrospective database in a single institution: from Tokyo Metropolitan Cancer Center.

BACKGROUND: Thymic epithelial tumors (TETs), which comprise thymoma and thymic carcinoma, are rare cancers with specific morphological and clinical features. Their clinical characteristics and outcomes have gradually been clarified by assessing large-scale, retrospective data obtained with international cooperation. METHODS: The study is a retrospective review of 187 Japanese patients with TETs who attended our institution from 1976 to 2012. Relevant clinical features of patients with TETs and their tumors, including histology, staging, treatment strategies, and overall survival, were investigated. Differences in survival were assessed by the Kaplan-Meier method and uni- and multi-variate Cox proportional hazards regression analyses. RESULTS: The 187 patients included 52 patients with stage I, 37 with stage II, 22 with stage III, and 76 with stage IVa/IVb tumors according to the Masaoka-Koga Staging System. As to histological type, five patients had type A, 33 type AB, 19 type B1, 39 type B2, and 15 type B3 thymomas, whereas 68 patients had thymic carcinoma, including 11 with neuroendocrine carcinomas according to the 2004 WHO classification. Either insufficient data were available to classify the tumors of the remaining eight patients or they had rare types. Immunological abnormalities were present in 26 patients, most of whom had thymomas (21.8% of the thymoma group). Most of the patients who presented with symptoms had myasthenia gravis or extensive thymic carcinoma. Secondary cancers were present in 25 patients (13.3%). The overall 5- and 10-year survival rates for thymoma were 85.4 and 71.5%, respectively, and those for thymic carcinoma were 33.8 and 2.3%, respectively. OS differed significantly between stage IVa thymomas and thymic carcinomas. The stage and whether the tumors were thymomas or thymic carcinomas were significant determinants of survival according to multivariate analysis. CONCLUSION: The efficacy of treatments for thymoma and thymic carcinoma should be investigated separately because these tumors differ in their clinical features and prognosis.

Electrocardiographic predictors of response to cardiac resynchronization therapy in patients with intraventricular conduction delay.

BACKGROUND: Little is known about predictors of response to cardiac resynchronization therapy (CRT) in patients with intraventricular conduction delay (IVCD). The purpose of this study was to investigate the benefits of CRT and significant variables on surface electrocardiogram (ECG) to predict response to CRT in those patients. METHODS AND RESULTS: Among the cohort of 152 CRT patients, 40 patients with IVCD were evaluated. Sixteen patients (40%) were responders. At baseline, responders had a wider QRS duration (158±18 vs. 144±18ms, P=0.02) and a higher frequency of left axis deviation (LADEV; 75% vs. 29%, P=0.004) compared with non-responders. After CRT, greater shortening of QRS duration (ΔQRS; 26±24 vs. 7±24ms, P=0.02), axis shift from LADEV to right axis deviation (RADEV; 69% vs. 13%, P<0.001), and both rightward forces in lead I and anterior forces in V1 (56% vs. 13%, P=0.003) were found more frequently in responders. Multivariable logistic regression analysis showed that LADEV at baseline, or ΔQRS and axis shift from LADEV to RADEV after CRT were independent predictors of response to CRT. CONCLUSIONS: Patients with IVCD may not respond to CRT, but LADEV at baseline and reversal of ventricular activation after CRT on surface ECG could be important to predict response to CRT.

Experience-Dependent Behavioral Plasticity in Avoiding Epigallocatechin Gallate (EGCG) Requires DAF-16/FOXO in the AIY Interneurons of Caenorhabditis elegans.

Bitterness and astringency are the aversive tastes in mammals. In humans, aversion to bitterness and astringency may be reduced depending on the eating experience. However, the cellular and molecular mechanisms underlying plasticity in preference to bitter and astringent tastants remain unknown. This study aimed to investigate the preference plasticity to bitter and astringent tea polyphenols, including catechins and tannic acids, in the model animal Caenorhabditis elegans. C. elegans showed avoidance behavior against epigallocatechin gallate (EGCG), tannic acid, and theaflavin. However, they displayed diminishing avoidance against EGCG depending on their EGCG-feeding regime at larval stages. Additionally, the behavioral plasticity in avoiding EGCG required the transcription factor DAF-16/FOXO. Isoform-specific deletion mutant analysis and cell-specific rescue analysis revealed that the function of daf-16 isoform b in AIY interneurons is necessary for experience-dependent behavioral plasticity to EGCG.

Impact of Masticatory Performance and the Tongue-Lip Motor Function on Incident Adverse Health Events in Patients with Metabolic Disease.

AIM: The present study aimed to determine whether decreased masticatory performance and tongue-lip motor function are associated with an increased incidence of adverse health events in patients with metabolic disease. METHODS: One thousand patients with metabolic diseases including diabetes, dyslipidemia, hypertension, and hyperuricemia were recruited. Masticatory performance was assessed using a gummy jelly test, wherein glucose elution from chewed gummy jelly was measured. The tongue-lip motor function was measured using repeatedly pronounced syllables per second. Their association with the incidence of adverse health events (a composite of all-cause death, cardiovascular disease, bone fracture, malignant neoplasm, pneumonia, and dementia) was investigated using the generalized propensity score (GPS) method. RESULTS: During a median follow-up period of 36.6 (interquartile range, 35.0-37.7) months, adverse health events were observed in 191 patients. The GPS adjusted dose-response function demonstrated that masticatory performance was inversely associated with the incidence of adverse health events. The 3-year incidence rate was 22.8% (95% confidence interval, 19.0-26.4%) for the lower quartile versus 13.6% (10.5-16.7%) for the upper quartile (P＜0.001). Similarly, the tongue-lip motor function was inversely associated with the incidence of adverse health events, with a 3-year incidence rate of 23.6% (20.0-27.0%) for the lower quartile versus 13.2% (10.4-15.9%) for the upper quartile (P＜0.001). CONCLUSIONS: Decreased masticatory performance and tongue-lip motor function were associated with an increased incidence of adverse health events in patients with metabolic disease.