Occult bacteremia in children with simple febrile seizure in the post-pneumococcal conjugate vaccine era

Purpose The authors aimed to investigate the utility of blood culture (BC) for children with simple febrile seizure (SFS) in the emergency department (ED) in the post-10/13-valent pneumococcal conjugate vaccine (PCV) era. Methods This study was performed at the ED of a tertiary care university-affiliated women and children’s hospital, and involved 3,237 previously healthy children aged 6-60 months who visited the ED with SFS from January 2013 through December 2017. The SFS was defined according to the International Classification of Diseases, 11th Revision codes related to seizure. The children were divided into 2 groups according to the vaccination rates of the period of their visit: the 70-PCV (70%, 2013-2014) and 97-PCV (97%, 2015-2017) groups. The primary outcome was the yield, defined as a true positivity of BC. In addition, we collected information on baseline characteristics, ED length of stay, inflammatory biomarkers, and ED outcomes. Results Of the 1,578 children with SFS who underwent BC, 1,357 belonged to the 97-PCV group. The median age of the study population was 22 months (interquartile range, 16.0-30.0), and 935 children (59.3%) were boys. Of the 41 children (2.6%) with positive BC results, 3 had the yield (0.2%): Staphylococcus aureus in 2 children and Streptococcus pneumoniae in the other. All 3 children belonged to the 97-PCV group. There were 38 contaminated BCs (2.4%; 95% confidence interval, 1.6%-3.2%). The 97-PCV group showed a shorter median ED length of stay (166.0 minutes [108.0-279.5] vs. 143.0 [109.5-209.5]; P = 0.010) and a lower rate of hospitalization (39.4% vs. 12.8%; P < 0.001). No differences between the 2 groups were found in the baseline characteristics and biomarkers. Conclusion This study suggests a low utility of BC in previously healthy children with SFS in emergency settings in the post-10/13-valent PCV era

Application of the Whole Genome-Based Bacterial Identification System, TrueBac ID, Using Clinical Isolates That Were Not Identified With Three Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Systems

Background: Next-generation sequencing is increasingly used for taxonomic identification of pathogenic bacterial isolates. We evaluated the performance of a newly introduced whole genome-based bacterial identification system, TrueBac ID (ChunLab Inc., Seoul, Korea), using clinical isolates that were not identified by three matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems and 16S rRNA gene sequencing. Methods: Thirty-six bacterial isolates were selected from a university-affiliated hospital and a commercial clinical laboratory. Species was identified by three MALDI-TOF MS systems: Bruker Biotyper MS (Bruker Daltonics, Billerica, MA, USA), VITEK MS (bioMerieux, Marcy l'Etoile, France), and ASTA MicrolDSys (ASTA Inc., Suwon, Korea). Whole genome sequencing was conducted using the Illumina MiSeq system (Illumina, San Diego, CA, USA), and genome-based identification was performed using the TrueBac ID cloud system (www.truebacid.com ). Results: TrueBac ID assigned 94% (34/36) of the isolates to known (N=25) or novel (N=4) species, genomospecies (N=3), or species group (N=2). The remaining two were identified at the genus level. Conclusions: TrueBac ID successfully identified the majority of isolates that MALDI-TOF MS failed to identify. Genome-based identification can be a useful tool in clinical laboratories, with its superior accuracy and database-driven operations.

Synergistic Effects of Simvastatin and Irinotecan against Colon Cancer Cells with or without Irinotecan Resistance

Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4±0.14 μM (r=0.98) and 62.5±0.18 μM (r=0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9±0.22 μM (r=0.98) and 195.9±0.16 μM (r=0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2:1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer

Crystal structure of hyperthermophilic esterase EstE1 and the relationship between its dimerization and thermostability properties

<p>Abstract</p> <p>Background</p> <p>EstE1 is a hyperthermophilic esterase belonging to the hormone-sensitive lipase family and was originally isolated by functional screening of a metagenomic library constructed from a thermal environmental sample. Dimers and oligomers may have been evolutionally selected in thermophiles because intersubunit interactions can confer thermostability on the proteins. The molecular mechanisms of thermostabilization of this extremely thermostable esterase are not well understood due to the lack of structural information.</p> <p>Results</p> <p>Here we report for the first time the 2.1-Å resolution crystal structure of EstE1. The three-dimensional structure of EstE1 exhibits a classic α/β hydrolase fold with a central parallel-stranded beta sheet surrounded by alpha helices on both sides. The residues Ser154, Asp251, and His281 form the catalytic triad motif commonly found in other α/β hydrolases. EstE1 exists as a dimer that is formed by hydrophobic interactions and salt bridges. Circular dichroism spectroscopy and heat inactivation kinetic analysis of EstE1 mutants, which were generated by structure-based site-directed mutagenesis of amino acid residues participating in EstE1 dimerization, revealed that hydrophobic interactions through Val274 and Phe276 on the β8 strand of each monomer play a major role in the dimerization of EstE1. In contrast, the intermolecular salt bridges contribute less significantly to the dimerization and thermostability of EstE1.</p> <p>Conclusion</p> <p>Our results suggest that intermolecular hydrophobic interactions are essential for the hyperthermostability of EstE1. The molecular mechanism that allows EstE1 to endure high temperature will provide guideline for rational design of a thermostable esterase/lipase using the lipolytic enzymes showing structural similarity to EstE1.</p

A clinical review of acute myocarditis in children

Purpose The aims of this study are to document our single-center experience with pediatric acute myocarditis and to investigate its clinical features and outcomes. Methods We performed a retrospective chart review of all children aged 12 months (55%) of age. The overall incidence of upper respiratory tract infection symptoms was 69%; general symptoms, 66%; cardiac symptoms, 24%; gastrointestinal symptoms, 17%; and neurologic symptoms, 10%. Twelve patients (41%) had cardiomegaly. Ten patients had electrocardiographic abnormalities (tachycardia, ST changes, T wave changes, and low voltage). Echocardiographic abnormalities were pericardial effusion or impaired contractility. Severe group consisted of 13 patients who were either transferred or died and contained more patients with cardiomegaly and electrocardiogram abnormalities, but this was statistically irrelevant. Most patients had elevated concentrations of cardiac biomarkers, but the median concentrations were not statistically different between the 2 groups. Main treatment modalities included antibiotics (90%), inotropics (59%), and intravenous immunoglobulin (76%). Conclusion Definite diagnostic criteria for acute myocarditis do not exist, so misdiagnosis can occur. Extracorporeal membrane oxygenation therapy for severe cases is available only in some hospitals, so proper treatment can be delayed. Further evaluation of the current situation regarding acute myocarditis will contribute towards proper treatment

Effect of elevated atmospheric carbon dioxide on the allelopathic potential of common ragweed

Background Allelopathy has been suggested as one potential mechanism facilitating the successful colonisation and expansion of invasive plants. The impacts of the ongoing elevation in atmospheric carbon dioxide (CO2) on the production of allelochemicals by invasive species are of great importance because they play a potential role in promoting biological invasion at the global scale. Common ragweed (Ambrosia artemisiifolia var. elatior), one of the most notorious invasive exotic plant species, was used to assess changes in foliar mono- and sesquiterpene production in response to CO2 elevation (389.12 ± 2.55 vs. 802.08 ± 2.69 ppm). Results The plant growth of common ragweed significantly increased in elevated CO2. The major monoterpenes in the essential oil extracted from common ragweed leaves were β-myrcene, dl-limonene and 1,3,6-octatriene, and the major sesquiterpenes were β-caryophyllene and germacrene-D. The concentrations of 1,3,6-octatriene (258%) and β-caryophyllene (421%) significantly increased with CO2 elevation. Conclusions These findings improve our understanding of how allelochemicals in common ragweed respond to CO2 elevation.The authors would like to acknowledge Dr. Samsik Kang (College of Pharmacy, Seoul National University) and Dr. Jonghee Kim (Department of Biology, Gyeongnam University) for the technical advice and supportive discussion and Dr. Changsuk Kim (National Institute of Agricultural Science and Technology) for the seed collection. This work has been supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)(2018R1C1B6005351). We are grateful to NRF (2016R1D1A1A02937049, 2017096A001719BB01) for the financial support

CAGE Binds to Beclin1, Regulates Autophagic Flux and CAGE-Derived Peptide Confers Sensitivity to Anti-cancer Drugs in Non-small Cell Lung Cancer Cells

The objective of this study was to determine the role of CAGE, a cancer/testis antigen, in resistance of non-small cell lung cancers to anti-cancer drugs. Erlotinib-resistant PC-9 cells (PC-9/ER) with EGFR mutations (ex 19 del + T790M of EGFR), showed higher level of autophagic flux than parental sensitive PC-9 cells. Erlotinib and osimertinib increased autophagic flux and induced the binding of CAGE to Beclin1 in PC-9 cells. The inhibition or induction of autophagy regulated the binding of CAGE to Beclin1 and the responses to anti-cancer drugs. CAGE showed binding to HER2 while HER2 was necessary for binding of CAGE to Beclin1. CAGE was responsible for high level of autophagic flux and resistance to anti-cancer drugs in PC-9/ER cells. A peptide corresponding to the DEAD box domain of CAGE, 266AQTGTGKT273, enhanced the sensitivity of PC-9/ER cells to erlotinib and osimertinib, inhibited the binding of CAGE to Beclin1 and regulated autophagic flux in PC-9/ER cells. Mutant CAGE-derived peptide 266AQTGTGAT273 or 266AQTGTGKA273 did not affect autophagic flux or the binding of CAGE to Beclin1. AQTGTGKT peptide showed binding to CAGE, but not to Beclin1. FITC-AQTGTGKT peptide showed co-localization with CAGE. AQTGTGKT peptide decreased tumorigenic potentials of PC-9/ER and H1975 cells, non-small cell lung cancer (NSCLC) cells with EGFR mutation (L885R/T790M), by inhibiting autophagic fluxand inhibiting the binding of CAGE to Beclin1. AQTGTGKT peptide also enhanced the sensitivity of H1975 cells to anti-cancer drugs. AQTGTGKT peptide showed tumor homing potential based on ex vivo homing assays of xenograft of H1975 cells. AQTGTGKT peptide restored expression levels of miR-143-3p and miR-373-5p, decreased autophagic flux and conferred sensitivity to anti-cancer drugs. These results present evidence that combination of anti-cancer drug with CAGE-derived peptide could overcome resistance of non-small cell lung cancers to anti-cancer drugs