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A 70-year-old man with hypertensive heart disease underwent catheter ablation of persistent atrial fibrillation. After completing the pulmonary vein isolation, atrial burst pacing induced an annular atrial tachycardia (AT). Overdrive pacing exhibited constant fusion, indicating a macroreentrant mechanism of the AT. However, the CARTO3 activation map created using the Octaray catheter (both Biosense Webster, Irvine, CA) exhibited a centrifugal spread with the earliest activation site at the 4 o'clock position of the tricuspid annulus. In contrast, the Ripple map revealed a clear reentrant circuit with its isthmus located at the 4–6 o'clock position of the tricuspid annulus. The local electrograms in these areas recorded systolic and diastolic potentials simultaneously, and the misannotation of the large far-field potentials caused this discrepant result. Handling low-amplitude complex fractionated electrograms remains a challenge in creating a precise activation mapping. The Ripple map, especially when combined with the Octaray catheter, was effective in dynamically visualizing all these electrograms and accurately delineating the reentrant circuit.

Abstract Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19–0.84; P-value = 0.015). In contrast, among patients with an uplift score

Abstract The coexistence of heart failure is frequent and associated with higher mortality in patients with type 2 diabetes (T2DM), and its management is a critical issue. The WATCH-DM risk score is a tool to predict heart failure in patients with type 2 diabetes mellitus (T2DM). We investigated whether it could estimate outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF). The WATCH-DM risk score was calculated in 418 patients with T2DM hospitalized for HFpEF (male 49.5%, age 80 ± 9 years, HbA1c 6.8 ± 1.0%), and they were divided into the “average or lower” (≤ 10 points), “high” (11–13 points) and “very high” (≥ 14 points) risk groups. We followed patients to observe all-cause death for 386 days (median). We compared the area under the curve (AUC) of the WATCH-DM score for predicting 1-year mortality with that of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and of the Barcelona Bio-Heart Failure Risk (BCN Bio-HF). Among the study patients, 108 patients (25.8%) had average or lower risk scores, 147 patients (35.2%) had high risk scores, and 163 patients (39.0%) had very high risk scores. The Cox proportional hazard model selected the WATCH-DM score as an independent predictor of all-cause death (HR per unit 1.10, 95% CI 1.03 to 1.19), and the “average or lower” risk group had lower mortality than the other groups (p = 0.047 by log-rank test). The AUC of the WATCH-DM for 1-year mortality was 0.64 (95% CI 0.45 to 0.74), which was not different from that of the MAGGIC score (0.72, 95% CI 0.63 to 0.80, p = 0.08) or that of BCN Bio-HF (0.70, 0.61 to 0.80, p = 0.25). The WATCH-DM risk score can estimate prognosis in T2DM patients with HFpEF and can identify patients at higher risk of mortality.

IntroductionEarly detection of depression is important for preventing depression-related suicides and reducing the risk of recurrence. This study explored the association between depression and intestinal microbiota and developed a depression risk-estimation method based on this.MethodsThe intestinal microbiota of Japanese patients with depression (33 males and 35 females) and disease-free controls (246 males and 384 females) in their 20’s to 60’s were compared by sex using 16S rRNA gene amplicon sequencing. A depression-risk estimation method was developed using structural equation modeling.ResultsIntestinal bacteria taxa that differed between depression and control groups were identified based on effect size (absolute value greater than 0.2). Neglecta was more abundant, while Coprobacter, Butyricimonas, Clostridium_XlVb, and Romboutsia were less abundant in the male depression group compared to the male control group. In the female depression group, Massilimicrobiota, Merdimonas, and Sellimonas were more abundant, whereas Dorea and Agathobacter were less abundant compared to the female control group. Several of the intestinal bacterial taxa that were less abundant in depression were associated with butyrate or hydrogen production. Using these depression-associated intestinal bacteria as indicators, risk-estimation models using structural equation modeling for depression were developed. In the risk-estimation models for males and females, the areas under the receiver operating characteristic curve were 0.72 and 0.70, respectively, indicating that these models can distinguish between individuals with and without depression.ConclusionsThis study provides insights into depression etiology and aids in its early detection and treatment.

Abstract The reproducibility of longitudinal strain measured by 2D speckle tracking echocardiography (2DSTE) may be affected by ultrasound settings. This study investigated the effect of transmit ultrasound frequency on global longitudinal strain (GLS) by 2DSTE. Apical, 2- and 4-chamber, and long-axis views were obtained in consecutive 162 patients using Philips ultrasound devices. Three different frequency presets were used sequentially: high resolution (HRES, 1.9 to 2.1 MHz), general (HGEN, 1.6 to 1.8 MHz), and penetration mode (HPEN, 1.3 to 1.6 MHz). GLS values were determined for each preset using the Philips Q-station software, resulting in GLS-HRES, GLS-HGEN, and GLS-HPEN. Among the 151 patients with successfully measured GLS, a significant difference in GLS was observed among the three presets (p

Abstract Background Sleep apnea (SA) is highly prevalent and should be treated in patients referred for catheter ablation (CA) of atrial fibrillation (AF). Watch‐type peripheral arterial tonometry (WP) for home SA testing has demonstrated a high correlation of the apnea‐hypopnea index (AHI) with Polysomnography (PSG), but the evidence of its accuracy in AF patients is not adequate. Methods This study was conducted under a retrospective, single‐center, observational design. We included 464 consecutive AF patients (age 65 ± 11 years, 76.5% male, 45.0% paroxysmal‐AF) who received both WP and PSG during the periprocedural period of the CA. We compared the AHI using the WP (WP‐AHI) to that using PSG (PSG‐AHI). Results The WP‐AHI was 25.9 ± 12.7 and PSG‐AHI 31.4 ± 18.9 (r = .48). Among 325 patients with a WP‐AHI

Background An optimal strategy for left atrial ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not been determined. Methods and Results We conducted an extended follow‐up of the multicenter randomized controlled EARNEST‐PVI (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial, which compared 12‐month rhythm outcomes in patients with persistent AF between patients randomized to a PVI‐alone strategy (n=248) or PVI‐plus strategy (n=248; PVI followed by left atrial additional ablation, including linear ablation or ablation targeting areas with complex fractionated electrograms). The present study extended the follow‐up period to 3 years after enrollment. Outcomes were compared not only between randomly allocated groups but also between on‐treatment groups categorized by actually created ablation lesions. Recurrence rate of AF or atrial tachycardia (AT) was lower in the randomly allocated to PVI‐plus group than the PVI‐alone group (29.0% versus 37.5%, P=0.036). On‐treatment analysis revealed that patients with PVI+linear ablation (n=205) demonstrated a lower AF/AT recurrence rate than those with PVI only (26.3% versus 37.8%, P=0.007). In contrast, patients with PVI+complex fractionated electrograms ablation (n=37) had an AF/AT recurrence rate comparable to that of patients with PVI only (40.5% versus 37.8%, P=0.76). At second ablation in 126 patients with AF/AT recurrence, ATs excluding common atrial flutter were more frequent in patients with PVI+linear ablation than in those with PVI only (32.6% versus 5.7%, P

Abstract Background Pulmonary vein (PV) reconnection is the main cause of atrial fibrillation (AF) recurrence. This study aimed to examine the effect of first‐pass PV isolation (PVI) on PV reconnection frequency during the procedure and on AF ablation outcomes. Methods This retrospective study included 446 patients with drug‐refractory AF (370 men, aged 64 ± 10 years) who underwent initial PVI using an open‐irrigated contact force catheter between January 2015 and October 2016. We investigated the effect of first‐pass PVI on PV reconnection during spontaneous PV reconnection and dormant conduction after an adenosine triphosphate challenge. Results First‐pass PVI was achieved in 69% (617/892) of ipsilateral PVs, of which we observed PV reconnection during the procedure in 134 (22%) PVs. This value was significantly lower than that observed in those without first‐pass PVI (50%, 138/275) (P

Background Modification of arrhythmogenic substrates with extensive ablation comprising linear and/or complex fractional atrial electrogram ablation in addition to pulmonary vein isolation (PVI‐plus) can theoretically reduce the recurrence of atrial fibrillation. The DR‐FLASH score (score based on diabetes mellitus, renal dysfunction, persistent form of atrial fibrillation, left atrialdiameter >45 mm, age >65 years, female sex, and hypertension) is reportedly useful for identifying patients with arrhythmogenic substrates. We hypothesized that, in patients with persistent atrial fibrillation, the DR‐FLASH score can be used to classify patients into those who require PVI‐plus and those for whom a PVI‐only strategy is sufficient. Methods and Results This study is a post hoc subanalysis of the a multicenter, randomized controlled, noninferiority trial investigating efficacy and safety of pulmonary vein isolation alone for recurrence prevention compared with extensive ablation in patients with persistent atrial fibrillation (EARNEST‐PVI trial). This analysis focuses on the relationship between DR‐FLASH score and the efficacy of different ablation strategies. We divided the population into 2 groups based on a DR‐FLASH score of 3 points. A total of 469 patients were analyzed. Among those with a DR‐FLASH score >3 (N=279), the event rate of atrial arrhythmia recurrence was significantly lower in the PVI‐plus arm than in the PVI‐only arm (hazard ratio [HR], 0.45 [95% CI, 0.28–0.72]; P3 and DR‐FLASH score ≤3 (P value for interaction=0.020). Conclusions The DR‐FLASH score is a useful tool for deciding the catheter ablation strategy for patients with persistent atrial fibrillation. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03514693.

Abstract Purpose Although usefulness of VISITAG SURPOINT (VS) on pulmonary vein isolation (PVI) in catheter ablation of atrial fibrillation has been reported, optimal VS thresholds can depend on the inter‐tag distance (ITD) and vice versa. We validated the efficacy of PVI with lower target ITDs and VS values than in previous studies. Methods Retrospective review of consecutive patients (N = 100) with paroxysmal (n = 32) or persistent AF (n = 68) undergoing VS‐guided ablation between 09/2018 and 08/2019 was conducted. All procedures were performed by two operators. Target VS values were 425 (anterior), 375 (posterior), and 325 (near the esophagus). Target ITD was 4 mm. Results Acute PVI was achieved in all cases, however, 13 residual gaps in 12 patients were observed after initial encirclement (first pass isolation: 88%). Ten gaps due to spontaneous PV reconnections (PVR) were found in nine patients (9%). These 23 gaps had similar median VS (gap‐related vs non‐gap: 429 vs 410, P = .4545) and power (36 vs 36W, P = .4843), higher contact force (13.8 vs 11.0g, P = .0061), and larger ITD (5.3 vs 3.7mm, P

Abstract Genetically modified mice are commonly used in biologic, medical, and drug discovery research, but conventional microinjection methods used for genetic modification require extensive training and practical experience. Here we present a fully automated system for microinjection into the pronucleus to facilitate genetic modification. We first developed software that automatically controls the microinjection system hardware. The software permits automatic rotation of the zygote to move the pronucleus to the injection pipette insertion position. We also developed software that recognizes the pronucleus in 3-dimensional coordinates so that the injection pipette can be automatically inserted into the pronucleus, and achieved a 94% insertion rate by linking the 2 pieces of software. Next, we determined the optimal solution injection conditions (30 hPa, 0.8–2.0 s) by examining the survival rate of injected zygotes. Finally, we produced transgenic (traditional DNA injection and piggyBac Transposon system) and knock-in (genomic editing) mice using our newly developed Integrated Automated Embryo Manipulation System (IAEMS). We propose that the IAEMS will simplify highly reproducible pronuclear stage zygote microinjection procedures.

Background: The impact of anemia on the safety and efficacy of anticoagulants in elderly patients with atrial fibrillation (AF) has not been elucidated. Method and Results: The J-ELD AF Registry is a large-scale, multicenter prospective observational study, of the one-year outcomes after administration of on-label doses of apixaban in Japanese patients with non-valvular AF aged ≥ 75 years. The entire cohort (3,015 patients from 110 institutions) was divided into three subgroups according to the WHO classification of anemia: normal (hemoglobin ≥ 13.0 g/dL in men and ≥ 12.0 g/dL in women, n = 1733, 57.5%), mild anemia (11.0 ≤ hemoglobin

Objective: In the past five decades, many small caliber vascular grafts have been developed as bypasses for infrapopliteal or coronary arteries. However, reliable grafts have not been obtained owing to poor patency, mainly caused by early thrombosis or neointimal hyperplasia in the intermediate period after implantation. We developed a novel small caliber heparin-loaded polyethylene terephthalate ultrafine microfiber (HL-PET) graft and evaluated the feasibility to overcome those main causes of graft failure in canine carotid artery implantation. Methods: The HL-PET graft with a diameter of 3 mm and length of 30 mm was made with combination of three key technologies: (1) weaving with PET ultrafine microfiber with a high biological porosity allowing for cell ingrowth, (2) heparin loading on microfiber surfaces, and (3) an outer coating with a flexible bioabsorbable polymer for prevention of blood leakage and graft kinking. Kink resistance, water permeability, and loaded heparin were assessed. One HL-PET graft each was implanted into a carotid artery of six animals. Graft patency rate and healing were assessed 24 weeks after implantation. Results: Among the six grafts, five were deemed patent (patency rate of >83%), with one occluded 20 weeks after implantation. Histopathology of the patent grafts showed neointima formation with confluent endothelial cell lining (estimated mean endothelial cell coverage area, 89 ± 18%). Intimal hyperplasia at the anastomotic sites and severe chronic inflammatory responses were not observed. Immunohistochemistry with antibodies to endothelial nitric oxide synthase, alpha 2 smooth muscle actin and calponin 1 revealed luminal surface endothelial cell layer with expression of endothelial nitric oxide synthase and vascular smooth muscle cells with contractile phenotype in the subintimal layer. Conclusions: The HL-PET graft showed no early postoperative thrombosis and was able to demonstrate a high patency rate with no severe biological response observed after 24 weeks. These results strongly suggest the potential of the HL-PET graft to be used for distal bypasses. : Clinical Relevance: The HL-PET graft achieved a high patency rate without early postoperative thrombosis or intimal hyperplasia in a small caliber artery implantation study. The histopathologic analysis demonstrated favorable healing property with a high antithrombogenicity. These results strongly suggested the possible use of the HL-PET graft as a bypass for infrapopliteal or coronary arteries.

In order to overview the impact of climate change on runoff from forested catchments over Asian countries, we collected water balance data from fifteen long-term catchment monitoring stations (total monitoring period 1975–2018, not continuous), spanning from Sabah, Malaysia (our southernmost site), to Hokkaido, Japan (our northernmost site). We then employed an elasticity analysis to the dataset to examine how the annual runoff from each catchment responded to inter-annual fluctuations in annual rainfall and annual mean air temperature. As a result, we found that (1) the annual runoff was sensitive to annual rainfall for all the catchments examined. In addition, (2) the annual runoff from seven of the fifteen catchments was sensitive to inter-annual changes in the mean air temperature, which was likely due to changes in forest evapotranspiration. Three catchments, however, exhibited an increased runoff in a hot year. Finally, (3) the annual rainfall from the previous year (carry-over soil moisture) was important in explaining the variation in annual runoff in two tropical montane forest catchments. This study may serve as one of the pilot studies toward a comprehensive understanding of the climate elasticity of runoff in countries over Asia, because the examined catchments are unevenly and sparsely distributed over the area.

Background Increasing age predisposes patients with atrial fibrillation to both thromboembolic and bleeding events; however, data on outcomes of very elderly patients (aged ≥85 years) receiving appropriate antithrombotic therapy are still limited. Methods and Results The J‐ELD AF (Multicenter Prospective Cohort Study to Investigate the Effectiveness and Safety of Apixaban in Japanese Elderly Atrial Fibrillation Patients) Registry is a multicenter prospective observational study of Japanese patients with nonvalvular atrial fibrillation aged ≥75 years taking on‐label doses (standard dose of 5 mg BID or reduced dose of 2.5 mg BID) of apixaban. The entire cohort (3031 patients from 110 institutions) was divided into 3 age groups: 75 to 79 years (n=1068, 35.2%), 80 to 84 years (n=1120, 37.0%), and ≥85 years (n=843, 27.8%). The event incidence rates (/100 person‐years) were 1.40, 1.55, and 1.95 for stroke or systemic embolism (log‐rank P=0.65); 1.70, 1.55, and 2.61 for bleeding requiring hospitalization (log‐rank P=0.33); 2.09, 2.60, and 5.29 for total deaths (log‐rank P

BackgroundTo increase the consultation rate of potential major depressive disorder (MDD) patients, we developed a contact-type fingertip photoplethysmography-based MDD screening system. With the outbreak of SARS-CoV-2, we developed an alternative to contact-type fingertip photoplethysmography: a novel web camera-based contact-free MDD screening system (WCF-MSS) for non-contact measurement of autonomic transient responses induced by a mental task.MethodsThe WCF-MSS measures time-series interbeat intervals (IBI) by monitoring color tone changes in the facial region of interest induced by arterial pulsation using a web camera (1920 × 1080 pixels, 30 frames/s). Artifacts caused by body movements and head shakes are reduced. The WCF-MSS evaluates autonomic nervous activation from time-series IBI by calculating LF (0.04–0.15 Hz) components of heart rate variability (HRV) corresponding to sympathetic and parasympathetic nervous activity and HF (0.15–0.4 Hz) components equivalent to parasympathetic activities. The clinical test procedure comprises a pre-rest period (Pre-R; 140 s), mental task period (MT; 100 s), and post-rest period (Post-R; 120 s). The WCF-MSS uses logistic regression analysis to discriminate MDD patients from healthy volunteers via an optimal combination of four explanatory variables determined by a minimum redundancy maximum relevance algorithm: HF during MT (HFMT), the percentage change of LF from pre-rest to MT (%ΔLF(Pre–R⇒MT)), the percentage change of HF from pre-rest to MT (%ΔHF(Pre–R⇒MT)), and the percentage change of HF from MT to post-rest (%ΔHF(MT⇒Post–R)). To clinically test the WCF-MSS, 26 MDD patients (16 males and 10 females, 20–58 years) were recruited from BESLI Clinic in Tokyo, and 27 healthy volunteers (15 males and 12 females, 18–60 years) were recruited from Tokyo Metropolitan University and RICOH Company, Ltd. Electrocardiography was used to calculate HRV variables as references.ResultThe WCF-MSS achieved 73% sensitivity and 85% specificity on 5-fold cross-validation. IBI correlated significantly with IBI from reference electrocardiography (r = 0.97, p < 0.0001). Logit scores and subjective self-rating depression scale scores correlated significantly (r = 0.43, p < 0.05).ConclusionThe WCF-MSS seems a promising contact-free MDD screening apparatus. This method enables web camera built-in smartphones to be used as MDD screening systems.

Background: Early recurrence of atrial tachyarrhythmia (ERAT) during a 90-day blanking period (BP) often occurs after atrial fibrillation (AF) ablation. Left atrial reverse remodeling (LARR), which is the reduction in LA volume (LAV), also occurs during the BP. Both ERAT and LARR are associated with late recurrence (LR, greater than 90 days after ablation). We investigated the association between ERAT and LARR following non-paroxysmal AF (NPAF) ablation. Methods: We retrospectively reviewed 330 consecutive patients undergoing initial NPAF ablation (median follow-up: 4.0 years). Based on the timing of the final ERAT, we divided the patients into No-ERAT (N = 154, without ERAT), Early (N = 39, 0–7 days after ablation), Intermediate (N = 67, 8–30), and Late-ERAT (N = 70, 31–90) groups. We assessed the extent of LARR, defined as the percentage of decrease in LAV (%ΔLAV). The %ΔLAV cutoff value was determined by receiver operating characteristic analysis, and incorporated into a multivariate analysis to assess the association between ERAT and LARR. Results: Late-ERAT was associated with LR (hazard ratio: 6.31, 95% confidence interval (CI): 4.21–9.47, p = 0.0001). The %ΔLAV in the Late-ERAT group was significantly smaller than the other groups (p

To investigate the effects of forest and the surrounding natural and anthropogenic sources on the bulk depositions on forested land, this study examined differences in ion concentrations between wet-only and bulk samples at two forested sites in Japan. The surrounding natural and anthropogenic sources at each site were different; Shirasaka is in a rural area and Tanashi is an urban environment. The volume weighted (vw) mean concentrations of K+ and Ca2+ in the bulk samples were significantly (p

Abstract High-density lipoprotein (HDL) interacts with various cells, particularly macrophages, in functional cell-HDL interactions. Here, we found that HDL protein quality and lipid quality play critical roles in HDL functions. HDL fractions from healthy volunteers (HDLHealthy) and patients with recurrent coronary atherosclerotic disease (HDLCAD) were prepared. To analyse functional HDL-macrophage interactions, macrophages were co-incubated with each HDL, and lipid mediator production was assessed by liquid chromatography/mass spectrometry-based metabololipidomics. HDLHealthy treatment attenuated the pro-inflammatory lipid mediator production, particularly that of leukotriene (LT) B4, and this treatment enhanced lipoxin (LX) B4 and resolvin (Rv) E2 production. HDLHealthy treatment enhanced the proteasome-mediated degradation of the LTB4-producing enzyme 5-lipoxygenase (LO) in activated macrophages; however, HDLCAD did not show these anti-inflammatory effects. HDLHealthy was engulfed by macrophages via clathrin-mediated endocytosis, which was a critical step in 5-LO/LTB4 regulation. We also found that HDLCAD showed higher levels of the LTB4-producing enzymes and thus promoted LTB4 production from HDLCAD. In addition, LTB4 attenuated HDL endocytosis, HDL-mediated 5-LO degradation in macrophages, and HDL-derived augmentation of macrophage phagocytosis. These results indicated that local LTB4 produced de novo from HDLCAD regulates HDL-macrophage functional interactions and plays critical roles in dysfunctional, inflammatory HDL characteristics.

Acquired tracheal stenosis remains a challenging problem for otolaryngologists. The objective of this study was to determine whether the Sendai virus (SeV)-mediated c-myc suppressor, a far upstream element (FUSE)-binding protein (FBP)-interacting repressor (FIR), modulates wound healing of the airway mucosa, and whether it prevents tracheal stenosis in an animal model of induced mucosal injury. A fusion gene-deleted, non-transmissible SeV vector encoding FIR (FIR-SeV/ΔF) was prepared. Rats with scraped airway mucosae were administered FIR-SeV/ΔF through the tracheostoma. The pathological changes in the airway mucosa and in the tracheal lumen were assessed five days after scraping. Untreated animals showed hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition causing lumen stenosis. By contrast, the administration of FIR-SeV/ΔF decreased the degree of tracheal stenosis (P < 0.05) and improved the survival rate (P < 0.05). Immunohistochemical staining showed that c-Myc expression was downregulated in the tracheal basal cells of the FIR-SeV/ΔF-treated animals, suggesting that c-myc was suppressed by FIR-SeV/ΔF in the regenerating airway epithelium of the injured tracheal mucosa. The airway-targeted gene therapy of the c-myc suppressor FIR, using a recombinant SeV vector, prevented tracheal stenosis in a rat model of airway mucosal injury.

Degradation of three chlorinated ethenes, trichloroethylene, trans-1,2-dichloroethylene and cis-1,2-dichloroethylene, by UV-light irradiated TiO2 catalyst prepared by the sol-gel method in dry air at ambient temperature have been examined by using FTIR measurement. The chlorinated ethenes rapidly decomposed to produce dichloroacethyl chloride, CO, HCl, and COCL2. For trans- and cis-1,2-DCE systems isomerization to each other is found to be the first step of the degradation. The C = C bond of the chlorinated ethenes interacts directly with TiO2 site and, consequently, the degradation results in several products on the catalyst surface in these systems.

Eicosapentaenoic acid-derived prostaglandin (PG) E3, PGF(3α), and thromboxane (TX) B3 are bioactive lipid mediators which have anti-cancer and anti-inflammatory effects. To exert their effects, PGE3, PGF(3α), and TXB3 must be released to the extracellular space from cells, but the release mechanism has been unclear. We therefore investigated the contribution of ATP-binding cassette transporter C4 (ABCC4), which has been known as a prostanoids efflux transporter, to the release of PGE3, PGF(3α), and TXB3.ATP-dependent transport of PGE3, PGF(3α), and TXB3 via ABCC4 was investigated by using inside-out membrane vesicles prepared from ABCC4-overexpressing HEK293 cells. To evaluate the contribution of ABCC4 to the release of PGE3, PGF(3α), and TXB3, we measured the extracellular and intracellular levels of PGE3, PGF(3α), and TXB3 in A549 cells when we used ABCC4 inhibitors (dipyridamole, MK571, and probenecid) or ABCC4 siRNAs. The quantification of PGE3, PGF(3α), and TXB3 was performed by using liquid chromatography-tandem mass spectrometry.The apparent Km values for ABCC4-mediated transport were 2.9±0.1 µM for PGE3, 12.1±1.3 µM for PGF(3α), and 11.9±1.4 µM for TXB3 and the ATP-dependent accumulation of PGE3, PGF(3α), and TXB3 into vesicles was decreased by using typical substrates and inhibitors of ABCC4. ABCC4 inhibitors and ABCC4 knockdown showed the reduction of extracellular/intracellular ratio of PGE3 (40-60% of control) and PGF(3α) (60-80% of control) in A549 cells.Our results suggest that PGE3, PGF(3α), and TXB3 are substrates of ABCC4 and ABCC4 partially contributes to the release of PGE3 and PGF(3α).

This paper reports the first case of fibroepithelial polyp arising independently of the external auditory canal. A 16-year-old female patient presented to our clinic for aural fullness of the left side. Physical examination revealed a papillomatous tumor at the posterior wall of the inlet of the left external auditory canal. After biopsy, which yielded a diagnosis of benign papilloma, the patient underwent tumor excision. Final diagnosis was fibroepithelial polyp. One week after resection, aural fullness had resolved. Fibroepithelial polyp is a benign lesion and occurs mainly in the skin, ureteropelvic system, and genitals. In the head and neck area, there are reports on fibroepithelial polyp of the tongue, piriform fossa, inferior nasal turbinate, and tonsil, in addition to the skin, but none on independent fibroepithelial polyp of the external auditory canal. Excision of fibroepithelial polyp of the external auditory canal is advisable, especially in the presence of any symptoms, and should be preceded by confirmation of nonmalignancy by biopsy, if possible.

Based on an analysis of documents from the second half of the 18th century, the article positions Franz Benda as an eminent musician at the Prussian Hofkapelle, who won the favour of Frederick II, initially as an excellent violin virtuoso, and subsequently as the king's adviser on music at large. Benda also influenced the recruiting of new court musicians, as well as e.g. the appointment of J. F. Reichardt as Kapellmeister in 1775. Frederick's appreciation of his service is evidenced not only by Benda's generous salary and his assignment as a mentor of young court musicians, but also by the privileged treatment, at least during a certain period, of his family members active in the court orchestra. The appendix offers a detailed list of salary payments to the individual Benda family members serving in the court orchestra, based on the orchestra's payroll records (Hofkapelletat). Detailed examination of the records also casts doubt on dating Benda's appointment as the concertmaster to 1771, which has so far been generally presented as an established fact. [ABSTRACT FROM AUTHOR]