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Background: Effective use of lung volume data measured on computed tomography (CT) requires reference values for specific populations. This study examined whether an equation previously generated for multiple ethnic groups in the United States, including Asians predominantly composed of Chinese people, in the Multi-Ethnic Study of Atherosclerosis (MESA) could be used for Japanese people and, if necessary, to optimize this equation. Moreover, the equation was used to characterize patients with chronic obstructive pulmonary disease (COPD) and lung hyperexpansion., Methods: This study included a lung cancer screening CT cohort of asymptomatic never smokers aged ≥40 years from two institutions (n = 364 and 419) to validate and optimize the MESA equation and a COPD cohort (n = 199) to test its applicability., Results: In all asymptomatic never smokers, the variance explained by the predicted values (R 2 ) based on the original MESA equation was 0.60. The original equation was optimized to minimize the root mean squared error (RMSE) by adjusting the scaling factor but not the age, sex, height, or body mass index terms of the equation. The RMSE changed from 714 ml in the original equation to 637 ml in the optimized equation. In the COPD cohort, lung hyperexpansion, defined based on the 95th percentile of the ratio of measured lung volume to predicted lung volume in never smokers (122 %), was observed in 60 (30 %) patients and was associated with centrilobular emphysema and air trapping on inspiratory/expiratory CT., Conclusions: The MESA equation was optimized for Japanese middle-aged and elderly adults., Competing Interests: Declaration of competing interest N.T. and T.H. received research grants from Daiichi Sankyo and FUJIFILM Co., Ltd., outside of the submitted work. S.S. received grants from Nippon Boehringer Ingelheim, Philips-Respironics, Fukuda Denshi, Fukuda Lifetec Keiji, and ResMed outside of the submitted work. None of these companies played a role in the design or analysis of the study or the writing of the manuscript. The other authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were β-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from MSD K.K., Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Hiroyuki Nishiyama received research funding from Chugai Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Junichi Inokuchi received research funding from Chugai Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC 90 ) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Little is known about the outcomes and predictors of adverse cardiac events in medically treated patients with atrial functional mitral regurgitation (FMR)., Methods: We screened 1405 consecutive patients with grade ≥ 3+ mitral regurgitation (MR) detected by echocardiography. After excluding patients with previous or early (within 3 months from diagnosis) mitral valve surgery, congenital heart disease, hypertrophic cardiomyopathy, severe aortic valve disease, or unknown etiology, the study population consisted of 319 patients with primary MR, 395 patients with FMR with left ventricular (LV) dysfunction, and 184 patients with atrial FMR. Atrial FMR was defined as FMR in patients without LV wall motion abnormality or dilatation., Results: The cumulative incidence of the composite of cardiac death and heart failure hospitalization at 3 years was 10.5% in primary MR, 37.5% in FMR with LV dysfunction, and 14.0% in atrial FMR (p < .001). In atrial FMR patients, LV end-diastolic volume index (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02-1.10), severe MR (grade 4+) (HR 2.73, 95% CI 1.21-6.12), being symptomatic (NYHA ≥ 2) (HR 2.82, 95% CI 1.15-6.92), and having ≥1 comorbidities (HR 3.96, 95% CI 1.74-9.00) were independently associated with an increased risk for adverse cardiac events by a multivariable Cox regression analysis., Conclusions: Outcomes of medically treated patients with atrial FMR were better than those of FMR with LV dysfunction, but worse than those of primary MR. In atrial FMR patients, LV dilatation, severe MR, being symptomatic, and the presence of comorbidities were independently associated with an increased risk for adverse cardiac events., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The susceptibility to neurological and psychiatric disorders reveals sexual dimorphism in the structure and function of human brains. Recent evidence has also demonstrated the sex-related differences in cellular components of the brain, including neurons, microglia, astrocytes, and endothelial cells. Oligodendrocyte precursor cells (OPCs) regulate the neuronal system in various ways and play crucial roles in brain homeostasis beyond their well-known role as a reservoir for mature oligodendrocytes. Although recent studies have shown regional diversities and heterogeneities of OPCs, sex-related differences in OPCs are largely unknown. Here, we revealed transcriptomic differences in OPCs isolated from male and female neonatal rat brains. Furthermore, we demonstrated sex-dependent differences in OPCs regarding proliferation, migration, differentiation, tolerance against ischemic stress, energy metabolism, and the ability to regulate the blood-brain barrier integrity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The LHFRS is a simple score derived from three factors (history of hypertension, history of coronary artery disease/myocardial infarction, and red blood cell distribution width) deployed for the risk stratification of AHF in Greek population. This study aimed to validate the Larissa Heart Failure Risk Score (LHFRS) in patients with acute heart failure (AHF) in a Japanese population., Methods: We performed post-hoc analysis of 1670 consecutive patients enrolled in the REALITY-AHF. In all, 964 patients were finally enrolled. Exclusion criteria included patients with anemia, malignancies and sepsis. The primary outcome was defined as a composite of all-cause mortality and/or heart failure readmission, and the secondary outcome was defined as all-cause mortality., Results: The median admission LHFRS value was 1 (interquartile range [IQR]: 0-2). During a median follow-up of 365 (IQR: 161-365) days, the primary and secondary outcomes were observed in 321 and 157 patients, respectively. LHFRS was an independent predictor of both the primary (adjusted hazard ratio per 1-point increase, 95% confidence interval: 1.17 [1.04-1.32], p = 0.011), and the secondary outcomes (1.31 [1.12-1.55], p = 0.001). Patients with higher LHFRS scores (≥2) exhibited significantly worse outcomes than those with lower scores (<2) both for the primary outcome (1.40 [1.07-1.83], p = 0.014) and the secondary outcome (1.60 [1.09-2.34], p = 0.015). Additionally, LHFRS revealed an excellent goodness of fit (observed versus predicted outcomes) for predicting both the primary and the secondary outcomes (p > 0.99 and p = 0.99, respectively)., Conclusion: The simple LHFRS was proved as a reliable predictor of outcomes in patients with AHF., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The response of porcine pancreatic elastase (PPE) to propanol was examined by various techniques including UV-vis spectrophotometry, spectrofluorometry and circular dichroism, as well as molecular docking and molecular simulation. These techniques were used to investigate the structural changes and elastase activity in the presence of propanol. This work was performed at three temperatures of 303, 313 and 323 K, with the pH value of 8.5 (Tris buffer). The results of the UV-vis spectrophotometry indicated the transfer of tryptophan to an environment with low hydrophobicity. Fluorescence measurements also revealed the quenching of fluorescence intensity was induced by propanol, and dynamic quenching was the proposed quenching mechanism. Kinetic studies also suggested the inhibitory effect (noncompetitive) of propanol on elastase. Further, Circular Dichroism (CD) spectra showed that propanol caused slight alterations in the secondary structures of PPE (0.3% increase for the α-helix and 0.5% decrease for the β-sheet). Addition of propanol decreased the T m (Melting Temperature) parameter from 332.8 K to 330.1 K., (Copyright © 2019. Published by Elsevier B.V.)

The increasing use of nanoparticles in various industries has triggered the need to study their interconnection with biological macromolecules. The goal of this study was to survey the SiO 2 -nanoparticles efficacy on the thermal denaturation, conformation and activity of elastase at three temperatures of 303, 313 and 323K in the Tris buffer at pH of 8.5. In this work, distinct techniques such as UV-vis Spectrophotometry, Spectrofluorometry, and circular dichroism were employed. The fluorescence studies showed that SiO 2 nanoparticles extremely reduced the intensity of elastase with the static mechanism. Thermodynamic parameter analysis also indicated that the process of binding of SiO 2 -nanoparticles to elastase was spontaneous, thereby suggesting that van der Waals forces or hydrogen bonding interactions played a key role in determining the complex stability. Far-UV circular dichroism studies further revealed that SiO 2 nanoparticles could cause 9.79% reduction in the content of the α-helix and 3.24% increase in the content of the β-sheet. Furthermore, kinetic parameters (V max and K cat /K m ) indicated that SiO 2 nanoparticles had an activation effect on the elastase activity. Melting temperature studies at the selected concentration of SiO 2 nanoparticles also showed that by adding SiO 2 nanoparticles, elastase thermal stability was slightly increased. Overall, these nanoparticles modified the structure of the elastase, ultimately changing the activity and stability of this enzyme., (Copyright © 2019. Published by Elsevier B.V.)

In this study, the impact of spermidine on the stability, conformation and activity of elastase was investigated at the pH of 8.5 (the optimum pH for elastase) and different temperatures (303, 313, and 323 K) using UV-vis spectrophotometry, Spectrofluorimetry, circular dichroism, and enzyme activity measurements. The empirical results were obtained and compared with those achieved by the molecular docking simulation. Spectrofluorometric results proved that with the addition of spermidine to the protein solution, the emission severity of elastase was extremely reduced. Further, the Stern-Volmer equation demonstrated that quenching was principally of the static type. Moreover, ∆H 0 and ∆S 0 showed a negative value, revealing that hydrogen bonds or van der Waals interactions played a critical role in the interaction between spermidine and elastase. Km and kcat [E] parameters also showed that spermidine acted as an activator for elastase. Far-UV circular dichroism also revealed that spermidine could alter the secondary structure of elastase via a partial increment within the content of the α-helix structure (from 7.8 to 8.6), while it was somewhat diminished in the β-sheet (from 29.4 to 28.8). Molecular docking simulation results also demonstrated that spermidine could bind to porcine elastase, and van der Waals forces or hydrogen bonding interactions played the main role in this binding. Spermidine, therefore, served as a partial stabilizer and an activator for the enzyme., (Copyright © 2019. Published by Elsevier B.V.)

Many discrete models of biological networks rely exclusively on Boolean variables and many tools and theorems are available for analysis of strictly Boolean models. However, multilevel variables are often required to account for threshold effects, in which knowledge of the Boolean case does not generalise straightforwardly. This motivated the development of conversion methods for multilevel to Boolean models. In particular, Van Ham's method has been shown to yield a one-to-one, neighbour and regulation preserving dynamics, making it the de facto standard approach to the problem. However, Van Ham's method has several drawbacks: most notably, it introduces vast regions of "non-admissible" states that have no counterpart in the multilevel, original model. This raises special difficulties for the analysis of interaction between variables and circuit functionality, which is believed to be central to the understanding of dynamic properties of logical models. Here, we propose a new multilevel to Boolean conversion method, with software implementation. Contrary to Van Ham's, our method doesn't yield a one-to-one transposition of multilevel trajectories; however, it maps each and every Boolean state to a specific multilevel state, thus getting rid of the non-admissible regions and, at the expense of (apparently) more complicated, "parallel" trajectories. One of the prominent features of our method is that it preserves dynamics and interaction of variables in a certain manner. As a demonstration of the usability of our method, we apply it to construct a new Boolean counter-example to the well-known conjecture that a local negative circuit is necessary to generate sustained oscillations. This result illustrates the general relevance of our method for the study of multilevel logical models., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab., Patients and Methods: We analyzed data on 74 patients with relapsed/refractory DLBCL, who were initially treated with R-CHOP (rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone) or an R-CHOP-like regimen., Results: There was a significant association between a low LMR (≤ 2.6) and shorter overall survival (OS; P < .001) and progression-free survival (PFS; P < .001) compared with the high LMR group (> 2.6). Multivariate analysis showed that LMR was an independent prognostic factor for OS (P < .001) and PFS (P < .001), as was the international prognostic index (IPI) at relapse for OS. In addition, the LMR had an incremental value for OS and PFS compared with the IPI at relapse., Conclusion: The LMR predicts OS and PFS outcomes in relapsed/refractory DLBCL patients treated with rituximab, and might facilitate better stratification among patients in low- and intermediate-risk IPI groups., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The ACC/AHA guidelines introduced a new classification of severe aortic stenosis (AS) mainly based on maximum jet velocity (Vmax) and mean pressure gradient (mPG), but not on aortic valve area (AVA). However, prognostic value of this new classification has not yet been fully evaluated., Methods and Results: We studied 1512 patients with asymptomatic severe AS enrolled in the CURRENT AS registry in whom surgery was not initially planned. Patients were divided into 2 groups: Group 1 (N=122) comprised patients who met the recommendation for surgery; high-gradient (HG)-AS (Vmax≥4.0m/s or mPG≥40mmHg) with ejection fraction (EF)<50%, or very HG-AS (Vmax≥5.0m/s or mPG≥60mmHg), and Group 2 (N=1390) comprised patients who did not meet this recommendation. Group 2 was further subdivided into HG-AS with preserved EF (HGpEF-AS, N=498) and low-gradient (LG)-AS, but AVA<1.0cm 2 (N=892). The excess risk of Group 1 relative to Group 2 for the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was significant (adjusted HR: 1.92, 95%CI: 1.37-2.68, P<0.001). The excess risk of HGpEF-AS relative to LG-AS for the primary outcome measure was also significant (adjusted HR: 1.45, 95%CI: 1.11-1.89, P=0.006). Among LG-AS patients, patients with reduced EF (<50%) (LGrEF-AS, N=103) had extremely high cumulative 5-year incidence of all-cause death (85.5%)., Conclusion: Trans-aortic valve gradient in combination with EF was a good prognostic marker in patients with asymptomatic AS. However, patients with LGrEF-AS had extremely poor prognosis when managed conservatively., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this study was to determine optimal patient selection and selection of a prosthetic ring size for tricuspid valve (TV) repair at the time of mitral valve (MV) repair., Methods: We prospectively enrolled 167 consecutive patients undergoing MV repair. TV repair was indicated if patients had at least one of the following conditions representing tricuspid annular dilatation: (1) tricuspid regurgitation (TR)≥moderate, (2) history of right heart failure, (3) atrial fibrillation, and (4) pulmonary hypertension. The size of the ring was targeted to a normal-sized systolic tricuspid annuls in relation to the patient's body surface area (BSA). Serial echocardiographic studies were performed preoperatively, at discharge, and at 1, 3, and 5years postoperatively., Results: Overall, 100 (60%) patients required TV repair, while it was not indicated for 67 (40%) patients. During follow-up, 26 patients showed progression or recurrent TR≥moderate. The TR grade at 5years after MV surgery was 0.8±0.9 in patients with TV repair and 0.9±0.7 in those without TV repair (P=0.69). There were no significant differences between patients with and without TV repair in a composite endpoint of death from any cause, re-do MV or TV surgery, and recurrence or progression of TR≥moderate (P=0.46)., Conclusions: Patient selection for TV repair considering not only the grade of TR but clinical signs representing tricuspid annular dilatation is feasible at the time of MV repair. TV repair targeting a normal systolic size in relation to the BSA is a simple and reproducible procedure., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: We previously reported on the feasibility of enhanced recovery after surgery (ERAS) protocol for gastric cancer with a prospective phase II study, but the superiority of this approach over non-ERAS perioperative management remains unclear. Preoperative carbohydrate loading, an important element of the ERAS protocol, has been shown to reduce insulin resistance, but its effects on clinical endpoints in gastric cancer surgery remain controversial. The aim of this study was to clarify the efficacy of the ERAS protocol for gastric cancer surgery, with particular focus on preoperative carbohydrate loading., Methods: In this ERAS case-control study, we enrolled 121 patients as a case group and 259 patients undergoing gastrectomy for gastric cancer with our conventional perioperative management as a control group. Matched-pair analysis was performed to balance the patients' characteristics for comparison analysis., Results: After matching, 108 patients were included in each group. Postoperative hospital stay was significantly shorter in the ERAS group than in the control group (8 days vs. 9 days, p < 0.001), while the incidence of Clavien-Dindo classification grade II or more postoperative complication was similar between the groups (11.1% vs. 15.7%, p = 0.325). No significant differences were found in serum albumin level, body weight, or grip strength between the groups before surgery and at 1 week and 1 month after surgery., Conclusion: Use of the ERAS protocol for gastric cancer shortened the length of postoperative hospital stay without increasing complications. Preoperative carbohydrate loading didn't improve the postoperative nutritional status or maintain the muscle strength postoperatively., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Genital chlamydial infection is a principal sexually transmitted infection worldwide. Chlamydia trachomatis can cause male urethritis, acute epididymitis, cervicitis, and pelvic inflammatory disease as sexually transmitted infections. Fortunately, homotypic resistant C. trachomatis strains have not been isolated to date; however, several studies have reported the isolation of heterotypic resistant strains from patients. In this surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 51 hospitals and clinics in 2009 and 38 in 2012. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 19 isolates in 2009 and 39 in 2012. In 2009 and 2012, the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, and azithromycin were 2 μg/ml and 1 μg/ml, 0.5 μg/ml and 0.5 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.063 μg/ml and 0.063 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.125 μg/ml and 0.125 μg/ml, 0.016 μg/ml and 0.016 μg/ml, and 0.063 μg/ml and 0.063 μg/ml, respectively. In summary, this surveillance project did not identify any resistant strain against fluoroquinolone, tetracycline, or macrolide agents in Japan., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Aortic valve replacement (AVR) is currently the standard therapy for severe aortic stenosis (AS), and regression of left ventricular (LV) hypertrophy after AVR has been reported. However, data regarding a temporal relation between LV mass and left atrial (LA) volume are limited, and their prognostic impacts have not been fully elucidated. We aimed to clarify the temporal patterns of LA and LV reverse remodeling and their associations with clinical outcomes., Methods: We retrospectively reviewed 198 consecutive patients who underwent AVR for severe AS. After excluding patients with prior cardiac surgery, atrial fibrillation, concomitant moderate to severe aortic regurgitation, or concurrent mitral valve surgery, 83 patients with echocardiographic LV mass index (LVMI) and LA volume index (LAVI) data before and 1 year after AVR were eligible for the outcome analysis and 29 patients with these 2 measures before surgery, 1 month, 1 year, and 3 years after surgery were eligible for the analysis of time-dependent change of LVMI and LAVI., Results: Significant reductions in LVMI and LAVI (both p<0.001) after surgery were observed over time. LA dilatation improved and reached a plateau 1 month after surgery, whereas LV hypertrophy improved more gradually and reached a plateau at 1 year. The presence of both LV hypertrophy and LA dilatation 1 year after surgery was associated with significantly higher mortality (patients with both conditions vs. patients with neither or one condition=22.6% vs. 7.3% at 3 years; p=0.031) and major adverse cardiac and cerebrovascular events (38.9% vs. 12.6% at 3 years; p=0.021)., Conclusions: LA reverse remodeling occurred rapidly after AVR for severe AS, and regression of LV hypertrophy was more gradual. The presence of both residual LV hypertrophy and LA dilatation 1 year after AVR was associated with poor long-term outcomes., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features. We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS). Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles. This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Worldwide, the most important concern in the treatment of sexually transmitted infections is the increase in antimicrobial resistant Neisseria gonorrhoeae strains including resistance to cephalosporins, penicillins, fluoroquinolones or macrolides. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the second nationwide surveillance study. Urethral discharge was collected from male patients with urethritis at 26 medical facilities from March 2012 to January 2013. Of the 151 specimens, 103 N. gonorrhoeae strains were tested for susceptibility to 20 antimicrobial agents. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) 90% of ceftriaxone increased to 0.125 μg/ml, and 11 (10.7%) strains were considered less susceptible with an MIC of 0.125 μg/ml. There were 11 strains resistant to cefixime, and the MICs of these strains were 0.5 μg/ml. The distributions of the MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin, were bimodal. Sitafloxacin, a fluoroquinolone, showed strong activity against all strains, including strains resistant to other three fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin. The azithromycin MICs in 2 strains were 1 μg/ml., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Early predictors of status epilepticus (SE)-associated mortality and morbidity have not been systematically studied in children, considerably impeding the identification of patients at risk., Objectives: To determine reliable early predictors of SE-associated mortality and morbidity and identify the etiology of SE-associated sequelae in Japanese children., Methods: We conducted a prospective multicenter study of clinical findings and initial laboratory data acquired at SE onset, and assessed outcomes at the last follow-up examination. In-hospital death during the acute period and neurological sequelae were classified as poor outcomes., Results: Of the 201 children who experienced their first SE episode, 16 exhibited poor outcome that was most commonly associated with acute encephalopathy. Univariate analysis revealed that the following were associated with poor outcomes: young age (⩽24 months); seizure duration >90 min; seizure intractability (failure of the second anticonvulsive drug); biphasic seizures; abnormal blood glucose levels (<61 or >250 mg/dL); serum aspartate aminotransferase (AST) ⩾56 U/L; and C-reactive protein (CRP) levels >2.00 mg/dL. Multivariate analysis revealed that young age, seizure intractability, abnormal blood glucose levels, and elevated AST and CRP levels were statistically significant., Conclusions: Young age and seizure intractability were highly predictive of poor outcomes in pediatric SE. Moreover, abnormal blood glucose levels and elevated AST and CRP levels were predictors that might be closely associated with the etiology, especially acute encephalopathy and severe bacterial infection (sepsis and meningitis) in Japanese children., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Neisseria gonorrhoeae is one of the most important pathogens causing sexually transmitted infection, and strains that are resistant to several antimicrobials are increasing. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the first nationwide surveillance. The urethral discharge was collected from male patients with urethritis at 51 medical facilities from April 2009 to October 2010. Of the 156 specimens, 83 N. gonorrhoeae strains were tested for susceptibility to 18 antimicrobial agents. The prevalence of β-lactamase-producing strains and chromosomally mediated resistant strains were 7.2 % and 16.5 %, respectively. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) of ceftriaxone for 7 strains (8.4 %) was 0.125 μg/ml. One strain was resistant to cefixime (MIC 0.5 μg/ml). The MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin, and tosufloxacin, showed a bimodal distribution. The MIC of sitafloxacin was lower than those of the three fluoroquinolones listed here, and it was found that the antimicrobial activity of sitafloxacin was stronger than that of the fluoroquinolones. The MIC of azithromycin in 2 strains was 2 μg/ml, but no high-level resistance to macrolides was detected.

The Japanese surveillance committee conducted the first nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for female acute uncomplicated cystitis at 43 hospitals throughout Japan from April 2009 to November 2010. In this study, the causative bacteria (Escherichia coli and Staphylococcus saprophyticus) and their susceptibility to various antimicrobial agents were investigated by isolation and culturing of bacteria from urine samples. In total, 387 strains were isolated from 461 patients, including E. coli (n = 301, 77.8 %), S. saprophyticus (n = 20, 5.2 %), Klebsiella pneumoniae (n = 13, 3.4 %), and Enterococcus faecalis (n = 11, 2.8 %). S. saprophyticus was significantly more common in premenopausal women (P = 0.00095). The minimum inhibitory concentrations of 19 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute manual. At least 87 % of E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, and 100 % of S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant E. coli strains and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 13.3 % and 4.7 %, respectively. It is important to confirm the susceptibility of causative bacteria for optimal antimicrobial therapy, and empiric antimicrobial agents should be selected by considering patient characteristics and other factors. However, the number of isolates of fluoroquinolone-resistant or ESBL-producing strains in gram-negative bacilli may be increasing in patients with urinary tract infections (UTIs) in Japan. Therefore, these data present important information for the proper treatment of UTIs and will serve as a useful reference for future surveillance studies.

Green tea is known to contain antiviral components that prevent influenza infection. A limited number of adult clinical studies have been undertaken, but there is a paucity of clinical evidence concerning children. We conducted an observational study to determine the association between green tea consumption and the incidence of influenza infection among schoolchildren. Anonymous questionnaire surveys were undertaken twice during the influenza season from November 2008 to February 2009 (endemic seasonal type A influenza infection); each survey was conducted for 2663 pupils across all elementary schools in Kikugawa City (a tea plantation area), Japan. Each questionnaire was completed and submitted by 2050 pupils (response rate, 77.0%; age range, 6-13 y). The adjusted OR associated with the consumption of green tea for ≥6 d/wk compared with <3 d/wk was 0.60 [(95% CI = 0.39-0.92); P = 0.02] in cases of influenza confirmed by the antigen test. Meanwhile, the adjusted OR inversely associated with the consumption of 1 cup/d to <3 cups/d (1 cup = 200 mL) and 3-5 cups/d compared with <1 cup/d were 0.62 [(95% CI = 0.41-0.95); P = 0.03] and 0.54 [(95% CI = 0.30-0.94); P = 0.03], respectively. However, there was no significant association with the consumption of >5 cups/d. Our findings thus suggest that the consumption of 1-5 cups/d of green tea may prevent influenza infection in children.

A newly developed endobronchial ultrasound processor system (EU-ME1; Olympus Ltd., Tokyo, Japan) improves the quality of ultrasound image by elevating cycles per minute. We report identification of mediastinal lymph node metastasis in a patient with small cell lung cancer. The new endobronchial ultrasound system images enabled visualization of metastatic site within the subcarinal lymph node by the combination of ultrasound image and Doppler mode.

Objectives: Recently, a combined 0.014 pressure/temperature sensor-mounted guide wire has been developed to simultaneously measure fractional flow reserve and coronary flow reserve (CFR) by thermodilution (CFR-thermo). The accuracy of CFR-thermo was compared with CFR obtained by flow rate (CFR-flow) in experimental models., Methods: Using an experimental model made from a straight-rigid tube (4 mm diameter) filled with 36 degrees C water, CFR-thermo and CFR-flow were measured under different conditions of sensor position and injected water temperature (0-40 degrees C). A side branch (2 mm diameter) was then placed at 4, 6, 8 and 10 cm from the injected site just proximal to the stenosis. The degree of stenosis ranged from 0 to 75% (0%, 25%, 50%, 75%). CFR-thermo and CFR-flow were calculated from the inverse ratio of the mean transit time and the flow ratio during high flow to low flow rates., Results: Under the conditions without the side branch, there were good correlations between CFR-thermo and CFR-flow if the temperature of the injected water was under 28 degrees C and the sensor was not placed within 4 cm from the injection site. With the side branch, CFR-thermo was smaller than CFR-flow although there were good correlations between CFR-thermo and CFR-flow. The value of CFR-thermo increased with more distal positions of the side branch to the injected site., Conclusions: Temperature of the injected water, and the position of the sensor, the side branch and the stenotic lesion may influence measurements of CFR-thermo. These effects should be considered when CFR is measured by the thermodilution method.

Noninvasive imaging of the coronary arteries is one of the most important but challenging goals in medical imaging. Recent methods being developed for visualization of the coronary arteries include transthoracic and transesophageal echocardiography, electron-beam computed tomography, and magnetic resonance imaging. Transesophageal echocardiography is a feasible noninvasive technique for imaging the left main coronary artery and detecting hemodynamically significant luminal obstruction. Recent technological advances in transthoracic Doppler echocardiography provide measurement of coronary flow velocity in the distal portion of left anterior descending artery, which is useful for the assessment of coronary flow reserve, and therefore coronary stenosis and restenosis after coronary intervention in left anterior descending artery lesions. Electron-beam computed tomography is a cross-sectional imaging technique with high spatial and temporal resolution. It is possible for image acquisition to be triggered by the patient's electrocardiogram and this technique is well suited to cardiac imaging. Electron-beam computed tomography might be useful to detect or rule out high-grade coronary artery stenoses and occlusions, when image quality is adequate. Recent improvements and progress in coronary magnetic resonance angiography stem from the use of respiratory motion compensation and fast imaging methods. The most commonly used breath-hold method was developed with a fast segmented two-dimensional sequence on thin sections oriented to capture the coronary vessel inplane. Sensitivity and specificity of coronary magnetic resonance angiography in detecting significant coronary artery disease are 90% and 92% using this method.

The color Doppler echocardiographic technique has been developed for automated cardiac flow measurement (ACM). This study evaluated the effect of imaging parameters on stroke volume measurement. Cardiac output derived from the ACM method was compared with that obtained from pulsed wave Doppler in 36 patients (26 men and 10 women, mean age 54 +/- 8 years) in whom clear two-dimensional and color Doppler images of the left ventricular outflow tract were obtained. The effects of frame rate, color gain and moving target indicator (MTI) filter on cardiac output were evaluated in 13 patients (8 men and 5 women, mean age 49 +/- 6 years). Using ACM at a frame rate of 30 Hz, optimal color gain setting and high-frequency MTI filter (cutoff frequency: 915 Hz), there was an excellent correlation in cardiac output between the ACM and pulsed wave Doppler methods (stroke volume: r = 0.91, SEE = 0.32 l/min). Using ACM at a frame rate of 30, 22 and 15 Hz, the differences in stroke volume were 4.4%, 5.2% and 8.6%, respectively. When color gain was reduced, left ventricular stroke volume reduction was 12.1% (-2 dB), 18.9% (-4 dB). In contrast, there was no significant change in stroke volume measurement when color gain was increased. There was a significant decrease in stroke volume using the low-frequency MTI filter [cutoff frequency: 467 Hz (-35.6%)] and medium-frequency MTI filter [cutoff frequency: 703 Hz (-13.4%)]. Color Doppler imaging parameters are extremely important for automated assessment of cardiac output.

Recognition of the involved lesions is extremely important in mitral valve repair for infective endocarditis. Transesophageal echocardiography (TEE) is more sensitive for the detection of lesions than transthoracic echocardiography, but localization of the lesions is sometimes difficult by TEE. Three-dimensional (3D) TEE provides images of the mitral valve similar to the view from the left atrium. This study evaluated the value of 3D echocardiography for the diagnosis of involved lesions in 12 patients who underwent surgery for mitral regurgitation due to infective endocarditis. The location of the lesion in the mitral valve was classified as the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet, respectively. In all patients, the involved sites were confirmed at operation. The sensitivities of 3D TEE for detecting the lesions at the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet were 100%, 78% and 67%, and 100%, 100% and 100%, respectively. The specificities were 90%, 100% and 78%, and 100%, 100% and 100%, respectively. The lesions diagnosed by 3D TEE coincided with lesions confirmed at operation in 23 (92%) of 25 lesions. 3D TEE is useful for the assessment of the involved lesion of the mitral valve in patients with infective endocarditis.

Abnormal coronary flow pattern and coronary vasodilator reserve have been identified in patients with hypertrophic cardiomyopathy (HCM) using invasive techniques. The characteristics of coronary flow velocity and coronary flow reserve were evaluated by noninvasive-recording of coronary flow velocity in the distal portion of the left anterior descending coronary artery in 7 patients with HCM and 7 normal subjects using transthoracic color Doppler echocardiography. Coronary flow velocity was measured at rest and during intravenous infusion of adenosine triphosphate (0.15 mg/kg/min). Diastolic peak velocity, diastolic mean velocity, the time from the beginning of diastole to peak velocity (TVP) and velocity half time from peak velocity was measured in each group. Coronary flow reserve was obtained as the ratio of hyperemic mean velocity to resting mean velocity. TVP was significantly prolonged in the patients with HCM compared with the normal subjects (159 +/- 38 vs 103 +/- 54 msec, p < 0.05). Velocity half time was significantly shorter in the patients with HCM compared with the normal subjects (304 +/- 138 vs 451 +/- 109 msec, p < 0.05). Although diastolic mean velocity during hyperemia was not different between the 2 groups (62 +/- 8 vs 70 +/- 19 cm/sec), diastolic mean velocity at rest was significantly higher in the patients with HCM than in the normal subjects (39 +/- 6 vs 26 +/- 7 cm/sec, p < 0.01). Therefore, coronary flow reserve was significantly lower in the patients with HCM than in the normal subjects (1.6 +/- 0.4 vs 2.7 +/- 0.4, p < 0.001). There was a good correlation between diastolic mean velocity and the ratio of interventricular septal to posterior left ventricular wall thickness (y = 0.024x + 0.46, r = 0.75). Transthoracic assessment of coronary flow velocity using color Doppler echocardiography reveals that coronary flow reserve is reduced in patients with HCM because of increased baseline resting diastolic mean velocity.

Recently, automated cardiac flow measurement (ACM) has been developed for measuring the volume flow rate of blood flow through the left ventricular outflow tract. Measurements of left ventricular cardiac output by the ACM method were compared with those by the thermal dilution method with a Swan-Ganz catheter in 27 patients (16 men and 11 women; aged 44 +/- 3 years) in whom clear two-dimensional and color Doppler images of the left ventricular outflow tract were obtained. The total time required for left ventricular stroke volume calculation by both ACM and pulsed Doppler methods was measured in 10 patients (six men and four women; aged 41 +/- 2 years). There was an excellent correlation in the measurements of cardiac output between the ACM and thermal dilution methods (y = 0.77x + 0.77, r = 0.84, SEE = 0.4 l/min). The total time required for left ventricular stroke volume calculation by the ACM method was significantly shorter than that by the pulsed Doppler method (92 +/- 10 vs 177 +/- 30 sec, p < 0.01). The ACM method is simple, quick, and accurate for the automated assessment of cardiac output.

The usefulness of three-dimensional echocardiography using intravascular ultrasound (3D-IVUS) for the measurement of plaque volume was evaluated by comparing plaque volume derived from 3D-IVUS with that directly measured in 10 autopsied iliac or femoral plaque models (5-15 mm long). Using IVUS (3.5 F, 30 MHz), sequential cross-sectional images for three-dimensional datasets were acquired with a motorized catheter pullback device connected to the three-dimensional reconstruction system. Three-dimensional reconstruction was performed from the sum of the two-dimensional cross-sectional views. Plaque volumes were calculated using a summation of disks algorithm based on the reconstructed multiple short-axis cross-sections from the three-dimensional data. Three-dimensional IVUS demonstrated a good correlation with direct measurement of plaque volume (y = 0.71x + 0.001, r = 0.80, SEE = 0.003 ml), so is useful for the measurement of plaque volumes in the experimental models.

Noninvasive assessment of the distal left anterior descending coronary artery and intramyocardial blood flow were attempted in 50 consecutive patients (28 males and 22 females, mean age [+/-SD] 58 +/- 12 years) using a 7.5 MHz transducer (Doppler frequency: 5 MHz) and a SSA-380A ultrasound digital system with special optimal settings for the color Doppler examination. Modified apical acoustic windows were used to visualize the blood flow in the distal left anterior descending coronary artery and the intramyocardial artery. By selecting a sample volume (2 mm wide) on the color trace of these blood flows, Doppler spectral tracing of the distal left anterior descending coronary artery and intramyocardial blood flows could be recorded using pulsed-wave Doppler system. Blood flow in the distal left anterior descending coronary artery was detected in 43 (86%, Vmax = 22 +/- 8.7 cm/sec, Vmean = 16 +/- 5.1 cm/sec) of 50 patients, and intramyocardial blood flow in 40 (80%, Vmax = 26 +/- 11.0 cm/sec, Vmean = 19 +/- 8.5 cm/sec) of 50 patients. Distal left anterior descending coronary artery and the intramyocardial blood flows can be imaged by transthoracic digital color Doppler echocardiography in the clinical setting.

Fructose-1,6-bisphosphatase deficiency is an inheritable disorder of gluconeogenesis. Sequence analysis of the cDNA of the fructose-1,6-bisphosphatase mRNA isolated from monocytes from a girl with this disease and her consanguineous parents revealed that the patient and her parents were a homozygote and heterozygotes for an insertion of one G residue at G957GGGG961, respectively. This mutation resulted in translation of a truncated enzyme protein, and the mutant protein showed no fructose-1,6- bisphosphatase activity in an overexpression experiment in Escherichia coli. However, this mutation is located in a region of the amino acid sequence which is not well conserved among mammals. A mutagenized clone was prepared from the normal clone. The extents of substitutions and deletions of the amino acid sequence were predicted to be less in the mutagenized protein than in the mutant protein. This mutagenized clone also expressed no fructose-1,6-bisphosphatase activity, although both of two normal clones from control monocytes and a control liver sample expressed an apparently normal level of fructose-1,6-bisphosphatase activity. Thus, this mutation is concluded to be responsible for fructose-1,6-bisphosphatase deficiency in this patient.