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Competing Interests: There are no conflicts of interest.

Blood oxygen saturation (SpO 2 ) is an essential indicator of a patient's general condition. However, conventional measurement methods have some issues such as time delay and interference by ambient light. Improved measurement methods must be developed, and there are no reports on intraoral measurements of SpO 2 using wearable devices. Therefore, we aimed to establish an intraoral SpO 2 measurement method for the first time. Twelve healthy adults participated in this study. The following steps were taken: (1) to identify the optimal measurement location, mid-perfusion index (PI) values were measured at six places on the mucosa of the maxilla, (2) to validate the optimal measurement pressure, PI values were obtained at different pressures, and (3) using the proposed mouthpiece device, SpO 2 values in the oral cavity and on the finger were analyzed during breath-holding. The highest PI values were observed in the palatal gingiva of the maxillary canine teeth, with high PI values at pressures ranging from 0.3 to 0.8 N. In addition, changes in SpO 2 were detected approximately 7 s faster in the oral cavity than those on the finger, which is attributed to their proximity to the heart. This study demonstrates the advantage of the oral cavity for acquiring biological information using a novel device.

We proposed a novel jaw movement tracking method that can measure in six degrees of freedom. The magnetic field generated by a permanent magnet paired with a small, low-power-consumption Hall effect magnetic sensor is used to estimate the relative distance between two objects-in this instance, the lower and upper jaws. By installing a microelectromechanical system (MEMS) orientation sensor in the device, we developed a mouthpiece-type sensing device that can measure voluntary mandibular movements in three-dimensional orientation and position. An evaluation of individuals wearing this device demonstrated its ability to measure mandibular movement with an accuracy of approximately 3 mm. Using the movement recording feature with six degrees of freedom also enabled the evaluation of an individual's jaw movements over time in three dimensions. In this method, all sensors are built onto the mouthpiece and the sensing is completed in the oral cavity. It does not require the fixation of a large-scale device to the head or of a jig to the teeth, unlike existing mandibular movement tracking devices. These novel features are expected to increase the accessibility of routine measurements of natural jaw movement, unrestricted by an individual's physiological movement and posture.

There is an urgent need for the development of brain drug delivery carriers based on middle-sized or macromolecules, to which in vitro blood-brain barrier (BBB) models are expected to contribute significantly through evaluation of BBB permeability. As part of efforts to develop such models, we have been working on human conditionally immortalized cell-based multicellular spheroidal BBB models (hiMCS-BBB models), and we herein introduce the model development protocol. Briefly, astrocytes are first seeded in an ultra-low attachment 3D cell culture plate, to make the central core (Day 0). Next, pericytes are added over the core, to form an outer layer (Day 1). Then, brain microvascular endothelial cells are further added to each well, to create the outmost monolayer serving as the BBB (Day 2). Finally, the spheroids cultured for two days (on Day 4) can be used for assays of interest ( e.g ., antibody permeability assays). Neither special equipment nor techniques are required to produce hiMCS-BBB models. Therefore, the protocol presented here will not only facilitate the model sharing among the BBB community but also provide some technical clues contributing to the development of similar MCS-BBB models using other cell sources, such as primary or iPS-derived BBB cells. Graphical abstract., Competing Interests: Competing interestsConflict of interest statements related to research funds are provided in the acknowledgments section, and the model development method herein has been applied for a patent (No. 2020-007041). There is another related patent application (No. 2020-065670). The authors declare that they do not have any other conflicts of interest., (Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.)

Blood-brain barrier (BBB)-permeable middle- or macromolecules (middle/macromolecules) have recently attracted significant attention as new drug delivery carriers into the human brain via receptor-mediated transcytosis (RMT). During the development process of such carriers, it is necessary to thoroughly evaluate their human BBB permeability levels. In such evaluations, our recently established human immortalized cell-based multicellular spheroidal BBB models (hiMCS-BBB models) have shown high potential. However, the specifics of those capabilities have yet to be elucidated. Therefore, in this study, we characterize the ability of the hiMCS-BBB models to evaluate RMT-mediated BBB penetration properties of middle/macromolecules. More specifically, we began by validating transferrin receptor (TfR)-mediated RMT functionalities using transferrin in the hiMCS-BBB models and then examined the BBB permeability levels of MEM189 antibodies (known BBB-permeable anti-TfR antibodies). The obtained results showed that, as with the case of transferrin, temperature-dependent uptake of MEM189 antibodies was observed in the hiMCS-BBB models, and the extent of that uptake increased in a time-dependent manner until reaching a plateau after around 2 h. To further expand the evaluation applicability of the models, we also examined the BBB permeability levels of the recently developed SLS cyclic peptide and observed that peptide uptake was also temperature-dependent. To summarize, our results show that the hiMCS-BBB models possess the ability to evaluate the RMT-mediated BBB-permeable properties of antibodies and peptides and thus have the potential to provide valuable tools for use in the exploration and identification of middle/macromolecules showing excellent BBB permeability levels, thereby contributing powerfully to the development of new drug delivery carriers for transporting drugs into the human brain.

Recently, the number of patients who request esthetically pleasing aligner-type orthodontic appliances (referred to as aligners) has been increasing. However, the orthodontic forces generated by these aligners are still unknown. This study aimed to verify whether the orthodontic force in aligners can be estimated by measuring near infrared 2D birefringence, and to visualize the orthodontic force. We measured the mechanical and photoelastic properties of transparent orthodontic thermoplastic specimens to correlate the optical retardation with the applied load. The results confirmed equivalence between the mechanical properties and the photoelasticity. In addition, the 2D retardation distribution that occurred when stress was applied to the sample was mapped and visualized. This indicates that it is possible to estimate and visualize the orthodontic force using the retardation obtained by near infrared 2D birefringence measurement.

Purpose: In vitro human blood-brain barrier (BBB) models in combination with central nervous system-physiologically based pharmacokinetic (CNS-PBPK) modeling, hereafter referred to as the "BBB/PBPK" method, are expected to contribute to prediction of brain drug concentration profiles in humans. As part of our ongoing effort to develop a BBB/PBPK method, we tried to clarify the relationship of in vivo BBB permeability data to those in vitro obtained from a human immortalized cell-based tri-culture BBB model (hiBBB), which we have recently created., Methods: The hiBBB models were developed and functionally characterized as previously described. The in vitro BBB permeabilities (Pe, × 10 -6  cm/s) of seventeen compounds were determined by permeability assays, and in vivo BBB permeabilities (Q ECF ) for eight drugs were estimated by CNS-PBPK modeling. The correlation of the Pe values with the Q ECF values was analyzed by linear regression analysis., Results: The hiBBB models showed intercellular barrier properties and several BBB transporter functions, which were enough to provide a wide dynamic range of Pe values from 5.7 ± 0.7 (rhodamine 123) to 2580.4 ± 781.9 (rivastigmine). Furthermore, the in vitro Pe values of the eight drugs showed a good correlation (R 2  = 0.96) with their in vivo Q ECF values estimated from human clinical data., Conclusion: We show that in vitro human BBB models provide clinically relevant BBB permeability that can be used as input for CNS-PBPK modeling. Therefore, our findings will encourage the development of a BBB/PBPK method as a promising approach for predicting brain drug concentration profiles in humans., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adenostemma lavenia (L.) Kuntze (Asteraceae) is widely distributed in tropical regions of East Asia, and both A. lavenia and A. madurense (DC) are distributed in Japan. In China and Taiwan, A. lavenia is used as a folk medicine for treating lung congestion, pneumonia, and hepatitis. However, neither phylogenic nor biochemical analysis of this plants has been performed to date. We have reported that the aqueous extract of Japanese A. lavenia contained high levels of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (11αOH-KA; a kaurenoic acid), which is a potent anti-melanogenic compound. Comparison of chloroplast DNA sequences suggested that A. lavenia is originated from A. madurense. Analyses of kaurenoic acids revealed that Japanese A. lavenia and A. madurense contained high levels of 11αOH-KA and moderate levels of 11α,15OH-KA, while Taiwanese A. lavenia mainly contained 9,11αOH-KA. The diverse biological activities (downregulation of Tyr, tyrosinase, gene expression [anti-melanogenic] and iNOS, inducible nitric oxide synthase, gene expression [anti-inflammatory], and upregulation of HO-1, heme-oxygenase, gene expression [anti-oxidative]) were associated with 11αOH-KA and 9,11αOH-KA but not with 11α,15OH-KA. Additionally, 11αOH-KA and 9,11αOH-KA decreased Keap1 (Kelch-like ECH-associated protein 1) protein levels, which was accompanied by upregulation of protein level and transcriptional activity of Nrf2 (NF-E2-related factor-2) followed by HO-1 gene expression. 11αOH-KA and 9,11αOH-KA differ from 11α,15OH-KA in terms of the presence of a ketone (αβ-unsaturated carbonyl group, a thiol modulator) at the 15 th position; therefore, thiol moieties on the target proteins, including Keap1, may be important for the biological activities of 11αOH-KA and 9,11αOH-KA and A. lavenia extract., (© 2021. The Japanese Society of Pharmacognosy.)

The temporal changes in ambulatory monitoring findings after cryoballoon (CB) ablation of atrial fibrillation (AF) have not been well elucidated. This study aims to compare the details of ambulatory monitoring after CB and radiofrequency catheter (RFC) ablation for AF. Of 724 consecutive AF patients who underwent initial ablation using a CB or RFC, 508 (254 pairs) were selected using propensity score matching. Ambulatory monitoring was performed at 1, 3, 6, 12, 24 and 36 months after the procedure. After 1, 3 and 6 months, the number of total heart beats (THBs) was larger in the CB group than in the RFC group. It gradually decreased and became significantly similar by 12 months after ablation. THBs significantly increased 1, 3, 6 and 12 months after ablation in both the RFC and CB groups and became statistically similar by 24 months after ablation. The atrial premature contraction burden was higher in the RFC group than in the CB group at 3 months after ablation. THB and APC burden after AF ablation were significantly different between the RF and CB groups. THBs returned to statistically similarity by 2 years after ablation in both groups., (© 2021. Springer Japan KK, part of Springer Nature.)

The optimal ablation strategy for persistent atrial fibrillation (PsAF) remains to be defined. We sought to compare very long-term outcomes between linear ablation and electrogram (EGM)-guided ablation for PsAF. In a retrospective analysis, long-term arrhythmia-free survival compared between two propensity-score matched cohorts, one with pulmonary vein isolation (PVI) and linear ablation including roof/mitral isthmus line (LINE-group, n = 52) and one with PVI and EGM-guided ablation (EGM-group; n = 52). Overall, 99% of patients underwent successful PVI. Complete block following linear ablation was achieved for 94% of roof lines and 81% of mitral lines (both lines blocked in 75%). AF termination by EGM-guided ablation was accomplished in 40% of patients. Non-PV foci were targeted in 7 (13%) in the LINE-group and 5 (10%) patients in the EGM-group (p = 0.76). During 100 ± 28 months of follow-up, linear ablation was associated with superior arrhythmia-free survival after the initial and last procedure (1.8 ± 0.9 procedures) compared with EGM-group (Logrank test: p = 0.0001 and p = 0.045, respectively). In multivariable analysis, longer AF duration and EGM-guided ablation remained as independent predictors of atrial arrhythmia recurrence. Linear ablation might be a more effective complementary technique to PVI than EGM-guided ablation for PsAF ablation., (© 2021. The Author(s).)

[Figure: see text].

While phrenic nerve palsy (PNP) due to cryoballoon pulmonary vein isolation (PVI) of atrial fibrillation (AF) was transient in most cases, no studies have reported the results of the long-term follow-up of PNP. This study aimed to summarize details and the results of long-term follow-up of PNP after cryoballoon ablation. A total of 511 consecutive AF patients who underwent cryoballoon ablation was included. During right-side PVI, the diaphragmatic compound motor action potential (CMAP) was reduced in 46 (9.0%) patients and PNP occurred in 29 (5.7%) patients (during right-superior PVI in 20 patients and right-inferior PVI in 9 patients). PNP occurred despite the absence of CMAP reduction in 0.6%. The PV anatomy, freezing parameters and the operator's proficiency were not predictors of PNP. While PNP during RSPVI persisted more than 4 years in 3 (0.6%) patients, all PNP occurred during RIPVI recovered until one year after the ablation. However, there was no significant difference in the recovery duration from PNP between PNP during RSPVI and RIPVI. PNP occurred during cryoballoon ablation in 5.7%. While most patients recovered from PNP within one year after the ablation, PNP during RSPVI persisted more than 4 years in 0.6% of patients.

Background: Ent- 11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (11αOH-KA) is a multifunctional biochemical found in some ferns, Pteris semipinnata , and its congeneric species. Although a number of therapeutic applications of 11αOH-KA have been proposed (e.g., anti-cancer, anti-inflammation, and skin whitening), the content of 11αOH-KA in these ferns is not high. Adenostemma lavenia (L.) O. Kuntze, an Asteraceae, has also been reported to contain 11αOH-KA. The decoction (hot water extract) of whole plants of A. lavenia is used as a folk remedy for inflammatory disorders, such as hepatitis and pneumonia, suggesting that 11αOH-KA may be the ingredient responsible for the medicinal properties of this plant., Methods: The anti-melanogenic activities of the water extracts of A. lavenia leaves and Pteris dispar Kunze (a cognate of P. semipinnata ) leaves were compared in mouse B16F10 melanoma cells. The amount of 11αOH-KA was measured by using liquid chromatography spectrometry. C57BL/6J mice were treated with the water extract of A. lavenia leaf, and the blood concentration of 11αOH-KA was measured. The in vivo efficacy of the water extract of A. lavenia leaf was evaluated according to tis anti-melanogenic activity by monitoring hair color., Results: Although both the extracts ( A. lavenia and P. dispar Kunze) showed high anti-melanogenic activities, only A. lavenia contained a high amount of 11αOH-KA, approximately 2.5% of the dry leaf weight. 11αOH-KA can be purified from A. lavenia leaves in two steps: water extraction followed by chloroform distribution. The treatment of mice with the water extract of A. lavenia leaf suppresses pigmentation in their hairs., Conclusions: Despite the small number of mice examined, the present preliminary result of the suppressed hair pigmentation suggests that the water extract of A. lavenia leaf and the ingredient that is possibly responsible for this-11αOH-KA-are new materials for oral cosmetics. The results may also be helpful in the future development of functional foods and methods to treat patients suffering from hyperpigmentation disorders, such as melasma.

Background: The presence of heart failure (HF) has been associated with poorer outcomes in patients undergoing catheter ablation (CA) for atrial fibrillation (AF). However, the effectiveness of CA amongst the subset of patients with tachycardia-induced cardiomyopathy (TIC) remains poorly defined., Methods and Results: In a retrospective analysis we compared outcomes of first-time CA for persistent AF in a cohort of patients with previously diagnosed TIC (n = 45; age 58 ± 8 years; 91% male) to those with structurally normal hearts (non-TIC; n = 440; age 55 ± 9 years; 95% male). TIC was defined as an impaired ventricular function (left ventricular ejection function [LVEF] <50%), which was reversed after the treatment of HF. We compared atrial arrhythmias (AAs) recurrence after the CA in the TIC and non-TIC cohorts. In the TIC group, LVEF improved from 35.8% ± 8.1% to 57.5% ± 8.3% after treatment of HF. During 3.3 ± 1.5 years follow-up, AAs-free survival after CA was significantly higher in the TIC group as compared with the non-TIC group (69% vs 42%; P = .001), despite a comparable CA strategy between the two groups. In multivariable analysis, absence of HF with TIC, longer AF duration, and complex fractionated atrial electrogram ablation were independent predictors of arrhythmia recurrence (OR, 1.02; 95% CI, 1.01-1.03; P < .01; OR, 0.40; 95% CI, 0.20-0.79; P < .01 and OR, 2.29; 95%CI; 1.27-4.11; P < .01, respectively). In addition, the outcome after the last procedure was superior in the TIC cohort (89% vs 72%; P = .03) with fewer CA procedures as compared with the non-TIC cohort (1.3 ± 0.5 vs 1.5 ± 0.7; P = .01)., Conclusions: Persistent patients with AF with TIC have a more favorable outcome after the CA as compared with those without., (© 2019 Wiley Periodicals, Inc.)

Objectives: This study examined the anatomical or procedural factors associated with severe pulmonary vein (PV) stenosis after cryoballoon PV isolation., Background: PV stenosis is a complication associated with cryoballoon ablation., Methods: The study included 170 consecutive patients with paroxysmal atrial fibrillation who underwent cryoballoon ablation. In addition to factors generally considered to be related to the occurrence of PV stenosis (PV size, cryoballoon application number and time, and minimum freezing temperature), we evaluated the following 4 factors: 1) depth of balloon position; 2) the PV angle (internal angle between each PV and horizontal line); 3) noncoaxial balloon placement (hemispherical occlusion); and 4) contact surface area between the cryoballoon and the PV wall (defined as the balloon contact ratio)., Results: Severe PV stenosis (≥75% area reduction) was observed in 9 (1.3%) PVs (6 left superior and 3 right superior PVs) in 9 patients. The PV size, cryoballoon application number and time, minimum freezing temperature, and the depth of cryoballoon position were not significantly associated with occurrence of severe PV stenosis, but the PV angle was significantly smaller in PVs with severe stenosis than it was in those without stenosis (25.6 ± 9.7° vs. 34.2 ± 6.4°; p < 0.001). Hemispherical occlusion was more frequently observed and balloon contact ratio was larger in PVs with severe stenosis (55.6% vs. 14.8%; p = 0.049) than in those without stenosis (0.70 ± 0.06 vs. 0.54 ± 0.08; p < 0.001)., Conclusions: A horizontally connecting PV, noncoaxial placement of cryoballoon, and a larger contact surface area of the cryoballoon were predictors of the occurrence of severe PV stenosis after cryoballoon ablation., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: One of the mechanisms of early recurrence of atrial fibrillation (ERAF) after AF ablation is considered to be the inflammatory reaction of the atrial tissue. The aim of this study is to compare the clinical significance of ERAF at each stage for true AF recurrence between cryoballoon (CB) and radiofrequency (RF) ablation., Methods: Among 798 paroxysmal AF patients who underwent an initial ablation, 460 patients (CB, n = 230; RF, n = 230) were selected by propensity score matching. Very ERAF (VERAF), ERAF-1M, ERAF-3M and true AF recurrence were defined as AF recurrence at 0-2, 3-30, 31-90 days and more than 90 days after the procedure, respectively., Results: The patient characteristics of the two groups were similar. ERAF was observed 21% and 27% in the CB and RF groups, respectively. In both the CB and RF group, VERAF, ERAF-1M and ERAF-3M were more frequently observed in patients with true AF recurrence than in those without. In a multivariable analysis, ERAF-1M and ERAF-3M were found to be independent predictors of true AF recurrence in both the CB (P = 0.04 and P<0.001, respectively) and RF groups (P = 0.02 and P = 0.001, respectively). However, while VERAF was associated with true AF recurrence after RF ablation (P = 0.03), it was not associated with true AF recurrence after CB ablation (P = 0.19)., Conclusion: The relationship between ERAF and true AF recurrence differed between the RF and CB ablation groups. While VERAF was associated with true AF recurrence after RF ablation, it was not a predictor of true AF recurrence after CB ablation., Competing Interests: The authors have declared that no competing interests exist.

Atrial fibrillation (AF) ablation requires transseptal puncture to access the left atrium. Recently, a radiofrequency (RF) needle was developed. The purpose of this study was to compare the incidence of MRI-confirmed acute cerebral embolism (ACE) during AF ablation procedures performed with RF needle versus mechanical needle transseptal puncture. This study consisted of 383 consecutive patients who underwent catheter ablation for AF that required transseptal puncture with mechanical or radiofrequency transseptal needles. Of those, 232 propensity score-matched patients (116 with each needle type) were included in the analysis. All patients had cerebral MRI performed 1 or 2 days after the procedure. Baseline characteristics were similar between the two groups. Total procedure time was significantly shorter in Group RF than Group non-RF (167 ± 50 vs. 181 ± 52 min, P = 0.01). ACE was detected by MRI in 59 (25%) patients. All patients with ACE were asymptomatic. Incidence of ACE was lower in Group RF than Group non-RF (19 vs. 32%, P = 0.02). B-type natriuretic peptide level was higher in the patients with ACE as compared to those without ACE (65.2 ± 68.7 vs. 44.7 ± 55.1 pg/ml, P = 0.02). In multivariable analysis, the use of RF needle and BNP level was related to the incidence of ACE (OR = 0.499, 95% CI 0.270-0.922, P = 0.03 and OR = 1.005, 95% CI 1.000-1.010, P = 0.03). Use of RF needle for transseptal puncture was associated with lower total procedure time and risk of ACE during catheter ablation of AF.

Atrial fibrillation (AF), especially asymptomatic cases, is often detected by medical checkups. We investigated the outcome of AF ablation in cases detected by medical checkups. We reviewed the data of 735 patients with AF (56 ± 10 years, paroxysmal: 441 patients) who underwent initial catheter ablation. All patients were divided into two groups based on their AF being diagnosed either by a medical checkup (group M) or not (group NM). AF was diagnosed by medical checkups in 263 (36%) patients. In Group M, the age was younger, time from the diagnosis to ablation shorter, left atrium dimension larger, and left ventricular ejection fraction lower than in Group NM. Male gender, persistent AF, and asymptomatic AF were more frequently seen in Group M than in Group NM. A mean of 13 ± 11 months after the initial ablation procedure, AF recurrence was more frequently observed in group M compared to group NM (P = 0.018). While the AF recurrence rate was similar in both groups in persistent AF patients (P = 0.87), it was more frequently observed in Group M than in Group NM in paroxysmal AF patients (P = 0.005). AF diagnosed by medical checkups was often associated with a worse outcome of catheter ablation, especially in paroxysmal AF patients.

Aims: Establishment of pulmonary vein isolation (PVI) during cryoballoon (CB) ablation is generally confirmed by use of an octapolar inner-lumen mapping catheter (Achieve®). The aim of this study is to evaluate the residual PV potential (PVP) using the conventional circular catheter after CB-PVI., Methods and Results: A total of 105 consecutive patients (418 PVs) with paroxysmal AF who underwent the initial CB-PVI were prospectively included in this study. Of those, 305 (73%) PVs with real-time recordings of PVP elimination by Achieve® catheter during successful PVI were included. After isolation of all 4 PVs, PV antral remapping by conventional circular mapping catheter was performed. After CB-PVI, residual PVP was detected in 4.3% (13/305) of PVs (1.2% of left-superior PV, 2.5% of left-inferior PV, none of right-superior PV, and 20% of right-inferior PV). Almost 60% of residual PV potential was located around the bottom portion of the right-inferior PV. In PVs with residual potential, PV trunk was shorter (12.7 ± 5.7 mm vs. 18.7 ± 7.9, P = 0.001), minimal balloon temperature was higher (-46.6 ± 5.9 °C vs. -50.9 ± 8.2, P = 0.02), and balloon warming time was shorter (35.6 ± 17.8 s vs. 50.0 ± 22.8, P = 0.006) than those without. All residual potentials were eliminated by additional touch up ablation. After the initial ablation procedure, 1-year AF-free rate was 79.5%., Conclusion: PV remapping after CB-PVI revealed residual antral PVP in 4.3% of PVs and in 20% of RIPVs in particular. The Achieve® catheter sometimes fails to detect complete PV antral isolation.

Described herein is a chiral magnesium bisphosphate-catalyzed asymmetric double C(sp 3 )-H bond functionalization triggered by a sequential hydride shift/cyclization process. This reaction consists of stereoselective domino C(sp 3 )-H bond functionalization: (1) a highly enantio- and diastereoselective C(sp 3 )-H bond functionalization by chiral magnesium bisphosphate (first [1,5]-hydride shift), and (2) a highly diastereoselective C(sp 3 )-H bond functionalization by an achiral catalyst (Yb(OTf) 3 , second [1,5]-hydride shift).

Cryoballoons (CBs) have proven to be effective for achieving pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Dissociated PV activity (DPVA) after successful radiofrequency PVI is sometimes observed inside the PV and has been found to prove the achievement of electrical disconnection from the left atrium. However, little is known about the incidence or characteristics of DPVA after CB-PVI. The aim of this study was to compare the incidence and characteristics of DPVA in patients undergoing CB and radiofrequency (RF) ablation for AF. Two hundred and ninety-four propensity score-matched patients from 440 consecutive patients who underwent initial catheter ablation for paroxysmal AF were included in the present study (CB-PVI 147, RF-PVI 147). DPVA was more frequently observed after CB-PVI than after RF-PVI (32 vs. 19% of the PVs, P < 0.001), especially in the left superior PV (52 vs. 29%, P < 0.001) and left inferior PV (22 vs. 7%, P < 0.001). The AF-free rate after the initial ablation in the patients with and without DPVA was similar in both the CB (P = 0.23) and RF (P = 0.39) groups. During repeat ablation procedures for recurrent AF, PV reconnection was similarly observed in PVs with and without DPVA during the initial procedure, both in the CB (30 vs. 44%, P = 0.29) and RF (65 vs. 58%, P = 0.41) groups. DPVA was more frequently observed after CB-PVI than after RF-PVI. The presence of DPVA was not related to the ablation outcome or chronic PV reconnection following CB-PVI.

Background: Little is known about the manner in which the superior vena cava (SVC) is activated during sinus rhythm., Objective: The purpose of this study was to assess the manner of caval activation with an ultra-high-density mapping system (Rhythmia, Boston Scientific, Marlborough, MA) and its utility for SVC isolation., Methods: Forty patients with atrial fibrillation (mean age 55 ± 12 years; paroxysmal atrial fibrillation in 23[58%]) who underwent SVC mapping with Rhythmia were studied. The location of the sinus node (SN), phrenic nerve (PN), and the manner of caval activation during sinus rhythm were analyzed. The SVC was isolated by radiofrequency applications at electrical connections, shown as breakthroughs on the Rhythmia map., Results: The SN location varied widely (lateral/posterior/anterior 60%/8%/32%), while the PN was mostly located in the lateral segment (lateral/anterior 82%/18%). In 36 patients who underwent SVC isolation, the mean number of breakthroughs was 2.5 ± 0.8. The first breakthrough predominantly located in the anterior aspect (anterior/septal/posterior/lateral 78%/14%/5%/3%), and atrial activation was conducted superiorly and clockwise from the SN (referred to as spiral activation) in 32 patients (89%). The mean rotation angle from the SN to the first breakthrough was 79° ± 41°. In addition, 10 patients (25%) showed the SN within the SVC. Although radiofrequency applications were needed at the PN capture site in 11 patients (31%) the SVC was successfully isolated without any complications in all patients., Conclusion: The SN location showed great heterogeneity; however, atrial activation predominantly showed a clockwise spiral form. This is the first report to use ultra-high-resolution mapping to demonstrate the manner of spiral activation, which is useful for the safe and efficient isolation of the SVC., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives and Methods: The number of patients who undergo Helicobacter pylori (HP) eradication therapy has been increasing since it became covered by insurance in Japan. As such, an increasing number of patients develop drug eruption as a result of HP eradication therapy. In the present study, we describe the clinical course of 28 patients who were treated at our hospital for drug eruption following HP eradication therapy between April 2008 and March 2016., Results and Discussion: The majority of the patients were women (21 women, 7 men). The average length of time from the start of treatment to the onset of eruption was 7.6 days. A drug-induced lymphocyte stimulation test (DLST) was performed in 10 patients. Amoxicillin was the most common cause of eruption, with 6 patients testing positive. Patients who were considered likely to have developed sensitivity prior to the treatment required the systemic administration of steroids. On the other hand, symptoms were relieved with topical steroids in some of the patients who were considered likely to have developed sensitivity during the course of treatment., Conclusion: Since penicillin antibiotics have long been used, some patients may have become sensitized without being aware of this. Our findings highlight the need for the careful management of patients developing sensitivity prior to treatment as they require the systemic administration of steroids.

Background: Asymptomatic cerebral embolism (ACE) is sometimes detected after cryoballoon ablation of atrial fibrillation. The removal of air bubbles from the cryoballoon before utilization may reduce the rate of ACE., Objective: This study aims to compare the incidence of ACE between a conventional and a novel balloon massaging method during cryoballoon ablation., Methods: Of 175 consecutive patients undergoing initial cryoballoon ablation of paroxysmal atrial fibrillation, 60 (34.3%) patients underwent novel balloon massaging with extracorporeal balloon inflation in saline water (group N) before the cryoballoon was inserted into the body. The remaining 115 (65.7%) patients underwent conventional balloon massaging in saline water while the balloon remained folded (group C). Of those, 86 propensity score-matched patients were included., Results: The baseline characteristics were similar between the 2 groups. In group N, even after balloon massaging in saline water was carefully performed, multiple air bubbles remained on the balloon surface when the cryoballoon was inflated in all cases. Postprocedural cerebral magnetic resonance imaging detected ACE in 14.0% of all patients. The incidence of ACE was significantly lower in group N than in group C (4.7% vs 23.3%; P = .01). According to multivariable analysis, the novel method was the sole factor associated with the presence of ACE (odds ratio 0.161; 95% confidence interval 0.033-0.736; P = .02)., Conclusion: Preliminary removal of air bubbles in heparinized saline water with extracorporeal balloon inflation reduced the incidence of ACE. Since conventional balloon massaging failed to remove air bubbles completely, this novel balloon massaging method should be recommended before cryoballoon utilization., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: In contrast with traditional radiofrequency ablation, little is known about the influence of cryoballoon ablation on the morphology of pulmonary veins (PVs). We evaluated the influence of cryoballoon ablation on the PV dimension (PVD) and investigated the factors associated with a reduction of the PVD., Methods and Results: Seventy-four patients who underwent cryoballoon ablation for paroxysmal atrial fibrillation were included in the present study. All subjects underwent contrast-enhanced computed tomography both before and at 3 months after the procedure. The PVD (cross-sectional area) was measured using a 3-dimensional electroanatomical mapping system. Each PV was evaluated according to the PVD reduction rate (ΔPVD), which was calculated as follows: (1-post-PVD/pre-PVD)×100 (%). Ninety-two percent of the PVs (271/296) were successfully isolated only by cryoballoon ablation; the remaining 8% of the PVs required touch-up ablation and were excluded from the analysis. Mild (25%-50%), moderate (50%-75%), and severe (≥75%) ΔPVD values were observed in 87, 14, and 3 PVs, respectively, including 1 case with severe left superior PV stenosis (ΔPVD: 94%) in a patient who required PV angioplasty. In multivariable analysis, a larger PV ostium and lower minimum freezing temperature during cryoballoon ablation were independently associated with PV narrowing (odds ratio, 1.773; P =0.01; and odds ratio, 1.137; P <0.001, respectively)., Conclusions: A reduction of the PVD was often observed after cryoballoon ablation for atrial fibrillation. A larger PV ostium and lower minimum freezing temperature during cryoballoon ablation were associated with an increased risk of PVD reduction., (© 2017 American Heart Association, Inc.)

Purpose: Catheter ablation for atrial fibrillation is performed with and without deep sedation, which could affect the arrhythmogenic activity during the procedure. We investigated the impact of sedation on electrophysiological properties in patients with AF who underwent catheter ablation., Methods: This study consisted of 255 consecutive patients with atrial fibrillation (229 males, persistent: 105 patients) who underwent a single-catheter ablation procedure. The patients were divided into the following two groups according to the depth of sedation during the procedure: group M (mild sedation with flunitrazepam in 138 patients) and group D (deep sedation with propofol in 117 patients). Peripheral oxygen saturation was continuously monitored via pulse oximetry throughout the procedure., Results: A spontaneous dissociated pulmonary vein activity after pulmonary vein isolation occurred more frequently in group M than in group D (29.1 vs 15.7%, P < 0.01). Adenosine-induced dormant pulmonary vein conduction was more frequently observed in group M than in group D (19.2 vs 13.0% P = 0.01). There were no significant differences in the incidence of non-pulmonary vein triggers between groups M and D (15.2 vs 11.1%, P = 0.53). The atrial fibrillation recurrence rate following the single procedure did not differ between the two groups (29.0 vs 26.5%, in groups M and D, P = 0.85)., Conclusions: Although deep sedation reduced the incidence of a dissociated pulmonary vein activity and dormant pulmonary vein conduction following pulmonary vein isolation, it did not affect the recurrence rate for atrial fibrillation after the procedure.

Background: The infusion of adenosine triphosphate after radiofrequency (RF) pulmonary vein (PV) isolation (PVI), which may result in acute transient PV-atrium reconnection, can unmask dormant conduction., Objective: The purpose of this study was to compare the incidence and characteristics of dormant conduction after cryoballoon (CB) and RF ablation of atrial fibrillation (AF)., Methods: Of 414 consecutive patients undergoing initial catheter ablation of paroxysmal AF, 246 (59%) propensity score-matched patients (123 CB-PVI and 123 RF-PVI) were included., Results: Dormant conduction was less frequently observed in patients who underwent CB-PVI than in those who underwent RF-PVI (4.5% vs 12.8% of all PVs; P < .0001). The incidence of dormant conduction in each PV was lower in patients who underwent CB-PVI than in those who underwent RF-PVI in the left superior PV (P < .0001) and right superior PV (P = .001). The site of dormant conduction was mainly located around the bottom of both inferior PVs after CB-PVI. Multivariable analysis revealed that a longer time to the elimination of the PV potential (odds ratio 1.018; 95% confidence interval 1.001-1.036; P = .04) and the necessity of touch-up ablation (odds ratio 3.242; 95% confidence interval 2.761-7.111; P < .0001) were independently associated with the presence of dormant conduction after CB-PVI. After the elimination of dormant conduction by additional ablation, the AF-free rate was similar in patients with and without dormant conduction after both CB-PVI and RF-PVI (P = .28 and P = .73, respectively)., Conclusion: The results of the propensity score-matched analysis showed that dormant PV conduction was less frequent after CB ablation than after RF ablation and was not associated with ablation outcomes., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Magnetophotonic crystals (MPCs) comprising cerium-substituted yttrium iron garnet (CeYIG) sandwiched by two Bragg mirrors were fabricated by vacuum annealing. CeYIG was deposited on Bragg mirrors at room temperature and annealed in 5 Pa of residual air. No ceria or other non-garnet phases were detected. Cerium 3 + ions substituted on the yttrium sites and no cerium 4 + ions were found. The Faraday rotation angle of the MPC was -2.92° at a wavelength of λ = 1570 nm was 30 times larger than that of the CeYIG film. These results showed good agreement with calculated values derived using a matrix approach.

Holographic memory is expected to become a high-capacity data storage. Magnetic volumetric holograms are rewritable holograms that are recorded as magnetization directions through thermomagnetic recording. However, the effective depth of magnetic holograms is limited by thermal diffusion that causes merging of magnetic fringes. In this study, we propose the insertion of heat-sink layers (HSLs) for retaining well-defined magnetic fringes during volumetric writing. Magnetophotonic microcavity media were used for demonstrating the HSL effect, and the structural design principle was established in numerical calculations. The results indicate that deep and clear magnetic fringes and an improvement in the diffraction efficiency can be achieved by the insertion of HSLs.

Hologram memory is a candidate for high-capacity data storage. Magnetic holograms formed as magnetization directions have been studied to realize rewritable hologram media. Recently, we reported that the magnetophotonic microcavity (MPM) can improve diffraction efficiency because of enhanced Faraday rotation angle and deep hologram writing. In this study, we demonstrated a clear reconstructed image from magnetic holograms in an MPM medium. The structural condition of MPMs for high diffraction efficiency was investigated, and the MPM medium was actually fabricated. The image reconstructed from the MPM medium had approximately twice the brightness of that reconstructed using a monolayer film.

An infant skin disease with clusters of nodules in the diaper contact area was reported as granuloma gluteale infantum. Recently, the number of elderly patients with this condition has increased, and it has been reported as diaper-area granuloma of the aged. These lesions are presumably caused by irritation from feces and urine. We observed similar cutaneous symptoms in six elderly patients, five of whom revealed clusters of nodules arranged in a circular pattern in the gluteal region presenting a peculiar clinical picture. They were all bedridden and wore cloth diapers. We speculate that wearing a cloth diaper seems to be a major factor behind this condition. Another factor was sitting during the day. A subject had lesions with nodules on the scrotum. The distribution of nodules appeared to be related to the body position and vigorous movement of the patient. In all cases, topical steroid therapies were not effective. They were all positive for bacteriuria. Chronic urinary tract infection further irritates the skin. It is necessary to reduce urine contact and keep the lesion clean., (© 2013 Japanese Dermatological Association.)

We report on microcavities comprising para-magnetic garnet and electro-optic films (MPMEO) for modulation of the polarization rotation angle of light at near-UV wavelengths with a slight intensity change, with applying a low voltage. The MPMEO are composed of para-magnetic garnet and electro-optic films sandwiched between two Bragg mirrors. The microcavity states in MPMEO are split and yield both the large rotation angle and high optical efficiency. Significant enhancement and modulation by applied voltages are verified through a conventional matrix calculation approach. High optical efficiency (>90%) and large modulation (~90 degree) of the polarization rotation are proved.

This study was concerned about an estimation of molecular diffusivity (D(m)) in liquid phase systems. An equation based on the absolute rate theory of diffusion was derived by considering the aggregation of not only solvent molecules, but also solute molecules. It was also studied how the replacement of the molar volume of a solvent with its molecular weight influences the accuracy in estimating D(m). The values of D(m) estimated by the equation were compared with those experimentally measured. The mean square deviation for the estimation of D(m) was calculated as being about 14% for 217 D(m) data measured in aqueous solutions of methanol and acetonitrile, which is comparable to that obtained by the Wilke-Chang equation. However, Dm of some solutes in carbon tetrachloride was more accurately estimated by this equation than by the Wilke-Chang equation. It is expected that the equation proposed in this study is effective for estimating D(m) in liquid phase systems.

This study deals with the application of the Wilke-Chang equation to the estimation of molecular diffusivity (Dm) in liquid phase systems including polar solutes and/or solvents. First, Dm of benzene in six different organic solvents was experimentally measured by the peak parking method. The value of association coefficient (α) was calculated from the Dm values by assuming that Dm can be represented by the Wilke-Chang equation. Then, the α value was correlated with the solubility parameter (δ) and ET of the solvents. Two different curved correlations were observed between α and the two physico-chemical parameters. This means that α of given solutes and solvents can be obtained from the values of δ and/or ET. Finally, Dm was estimated by a modified Wilke-Chang equation, which is derived by considering the aggregation of not only solvent molecules but also solute molecules. Although α is necessary for the estimation, it was calculated from δ for various solutes and solvents. The Dm values estimated were compared with those reported in literature. The mean square deviation between the Dm values was calculated less than 19% for 71 Dm data. It was demonstrated that the modified Wilke-Chang equation can be used for estimating Dm in liquid phase systems containing polar solutes and solvents., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a malignant lymphoma with a relatively good prognosis, consisting of CD30-positive, undifferentiated, large cells. We report an elderly patient with C-ALCL which recurred after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) therapy, but was effectively treated with the third-generation etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone and bleomycin (VNCOP-B) regimen. It is characterized by the completion of treatment in 8 weeks, its applicability on an outpatient basis, and a low incidence of cardiotoxicity and mucosal symptoms. Although our patient had no side-effects during chemotherapy, patients should be carefully monitored for side-effects, especially infection. In conclusion, the VNCOP-B regimen might be an effective treatment for elderly patients with good performance status, CHOP-resistant patients or patients with aggressive non-Hodgkin's lymphoma.

We obtained an antibody, anti-inner root sheath cells antibody (anti-IRSC Ab), that reacted with the inner root sheath (IRS) cells especially trichohyalin granules (THG). In order to compare the properties of anti-IRSC Ab and AE15, which is a specific monoclonal antibody against THG, histochemical and biochemical examinations were performed. In vivo localization with anti-IRSC Ab and AE15 indicated that both antibodies reacted with THG, but anti-IRSC Ab reacted with THG in the suprabulbar region of the Huxley layer, whereas AE15 reacted with THG in the suprabulbar region and upper bulbar portion of the Huxley layer, as shown by immunohistochemical and immunoelectron microscopic analyses. The results of immunoblot analysis showed that anti-IRSC Ab reacted with a protein spot at 45 kDa, pI 6.5, but AE15 reacted with high molecular weight proteins at pI 5.5. Furthermore, anti-IRSC Ab reacted with specimens of squamous cell carcinoma (SCC) but did not react with those of basal cell carcinoma (BCC). In contrast, AE15 reacted with neither SCC nor BCC. These findings suggest that anti-IRSC Ab and AE 15 recognized different component proteins in THG, and therefore indicated that THG, like as keratohyalin granules, might consist of several proteins. It is the novel finding that the anti-IRSC Ab positive substance in THG in the normal hair and SCC cells.

Human mast cells are well known to produce a serine protease, tryptase, which appears to play a pathogenic role in various skin inflammations. It was previously reported that a rat homologue of bikunin may inhibit tryptase activity. Various type of cells (i.e. keratinocytes) are able to produce this protein inhibitor, it still remains unclear if bikunin is present in dermal inflammatory milieu, in which mast cells, through secretion of tryptase, play an inflammatory role. Therefore, the purpose of the present study was to exploit expression and production of bikunin in dermis and dermal constituents. We first compared the dermal mast cells in psoriatic lesions with those in lesional skin of atopic dermatitis or of chronic eczema by use of immunoelectron microscopy and immunohistochemical analyses using antibodies to bikunin and tryptase. Then, we tested what kinds of cytokines may regulate the de novo synthesis of bikunin. To do so, RNA was extracted from a human mastocytic cell line, HMC-1, reverse-transcribed, and semiquantitative RT-PCR was performed using primers specific for bikunin. With immunoelectron microscopy, bikunin was found to localize on the cell membrane, while tryptase was in the secretary granules of the mast cells. In psoriatic lesions, around 70% of dermal mast cells were positive for both tryptase and bikunin, and the remaining was mostly positive for tryptase, but the expression of bikunin was under the detection limit of the experimental setting. This observation was seen in only psoriatic lesions, even in almost cured lesions, while in atopic dermatitis or chronic eczema only mast cells doubly positive for bikunin and tryptase were seen. In HMC-1, bikunin was constitutively expressed at an mRNA level, which was upregulated by stimulation with interleukine-4, but was suppressed by interferon-gamma. Bearing in mind the concept that in psoriasis local cytokine milieu is shifted toward a Th1 pattern (predominant secretion of interferon-gamma), tryptase-positive, bikunin-negative mast cells may be induced.

Skin samples from patients with extra-mammary Paget disease, Bowen's disease, atopic dermatitis, psoriasis and non-lesional skin of nevus pigmentosus were immunohistochemically examined with an anti-soluble erythropoietin receptor antibody (anti-sEPOR antibody), and only the dermal mast cells positively stained in all skin samples were examined. These positively stained dermal cells were proved to be mast cells by double staining with anti-sEPOR antibody and either with anti-bikunin antibody or anti-tryptase antibody. Immunoelectron microscopically these EPOR were found in the secretory granules of the dermal mast cells. Further, EPOR in the mast cells may be consisting of only the extracellular domain of erythropoietin receptor molecule as the mast cells were immunohistochemically not reacted with an antibody to the C-terminal peptide of EPOR. Human mast cell line, HMC-1 cells has immunohistochemically the erythropoietin receptor, which was consisting of a 43 kDa major protein and a 20 kDa minor protein in the immunoelectrophoresis. These data may indicate that EPOR in the mast cells may not be the whole molecule, but probably the soluble one of EPOR.