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2D van der Waals ferroelectrics have emerged as an attractive building block with immense potential to provide multifunctionality in nanoelectronics. Although several accomplishments have been reported in ferroelectric switching for out-of-plane ferroelectrics down to the monolayer, a purely in-plane ferroelectric has not been experimentally validated at the monolayer thickness. Herein, an in-plane ferroelectricity is demonstrated for micrometer-size monolayer SnS at room temperature. SnS has been commonly regarded to exhibit the odd-even effect, where the centrosymmetry breaks only in the odd-number layers to exhibit ferroelectricity. Remarkably, however, a robust room temperature ferroelectricity exists in SnS below a critical thickness of 15 layers with both an odd and even number of layers, suggesting the possibility of controlling the stacking sequence of multilayer SnS beyond the limit of ferroelectricity in the monolayer. This work will pave the way for nanoscale ferroelectric applications based on SnS as a platform for in-plane ferroelectrics.

The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC 90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 μg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum β-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum β-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports., Competing Interests: Declaration of Competing Interest Shingo Yamamoto has received speaker's honorarium from Daiichi Sankyo Co., Ltd., and scholarship donations from Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd, Pfizer Japan Inc., and Bayer Yakuhin, Ltd. Satoshi Takahashi has received speaker honoraria from Daiichi Sankyo Co., Ltd. and MSD K.K., and research grants from Shino-Test Corporation and Abbott Japan Co., Ltd. Ryoichi Hamasuna has received speaker's honorarium from Daiichi Sankyo Co. Ltd. Shinichiro Minamitani is an employee of Daiichi Sankyo Co., Ltd. Tetsuya Matsumoto has received speaker's honorarium from MSD K.K. and Pfizer Japan Inc. Hiroshi Kiyota and Hiroki Yamada have received scholarship donations from Taisho Toyama Pharmaceutical Co., Ltd., Toyama Chemical Co., Ltd., Daiichi Sankyo Co., Ltd., Astellas Pharma Inc., Taiho Pharmaceutical Co., Ltd., and Sanofi K.K. Kazuhiro Tateda received speaker honoraria from Pfizer Japan Inc., MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. and Meiji Seika Pharma Co., Ltd., research funding from Meiji Seika Pharma Co., Ltd., Nippon Becton Dickinson Company, Ltd., Asahi Kasei Pharma Corporation, Eidia Co., Ltd., Eiken Chemical Co. Ltd., Nissui Pharmaceutical Co., Ltd., Spero OpCo, Inc., Shimadzu Corporation, Hitachi Ltd., Kyorin Pharmaceutical Co., Ltd., MSD K.K., Denka Company Limited, KD-ICONS Co. Ltd., and grant support from Taisho Toyama Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Asahi Kasei Pharma Corporation, Shionogi & Co., Ltd., Meiji Seika Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Astellas Pharma Inc., and FUJIFILM Toyama Chemical Co., Ltd., and scholarship donations from Taisho Toyama Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Asahi Kasei Pharma Corporation, Shionogi & Co., Ltd., Meiji Seika Pharma Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Astellas Pharma Inc. and FUJIFILM Toyama Chemical Co., Ltd., and has an endowed department sponsored by Meiji Seika Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Astellas Pharma Inc., Taisho Toyama Pharmaceutical Co., Ltd., MSD K.K. and Daiichi Sankyo Co., Ltd. Hiroyuki Nishiyama has received speaker's honorarium from MSD K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd. and Astellas Pharma Inc., research funding from Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd., and scholarship donations from Astellas Pharma Inc., Novartis Pharma K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Li metal electrode is the ultimate choice use in Li ion batteries as high-energy storage systems. An obstacle to its practical realization is Li dendrite formation. In this study, the desolvation resistance of the Li metal electrode, which is strongly related to the inhibition of Li dendrite formation, is investigated. By applying a Laplace transform impedance technique, the desolvation/solvation resistances were successfully separated and analyzed in cells using liquid electrolytes containing different lithium salts, revealing asymmetry in the desolvation/solvation resistances of Li metal electrodes. The desolvation resistances, which supposedly require large amounts of energy derived from the strong interaction between Li + ion and solvents, were smaller than the solvation resistances. It has also been revealed that the larger resistance in the desolvation process is effective for suppressing Li dendrite formation further.

Solid electrolytes with high Mg-ion conductivity are required to develop solid-state Mg-ion batteries. The migration energies of the Mg 2+ ions of 5,576 Mg compounds tabulated from the inorganic crystal structure database (ICSD) were evaluated via high-throughput calculations. Among the computational results, we focused on the Mg 2+ ion diffusion in Mg 0.6 Al 1.2  Si 1.8 O 6 , as this material showed a relatively low migration energy for Mg 2+ and was composed solely of ubiquitous elements. Furthermore, first-principles molecular dynamics calculations confirmed a single-phase Mg 2+ ion conductor. The bulk material with a single Mg 0.6 Al 1.2 Si 1.8 O 6 phase was successfully prepared using the sol-gel method. The relative density of the sample was 81%. AC impedance measurements indicated an electrical conductivity of 1.6 × 10 -6 Scm -1 at 500°C. The activation energy was 1.32 eV, which is comparable to that of monoclinic-type Mg 0.5 Zr 2 (PO 4 ) 3 ., (© 2020 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

Efficient and large-scale removal of humic acid (HA) from aqueous environments is required since HA causes human health and esthetic issues. Hydro-garnet compounds, Ca 3 Al 2 (SiO 4 ) 3- x (OH) 4 x , have recently been suggested as HA adsorbents not only due to their superior adsorption behaviors but also because they are ubiquitous element-derived compounds. In this study, the adsorption behavior of formic acid to hydro-garnets was investigated by means of first-principles density functional theory (DFT) computations. Formic acid was chosen owing to its reasonable computational cost and inclusion of carboxylic acid as HA. Comparisons of adsorption energies for formic acid among various compounds (including platinum and kaolinite) indicate that hydro-garnet compounds are promising due to their lower (more stable) adsorption energies. Also, the optimization of composition x enables selective adsorption of formic acid against solvent water molecules. Relationships between surface electronic/atomistic structures and adsorption properties are discussed., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background: This study tested the effectiveness of a supported self-management (SSM) intervention to reduce symptoms of depression among adults compared with enhanced treatment as usual in community-based and primary care settings in Vietnam., Methods: The cluster randomized trial included 376 adults in 32 communes in eight provinces. Eligible participants scored > 7 on the SRQ-20 depression scale. Patients with severe symptoms were excluded and referred to tertiary care. Randomization took place at the commune level. The immediate intervention group included 16 communes with 190 participants and the delayed group included 16 communes with 186 participants. Participants in communes randomized to the immediate intervention group received a two-month course of SSM, consisting of a workbook and supportive coaching. Those in communes randomized to the delayed group received enhanced treatment as usual and, for ethical purposes, received the SSM intervention after 4 months. The primary outcome is the effect of SSM on reduction in depression scores as indicated by a reduced proportion of participants with SRQ-20 scores > 7 at 2 months after commencement of SSM intervention. Blinding was not possible during intervention delivery but outcome assessors were blinded. Analysis was intention-to-treat., Results: At 2 months, 26.4% of the intervention group and 42.3% of the delayed group had SRQ-20 scores > 7. The adjusted odds ratio of having depression between the intervention and control was 0.42 (p < 0.0001), 95% CI (0.28, 0.63). Receiving the intervention thus reduces the odds of having depression by 58%, compared with receiving the control after 2 months of treatment. No adverse events were reported., Conclusions: Results suggest that SSM is effective for decreasing depression symptoms among adults in community-based settings in Vietnam. Trial Registration This trial is registered at ClinicalTrials.gov, number NCT03001063., Competing Interests: Competing interestsNVH is a representative of MOLISA, which provided matched funding for the study. He did not influence the study design, data collection or interpretation of results. All other authors have no conflict to declare., (© The Author(s) 2020.)

Sequence data is now widely used to observe relationships among organisms. However, understanding structure of the qualitative data is challenging. Conventionally, the relationships are analysed using a dendrogram that estimates a tree shape. This approach has difficulty in verifying the appropriateness of the tree shape; rather, horizontal gene transfers and mating can make the shape of the relationship as networks. As a connection-free approach, principal component analysis (PCA) is used to summarize the distance matrix, which records distances between each combination of samples. However, this approach is limited regarding the treatment of information of sequence motifs; distances caused by different motifs are mixed up. This hides clues to figure out how the samples are different. As any bases may change independently, a sequence is multivariate data essentially. Hence, differences among samples and bases that contribute to the difference should be observed coincidentally. To archive this, the sequence matrix is transferred to boolean vector and directly analysed by using PCA. The effects are confirmed in diversity of Asiatic lion and human as well as environmental DNA. Resolution of samples and robustness of calculation is improved. Relationship of a direction of difference and causative nucleotides has become obvious at a glance.

Shiga toxin-producing Escherichia coli (STEC) can cause severe gastrointestinal disease and colonization among food handlers. In Japan, STEC infection is a notifiable disease, and food handlers are required to undergo routine stool examination for STEC. However, the molecular epidemiology of STEC is not entirely known. We investigated the genomic characteristics of STEC from patients and asymptomatic food handlers in Miyagi Prefecture, Japan. Whole-genome sequencing (WGS) was performed on 65 STEC isolates obtained from 38 patients and 27 food handlers by public health surveillance in Miyagi Prefecture between April 2016 and March 2017. Isolates of O157:H7 ST11 and O26:H11 ST21 were predominant (n = 19, 29%, respectively). Non-O157 isolates accounted for 69% (n = 45) of all isolates. Among 48 isolates with serotypes found in the patients (serotype O157:H7 and 5 non-O157 serotypes, O26:H11, O103:H2, O103:H8, O121:H19 and O145:H28), adhesion genes eae, tir, and espB, and type III secretion system genes espA, espJ, nleA, nleB, and nleC were detected in 41 to 47 isolates (85-98%), whereas isolates with other serotypes found only in food handlers were negative for all of these genes. Non-O157 isolates were especially prevalent among patients younger than 5 years old. Shiga-toxin gene stx1a, adhesion gene efa1, secretion system genes espF and cif, and fimbrial gene lpfA were significantly more frequent among non-O157 isolates from patients than among O157 isolates from patients. The most prevalent resistance genes among our STEC isolates were aminoglycoside resistance genes, followed by sulfamethoxazole/trimethoprim resistance genes. WGS revealed that 20 isolates were divided into 9 indistinguishable core genomes (<5 SNPs), demonstrating clonal expansion of these STEC strains in our region, including an O26:H11 strain with stx1a+stx2a. Non-O157 STEC with multiple virulence genes were prevalent among both patients and food handlers in our region of Japan, highlighting the importance of monitoring the genomic characteristics of STEC., Competing Interests: The authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Plasma levels of chemerin, an adipocytokine produced from the adipose tissues and liver, are associated with metabolic syndrome and coronary artery disease (CAD). Chemerin and its analog, chemerin-9, are known to bind to their receptor, ChemR23. However, whether chemerin and chemerin-9 affect atherogenesis remains to be elucidated. We investigated the expression of chemerin and ChemR23 in human coronary arteries and cultured human vascular cells. The effects of chemerin and chemerin-9 on atheroprone phenomena were assessed in human THP1 monocytes, human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs) and aortic lesions in Apoe -/- mice. In patients with CAD, a small amount of ChemR23, but not chemerin, was expressed within atheromatous plaques in coronary arteries. Chemerin and ChemR23 were expressed at high levels in THP1 monocytes, THP1-derived macrophages, and HUVECs; however, their expression in HASMCs was weak. Chemerin and chemerin-9 significantly suppressed the tumor necrosis factor-α (TNF-α)-induced mRNA expression of adhesion and pro-inflammatory molecules in HUVECs. Chemerin and chemerin-9 significantly attenuated the TNF-α-induced adhesion of THP1 monocytes to HUVECs and macrophage inflammatory phenotype. Chemerin and chemerin-9 suppressed oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation associated with down-regulation of CD36 and up-regulation of ATP-binding cassette transporter A1 (ABCA1). In HASMCs, chemerin and chemerin-9 significantly suppressed migration and proliferation without inducing apoptosis. In the Apoe -/- mice, a 4-week infusion of chemerin-9 significantly decreased the areas of aortic atherosclerotic lesions by reducing intraplaque macrophage and SMC contents. Our results indicate that chemerin-9 prevents atherosclerosis. Therefore, the development of chemerin analogs/ChemR23 agonists may serve as a novel therapeutic target for atherosclerotic diseases., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16-40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Flavophospholipol (FPL) is an antimicrobial feed additive that has been approved for use in livestock animals and has the potential to decrease horizontal dissemination of antimicrobial resistance genes. Since previous studies showed that FPL has an inhibitory effect on plasmid transfer, in vitro experiments have proven the efficacy of FPL in reducing the conjugative transfer of plasmids encoding the extended-spectrum β-lactamase (ESBL) and vanA genes. These are among the most important antimicrobial resistance loci known. ESBL-producing Escherichia coli and vancomycin-resistant Enterococcus faecalis (VRE) were exposed to several concentrations of FPL, and transfer frequency and plasmid curing activity were determined. FPL inhibited the conjugative transfer of plasmids harboring ESBL and vanA genes in a concentration-dependent manner in all strains. Further transfer experiments revealed that FPL could decrease or increase transfer frequency depending on plasmid type when transfer frequency was at low levels. The plasmid curing activity of FPL was also observed in ESBL-producing E. coli in a concentration-dependent manner, suggesting that they partially contribute to the inhibition of conjugative transfer. These results suggest that the use of FPL as a feed additive might decrease the dissemination of ESBL and vanA genes among livestock animals.

Remarkable optical/electrical features are expected in two-dimensional group-IV monochalcogenides (MXs; M = Sn/Ge and X = S/Se) with a uniquely distorted layered structure. The lone pair electrons in the group-IV atoms are the origin of this structural distortion, while they also cause a strong interlayer force and high chemical reactivity. The fabrication of chemically stable few-to-monolayer MX has been a significant challenge. We have observed that, once the SnS surface is oxidized, the SnO x top layer works as a passivation layer for the SnS layer underneath. In this work, the SnO x /SnS hetero-structure is studied structurally, optically, and electrically. When tape-exfoliated bulk SnS is oxygen-annealed under a reduced pressure at 10 Pa, surface oxidation and SnS sublimation proceed simultaneously, resulting in a monolayer-thick SnS layer with the SnO x passivation layer. The field-effect transistor of nine-layer SnS prepared via mechanical exfoliation exhibits a p-type characteristic because of intrinsic Sn vacancies, whereas ambipolar behavior is observed for the monolayer-thick SnS obtained via oxygen annealing probably owing to the additional n-type doping by S vacancies. This work on monolayer-thick SnS fabrication can be applied to other unstable lone pair analogues and can facilitate future research on MXs.

Background: Clostridium butyricum MIYAIRI 588 (CBM 588) is a probiotic bacterium that is used as an anti-diarrheal medicine in Japan. However, the impact of this probiotic on the gut microbiome has not been fully elucidated, especially, when used with antimicrobials., Material and Methods: In an in vivo study, CBM 588 monotherapy, clindamycin monotherapy, CBM 588 and clindamycin (combination therapy), or normal saline (control) was orally administered to mice for 4 days, and fecal samples were collected for 18 days to enumerate C. butyricum. We also extracted DNA from these fecal samples for metagenomics analysis by amplification of the V3-V4 region of the bacterial 16S rRNA gene and MiSeq Illumina sequencing. In addition, the concentrations of some short chain fatty acids were assessed in the fecal samples. A histological analysis was also conducted., Results: On day 4 (the last treatment day), there was no difference in the total counts of C. butyricum between the CBM 588 monotherapy and combination therapy groups (5.21 ± 0.78 vs. 5.13 ± 0.45 log 10  cfu/g, p = 0.86). Clindamycin treatment resulted in dramatic increases in the phylum Firmicutes, especially Enterobacteriaceae, Clostridiaceae, Lactobacillus, and Enterococcus, compared with the other groups during the treatment period. CBM 588 treatment modified the bacterial community composition at lower phylogenetic levels. Some bacterial taxa, such as Bifidobacterium, Coprococcus, and Bacteroides, were significantly increased in the combination therapy group when compared with the other groups. In the metabolic analysis, CBM 588 enhanced lactic acid production. It also enhanced the efficiency of lactic acid use for the production of butyric acid. Only the clindamycin monotherapy group showed abnormal colon tissue, with superficial epithelial necrosis and the presence of inflammatory cells., Conclusion: CBM 588 treatment modulated the gut microbiota composition under dysbiosis due to the use of an antimicrobial with strong activity against anaerobes and significantly reduced epithelial damage., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Comments made by readers in response to news articles about current events can provide profound insights into public understanding of and perspectives on those events. Here, in follow up to a paper published last year in this journal, we examined reader comments to articles in newspapers and magazines about neurosurgical interventions for treating psychiatric illness., Method: We conducted a thematic analysis of these comments (N = 662 coded units of data) posted in response to 115 newspaper and magazine articles from four countries (Canada, USA, Germany, and Spain) between 2006 and 2017. The comments were coded using an iteratively refined coding scheme that was structured around four a priori categories based on results from the parent study and two new categories that emerged., Results: We found many references to historical psychosurgery and mostly negative and pessimistic comments about ablative neurosurgical interventions. Comments to deep brain stimulation were more positive, and comments to optogenetics most controversial. We also found many expressions of distrust of medical professionals in the context of interventions on the brain and concerns about social and individual control., Conclusions: Overall, results suggest there is still much work to be done to raise public awareness about re-emerging and new neurosurgical interventions. Balanced discussion is needed if these approaches are to find a place in health care for psychiatric disorders.

Sodium ion batteries meet the demand for large-scale energy storage, such as in electric vehicles, due to the material abundance of sodium. In this report, nanotube-type Na 2 V 3 O 7 is proposed as a cathode material because of its fast sodium diffusivity, an important requirement for sodium ion batteries, through the investigation of ~4300 candidates via a high-throughput computation. High-rate performance was confirmed, showing ~65% capacity retention at a current density of 10C at room temperature, despite the large particle size of >5 μm. A good cycle performance of ca. 94% in capacity retention after 50 cycles was obtained owing to a small volumetric change of <0.4%.

Background: ABO-incompatible living related kidney transplantation (ABO-iLKT) has increased the possibilities for kidney transplantation in patients with end stage renal disease. Due to advancements in immunosuppressive agents and the identification of immunological conditions following ABO-iLKT, this transplantation technique has achieved the same success rate as ABO-compatible LKT. However, some patients continue to generate anti-blood type antibodies, despite conventional immunosuppressant treatment., Case Presentation: A 60-year-old man was referred to our hospital for kidney transplantation. The proposed transplant was ABO incompatible, from a donor with blood-type A to a recipient with blood-type O. The recipient's anti-A blood-type IgG antibody titer was measured at 4096-fold dilution. Following desensitization therapy, including mycophenolate mofetil (MMF) 750 mg/day for 3 months, intravenous Rituximab 200 mg, and two sessions of double filtration plasmapheresis, the anti-A blood-type IgG antibody titer decreased to only 516-fold dilution and did not meet our target of less than 128-fold dilution. MMF was thus continued for an additional 4 months and four additional sessions of plasmapheresis were undertaken. Following these interventions, antibody titers decreased to 128-fold dilution and ABO-iLKT was performed. Following transplant, antibody-mediated rejection was not observed and renal function was preserved. However, a post-operative renal biopsy 1.5 months later showed evidence of T-cell-mediated rejection IB. The patient was treated with steroids, with no increase in serum creatinine., Conclusion: Our findings suggest that the long-term single MMF desensitization therapy could be a suitable option for ABO-iLKT with high refractory and rebound anti-blood type antibody. Further studies are required to establish the optimal immunosuppression regimen to control B cell- mediated immunity in ABO-iLKT.

The pathogenesis in the exacerbation of neuromyelitis optica spectrum disorder (NMOSD) involves mainly the serum anti-aquaporin-4 (AQP4) immunoglobulin G antibody (anti-AQP4 antibody). If high-dose corticosteroid treatment is not achieved during remission, rescue plasmapheresis is recommended. However, there are few reports on the therapeutic efficacy of repetitive immunoadsorption plasmapheresis (IAPP) for the recurrent exacerbation of NMOSD with a fluctuating anti-AQP4 antibody level. A 36-year-old man presented with a reduction of visual acuity (VA) on the right eye (OD) to 20/250. At this reduction of VA OD, magnetic resonance imaging (MRI) showed right optic nerve swelling without cerebral, brainstem, or spinal cord lesions. The anti-AQP4 antibody was detected in the serum. We diagnosed the patient with NMOSD and treated him with high-dose corticosteroid therapy. To prevent exacerbation with this treatment, the sixth session of the first IAPP course was adopted and VA OD improved to 20/100. Seven months later, VA OD deteriorated to 20/125 and ocular pain occurred. At that time, the anti-AQP4 antibody was not detected, although MRI revealed the recurrence of right optic neuritis. A second IAPP course with seven sessions was conducted with a concomitant administration of 1000 mg methylprednisolone every 10 days for 30 days. Ocular pain improved, although VA OD had continued to decline during these treatments and was eventually preserved at 20/400. In conclusion, IAPP is effective for the treatment of exacerbated NMOSD with a seropositive anti-AQP4 antibody. However, further study is necessary to develop treatments for relapsing NMOSD with a seronegative anti-AQP4 antibody.

Optimistic people have reduced risk for cardiovascular disease and cardiovascular-related mortality compared with their less optimistic peers. One explanation for this is that optimistic people may be more likely to engage in healthy behavior like exercising frequently, eating fruits and vegetables, and avoiding cigarette smoking. However, researchers have not formally determined the extent or direction of optimism's association with health behaviors. Moreover, it is unclear whether optimism temporally precedes health behaviors or whether the relationship is because of shared common causes. We conducted random effects meta-analyses examining optimism's association with 3 health behaviors relevant for the prevention of cardiovascular disease. PubMed and PsycINFO databases were searched for studies published through November 2017 reporting on optimism's relationship with physical activity, diet, and cigarette smoking. We identified 34 effect sizes for physical activity (n=90 845), 15 effect sizes for diet (n=47 931), and 15 effect sizes for cigarette smoking (n=15 052). Findings suggested that more optimistic individuals tended to engage in healthier behaviors compared with less optimistic individuals, but effect sizes were modest ( r activity =0.07, P <0.0001; r diet =0.12, P <0.0001; and r smoking =0.07, P =0.001). Most evidence was cross-sectional (≥53% of effect sizes) and did not consider sociodemographic characteristics (<53% of effect sizes) or psychological distress (<27% of effect sizes) as potential confounders. Optimism is associated with healthier behaviors that protect against cardiovascular disease, although most evidence was relatively low quality. Additional longitudinal and experimental research is required to determine whether optimism causally contributes to healthy behaviors and whether optimism could be an effective target for preventing cardiovascular disease., (© 2018 American Heart Association, Inc.)

Objective: Aspiration of subglottic secretion is a widely used intervention to prevent ventilator-associated pneumonia (VAP). This study aimed to compare the efficacy of continuous and intermittent subglottic secretion drainage (SSD) in preventing VAP., Methods: A single-center randomized controlled trial was conducted on adult postoperative patients who were expected to undergo mechanical ventilation for more than 48 hours. Primary outcome measure was incidence of VAP and secondary outcome measures were length of mechanical ventilation and intensive-care unit (ICU) stay., Results: Fifty-nine patients received continuous SSD, while 60 patients received intermittent SSD. Of these 119 patients, 88 (74%) were excluded and 15 and 16 patients were allocated to receive continuous and intermittent SSD, respectively. VAP was detected in 4 (26.7%) and 7 (43.8%) patients in the continuous and intermittent groups, respectively, (p=0.320). The length of mechanical ventilation was significantly shorter (p=0.034) in the continuous group (99.5±47.1 h) than in the intermittent group (159.9±94.5 h). The length of ICU stay was also shorter (p=0.0097) in the continuous group (6.3±2.1 days) than the intermittent group (9.8±4.8 days)., Conclusions: Although continuous SSD did not reduce the incidence of VAP, it reduced the length of mechanical ventilation and ICU stay when compared to intermittent SSD., Competing Interests: CONFLICTS OF INTEREST We have nothing to declare for this study.

Background: Surgical approaches to treat psychiatric disorders have made a comeback. News media plays an essential role in exposing the public to trends in health care such as the re-emergence of therapeutic interventions in psychiatric neurosurgery that were set aside for decades, and in shaping attitudes and acceptance to them., Method: We conducted an analysis of media articles covering all types of psychiatric neurosurgery published in Canada, USA, Germany, and Spain between the years 1960 and 2015. We applied both quantitative and qualitative methods to elucidate patterns of reporting for conditions, themes and tone, across geographic regions, time, and for type of intervention., Results: Coverage of psychiatric neurosurgery has surged since 2001 and is largely consistent across the countries examined. It focuses on depression and deep brain stimulation, and is explicit about historical context. The tone of coverage becomes more positive for Canada, USA and Spain over time; the tone of coverage from Germany remains cautious. Identity and privacy are among the few ethical and philosophical issues raised, notably in the German press., Conclusions: The focused and optimistic attention to contemporary psychiatric neurosurgery in the media, but inattention to ethical issues, places an extra burden on functional neurosurgeons, psychiatrists, and other frontline health professionals to attend to queries from patients and policy makers about the full range of relevant emergent and emerging interventions and the mental health issues to which they may beneficially apply.

Aims/introduction: The distributer of the anti-glutamic acid decarboxylase antibody assay kit using radioimmunoassay (RIA) recently announced its discontinuation, and proposed an alternative kit using enzyme-linked immunosorbent assay (ELISA). The aim of the present study was to investigate the diagnostic values of the anti-glutamic acid decarboxylase antibody by RIA and ELISA among type 1 diabetes mellitus patients and control participants., Materials and Methods: A total of 79 type 1 diabetes mellitus patients and 79 age-matched controls were enrolled and assessed using RIA and ELISA. Sensitivity, specificity, positive predictive values and negative predictive values were calculated for cut-off values (RIA = 1.5 U/mL and ELISA = 5.0 U/mL, respectively). Kappa coefficients were used to test for agreements between the RIA and ELISA methods regarding the diagnosis of type 1 diabetes mellitus., Results: The sensitivity, specificity, positive predictive values, and negative predictive values for diagnosing type 1 diabetes mellitus were 57.0, 97.5, 95.7, and 69.4% by RIA, and 60.8, 100.0, 100.0 and 71.8% by ELISA, respectively. The diagnosis of type 1 diabetes mellitus using the RIA and ELISA methods showed substantial agreement with the kappa values of 0.74 for all participants, and of 0.64 for the acute type; however, there was moderate agreement with the kappa value of 0.56 for the slowly progressive type., Conclusions: The present study suggests that both anti-glutamic acid decarboxylase antibody by RIA and ELISA was useful for diagnosing type 1 diabetes mellitus. However, in the slowly progressive type, the degree of agreement of these two kits was poorer compared with those in all participants or in the acute type., (© 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Kisspeptin-10 (KP-10), a potent vasoconstrictor and inhibitor of angiogenesis, and its receptor, GPR54, have currently received much attention in relation to pre-eclampsia. However, it still remains unknown whether KP-10 could affect atherogenesis., Methods and Results: We evaluated the effects of KP-10 on human umbilical vein endothelial cells, human monocyte-derived macrophages, human aortic smooth muscle cells in vitro, and atherosclerotic lesions in apolipoprotein E-deficient (ApoE -/- ) mice in vivo. KP-10 significantly increased the adhesion of human monocytes to human umbilical vein endothelial cells, which was significantly inhibited by pretreatment with P234, a GPR54 antagonist. KP-10 stimulated mRNA expression of tumor necrosis factor-α, interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1, vascular adhesion molecule-1, and E-selectin in human umbilical vein endothelial cells. KP-10 significantly enhanced oxidized low-density lipoprotein-induced foam cell formation associated with upregulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in human monocyte-derived macrophages. In human aortic smooth muscle cells, KP-10 significantly suppressed angiotensin II-induced migration and proliferation, but enhanced apoptosis and activities of matrix metalloproteinase (MMP)-2 and MMP-9 by upregulation of extracellular signal-regulated kinase 1 and 2, p38, Bcl-2-associated X protein, and caspase-3. Four-week-infusion of KP-10 into ApoE -/- mice significantly accelerated the development of aortic atherosclerotic lesions with increased monocyte/macrophage infiltration and vascular inflammation as well as decreased intraplaque vascular smooth muscle cells contents. Proatherosclerotic effects of endogenous and exogenous KP-10 were completely canceled by P234 infusion in ApoE -/- mice., Conclusions: Our results suggest that KP-10 may contribute to accelerate the progression and instability of atheromatous plaques, leading to plaque rupture. The GPR54 antagonist may be useful for prevention and treatment of atherosclerosis. Thus, the KP-10/GPR54 system may serve as a novel therapeutic target for atherosclerotic diseases., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Novel APOBEC1 target 1 (Nat1) (also known as "p97," "Dap5," and "Eif4g2") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared with eIF4G1, NAT1 preferentially interacted with eIF2, fragile X mental retardation proteins (FMR), and related proteins and especially with members of the proline-rich and coiled-coil-containing protein 2 (PRRC2) family. We also found that Nat1-null mES cells possess a transcriptional profile similar, although not identical, to the ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and glycogen synthase kinase 3 (GSK3) signaling pathways. In Nat1-null mES cells, the ERK pathway is suppressed even without inhibitors. Ribosome profiling revealed that translation of mitogen-activated protein kinase kinase kinase 3 (Map3k3) and son of sevenless homolog 1 (Sos1) is suppressed in the absence of Nat1 Forced expression of Map3k3 induced differentiation of Nat1-null mES cells. These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation., Competing Interests: S.Y. is a scientific advisor of iPS Academia Japan without salary.

Appropriate policies to improve air quality by reducing anthropogenic emissions are urgently needed. This is typified by the particulate matter (PM) problem and it is well known that one type of PM, sulfate aerosol (SO 4 2- ), has a large-scale impact due to long range transport. In this study we evaluate the source-receptor relationships of SO 4 2- over East Asia for 2005, when anthropogenic sulfur dioxide (SO 2 ) emissions from China peaked. SO 2 emissions from China have been declining since 2005-2006, so the possible maximum impact of Chinese contributions of SO 4 2- is evaluated. This kind of information provides a foundation for policy making and the estimation of control effects. The tagged tracer method was applied to estimate the source apportionment of SO 4 2- for 31 Chinese province-scale regions. In addition, overall one-year source apportionments were evaluated to clarify the seasonal dependency. Model performance was confirmed by comparing with ground-based observations over mainland China, Taiwan, Korea, and Japan, and the model results fully satisfied the performance goal for PM. We found the following results. Shandong and Hebei provinces, which were the largest and second largest SO 2 sources in China, had the greatest impact over the whole of East Asia with apportionments of around 10-30% locally and around 5-15% in downwind receptor regions during the year. Despite large SO 2 emissions, the impact of south China (e.g., Guizhou, Guangdong, and Sichuan provinces) was limited to local impact. These results suggest that the reduction policy in south China contributes to improving the local air quality, whereas policies in north and central China are beneficial for both the whole of China and downwind regions. Over Taiwan, Korea, and Japan, the impact of China was dominant; however, local contributions were important during summer., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. 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.)

Acute kidney injury (AKI) is the main cause of death for victims of hematoxic snakebites. A few studies have described improvement in AKI rates in snakebite cases, but the reasons for the improvement have not been investigated. Eighty-six patients with Protobothrops flavoviridis bites admitted to a single center from January 2003 through March 2014 were included in the study. Clinical variables, including age, sex, blood pressure (BP), and serum creatinine (S-Cre), on admission were compared between patients with and without AKI. One patient died of disseminated intravascular coagulation following AKI (mortality rate 1.1%). Six patients developed AKI with rhabdomyolysis. Systolic BP, S-Cre, serum creatine kinase, white blood cell count, and platelet count differed significantly between the AKI and non-AKI groups (P = 0.01). Three of the six patients were physically challenged to a degree that made it difficult for them to move or communicate, and these difficulties likely exacerbated the severity of snakebite complications. Our study demonstrated that the risk of snakebite-induced AKI for physically challenged patients was high. To further reduce mortality due to snakebite-induced AKI, we need to make it possible for physically challenged patients to receive first aid sooner., (© The American Society of Tropical Medicine and Hygiene.)

To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 μg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased., (Copyright © 2015. Published by Elsevier Ltd.)

Heat stress is a major factor inducing oxidative disturbance in cells. In the present study, we investigated the mechanism of overproduction of reactive oxygen species (ROS) in cultured avian muscle cells in response to heat stress, and also focused attention on the interaction of mitochondrial superoxide anions with altered NADPH oxidase (NOX), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) mRNA levels in heat-stressed cells. Exposure of cells to heat stress conditions (41°C, 6h) resulted in increased mitochondrial superoxide and intracellular ROS levels, and increased carbonyl protein content as compared with that of normal cells (37°C). The mitochondrial uncoupler 2,4-dinitrophenol lowered intracellular ROS levels in heat-stressed cells. Heat stress increased NOX4 mRNA and decreased HO-1 mRNA levels, while SOD1 and SOD2 mRNA levels remained relatively stable in heat-stressed cells. Addition of the superoxide scavenger 4-hydroxy TEMPO to the culture medium of heat-stressed cells restored mitochondrial superoxide and intracellular ROS levels as well as NOX4 and HO-1 mRNA levels to near-normal values. We suggest that mitochondrial superoxide production could play an influential role in augmenting oxidative damage to avian muscle cells, possibly via the up-regulation of NOX4 and down-regulation of HO-1 in heat-stressed avian muscle cells., (Copyright © 2015 Elsevier Ltd. 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.)

Objectives: To determine current epidemiology and treatment patterns of urogenital tuberculosis in Japan., Methods: A questionnaire was sent to the urological departments of 1203 Japanese hospitals. Clinical data was reviewed retrospectively; no time range was specified., Results: Of the 1203 hospitals, 399 returned questionnaires with information about 355 urogenital tuberculosis patients. Of the 399, 153 institutions reported at least one patient, and 201 patients were identified between 2000 and 2007. Infections were located in the kidneys (n = 242), ureter (n = 96), bladder (n = 100), epididymis or testes (n = 81) and prostate (n = 9)., Conclusions: Urogenital tuberculosis is rare in Japan, but patients do exist, and we should not ignore them., (© 2014 The Japanese Urological Association.)

Objectives: The increasing prevalence of resistant bacteria such as fluoroquinolone-resistant or extended-spectrum β-lactamase-producing strains in pathogens causing acute uncomplicated cystitis has been of concern in Japan. Faropenem sodium is a penem antimicrobial that demonstrates a wide antimicrobial spectrum against both aerobic and anaerobic bacteria. It is stable against a number of β-lactamases., Methods: We compared 3 and 7 day administration regimens of faropenem in a multicentre, randomized, open-label, controlled study., Results: In total, 200 female patients with cystitis were enrolled and randomized into 3 day (N = 97) or 7 day (N = 103) treatment groups. At the first visit, 161 bacterial strains were isolated from 154 participants, and Escherichia coli accounted for 73.9% (119/161) of bacterial strains. At 5-9 days after the completion of treatment, 73 and 81 patients from the 3 day and 7 day groups, respectively, were evaluated by intention-to-treat analysis; the microbiological efficacies were 58.9% eradication (43/73), 20.5% persistence (15/73) and 8.2% replaced (6/73), and 66.7% eradication (54/81), 6.2% persistence (5/81) and 7.4% replaced (6/81), respectively (P = 0.048). The clinical efficacies were 76.7% (56/73) and 80.2% (65/81), respectively (P = 0.695). Adverse events due to faropenem were reported in 9.5% of participants (19/200), and the most common adverse event was diarrhoea., Conclusions: The 7 day regimen showed a superior rate of microbiological response. E. coli strains were in general susceptible to faropenem, including fluoroquinolone- and cephalosporin-resistant strains., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We retrospectively investigated the incidence of genitourinary tract infection in 5895 patients who underwent transrectal and/or transperineal prostate biopsy procedure between January and December 2011 at 46 institutions belonging to Japanese Research Group for Urinary Tract Infection (JRGU). The total rate of genitourinary tract infection after prostate biopsy was 0.76%, while that following transrectal procedure was 0.83% and following transperineal procedure was 0.57%, which were not significantly different. In contrast, febrile infection associated with a fever (≥38 °C) occurred significantly more frequently after transrectal (0.71%) than transperineal (0.16%) approach (P = 0.04). Notably, in infectious cases, Escherichia coli was most frequently isolated. Of the 9 E. coli strains isolated by urine culture, 6 (66.7%) produced extended spectrum β-lactamase (ESBL) and 7 (77.8%) showed levofloxacin resistance. Similarly, of 6 E. coli strains isolated by blood culture, 4 (66.7%) produced ESBL and 6 (100%) showed levofloxacin resistance. When the efficacy of antimicrobial prophylaxis (AMP) with levofloxacin for the patients undergoing transrectal or transperineal biopsy was compared between a single dose (500 mg) and that given for 2 or more days, no significant difference was observed for the rate of infection (transrectal: 0.82% vs. 1.04%, p = 0.94; transperineal: 0.30% vs. 0.46%, p = 0.68). Although a single dose of levofloxacin for AMP is sufficient to prevent genitourinary infection after transrectal or transperineal prostate biopsy, and recommended in this era of increased multi-drug resistant pathogens, the increase in fluoroquinolone-resistant E. coli and ESBL-producing E. coli has emerged as a profound problem for surveillance., (Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Improvement of air quality models is required so that they can be utilized to design effective control strategies for fine particulate matter (PM2.5). The Community Multiscale Air Quality modeling system was applied to the Greater Tokyo Area of Japan in winter 2010 and summer 2011. The model results were compared with observed concentrations of PM2.5 sulfate (SO4(2-)), nitrate (NO3(-)) and ammonium, and gaseous nitric acid (HNO3) and ammonia (NH3). The model approximately reproduced PM2.5 SO4(2-) concentration, but clearly overestimated PM2.5 NO3(-) concentration, which was attributed to overestimation of production of ammonium nitrate (NH4NO3). This study conducted sensitivity analyses of factors associated with the model performance for PM2.5 NO3(-) concentration, including temperature and relative humidity, emission of nitrogen oxides, seasonal variation of NH3 emission, HNO3 and NH3 dry deposition velocities, and heterogeneous reaction probability of dinitrogen pentoxide. Change in NH3 emission directly affected NH3 concentration, and substantially affected NH4NO3 concentration. Higher dry deposition velocities of HNO3 and NH3 led to substantial reductions of concentrations of the gaseous species and NH4NO3. Because uncertainties in NH3 emission and dry deposition processes are probably large, these processes may be key factors for improvement of the model performance for PM2.5 NO3(-)., Implications: The Community Multiscale Air Quality modeling system clearly overestimated the concentration of fine particulate nitrate in the Greater Tokyo Area of Japan, which was attributed to overestimation of production of ammonium nitrate. Sensitivity analyses were conducted for factors associated with the model performance for nitrate. Ammonia emission and dry deposition of nitric acid and ammonia may be key factors for improvement of the model performance.

Ifosfamide combined with other antineoplastic agents has been effective in the treatment of osteosarcoma, although adverse effects are reported in the increasing use of ifosfamide. The most serious complications among the ifosfamide intoxications are neurotoxicity and nephrotoxicity. We report on a patient who suffered from ifosfamide-induced neurotoxicity and nephrotoxicity and rhabdomyolysis after chemotherapy, and was successfully treated with blood purification therapy. The patient had osteosarcoma with multiple lung metastases, wherein the chemotherapy included ifosfamide (3 g/m(2)) and VP-16 (60 mg/m(2)) per day for 3 days. The first day after chemotherapy, the patient experienced impaired consciousness and renal function. Based on the clinical course and laboratory data, the diagnosis was ifosfamide-induced neurotoxicity and the acute kidney injury caused by ifosfamide-induced nephrotoxicity and rhabdomyolysis. As a detoxification treatment, blood purification procedures were performed daily for 3 days. Thirty-six hours after the first hemodialysis session, the symptoms of neurotoxicity disappeared. In the lead-up to the 10th day following intoxication, the serum creatinine recovered to the baseline level. Serum ifosfamide concentration decreased from 41.9 to 12.1 ng/ml by the second session of blood purification. Despite the absence of an established detoxification method when complications present simultaneously, blood purification therapy should be considered for treating severe concurrent neurotoxicity and nephrotoxicity and rhabdomyolysis.

Metals are effectively used in biological systems under the strict regulation for exploiting their specific and broad reactivities. For example, manganese (Mn) can induce catecholamines-mediated oxidative biological damage in cooperation with iron (Fe) and/or copper (Cu). In children, the damage could induce developmental disorders such as attention deficit hyperactivity disorder (ADHD). We hypothesize that infant neurons are more labile to metals than adult ones due to the prematured protection systems and sensitive differentiating cells. An experimental system reconstituting neural differentiation is expected to assess the influences of endogenous/exogenous factors including metals. In this study, we investigated an impact of Mn together with Fe and dopamine (DA) on neural differentiation of mouse embryonic stem cells (mESCs). The differentiation of mESCs was initiated by embryoid bodies (EBs) formation in the presence of all-trans retinoic acid, and then EBs were treated with Mn, Fe and/or DA. Then, the mRNA levels of neural differentiation marker genes (Nestin, Emx2, Mtap2, Th, Olig2 and Gfap) were examined using realtime RT-PCR analysis. Mn or DA alone reduced Mtap2, Th and Olig2 expression levels and increased Nestin. Moreover, combined treatment of Mn and DA also increased Nestin expression level. On the other hand, Fe alone reduced Mtap2, Th and Olig2 expression levels, and increased Emx2. Combined treatments of Fe with Mn or DA also tended to increase Emx2 expression level. These effects emerged at about 100 times less concentration than that inducing cytotoxicity in human neuroblastoma. The present study showed that Mn inhibits neural development, and that our mESCs system can be a useful tool to elucidate the toxicity mechanism as well as to evaluate the effects of metals and chemicals on differentiating cells.

To propose an appropriate prophylactic antimicrobial therapy for patients undergoing brachytherapy, we evaluated the relationships between various antimicrobial prophylaxis (AMP) protocols and the incidence of postimplant infections in a multicenter cohort study conducted in Japan. The records of 826 patients with localized prostate cancer who underwent a transperineal (125)I brachytherapy procedure between January 2009 and December 2010 were retrospectively reviewed. Perioperative infections, including surgical site and remote infections, were recorded up to postoperative day 30. A total of 6 (0.73%) patients had a perioperative infection following seed implantation, of whom all received AMP for 1 or more days. None of the patients who received a single-dose protocol of AMP using fluoroquinolone p.o. or penicillin with a beta-lactamase inhibitor i.v. developed a perioperative infection. Statistical analysis showed that a single-dose protocol was more significantly related to a lower risk of perioperative infection as compared to the other AMP protocols examined (p = 0.045). Furthermore, our results indicated that bacteriuria and preoperative hair removal were risk factors of perioperative infection with statistical significance (p = 0.007, p = 0.004). Analysis of patient clinical parameters, including age, American Society of Anesthesiologists score, diabetes mellitus, prostate volume, numbers of implanted seeds and needle punctures, operation time, and indwelling duration time of the Foley catheter, did not reveal significant differences in terms of perioperative infection. Our results indicated that a single-dose AMP protocol is sufficient to prevent perioperative infections following seed implantation. On the other hand, AMP is only one of several measures to prevent perioperative infectious complications. It is necessary to know that the patient must have no bacteriuria and that preoperative hair removal should be avoided.

Introduction: We report the case of a patient who developed symptoms of acute cerebellar ataxia (ACA) after administration of the human papilloma virus (HPV)-16/18 vaccine., Patient and Method: This patient developed symptoms of ACA, including nausea, vertigo, severe limb and truncal ataxia, and bilateral spontaneous continuous horizontal nystagmus with irregular rhythm, 12 days after administration of the HPV-16/18 AS04-adjuvanted cervical cancer vaccine. After this, the patient received methylprednisolone pulse and intravenous immunoglobulin (IVIG) therapies as well as immunoadsorption plasmapheresis., Results: Severe ACA symptoms did not improve after methylprednisolone pulse and IVIG therapies, but the patient recovered completely after immunoadsorption plasmapheresis., Conclusion: This temporal association strongly suggests that ACA was induced by the vaccination., (Georg Thieme Verlag KG Stuttgart · New York.)

The purpose of this prospective, randomized, multicenter trial was to evaluate the effects of a steroid-avoiding immunosuppression protocol on hepatitis C virus (HCV)-positive recipients of living donor liver transplantation (LDLT). Seventy-five HCV-positive LDLT recipients were included in this study, and they were randomized to receive tacrolimus (TAC) plus a corticosteroid (ST; n = 35) or TAC plus mycophenolate mofetil (MMF; n = 40). Biopsy-proven acute rejection (BPAR) was treated with steroid pulse therapy in both groups. Protocol biopsy was performed 3, 6, and 12 months after LDLT and annually thereafter. Histological recurrence of HCV (fibrosis stage ≥ F1 according to the METAVIR score), BPAR resistant to 2 sets of steroid pulse therapy, hepatocellular carcinoma (HCC) recurrence, retransplantation, and patient death were defined as events, and the primary endpoint was event-free survival. The median follow-up was 55 months. The event-free survival rates at 1, 3, and 5 years were 38.2%, 11.8%, and 5.9%, respectively, for the ST group and 25.0%, 17.5%, and 14.6%, respectively, for the MMF group (P = 0.45). The overall 5-year patient survival rates were similar for the ST group (82.7%) and the MMF group (81.0%, P = 0.28). Steroid-resistant BPAR occurred in only 1 patient from the MMF group. HCC recurrence occurred for 1 patient from the ST group and 2 patients from the MMF group. HCV recurrence rates with a fibrosis stage ≥ F1 1 and 3 years after LDLT were 59.4% and 85.9%, respectively, for the ST group and 74.2% and 81.9%, respectively, for the MMF group (P = 0.57). In conclusion, our steroid-avoidance regimen had no apparent impact on LDLT outcomes for HCV-positive recipients., (© 2013 American Association for the Study of Liver Diseases.)

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.

Peripheral arterial disease (PAD) is very common in dialysis patients, who tend to have diffuse calcification and severe peripheral arterial stenosis that make it difficult to treat limbs using only surgical or endovascular interventions. Better ways to treat this condition are therefore required and also follow-up studies to evaluate the effects of these treatments on the microcirculation. A 59-year-old man who had a cadaveric kidney transplant five years previously after 25 years of regular hemodialysis complained of pain at rest in his right lower limb and subsequently developed an intractable decubitus ulcer on his right fifth toe (Fontaine IV). Digital subtraction angiography revealed a severe obstruction of the right femoral artery and diffuse stenosis of the right superficial femoral artery. The patient underwent percutaneous transluminal angioplasty (PTA) and six sessions of low-density lipoprotein apheresis (LDL apheresis). At the end of these sessions his complaints were almost completely alleviated. The mean elevation in skin temperature after each session was (1.58 ± 0.99)°C [mean ± SD] over the right dorsalis pedis artery and (1.52 ± 0.88)°C at the tip of the right fifth toe. Ultrasound-measured blood flow rates in the right dorsalis pedis artery were 9.2 cm/s before PTA and 20.2 cm/s one month after PTA. Hemodialysis was resumed 3 days after the PTA due to contrast-induced nephropathy. The combination of PTA and LDL apheresis is useful for treating PAD in hemodialysis patients, with the changes in peripheral artery patency are able to be evaluated effectively by measuring skin temperature., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To survey the present condition of administration method of the antimicrobial prophylactic (AMP) agents for the perioperative infection in Japan on revising "The Japanese guidelines for prevention of perioperative infections in urologic field (2006)"., Patients and Methods: With the approval of the Japanese Urological Association (JUA) in 2011, all of the principal urological training institutions certified by JUA (n = 836) were encouraged to participate to survey their adherence to the JUA guidelines (published in 2006) for AMP to prevent perioperative infection in urological field, and 446 (53.3%) institutions responded to the questionnaire., Results: The rates of following the JUA guidelines of, "completely", "mainly", "not too much", and "not at all" were 6.5%, 69.7%, 22.0% and 1.6%, respectively. The guidelines were followed for open clean operations in 48.5%, open clean-contaminated operations in 66.4%, open contaminated operations in 61.8%, laparoscopic clean operations in 54.1%, laparoscopic clean-contaminated operations in 61.2%, transurethral resection of bladder tumor in 71.5%, transurethral resection of prostate in 68.9%, ureteroscopy and transurethral ureterolithotomy in 68.2%, prostate biopsy in 43.2%, and cystoscopy were in 42.2%, respectively. However, in terms of duration of AMP administration, the longer duration than those recommended by the guidelines were observed for clean surgery, transurethral resection of bladder tumor, ureteroscopy and transurethral ureterolithotomy, prostate biopsy, and cystoscopy., Conclusions: In terms of kinds of AMP, the guidelines were almostly followed in all operative procedures. However, the duration of AMP administration were longer than those recommended by the guidelines. On revision of "Japanese guidelines for prevention of perioperative infections in urologic field (2006)", these data would be taken into consideration to avoid dissociation between the guidelines and the practical side in the urologists.

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.

Zeolite-geopolymer hybrid materials have been formed when kaolin was used as a starting material. Their characteristics are of interest because they can have a wide pore size distribution with micro- and meso-pores due to the zeolite and geopolymer, respectively. In this study, Zeolite-geopolymer hybrid bulk materials were fabricated using four kinds of kaolinitic clays (a halloysite and three kinds of kaolinite). The kaolinitic clays were first calcined at 700 °C for 3 h to transform into the amorphous aluminosilicate phases. Alkali-activation treatment of the metakaolin yielded bulk materials with different amounts and types of zeolite and different compressive strength. This study investigated the effects of the initial kaolinitic clays on the amount and types of zeolite in the resultant geopolymers as well as the strength of the bulk materials. The kaolinitic clays and their metakaolin were characterized by XRD analysis, chemical composition, crystallite size, 29 Si and 27 Al MAS NMR analysis, and specific surface area measurements. The correlation between the amount of zeolite formed and the compressive strength of the resultant hybrid bulk materials, previously reported by other researchers was not positively observed. In the studied systems, the effects of Si/Al and crystalline size were observed. When the atomic ratio of Si/Al in the starting kaolinitic clays increased, the compressive strength of the hybrid bulk materials increased. The crystallite size of the zeolite in the hybrid bulk materials increased with decreasing compressive strength of the hybrid bulk materials.

Objective: The "Japanese guidelines for prevention of perioperative infections in urological field" was edited by the Japanese Urological Association in 2007. They are the first Japanese guidelines for antimicrobial prophylaxis specifically to prevent perioperative infections in the urological field. We report here the results of a multicenter prospective study conducted to examine the validity and usefulness of these guidelines., Patients and Methods: The subjects were 513 patients who had undergone urological surgeries between July and September 2008 at 10 nationwide university institutions in the Japanese Society of UTI Cooperative Study Group. These surgeries were transurethral resection of bladder (TURBT), transurethral resection of prostate (TURP), adrenalectomy, nephrectomy, nephroureterectomy, radical prostatectomy and total cystectomy. Analysis was performed on patient information, surgical procedures, types and durations of administration of prophylactic antibiotic agents, and the presence of surgical site infections (SSI) and remote infections (RI)., Results: Of 513 patients, 387 (75.4%) were administered prophylactic antibiotic agents according to the guidelines. In these patients, the incidences of SSI and RI were 5.9% and 4.1%, respectively. Multivariate analysis showed that significant factors for SSI were the surgical risk (according to the ASA physical status classification system), diabetes, and operation time, and that the only significant factor for RI was the operation time., Conclusions: More large-scale study and evidences are necessary in order to demonstrate the validity and usefulness of these guidelines.

We examined the rate of relapse, as a variable index, in patients with urinary tract infection (UTI) who suffered from multiple relapses when using cranberry juice (UR65). A randomized, placebo-controlled, double-blind study was conducted from October 2007 to September 2009 in Japan. The subjects were outpatients aged 20 to 79 years who were randomly divided into two groups. One group received cranberry juice (group A) and the other a placebo beverage (group P). To keep the conditions blind, the color and taste of the beverages were adjusted. The subjects drank 1 bottle (125 mL) of cranberry juice or the placebo beverage once daily, before going to sleep, for 24 weeks. The primary endpoint was relapse of UTI. In the group of females aged 50 years or more, there was a significant difference in the rate of relapse of UTI between groups A and P (log-rank test; p = 0.0425). In this subgroup analysis, relapse of UTI was observed in 16 of 55 (29.1 %) patients in group A and 31 of 63 (49.2 %) in group P. In this study, cranberry juice prevented the recurrence of UTI in a limited female population with 24-week intake of the beverage.