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Describes a dual line emission tomography system for the CDX-U tokamak at the Princeton Plasma Physics Laboratory in Princeton, New Jersey. Filtered diode arrays; Difficulty of measuring magnetohydrodynamic activity with good spatial and temporal resolution from soft x-ray continuum emission.

Background: Zolpidem is used for insomnia in pregnant and lactating women. Although zolpidem has been shown to cross the placenta and to be secreted into breast milk, it would not be expected to cause any adverse effects in newborn and breastfed infants. However, there is no relevant information on serum zolpidem levels in the newborn and breastfed infant from zolpidem-treated mother. This study aimed to present the outcomes of zolpidem exposure into infant who was delivered or breastfed by a zolpidem-treated mother. Methods: In this case series, zolpidem-treated pregnant women were recruited between September 2019 and April 2022, and maternal serum, cord blood, breast milk, and infants' serum were collected, and the zolpidem concentration in each sample was evaluated. Childbirth outcomes, including 1-month health care checkup, were also evaluated. Results: Three cases were recruited during investigation period. No spontaneous abortion or preterm live deliveries occurred. Oxygen intervention was required in one term infant, but the findings resolved on postpartum day 1. No medical intervention was required in other three infants. Zolpidem was not detected in infants' serum even after breastfeeding. There are no abnormal developmental findings in any of the infants in their 1-month health checkups. Conclusions: Zolpidem transferred into fetal circulation in utero and breast milk, however no harmful findings existed in infants during pregnancy and lactation. Exposure doses through breastfeeding is small, which may be a cause of rare detection from the infants' serum. Due to the limited number of cases, larger studies and integrated review are needed.

Background: Hypnotics are frequently used for insomnia in pregnant and lactating women. This case study assessed zolpidem concentrations in the cord blood and breast milk and ramelteon concentrations in the breast milk of a woman who was treated with zolpidem and ramelteon for insomnia. Materials and Methods: Zolpidem concentrations were measured in maternal serum, breast milk, and cord blood. Concentrations of ramelteon and M-II, an active ramelteon metabolite, were measured in maternal serum and breast milk. Case Report: A 46-year-old female patient diagnosed with insomnia received 5-10 mg/day zolpidem during pregnancy and lactation and 8 mg/day ramelteon during lactation. A male infant weighing 3,329 g was born at 38 weeks' gestation, with no congenital abnormalities found during pregnancy or at birth. The infant was normal at the 1-month postpartum checkup. The maternal/placental ratio of zolpidem concentrations was 0.1 at 7.4 hours after maternal dosing, similar to that reported in previous studies. The calculated relative infant dose through breast milk based on the maximum drug concentration in breast milk at 2.2 hours after maternal dosing was 2.7% for zolpidem and 0.2% for ramelteon. Ramelteon and its metabolite (M-II) concentrations in the breast milk were equivalent to those in the maternal serum, although the infant exposure of these drugs was low for an oral dose. Conclusions: In the current case, zolpidem transferred into the placenta and breast milk, and ramelteon transferred into the breast milk. Further studies should assess the safety of zolpidem and ramelteon in fetus and breastfed infants.

Introduction: From 2018, IR Biotyper (IRBT; Bruker Daltonik GmbH, Germany) based on the Fourier transform infrared spectrophotometer has begun to be introduced as a new strain classification method in the field of clinical microbiological examination. We compared it with molecular epidemiology method to evaluate the usefulness of strain classification by IRBT., Method: Homology of strain classification with molecular epidemiology method (Multilocus Sequencing Typing; MLST and PCR-based ORF Typing; POT) for 48 strains of Pseudomonas aeruginosa with different detection times from multiple institutions to evaluate the accuracy of IRBT was compared., Results: IRBT used "KBM" SCD agar medium for preculture and was classified into 12 types when classified by Cut-off value 0.181, 8 types by MLST, and 13 types by POT. In the Adjusted Wallace between IRBT and molecular epidemiology method, MLST was 0.458 (95% CI; 0.295 to 0.620) and POT was 0.330 (95% CI; 0.135 to 0.525), indicating a discrepancy in strain classification., Conclusion: No correlation was found between IRBT and the classification results by the molecular epidemiology method. In the molecular epidemiology method, strains are classified by matching only specific gene regions, but IRBT irradiates a sample with an infrared laser and classifies the strains according to the difference in absorption spectrum according to the molecular structure, so the measurement principle is different. When classifying strains by IRBT, it is desirable to grasp the clinical information of the detected strains and to target multiple strains isolated at the same facility at the same time.

Introduction: Carbapenemase-producing Enterobacteriaceae (CPE) is a major global health threat, and development of rapid detection methods is desired. Here, we established a cost-effective and relatively rapid CPE detection method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)., Methods: We examined 134 CPE strains (IMP-type, NDM-type, VIM-type, KPC-type, OXA-48-like-type, and GES-type) and 107 non-CPE strains, previously confirmed by genetic tests. The proposed MALDI-TOF MS method involves mixing of a carbapenem drug [here, the commercially available imipenem (IPM) KB disc] and the bacterial strains to be tested, and the consequent drug hydrolysis owing to bacterial carbapenemase activity is confirmed by a waveform spectrum before and after 2 h of the mixing. As metallo-beta-lactamases require zinc in their active site, the false-negatives obtained from our method were cultured in presence of zinc sulfate solution and tested again., Results: Based on the presence or absence of the IPM (+cyano-4-hydroxy-cinnamic acid)-specific waveform peak near 489.45 m/z (±500 ppm), the detection sensitivity and specificity of our method for CPE were determined to be 94.8% and 91.6%, respectively. Seven false-negatives of IMP-type (4), VIM-type (2), and GES-type (1) were found, of which the IMP- and VIM-types tested positive as CPE after culture with zinc sulfate solution. Thus, the overall detection sensitivity improved to 99.3%., Conclusion: Our study proposes a new approach for CPE detection using MALDI-TOF MS. Moreover, we propose cultivation of test strains with zinc sulfate solution for efficient detection of IMP-type CPE, not only for MALDI-TOF MS, but also for other detection methods., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

There is a report that an infection by medicine resistant bacteria will be the number one cause of death in 2050 according to the recommendation of WHO, and the CPE (carbapenem-producing Enterobacteriaceae ) infection is regarded as a problem in particular. When detecting CPE, it is important how to detect stealth type CPE sensitive to carbapenem series medicines. So we used the 2 types of screening culture medium, "KBM" CRE-JU culture medium ‹KOJINBAIO› (CRE-JU culture medium) and the FRPM culture medium, and tried to detect drug-resistant gram-negative bacilli such as CPE, stealth type CPE, ESBL-producing bacteria, and excess AmpC-producing bacteria (AmpC-producing bacteria), etc. in combination of this culture mediums. As a result, CRE-JU culture medium showed a difference in the growth of CPE depending on the amount of inoculated bacteria while β-lactamase non-producing strain and other strains except for high concentration ESBL-producing bacteria and AmpC-producing bacteria were un-growing. Most of the CRE, stealth type CPE, ESBL-producing bacteria and AmpC-producing bacteria grew in the FRPM culture medium while most of the β-lactamase non-producing strains with a MIC value of meropenem (MEPM) of 2 µg/mL or less were un-growing. From these results, it was suggested that when a strain grown on CRE-JU and FRPM culture mediums, it could be distinguished as CPE, and when strains grown on FRPM culture medium which were un-grown on CRE-JU culture medium, it could be distinguished as drug-resistant bacteria such as stealth type CPE, ESBL-producing bacteria, and AmpC-producing bacteria. When strains not grown on CRE-JU and FRPM culture mediums, it could be distinguished as sensitive.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 49.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 9.2% and 0.4%, respectively., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To study how and to what degree the rapid pathogen identification by MALDI-TOF MS coupled with rapid disk diffusion test improve the current clinical practice of patients with bacteremia in a tertiary teaching hospital with full-time ID consultation service., Patients and Methods: MALDI-TOF MS and 8H disk diffusion tests were directly applied to the positive blood cultures samples and the results were reflected on antimicrobial therapy (n = 119). The appropriateness of antimicrobial selection through these interventions was verified with conventional culture results in comparison with historical control (n = 129). The mortality of patients between the two periods was also compared., Results: The appropriateness of antimicrobial selection was higher (99.2%) in the intervention than in the control group (93.8%) (p 0.024), but there was no difference in 28-day mortality between the two periods (16.8%, 14.8%) (p 0.668). The duration of presumptive antimicrobial therapy with anti-MRSA agents and carbapenem antibiotics did not differ between the two periods indicating that the intervention was not effective in decreasing the unnecessary antibiotics. On the other hand, some bacteremic patients with pathogens whose drug susceptibilities were invariably sensitive to the standard class of antibiotics definitely benefitted from the intervention., Conclusion: The intervention utilizing MALDI-TOF MS and the rapid disk diffusion test may not demonstrate overall improvement in bacteremia mortality in the institution with full-time infectious disease consultants. Its utility has yet to be evaluated in different setting hospitals., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We investigated the velocity of an asymmetric camphor boat moving on aqueous solutions with glycerol. The viscosity was controlled by using several concentrations of glycerol into the solution. The velocity decreased with an increase in the glycerol concentration. We proposed a phenomenological model, and we showed that the velocity decreased with an increase in the viscosity according to power law. Our experimental result agreed with the one obtained from our model. These results suggest that a decay length of the camphor concentration at the front side of the boat is sufficiently shorter than that of the rear side.

TIPE2 (TNF-α-induced protein 8-like 2) is a novel death effector domain protein and is a negative regulator of the innate and adaptive immune response. Although it has been demonstrated that caspase-8 contributes to the negative regulation of TIPE2, the negative regulatory mechanism is not entirely understood. Here, we demonstrate that TIPE2 interacts with TGF-β-activated kinase 1 (TAK1), a crucial regulatory molecule of inflammatory and immune signals, and consequently acts as a powerful negative regulator of TAK1. The interaction between endogenous TIPE2 and TAK1 was observed in RAW264.7 macrophage-like cells and mouse primary cells derived from spleen and thymus. The TIPE2 amino acid 101-140 region interacted with TAK1 by binding to the amino acid 200-291 region of the internal kinase domain of TAK1. TIPE2 interfered with the formation of the TAK1-TAB1-TAB2 complex and subsequently inhibited activation of TAK1 and its downstream molecules. Importantly, silencing TIPE2 through RNA interference attenuated the inhibitory action of TIPE2 on LPS- and TNF-α-stimulated TAK1 activity. Exogenous TIPE2 101-140, the region that interacts with TAK1, also inhibited LPS- and TNF-α-stimulated NF-κB reporter activity. Interestingly, cell-permeable TIPE2 protein maintained its binding ability with TAK1 and exhibited the same inhibitory action of native TIPE2 on TLR4 signaling in vitro Thus, cell-permeable TIPE2 protein is a potential candidate for intracellular protein therapy for TAK1-related diseases. The present study demonstrates that TIPE2 acts as a novel negative regulator of inflammatory and immune responses through TAK1 signaling., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Microflex LT (Bruker Daltonics) and VITEK MS (bioMérieux) are bacterial identification systems that are based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). For VITEK MS, two identification softwares, VITEK MS IVD (IVD) and SARAMIS (SARAMIS), are available. Microflex LT is equipped with MALDI Biotyper RTC software (Biotyper). Although the identification accuracy of each instrument has been compared for various bacteria, no detailed examination has been conducted for the identification accuracy of Clostridium difficile. In this report, we compared the three identification softwares for identification reproducibility in three ATCC C. difficile strains and identification accuracy in 50 clinical C. difficile isolates. The results showed 100, 91.7 and 100 % identification reproducibility accuracy of ATCC strains when examined by IVD, SARAMIS and Biotyper software, respectively. For the identification of the clinical isolates, all three softwares exhibited satisfactory identification accuracy of C. difficile. Among the 50 clinical isolates, seven showed identical toxin genotype corresponding to the exact ribotype. However, MALDI-TOF MS failed to identify them as the identical type. Based on the above results, we concluded that both types of MALDI-TOF MS reproducibly identified C. difficile; however, they are currently not suitable for typing of C. difficile clones.

Enterococcus consists human bowel flora, but sometimes behave as an important nosocomial pathogen. In order to identify clinical characteristics that help discriminate between ampicillin-susceptible and ampicillin-resistant enterococcal bacteremia in advance for antimicrobial susceptibility testing, a retrospective eight-year study was carried out in patients with enterococcal bacteremia experienced in Saga University Hospital, Japan. A total of 143 patients were included in the analysis: 85 (59.4%) with bacteremia caused by ampicillin-susceptible enterococci and 58 (40.6%) by ampicillin-resistant strains. Hospital-acquired bacteremia was present in 79.0% (113/143) of patients. Abdominal infections, urinary tract infections, and unknown source were predominant foci for the two groups. Patients with ampicillin-resistant enterococcal bacteremia was significantly associated with hematological cancer, immunosuppressive therapy, prior use of antibiotics, and mucositis associated with febrile neutropenia. The 28-day mortality was significantly higher in ampicillin-resistant enterococcal bacteremia. On multivariate analysis, independent risk factors for ampicillin-resistant enterococci were as follows: prior exposures to penicillins and carbapenems, and bacteremia related to mucositis with febrile neutropenia. These findings would assist physicians in deciding whether glycopeptide antibiotics should be included as an empiric antibiotic therapy in patients with suspected enterococcal infections and also those with persistent neutropenic fever refractory to fourth generation cephalosporin. A few cases of MALDI-TOF MS-identified Enterococcus faecium that turned out ampicillin-sensitive were also described to emphasize the importance of taking epidemiological aspects of patients into considerations when deciding initial antimicrobial treatment., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We investigated the relevance of direct identification method for bacteria from blood culture bottles using MALDI Biotyper(Bruker Co.). One hundred fourteen bacterial strains obtained from blood culture bottles were analyzed using the pretreatment method recommended by Bruker Corporation. The identification rate with recommended pretreatment was 76.3% (87/114). Twenty seven samples that were not identified with the pretreatment method were further analyzed using our modified method. Of these, twelve were identified, improving the identification rate to 86.8% (99/114). These results suggest that our modified pretreatment combined with pretreatment method recommended by Bruker Corporation yields improved identification of bacteria from blood culture bottles using MALDI Biotyper system.

MicroScan Rapid plus Neg II Series and MicroScan Rapid plus Pos Series by Siemens Healthcare Diagnostics K.K. are the panels which enable to measure identification and antimicrobial susceptibility testing quickly and we have confirmed that it is useful for detecting drug resistance bacteria. As the identification result of comparing Rapid plus series with the current panel by using 143 strains of various drug resistance bacteria, Gram positive cocci was 87. 7%, glucose fermenter was 100% and glucose non-fermenter was 77.3 in Gram negative bacilli. On the evaluation of antimicrobial susceptibility testing, Rapid plus series, in comparison with the current panel, confirmed the lower tendency of MIC value on some drugs, but it basically presented the good concordance rate. In terms of the reporting time of antimicrobial agent, non-fermenter or MRCNS reported the result as needed after 8 hours and it took a little longer time for the report of antimicrobial agent. On the other hand, 80% or higher of antimicrobial agent on panel was reported for intestinal bacteria in 4.5 hours and for MRSA in 6.5 hours. It enabled to report the testing result on the same day. Due to the results above, Rapid plus series was highly valued on the usability, such as the early detection of drug resistance bacteria and the selection of therapeutic agents.

Minimum inhibitory concentrations (MICs) of vancomycin (VCM) and teicoplanin (TEIC) were measured using a novel susceptibility test based on the chemiluminescence assay method (CA) (Rapid-Lumi Eiken; Eiken Chemicals, Tokyo, Japan) against 84 strains of Staphylococcus aureus, consisting of 82 strains of methicillin-resistant S. aureus (MRSA) from clinical isolated, S. aureus Mu3 involving beta-lactam antibiotic induced vancomycin (VCM) resistant MRSA (BIVR) and methicillin-susceptible S. aureus ATCC 29213. The results were in good accordance with the values determined by Clinical and Laboratory Standards Institute (CLSI): i.e., 100% (84/84) of consistency for VCM and 95% (80/84) for TEIC, respectively. In addition, BIVR strains were properly estimated from the results of the CA method and using the BIVR detection method with Mu3 agar (Mu3 Agar method), even though the incubation times was very short (2-4 h). In conclusion, it was found that the new method is reliable and rapid to detect BIVR strains in clinical laboratories.