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A new type of dual spin valve (DSV) structure with enhanced giant magnetoresistance (GMR) ratio is proposed, and the performance is characterized by the prototype read heads. The bottom part of DSV is kept as a synthetic pinned structure and only the top part adopts a monolayer pinned structure. The top monolayer pin DSV (TM-DSV) showed three percentage points higher GMR ratio and 20% higher [DELTA]R value. After the mechanical lapping process, the monolayer pinned layer can be stabilized by not only sense current but also large stress induced anisotropy due to Villari effect. After the quantitative analysis, the induced stress is measured to be about 4.2 x [10.sup.9] N/[m.sup.2]. The bias point was tuned by adjustment of Cu spacer layer thickness using the RKKY interaction between pinned layer and free layer. There is no reliability concern related to the monolayer pinned structure. In a perpendicular magnetic recording system, TM-DSV technology could successfully demonstrate the output of 35.5 mV/[micro]m and ~170 Gbits/[in.sup.2] density feasibility. Index Terms--DSV, monolayer pin, RKKY interaction, stress induced anisotropy, synthetic pin, Villari effect.

What is known and objective The implementation of appropriate epidemiological methodology using medical information databases ( MIDs) to evaluate the effects of regulatory actions has been highly anticipated. To assess scientific methods for active pharmacovigilance using MIDs, we conducted a quantitative assessment of the impact of two regulatory actions by the Japanese government: (i) restriction of use of oseltamivir in teenagers in March 2007 and (ii) caution against the co-administration of omeprazole ( OPZ) with clopidogrel ( CPG) in April 2010. Methods Data were obtained from four hub hospitals in Japan. We measured the seasonal proportion of patients prescribed oseltamivir to those prescribed neuraminidase inhibitors for the 2002/2003 to 2010/2011 seasons. The monthly proportion of patients co-administered OPZ and CPG ( OPZ+ CPG) to those prescribed CPG was measured from May 2009 to April 2011. We evaluated the changes observed with implementation of the regulatory actions. To estimate the impact of the actions, we conducted segmented regression analysis using interrupted time series data. The impact was assessed by two parameter estimates of the regression model: the change in level for short-term effects and change in trend for long-term effects. Results and discussion The use of oseltamivir in the target 10-19 years age group showed a significant and large decline (63·16%) immediately after the intervention ( P = 0·0008). No change was observed in OPZ+ CPG, although there was a relative inhibitory trend for OPZ+ CPG compared with co-administration of lansoprazole or rabeprazole with CPG as the control group. When restricted to new users of CPG, the stratified results were consistent with the overall results. What is new and conclusion The current analysis demonstrates the effectiveness of two regulatory actions. The results of the current study indicate that MID research can contribute to assessing and improving pharmacovigilance activities. [ABSTRACT FROM AUTHOR]

Objectives: To promote the exchange of knowledge and standardization of medical procedures and medical systems in the Asia-Pacific region, we established a medical network with high-quality moving images over broadband Internet lines in February 2003.Methods: Real-time teleconferences and live demonstrations with medical-quality videos, broadcast via the Digital Video Transport System, have been used to teach surgical techniques and other medical procedures across national borders. The Asia-Pacific Advanced Network (APAN) committee in August 2005 formally approved our proposal to establish a medical working group within APAN. The network was expanded by the launch of the Trans-Eurasia Information Network 2 in 2006. By the end of 2006, we had conducted 82 events, in 10 countries in the Asia-Pacific region. The multi-station event has increased every year.Results: There have been no serious transmission problems or ethical conflicts so far. With these experiences and current achievements, we hope to extend this advanced network system to the entire Asia-Pacific.Conclusion: This system is a promising and very useful tool for the standardization of medical system and procedures across national borders. Drawing upon these experiences and current achievements, we hope to extend this advanced network system to the entire Asia-Pacific region. [ABSTRACT FROM AUTHOR]

Pulmonary vein (PV) antrum isolation (PVAI) that involves electrically isolating PV foci is a useful treatment strategy for atrial fibrillation (AF). However, non-PV triggers during/after the PVAI are observed in approximately 30 % of AF cases, contributing to AF recurrence. We present the case of an 84-year-old woman who underwent ablation of recurrent symptomatic paroxysmal AF in our hospital. AF was easily induced following spontaneous activity (SA) from non-PV triggers even after completing the PVAI, left atrial posterior wall isolation with roof and bottom lines, and superior vena cava isolation. Interestingly, the area of the earliest activation site of the SAs initiating AF and that with a fractionation mapping score of ≥4 corresponded. AF was steadily terminated during ablation of this fractionated area, and the programmed stimulation could no longer induce any SA or AF. This case report demonstrated that the area with a score of ≥4 points on the fractionation mapping calculated by EnSite™ (Abbott, Abbott Park, IL, USA) during sinus rhythm may contribute to the initiation and maintenance of paroxysmal AF. In patients whose AF does not resolve during ablation, physicians may consider performing an additional targeted ablation of the area with a fractionation mapping score of ≥4, even in patients with paroxysmal AF., Learning Objective: The area with a fractionation mapping score of ≥4 calculated by EnSite™ during sinus rhythm might play an important role in producing spontaneous activities and initiating and maintaining paroxysmal atrial fibrillation (AF). Thus, if the AF does not terminate during ablation, physicians should consider performing an additional targeted ablation of the area with a fractionation mapping score of ≥4, even if it is paroxysmal., Competing Interests: None declared., (© 2024 Japanese College of Cardiology. Published by Elsevier Ltd.)

The presence of epicardial connections (ECs) between the pulmonary veins (PVs) and atrium may contribute to atrial fibrillation (AF) recurrence. This study aimed to determine the impact of sleep-disordered breathing (SDB) on the presence of ECs and the interplay between SDB and ECs on AF recurrence.We retrospectively reviewed 400 consecutive non-valvular AF patients. Among them, 235 patients exhibiting a 3% oxygen desaturation index (ODI) of ≥ 10 events/hour underwent polysomnography to evaluate the SDB severity, measured by the apnea-hypopnea index (AHI). To facilitate the ablation of AF and ECs, a high-density mapping catheter (HDMC) was employed. AF recurrence was evaluated over a 12-month period post-AF ablation.The key findings included: 1) 63% of AF patients with ECs had SDB with an AHI ≥ 20 events/hour. 2) Despite achieving complete PV isolations and precise EC ablation using an HDMC, SDB presence was associated with an increased AF recurrence. 3) Continuous positive airway pressure therapy for SDB improved AF recurrence among the AF patients with both ECs and SDB (57% versus 73%; P = 0.016). 4) AHI (odds ratio [OR] = 1.91, ≥ 28.4 events/hour) and left atrial volume (LAV) (OR = 1.42, ≥ 128.3 mL) were independent predictors of the presence of ECs, and AHI (OR = 1.44, ≥ 27.8 events/hour) was an independent predictor of the presence of AF recurrence.It is essential for physicians to recognise the potential complexity of ECs and SDB in AF patients. Thus, screening and treating SDB in AF patients presenting with ECs might play a pivotal role in suppressing AF recurrence.

Background & Aims: Metabolic and transcriptional programs respond to extracellular matrix-derived cues in complex environments, such as the tumor microenvironment. Here, we demonstrate how lysyl oxidase (LOX), a known factor in collagen crosslinking, contributes to the development and progression of cholangiocarcinoma (CCA)., Methods: Transcriptomes of 209 human CCA tumors, 143 surrounding tissues, and single-cell data from 30 patients were analyzed. The recombinant protein and a small molecule inhibitor of the LOX activity were used on primary patient-derived CCA cultures to establish the role of LOX in migration, proliferation, colony formation, metabolic fitness, and the LOX interactome. The oncogenic role of LOX was further investigated by RNAscope and in vivo using the AKT/NICD genetically engineered murine CCA model., Results: We traced LOX expression to hepatic stellate cells and specifically hepatic stellate cell-derived inflammatory cancer-associated fibroblasts and found that cancer-associated fibroblast-driven LOX increases oxidative phosphorylation and metabolic fitness of CCA, and regulates mitochondrial function through transcription factor A, mitochondrial. Inhibiting LOX activity in vivo impedes CCA development and progression. Our work highlights that LOX alters tumor microenvironment-directed transcriptional reprogramming of CCA cells by facilitating the expression of the oxidative phosphorylation pathway and by increasing stemness and mobility., Conclusions: Increased LOX is driven by stromal inflammatory cancer-associated fibroblasts and correlates with diminished survival of patients with CCA. Modulating the LOX activity can serve as a novel tumor microenvironment-directed therapeutic strategy in bile duct pathologies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to clarify (1) the association among the atrial fibrillation (AF) type, sleep-disordered breathing (SDB), heart failure (HF), and left atrial (LA) enlargement, (2) the independent predictors of LA enlargement, and (3) the effects of ablation on those conditions in patients with AF. The study's endpoint was LA enlargement (LA volume index [LAVI] ≥ 78 mL/m 2 ).Of 423 patients with nonvalvular AF, 236 were enrolled. We evaluated the role of the clinical parameters such as the AF type, SDB severity, and HF in LA enlargement. Among them, 141 patients exhibiting a 3% oxygen desaturation index (ODI) of ≥ 10 events/hour underwent polysomnography to evaluate the SDB severity measured by the apnea-hypopnea index (AHI). The LA enlargement and HF were characterized by the LA diameter/LAVI, an increase in the B-type natriuretic peptide level, and a lower left ventricular ejection fraction.This study showed that non-paroxysmal AF (NPAF) rather than paroxysmal AF (PAF), the SDB severity, LA enlargement, and HF progression had bidirectional associations and exacerbated each other, which generated a vicious cycle that contributed to the LA enlargement. NPAF (OR = 4.55, P < 0.001), an AHI of ≥ 25.10 events/hour (OR = 1.55, P = 0.003), and a 3% ODI of ≥ 15.43 events/hour (OR = 1.52, P = 0.003) were independent predictors of an acceleration of the LA enlargement. AF ablation improved the HF and LA enlargement.To break this vicious cycle, AF ablation may be the basis for suppressing the LA enlargement and HF progression subsequently eliminating the substrates for AF and SDB in patients with AF.

NSD2 is a histone methyltransferase predominantly catalyzing di-methylation of histone H3 on lysine K36. Increased NSD2 activity due to mutations or fusion-events affecting the gene encoding NSD2 is considered an oncogenic event and a driver in various cancers, including multiple myelomas carrying t(4;14) chromosomal translocations and acute lymphoblastic leukemia's expressing the hyperactive NSD2 mutant E1099 K. Using DNA-encoded libraries, we have identified small molecule ligands that selectively and potently bind to the PWWP1 domain of NSD2, inhibit NSD2 binding to H3K36me2-bearing nucleosomes, but do not inhibit the methyltransferase activity. The ligands were subsequently converted to selective VHL1-recruiting NSD2 degraders and by using one of the most efficacious degraders in cell lines, we show that it leads to NSD2 degradation, decrease in K3 K36me2 levels and inhibition of cell proliferation., (© 2023 Wiley-VCH GmbH.)

Background: The use of international telemedicine conferences for doctor-to-doctor education has increased following the coronavirus disease 2019 pandemic to ensure health and safety. Previous studies have shown that administrative tasks are an obstacle to promoting international telemedicine conferences but have not identified the type of system needed to alleviate this burden., Objective: The Asia-Pacific Advanced Network Medical Working Group (APAN-MWG) is an international telemedicine network that includes 1171 medical institutions and 3653 members as of July 21, 2021. The APAN-MWG has supported international telemedicine conferences since 2005 and implemented a program management system in 2014. The present study explores the conference organizers' tasks and evaluates the APAN-MWG management system through a survey of organizers., Methods: We developed a system called med-hok for managing conference programs, international medical institutions, and their members. We investigated all event programs using the med-hok system from June 3, 2015 to July 21, 2021. The target samples included 64 conference programs in 12 series hosted by 13 program organizers. The effectiveness of the system was evaluated using a four-point Likert scale (very good, good, poor, and very poor). The User Experience Questionnaire (UEQ) was used to assess user experience., Results: The survey response rate of the program organizers, who hosted 11 different program series in 7 Asian countries, was 92% (12/13). The administrative tasks for managing the programs were primarily handled by physicians (67%, 8/12), followed by technicians (17%, 2/12). The average program scope encompassed 7 countries, 10 institutions, and 44 members. The largest program comprised 194 members from 49 institutions in 25 countries and was managed by two physicians and one technician. Most program organizers (8/12, 67%) indicated that verifying member information was the most burdensome aspect of organizing teleconferences. Over 90% of respondents positively evaluated med-hok in the following areas: "Confirmation of institution information," "Confirmation of member information," "Confirmation of technical information," "Maintaining the latest status of the program," "Announcing and publicizing the event," and "Formatting and correcting misspellings." They rated user experience positively for all aspects (attractiveness: 1.22; practical quality: 1.42; and hedonic quality: 1.24)., Conclusions: Many tasks of organizing casual international telemedicine conferences are handled by physicians and technicians with no operating funds or staff, unlike those in large academic conferences. The proposed system was found to help program organizers manage participants and communicate information effectively. These findings suggest that international telemedicine networks should implement an administrative support system to conduct program operations efficiently., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

A 74-year-old man was admitted to our hospital to undergo radiofrequency catheter ablation (RFCA) of persistent atrial fibrillation (AF). We found that he had a history of heparin-induced thrombocytopenia (HIT). Thus, a direct thrombin inhibitor, Argatroban Hydrate (Argatroban ® ), was used instead of heparin as anticoagulation therapy during the RFCA procedure. Finally, the AF was successfully treated by RFCA without any complications. Given these findings, the direct thrombin inhibitor Argatroban ® may be effective and feasible for anticoagulation therapy during RFCA procedures for AF in patients with HIT, such as the present case.

Background: The existence of epicardial connection(s) (ECs) between the pulmonary veins (PVs) and atrium may hinder establishing a complete PV antrum isolation (AI) (PVAI) in patients with atrial fibrillation (AF). Thus, the purpose of this study was to determine the prevalence and location of ECs inside the conventional PVAI lines., Methods and results: Three-hundred consecutive patients with non-valvular AF were evaluated. This study revealed that: (1) the prevalence of patients with ECs and the number of ECs per patient between the PVs and atrium became significantly greater, respectively, in accordance with the progression of paroxysmal to long-lasting AF and left atrial enlargement; (2) some ECs were located at sites far distal to the PVAI lines; (3) 25% of ECs could be detected only by high-density mapping catheters, but not by conventional circular mapping catheters; (4) a B-type natriuretic peptide (BNP) level of 176.6pg/mL and left atrial volume (LAV) of 129.0 mL may be important predictors of the presence of ECs; and (5) the rate of conduction of ECs from the right PVs was dominantly to the atrium and His-bundle, and that from the left PVs to the coronary sinus was most dominant., Conclusions: The PVAI may not be completed by using only a conventional PVAI method, and additional EC ablation inside the PVAI lines detected using high-density mapping may be able to achieve a more complete PVAI.

Organs are anatomically compartmentalised to cater for specialised functions. In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. While several studies indicate the critical importance of non-epithelial cells during development and homeostasis, the extent to which these cells contribute to regionalisation during morphogenesis remains unexplored. Here, we identify a mesenchymal-epithelial crosstalk that shapes the developing SI during late morphogenesis. We find that subepithelial mesenchymal cells are characterised by gradients of factors supporting Wnt signalling and stimulate epithelial growth in vitro. Such a gradient impacts epithelial gene expression and regional villus formation along the anterior-posterior axis of the SI. Notably, we further provide evidence that Wnt signalling directly regulates epithelial expression of Sonic Hedgehog (SHH), which, in turn, acts on mesenchymal cells to drive villi formation. Taken together our results uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments that is central for anterior-posterior regionalisation and correct formation of the SI., (© 2022. The Author(s).)

We examined osteoporosis medication use and factors affecting persistence in 497 patients with fragility hip fractures. Only 25.5% of patients received continuous medication for 3 years, and 44.1% of patients received no treatment. Low Barthel index at discharge was a risk factor for both non-treatment and non-persistence to osteoporosis medication., Purpose: Fragility hip fractures (FHF) caused by osteoporosis decrease the quality of life and worsen life expectancy. Use of osteoporosis medication may be an efficient method in the prevention of secondary FHF. However, previous studies have reported low rates of osteoporosis medication and persistence after FHF. This study aimed to evaluate osteoporosis medication use and factors affecting persistence in patients with FHF in the northern Kyushu area of Japan., Methods: A total of 497 FHF patients aged ≥ 60 years with a 3-year follow-up were included. We prospectively collected data from questionnaires sent every 6 months regarding compliance with osteoporosis medication. We compared baseline characteristics among three groups: no treatment (NT), no persistence (NP), and persistence (P), and conducted multivariable regression models to determine covariates associated with non-treatment (NT vs. NP/P) and non-persistence (NP vs. P)., Results: There were 219 (44.1%), 151 (30.4%), and 127 (25.5%) patients in the NT, NP, and P groups, respectively. Factors associated with non-treatment were male sex, chronic kidney disease, no previous osteoporosis treatment, and low Barthel index (BI) at discharge. The only factor associated with non-persistence was a low BI at discharge. Factors associated with a low BI at discharge were male sex, older age, trochanteric fracture, and surgical delay., Conclusion: Low BI at discharge is a risk factor for both non-treatment and non-persistence to osteoporosis medication. Therefore, appropriate interventions to improve BI may result in persistence to osteoporosis medication., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background: Hemostasis at the femoral venous access site after cryoballoon ablation (CA) for atrial fibrillation (AF) is often prolonged because of aggressive anticoagulation and the use of 15-Fr-caliber sheaths. The Nepcell S TM (NC) is a newly developed hemostatic pad made of fibrosed calcium alginate extracted from natural seaweed. The calcium ions from the NC accelerate the clotting cascade. This single-center randomized clinical trial assessed the efficacy and safety of the NC in patients undergoing CA for AF. Methods and Results: In all, 62 patients undergoing CA for non-valvular paroxysmal AF were randomly assigned to either the NC or control group. The primary endpoints of this study were time to hemostasis, internal hemorrhage, and rebleeding. Secondary endpoints were the length of hospital stay (LOS) and vascular complications at 1 month. The time to hemostasis was significantly shorter in NC than control group (mean [±SD] 377±216 vs. 505±241 s; P=0.031). The frequency of internal hemorrhaging (6% vs. 37%; P=0.003) and rebleeding (0% vs. 13%; P=0.033) was lower in the NC than control group, contributing to a decreased LOS in the NC group (3.56±0.67 vs. 4.23±0.73 days; P<0.001). There were no NC-related vascular complications at the 1-month echographic examination. Conclusions: The use of NC was associated with a shorter hemostasis time and fewer bleeding complications in patients undergoing CA for AF, leading to a shorter LOS., Competing Interests: The authors declare no conflict of interests for this article., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Objective We previously reported that, among asymptomatic patients with type 2 diabetes mellitus (T2DM) without a history of cardiovascular disease (CVD), up to 19% of the patients with myocardial ischemia were detected by annual cardiovascular screening tests (ACVSTs). Thus, the present study assessed the long-term clinical outcomes of ACVSTs in those patients. Methods Six hundred and fifty-seven outpatients with T2DM who received ACVSTs at least once or not at all from April 2014 to March 2018 were defined as the S and NS groups, respectively. The data were compared between these two groups. Results This study revealed that, among outpatients with T2DM in our hospital over those four years, with the increasing frequency of receiving ACVSTs, 1) the frequency of the internal use of statins, anti-platelets, and renin-angiotensin system inhibitors, which are well-known as medications for preventing CVD, significantly increased; 2) low-density lipoprotein-cholesterol and triglyceride levels significantly improved; 3) levels of highly sensitive C-protein, a strong predictors of CVD, were significantly suppressed; 4) the progression of renal dysfunction was significantly suppressed; 5) the cumulative of four-point major adverse cardiovascular events and admissions due to heart failure significantly decreased; and 6) the cumulative of all-cause mortality was significantly suppressed. Conclusions Given the above, it may be important to continue ACVSTs in outpatients with T2DM without a history of CVD for several years.

Objective The serum cholinesterase (ChE) level has been used for the evaluation of the nutritional status in daily practice. It has been reported that the serum ChE level is significantly more elevated in patients with three-vessel coronary disease than in normal subjects. Thus, the aim of this study was to assess the influence of serum ChE levels in patients suspected of having stable coronary artery disease (CAD). Methods The relationship between myocardial ischemia and the serum ChE levels was evaluated in 559 consecutive patients suspected of having stable CAD without a history of cardiovascular disease admitted to our hospitals to undergo coronary angiography. Results This study revealed that, in patients suspected of having stable CAD, 1) the frequency of myocardial ischemia was significantly increased in accordance with the serum ChE levels (p<0.001); 2) higher ChE levels were associated with a higher body mass index (p<0.001) and the co-existence of dyslipidemia (p<0.001), including higher values of low-density lipoprotein-cholesterol (p<0.001) and triglycerides (p<0.001) and serum albumin (p<0.001), as well as a younger age (p<0.001); 3) the specificity and sensitivity of myocardial ischemia were 0.599 and 0.658 at the ChE level of 286 IU/L, respectively; and 4) an increased serum ChE (OR=1.66, p<0.001) was an independent risk factor for myocardial ischemia, in patients suspected of having stable CAD. Conclusion The serum ChE level may be an important diagnostic biomarker in patients suspected of having stable CAD.

Background: Pulmonary vein (PV) antrum isolation (PVAI) has proven to be a useful strategy for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) worldwide. However, non-PV foci, especially from the superior vena cava (SVC), play an important role in initiating and maintaining AF., Methods: In all, 427 consecutive patients with non-valvular AF who were admitted to our hospitals to undergo RFCA of AF using an EnSite ™ system were evaluated. The length from the top of the sinus node to the top of the myocardial sleeve of SVC (L-SVC), longer and shorter diameter of SVC of 1 cm above of junction of right atrium and SVC, and local activation time (LAT) of SVC were measured. Then, the SVC firing was evaluated by an intravenous administration of isoproterenol and adenosine triphosphate., Results: L-SVC, longer and shorter diameter of SVC, and LAT of SVC were significantly longer in the SVC firing group than non-SVC firing group ( P  < .05). Moreover, in accordance with the L-SVC, the frequency of the SVC firing significantly increased ( P  < .001). A univariate analysis and multivariate statistical analysis revealed that L-SVC longer than 37.0 mm (odds ratio 6.39) and longer diameter of SVC (odds ratio 6.78) were independent risk factors for SVC firing in patients with AF who underwent RFCA of AF., Conclusions: In view of these findings, L-SVC longer than 37.0 mm longer diameter SVC longer than 17.0 mm may be one of the important predictors of SVC firing in patients with AF., Competing Interests: The authors report no relationships that could be construed as a conflict of interest., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Objective We recently reported that routine cardiac computed tomography (CT) scans for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) could steadily detect coronary artery lesions (CALs) and could accurately detect myocardial ischemia in 9% of patients with AF who underwent RFCA of AF. The aim of this study was to identify the independent risk factor (s) of myocardial ischemia in those patients. Methods Patient characteristics, blood test, CALs, Ordinal coronary calcium scoring (OCCS), and myocardial Ischemia (MI) were evaluated in 757 consecutive patients who underwent RFCA of AF. Results There were 685 and 72 patients without and with myocardial ischemia, respectively. A univariate analysis and multivariate statistical analysis revealed that a male gender (Odds ratio 2.11), a high number of co-existing coronary risk factors (NCCRF ≥3) (Odds ratio 2.03), an elevated brain natriuretic peptide level (BNP ≥100 pg/mL) (Odds ratio 3.37), an enlarged left atrial volume (≥90 mL) (Odds ratio 2.91), and a high OCCS (≥4) (Odds ratio 13.0) were independent risk factors of myocardial ischemia in patients undergoing RFCA of AF. Conclusion The high OCCS (≥4) by cardiac CT was the strongest independent risk factor of myocardial ischemia in those patients. However, physicians may be able to find the high risk patients of myocardial ischemia by evaluating a male gender, in the presence of a high NCCRF (≥3) and elevated BNP (≥100 pg/mL) without OCCS by cardiac CT in patients undergoing RFCA of AF.

Introduction: We previously reported the clinical benefits of radiofrequency catheter ablation (RFCA) of premature ventricular contractions (PVCs) from the right ventricular outflow tract or near the His-bundle, which can often deteriorate the clinical status. PVCs from the mitral valve (MA-PVCs) also often deteriorate the patients' clinical status. This study aimed to evaluate the effect of ablating MA-PVCs with RFCA from a trans-interatrial septal approach on the clinical status in symptomatic patients with frequent MA-PVCs without structural heart disease., Methods: The frequency of PVCs per the total heart beats by 24-hours Holter monitoring and New York Heart Association (NYHA) functional class in 22 patients with MA-PVCs were evaluated before and 6 months after RFCA., Results: Procedural success was achieved in 20 (91%) of 22 patients. Of the 22 patients, in 15 (68%) and 1 (5%) patient, a successful RFCA on the left ventricular side of the MA using the trans-interatrial septal approach and trans-coronary sinus approach was achieved. Interestingly, in four (18%) patients, a successful RFCA on the left atrial (LA) side of the MA using a trans-interatrial septal approach was achieved. Ablating MA-PVCs readily improved the NYHA functional class compared to that before. A ≥0.62 peak deflection index and ≤30 years old may be one of the important predictors of successfully ablated MA-PVCs from the LA side of the MA., Conclusions: RFCA produces clinical benefits in patients with MA-PVCs. Further, it may be necessary to initially consider a trans-interatrial septal approach to ablate these PVCs., (© 2020 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Almost all institutions routinely perform cardiac computed tomography (CT) before radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) to evaluate the cardiac anatomy. The ideal timing of the CT image acquisition is different between for RFCA of AF and for evaluation of coronary artery lesions (CALs). Thus, the aim of this study was to assess whether 64- or 320-line routine cardiac CT scans before RFCA of AF could evaluate both coronary artery lesions and pulmonary veins (LA-PVs) anatomy at the timing of the image acquisition of the LA-PVs in patients with AF who underwent RFCA of AF. The CALs were evaluated in 606 consecutive patients who underwent RFCA of AF assessed by the ideal timing of the CT image acquisition for RFCA of AF, and myocardial ischemia (MI) was also evaluated in patients with severe coronary stenosis (≥ 50%) and unevaluable CALs due to their severe coronary calcification and banding artifact by additional examinations combined with exercise stress testing, 201 Tl scintigraphy, and/or fractionated flow reserve measurements. This study revealed that, in patients with AF who underwent RFCA of AF, (1) both 64- and 320-line cardiac CT scans for RFCA of AF could evaluate CALs in 93% of those patients, (2) the prevalence of MI was 9%, (3) significant relationships between the CHADS 2 score and prevalence of MI were observed (p = 0.003), and (4) the positive predict values of MI in patients with severe coronary stenosis (≥ 50%) and unevaluable CALs also significantly increased in accordance with the CHADS 2 score (p = 0.003). The evaluation of CALs and MI by routine cardiac CT for RFCA of AF combined with the additional examinations may be one of the most feasible modalities for patients with AF.

A 66-year-old female, whom received a pulmonary vein (PV) isolation (PVAI) with linear ablation of the carina lines between the superior and inferior PVs of both the right and left PVs for atrial fibrillation (AF), was admitted to receive a radiofrequency catheter ablation (RFCA) of symptomatic drug-refractory atrial tachycardia (AT). The EnSite TM analysis by the Advisor TM HD Grid catheter during the AT could easily detect that the carina between the right superior and inferior PVs exhibited a low voltage area (< 0.5 mV), in addition to the fact that the electrical activation turned around the right PVs in a figure 8, even though mapping was performed during AT. This AT was steadily terminated, after commencing the radiofrequency energy delivery to the carina of the right PVs., Competing Interests: None, (Copyright © Japan Medical Association.)

Purpose: Fragility hip fractures (FHFs) are associated with a high risk of mortality, but the relative contribution of various factors remains controversial. This study aimed to evaluate predictive factors of mortality at 1 year after discharge in Japan., Methods: A total of 497 patients aged 60 years or older who sustained FHFs during follow-up were included in this study. Expected variables were finally assessed using multivariable Cox proportional hazards models., Results: The 1-year mortality rate was 9.1% (95% confidence interval: 6.8-12.0%, n = 45). Log-rank test revealed that previous fractures ( p = 0.003), Barthel index (BI) at discharge ( p = 0.011), and place-to-discharge ( p = 0.004) were significantly associated with mortality for male patients. Meanwhile, body mass index (BMI; p = 0.023), total Charlson comorbidity index (TCCI; p = 0.005), smoking ( p = 0.007), length of hospital stay (LOS; p = 0.009), and BI ( p = 0.004) were the counterparts for females. By multivariate analyses, previous vertebral fractures (hazard ratio (HR) 3.33; p = 0.044), and BI <30 (HR 5.42, p = 0.013) were the predictive variables of mortality for male patients. BMI <18.5 kg/m 2 (HR 2.70, p = 0.023), TCCI ≥5 (HR 2.61, p = 0.032), smoking history (HR 3.59, p = 0.018), LOS <14 days (HR 13.9; p = 0.007), and BI <30 (HR 2.76; p = 0.049) were the counterparts for females., Conclusions: Previous vertebral fractures and BI <30 were the predictive variables of mortality for male patients, and BMI <18.5 kg/m 2 , TCCI ≥5, smoking history, LOS <14 days, and BI <30 were those for females. Decreased BI is one of the independent and preventable risk factors. A comprehensive therapeutic approach should be considered to prevent deterioration of activities of daily living and a higher risk of mortality.

The sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating 1,2 . Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cell fate decisions. Following an expansion phase, equipotent progenitors transition into a phase of homeostatic turnover, which is correlated with changes in the mechanical properties of the stroma and spatial restrictions on gland size. Expression of the oncogene KrasG12D results in a release from these constraints and unbridled gland expansion. Quantitative clonal fate analysis reveals that, during this phase, the primary effect of the Kras oncogene is to drive a constant fate bias with little effect on cell division rates. These findings provide insight into the developmental programme of the SG, as well as the mechanisms that drive tumour progression and gland dysfunction.

The utilization of electronic medical records and multimodal medical data is an ideal approach to build a real-time and precision registry type study with a smaller effort and cost, which may fill a gap between evidence-based medicine and the real-world clinical practice. The Japan Ischemic heart disease Multimodal Prospective data Acquisition for preCision Treatment (J-IMPACT) project aimed to build an clinical data registry system that electronically collects not only medical records, but also multimodal data, including coronary angiography and percutaneous coronary intervention (PCI) report, in standardized data formats for clinical studies.The J-IMPACT system comprises the standardized structured medical information exchange (SS-MIX), coronary angiography and intervention reporting system (CAIRS), and multi-purpose clinical data repository system (MCDRS) interconnected within the institutional network. In order to prove the concept, we acquired multimodal medical data of 6 consecutive cases that underwent PCI through the J-IMPACT system in a single center. Data items regarding patient background, laboratory data, prescriptions, and PCI/cardiac catheterization report were correctly acquired through the J-IMPACT system, and the accuracy of the multimodal data of the 4 categories was 100% in all 6 cases.The application of J-IMPACT system to clinical studies not only fills the gaps between randomized clinical trials and real-world medicine, but may also provide real-time big data that reinforces precision treatment for each patient.

Objective: This study aimed to investigate the effects of radiofrequency catheter ablation (RFCA) and clinical and electrophysiological characteristics in symptomatic patients with premature ventricular contractions (PVCs) from near the His-bundle (His-PVCs)., Methods: The patient characteristics, prevalence of complications with any life style related disease (ALSRD) including hypertension, dyslipidemia, or diabetes mellitus, and/or cardiovascular disease (CVD) including coronary artery disease, cerebrovascular disease, renal dysfunction, or cardiomyopathy, clinical status, frequency of PVCs evaluated by 24hour Holter monitoring, echocardiography including the left ventricular diastolic dysfunction (LVDD) parameters, and electrophysiological findings were evaluated in 14 consecutive symptomatic patients with His-PVCs., Results: The prevalence of males, being elderly and/or slightly obese, current and/or history of smoking, ALSRD or CVD related complications, and LVDD probably resulting from ALSRD and/or CVD complications were higher in patients with His-PVCs. RFCA of His-PVCs steadily decreased the PVC frequency and improved the systolic function, LV dilation, and clinical status, but not the LVDD. There was a significant relationship between the accordance rate of the QRS polarity between sinus rhythm and His-PVCs and the distance between the successful ablation site and His-bundle., Conclusion: The analysis of the QRS duration and accordance rate of the QRS polarity between sinus rhythm and His-PVCs before the RFCA may help to determine the distance between the origin of the PVCs and His-bundle. Further, the appropriate ablation catheter may be selected during the RFCA procedure. Finally, RFCA may be one of the most effective, feasible, and safest therapies for symptomatic patients with His-PVCs., Competing Interests: Authors declare no conflict of interests for this article.

Two cases with severe pectus excavatum and symptomatic atrial fibrillation (AF) underwent radiofrequency catheter ablation (RFCA). Their chest X-ray and computed tomography (CT) findings revealed lateral displacement and clockwise rotation of their hearts, and severe right atrial and mild right ventricular compression against the sternum, but no left atrium compression against the spinal column. The procedure was therefore carefully performed under guidance with CT, intra-cardiac echography, atriography, and a three-dimensions mapping system. Finally, the AF was successfully treated by RFCA without any complications. These findings underscore the importance of understanding cases of abnormal anatomy and carefully designing a strategy before performing any procedure.

Osteoporosis has become a worldwide public health problem, in part due to the fact that it increases the risk of fragility hip fractures (FHFs). The epidemiological assessment of FHFs is critical for their prevention; however, datasets for FHFs in Japan remain scarce. This was a multicenter, prospective, observational study in the northern district of Kyushu Island. Inclusion criteria were age > 60 years with a diagnosis of FHF and acquisition of clinical data by an electronic data capture system. Of 1294 registered patients, 1146 enrolled in the study. Nearly one third of patients (31.8%) had a history of previous fragility fractures. The percentage of patients receiving osteoporosis treatment on admission was 21.5%. Almost all patients underwent surgical treatment (99.1%), though fewer than 30% had surgery within 48 h after hospitalization. Bone mineral density (BMD) was evaluated during hospitalization in only 50.4% of patients. The rate of osteoporosis treatment increased from 21.5% on admission to 39.3% during hospitalization. The main reasons that prescribers did not administer osteoporosis treatment during hospitalization were forgetfulness (28.4%) and clinical judgment (13.6%). Age and female ratio were significantly higher in patients with previous FHFs than in those without. There was a significant difference in the rate of osteoporosis treatment or L-spine BMD values in patients with or without previous FHFs on admission. In conclusion, this study confirmed that the evaluation and treatment of osteoporosis and FHFs is still suboptimal in Japan, even in urban districts.

A 72-year-old woman with symptomatic and drug-refractory paroxysmal atrial fibrillation (AF) underwent radiofrequency catheter ablation (RFCA). She had a history of a total right lung excision. Her chest X-ray and computed tomography (CT) revealed a severely sight-sided dislocation of the heart. Thus, the procedure was carefully performed under guidance of a CT, intracardiac echogram, atriography, and 3D mapping system. Finally, the AF was successfully treated by RFCA without any complications.

Objective: Plaque erosion is increasing its importance as one of the mechanisms of acute coronary syndromes in this statin era. However, the clinical efficacy of currently used lipid-lowering agents in the prevention of thrombotic complications associated with plaque erosion has not been clarified. Therefore, we examined the therapeutic effects of ezetimibe or rosuvastatin monotherapy on spontaneous atherothrombotic occlusion., Approach and Results: Femoral arteries of Japanese white rabbits, fed a high-cholesterol diet, were injured by balloon catheter, and then angiotensin II was continuously administrated. In 94% of these arteries, spontaneous thrombotic occlusions were observed after 5 weeks (median) of balloon injury. Histochemical analyses indicated that the injured arteries had similar pathological features to human plaque erosions; (1) spontaneous thrombotic occlusion, (2) lack of endothelial cells, and (3) tissue factor expression in vascular smooth muscle cells. Ezetimibe (1.0 mg/kg per day), but not rosuvastatin (0.6 mg/kg per day), significantly decreased thrombotic occlusion of arteries accompanied with accelerated re-endothelialization and the decreases of serum oxysterols despite the comparable on-treatment serum cholesterol levels. The 7-ketocholesterol inhibited the migration of human umbilical vein endothelial cells. Both 7-ketocholesterol and 27-hydroxycholesterol increased tissue factor expression in cultured rat vascular smooth muscle cells. Tissue factor expression was also induced by serum from vehicle- or rosuvastatin-treated rabbits, but the induction was attenuated with serum from ezetimibe-treated rabbits., Conclusions: We have established a novel rabbit model of spontaneous atherothromobotic occlusion without plaque rupture that is feasible to test the therapeutic effects of various pharmacotherapies. Ezetimibe may decrease atherothrombotic complications after superficial plaque erosion by reducing serum oxysterols., (© 2018 American Heart Association, Inc.)

We experienced a 41-year-old male with premature ventricular complexes/ventricular tachycardia from the left coronary cusp and distal great cardiac vein of the left ventricular outflow tract successfully treated by radiofrequency catheter ablation utilizing a 3D mapping system (EnSiteNavX/Velocity™ Cardiac Mapping System, St. Jude Medical, St. Paul, MN, USA) without any complications. < Learning objective: The approach from the distal great cardiac vein should be considered as a potential approach and may be one of the effective strategies for ablation of left ventricular outflow tract-premature ventricular complexes/ventricular tachycardia (PVC/VTs). Radiofrequency catheter ablation of frequent PVC/VTs may improve the clinical status and cardiac function.>.

Sub-diffraction imaging of plasma membrane localized proteins, such as the SNARE (Soluble NSF Attachment Protein Receptor) proteins involved in exocytosis, in fixed cells have resulted in images with high spatial resolution, at the expense of dynamical information. Here, we have imaged localized fluorescence bursts of DRONPA-fused SNAP-25 molecules in live chromaffin cells by Total Internal Reflection Fluorescence (TIRF) imaging. We find that this method allows tracking protein cluster dynamics over relatively long times (∼20 min.), partly due to the diffusion into the TIRF field of fresh molecules, making possible the simultaneous identification of cluster size, location and temporal evolution. The results indicate that the DRONPA-fused SNAP-25 clusters display rich dynamics, going from staying constant to disappearing and reappearing in specific cluster domains within minutes.

Background: Moving images are often essential in medical education, to learn new procedures and advanced skills, but, in the past, high-quality movie transmission was technically much more challenging than transmitting still pictures because of technological limitations and cost., Materials and Methods: We established a new system, taking advantage of two advanced technologies, the digital video transport system (DVTS) and the research and education network (REN), which enabled satisfactory telemedicine on a routine basis., Results: Between 2003 and 2013, we organized 360 programs connecting 221 hospitals or facilities in 34 countries in Asia and beyond. The two main areas were endoscopy and surgery, with 113 (31%) and 106 (29%) events, respectively. Teleconferences made up 76% of the total events, with the remaining 24% being live demonstrations. Multiple connections were more popular (63%) than one-to-one connections (37%). With continuous technological development, new high-definition H.323 and Vidyo(®) (Hackensack, NJ) systems were used in 47% and 39% of events in 2011 and 2012, respectively. The evaluation by questionnaires was favorable on image and sound quality as well as programs., Conclusions: Remote medical education with moving images was well accepted in Asia with changing needs and developing technologies.

This paper focuses on new technologies that are practically useful for telemedicine. Three representative systems are introduced: a Digital Video Transport System (DVTS), an H.323 compatible videoconferencing system, and Vidyo. Based on some of our experiences, we highlight the advantages and disadvantages of each technology, and point out technologies that are especially targeted at doctors and technicians, so that those interested in using similar technologies can make appropriate choices and achieve their own goals depending on their specific conditions.

The fluorescence of silver clusters encapsulated by single stranded oligo-DNA (24 cytosine base pairs, C(24):Ag(n)) was used to monitor the transfection of this new silver/DNA fluorophore inside living HeLa cells. For this, the C(24):Ag(n) molecules were complexed with a commercially available transfection reagent Lipofectamine and the internalization of C(24):Ag(n) was followed with confocal fluorescence microscopy. Bright near-infrared fluorescence was observed from inside the transfected HeLa cells, when exciting with 633 nm excitation, opening up the possibility for the use of these C(24):Ag(n) clusters for biological labelling and imaging of living cells and for monitoring the transfection process with limited harm to the living cells.

DNA-encapsulated silver clusters are readily conjugated to proteins and serve as alternatives to organic dyes and semiconductor quantum dots. Stable and bright on the bulk and single molecule levels, Ag nanocluster fluorescence is readily observed when staining live cell surfaces. Being significantly brighter and more photostable than organics and much smaller than quantum dots with a single point of attachment, these nanomaterials offer promising new approaches for bulk and single molecule biolabeling.

Single-stranded oligonucleotides stabilize highly fluorescent Ag nanoclusters, with emission colors tunable via DNA sequence. We utilized DNA microarrays to optimize these scaffold sequences for creating nearly spectrally pure Ag nanocluster fluorophores that are highly photostable and exhibit great buffer stability. Five different nanocluster emitters have been created with tunable emission from the blue to the near-IR and excellent photophysical properties. Ensemble and single molecule fluorescence studies show that oligonucleotide encapsulated Ag nanoclusters exhibit significantly greater photostability and higher emission rates than commonly used cyanine dyes.

The water-soluble, near-IR-emitting DNA-encapsulated silver nanocluster presented herein exhibits extremely bright and photostable emission on the single-molecule and bulk levels. The photophysics have been elucidated by intensity-dependent correlation analysis and suggest a heavy atom effect of silver that rapidly depopulates an excited dark level before quenching by oxygen, thereby conferring great photostability, very high single-molecule emission rates, and essentially no blinking on experimentally relevant time scales (0.1 to >1,000 ms). Strong antibunching is observed from these biocompatible species, which emit >10(9) photons before photobleaching. The significant dark-state quantum yield even enables bunching from the emissive state to be observed as a dip in the autocorrelation curve with only a single detector as the dark state precludes emission from the emissive level. These species represent significant improvements over existing dyes, and the nonpower law blinking kinetics suggest that these very small species may be alternatives to much larger and strongly intermittent semiconductor quantum dots.

The reduction of silver cations bound to the oligonucleotide dC(12) was used to form silver nanoclusters. Mass spectra show that the oligonucleotides have 2-7 silver atoms that form multiple species, as evident from the number of transitions in the fluorescence and absorption spectra. The variations in the concentrations of the nanoclusters with time are attributed to the changing reducing capacity of the solution, and the formation of oxidized nanoclusters is proposed. Via mass spectrometry and circular dichroism spectroscopy, double-stranded structures with Ag(+)-mediated interactions between the bases are observed, but these structures are not maintained with the reduced nanoclusters. Through variations in the pH, the nanoclusters are shown to bind with the N3 of cytosine.

Abstract Much has been written concerning the difficulties faced by visually handicapped persons when they access the internet. To solve some of the problems and to make web pages more accessible, we developed a tool we call the "Easy Bar," which works as a toolbar on the web browser. The functions of the Easy Bar are to change the size of web texts and images, to adjust the color, and to clear cached data that is automatically saved by the web browser. These functions are executed with ease by clicking buttons and operating a pull-down list. Since the icons built into Easy Bar are quite large, it is not necessary for the user to deal with delicate operations. The functions of Easy Bar run on any web page without increasing the processing time. For the visually handicapped, Easy Bar would contribute greatly to improved web accessibility to medical information.

Electrically contacted gold-nanocluster arrays formed within electromigration-induced break junctions exhibit bright, field-dependent electroluminescence in the near infrared (650-800 nm). Intensity autocorrelation of spatially isolated individual nanocluster emission driven at high electrical frequency (f(ac)= approximately 200 MHz) reveals antibunched electroluminescence at room temperature. These results demonstrate the single quantum nature of several-atom gold molecules and suggest their use as room-temperature electrically driven single-photon sources.

A service information system using the Internet, which connected the various people who are related to medical treatment and nursing welfare, was constructed. An intractable neurological disease patient who lives in the Onga district, Fukuoka, Japan, and the people who are related to the service were chosen as test users in an experimental model. The communicated service information was divided into open-use data (electronic bulletin board, welfare service, medical care service, and link to private company service home page) and closed-use data (the individual patient's hysterics). The open data server was installed in an Internet service provider The open data could be accessed not only by the patient, but also by the family, information center, companies, hospitals, and nursing commodity store related to patient's nursing and medical treatment. Closed data server was installed in an information center (public health center). Only patient and information center staff can access the closed data. Patients should search and collect the service information of various medical and welfare services by themselves. Therefore, services prepared for the patient are difficult to know, and they cannot be sufficiently utilized. With the use of this information system, all usable service information became accessible, and patients could easily use it. The electronic bulletin board system (BBS) was used by patients for knowing each other or each others' family, and was used as a device for exchange of wisdom. Also, the questions for the specialist, such as doctor, dentist, teacher, physical therapist, care manager, welfare office staff member, and public health nurse, and the answers were shown on the BBS. By arranging data file, a reference of various patients in question and answer, which appeared in this BBS, was made as "advisory hints" and was added to the open data. The advisory hints became the new service information for the patients and their family. This BBS discovered the possibility of becoming an important information source for companies, hospital and, administration to know the requirements of patients and their families and the kind of services to be served. Although suppliers provide medical and welfare services for the patient, there is a tendency that the service information is sent by the suppliers at their own convenience. The information system in which various people participated was constructed in order to collect information for the patient, taking a patient-oriented approach. The result of the model test showed that this information system using Internet technology is a good system for both the service supplier and its receiver.

Problems involving electromagnetic interference (EMI) with electronic medical equipment are well-documented. However, no systematic investigation of EMI has been done. We have systematically investigated the causes of EMI. The factors involved in EMI were determined as follows: 1) Electric-field intensity induced by invasive radio waves from outside a hospital. 2) Residual magnetic-flux density at welding points in a building. 3) Electric-field intensity induced by conveyance systems with a linear motor. 4) The shielding capacity of hospital walls. 5) The shielding capacity of commercial shields against a wide range frequency radio waves. 6) The immunity of electronic medical equipment. 7) EMI by cellular telephone and personal handy-phone system handsets. From the results of our investigation, we developed a following practical procedure to prevent EMI. 1) Measurement of electric-field intensity induced by invasive radio waves from outside the hospital and industrial systems in the hospital. 2) Measurement of residual magnetic-flux density at electric welding points of hospital buildings with steel frame structures. 3) Control of the electromagnetic environment by utilizing the shielding capacity of walls. 4) Measurement of the immunity of electronic medical equipment. And 5) Installation of electronic gate equipment at the building entrance to screen for handsets.