Successful cessation of transmitting healthcare-associated infections due to Burkholderia cepacia complex in a neonatal intensive care unit in a Japanese children's hospital

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia cepacia </it>strains have been known to possess the capability to cause serious infections especially in neonatal intensive care units (NICUs), and their multi-drug resistances become a severe threat in hospital settings. The aim of this investigation was to evaluate the <it>B. cepacia </it>complex infections in the NICU in Nagano Children's Hospital, Azumino 399-8288, Japan, and to report the intervention leading to the successful cessation of the outbreak.</p> <p>Methodology</p> <p>The incidence of isolation and antimicrobial susceptibilities of nosocomial <it>Burkholderia cepacia </it>complex strains during a four-year period were retrospectively examined by clinical microbiological records, and by pulsed-field gel electrophoresis analyses along with the bacteriological verification of disinfectant device itself and procedures for its maintenance routinely used in the NICU.</p> <p>Results</p> <p>During the period surveyed between 2007 and 2009, only an isolate per respective year of <it>B. cepacia </it>complex was recovered from each neonate in the NICU. However, in 2010, the successive 6 <it>B. cepacia </it>complex isolates were recovered from different hospitalized neonates. Among them, an isolate was originated from peripheral blood of a neonate, apparently giving rise to systemic infection. In addition, the hospitalized neonate with bacteremia due to <it>B. cepacia </it>complex also exhibited positive cultures from repeated catheterized urine samples together with tracheal aspirate secretions. However other 5 isolates were considered as the transients or contaminants having little to do with infections. Moreover, the 5 isolates between July and October in 2010 revealed completely the same electrophoresis patterns by means of pulsed-field gel electrophoresis analyses, strongly indicating that they were infected through the same medical practices, or by transmission of the same contaminant.</p> <p>Conclusions</p> <p>A small outbreak due to <it>B. cepacia </it>complex was brought about in the NICU in 2010, which appeared to be associated with the same genomovar of <it>B. cepacia </it>complex. The source or the rout of infection was unknown in spite of the repeated epidemiological investigation. It is noteworthy that no outbreak due to <it>B. cepacia </it>complex was noted in the NICU after extensive surveillance intervention.</p

First isolation of Dysgonomonas mossii from intestinal juice of a patient with pancreatic cancer

ArticleARCHIVES OF MEDICAL RESEARCH. 37(7): 914-916 (2006)journal articl

Mitigation of off-target toxicity in CRISPR-Cas9 screens for essential non-coding elements.

Pooled CRISPR-Cas9 screens are a powerful method for functionally characterizing regulatory elements in the non-coding genome, but off-target effects in these experiments have not been systematically evaluated. Here, we investigate Cas9, dCas9, and CRISPRi/a off-target activity in screens for essential regulatory elements. The sgRNAs with the largest effects in genome-scale screens for essential CTCF loop anchors in K562 cells were not single guide RNAs (sgRNAs) that disrupted gene expression near the on-target CTCF anchor. Rather, these sgRNAs had high off-target activity that, while only weakly correlated with absolute off-target site number, could be predicted by the recently developed GuideScan specificity score. Screens conducted in parallel with CRISPRi/a, which do not induce double-stranded DNA breaks, revealed that a distinct set of off-targets also cause strong confounding fitness effects with these epigenome-editing tools. Promisingly, filtering of CRISPRi libraries using GuideScan specificity scores removed these confounded sgRNAs and enabled identification of essential regulatory elements

Quadrupolar XMCD at the Fe K -edge in Fe phthalocyanine film on Au: Insight into the magnetic ground state

Under the terms of the Creative Commons Attribution license.-- et al.The observation of an anomalous quadrupolar signal in x-ray magnetic circular dichroism (XMCD) at the Fe K-edge of iron phthalocyanine (FePc) films is reported. All ground states previously suggested for FePc are incompatible with the experimental data. Based on ab initio molecular orbital multiplet calculations of the isolated FePc molecule, we propose a model for the magnetic ground state of the FePc film that explains the XMCD data and reproduces the observed values of the orbital moments in the perpendicular and planar directions.The financial support of the Spanish financial agency MINECO MAT2011-23791 and MAT2014-53921-R, Aragonese DGA-IMANA E34 (co-funded by Fondo Social Europeo), and European Union FEDER funds is acknowledged. The research at UCSD was supported by the Office of Basic Energy Science, US Department of Energy, BES-DMS, funded by the Department of Energy Office of Basic Energy Science, DMR, under Grant No. DE FG03 87ER-45332.Peer Reviewe

First case of bacteremia due to chromosome-encoded CfxA3-beta-lactamase-producing Capnocytophaga sputigena in a pediatric patient with acute erythroblastic leukemia

ArticleEUROPEAN JOURNAL OF MEDICAL RESEARCH. 13(3): 133-135 (2008)journal articl

A case of wound dual infection with Pasteurella dagmatis and Pasteurella Canis resulting from a dog bite - limitations of Vitek-2 system in exact identification of Pasteurella species

<p>Abstract</p> <p>Background</p> <p><it>Pasteurella </it>species, widely known as indigenous orgganisms in the oral and gastrointestinal floras of many wild and domestic animals, are important pathogens in both animals and humans. Human infections due to <it>Pasteurella </it>species are in most cases associated with infected injuries following animal bites. We encountered a rare case of dual infections caused by different two <it>Pasteurella </it>species occurred in a previously healthy 25-year-old female sustaining injury by a dog-bite.</p> <p>Methodology</p> <p>Exudates from the open wound of her dog-bite site, together with the saliva of the dog were submitted for bacteriological examination. Predominantly appearing grayish-white smooth colonies with almost the same colonial properties but slightly different glistening grown on chocolate and sheep blood agar plates were characterized morphologically by Gram's stain, biochemically by automated instrument using Vitek 2 system using GN cards together with commercially available kit system, ID-Test HN-20 rapid panels, and genetically by sequencing the 16S rRNA genes of the organism using a Taq DyeDeoxy Terminator Cycle Sequencing and a model 3100 DNA sequencer instrument.</p> <p>Results</p> <p>The causative isolates from the dog-bite site were finally identified as <it>P</it>. <it>canis </it>and <it>P</it>. <it>dagmatis </it>from the findings of the morphological, cultural, and biochemical properties together with the comparative sequences of the 16S rRNA genes. Both the isolates were highly susceptible to many antibiotics and the patient was successfully treated with the administration of so-called the first generation cephalosporin, cefazolin followed by so-called the third generation cephalosporin, cefcapene pivoxil. The isolate from the dog was subsequently identified as <it>P</it>. <it>canis</it>, the same species as the isolate from the patient.</p> <p>Conclusions</p> <p>To the best of our knowledge, this was the second report of a dual infection with <it>Pasteurella </it>species consisting of <it>P</it>. <it>dagmatis </it>and <it>P. canis </it>resulting from a dog-bite, followed by the first report of dual infections due to <it>P</it>. <it>dagmatis </it>and <it>P. multocida </it>in 1988. Our isolate finally identified as <it>P</it>. <it>dagmatis </it>was misidentified as <it>P</it>. <it>pneumotripica by </it>means of the Vitek 2 system. The species name "<it>P</it>. <it>dagmatis" </it>was not included in the database of the system. It is also important for routine clinical microbiology laboratories to know the limitation of the automated Vitek 2 system for the accurate identification of <it>Pasteurella </it>species especially <it>P</it>. <it>dagmatis</it>. It should be emphasized that there still exists much room for improvement in Vitek 2 system. Significant improvement of Vitek 2 system especially in the identification of <it>Pasteurella </it>species is urgently desired.</p

Molecular tilting and columnar stacking of Fe phthalocyanine thin films on Au(111)

Scanning tunneling microscopy and x-ray absorption spectroscopic results at the Fe K edge of Fe phthalocyanine (FePc) thin films grown on Au substrates, together with theoretical calculations, allow us to refine the structure of the film. In particular, we show that the columnar stacking of the FePc molecules is different from that found in bulk ¿ and ß phases. Moreover, the molecules do not lay parallel to the surface of the substrate. These structural findings are relevant to understand magnetism of FePc films.The financial support of the Spanish financial agency MINECO MAT2011-2379 and MAT2014-53921-R, Aragonese DGA-IMANA E34 (co-funded by European Social Fund), as well as European Union FEDER funds is acknowledged. The sample preparation and initial structural characterization were supported by the Office of Basic Energy Science, U.S. Department of Energy, BES-DMS funded by the Department of Energy’s Office of Basic Energy Science, DMR under Grant No. DE FG03 87ER-45332 and NSF DMR 0847552.Peer Reviewe

Thermal dosimetry characteristics of deep regional heating of non-muscle invasive bladder cancer.

PURPOSE: The aim of this paper is to report thermal dosimetry characteristics of external deep regional pelvic hyperthermia combined with intravesical mitomycin C (MMC) for treating bladder cancer following transurethral resection of bladder tumour, and to use thermal data to evaluate reliability of delivering the prescribed hyperthermia dose to bladder tissue. MATERIALS AND METHODS: A total of 14 patients were treated with MMC and deep regional hyperthermia (BSD-2000, Sigma Ellipse or Sigma 60). The hyperthermia objective was 42° ± 2 °C to bladder tissue for ≥40 min per treatment. Temperatures were monitored with thermistor probes and recorded values were used to calculate thermal dose and evaluate treatment. Anatomical characteristics were examined for possible correlations with heating. RESULTS: Combined with BSD-2000 standard treatment planning and patient feedback, real-time temperature monitoring allowed thermal steering of heat sufficient to attain the prescribed thermal dose to bladder tissue within patient tolerance in 91.6% of treatments. Mean treatment time for bladder tissue \u3e40 °C was 61.9 ± 11.4 min and mean thermal dose was 21.3 ± 16.5 CEM43. Average thermal doses obtained in normal tissues were 1.6 ± 1.2 CEM43 for the rectum and 0.8 ± 1.3 CEM43 in superficial normal tissues. No significant correlation was seen between patient anatomical characteristics and thermal dose achieved in bladder tissue. CONCLUSIONS: This study demonstrates that a hyperthermia prescription of 42° ± 2 °C for 40-60 min can be delivered safely to bladder tissue with external radiofrequency phased array applicators for a typical range of patient sizes. Using the available thermometry and treatment planning, the BSD-2000 hyperthermia system was shown to be an effective method of focusing heat regionally around the bladder with good patient tolerance

The Mitochondrial Deoxyguanosine Kinase is Required for Cancer Cell Stemness in Lung Adenocarcinoma

The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. The restoration of mitochondrial OXPHOS in DGUOK KO lung cancer cells using NDI1 was able to prevent AMPK-mediated phosphorylation of YAP and to rescue CSC stemness. Genetic targeting of DGUOK using doxycycline-inducible CRISPR/Cas9 was able to markedly induce tumor regression. Our findings reveal a novel role for mitochondrial dNTP metabolism in lung cancer tumor growth and progression, and implicate that the mitochondrial deoxynucleotide salvage pathway could be potentially targeted to prevent CSC-mediated therapy resistance and metastatic recurrence