Emerging Carbapenem-Resistant Pseudomonas aeruginosa Isolates Carrying bla_IMP Among Burn Patients in Isfahan, Iran

Background: Metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa is a significant pathogen in burn patients. Objectives: The aim of this study was to determine the prevalence of carbapenem-resistant P. aeruginosa isolates, including those resistant to imipenemase (IMP), in a burn unit in Isfahan, Iran. Patients and Methods: One hundred and fifty P. aeruginosa isolates from burn patients were tested for antibiotic susceptibility by the disc diffusion method in accordance with CLSI guidelines. Production of MBL was identified with the EDTA disk method. DNA was purified from the MBL-positive isolates, and detection of the blaIMP gene was performed with PCR. Results: Fifty-seven out of 150 (38%) isolates were multi-drug resistant (MDR), and 93 (62%) were extensively-drug resistant (XDR). Among all isolates, the resistance rate to ciprofloxacin, tobramycin, imipenem, meropenem, amikacin, ceftazidime, and cefepime was higher than 90%, while the resistance rates to piperacillin/tazobactam and aztreonam were 70.7% and 86%, respectively. Colistin and polymyxin B remained the most effective studied antibiotics. All of the imipenem-resistant P. aeruginosa isolates were MBL-positive, and 107 out of 144 (74.3%) of the MBL isolates were positive for the blaIMP gene. Conclusions: The results of this study show that the rate of P. aeruginosa-caused burn wound infections was very high, and many of the isolates were resistant to three or more classes of antimicrobials. Such extensive resistance to antimicrobial classes is important because few treatment options remain for patients with burn wound infections. blaIMP-producing P. aeruginosa isolates are a rising threat in burn-care units, and should be controlled by conducting infection-control assessments

Results from the VALUE perfect predictor experiment: process-based evaluation

Comunicación presentada en: EGU General Assembly 2016 celebrada del 17 al 22 de abril de 2016 en Viena, Austria

Microenvironmental regulation of telomerase isoforms in human embryonic stem cells

Recent evidence points to extra-telomeric, noncanonical roles for telomerase in regulating stem cell function. In this study, human embryonic stem cells (hESCs) were cultured in 20% or 2% O2 microenvironments for up to 5 days and evaluated for telomerase reverse transcriptase (TERT) expression and telomerase activity. Results showed increased cell survival and maintenance of the undifferentiated state with elevated levels of nuclear TERT in 2% O 2-cultured hESCs despite no significant difference in telomerase activity compared with their high-O2-cultured counterparts. Pharmacological inhibition of telomerase activity using a synthetic tea catechin resulted in spontaneous hESC differentiation, while telomerase inhibition with a phosphorothioate oligonucleotide telomere mimic did not. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed variations in transcript levels of full-length and alternate splice variants of TERT in hESCs cultured under varying O2 atmospheres. Steric-blocking of Δα and Δβ hTERT splicing using morpholino oligonucleotides altered the hTERT splicing pattern and rapidly induced spontaneous hESC differentiation that appeared biased toward endomesodermal and neuroectodermal cell fates, respectively. Together, these results suggest that post-transcriptional regulation of TERT under varying O2 microenvironments may help regulate hESC survival, self-renewal, and differentiation capabilities through expression of extra-telomeric telomerase isoforms. © 2014, Mary Ann Liebert, Inc

Distribution of telecom Time-Bin Entangled Photons through a 7.7 km Hollow-Core Fiber

State of the art classical and quantum communication rely on standard optical fibers with solid cores to transmit light over long distances. However, recent advances have led to the emergence of hollow-core optical fibers (HCFs), which due to the novel fiber geometry, show remarkable optical guiding properties, which are not as limited by the material properties as solid-core fibers. In this paper, we explore the transmission of entangled photons through a novel 7.7 km HCF, presenting the first successful demonstration of entanglement distribution via long-distance HCF. Our study highlights the low latency and low chromatic dispersion intrinsic to HCF, which can increase the secure key rate in time-bin based quantum key distribution protocols.Comment: 9 pages (incl. 2 pages appendix), 5 figure

Full Thickness Cartilage Palisade Tympanoplasty with Malleus Interposition; A Study of the Long Term Results

The aim of this retrospective study is to review long term results of full-thickness cartilage palisade tympanoplasty (FTCPT) with malleus head interposition performed on 51 patients (56 ears); 36 women and 15 men (7-73 years, 44 years average). The pathology of ears which encourages this technique of tympanoplasty is presented. On average 12 years after surgery we have elaborated anatomic and functional results. Anatomic results were categorized based on empiric evaluation of the new tympanic membrane status: 40 (71%) tympanic membranes without anatomic irregularities, 14(25%) with irregularities and 2(4%) with secondary perforation. Functional results (tonal audiogram) are based on pure tone average air-bone gap (PTA-ABG) at 4 frequencies. Main functional results of 51 ears (51 audiograms performed): pre- and post-operative average PTA-ABGs were 27.07±9.98 and 10.77±7.85 dB (t=10.36; p<0.001). In the group of ears with a tympanic membrane with no anatomic irregularities, pre- and post-operative average PTA-ABGs were 27.30±10.56 and 10.82±8.33 dB (t=8.09; p<0.001). In the group of ears with cartilage resorption, pre- and post-operative PTA-ABGs were 24.92±8.19 and 9.33±6.58 dB (t=6.21; p<0.001). The differences between the two groups are irrelevant. Postoperative PTA-ABG values of ears after first surgery (n=34) and revision surgery (n=17) was significantly different (8.75±5.75 and 15.16±9.62 dB) (t=2.60; p=0.016). In spite of the thickness of the new tympanal membrane, FTCPT is a successful technique for solving advanced ear pathology

Validation of spatial variability in downscaling results from the VALUE perfect predictor experiment

The spatial dependence of meteorological variables is crucial for many impacts, for example, droughts, floods, river flows, energy demand, and crop yield. There is thus a need to understand how well it is represented in downscaling (DS) products. Within the COST Action VALUE, we have conducted a comprehensive analysis of spatial variability in the output of over 40 different DS methods in a perfect predictor setup. The DS output is evaluated against daily precipitation and temperature observations for the period 1979?2008 at 86 sites across Europe and 53 sites across Germany. We have analysed the dependency of correlations of daily temperature and precipitation series at station pairs on the distance between the stations. For the European data set, we have also investigated the complexity of the downscaled data by calculating the number of independent spatial degrees of freedom. For daily precipitation at the German network, we have additionally evaluated the dependency of the joint exceedance of the wet day threshold and of the local 90th percentile on the distance between the stations. Finally, we have investigated regional patterns of European monthly precipitation obtained from rotated principal component analysis. We analysed Perfect Prog (PP) methods, which are based on statistical relationships derived from observations, as well as Model Output Statistics (MOS) approaches, which attempt to correct simulated variables. In summary, we found that most PP DS methods, with the exception of multisite analog methods and a method that explicitly models spatial dependence yield unrealistic spatial characteristics. Regional climate model?based MOS methods showed good performance with respect to correlation lengths and the joint occurrence of wet days, but a substantial overestimation of the joint occurrence of heavy precipitation events. These findings apply to the spatial scales that are resolved by our observation network, and similar studies with higher resolutions, which are relevant for small hydrological catchment, are desirable.Funding Information: EU. Grant Number: EU COST Action ES110

Novel Thieno [2,3-b]pyridine Anticancer Compound Lowers Cancer Stem Cell Fraction Inducing Shift of Lipid to Glucose Metabolism.

Due to the role of cancer stem cells (CSCs) in tumor resistance and glycosphingolipid (GSL) involvement in tumor pathogenesis, we investigated the effect of a newly synthesized compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide 1 on the percentage of CSCs and the expression of six GSLs on CSCs and non-CSCs on breast cancer cell lines (MDA-MB-231 and MCF-7). We also investigated the effect of 1 on the metabolic profile of these cell lines. The MTT assay was used for cytotoxicity determination. Apoptosis and expression of GSLs were assessed by flow cytometry. A GC-MS-coupled system was used for the separation and identification of metabolites. Compound 1 was cytotoxic for both cell lines, and the majority of cells died by treatment-induced apoptosis. The percentage of CSCs was significantly lower in the MDA-MB-231 cell line. Treatment with 1 caused a decrease of CSC IV6Neu5Ac-nLc4Cer+ MDA-MB-231 cells. In the MCF-7 cell line, the percentage of GalNAc-GM1b+ CSCs was increased, while the expression of Gg3Cer was decreased in both CSC and non-CSC. Twenty-one metabolites were identified by metabolic profiling. The major impact of the treatment was in glycolysis/gluconeogenesis, pyruvate and inositol metabolism. Compound 1 exhibited higher potency in MBA-MB-231 cells, and it deserves further examination

Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation

Background Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project. Methods Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1- KO/hCD46/hTBM) as donors and captive-bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non-ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin-containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti-non-Gal-antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient's kidney, liver and coagulation functions. Results In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti-non-Gal-antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi-organ failure in more than half of the xenotransplantation experiments. In contrast, cold non-ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long-term results after cardiac xenotransplantation