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Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

We demonstrated efficient two-color two-step laser ionization schemes in the combined use of λ

Background There has been growing evidence that the glucose fluctuation is an important contributing factor to the development of coronary artery disease. However, whether large glucose fluctuation, especially hypoglycemia, may be associated with acute myocardial infarction (AMI) remains largely unknown. Aim As new continuous glucose monitoring (CGM) has recently become available to evaluate glucose fluctuation from immediately after an emergency visit, this study sought to investigate glucose fluctuation and the occurrence of hypoglycemia in patients with AMI. Methods In this prospective study, 93 consecutive patients with AMI from April 2017 to November 2018 were enrolled. Subcutaneous interstitial glucose levels were monitored from emergency room to discharge using the CGM System. Based on the CGM data, 24-h mean glucose levels, the time in hyperglycemia and hypoglycemia and the occurrence of hypoglycemia, defined as less than 70 mg/dL, were measured, and the mean amplitude of glycemic excursions (MAGE) were calculated. Results The majority of patients [n=57, 61% (non-DM)] did not have diabetes and 36 patients had diabetes (DM). The occurrence of hypoglycemia within 24 hours after admission was observed in 49 patients [DM: n=11 (30.6%), non-DM: n=38 (66.7%)]. MAGE within 24 hours after admission were 100±47 in DM patients and 67±20 in non-DM patients. The mean time in hypoglycemia within 24 hours after admission was 148 minutes [DM: 100±260 minutes, non-DM: 178±287 minutes]. The occurrence of hypoglycemia during a hospital stay (mean 11.5 days) was detected in 76 patients [DM: n=28 (77.8%), non-DM: n=48 (84.2%)]. Representative case of hypoglycemia Conclusion Not only in DM patients but also in non-DM patients with AMI, large glucose fluctuation and high incidence of hypoglycemia were observed using new CGM system. Further investigations should address the rationale for the early detection and control of glucose fluctuation for AMI patients.

Supplemental Material for Utility of osteopontin in cerebrospinal fluid as a diagnostic marker for neuropsychiatric systemic lupus erythematosus by K Kitagori, H Yoshifuji, T Oku, T Ayaki, A Kuzuya, T Nakajima, S Akizuki, R Nakashima, K Murakami, K Ohmura, Y Hirayama, R Takahashi and T Mimori in Lupus

Objectives The objective of this study was to test the correlation of urinary podocyte number (U-Pod) and urinary podocalyxin levels (U-PCX) with histology of lupus nephritis. Methods This was an observational, cross-sectional study. Sixty-four patients were enrolled: 40 with lupus nephritis and 24 without lupus nephritis (12 lupus nephritis patients in complete remission and 12 systemic lupus erythematosus patients without lupus nephritis). Urine samples were collected before initiating treatment. U-Pod was determined by counting podocalyxin-positive cells, and U-PCX was measured by sandwich ELISA, normalized to urinary creatinine levels (U-Pod/Cr, U-PCX/Cr). Results Lupus nephritis patients showed significantly higher U-Pod/Cr and U-PCX/Cr compared with patients without lupus nephritis. U-Pod/Cr was high in proliferative lupus nephritis (class III±V/IV±V), especially in pure class IV (4.57 (2.02–16.75)), but low in pure class V (0.30 (0.00–0.71)). U-Pod/Cr showed a positive correlation with activity index ( r=0.50, P=0.0012) and was independently associated with cellular crescent formation. In contrast, U-PCX/Cr was high in both proliferative and membranous lupus nephritis. Receiver operating characteristic analysis revealed significant correlation of U-Pod/Cr with pure class IV, class IV±V and cellular crescent formation, and the combined values of U-Pod/Cr and U-PCX/Cr were shown to be associated with pure class V. Conclusions U-Pod/Cr and U-PCX/Cr correlate with histological features of lupus nephritis.

Introduction/Background Endothelial dysfunction occurs in chronic kidney disease (CKD) and increases the risk for cardiovascular disease. The mechanisms of endothelial dysfunction seem to evolve throughout kidney disease progression. In the present study, we investigate short-term and long-term effects of the vascular endothelium of intra-dialytic exercise for patients with end stage renal disease. Material and method Total 15 of subjects, included seven patients (32–89 years) with CKD and eight healthy adults participated in this study. The subjects were exercised handgrip training for the 2weeks home-based training program consisted of 7 daily handgrip session of 12 minutes each at the Borg rating of perceived exertion (RPE) for 11–13. The primary outcome was peripheral endothelial function. Secondary outcomes were physical function and biochemical tests such as cholesterol, IL6 and TNF-alpha. Results After the first intervention as the short-term effects, the patients in CKD group and healthy adults had significant improvement in peripheral endothelial function (P Conclusion In this study, the safety and efficacy of conventional handgrip training were confirmed without a sudden drop of blood pressure or any other side effects. Exercise training for handgrip is very convenient, has the potential to improve endothelial dysfunction. These results indicate that the exercise for handgrip training may improve the patient's condition equally to the lower limb exercise.

Fusarium oxysporum f. sp. fragariae is a fungal pathogen causing Fusarium wilt on strawberry. Polymerase chain reaction (PCR) primers that can discriminate F. oxysporum f. sp. fragariae from nonpathogenic F. oxysporum would greatly assist pathogen identification. In order to develop a molecular diagnostic tool for this pathogen, transposable elements in the pathogen were characterized and used for designing a specific set of PCR primers. Portions of the transposable elements Fot3, Han, Hop, Hornet1, and Skippy were detected in all 33 strains of F. oxysporum f. sp. fragariae tested by PCR, whereas Foxy was detected in 32 strains and Impala sequences were detected in 30 strains. Two types of sequences were detected for Hop, two types for Impala, and three types for Skippy. The genomic region between Han and Skippy was amplified by an inter-retrotransposon amplified polymorphism technique, and PCR primers (FofraF and FofraR) to specifically identify F. oxysporum f. sp. fragariae were designed from this region. The developed PCR primers discriminated F. oxysporum f. sp. fragariae strains from nonpathogenic F. oxysporum strains and five other formae speciales. Conidia of F. oxysporum f. sp. fragariae could be detected in brown lowland-type soil by PCR using the primers. After preculturing the soil sample on FoG2 medium, 1 × 102 conidia/g of soil could be detected; without preculturing, 1 × 103 conidia/g of soil were detected.

International audience; Production of neutron-rich nuclei around N = 126 by multinucleon transfer reactions has recently gained a renewal of interest both theoretically and experimentally. We are now advancing the KISS project at RIKEN to produce those nuclei by multinucleon transfer reactions and measure their lifetimes to investigate the astrophysical environments of the r-process. To investigate the relevance of the production mechanism, we performed measurements for the reaction system 136Xe + 198Pt, using the spectrometer VAMOS++ and the gamma-ray array EXOGAM at GANIL. Cross sections deduced from the measurements for neutron-rich nuclei around N = 126 show a modest enhancement when compared with the GRAZING calculations, indicating the advantage of the multinucleon transfer reactions as compared with fragmentation for production of N = 126 neutron-rich isotones. The possibility for production of neutron-rich nuclei around uranium beyond N = 126 by multinucleon transfer reactions is also discussed.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

The southern Chinese Osmunda ×mildei has been suggested to be an intersubgeneric hybrid, i.e., O. japonica (subgenus Osmunda) × O. angustifolia (subgenus Plenasium) or O. japonica × O. vachellii (subgenus Plenasium). These interpretations were based on morphological, cytological, and/or chloroplast DNA data, yet the parents of the hybrid remained unclear. Molecular phylogenetic relationships inferred here from chloroplast rbcL sequences and three nuclear DNA markers show that O. ×mildei is most likely a hybrid between the paternal O. japonica and the maternal O. vachellii.

イチゴ炭疽病菌の地下部からの侵入感染の可能性を検討するために，病原菌の浸根接種，灌注接種と噴霧接種による子苗の発病を比較した．その結果，浸根接種や灌注接種では，葉の汚斑症状や葉柄の黒斑症状が見られず，葉柄基部が黒変して株全体が萎凋枯死した．これらの株では新根の発生が少なく，根の部分的褐変や黒変が認められた．発病程度は浸根接種株で最も激しく，噴霧接種株がこれに次ぎ，灌注接種株では弱く，病勢進展もやや遅れた．発病株から炭疽病菌を分離した結果，噴霧接種株は葉，葉柄から高率に分離されたのに対し，浸根接種株は葉，葉柄，根冠部および根から高率に分離された．以上の結果から，炭疽病菌は葉や葉柄などの地上部感染だけでなく，根冠部や根からも侵入して感染すると考えられた．育苗培養土としてピートモス，オガクズ，砂土および土壌を入れた鉢をイチゴ発病株に隣接して置き，頭上灌水で管理したところ，ピートモスやオガクズなどの鉢土表面から炭疽病菌が高率に検出され，これらの鉢土に子苗を植え付けると苗が発病した．発病株は葉や葉柄の黒斑症状は認められなかったが，いずれも萎凋症状を呈した．このことから，鉢土中の病原菌が伝染源となり，苗に発病を引き起こすことが示唆された．イチゴ炭疽病菌の分生子で汚染した土壌は，ジエトフェンカルブ・チオファネートメチル水和剤の1000倍液を灌注することにより，高い防除効果が認められた．

We have measured quasi-elastic backward scattering in the reactions of 48 Ti , 54 Cr , 56 Fe , 64 Ni , 70 Zn , 76 Ge and 86 Kr + 208 Pb to study the nucleus-nucleus interaction in Pb -based cold fusion. The barrier distributions were obtained from the first derivative of the measured excitation functions of quasi-elastic scattering cross sections normalized to the Rutherford scattering cross sections. The centroids of the barrier distributions showed deviations from several predicted barrier heights toward the low energy side except for the Christensen-Winther potential and the Aküz-Winther potential. The shapes of the barrier distributions were well reproduced by the results of a coupled-channel calculation taking account of the coupling effects of multi-phonon excitations of the quadrupole vibration for the projectiles and of the octupole vibration for the 208 Pb target. The present barrier distributions were also well reproduced by a semiclassical calculation taking into account the couplings of transfer channels and single-phonon excitations in the projectiles and the target.

Background and purpose: Although microsomal prostaglandin E synthase (mPGES)-1 is known to contribute to stroke injury, the underlying mechanisms remain poorly understood. This study examines the hypothesis that EP3 receptors contribute to stroke injury as downstream effectors of mPGES-1 neurotoxicity through Rho kinase activation. Experimental approach: We used a glutamate-induced excitotoxicity model in cultured rat and mouse hippocampal slices and a mouse middle cerebral artery occlusion–reperfusion model. Effects of an EP3 receptor antagonist on neuronal damage in mPGES-1 knockout (KO) mice was compared with that in wild-type (WT) mice. Key results: In cultures of rat hippocampal slices, the mRNAs of EP1–4 receptors were constitutively expressed and only the EP3 receptor antagonist ONO-AE3-240 attenuated and only the EP3 receptor agonist ONO-AE-248 augmented glutamate-induced excitotoxicity in CA1 neurons. Hippocampal slices from mPGES-1 KO mice showed less excitotoxicity than those from WT mice and the EP3 receptor antagonist did not attenuate the excitotoxicity. In transient focal ischaemia models, injection (i.p.) of an EP3 antagonist reduced infarction, oedema and neurological dysfunction in WT mice, but not in mPGES-1 KO mice, which showed less injury than WT mice. EP3 receptor agonist-induced augmentation of excitotoxicity in vitro was ameliorated by the Rho kinase inhibitor Y-27632 and Pertussis toxin. The Rho kinase inhibitor HA-1077 also ameliorated stroke injury in vivo. Conclusion and implications: Activity of mPGES-1 exacerbated stroke injury through EP3 receptors and activation of Rho kinase and/or Gi. Thus, mPGES-1 and EP3 receptors may be valuable therapeutic targets for treatment of human stroke. This article is commented on by Andreasson, pp. 844–846 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00715.x

Background and purpose: Although both microsomal prostaglandin E synthase (mPGES)-1 and cyclooxygenase (COX)-2 are critical factors in stroke injury, but the interactions between these enzymes in the ischaemic brain is still obscure. This study examines the hypothesis that mPGES-1 activity is required for COX-2 to cause neuronal damage in ischaemic injury. Experimental approach: We used a glutamate-induced excitotoxicity model in cultures of rat or mouse hippocampal slices and a mouse middle cerebral artery occlusion-reperfusion model in vivo. The effect of a COX-2 inhibitor on neuronal damage in mPGES-1 knockout (KO) mice was compared with that in wild-type (WT) mice. Key results: In rat hippocampal slices, glutamate-induced excitotoxicity, as well as prostaglandin (PG) E2 production and PGES activation, was significantly attenuated by either MK-886 or NS-398, inhibitors of mPGES-1 and COX-2 respectively; however, co-application of these inhibitors had neither an additive nor a synergistic effect. The protective effect of NS-398 on the excitotoxicity observed in WT slices was completely abolished in mPGES-1 KO slices, which showed less excitotoxicity than WT slices. In the transient focal ischaemia model, mPGES-1 and COX-2 were co-localized in the infarct region of the cortex. Injection of NS-398 reduced not only ischaemic PGE2 production, but also ischaemic injuries in WT mice, but not in mPGES-1 KO mice, which showed less dysfunction than WT mice. Conclusion and implications: Microsomal prostaglandin E synthase-1 and COX-2 are co-induced by excess glutamate in ischaemic brain. These enzymes are co-localized and act together to exacerbate stroke injury, by excessive PGE2 production.

In the field-reversed configuration (FRC) plasma, rotational instability with toroidal mode number n = 2 is known as a sole destructive MHD instability. Though an ideal FRC is unstable for higher n interchange instabilities, those have never been observed in past experiments. As a possible stabilized mechanism, self-generated toroidal rotation and its shear have been investigated experimentally.

Objective. Auto-antibodies to signal recognition particle (SRP) are known to be specific to PM among rheumatic disorders, but the specificity in myopathic diseases remains unclear. The clinical utility of anti-SRP antibody in the differential diagnosis of myopathies has not been studied. The aim of the present study was to elucidate whether detection of anti-SRP antibody can discriminate of PM from muscular dystrophy (MD). Methods. We report a patient with a childhood onset myopathy, in whom it was clinically difficult to make a differential diagnosis of PM or MD for 21 yrs, despite repeated muscle biopsies. Myositis-specific auto-antibodies to RNA-associated antigens were screened in this particular case as well as in 105 serum samples from various types of MD and 84 from PM patients using RNA immunoprecipitation. The MD and PM serum samples were obtained from different institutions. The presence of anti-SRP antibody was confirmed by RNA immunoprecipitation combined with immunodepletion of SRP from the antigen. Results. Anti-SRP antibody was positive in the present patient, supporting the diagnosis of PM. Anti-SRP antibody was detected in seven (8.3%) patients with PM, but in none of the patients with MD. Myositis-specific auto-antibodies were not detected in any of the patients with MD. Conclusion. Anti-SRP antibody is useful for discriminating PM from MD among patients with myopathies.

We investigated the reaction dynamics induced by the 7Be,8B+208Pb collisions at energies around the Coulomb barrier. Charged particles originated by both the col- lisions were detected by means of 6 ΔE-Eres telescopes of a newly developed detector array. Experimental data were analysed within the framework of the Optical Model and the total reaction cross-sections were compared together and with the 6,7Li+208Pb colli-sion data. According to the preliminary results, 7Be nucleus reactivity is rather similar to the 7Li one whereas the 8B+208Pb total reaction cross section appears to be much larger than those measured for reactions induced by the other weakly-bound projectiles on the same target.

Expérience GANIL/VAMOS/EXOGAM; International audience; Absolute cross sections for isotopically identified products formed in multinucleon transfer in the136Xe + 198Pt system at ∼ 8 MeV=nucleon are reported. The isotopic distributions obtained using a largeacceptance spectrometer demonstrated the production of the “hard-to-reach” neutron-rich isotopes forZ < 78 around the N = 126 shell closure far from stability. The main contribution to the formation of theseexotic nuclei is shown to arise in collisions with a small kinetic energy dissipation. The presentexperimental finding corroborates for the first time recent predictions that multinucleon transfer reactionswould be the optimum method to populate and characterize neutron-rich isotopes around N = 126 whichare crucial for understanding both astrophysically relevant processes and the evolution of “magic” numbersfar from stability.