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Xingyu Zhang, Di Chen, Guifeng Xu, Weichun Huang, Xing Wang
Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center...
2018: PloS One
Yoshitaka Inui, Takashi Ichihara, Masaki Uno, Masanobu Ishiguro, Kengo Ito, Katsuhiko Kato, Hajime Sakuma, Hidehiko Okazawa, Hiroshi Toyama
OBJECTIVE: Statistical image analysis of brain SPECT images has improved diagnostic accuracy for brain disorders. However, the results of statistical analysis vary depending on the institution even when they use a common normal database (NDB), due to different intrinsic spatial resolutions or correction methods. The present study aimed to evaluate the correction of spatial resolution differences between equipment and examine the differences in skull bone attenuation to construct a common NDB for use in multicenter settings...
March 19, 2018: Annals of Nuclear Medicine
Xiangpeng Hu, Hongwei Kan, Alex Boye, Yufeng Jiang, Chao Wu, Yan Yang
The transforming growth factor (TGF)-β/Smad signaling pathway is involved in hepatocellular carcinoma development. Smad2 and Smad3 are phosphorylated following TGF-β1 stimulation and subsequently oligomerize with Smad4 to form the Smad2/3/4 complex, which translocates into the nucleus and regulates target genes, including plasminogen activator inhibitor type 1 (PAI1). Importin (Imp)7 and Imp8 are responsible for transporting phosphorylated (p)Smad2/3 and Smad4 into the nucleus. In our previous study, it was demonstrated that mitogen-activated protein kinase (MAPK) inhibitors, including inhibitors of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 could inhibit the transcription of PAI1, but ERK inhibitor had no significant effect on the phosphorylation of Smad2/3, and the formation of Smad2/3/4 complexes, which was different from the effect of JNK or p38 inhibitor...
April 2018: Oncology Letters
Karmen Godič Torkar, Branka Bedenić
The susceptibility of 66 clinical and environmental B. cereus isolates were tested to selected antimicrobials by a broth microdilution method. All strains were resistant to β-lactams and susceptible to gentamicin and imipenem. Sixty-five (98.5%) isolates were susceptible to meropenem and ciprofloxacin and 74.2% to azithromycin. Significant differences in MIC values between environmental and clinical isolates were not demonstrated (p > 0.05). According to the disc diffusion method, 80.3%-98.5% of the strains were resistant to one or more of four cephalosporins...
March 15, 2018: Microbial Pathogenesis
Laurent Dortet, Sandrine Bernabeu, Camille Gonzalez, Thierry Naas
The objective of this study was to assess the performance of the Carbapenemase Detection Set™ (CDS; Mast Diagnostics) in association with i) the EUCAST meropenem screening cut-off and ii) the faropenem-temocillin algorithm (FTa) for the screening of carbapenemase-producing Enterobacteriaceae (CPE). A total of 200 well-characterized enterobacterial isolates with reduced susceptibility to at least one carbapenem including 63 non-CPEs and 137 CPEs belonging to different Ambler classes were initially screened for CPEs using i) the EUCAST meropenem cut-off (diameter <25 mm) and ii) the FTa...
February 17, 2018: Diagnostic Microbiology and Infectious Disease
Ana Trapero, Angela Pacitto, Vinayak Singh, Mohamad Sabbah, Anthony G Coyne, Valerie Mizrahi, Tom L Blundell, David B Ascher, Chris Abell
Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5´-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible (Mth) IMPDH(ΔCBS) inhibitors identified a low affinity phenylimidazole derivative...
March 16, 2018: Journal of Medicinal Chemistry
Masha M Rosenberg, Alfred G Redfield, Mary Roberts, Lizbeth Hedstrom
The ability of enzymes to modulate the dynamics of bound substrates and cofactors is a critical feature of catalysis, but the role of dynamics has largely been approached from the perspective of the protein. Here we use an underappreciated NMR technique, subtesla high resolution field cycling31 P NMR relaxometry, to interrogate the dynamics of enzyme bound substrates and cofactors in guanosine-5'-monophosphate reductase (GMPR). These experiments reveal distinct binding modes and dynamic profiles associated with the31 P nuclei in the Michaelis complexes for the deamination and hydride transfer steps of the catalytic cycle...
March 16, 2018: Biochemistry
Patrice Rassam, Kathleen R Long, Renata Kaminska, David J Williams, Grigorios Papadakos, Christoph G Baumann, Colin Kleanthous
Gram-negative bacteria depend on energised protein complexes that connect the two membranes of the cell envelope. However, β-barrel outer-membrane proteins (OMPs) and α-helical inner-membrane proteins (IMPs) display quite different organisation. OMPs cluster into islands that restrict their lateral mobility, while IMPs generally diffuse throughout the cell. Here, using live cell imaging of Escherichia coli, we demonstrate that when transient, energy-dependent transmembrane connections are formed, IMPs become subjugated by the inherent organisation of OMPs and that such connections impact IMP function...
March 14, 2018: Nature Communications
Aisha G Al-Ghaithi, Ali M Al-Subhi, Issa H Al-Mahmooli, Abdullah M Al-Sadi
" Candidatus Phytoplasma aurantifolia" is associated with witches' broom disease of lime in Oman and the UAE. A previous study showed that an infection by phytoplasma may not necessarily result in the physical appearance of witches' broom symptoms in some locations in Oman and the UAE. This study investigated whether phytoplasma strains belonging to " Ca. P. aurantifolia" (based on the 16S rRNA gene analysis) in locations where disease symptoms are expressed are different from phytoplasma in locations where disease symptoms are not expressed...
2018: PeerJ
Behnaz Soltani, Hamid Heidari, Hadi Sedigh Ebrahim-Saraie, Nahal Hadi, Jalal Mardaneh, Mohammad Motamedifar
The emergence of multiple drug-resistant (MDR) Acinetobacter baumannii strains has become a global problem. This study aimed to evaluate the occurrence of antibiotic resistance and to investigate the presence of antibiotic resistance determinants among A. baumannii isolates obtained from hospitalized patients in Iran. This cross-sectional study was performed on 92 A. baumannii isolates in the years 2015-2016. Antimicrobial susceptibility testing was carried out by the disk diffusion method. The presence of antibiotic resistance determinants was detected by the PCR method...
March 1, 2018: Le Infezioni in Medicina
Yuria Shinohara, Mitsutoshi Tsukimoto
Damaged tissues and cells release intracellular purine nucleotides, which serve as intercellular signaling factors. We previously showed that exogenously added adenine nucleotide (250 μM ATP) suppressed the activation of murine splenic T lymphocytes. Here, we examined the effects of other purine nucleotides/nucleosides on mouse T cell activation. First, we found that pretreatment of mouse spleen T cells with 250 μM GTP, GDP, GMP, guanosine, ITP, IDP, IMP or inosine significantly reduced the release of stimulus-inducible cytokine IL-2...
March 7, 2018: Biochemical and Biophysical Research Communications
Li Fan, Zhe Wang, Qiang Wang, Zhijian Xiong, Ying Xu, Dandan Li, Shiwen Zhou
Objective: Acinetobacter baumannii is an opportunistic pathogen found in immunocompromised patients, especially cancer patients. This study was to investigate the clinical characteristics of cancer patients and the antimicrobial resistance of A.baumannii isolates. Materials and Methods: Clinical isolates were collected from the oncology department of a general teaching hospital, and the clinical and demographic information of patients was obtained from the hospital's information system...
January 2018: Journal of Cancer Research and Therapeutics
Michael A Pfaller, Michael D Huband, Rodrigo E Mendes, Robert K Flamm, Mariana Castanheira
We evaluated meropenem-vaborbactam activity against 11,559 Enterobacteriaceae isolates, including 330 carbapenem-resistant phenotypes (CRE) and carbapenemase genotypes collected worldwide during 2015. Meropenem-vaborbactam (inhibitor at 8 mg/L) and comparators were susceptibility tested using reference broth microdilution methods. CRE isolates were screened for the presence of genes encoding carbapenemases and 292 (88.5%) of the CRE isolates carried these resistance genes. A total of 209 (63.3% of the CRE; 1...
March 3, 2018: International Journal of Antimicrobial Agents
E K Niedermayer, O N Genther-Schroeder, D D Loy, S L Hansen
To determine the effects of trace mineral supplementation and hormone implant strategy on growth and carcass characteristics of cattle, 72 Angus-cross steers (388 ± 17 kg) were blocked by BW (6 steers per pen) to a 2 × 3 factorial. Factors included growth stimulating implant (GS): d 0 with Component TE-IS, reimplanted d 56 with Component TE-200 (IMP) or no implant (NoIMP), and TM supplementation (TM): no supplemental TM (CON), TM supplemented at national (NAESM, 2016) recommendations of 10 Cu, 30 Zn, 20 Mn, 0...
February 28, 2018: Journal of Animal Science
Jian Wang, Hui-Suo Yang, Bing Deng, Meng-Jing Shi, Xiang-Da Li, Qing-Gong Nian, Wen-Jing Song, Feng Bing, Qing-Feng Li
BACKGROUND: Influenza is an acute respiratory infectious disease with a high incidence rate in the Chinese army, which directly disturbs military training and affects soldiers' health. Influenza surveillance systems are widely used around the world and play an important role in influenza epidemic prevention and control. METHODS: As a theater centers for disease prevention and control, we established an influenza monitoring platform (IMP) in 2014 to strengthen the monitoring of influenza-like illness and influenza virus infection...
November 20, 2017: Military Medical Research
Jan Van Impe, Cindy Smet, Brijesh Tiwari, Ralf Greiner, Shikha Ojha, Višnja Stulić, Tomislava Vukušić, Anet Režek Jambrak
Despite of the constant development of novel thermal and non-thermal technologies, knowledge on the mechanisms of microbial inactivation is still very limited. Technologies such as high pressure, ultraviolet light, pulsed light, ozone, power ultrasound and cold plasma (advanced oxidation processes) have shown promising results for inactivation of microorganisms. The efficacy of inactivation is greatly enhanced by combination of conventional (thermal) with non-thermal, or non-thermal with another non-thermal technique...
March 4, 2018: Journal of Applied Microbiology
Yiping Lu, Lei Wang, Fei Teng, Jianing Zhang, Meirong Hu, Yong Tao
Myo-inositol (inositol) is important in the cosmetics, pharmaceutical and functional food industries. Here, we report a novel pathway to produce inositol from glucose by a trienzymatic cascade system involving polyphosphate glucokinase (PPGK), inositol 1-phosphate synthase (IPS) and inositol monophosphatase (IMP). The system contained three highly active enzymes, AspPPGK from Arthrobacter sp. OY3WO11, TbIPS from Trypanosoma brucei TREU927, and EcIMP from Escherichia coli. A trienzymatic cascade reaction was implemented, and the conversion ratio from glucose to inositol reached 90%, which is promising for the enzymatic synthesis of inositol without ATP supplementation...
May 2018: Enzyme and Microbial Technology
Hanna E Sidjabat, Jolene Gien, David Kvaskoff, Keith Ashman, Kanchan Vaswani, Sarah Reed, Ross P McGeary, David L Paterson, Amanda Bordin, Gerhard Schenk
Antibiotic resistance associated with the clinically significant carbapenemases KPC, NDM and OXA-48 in Enterobacteriaceae is emerging as worldwide. In Australia, IMP-producing Enterobacteriaceae are the most prevalent carbapenemase-producing Enterobacteriaceae (CPE). Genomic characteristics of such CPE are well described, but the corresponding proteome is poorly characterised. We have thus developed a method to analyse dynamic changes in the proteome of CPE under antibiotic pressure. Specifically, we have investigated the effect of meropenem at sub-lethal concentrations to develop a better understanding of how antibiotic pressure leads to resistance...
March 1, 2018: Scientific Reports
Robert F Potter, Meghan A Wallace, Allison R McMullen, Jerome Prusa, Christina L Stallings, Carey-Ann D Burnham, Gautam Dantas
OBJECTIVES: A carbapenem resistant Providencia rettgeri (PR1) isolate was recovered from a wound infection in Missouri, USA. This isolate possessed an EDTA inhibitable carbapenemase that was unidentified using the Xpert CARBA-R assay. Our objective was to elucidate the molecular determinant of carbapenem resistance in this isolate. We then sought to test the transmissibility of blaIMP-27 loci in clinical P. rettgeri and Proteus mirabilis isolates. METHODS: In October 2016 the novel ambler Class B carbapenemase blaIMP-27 , was reported in two different Proteus mirablis (PM185 and PM187) isolates...
February 26, 2018: Clinical Microbiology and Infection
Fernanda Caroline Wolff, Thaís Luise Dillenburg, Marina Venzon Antunes, Rafael Linden, Sandrine Comparsi Wagner, Simone G Verza
Imatinib mesylate (IM) is an anti-neoplasic drug used for the treatment of cancer. Recently new guidelines specify daily doses and concentration limits for genotoxic impurities (GTIs) in pharmaceutical final products. So, in this work an analytical method by UHPLC-MS/MS was developed, validated and applied to characterize IM tablets for two GTIs: N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidine amine (Imp. 1), and N-[4-methyl-3-(4-methyl-3-yl-pyrimidin-2-ylamino)-phenyl]-4- chloromethyl benzamide (Imp...
February 27, 2018: Biomedical Chromatography: BMC
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