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Background: Idarucizumab, a dabigatran-specific reversal agent, was launched in Japan in 2016. The J-Dabigatran Surveillance 2 study was designed to assess the characteristics and outcomes of dabigatran-treated patients after the launch of idarucizumab., Methods: Patient characteristics and outcomes, including thromboembolic and bleeding events, of dabigatran-naïve patients with non-valvular atrial fibrillation (NVAF) who received dabigatran etexilate [110 mg or 150 mg twice-daily (b.i.d.)] for the prevention of ischemic stroke and systemic embolism were investigated and presented descriptively. Absolute standardized differences (ASD) in baseline characteristics compared with the first J-Dabigatran Surveillance (J-Dabi1; 2011-2013) study were included., Results: In total, 5660 patients were enrolled and 5436 were analyzed in this study; 3516 and 1898 received 110 mg b.i.d. and 150 mg b.i.d. dabigatran, respectively; 22 received other doses. The overall duration of follow-up (mean ± standard deviation) was 287 ± 179 days. Baseline characteristics, including stroke/bleeding-risk scores, were typical of this patient population. Overall, paroxysmal, persistent, permanent, and symptomatic atrial fibrillation were observed for 53.2%, 27.1%, 13.7%, and 53.9% of patients, respectively (J-Dabi1 ASD: 0.2, 0.0, 0.3, and 0.2, respectively). Catheter ablation was selected in 27.9% of patients (J-Dabi1 ASD: 0.6). Rates of clinical outcomes were low in the study (mostly <2%/year). The incidence rate of major bleeding was 1.1%/year (n = 46) and stroke/transient ischemic attack/systemic embolism was 1.7%/year (n = 71). Twelve (0.2%) patients received idarucizumab, commonly for serious bleeding events, and most recovered., Conclusions: Dabigatran continues to be safe and well tolerated in patients with NVAF for stroke and systemic embolism prevention and continues to be prescribed appropriately. Treatment outcomes have not changed since the availability of idarucizumab. Since the J-Dabi1 study, treatment guidelines for anticoagulation use in NVAF have been updated based on emerging clinical evidence, accounting for differences in patient characteristics, and making dabigatran a preference for distinct patient populations., Competing Interests: Declaration of competing interest Takeshi Yamashita has received remuneration from Boehringer Ingelheim, Daiichi Sankyo, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Novartis, Otsuka Pharmaceutical, Ono Pharmaceutical, and Toa Eiyo, and research funding from Boehringer Ingelheim, Bristol-Myers Squibb, Bayer Healthcare, and Daiichi Sankyo; Shinichiro Uchiyama has received remuneration from Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo, and Sanofi; Hirotsugu Atarashi has received remuneration from Boehringer Ingelheim and Daiichi Sankyo; Ken Okumura has received remuneration from Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo, and Pfizer; Yukihiro Koretsune has received remuneration from Daiichi Sankyo, Boehringer Ingelheim, Bayer Healthcare, Bristol-Myers Squibb, and Pfizer; Masahiro Yasaka has received remuneration from Boehringer Ingelheim, Bayer Healthcare, and Daiichi Sankyo, and research funding from Boehringer Ingelheim; Junichi Wakayama is an employee of EPS Corporation; Taku Fukaya is an employee of Nippon Boehringer Ingelheim; Hiroshi Inoue has received remuneration from Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo, and Bristol-Myers Squibb., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We developed a method to measure the rupture forces between antibody and antigen by atomic force microscopy (AFM). Previous studies have reported that in the measurement of antibody-antigen interaction using AFM, the specific intermolecular forces are often obscured by nonspecific adhesive binding forces between antibody immobilized cantilever and substrate surfaces on which antigen or nonantigen are fixed. Here, we examined whether detergent and nonreactive protein, which have been widely used to reduce nonspecific background signals in ordinary immunoassay and immunoblotting, could reduce the nonspecific forces in the AFM measurement. The results showed that, in the presence of both nonreactive protein and detergent, the rupture forces between anti-ferritin antibodies immobilized on a tip of cantilever and ferritin (antigen) on the substrate could be successfully measured, distinguishing from nonspecific adhesive forces. In addition, we found that approach/retraction velocity of the AFM cantilever was also important in the reduction of nonspecific adhesion. These insights will contribute to the detection of specific molecules at nanometer scale region and the investigation of intermolecular interaction by the use of AFM.

Low-resolution three-dimensional structures of acto-myosin subfragment-1 (S1) complexes were retrieved from X-ray fiber diffraction patterns, recorded either in the presence or absence of ADP. The S1 was obtained from various myosin-II isoforms from vertebrates, including rabbit fast-skeletal and cardiac, chicken smooth and human non-muscle IIA and IIB species, and was diffused into an array of overstretched, skinned skeletal muscle fibers. The S1 attached to the exposed actin filaments according to their helical symmetry. Upon addition of ADP, the diffraction patterns from acto-S1 showed an increasing magnitude of response in the order as listed above, with features of a lateral compression of the whole diffraction pattern (indicative of increased radius of the acto-S1 complex) and an enhancement of the fifth layer-line reflection. The structure retrieval indicates that these changes are mainly due to the swing of the light chain (LC) domain in the direction consistent with the cryo-electron microscopic results. In the non-muscle isoforms, the swing is large enough to affect the manner of quasi-crystal packing of the S1-decorated actin filaments and their lattice dimension, with a small change in the twist of actin filaments. Variations also exist in the behavior of the 50K-cleft, which apparently opens upon addition of ADP to the non-muscle isoforms but not to other isoforms. The fast-skeletal S1 remains as the only isoform that does not clearly exhibit either of the structural changes. The results indicate that the "conventional" myosin-II isoforms exhibit a wide variety of structural behavior, possibly depending on their functions and/or the history of molecular evolution.