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A nationwide surveillance of the antimicrobial susceptibility of pediatric patients to bacterial pathogens was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in Japan in 2017. The isolates were collected from 18 medical facilities between March 2017 and May 2018 by the three societies. Antimicrobial susceptibility testing was conducted at the central laboratory (Infection Control Research Center, Kitasato University, Tokyo) according to the methods recommended by the Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 926 strains (331 Streptococcus pneumoniae, 360 Haemophilus influenzae, 216 Moraxella catarrhalis, 5 Streptococcus agalactiae, and 14 Escherichia coli). The ratio of penicillin-resistant S. pneumoniae was 0% based on CLSI M100-ED29 criteria. However, three meropenem or tosufloxacin resistant S. pneumoniae isolates were obtained. Among H. influenzae, 13.1% of them were found to be β-lactamase-producing ampicillin resistant strains, while 20.8% were β-lactamase non-producing ampicillin-resistant strains. No capsular type b strains were detected. In M. catarrhalis, 99.5% of the isolates were β-lactamase-producing strains. All S. agalactiae and E. coli strains were isolated from sterile body sites (blood or cerebrospinal fluid). The ratio of penicillin-resistant S. agalactiae was 0%, while that of extended spectrum β-lactamase-producing E. coli was 14.3%., Competing Interests: Declaration of competing interest Naruhiko Ishiwada received speaker honoraria from Taisho Toyama Pharmaceutical Co., Ltd. and Japan Vaccine Co., Ltd. and grant support from Pfizer Japan Inc. and MSD K.K. Kazuo Fujimaki is employee of Fujifilm Toyama Chemical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K. and Pfizer Japan Inc. Hiroshi Kiyota 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. Hideaki Hanaki received consulting fee from Taiko Pharmaceutical Co., Ltd. Kazunobu Ouchi received speaker honoraria from MSD K.K., Taisho Toyama Pharmaceutical Co., Ltd., FUJIFILM Corporation., Astellas Pharma Inc. and Pfizer Japan Inc. and received scholarship donations from Daiichi Sankyo Co., Ltd., ASAHI KASEI PHARMA CORPORATION., Taisho Toyama Pharmaceutical Co., Ltd., FUJIFILM Corporation. and Shionogi & Co., Ltd. Satoshi Iwata received speaker honoraria from Astellas Pharma Inc., Meiji Seika Pharma Co., Ltd. and Pfizer Japan Inc. and advisory role of Pfizer Japan Inc., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: A multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML)., Methods: The study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients., Results: The median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003)., Conclusion: Elevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Few studies have examined the relationship between social function and brain activation in non-clinical populations. The aim of the present study was to assess this relationship and examine the underlying cortical mechanisms in a non-clinical population. Eighty healthy volunteers performed a serial arithmetic task according to the Uchida-Kraepelin performance test while hemoglobin concentration changes were assessed on the surface of the prefrontal cortex (PFC) using 32-channel near-infrared spectroscopy. Participants were also assessed for quality of life (QOL) using the Short-Form 36-item Questionnaire (SF-36), for affective symptoms using the Zung Self-rating Depression Scale (SDS), for apathy using the Apathy Scale, for feelings of stress using the Stress Arousal Checklist (SACL), and for task performance using the number of answers in a serial arithmetic task. Activity in the frontopolar PFC displayed a significant positive correlation with social functioning on the SF-36. SDS and SACL scores correlated negatively with social functioning. Furthermore, in multiple regression analysis, social functioning was predicted by activity of the frontopolar PFC and SDS scores. These results suggest that the association between changes in cortical activation and sub-threshold affective symptoms may objectively identify individuals with QOL on social functioning., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Maternally provided mRNAs and proteins direct early development and activate the zygotic genome. Using microarrays, we examined the dynamics of transcriptomes during the early development of a basal chordate, Ciona intestinalis. Microarray analysis of unfertilized eggs, as well as 8-, and 16- and 32-cell embryos revealed that nearly half of the genes encoded in the genome were expressed maternally, and that approximately only one-fourth of these genes were expressed at similar levels among eggs obtained from different individuals. Genes encoding proteins involved in protein phosphorylation were enriched in this latter group. More than 90% of maternal RNAs were not reduced before the 16-cell stage when the zygotic developmental program begins. Additionally we obtained gene expression profiles of individual blastomeres from the 8- and 16-cell embryos. On the basis of these profiles, we concluded that the posterior-most localization, which has been reported for over 20 different transcripts, is the only major localization pattern of maternal transcripts. Our data also showed that maternal factors establish only nine distinct patterns of zygotic gene expression at the 16-cell stage. Therefore, one of the main developmental functions of maternally supplied information is to establish these nine distinct expression patterns in the 16-cell embryo. The dynamics of transcriptomes in early-stage embryos provides a foundation for studying how maternal information starts the zygotic program., (© 2013 Published by Elsevier Inc.)

The optimal treatments for relapsed acute promyelocytic leukemia (APL) remain equivocal. We conducted a phase 2 study to evaluate the efficacy and feasibility of a sequential treatment consisting of induction and consolidation with arsenic trioxide (ATO), peripheral blood stem cell (PBSC) harvest after high-dose cytarabine chemotherapy, and autologous hematopoietic cell transplantation (HCT). Between 2005 and 2009, 35 patients (26 with hematologic and 9 with molecular relapse) were enrolled. Induction therapy resulted in complete remission in 81% of those with hematologic relapse, and most patients became negative for PML-RARα after the first ATO consolidation course, but 4 remained positive. Administration of the second ATO consolidation course further decreased the transcript levels in 3 patients. In total, 25 patients proceeded to PBSC harvest, all of whom successfully achieved the target CD34+ cell doses, and 23 underwent autologous HCT with PML-RARα-negative PBSC graft. Posttransplant relapse occurred in 3 patients, and there was no transplant-related mortality. With a median follow-up of 4.9 years, the 5-year event-free and overall survival rates were 65% and 77%, respectively. These findings demonstrate the outstanding efficacy and feasibility of the sequential treatment featuring ATO and autologous HCT for relapsed APL. This study was registered at http://www.umin.ac.jp/ctr/ as #C000000302.

Background: Protein phosphatase 2A (PP2A) is a major kinase phosphatase that plays an important role in regulating the activities of protein kinase cascades. It has been revealed that stress changes neuronal gene expression by activating these cascades. We examined the expression of the catalytic subunit C and serine and threonine phosphatase activity of PP2A in the rat frontal cortex and hippocampus following various immobilization stress paradigms., Methods: Immunoblot and immunohistochemical analyses were performed to examine the expression of PP2A. The level of phosphatase activity of PP2A was determined as the amount of free phosphate generated from a synthetic phosphopeptide., Results: Immunoblot analysis revealed no significant change in the level of PP2A immunoreactivity in response to either a single or repeated stress. Immunohistochemical analysis revealed that neither a single nor repeated stress changed PP2A immunoreactivity in the hippocampus; however, the levels of serine and threonine phosphatase activity in the frontal cortex and hippocampus were significantly upregulated in response to a single or repeated stress., Conclusions: These results demonstrated that both a single and repeated immobilization stress upregulated the activity of PP2A in the rat brain, suggesting that PP2A may be involved, at least in part, in the downregulation of protein kinase activation induced by stress.

Intracytoplasmic free calcium ions (Ca++) are maintained at a very low concentration in mammalian tissue by extruding Ca++ from the cytoplasm against a steep extracellular Ca++ concentration gradient, mainly through the activity of plasma membrane Ca++ pump-ATPase. The present study aimed to elucidate how endothelin-1 (ET-1) affects the morphology of sinusoidal endothelial fenestrae and ultrastructural distribution of plasma membrane ATPases and intracytoplasmic free Ca++ in isolated rat hepatic sinusoidal endothelial cells. Sinusoidal endothelial fenestrae were observed by scanning electron microscope. Ando's electron cytochemical method was used for ultrastructural localization of Ca++-Mg++-ATPase activity, electron immunogold postembedding method for Ca++ pump-ATPase immunoactivity, and antimonate method for intracytoplasmic free Ca++. Addition of ET-1 to sinusoidal endothelial cells significantly decreased Ca++-Mg++-ATPase activity and Ca++ pump-ATPase expression and increased intracytoplasmic free Ca++ concentration, concomitant with a decrease in diameter of sinusoidal endothelial fenestrae. Co-treatment with Bosentan abolished the actions of ET-1. These results suggest that ET-1 suppresses Ca++-Mg++-ATPase activity and Ca++ pump-ATPase expression on the plasma membrane of sinusoidal endothelial fenestrae, thereby attenuating the extrusion of intracytoplasmic free Ca++ into the extracellular space, leading to an increased concentration of intracytoplasmic free calcium ions and contraction of sinusoidal endothelial fenestrae.

Integrin-mediated adhesion induces the formation of focal adhesions that link the extracellular matrix and intracellular actin cytoskeletal networks. We previously showed that integrin-linked kinase (ILK), which can interact with beta1 and beta3 integrins, and its interacting protein, affixin, play an essential role in the initial assembly of focal adhesion structures and actin stress fibers. Although the relevant structures are also observed in integrin alphaIIbbeta3 in platelets, the precise underlying molecular mechanism remains unclarified. Here, we found that ILK stably forms a complex with ss-affixin in platelets. Thrombin stimulation induces their association with integrin beta3, which is followed by their incorporation into the Triton-insoluble membrane-cytoskeletal fraction. During the course of thrombin-induced platelet aggregation, ILK activity was enhanced within 90s to 2.1-fold of the basal level, independent of phosphatidylinositol 3-kinase. Taken together with the observation that the treatment with an anti-integrin beta3 antibody stimulates ILK activity without inducing platelet aggregation, these results suggest that the outside-in signaling induced by fibrinogen binding to integrin enhances ILK activity and results in the initial phase to reorganize the actin cytoskeleton.