Science.gov

Sample records for 4th generation fluoroquinolones

  1. Bifrost: A 4th Generation Launch Architecture Concept

    NASA Astrophysics Data System (ADS)

    Rohrschneider, R. R.; Young, D.; St.Germain, B.; Brown, N.; Crowley, J.; Maatsch, J.; Olds, J. R.

    2002-01-01

    A 4th generation launch architecture is studied for the purpose of drastically reducing launch costs and hence enabling new large mass missions such as space solar power and human exploration of other planets. The architecture consists of a magnetic levitation launch tube placed on the equator with the exit end elevated to approximately 20 km. Several modules exist for sending manned and unmanned payloads into Earth orbit. Analysis of the launch tube operations, launch trajectories, module aerodynamics, propulsion modules, and system costs are presented. Using the hybrid logistics module, it is possible to place payloads into low Earth orbit for just over 100 per lb.

  2. JLab CW Cryomodules for 4th Generation Light Sources

    SciTech Connect

    Rimmer, Robert; Bundy, Richard; Cheng, Guangfeng; Ciovati, Gianluigi; Clemens, William; Daly, Edward; Henry, James; Hicks, William; Kneisel, Peter; Manning, Stephen; Manus, Robert; Marhauser, Frank; Preble, Joseph; Reece, Charles; Smith, Karl; Stirbet, Mircea; Turlington, Larry; Wang, Haipeng; Wilson, Katherine

    2008-01-23

    Fourth generation light sources hold the prospect of unprecedented brightness and optical beam quality for a wide range of scientific applications. Many of the proposed new facilities will rely on large superconducting radio frequency (SRF) based linacs to provide high energy, low emittance CW electron beams. For high average power applications there is a growing acceptance of energy recovery linac (ERL) technology as the way to support large recirculating currents with modest RF power requirements. CW SRF and high current ERLs are two core competencies at Jefferson Lab. JLab has designed and built a number of CW cryomodules of several different types starting with the original CEBAF design, with variations for higher current in the two generations of JLab’s free-electron laser (FEL), through two intermediate prototypes to the final high-performance module for the 12 GeV upgrade. Each of these represent fully engineered and tested configurations with a variety of specifications that could be considered for possible use in fourth generation light sources. Furthermore JLab has been actively pursuing advanced concepts for highcurrent high-efficiency cryomodules for next generation ERL based FEL’s. These existing and proposed designs span the range from about 1mA single-pass to over 100 mA energy recovered current capability. Specialized configurations also exist for high-current non-energy recovered sections such as the injector region where very high RF power is required. We discuss the performance parameters of these existing and proposed designs and their suitability to different classes of fourth generation light sources.

  3. TID Test Results for 4th Generation iPad(TradeMark)

    NASA Technical Reports Server (NTRS)

    Guertin, S. M.; Allen, G. R.; McClure, S. S.; LaBel, K. A.

    2013-01-01

    TID testing of 4th generation iPads is reported. Of iPad subsystems, results indicate that the charging circuitry and display drivers fail at lowest TID levels. Details of construction are investigated for additional testing of components.

  4. The 4th Generation Light Source at Jefferson Lab

    SciTech Connect

    Stephen Benson; George Biallas; James Boyce; Donald Bullard; James Coleman; David Douglas; H. Dylla; Richard Evans; Pavel Evtushenko; Albert Grippo; Christopher Gould; Joseph Gubeli; David Hardy; Carlos Hernandez-Garcia; Kevin Jordan; John Klopf; Steven Moore; George Neil; Thomas Powers; Joseph Preble; Daniel Sexton; Michelle D. Shinn; Christopher Tennant; Richard Walker; Shukui Zhang; Gwyn Williams

    2007-04-25

    A number of "Grand Challenges" in Science have recently been identified in reports from The National Academy of Sciences, and the U.S. Dept. of Energy, Basic Energy Sciences. Many of these require a new generation of linac-based light source to study dynamical and non-linear phenomena in nanoscale samples. In this paper we present a summary of the properties of such light sources, comparing them with existing sources, and then describing in more detail a specific source at Jefferson Lab. Importantly, the JLab light source has developed some novel technology which is a critical enabler for other new light sources.

  5. The 4th generation light source at Jefferson Lab

    NASA Astrophysics Data System (ADS)

    Benson, S.; Biallas, G.; Boyce, J.; Bullard, D.; Coleman, J.; Douglas, D.; Dylla, F.; Evans, R.; Evtushenko, P.; Grippo, A.; Gould, C.; Gubeli, J.; Hardy, D.; Hernandez-Garcia, C.; Jordan, K.; Klopf, J. M.; Moore, W.; Neil, G.; Powers, T.; Preble, J.; Sexton, D.; Shinn, M.; Tennant, C.; Walker, R.; Zhang, S.; Williams, G. P.

    2007-11-01

    A number of "Grand Challenges" in Science have recently been identified in reports from The National Academy of Sciences, and the US Department of Energy, Basic Energy Sciences. Many of these require a new generation of linac-based light source to study dynamical and non-linear phenomena in nanoscale samples. In this paper we present a summary of the properties of such light sources, comparing them with existing sources, and then describing in more detail a specific source at Jefferson Lab (JLab). Importantly, the JLab light source has developed some novel technology which is a critical enabler for other new light sources.

  6. Design of a Nb3Sn Magnet for a 4th Generation ECR Ion Source

    SciTech Connect

    Prestemon, S,; Trillaud, F.; Caspi, S.; Ferracin, P.; Sabbi, G. L.; Lyneis, C. M.; Leitner, D.; Todd, D. S.; Hafalia, R.

    2008-08-17

    The next generation of Electron Cyclotron Resonant (ECR) ion sources are expected to operate at a heating radio frequency greater than 40 GHz. The existing 3rd generation systems, exemplified by the state of the art system VENUS, operate in the 10-28 GHz range, and use NbTi superconductors for the confinement coils. The magnetic field needed to confine the plasma scales with the rf frequency, resulting in peak fields on the magnets of the 4th generation system in excess of 10 T. High field superconductors such as Nb{sub 3}Sn must therefore be considered. The magnetic design of a 4th. generation ECR ion source operating at an rf frequency of 56 GHz is considered. The analysis considers both internal and external sextupole configurations, assuming commercially available Nb{sub 3}Sn material properties. Preliminary structural design issues are discussed based on the forces and margins associated with the coils in the different configurations, leading to quantitative data for the determination of a final magnet design.

  7. Quark masses and mixings in the RS1 model with a condensing 4th generation

    NASA Astrophysics Data System (ADS)

    Hernández, A. E. Cárcamo; Dib, Claudio O.; Neill, Nicolás A.; Zerwekh, Alfonso R.

    2012-02-01

    We study the hierarchy of quark masses and mixings in a model based on a 5-dimensional spacetime with constant curvature of Randall-Sundrum type with two branes, where the Electroweak Symmetry Breaking is caused dynamically by the condensation of a 4th generation of quarks, due to underlying physics from the 5D bulk and the first KK gluons. We first study the hierarchy of quark masses and mixings that can be obtained from purely adjusting the profile localizations, finding that realistic masses are not reproduced unless non trivial hierarchies of underlying 4-fermion interactions from the bulk are included. Then we study global U(1) symmetries that can be imposed in order to obtain non-symmetric modified Fritzsch-like textures in the mass matrices that reproduce reasonably well quark masses and CKM mixings.

  8. Conditions for the generation of cytotoxic CD4(+) Th cells that enhance CD8(+) CTL-mediated tumor regression.

    PubMed

    Li, Kunyu; Baird, Margaret; Yang, Jianping; Jackson, Chris; Ronchese, Franca; Young, Sarah

    2016-08-01

    Adoptive cell therapies (ACTs) using tumor-reactive T cells have shown clinical benefit and potential for cancer treatment. While the majority of the current ACT are focused on using CD8(+) cytotoxic T lymphocytes (CTL), others have shown that the presence of tumor-reactive CD4(+) T helper (Th) cells can greatly enhance the anti-tumor activity of CD8(+) CTL. However, difficulties in obtaining adequate numbers of CD4(+) Th cells through in vitro expansion can limit the application of CD4 Th cells in ACT. This study aims to optimize the culture conditions for mouse CD4 T cells to provide basic information for animal studies of ACT using CD4 T cells. Taking advantage of the antigen-specificity of CD4(+) Th cells from OT-II transgenic mice, we examined different methodologies for generating antigen-specific CD4(+) Th1 cells in vitro. We found that cells grown in complete advanced-DMEM/F12 medium supplemented with low-dose IL-2 and IL-7 induced substantial cell expansion. These Th cells were Th1-like, as they expressed multiple Th1-cytokines and exhibited antigen-specific cytotoxicity. In addition co-transfer of these CD4(+) Th1-like cells with CD8(+) CTL significantly enhanced tumor regression, leading to complete cure in 80% of mice bearing established B16-OVA. These observations indicate that the CD4(+) Th1-like cells generated using the method we optimized are functionally active to eliminate their target cells, and can also assist CD8(+) CTL to enhance tumor regression. The findings of this study provide valuable data for further research into in vitro expansion of CD4(+) Th1-like cells, with potential applications to cancer treatment involving ACT. PMID:27588200

  9. Conditions for the generation of cytotoxic CD4+ Th cells that enhance CD8+ CTL-mediated tumor regression

    PubMed Central

    Li, Kunyu; Baird, Margaret; Yang, Jianping; Jackson, Chris; Ronchese, Franca; Young, Sarah

    2016-01-01

    Adoptive cell therapies (ACTs) using tumor-reactive T cells have shown clinical benefit and potential for cancer treatment. While the majority of the current ACT are focused on using CD8+ cytotoxic T lymphocytes (CTL), others have shown that the presence of tumor-reactive CD4+ T helper (Th) cells can greatly enhance the anti-tumor activity of CD8+ CTL. However, difficulties in obtaining adequate numbers of CD4+ Th cells through in vitro expansion can limit the application of CD4 Th cells in ACT. This study aims to optimize the culture conditions for mouse CD4 T cells to provide basic information for animal studies of ACT using CD4 T cells. Taking advantage of the antigen-specificity of CD4+ Th cells from OT-II transgenic mice, we examined different methodologies for generating antigen-specific CD4+ Th1 cells in vitro. We found that cells grown in complete advanced-DMEM/F12 medium supplemented with low-dose IL-2 and IL-7 induced substantial cell expansion. These Th cells were Th1-like, as they expressed multiple Th1-cytokines and exhibited antigen-specific cytotoxicity. In addition co-transfer of these CD4+ Th1-like cells with CD8+ CTL significantly enhanced tumor regression, leading to complete cure in 80% of mice bearing established B16-OVA. These observations indicate that the CD4+ Th1-like cells generated using the method we optimized are functionally active to eliminate their target cells, and can also assist CD8+ CTL to enhance tumor regression. The findings of this study provide valuable data for further research into in vitro expansion of CD4+ Th1-like cells, with potential applications to cancer treatment involving ACT. PMID:27588200

  10. A laboratory model of post-Newtonian gravity with high power lasers and 4th generation light sources

    NASA Astrophysics Data System (ADS)

    Gregori, G.; Levy, M. C.; Wadud, M. A.; Crowley, B. J. B.; Bingham, R.

    2016-04-01

    Using the post-Newtonian formalism of gravity, we attempt to calculate the x-ray Thomson scattering cross section of electrons that are accelerated in the field of a high intensity optical laser. We show that our results are consistent with previous calculations, suggesting that the combination of high power laser and 4th generation light sources may become a powerful platform to test models exploring high order corrections to the Newtonian gravity.

  11. [Antidepressives of the 3rd, 4th and 5th generation].

    PubMed

    Svestka, J

    1994-02-01

    Antidepressants are classified into five generations. Preparations of the first generation affect various neurotransmitter systems and are therefore associated with many undesirable effects (e.g. tricyclic antidepressants, maprotiline). The second generation of antidepressants is already devoid of anticholinergic action and their adrenolytic and antihistaminic effects are weaker (e.g. mianserine, mirtazapine, trazodone). The antidepressant action of preparations of the third generation is mediated only by one of the three main neurotransmitter systems for depression (5-HT, noradrenaline, dopamine) and does not affect muscarine, histamine and adrenergic cerebral systems (e.g. SSRI, ipsapirone, viloxazine, reboxetine, bupropione). Recently antidepressants of the fourth generation were synthetized which influence only the serotonin, and noradrenaline or dopamine system (e.g. milnacipran, befloxatone). The fifth generation of antidepressants foresees the exclusive action on 5-HT, noradrenaline and dopamine systems of the CNS in varying ratios (e.g. venlafaxine, cericlamine). PMID:8174184

  12. Design of Hanford Site 4th Generation Multi Function Corrosion Monitoring System

    SciTech Connect

    NORMAN, E.C.

    2000-08-30

    This document describes the design of the fourth-generation corrosion monitoring system scheduled to be installed in DST 241-AN-104 early in fiscal year 2001. A fourth-generation multi-function corrosion monitoring system has been designed for installation into a DST in the 241-AN farm at the Hanford Site in FY 2001. Improvements and upgrades from the third-generation system (installed in 241-AN-105) that have been incorporated into the fourth-generation system include: Addition of a built-in water lance to assist installation of probe into tanks with a hard crust layer at the surface of the waste; and Improvement of the electrode mounting apparatus used to attach the corrosion monitoring electrodes to the stainless steel probe body (new design simplifies probe assembly/wiring). These new features improve on the third-generation design and yield a system that is easier to fabricate and install, provides for a better understanding of the relationship between corrosion and other tank operating parameters, and optimizes the use of the riser that houses the probe in the tank.

  13. The ARC-EN-CIEL French 4th Generation Light Source

    SciTech Connect

    Bruni, C.; Couprie, M. E.; Chubar, O.; Loulergue, A.; Nahon, L.; Carre, B.; Garzella, D.; Labat, M.; Lambert, G.; Monot, P.; Jablonka, M.; Meot, F.; Ortega, J. M.; Nutarelli, D.

    2007-01-19

    ARC-EN-CIEL (Accelerator-Radiation Complex for Enhanced Coherent Intense Extended Light) proposal is based on a CW 1 GeV superconducting linear accelerator delivering high charge, subpicosecond, low emittance electron bunches with a high repetition rate (1 kHz). The FEL uses High Harmonics Generation in gases in a High Gain Harmonic Generation scheme, leading to a rather compact solution. The radiation extends down to 0.8 nm with the non-linear harmonics and reproduces the good longitudinal and transverse coherence of the harmonics generated in gas. Optional beam loops, foreseen to increase the beam current or the energy, will accommodate infrared CSR source, femtosecond undulator sources in the VUV and X-ray ranges, and a FEL oscillator in the 10 nm range. An important synergy is expected between accelerator and laser communities, in particular for electron plasma acceleration tests.

  14. Rare decays of the Z and the standard model, 4th generation, and beyond

    SciTech Connect

    Weiler, T.J.

    1989-01-01

    Several issues in rare decays of the Z are addressed. The rate for flavor-changing Z decay grows as the fourth power of the fermion masses internal to the quantum loop, and so offers a window to the existence of ultraheavy (m > M{sub W}) fermions. In the standard model, with three generations, BR(Z {yields} bs) < 10{sup -7} and BR(Z{yields}tc)<10{sup -13}. With four generations, BR(Z {yields} bb{sub 4}) may be as large as 10{sup -5} if m{sub b4} < M{sub Z}; and similarly for BR(Z {yields} N{sub 4}v), where N{sub 4} is the possibly heavy fourth generation neutrino. In supersymmetric and other two Higgs doublet models, BR(Z {yields} tc) may be as large as 5 {times} 10{sup -6} in the three generation scheme. With minimal supersymmetry, the reaction Z {yields} H{gamma} is guaranteed to go, with a parameter-dependent branching ratio of 10{sup -6 {plus minus} 3}. With mirror fermions or exotic E{sub 6} fermions, the branching ratios for Z {yields} ct (70 GeV), Z {yields} {mu}{tau}, and Z {yields} bb{sub 4} (70 GeV) are typically 10{sup -4}, 10{sup -4}, and 10{sup -3} respectively, clearly measurable at LEP. Depending on unknown quark masses, the Z may mix with vector (b{sub 4}{bar b}{sub 4}) and the W may mix with vector (t{bar b}) or (t{bar s}). CP violating asymmetries in flavor-changing Z decay are immeasurably small in the standard model, but may be large in supersymmetric and other nonstandard models. 28 refs.

  15. Negative Delta-Rho in the "standard Model" from 4TH-GENERATION Bound States

    NASA Astrophysics Data System (ADS)

    McCoy, Richard Thomas, III

    The possible consequences of heavy fourth-generation "vector meson" bound states, formed by the exchange of the Higgs boson, are discussed within the context of the Standard Model with either one or two Higgs doublets. It is suggested that such bound states could make negative contributions to the rho parameter, thereby loosening the perturbative constraint upon the mass of the top quark (our model would permit rm m_{t} to be as large as 365 GeV in the one Higgs doublet scenario, for example) and/or the masses, mass splittings, and other characteristics of a potential fourth generation of heavy fermions. In the two Higgs doublet scenario, the contributions to the rho parameter coming solely from the scalar sector are also considered. It is found in that scenario that the way fermions couple to the Higgs doublets crucially determines whether or not one can have a heavy (>150 GeV) top quark, a light ( <80 GeV) charged scalar and/or rare "monojet" Z decays such as Z to Nnu _tau, where N is the fourth-generation neutral lepton.

  16. Laboratory Astrophysics with High Power Lasers and 4th Generation Light Sources

    NASA Astrophysics Data System (ADS)

    Gregori, Gianluca

    2013-10-01

    The combination of high power optical lasers and free electron lasers operating at short wavelength (in the x-ray regime) has opened new avenues for laboratory astrophysics, where exotic states of matter can now be generated and probed with high accuracy. We will review a few examples of recent experiments performed at the Linac Coherent Light Source (LCLS) free electron laser operating in Stanford (CA), but also discuss future applications. We will focus our discussion on the following three examples: 1) Laboratory analogues of white dwarf envelopes and the physics of strongly coupled plasmas near crystallization; 2) scaled laboratory experiments to investigate magnetized and radiative shocks; and 3) possible proposals for testing strong gravity analogues using x-ray Thomson scattering. This work was partially the European Research Council under the European Community's Seventh Framework Programme.

  17. 4th Annual SATN Conference 2011: Curriculum Transformation at Universities of Technology: Towards Development of New Generation Universities

    ERIC Educational Resources Information Center

    Mthembu, T.

    2012-01-01

    The South African Technology Network (SATN) would like to thank the Editor of the "South African Journal of Higher Education" (SAJHE) for the opportunity to publish papers read at the 4th Annual SATN Conference that was hosted by Central University of Technology and held in Bloemfontein in November 2011. The journal makes it possible for…

  18. Use of fluoroquinolones and third-generation cephalosporins in the emergency department: an 11-year survey.

    PubMed

    Montassier, Emmanuel; Corvec, Stephane; Hardouin, Jean-Benoit; Potel, Gilles; Batard, Eric

    2014-12-01

    Fluoroquinolones and third-generation cephalosporins are particularly prone to select bacterial resistance to antibiotics. We aimed to assess the temporal trends of antibiotic use in the emergency department adults unit of an academic hospital between 2002 and 2012. Antibiotic use was converted in defined daily doses (DDD). The total antibiotic consumption tended to decrease, from 53.1±8.5 to 48.6±11.9 DDD/1000 patient visits (estimate decrease per year, -0.9±0.5 DDD/1000 visits, P=0.07). Use of third-generation cephalosporins increased significantly, from 9.7% of total antibiotic use to 22.6% (estimate per year, 1.2±0.2%, P<0.0001), whereas use of fluoroquinolones decreased from 19.5 to 12.3% (estimate per year, -0.7±0.2%, P<0.003). Given their ability to select bacterial resistance, especially extended-spectrum β-lactamases, particular attention should be paid to increasing use of third-generation cephalosporins in the emergency department. PMID:24487125

  19. 2.5 Gbps clock data recovery using 1/4th-rate quadricorrelator frequency detector and skew-calibrated multi-phase clock generator

    NASA Astrophysics Data System (ADS)

    Tontisirin, S.; Tielert, R.

    2006-09-01

    A Gb/s clock and data recovery (CDR) circuit using 1/4th-rate digital quadricorrelator frequency detector and skew-calibrated multi-phase voltage-controlled oscillator is presented. With 1/4th-rate clock architecture, the coil-free oscillator can have lower operation frequency providing sufficient low-jitter operation. Moreover, it is an inherent 1-to-4 DEMUX. The skew calibration scheme is applied to reduce phase offset in multi-phase clock generator. The CDR with frequency detector can have small loop bandwidth, wide pull-in range and can operate without the need for a local reference clock. This 1/4th-rate CDR is implemented in standard 0.18 μm CMOS technology. It has an active area of 0.7 mm2 and consumes 100 mW at 1.8 V supply. The CDR has low jitter operation in a wide frequency range from 1-2.25 Gb/s. Measurement of Bit-Error Rate is less than 10-12 for 2.25 Gb/s incoming data 27-1 PRBS, jitter peak-to-peak of 0.7 unit interval (UI) modulation at 10 MHz.

  20. Comparative clinical study of conjunctival toxicities of newer generation fluoroquinolones without the influence of preservatives

    PubMed Central

    Park, Han Sang; Lee, Jun Hun; Kim, Hong Kyun

    2015-01-01

    AIM To compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives. METHODS In a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%). After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm2/d) compared in each group using Kruskal-Wallis tests. RESULTS There were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group), 10.31±2.96d (gatifloxacin group), and 13.50±4.10d (moxifloxacin group), P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm2/d (levofloxacin group), 5.52±1.68 mm2/d (gatifloxacin group), and 4.40±1.30 mm2/d (moxifloxacin group), P=0. 003. CONCLUSION Without the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin. PMID:26682177

  1. Fluoroquinolone and Third-Generation-Cephalosporin Resistance among Hospitalized Patients with Urinary Tract Infections Due to Escherichia coli: Do Rates Vary by Hospital Characteristics and Geographic Region?

    PubMed

    Bidell, Monique R; Palchak, Melissa; Mohr, John; Lodise, Thomas P

    2016-05-01

    This analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to Escherichia coli showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rates exceeded 25% regardless of geographic location or hospital characteristics. The findings suggest that fluoroquinolones should be reserved and third-generation cephalosporins be used with caution as empirical agents for hospitalized patients with UTIs due to E. coli. PMID:26926640

  2. Efficient 2(nd) and 4(th) harmonic generation of a single-frequency, continuous-wave fiber amplifier.

    PubMed

    Sudmeyer, Thomas; Imai, Yutaka; Masuda, Hisashi; Eguchi, Naoya; Saito, Masaki; Kubota, Shigeo

    2008-02-01

    We demonstrate efficient cavity-enhanced second and fourth harmonic generation of an air-cooled, continuous-wave (cw), single-frequency 1064 nm fiber-amplifier system. The second harmonic generator achieves up to 88% total external conversion efficiency, generating more than 20-W power at 532 nm wavelength in a diffraction-limited beam (M(2) < 1.05). The nonlinear medium is a critically phase-matched, 20-mm long, anti-reflection (AR) coated LBO crystal operated at 25 degrees C. The fourth harmonic generator is based on an AR-coated, Czochralski-grown beta-BaB(2)O(4) (BBO) crystal optimized for low loss and high damage threshold. Up to 12.2 W of 266-nm deep-UV (DUV) output is obtained using a 6-mm long critically phase-matched BBO operated at 40 degrees C. This power level is more than two times higher than previously reported for cw 266-nm generation. The total external conversion efficiency from the fundamental at 1064 nm to the fourth harmonic at 266 nm is >50%. PMID:18542230

  3. Third and fourth generation fluoroquinolone antibacterials: a systematic review of safety and toxicity profiles.

    PubMed

    Sousa, Joana; Alves, Gilberto; Fortuna, Ana; Falcão, Amilcar

    2014-01-01

    In the last decade, several third and fourth generation fluoroquinolones (FQs) have been approved for clinical use. These new agents exhibit a more potent and broader-spectrum antibacterial activity and improved pharmacokinetic properties in comparison to the earlier FQs. Although new FQs are generally safe and well tolerated, moderate-to-severe toxicity events have been reported for some of them, leading to their restriction, suspension or even withdrawal from the market. The most common FQ-related adverse effects (AEs) are usually mild and involve the gastrointestinal tract (e.g. nausea and diarrhea) and the central nervous system (e.g. headache and dizziness). Uncommon, but severe AEs (e.g. arthropathy, QTc interval prolongation, dysglycaemia and phototoxicity) and idiosyncratic reactions (e.g. hepatitis and hemolytic anemia) have also been reported and will be discussed throughout this paper. The evidence currently available suggests that AEs can be inherent to the FQ class or can be associated with a particular chemical moiety of the molecular structure of each FQ, thus varying in frequency, severity and nature. The main goal of this review is to provide a systematic evaluation of safety and tolerability data of the newer FQs with emphasis on those currently marketed. PMID:24410307

  4. BEAM DYNAMICS STUDIES OF A HIGH-REPETITION RATE LINAC-DRIVER FOR A 4TH GENERATION LIGHT SOURCE

    SciTech Connect

    Ventturini, M.; Corlett, J.; Emma, P.; Papadopoulos, C.; Penn, G.; Placidi, M.; Qiang, J.; Reinsch, M.; Sannibale, F.; Steier, C.; Sun, C.; Wells, R.

    2012-05-18

    We present recent progress toward the design of a super-conducting linac driver for a high-repetition rate FEL-based soft x-ray light source. The machine is designed to accept beams generated by the APEX photo-cathode gun operating with MHz-range repetition rate and deliver them to an array of SASE and seeded FEL beamlines. We review the current baseline design and report results of beam dynamics studies.

  5. Testing quantum mechanics in non-Minkowski space-time with high power lasers and 4th generation light sources

    PubMed Central

    Crowley, B. J. B.; Bingham, R.; Evans, R. G.; Gericke, D. O.; Landen, O. L.; Murphy, C. D.; Norreys, P. A.; Rose, S. J.; Tschentscher, Th; Wang, C. H.-T; Wark, J. S.; Gregori, G.

    2012-01-01

    A common misperception of quantum gravity is that it requires accessing energies up to the Planck scale of 1019 GeV, which is unattainable from any conceivable particle collider. Thanks to the development of ultra-high intensity optical lasers, very large accelerations can be now the reached at their focal spot, thus mimicking, by virtue of the equivalence principle, a non Minkowski space-time. Here we derive a semiclassical extension of quantum mechanics that applies to different metrics, but under the assumption of weak gravity. We use our results to show that Thomson scattering of photons by uniformly accelerated electrons predicts an observable effect depending upon acceleration and local metric. In the laboratory frame, a broadening of the Thomson scattered x ray light from a fourth generation light source can be used to detect the modification of the metric associated to electrons accelerated in the field of a high power optical laser. PMID:22768381

  6. Gas dynamics and heat transfer in a packed pebble-bed reactor for the 4th generation nuclear energy

    NASA Astrophysics Data System (ADS)

    Abdulmohsin, Rahman

    -AlOx-Al junctions, we show that, despite excellent temperature stability, temperature fluctuations induce observable critical current fluctuations. Particularly, becuase 1/ f critical current noise has decreased with improved fabrication techniques in recent years, it is important to understand and eliminate this additional noise source. Next, we introduce a numerical method of calculating the mean square flux noise F2 from independently fluctuating spins on the surface of thin-film loops of arbitrary geometry. By reciprocity, F2 is proportional to Br2 , where B(r) is the magnetic field generated by a circulating current around the loop and r varies over the loop surface. By discretizing the loop nonuniformly, we efficiently and accurately compute the current distribution and resulting magnetic field, which may vary rapidly across the loop. We use this method to compute F2 in a number of scenarios in which we systematically vary physical parameters of the loop. We compare our simulations to an earlier analytic result predicting that F2 ∝ R/W in the limit where the loop radius R is much greater than the linewidth W. We further show that the previously neglected contribution of edge spins to F2 is significant---even dominant---in narrow-linewidth loops. To calculate theoretical dephasing rates in qubits, we consider flux noise with a spectral density Sphi( f) = A2/ (f/1 Hz) alpha, where A is of the order of 1 muphi 0 Hz--1/2 and 0.6 ≤ alpha ≤ 1.2; applied flux, our calculations of the dependence of the pure dephasing time tau φ Ramsey and echo pulse sequences on alpha for fixed A show that tauφ decreases rapidly as alpha is reduced. We find that tauφ is relatively insensitive to the noise bandwidth, f1 ≤ f ≤ f2 for all alpha provided the ultraviolet cutoff frequency f2 > 1/tauφ. We calculate the ratio tauφ,E/tau φ, R of the echo (E) and Ramsey (R) sequences, and the dependence of the decay function on alpha and f2. We investigate the case in which S phi(f0) is fixed

  7. A prototype for computer management of petroleum data and generation of maps and sections using 4th dimension{sup {trademark}}

    SciTech Connect

    French, D.E.; McBane, J.D.

    1996-06-01

    A commercial relational database program available for Macintosh and Windows-based computers known as 4th Dimension, has been adapted for use as a tool for storage, manipulation, and presentation of petroleum industry data. The database organization, input and output layouts, and manipulation routines are collectively referred to as WellFile4. Well data, land-survey data, production statistics, and stratigraphic information can be entered into the database from the keyboard or by importing files purchased from data vendors. The data can then be organized into files that can be searched and sorted based upon user-defined criteria. Selected subsets of data can be printed in various custom report formats. A graphics-editing module, 4D Draw, is used to generate maps, cross sections, and borehole-completion profiles. Maps can incorporate well-header information, formation tops, isopach values, or production data. Production data can also be presented as a bubble map. Maps can also include data selected from tables generated by a spreadsheet module, 4D Calc. Seismic-time values can be treated with appropriate velocity functions using the spreadsheet to derive depth values for posting to the base map. Structural or stratigraphic cross sections can be generated by selecting wells or seismic shot points from a map, and vertical exaggeration can be determined by the user. Maps can be modified extensively by the user before printing or plotting, and can be saved as a document that can be opened by other programs. Production statistics can be compiled based upon location, stratigraphic interval, or other criteria into a single set of data and presented as a chart or table. These can be printed or saved as a text file for use by other spreadsheet or chart-generation programs.

  8. The 4th Thermodynamic Principle?

    SciTech Connect

    Montero Garcia, Jose de la Luz; Novoa Blanco, Jesus Francisco

    2007-04-28

    It should be emphasized that the 4th Principle above formulated is a thermodynamic principle and, at the same time, is mechanical-quantum and relativist, as it should inevitably be and its absence has been one of main the theoretical limitations of the physical theory until today.We show that the theoretical discovery of Dimensional Primitive Octet of Matter, the 4th Thermodynamic Principle, the Quantum Hexet of Matter, the Global Hexagonal Subsystem of Fundamental Constants of Energy and the Measurement or Connected Global Scale or Universal Existential Interval of the Matter is that it is possible to be arrived at a global formulation of the four 'forces' or fundamental interactions of nature. The Einstein's golden dream is possible.

  9. Fluoroquinolone resistance in Campylobacter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluoroquinolone-resistant Campylobacter jejuni and C. coli are common in animals because of the use of fluoroquinolones as therapeutic agents in animal husbandry, particularly in chickens and other poultry. Campylobacter is a commensal in poultry, and therefore, poultry and poultry products are the...

  10. 17. 4th floor roof, view south, 4th and 5th floor ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. 4th floor roof, view south, 4th and 5th floor setback to left and atrium structure to right - Sheffield Farms Milk Plant, 1075 Webster Avenue (southwest corner of 166th Street), Bronx, Bronx County, NY

  11. Trace analysis of quinolone and fluoroquinolone antibiotics from wastewaters by liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Xiao, Yang; Chang, Hong; Jia, Ai; Hu, Jianying

    2008-12-19

    A sensitive liquid chromatography-electrospray tandem mass spectrometry method, combined with solid-phase extraction and a weak cation exchange cartridge cleanup, was established for twenty quinolone and fluoroquinolone antibiotics (pipemidic acid, flerofloxacin, ofloxacin, pefloxacin, enoxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, lomefloxacin, difloxacin, sarafloxacin, gatifloxacin, sparfloxacin, moxifloxacin, cinoxacin, oxolinic acid, nalidixic acid, flumequine, and piromidic acid) in influent, effluent, and river waters. For the various water matrices considered, the overall recoveries were from 64% to 127% except for piromidic acid (27-33%), and no obvious matrix effect was observed. The method detection limits for the twenty target antibiotics in the influent, effluent, and surface water samples were 1.6-50 ng/L, 0.6-50 ng/L, and 0.8-50 ng/L, respectively. This method was applied to analyze residual quinolone and fluoroquinolone antibiotics in wastewater and surface water samples from Beijing, China. Eight antibiotics (12 (pipemidic acid)-1208 ng/L (ofloxacin)) were detected in wastewater, and seven (1.3 (lomefloxacin)-535 ng/L (ofloxacin)) were detected in surface water samples. Gatifloxacin, a 4th generation fluoroquinolone antibiotic, was detected for the first time in influent (111 ng/L), effluent (56 ng/L), and river water (16-42 ng/L). PMID:19007934

  12. Photohaptenic properties of fluoroquinolones.

    PubMed

    Tokura, Y; Nishijima, T; Yagi, H; Furukawa, F; Takigawa, M

    1996-11-01

    Although quinolone antibacterial agents have both phototoxicity and photoallergenicity, the latter's potency has been poorly investigated compared with the former's. Some of the photoallergic chemicals serve as photohaptens, which lead to T-cell-mediated immune reactions after photobinding to protein by UVA radiation. We examined the photohaptenic potential of fluoroquinolones, including lomefloxacin (LFLX), ciplofloxacin, norfloxacin, ofloxacin, levofloxacin, fleroxacin, enoxacin and sparfloxacin (SPFX). The absorption spectra of the quinolones were altered by UVA irradiation, with an exception of SPFX that seems to be photostable toward UVA. Bovine serum albumin and murine epidermal cells were coupled with these fluoroquinolones other than SPFX by exposure to UVA. Subcutaneous inoculation of fluoroquinolone-photomodified epidermal cells induced and elicited a delayed-type hypersensitivity reaction in mice. However, epidermal cells incubated with LFLX without UVA exposure also induced and elicited a significant hypersensitivity reaction to a lesser degree than LFLX-photomodified epidermal cells. Furthermore, there was cross-reactivity between LFLX-photomodified epidermal cells and simply LFLX-incubated cells. This suggests that cells can be weakly modified with LFLX even in the dark and that UVA irradiation promotes this modification. Our study demonstrated that fluoroquinolones have photohaptenic properties to which their photoallergenicity is probably ascribed. PMID:8931383

  13. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  14. Laboratory survey of fluoroquinolone activity.

    PubMed

    Bellido, F; Pechère, J C

    1989-01-01

    Fluoroquinolones are active against a wide variety of bacteria. The antibacterial spectra of fluoroquinolones encompass staphylococci, Bacillus species, and Corynebacterium species implicated in infections of the immunocompromised host; Enterobacteriaceae; most intestinal pathogens; and many gram-negative organisms commonly causing nosocomial infections. Haemophilus influenzae, Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis are highly susceptible to this class of drugs. Because of their ability to penetrate into phagocytes, fluoroquinolones have been tested against intracellular pathogens: Legionella species, Rickettsia conorii, Rickettsia rickettsii, and Brucella melitensis are very sensitive; Chlamydia trachomatis and the mycoplasmas are borderline; and some antimycobacterial activities deserve further investigation. Species that are generally resistant include Pseudomonas maltophilia, Pseudomonas cepacia, Pseudomonas pseudomallei, Alcaligenes species, Nocardia species, Bordetella bronchiseptica, and most anaerobes. PMID:2672262

  15. Hypersensitivity to fluoroquinolones

    PubMed Central

    Fernández, Tahia D.; Ariza, Adriana; Palomares, Francisca; Montañez, María I.; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J.

    2016-01-01

    Abstract Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity–specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = −0.446; P < 0.001 for CD63 and Spearman r = −0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID:27281069

  16. In vitro potency and efficacy favor later generation fluoroquinolones for treatment of canine and feline Escherichia coli uropathogens in the United States.

    PubMed

    Liu, Xiaoqiang; Boothe, Dawn M; Jin, Yaping; Thungrat, Kamoltip

    2013-02-01

    Information regarding in vitro activity of newer fluoroquinolones (FQs) is limited despite increasing resistance in canine or feline pathogenic Escherichia coli (E. coli). This study describes in vitro potency and efficacy toward E. coli of seven FQs grouped according to similarities in chemical structure: enrofloxacin, ciprofloxacin, orbifloxacin (first-group), levofloxacin, marbofloxacin (second-group) and pradofloxacin, moxifloxacin (third-group; latest S, S-pyrrolidino-piperidine at C-7). Potency measures included minimum inhibitory concentration (MIC) (geometric mean MIC, MIC(50), MIC(90)); and mutant prevention concentration (MPC) for FQ susceptible isolates only. In vitro efficacy measures included relative susceptibility (MIC(BP-S):MIC) or resistance (MIC:MIC(BP-R)) and mutant selection window (MSW) (MPC:MIC). For enrofloxacin susceptible isolates, mean MIC (μg/ml) was least for each third-group drug and ciprofloxacin and greatest for enrofloxacin and orbifloxacin (P = 0.006). For enrofloxacin susceptible isolates, MPC were below MIC:MIC(BP-R) and least for pradofloxacin (0.29 ± 0.16 μg/ml) and greatest for enrofloxacin (1.55 ± 0.55 μg/ml) (P = 0.006). MSW was least for pradofloxacin (55 ± 30) and greatest for ciprofloxacin (152 ± 76) (P = 0.0024). MIC(BP-S):MIC was greatest (P = 0.025) for pradofloxacin (190.1 ± 0.61) and least for enrofloxacin (23.53 ± 0.83). For FQ susceptible isolates, FQs MIC:MIC(BP-R) may serve as a surrogate for MPC. Because in vitro efficacy was greatest for pradofloxacin; it might be preferred for treatment of urinary tract infections (UTIs) associated with FQ susceptible E. coli uropathogens. PMID:23136054

  17. Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis

    PubMed Central

    Jacobson, Karen R.; Franke, Molly F.; Kaur, Devinder; Sloutsky, Alex; Mitnick, Carole D.; Murray, Megan

    2016-01-01

    Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the gyr genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of gyr mutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full gyrA and gyrB open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that gyrB mutations contribute to fluoroquinolone resistance both individually and through interactions with gyrA mutations. These effects were statistically significant. In these clinical isolates, several gyrA and gyrB mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of gyr mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of gyr mutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment. PMID:26763957

  18. Gyrase Mutations Are Associated with Variable Levels of Fluoroquinolone Resistance in Mycobacterium tuberculosis.

    PubMed

    Farhat, Maha R; Jacobson, Karen R; Franke, Molly F; Kaur, Devinder; Sloutsky, Alex; Mitnick, Carole D; Murray, Megan

    2016-03-01

    Molecular diagnostics that rapidly and accurately predict resistance to fluoroquinolone drugs and especially later-generation agents promise to improve treatment outcomes for patients with multidrug-resistant tuberculosis and prevent the spread of disease. Mutations in the gyr genes are known to confer most fluoroquinolone resistance, but knowledge about the effects of gyr mutations on susceptibility to early- versus later-generation fluoroquinolones and about the role of mutation-mutation interactions is limited. Here, we sequenced the full gyrA and gyrB open reading frames in 240 multidrug-resistant and extensively drug-resistant tuberculosis strains and quantified their ofloxacin and moxifloxacin MIC by testing growth at six concentrations for each drug. We constructed a multivariate regression model to assess both the individual mutation effects and interactions on the drug MICs. We found that gyrB mutations contribute to fluoroquinolone resistance both individually and through interactions with gyrA mutations. These effects were statistically significant. In these clinical isolates, several gyrA and gyrB mutations conferred different levels of resistance to ofloxacin and moxifloxacin. Consideration of gyr mutation combinations during the interpretation of molecular test results may improve the accuracy of predicting the fluoroquinolone resistance phenotype. Further, the differential effects of gyr mutations on the activity of early- and later-generation fluoroquinolones requires further investigation and could inform the selection of a fluoroquinolone for treatment. PMID:26763957

  19. Systemic use of fluoroquinolone in children

    PubMed Central

    Choi, Soo-Han; Kim, Eun Young

    2013-01-01

    Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children. PMID:23741232

  20. [Resistance to fluoroquinolone among Klebsiella spp strains producing extended-spectrum betalactamases isolated from urine].

    PubMed

    Tlamçani, Z; Ellaia, K; Benomar, A; Kabbaj, H; Alaoui, Ae; Seffar, M

    2009-01-01

    The aim of the study was to assess the frequency of resistance to fluoroquinolones in extended-spectrum beta-lactamase (ESBLs) Klebsiella spp isolated from urines of consulting and hospitalized patients in Rabat Specialities Hospital. A retrospective survey was made over 3 years (2006-2008). Two hundred ant fifty three patients presented with confirmed urinary tractus infection (UTI). Klebsiella spp was the etiologic agent in 28% (72/253) of reported UTI. Among them, 86% of Klebsiella pneumoniae and 14% of Klebsiella oxytoca. The frequency of Klebsiella spp resistance to fluoroquinolones was 33% and to third generation cephalosporins was 35%. Thirteen Klebsiella spp strains were producing extended-spectrum beta-lactamase witch corresponds to 18% of all the klebsiella. The extended-spectrum beta-lactamase strains with resistance to fluoroquinolones were 85% (11/13) or 15 % of all klebsiella (11/72). None of those strains was resistant to imipenem. In conclusions resistance of enterobacteries such as Klebsiella spp to fluoroquinolones is becoming worrying among consulting and hospitalized patients. Eleven strains multiresistant (ESBL + resistance to fluoroquinolones), isolated probably because of plasmids carrying genes of ESBL and fluoroquinolones resistances. This increasingly frequent resistance mechanism should lead to a more careful use of first line fluoroquinolones for UTI. PMID:19789127

  1. European Code against Cancer, 4th Edition: Tobacco and cancer.

    PubMed

    Leon, Maria E; Peruga, Armando; McNeill, Ann; Kralikova, Eva; Guha, Neela; Minozzi, Silvia; Espina, Carolina; Schüz, Joachim

    2015-12-01

    Tobacco use, and in particular cigarette smoking, is the single largest preventable cause of cancer in the European Union (EU). All tobacco products contain a wide range of carcinogens. The main cancer-causing agents in tobacco smoke are polycyclic aromatic hydrocarbons, tobacco-specific N-nitrosamines, aromatic amines, aldehydes, and certain volatile organic compounds. Tobacco consumers are also exposed to nicotine, leading to tobacco addiction in many users. Cigarette smoking causes cancer in multiple organs and is the main cause of lung cancer, responsible for approximately 82% of cases. In 2012, about 313,000 new cases of lung cancer and 268,000 lung cancer deaths were reported in the EU; 28% of adults in the EU smoked tobacco, and the overall prevalence of current use of smokeless tobacco products was almost 2%. Smokeless tobacco products, a heterogeneous category, are also carcinogenic but cause a lower burden of cancer deaths than tobacco smoking. One low-nitrosamine product, snus, is associated with much lower cancer risk than other smokeless tobacco products. Smoking generates second-hand smoke (SHS), an established cause of lung cancer, and inhalation of SHS by non-smokers is still common in indoor workplaces as well as indoor public places, and more so in the homes of smokers. Several interventions have proved effective for stopping smoking; the most effective intervention is the use of a combination of pharmacotherapy and behavioural support. Scientific evidence leads to the following two recommendations for individual action on tobacco in the 4th edition of the European Code Against Cancer: (1) "Do not smoke. Do not use any form of tobacco"; (2) "Make your home smoke-free. Support smoke-free policies in your workplace". PMID:26272517

  2. Fluoroquinolone-induced Achilles tendinitis.

    PubMed

    Tam, P K; Ho, Carmen T K

    2014-12-01

    We report a case of Achilles tendinitis after intake of ciprofloxacin for treatment of respiratory tract infection. Fluoroquinolone-induced tendinopathy is an uncommon but increasingly recognised adverse effect of this antibiotic class. Most of the cases occur in the Achilles tendon and may lead to tendon rupture. Possible predisposing risk factors include use of steroid, patients with renal impairment or renal transplant, old age, and being an athlete. The drug should be stopped once this condition is suspected. Symptomatic treatment should be given and orthopaedic referral is desirable if tendon rupture occurs. PMID:25488035

  3. Prulifloxacin: a new antibacterial fluoroquinolone.

    PubMed

    Prats, Guillem; Rossi, Vilma; Salvatori, Enrica; Mirelis, Beatriz

    2006-02-01

    In the last few years, the antimicrobial activity, efficacy and relative safety of fluoroquinolones have made them attractive for the treatment of community-acquired and nosocomial infections. Prulifloxacin is a new fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and -negative bacteria. Prulifloxacin is available for oral use, and after absorption is metabolized in to the active form, ulifloxacin. It exhibits good penetration in target tissues and a long elimination half-life, allowing once-daily administration. A number of randomized, controlled clinical trials carried out in Europe demonstrated the efficacy of prulifloxacin in the treatment of urinary tract (acute uncomplicated and complicated) and respiratory tract infections (acute exacerbations of chronic bronchitis), in comparison with the most widely used drugs such as ciprofloxacin, co-amoxiclav and pefloxacin. Prulifloxacin was generally well tolerated. The most frequent adverse reactions observed in clinical trials were gastric pain, diarrhea, nausea and skin rash. This review focuses on the characteristics of prulifloxacin, summarizing the relevant preclinical and clinical data. PMID:16441207

  4. 4th International Plant Biomechanics Conference Proceedings (Abstracts)

    SciTech Connect

    Frank W. Telewski; Lothar H. Koehler; Frank W. Ewers

    2003-07-20

    The 4th International Plant Biomechanics Conference facilitated an interdisciplinary exchange between scientists, engineers, and educators addressing the major questions encountered in the field of Plant Biomechanics. Subjects covered by the conference include: Evolution; Ecology; Mechanoreception; Cell Walls; Genetic Modification; Applied Biomechanics of Whole Plants, Plant Products, Fibers & Composites; Fluid Dynamics; Wood & Trees; Fracture Mechanics; Xylem Pressure & Water Transport; Modeling; and Introducing Plant Biomechanics in Secondary School Education.

  5. Activities of newer fluoroquinolones against Shigella sonnei.

    PubMed Central

    John, J F; Atkins, L T; Maple, P A; Bratoeva, M

    1992-01-01

    The activities of six fluoroquinolones were determined for 117 separate strains of Shigella sonnei. The order of increasing activity (MICs for 90% of strains tested) was enoxacin (0.25 micrograms/ml), temafloxacin (0.032 micrograms/ml), sparfloxacin (0.016 micrograms/ml), CI-960 (0.008 micrograms/ml), ciprofloxacin (0.008 micrograms/ml), and PD-131628-2 (0.008 micrograms/ml). These data, along with results of killing and mutational rate studies, showed that all six fluoroquinolones were highly inhibitory against S. sonnei and five fluoroquinolones were rapidly and persistently bactericidal. PMID:1444317

  6. Fluoroquinolone antibiotics and type 2 diabetes mellitus.

    PubMed

    Telfer, Stephen J

    2014-09-01

    Exposure to fluoroquinolone antibiotics is postulated as a risk factor for subsequent development of type 2 diabetes. It is hypothesized that fluoroquinolones induce an intracellular magnesium deficit that can lead to insulin resistance. A temporal correlation is reported between the rate of outpatient prescription of quinolones and the incidence of diabetes during the period 1980-2011 with a lag of approximately two years (R(2)=0.86, P<10(-9)). The increase in incidence of diabetes after 1990 and the recent decrease in the number of new cases are both reflected in the fluoroquinolone prescription rates. A geographical correlation is reported (adj. R(2)=0.7, P<0.0001) between rates of increase in prevalence of diabetes in each U.S. state and a model using only local rates of outpatient fluoroquinolone prescription, local rates of increase in the prevalence of obesity, and local rates of population growth as predictor variables. Prescription rates of non-quinolone antibiotics correlated less well with the local rates of increase in prevalence of diabetes. The data are consistent with fluoroquinolone exposure predisposing an individual to develop diabetes with a probability that strongly depends upon factors that also lead to an increase in obesity. According to the hypothesis, much of the increase in the incidence of type 2 diabetes in the U.S. from 1990 to the present can be attributed to fluoroquinolone exposure. PMID:24947193

  7. A 95 GHz, 4th harmonic gyro-oscillator

    SciTech Connect

    Hargreaves, T.A.; Scheitrum, G.P.; Bemis, T.; Higgins, L.

    1994-12-31

    There is currently an interest in medium power ({approximately}100 kW), compact 95 GHz amplifiers for future radar applications. Size, weight, and efficiency are critical for airborne applications. Litton has been investigating a 4th harmonic, 4-cavity gyro-amplifier. The key to success of the amplifier is the axis-encircling electron beam from a new type of electron gun, the advanced center post (ACP) gun. Gun simulations incorporating the actual magnetic field and thermal velocity spread in the emitted electrons show that axial velocity spreads of less than 2% are attainable, which is significantly better than other gun concepts. The amplifier utilizes coaxial-magnetron-type cavities operating in the {pi} mode. In this cavity, vanes extend nearly down to the electron beam`s outside diameter. The majority of the RF stored energy in the system is in the coaxial cavity, so that the resonant frequency and quality factor of each coaxial magnetron cavity may be adjusted by varying only the coaxial cavity. Several components are being tested individually. To test the cavity design, a 4th harmonic oscillator based on a coaxial magnetron cavity has been designed. Results of the oscillator testing will be presented.

  8. Impacts of a Discussion-Based Academic Language Program on Classroom Interactions in 4th through 7th Grades

    ERIC Educational Resources Information Center

    LaRusso, Maria; Jones, Stephanie M.; Kim, Ha Yeon; Kim, James; Donovan, Suzanne; Snow, Catherine

    2016-01-01

    This paper presents an exploratory analysis of treatment-control differences in the quality of classroom interactions in 4th through 7th grade urban classrooms. Word Generation (WG) is a research-based academic language program for middle school students designed to teach novel vocabulary and literacy through language arts, math, science, and…

  9. Fluoroquinolone-Resistant Enteric Bacteria in Sub-Saharan Africa: Clones, Implications and Research Needs

    PubMed Central

    Chattaway, Marie A.; Aboderin, Aaron O.; Fashae, Kayode; Okoro, Chinyere K.; Opintan, Japheth A.; Okeke, Iruka N.

    2016-01-01

    Fluoroquinolones came into widespread use in African countries in the early 2000s, after patents for the first generation of these drugs expired. By that time, quinolone antibacterial agents had been used intensively worldwide and resistant lineages of many bacterial species had evolved. We sought to understand which Gram negative enteric pandemic lineages have been reported from Africa, as well as the nature and transmission of any indigenous resistant clones. A systematic review of articles indexed in the Medline and AJOL literature databases was conducted. We report on the findings of 43 eligible studies documenting local or pandemic fluoroquinolone-resistant enteric clones in sub-Sahara African countries. Most reports are of invasive non-typhoidal Salmonella and Escherichia coli lineages and there have been three reports of cholera outbreaks caused by fluoroquinolone-resistant Vibrio cholerae O1. Fluoroquinolone-resistant clones have also been reported from commensals and animal isolates but there are few data for non-Enterobacteriaceae and almost none for difficult-to-culture Campylobacter spp. Fluoroquinolone-resistant lineages identified in African countries were universally resistant to multiple other classes of antibacterial agents. Although as many as 972 non-duplicate articles refer to fluoroquinolone resistance in enteric bacteria from Africa, most do not report on subtypes and therefore information on the epidemiology of fluoroquinolone-resistant clones is available from only a handful of countries in the subcontinent. When resistance is reported, resistance mechanisms and lineage information is rarely investigated. Insufficient attention has been given to molecular and sequence-based methods necessary for identifying and tracking resistant clones in Africa and more research is needed in this area. PMID:27148238

  10. Fluoroquinolone-Resistant Enteric Bacteria in Sub-Saharan Africa: Clones, Implications and Research Needs.

    PubMed

    Chattaway, Marie A; Aboderin, Aaron O; Fashae, Kayode; Okoro, Chinyere K; Opintan, Japheth A; Okeke, Iruka N

    2016-01-01

    Fluoroquinolones came into widespread use in African countries in the early 2000s, after patents for the first generation of these drugs expired. By that time, quinolone antibacterial agents had been used intensively worldwide and resistant lineages of many bacterial species had evolved. We sought to understand which Gram negative enteric pandemic lineages have been reported from Africa, as well as the nature and transmission of any indigenous resistant clones. A systematic review of articles indexed in the Medline and AJOL literature databases was conducted. We report on the findings of 43 eligible studies documenting local or pandemic fluoroquinolone-resistant enteric clones in sub-Sahara African countries. Most reports are of invasive non-typhoidal Salmonella and Escherichia coli lineages and there have been three reports of cholera outbreaks caused by fluoroquinolone-resistant Vibrio cholerae O1. Fluoroquinolone-resistant clones have also been reported from commensals and animal isolates but there are few data for non-Enterobacteriaceae and almost none for difficult-to-culture Campylobacter spp. Fluoroquinolone-resistant lineages identified in African countries were universally resistant to multiple other classes of antibacterial agents. Although as many as 972 non-duplicate articles refer to fluoroquinolone resistance in enteric bacteria from Africa, most do not report on subtypes and therefore information on the epidemiology of fluoroquinolone-resistant clones is available from only a handful of countries in the subcontinent. When resistance is reported, resistance mechanisms and lineage information is rarely investigated. Insufficient attention has been given to molecular and sequence-based methods necessary for identifying and tracking resistant clones in Africa and more research is needed in this area. PMID:27148238

  11. Overexpression of Salmonella enterica serovar Typhi recA gene confers fluoroquinolone resistance in Escherichia coli DH5α.

    PubMed

    Yassien, M A M; Elfaky, M A

    2015-11-01

    A spontaneous fluoroquinolone-resistant mutant (STM1) was isolated from its parent Salmonella enterica serovar Typhi (S. Typhi) clinical isolate. Unlike its parent isolate, this mutant has selective resistance to fluoroquinolones without any change in its sensitivity to various other antibiotics. DNA gyrase assays revealed that the fluoroquinolone resistance phenotype of the STM1 mutant did not result from alteration of the fluoroquinolone sensitivity of the DNA gyrase isolated from it. To study the mechanism of fluoroquinolone resistance, a genomic library from the STM1 mutant was constructed in Escherichia coli DH5α and two recombinant plasmids were obtained. Only one of these plasmids (STM1-A) conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. The chromosomal insert from STM1-A, digested with EcoRI and HindIII restriction endonucleases, produced two DNA fragments and these were cloned separately into pUC19 thereby generating two new plasmids, STM1-A1 and STM1-A2. Only STM1-A1 conferred the selective fluoroquinolone resistance phenotype to E. coli DH5α. Sequence and subcloning analyses of STM1-A1 showed the presence of an intact RecA open reading frame. Unlike that of the wild-type E. coli DH5α, protein analysis of a crude STM1-A1 extract showed overexpression of a 40 kDa protein. Western blotting confirmed the 40 kDa protein band to be RecA. When a RecA PCR product was cloned into pGEM-T and introduced into E. coli DH5α, the STM1-A11 subclone retained fluoroquinolone resistance. These results suggest that overexpression of RecA causes selective fluoroquinolone resistance in E. coli DH5α. PMID:26375447

  12. Special Issue: 4th International Workshop on Space Radiation (IWSRR)

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.

    2007-01-01

    This special issue of the journal "Radiation and Environmental Biophysics" contains 20 peer-reviewed papers contributed by leading space radiation researcher's world-wide attending the 4th IWSRR. Manuscripts cover a broad range of topics ranging from radiation environments and transport in shielding and planetary surfaces to new results in understanding the biological effects of protons and high-charge and energy (HZE) nuclei on the risk of cancer, and degenerative diseases such as central nervous system effects, heart disease, and cataracts. The issue provides a snapshot of the state-of-the-art of the research in this field, demonstrating both the important results gathered in the past few years with experiments at accelerators, and the need for more research to quantify the risk and develop countermeasures.

  13. [Time--the 4th dimision in medicine and psychotherapy].

    PubMed

    Bergmann, Günther

    2003-01-01

    Time is presented as well in his historical meaning and as 4th dimension in its medical and psychotherapeutic context. In this medical and psychotherapeutic process it has an important function and is a variable of a process procedure. The difference between "kairos" = (the right point of time) and "chronos" = (the period of time) is historically meanful. The subjective experienced time is as well emphasized by the development of time in the relation to the development of the "self" as in the subjective experience of time in medical and psychotherapeutic situations. There are also changed conceptions and understandings of time running parallel to the development of nature sciences. The importance of time is explained for the medical practice and the meeting with the patient--especially for chronic diseases. The connection of confidence and time is particularly emphasized in the systemic approach. PMID:12764877

  14. European Code against Cancer 4th Edition: Breastfeeding and cancer.

    PubMed

    Scoccianti, Chiara; Key, Timothy J; Anderson, Annie S; Armaroli, Paola; Berrino, Franco; Cecchini, Michele; Boutron-Ruault, Marie-Christine; Leitzmann, Michael; Norat, Teresa; Powers, Hilary; Schüz, Joachim; Wiseman, Martin; Romieu, Isabelle

    2015-12-01

    Breast cancer is the most frequent cancer in women, and incidence rates have been rising in European Union (EU) countries over recent decades due in part to a sharp decline in breastfeeding practices. Evidence for a protective association between breastfeeding and the risk of breast cancer at all ages is convincing, and modest protective relationships between breastfeeding and the risk of endometrial and ovarian cancers have been suggested. The reduction in breast cancer risk is estimated at 2% for an increase of 5 months of lifetime breastfeeding. The longer women breastfeed, the more they are protected against breast cancer. In addition, breastfeeding is associated with several health benefits for both the mother and the breastfed child. Taking all this evidence into account, the 4th edition of the European Code against Cancer recommends: "Breastfeeding reduces the mother's cancer risk. If you can, breastfeed your baby". PMID:26116994

  15. The Epilepsy Foundation's 4th Biennial Epilepsy Pipeline Update Conference.

    PubMed

    French, Jacqueline A; Schachter, Steven C; Sirven, Joseph; Porter, Roger

    2015-05-01

    On June 5 and 6, 2014, the Epilepsy Foundation held its 4th Biennial Epilepsy Pipeline Update Conference, an initiative of the Epilepsy Therapy Project, which showcased the most promising epilepsy innovations from health-care companies and academic laboratories dedicated to pioneering and advancing drugs, biologics, technologies, devices, and diagnostics for epilepsy. Speakers and attendees included emerging biotech and medical technology companies, major pharmaceutical and device companies, as well as investigators and innovators at the cutting-edge of epilepsy. The program included panel discussions on collaboration between small and large companies, how to get products in need of funding to the marketplace, who is currently funding epilepsy and CNS innovation, and how the NIH facilitates early-stage drug development. Finally, the conference featured the third annual "Shark Tank" competition. The presentations are summarized in this paper, which is followed by a compilation of the meeting poster abstracts. PMID:25922152

  16. Methods for analysis of fluoroquinolones in biological fluids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methods for analysis of 10 selected fluoroquinolone antibiotics in biological fluids are reviewed. Approaches for sample preparation, detection methods, limits of detection and quantitation and recovery information are provided for both single analyte and multi-analyte fluoroquinolone methods....

  17. Fluoroquinolone-induced gene transfer in multidrug-resistant Salmonella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity. Bacterial exposure to fluoroquinolones can cause DNA damage and induce a bacterial SOS response to stimulate repair of damaged DNA. Certain prophages (integrated in bacterial chromosomes) ...

  18. 76 FR 37649 - Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... SECURITY Coast Guard 33 CFR Part 165 Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce safety zone for the annual July 4th Fireworks Display (Tahoe City 4th of...

  19. 77 FR 39172 - Safety Zone: Skagway Harbor, Skagway, AK for 4th of July Fireworks

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-02

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone: Skagway Harbor, Skagway, AK for 4th of July... 4th of July Fireworks display. Persons desiring to transit within this safety zone must contact the... Inlet for the City of Skagway, Alaska, sponsored 4th of July fireworks display. A no-action...

  20. PREFACE: 4th International Symposium on Functional Materials (ISFM2011)

    NASA Astrophysics Data System (ADS)

    Yin, Shu; Sekino, Tohru; Tanaka, Shun-ichiro; Sato, Tsugio; Lu, Li; Xue, Dongfeng

    2012-01-01

    The 4th International Symposium on Functional Materials (ISFM2011) was held in Sendai, Japan, on 2-6 August 2011. This Special Issue of Journal of Physics: Conference Series (JPCS) consists of partial manuscripts which were presented at ISFM2011. Advanced materials have experienced a dramatic increase in demand for research, development and applications. The aim of the International Symposium on Functional Materials (ISFM) was to provide an overview of the present status with historical background and to foresee future trends in the field of functional materials. The 4th symposium, ISFM 2011, covered a wide variety of topics within state-of-the-art advanced materials science and technology, and focused especially on four major categories including: Environmental Materials, Electronic Materials, Energy Materials and Biomedical Materials. As you know, a massive earthquake and the Tsunami that followed occurred near the Tohoku region on 11 March 2011. After the earthquake, although there were many difficulties in continuing to organize the symposium, we received warm encouragement from many researchers and societies, especially from the members of the International Advisory Committee and Organizing Committee, so that ISFM2011 could be held on schedule. We are honored that ISFM2011 was the first formal international academic conference held in the Tohoku area of Japan after the 11 March earthquake. About 140 participants from 14 countries took part in the ISFM2011 symposium, which included five plenary talks by world-leading scientists, 32 invited talks, and many oral and poster presentations. We are delighted to see that many researchers are interested in the synthesis and the properties as well as the applications of functional materials. Many fruitful and exciting research achievements were presented in the symposium. We believe that this symposium provided a good chance for scientists to communicate and exchange opinions with each other. We would also like to

  1. Managing haemophilia for life: 4th Haemophilia Global Summit.

    PubMed

    Astermark, J; Dolan, G; Hilberg, T; Jiménez-Yuste, V; Laffan, M; Lassila, R; Lobet, S; Martinoli, C; Perno, C-F

    2014-07-01

    The 4th Haemophilia Global Summit was held in Potsdam, Germany, in September 2013 and brought together an international faculty of haemophilia experts and delegates from multidisciplinary backgrounds. The programme was designed by an independent Scientific Steering Committee of haemophilia experts and explored global perspectives in haemophilia care, discussing practical approaches to the optimal management of haemophilia now and in the future. The topics outlined in this supplement were selected by the Scientific Steering Committee for their relevance and potential to influence haemophilia care globally. In this supplement from the meeting, Jan Astermark reviews current understanding of risk factors for the development of inhibitory antibodies and discusses whether this risk can be modulated and minimized. Factors key to the improvement of joint health in people with haemophilia are explored, with Carlo Martinoli and Víctor Jiménez-Yuste discussing the utility of ultrasound for the early detection of haemophilic arthropathy. Other aspects of care necessary for the prevention and management of joint disease in people with haemophilia are outlined by Thomas Hilberg and Sébastian Lobet, who highlight the therapeutic benefits of physiotherapy and sports therapy. Riitta Lassila and Carlo-Federico Perno describe current knowledge surrounding the risk of transmission of infectious agents via clotting factor concentrates. Finally, different types of extended half-life technology are evaluated by Mike Laffan, with a focus on the practicalities and challenges associated with these products. PMID:24924596

  2. European Code against Cancer 4th Edition: Diet and cancer.

    PubMed

    Norat, Teresa; Scoccianti, Chiara; Boutron-Ruault, Marie-Christine; Anderson, Annie; Berrino, Franco; Cecchini, Michele; Espina, Carolina; Key, Tim; Leitzmann, Michael; Powers, Hilary; Wiseman, Martin; Romieu, Isabelle

    2015-12-01

    Lifestyle factors, including diet, have long been recognised as potentially important determinants of cancer risk. In addition to the significant role diet plays in affecting body fatness, a risk factor for several cancers, experimental studies have indicated that diet may influence the cancer process in several ways. Prospective studies have shown that dietary patterns characterised by higher intakes of fruits, vegetables, and whole-grain foods, and lower intakes of red and processed meats and salt, are related to reduced risks of death and cancer, and that a healthy diet can improve overall survival after diagnosis of breast and colorectal cancers. There is evidence that high intakes of fruit and vegetables may reduce the risk of cancers of the aerodigestive tract, and the evidence that dietary fibre protects against colorectal cancer is convincing. Red and processed meats increase the risk of colorectal cancer. Diets rich in high-calorie foods, such as fatty and sugary foods, may lead to increased calorie intake, thereby promoting obesity and leading to an increased risk of cancer. There is some evidence that sugary drinks are related to an increased risk of pancreatic cancer. Taking this evidence into account, the 4th edition of the European Code against Cancer recommends that people have a healthy diet to reduce their risk of cancer: they should eat plenty of whole grains, pulses, vegetables and fruits; limit high-calorie foods (foods high in sugar or fat); avoid sugary drinks and processed meat; and limit red meat and foods high in salt. PMID:26164653

  3. Rapid evolution of fluoroquinolone-resistant Escherichia coli in Nigeria is temporally associated with fluoroquinolone use

    PubMed Central

    2011-01-01

    Background Antibiotic resistance has necessitated fluoroquinolone use but little is known about the selective forces and resistance trajectory in malaria-endemic settings, where selection from the antimalarial chloroquine for fluoroquinolone-resistant bacteria has been proposed. Methods Antimicrobial resistance was studied in fecal Escherichia coli isolates in a Nigerian community. Quinolone-resistance determining regions of gyrA and parC were sequenced in nalidixic acid resistant strains and horizontally-transmitted quinolone-resistance genes were sought by PCR. Antimicrobial prescription practices were compared with antimicrobial resistance rates over a period spanning three decades. Results Before 2005, quinolone resistance was limited to low-level nalixidic acid resistance in fewer than 4% of E. coli isolates. In 2005, the proportion of isolates demonstrating low-level quinolone resistance due to elevated efflux increased and high-level quinolone resistance and resistance to the fluoroquinolones appeared. Fluoroquinolone resistance was attributable to single nucleotide polymorphisms in quinolone target genes gyrA and/or parC. By 2009, 35 (34.5%) of isolates were quinolone non-susceptible with nine carrying gyrA and parC SNPs and six bearing identical qnrS1 alleles. The antimalarial chloroquine was heavily used throughout the entire period but E. coli with quinolone-specific resistance mechanisms were only detected in the final half decade, immediately following the introduction of the fluoroquinolone antibacterial ciprofloxacin. Conclusions Fluoroquinolones, and not chloroquine, appear to be the selective force for fluoroquinolone-resistant fecal E. coli in this setting. Rapid evolution to resistance following fluoroquinolone introduction points the need to implement resistant containment strategies when new antibacterials are introduced into resource-poor settings with high infectious disease burdens. PMID:22060770

  4. PREFACE: 4th International Hadron Physics Conference (TROIA'14)

    NASA Astrophysics Data System (ADS)

    Dağ, Hüseyin; Erkol, Güray; Küçükarslan, Ayşe; Özpineci, Altuğ

    2014-11-01

    The 4th International Conference on Hadron Physics, TROIA'14, was held at Canakkale, Turkey on 1-5 July 2014. Ozyegin University, Middle East Technical University, Canakkale Onsekiz Mart University, Turkish Atomic Energy Authority and HadronPhysics2 Consortium sponsored the conference. It aimed at bringing together the experts and the young scientists working on experimental and theoretical hadron physics. About 50 participants from 10 countries attended the conference. The topics covered included: . Chiral Perturbation Theory . QCD Sum Rules . Effective Field Theory . Exotic Hadrons . Hadron Properties from Lattice QCD . Experimental Results and Future Perspectives . Hadronic Distribution Amplitudes The conference presentations were organized such that the morning sessions contained invited talks and afternoon sessions were devoted to contributed talks. The speakers of the invited talks were: C. Alexandrou, A. Gal, L. Tolos, J.R. Pelaez and M. Schindler. We had also guest speakers D. A. Demir and T. Senger. The conference venue was a resort hotel around Canakkale. As a social program, a guided full-day excursion to the excavation site of the ancient Troia town and Assos was organized. We believe that this conference provided a medium for young scientists and experts in the field to effectively communicate and share ideas. We would like to express our sincere thanks to supporting agencies and to all participants for their contributions and stimulating discussions. We are also grateful to the Scientific Secretary, Bora Işıldak, and all other members of the Organizing Committee for their patience and efforts. 30.10.2014 The Editors

  5. European Code against Cancer, 4th Edition: Cancer screening.

    PubMed

    Armaroli, Paola; Villain, Patricia; Suonio, Eero; Almonte, Maribel; Anttila, Ahti; Atkin, Wendy S; Dean, Peter B; de Koning, Harry J; Dillner, Lena; Herrero, Rolando; Kuipers, Ernst J; Lansdorp-Vogelaar, Iris; Minozzi, Silvia; Paci, Eugenio; Regula, Jaroslaw; Törnberg, Sven; Segnan, Nereo

    2015-12-01

    In order to update the previous version of the European Code against Cancer and formulate evidence-based recommendations, a systematic search of the literature was performed according to the methodology agreed by the Code Working Groups. Based on the review, the 4th edition of the European Code against Cancer recommends: "Take part in organized cancer screening programmes for: Bowel cancer (men and women); Breast cancer (women); Cervical cancer (women)." Organized screening programs are preferable because they provide better conditions to ensure that the Guidelines for Quality Assurance in Screening are followed in order to achieve the greatest benefit with the least harm. Screening is recommended only for those cancers where a demonstrated life-saving effect substantially outweighs the potential harm of examining very large numbers of people who may otherwise never have, or suffer from, these cancers, and when an adequate quality of the screening is achieved. EU citizens are recommended to participate in cancer screening each time an invitation from the national or regional screening program is received and after having read the information materials provided and carefully considered the potential benefits and harms of screening. Screening programs in the European Union vary with respect to the age groups invited and to the interval between invitations, depending on each country's cancer burden, local resources, and the type of screening test used For colorectal cancer, most programs in the EU invite men and women starting at the age of 50-60 years, and from then on every 2 years if the screening test is the guaiac-based fecal occult blood test or fecal immunochemical test, or every 10 years or more if the screening test is flexible sigmoidoscopy or total colonoscopy. Most programs continue sending invitations to screening up to the age of 70-75 years. For breast cancer, most programs in the EU invite women starting at the age of 50 years, and not before the age

  6. Urban Infrasound Observations - Examples from July 4th 2012

    NASA Astrophysics Data System (ADS)

    McComas, S.; Hayward, C.; Golden, P.; McKenna, M.; Simpson, C.

    2012-12-01

    , the Heroy Building Rooftop Array, is a two-element 30m line on a single rooftop. Large-scale fireworks displays in Dallas on 4 July 2012 provided an opportunity to identify and characterize known signals in an urban setting. The identified events were associated with one of these fireworks displays about 2 km from the arrays. Signals from these sources were used to tune processing parameters for an automatic coherent detection process, Progressive Multichannel Correlation Method (PMCC). PMCC was then used to scan the data for all possible firework sources in the urban environment and determine temporal, back azimuth, apparent velocity, and frequency information about the sources. The signal frequencies seen were 10-80 Hz and documented the details of the nearly 30 minute firework show. The resulting PMCC analysis showed potential to effectively identify other, lower frequency sources in the urban environment. These data were also is used to characterize the noise environment. Significant roof-to-roof noise differences may be related to the building configurations and mechanical equipment, as well as the interactions of the winds with the structures. During the evening of July 4th , additional ground deployed infrasound gauges provided a comparison of free surface and rooftop measurements. Permission to publish was granted by Director, Geotechnical and Structures Laboratory.

  7. 75 FR 35649 - Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... SECURITY Coast Guard 33 CFR Part 165 Safety Zone; Northern California Annual Fireworks Events, July 4th Fireworks Display AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce the Tahoe City 4th of July Fireworks Display safety zone, from 9 a.m. through 10...

  8. The Effects of Cooperative Learning Strategies on Vocabulary Skills of 4th Grade Students

    ERIC Educational Resources Information Center

    Bilen, Didem; Tavil, Zekiye Müge

    2015-01-01

    This study was carried out to investigate the effects of cooperative learning strategies on the vocabulary skills of 4th grade students. The study was also designed to ascertain the attitudes of the students in the experimental group towards cooperative learning. Out of 96 4th grade students enrolled in the private school where the study took…

  9. The school nutrition program's role in weight management of 4th grade elementary students

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We are attempting to uncover the school nutrition program's role in weight management of 4th grade elementary students. Data was collected within a time frame for the food frequency questionnaire (FFQ) set at two months at the WT Cheney Elementary School and South Wood Elementary for 4th grade stud...

  10. 75 FR 34636 - Safety Zone; Jameson Beach 4th of July Fireworks Display

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Jameson Beach 4th of July Fireworks Display... temporary safety zone in the navigable waters of Lake Tahoe, for the Jameson Beach 4th of July Fireworks... has a substantial direct effect on State or local governments and would either preempt State law...

  11. 75 FR 34639 - Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... Celebration, Cockrell's Creek, Reedville, VA in the Federal Register (75 FR 26157). We received no comments on... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Reedville July 4th Celebration, Cockrell's... the Reedville July 4th Celebration event. This action is intended to restrict vessel traffic...

  12. 76 FR 37650 - Safety Zone; 4th of July Festival Berkeley Marina Fireworks Display Berkeley, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; 4th of July Festival Berkeley Marina... Berkeley Pier, Berkeley, CA in support of the 4th of July Festival Berkeley Marina Fireworks Display... used in the fireworks display. Background and Purpose The City of Berkeley Marina will sponsor the...

  13. 75 FR 26157 - Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ... Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public meeting. But you may... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Reedville July 4th Celebration, Cockrell's..., VA in support of the Reedville July 4th Celebration event. This action is intended to restrict...

  14. Science Content Courses: Workshop in Food Chemistry for 4th Grade School Teachers

    ERIC Educational Resources Information Center

    Chaiyapechara, S.; Dong, F. M.

    2004-01-01

    A science content course in food chemistry was offered as a 4-day summer workshop from 1999 to 2001 to 4th grade school teachers in the Seattle School District. The objectives of the workshop were to increase the teachers' knowledge of food science, to perform simple experiments that could be used in the 4th grade classroom, and to help the…

  15. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains

    PubMed Central

    Teatero, Sarah; Patel, Samir N.

    2016-01-01

    Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID:27559344

  16. Fluoroquinolone Resistance among Clonal Complex 1 Group B Streptococcus Strains.

    PubMed

    Neemuchwala, Alefiya; Teatero, Sarah; Patel, Samir N; Fittipaldi, Nahuel

    2016-01-01

    Fluoroquinolone resistance in group B Streptococcus is increasingly being reported worldwide. Here, we correlated fluoroquinolone resistance with mutations in gyrA, gyrB, parC, and parE genes, identified by mining whole-genome sequencing (WGS) data of 190 clonal complex 1 group B Streptococcus strains recovered from patients with invasive diseases in North America. We report a high prevalence of fluoroquinolone resistance (12%) among GBS strains in our collection. Our approach is the first step towards accurate prediction of fluoroquinolone resistance from WGS data in this opportunistic pathogen. PMID:27559344

  17. Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

    PubMed

    Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N; Harris, Anthony D; Smith, Catherine A; Maslow, Joel

    2008-04-01

    We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples. PMID:18279070

  18. Efficient Recovery of Fluoroquinolone-Susceptible and Fluoroquinolone-Resistant Escherichia coli Strains From Frozen Samples

    PubMed Central

    Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N.; Harris, Anthony D.; Smith, Catherine A.; Maslow, Joel

    2010-01-01

    We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples. PMID:18279070

  19. Clostridium difficile: emergence of hypervirulence and fluoroquinolone resistance.

    PubMed

    Razavi, B; Apisarnthanarak, A; Mundy, L M

    2007-10-01

    Clostridium difficile is a well-known cause of sporadic and healthcare-associated diarrhea. Multihospital outbreaks due to a single strain and outbreaks associated with antibiotic selective pressure, especially clindamycin, have been well documented. Severe cases and fatalities from C. difficile are uncommon. The recent global emergence of a hypervirulent strain containing binary toxin (Toxinotype III ribotype 027), with or without deletion in a regulatory gene (tcdC gene), together with high-level resistance to third generation fluoroquinolones, has been associated with increased morbidity and mortality. Although the defective regulatory gene locus is associated with increased toxin production in vitro, the in vivo significance of this mutation and of the binary toxin remains undefined. To date, treatment strategies have not evolved in response to the emergence of this hypervirulaent strain. We provide a critical, quantitative summary of the evolving clinical and molecular epidemiology of C. difficile along with implications relevant to future treatment strategies. PMID:17885732

  20. The 1992 4th NASA SERC Symposium on VLSI Design

    NASA Technical Reports Server (NTRS)

    Whitaker, Sterling R.

    1992-01-01

    Papers from the fourth annual NASA Symposium on VLSI Design, co-sponsored by the IEEE, are presented. Each year this symposium is organized by the NASA Space Engineering Research Center (SERC) at the University of Idaho and is held in conjunction with a quarterly meeting of the NASA Data System Technology Working Group (DSTWG). One task of the DSTWG is to develop new electronic technologies that will meet next generation electronic data system needs. The symposium provides insights into developments in VLSI and digital systems which can be used to increase data systems performance. The NASA SERC is proud to offer, at its fourth symposium on VLSI design, presentations by an outstanding set of individuals from national laboratories, the electronics industry, and universities. These speakers share insights into next generation advances that will serve as a basis for future VLSI design.

  1. Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use

    PubMed Central

    Dalhoff, Axel

    2012-01-01

    This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except S. pneumoniae and H. influenzae, causing community-acquired respiratory tract infections. However, 10 to 30% of these isolates harbored first-step mutations conferring low level fluoroquinolone resistance. Fluoroquinolone resistance increased in Enterobacteriaceae causing community acquired or healthcare associated urinary tract infections and intraabdominal infections, exceeding 50% in some parts of the world, particularly in Asia. One to two-thirds of Enterobacteriaceae producing extended spectrum β-lactamases were fluoroquinolone resistant too. Furthermore, fluoroquinolones select for methicillin resistance in Staphylococci. Neisseria gonorrhoeae acquired fluoroquinolone resistance rapidly; actual resistance rates are highly variable and can be as high as almost 100%, particularly in Asia, whereas resistance rates in Europe and North America range from <10% in rural areas to >30% in established sexual networks. In general, the continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some guidelines, for example, treatment of urinary tract, intra-abdominal, skin and skin structure infections, and traveller's diarrhea, or even precludes the use in indications like sexually transmitted diseases and enteric fever. PMID:23097666

  2. An Assessment of 4th, 8th, and 11th Grade Students' Knowledge Related to Marine Science and Natural Resource Issues.

    ERIC Educational Resources Information Center

    Brody, Michael J.; Koch, Helmut

    In an effort to contribute information for science teachers and curriculum developers in Maine, this study generated base line data on 4th, 8th, and 11th grade students' knowledge of marine science and natural resources principles in relation to the Gulf of Maine. Five concept maps representing 15 major content principles were developed. Two…

  3. Risk Factors for Fluoroquinolone Resistance in Ocular Cultures

    PubMed Central

    Lee, Junsung

    2015-01-01

    Purpose To identify the risk factors associated with fluoroquinolone resistance in patients undergoing cataract surgery. Methods A total of 1,125 patients (1,125 eyes) who underwent cataract surgery at Veterans Health Service Medical Center from May 2011 to July 2012 were enrolled in this study. Conjunctival cultures were obtained from the patients on the day of surgery before instillation of any ophthalmic solutions. The medical records of patients with positive coagulase negative staphylococcus (CNS) and Staphylococcus aureus (S. aureus) cultures were reviewed to determine factors associated with fluoroquinolone resistance. Results Of 734 CNS and S. aureus cultures, 175 (23.8%) were resistant to ciprofloxacin, levofloxacin, gatifloxacin, or moxifloxacin. Use of fluoroquinolone within 3 months and within 1 year before surgery, topical antibiotic use other than fluoroquinolone, systemic antibiotic use, recent hospitalization, ocular surgery, intravitreal injection and use of eyedrops containing benzalkonium chloride were significantly more frequent in resistant isolates than in susceptible isolates. In multivariable logistic regression analysis, ocular surgery (odds ratio [OR], 8.457), recent hospitalization (OR, 6.646) and use of fluoroquinolone within 3 months before surgery (OR, 4.918) were significant predictors of fluoroquinolone resistance, along with intravitreal injection (OR, 2.976), systemic antibiotic use (OR, 2.665), use of eyedrops containing benzalkonium chloride (OR, 2.323), use of fluoroquinolone within 1 year before surgery (OR, 1.943) and topical antibiotic use other than fluoroquinolone (OR, 1.673). Conclusions Recent topical fluoroquinolone use, hospitalization and ocular surgery were significantly associated with fluoroquinolone resistance in CNS and S. aureus isolates from ocular culture. PMID:25646055

  4. 4th Annual DOE-ERSP PI Meeting: Abstracts

    SciTech Connect

    Hazen, Terry C.

    2009-03-01

    This contains abstracts from the 2009 Annual Environmental Remediation Sciences Program (ERSP) Principal Investigators (PI) Meeting. The ERSP seeks to advance fundamental science to understand, predict, and mitigate the impacts of environmental contamination from past nuclear weapons production and provide a scientific basis for the long-term stewardship of nuclear waste disposal. These ambitious goals cannot be achieved by any one project alone. Therefore, ERSP funds a combination of research programs at the DOE national laboratories, individual projects at universities and federal agencies, and large long(er)-term field site research. Integration of these activities to advance the ERSP goals is a constant challenge, but made significantly simpler by bringing together all funded ERSP researchers once a year to discuss the very latest research results. It is at these meetings where new ideas and/or scientific advancements in support of ERSP goals can be discussed and openly debated among all PIs in the program. The ERSP thrives, in part, on the new ideas, concepts, scientific connections, and collaborations generated as a result of these meetings. The annual PI Meeting is very much a working meeting with three major goals: (1) to provide opportunities for scientific interaction among the ERSP scientists, a critical element for the program; (2) to provide the ERSP program staff with an opportunity to evaluate the progress of each program and project; and (3) to showcase the ERSP to interested parties within DOE and within other federal agencies In addition to program managers from within OBER, there will be representatives from other offices within DOE and other federal agencies in attandance at the meeting.

  5. 29. VIEW OF 4TH FLOOR'S TELEPHONE RACKS WITH CABLE TRAYS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. VIEW OF 4TH FLOOR'S TELEPHONE RACKS WITH CABLE TRAYS ABOVE. THESE ARE NEWER APPARATUS AND NOT ORIGINAL. - Pacific Telephone & Telegraph Company Building, 1519 Franklin Street, Oakland, Alameda County, CA

  6. 16. 4th floor roof, view west, north side of setback ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. 4th floor roof, view west, north side of setback to left and delivery stair bulkhead to right - Sheffield Farms Milk Plant, 1075 Webster Avenue (southwest corner of 166th Street), Bronx, Bronx County, NY

  7. 18. DETAILED OFFSHORE VIEW OF 4TH TEE, LOOKING NORTHWEST, SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    18. DETAILED OFFSHORE VIEW OF 4TH TEE, LOOKING NORTHWEST, SHOWING TRANSITION FROM WOOD BENTS TO CONCRETE BENTS - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  8. Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story.

    PubMed

    Nelson, Jennifer M; Chiller, Tom M; Powers, John H; Angulo, Frederick J

    2007-04-01

    Campylobacter species cause 1.4 million infections each year in the United States. Fluoroquinolones (e.g., ciprofloxacin) are commonly used in adults with Campylobacter infection and other infections. Fluoroquinolones (e.g., enrofloxacin) are also used in veterinary medicine. Human infections with fluoroquinolone-resistant Campylobacter species have become increasingly common and are associated with consumption of poultry. These findings, along with other data, prompted the US Food and Drug Administration to propose the withdrawal of fluoroquinolone use in poultry in 2000. A lengthy legal hearing concluded with an order to withdraw enrofloxacin from use in poultry (effective in September 2005). Clinicians are likely to continue to encounter patients with fluoroquinolone-resistant Campylobacter infection and other enteric infection because of the continued circulation of fluoroquinolone-resistant Campylobacter species in poultry flocks and in persons returning from foreign travel who have acquired a fluoroquinolone-resistant enteric infection while abroad. Judicious use of fluoroquinolones and other antimicrobial agents in human and veterinary medicine is essential to preserve the efficacy of these important chemotherapeutic agents. PMID:17342653

  9. Physics Computing '92: Proceedings of the 4th International Conference

    NASA Astrophysics Data System (ADS)

    de Groot, Robert A.; Nadrchal, Jaroslav

    1993-04-01

    * Ordered Particle Simulations for Serial and MIMD Parallel Computers * "NOLP" -- Program Package for Laser Plasma Nonlinear Optics * Algorithms to Solve Nonlinear Least Square Problems * Distribution of Hydrogen Atoms in Pd-H Computed by Molecular Dynamics * A Ray Tracing of Optical System for Protein Crystallography Beamline at Storage Ring-SIBERIA-2 * Vibrational Properties of a Pseudobinary Linear Chain with Correlated Substitutional Disorder * Application of the Software Package Mathematica in Generalized Master Equation Method * Linelist: An Interactive Program for Analysing Beam-foil Spectra * GROMACS: A Parallel Computer for Molecular Dynamics Simulations * GROMACS Method of Virial Calculation Using a Single Sum * The Interactive Program for the Solution of the Laplace Equation with the Elimination of Singularities for Boundary Functions * Random-Number Generators: Testing Procedures and Comparison of RNG Algorithms * Micro-TOPIC: A Tokamak Plasma Impurities Code * Rotational Molecular Scattering Calculations * Orthonormal Polynomial Method for Calibrating of Cryogenic Temperature Sensors * Frame-based System Representing Basis of Physics * The Role of Massively Data-parallel Computers in Large Scale Molecular Dynamics Simulations * Short-range Molecular Dynamics on a Network of Processors and Workstations * An Algorithm for Higher-order Perturbation Theory in Radiative Transfer Computations * Hydrostochastics: The Master Equation Formulation of Fluid Dynamics * HPP Lattice Gas on Transputers and Networked Workstations * Study on the Hysteresis Cycle Simulation Using Modeling with Different Functions on Intervals * Refined Pruning Techniques for Feed-forward Neural Networks * Random Walk Simulation of the Motion of Transient Charges in Photoconductors * The Optical Hysteresis in Hydrogenated Amorphous Silicon * Diffusion Monte Carlo Analysis of Modern Interatomic Potentials for He * A Parallel Strategy for Molecular Dynamics Simulations of Polar Liquids on

  10. Physics Computing '92: Proceedings of the 4th International Conference

    NASA Astrophysics Data System (ADS)

    de Groot, Robert A.; Nadrchal, Jaroslav

    1993-04-01

    * Ordered Particle Simulations for Serial and MIMD Parallel Computers * "NOLP" -- Program Package for Laser Plasma Nonlinear Optics * Algorithms to Solve Nonlinear Least Square Problems * Distribution of Hydrogen Atoms in Pd-H Computed by Molecular Dynamics * A Ray Tracing of Optical System for Protein Crystallography Beamline at Storage Ring-SIBERIA-2 * Vibrational Properties of a Pseudobinary Linear Chain with Correlated Substitutional Disorder * Application of the Software Package Mathematica in Generalized Master Equation Method * Linelist: An Interactive Program for Analysing Beam-foil Spectra * GROMACS: A Parallel Computer for Molecular Dynamics Simulations * GROMACS Method of Virial Calculation Using a Single Sum * The Interactive Program for the Solution of the Laplace Equation with the Elimination of Singularities for Boundary Functions * Random-Number Generators: Testing Procedures and Comparison of RNG Algorithms * Micro-TOPIC: A Tokamak Plasma Impurities Code * Rotational Molecular Scattering Calculations * Orthonormal Polynomial Method for Calibrating of Cryogenic Temperature Sensors * Frame-based System Representing Basis of Physics * The Role of Massively Data-parallel Computers in Large Scale Molecular Dynamics Simulations * Short-range Molecular Dynamics on a Network of Processors and Workstations * An Algorithm for Higher-order Perturbation Theory in Radiative Transfer Computations * Hydrostochastics: The Master Equation Formulation of Fluid Dynamics * HPP Lattice Gas on Transputers and Networked Workstations * Study on the Hysteresis Cycle Simulation Using Modeling with Different Functions on Intervals * Refined Pruning Techniques for Feed-forward Neural Networks * Random Walk Simulation of the Motion of Transient Charges in Photoconductors * The Optical Hysteresis in Hydrogenated Amorphous Silicon * Diffusion Monte Carlo Analysis of Modern Interatomic Potentials for He * A Parallel Strategy for Molecular Dynamics Simulations of Polar Liquids on

  11. Systematically frameshifting by deletion of every 4th or 4th and 5th nucleotides during mitochondrial transcription: RNA self-hybridization regulates delRNA expression.

    PubMed

    Seligmann, Hervé

    2016-01-01

    In mitochondria, secondary structures punctuate post-transcriptional RNA processing. Recently described transcripts match the human mitogenome after systematic deletions of every 4th, respectively every 4th and 5th nucleotides, called delRNAs. Here I explore predicted stem-loop hairpin formation by delRNAs, and their associations with delRNA transcription and detected peptides matching their translation. Despite missing 25, respectively 40% of the nucleotides in the original sequence, del-transformed sequences form significantly more secondary structures than corresponding randomly shuffled sequences, indicating biological function, independently of, and in combination with, previously detected delRNA and thereof translated peptides. Self-hybridization decreases delRNA abundances, indicating downregulation. Systematic deletions of the human mitogenome reveal new, unsuspected coding and structural informations. PMID:27018206

  12. Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk?

    PubMed

    Bidell, Monique R; Lodise, Thomas P

    2016-06-01

    Fluoroquinolone antibiotics recently have gained increased national attention due to safety concerns. A well-described and serious adverse event associated with receipt of fluoroquinolones is tendinitis and tendon rupture. These tendon injuries can result in long-term sequelae, including chronic pain and mobility restrictions, and may warrant surgery. Due to the severity of these adverse events, a black box warning is included in the product labeling of all fluoroquinolones. In light of the mounting concerns surrounding fluoroquinolone-associated toxicities, the purpose of this clinical review is to provide a comprehensive summary of the risk of tendinopathy associated with levofloxacin, one of the most widely prescribed antibiotics in the United States, across in vitro, animal, and clinical studies, relative to other antibiotics. As part of this review, clinical presentation and onset, proposed mechanisms, patient-specific risk factors, and management of fluoroquinolone-induced tendon injury are summarized. Data were obtained from a comprehensive PubMed literature search and a review of U.S. Food and Drug Administration documents. Although tendinopathy is considered a fluoroquinolone class-wide toxicity, data from in vitro studies, animal studies, patient-level analyses, and large national and international surveillance reports suggest that levofloxacin, as well as its parent compound ofloxacin, possess higher propensities to cause tendon damage relative to other fluoroquinolones. Risk with ofloxacin and levofloxacin appears to be exposure dependent, with higher doses and longer durations being most commonly associated with tendinopathy. Other well-described patient risk factors for fluoroquinolone-associated tendinopathy include older age (older than 60 yrs), receipt of concomitant corticosteroid therapy, presence of renal dysfunction, and history of solid organ transplantation. Given widespread use of levofloxacin across patient care settings, knowledge of both

  13. 75 FR 38721 - Safety Zone; Munising 4th of July Fireworks, South Bay, Lake Superior, Munising, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Munising 4th of July Fireworks, South Bay... is intended to restrict vessels from a portion of South Bay during the Munising 4th of July Fireworks... from hazards associated with the Munising 4th of July Fireworks display. Based on the explosive...

  14. 75 FR 34369 - Safety Zones; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... Chicago's July 4th Celebration Fireworks, Chicago, Illinois in the Federal Register (75 FR 22330). We... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zones; City of Chicago's July 4th Celebration... associated with the City of Chicago's July 4th Celebration Fireworks. The Captain of the Port, Sector...

  15. 75 FR 34379 - Safety Zone; Mackinac Island 4th of July Fireworks, Lake Huron, Mackinac Island, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Mackinac Island 4th of July Fireworks, Lake... intended to restrict vessels from a portion of Lake Huron during the Mackinac Island 4th of July Fireworks... with the Mackinac Island 4th of July fireworks display. The fireworks display will occur between 9:45...

  16. 75 FR 38718 - Safety Zone; Sault Sainte Marie 4th of July Fireworks, St. Mary's River, Sault Sainte Marie, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Sault Sainte Marie 4th of July Fireworks... the Sault Sainte Marie 4th of July Fireworks display, July ] 4, 2010. This temporary safety zone is... with the Sault Sainte Marie 4th of July Fireworks display. The fireworks display is planned to...

  17. Fluoroquinolones in the treatment of bronchopulmonary disease in cystic fibrosis.

    PubMed

    Hurley, Matthew; Smyth, Alan

    2012-12-01

    Fluoroquinolones are commonly used to treat lung infections in patients with cystic fibrosis. These patients are susceptible to lung infection with common bacteria such as Staphylococcus aureus and Haemophilus influenzae, but are also prone to infection by opportunistic bacteria, including Pseudomonas aeruginosa. The good oral bioavailability and broad antimicrobial spectrum of activity, including antipseudomonal properties, make this class of antimicrobial attractive. We review the evidence assessing the use of fluoroquinolones in the context of preventing and eradicating early lung infection and in managing chronic lung infection and pulmonary exacerbations. The safety of fluoroquinolones and the use of newer agents in the class are also discussed. PMID:22968160

  18. Torsades de pointes associated with fluoroquinolones.

    PubMed

    Owens, Robert C; Ambrose, Paul G

    2002-05-01

    Recent attention has been called to the interpretation of studies of antiinfective agents demonstrating effects on the QTc interval. It seems that the effects of many of these agents on the QTc interval are small, but in some patient populations, these drugs may cause morbidity and mortality related to TdP. It would be beneficial to researchers and clinicians alike for the FDA to standardize the types of studies designed to assess the QTc interval prolongation potential of a drug, methodologies, and interpretation criteria. To this end, it would increase the efficiency of the drug-approval process, give regulatory agencies and clinicians guidance, and increase patient safety. In summary we congratulate Dr. Frothingham for attempting to address the challenging issue of postmarketing safety surveillance. A critical review of his analysis of fluoroquinolone-associated TdP as well as other data on this potentially life-threatening adverse event support the following conclusions: Information from spontaneous reports is generally useful as an early warning system for excess adverse events, but reporting rates are not synonymous with incidence rates. The deficiencies of Dr. Frothingham's analysis lead to serious questions regarding the validity of both the numerators and denominators used in the incidence calculations (e.g., exclusion of European results, use ot extrapolated outpatient prescriptions, failure to account for inpatient versus outpatient utilization, failure to apply the appropriate statistical test to a rarely occurring, adverse event) and call into question conclusions about the relative risk of TdP with different fluoroquinolones. The association between which of the fluoroquinolones was administered to high-risk patients, which is important in the multiple-hit hypothesis, remains nebulous (e.g., failure to separate cases by route of drug administration and failure to identify which fluoroquinolones were given to patients with electrolyte abnormalities

  19. Emergence of fluoroquinolone-resistant Neisseria meningitidis--Minnesota and North Dakota, 2007-2008.

    PubMed

    2008-02-22

    Meningoccocal disease causes substantial morbidity and mortality; approximately 10% of cases are fatal. Among those who survive, 10%-15% have long-term sequelae. Nasopharyngeal carriage of Neisseria meningitidis is a precursor to disease; however, the majority of carriers do not develop disease. Household and other close contacts of persons with meningococcal disease have a higher risk for carriage and therefore invasive disease. These persons should receive antibiotic chemoprophylaxis to eliminate nasopharyngeal carriage of N. meningitidis as soon as possible. The rate of secondary disease for close contacts is highest immediately after onset of disease in the index patient; secondary cases rarely occur after 14 days. Ciprofloxacin, a second-generation fluoroquinolone, is an effective single-dose oral chemoprophylaxis agent. Although isolated cases of ciprofloxacin-resistant meningoccocal disease have been described in Argentina, Australia, China, France, India, and Spain, resistance has not been reported in North America. This report describes a cluster of three cases of fluoroquinolone-resistant meningococcal disease that occurred among residents of the border area of North Dakota and Minnesota during January 2007-January 2008. The first of these cases was epidemiologically linked and had closely related molecular features to a 2006 case of fluoroquinolone-susceptible meningococcal disease that occurred in the same geographic region. Until further notice, ciprofloxacin should not be used for chemoprophylaxis of close contacts of persons with meningococcal disease in selected counties in North Dakota and Minnesota. Ceftriaxone, rifampin, and azithromycin are alternative agents. PMID:18288075

  20. Relationship of quantitative structure and pharmacokinetics in fluoroquinolone antibacterials

    PubMed Central

    Cheng, Die; Xu, Wei-Ren; Liu, Chang-Xiao

    2007-01-01

    AIM: To study the relationship between quantitative structure and pharmacokinetics (QSPkR) of fluoroquinolone antibacterials. METHODS: The pharmacokinetic (PK) parameters of oral fluoroquinolones were collected from the litera-ture. These pharmacokinetic data were averaged, 19 compounds were used as the training set, and 3 served as the test set. Genetic function approximation (GFA) module of Cerius2 software was used in QSPkR analysis. RESULTS: A small volume and large polarizability and surface area of substituents at C-7 contribute to a large area under the curve (AUC) for fluoroquinolones. Large polarizability and small volume of substituents at N-1 contribute to a long half life elimination. CONCLUSION: QSPkR models can contribute to some fluoroquinolones antibacterials with excellent pharmacokinetic properties. PMID:17552035

  1. FIB–SEM tomography of 4th generation PWA 1497 superalloy

    SciTech Connect

    Ziętara, Maciej Kruk, Adam Gruszczyński, Adam Czyrska-Filemonowicz, Aleksandra

    2014-01-15

    The effect of creep deformation on the microstructure of the PWA 1497 single crystal Ni-base superalloy developed for turbine blade applications was investigated. The aim of the present study was to characterize quantitatively a superalloy microstructure and subsequent development of rafted γ′ precipitates in the PWA 1497 during creep deformation at 982 °C and 248 MPa up to rupture. The PWA1497 microstructure was characterized by scanning electron microscopy and FIB–SEM electron tomography. The 3D reconstruction of the PWA1497 microstructure is presented and discussed. - Highlights: • The microstructure of PWA1497 superalloy was examined using FIB–SEM tomography. • In case of modern single crystal superalloys, measurements of A{sub A} are adequate for V{sub V}. • During creep the γ channel width increases from 65 to 193 nm for ruptured specimen. • Tomography is a useful technique for quantitative studies of material microstructure.

  2. Towards 4th generation biomaterials: a covalent hybrid polymer-ormoglass architecture

    NASA Astrophysics Data System (ADS)

    Sachot, N.; Mateos-Timoneda, M. A.; Planell, J. A.; Velders, A. H.; Lewandowska, M.; Engel, E.; Castaño, O.

    2015-09-01

    Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials.Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04275e

  3. Porting LEON3FT/GRLIB to 4th Generation Flash-Based Devices

    NASA Astrophysics Data System (ADS)

    Andersson, Jan; Habinc, Sandi; Prinetto, Paolo; Trotta, Pascal

    2015-09-01

    Cobham Gaisler develops the LEON3FT SPARC V8 fault-tolerant microprocessor that is available both as IP cores part of an IP library (GRLIB) that allows users to design their own custom system-on-chip (SoC) designs, and also as part of ready-made designs and devices. Cobham Gaisler has recently added support for Microsemi IGLOO2, and experimental support for Microsemi radiation-tolerant RTG4, devices to GRLIB.

  4. Injector Beam Dynamics for a High-Repetition Rate 4th-Generation Light Source

    SciTech Connect

    Papadopoulos, C. F.; Corlett, J.; Emma, P.; Filippetto, D.; Penn, G.; Qiang, J.; Reinsch, M.; Sannibale, F.; Steier, C.; Venturini, M.; Wells, R.

    2013-05-20

    We report on the beam dynamics studies and optimization methods for a high repetition rate (1 MHz) photoinjector based on a VHF normal conducting electron source. The simultaneous goals of beamcompression and reservation of 6-dimensional beam brightness have to be achieved in the injector, in order to accommodate a linac driven FEL light source. For this, a parallel, multiobjective optimization algorithm is used. We discuss the relative merits of different injector design points, as well as the constraints imposed on the beam dynamics by technical considerations such as the high repetition rate.

  5. Process Test Plan for 4TH Generation Hanford Corrosion Monitoring System

    SciTech Connect

    NORMAN, E.C.

    2000-06-20

    Instrumentation and cabinets for the 241-AN-107 and 241-AN-102 corrosion monitoring systems will be upgraded in FY 2000. The bulk of the field work involved in this task will involve placement of the corrosion monitoring data collection hardware closer to the risers that house the existing corrosion probes. This will be accomplished by placing a new climate controlled cabinet by the risers containing corrosion probes on these two tanks (one cabinet per tank). Once installed the systems will feed data back to a centralized corrosion monitoring station in the 241-AN-271 instrument building. The upgraded systems will be operated under the bounds of this Process Test Plan (PTP) for six principle reasons. These reasons were established prior to installing the original systems in 1997 (241-AN-107) and 1998 (241-AN-102). They are as follows: (1) Acquire corrosion data on the waste in 241-AN-107 and 241-AN-102. (2) Provide supporting data to the site's Integrity Assessment program. (3) Demonstrate that corrosion monitoring by evaluation of electrochemical noise data is possible in waste tank systems, particularly with regard to the detection of general corrosion and (if present) pitting and stress corrosion cracking. (4) Demonstrate the durability of the design of the corrosion monitoring equipment. (5) Extend tank life and reduce annual operations cost. (6) Provide basis to control corrosion in double shell tanks though the use of direct corrosion monitoring rather than waste sampling and analysis. The designs of the existing corrosion probes in 241-AN-107 and 241-AN-102 were reviewed and documented prior to the original installation activities in 1997 and 1998. Initial programmatic documentation for Hanford's corrosion monitoring program was also established prior to the original installation activities.

  6. Towards 4th generation biomaterials: a covalent hybrid polymer-ormoglass architecture.

    PubMed

    Sachot, N; Mateos-Timoneda, M A; Planell, J A; Velders, A H; Lewandowska, M; Engel, E; Castaño, O

    2015-10-01

    Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials. PMID:26332471

  7. 20. TYPICAL VIEW OF FRONT WINDOWS FROM 4TH TO 9TH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. TYPICAL VIEW OF FRONT WINDOWS FROM 4TH TO 9TH FLOOR WITH WHITE GLAZED TERRA COTTA SILL AND HEADERS. MULLIONS ARE ORANGE BROWN BRICKS LIKE THE WALLS. BRICKS ARE IN FLEMISH BOND PATTERN. - Pacific Telephone & Telegraph Company Building, 1519 Franklin Street, Oakland, Alameda County, CA

  8. Using 4th order Runge-Kutta method for solving a twisted Skyrme string equation

    NASA Astrophysics Data System (ADS)

    Hadi, Miftachul; Anderson, Malcolm; Husein, Andri

    2016-03-01

    We study numerical solution, especially using 4th order Runge-Kutta method, for solving a twisted Skyrme string equation. We find numerically that the value of minimum energy per unit length of vortex solution for a twisted Skyrmion string is 20.37 × 1060 eV/m.

  9. 77 FR 39408 - Safety Zone; Buffalo July 4th Fireworks, Lake Erie, Buffalo, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking A... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Buffalo July 4th Fireworks, Lake Erie, Buffalo, NY AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard...

  10. Assessment of an Engineering Technology Outreach Program for 4th-7th Grade Girls

    ERIC Educational Resources Information Center

    Dell, Elizabeth M.; Christman, Jeanne; Garrick, Robert D.

    2011-01-01

    This paper describes a workshop led by female Engineering Technology students, with support from female faculty, to provide an introduction to Engineering Technology to 4th-7th grade girls through a series of interactive laboratory experiments. This outreach program was developed to improve attitudes towards science and engineering in middle…

  11. 75 FR 33170 - Safety Zone; City of Martinez 4th of July Fireworks, Martinez, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; City of Martinez 4th of July Fireworks, Martinez, CA AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone for the launching of fireworks being sponsored by the City of...

  12. Improving Social Interaction among 4th Grade Students through Social Skills Instruction.

    ERIC Educational Resources Information Center

    Dunleavy, Shannon; Karwowski, Sandra; Shudes-Eitel, Jennifer

    This action research project implemented a program for improving social skills in order to establish positive interaction among 4th grade students at a northern Chicago suburban school. Social skills deficiency was documented through behavior checklists and referrals, teacher observations and student reflection. Teachers reported that low incomes,…

  13. Relationships between Grade Levels, Personal Factors, and Instructional Variation among 4th-12th Grade Teachers

    ERIC Educational Resources Information Center

    White, Jacquelyn M.

    2011-01-01

    The purpose of this quantitative correlational study was to investigate relationships between grade levels, personal factors of teachers, and instructional variety used by 4th-12th grade teachers in Kern County, California. The population under investigation included 2,844 teachers. 235 elementary, middle school/junior high, and secondary teachers…

  14. 77 FR 56208 - Filing Dates for the Kentucky Special Election in the 4th Congressional District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... From the Federal Register Online via the Government Publishing Office FEDERAL ELECTION COMMISSION Filing Dates for the Kentucky Special Election in the 4th Congressional District AGENCY: Federal Election Commission. ACTION: Notice of filing dates for special election. SUMMARY: Kentucky has scheduled a...

  15. Reading Development and Achievement of 4th-Grade Hmong Students

    ERIC Educational Resources Information Center

    Mahowald, Megan; Loughnane, Megan

    2016-01-01

    Researchers and practitioners alike have noted that Hmong students in the United States do not achieve as well as their monolingual peers and other bilingual students. The current mixed-methods study is designed to describe reading development and achievement of 4th-grade Hmong students in one large, urban school district. This study explores the…

  16. MAIN GATE, INTERSECTION OF 4TH AVE (200 NORTH) AND N ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    MAIN GATE, INTERSECTION OF 4TH AVE (200 NORTH) AND N STREET (895 EAST), SALT LAKE CITY, UT. VIEW LOOKING EAST THROUGH MAIN CEMETERY GATE TO CEMETERY'S MAIN STREET, REPHOTOGRAPH OF HISTORIC SHIPLER PHOTO # 18276, UTAH STATE HISTORICAL SOCIETY COLLECTION. - Salt Lake City Cemetery, 200 N Street, Salt Lake City, Salt Lake County, UT

  17. Polarimetric Microwave Emission from Snow Surface: 4th Strokes Component Analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of ice on the polarimetric 4th Stokes component observations is investigated using WindSat data over Antarctica. The difference in the magnitude of the signal observed during (July 2003) and summer (February 2004) months is investigated using a second harmonic sine function of the azimuth...

  18. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Safety Zone: Macy's July 4th Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND LIMITED ACCESS AREAS Specific Regulated Navigation...

  19. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zone: Macy's July 4th... OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND...

  20. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Safety Zone: Macy's July 4th... OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND...

  1. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Safety Zone: Macy's July 4th... OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND...

  2. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CFR 165.23 apply. (2) No vessels, except the Staten Island Ferries, will be allowed to transit the... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Safety Zone: Macy's July 4th... OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION AREAS AND...

  3. 11. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO NORTHEAST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO NORTHEAST, WITH WRAPPER (LEFT), PRESS (CENTER), AND CUTTER (RIGHT, BEHIND CHUTE); BUCKET CONVEYOR AT RIGHT MOVED WASTE FROM PRESS TO 5TH FLOOR FOR RE-MANUFACTURE - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  4. 4th level of 1945 warehouse indicating drag conveyor. From here ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4th level of 1945 warehouse indicating drag conveyor. From here screenings were pumped from the elevator leg to this conveyor. The grains were ground, then conveyed back down to the first floor for bagging. - Stewart Company Grain Elevator, 16 West Carson Street, Pittsburgh, Allegheny County, PA

  5. 94. VIEW OF PILINGS ON SOUTHEAST SIDE, WITH 4TH TEE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    94. VIEW OF PILINGS ON SOUTHEAST SIDE, WITH 4TH TEE IN THE BACKGROUND, FACING WEST-SOUTHWEST FROM SOUTHEAST CORNER OF THE TACKLE BOX. RAMP OF PIER EXTENSION IS VISIBLE ON RIGHT - Huntington Beach Municipal Pier, Pacific Coast Highway at Main Street, Huntington Beach, Orange County, CA

  6. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells*

    PubMed Central

    Badal, Sujan; Her, Yeng F.; Maher, L. James

    2015-01-01

    Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects include renal damage and, strangely, tendinopathies. The pathological mechanisms underlying these toxicities are poorly understood. Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent. We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar concentrations, these antibiotics inhibited jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted to stabilize transcription factor HIF-1α by inhibition of the oxygen-dependent hypoxia-inducible transcription factor prolyl hydroxylation. In dramatic contrast to this prediction, HIF-1α protein was eliminated by FQ treatment. We explored possible mechanisms for this unexpected effect and show that FQ inhibit HIF-1α mRNA translation. Thus, FQ antibiotics induce global epigenetic changes, inhibit collagen maturation, and block HIF-1α accumulation. We suggest that these mechanisms explain the classic renal toxicities and peculiar tendinopathies associated with FQ antibiotics. PMID:26205818

  7. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells.

    PubMed

    Badal, Sujan; Her, Yeng F; Maher, L James

    2015-09-01

    Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects include renal damage and, strangely, tendinopathies. The pathological mechanisms underlying these toxicities are poorly understood. Here, we show that the FQ drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators comparable with deferoxamine, a clinically useful iron-chelating agent. We show that iron chelation by FQ leads to epigenetic effects through inhibition of α-ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar concentrations, these antibiotics inhibited jumonji domain histone demethylases, TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation of methylated histones and DNA and inhibition of proline hydroxylation in collagen, respectively. These effects may explain FQ-induced nephrotoxicity and tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted to stabilize transcription factor HIF-1α by inhibition of the oxygen-dependent hypoxia-inducible transcription factor prolyl hydroxylation. In dramatic contrast to this prediction, HIF-1α protein was eliminated by FQ treatment. We explored possible mechanisms for this unexpected effect and show that FQ inhibit HIF-1α mRNA translation. Thus, FQ antibiotics induce global epigenetic changes, inhibit collagen maturation, and block HIF-1α accumulation. We suggest that these mechanisms explain the classic renal toxicities and peculiar tendinopathies associated with FQ antibiotics. PMID:26205818

  8. Fluoroquinolones in children: update of the literature.

    PubMed

    Bacci, Caterina; Galli, Luisa; de Martino, Maurizio; Chiappini, Elena

    2015-10-01

    The use of fluoroquinolones (FQ), antibiotics, which have excellent pharmacokinetic and pharmacodynamic characteristics and a broad spectrum of action, has increased dramatically in recent years, both in adults and children. Numerous safety and efficacy data are now available on FQ use in children, particularly regarding the treatment of complicated infections of the urinary tract, typhoid fever, pneumonia, acute external otitis, acute media otitis, meningoencephalitis, sepsis in neutropenic children and multidrug-resistant tuberculosis (MDR-TB), though sometimes studies have the limitations that they were conducted in selected populations, such as children with cystic fibrosis. Despite available safety data are encouraging, there is still an open debate on the toxicity of this class of antibiotics on weight-bearing joints in children. Not being able to exclude the possibility that, in rare cases, this event is likely to occur, their use in children should be limited to cases where the cost-benefit has been carefully examined, for example, in the case of sepsis or other severe infections from multi-resistant bacteria and not responsive to other classes of drugs. Furthermore, considering the increased use of FQ in children, it is possible that there is an increase in the incidence of infections from resistant germs (such as Escherichia coli, and pneumococci), as occurred in adults. In order to limit the diffusion of resistance, a judicious and appropriate use of this class of drugs is recommended. PMID:26099190

  9. THE FIRST LASING OF 193 NM SASE, 4TH HARMONIC HGHG AND ESASE AT THE NSLS SDL.

    SciTech Connect

    WANG, X.J.; SHEN Y.; WATANABE, T.; MURPHY, J.B.; ROSE, J.; TSANG, T.

    2006-08-28

    The first lasing of three types of single-pass high-gain FELs, SASE at 193 nm, 4th harmonic HGHG at 199 nm and ESASE at the Source Development Lab (SDL) of Brookhaven National Laboratory (BNL) is reported. The saturation of 4th harmonic HGHG and ESASE FELs was observed. We also observed the spectral broadening and instability of the 4th harmonic HGHG.

  10. Fluoroquinolone antibiotics: an emerging class of environmental micropollutants.

    PubMed

    Van Doorslaer, Xander; Dewulf, Jo; Van Langenhove, Herman; Demeestere, Kristof

    2014-12-01

    The aim of this review paper is to provide a comprehensive overview of different chemical and environmental aspects concerning fluoroquinolone antibiotics as emerging contaminants. A literature survey has been performed based on 204 papers from 1998 to mid-2013, resulting in a dataset consisting out of 4100 data points related to physical-chemical properties, environmental occurrence, removal efficiencies, and ecotoxicological data. In a first part, an overview is given on relevant physical-chemical parameters to better understand the behavior of fluoroquinolones during wastewater treatment and in the environment. Secondly, the route of these antibiotics after their application in both human and veterinary surroundings is discussed. Thirdly, the occurrence of fluoroquinolone residues is discussed for different environmental matrices. The final part of this review provides a tentative risk assessment of fluoroquinolone compounds and their transformation products in surface waters by means of hazard quotients. Overall, this review shows that fluoroquinolone antibiotics have a wide spread use and that their behavior during wastewater treatment is complex with an incomplete removal. As a result, it is observed that these biorecalcitrant compounds are present in different environmental matrices at potentially hazardous concentrations for the aquatic environment. The latter calls for actions on both the consumption as well as the wastewater treatment aspect to diminish the discharge of these biological active compounds. PMID:25226071

  11. 11th National Meeting of Organic Chemistry and 4th Meeting of Therapeutic Chemistry

    PubMed Central

    Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B.; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho e Melo, Teresa M.V.D.; Freitas, Victor

    2016-01-01

    For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. PMID:27102166

  12. 11(th) National Meeting of Organic Chemistry and 4(th) Meeting of Therapeutic Chemistry.

    PubMed

    Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho E Melo, Teresa M V D; Freitas, Victor

    2016-01-01

    For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. PMID:27102166

  13. 10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. 4TH FLOOR, HOTEL SOAP LINE No. 6 TO SOUTHWEST, WITH AUTOMATIC CUTTER (LEFT), PRESS (CENTER), AND WRAPPER (RIGHT); LARGE CHUTE AT CENTER FROM 5TH FLOOR BINS TO 3RD FLOOR SOAP MILLS; OVERHEAD AND FLOOR (LOWER RIGHT) FINISHED GOODS CONVEYORS TO G BLOCK (HAER NO. NJ-71-NN) - Colgate & Company Jersey City Plant, Building No. B-14, 54-58 Grand Street, Jersey City, Hudson County, NJ

  14. Spontaneous bilateral patellar tendon rupture: case report and review of fluoroquinolone-induced tendinopathy.

    PubMed

    Rosa, Bárbara; Campos, Pedro; Barros, André; Karmali, Samir; Gonçalves, Ricardo

    2016-07-01

    The present case emphasizes the importance of adhering to strict indications when prescribing fluoroquinolones. Although rare, drug-induced tendinopathy is not confined to fluoroquinolones. The patient's and physician's awareness should be increased to reduce fluoroquinolones-associated morbidity, particularly in patients with previously described risk factors. PMID:27386128

  15. Recombinagenic and mutagenic activities of fluoroquinolones in Drosophila melanogaster.

    PubMed

    Thomé, Simone; Bizarro, Cassiane Rosa; Lehmann, Mauricio; de Abreu, Bianca Regina Ribas; de Andrade, Heloisa Helena Rodrigues; Cunha, Kênya Silva; Dihl, Rafael Rodrigues

    2012-02-18

    Fluoroquinolones are widely used in human and in veterinary medicine due to their broad-spectrum antibacterial activity. They act by inhibiting type II DNA topoisomerases (gyrase and topoisomerase IV). Because of the sequence homology between prokaryotic and eukaryotic topoisomerases II, fluoroquinolones can pose a hazard to eukaryotic cells. However, published information concerning the genotoxic profiles of these drugs in vivo is sparse and inconsistent. We have assessed the activities of three fluoroquinolones, ciprofloxacin, enrofloxacin and norfloxacin, in the Drosophila melanogaster Somatic Mutation and Recombination Test (SMART) and measured their mutagenic and recombinagenic potentials. Norfloxacin was non-genotoxic. Ciprofloxacin and enrofloxacin induced significant increases in spot frequencies in trans-heterozygous flies. To test the roles of somatic recombination and mutation in the observed genotoxicity, balancer-heterozygous flies were also analyzed. Ciprofloxacin and enrofloxacin were preferential inducers of homologous recombination in proliferative cells, an event linked to loss of heterozygosity. PMID:22142834

  16. Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Ulu, Sevgi Tatar

    2009-02-01

    Simple, rapid and highly sensitive spectrofluorimetric method is presented for the determination of four fluoroquinolone (FQ) drugs, ciprofloxacin, enoxacin, norfloxacin and moxifloxacin in pharmaceutical preparations. Proposed method is based on the derivatization of FQ with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 9.0 to yield a yellow product. The optimum experimental conditions have been studied carefully. Beer's law is obeyed over the concentration range of 23.5-500 ng mL -1 for ciprofloxacin, 28.5-700 ng mL -1 for enoxacin, 29.5-800 ng mL -1 for norfloxacin and 33.5-1000 ng mL -1 for moxifloxacin using NBD-Cl reagent, respectively. The detection limits were found to be 7.0 ng mL -1 for ciprofloxacin, 8.5 ng mL -1 for enoxacin, 9.2 ng mL -1 for norfloxacin and 9.98 ng mL -1 for moxifloxacin, respectively. Intra-day and inter-day relative standard deviation and relative mean error values at three different concentrations were determined. The low relative standard deviation values indicate good precision and high recovery values indicate accuracy of the proposed methods. The method is highly sensitive and specific. The results obtained are in good agreement with those obtained by the official and reference method. The results presented in this report show that the applied spectrofluorimetric method is acceptable for the determination of the four FQ in the pharmaceutical preparations. Common excipients used as additives in pharmaceutical preparations do not interfere with the proposed method.

  17. SOS response and its regulation on the fluoroquinolone resistance

    PubMed Central

    Qin, Ting-Ting; Kang, Hai-Quan; Ma, Ping; Li, Peng-Peng; Huang, Lin-Yan

    2015-01-01

    Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change—mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo. PMID:26807413

  18. BET 2: Do fluoroquinolones increase the incidence of tendinopathy?

    PubMed

    Baombe, Janos P; Ford, Rebecca

    2016-07-01

    A shortcut review of the literature was carried out to establish whether the use of fluoroquinolones was associated with an increased risk of tendinopathy in adult patients. 10 trials were found to be directly relevant to the three-part question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that there is an association between the use of fluoroquinolones and a broad range of tendinopathies. PMID:27330182

  19. Can astronomy enhance UNESCO World Heritage recognition? The paradigm of 4th Dynasty Egyptian pyramids

    NASA Astrophysics Data System (ADS)

    Belmonte, Juan Antonio

    2015-08-01

    The pyramids of Egypt, notably those of the 4th Dinasty as Giza, have always be considered an unmistikable part of human world heritage as the only surviving wonders of the Ancient World. Their majesty, technical hability and innovative character have always beeen considered as representative of ancient Egyptian ingenuity. However, past and present fringe theories about the pyramids and astronomy have always polluted the role of our discipline in the design, construction and symbolism of these impressive monuments. This is indeed unfear. Fortunately, things have started to change in the last couple of decades and now astronomy is interpreted as a neccessary tool for the correct interpretation of the astral eschatology present in the 5th and 6th Dynasty Texts of the Pyramids. Although the pyramid complexes of the 4th Dynasty are mute, there is however recent research showing that a strong astral symbolism could be hidden in many aspects of the complex architecture and in the design of these exceptional monuments. This idea comes from several hints obtained not only from planning and construction, but also from epigraphy and the analysis of celestial and local landscapes. Chronology also plays a most relevant role on this. The pyramid complexes of the 4th Dynasty at Meidum, Dahshur, Giza and Abu Rowash -- all of which enjoy UNESCO World Heritage recognition -- willl be scrutinized. As a consequence, we will show how astronomy can certainly enhance the face value of these extraordinary monuments as a definitive proof of the ancient Egyptian quest for Ma'at, i.e. their perennial obsesion for Cosmic Order.

  20. miR-155 Inhibition Sensitizes CD4+ Th Cells for TREG Mediated Suppression

    PubMed Central

    Rust, Werner; Labhart, Paul; Alexiadis, Vassili; Becker, Christian; Hafner, Mathias; Weith, Andreas; Lenter, Martin C.; Jonuleit, Helmut; Schmitt, Edgar; Mennerich, Detlev

    2009-01-01

    Background In humans and mice naturally occurring CD4+CD25+ regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance. Principal Findings DNA-Microarray analyses of human as well as murine conventional CD4+ Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice and performing FoxP3 ChIP-Seq experiments using activated human T lymphocytes, we show that the expression and maturation of miR-155 seem to be not necessarily regulated by FoxP3. In order to address the functional relevance of elevated miR-155 levels, we transfected miR-155 inhibitors or mature miR-155 RNAs into freshly-isolated human and mouse primary CD4+ Th cells and nTregs and investigated the resulting phenotype in nTreg suppression assays. Whereas miR-155 inhibition in conventional CD4+ Th cells strengthened nTreg cell-mediated suppression, overexpression of mature miR-155 rendered these cells unresponsive to nTreg cell-mediated suppression. Conclusion Investigation of FoxP3 downstream targets, certainly of bound and regulated miRNAs revealed the associated function between the master regulator FoxP3 and miRNAs as regulators itself. miR-155 is shown to be crucially involved in nTreg cell mediated tolerance by regulating the susceptibility of conventional human as well as murine CD4+ Th cells to nTreg cell-mediated suppression. PMID:19777054

  1. Proceedings of the 4th International Workshop on Tritium Effects in Plasma Facing Components

    SciTech Connect

    R. A. Causey

    1999-02-01

    The 4th International Workshop on Tritium Effects in Plasma Facing Components was held in Santa Fe, New Mexico on May 14-15, 1998. This workshop occurs every two years, and has previously been held in Livermore/California, Nagoya/Japan, and the JRC-Ispra Site in Italy. The purpose of the workshop is to gather researchers involved in the topic of tritium migration, retention, and recycling in materials used to line magnetic fusion reactor walls and provide a forum for presentation and discussions in this area. This document provides an overall summary of the workshop, the workshop agenda, a summary of the presentations, and a list of attendees.

  2. Proceedings of the 4th International Conference and Exhibition: World Congress on Superconductivity, volume 1

    NASA Technical Reports Server (NTRS)

    Krishen, Kumar (Editor); Burnham, Calvin (Editor)

    1995-01-01

    The papers presented at the 4th International Conference Exhibition: World Congress on Superconductivity held at the Marriott Orlando World Center, Orlando, Florida, are contained in this document and encompass the research, technology, applications, funding, political, and social aspects of superconductivity. Specifically, the areas covered included: high-temperature materials; thin films; C-60 based superconductors; persistent magnetic fields and shielding; fabrication methodology; space applications; physical applications; performance characterization; device applications; weak link effects and flux motion; accelerator technology; superconductivity energy; storage; future research and development directions; medical applications; granular superconductors; wire fabrication technology; computer applications; technical and commercial challenges, and power and energy applications.

  3. Multi-Dimensional Asymptotically Stable 4th Order Accurate Schemes for the Diffusion Equation

    NASA Technical Reports Server (NTRS)

    Abarbanel, Saul; Ditkowski, Adi

    1996-01-01

    An algorithm is presented which solves the multi-dimensional diffusion equation on co mplex shapes to 4th-order accuracy and is asymptotically stable in time. This bounded-error result is achieved by constructing, on a rectangular grid, a differentiation matrix whose symmetric part is negative definite. The differentiation matrix accounts for the Dirichlet boundary condition by imposing penalty like terms. Numerical examples in 2-D show that the method is effective even where standard schemes, stable by traditional definitions fail.

  4. Proceedings of the 4th International Conference and Exhibition: World Congress on Superconductivity, Volume 2

    NASA Technical Reports Server (NTRS)

    Krishen, Kumar (Editor); Burnham, Calvin (Editor)

    1995-01-01

    This document contains papers presented at the 4th International Conference Exhibition: World Congress on Superconductivity held June 27-July 1, 1994 in Orlando, Florida. These documents encompass research, technology, applications, funding, political, and social aspects of superconductivity. The areas covered included: high-temperature materials; thin films; C-60 based superconductors; persistent magnetic fields and shielding; fabrication methodology; space applications; physical applications; performance characterization; device applications; weak link effects and flux motion; accelerator technology; superconductivity energy; storage; future research and development directions; medical applications; granular superconductors; wire fabrication technology; computer applications; technical and commercial challenges; and power and energy applications.

  5. The ratio of 2nd to 4th digit length: a new predictor of disease predisposition?

    PubMed

    Manning, J T; Bundred, P E

    2000-05-01

    The ratio between the length of the 2nd and 4th digits is: (a) fixed in utero; (b) lower in men than in women; (c) negatively related to testosterone and sperm counts; and (d) positively related to oestrogen concentrations. Prenatal levels of testosterone and oestrogen have been implicated in infertility, autism, dyslexia, migraine, stammering, immune dysfunction, myocardial infarction and breast cancer. We suggest that 2D:4D ratio is predictive of these diseases and may be used in diagnosis, prognosis and in early life-style interventions which may delay the onset of disease or facilitate its early detection. PMID:10859702

  6. Spiritual Health Scale 2011: Defining and Measuring 4th Dimension of Health

    PubMed Central

    Dhar, Neera; Chaturvedi, SK; Nandan, Deoki

    2011-01-01

    In the midst of physical comforts provided by the unprecedented developments in all spheres of life, the humanity is at cross roads and looking at something beyond these means. Spirituality has now been identified globally as an important aspect for providing answers to many questions related to health and happiness. The World Health Organization is also keen at looking beyond physical, mental and social dimensions of the health, and the member countries are actively exploring the 4th Dimension of the health i.e. the spiritual health and its impact on the overall health and happiness of an individual. National Institute of Health and Family Welfare (NIHFW), realized this need and initiated a research study in this direction. In this study, an effort was made to define this 4th Dimension of health from a common worldly person's perspective and measure it. 3 Domains, 6 Constructs and 27 Determinants of spiritual health were identified through a scientific process. A statistically reliable and valid Spiritual Health Scale (SHS 2011) containing 114 items has been developed. Construct validity and test- retest reliability has been established for urban educated adult population. The scale is first of its kind in the world to measure the spiritual health of a common worldly person, which is devoid of religious and cultural bias. Its items have universal applicability. PMID:22279257

  7. Computational aspects of the nonlinear normal mode initialization of the GLAS 4th order GCM

    NASA Technical Reports Server (NTRS)

    Navon, I. M.; Bloom, S. C.; Takacs, L.

    1984-01-01

    Using the normal modes of the GLAS 4th Order Model, a Machenhauer nonlinear normal mode initialization (NLNMI) was carried out for the external vertical mode using the GLAS 4th Order shallow water equations model for an equivalent depth corresponding to that associated with the external vertical mode. A simple procedure was devised which was directed at identifying computational modes by following the rate of increase of BAL sub M, the partial (with respect to the zonal wavenumber m) sum of squares of the time change of the normal mode coefficients (for fixed vertical mode index) varying over the latitude index L of symmetric or antisymmetric gravity waves. A working algorithm is presented which speeds up the convergence of the iterative Machenhauer NLNMI. A 24 h integration using the NLNMI state was carried out using both Matsuno and leap-frog time-integration schemes; these runs were then compared to a 24 h integration starting from a non-initialized state. The maximal impact of the nonlinear normal mode initialization was found to occur 6-10 hours after the initial time.

  8. PREFACE: 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSquare2015)

    NASA Astrophysics Data System (ADS)

    Vlachos, Dimitrios; Vagenas, Elias C.

    2015-09-01

    The 4th International Conference on Mathematical Modeling in Physical Sciences (IC-MSQUARE) took place in Mykonos, Greece, from Friday 5th June to Monday 8th June 2015. The Conference was attended by more than 150 participants and hosted about 200 oral, poster, and virtual presentations. There were more than 600 pre-registered authors. The 4th IC-MSQUARE consisted of different and diverging workshops and thus covered various research fields where Mathematical Modeling is used, such as Theoretical/Mathematical Physics, Neutrino Physics, Non-Integrable Systems, Dynamical Systems, Computational Nanoscience, Biological Physics, Computational Biomechanics, Complex Networks, Stochastic Modeling, Fractional Statistics, DNA Dynamics, Macroeconomics etc. The scientific program was rather intense as after the Keynote and Invited Talks in the morning, three parallel oral and one poster session were running every day. However, according to all attendees, the program was excellent with a high quality of talks creating an innovative and productive scientific environment for all attendees. We would like to thank the Keynote Speaker and the Invited Speakers for their significant contribution to IC-MSQUARE. We also would like to thank the Members of the International Advisory and Scientific Committees as well as the Members of the Organizing Committee.

  9. Crime rates and sedentary behavior among 4th grade Texas school children

    PubMed Central

    Brown, H Shelton; Pérez, Adriana; Mirchandani, Gita G; Hoelscher, Deanna M; Kelder, Steven H

    2008-01-01

    Introduction Although per capita crime has generally fallen over the period which coincides with the obesity epidemic, it has not fallen uniformly across communities. It also has not fallen enough to allay fears on the part of parents. Over the past 30 years, technological changes have made the indoor alternatives to playing outside, where children are more vulnerable to criminal activity, more enjoyable (cable TV, video games, and the internet) and comfortable (the spread of air conditioning to low income neighborhoods). We determined whether indoor sedentary behavior patterns are associated with community crime statistics. 4th graders in the U.S. are typically 9 or 10 years old. Methods We used data from the 2004–2005 Texas School Physical Activity and Nutrition (SPAN) survey linked with U.S. Department of Justice, Office of Justice Programs, Bureau of Justice Statistics data for the years 2000 through 2005 and Texas State data on sexual offenders. The probability-based sample included a total of 7,907 children in grade four. Multistage probability sampling weights were used. The dependent variables included were hours of TV watching, video game playing, computer use and total indoor sedentary behavior after school. Incremental Relative Rates were computed for community crime rates including robberies, all violent crimes, murders, assaults, property crimes, rapes, burglaries, larcenies and motor vehicle thefts as well as for sexual offenders living in the neighborhood. The neighborhood refers to the areas where the students at each school live. In the case of sexual offenders, sexual offenders per capita are estimated using the per capita rate in the zip code of the school attended; all other crime statistics are estimated by the crimes per capita in the police department jurisdiction covering the school attended. After controlling for sex, age, and African-American and Hispanic, cross-sectional associations were determined using multivariate Poisson regression

  10. Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis.

    PubMed

    Blower, Tim R; Williamson, Benjamin H; Kerns, Robert J; Berger, James M

    2016-02-16

    Mycobacterium tuberculosis (Mtb) infects one-third of the world's population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-Å resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone-gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone-enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance. PMID:26792525

  11. European Code against Cancer 4th Edition: Alcohol drinking and cancer.

    PubMed

    Scoccianti, Chiara; Cecchini, Michele; Anderson, Annie S; Berrino, Franco; Boutron-Ruault, Marie-Christine; Espina, Carolina; Key, Timothy J; Leitzmann, Michael; Norat, Teresa; Powers, Hilary; Wiseman, Martin; Romieu, Isabelle

    2015-12-01

    Alcohol consumption is the third leading risk factor for disease and mortality in Europe. The International Agency for Research on Cancer (IARC) Monographs provide strengthened evidence that the consumption of alcoholic beverages is causally associated with cancers of the oral cavity, pharynx, larynx, oesophagus, liver, colorectum and female breast, even for low and moderate alcohol intakes. The risk of cancer increases in a dose-dependent manner, and the higher the amount of alcohol consumed, the higher the risk of developing cancer. Several biological mechanisms explain the carcinogenicity of alcohol; among them, ethanol and its genotoxic metabolite acetaldehyde play a major role. Taking all this evidence into account, a recommendation of the 4th edition of the European Code against Cancer (ECAC) is: "If you drink alcohol of any type, limit your intake. Not drinking alcohol is better for cancer prevention." PMID:26115567

  12. General Chemistry Collection for Students (CD-ROM), Abstract of Special Issue 16, 4th Edition

    NASA Astrophysics Data System (ADS)

    2000-07-01

    The General Chemistry Collection contains both new and previously published JCE Software programs that are intended for use by introductory-level chemistry students. These peer-reviewed programs for Macintosh and for Windows are available on a single CD-ROM for convenient distribution to and access by students, and the CD may be adopted for students to purchase as they would a textbook. General Chemistry Collection covers a broad range of topics providing students with interesting information, tutorials, and simulations that will be useful to them as they study chemistry for the first time. There are 22 programs included in the General Chemistry Collection 4th Edition. Their titles and the general chemistry topics they cover are listed in Table 1. Features in This Edition General Chemistry Collection, 4th edition includes:

    • Lessons for Introductory Chemistry and INQUAL-S, two new programs not previously published by JCE Software (abstracts appear below)
    • Writing Electron Dot Structures (1) and Viscosity Measurement: A Virtual Experiment for Windows (2), two programs published individually by JCE Software
    • Periodic Table Live! LE, a limited edition of Periodic Table Live!, 2nd Edition (3) (this replaces Chemistry Navigator (4) and Illustrated Periodic Table (5))
    • Many of the programs from previous editions (6)1
    Hardware and Software Requirements System requirements are given in Table 2. Some programs have additional requirements. See the individual program abstracts at JCE Online, or documentation included on the CD-ROM for more specific information. Licensing and Discounts for Adoptions The General Chemistry Collection is intended for use by individual students. Institutions and faculty members may adopt General Chemistry Collection 4th Edition as they would a textbook. We can arrange for CDs to be packaged with laboratory manuals or other course materials or to be sold for direct distribution to students through the campus

  13. Breakthrough in cardiac arrest: reports from the 4th Paris International Conference.

    PubMed

    Kudenchuk, Peter J; Sandroni, Claudio; Drinhaus, Hendrik R; Böttiger, Bernd W; Cariou, Alain; Sunde, Kjetil; Dworschak, Martin; Taccone, Fabio Silvio; Deye, Nicolas; Friberg, Hans; Laureys, Steven; Ledoux, Didier; Oddo, Mauro; Legriel, Stéphane; Hantson, Philippe; Diehl, Jean-Luc; Laterre, Pierre-Francois

    2015-12-01

    Jean-Luc Diehl The French Intensive Care Society organized on 5th and 6th June 2014 its 4th "Paris International Conference in Intensive Care", whose principle is to bring together the best international experts on a hot topic in critical care medicine. The 2014 theme was "Breakthrough in cardiac arrest", with many high-quality updates on epidemiology, public health data, pre-hospital and in-ICU cares. The present review includes short summaries of the major presentations, classified into six main chapters: Epidemiology of CA Pre-hospital management Post-resuscitation management: targeted temperature management Post-resuscitation management: optimizing organ perfusion and metabolic parameters Neurological assessment of brain damages Public healthcare. PMID:26380990

  14. The 4th annual European League Against Rheumatism congress in Lisbon: a personal perspective

    PubMed Central

    Wollheim, Frank A

    2004-01-01

    The 4th annual European League Against Rheumatism congress, held in Lisbon, 18–21 June 2003, had a record turnout of more than 8600 delegates and the abstract submissions increased to 2600. A heat wave and a somewhat substandard venue hampered some of the activities, notably the poster sessions. The scientific program was comprehensive and of a high class, and it was organized in 10–12 parallel sessions. The European League Against Rheumatism standing committees are expanding their activities and stimulating European cooperation (e.g. by creating databases and guidelines, and by starting research programs). The standing committees presented several areas where European cooperative work is in progress. Advances in drug therapy were a prominent theme and were well presented. Commercialism remains a problem for this meeting as for other similar large meetings, where satellite symposia surround the scientific program of the congress and often duplicate this. PMID:14979931

  15. FAST DISPLACEMENT PROBABILITY PROFILE APPROXIMATION FROM HARDI USING 4TH-ORDER TENSORS.

    PubMed

    Barmpoutis, Angelos; Vemuri, Baba C; Forder, John R

    2008-05-14

    Cartesian tensor basis have been widely used to approximate spherical functions. In Medical Imaging, tensors of various orders have been used to model the diffusivity function in Diffusion-weighted MRI data sets. However, it is known that the peaks of the diffusivity do not correspond to orientations of the underlying fibers and hence the displacement probability profiles should be employed instead. In this paper, we present a novel representation of the probability profile by a 4(th) order tensor, which is a smooth spherical function that can approximate single-fibers as well as multiple-fiber structures. We also present a method for efficiently estimating the unknown tensor coefficients of the probability profile directly from a given high-angular resolution diffusion-weighted (HARDI) data set. The accuracy of our model is validated by experiments on synthetic and real HARDI datasets from a fixed rat spinal cord. PMID:20046536

  16. Report on the 4th International IUPAP Women in Physics Conference

    NASA Astrophysics Data System (ADS)

    Correa, Cynthia

    2011-10-01

    Stellenbosch, South Africa was the site of the 4^th International Union of Pure and Applied Physics (IUPAP) International Conference on Women in Physics, which took place on April 5^th-8^th. This conference brought together the diverse contributions of 250 female physicist attendees from nearly 60 countries worldwide to dissect the challenges faced by female physicists worldwide and to propose strategies to attract and retain more girls and women to the field. Having served as a member of the U.S. Delegation, I will discuss the resolutions reached and highlight the most important results of Global Survey of Physicists, where nearly 15,000 physicists shine light on how gender affects their lives and careers.

  17. Food-based Science Curriculum Increases 4(th) Graders Multidisciplinary Science Knowledge.

    PubMed

    Hovland, Jana A; Carraway-Stage, Virginia G; Cela, Artenida; Collins, Caitlin; Díaz, Sebastián R; Collins, Angelo; Duffrin, Melani W

    2013-10-01

    Health professionals and policymakers are asking educators to place more emphasis on food and nutrition education. Integrating these topics into science curricula using hand-on, food-based activities may strengthen students' understanding of science concepts. The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. Previous studies have shown that students experiencing the FoodMASTER curriculum were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. The purpose of this study was to: 1) assess 4(th) graders food-related multidisciplinary science knowledge, and 2) compare gains in food-related science knowledge after implementation of an integrated, food-based curriculum. During the 2009-2010 school year, FoodMASTER researchers implemented a hands-on, food-based intermediate curriculum in eighteen 4(th) grade classrooms in Ohio (n=9) and North Carolina (n=9). Sixteen classrooms in Ohio (n=8) and North Carolina (n=8), following their standard science curricula, served as comparison classrooms. Students completed a researcher-developed science knowledge exam, consisting of 13 multiple-choice questions administered pre- and post-test. Only subjects with pre- and post-test scores were entered into the sample (Intervention n=343; Control n=237). No significant differences were observed between groups at pre-test. At post-test, the intervention group scored (9.95±2.00) significantly higher (p=.000) than the control group (8.84±2.37) on a 13-point scale. These findings suggest the FoodMASTER intermediate curriculum is more effective than a standard science curriculum in increasing students' multidisciplinary science knowledge related to food. PMID:25152539

  18. Report of the 4th World Climate Research Programme International Conference on Reanalyses

    NASA Technical Reports Server (NTRS)

    Bosilovich, Michael G.; Rixen, Michel; van Oevelen, Peter; Asrar, Ghassem; Compo, Gilbert; Onogi, Kazutoshi; Simmons, Adrian; Trenberth, Kevin; Behringer, Dave; Bhuiyan, Tanvir Hossain; Capps, Shannon; Chaudhuri, Ayan; Chen, Junye; Chen, Linling; Colasacco-Thumm, Nicole; Escobar, Maria Gabriela; Ferguson, Craig R.; Ishibashi, Toshiyuki; Liberato, Margarida L. R.; Meng, Jesse; Molod, Andrea; Poli, Paul; Roundy, Joshua; Willett, Kate; Wollen, Jack

    2012-01-01

    The 4th WCRP International Conference on Reanalyses provided an opportunity for the international community to review and discuss the observational and modelling research, as well as process studies and uncertainties associated with reanalysis of the Earth System and its components. Characterizing the uncertainty and quality of reanalyses is a task that reaches far beyond the international community of producers, and into the interdisciplinary research community, especially those using reanalysis products in their research and applications. Reanalyses have progressed greatly even in the last 5 years, and newer ideas, projects and data are coming forward. While reanalysis has typically been carried out for the individual domains of atmosphere, ocean and land, it is now moving towards coupling using Earth system models. Observations are being reprocessed and they are providing improved quality for use in reanalysis. New applications are being investigated, and the need for climate reanalyses is as strong as ever. At the heart of it all, new investigators are exploring the possibilities for reanalysis, and developing new ideas in research and applications. Given the many centres creating reanalyses products (e.g. ocean, land and cryosphere research centres as well as NWP and atmospheric centers), and the development of new ideas (e.g. families of reanalyses), the total number of reanalyses is increasing greatly, with new and innovative diagnostics and output data. The need for reanalysis data is growing steadily, and likewise, the need for open discussion and comment on the data. The 4th Conference was convened to provide a forum for constructive discussion on the objectives, strengths and weaknesses of reanalyses, indicating potential development paths for the future.

  19. European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer.

    PubMed

    Friis, Søren; Kesminiene, Ausrele; Espina, Carolina; Auvinen, Anssi; Straif, Kurt; Schüz, Joachim

    2015-12-01

    The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events. PMID:26390952

  20. Food-based Science Curriculum Increases 4th Graders Multidisciplinary Science Knowledge

    PubMed Central

    Hovland, Jana A.; Carraway-Stage, Virginia G.; Cela, Artenida; Collins, Caitlin; Díaz, Sebastián R.; Collins, Angelo; Duffrin, Melani W.

    2013-01-01

    Health professionals and policymakers are asking educators to place more emphasis on food and nutrition education. Integrating these topics into science curricula using hand-on, food-based activities may strengthen students’ understanding of science concepts. The Food, Math, and Science Teaching Enhancement Resource (FoodMASTER) Initiative is a compilation of programs aimed at using food as a tool to teach mathematics and science. Previous studies have shown that students experiencing the FoodMASTER curriculum were very excited about the activities, became increasingly interested in the subject matter of food, and were able to conduct scientific observations. The purpose of this study was to: 1) assess 4th graders food-related multidisciplinary science knowledge, and 2) compare gains in food-related science knowledge after implementation of an integrated, food-based curriculum. During the 2009–2010 school year, FoodMASTER researchers implemented a hands-on, food-based intermediate curriculum in eighteen 4th grade classrooms in Ohio (n=9) and North Carolina (n=9). Sixteen classrooms in Ohio (n=8) and North Carolina (n=8), following their standard science curricula, served as comparison classrooms. Students completed a researcher-developed science knowledge exam, consisting of 13 multiple-choice questions administered pre- and post-test. Only subjects with pre- and post-test scores were entered into the sample (Intervention n=343; Control n=237). No significant differences were observed between groups at pre-test. At post-test, the intervention group scored (9.95±2.00) significantly higher (p=.000) than the control group (8.84±2.37) on a 13-point scale. These findings suggest the FoodMASTER intermediate curriculum is more effective than a standard science curriculum in increasing students’ multidisciplinary science knowledge related to food. PMID:25152539

  1. SOS Response Induces Persistence to Fluoroquinolones in Escherichia coli

    PubMed Central

    Dörr, Tobias; Lewis, Kim; Vulić, Marin

    2009-01-01

    Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo. PMID:20011100

  2. Structure-Activity Relationship of Fluoroquinolones Against K. pneumoniae

    NASA Astrophysics Data System (ADS)

    Li, Xiao-hong; Zhang, Rui-zhou; Cheng, Xin-lu; Yang, Xiang-dong

    2007-04-01

    The structure-activity relationship of fluoroquinolones, which show anti-K. pneumoniae activity, was studied by using principal component analysis (PCA) and hierarchical cluster analysis (HCA). The PCA results showed that the lowest unoccupied molecular orbital energy, energy difference between the highest occupied and the lowest unoccupied molecular orbital, dipole moment, net atomic charge on atom I, molecular polarizability, partition coefficient and molecular refractivity of these compounds are responsible for the separation between high-activity and low-activity groups. The HCA results were similar to those obtained with PCA. By using the chemometric results, four synthetic compounds were analyzed through PCA and HCA, and three of them are proposed as active molecules against K. pneumoniae which is consistent with the results of clinical experiments. The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with anti-K. pneumoniae activity.

  3. Fluoroquinolone Therapy in Staphylococcus aureus Infections: Where Do We Stand?

    PubMed Central

    Gade, Neeta D; Qazi, Mohiuddin S

    2013-01-01

    Aim: The study aimed to evaluate the utility of various commonly used fluoroquinolones against Staphylococcus aureus isolates. Materials and Methods: A total of 250 isolates of S. aureus were studied from different clinical specimens like blood, pus, wound swabs, sputum, ear swabs, and body fluids between November 2009 and December 2011. All the isolates were tested for their susceptibility to fluoroquinolones and other antimicrobial agents by Kirby-Bauer disc diffusion method using criteria of standard zone of inhibition. Methicillin-resistant S. aureus (MRSA) detection was done by cefoxitin disk diffusion method. The MRSA isolates were tested for minimum inhibitory concentration (MIC) to vancomycin by E-test strips. All the MRSA strains were sent to National Staphylococcal Phage-typing Centre, Maulana Azad Medical College, New Delhi for phage typing. Results: A total of 107 strains of S. aureus (42.8%) were detected as MRSA. Multidrug resistance was observed among the MRSA strains more commonly than among the MSSA stains. Among the fluoroquinolones, maximum resistance in MRSA was seen to ciprofloxacin (92.5%), followed by ofloxacin (80.4%). None of the S. aureus isolates showed resistance to vancomycin and linezolid. The MICs of vancomycin for the MRSA tested ranged from 0.5 to 2 μg/ml. Phage typing pattern of 107 MRSA isolates revealed that 37 (34.6%) MRSA isolates were nontypeable and 70 (65.4%) were typeable. Conclusion: Ciprofloxacin can no longer be used in empirical therapy against MRSA infections. Use of other members of fluoroquinolone should be limited only to those strains that show laboratory confirmation of their susceptibility. Vancomycin remains the drug of choice to treat MRSA infections. PMID:24701103

  4. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

    PubMed

    Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-05-01

    DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases. PMID:24497635

  5. Gatifloxacin, gemifloxacin, and moxifloxacin: the role of 3 newer fluoroquinolones.

    PubMed

    Saravolatz, Louis D; Leggett, James

    2003-11-01

    Gatifloxacin, gemifloxacin, and moxifloxacin are the newest fluoroquinolones and show excellent in vitro activity against a wide variety of respiratory tract pathogens, many gram-negative aerobic organisms, and Bacteroides fragilis. These agents may be administered as oral and/or intravenous formulations with excellent bioavailability. The pharmacodynamics of these 3 new fluoroquinolones is more favorable than that of levofloxacin or ciprofloxacin for Streptococcus pneumoniae. All 3 agents are approved for the treatment of acute exacerbation of chronic bronchitis and community-acquired pneumonia. In addition, gatifloxacin and moxifloxacin are approved for the treatment of sinusitis. The toxicity of these 3 agents appears to be similar to that of the other fluoroquinolones in terms of gastrointestinal and central nervous system disturbances. All 3 agents have a low risk of phototoxicity, but gemifloxacin is associated with an increased risk of skin rash that is not a photoreaction. These agents can be useful for treatment of bacterial respiratory tract infections in patients who are allergic to beta-lactams, but caution must be exercised to avoid the potential for selection of widespread resistance, which may occur with indiscriminate use. PMID:14557966

  6. PREFACE: 4th International Conference on Safe Production and Use of Nanomaterials (Nanosafe2014)

    NASA Astrophysics Data System (ADS)

    Tardif, F.; Damlencourt, J.-F.; Schuster, F.; Gaultier, V.

    2015-05-01

    This volume contains a collection of contributions presented at the 4th International Conference on Safe Production and Use of Nanomaterials (NANOSAFE 2014) held in Grenoble, France, from 18th to 20th November 2014. The issues of fast progress in the field of Nanosafety are up to the potential benefits that nanotechnology can bring to mankind. Making more efficient - more sustainable - easier to share mineral resources, increasing the yields of new energy technologies, enabling drugs that act selectively and locally are just few examples of the wide range of nanomaterial applications that currently benefit humanity. Nevertheless, the dynamic development of nanomaterials requires the adhesion from the general public who rightly demand major progresses in Nanosafety as a prerequisite. This is our exciting responsibility and challenge! Following the successful outcome of the three past international conferences on safe production and use of nanomaterials: Nanosafe 2008, 2010 and 2012, the organizing committee has the pleasure to welcoming you again to Minatec, Grenoble with some of the most famous specialists in the field. This year, two new topics have been added dealing with the "New Application of Nanomaterials" and "Nano-responsible Development" in addition to the usual issues addressed in previous Nanosafe conferences such as Expology, Detection and Characterization, Toxicology, Environmental Interactions, Nanomaterials Release, Life Cycle Analysis, Regulation and Standardization, Risk Management. The debates in 2012 proved highly successful so this formula has been kept in 2014 with 3 round tables: Nano-Responsible Development, Risks and Benefits for the Environment, Toxicology Progress. In this 4th edition, there were more than 330 registered participants from 28 different countries including 160 oral presentation covering the whole Nanosafety issues in 12 sessions, satellite workshops and round tables. This high number of participants makes this edition one of

  7. Continuum Kinetic Plasma Modeling Using a Conservative 4th-Order Method with AMR

    NASA Astrophysics Data System (ADS)

    Vogman, Genia; Colella, Phillip

    2012-10-01

    When the number of particles in a Debye sphere is large, a plasma can be accurately represented by a distribution function, which can be treated as a continuous incompressible fluid in phase space. In the most general case the evolution of such a distribution function is described by the 6D Boltzmann-Maxwell partial differential equation system. To address the challenges associated with solving a 6D hyperbolic governing equation, a simpler 3D Vlasov-Poisson system is considered. A 4th-order accurate Vlasov-Poisson model has been developed in one spatial and two velocity dimensions. The governing equation is cast in conservation law form and is solved with a finite volume representation. Adaptive mesh refinement (AMR) is used to allow for efficient use of computational resources while maintaining desired levels of resolution. The model employs a flux limiter to remedy non-physical effects such as numerical dispersion. The model is tested on the two-stream, beam-plasma, and Dory-Guest-Harris instabilities. All results are compared with linear theory.

  8. PREFACE: 4th National Conference on Processing and Characterization of Materials (NCPCM 2014)

    NASA Astrophysics Data System (ADS)

    2015-02-01

    This volume contains selected full length technical papers amongst forty oral presentations made in the 4th National Conference on Processing and Characterization of Materials (NCPCM 2014), NIT Rourkela, Rourkela, Odisha, India, December 5 - 6, 2014. The first conference of the NCPCM series was held at the same place in December 2011. Seeing the enthusiasm of the participants, it was decided to organize such conference in Rourkela every year. The basic idea was to establish a periodical national forum for multi-scale approaches in processing and characterization of materials in the eastern part of India. The conference NCPCM 2014 has successfully carried the tradition of previous conferences; more than fifty participants from twenty different organizations across India have registered. The conference was consisted of six technical sessions of about fifty contributory talks along with three keynote lectures. A metallography contest was also organized during the event. Out of these, thirty four best peer-reviewed contributions are published in this volume of IOP Conference Series: Materials Science and Engineering. We would like to thank all the contributors, members of the organizing committee, session chairs as well as colleagues and students who helped with the preparation of the conference and, particularly, with the preparation of this volume. We convey our heartiest gratitude to the sponsors and advertisers for their contribution.

  9. European Code against Cancer 4th Edition: 12 ways to reduce your cancer risk.

    PubMed

    Schüz, Joachim; Espina, Carolina; Villain, Patricia; Herrero, Rolando; Leon, Maria E; Minozzi, Silvia; Romieu, Isabelle; Segnan, Nereo; Wardle, Jane; Wiseman, Martin; Belardelli, Filippo; Bettcher, Douglas; Cavalli, Franco; Galea, Gauden; Lenoir, Gilbert; Martin-Moreno, Jose M; Nicula, Florian Alexandru; Olsen, Jørgen H; Patnick, Julietta; Primic-Zakelj, Maja; Puska, Pekka; van Leeuwen, Flora E; Wiestler, Otmar; Zatonski, Witold

    2015-12-01

    This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer. PMID:26164654

  10. 4th-International Symposium on Ultrafast Surface Science - Final Report

    SciTech Connect

    Hrvoje Petek

    2005-01-26

    The 4-th International Symposium on Ultrafast Surface Dynamics (UDS4) was held at the Telluride Summer Research Center on June 22-27, 2003. The International Organizing Committee consisting of Hrvoje Petek (USA), Xiaoyang Zhu (USA), Pedro Echenique (Spain) and Maki Kawai (Japan) brought together a total of 51 participants 16 of whom were from Europe, 10 from Japan, and 25 from the USA. The focus of the conference was on ultrafast electron or light induced processes at well-defined surfaces. Ultrafast surface dynamics concerns the transfer of charge and energy at solid surfaces on the femtosecond time scale. These processes govern rates of fundamental steps in surface reactions, interfacial electron transfer in molecular electronics, and relaxation in spin transport. Recent developments in femtosecond laser technology make it possible to measure by a variety of nonlinear optical techniques directly in the time domain the microscopic rates underlying these interfacial processes. Parallel progress in scanning probe microscopy makes it possible at a single molecular level to perform the vibrational and electronic spectroscopy measurements, to induce reactions with tunneling electrons, and to observe their outcome. There is no doubt that successful development in the field of ultrafast surface dynamics will contribute to many important disciplines.

  11. Multiwavelength Analysis of a Moving Type-IV Radio Burst on 4th March 2012

    NASA Astrophysics Data System (ADS)

    Veluchamy, V.; Chen, Y.; Feng, S.; Du, G.; Song, H.; Kong, X.

    2015-12-01

    We performed a multiwavelength analysis of a moving Type-IV radio burst on 4th march 2012. The Type-IV radio burst is observed between 10:39 - 11:00 UT in the frequency range of 300 - 20 MHz. From the radio heliographic observation, the radio source of the type-IV burst is traced and their sky plane speed is estimated as ~ 370 km/s. A plasmoid structure is ejected during the impulsive phase of the flare, at the same time of the type-IV burst and the structure is clearly observed at SDO/AIA 131 Å channel. From this, we find that the radio source moves with the plasmoid. The high brightness temperature profile in the range of 108 - 109 K and the moderate polarization between -50 - 30 % supports the plasma emission mechanism. Further the differential emission measure (DEM) analysis will be carried out and their results will be presented to provide more evidence of the emission mechanism.

  12. European Code against Cancer 4th Edition: Ultraviolet radiation and cancer.

    PubMed

    Greinert, Rüdiger; de Vries, Esther; Erdmann, Friederike; Espina, Carolina; Auvinen, Anssi; Kesminiene, Ausrele; Schüz, Joachim

    2015-12-01

    Ultraviolet radiation (UVR) is part of the electromagnetic spectrum emitted naturally from the sun or from artificial sources such as tanning devices. Acute skin reactions induced by UVR exposure are erythema (skin reddening), or sunburn, and the acquisition of a suntan triggered by UVR-induced DNA damage. UVR exposure is the main cause of skin cancer, including cutaneous malignant melanoma, basal-cell carcinoma, and squamous-cell carcinoma. Skin cancer is the most common cancer in fair-skinned populations, and its incidence has increased steeply over recent decades. According to estimates for 2012, about 100,000 new cases of cutaneous melanoma and about 22,000 deaths from it occurred in Europe. The main mechanisms by which UVR causes cancer are well understood. Exposure during childhood appears to be particularly harmful. Exposure to UVR is a risk factor modifiable by individuals' behaviour. Excessive exposure from natural sources can be avoided by seeking shade when the sun is strongest, by wearing appropriate clothing, and by appropriately applying sunscreens if direct sunlight is unavoidable. Exposure from artificial sources can be completely avoided by not using sunbeds. Beneficial effects of sun or UVR exposure, such as for vitamin D production, can be fully achieved while still avoiding too much sun exposure and the use of sunbeds. Taking all the scientific evidence together, the recommendation of the 4th edition of the European Code Against Cancer for ultraviolet radiation is: "Avoid too much sun, especially for children. Use sun protection. Do not use sunbeds." PMID:26096748

  13. 4th annual primary care ethics conference: ethics education and lifelong learning

    PubMed Central

    Spicer, John; McKenzie-Edwards, Emma; Misselbrook, David

    2014-01-01

    Primary care ethics is a field of study that has recently found new life, with calls to establish the relevance of ethical discussion in general practice, to gather a body of literature and to carve out an intellectual space for primary care on the academic landscape of bioethics. In this report, we reflect on the key strands of the 4th primary care ethics conference held at the Royal Society of Medicine, on a theme of ethics education and lifelong learning: first, to produce insights that have relevance for policy and practice; and second, to illustrate the idea that not only is ethics relevant in primary care, but primary care is relevant in medical ethics. Core themes included the advantages and disadvantages of prescriptive ways of doing ethics in education, ethical reflection and potential risk to professional status, the need to deal with societal change and to take on board the insights gained from empirical work, whether this is about different kinds of fatherhood, or work on the causes of moral distress in healthcare workers. PMID:25949739

  14. Cutting orientations for non-complex parts in 4th axis machining

    NASA Astrophysics Data System (ADS)

    Osman Zahid, M. N.; Case, K.; Watts, D. M.

    2016-02-01

    The application of Computer Numerically Controlled (CNC) machining for Rapid Manufacturing processes (CNC-RM) exploits the innate potential of 4th axis machining. The use of an indexer allows the workpiece to be rotated to various orientations which directly increased the region accessible to the cutting tool. However, in order to avoid thin webs and preserve tool life, cutting must be executed with a minimum of three orientations even for geometrically simple parts. Recent findings have suggested the separation of cutting orientations into roughing and finishing operations. Thus, the selection of orientations in finishing processes becomes more flexible and independent. This study was conducted to identify the effects of using a minimum of two cutting orientations in finishing operations for CNC-RM applications. This method is only applicable for non-complex parts where all the features can be machined from two directions. The results of the study illustrate the positive effects of minimizing the number of orientations. Despite improvement in machining operations, the complexity in defining the cutting orientations was also reduced.

  15. European Code against Cancer 4th Edition: Ionising and non-ionising radiation and cancer.

    PubMed

    McColl, Neil; Auvinen, Anssi; Kesminiene, Ausrele; Espina, Carolina; Erdmann, Friederike; de Vries, Esther; Greinert, Rüdiger; Harrison, John; Schüz, Joachim

    2015-12-01

    Ionising radiation can transfer sufficient energy to ionise molecules, and this can lead to chemical changes, including DNA damage in cells. Key evidence for the carcinogenicity of ionising radiation comes from: follow-up studies of the survivors of the atomic bombings in Japan; other epidemiological studies of groups that have been exposed to radiation from medical, occupational or environmental sources; experimental animal studies; and studies of cellular responses to radiation. Considering exposure to environmental ionising radiation, inhalation of naturally occurring radon is the major source of radiation in the population - in doses orders of magnitude higher than those from nuclear power production or nuclear fallout. Indoor exposure to radon and its decay products is an important cause of lung cancer; radon may cause approximately one in ten lung cancers in Europe. Exposures to radon in buildings can be reduced via a three-step process of identifying those with potentially elevated radon levels, measuring radon levels, and reducing exposure by installation of remediation systems. In the 4th Edition of the European Code against Cancer it is therefore recommended to: "Find out if you are exposed to radiation from naturally high radon levels in your home. Take action to reduce high radon levels". Non-ionising types of radiation (those with insufficient energy to ionise molecules) - including extremely low-frequency electric and magnetic fields as well as radiofrequency electromagnetic fields - are not an established cause of cancer and are therefore not addressed in the recommendations to reduce cancer risk. PMID:26126928

  16. Project ASTRO: Local Coalitions for Bringing Astronomers to 4th - 9th Grade Classrooms

    NASA Astrophysics Data System (ADS)

    Fraknoi, Andrew

    1998-05-01

    We report on Project ASTRO, an NSF and NASA funded program that now links professional and amateur astronomers with local 4th through 9th grade teachers in 10 sites around the country. Each site matches and trains about 20-25 astronomer-teacher partnerships per year, focusing on hands-on, age-appropriate activities, demonstrations of the scientific method, as well as family and community outreach. Over 10,000 copies of the project's 813-page UNIVERSE AT YOUR FINGERTIPS resource and activity notebook (published by the A.S.P) are now in use in educational institututions around the world. The project's HOW-TO-MANUAL is being used as a practical guide to establishing astronomer-teacher partnerships where no formal ASTRO site exists, and a 12-minute video explaining and demonstrating the project is also available. In each of the ten sites, a coalition of educational and scientific institutions is assisting the project with in-kind donations, publicity, personnel, training, materials, etc. We are conducting an experiment (at the behest of NSF) to see to what degree the sites can become self-supporting over time. (One site, in Salt Lake City, has already received full funding from a local foundation.) We will discuss the progress of the project and will have a variety of sample materials available, including our annotated catalog of national astronomy and space science education projects (see associated URL).

  17. A Teaching Model for Scaffolding 4th Grade Students' Scientific Explanation Writing

    NASA Astrophysics Data System (ADS)

    Yang, Hsiu-Ting; Wang, Kuo-Hua

    2014-08-01

    Improving students scientific explanations is one major goal of science education. Both writing activities and concept mapping are reported as effective strategies for enhancing student learning of science. The purpose of this study was to examine the effect of a teaching model, named the DCI model, which integrates a Descriptive explanation writing activity, Concept mapping, and an Interpretive explanation writing activity, is introduced in a 4th grade science class to see if it would improve students' scientific explanations and understanding. A quasi-experimental design, including a non-randomized comparison group and a pre- and post-test design, was adopted for this study. An experimental group of 25 students were taught using the DCI teaching model, while a comparison group received a traditional lecture teaching. A rubric and content analysis was used to assess students' scientific explanations. The independent sample t test was used to measure difference in conceptual understanding between the two groups, before and after instruction. Then, the paired t test analysis was used to understand the promotion of the DCI teaching model. The results showed that students in the experimental group performed better than students in the comparison group, both in scientific concept understanding and explanation. Suggestions for using concept mapping and writing activities (the DCI teaching model) in science classes are provided in this study.

  18. Need for Specific Sugar-Sweetened Beverage Lessons for 4th and 5th Graders

    PubMed Central

    Bea, Jennifer W.; Jacobs, Laurel; Waits, Juanita; Hartz, Vern; Martinez, Stephanie H.; Standfast, Rebecca D.; Farrell, Vanessa A.; Bawden, Margine; Whitmer, Evelyn; Misner, Scottie

    2015-01-01

    Objective Consumption of sugar-sweetened beverages (SSB) is linked to obesity. We hypothesized that school-based nutrition education would decrease SSB consumption. Design Self-selected interventional cohort with random selection for pre and post measurements Setting Arizona SNAP-Ed eligible schools Participants Randomly selected (9%) 4th and 5th grade classroom students Intervention The University of Arizona Nutrition Network (UANN) provided general nutrition education training and materials to teachers, to be delivered to their students. The UANN administered behavioral questionnaires to students in both Fall and Spring. Main Outcome Measure(s) Change in SSB consumption Analyses Descriptive statistics were computed for student demographics and beverage consumption on the day prior to testing. Paired t-tests evaluated change in classroom averages. Linear regression assessed potential correlates of SSB consumption. Results Fall mean SSB consumption was 1.1 (±0.2) times; mean milk and water intake were 1.6 (±0.2) and 5.2 (±0.7) times, respectively. Beverage consumption increased (3.2%) in springtime, with increased SSBs (14.4%) accounting for the majority (p=0.006). Change in SSB consumption was negatively associated with baseline SSB and water consumption, but positively associated with baseline milk fat (p≤0.05). Conclusions and Implications The results suggest the need for beverage specific education to encourage children to consume more healthful beverages in warmer weather. PMID:25239840

  19. Humoral immunity and CD4+ Th1 cells are both necessary for a fully protective immune response upon secondary infection with Brucella melitensis.

    PubMed

    Vitry, Marie-Alice; Hanot Mambres, Delphine; De Trez, Carl; Akira, Shizuo; Ryffel, Bernhard; Letesson, Jean-Jacques; Muraille, Eric

    2014-04-15

    Brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. Given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. Efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against Brucella. In this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response following priming by the injection of heat-killed or live Brucella melitensis 16M. Using a panel of gene-deficient mice, we demonstrated that during a secondary recall response, both the Brucella-specific humoral response and CD4+ Th1 cells must act together to confer protective immunity in the spleen to B. melitensis infection. Humoral protective immunity is induced by the inoculation of both heat-killed and live bacteria, and its development does not require T cells, MyD88/IL-12p35 signaling pathways, or an activation-induced deaminase-mediated isotype switch. In striking contrast, the presence of memory IFN-γ-producing CD4+ Th1 cells requires the administration of live bacteria and functional MyD88/IL-12p35 pathways. In summary, our work identifies several immune markers closely associated with protective immune memory and could help to define a rational strategy to obtain an effective human vaccine against brucellosis. PMID:24646742

  20. The Neumann system for the 4th-order eigenvalue problem and constraint flows of the coupled KdV-type equations

    NASA Astrophysics Data System (ADS)

    Zhao, Ye; Gu, Zhuquan; Liu, Yafeng

    2012-07-01

    In this paper, the Neumann system for the 4th-order eigenvalue problem Ly = (∂4+ q∂2+∂2 q+ ip∂+ i∂ p+ y = Λy) has been given. By means of the Neumann constraint condition, the perfect constraint set Γ and the relations between the potentials { q, p, r} and the eigenvector y are obtained. Then, based on the Euler-Lagrange function and Legendre transformations, a reasonable Jacobi-Ostrogradsky coordinate system has been found, which can be equal to the real Hamiltonian canonical coordinate system in R 8 N . Using Cao's method and Moser's constraint manifold, the Lax pairs of the evolution equation hierarchy with the 4th-order eigenvalue problems are nonlinearized. So a new finite-dimensional integrable Hamilton system on the constraint submanifold R 8 N-4 is generated. Moreover, the solutions of the evolution equations for the infinite-dimensional soliton systems are obtained by the involutive flow of the finite-dimensional completely integrable systems.

  1. Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis

    PubMed Central

    Williamson, Benjamin H.; Kerns, Robert J.; Berger, James M.

    2016-01-01

    Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-Å resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone–gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone–enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance. PMID:26792525

  2. Terbium-sensitized luminescence screening method for fluoroquinolones in beef serum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enrofloxacin is one of only two fluoroquinolone antibiotics approved for use in cattle in the U.S. Microbial screening methods commonly used for monitoring veterinary drug residues are not sensitive or selective for fluoroquinolones. In this work, a luminescence-based screening assay was developed...

  3. Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals

    PubMed Central

    Kang, Min-Hee; Chae, Min-Joo; Yoon, Jang-Won; Lee, So-Young; Yoo, Jong-Hyun; Park, Hee-Myung

    2014-01-01

    Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern. PMID:24982521

  4. Resistance to fluoroquinolones and methicillin in ophthalmic isolates of Staphylococcus pseudintermedius from companion animals.

    PubMed

    Kang, Min-Hee; Chae, Min-Joo; Yoon, Jang-Won; Lee, So-Young; Yoo, Jong-Hyun; Park, Hee-Myung

    2014-07-01

    Resistance to fluoroquinolones and methicillin was determined for 49 ophthalmic isolates of Staphylococcus pseudintermedius from dogs with and without ophthalmic disease. Resistance was observed for ciprofloxacin (40.8%), ofloxacin (38.8%), enrofloxacin (38.8%), levofloxacin (34.7%), and moxifloxacin (4.1%). Eighteen isolates, 16 of which were resistant to oxacillin, were mecA-positive. Nine of the 16 oxacillin-resistant mecA-positive S. pseudintermedius isolates were resistant to more than one fluoroquinolone and 2 isolates were resistant to 5 fluoroquinolones. The frequency of mecA gene occurrence and fluoroquinolone resistance was twice as high among S. pseudintermedius isolates derived from dogs with ophthalmic disease compared with isolates for dogs without ophthalmic disease. The high prevalence of methicillin and fluoroquinolone resistance in S. pseudintermedius from dogs with ophthalmic disease is a concern. PMID:24982521

  5. Growth and development in preterm infants receiving fluoroquinolones.

    PubMed

    Martell, M; de Ben, S; Weinberger, M; Beltrami, G

    1996-01-01

    Growth and development were followed in 7 preterm newborn infants who received fluoroquinolones in the neonatal period. Quinolones were used as a "life saving" therapy in cases of sepsis caused by bacterial agents sensitive only to these drugs. Two other groups of neonates matched for gender, birth weight and gestational age served as controls. Although the quinolone group had more severe illness, no statistically significant differences were observed in growth and development between the groups. No osteoarticular problems or joint deformities were observed in the quinolone group. Therefore, quinolones could be a therapeutic option for newborns with sepsis caused by multiply resistant organisms. PMID:8827579

  6. Improved fluoroquinolone detection in ELISA through engineering of a broad-specific single-chain variable fragment binding simultaneously to 20 fluoroquinolones.

    PubMed

    Wen, Kai; Nölke, Greta; Schillberg, Stefan; Wang, Zhanhui; Zhang, Suxia; Wu, Congming; Jiang, Haiyang; Meng, Hui; Shen, Jianzhong

    2012-07-01

    Fluoroquinolones (FQs) are a group of synthetic, broad-spectrum antibacterial agents. Due to its extensive use in animal industry and aquaculture, residues of these antibiotics and the emergence of bacteria resistant to FQs have become a major public health issue. To prepare a generic antibody capable of recognizing nearly all FQs, a single-chain variable fragment (scFv) was generated from the murine hybridoma cells C49H1 producing a FQ-specific monoclonal antibody. This scFv was characterized by indirect competitive enzyme-linked immunosorbent assay (ciELISA), and it showed identical binding properties to parental monoclonal antibody: it was capable of recognizing 17 of 20 targeted FQs below maximum residue limits, except for sarafloxacin (SAR), difloxacin (DIF), and trovafloxacin (TRO) which are highly concerned members in the FQs family. In order to broaden the specificity of this scFv to SAR and its analogues (DIF and TRO), protein homology modeling and antibody-ligands docking analysis were employed to identify the potential key amino acid residues involved in hapten antibody. A mutagenesis phage display library was generated by site directed mutagenesis randomizing five aminoacid residues in the third heavy-chain complementarity determining region. After one round of panning against biotinylated norfloxacin (NOR) and four rounds of panning against biotinylated SAR, scFv variants we screened showed up to 10-fold improved IC(50) against SAR, DIF, and TRO in ciELISA while the specificity against other FQs was fully retained. PMID:22549819

  7. The Ratio of 2nd to 4th Digit Length in Korean Alcohol-dependent Patients

    PubMed Central

    Han, Changwoo; Bae, Hwallip; Lee, Yu-Sang; Won, Sung-Doo; Kim, Dai Jin

    2016-01-01

    Objective The ratio of 2nd to 4th digit length (2D:4D) is a sexually dimorphic trait. Men have a relatively shorter second digit than fourth digit. This ratio is thought to be influenced by higher prenatal testosterone level or greater sensitivity to androgen. The purpose of this study is to investigate the relationship between alcohol dependence and 2D:4D in a Korean sample and whether 2D:4D can be a biologic marker in alcohol dependence. Methods In this study, we recruited 87 male patients with alcohol dependence from the alcohol center of one psychiatric hospital and 52 healthy male volunteers who were all employees in the same hospital as controls. We captured images of the right and left hands of patients and controls using a scanner and extracted data with a graphics program. We measured the 2D:4D of each hand and compared the alcohol dependence group with the control group. We analyzed these ratios using an independent-samples t-test. Results The mean 2D:4D of patients was 0.934 (right hand) and 0.942 (left hand), while the mean 2D:4D of controls was 0.956 (right hand) and 0.958 (left hand). Values for both hands were significantly lower for patients than controls (p<0.001, right hand; p=0.004, left hand). Conclusion Patients who are alcohol dependent have a significantly lower 2D:4D than controls, similar to the results of previous studies, which suggest that a higher prenatal testosterone level in the gonadal period is related to alcoholism. Furthermore, 2D:4D is a possible predictive marker of alcohol dependence. PMID:27121425

  8. PREFACE: 4th International Workshop on Statistical Physics and Mathematics for Complex Systems (SPMCS)

    NASA Astrophysics Data System (ADS)

    Wang, Alexandre; Abe, Sumiyoshi; Li, Wei

    2015-04-01

    This volume contains 24 contributed papers presented at the 4th International Workshop on Statistical Physics and Mathematics for Complex Systems (SPMCS) held during October 12-16, 2014 in Yichang, China. Each paper was peer-reviewed by at least one referee chosen from a distinguished international panel. The previous three workshops of this series were organized in 2008, 2010, and 2012, in Le Mans, France, Wuhan, China, and Kazan, Russia, respectively. The SPMCS international workshop series is destined mainly to communicate and exchange research results and information on the fundamental challenges and questions in the vanguard of statistical physics, thermodynamics and mathematics for complex systems. More specifically, the topics of interest touch, but are not limited to, the following: • Fundamental aspects in the application of statistical physics and thermodynamics to complex systems and their modeling • Finite size and non-extensive system • Fluctuation theorems and equalities, quantum thermodynamics • Variational principle for random dynamics • Fractal geometry, fractional mathematics More than 50 participants from 7 countries participated in SPMCS-2014. 35 oral contributions were presented at the workshop. We would like to take this opportunity to thank the members of the Scientific Program Committee, many of whom acted as reviewers of the papers and responded promptly. We would also like to thank the organizing committee, the session chairs, the technicians and the students for the smooth running of the whole workshop. Thanks also go to China Three Gorges University who provided generous support for the conference venue, as well as exquisite refreshments for the tea breaks. The workshop was also partially supported by Central China Normal University and the Programme of Introducing Talents of Discipline to Universities under grant NO. B08033. Special thanks are due to Ms Juy Zhu who has done excellent editing work with great effort.

  9. 4th International Conference on Energy and Environment 2013 (ICEE 2013)

    NASA Astrophysics Data System (ADS)

    Chakrabarty, Chandan Kumar; Shamsuddin, Abd Halim Bin; Ahmad, Ibrahim Bin; Desa, Mohamed Nor Bin Mohamed; Din, Norashidah Bte Md; Bte Mohd, Lariyah; Hamid, Nasri A.; See, Ong Hang; Hafiz Nagi, Farrukh; Yong, Lee Choon; Pasupuleti, Jagadeesh; Mei, Goh Su; Abdullah, Fairuz Bin; Satgunam, Meenaloshini

    2013-06-01

    The 4th International Conference on Energy & Environment 2013 (ICEE2013) was organized by the Universiti Tenaga Nasional (UNITEN) to provide a platform for creating and sharing ideas among engineers, researchers, scientists, industrialists and students in sustainable green energy and technologies. The theme 'Shaping a Sustainable Future through Advancement in Green Energy Technology' is in line with the University's vision to be a leading global energy university that shapes a sustainable future. The general scopes of the conference are renewable energy, smart grid, green technology, energy policies and economics, sustainable green energy and environment, sustainable education, international cooperation and innovation and technology transfer. Five international keynote speakers delivered their speeches in specialized areas of green energy technology and sustainability. In addition, the conference highlights several special parallel sessions by notable invited presenters in their niche areas, which are: Hybrid Energy Power Quality & Distributed Energy Smart Grid Nuclear Power & Technologies Geohazard Management Greener Environment for Sustainability Advances in Computational Fluid Dynamics The research papers presented in ICEE2013 are included in this volume of IOP Conference Series: Earth and Environmental Science (EES). EES is abstracted and indexed in SCOPUS, GeoBase, GeoRef, Compendex, Inspec, Chemical Abstracts Service, NASA Astrophysics Data System, and International Nuclear Information System (INIS). With the comprehensive programme outline, the organizing committee hopes that the ICEE2013 was a notable intellectual sharing session for the research and academic community in Malaysia and regionally. The organizing committee expresses gratitude to the ICEE2013 delegates for their great support and contributions to the event.

  10. PREFACE: 4th International Conference on: Preservation and Conservation Issues in Digital Printing and Digital Photography

    NASA Astrophysics Data System (ADS)

    Fricker, A.; Green, P.

    2010-04-01

    These conference proceedings contain the written papers of the contributions presented at the 4th International Conference on: Preservation and Conservation Issues in Digital Printing and Digital Photography. The conference was held at the Institute of Physics, London, UK on 27th-28th May 2010. Previous conferences in this series took place in 2000, 2003 and 2006. The aim of this conference series is to inform those responsible for the preservation of digitally printed materials about developments in digital photography and printing technologies. We aim to examine progress in research on inks and substrates and their significance for conservation and preservation issues and techniques. We also hope to develop links between related industries and the conservation/preservation world. Research areas explored in this conference include current developments and future trends in digital printing and photographic technologies; the effect of environmental, storage and salvage conditions on the durability of digital prints and photographs; image processing techniques; image permanence considerations and standards for fastness, permanence and the role of scanning and file formats. We would like to thank all participants for their contribution to the conference programme and these proceedings. Our thanks go to Ms C. Gu and Mr M. Sandy for chairing conference sessions. We are also grateful to Dawn Stewart and the Institute of Physics Conference Team for their invaluable support and assistance in arranging the conference and reception. Finally we would like to extend our thanks to the Society of Imaging Science and Technology (IS&T) for their sponsorship support. The Editors Acknowledgements Conference Organising Committee: Ms A Fricker and Dr. P Green (London College of Communication, University of the Arts London). Proceedings edited and compiled by Ms A Fricker and Dr. P Green.

  11. European Code against Cancer 4th Edition: Environment, occupation and cancer.

    PubMed

    Espina, Carolina; Straif, Kurt; Friis, Søren; Kogevinas, Manolis; Saracci, Rodolfo; Vainio, Harri; Schüz, Joachim

    2015-12-01

    People are exposed throughout life to a wide range of environmental and occupational pollutants from different sources at home, in the workplace or in the general environment - exposures that normally cannot be directly controlled by the individual. Several chemicals, metals, dusts, fibres, and occupations have been established to be causally associated with an increased risk of specific cancers, such as cancers of the lung, skin and urinary bladder, and mesothelioma. Significant amounts of air pollutants - mainly from road transport and industry - continue to be emitted in the European Union (EU); an increased occurrence of lung cancer has been attributed to air pollution even in areas below the EU limits for daily air pollution. Additionally, a wide range of pesticides as well as industrial and household chemicals may lead to widespread human exposure, mainly through food and water. For most environmental pollutants, the most effective measures are regulations and community actions aimed at reducing and eliminating the exposures. Thus, it is imperative to raise awareness about environmental and occupational carcinogens in order to motivate individuals to be proactive in advocating protection and supporting initiatives aimed at reducing pollution. Regulations are not homogeneous across EU countries, and protective measures in the workplace are not used consistently by all workers all the time; compliance with regulations needs to be continuously monitored and enforced. Therefore, the recommendation on Environment and Occupation of the 4th edition of the European Code against Cancer, focusing on what individuals can do to reduce their cancer risk, reads: "In the workplace, protect yourself against cancer-causing substances by following health and safety instructions." PMID:26164655

  12. Learning Natural Selection in 4th Grade with Multi-Agent-Based Computational Models

    NASA Astrophysics Data System (ADS)

    Dickes, Amanda Catherine; Sengupta, Pratim

    2013-06-01

    In this paper, we investigate how elementary school students develop multi-level explanations of population dynamics in a simple predator-prey ecosystem, through scaffolded interactions with a multi-agent-based computational model (MABM). The term "agent" in an MABM indicates individual computational objects or actors (e.g., cars), and these agents obey simple rules assigned or manipulated by the user (e.g., speeding up, slowing down, etc.). It is the interactions between these agents, based on the rules assigned by the user, that give rise to emergent, aggregate-level behavior (e.g., formation and movement of the traffic jam). Natural selection is such an emergent phenomenon, which has been shown to be challenging for novices (K16 students) to understand. Whereas prior research on learning evolutionary phenomena with MABMs has typically focused on high school students and beyond, we investigate how elementary students (4th graders) develop multi-level explanations of some introductory aspects of natural selection—species differentiation and population change—through scaffolded interactions with an MABM that simulates predator-prey dynamics in a simple birds-butterflies ecosystem. We conducted a semi-clinical interview based study with ten participants, in which we focused on the following: a) identifying the nature of learners' initial interpretations of salient events or elements of the represented phenomena, b) identifying the roles these interpretations play in the development of their multi-level explanations, and c) how attending to different levels of the relevant phenomena can make explicit different mechanisms to the learners. In addition, our analysis also shows that although there were differences between high- and low-performing students (in terms of being able to explain population-level behaviors) in the pre-test, these differences disappeared in the post-test.

  13. 77 FR 39422 - Eighth Coast Guard District Annual Safety Zones; Niceville July 4th Fireworks Show; Boggy Bayou...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Eighth Coast Guard District Annual Safety Zones; Niceville July 4th Fireworks Show; Boggy Bayou; Niceville, FL AGENCY: Coast Guard, DHS. ACTION: Notice of enforcement of regulation. SUMMARY: The Coast Guard will enforce a Safety Zone for the Niceville July...

  14. 75 FR 34374 - Safety Zone; Stockton Ports Baseball Club/City of Stockton, 4th of July Fireworks Display...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-17

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Stockton Ports Baseball Club/City of... Ports Baseball Club and the City of Stockton will sponsor the Stockton Ports Baseball Club/City of... Ports Baseball Club/City of Stockton 4th of July Fireworks Display, Stockton, CA. (a) Location....

  15. 78 FR 23869 - Safety Zone; Redwood City 4th of July Fireworks Show; Port of Redwood City, Redwood City, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ..., telephone 202-366-9826. SUPPLEMENTARY INFORMATION: Table of Acronyms DHS Department of Homeland Security FR... Federal Register (73 FR 3316). 4. Public Meeting We do not plan to hold public meetings on this proposed... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Redwood City 4th of July Fireworks...

  16. 78 FR 39998 - Safety Zone; Grand Haven 4th of July Fireworks; Grand River; Grand Haven, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-03

    ...-9826. SUPPLEMENTARY INFORMATION: Table of Acronyms DHS Department of Homeland Security FR Federal... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Grand Haven 4th of July Fireworks; Grand... a State, local, or tribal government, in the aggregate, or by the private sector of...

  17. Examining General and Specific Factors in the Dimensionality of Oral Language and Reading in 4th-10th Grades

    ERIC Educational Resources Information Center

    Foorman, Barbara R.; Koon, Sharon; Petscher, Yaacov; Mitchell, Alison; Truckenmiller, Adrea

    2015-01-01

    The objective of this study was to explore dimensions of oral language and reading and their influence on reading comprehension in a relatively understudied population--adolescent readers in 4th through 10th grades. The current study employed latent variable modeling of decoding fluency, vocabulary, syntax, and reading comprehension so as to…

  18. 78 FR 23866 - Safety Zone; Crescent City 4th of July Fireworks; Crescent City Harbor, Crescent City, CA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    .... SUPPLEMENTARY INFORMATION: Table of Acronyms DHS Department of Homeland Security FR Federal Register NPRM Notice... public dockets in the January 17, 2008, issue of the Federal Register (73 FR 3316). 4. Public Meeting We... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Crescent City 4th of July...

  19. 75 FR 35294 - Safety Zone; Marquette 4th of July Fireworks, Marquette Harbor, Lake Superior, Marquette, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ...The Coast Guard is establishing a temporary safety zone on Marquette Harbor, Lake Superior, Marquette, MI. This zone is intended to restrict vessels from a portion of Marquette Harbor during the Marquette 4th of July Fireworks display. This temporary safety zone is necessary to protect spectators and vessels from the hazards associated with a firework...

  20. 78 FR 39606 - Safety Zone; City of Menominee 4th of July Fireworks, Green Bay, Menominee, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ... Security FR Federal Register NPRM Notice of Proposed Rulemaking TFR Temporary Final Rule A. Regulatory... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; City of Menominee 4th of July Fireworks... that may result in the expenditure by a State, local, or tribal government, in the aggregate, or by...

  1. 76 FR 38015 - Safety Zones; July 4th Weekend Fireworks Displays Within the Captain of the Port St. Petersburg...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zones; July 4th Weekend Fireworks Displays Within... under Executive Order 13132, Federalism, if it has a substantial direct effect on State or local governments and would either preempt State law or impose a substantial direct cost of compliance on them....

  2. Teacher Implementation of Reform-Based Mathematics and Implications for Algebra Readiness: A Qualitative Study of 4th Grade Classrooms

    ERIC Educational Resources Information Center

    Sher, Stephen Korb

    2011-01-01

    This study looked at 4th grade classrooms to see "how" teachers implement NCTM standards-based or reform-based mathematics instruction and then analyzed it for the capacity to improve students' "algebra readiness." The qualitative study was based on classroom observations, teacher and administrator interviews, and teacher surveys. The study took…

  3. Proceedings of the International Conference on Educational Data Mining (EDM) (4th, Eindhoven, the Netherlands, July 6-8, 2011)

    ERIC Educational Resources Information Center

    Pechenizkiy, Mykola; Calders, Toon; Conati, Cristina; Ventura, Sebastian; Romero, Cristobal; Stamper, John

    2011-01-01

    The 4th International Conference on Educational Data Mining (EDM 2011) brings together researchers from computer science, education, psychology, psychometrics, and statistics to analyze large datasets to answer educational research questions. The conference, held in Eindhoven, The Netherlands, July 6-9, 2011, follows the three previous editions…

  4. Comparing Science Learning among 4th-, 5th-, and 6th-Grade Students: STS versus Textbook-Based Instruction

    ERIC Educational Resources Information Center

    Yager, Robert E.; Choi, AeRan; Yager, Stuart O.; Akcay, Hakan

    2009-01-01

    Fifteen 4th-, 5th-, and 6th-grade teachers from five school districts each taught two sections of science--one with a Science-Technology-Society (STS) approach and the other with a more traditional textbook approach in which basic science concepts were the major organizers. Local, current, and personally relevant issues provided the context and…

  5. The Influence of Neighborhood Density and Word Frequency on Phoneme Awareness in 2nd and 4th Grades

    ERIC Educational Resources Information Center

    Hogan, Tiffany P.; Bowles, Ryan P.; Catts, Hugh W.; Storkel, Holly L.

    2011-01-01

    Purpose: The purpose of this study was to test the hypothesis that two lexical characteristics--neighborhood density and word frequency--interact to influence performance on phoneme awareness tasks. Methods: Phoneme awareness was examined in a large, longitudinal dataset of 2nd and 4th grade children. Using linear logistic test model, the relation…

  6. Communicating Science to Impact Learning? A Phenomenological Inquiry into 4th and 5th Graders' Perceptions of Science Information Sources

    ERIC Educational Resources Information Center

    Gelmez Burakgazi, Sevinc; Yildirim, Ali; Weeth Feinstein, Noah

    2016-01-01

    Rooted in science education and science communication studies, this study examines 4th and 5th grade students' perceptions of science information sources (SIS) and their use in communicating science to students. It combines situated learning theory with uses and gratifications theory in a qualitative phenomenological analysis. Data were gathered…

  7. Impact of a Health and Media Literacy Curriculum on 4th-Grade Girls: A Qualitative Study

    ERIC Educational Resources Information Center

    Fuller, Heidi A.; Damico, Amy M.; Rodgers, Shannon

    2004-01-01

    Recent research indicates that young girls are preoccupied with their body size and that the media may be a contributing factor. This study aimed to discover the impact of an interdisciplinary media literacy intervention curriculum on 4th-grade girls in an urban elementary school. The authors developed and implemented a series of lessons that…

  8. Native American Students' Understanding of Geologic Time Scale: 4th-8th Grade Ojibwe Students' Understanding of Earth's Geologic History

    ERIC Educational Resources Information Center

    Nam, Younkyeong; Karahan, Engin; Roehrig, Gillian

    2016-01-01

    Geologic time scale is a very important concept for understanding long-term earth system events such as climate change. This study examines forty-three 4th-8th grade Native American--particularly Ojibwe tribe--students' understanding of relative ordering and absolute time of Earth's significant geological and biological events. This study also…

  9. 76 FR 72957 - 4th Annual Trauma Spectrum Conference: Bridging the Gap Between Research and Clinical Practice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... HUMAN SERVICES National Institutes of Health 4th Annual Trauma Spectrum Conference: Bridging the Gap Between Research and Clinical Practice of Psychological Health and Traumatic Brain Injury: Prevention... Psychological Health and Traumatic Brain Injury: Prevention, Diagnosis, Treatment and Recovery for the Iraq...

  10. Using Inquiry-Based Instruction to Teach Research Methods to 4th-Grade Students in an Urban Setting

    ERIC Educational Resources Information Center

    Hamm, Ellen M.; Cullen, Rebecca; Ciaravino, Melissa

    2013-01-01

    When a college professor who teaches research methods to graduate education students was approached by a local public urban elementary school to help them teach research skills to 4th-graders, it was thought that the process would be simple--take what we did at the college level and differentiate it for the childhood classroom. This article will…

  11. Characterization of HCV Specific CD4+Th17 Immunity in Recurrent Hepatitis C Induced Liver Allograft Fibrosis

    PubMed Central

    Basha, H. Ilias; Subramanian, Vijay; Seetharam, A.; Nath, D.S.; Ramachandran, S.; Anderson, C.D.; Shenoy, S.; Chapman, W.C.; Crippin, J.S.; Mohanakumar, T.

    2011-01-01

    Hepatitis C Virus (HCV) recurrence with accelerated fibrosis following orthotopic liver transplantation (OLT) is a universal phenomenon. To evaluate mechanisms contributing to HCV induced allograft fibrosis/cirrhosis, we investigated HCV specific CD4+Th17 cells and their induction in OLT recipients with recurrence utilizing 51 HCV+ OLT recipients, 15 healthy controls and 9 HCV- OLT recipients. Frequency of HCV specific CD4+ Tcells secreting IFN-γ, IL-17 and IL-10 was analyzed by ELISpot. Serum cytokines and chemokines were analyzed by LUMINEX. Recipients with recurrent HCV induced allograft inflammation and fibrosis/cirrhosis demonstrated a significant increase in frequency of HCV specific CD4+Th17 cells. Increased pro-inflammatory mediators (IL-17, IL-1β, IL-6, IL-8, MCP-1), decreased IFN-γ, and increased IL-4, IL-5 and IL-10 levels were identified. OLT recipients with allograft inflammation and fibrosis/cirrhosis demonstrated increased frequency of Foxp3+ regulatory T cells (Tregs) that inhibited HCV specific CD4+Th1 but not Th17 cells. This suggests that recurrent HCV infection in OLT recipients induces an inflammatory milieu characterized by increased IL-6, IL-1β and decreased IFN-γ which facilitates induction of HCV specific CD4+Th17 cells. These cells are resistant to suppression by Tregs and may mediate an inflammatory cascade leading to cirrhosis in OLT recipients following HCV recurrence. PMID:21446979

  12. 75 FR 38723 - Safety Zone; St. Ignace 4th of July Fireworks, East Moran Bay, Lake Huron, St. Ignace, MI

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-06

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; St. Ignace 4th of July Fireworks, East Moran Bay, Lake Huron, St. Ignace, MI AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone on East Moran Bay, Lake Huron, St....

  13. Biofilm and fluoroquinolone resistance of canine Escherichia coli uropathogenic isolates

    PubMed Central

    2014-01-01

    Background Escherichia coli is the most common uropathogen involved in urinary tract infection (UTI). Virulence of strains may differ, and may be enhanced by antimicrobial resistance and biofilm formation, resulting in increased morbidity and recurrent infections. The aim of this study was to evaluate the in vitro biofilm forming capacity of E. coli isolates from dogs with UTI, by using fluorescent in situ hybridization, and its association with virulence genes and antimicrobial resistance. Findings The proportion of biofilm-producing isolates significantly increased with the length of incubation time (P < 0.05). Biofilm production was significantly associated with fluoroquinolone resistance at all incubation time points and was independent of the media used (P < 0.05). Biofilm production was not associated with cnf1, hly, pap and sfa genes (P > 0.05), but was significantly associated with afa, aer and the β-lactamase genes (P < 0.05). Conclusions To the best of our knowledge, this is the first report showing significant association between biofilm production and fluoroquinolone resistance in E. coli isolates from dogs with UTI. Biofilm formation may contribute to UTI treatment failure in dogs, through the development of bacterial reservoirs inside bladder cells, allowing them to overcome host immune defenses and to establish recurrent infections. PMID:25099929

  14. PREFACE: 4th Global Conference on Materials Science and Engineering (CMSE 2015)

    NASA Astrophysics Data System (ADS)

    Ruda, H. E.; Khotsianovsky, A.

    2015-12-01

    IOP Conference Series: Materials Science and Engineering is publishing a volume of conference proceedings that contains a selection of papers presented at the 4th Global Conference on Materials Science and Engineering (CMSE 2015), which is an annual event that started in 2012. CMSE 2015, technically supported by the Institute of Applied Physics and Materials Engineering of University of Macau, organized by Wuhan Advance Materials Society, was successfully held at the University of Macau-new campus located on Hengqin Island from August 3rd-6th, 2015. It aims to bring together leading academic scientists, researchers and scholars to exchange and share their experience and research results on all aspects of Materials Science and Engineering, and to discuss the practical challenges encountered and the solutions adopted. Macau, one of the two special administrative regions of the People's Republic of China, where East meets West, turned out to be an ideal meeting place for domestic and overseas participants of this annual international conference. The conference program included keynote presentations, special sessions, oral and poster contributions. From several hundred submissions, 52 of the most promising and mainstream, IOP-relevant, contributions were included in this volume. The submissions present original ideas or results of general significance, supported by clear reasoning, compelling evidence and methods, theories and practices relevant to the research. The authors state clearly the problems and the significance of their research to theory and practice. Being a successful conference, this event gathered more than 200 qualified and high-level researchers and experts from over 40 countries, including 10 keynote speakers from 6 countries, which created a good platform for worldwide researchers and engineers to enjoy the academic communication. Taking advantage of this opportunity, we would like to thank all participants of this conference, and particularly the

  15. FOREWORD: 4th International Workshop on New Computational Methods for Inverse Problems (NCMIP2014)

    NASA Astrophysics Data System (ADS)

    2014-10-01

    This volume of Journal of Physics: Conference Series is dedicated to the scientific contributions presented during the 4th International Workshop on New Computational Methods for Inverse Problems, NCMIP 2014 (http://www.farman.ens-cachan.fr/NCMIP_2014.html). This workshop took place at Ecole Normale Supérieure de Cachan, on May 23, 2014. The prior editions of NCMIP also took place in Cachan, France, firstly within the scope of ValueTools Conference, in May 2011 (http://www.ncmip.org/2011/), and secondly at the initiative of Institut Farman, in May 2012 and May 2013, (http://www.farman.ens-cachan.fr/NCMIP_2012.html), (http://www.farman.ens-cachan.fr/NCMIP_2013.html). The New Computational Methods for Inverse Problems (NCMIP) Workshop focused on recent advances in the resolution of inverse problems. Indeed, inverse problems appear in numerous scientific areas such as geophysics, biological and medical imaging, material and structure characterization, electrical, mechanical and civil engineering, and finances. The resolution of inverse problems consists of estimating the parameters of the observed system or structure from data collected by an instrumental sensing or imaging device. Its success firstly requires the collection of relevant observation data. It also requires accurate models describing the physical interactions between the instrumental device and the observed system, as well as the intrinsic properties of the solution itself. Finally, it requires the design of robust, accurate and efficient inversion algorithms. Advanced sensor arrays and imaging devices provide high rate and high volume data; in this context, the efficient resolution of the inverse problem requires the joint development of new models and inversion methods, taking computational and implementation aspects into account. During this one-day workshop, researchers had the opportunity to bring to light and share new techniques and results in the field of inverse problems. The topics of the

  16. Analysis of Mechanism-Based Inhibition of CYP 3A4 by a Series of Fluoroquinolone Antibacterial Agents.

    PubMed

    Watanabe, Akiko; Takakusa, Hideo; Kimura, Takako; Inoue, Shin-Ichi; Kusuhara, Hiroyuki; Ando, Osamu

    2016-10-01

    A series of fluoroquinolone compounds (compounds 1-9), which contain a common quinolone scaffold, inactivated the metabolic activity of CYP3A. The purpose of this study was to identify mechanism-based inhibition (MBI) among these fluoroquinolone compounds by metabolite profiling to elucidate the association of the substructure and MBI potential. Reversibility of MBI after incubation with potassium ferricyanide differed among the test compounds. Representative quasi-irreversible inhibitors form a metabolite-intermediate (MI) complex with the heme of CYP3A4 according to absorption analysis. Metabolite profiling identified the cyclopropane ring-opened metabolites from representative irreversible inhibitors, suggesting irreversible binding of the carbon-centered radical species with CYP3A4. On the other hand, the oxime form of representative quasi-irreversible inhibitors was identified, suggesting generation of a nitroso intermediate that could form the MI complex. Metabolites of compound 10 with a methyl group at the carbon atom at the root of the amine moiety of compound 8 include the oxime form, but compound 10 did not show quasi-irreversible inhibition. The docking study with CYP3A4 suggested that a methyl moiety introduced at the carbon atom at the root of the primary amine disrupts formation of the MI complex between the heme and the nitroso intermediate because of steric hindrance. This study identified substructures of fluoroquinolone compounds associated with the MBI mechanism; introduction of substituted groups inducing steric hindrance with the heme of P450 can prevent formation of an MI complex. Our series of experiments may be broadly applicable to prevention of MBI at the drug discovery stage. PMID:27469000

  17. Mutant Prevention Concentrations for Single-Step Fluoroquinolone-Resistant Mutants of Wild-Type, Efflux-Positive, or ParC or GyrA Mutation-Containing Streptococcus pneumoniae Isolates

    PubMed Central

    Smith, Heather J.; Walters, Michael; Hisanaga, Tamiko; Zhanel, George G.; Hoban, Daryl J.

    2004-01-01

    Three fluoroquinolone-susceptible and five fluoroquinolone-resistant (two with ParC Ser79Phe mutations, one with a GyrA Ser81Phe mutation, and two that were efflux positive) Streptococcus pneumoniae isolates were exposed to one, two, four, eight, and sixteen times the MICs of ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin. Mutational frequencies were calculated at each multiple of the MIC for which growth was observed. Mutant prevention concentrations (MPCs) and the multiple of the MIC at the MPC (MPMIC) were evaluated. All resulting mutants were sequenced for quinolone resistance-determining region changes in GyrA and ParC and were evaluated for reserpine-sensitive efflux. The MPC order was generally ciprofloxacin > levofloxacin > gatifloxacin > moxifloxacin > gemifloxacin. The MPMIC order varied depending on the genetic constitution of the original isolates from which the mutants were generated. For those mutants created from fluoroquinolone-susceptible isolates (those that had wild-type ParC and GyrA and were efflux negative), the MPMIC order was ciprofloxacin = moxifloxacin > gemifloxacin > levofloxacin > gatifloxacin. The MPMICs of each fluoroquinolone for mutants created from isolates with a ParC mutation (with wild-type GyrA and efflux negative) were similar. A similar occurrence was observed with the mutants created from the efflux-positive isolates (with wild-type ParC and GyrA). The MPMIC order for the mutants created from the isolate with a GyrA mutation (with wild-type ParC and efflux negative) was ciprofloxacin = gemifloxacin > levofloxacin = moxifloxacin > gatifloxacin. Gatifloxacin, levofloxacin, and moxifloxacin may be intrinsically more able to prevent the development of resistance by fluoroquinolone-susceptible isolates, isolates that are efflux positive, or isolates that carry a GyrA mutation. However, once a ParC mutation is present, the MPC increases dramatically for all fluoroquinolones. PMID:15388458

  18. Computational Fluid Dynamics (CFD) study of the 4th generation prototype of a continuous flow Ventricular Assist Device (VAD).

    PubMed

    Song, Xinwei; Wood, Houston G; Olsen, Don

    2004-04-01

    The continuous flow ventricular assist device (VAD) is a miniature centrifugal pump, fully suspended by magnetic bearings, which is being developed for implantation in humans. The CF4 model is the first actual prototype of the final design product. The overall performances of blood flow in CF4 have been simulated using computational fluid dynamics (CFD) software: CFX, which is commercially available from ANSYS Inc. The flow regions modeled in CF4 include the inlet elbow, the five-blade impeller, the clearance gap below the impeller, and the exit volute. According to different needs from patients, a wide range of flow rates and revolutions per minute (RPM) have been studied. The flow rate-pressure curves are given. The streamlines in the flow field are drawn to detect stagnation points and vortices that could lead to thrombosis. The stress is calculated in the fluid field to estimate potential hemolysis. The stress is elevated to the decreased size of the blood flow paths through the smaller pump, but is still within the safe range. The thermal study on the pump, the blood and the surrounding tissue shows the temperature rise due to magnetoelectric heat sources and thermal dissipation is insignificant. CFD simulation proved valuable to demonstrate and to improve the performance of fluid flow in the design of a small size pump. PMID:15179847

  19. Fluoroquinolone Use in a Child Associated with Development of Osteochondritis Dissecans

    PubMed Central

    Jacobs, John; Shea, Kevin; Oxford, Julia; Carey, James

    2014-01-01

    SUMMARY Several etiological theories have been proposed for the development of osteochondritis dissecans. Cartilage toxicity after fluoroquinolone use has been well documented in vitro. We present a case report of a 10-year-old child who underwent a prolonged 18-month course of ciprofloxacin therapy for chronic urinary tract infections. This patient later developed an osteochondritis dissecans lesion of the medial femoral condyle. We hypothesize that the fluoroquinolone therapy disrupted normal endochondral ossification, resulting in development of osteochondritis dissecans. The etiology of osteochondritis dissecans is still unclear, and this case describes an association between fluoroquinolone use and osteochondritis dissecans development. PMID:25228675

  20. Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study

    PubMed Central

    Svanström, Henrik; Melbye, Mads; Pasternak, Björn; Hviid, Anders

    2016-01-01

    Objective To evaluate if oral fluoroquinolone use is associated with an increased risk of serious arrhythmia. Design Bi-national cohort study, linking register data on filled prescriptions, cases of serious arrhythmia, and patient characteristics. Setting Denmark, 1997-2011; Sweden, 2006-13. Participants The study cohort was derived from a source population of all Danish and Swedish adults, aged 40 to 79 years. 909 656 courses of fluoroquinolone use (ciprofloxacin 82.6%, norfloxacin 12.1%, ofloxacin 3.2%, moxifloxacin 1.2%, and other fluoroquinolones 0.9%) and 909 656 courses of penicillin V use, matched 1:1 on propensity score, were included. Main outcome measure The main outcome was risk of serious arrhythmia (fatal and non-fatal), comparing courses of fluoroquinolone use with courses of penicillin V use (an antibiotic with no pro-arrhythmic effect). The risk period of interest was current use, defined as days 0-7 of treatment. Subgroup analyses were conducted according to country, sex, age, underlying cardiovascular disease, concomitant use of drugs known to increase the risk of torsades de pointes, fluoroquinolone type, and levels of arrhythmia risk score. Results 144 cases of serious arrhythmia occurred during follow-up, 66 among current fluoroquinolone users (incidence rate 3.4 per 1000 person years) and 78 among current penicillin users (4.0 per 1000 person years); comparing oral fluoroquinolone treatment with penicillin V, the rate ratio was 0.85 (95% confidence interval 0.61 to 1.18). Compared with penicillin V, the absolute risk difference was −13 (95% confidence interval −35 to 16) cases of serious arrhythmia per 1 000 000 courses of fluoroquinolones. The risk of serious arrhythmia was not statistically significantly increased in any of the subgroups, including analyses by fluoroquinolone type. Conclusions Contrary to previous reports, oral fluoroquinolone treatment was not associated with an increased risk of serious arrhythmia in the

  1. Fluorescence characteristic study of the ternary complex of fluoroquinolone antibiotics and cobalt (II) with ATP

    NASA Astrophysics Data System (ADS)

    Wu, Shuqing; Zhang, Wujuan; Chen, Xingguo; Hu, Zhide; Hooper, Martin; Hooper, Beveley; Zhao, Zhengfeng

    2001-05-01

    The results from the measurement of the fluorescence spectra of fluoroquinolone antibiotics including ofloxacin (OF), norfloxacin (NOR) and ciprofloxacin (CIP) complexed with cobalt (II) and ATP give information concerning the antibiotics-nucleotide interactions. From the fluorescence spectral data, it appears that the fluoroquinolone antibiotic cannot directly complex with ATP but indirectly complex with cobalt (II), which is playing an intermediary role. The interaction of fluoroquinolone antibiotic with the nucleotide occurs mainly through the phosphate group. The conclusion offers a more complete mechanism, which is important for understanding the interaction of these drugs with DNA.

  2. Molecular mechanism of fluoroquinolones modulation on corneal fibroblast motility.

    PubMed

    Chen, Tsan-Chi; Tsai, Tzu-Yun; Chang, Shu-Wen

    2016-04-01

    Topical fluoroquinolones are widely used to prevent ocular infections after ophthalmic surgery. However, they have been shown to affect the corneal cell motility, whose mechanism remains indefinite. The purpose of this study was to investigate how fluoroquinolones affect corneal stromal cell motility. Human corneal fibroblasts (HCFs) were incubated in ciprofloxacin (CIP), levofloxacin (LEV), or moxifloxacin (MOX) at 0, 10, 50, and 100 μg/ml for up to 3 days. Effect of CIP, LEV, or MOX on HCF migration was monitored using migration assay. HCF viability was determined by WST-1 assay. Expression of focal adhesion kinase (FAK), paxillin (PXN), and their phosphorylated forms were analyzed by immunoblotting. Binding affinity between FAK and PXN was determined by co-immunoprecipitation. Our results revealed that CIP and MOX, but not LEV, noticeably retarded HCF migration. HCF proliferation was significantly reduced by CIP (38.2%), LEV (29.5%), and MOX (21.3%), respectively (p = 0.002). CIP and MOX suppressed the phosphorylation of PXN at tyrosines (10.2 ± 4.3%, p < 0.001; 11.7 ± 2.4%, p < 0.001, respectively), including tyrosine 118 (33.3 ± 5.2%, p < 0.001; 34.0 ± 4.4%, p < 0.001, respectively). CIP and MOX diminished the binding affinity between FAK and PXN (8.2 ± 1.8%, p < 0.001; 9.0 ± 4.5%, p < 0.001, respectively). Nevertheless, tyrosine dephosphorylation and FAK dissociation of PXN were not found in LEV-treated HCFs. None of these fluoroquinolones affect phosphorylation of FAK-Y397. We conclude that CIP and MOX, but not LEV, might delay corneal fibroblast migration via interfering with recruitment of PXN to focal adhesions and dephosphorylation of PXN at the tyrosines. PMID:26546726

  3. PREFACE: The 4th Symposium on the Mechanics of Slender Structures (MoSS2013)

    NASA Astrophysics Data System (ADS)

    Cao, Dengqing; Kaczmarczyk, Stefan

    2013-07-01

    This volume of Journal of Physics: Conference Series contains papers presented at the 4th Symposium on the Mechanics of Slender Structures (MoSS2013) run under the auspices of the Institute of Physics Applied Mechanics Group and hosted by Harbin Institute of Technology (China) from 7-9 January 2013. The conference has been organized in collaboration with the Technical Committee on Vibration and Sound of the American Society of Mechanical Engineers and follows a one day seminar on Ropes, Cables, Belts and Chains: Theory and Applications and the MoSS2006 symposium held at the University of Northampton (UK) in 2004 and 2006, respectively, the MoSS2008 symposium held at the University of Maryland Baltimore County (USA) in 2008 and the MoSS2010 symposium hosted by Mondragon University and held in San Sebastian (Spain) in 2010. The remit of the Symposium on the Mechanics of Slender Structures series involves a broad range of scientific areas. Applications of slender structures include terrestrial, marine and space systems. Moving elastic elements such as ropes, cables, belts and tethers are pivotal components of many engineering systems. Their lengths often vary when the system is in operation. The applications include vertical transportation installations and, more recently, space tether propulsion systems. Traction drive elevator installations employ ropes and belts of variable length as a means of suspension, and also for the compensation of tensile forces over the traction sheave. In cranes and mine hoists, cables and ropes are subject to length variation in order to carry payloads. Tethers experiencing extension and retraction are important components of offshore and marine installations, as well as being proposed for a variety of different space vehicle propulsion systems based on different applications of momentum exchange and electrodynamic interactions with planetary magnetic fields. Furthermore, cables and slender rods are used extensively in civil engineering

  4. PREFACE: 4th Workshop on Theory, Modelling and Computational Methods for Semiconductors (TMCSIV)

    NASA Astrophysics Data System (ADS)

    Tomić, Stanko; Probert, Matt; Migliorato, Max; Pal, Joydeep

    2014-06-01

    These conference proceedings contain the written papers of the contributions presented at the 4th International Conference on Theory, Modelling and Computational Methods for Semiconductor materials and nanostructures. The conference was held at the MediaCityUK, University of Salford, Manchester, UK on 22-24 January 2014. The previous conferences in this series took place in 2012 at the University of Leeds, in 2010 at St William's College, York and in 2008 at the University of Manchester, UK. The development of high-performance computer architectures is finally allowing the routine use of accurate methods for calculating the structural, thermodynamic, vibrational, optical and electronic properties of semiconductors and their hetero- and nano-structures. The scope of this conference embraces modelling, theory and the use of sophisticated computational tools in semiconductor science and technology, where there is substantial potential for time-saving in R&D. Theoretical approaches represented in this meeting included: Density Functional Theory, Semi-empirical Electronic Structure Methods, Multi-scale Approaches, Modelling of PV devices, Electron Transport, and Graphene. Topics included, but were not limited to: Optical Properties of Quantum Nanostructures including Colloids and Nanotubes, Plasmonics, Magnetic Semiconductors, Photonic Structures, and Electronic Devices. This workshop ran for three days, with the objective of bringing together UK and international leading experts in the theoretical modelling of Group IV, III-V and II-VI semiconductors, as well as students, postdocs and early-career researchers. The first day focused on providing an introduction and overview of this vast field, aimed particularly at students, with several lectures given by recognized experts in various theoretical approaches. The following two days showcased some of the best theoretical research carried out in the UK in this field, with several contributions also from representatives of

  5. Transfer of a CD4+ Th1 cell line to nude mice effects clearance of Rhodococcus equi from the lung.

    PubMed Central

    Kanaly, S T; Hines, S A; Palmer, G H

    1996-01-01

    Rhodococcus equi, and intracellular respiratory pathogen, causes sever e granulomatous pneumonia in humans with AIDS and in young horses. Pulmonary clearance of R. equi requires functional CD4+ T cells and gamma interferon (IFN-gamma) expression from bronchial lymph node cells. The purpose of this study was to investigate whether R. equi-specific CD4+ Th1 cells could effect clearance of R. equi from the lung. Adoptive transfer of a clearance of R. equi from the lungs. In contrast, mice transfused with a R. equi-specific CD4+ Th2 cell line expressed interleukin-4 but not IFN-gamma mRNA, failed to clear pulmonary infection, and developed granulomas in the lung. Control mice, which did not receive cells, did not produce IFN-gamma or interleukin-4 and developed small pulmonary granulomas. These results clearly show that a Th1 response is sufficient to effect pulmonary clearance of R. equi. PMID:8606068

  6. A selected review of abstracts from the 4th Quadrennial Meeting of the World Federation of Neuro-Oncology.

    PubMed

    Chamberlain, Marc C

    2014-03-01

    The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology (WFNO), San Francisco, CA, USA, 21-24 November 2013 The 4th Quadrennial Meeting of the World Federation of Neuro-Oncology (WFNO) was the largest neuro-oncology meeting that meets once every 4 years and brings together clinicians and scientists from all parts of the world whose focus is on new brain cancer clinical trials and research primarily pertaining to gliomas. The WFNO 2013 meeting included 1 education day, 2.5 days of presentation, 13 sunrise sessions, one town hall meeting, one mini-symposium, 130 oral presentations and 900 abstracts. This short meeting review highlights select adult clinical abstracts presented at WFNO 2013 that will only in part encompass the contents of a large and multifaceted meeting. PMID:25055016

  7. Safety profile of grepafloxacin compared with other fluoroquinolones.

    PubMed

    Stahlmann, R; Schwabe, R

    1997-12-01

    Preclinical investigations with grepafloxacin showed that its toxicological profile is similar to that of other fluoroquinolones. The photosensitizing effect of grepafloxacin was relatively weak and similar to that of ciprofloxacin. Grepafloxacin did not cause convulsions in mice when administered in conjunction with the non-steroidal anti-inflammatory drug fenbufen. Intravenous injection of grepafloxacin caused transient dysrhythmias in rabbits at a dosage of 10 mg/kg and ventricular tachycardia at 30 mg/kg iv. Joint cartilage lesions were found in juvenile dogs after iv treatment with 100 mg/kg daily. Plasma concentrations (19-24 mg/L) under these conditions were approximately ten times above a therapeutic level. Data derived from patients who had been treated with grepafloxacin in phase II and phase III multiple-dose studies (400 mg, n = 1069; 600 mg, n = 925) were available for an analysis of the patients' tolerance of the drug. The most common adverse events observed for the 400 mg and 600 mg treatments during these studies were gastrointestinal reactions, such as nausea (11% and 15%, respectively), vomiting (1% and 6%) and diarrhoea (3% and 4%). In both groups a considerable number of patients (9% and 17%) reported an unpleasant taste; this was less common in the pooled controls (1%) after treatment with drugs such as doxycycline, ciprofloxacin, amoxycillin or cefixime. Headache occurred in 4% (400 mg) and 5% (600 mg) and insomnia in 1% (400 mg) or 2% (600 mg) of the patients. Similar incidences were found for photosensitivity (1% and 2%, respectively) and for rash (1% and 2%) in the 400 mg and 600 mg groups. So far, tolerance of the new compound seems to be similar to that of other fluoroquinolones. However, incidences of nausea, vomiting and unpleasant taste were rather high during the first clinical trials, particularly after treatment with 600 mg daily. Further data are necessary for a sound evaluation of the tolerance of grepafloxacin. PMID:9484877

  8. Synthesis and biological evaluation of novel structural hybrids of benzofuroxan derivatives and fluoroquinolones.

    PubMed

    Chugunova, Elena; Akylbekov, Nurgali; Bulatova, Adelya; Gavrilov, Nikolai; Voloshina, Alexandra; Kulik, Natalia; Zobov, Vladimir; Dobrynin, Alexey; Syakaev, Victor; Burilov, Alexander

    2016-06-30

    A series of novel hybrids based on benzofuroxan derivatives and fluoroquinolones (4a-d-6a-d) have been synthesized. Unexpectedly, the reactions have resulted in salt products formation during the hydrolysis of benzofuroxans by water molecules being present in the solvent instead of usual substitution products. All the compounds have been screened for antimicrobial and toxic activities. All resulting compounds retain high activity characteristic for fluoroquinolones. Many of the salts based on benzofuroxans and fluoroquinolones have higher activity than starting fluoroquinolones against Bacillus cereus 8035. Among the screened compounds, the compound 4d has shown the best antibacterial activity against B. cereus 8035, 8 times higher than the original Lomefloxacin (MBC value 1.5 μg/mL). PMID:27061980

  9. Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

    PubMed Central

    Wacker, Evelin; Meister, Reinhard; Panse, Mary; Weber-Schoendorfer, Corinna; Oppermann, Marc; Schaefer, Christof

    2014-01-01

    Fluoroquinolones are avoided during pregnancy due to developmental toxicity in animals. The aim of this study was to assess the fetal risk after intrauterine fluoroquinolone exposure. We performed an observational study of a prospectively ascertained cohort of pregnant women exposed to a fluoroquinolone during the first trimester. Pregnancy outcomes were compared to those of a cohort exposed to neither fluoroquinolones nor teratogenic or fetotoxic drugs. The outcomes evaluated were major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance), spontaneous abortion, and elective termination of pregnancy. Pregnancy outcomes of 949 women with fluoroquinolone treatment were compared with those of 3,796 nonexposed controls. Neither the rate of major birth defects (2.4%; adjusted odds ratio [ORadj], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HRadj], 1.01; 95% CI, 0.8 to 1.3) was increased. However, there was a nonsignificant increase in major birth defects after exposure to moxifloxacin (6/93, 6.5%; crude odds ratio [ORcrude], 2.40; 95% CI, 0.8 to 5.6). Neither a critical exposure time window within the first trimester nor a specific pattern of birth defects was demonstrated for any of the fluoroquinolones. The rate of electively terminated pregnancies was increased among the fluoroquinolone-exposed women (HRadj, 1.32; 95% CI, 1.03 to 1.7). The gestational ages at delivery and birth weights did not differ between groups. Our study did not detect an increased risk of spontaneous abortion or major birth defects. These reassuring findings support the recommendation to allow fluoroquinolone use in early pregnancy in selected cases. After the use of moxifloxacin, a detailed fetal ultrasound examination should be considered. PMID:24841264

  10. Emergence of Fluoroquinolone-Resistant Haemophilus influenzae Strains among Elderly Patients but Not among Children▿

    PubMed Central

    Yokota, Shin-ichi; Ohkoshi, Yasuo; Sato, Kiyoshi; Fujii, Nobuhiro

    2008-01-01

    We screened 457 Haemophilus influenzae strains isolated in Japan during 2002 to 2004 and identified 12 fluoroquinolone-resistant strains (2.6%). The resistant strains were divided into three genotypes (eight, three, and one of each type). These were isolated from patients over 58 years of age. Several fluoroquinolone-resistant clones appeared to have invaded the population of elderly patients in a particular area, Sapporo city. PMID:17977993

  11. The use of fluoroquinolones in neutropenic patients--analysis of adverse effects.

    PubMed

    Rubinstein, E; Potgieter, P; Davey, P; Norrby, S R

    1994-07-01

    The fluoroquinolones have been extensively used in the neutropenic patient. When fluoroquinolone monotherapy was used as prophylaxis, frequently for extended periods, the rate of adverse effect of ciprofloxacin (6.9%) ofloxacin (11.6%) and norfloxacin (5.5%) were significantly lower than those of the comparator agents--co-trimoxazole, vancomycin and polymycin. Rash and gastrointestinal upset were the commonest adverse effects associated with the fluoroquinolones. When used as monotherapy for bacterial infections, often intravenously and in high dosages, the cumulative rate of adverse effects caused by the fluoroquinolones (12.6%) was similar to that caused by the comparator agents (10.3%), but significantly higher than reported for non-neutropenic patients (6.4%) and for prophylactic use. The main adverse events were also rashes (15.4%) and gastrointestinal upset (6.1%). When fluoroquinolones were used as therapy of bacterial infections in combination with other agents, the incidence of adverse events was 14.9%, which was similar to the comparator agents (13.5%). Adverse events were also similar except that nephrotoxicity was commonest with comparator combinations (4.0%). The data suggest that fluoroquinolone prophylaxis in neutropenic patients, even for prolonged periods, is safer than the comparator agents, but is associated with more frequent adverse events than in non-neutropenic patients. Fluoroquinolone therapy, frequently with high dosages, is associated with similar rate of adverse events as the comparator agents. When used in combination with the other antibiotics, fluoroquinolones are as safe as the comparator agents. PMID:7961217

  12. Molecular Characterization of Fluoroquinolone Resistance in Nontypeable Haemophilus influenzae Clinical Isolates

    PubMed Central

    Puig, Carmen; Tirado-Vélez, José Manuel; Calatayud, Laura; Tubau, Fe; Garmendia, Junkal; Ardanuy, Carmen; Marti, Sara

    2014-01-01

    Nontypeable Haemophilus influenzae (NTHi) is a common cause of respiratory infections in adults, who are frequently treated with fluoroquinolones. The aims of this study were to characterize the genotypes of fluoroquinolone-resistant NTHi isolates and their mechanisms of resistance. Among 7,267 H. influenzae isolates collected from adult patients from 2000 to 2013, 28 (0.39%) were ciprofloxacin resistant according to Clinical and Laboratory Standards Institute (CLSI) criteria. In addition, a nalidixic acid screening during 2010 to 2013 detected five (0.23%) isolates that were ciprofloxacin susceptible but nalidixic acid resistant. Sequencing of their quinolone resistance-determining regions and genotyping by pulse-field gel electrophoresis and multilocus sequence typing of the 25 ciprofloxacin-resistant isolates available and all 5 nalidixic acid-resistant isolates were performed. In the NTHi isolates studied, two mutations producing changes in two GyrA residues (Ser84, Asp88) and/or two ParC residues (Ser84, Glu88) were associated with increased fluoroquinolone MICs. Strains with one or two mutations (n = 15) had ciprofloxacin and levofloxacin MICs of 0.12 to 2 μg/ml, while those with three or more mutations (n = 15) had MICs of 4 to 16 μg/ml. Long persistence of fluoroquinolone-resistant strains was observed in three chronic obstructive pulmonary disease patients. High genetic diversity was observed among fluoroquinolone-resistant NTHi isolates. Although fluoroquinolones are commonly used to treat respiratory infections, the proportion of resistant NTHi isolates remains low. The nalidixic acid disk test is useful for detecting the first changes in GyrA or in GyrA plus ParC among fluoroquinolone-susceptible strains that are at a potential risk for the development of resistance under selective pressure by fluoroquinolone treatment. PMID:25385097

  13. Fluoroquinolone Resistance Does Not Impose a Cost on the Fitness of Clostridium difficile In Vitro

    PubMed Central

    Wasels, François; Kuehne, Sarah A.; Cartman, Stephen T.; Barbanti, Fabrizio; Minton, Nigel P.; Mastrantonio, Paola

    2014-01-01

    Point mutations conferring resistance to fluoroquinolones were introduced in the gyr genes of the reference strain Clostridium difficile 630. Only mutants with the substitution Thr-82→Ile in GyrA, which characterizes the hypervirulent epidemic clone III/027/NAP1, were resistant to all fluoroquinolones tested. The absence of a fitness cost in vitro for the most frequent mutations detected in resistant clinical isolates suggests that resistance will be maintained even in the absence of antibiotic pressure. PMID:25534738

  14. Colonization with Extraintestinal Pathogenic Escherichia coli among Nursing Home Residents and Its Relationship to Fluoroquinolone Resistance

    PubMed Central

    Maslow, Joel N.; Lautenbach, Ebbing; Glaze, Thomas; Bilker, Warren; Johnson, James R.

    2004-01-01

    In a cross-sectional fecal prevalence survey involving 49 residents of a Veterans Affairs nursing home, 59% of subjects were colonized with extraintestinal pathogenic Escherichia coli (ExPEC), 22% were colonized with adhesin-positive E. coli, and 51% were colonized with fluoroquinolone-resistant E. coli. Among 80 unique isolates, adhesins correlated negatively and aerobactin correlated positively with fluoroquinolone resistance. PMID:15328142

  15. Study on three-dimensional fluorescent spectral characteristics of fluoroquinolones in varying media

    NASA Astrophysics Data System (ADS)

    Liu, Zhihong; Huang, Zuyun; Cai, Ruxiu

    2000-08-01

    Behaviors of fluoroquinolones in varying media were observed by employing their intrinsic fluorescence. Spectral characteristics in reversed micelles (Aerosol OT/ n-octane) were compared with those in aqueous solution and micelles (sodium dodecyl sulfonate). Those differences in interactions between fluoroquinolones and the various media were clearly illustrated by three-dimensional fluorescent spectra. The influences of other environmental factors on spectral characteristics (pH, SDS concentration, etc.) were also investigated.

  16. Something going on in Milan: a review of the 4th International PhD Student Cancer Conference.

    PubMed

    Segré, C

    2010-01-01

    The 4th International PhD Student Cancer Conference was held at the IFOM-IEO-Campus in Milan from 19-21 May 2010 http://www.semm.it/events_researchPast.phpThe Conference covered many topics related to cancer, from basic biology to clinical aspects of the disease. All attendees presented their research, by either giving a talk or presenting a poster. This conference is an opportunity to introduce PhD students to top cancer research institutes across Europe.THE CORE PARTICIPANTING INSTITUTES INCLUDED: European School of Molecular Medicine (SEMM)-IFOM-IEO Campus, MilanBeatson Institute for Cancer Research (BICR), GlasgowCambridge Research Institute (CRI), Cambridge, UKMRC Gray Institute of Radiation Biology (GIROB), OxfordLondon Research Institute (LRI), LondonPaterson Institute for Cancer Research (PICR), ManchesterThe Netherlands Cancer Institute (NKI), Amsterdam'You organizers have crushed all my prejudices towards Italians. Congratulations, I enjoyed the conference immensely!' Even if it might have sounded like rudeness for sure this was supposed to be a genuine compliment (at least, that's how we took it), also considering that it was told by a guy who himself was the fusion of two usually antithetical concepts: fashion style and English nationality.The year 2010 has marked an important event for Italian research in the international scientific panorama: the European School of Molecular Medicine (SEMM) had the honour to host the 4th International PhD Student Cancer Conference, which was held from 19-21 May 2010 at the IFOM-IEO-Campus (http://www.semm.it/events_researchPast.php) in Milan.The conference was attended by more than one hundred students, coming from a selection of cutting edge European institutes devoted to cancer research. The rationale behind it is the promotion of cooperation among young scientists across Europe to debate about science and to exchange ideas and experiences. But that is not all, it is also designed for PhD students to get in touch

  17. Quantitative comparison of the convulsive activity of combinations of twelve fluoroquinolones with five nonsteroidal antiinflammatory agents.

    PubMed

    Kim, Jahye; Ohtani, Hisakazu; Tsujimoto, Masayuki; Sawada, Yasufumi

    2009-01-01

    Concomitant administration of certain fluoroquinolone antimicrobials and nonsteroidal antiinflammatory agents (NSAIDs) induces serious convulsion in humans. There are differences in convulsive activity among fluoroquinolones and in the potentiation of fluoroquinolone-induced convulsion among NSAIDs, but a comprehensive, quantitative comparison has not been carried out. This study evaluates the inhibitory effects of twelve fluoroquinolones (ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin, pazufloxacin, prulifloxacin, sparfloxacin, and tosufloxacin) alone or in the presence of an NSAID (4-biphenylacetic acid, diclofenac sodium, loxoprofen, lornoxicam or zaltoprofen) on the GABA(A) receptor binding of [(3)H]muscimol in an in vitro study using mice synaptic plasma membrane. The rank order of inhibitory effects of the fluoroquinolones was prulifloxacin asymptotically equal to norfloxacin > ciprofloxacin > or = enoxacin > gatifloxacin > or = ofloxacin asymptotically equal to tosufloxacin asymptotically equal to lomefloxacin > levofloxacin > or = sparfloxacin > or = pazufloxacin asymptotically equal to fleroxacin. 4-Biphenylacetic acid most potently enhanced the inhibitory effects of the fluoroquinolones, while zaltoprofen, loxoprofen, lornoxicam and diclofenac had essentially no effect. The clinical risk of convulsion for each combination was estimated using a pharmacodynamic model based on receptor occupancy using the in vitro data set obtained and pharmacokinetic parameters in humans collected from the literature. The combinations of 4-biphenylacetic acid with prulifloxacin and enoxacin were concluded to be the most hazardous. PMID:19430173

  18. Caldecott 4th bore tunnel project: influence of ground water flows and inflows triggered by tectonic fault zones?

    NASA Astrophysics Data System (ADS)

    Neuhuber, G.; G. Neuhuber1, W. Klary1, A. Nitschke1, B. Thapa2, Chris Risden3, T. Crampton4, D. Zerga5

    2011-12-01

    The 4th Bore is a highway tunnel on California State Route 24 currently under construction. The 4th Bore is undertaken by the California State Department of Transportation (CALTRANS) and the Contra Costa County Transportation Commission (CCTC) to alleviate traffic congestion on SR24 connecting the cities of Oakland and Orinda in the San Francisco East Bay Area. The cost for the 4th Bore is estimated at $ 390.8 Mill. The 3,249 ft long 4th Bore tunnel will have excavated dimensions of approximately 40 ft height and 49 ft width. A total of 7 cross passages will run between the 3rd and the new 4th bore. Geology and Hydrogeology: The project is located in the Oakland Berkeley Hills of the SF Bay Area. The Caldecott Tunnels lie within the easterly assemblage of the Hayward fault zone province which consists of a sequence of sedimentary and volcanic rocks that accumulated in the interval between about 16 and 8.4 Ma (Miocene). The basal rocks of these Tertiary deposits consist of deep marine basin sediments of the Monterey Group. These rocks are overlain uncomfortably by an interbedded sequence of terrestrial sediments (Orinda Formation) and volcanic rocks (Moraga Formation). The Tertiary rocks have been folded into large amplitude, NW trending folds that are cut by N trending strike and slip faults. The SF Bay Region, which is crossed by 4 major faults (San Gregorio, San Andreas, Hayward, and Calaveras), is considered one of the more seismically active regions of the world. The active Hayward fault lies 0.9mi to the west of the Caldecott Tunnels and is the closest major fault to the project area. The tunnel is at the moment under top heading construction: West Portal (360ft) and East Portal (1,968.5ft). While major faults typically influence groundwater flow, characterization of such influences is extremely difficult because of the heterogeneity of the hydraulic systems and the different lithological parameters and influences. Four major inactive fault zones striking

  19. Fluoroquinolones and Tendinopathy: A Guide for Athletes and Sports Clinicians and a Systematic Review of the Literature

    PubMed Central

    Lewis, Trevor; Cook, Jill

    2014-01-01

    Context: Fluoroquinolone antibiotics have been used for several decades and are effective antimicrobials. Despite their usefulness as antibiotics, a growing body of evidence has accumulated in the peer-reviewed literature that shows fluoroquinolones can cause pathologic lesions in tendon tissue (tendinopathy). These adverse effects can occur within hours of commencing treatment and months after discontinuing the use of these drugs. In some cases, fluoroquinolone usage can lead to complete rupture of the tendon and substantial subsequent disability. Objective: To discuss the cause, pharmacology, symptoms, and epidemiology of fluoroquinolone-associated tendinopathy and to discuss the clinical implications with respect to athletes and their subsequent physiotherapy. Data Sources: We searched MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), Allied and Complementary Medicine Database (AMED), and SPORTDiscus databases for available reports of fluoroquinolone-related tendinopathy (tendinitis, tendon pain, or rupture) published from 1966 to 2012. Search terms were fluoroquinolones or quinolones and tendinopathy, adverse effects, and tendon rupture. Included studies were written in or translated into English. Non—English–language and non-English translations of abstracts from reports were not included (n = 1). Study Selection: Eligible studies were any available reports of fluoroquinolone-related tendinopathy (tendinitis, tendon pain, or rupture). Both animal and human histologic studies were included. Any papers not focusing on the tendon-related side effects of fluoroquinolones were excluded (n = 71). Data Extraction: Data collected included any cases of fluoroquinolone-related tendinopathy, the particular tendon affected, type of fluoroquinolone, dosage, and concomitant risk factors. Any data outlining the adverse histologic effects of fluoroquinolones also were collected. Data Synthesis: A total of 175 papers, including 89 case reports and 8

  20. Induction of prophages by fluoroquinolones in Streptococcus pneumoniae: implications for emergence of resistance in genetically-related clones.

    PubMed

    López, Elena; Domenech, Arnau; Ferrándiz, María-José; Frias, Maria João; Ardanuy, Carmen; Ramirez, Mario; García, Ernesto; Liñares, Josefina; de la Campa, Adela G

    2014-01-01

    Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an important role. Prophage induction by fluoroquinolones was confirmed in 4 clinical isolates by using Southern blot hybridization. Clinical isolates (105 fluoroquinolone-resistant and 160 fluoroquinolone-susceptible) were tested for lysogeny by using a PCR assay and functional prophage carriage was studied by mitomycin C induction. Fluoroquinolone-resistant strains harbored fewer inducible prophages (17/43) than fluoroquinolone-susceptible strains (49/70) (P = 0.0018). In addition, isolates of clones associated with fluoroquinolone resistance [CC156 (3/25); CC63 (2/20), and CC81 (1/19)], had lower frequency of functional prophages than isolates of clones with low incidence of fluoroquinolone resistance [CC30 (4/21), CC230 (5/20), CC62 (9/21), and CC180 (21/30)]. Likewise, persistent strains from patients with chronic respiratory diseases subjected to fluoroquinolone treatment had a low frequency of inducible prophages (1/11). Development of ciprofloxacin resistance was tested with two isogenic strains, one lysogenic and the other non-lysogenic: emergence of resistance was only observed in the non-lysogenic strain. These results are compatible with the lysis of lysogenic isolates receiving fluoroquinolones before the development of resistance and explain the inverse relation between presence of inducible prophages and fluoroquinolone-resistance. PMID:24718595

  1. Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple sclerosis lesions

    PubMed Central

    Skundric, Dusanka S; Cai, Juan; Cruikshank, William W; Gveric, Djordje

    2006-01-01

    Background Multiple sclerosis (MS) is a central nervous system-specific autoimmune, demyelinating and neurodegenerative disease. Infiltration of lesions by autoaggressive, myelin-specific CD4+Th1 cells correlates with clinical manifestations of disease. The cytokine IL-16 is a CD4+ T cell-specific chemoattractant that is biased towards CD4+ Th1 cells. IL-16 precursor is constitutively expressed in lymphocytes and during CD4+ T cell activation; active caspase-3 cleaves and releases C-terminal bioactive IL-16. Previously, we used an animal model of MS to demonstrate an important role for IL-16 in regulation of autoimmune inflammation and subsequent axonal damage. This role of IL-16 in MS is largely unexplored. Here we examine the regulation of IL-16 in relation to CD4+ Th1 infiltration and inflammation-related changes of axonal cytoskeleton in MS lesions. Methods We measured relative levels of IL-16, active caspase-3, T-bet, Stat-1 (Tyr 701), and phosphorylated NF(M+H), in brain and spinal cord lesions from MS autopsies, using western blot analysis. We examined samples from 39 MS cases, which included acute, subacute and chronic lesions, as well as adjacent, normal-appearing white and grey matter. All samples were taken from patients with relapsing remitting clinical disease. We employed two-color immunostaining and confocal microscopy to identify phenotypes of IL-16-containing cells in frozen tissue sections from MS lesions. Results We found markedly increased levels of pro- and secreted IL-16 (80 kD and 22 kD, respectively) in MS lesions compared to controls. Levels of IL-16 peaked in acute, diminished in subacute, and were elevated again in chronic active lesions. Compared to lesions, lower but still appreciable IL-6 levels were measured in normal-appearing white matter adjacent to active lesions. Levels of IL-16 corresponded to increases in active-caspase-3, T-bet and phosphorylated Stat-1. In MS lesions, we readily observed IL-16 immunoreactivity confined to

  2. 4th Quarter Transportation Report FY 2014: Radioactive Waste Shipments to and from the Nevada National Security Site (NNSS)

    SciTech Connect

    Gregory, Louis

    2014-12-02

    This report satisfies the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Field Office (NNSA/NFO) commitment to prepare a quarterly summary report of radioactive waste shipments to and from the Nevada National Security Site (NNSS) Radioactive Waste Management Complex (RWMC) at Area 5. There were no shipments sent for offsite treatment and returned to the NNSS this quarter. There was one shipment of two drums sent for offsite treatment and disposal. This report summarizes the 4th quarter of Fiscal Year (FY) 2014 low-level radioactive waste (LLW) and mixed low-level radioactive waste (MLLW) shipments. This report also includes annual summaries for FY 2014.

  3. Fluoroquinolone Resistance Mechanisms of Shigella flexneri Isolated in Bangladesh

    PubMed Central

    Azmi, Ishrat J.; Khajanchi, Bijay K.; Akter, Fatema; Hasan, Trisheeta N.; Shahnaij, Mohammad; Akter, Mahmuda; Banik, Atanu; Sultana, Halima; Hossain, Mohammad A.; Ahmed, Mohammad K.; Faruque, Shah M.; Talukder, Kaisar A.

    2014-01-01

    Objective To investigate the prevalence and mechanisms of fluoroquinolone resistance in Shigella species isolated in Bangladesh and to compare with similar strains isolated in China. Methods A total of 3789 Shigella isolates collected from Clinical Microbiology Laboratory of icddr,b, during 2004–2010 were analyzed for antibiotic susceptibility. Analysis of plasmids, plasmid-mediated quinolone-resistance genes, PFGE, and sequencing of genes of the quinolone-resistance-determining regions (QRDR) were conducted in representative strains isolated in Bangladesh and compared with strains isolated in Zhengding, China. In addition, the role of efflux-pump was studied by using the efflux-pump inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP). Results Resistance to ciprofloxacin in Shigella species increased from 0% in 2004 to 44% in 2010 and S. flexneri was the predominant species. Of Shigella spp, ciprofloxacin resistant (CipR) strains were mostly found among S. flexneri (8.3%), followed by S. sonnei (1.5%). Within S. flexneri (n = 2181), 14.5% were resistance to ciprofloxacin of which serotype 2a was predominant (96%). MIC of ciprofloxacin, norfloxacin, and ofloxacin were 6–32 mg/L, 8–32 mg/L, and 8–24 mg/L, respectively in S. flexneri 2a isolates. Sequencing of QRDR genes of resistant isolates showed double mutations in gyrA gene (Ser83Leu, Asp87Asn/Gly) and single mutation in parC gene (Ser80Ile). A difference in amino acid substitution at position 87 was found between strains isolated in Bangladesh (Asp87Asn) and China (Asp87Gly) except for one. A novel mutation at position 211 (His→Tyr) in gyrA gene was detected only in the Bangladeshi strains. Susceptibility to ciprofloxacin was increased by the presence of CCCP indicating the involvement of energy dependent active efflux pumps. A single PFGE type was found in isolates from Bangladesh and China suggesting their genetic relatedness. Conclusions Emergence of fluoroquinolone resistance in Shigella

  4. Proceedings of the 4th Conference on Aerospace Materials, Processes, and Environmental Technology

    NASA Technical Reports Server (NTRS)

    Griffin, D. E. (Editor); Stanley, D. C. (Editor)

    2001-01-01

    The next millennium challenges us to produce innovative materials, processes, manufacturing, and environmental technologies that meet low-cost aerospace transportation needs while maintaining US leadership. The pursuit of advanced aerospace materials, manufacturing processes, and environmental technologies supports the development of safer, operational, next-generation, reusable, and expendable aeronautical and space vehicle systems. The Aerospace Materials, Processes, and Environmental Technology Conference (AMPET) provided a forum for manufacturing, environmental, materials, and processes engineers, scientists, and managers to describe, review, and critically assess advances in these key technology areas.

  5. Collaborative interactions between type 2 innate lymphoid cells and antigen-specific CD4+ Th2 cells exacerbate murine allergic airway diseases with prominent eosinophilia.

    PubMed

    Liu, Bo; Lee, Jee-Boong; Chen, Chun-Yu; Hershey, Gurjit K Khurana; Wang, Yui-Hsi

    2015-04-15

    Type-2 innate lymphoid cells (ILC2s) and the acquired CD4(+) Th2 and Th17 cells contribute to the pathogenesis of experimental asthma; however, their roles in Ag-driven exacerbation of chronic murine allergic airway diseases remain elusive. In this study, we report that repeated intranasal rechallenges with only OVA Ag were sufficient to trigger airway hyperresponsiveness, prominent eosinophilic inflammation, and significantly increased serum OVA-specific IgG1 and IgE in rested mice that previously developed murine allergic airway diseases. The recall response to repeated OVA inoculation preferentially triggered a further increase of lung OVA-specific CD4(+) Th2 cells, whereas CD4(+) Th17 and ILC2 cell numbers remained constant. Furthermore, the acquired CD4(+) Th17 cells in Stat6(-/-)/IL-17-GFP mice, or innate ILC2s in CD4(+) T cell-ablated mice, failed to mount an allergic recall response to OVA Ag. After repeated OVA rechallenge or CD4(+) T cell ablation, the increase or loss of CD4(+) Th2 cells resulted in an enhanced or reduced IL-13 production by lung ILC2s in response to IL-25 and IL-33 stimulation, respectively. In return, ILC2s enhanced Ag-mediated proliferation of cocultured CD4(+) Th2 cells and their cytokine production, and promoted eosinophilic airway inflammation and goblet cell hyperplasia driven by adoptively transferred Ag-specific CD4(+) Th2 cells. Thus, these results suggest that an allergic recall response to recurring Ag exposures preferentially triggers an increase of Ag-specific CD4(+) Th2 cells, which facilitates the collaborative interactions between acquired CD4(+) Th2 cells and innate ILC2s to drive the exacerbation of a murine allergic airway diseases with an eosinophilic phenotype. PMID:25780046

  6. Sunlight-induced degradation of fluoroquinolones in wastewater effluent: Photoproducts identification and toxicity.

    PubMed

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Pretali, Luca; Ferri, Elida Nora; Profumo, Antonella

    2015-09-01

    The photodegradation of Ciprofloxacin (CIP), Enrofloxacin (ENR), Danofloxacin (DAN), Marbofloxacin (MAR) and Levofloxacin (LEV), five widely used fluoroquinolones (FQs), was studied in urban WWTP secondary effluent, under solar light. The degradation profiles and the kinetic constants were determined at the micrograms per litre levels (20-50 μg L(-1)). The photo-generated products were identified by high-pressure liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The toxicity of the photoproducts was assessed by Vibrio fischeri light emission inhibition assay performed on irradiated and not-irradiated FQs solutions, at environmentally significant concentrations. Attention was focused on the evaluation of the photoproducts contribution to the overall biotoxic effect of these emerging pollutants. Data from chronic exposure experiments (24-48 h) were primarily considered. Results confirmed the major usefulness of chronic toxicity data with respect to the acute assay ones and proved the not negligible biotoxicity of the FQs photodegradation products. PMID:25966937

  7. Electrochemiluminescence of terbium (III)-two fluoroquinolones-sodium sulfite system in aqueous solution

    NASA Astrophysics Data System (ADS)

    Chen, Shi-lv; Ding, Fen; Liu, Yu; Zhao, Hui-chun

    2006-05-01

    The electrochemiluminescence (ECL) of Tb 3+-enoxacin-Na 2SO 3 system (ENX system) and Tb 3+-ofloxacin-Na 2SO 3 system (OFLX system) in aqueous solution is reported. ECL is generated by the oxidation of Na 2SO 3, which is enhanced by Tb 3+-fluoroquinolone (FQ) complex. The ECL intensity peak versus potential corresponds to oxidation of Na 2SO 3, and the ECL emission spectra (the peaks are at 490, 545, 585 and 620 nm) match the characteristic emission spectrum of Tb 3+, indicating that the emission is from the excited state of Tb 3+. The mechanism of ECL is proposed and the difference of ECL intensity between ENX system and OFLX system is explained. Conditions for ECL emission were optimized. The linear range of ECL intensity versus concentrations of pharmaceuticals is 2.0 × 10 -10-8.0 × 10 -7 mol l -1 for ENX and 6.0 × 10 -10-6.0 × 10 -7 mol l -1 for OFLX, respectively. A theoretical limit of detection is 5.4 × 10 -11 mol l -1 for ENX and 1.6 × 10 -10 mol l -1 for OFLX, respectively. The ECL was satisfactorily applied to the determination of the two FQs in dosage form and urine sample.

  8. Correlation of different phenotypic drug susceptibility testing methods for four fluoroquinolones in Mycobacterium tuberculosis

    PubMed Central

    Coeck, Nele; de Jong, Bouke C.; Diels, Maren; de Rijk, Pim; Ardizzoni, Elisa; Van Deun, Armand; Rigouts, Leen

    2016-01-01

    Background Molecular resistance testing fails to explain all fluoroquinolone resistance, with a continued need for a suitable rapid phenotypic drug susceptibility testing method. Objective To evaluate the optimal method for phenotypic fluoroquinolone susceptibility testing. Methods Using Löwenstein–Jensen medium, Middlebrook 7H11 agar, BACTEC-MGIT 960 and the resazurin microtitre plate assay, we determined susceptibility to fluoroquinolones in Mycobacterium tuberculosis and investigated cross-resistance between ofloxacin, levofloxacin, moxifloxacin and gatifloxacin. We compared MICs of all four fluoroquinolones for 91 strains on Löwenstein–Jensen (as the gold standard) with their MICs in resazurin plates, and with ofloxacin susceptibility at a single concentration in MGIT and on 7H11 agar, in addition to sequencing of the gyrAB genes. Results and conclusions Applying a cut-off of 2 mg/L ofloxacin, 1 mg/L levofloxacin and 0.5 mg/L moxifloxacin and gatifloxacin in all methods, some discordance between solid medium and MGIT methods was observed, yet this tended to be explained by MICs around the cut-off. The high discordance between Löwenstein–Jensen (LJ) and resazurin plates suggests that the currently applied cut-offs for all fluoroquinolones in the resazurin method should decrease and minor changes in colour (from blue to purple) be considered as meaningful. High-level resistance in all assays to all drugs correlated well with the presence of gyrA mutations, in support of recent findings that fluoroquinolone resistance should be tested at different concentrations, as patients with lower levels of resistance may continue to benefit from high-dose fluoroquinolone-based therapy. PMID:26851609

  9. Proceedings of the 4th Workshop of Young Researchers in Astronomy & Astrophysics

    NASA Astrophysics Data System (ADS)

    Forgács-Dajka, E.

    2006-09-01

    Preface: It is a great pleasure for the Organizers to present the proceedings already the Fourth Workshop of Young Researchers in Astronomy & Astrophysics. Six years ago the Organizers of the first meeting of these conference series declared that their intention is to begin a long-lasting tradition of such biennial conference series where the young postgraduate scientists can meet each other as well as with senior scholars on the wide fields of astronomy & astrophysics, and they can present their results, getting important experiences in presentation oral lectures. And, of course, vice versa this is a great possibility for the senior astronomers and astrophysicists to know the new generation, and form new connections.I am glad to say that the idea became successful. On the present, fourth meeting almost 50 lectures -- which covers many areas of astrophysics and related topics from solar physics to cosmology -- was presented by the young researchers affiliated to all those Hungarian scientific institutes, where astronomy and/or astrophysics are studied. It is a new and happily sequel, that a lot of hungarian young researchers who are working abroad came back to Hungary for a while to present their science. Like a bridge between the generation, a significant part of the lecturers are already not PhD students. They are mainly postdoctoral researchers who attended on the first conferences as young scientists, but feel theirself young in their hearts, and return back from meetings to meetings due to their nice memories. They are highly welcomed in the future, too. Furthermore, last, but not least I mention, that as a manifestation of the great honour of the senior generations to the young scientists several leading Hungarian experts of the different fields kindly accepted our invitation to present invited lectures on their research topics. The above mentiond topics of the present conference were as follows: Solar physics, Space Physics, Celestial Mechanics

  10. Weighing the adverse cardiac effects of fluoroquinolones: A risk perspective.

    PubMed

    Mehrzad, Raman; Barza, Michael

    2015-11-01

    A rare side effect of fluoroquinolone (FQ) antibiotics is QT prolongation, which may result in serious arrhythmias. Most published comparative trials describe the relative risks among the drug class but do not focus on the incidence of serious arrhythmias. It is important for the prescriber to have a sense not only of relative risk but also of incidence to balance the risks against the other attributes of the individual members of the drug class. A review of English-language literature was performed to identify trials that provide data on the relative risk and, when able to be calculated, the incidence of adverse cardiac events among the commonly used FQs. Moxifloxacin had a several-fold higher risk of cardiac arrhythmias than levofloxacin or ciprofloxacin in randomized trials. However, the actual event rate was low in 2 of 3 studies. Given inconsistencies among the studies and the relative rarity of the events, the clinician need not base the choice of drug primarily on concern for a cardiac arrhythmia except in patients at the highest risk of such an event. PMID:26011799

  11. Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones

    PubMed Central

    Cama, Jehangir; Schaich, Michael; Al Nahas, Kareem; Hernández-Ainsa, Silvia; Pagliara, Stefano; Keyser, Ulrich F.

    2016-01-01

    Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug – we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community. PMID:27604156

  12. Direct Optofluidic Measurement of the Lipid Permeability of Fluoroquinolones.

    PubMed

    Cama, Jehangir; Schaich, Michael; Al Nahas, Kareem; Hernández-Ainsa, Silvia; Pagliara, Stefano; Keyser, Ulrich F

    2016-01-01

    Quantifying drug permeability across lipid membranes is crucial for drug development. In addition, reduced membrane permeability is a leading cause of antibiotic resistance in bacteria, and hence there is a need for new technologies that can quantify antibiotic transport across biological membranes. We recently developed an optofluidic assay that directly determines the permeability coefficient of autofluorescent drug molecules across lipid membranes. Using ultraviolet fluorescence microscopy, we directly track drug accumulation in giant lipid vesicles as they traverse a microfluidic device while exposed to the drug. Importantly, our measurement does not require the knowledge of the octanol partition coefficient of the drug - we directly determine the permeability coefficient for the specific drug-lipid system. In this work, we report measurements on a range of fluoroquinolone antibiotics and find that their pH dependent lipid permeability can span over two orders of magnitude. We describe various technical improvements for our assay, and provide a new graphical user interface for data analysis to make the technology easier to use for the wider community. PMID:27604156

  13. Application of the FUN3D Unstructured-Grid Navier-Stokes Solver to the 4th AIAA Drag Prediction Workshop Cases

    NASA Technical Reports Server (NTRS)

    Lee-Rausch, Elizabeth M.; Hammond, Dana P.; Nielsen, Eric J.; Pirzadeh, S. Z.; Rumsey, Christopher L.

    2010-01-01

    FUN3D Navier-Stokes solutions were computed for the 4th AIAA Drag Prediction Workshop grid convergence study, downwash study, and Reynolds number study on a set of node-based mixed-element grids. All of the baseline tetrahedral grids were generated with the VGRID (developmental) advancing-layer and advancing-front grid generation software package following the gridding guidelines developed for the workshop. With maximum grid sizes exceeding 100 million nodes, the grid convergence study was particularly challenging for the node-based unstructured grid generators and flow solvers. At the time of the workshop, the super-fine grid with 105 million nodes and 600 million elements was the largest grid known to have been generated using VGRID. FUN3D Version 11.0 has a completely new pre- and post-processing paradigm that has been incorporated directly into the solver and functions entirely in a parallel, distributed memory environment. This feature allowed for practical pre-processing and solution times on the largest unstructured-grid size requested for the workshop. For the constant-lift grid convergence case, the convergence of total drag is approximately second-order on the finest three grids. The variation in total drag between the finest two grids is only 2 counts. At the finest grid levels, only small variations in wing and tail pressure distributions are seen with grid refinement. Similarly, a small wing side-of-body separation also shows little variation at the finest grid levels. Overall, the FUN3D results compare well with the structured-grid code CFL3D. The FUN3D downwash study and Reynolds number study results compare well with the range of results shown in the workshop presentations.

  14. PREFACE: 4th International Workshop & Summer School on Plasma Physics 2010

    NASA Astrophysics Data System (ADS)

    2014-06-01

    Fourth International Workshop & Summer School on Plasma Physics 2010 The Fourth International Workshop & Summer School on Plasma Physics (IWSSPP'10) is organized by St. Kliment Ohridsky University of Sofia, with co-organizers TCPA Foundation, Association EURATOM/IRNRE, The Union of the Physicists in Bulgaria, and the Bulgarian Academy of Sciences. It was held in Kiten, Bulgaria, at the Black Sea Coast, from July 5 to July 10, 2010. The scientific programme covers the topics Fusion Plasma and Materials; Plasma Modeling and Fundamentals; Plasma Sources, Diagnostics and Technology. As the previous issues of this scientific meeting (IWSSPP'05, J. Phys.: Conf. Series 44 (2006) and IWSSPP'06, J. Phys.: Conf. Series 63 (2007), IWSSPP'08, J. Phys.: Conf. Series 207 (2010), its aim was to stimulate the creation and support of a new generation of young scientists for further development of plasma physics fundamentals and applications, as well as to ensure an interdisciplinary exchange of views and initiate possible collaborations by bringing together scientists from various branches of plasma physics. This volume of Journal of Physics: Conference Series includes 34 papers (invited lectures, contributed talks and posters) devoted to various branches of plasma physics, among them fusion plasma and materials, dc and microwave discharge modelling, transport phenomena in gas discharge plasmas, plasma diagnostics, cross sections and rate constants of elementary processes, material processing, plasma-chemistry and technology. Some of them have been presented by internationally known and recognized specialists in their fields; others are MSc or PhD students' first steps in science. In both cases, we believe they will raise readers' interest. We would like to thank the members of both the International Advisory Committee and the Local Organizing Committee, the participants who sent their manuscripts and passed through the (sometimes heavy and troublesome) refereeing and editing

  15. An Ecological Study of Food Desert Prevalence and 4th Grade Academic Achievement in New York State School Districts

    PubMed Central

    Frndak, Seth E.

    2014-01-01

    Background This ecological study examines the relationship between food desert prevalence and academic achievement at the school district level. Design and methods Sample included 232 suburban and urban school districts in New York State. Multiple open-source databases were merged to obtain: 4th grade science, English and math scores, school district demographic composition (NYS Report Card), regional socioeconomic indicators (American Community Survey), school district quality (US Common Core of Data), and food desert data (USDA Food Desert Atlas). Multiple regression models assessed the percentage of variation in achievement scores explained by food desert variables, after controlling for additional predictors. Results The proportion of individuals living in food deserts significantly explained 4th grade achievement scores, after accounting for additional predictors. School districts with higher proportions of individuals living in food desert regions demonstrated lower 4th grade achievement across science, English and math. Conclusions Food deserts appear to be related to academic achievement at the school district level among urban and suburban regions. Further research is needed to better understand how food access is associated with academic achievement at the individual level. Significance for public health The prevalence of food deserts in the United States is of national concern. As poor nutrition in United States children continues to spark debate, food deserts are being evaluated as potential sources of low fruit and vegetable intake and high obesity rates. Cognitive development and IQ have been linked to nutrition patterns, suggesting that children in food desert regions may have a disadvantage academically. This research evaluates if an ecological relationship between food desert prevalence and academic achievement at the school district level can be demonstrated. Results suggest that food desert prevalence may relate to poor academic performance at

  16. A nosocomial outbreak due to Enterobacter cloacae strains with the E. hormaechei genotype in patients treated with fluoroquinolones.

    PubMed Central

    Davin-Regli, A; Bosi, C; Charrel, R; Ageron, E; Papazian, L; Grimont, P A; Cremieux, A; Bollet, C

    1997-01-01

    During a 7-month period, we isolated 21 highly fluoroquinolone-resistant Enterobacter cloaecae strains in units from two hospitals in Marseille, France. Random amplification of polymorphic DNA showed clonal identity between isolates which, furthermore, presented the Enterobacter hormaechei genotype on DNA-DNA hybridization. The emergence of this clone was observed only in patients treated with fluoroquinolones. PMID:9157119

  17. Medical Standby: An Experience at the 4th National Youth Camping and Motivation Program Organized by Maksak Malaysia

    PubMed Central

    Zakaria, Mohd Idzwan; Isa, Ridzuan Mohd; Shah Che Hamzah, Mohd Shaharudin; Ayob, Noor Azleen

    2006-01-01

    Medical standby is the provision of emergency medical care and first aid for participants and/or spectators in a pre-planned event. This article describes the framework and the demographics of a medical standby at the 4th National Youth Camping and Motivation Program in Pasir Puteh, Kelantan from 30th July until the 3rd August 2004. The framework of the medical team is described based on the work process of any medical stand by. A medical encounter form was created for the medical standby defining the type of case seen (medical or trauma), name, age, race and diagnosis of the patient. We concluded that interagency collaboration during the initial planning and during the event itself is needed to ensure the smooth running of the medical standby. Most of the medical encounters were minor illnesses which are similar to previous studies and there was no case transferred to the hospital during that period. PMID:22589590

  18. Medical Standby: An Experience at the 4(th) National Youth Camping and Motivation Program Organized by Maksak Malaysia.

    PubMed

    Zakaria, Mohd Idzwan; Isa, Ridzuan Mohd; Shah Che Hamzah, Mohd Shaharudin; Ayob, Noor Azleen

    2006-01-01

    Medical standby is the provision of emergency medical care and first aid for participants and/or spectators in a pre-planned event. This article describes the framework and the demographics of a medical standby at the 4(th) National Youth Camping and Motivation Program in Pasir Puteh, Kelantan from 30(th) July until the 3(rd) August 2004. The framework of the medical team is described based on the work process of any medical stand by. A medical encounter form was created for the medical standby defining the type of case seen (medical or trauma), name, age, race and diagnosis of the patient. We concluded that interagency collaboration during the initial planning and during the event itself is needed to ensure the smooth running of the medical standby. Most of the medical encounters were minor illnesses which are similar to previous studies and there was no case transferred to the hospital during that period. PMID:22589590

  19. Macracanthorhynchus hirudinaceus Eggs in Canine Coprolite from the Sasanian Era in Iran (4(th)/5(th) Century CE).

    PubMed

    Mowlavi, Gholamreza; Makki, Mahsasadat; Heidari, Zahra; Rezaeian, Mostafa; Mohebali, Mehdi; Araujo, Adauto; Boenke, Nicole; Aali, Abolfazl; Stollner, Thomas; Mobedi, Iraj

    2015-01-01

    Present paper is the second publication introducing the paleoparasitological findings from animal coprolites obtained from archeological site of Chehrabad salt mine in northwestern Iran. The current archeological site is located in northwest of Iran, dated to the Sassanian Era (4(th)/5(th) century CE). In the summer 2012 the carnivore coprolite was obtained within the layers in the mine and were thoroughly analyzed for parasites using TSP rehydration technique. Eggs of 0 were successfully retrieved from the examined coprolite and were confidently identified based on reliable references. Identifying of M. hirudinaceus eggs in paleofeces with clear appearance as demonstrated herein, is much due to appropriate preservation condition has been existed in the salt mine .The present finding could be regarded as the oldest acanthocephalan infection in Iran. PMID:26246822

  20. Macracanthorhynchus hirudinaceus Eggs in Canine Coprolite from the Sasanian Era in Iran (4th/5th Century CE)

    PubMed Central

    MOWLAVI, Gholamreza; MAKKI, Mahsasadat; HEIDARI, Zahra; REZAEIAN, Mostafa; MOHEBALI, Mehdi; ARAUJO, Adauto; BOENKE, Nicole; AALI, Abolfazl; STOLLNER, Thomas; MOBEDI, Iraj

    2015-01-01

    Present paper is the second publication introducing the paleoparasitological findings from animal coprolites obtained from archeological site of Chehrabad salt mine in northwestern Iran. The current archeological site is located in northwest of Iran, dated to the Sassanian Era (4th/5th century CE). In the summer 2012 the carnivore coprolite was obtained within the layers in the mine and were thoroughly analyzed for parasites using TSP rehydration technique. Eggs of 0 were successfully retrieved from the examined coprolite and were confidently identified based on reliable references. Identifying of M. hirudinaceus eggs in paleofeces with clear appearance as demonstrated herein, is much due to appropriate preservation condition has been existed in the salt mine .The present finding could be regarded as the oldest acanthocephalan infection in Iran. PMID:26246822

  1. [Guideline for the additional test positions according to the EPQC 4th Edition for Digital Mammography Systems].

    PubMed

    Sommer, A; Lenzen, H; Blaser, D; Ehlers, S-E; Schopphoven, S; John, C

    2009-09-01

    Within the physical-technical quality assurance of the German breast cancer screening program all digital mammography systems have to perform the contrast resolution test and the determination of the average glandular dose based on the European guidelines for quality assurance in breast cancer screening and diagnosis (4th Edition). Since 1.1.2009 this applies to digital systems outside the screening program too. To accomplish uniform measurements in all federal states of Germany, the physical board of the reference centers developed together a special guideline for these test position. This Guideline describes the determination of the average glandular dose for different types of mammography systems, the CDMAM image acquisition and the CDMAM image evaluation as well. This guideline was verified by the German task group "Röntgenverordnung". PMID:19676011

  2. Neurobehavioral Evaluation System (NES): comparative performance of 2nd-, 4th-, and 8th-grade Czech children.

    PubMed

    Otto, D A; Skalik, I; House, D E; Hudnell, H K

    1996-01-01

    The Neurobehavioral Evaluation System was designed for field studies of workers, but many NES tests can be performed satisfactorily by children as young as 7 or 8 years old and a few tests, such as simple reaction time, can be performed by preschool children. However, little comparative data from children of different ages or grade levels are available. Studies of school children in the Czech Republic indicate that 2nd-grade children could perform the following NES tests satisfactorily: Finger Tapping, Visual Digit Span. Continuous Performance, Symbol-Digit Substitution, Pattern Comparison, and simpler conditions of Switching Attention. Comparative scores of boys and girls from the 2nd, 4th, and 8th grades and power analyses to estimate appropriate sample size were presented. Performance varied systematically with grade level and gender. Larger samples were needed with younger children to achieve comparable levels of statistical power. Gender comparisons indicated that boys responded faster, but made more errors than girls. PMID:8866533

  3. The influence of neighborhood density and word frequency on phoneme awareness in 2nd and 4th grades

    PubMed Central

    Hogan, Tiffany P.; Bowles, Ryan P.; Catts, Hugh W.; Storkel, Holly L.

    2010-01-01

    Purpose The purpose of this study was to test the hypothesis that two lexical characteristics – neighborhood density and word frequency – interact to influence performance on phoneme awareness tasks. Methods Phoneme awareness was examined in a large, longitudinal dataset of 2nd and 4th grade children. Using linear logistic test model, the relation between words' neighborhood density, word frequency, and phoneme awareness performance was examined across grades while covarying type and place of deletion. Results A predicted interaction was revealed: words from dense neighborhoods or those with high frequency were more likely to yield correct phoneme awareness responses across grades. Conclusions Findings support an expansion to the lexical restructuring model to include interactions between neighborhood density and word frequency to account for phoneme awareness. PMID:20691979

  4. 4th Annual Conference for African-American Researchers in the Mathematical Sciences (CAARMS4). Preliminary Program

    SciTech Connect

    Tapia, Richard

    1998-06-01

    In June, The Center for Research on Parallel Computation (CRPC), an NSF-funded Science and Technology Center, hosted the 4th Annual Conference for African-American Reserachers in the Mathematical Sciences (CAARMS4) at Rice University. The main goal of this conference was to highlight current work by African-American researchers and graduate students in mathematics. This conference strengthened the mathematical sciences by encouraging the increased participation of African-American and underrepresented groups into the field, facilitating working relationships between them and helping to cultivate their careers. In addition to the talks there was a graduate student poster session and tutorials on topics in mathematics and computer science. These talks, presentations, and discussions brought a broader perspective to the critical issues involving minority participation in mathematics.

  5. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria

    PubMed Central

    Parkinson, Elizabeth I.; Bair, Joseph S.; Nakamura, Bradley A.; Lee, Hyang Y.; Kuttab, Hani I.; Southgate, Emma H.; Lezmi, Stéphane; Lau, Gee W.; Hergenrother, Paul J.

    2015-01-01

    Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections. PMID:25907309

  6. Application of PCA and HCA to the Structure-Activity Relationship Study of Fluoroquinolones

    NASA Astrophysics Data System (ADS)

    Li, Xiao-hong; Zhang, Xian-zhou; Cheng, Xin-lu; Yang, Xiang-dong; Zhu, Zun-lue

    2006-04-01

    Density functional theory (DFT) was used to calculate molecular descriptors (properties) for 12 fluoroquinolone with anti-S.pneumoniae activity. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to reduce dimensionality and investigate in which variables should be more effective for classifying fluoroquinolones according to their degree of an-S.pneumoniae activity. The PCA results showed that the variables ELUMO, Q3, Q5, QA, logP, MR, VOL and ΔEHL of these compounds were responsible for the anti-S.pneumoniae activity. The HCA results were similar to those obtained with PCA. The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with anti-S.pneumoniae activity. By using the chemometric results, 6 synthetic compounds were analyzed through the PCA and HCA and two of them are proposed as active molecules with anti-S.pneumoniae, which is consistent with the results of clinic experiments.

  7. Molecular diagnosis of fluoroquinolone resistance in Mycobacterium tuberculosis.

    PubMed

    Bernard, Christine; Veziris, Nicolas; Brossier, Florence; Sougakoff, Wladimir; Jarlier, Vincent; Robert, Jérôme; Aubry, Alexandra

    2015-03-01

    As a consequence of the use of fluoroquinolones (FQ), resistance to FQ has emerged, leading to cases of nearly untreatable and extensively drug-resistant tuberculosis. Mutations in DNA gyrase represent the main mechanism of FQ resistance. A full understanding of the pattern of mutations found in FQ-resistant (FQ(r)) clinical isolates, and of their proportions, is crucial for improving molecular methods for the detection of FQ resistance in Mycobacterium tuberculosis. In this study, we reviewed the detection of FQ resistance in isolates addressed to the French National Reference Center for Mycobacteria from 2007 to 2012, with the aim of evaluating the performance of PCR sequencing in a real-life context. gyrA and gyrB sequencing, performed prospectively on M. tuberculosis clinical isolates, was compared for FQ susceptibility to 2 mg/liter ofloxacin by the reference proportion method. A total of 605 isolates, of which 50% were multidrug resistant, were analyzed. The increase in FQ(r) strains among multidrug-resistant (MDR) strains during the time of the study was alarming (8% to 30%). The majority (78%) of the isolates with gyrA mutations were FQ(r), whereas only 36% of those with gyrB mutations were FQ(r). Only 12% of the FQ(r) isolates had a single mutation in gyrB. Combined gyrA and gyrB sequencing led to >93% sensitivity for detecting resistance. The analysis of the four false-positive and the five false-negative results of gyrA and gyrB sequencing illustrated the actual limitations of the reference proportion method. Our data emphasize the need for combined gyrA and gyrB sequencing in the investigation of FQ susceptibility in M. tuberculosis and challenge the validity of the current phenotype-based approach as the diagnostic gold standard for determining FQ resistance. PMID:25534742

  8. Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells

    PubMed Central

    Cavet, M E; West, M; Simmons, N L

    1997-01-01

    Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial secretion of the fluoroquinolone antibiotic ciprofloxacin. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to competitive inhibition by sulphate, thiosulphate, oxalate, succinate and para-amino hippurate, probenecid (10 mM), taurocholate (100 μM) or bromosulphophthalein (100 μM). Similarly tetraethylammonium and N-′methylnicotinamide (10 mM) were without effect. Net secretion of ciprofloxacin was inhibited by the organic exchange inhibitor 4,4′-diisothiocyanostilbene-2-2′-disulphonic acid (DIDS, 400 μM). Net secretion of ciprofloxacin was partially inhibited by 100 μM verapamil, whilst net secretion of the P-glycoprotein substrate vinblastine was totally abolished under these conditions. Ciprofloxacin secretion was unaltered after preincubation of cells with two anti-P-glycoprotein antibodies (UIC2 and MRK16), which both significantly reduced secretory vinblastine flux (measured in the same cell batch). Ciprofloxacin (3 mM) failed to inhibit vinblastine net secretion in Caco-2 epithelia, and was not itself secreted by the P-glycoprotein expressing and vinblastine secreting dog kidney cell line, MDCK. Net secretion and cellular uptake of ciprofloxacin (at 0.1 mM) were not subject to alterations of either cytosolic or medium pH, or dependent on the presence of medium Na+, Cl− or K+ in the bathing media. The substrate specificity of the ciprofloxacin secretory transport in Caco-2 epithelia is distinct from both the renal organic anion and cation transport. A role for P-glycoprotein in ciprofloxacin secretion may also be excluded. A novel transport mechanism, sensitive to both DIDS and verapamil mediates secretion of ciprofloxacin by human intestinal Caco-2 epithelia. PMID:9283689

  9. The Molecular Genetics of Fluoroquinolone Resistance in Mycobacterium tuberculosis.

    PubMed

    Mayer, Claudine; Takiff, Howard

    2014-08-01

    The fluoroquinolones (FQs) are synthetic antibiotics effectively used for curing patients with multidrug-resistant tuberculosis (TB). When a multidrug-resistant strain develops resistance to the FQs, as in extensively drug-resistant strains, obtaining a cure is much more difficult, and molecular methods can help by rapidly identifying resistance-causing mutations. The only mutations proven to confer FQ resistance in M. tuberculosis occur in the FQ target, the DNA gyrase, at critical amino acids from both the gyrase A and B subunits that form the FQ binding pocket. GyrA substitutions are much more common and generally confer higher levels of resistance than those in GyrB. Molecular techniques to detect resistance mutations have suboptimal sensitivity because gyrase mutations are not detected in a variable percentage of phenotypically resistant strains. The inability to find gyrase mutations may be explained by heteroresistance: bacilli with a resistance-conferring mutation are present only in a minority of the bacterial population (>1%) and are therefore detected by the proportion method, but not in a sufficient percentage to be reliably detected by molecular techniques. Alternative FQ resistance mechanisms in other bacteria--efflux pumps, pentapeptide proteins, or enzymes that inactivate the FQs--have not yet been demonstrated in FQ-resistant M. tuberculosis but may contribute to intrinsic levels of resistance to the FQs or induced tolerance leading to more frequent gyrase mutations. Moxifloxacin is currently the best anti-TB FQ and is being tested for use with other new drugs in shorter first-line regimens to cure drug-susceptible TB. PMID:26104201

  10. Involvement of breast cancer resistance protein (ABCG2) in the biliary excretion mechanism of fluoroquinolones.

    PubMed

    Ando, Tomohiro; Kusuhara, Hiroyuki; Merino, Gracia; Alvarez, Ana I; Schinkel, Alfred H; Sugiyama, Yuichi

    2007-10-01

    Fluoroquinolones are effective antibiotics for the treatment of bile duct infections. It has been shown that the biliary excretion of grepafloxacin is partly accounted for by multidrug resistance-associated protein 2 (MRP2/ABCC2), whereas neither MRP2 nor P-glycoprotein is involved in the biliary excretion of ulifloxacin. In the present study, we examined the involvement of breast cancer resistance protein (BCRP/ABCG2) in the biliary excretion of fluoroquinolones (grepafloxacin, ulifloxacin, ciprofloxacin, and ofloxacin). In Madin-Darby canine kidney II cells expressing human BCRP or mouse Bcrp, the basal-to-apical transport of grepafloxacin and ulifloxacin was greater than that of the mock control, which was inhibited by a BCRP inhibitor, 3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-3-yl)-propionic acid tert-butyl ester (Ko143). Plasma and bile concentrations of fluoroquinolones were determined in wild-type and Bcrp(-/-) mice after i.v. bolus injection. The cumulative biliary excretion of fluoroquinolones was significantly reduced in Bcrp(-/-) mice, resulting in a reduction of the biliary excretion clearances to 86, 50, 40, and 16 of the control values, for ciprofloxacin, grepafloxacin, ofloxacin, and ulifloxacin, respectively. Preinfusion of sulfobromophthalein significantly inhibited the biliary excretion of grepafloxacin in Bcrp(-/-) mice. There was no change in the tissue/plasma concentration ratios of fluoroquinolones in the liver or brain, whereas those in the kidney were increased 3.6- and 1.5-fold for ciprofloxacin and grepafloxacin, respectively, in Bcrp(-/-) mice but were unchanged for ofloxacin and ulifloxacin. The present study shows that BCRP mediates the biliary excretion of fluoroquinolones and suggests that it is also involved in the tubular secretion of ciprofloxacin and grepafloxacin. PMID:17639028

  11. Evaluation of the appropriate use of commonly prescribed fluoroquinolones and the risk of dysglycemia

    PubMed Central

    Kabbara, Wissam K; Ramadan, Wijdan H; Rahbany, Peggy; Al-Natour, Souhaila

    2015-01-01

    Background Fluoroquinolones are among the most widely prescribed antibiotics. However, concerns about increasing resistant microorganisms and the risk of dysglycemia associated with the use of these agents have emerged. Objective The primary objective of the study was to evaluate the appropriate use of commonly prescribed fluoroquinolones, including appropriate indication, dose, dose adjustment in renal impairment, and duration of treatment. The secondary objective was to investigate the dysglycemic effect of fluoroquinolone use (hypoglycemia and/or hyperglycemia) in diabetic and nondiabetic patients. Methods A prospective observational study at a teaching hospital in Lebanon was conducted over a 6-month period. A total of 118 patients receiving broad-spectrum fluoroquinolones (levofloxacin, ciprofloxacin, and moxifloxacin) were identified. Patients were mainly recruited from internal medicine floors and intensive care units. Results The final percentage for the appropriate indication, dose, and duration of fluoroquinolone therapy was 93.2%, 74.6%, and 57.6%, respectively. A total of 57.1% of the patients did not receive the appropriate dose adjustment according to their level of renal impairment. In addition, dysglycemia occurred in both diabetic and nondiabetic patients. Dysglycemia was more frequently encountered with ciprofloxacin (50.0%), followed by levofloxacin (42.4%) and moxifloxacin (7.6%). Hyperglycemia was more common than hypoglycemia in all groups. The highest incidence of hyperglycemia occurred with levofloxacin (70.0%), followed by ciprofloxacin (39.0%) and moxifloxacin (33.3%). In contrast, hypoglycemia did not occur in the ciprofloxacin group, but it was more common with moxifloxacin (11.1%) and levofloxacin (6.0%). Conclusion The major clinical interventions for the future will adjust the dose and duration of therapy with commonly prescribed fluoroquinolones. The incidence of hypoglycemia was less common than hyperglycemia. PMID:25960658

  12. Hypersensitivity to fluoroquinolones: The expression of basophil activation markers depends on the clinical entity and the culprit fluoroquinolone.

    PubMed

    Fernández, Tahia D; Ariza, Adriana; Palomares, Francisca; Montañez, María I; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J

    2016-06-01

    Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity-specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = -0.446; P < 0.001 for CD63 and Spearman r = -0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID:27281069

  13. Feasibility and impact of an intensified antibiotic stewardship programme targeting cephalosporin and fluoroquinolone use in a tertiary care university medical center

    PubMed Central

    2014-01-01

    Background Restricted use of third-generation cephalosporins and fluoroquinolones has been linked to a reduced incidence of hospital-acquired infections with multidrug-resistant bacteria. We implemented an intensified antibiotic stewardship (ABS) programme in the medical service of a university hospital center aiming at a reduction by at least 30% in the use of these two drug classes. Methods The ABS programme was focused on the 300-bed medical service. Prescription of third-generation cephalosporins was discouraged, whereas the use of penicillins was encouraged. Monthly drug use density was measured in WHO-ATC defined and locally recommended daily doses (DDD and RDD) per 100 patient days, to evaluate trends before (01/2008 to 10/2011) and after starting the intervention (1/2012 to 3/2013). The effect was analysed using interrupted time-series analysis with six non-intervention departments as controls. Results Following initiation of the ABS intervention, overall antibiotic use in the medical service declined (p < 0.001). There was a significant intervention-related decrease in the use of cephalosporins and fluoroquinolones (p < 0.001) outperforming the decreasing baseline trend. Trend changes observed in some of the control departments were smaller, and the difference between trend changes in the medical service and those in control departments were highly significant for overall use and cephalosporin use reductions (p < 0.001) as well as for the increasing use of penicillins (p < 0.001). Mean use density levels (in RDD per 100 patient days) dropped for cephalosporins from 16.3 to 10.3 (−37%) and for fluoroquinolones from 17.7 to 10.1 (−43%), respectively. During the same period, the use of penicillins increased (15.4 to 18.2; 18%). The changes in expenditures for antibiotics in the medical service compared to control services minus programme costs indicated initial net cost savings likely to be associated with the programme. Conclusion An

  14. Streptococcus pneumoniae DNA Gyrase and Topoisomerase IV: Overexpression, Purification, and Differential Inhibition by Fluoroquinolones

    PubMed Central

    Pan, Xiao-Su; Fisher, L. Mark

    1999-01-01

    Streptococcus pneumoniae gyrA and gyrB genes specifying the DNA gyrase subunits have been cloned into pET plasmid vectors under the control of an inducible T7 promoter and have been separately expressed in Escherichia coli. Soluble 97-kDa GyrA and 72-kDa GyrB proteins bearing polyhistidine tags at their respective C-terminal and N-terminal ends were purified to apparent homogeneity by one-step nickel chelate column chromatography and were free of host E. coli topoisomerase activity. Equimolar amounts of the gyrase subunits reconstituted ATP-dependent DNA supercoiling with comparable activity to gyrase of E. coli and Staphylococcus aureus. In parallel, S. pneumoniae topoisomerase IV ParC and ParE subunits were similarly expressed in E. coli, purified to near homogeneity as 93- and 73-kDa proteins, and shown to generate efficient ATP-dependent DNA relaxation and DNA decatenation activities. Using the purified enzymes, we examined the inhibitory effects of three paradigm fluoroquinolones—ciprofloxacin, sparfloxacin, and clinafloxacin—which previous genetic studies with S. pneumoniae suggested act preferentially through topoisomerase IV, through gyrase, and through both enzymes, respectively. Surprisingly, all three quinolones were more active in inhibiting purified topoisomerase IV than gyrase, with clinafloxacin showing the greatest inhibitory potency. Moreover, the tested agents were at least 25-fold more effective in stabilizing a cleavable complex (the relevant cytotoxic lesion) with topoisomerase IV than with gyrase, with clinafloxacin some 10- to 32-fold more potent against either enzyme, in line with its superior activity against S. pneumoniae. The uniform target preference of the three fluoroquinolones for topoisomerase IV in vitro is in apparent contrast to the genetic data. We interpret these results in terms of a model for bacterial killing by quinolones in which cellular factors can modulate the effects of target affinity to determine the cytotoxic

  15. In vitro activity of T-3761, a new fluoroquinolone.

    PubMed Central

    Muratani, T; Inoue, M; Mitsuhashi, S

    1992-01-01

    The in vitro activity of T-3761, a new fluoroquinolone antimicrobial agent which has an oxazine ring structure with a cyclopropyl moiety at C-10, was compared with those of other agents against 2,854 clinical isolates. T-3761 had a broad spectrum of activity and had potent activity against gram-positive and -negative bacteria. The MICs of T-3761 against 90% of the methicillin-susceptible Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, and Clostridium spp. tested were 0.39 to 6.25 micrograms/ml. Its activity was comparable to those of ciprofloxacin and ofloxacin and four- to eightfold greater than those of norfloxacin and fleroxacin, but its activity was two- to eightfold less than that of tosufloxacin. Some isolates of ciprofloxacin-resistant S. aureus (MIC of ciprofloxacin, greater than or equal to 3.13 micrograms/ml) were still susceptible to T-3761 (MIC of T-3761, less than or equal to 0.78 micrograms/ml). The MICs of T-3761 against 90% of the streptococci and enterococci tested were 3.13 to 100 micrograms/ml. Its activity was equal to or 2- or 4-fold greater than those of norfloxacin and fleroxacin, equal to or 2- or 4-fold less than those of ofloxacin and ciprofloxacin, and 4- to 16-fold less than that of tosufloxacin. The activity of T-3761 against gram-negative bacteria was usually fourfold greater than those of norfloxacin, ofloxacin, and fleroxacin. Many isolates which were resistant to nonfluoroquinolone agents, such as minocycline- or imipenem-resistant S. aureus, ceftazidime-resistant members of the family Enterobacteriaceae, gentamicin- or imipenem-resistant Pseudomonas aeruginosa, and ampicillin-resistant Haemophilus influenzae and Neisseria gonorrhoeae, were susceptible to T-3761. The MBCs of T-3761 were either equal to or twofold greater than the MICs. The number of viable cells decreased rapidly during incubation with T-3761 at one to four times the MIC. At a concentration of four times the MIC, the

  16. [A development of Byzantine Christian charities during the 4(th)-7(th) centuries and the birth of the hospital].

    PubMed

    Nam, Sung Hyun

    2015-04-01

    This study aims to examine the beginning and the development of Christian Charities during the 4(th)-6(th) centuries which would eventually result in the birth of the hospital in modern sense in the first half of the 7(th) century. For this purpose, I looked carefully into various primary sources concerning the early Christian institutions for the poor and the sick. Above all, it's proper to note that the first xenodocheion where hospitality was combined with a systematic caring, is concerned with the Trinitarian debate of the 4(th) century. In 356, Eustathios, one of the leaders of homoiousios group, established xenodocheion to care for the sick and the lepers in Sebaste of Armenia, whereas his opponent Aetios, doctor and leader of the heteroousios party, was reckoned to have combined the medical treatment with his clerical activities. Then, Basil of Caesarea, disciple of Eustathios of Sebaste, also founded in 372 a magnificent benevolent complex named 'Basileias' after its founder. I scrupulously analysed several contemporary materials mentioning the charitable institution of Caesarea which was called alternatively katagogia, ptochotropheion, xenodocheion. John Chrysostome also founded several nosokomeia in Constantinople at the end of the 4(th) century and the beginning of the 5(th) century. Apparently, the contemporary sources mention that doctors existed for these Charities, but there is no sufficient proof that these 'Christian Hospitals,' Basileias or nosokomeia of Constantinople were hospitals in modern sense. Imperial constitutions began to mention ptochotropheion, xenodocheion and orphanotropheion since the second half of the 5(th) century and then some Justinian laws evoked nosokomium, brephotrophia, gerontocomia. These laws reveal that 'Christian Hospitals' were well clarified and deeply rooted in Byzantine society already in these periods. And then, new benevolent institutions emerged in the 6(th) century: nosokomeia for a specific class and

  17. Detection of a wide variety of human and veterinary fluoroquinolone antibiotics in municipal wastewater and wastewater-impacted surface water.

    PubMed

    He, Ke; Soares, Ana Dulce; Adejumo, Hollie; McDiarmid, Melissa; Squibb, Katherine; Blaney, Lee

    2015-03-15

    As annual sales of antibiotics continue to rise, the mass of these specially-designed compounds entering municipal wastewater treatment systems has also increased. Of primary concern here is that antibiotics can inhibit growth of specific microorganisms in biological processes of wastewater treatment plants (WWTPs) or in downstream ecosystems. Growth inhibition studies with Escherichia coli demonstrated that solutions containing 1-10 μg/L of fluoroquinolones can inhibit microbial growth. Wastewater samples were collected on a monthly basis from various treatment stages of a 30 million gallon per day WWTP in Maryland, USA. Samples were analyzed for the presence of 11 fluoroquinolone antibiotics. At least one fluoroquinolone was detected in every sample. Ofloxacin and ciprofloxacin exhibited detection frequencies of 100% and 98%, respectively, across all sampling sites. Concentrations of fluoroquinolones in raw wastewater were as high as 1900 ng/L for ciprofloxacin and 600 ng/L for ofloxacin. Difloxacin, enrofloxacin, fleroxacin, moxifloxacin, norfloxacin, and orbifloxacin were also detected at appreciable concentrations of 9-170 ng/L. The total mass concentration of fluoroquinolones in raw wastewater was in the range that inhibited E. coli growth, suggesting that concerns over antibiotic presence in wastewater and wastewater-impacted surface water are valid. The average removal efficiency of fluoroquinolones during wastewater treatment was approximately 65%; furthermore, the removal efficiency for fluoroquinolones was found to be negatively correlated to biochemical oxygen demand removal and positively correlated to phosphorus removal. PMID:25483174

  18. Electrochemical Detection of Fluoroquinolone Antibiotics in Milk Using a Magneto Immunosensor

    PubMed Central

    Pinacho, Daniel G.; Sánchez-Baeza, Francisco; Pividori, María-Isabel; Marco, María-Pilar

    2014-01-01

    An amperometric magneto-immunosensor (AMIS) for the detection of residues of fluoroquinolone antibiotics in milk samples is described for the first time. The immunosensor presented combines magnetic beads biomodified with an antibody with a broad recognition profile of fluoroquinolones, a haptenized enzyme and a magnetic graphite–epoxy composite (m-GEC) electrode. After the immunochemical reaction with specific enzyme tracer, the antibody biomodified magnetic beads are easily captured by an electrode made of graphite-epoxy composite containing a magnet, which also acts as transducer for the electrochemical detection. In spite of the complexity of milk, the use of magnetic beads allows elimination of potential interferences caused by the matrix components; hence the AMIS could perform quantitative measurements, directly in these samples, without any additional sample cleanup or extraction step. The immunosensor is able to detect up to seven different fluoroquinolones far below the MRLs defined by the UE for milk; for example ciprofloxacin is detected directly in milk with an IC50 of 0.74 μg/L and a LOD of 0.009 μg/L. This strategy offers great promise for rapid, simple, cost-effective, and on-site analysis fluoroquinolones in complex samples. PMID:25171120

  19. [Use of fluoroquinolones in intensive care units in a multi-drug-resistance era].

    PubMed

    Esposito, Silvano; Fiore, Marco

    2007-09-01

    Despite the high level of antibiotic resistance in ICUs, fluoroquinolones remain the most frequent utilized antibiotic in these settings. Since the discovery of this class of antibiotics several mechanisms have been identified as responsible for resistance to fluoroquinolones and more recently a new one have been studied which is responsible for transferable resistance, which acts by means of an enzymatic inactivaction affecting only some members of the fluoroquinolones class. In fact, the cr variant of the gene aac(6)-Ib translates an aminoglycosides acetiltrasferases which confers a reduced susceptibility to those fluoroquinolones carrying this substrate, as ciprofloxacin and norfloxacin, but not to others such as levofloxacin. It is therefore interesting to speculate that the use of levofloxacin could avoid the development of resistance in those bacteria presenting this enzyme but not in those carrying a Qnr gene. The application of these new aspects of molecular biology in the clinical practice together with the knowledge of the risk factors could in the future contribute to reduce the development of antibiotic resistance. The ID consultation, the use of practical and reliable guidelines, the use of antibiotic association based on local epidemiology would represent further strategies to minimize the antibiotic resistance development optimizing the therapeutic choice. PMID:17940399

  20. Terbium-sensitised luminescence screening method for fluoroquinolones in beef serum.

    PubMed

    Schneider, Marilyn J; Yun, Limei; Lehotay, Steven J

    2013-01-01

    Enrofloxacin and danofloxacin are the only fluoroquinolone antibiotics approved for use in cattle in the United States. Microbial screening methods commonly used for monitoring veterinary drug residues are not sensitive or selective for fluoroquinolones. In this work, a luminescence-based screening assay was developed to detect fluoroquinolones in beef serum. This approach takes advantage of the DNA-enhanced luminescence signal of a fluoroquinolone-Tb⁺³ complex. In this method, serum samples were extracted with acidified acetonitrile in the presence of magnesium sulfate. After centrifugation, evaporation of the supernatant was followed by dissolution of the residue in buffer and filtration. Addition of Tb⁺³ and DNA then allowed a reading of the luminescence signal. The technique was illustrated using enrofloxacin, and provided good recoveries (73-88%) at 25, 50 and 100 ng ml⁻¹, with reasonable RSDs averaging at 11%. The LOD was 2.5 ng ml⁻¹ based on the variability of response of control serum samples from 18 different steers. The method provided no false-positive or false-negative results while screening blind samples for enrofloxacin and was demonstrated to be quantitative over a range of 0-100 ng ml⁻¹. PMID:23472630

  1. Biological cost of fluoroquinolone resistance in Escherichia coli implicated in polyclonal infection.

    PubMed

    Bémer, P; Corvec, S; Guitton, C; Giraudeau, C; Le Gargasson, G; Espaze, E; Drugeon, H

    2007-07-01

    Polyclonal Escherichia coli strains were isolated in a transplanted patient who experienced successive septic shocks. Fluoroquinolone susceptible and resistant strains were corresponding to different PFGE fragment profiles. The gyrA S83L mutation was associated with a reduction in biological fitness. Resistant strain was selected by a long-term single use of ofloxacin. PMID:16884861

  2. [Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

    PubMed

    Gao, Liu-zhou; Xie, Yu-suo; Yan, Qiang; Wu, Shu-min; Ni, Li-li; Zhao, Hui; Huang, Wen-long; Hu, Guo-qiang

    2015-08-01

    To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues. PMID:26669001

  3. Screening of fluoroquinolone residues in caprine milk using a 5-kg luminescence photometer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A terbium-sensitized luminescence (TSL) method was developed to screen presence of residues of four fluoroquinolones (FQ) registered in caprine milk in the European Union: enrofloxacin, ciprofloxacin, flumequine, and danofloxacin. After extraction in McIlvaine buffer and SPE cleanup, TSL was measure...

  4. Fluoroquinolone-resistant uncomplicated urinary tract infections, Chinese herbal medicine may provide help.

    PubMed

    Tong, Yanqing; Jing, Yue; Zhao, Dongkai; Zhang, Liping; Zeng, Shiming

    2011-01-01

    We assessed the effects of Chinese herbs on the uncomplicated urinary tract infections (UTIs) in women caused by fluoroquinolone-resistant strains. A total of 56 pre-menopausal women with uncomplicated UTIs caused by fluoroquinolone-resistant strains were included. Urine cultures were carried out. All organisms were proved to be fluoroquinolone-resistant at baseline. The patients were orally administrated Chinese herbal concoction for ten days. Chinese herbal concoction eradicated the primary pathogen in 71.4% of the patients at the 1-week follow-up. Among the 20 patients who had bacteriologic failures in the Day 5 of treatment, 2 developed superinfection. Of the failures in the group, Proteus mirabilis, Staphylococcus epidermidis and Providencia rettgeri were implicated in 50.0%, 50.0% and 100.0% of the failures, respectively. The clinical outcomes were also good, with cure or improvement for more than 80% of all subjects. About 14% of the study subjects reported at least one potential adverse event. The adverse events most frequently reported were nausea and diarrhea. All patients tolerated the symptoms. The adverse reactions did not prevail after discontinuation of the medication. Chinese herbal therapy may be an acceptable alternative for the treatment of uncomplicated UTIs caused by fluoroquinolone-resistant uropathogens. PMID:22754063

  5. Wildlife contamination with fluoroquinolones from livestock: Widespread occurrence of enrofloxacin and marbofloxacin in vultures.

    PubMed

    Blanco, Guillermo; Junza, Alexandra; Segarra, David; Barbosa, José; Barrón, Dolores

    2016-02-01

    There is much recent interest in the presence and impact of veterinary pharmaceuticals in wildlife. Livestock carcasses are often disposed of in supplementary feeding stations for avian scavengers, as a management and conservation tool for these species worldwide. In feeding stations, vultures and other scavengers can consume carcasses almost immediately after disposal, which implies the potential ingestion of veterinary pharmaceuticals as a non-target consequence of supplementary feeding. Using UPLC-MS/MS and HPLC-TOF, we evaluated the presence and concentration of fluoroquinolone residues in plasma of nestling vultures feeding on domestic livestock carrion. Three different fluoroquinolones (marbofloxacin, enrofloxacin and its metabolite ciprofloxacin) and a non-targeted β-lactam (nafcillin) were detected in vulture plasma. The high proportion of individuals (92%) with fluoroquinolone residues at variable concentrations (up to ∼20 μg L(-1) of enrofloxacin and ∼150 μg L(-1) of marbofloxacin) sampled in several geographically distant colonies and on different dates suggests that these and other drugs were potentially ingested throughout nestling development. Contamination with veterinary fluoroquinolones and other pharmaceuticals should be considered as an unintended but alarming consequence of food management in threatened wildlife. PMID:26498102

  6. Changes in Fluoroquinolone Use for Gonorrhea Following Publication of Revised Treatment Guidelines

    PubMed Central

    Dowell, Deborah; Tian, Lin H.; Stover, Jeffrey A.; Donnelly, Jennifer A.; Martins, Summer; Erbelding, Emily J.; Pino, Raul; Newman, Lori M.

    2012-01-01

    Objectives. We evaluated the impact of revised national treatment recommendations on fluoroquinolone use for gonorrhea in selected states. Methods. We evaluated gonorrhea cases reported through the Sexually Transmitted Disease Surveillance Network as treated between July 1, 2006 and May 31, 2008, using interrupted time series analysis. Outcomes were fluoroquinolone treatment overall, by area, and by practice setting. Results. Of 16 126 cases with treatment dates in this period, 15 669 noted the medication used. After revised recommendations were released, fluoroquinolone use decreased abruptly overall (21.5%; 95% confidence interval [CI] = 15.9%, 27.2%), in most geographic areas evaluated, and in sexually transmitted disease clinics (28.5%; 95% CI = 19.0%, 37.9%). More gradual decreases were seen in primary care (8.6%; 95% CI = 2.6%, 14.6%), and in emergency departments, urgent care, and hospitals (2.7%; 95% CI = 1.7%, 3.7%). Conclusions. Fluoroquinolone use decreased after the publication of revised national guidelines, particularly in sexually transmitted disease clinics. Additional mechanisms are needed to increase the speed and magnitude of changes in prescribing in primary care, emergency departments, urgent care, and hospitals. PMID:22095341

  7. Electrochemical detection of fluoroquinolone antibiotics in milk using a magneto immunosensor.

    PubMed

    Pinacho, Daniel G; Sánchez-Baeza, Francisco; Pividori, María-Isabel; Marco, María-Pilar

    2014-01-01

    An amperometric magneto-immunosensor (AMIS) for the detection of residues of fluoroquinolone antibiotics in milk samples is described for the first time. The immunosensor presented combines magnetic beads biomodified with an antibody with a broad recognition profile of fluoroquinolones, a haptenized enzyme and a magnetic graphite-epoxy composite (m-GEC) electrode. After the immunochemical reaction with specific enzyme tracer, the antibody biomodified magnetic beads are easily captured by an electrode made of graphite-epoxy composite containing a magnet, which also acts as transducer for the electrochemical detection. In spite of the complexity of milk, the use of magnetic beads allows elimination of potential interferences caused by the matrix components; hence the AMIS could perform quantitative measurements, directly in these samples, without any additional sample cleanup or extraction step. The immunosensor is able to detect up to seven different fluoroquinolones far below the MRLs defined by the UE for milk; for example ciprofloxacin is detected directly in milk with an IC50 of 0.74 µg/L and a LOD of 0.009 µg/L. This strategy offers great promise for rapid, simple, cost-effective, and on-site analysis fluoroquinolones in complex samples. PMID:25171120

  8. Fluoroquinolone resistance detection in Campylobacter coli and Campylobacter jejuni by Luminex xMAP technology.

    PubMed

    Barco, Lisa; Lettini, Antonia Anna; Dalla Pozza, Maria Cristina; Ramon, Elena; Fasolato, Manuela; Ricci, Antonia

    2010-09-01

    The proportion of Campylobacter spp. isolates that are resistant to fluoroquinolones, the drugs of choice for campylobacteriosis, has been increasing worldwide. We developed an innovative method based on a Luminex xMAP DNA suspension array that allows the identification of Campylobacter species and, simultaneously, the detection of the most common point mutation in the gyrA gene (substitution from threonine 86 to isoleucine 86) that is responsible for fluoroquinolone resistance. Ninety-six Campylobacter coli and Campylobacter jejuni isolates collected from turkeys were first investigated by microdilution test to characterize the antimicrobial resistance patterns. The isolates, amplified for the quinolone resistance determining region of the gyrA gene, were then tested using Luminex suspension array. The reliability of the method was demonstrated by the total concordance between the results obtained using Luminex and those of the sequencing of gyrA polymerase chain reaction products. The genotypic characterization of fluoroquinolone resistance using Luminex was also consistent with the data on phenotypical resistance obtained by microdilution test. The results of this study strongly support the potential of Luminex xMAP technology as an efficient molecular method for the rapid and accurate identification of C. coli and C. jejuni isolates and the characterization of the major determinant of fluoroquinolone resistance. PMID:20500084

  9. Activities of Telithromycin, Erythromycin, Fluoroquinolones, and Doxycycline against Campylobacter Strains Isolated from Finnish Subjects

    PubMed Central

    Schönberg-Norio, Daniela; Hänninen, Marja-Liisa; Katila, Marja-Leena; Kaukoranta, Suvi-Sirkku; Koskela, Markku; Eerola, Erkki; Uksila, Jaakko; Pajarre, Sini; Rautelin, Hilpi

    2006-01-01

    The in vitro susceptibilities of 478 Campylobacter jejuni and Campylobacter coli strains isolated from Finnish subjects during 2002 to 2004 were determined. Susceptibility to erythromycin remained high, and telithromycin did not offer any advantage over erythromycin. Reduced susceptibilities to fluoroquinolones and doxycycline were detected almost exclusively among isolates of foreign origin. PMID:16495275

  10. Dissimilar Fitness Associated with Resistance to Fluoroquinolones Influences Clonal Dynamics of Various Multiresistant Bacteria.

    PubMed

    Fuzi, Miklos

    2016-01-01

    Fitness cost associated with resistance to fluoroquinolones was recently shown to vary across clones of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing Klebsiella pneumoniae. The resulting dissimilar fitness should have influenced the clonal dynamics and thereby the rates of resistance for these pathogens. Moreover, a similar mechanism was recently proposed for the emergence of the H30 and H30R lineages of ESBL-producing E. coli and the major international clone (ribotype 027) of Clostridium difficile. Furthermore, several additional international clones of various multiresistant bacteria are suspect to have been selected by an analogous process. An ability to develop favorable mutations in the gyrase and topoisomerase IV genes seems to be a prerequisite for pathogens to retain fitness while showing high-level resistance to fluoroquinolones. Since, the consumption of other "non-fluoroquinolone" groups of antibiotics have also contributed to the rise in resistance rates a more judicious use of antibiotics in general and of fluoroquinolones in particular could ameliorate the international resistance situation. PMID:27458434

  11. Design of a portable fluoroquinolone analyzer based on terbium-sensitized luminescence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A portable fluoroquinolone (FQ) analyzer is developed in this laboratory based on terbium-sensitized luminescence (TSL). The optical, hardware and software design aspects are described in detail. A 327-nm light emitting diode (LED) is used in pulsed mode as the excitation source; and a photomultip...

  12. Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluoroquinolones are broad spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity, which can cause damage DNA and result in bacterial cell death. In response to DNA damage, bacteria induce an SOS response to stimulate repair of damaged DNA. However, the SOS response may al...

  13. Communicating Science to Impact Learning? A Phenomenological Inquiry into 4th and 5th Graders' Perceptions of Science Information Sources

    NASA Astrophysics Data System (ADS)

    Gelmez Burakgazi, Sevinc; Yildirim, Ali; Weeth Feinstein, Noah

    2016-04-01

    Rooted in science education and science communication studies, this study examines 4th and 5th grade students' perceptions of science information sources (SIS) and their use in communicating science to students. It combines situated learning theory with uses and gratifications theory in a qualitative phenomenological analysis. Data were gathered through classroom observations and interviews in four Turkish elementary schools. Focus group interviews with 47 students and individual interviews with 17 teachers and 10 parents were conducted. Participants identified a wide range of SIS, including TV, magazines, newspapers, internet, peers, teachers, families, science centers/museums, science exhibitions, textbooks, science books, and science camps. Students reported using various SIS in school-based and non-school contexts to satisfy their cognitive, affective, personal, and social integrative needs. SIS were used for science courses, homework/project assignments, examination/test preparations, and individual science-related research. Students assessed SIS in terms of the perceived accessibility of the sources, the quality of the content, and the content presentation. In particular, some sources such as teachers, families, TV, science magazines, textbooks, and science centers/museums ("directive sources") predictably led students to other sources such as teachers, families, internet, and science books ("directed sources"). A small number of sources crossed context boundaries, being useful in both school and out. Results shed light on the connection between science education and science communication in terms of promoting science learning.

  14. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells

    PubMed Central

    Kiniwa, Yukiko; Li, Jiang; Wang, Mingjun; Sun, Chuang; Lee, Jeffrey E.; Wang, Rong-Fu; Wang, Helen Y.

    2015-01-01

    Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8+ T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4+ T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4+ T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4+ Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4+ T cell-mediated immunotherapy in melanoma. PMID:25993655

  15. A study of personality factors and interaction in 4th-year dental students and their teachers.

    PubMed

    Watts, T L; Millard, L

    1997-02-01

    No previous investigation has considered dental student and teaching staff opinions on their relationship with each other. In a day when students are increasingly asked for feedback on the quality of teaching by staff, such investigations are of particular interest. This exploratory study was designed to compare the personality characteristics of a clinical year of dental students with those of the teaching staff they most frequently encountered, and to investigate these factors for possible associations with the quality of perceived teaching-learning interaction between the 2 groups. A complete 4th year of dental students (n = 87), and those teachers whom they met regularly (n = 80), were asked to participate. Subjects completed a form of the Myers-Briggs personality questionnaire simplified for use in education, and were asked to assess their relationship with persons in the other group. All the students and 75% of the staff, after follow-up, returned usable data. There was close similarity between staff and student personality profiles, and perception of working relationships by both groups was largely independent of personality factors and temperament. There were differences in staff perception of their relationship with extrovert and introvert students. Students showed minor differences in their perception of staff relationships with respect to two other personality factors. These findings indicate a substantial similarity between staff and students, and suggest a mature and stable relationship between people in the 2 groups. PMID:9567907

  16. Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses.

    PubMed

    McKimm-Breschkin, Jennifer L; Fry, Alicia M

    2016-05-01

    The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2-4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focused on the discovery and development of inhibitors of several virus targets and key host cell factors involved in virus replication or mediating the inflammatory response. Virus targets included the influenza haemagglutinin, neuraminidase and M2 proteins, and both the respiratory syncytial virus and influenza polymerases and nucleoproteins. Therapies for rhinoviruses and MERS and SARS coronaviruses were also discussed. With the emerging development of monoclonal antibodies as therapeutics, the potential implications of antibody-dependent enhancement of disease were also addressed. Topics covered all aspects from structural and molecular biology to preclinical and clinical studies. The importance of suitable clinical trial endpoints and regulatory issues were also discussed from the perspectives of both industry and government. This meeting summary provides an overview, not only for the conference participants, but also for those interested in the current status of antivirals for respiratory viruses. PMID:26872862

  17. Quality of Education Predicts Performance on the Wide Range Achievement Test-4th Edition Word Reading Subtest

    PubMed Central

    Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S.; Dean, Andy C.; Thames, April D.

    2014-01-01

    The current study examined whether self-rated education quality predicts Wide Range Achievement Test-4th Edition (WRAT-4) Word Reading subtest and neurocognitive performance, and aimed to establish this subtest's construct validity as an educational quality measure. In a community-based adult sample (N = 106), we tested whether education quality both increased the prediction of Word Reading scores beyond demographic variables and predicted global neurocognitive functioning after adjusting for WRAT-4. As expected, race/ethnicity and education predicted WRAT-4 reading performance. Hierarchical regression revealed that when including education quality, the amount of WRAT-4's explained variance increased significantly, with race/ethnicity and both education quality and years as significant predictors. Finally, WRAT-4 scores, but not education quality, predicted neurocognitive performance. Results support WRAT-4 Word Reading as a valid proxy measure for education quality and a key predictor of neurocognitive performance. Future research should examine these findings in larger, more diverse samples to determine their robust nature. PMID:25404004

  18. Quality of education predicts performance on the Wide Range Achievement Test-4th Edition Word Reading subtest.

    PubMed

    Sayegh, Philip; Arentoft, Alyssa; Thaler, Nicholas S; Dean, Andy C; Thames, April D

    2014-12-01

    The current study examined whether self-rated education quality predicts Wide Range Achievement Test-4th Edition (WRAT-4) Word Reading subtest and neurocognitive performance, and aimed to establish this subtest's construct validity as an educational quality measure. In a community-based adult sample (N = 106), we tested whether education quality both increased the prediction of Word Reading scores beyond demographic variables and predicted global neurocognitive functioning after adjusting for WRAT-4. As expected, race/ethnicity and education predicted WRAT-4 reading performance. Hierarchical regression revealed that when including education quality, the amount of WRAT-4's explained variance increased significantly, with race/ethnicity and both education quality and years as significant predictors. Finally, WRAT-4 scores, but not education quality, predicted neurocognitive performance. Results support WRAT-4 Word Reading as a valid proxy measure for education quality and a key predictor of neurocognitive performance. Future research should examine these findings in larger, more diverse samples to determine their robust nature. PMID:25404004

  19. Advances in Urea cycle Neuroimaging: Proceedings from the 4th International symposium on Urea cycle disorders, Barcelona, Spain, September 2013

    PubMed Central

    Pacheco-Colon, Ileana; Fricke, Stanley; VanMeter, John; Gropman, M.D.

    2014-01-01

    Our previous imaging research performed as part of a Urea Cycle Rare Disorders Consortium (UCRDC) grant, has identified specific biomarkers of neurologic injury in ornithine transcarbamylase deficiency, OTCD. While characterization of mutations can be achieved in most cases, this information does not necessarily predict the severity of the underlying neurological syndrome. The biochemical consequences of any mutation may be modified additionally by a large number of factors, including contributions of other enzymes and transport systems that mediate flux through the urea cycle, diet and other environmental factors. These factors likely vary from one patient to another, and they give rise to heterogeneity of clinical severity. Affected cognitive domains include non-verbal learning, fine motor processing, reaction time, visual memory, attention, and executive function. Deficits in these capacities may be seen in symptomatic patients, as well as asymptomatic carriers with normal IQ and correlate with variances in brain structure and function in these patients. Using neuroimaging we can identify biomarkers that reflect the downstream impact of UCDs on cognition. This manuscript is a summary of the presentation from the 4th International Consortium on Urea cycle disorders held in, Barcelona, Spain, September 2, 2014. PMID:25066103

  20. Pregnancy Outcome Following Gestational Exposure to Fluoroquinolones: a Multicenter Prospective Controlled Study

    PubMed Central

    Loebstein, Ronen; Addis, Antonio; Ho, Elaine; Andreou, Roseann; Sage, Suzanne; Donnenfeld, Alan E.; Schick, Betsy; Bonati, Maurizio; Moretti, Myla; Lalkin, Arieh; Pastuszak, Anne; Koren, Gideon

    1998-01-01

    Concerns regarding the teratogenicity of fluoroquinolones have resulted in their restricted use during gestation. This is despite an increasing need for their use due to emerging bacterial resistance. The objectives of the present investigation were to evaluate pregnancy and fetal outcomes following maternal exposure to fluoroquinolones and to examine whether in utero exposure to quinolones is associated with clinically significant musculoskeletal dysfunctions. We prospectively enrolled and followed up 200 women exposed to fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin) during gestation. Pregnancy outcome was compared with that for 200 controls matched for age and for smoking and alcohol consumption habits. Controls were exposed to nonteratogenic, nonembryotoxic antimicrobial agents matched by indication, duration of therapy (±3 days), and trimester of exposure. Rates of major congenital malformations did not differ between the group exposed to quinolones in the first trimester (2.2%) and the control group (2.6%) (relative risk, 0.85; 95% confidence interval, 0.21 to 3.49). Women treated with quinolones had a tendency for an increased rate of therapeutic abortions compared with the rate among women exposed to nonteratogens (relative risk, 4.50; 95% confidence interval, 0.98 to 20.57), resulting in lower live-birth rates (86 versus 94%; P = 0.02). The rates of spontaneous abortions, fetal distress, and prematurity and the birth weight did not differ between the groups. Gross motor developmental milestone achievements did not differ between the children of the mothers in the two groups. We concluded that the use of fluoroquinolones during embryogenesis is not associated with an increased risk of major malformations. There were no clinically significant musculoskeletal dysfunctions in children exposed to fluoroquinolones in utero. The higher rate of therapeutic abortions observed in quinolone-exposed women compared to that for their controls may be secondary

  1. Clinical implications of reduced susceptibility to fluoroquinolones in paediatric Shigella sonnei and Shigella flexneri infections

    PubMed Central

    Thompson, Corinne N.; Thieu, Nga Tran Vu; Vinh, Phat Voong; Duc, Anh Nguyen; Wolbers, Marcel; Vinh, Ha; Campbell, James I.; Ngoc, Dung Tran Thi; Hoang, Nguyen Van Minh; Thanh, Tuyen Ha; The, Hao Chung; Nguyen, To Nguyen Thi; Lan, Nguyen Phu Huong; Parry, Christopher M.; Chau, Nguyen Van Vinh; Thwaites, Guy; Thanh, Duy Pham; Baker, Stephen

    2016-01-01

    Objectives We aimed to quantify the impact of fluoroquinolone resistance on the clinical outcome of paediatric shigellosis patients treated with fluoroquinolones in southern Vietnam. Such information is important to inform therapeutic management for infections caused by this increasingly drug-resistant pathogen, responsible for high morbidity and mortality in young children globally. Methods Clinical information and bacterial isolates were derived from a randomized controlled trial comparing gatifloxacin with ciprofloxacin for the treatment of paediatric shigellosis. Time–kill experiments were performed to evaluate the impact of MIC on the in vitro growth of Shigella and Cox regression modelling was used to compare clinical outcome between treatments and Shigella species. Results Shigella flexneri patients treated with gatifloxacin had significantly worse outcomes than those treated with ciprofloxacin. However, the MICs of fluoroquinolones were not significantly associated with poorer outcome. The presence of S83L and A87T mutations in the gyrA gene significantly increased MICs of fluoroquinolones. Finally, elevated MICs and the presence of the qnrS gene allowed Shigella to replicate efficiently in vitro in high concentrations of ciprofloxacin. Conclusions We found that below the CLSI breakpoint, there was no association between MIC and clinical outcome in paediatric shigellosis infections. However, S. flexneri patients had worse clinical outcomes when treated with gatifloxacin in this study regardless of MIC. Additionally, Shigella harbouring the qnrS gene are able to replicate efficiently in high concentrations of ciprofloxacin and we hypothesize that such strains possess a competitive advantage against fluoroquinolone-susceptible strains due to enhanced shedding and transmission. PMID:26679253

  2. Benefits of a 4th Ice Class in the Simulated Radar Reflectivities of Convective Systems Using a Bulk Microphysics Scheme

    NASA Technical Reports Server (NTRS)

    Lang, Stephen E.; Tao, Wei-Kuo; Chern, Jiun-Dar; Wu, Di; Li, Xiaowen

    2015-01-01

    Numerous cloud microphysical schemes designed for cloud and mesoscale models are currently in use, ranging from simple bulk to multi-moment, multi-class to explicit bin schemes. This study details the benefits of adding a 4th ice class (hail) to an already improved 3-class ice bulk microphysics scheme developed for the Goddard Cumulus Ensemble model based on Rutledge and Hobbs (1983,1984). Besides the addition and modification of several hail processes from Lin et al. (1983), further modifications were made to the 3-ice processes, including allowing greater ice super saturation and mitigating spurious evaporationsublimation in the saturation adjustment scheme, allowing graupelhail to become snow via vapor growth and hail to become graupel via riming, and the inclusion of a rain evaporation correction and vapor diffusivity factor. The improved 3-ice snowgraupel size-mapping schemes were adjusted to be more stable at higher mixing rations and to increase the aggregation effect for snow. A snow density mapping was also added. The new scheme was applied to an intense continental squall line and a weaker, loosely-organized continental case using three different hail intercepts. Peak simulated reflectivities agree well with radar for both the intense and weaker case and were better than earlier 3-ice versions when using a moderate and large intercept for hail, respectively. Simulated reflectivity distributions versus height were also improved versus radar in both cases compared to earlier 3-ice versions. The bin-based rain evaporation correction affected the squall line case more but did not change the overall agreement in reflectivity distributions.

  3. Breakfast patterns among low-income, ethnically-diverse 4th-6th grade children in an urban area

    PubMed Central

    2014-01-01

    Background Increasing school breakfast participation has been advocated as a method to prevent childhood obesity. However, little is known about children’s breakfast patterns outside of school (e.g., home, corner store). Policies that increase school breakfast participation without an understanding of children’s breakfast habits outside of school may result in children consuming multiple breakfasts and may undermine efforts to prevent obesity. The aim of the current study was to describe morning food and drink consumption patterns among low-income, urban children and their associations with relative weight. Methods A cross-sectional analysis was conducted of data obtained from 651 4th-6th graders (51.7% female, 61.2% African American, 10.7 years) in 2012. Students completed surveys at school that included all foods eaten and their locations that morning. Height and weight were measured by trained research staff. Results On the day surveyed, 12.4% of youth reported not eating breakfast, 49.8% reported eating one breakfast, 25.5% reported eating two breakfasts, and 12.3% reported eating three or more breakfasts. The number of breakfasts consumed and BMI percentile showed a significant curvilinear relationship, with higher mean BMI percentiles observed among children who did not consume any breakfast and those who consumed ≥ 3 breakfasts. Sixth graders were significantly less likely to have consumed breakfast compared to younger children. A greater proportion of obese youth had no breakfast (18.0%) compared to healthy weight (10.1%) and overweight youth (10.7%, p = .01). Conclusions When promoting school breakfast, policies will need to be mindful of both over- and under-consumption to effectively address childhood obesity and food insecurity. Clinical trial registration NCT01924130 from http://clinicaltrials.gov/. PMID:24928474

  4. Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections

    PubMed Central

    Jones, Travis M; Johnson, Steven W; DiMondi, V Paul; Wilson, Dustin T

    2016-01-01

    JNJ-Q2 is a novel, fifth-generation fluoroquinolone that has excellent in vitro and in vivo activity against a variety of Gram-positive and Gram-negative organisms. In vitro studies indicate that JNJ-Q2 has potent activity against pathogens responsible for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), such as Staphylococcus aureus and Streptococcus pneumoniae. JNJ-Q2 also has been shown to have a higher barrier to resistance compared to other agents in the class and it remains highly active against drug-resistant organisms, including methicillin-resistant S. aureus, ciprofloxacin-resistant methicillin-resistant S. aureus, and drug-resistant S. pneumoniae. In two Phase II studies, the efficacy of JNJ-Q2 was comparable to linezolid for ABSSSI and moxifloxacin for CABP. Furthermore, JNJ-Q2 was well tolerated, with adverse event rates similar to or less than other fluoroquinolones. With an expanded spectrum of activity and low potential for resistance, JNJ-Q2 shows promise as an effective treatment option for ABSSSI and CABP. Considering its early stage of development, the definitive role of JNJ-Q2 against these infections and its safety profile will be determined in future Phase III studies. PMID:27354817

  5. Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.

    PubMed

    Jones, Travis M; Johnson, Steven W; DiMondi, V Paul; Wilson, Dustin T

    2016-01-01

    JNJ-Q2 is a novel, fifth-generation fluoroquinolone that has excellent in vitro and in vivo activity against a variety of Gram-positive and Gram-negative organisms. In vitro studies indicate that JNJ-Q2 has potent activity against pathogens responsible for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP), such as Staphylococcus aureus and Streptococcus pneumoniae. JNJ-Q2 also has been shown to have a higher barrier to resistance compared to other agents in the class and it remains highly active against drug-resistant organisms, including methicillin-resistant S. aureus, ciprofloxacin-resistant methicillin-resistant S. aureus, and drug-resistant S. pneumoniae. In two Phase II studies, the efficacy of JNJ-Q2 was comparable to linezolid for ABSSSI and moxifloxacin for CABP. Furthermore, JNJ-Q2 was well tolerated, with adverse event rates similar to or less than other fluoroquinolones. With an expanded spectrum of activity and low potential for resistance, JNJ-Q2 shows promise as an effective treatment option for ABSSSI and CABP. Considering its early stage of development, the definitive role of JNJ-Q2 against these infections and its safety profile will be determined in future Phase III studies. PMID:27354817

  6. Autism: Proceedings of Annual Meeting of the National Society for Autistic Children (4th, June 22-24, 1972, Flint Michigan).

    ERIC Educational Resources Information Center

    National Society for Autistic Children, Syracuse, NY.

    Presented are proceedings of the 4th annual (1972) meeting of the National Society for Autistic Children including 11 papers given at the meeting. Listed are officers and board members of the society, the convention committee members, and recipients of citations and awards. The president's report notes past goals, accomplishments, and future…

  7. Examining Differentiation and Utilization of iPads across Content Areas in an Independent, PreK-4th Grade Elementary School

    ERIC Educational Resources Information Center

    Milman, Natalie B.; Carlson-Bancroft, Angela; Vanden Boogart, Amy

    2014-01-01

    This mixed methods case study examined the implementation of a 1:1 iPad initiative in a suburban, co-educational, independent, preK-4th grade elementary school in the United States. This article focuses on how teachers used iPads to differentiate instruction and across multiple content areas. Findings show the processes by which teachers employed…

  8. The Relationship of Values in Elementary School 4th Grade Social Studies Textbook with the Attainments and Their Level of Being Included in Student Workbooks

    ERIC Educational Resources Information Center

    Kilic, Abdurrahman

    2012-01-01

    In this study, the relationship of values in elementary school 4th grade Social Studies textbook with the attainments and their level of being included in student workbook are tried to be determined. Case study, which is a qualitative research method, was applied for this research. To collect data, document analysis technique, which is among the…

  9. The Effect of Direct Instruction Strategy on Math Achievement of Primary 4th and 5th Grade Students with Learning Difficulties

    ERIC Educational Resources Information Center

    Al-Makahleh, Ahmad Abdulhameed Aufan

    2011-01-01

    This study seeks to verify the effect of direct instruction strategy on Math achievment of students with learning difficulties in the fourth and fifth grade levels and measure the improvement in their attitudes to Mathematics. Sample consisted of sixty (60) students with Math learning difficulties attending 4th and 5th grade level resource rooms…

  10. Color Duplex Assessment of 4th and 5th Internal Mammary Artery Perforators: The Pedicles of the Medially Based Lower Pole Breast Flaps

    PubMed Central

    Abdel-Monem, Kareem; Elshahat, Ahmed; Abou-Gamrah, Sherif; Eldin Abol-Atta, Hossam; Abd Eltawab, Reda; Massoud, Karim

    2012-01-01

    Objective: Reconstruction of a breast after mastectomy using the contralateral lower pole breast flap is an appealing procedure because it uses the tissues that were going to be excised during reduction of the sound breast to achieve symmetry. Literature mentioned that these flaps are supplied by the lower internal mammary artery perforators (IMAPs) with no further details. The aim of this study was to determine the site, size, and number of the 4th and 5th IMAPs by using preoperative color Duplex ultrasound and intraoperative exploration. Method: Twenty breasts in 10 patients who presented for reduction mammoplasty were included in this study. Preoperative color duplex was used to determine IMAPs in the 4th and 5th intercostal spaces. These perforators were localized intraoperatively. Intravenous fluorescein injection was used to determine the perfusion of the lower pole breast flap on the basis of these perforators. Results: Statistically, the 4th IMAPs diameters were significantly larger than the 5th IMAPs diameters (P < .05). The lower pole breast flap was perfused through these perforators. Conclusion: Color Duplex ultrasound is an accurate tool to preoperatively determine the 4th and 5th IMAPs. PMID:22292100

  11. The Effect of the Conceptual Change Oriented Instruction through Cooperative Learning on 4th Grade Students' Understanding of Earth and Sky Concepts

    ERIC Educational Resources Information Center

    Celikten, Oksan; Ipekcioglu, Sevgi; Ertepinar, Hamide; Geban, Omer

    2012-01-01

    The purpose of this study was to compare the effectiveness of the conceptual change oriented instruction through cooperative learning (CCICL) and traditional science instruction (TI) on 4th grade students' understanding of earth and sky concepts and their attitudes toward earth and sky concepts. In this study, 56 fourth grade students from the…

  12. Meeting Materials for the 4th NRC Meeting on the Guidance for and the Review of EPA's Toxicological Assessment of Inorganic Arsenic

    EPA Science Inventory

    On December 2-3, 2015, the National Research Council (NRC) hosted the 4th meeting of the committee formed to peer review the draft IRIS assessment of inorganic arsenic. EPA presented background and overview materials during the public session on December 2nd. This information co...

  13. U.S. Dietary and Physical Activity Guideline Knowledge and Corresponding Behaviors among 4th and 5th Grade Students: A Multi-Site Pilot Study

    ERIC Educational Resources Information Center

    Bea, Jennifer W.; Martinez, Stephanie; Armstrong-Florian, Traci; Farrell, Vanessa; Martinez, Cathy; Whitmer, Evelyn; Hartz, Vern; Blake, Samuel; Nicolini, Ariana; Misner, Scottie

    2014-01-01

    Knowledge of U.S. dietary and physical activity recommendations and corresponding behaviors were surveyed among 4th and 5th graders in five Arizona counties to determine the need for related education in SNAP-Ed eligible schools. A <70% target response rate was the criterion. Participants correctly identified recommendations for: fruit, 20%;…

  14. Nation and Language: Modern Aspects of Socio-Linguistic Development. Proceedings of the 4th International Conference (Lithuania, October 21-22, 2010)

    ERIC Educational Resources Information Center

    Online Submission, 2010

    2010-01-01

    The 4th international conference "Nation and Language: Modern Aspects of Socio-Linguistic Development" continues an eight-year old tradition. The conference is organized by Kaunas University of Technology Panevezys Institute and aims to bring scientists and researchers together for a general scientific discussion on new trends in sociolinguistic,…

  15. Analysis of the factors that significantly influence the stability of fluoroquinolone-metal complexes.

    PubMed

    Urbaniak, Bartosz; Kokot, Zenon J

    2009-08-01

    The aim of the present study was to evaluate factors contributing to the differences between the overall stability constants (logbeta(pqr)) of the fluoroquinolone-metal ion complexes. The experiments were performed using potentiometric titration method in wide pH range. The overall stability constants (logbeta(pqr)) were determined using the Hyperquad program. Complexation equilibria of eight different fluoroquinolones with six divalent and trivalent metal ions were investigated in this study. The authors employed a multifactorial ANOVA analysis, fixed effect model to describe the influence of particular variables affecting the stability of the analyzed complex species. Four different variables were set at different levels labeled. The ligand number (LF) was the first factor. LF determined the number of fluorochinolone molecules in the complex structure, and could take the values 1, 2 or 3. The second factor (Me) was connected with the type of the metal ion bonded in the complex. Since six different metal cations were studied, the Me factor was described with six levels. The number of hydrogen or hydroxide groups substituted into the complex molecule was the third variable (HR) with many levels labeled: q, a, s, d, f and g. The last factor FQ described the type of the fluorochinolone used for complex formations. All variables analyzed here were statistically significant (p value lower than 0.01), which indicates that all of them strongly affect the logbeta(pqr) value. Binary interactions (LF-Me, LF-FQ, Me-HR and Me-FQ) between variables were also stated, which suggests that the effects of these variables were higher than we could calculate based on the effect of each variable alone. The ANOVA analysis has shown that the following factors Me, LF and HR were the most important for the stability of the fluoroquinolone-metal ion complexes. It was also found that according to the FQ factor (type of ligand molecule) all analyzed fluoroquinolones formed stable complexes

  16. Contribution of Target Gene Mutations and Efflux to Decreased Susceptibility of Salmonella enterica Serovar Typhimurium to Fluoroquinolones and Other Antimicrobials▿

    PubMed Central

    Chen, Sheng; Cui, Shenghui; McDermott, Patrick F.; Zhao, Shaohua; White, David G.; Paulsen, Ian; Meng, Jianghong

    2007-01-01

    The mechanisms involved in fluoroquinolone resistance in Salmonella enterica include target alterations and overexpression of efflux pumps. The present study evaluated the role of known and putative multidrug resistance efflux pumps and mutations in topoisomerase genes among laboratory-selected and naturally occurring fluoroquinolone-resistant Salmonella enterica serovar Typhimurium strains. Strains with ciprofloxacin MICs of 0.25, 4, 32, and 256 μg/ml were derived in vitro using serovar Typhimurium S21. These mutants also showed decreased susceptibility or resistance to many nonfluoroquinolone antimicrobials, including tetracycline, chloramphenicol, and several β-lactams. The expression of efflux pump genes acrA, acrB, acrE, acrF, emrB, emrD, and mdlB were substantially increased (≥2-fold) among the fluoroquinolone-resistant mutants. Increased expression was also observed, but to a lesser extent, with three other putative efflux pumps: mdtB (yegN), mdtC (yegO), and emrA among mutants with ciprofloxacin MICs of ≥32 μg/ml. Deletion of acrAB or tolC in S21 and its fluoroquinolone-resistant mutants resulted in increased susceptibility to fluoroquinolones and other tested antimicrobials. In naturally occurring fluoroquinolone-resistant serovar Typhimurium strains, deletion of acrAB or tolC increased fluoroquinolone susceptibility 4-fold, whereas replacement of gyrA double mutations (S83F D87N) with wild-type gyrA increased susceptibility >500-fold. These results indicate that a combination of topoisomerase gene mutations, as well as enhanced antimicrobial efflux, plays a critical role in the development of fluoroquinolone resistance in both laboratory-derived and naturally occurring quinolone-resistant serovar Typhimurium strains. PMID:17043131

  17. Type II Topoisomerase Mutations in Fluoroquinolone-Resistant Clinical Strains of Pseudomonas aeruginosa Isolated in 1998 and 1999: Role of Target Enzyme in Mechanism of Fluoroquinolone Resistance

    PubMed Central

    Akasaka, Takaaki; Tanaka, Mayumi; Yamaguchi, Akihito; Sato, Kenichi

    2001-01-01

    The major mechanism of resistance to fluoroquinolones for Pseudomonas aeruginosa is the modification of type II topoisomerases (DNA gyrase and topoisomerase IV). We examined the mutations in quinolone-resistance-determining regions (QRDR) of gyrA, gyrB, parC, and parE genes of recent clinical isolates. There were 150 isolates with reduced susceptibilities to levofloxacin and 127 with reduced susceptibilities to ciprofloxacin among 513 isolates collected during 1998 and 1999 in Japan. Sequencing results predicted replacement of an amino acid in the QRDR of DNA gyrase (GyrA or GyrB) for 124 of the 150 strains (82.7%); among these, 89 isolates possessed mutations in parC or parE which lead to amino acid changes. Substitutions of both Ile for Thr-83 in GyrA and Leu for Ser-87 in ParC were the principal changes, being detected in 48 strains. These replacements were obviously associated with reduced susceptibilities to levofloxacin, ciprofloxacin, and sparfloxacin; however, sitafloxacin showed high activity against isolates with these replacements. We purified GyrA (The-83 to Ile) and ParC (Ser-87 to Leu) by site-directed mutagenesis and compared the inhibitory activities of the fluoroquinolones. Sitafloxacin showed the most potent inhibitory activities against both altered topoisomerases among the fluoroquinolones tested. These results indicated that, compared with other available quinolones, sitafloxacin maintained higher activity against recent clinical isolates with multiple mutations in gyrA and parC, which can be explained by the high inhibitory activities of sitafloxacin against both mutated enzymes. PMID:11451683

  18. Fluoroquinolone and Macrolide Exposure Predict Clostridium difficile Infection with the Highly Fluoroquinolone- and Macrolide-Resistant Epidemic C. difficile Strain BI/NAP1/027

    PubMed Central

    Wieczorkiewicz, Jeffrey T.; Lopansri, Bert K.; Cheknis, Adam; Osmolski, James R.; Hecht, David W.; Gerding, Dale N.

    2015-01-01

    Antibiotics have been shown to influence the risk of infection with specific Clostridium difficile strains as well as the risk of C. difficile infection (CDI). We performed a retrospective case-control study of patients infected with the epidemic BI/NAP1/027 strain in a U.S. hospital following recognition of increased CDI severity and culture of stools positive by C. difficile toxin immunoassay. Between 2005 and 2007, 72% (103/143) of patients with first-episode CDIs were infected with the BI strain by restriction endonuclease analysis (REA) typing. Most patients received multiple antibiotics within 6 weeks of CDI onset (median of 3 antibiotic classes). By multivariate analysis, fluoroquinolone and macrolide exposure was more frequent among BI cases than among non-BI-infected controls (odds ratio [OR] for fluoroquinolones, 3.2; 95% confidence interval [CI], 1.3 to 7.5; (P < 0.001; OR for macrolides, 5.2; 95% CI, 1.1 to 24.0; P = 0.04)). In contrast, clindamycin use was less frequent among the BI cases than among the controls (OR, 0.1; 95% CI, 0.03 to 0.4; P = 0.001). High-level resistance to moxifloxacin and azithromycin was more frequent among BI strains (moxifloxacin, 49/102 [48%] BI versus 0/40 non-BI, P = 0.0001; azithromycin, 100/102 [98%] BI versus 22/40 [55%] non-BI, P = 0.0001). High-level resistance to clindamycin was more frequent among non-BI strains (22/40 [55%] non-BI versus 7/102 [7%] BI, P = 0.0001). Fluoroquinolone use, macrolide use, and C. difficile resistance to these antibiotic classes were associated with infection by the epidemic BI strain of C. difficile in a U.S. hospital during a time when CDI rates were increasing nationally due to the highly fluoroquinolone-resistant BI/NAP1/027 strain. PMID:26525793

  19. Fluoroquinolone-resistant Campylobacter infections: eating poultry outside of the home and foreign travel are risk factors.

    PubMed

    Kassenborg, Heidi D; Smith, Kirk E; Vugia, Duc J; Rabatsky-Ehr, Therese; Bates, Martha R; Carter, Michael A; Dumas, Nellie B; Cassidy, Maureen P; Marano, Nina; Tauxe, Robert V; Angulo, Frederick J

    2004-04-15

    A 12-month, population-based, case-control study of Campylobacter infections was conducted at Foodborne Disease Active Surveillance Network surveillance areas during 1998-1999. Of 858 Campylobacter isolates tested for antimicrobial susceptibility to the fluoroquinolone ciprofloxacin, 94 (11%) were resistant. Travel outside of the United States was reported by 27 (42%) of 64 patients with fluoroquinolone-resistant Campylobacter infection and by 51 (9%) of 582 patients with fluoroquinolone-susceptible Campylobacter infection (odds ratio [OR], 7.6; 95% confidence interval [CI], 4.3-13.4). When patients with domestically acquired fluoroquinolone-resistant Campylobacter infection were compared with matched healthy control subjects in a multivariate analysis, those infected were 10 times more likely to have eaten chicken or turkey cooked at a commercial establishment (18 [55%] of 33 case patients vs. 7 [21%] of 33 controls; matched OR, 10.0; 95% CI, 1.3-78). Although travel outside of the United States was associated with fluoroquinolone-resistant Campylobacter infection, most infections among study participants were domestically acquired. This study provides additional evidence that poultry is an important source of domestically acquired fluoroquinolone-resistant Campylobacter infection. Control measures should include efforts to improve food handling in commercial establishments. PMID:15095200

  20. A Brief Boot Camp for 4th-Year Medical Students Entering into Pediatric and Family Medicine Residencies

    PubMed Central

    Adler, Mark; Mangold, Karen; Trainor, Jennifer

    2016-01-01

    The transition from medical student to intern is a challenging process characterized by a steep learning curve. Focused courses targeting skills necessary for success as a resident have increased self-perceived preparedness, confidence, and medical knowledge. Our aim was to create a brief educational intervention for 4th-year medical students entering pediatric, family practice, and medicine/pediatric residencies to target skills necessary for an internship. The curriculum used a combination of didactic presentations, small group discussions, role-playing, facilitated debriefing, and simulation-based education. Participants completed an objective structured clinical exam requiring synthesis and application of multiple boot camp elements before and after the elective. Participants completed anonymous surveys assessing self-perceived preparedness for an internship, overall and in regards to specific skills, before the elective and after the course. Participants were asked to provide feedback about the course. Using checklists to assess performance, students showed an improvement in performing infant lumbar punctures (47.2% vs 77.0%; p < 0.01, 95% CI for the difference 0.2, 0.4%) and providing signout (2.5 vs. 3.9 (5-point scale) p < 0.01, 95% CI for the difference 0.6, 2.3). They did not show an improvement in communication with a parent. Participants demonstrated an increase in self-reported preparedness for all targeted skills, except for obtaining consults and interprofessional communication. There was no increase in reported overall preparedness. All participants agreed with the statements, “The facilitators presented the material in an effective manner,” “I took away ideas I plan to implement in internship,” and “I think all students should participate in a similar experience.” When asked to assess the usefulness of individual modules, all except order writing received a mean Likert score > 4. A focused boot camp addressing key knowledge and skills

  1. A Brief Boot Camp for 4th-Year Medical Students Entering into Pediatric and Family Medicine Residencies.

    PubMed

    Burns, Rebekah; Adler, Mark; Mangold, Karen; Trainor, Jennifer

    2016-01-01

    The transition from medical student to intern is a challenging process characterized by a steep learning curve. Focused courses targeting skills necessary for success as a resident have increased self-perceived preparedness, confidence, and medical knowledge. Our aim was to create a brief educational intervention for 4th-year medical students entering pediatric, family practice, and medicine/pediatric residencies to target skills necessary for an internship. The curriculum used a combination of didactic presentations, small group discussions, role-playing, facilitated debriefing, and simulation-based education. Participants completed an objective structured clinical exam requiring synthesis and application of multiple boot camp elements before and after the elective. Participants completed anonymous surveys assessing self-perceived preparedness for an internship, overall and in regards to specific skills, before the elective and after the course. Participants were asked to provide feedback about the course. Using checklists to assess performance, students showed an improvement in performing infant lumbar punctures (47.2% vs 77.0%; p < 0.01, 95% CI for the difference 0.2, 0.4%) and providing signout (2.5 vs. 3.9 (5-point scale) p < 0.01, 95% CI for the difference 0.6, 2.3). They did not show an improvement in communication with a parent. Participants demonstrated an increase in self-reported preparedness for all targeted skills, except for obtaining consults and interprofessional communication. There was no increase in reported overall preparedness. All participants agreed with the statements, "The facilitators presented the material in an effective manner," "I took away ideas I plan to implement in internship," and "I think all students should participate in a similar experience." When asked to assess the usefulness of individual modules, all except order writing received a mean Likert score > 4. A focused boot camp addressing key knowledge and skills required for

  2. PREFACE: 9th World Congress on Computational Mechanics and 4th Asian Pacific Congress on Computational Mechanics

    NASA Astrophysics Data System (ADS)

    Khalili, N.; Valliappan, S.; Li, Q.; Russell, A.

    2010-07-01

    The use for mathematical models of natural phenomena has underpinned science and engineering for centuries, but until the advent of modern computers and computational methods, the full utility of most of these models remained outside the reach of the engineering communities. Since World War II, advances in computational methods have transformed the way engineering and science is undertaken throughout the world. Today, theories of mechanics of solids and fluids, electromagnetism, heat transfer, plasma physics, and other scientific disciplines are implemented through computational methods in engineering analysis, design, manufacturing, and in studying broad classes of physical phenomena. The discipline concerned with the application of computational methods is now a key area of research, education, and application throughout the world. In the early 1980's, the International Association for Computational Mechanics (IACM) was founded to promote activities related to computational mechanics and has made impressive progress. The most important scientific event of IACM is the World Congress on Computational Mechanics. The first was held in Austin (USA) in 1986 and then in Stuttgart (Germany) in 1990, Chiba (Japan) in 1994, Buenos Aires (Argentina) in 1998, Vienna (Austria) in 2002, Beijing (China) in 2004, Los Angeles (USA) in 2006 and Venice, Italy; in 2008. The 9th World Congress on Computational Mechanics is held in conjunction with the 4th Asian Pacific Congress on Computational Mechanics under the auspices of Australian Association for Computational Mechanics (AACM), Asian Pacific Association for Computational Mechanics (APACM) and International Association for Computational Mechanics (IACM). The 1st Asian Pacific Congress was in Sydney (Australia) in 2001, then in Beijing (China) in 2004 and Kyoto (Japan) in 2007. The WCCM/APCOM 2010 publications consist of a printed book of abstracts given to delegates, along with 247 full length peer reviewed papers published with

  3. A Case of Fluoroquinolone-Resistant Leprosy Discovered after 9 Years of Misdiagnosis

    PubMed Central

    Ramarozatovo, Lala S.; Ranaivo, Irina M.; Andrianarison, Malalaniaina; Cambau, Emmanuelle

    2016-01-01

    We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V). After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed. PMID:27579195

  4. Adverse drug reactions to fluoroquinolones at a tertiary care hospital in northern India.

    PubMed

    Uppal, R; Jhaj, R; Malhotra, S

    1998-11-01

    Use of fluoroquinolones has increased considerably in the last 5-6 years in our hospitals. With a view to ascertain their safety and the type of adverse drug reactions (ADRs) in our population, spontaneous reports were collected and analysed to ciprofloxacin (the most prescribed fluoroquinolone in our hospital) over a period of three and a half years. The pattern of reactions were rash in 18, severe reactions like Steven Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in 4, gastritis and diarrhoea in 3, shivering and rigors in 2, hemorrhagic purpuric spots in 2 and oedema of eye and lids with topical application in 1 patient. Most cases recovered on stoppage of the drug and symptomatic treatment. However, one case of SJS and one of TEN proved fatal. Care needs to be exercised in their use and they do not appear to be innocuous to severe and disturbing ADRs. PMID:11229222

  5. A Case of Fluoroquinolone-Resistant Leprosy Discovered after 9 Years of Misdiagnosis.

    PubMed

    Raharolahy, Onivola; Ramarozatovo, Lala S; Ranaivo, Irina M; Sendrasoa, Fandresena A; Andrianarison, Malalaniaina; Andrianarivelo, Mala Rakoto; Cambau, Emmanuelle; Rabenja, Fahafahantsoa Rapelanoro

    2016-01-01

    We report a case of misdiagnosed leprosy in a 21-year-old Malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. The patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. Initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. Subsequent long-term self-medication with ciprofloxacin and corticosteroid did not heal the foul and nonhealing ulcers on the legs and under the right sole. Histopathological findings were compatible with lepromatous leprosy. Skin biopsy was positive for acid-fast bacilli and PCR assay confirmed the presence of a fluoroquinolone-resistant strain of Mycobacterium leprae (gyrA A91V). After 6 months of standard regimen with rifampicin, clofazimine, and dapsone, clinical outcome significantly improved. Clinical characteristics and possible epidemiological implications are discussed. PMID:27579195

  6. Fluoroquinolone Resistance Among Gram-Negative Urinary Tract Pathogens: Global Smart Program Results, 2009-2010

    PubMed Central

    Bouchillon, Sam; Hoban, Daryl J; Badal, Robert; Hawser, Stephen

    2012-01-01

    OBJECTIVES: To determine the rates of fluoroquinolone resistant (FQR) in gram-negative bacilli urinary tract infections (UTIs) in a global population. METHODS: The Study for Monitoring Antimicrobial Resistance Trends (SMART) collected 1,116 FQR gram-negative urinary pathogens from hospitalized patients in 33 countries during 2009-2010. Amikacin, ertapenem, and imipenem were the most active agents tested against FQR UTI pathogens, including extended-spectrum beta-lactamase producers. RESULTS: FQR rates vary widely country to country with a range of 6% to 75%. Regional FQR rates were 23.5% in North America, 29.4% in Europe, 33.2% in Asia, 38.7% in Latin America, and 25.5% in the South Pacific. CONCLUSIONS: These observations suggest that fluoroquinolones may no longer be effective as first-line therapy for gram-negative UTI in hospitalized patients. PMID:23002406

  7. Synthesis and biological properties of conjugates between fluoroquinolones and a N3''-functionalized pyochelin.

    PubMed

    Noël, Sabrina; Gasser, Véronique; Pesset, Bénédicte; Hoegy, Françoise; Rognan, Didier; Schalk, Isabelle J; Mislin, Gaëtan L A

    2011-12-21

    Pyochelin is a siderophore common to Pseudomonas aeruginosa and several other pathogenic bacteria. A pyochelin functionalized at the N3'' position with a propyl-amine extension was previously synthesized. In the present work we proved that this analog binds FptA, the pyochelin outer membrane receptor, and transports iron(III) efficiently into bacteria. This functionalized pyochelin seemed to be a good candidate for antibiotic vectorization in the framework of a Trojan horse prodrug strategy. In this context, conjugates between pyochelin and three fluoroquinolones (norfloxacin, ciprofloxacin and N-desmethyl-ofloxacin) were synthesized with a spacer arm that was either stable or hydrolyzable in vivo. Some pyochelin-fluoroquinolone conjugates had antibacterial activities in growth inhibition experiments on several P. aeruginosa strains. However, these activities were weaker than those of the antibiotic alone. These properties appeared to be related to both the solubility and bioavailability of conjugates and to the stability of the spacer arm used. PMID:22052022

  8. Occurrence of highly fluoroquinolone-resistant and methicillin-resistant Staphylococcus aureus in domestic animals.

    PubMed

    Lin, Ann E; Davies, Julian E

    2007-07-01

    We describe phenotypic and genotypic analyses carried out on multidrug-resistant Staphylococcus aureus isolated from domestic animals. The sequence type ST239 methicillin-resistant Staphylococcus aureus isolated from dogs were highly resistant to fluoroquinolones, and new combinations of GyrA and GrlA mutations were identified. These findings are consistent with a role for animal carriage in the dissemination of important human pathogens in the community. PMID:17898848

  9. Fluoroquinolones in the Wenyu River catchment, China: Occurrence simulation and risk assessment.

    PubMed

    Hao, Xuewen; Cao, Yan; Zhang, Lai; Zhang, Yongyong; Liu, Jianguo

    2015-12-01

    Concern is increasing regarding the environmental impact of the high usage rate and intensive release of antibiotics used for human and animal therapy in major urban areas of China. In the present study, regional environmental distribution simulations and risk assessments for 3 commonly used fluoroquinolones in the Wenyu River catchment were conducted using a typical catchment model widely used in Europe. The fluoroquinolone antibiotics investigated (ofloxacin, norfloxacin, and ciprofloxacin) are consumed at high levels for personal health care in China. These antibiotics were simulated in the aquatic environment of the Wenyu River catchment across the Beijing City area for annual average concentrations, with regional predicted environmental concentrations (PECs) of approximately 711 ng/L, 55.3 ng/L, and 22.2 ng/L and local PECs up to 1.8 µg/L, 116 ng/L, and 43 ng/L, respectively. Apart from hydrological conditions, the concentrations of fluoroquinolones were associated closely with the sewage treatment plants (STPs) and their serving population, as well as hospital distributions. The presence of these fluoroquinolones in the catchment area of the present study showed significant characteristics of the occurrence of pharmaceuticals in the aquatic environment in an urban river, with typical "down-the-drain" chemicals. Significantly high concentrations of specific antibiotics indicated non-negligible risks caused by the intensive use in the local aquatic environment in a metropolitan area, particularly ofloxacin in upstream Shahe Reservoir, middle stream and downstream Qing River, and Liangma River to the Ba River segment. Specific treatment measures for these pharmaceuticals and personal care products in STPs are required for such metropolitan areas. PMID:26178666

  10. Synthesis and antibacterial evaluation of a novel tricyclic oxaborole-fused fluoroquinolone.

    PubMed

    Li, Xianfeng; Zhang, Yong-Kang; Plattner, Jacob J; Mao, Weimin; Alley, M R K; Xia, Yi; Hernandez, Vincent; Zhou, Yasheen; Ding, Charles Z; Li, Jinpeng; Shao, Zhijun; Zhang, Hongwei; Xu, Musheng

    2013-02-15

    We have designed and synthesized a novel class of compounds based on fluoroquinolone antibacterial prototype. The design concept involved the replacement of the 3-carboxylic acid in ciprofloxacin with an oxaborole-fused ring as an acid-mimicking group. The synthetic method employed in this work provides a good example of incorporating boron atom in complex molecules with multiple functional groups. The antibacterial activity of the newly synthesized compounds has been evaluated. PMID:23312945

  11. Dissimilar Fitness Associated with Resistance to Fluoroquinolones Influences Clonal Dynamics of Various Multiresistant Bacteria

    PubMed Central

    Fuzi, Miklos

    2016-01-01

    Fitness cost associated with resistance to fluoroquinolones was recently shown to vary across clones of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamase-producing Klebsiella pneumoniae. The resulting dissimilar fitness should have influenced the clonal dynamics and thereby the rates of resistance for these pathogens. Moreover, a similar mechanism was recently proposed for the emergence of the H30 and H30R lineages of ESBL-producing E. coli and the major international clone (ribotype 027) of Clostridium difficile. Furthermore, several additional international clones of various multiresistant bacteria are suspect to have been selected by an analogous process. An ability to develop favorable mutations in the gyrase and topoisomerase IV genes seems to be a prerequisite for pathogens to retain fitness while showing high-level resistance to fluoroquinolones. Since, the consumption of other “non-fluoroquinolone” groups of antibiotics have also contributed to the rise in resistance rates a more judicious use of antibiotics in general and of fluoroquinolones in particular could ameliorate the international resistance situation. PMID:27458434

  12. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones

    PubMed Central

    Malik, Muhammad; Mustaev, Arkady; Schwanz, Heidi A.; Luan, Gan; Shah, Nirali; Oppegard, Lisa M.; de Souza, Ernane C.; Hiasa, Hiroshi; Zhao, Xilin; Kerns, Robert J.; Drlica, Karl

    2016-01-01

    Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions in Escherichia coli GyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment of E. coli cultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance. PMID:26984528

  13. Suppression of gyrase-mediated resistance by C7 aryl fluoroquinolones.

    PubMed

    Malik, Muhammad; Mustaev, Arkady; Schwanz, Heidi A; Luan, Gan; Shah, Nirali; Oppegard, Lisa M; de Souza, Ernane C; Hiasa, Hiroshi; Zhao, Xilin; Kerns, Robert J; Drlica, Karl

    2016-04-20

    Fluoroquinolones form drug-topoisomerase-DNA complexes that rapidly block transcription and replication. Crystallographic and biochemical studies show that quinolone binding involves a water/metal-ion bridge between the quinolone C3-C4 keto-acid and amino acids in helix-4 of the target proteins, GyrA (gyrase) and ParC (topoisomerase IV). A recent cross-linking study revealed a second drug-binding mode in which the other end of the quinolone, the C7 ring system, interacts with GyrA. We report that addition of a dinitrophenyl (DNP) moiety to the C7 end of ciprofloxacin (Cip-DNP) reduced protection due to resistance substitutions inEscherichia coliGyrA helix-4, consistent with the existence of a second drug-binding mode not evident in X-ray structures of drug-topoisomerase-DNA complexes. Several other C7 aryl fluoroquinolones behaved in a similar manner with particular GyrA mutants. Treatment ofE. colicultures with Cip-DNP selectively enriched an uncommon variant, GyrA-A119E, a change that may impede binding of the dinitrophenyl group at or near the GyrA-GyrA interface. Collectively the data support the existence of a secondary quinolone-binding mode in which the quinolone C7 ring system interacts with GyrA; the data also identify C7 aryl derivatives as a new way to obtain fluoroquinolones that overcome existing GyrA-mediated quinolone resistance. PMID:26984528

  14. Toward an understanding of the mode of action of fluoroquinolone drugs

    NASA Astrophysics Data System (ADS)

    Neugebauer, U.; Schmid, U.; Baumann, K.; Holzgrabe, U.; Schmitt, M.; Popp, J.

    2007-07-01

    Fluoroquinolones are important antibacterial drugs. They were found to interfere with the gyrase-DNA complex which causes cell death. However, the detailed mode of action on a molecular level is so far not understood. In this contribution Raman spectroscopy is chosen as a non-invasive technique to first characterize the individual involved components: fluoroquinolone drugs, and the biological targets DNA and gyrase; and second to study the influence of the fluoroquinolones on bacteria in in-vivo experiments. The use of UV resonance Raman spectroscopy with excitation at 244 nm allows the investigation of the drugs and the biological targets in aqueous solution at biological low concentrations (a few μM). Raman bands associated with the action of the enzyme gyrase could be identified in in-vitro mixing experiments. In-vivo experiments with bacteria experiencing varying drug concentrations revealed changes in the vibrational bands of the protein and DNA components within the bacterial cell caused by the action of the drug. Due to the complexity of the bacterial spectra advanced multivariate statistics in combination with variable selection methods proved to be useful in the data analysis.

  15. Structural Insights into the Fluoroquinolone Resistance Mechanism of Shigella flexneri DNA Gyrase and Topoisomerase IV.

    PubMed

    Tamanna; Ramana, Jayashree

    2016-07-01

    Traveler's diarrhea (TD) is an important public health concern that can result from a variety of intestinal pathogens, including bacteria, parasites, and virus. A number of antibiotics are being used to cure TD, but due to widespread use of these antibiotics, the pathogens are becoming resistant to them. In this work, we performed docking studies of DNA gyraseA (GyrA) and topoisomerase IV (ParC) of Shigella flexneri and their mutants with two different fluoroquinolones, ciprofloxacin and norfloxacin, to understand their resistance mechanism at the structural level. S. flexneri strains with mutations at serine 83 to leucine and aspartic acid 87 to glutamate or asparagine of GyrA and that of serine 80 to isoleucine in ParC have decreased susceptibility to fluoroquinolones. This analysis revealed that interaction of ciprofloxacin/norfloxacin with all the mutants was weaker than the interaction of ciprofloxacin/norfloxacin with the wild type. This study highlights the importance of aspartic acid and serine in GyrA and that of serine in ParC, forming bonds with ciprofloxacin/norfloxacin, which may play a crucial role in antibiotic resistance. This work corelates very well with the experimental outcomes and gives a good explanation for fluoroquinolone resistance in S. flexneri. PMID:26859259

  16. Generations.

    PubMed

    Chambers, David W

    2005-01-01

    Groups naturally promote their strengths and prefer values and rules that give them an identity and an advantage. This shows up as generational tensions across cohorts who share common experiences, including common elders. Dramatic cultural events in America since 1925 can help create an understanding of the differing value structures of the Silents, the Boomers, Gen Xers, and the Millennials. Differences in how these generations see motivation and values, fundamental reality, relations with others, and work are presented, as are some applications of these differences to the dental profession. PMID:16623137

  17. Comparison of rhodomine-WT and sodium chloride tracer transport in a 4th order arctic river

    NASA Astrophysics Data System (ADS)

    Smull, E. M.; Wlostowski, A. N.; Gooseff, M. N.; Bowden, W. B.; Wollheim, W. M.

    2012-12-01

    Conservative tracers are useful for tracking a parcel of water through a river reach and understanding tracer transport phenomena (i.e. advection, dispersion, and transient storage). Rhodomine- WT (RWT) and sodium chloride (NaCl) are two popular stream tracers. NaCl is considered to be conservative and relatively inexpensive, yet it cannot be detected at very low concentrations. On the other hand, RWT can be detected at very low concentrations (<0.1 ppb), but it is known to photo-degrade and sorb to organic materials. Previous work has compared these tracers with small-scale laboratory analyses and field experiments on small headwater streams. The limitations and advantages to each of these tracers, as applied to large river slug injections, are not clearly understood. This work seeks to answer the following questions: 1) Does RWT improve the tracer window of detection (time of tracer arrival to time of tracer non-detection), compared to NaCl? 2) Are there differences in the late-time tailing behavior of each tracer? More specifically, can we compare RWT and NaCl breakthrough curve tail shapes to understand processes contributing to late time solute transport (transient storage or sorption-desorption)? During the summer of 2012, combined slug additions of RWT and NaCl were injected into a 1.5-kilometer reach on the Kuparuk River, a 4th order tundra river underlain by continuous permafrost located on Alaska's North Slope. Fluorescence and electrical conductivity were continuously logged at the upstream and downstream ends of the reach. Preliminary results show that the window of detection is expanded when using RWT under both high and low flow conditions by 0.2 times the advective transport timescale. Tail shapes are more similar under higher discharge conditions and dissimilar under lower discharge conditions. For example, using an exponential regression model (c(t) = eat) to quantify tail shapes, at Q = 500 l/s the exponential coefficient ratio, aRWT:aNaCl, is 0

  18. Different mechanisms for the photoinduced production of oxidative DNA damage by fluoroquinolones differing in photostability.

    PubMed

    Spratt, T E; Schultz, S S; Levy, D E; Chen, D; Schlüter, G; Williams, G M

    1999-09-01

    Several fluoroquinolone antibacterial agents exhibit an adverse phototoxic effect in humans and are photo-cocarcinogenic in mice. The UV-induced production of reactive oxygen species plays a role in the toxicity and may be involved in carcinogenicity. Four fluoroquinolones were examined for the ability to photochemically produce oxidative damage in naked DNA. The major structural difference in the fluoroquinolones that would have an effect on their photostability is the functionality at the 8-position. At this position, 1-cyclopropyl-7-(2,8-diazbicyclo[4.3.0]non-8-yl)-6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (BAY y3118) contains a chlorine atom, lomefloxacin a fluorine atom, ciprofloxacin a proton, and moxifloxacin a methoxy group. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in calf thymus DNA was assessed by HPLC with electrochemical detection, and strand breaks were measured in pBR322 with agarose gel electrophoresis. The relative photolability of the fluoroquinolones correlated to the extent of production of 8-oxodGuo and strand breaks, with both UVA and UVB irradiation, in the following order: BAY y3118 approximately lomefloxacin > ciprofloxacin > moxifloxacin. Experiments were performed to determine whether the mechanism of damage was due to a type I (radical) or type II (singlet oxygen) pathway. Nitrogen depletion of oxygen resulted in a decrease in the extent of formation of 8-oxodGuo, suggesting that oxygen was involved. The use of selective radical or singlet oxygen inhibitors was inconclusive with respect to which pathway was involved. The use of D(2)O as a solvent, which would extend the lifetime of singlet oxygen, suggested that this species is involved in the formation of 8-oxodGuo by moxifloxacin and ciprofloxacin, but not by lomefloxacin and BAY y3118. Similarly, it was found that singlet oxygen was not involved in strand break formation. Thus, the evidence suggests that fluoroquinolones can photochemically

  19. Molecular modeling assisted hapten design to produce broad selectivity antibodies for fluoroquinolone antibiotics.

    PubMed

    Pinacho, Daniel G; Sánchez-Baeza, Francisco; Marco, M-Pilar

    2012-05-15

    Antibodies with a wide recognition profile of fluoroquinolone antibiotics have been produced based on chemical criteria, theoretical studies, and molecular modeling assisted hapten design. The immunizing hapten preserves the most important and characteristic epitopes of this antibiotic family. The studies have taken into consideration the zwitterionic character of most of the fluoroquinolones and the relative concentration of the different species in equilibrium at physiologic pH. The hapten is prepared in the form of a stable prehapten through a 5 step synthetic pathway. Immediately before conjugation, the immunizing hapten is obtained by removing the diphenylmethane protecting group. The specificity of the antibodies obtained is directed toward the common area defined by the fluorine atom at position 6 and the β-ketoacid moiety. The ELISA developed is able to recognize with very good detectability important fluoroquinolones used in the veterinary field such as ciprofloxacin (CPFX, IC(50), 0.35 μg L(-1)), enrofloxacin (ERFX, IC(50), 0.65 μg L(-1)), danofloxacin (DNFX, IC(50), 7.31 μg L(-1)), difloxacin (DFX, IC(50), 0.91 μg L(-1)), sarafloxacin (SRFX, IC(50), 0.96 μg L(-1)), norfloxacin (NRFX, IC(50), 0.78 μg L(-1)), ofloxacin (OFX, IC(50), 1.84 μg L(-1)), flumequine (Flume, IC(50), 3.91 μ gL(-1)), marbofloxacin (MBFX, IC(50), 4.30 μ gL(-1)), and oxolinic acid (OXO, IC(50), 23.53 μg L(-1)). The results presented here demonstrate that the antibody affinity is strongly affected by the presence of divalent cations, owing to their complexation with the fluoroquinolone molecules. Moreover, the outcome from the effect of the pH on the immunochemical assays suggests that the selectivity could be modulated with the pH due to the zwitterionic character of the fluoroquinolones and as a function of their different pK(a) values. PMID:22545705

  20. Genetic characterization of fluoroquinolone-resistant Escherichia coli associated with bovine mastitis in India

    PubMed Central

    Balakrishnan, Sangeetha; Antony, Prabhakar Xavier; Mukhopadhyay, Hirak Kumar; Pillai, Raghavan Madhusoodanan; Thanislass, Jacob; Padmanaban, Vijayalakshmi; Srinivas, Mouttou Vivek

    2016-01-01

    Aim: The present study was undertaken to characterize the mutation in gyrA (DNA gyrase) and parC (topoisomerase IV) genes responsible for fluoroquinolone resistance in Escherichia coli isolates associated with the bovine mastitis. Materials and Methods: A total of 92 milk samples from bovine mastitis cases were sampled in and around Puducherry (Southern India). Among these samples, 30 isolates were bacteriologically characterized as E. coli. Minimum inhibitory concentrations (MIC) of fluoroquinolones of these 30 E. coli isolates were evaluated by resazurin microtiter assay. Then, the quinolone resistance determining region (QRDR) (gyrA and parC genes) of these E. coli isolates was genetically analyzed for determining the chromosomal mutation causing fluoroquinolone resistance. Results: E. coli isolates showed a resistance rate of 63.33%, 23.33% and 30.03% to nalidixic acid, ciprofloxacin and enrofloxacin, respectively. Mutations were found at 83rd and 87th amino acid position of gyrA gene, and at 80th and 108th amino acid position of parC gene in our study isolates. Among these five isolates, one had a single mutation at 83 amino acid position of gyrA with reduced susceptibility (0.5 µg/ml) to ciprofloxacin. Then, in remaining four isolates, three isolates showed triple mutation (at gyrA: S83⟶L and D87⟶N; at parC: S80⟶I) and the fifth isolate showed an additional mutation at codon 108 of parC (A108⟶T) with the increased ciprofloxacin MIC of 16-128 µg/ml. The most common mutation noticed were at S83⟶L and D87⟶N of gyrA and S80⟶I of ParC. Conclusion: The study confirms the presence of mutation/s responsible for fluoroquinolone resistance in QRDR of gyrA and parC genes of E. coli isolates of animal origin, and there is increased rate of fluoroquinolone resistance with high-level of MIC. The mutations observed in this study were similar to that of human isolates. PMID:27536030

  1. Syntheses and single-crystal structures of CsTh(MoO 4) 2Cl and Na 4Th(WO 4) 4

    NASA Astrophysics Data System (ADS)

    Bang Jin, Geng; Soderholm, L.

    2011-02-01

    Colorless crystals of CsTh(MoO 4) 2Cl and Na 4Th(WO 4) 4 have been synthesized at 993 K by the solid-state reactions of ThO 2, MoO 3, CsCl, and ThCl 4 with Na 2WO 4. Both compounds have been characterized by the single-crystal X-ray diffraction. The structure of CsTh(MoO 4) 2Cl is orthorhombic, consisting of two adjacent [Th(MoO 4) 2] layers separated by an ionic CsCl sublattice. It can be considered as an insertion compound of Th(MoO 4) 2 and reformulated as Th(MoO 4) 2·CsCl. The Th atom coordinates to seven monodentate MoO 4 tetrahedra and one Cl atom in a highly distorted square antiprism. Na 4Th(WO 4) 4 adopts a scheelite superlattice structure. The three-dimensional framework of Na 4Th(WO 4) 4 is constructed from corner-sharing ThO 8 square antiprisms and WO 4 tetrahedra. The space within the channels is filled by six-coordinate Na ions. Crystal data: CsTh(MoO 4) 2Cl, monoclinic, P2 1/ c, Z=4, a=10.170(1) Å, b=10.030(1) Å, c=9.649(1) Å, β=95.671(2)°, V=979.5(2) Å 3, R( F)=2.65% for I>2 σ( I); Na 4Th(WO 4) 4, tetragonal, I4 1/ a, Z=4, a=11.437(1) Å, c=11.833(2) Å, V=1547.7(4) Å 3, R( F)=3.02% for I>2 σ( I).

  2. Fluoroquinolone-resistance mechanisms and phylogenetic background of clinical Escherichia coli strains isolated in south-east Poland.

    PubMed

    Korona-Glowniak, Izabela; Skrzypek, Kinga; Siwiec, Radosław; Wrobel, Andrzej; Malm, Anna

    2016-09-01

    Fluorochinolones are a class of broad-spectrum antimicrobials in the treatment of several infections, including those caused by Escherichia coli. Due to the increasing resistance of bacteria to antimicrobials, an understanding of fluoroquinolone resistance is important for infection control. The aim of this study was to determine susceptibility of clinical E. coli strains to fluoroquinolones and characterize their mechanisms of quinolone resistance. Totally, 79 non-duplicate clinical E. coli isolates included in this study were mainly from skin lesion -36 (45.6%) isolates; 54 (68.4%) isolates were assigned to phylogenetic B2 group. Resistance to ciprofloxacin was found in 20 isolates. In the quinolone resistance-determining region (QRDR) region of gyrA and parC, 4 types of point mutations were detected. Mutations in parC gene were found in all strains with gyrA mutations. Predominance of double mutation in codon 83 and 87 of gyrA (90%) and in codon 80 of parC (90%) was found. Moreover, plasmid-mediated quinolone resistance (PMRQ) determinants (qnrA or qnrB and/or aac(6')-Ib-cr) were present in 5 (25%) out of 20 fluoroquinolone-resistant isolates. Resistance to fluoroquinolones in all of the tested clinical E. coli isolates correlated with point mutations in both gyrA and parC. The majority of fluoroquinolone-resistant strains belonged to D and B2 phylogenetic groups. PMID:27602420

  3. Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains

    PubMed Central

    Park, Miseon

    2014-01-01

    Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria. PMID:25587280

  4. Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains.

    PubMed

    Park, Miseon; Rafii, Fatemeh

    2014-01-01

    Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria. PMID:25587280

  5. Guest Editor's introduction: Selected papers from the 4th USENIX Conference on Object-Oriented Technologies and Systems

    NASA Astrophysics Data System (ADS)

    Sventek, Joe

    1998-12-01

    Hewlett-Packard Laboratories, 1501 Page Mill Road, Palo Alto, CA 94304, USA Introduction The USENIX Conference on Object-Oriented Technologies and Systems (COOTS) is held annually in the late spring. The conference evolved from a set of C++ workshops that were held under the auspices of USENIX, the first of which met in 1989. Given the growing diverse interest in object-oriented technologies, the C++ focus of the workshop eventually became too narrow, with the result that the scope was widened in 1995 to include object-oriented technologies and systems. COOTS is intended to showcase advanced R&D efforts in object-oriented technologies and software systems. The conference emphasizes experimental research and experience gained by using object-oriented techniques and languages to build complex software systems that meet real-world needs. COOTS solicits papers in the following general areas: application of, and experiences with, object-oriented technologies in particular domains (e.g. financial, medical, telecommunication); the architecture and implementation of distributed object systems (e.g. CORBA, DCOM, RMI); object-oriented programming and specification languages; object-oriented design and analysis. The 4th meeting of COOTS was held 27 - 30 April 1998 at the El Dorado Hotel, Santa Fe, New Mexico, USA. Several tutorials were given. The technical program proper consisted of a single track of six sessions, with three paper presentations per session. A keynote address and a provocative panel session rounded out the technical program. The program committee reviewed 56 papers, selecting the best 18 for presentation in the technical sessions. While we solicit papers across the spectrum of applications of object-oriented technologies, this year there was a predominance of distributed, object-oriented papers. The accepted papers reflected this asymmetry, with 15 papers on distributed objects and 3 papers on object-oriented languages. The papers in this special issue are

  6. Co-selection may explain high rates of ciprofloxacin non-susceptible Escherichia coli from retail poultry reared without prior fluoroquinolone exposure.

    PubMed

    Ingram, Paul Robert; Rogers, Benjamin A; Sidjabat, Hanna E; Gibson, Justine S; Inglis, Timothy J J

    2013-11-01

    Australia has never permitted fluoroquinolone use in food-producing animals. We examined local retail poultry for contamination with fluoroquinolone non-susceptible Escherichia coli, then explored the hypothesis that their presence may be due to co-selection of resistance determinants. Between August and November 2010, samples from 30 locally produced, uncooked retail poultry carcasses from four different processing centres underwent selective enrichment culture for ciprofloxacin non-susceptible E. coli. Their chromosomal- and plasmid-mediated resistance determinants were characterized, and phylogenetic analysis and transformation experiments were performed. Unexpectedly, we found nine (30 %) of our small collection of poultry samples carried fluoroquinolone non-susceptible E. coli of which nearly half possessed aac(6')-Ib-cr, a novel plasmid-mediated gene encoding an aminoglycoside acetylating enzyme that also confers fluoroquinolone resistance. All nine isolates were co-resistant to amoxicillin, gentamicin, tetracycline and trimethoprim/sulfamethoxazole--all antibiotic classes that are registered for use in poultry reared for food production within Australia. Their unique phylogenetic relatedness suggested clonal dissemination driven by non-fluoroquinolone selective pressures. aac(6')-Ib-cr was successfully transformed and selected for using non-fluoroquinolone antibiotic pressure. Vertical and perhaps horizontal co-selection may be contributing to the emergence of fluoroquinolone resistance in poultry and could play a similar role in the human setting. This suggests that preservation of the usefulness of fluoroquinolones may require more than just restriction of their use in isolation from other interventions. PMID:24136884

  7. Cluster-based molecular docking study for in silico identification of novel 6-fluoroquinolones as potential inhibitors against Mycobacterium tuberculosis.

    PubMed

    Minovski, Nikola; Perdih, Andrej; Novic, Marjana; Solmajer, Tom

    2013-04-01

    A classical protein sequence alignment and homology modeling strategy were used for building three Mycobacterium tuberculosis-DNA gyrase protein models using the available topoII-DNA-6FQ crystal structure complexes originating from different organisms. The recently determined M. tuberculosis-DNA gyrase apoprotein structures and topoII-DNA-6FQ complexes were used for defining the 6-fluoroquinolones (6-FQs) binding pockets. The quality of the generated models was initially validated by docking of the cocrystallized ligands into their binding site, and subsequently by quantitative evaluation of their discriminatory performances (identification of active/inactive 6-FQs) for a set of 145 6-FQs with known biological activity values. The M. tuberculosis-DNA gyrase model with the highest estimated discriminatory power was selected and used afterwards in an additional molecular docking experiment on a mixed combinatorial set of 427 drug-like 6-FQ analogs for which the biological activity values were predicted using a prebuilt counter-propagation artificial neural network model. A novel three-level Boolean-based [T/F (true/false)] clustering algorithm was used to assess the generated binding poses: Level 1 (geometry properties assessment), Level 2 (score-based clustering and selection of the (T)-signed highly scored Level 1 poses), and Level 3 (activity-based clustering and selection of the most "active" (T)-signed Level 2 hits). The frequency analysis of occurrence of the fragments attached at R(1) and R(7) position of the (T)-signed 6-FQs selected in Level 3 revealed several novel attractive fragments and confirmed some previous findings. We believe that this methodology could be successfully used in establishing novel possible structure-activity relationship recommendations in the 6-FQs optimization, which could be of great importance in the current antimycobacterial hit-to-lead processes. PMID:23280926

  8. Effect of Combined Fluoroquinolone and Azole Use on QT Prolongation in Hematology Patients

    PubMed Central

    Wilson, John W.; Estes, Lynn L.

    2013-01-01

    QTc prolongation is a risk factor for development of torsades de pointes (TdP). Combination therapy with fluoroquinolones and azoles is used in patients with hematologic malignancies for prophylaxis and treatment of infection. Both drug classes are implicated as risk factors for QTc prolongation. The cumulative effect on and incidence of QTc prolongation for this combination have not been previously described. A retrospective chart review was performed with hospitalized inpatients from 1 September 2008 to 31 January 2010 comparing QTc interval data from electrocardiogram (ECG) assessment at baseline and after the initiation of combination therapy. Ninety-four patients were eligible for inclusion. The majority, 88 patients (93.6%), received quinolone therapy with levofloxacin. Fifty-three patients (56.4%) received voriconazole; 40 (42.6%) received fluconazole. The overall mean QTc change from baseline was 6.1 (95% confidence interval [CI], 0.2 to 11.9) ms. Twenty-one (22.3%) of the studied patients had clinically significant changes in the QTc while receiving combination fluoroquinolone-azole therapy. Statistically significant risk factors for clinically significant changes in QTc were hypokalemia (P = 0.03) and a left-ventricular ejection fraction of <55% (P = 0.02). Low magnesium (P = 0.11), exposure to 2 or more drugs with the potential to prolong the QTc interval (P = 0.17), and female sex (P = 0.21) trended toward significance. Combination therapy with fluoroquinolone and azole antifungals is associated with increased QTc from baseline in hospitalized patients with hematologic malignancies. One in five patients had a clinically significant change in the QTc, warranting close monitoring and risk factor modification to prevent the possibility of further QTc prolongation and risk of TdP. PMID:23229485

  9. Involvement of Holliday Junction Resolvase in Fluoroquinolone-Mediated Killing of Mycobacterium smegmatis

    PubMed Central

    Long, Quanxin; Du, Qinglin; Fu, Tiwei; Drlica, Karl

    2014-01-01

    The absence of the Holliday-junction Ruv resolvase of Mycobacterium smegmatis increased the bacteriostatic and bactericidal activities of the fluoroquinolone moxifloxacin, an important antituberculosis agent. The treatment of ruvAB-deficient cells with thiourea and 2,2′-bipyridyl lowered moxifloxacin lethality to wild-type levels, indicating that the absence of ruvAB stimulates a lethal pathway involving reactive oxygen species. A hexapeptide that traps the Holliday junction substrate of RuvAB potentiated moxifloxacin-mediated lethality, supporting the development of small-molecule enhancers for moxifloxacin activity against mycobacteria. PMID:25534729

  10. Synthesis and molecular modeling of antimicrobial active fluoroquinolone-pyrazine conjugates with amino acid linkers.

    PubMed

    Panda, Siva S; Detistov, Oleksandr S; Girgis, Adel S; Mohapatra, Prabhu P; Samir, Ahmed; Katritzky, Alan R

    2016-05-01

    Novel fluoroquinolone-pyrazine conjugates 7a-h with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antimicrobial bioassay showed that the synthesized bis-conjugates have antimicrobial properties comparable to the parent drugs. Compound 7h showed superior antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes (MIC=74.6μM and 149.3μM, respectively). This matched well with the estimated values obtained from 3D-pharmacophore and 2D-QSAR studies (MIC=67μM and 92.9μM, respectively). PMID:27025339

  11. Synthesis and In-vitro Antibacterial Activities of Acetylanthracene and Acetylphenanthrene Derivatives of Some Fluoroquinolones

    PubMed Central

    Shamsa, Fazel; Foroumadi, Alireza; Shamsa, Hashim; Samadi, Nasrin; Faramarzi, Mohammad Ali; Shafiee, Abbas

    2011-01-01

    Novel analogues of N-piperazinyl fluoroquinolones were prepared and evaluated against a panel of Gram-positive and Gram-negative bacteria, to study the effect of introducing bulky anthracene and phenanthrene moieties on the antibacterial effects of norfloxacin, ciprofloxacin and gatifloxacin. Although most of the novel synthesized compounds had lower antibacterial effects, some derivatives showed better activity in comparison with mother drugs based on molar concentration; for example, the 3-acetyl phenanthrene analogue of norfloxacin was more effective than E. coli and K. pneumonia. PMID:24250347

  12. [Fluoroquinolones to prevent bacterial infection in children with chemotherapy induced neutropenia: is it reasonable?].

    PubMed

    Dubos, F; Delebarre, M; Lagrée, M

    2013-11-01

    Chemotherapy-induced febrile neutropenia is a frequent event in children with cancer, with a high morbidity. Antibiotic prophylaxis has been proposed for many years to prevent infectious diseases in patients with neutropenia. Fluoroquinolone prophylaxis induced a significant reduction of mortality and infectious morbidities in these situations. Less data are available in children with neutropenia. The emergence of antimicrobial resistance involving not only quinolones, but also cephalosporins, aminoglycosides and penems, is the main long term risk. This article summarise the usefulness of the prophylactic antibiotic treatment and its perspective in children with cancer. PMID:24360309

  13. The 4th Bi-annual international African-Caribbean Cancer Consortium conference: building capacity to address cancer health disparities in populations of African descent.

    PubMed

    Blackman, Elizabeth; Campbell, Jasmine; Bowen, Carlene; Delmoor, Ernestine; Jean-Louis, Gilda; Noumbissi, Raphiatou; O'Garro, Yvonne; Richards-Waritay, Oni; Straughter, Stanley; Tolbert, Vera; Wilson, Barbara; Ragin, Camille

    2014-01-01

    This is a brief summary of the 4(th) International Meeting of the African-Caribbean Cancer Consortium (AC3), organized and sponsored by Fox Chase Cancer Center (FCCC), and held on July 21-22, 2012 at the Lincoln University Graduate Center, Lincoln Plaza, Philadelphia, Pennsylvania. AC3 investigators gathered in Philadelphia, PA to present the results of our ongoing collaborative research efforts throughout the African Diaspora. The general theme addressed cancer health disparities and presentations represented all cancer types. However, there was particular emphasis on women's cancers, related to human papillomavirus (HPV) and human immunodeficiency virus (HIV) infections. PMID:26422007

  14. 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

    PubMed

    Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

    2016-03-15

    4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. PMID:26867486

  15. Structure-absorption relationships of a series of 6-fluoroquinolones.

    PubMed Central

    Escribano, E; Calpena, A C; Garrigues, T M; Freixas, J; Domenech, J; Moreno, J

    1997-01-01

    The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K(abs)) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MIC90s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K(abs), on the one hand, and lipophilic parameters and other physicochemical and structural parameters estimated. Of the nonlinear functions examined, the hyperbolic had the best correlation between K(abs) and P, which was in accordance with the Wagner-Sedman (J. G. Wagner and A. J. Sedman, J. Pharmacokinet. Biopharm. 1:23-50, 1973) equation, whereas, after application of the stepwise multiple linear regression method, a multiple linear correlation with some predictive value could be established only between K(abs) as a dependent variable and log P and log S0 as independent variables. In conclusion, the K(abs) and MIC90 of the quinolone CNV 8902 suggest that it is a sufficiently interesting compound to warrant the investigation of its potential therapeutic use orally. PMID:9303400

  16. Structure-absorption relationships of a series of 6-fluoroquinolones.

    PubMed

    Escribano, E; Calpena, A C; Garrigues, T M; Freixas, J; Domenech, J; Moreno, J

    1997-09-01

    The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K(abs)) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MIC90s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K(abs), on the one hand, and lipophilic parameters and other physicochemical and structural parameters estimated. Of the nonlinear functions examined, the hyperbolic had the best correlation between K(abs) and P, which was in accordance with the Wagner-Sedman (J. G. Wagner and A. J. Sedman, J. Pharmacokinet. Biopharm. 1:23-50, 1973) equation, whereas, after application of the stepwise multiple linear regression method, a multiple linear correlation with some predictive value could be established only between K(abs) as a dependent variable and log P and log S0 as independent variables. In conclusion, the K(abs) and MIC90 of the quinolone CNV 8902 suggest that it is a sufficiently interesting compound to warrant the investigation of its potential therapeutic use orally. PMID:9303400

  17. Sequential Acquisition of Virulence and Fluoroquinolone Resistance Has Shaped the Evolution of Escherichia coli ST131

    PubMed Central

    Alsheikh-Hussain, Areej S.; Ashcroft, Melinda M.; Khanh Nhu, Nguyen Thi; Roberts, Leah W.; Stanton-Cook, Mitchell

    2016-01-01

    ABSTRACT Escherichia coli ST131 is the most frequently isolated fluoroquinolone-resistant (FQR) E. coli clone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publically available genomes from different countries and used this data set to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986 and illustrate the impact of this pivotal event on the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131. PMID:27118589

  18. Quantification of Fluoroquinolone Uptake through the Outer Membrane Channel OmpF of Escherichia coli.

    PubMed

    Cama, Jehangir; Bajaj, Harsha; Pagliara, Stefano; Maier, Theresa; Braun, Yvonne; Winterhalter, Mathias; Keyser, Ulrich F

    2015-11-01

    Decreased drug accumulation is a common cause of antibiotic resistance in microorganisms. However, there are few reliable general techniques capable of quantifying drug uptake through bacterial membranes. We present a semiquantitative optofluidic assay for studying the uptake of autofluorescent drug molecules in single liposomes. We studied the effect of the Escherichia coli outer membrane channel OmpF on the accumulation of the fluoroquinolone antibiotic, norfloxacin, in proteoliposomes. Measurements were performed at pH 5 and pH 7, corresponding to two different charge states of norfloxacin that bacteria are likely to encounter in the human gastrointestinal tract. At both pH values, the porins significantly enhance drug permeation across the proteoliposome membranes. At pH 5, where norfloxacin permeability across pure phospholipid membranes is low, the porins increase drug permeability by 50-fold on average. We estimate a flux of about 10 norfloxacin molecules per second per OmpF trimer in the presence of a 1 mM concentration gradient of norfloxacin. We also performed single channel electrophysiology measurements and found that the application of transmembrane voltages causes an electric field driven uptake in addition to concentration driven diffusion. We use our results to propose a physical mechanism for the pH mediated change in bacterial susceptibility to fluoroquinolone antibiotics. PMID:26478537

  19. Determination of residual fluoroquinolones in honey by liquid chromatography using metal chelate affinity chromatography.

    PubMed

    Yatsukawa, Yoh-Ichi; Ito, Hironobu; Matsuda, Takahiro; Nakamura, Munetomo; Watai, Masatoshi; Fujita, Kazuhiro

    2011-01-01

    A new analytical method for the simultaneous determination of seven fluoroquinolones, namely, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, orbifloxacin, sarafloxacin, and difloxacin, especially in dark-colored honey, has been developed. Fluoroquinolone antibiotics were extracted from samples with MacIlvaine buffer solution (pH 4.0) containing EDTA disodium salt dihydrate. The extracts were treated with both a polymeric cartridge and a metal chelate affinity column preloaded with ferric ion (Fe3+). LC separation with fluorescence detection was performed at 40 degrees C using an Inertsil ODS-4 analytical column (150 x 4.6 mm, 3 microm). The mobile phase was composed of 20 mM/L citrate buffer solution (pH 3.1)-acetonitrile mixture (70 + 30, v/v) containing 1 mM/L sodium dodecyl sulfate. Lomefloxacin was used as an internal standard. The developed method was validated according to the criteria of European Commission Decision 2002/657/EC. Decision limits and detection capabilities were below 2.9 and 4.4 microg/kg, respectively. PMID:21919363

  20. Active efflux of fluoroquinolones in Mycobacterium smegmatis mediated by LfrA, a multidrug efflux pump.

    PubMed Central

    Liu, J; Takiff, H E; Nikaido, H

    1996-01-01

    The lfrA gene cloned from chromosomal DNA of quinolone-resistant Mycobacterium smegmatis mc2-552 conferred low-level resistance to fluoroquinolones when present on multicopy plasmids. Sequence analysis suggested that lfrA encodes a membrane efflux pump of the major facilitator family (H. E. Takiff, M. Cimino, M. C. Musso, T. Weisbrod, R. Martinez, M. B. Delgado, L Salazar, B. R. Bloom, and W. R. Jacbos, Jr., Proc. Natl. Acad. Sci. USA 93:362-366, 1996). In this work, we studied the role of LfrA in the accumulation of fluoroquinolones by M. smegmatis. The steady-state accumulation level of a hydrophilic quinolone, norfloxacin, by M. smegmatis harboring a plasmid carrying the lfrA gene was about 50% of that by the parent strain but was increased to the same level as that of the parent strain by addition of a proton conductor, carbonyl cyanide m-chorophenylhydrazone. Norfloxacin efflux mediated by LfrA was competed for strongly by ciprofloxacin but not by nalidixic acid. Furthermore, we showed that portions of norfloxacin accumulated by starved cells were pumped out upon reenergization of the cells, and the rates of this efflux showed evidence of saturation at higher intracellular concentrations of the drug. These results suggest that the LfrA polypeptide catalyzes the active efflux of several quinolones. PMID:8682782

  1. Hidden Selection of Bacterial Resistance to Fluoroquinolones In Vivo: The Case of Legionella pneumophila and Humans

    PubMed Central

    Shadoud, Lubana; Almahmoud, Iyad; Jarraud, Sophie; Etienne, Jérôme; Larrat, Sylvie; Schwebel, Carole; Timsit, Jean-François; Schneider, Dominique; Maurin, Max

    2015-01-01

    Background Infectious diseases are the leading cause of human morbidity and mortality worldwide. One dramatic issue is the emergence of microbial resistance to antibiotics which is a major public health concern. Surprisingly however, such in vivo adaptive ability has not been reported yet for many intracellular human bacterial pathogens such as Legionella pneumophila. Methods We examined 82 unrelated patients with Legionnaire's disease from which 139 respiratory specimens were sampled during hospitalization and antibiotic therapy. We both developed a real time PCR assay and used deep-sequencing approaches to detect antibiotic resistance mutations in L. pneumophila and follow their selection and fate in these samples. Findings We identified the in vivo selection of fluoroquinolone resistance mutations in L. pneumophila in two infected patients treated with these antibiotics. By investigating the mutational dynamics in patients, we showed that antibiotic resistance occurred during hospitalization most likely after fluoroquinolone treatment. Interpretation In vivo selection of antibiotic resistances in L. pneumophila may be associated with treatment failures and poor prognosis. This hidden resistance must be carefully considered in the therapeutic management of legionellosis patients and in the control of the gradual loss of effectiveness of antibiotics. PMID:26501115

  2. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

    PubMed Central

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

    The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux. PMID:26528273

  3. Consensus Report of the 4th International Forum for Gadolinium-Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid Magnetic Resonance Imaging

    PubMed Central

    Zech, Christoph J; Bolondi, Luigi; Jonas, Eduard; Kim, Myeong-Jin; Matsui, Osamu; Merkle, Elmar M.; Sakamoto, Michiie; Choi, Byung Ihn

    2011-01-01

    This paper reports on issues relating to the optimal use of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA MR imaging) together with the generation of consensus statements from a working group meeting, which was held in Seoul, Korea (2010). Gd-EOB-DTPA has been shown to improve the detection and characterization of liver lesions, and the information provided by the hepatobiliary phase is proving particularly useful in differential diagnoses and in the characterization of small lesions (around 1-1.5 cm). Discussion also focused on advances in the role of organic anion-transporting polypeptide 8 (OATP8) transporters. Gd-EOB-DTPA is also emerging as a promising tool for functional analysis, enabling the calculation of post-surgical liver function in the remaining segments. Updates to current algorithms were also discussed. PMID:21852900

  4. Surface interactions and degradation of a fluoroquinolone antibiotic in the dark in aqueous TiO2 suspensions.

    PubMed

    Peterson, Jonathan W; Gu, Baohua; Seymour, Michael D

    2015-11-01

    Fluoroquinolone antibiotics (FQs) are important drugs used in human and veterinary medicine. Their detection in natural waters and waste water treatment plants, along with increased resistance to FQs among some bacteria, have generated an increased interest in the fate of these drugs in the environment. Partitioning of FQs between an aqueous solution and attendant substrates depends, in part, on the surface reactivity of the adsorbent, commonly a function of particle size, surface charge, and functional groups. This study investigated the surface interactions between the FQ drug ofloxacin (OFL) and titanium oxide (TiO2), a common catalyst and widely-observed constituent in many consumer products. Raman and fluorescence spectroscopic techniques, as well as LC/MS, were used to determine the OFL moieties present on TiO2 surfaces and in attendant solutions. Raman spectra indicate that the CO (ketone) group of the quinolone core, the NH(+) of the piperazinyl ring, and CH3 of benzoxazine core are the most active in sorption onto the TiO2 surface. Raman spectra also show that the sorbed benzoxazine-quinolone core and piperazinyl moieties are readily desorbed from the surface by re-suspending samples in water. Importantly, we found that OFL could be degraded by reacting with TiO2 even in the dark. Complementary LC/MS analysis of the attendant supernatants indicates the presence of de-piperazinylated and de-carboxylated OFL breakdown products in supernatant solutions. Together, both Raman and LC/MS analyses indicate that TiO2 breaks the compound into piperazinyl and carboxylate groups which attach to the surface, whereas de-carboxylated and hydroxylated quinolone moieties remain in solution. The present study thus identifies the sorption mechanisms and breakdown products of OFL during dark reactions with TiO2, which is critically important for understanding the fate and transport of OFL as it enters the soil and aquatic environment. PMID:26086371

  5. The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon

    2016-01-01

    Background Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis. Methods We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included. Results Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20–1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59–0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46–2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate. Conclusions Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis. PMID:27455053

  6. A nucleotide mutation associated with fluoroquinolone resistance observed in gyrA of in vitro obtained Rhodococcus equi mutants.

    PubMed

    Niwa, Hidekazu; Hobo, Seiji; Anzai, Toru

    2006-06-15

    In this study, the quinolone resistance-determining region (QRDR) in gyrA and gyrB of in vitro fluoroquinolone-resistant Rhodococcus equi mutants was sequenced. These mutants were selected from four R. equi strains on blood agar plates containing ciprofloxacin or enrofloxacin. Each mutant became 8- to 64 or greater-fold resistant to fluoroquinolones compared with their parent strains. From the results of sequence analysis of QRDR in gyrA and gyrB, a nucleotide mutation of codon GAC for GGC in gyrA was detected in all mutants, but no mutation was observed in gyrB. This mutation leads to amino acid substitution of Asp for Gly in putative GyrA in R. equi. The position of this substitution corresponds to position 87 of GyrA in Escherichia coli. Our results suggest that the mutation of QRDR in gyrA, which was observed in in vitro fluoroquinolone-resistant R. equi mutants in this study, is closely associated with fluoroquinolone resistance. PMID:16563665

  7. A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure

    PubMed Central

    Pham Thanh, Duy; Karkey, Abhilasha; Dongol, Sabina; Ho Thi, Nhan; Thompson, Corinne N; Rabaa, Maia A; Arjyal, Amit; Holt, Kathryn E; Wong, Vanessa; Tran Vu Thieu, Nga; Voong Vinh, Phat; Ha Thanh, Tuyen; Pradhan, Ashish; Shrestha, Saroj Kumar; Gajurel, Damoder; Pickard, Derek; Parry, Christopher M; Dougan, Gordon; Wolbers, Marcel; Dolecek, Christiane; Thwaites, Guy E; Basnyat, Buddha; Baker, Stephen

    2016-01-01

    The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(p<0.001). H58 is the dominant S. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure. Clinical trial registration: ISRCTN63006567. DOI: http://dx.doi.org/10.7554/eLife.14003.001 PMID:26974227

  8. A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system

    PubMed Central

    Maruri, Fernanda; Sterling, Timothy R.; Kaiga, Anne W.; Blackman, Amondrea; van der Heijden, Yuri F.; Mayer, Claudine; Cambau, Emmanuelle; Aubry, Alexandra

    2012-01-01

    Fluoroquinolone resistance in Mycobacterium tuberculosis has become increasingly important. A review of mutations in DNA gyrase, the fluoroquinolone target, is needed to improve the molecular detection of resistance. We performed a systematic review of studies reporting mutations in DNA gyrase genes in clinical M. tuberculosis isolates. From 42 studies that met inclusion criteria, 1220 fluoroquinolone-resistant M. tuberculosis isolates underwent sequencing of the quinolone resistance-determining region (QRDR) of gyrA; 780 (64%) had mutations. The QRDR of gyrB was sequenced in 534 resistant isolates; 17 (3%) had mutations. Mutations at gyrA codons 90, 91 or 94 were present in 654/1220 (54%) resistant isolates. Four different GyrB numbering systems were reported, resulting in mutation location discrepancies. We propose a consensus numbering system. Most fluoroquinolone-resistant M. tuberculosis isolates had mutations in DNA gyrase, but a substantial proportion did not. The proposed consensus numbering system can improve molecular detection of resistance and identification of novel mutations. PMID:22279180

  9. Production of the broad specific monoclonal antibody against sarafloxacin for rapid immunoscreening of 12 fluoroquinolones in meat.

    PubMed

    Liu, Yan Z; Zhao, Guo X; Wang, Ping; Liu, Jing; Zhang, Hui C; Wang, Jian P

    2013-01-01

    The objective of this study was to produce a generic antibody for immunoassay of fluoroquinolone drugs in meat. Two novel haptens of sarafloxacin were synthesized that were used to produce the monoclonal antibodies. The obtained monoclonal antibodies simultaneously recognized 12 fluoroquinolone drugs (sarafloxacin, diflocaxin, marbofloxacin, ofloxacin, ciprofloxacin, enrofloxacin, norfloxacin, pefloxacin, lomefloxacin, amifloxacin, enofloxacin and danofloxacin). After evaluation of different coating antigen/antibody combinations, a heterologous competitive indirect enzyme linked immunosorbent assay (ELISA) was developed to determine the 12 drugs. The crossreactivities to these analytes were in the range of 18%-113% and the limits of detection were in the range of 0.8-6.5 ng/mL depending on the compound. Eight fluoroquinolones licensed as veterinary drugs in China were fortified into blank chicken for ELISA analysis. The recoveries were in the range of 67.6%-94.6% with coefficients of variation lower than 12.4%. Therefore, this method could be used as a screen tool for routine monitoring of the residues of these fluoroquinolone drugs in animal derived foods. PMID:23305282

  10. A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure.

    PubMed

    Pham Thanh, Duy; Karkey, Abhilasha; Dongol, Sabina; Ho Thi, Nhan; Thompson, Corinne N; Rabaa, Maia A; Arjyal, Amit; Holt, Kathryn E; Wong, Vanessa; Tran Vu Thieu, Nga; Voong Vinh, Phat; Ha Thanh, Tuyen; Pradhan, Ashish; Shrestha, Saroj Kumar; Gajurel, Damoder; Pickard, Derek; Parry, Christopher M; Dougan, Gordon; Wolbers, Marcel; Dolecek, Christiane; Thwaites, Guy E; Basnyat, Buddha; Baker, Stephen

    2016-01-01

    The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(pS. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure. PMID:26974227

  11. Study on the interaction between fluoroquinolones and erythrosine by absorption, fluorescence and resonance Rayleigh scattering spectra and their application

    NASA Astrophysics Data System (ADS)

    Wang, Jian; Liu, Zhongfang; Liu, Jiangtao; Liu, Shaopu; Shen, Wei

    2008-03-01

    In pH 4.4-4.5 Britton-Robinson (BR) buffer solution, fluoroquinolone antibiotics (FLQs) including ciprofloxacin (CIP), norfloxacin (NOR), levofloxacin (LEV) and lomefloxacin (LOM) could react with erythrosine (Ery) to form 1:1 ion-association complexes, which not only resulted in the changes of the absorption spectra and the quenching of fluorescence, but also resulted in the great enhancement of resonance Rayleigh scattering (RRS). These offered some indications of the determination of fluoroquinolone antibiotics by spectrophotometric, fluorescence and resonance Rayleigh scattering methods. The detection limits for fluoroquinolone antibiotics were in the range of 0.097-0.265 μg/mL for absorption methods, 0.022-0.100 μg/mL for fluorophotometry and 0.014-0.027 μg/mL for RRS method, respectively. Among them, the RRS method had the highest sensitivity. In this work, the spectral characteristics of the absorption, fluorescence and RRS, the optimum conditions of the reactions and the properties of the analytical chemistry were investigated. The methods have been successfully applied to determination of some fluoroquinolone antibiotics in human urine samples and tablets. Taking CIP-Ery system as an example, the charge distribution, the enthalpy of formation and the mean polarizability were calculated by density function theory (DFT) method. In addition, the reasons for the enhancement of scattering spectra were discussed.

  12. Multiresidue Determination of Fluoroquinolone Antibiotics in Chicken Serum and Muscle using Liquid Chromatography-Fluorescence-Mass Spectrometryn

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A multiresidue method has been developed for determination of fluoroquinolone (FQ) antibiotics in chicken serum and muscle. FQs are extracted from either serum or muscle with acetonitrile/ammonium hydroxide and the extracts are defatted, evaporated and resuspended in buffer, then filtered and analy...

  13. International Symposium on Wind Energy Systems, 4th, Stockholm, Sweden, September 21-24, 1982, Proceedings. Volumes 1 & 2

    NASA Astrophysics Data System (ADS)

    Stephens, H. S.; Goodes, D. H.

    Progress in theoretical, meteorological, and hardware development sectors of wind energy utilization is assessed for various national programs. Wind regime characterization studies in Agentina, China, Indonesia, Norway, the U.S., Canada, Sweden, Hawaii, and offshore of the U.K. are reported. Data gained from wind turbine test sites in the U.S., Denmark, Holland, Germany, and the Netherlands are outlined. Attention is focused on the economics of wind turbine production for utility, agricultural, and third party purposes, with mention made of utilizing the resource appropriately for areas of installation of the wind powered machinery. Analyses are made of diurnal wind variations compared to diurnal demands on conventinal electricity generating power stations. Performance projections are made for wind farms featuring multi-MW machines, taking into account grid inteconnection factors, electrical control, power ramps, and environmental considerations. Mention is made of aeroelastics, dynamics, and the aerodynamics of wind turbines and rotor blades. Finally, icing, noise, fatigue failure, and blade throw problem are discussed, together with wind turbine licensing procedures in Denmark. No invidivual items are abstracted in these volumes

  14. Oral fluoroquinolones and the incidence of rhegmatogenous retinal detachment and symptomatic retinal breaks: a population-based study

    PubMed Central

    Kapoor, Kapil G.; Hodge, David O.; St Sauver, Jennifer L.; Barkmeier, Andrew J.

    2016-01-01

    Objective To examine whether oral fluoroquinolone antibiotics are associated with an increase in subsequent rhegmatogenous retinal detachment and symptomatic retinal breaks in a large, population-based cohort. Design Population-based cohort study Participants and Controls Adult residents of Olmsted County, Minnesota who were prescribed oral fluoroquinolone medications from 1/01/03 – 6/30/11. Comparison cohorts consisted of patients prescribed oral macrolide and β-lactam antibiotics during the study period. Methods Procedure codes were used to identify retinal detachment repair and prophylaxis procedures occurring within 1 year of prescription dates. Travel clinic, pro re nata, and self-treatment prescriptions were excluded. Patients with tractional retinal detachment, previous retinal detachment repair, endophthalmitis, and necrotizing retinitis were excluded, as were those with intraocular surgery or severe head/eye trauma ≤ 90 days prior to the procedure. Main Outcome Measures Rates of retinal detachment repair and prophylaxis procedures within 7, 30, 90, and 365 days of the first prescription were calculated and compared between antibiotic prescription cohorts using Chi-square tests. Retinal detachment repair rates were also compared to the expected Olmsted County, Minnesota rates using the one-sample log rank test. Results Oral fluoroquinolones were prescribed for 38,046 patients (macrolide n=48,074, β-lactam n=69,079) during the study period. Retinal detachment repair procedures were performed within 365 days of the first prescription in 0.03% (95% confidence interval [CI] 0.01–0.06%) of the fluoroquinolone, 0.02% (95% CI 0.01–0.03%) of the macrolide, and 0.03% (95% CI 0.02–0.05%) of the β-lactam cohorts (p>0.05). Retinal detachment prophylaxis procedures for symptomatic retinal breaks were performed within 365 days of the first prescription in 0.01% (95% CI 0.00–0.03%) of the fluoroquinolone, 0.02% (95% CI 0.01–0.04%) of the macrolide, and 0

  15. Quantitative risk from fluoroquinolone-resistant Salmonella and Campylobacter due to treatment of dairy heifers with enrofloxacin for bovine respiratory disease.

    PubMed

    Hurd, H Scott; Vaughn, Michael B; Holtkamp, Derald; Dickson, James; Warnick, Lorin

    2010-11-01

    The objective of this study was to evaluate the human health impact of using fluoroquinolones to treat bovine respiratory disease (BRD) in dairy heifers less than 20 months of age. Specifically, this study quantified the probability of persistent symptoms in humans treated with a fluoroquinolone, for a fluoroquinolone-resistant Campylobacter, Salmonella, or multidrug-resistant (MDR) Salmonella infection acquired following the consumption of ground beef. To comply with a Food and Drug Administration requirement for approval of enrofloxacin use in dairy heifers, a binomial event tree was constructed following Food and Drug Administration guidance 152. Release was estimated from the slaughter of dairy cattle carrying fluoroquinolone-resistant bacteria attributed to the proposed use in dairy heifers. For exposure, human foodborne exposure to Campylobacter, Salmonella, and MDR Salmonella after consumption of ground beef was estimated. The consequence assessment included illness, fluoroquinolone treatment, and persistent symptoms in patients treated with a fluoroquinolone. Using best available data to estimate the parameters and probabilities of each event, stochastic simulation was used to represent uncertainty and variability in many of the parameters. A scenario analysis was performed to evaluate the uncertainty of the following parameters: (1) probability of resistance development in treated animals, (2) portion of illnesses attributable to ground beef, and (3) probability of persistent symptoms in patients 18 years of age and over treated with a fluoroquinolone. The population at risk was restricted to people 18 years of age and over, as fluoroquinolones are not labeled for treatment of gastroenteritis in children. The mean annual increased risk of cases in the U.S. population (18 years of age and over) where compromised fluoroquinolone treatment resulted in persistent symptoms was estimated to be 1 in 61 billion (one case every 293 years) for Salmonella, 1 in 33

  16. Increased expression of fibronectin-binding proteins by fluoroquinolone-resistant Staphylococcus aureus exposed to subinhibitory levels of ciprofloxacin.

    PubMed Central

    Bisognano, C; Vaudaux, P E; Lew, D P; Ng, E Y; Hooper, D C

    1997-01-01

    Bacterial adhesion, which plays an important role in Staphylococcus aureus colonization and infection, may be altered by the presence of antibiotics or/and antibiotic resistance determinants. This study evaluated the effect of fluoroquinolone resistance determinants on S. aureus adhesion to solid-phase fibronectin, which is specifically mediated by two surface-located fibronectin-binding proteins. Five isogenic mutants, derived from strain NCTC 8325 and expressing various levels of quinolone resistance, were tested in an in vitro bacterial adhesion assay with polymethylmethacrylate coverslips coated with increasing amounts of fibronectin. These strains contained single or combined mutations in the three major loci contributing to fluoroquinolone resistance, namely, grlA, gyrA, and flqB, which code for altered topoisomerase IV, DNA gyrase, and increased norA-mediated efflux of fluoroquinolones, respectively. Adhesion characteristics of the different quinolone-resistant mutants grown in the absence of fluoroquinolone showed only minor differences from those of parental strains. However, more important changes in adhesion were exhibited by mutants highly resistant to quinolones following their exponential growth in the presence of one-quarter MIC of ciprofloxacin. Increased bacterial adhesion of the highly quinolone-resistant mutants, which contained combined mutations in grlA and gyrA, was associated with and explained by the overexpression of their fibronectin-binding proteins as assessed by Western ligand affinity blotting. These findings contradict the notion that subinhibitory concentrations of antibiotics generally decrease the expression of virulence factors by S. aureus. Perhaps the increased adhesion of S. aureus strains highly resistant to fluoroquinolones contributes in part to that emergence in clinical settings. PMID:9145842

  17. Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death

    PubMed Central

    Guinan, Eva C.; Barbon, Christine M.; Kalish, Leslie A.; Parmar, Kalindi; Kutok, Jeff; Mancuso, Christy J.; Stoler-Barak, Liat; Suter, Eugénie E.; Russell, Janice D.; Palmer, Christine D.; Gallington, Leighanne C.; Voskertchian, Annie; Vergilio, Jo-Anne; Cole, Geoffrey; Zhu, Kaya; D’Andrea, Alan; Soiffer, Robert; Weiss, Jerrold P.; Levy, Ofer

    2014-01-01

    Identification of safe, effective treatment strategies to mitigate toxicity after extensive radiation exposure has proven challenging. Only a limited number of candidate approaches have emerged, and the Federal Drug Administration has yet to approve any agent for a mass-casualty radiation disaster indication. As preparative treatments for hematopoietic stem cell transplantation (HSCT) produce toxicities similar to such radiation exposures, we studied patients early after myeloablative HSCT to identify new approaches to this problem. Patients rapidly developed endotoxemia and reduced plasma bactericidal/permeability-increasing protein (BPI), a potent endotoxin-neutralizing protein, in association with neutropenia. We hypothesized that a treatment supplying similar endotoxin-neutralizing activity might replace the BPI deficit and mitigate radiation toxicity. We tested this idea in mice. A single 7 Gy radiation dose, which was 95% lethal by 30 days, was followed 24 hours later by twice daily subcutaneous injections of the recombinant BPI fragment rBPI21 or vehicle alone for 14 or 30 days, with or without an oral fluoroquinolone antibiotic with broad-spectrum anti-bacterial activity including that against endotoxin-bearing Gram-negative bacteria. Compared to either fluoroquinolone alone or vehicle/fluoroquinolone, combined rBPI21/fluoroquinolone treatment improved survival, accelerated hematopoietic recovery and promoted expansion of stem and progenitor cells. The observed efficacy of rBPI21 and fluoroquinolones initiated 24 hours after lethal irradiation, combined with their favorable bioactivity and safety profiles in critically-ill humans, suggest the potential clinical utility of this radiation mitigation strategy and support its further evaluation. PMID:22116933

  18. Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia

    PubMed Central

    Wang, Chi-Chuan; Lin, Chia-Hui; Lin, Kuan-Yin; Chuang, Yu-Chung; Sheng, Wang-Huei

    2016-01-01

    Abstract Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics. This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups. After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77–0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92–1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30–1.62) between the 2 groups. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted. PMID:26871827

  19. Climatic changes and social transformations in the Near East and North Africa during the 'long' 4th millennium BC: A comparative study of environmental and archaeological evidence

    NASA Astrophysics Data System (ADS)

    Clarke, Joanne; Brooks, Nick; Banning, Edward B.; Bar-Matthews, Miryam; Campbell, Stuart; Clare, Lee; Cremaschi, Mauro; di Lernia, Savino; Drake, Nick; Gallinaro, Marina; Manning, Sturt; Nicoll, Kathleen; Philip, Graham; Rosen, Steve; Schoop, Ulf-Dietrich; Tafuri, Mary Anne; Weninger, Bernhard; Zerboni, Andrea

    2016-03-01

    This paper explores the possible links between rapid climate change (RCC) and social change in the Near East and surrounding regions (Anatolia, central Syria, southern Israel, Mesopotamia, Cyprus and eastern and central Sahara) during the 'long' 4th millennium (∼4500-3000) BC. Twenty terrestrial and 20 marine climate proxies are used to identify long-term trends in humidity involving transitions from humid to arid conditions and vice versa. The frequency distribution of episodes of relative aridity across these records is calculated for the period 6300-2000 BC, so that the results may be interpreted in the context of the established arid episodes associated with RCC around 6200 and 2200 BC (the 8.2 and 4.2 kyr events). We identify two distinct episodes of heightened aridity in the early-mid 4th, and late 4th millennium BC. These episodes cluster strongly at 3600-3700 and 3100-3300 BC. There is also evidence of localised aridity spikes in the 5th and 6th millennia BC. These results are used as context for the interpretation of regional and local archaeological records with a particular focus on case studies from western Syria, the middle Euphrates, southern Israel and Cyprus. Interpretation of the records involves the construction of plausible narratives of human-climate interaction informed by concepts of adaptation and resilience from the literature on contemporary (i.e. 21st century) climate change and adaptation. The results are presented alongside well-documented examples of climatically-influenced societal change in the central and eastern Sahara, where detailed geomorphological studies of ancient environments have been undertaken in tandem with archaeological research. While the narratives for the Near East and Eastern Mediterranean remain somewhat speculative, the use of resilience and adaptation frameworks allows for a more nuanced treatment of human-climate interactions and recognises the diversity and context-specificity of human responses to climatic

  20. Development of a Pefloxacin Disk Diffusion Method for Detection of Fluoroquinolone-Resistant Salmonella enterica.

    PubMed

    Skov, Robert; Matuschek, Erika; Sjölund-Karlsson, Maria; Åhman, Jenny; Petersen, Andreas; Stegger, Marc; Torpdahl, Mia; Kahlmeter, Gunnar

    2015-11-01

    Fluoroquinolones (FQs) are among the drugs of choice for treatment of Salmonella infections. However, fluoroquinolone resistance is increasing in Salmonella due to chromosomal mutations in the quinolone resistance-determining regions (QRDRs) of the topoisomerase genes gyrA, gyrB, parC, and parE and/or plasmid-mediated quinolone resistance (PMQR) mechanisms including qnr variants, aac(6')-Ib-cr, qepA, and oqxAB. Some of these mutations cause only subtle increases in the MIC, i.e., MICs ranging from 0.12 to 0.25 mg/liter for ciprofloxacin (just above the wild-type MIC of ≤0.06 mg/liter). These isolates are difficult to detect with standard ciprofloxacin disk diffusion, and plasmid-mediated resistance, such as qnr, is often not detected by the nalidixic acid screen test. We evaluated 16 quinolone/fluoroquinolone disks for their ability to detect low-level-resistant Salmonella enterica isolates that are not serotype Typhi. A total of 153 Salmonella isolates characterized for the presence (n = 104) or absence (n = 49) of gyrA and/or parC topoisomerase mutations, qnrA, qnrB, qnrD, qnrS, aac(6')-Ib-cr, or qepA genes were investigated. All isolates were MIC tested by broth microdilution against ciprofloxacin, levofloxacin, and ofloxacin and by disk diffusion using EUCAST or CLSI methodology. MIC determination correctly categorized all isolates as either wild-type isolates (MIC of ≤0.06 mg/liter and absence of resistance genes) or non-wild-type isolates (MIC of >0.06 mg/liter and presence of a resistance gene). Disk diffusion using these antibiotics and nalidixic acid failed to detect some low-level-resistant isolates, whereas the 5-μg pefloxacin disk correctly identified all resistant isolates. However, pefloxacin will not detect isolates having aac(6')-Ib-cr as the only resistance determinant. The pefloxacin disk assay was approved and implemented by EUCAST (in 2014) and CLSI (in 2015). PMID:26292292

  1. Emergence of fluoroquinolone-resistant Escherichia coli at a cancer center.

    PubMed Central

    Kern, W V; Andriof, E; Oethinger, M; Kern, P; Hacker, J; Marre, R

    1994-01-01

    Prophylactic treatment with fluoroquinolones of patients with profound neutropenia has been found to be useful for preventing gram-negative bacteremia and has become a standard preventive-therapy strategy in many cancer centers, but the development of bacterial resistance is a cause of concern. During the past few years, we have observed an increasing number of patients with leukemia from whom fluoroquinolone-resistant strains of Escherichia coli were isolated. The increase was significant in this patient population, and among patients with other underlying diseases, the rates of isolation of such strains per number of discharges were significantly lower and did not increase. Most of the leukemia case patients (16 of 19) had been pretreated with an oral quinolone (ofloxacin), with cumulative doses until the first isolation of a resistant E. coli strain ranging from 0 to 97.8 g (median, 14.4 g). Repeated isolation of such strains was seen in 8 of 17 patients during a follow-up period of > or = 4 weeks and in 1 of 6 patients during a follow-up period of > or = 16 weeks. Ten patients developed bacteremia (mortality, 1 of 10). On the basis of the number of patients with leukemia admitted to the hematology-oncology service, the incidence of bacteremia caused by fluoroquinolone-resistant E. coli increased from < 0.5% in 1988-1989 and 0.8% in 1990-1991 to 4.5% in 1992-1993 (P < 0.01). MICs for nine isolates obtained from cultures of blood from different patients ranged between 8 and 16 microgram/ml (ciprofloxacin and PD 131628), 8 and 32 microgram/ml (ofloxacin and BAY Y 3118), and 16 and 32 microgram/ml (sparfloxacin) and indicated resistance to trimethoprim-sulfamethoxazole, ampicillin, doxycycline, and chloramphenicol. Of nine isolates obtained from cultures of blood from different patients and that were subjected to genomic DNA typing by pulsed-field gel electrophoresis of XbaI digests, seven were typeable. Among these, four different genotypes were identified

  2. Stimulated electromagnetic emission and plasma line during pump wave frequency stepping near 4th electron gyroharmonic at HAARP

    NASA Astrophysics Data System (ADS)

    Grach, Savely; Sergeev, Evgeny; Shindin, Alexey; Mishin, Evgeny; Watkins, Brenton

    < f^* and mainly from altitudes h where f_0 <4f_c. The height h decreased with increasing f_0 in accordance with the altitude dependence 4f_c(h), the difference Delta f_g = f_0 - 4f_c was kept constant during either sweeping up [-(4-8 kHz)] or sweeping down [-(18-22 kHz)]. This corresponds to the difference between the altitude where f_0=4f_c and the PL generation altitude by Delta h sim 1.5-3 km and 7-8 km, respectively. During stepping up, the PL was observed also from the ranges where f_0 > 4f_c. In this case we obtained Delta f_g sim 8-13 kHz corresponding to Delta h sim - 4 km. The PL has never been observed for f_0>f^*$. \\ 1. Sergeev E., Grach S., et al. //Phys. Rev. Lett., 110 (2013), 065002.

  3. Computational modes and the Machenauer N.L.N.M.I. of the GLAS 4th order model. [NonLinear Normal Mode Initialization in numerical weather forecasting

    NASA Technical Reports Server (NTRS)

    Navon, I. M.; Bloom, S.; Takacs, L. L.

    1985-01-01

    An attempt was made to use the GLAS global 4th order shallow water equations to perform a Machenhauer nonlinear normal mode initialization (NLNMI) for the external vertical mode. A new algorithm was defined for identifying and filtering out computational modes which affect the convergence of the Machenhauer iterative procedure. The computational modes and zonal waves were linearly initialized and gravitational modes were nonlinearly initialized. The Machenhauer NLNMI was insensitive to the absence of high zonal wave numbers. The effects of the Machenhauer scheme were evaluated by performing 24 hr integrations with nondissipative and dissipative explicit time integration models. The NLNMI was found to be inferior to the Rasch (1984) pseudo-secant technique for obtaining convergence when the time scales of nonlinear forcing were much smaller than the time scales expected from the natural frequency of the mode.

  4. The 4th Schizophrenia International Research Society Conference, 5-9 April 2014, Florence, Italy: a summary of topics and trends.

    PubMed

    Abayomi, Olukayode; Amato, Davide; Bailey, Candace; Bitanihirwe, Byron; Bowen, Lynneice; Burshtein, Shimon; Cullen, Alexis; Fusté, Montserrat; Herrmann, Ana P; Khodaie, Babak; Kilian, Sanja; Lang, Qortni A; Manning, Elizabeth E; Massuda, Raffael; Nurjono, Milawaty; Sadiq, Sarosh; Sanchez-Gutierrez, Teresa; Sheinbaum, Tamara; Shivakumar, Venkataram; Simon, Nicholas; Spiteri-Staines, Anneliese; Sirijit, Suttajit; Toftdahl, Nanna Gilliam; Wadehra, Sunali; Wang, Yi; Wigton, Rebekah; Wright, Susan; Yagoda, Sergey; Zaytseva, Yuliya; O'Shea, Anne; DeLisi, Lynn E

    2014-11-01

    The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5-9, 2014 and this year had as its emphasis, "Fostering Collaboration in Schizophrenia Research". Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. PMID:25306204

  5. THE 4th SCHIZOPHRENIA INTERNATIONAL RESEARCH SOCIETY CONFERENCE, 5–9 APRIL 2014, FLORENCE, ITALY: A summary of topics and trends

    PubMed Central

    Abayomi, Olukayode; Amato, Davide; Bailey, Candace; Bitanihirwe, Byron; Bowen, Lynneice; Burshtein, Shimon; Cullen, Alexis; Fusté, Montserrat; Herrmann, Ana P; Khodaie, Babak; Kilian, Sanja; Lang, Qortni A; Manning, Elizabeth E; Massuda, Raffael; Nurjono, Milawaty; Sadiq, Sarosh; Sanchez-Gutierrez, Teresa; Sheinbaum, Tamara; Shivakumar, Venkataram; Simon, Nicholas; Spiteri-Staines, Anneliese; Sirijit, Suttajit; Toftdahl, Nanna Gilliam; Wadehra, Sunali; Wang, Yi; Wigton, Rebekah; Wright, Susan; Yagoda, Sergey; Zaytseva, Yuliya; O’Shea, Anne; DeLisi, Lynn E.

    2015-01-01

    The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5–9, 2014.and this year had as its emphasis, “Fostering Collaboration in Schizophrenia Research”. Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. PMID:25306204

  6. Limbic system development underlies the emergence of classical fear conditioning during the 3rd and 4th weeks of life in the rat

    PubMed Central

    Deal, Alex L.; Erickson, Kristen J.; Shiers, Stephanie I.; Burman, Michael A.

    2016-01-01

    Classical fear conditioning creates an association between an aversive stimulus and a neutral stimulus. Although the requisite neural circuitry is well understood in mature organisms, the development of these circuits is less well studied. The current experiments examine the ontogeny of fear conditioning and relate it to neuronal activation assessed through immediate early gene (IEG) expression in the amygdala, hippocampus, perirhinal cortex, and hypothalamus of periweanling rats. Rat pups were fear conditioned, or not, during the 3rd or 4th weeks of life. Neuronal activation was assessed by quantifying expression of FBJ osteosarcoma oncogene (FOS) using immunohistochemistry (IHC) in Experiment 1. Fos and early growth response gene-1 (EGR1) expression was assessed using qRT-PCR in Experiment 2. Behavioral data confirm that both auditory and contextual fear continue to emerge between PD 17 and 24. The IEG expression data are highly consistent with these behavioral results. IHC results demonstrate significantly more FOS protein expression in the basal amygdala of fear conditioned PD 23 subjects compared to control subjects, but no significant difference at PD 17. qRT-PCR results suggest specific activation of the amygdala only in older subjects during auditory fear expression. A similar effect of age and conditioning status was also observed in the perirhinal cortex during both contextual and auditory fear expression. Overall, the development of fear conditioning occurring between the 3rd and 4th weeks of life appears to be at least partly attributable to changes in activation of the amygdala and perirhinal cortex during fear conditioning or expression. PMID:26820587

  7. Phase 2 clinical trial of rapamycin-resistant donor CD4+ Th2/Th1 (T-Rapa) cells after low-intensity allogeneic hematopoietic cell transplantation

    PubMed Central

    Fowler, Daniel H.; Mossoba, Miriam E.; Steinberg, Seth M.; Halverson, David C.; Stroncek, David; Khuu, Hahn M.; Hakim, Frances T.; Castiello, Luciano; Sabatino, Marianna; Leitman, Susan F.; Mariotti, Jacopo; Gea-Banacloche, Juan C.; Sportes, Claude; Hardy, Nancy M.; Hickstein, Dennis D.; Pavletic, Steven Z.; Rowley, Scott; Goy, Andre; Donato, Michele; Korngold, Robert; Pecora, Andrew; Levine, Bruce L.; June, Carl H.; Gress, Ronald E.; Bishop, Michael R.

    2013-01-01

    In experimental models, ex vivo induced T-cell rapamycin resistance occurred independent of T helper 1 (Th1)/T helper 2 (Th2) differentiation and yielded allogeneic CD4+ T cells of increased in vivo efficacy that facilitated engraftment and permitted graft-versus-tumor effects while minimizing graft-versus-host disease (GVHD). To translate these findings, we performed a phase 2 multicenter clinical trial of rapamycin-resistant donor CD4+ Th2/Th1 (T-Rapa) cells after allogeneic-matched sibling donor hematopoietic cell transplantation (HCT) for therapy of refractory hematologic malignancy. T-Rapa cell products, which expressed a balanced Th2/Th1 phenotype, were administered as a preemptive donor lymphocyte infusion at day 14 post-HCT. After T-Rapa cell infusion, mixed donor/host chimerism rapidly converted, and there was preferential immune reconstitution with donor CD4+ Th2 and Th1 cells relative to regulatory T cells and CD8+ T cells. The cumulative incidence probability of acute GVHD was 20% and 40% at days 100 and 180 post-HCT, respectively. There was no transplant-related mortality. Eighteen of 40 patients (45%) remain in sustained complete remission (range of follow-up: 42-84 months). These results demonstrate the safety of this low-intensity transplant approach and the feasibility of subsequent randomized studies to compare T-Rapa cell-based therapy with standard transplantation regimens. This trial was registered at www.cancer.gov/clinicaltrials as #NCT 00077480. PMID:23426943

  8. Pharmacokinetic-Pharmacodynamic Contributions to the Convulsant Activity of Fluoroquinolones in Rats

    PubMed Central

    Delon, Annie; Bouquet, Serge; Huguet, Francois; Brunet, Valerie; Courtois, Philippe; Couet, William

    1999-01-01

    The in vivo convulsant activities in rats of five representative fluoroquinolones (FQs), norfloxacin, enoxacin, sparfloxacin, fleroxacin, and pefloxacin, were compared. The experimental approach allowed distinction between the drugs’ ability to reach the pharmacological receptors at the level of the central nervous system (pharmacokinetic contribution) and their ability to interact with these receptors (pharmacodynamic contribution). The presence of a methyl group on the piperazine moiety decreased the pharmacodynamic contribution to the convulsant activity by severalfold, and the ratios of concentrations of the FQs in cerebrospinal fluid (CSF) to concentrations of unbound FQs in plasma varied from about 5 to 75% as a function of lipophilicity. Interestingly, FQs with the highest intrinsic convulsant activities had the lowest levels of diffusion in CSF and vice versa. This in vivo approach provides information complementary to that of in vitro experiments and should be recommended for early preclinical assessment of a new FQ’s epileptogenic risk. PMID:10348785

  9. Designing Fluoroquinolone Breakpoints for Streptococcus pneumoniae by Using Genetics instead of Pharmacokinetics-Pharmacodynamics

    PubMed Central

    Smith, H. J.; Noreddin, A. M.; Siemens, C. G.; Schurek, K. N.; Greisman, J.; Hoban, C. J.; Hoban, D. J.; Zhanel, G. G.

    2004-01-01

    We determined fluoroquinolone microbiological resistance breakpoints for Streptococcus pneumoniae by using genetic instead of pharmacokinetic-pharmacodynamic parameters. The proposed microbiological breakpoints define resistance as the MIC at which >50% of the isolates carry quinolone resistance-determining region mutations and/or, if data are available, when Monte Carlo simulations demonstrate a <90% chance of bacteriological eradication. The proposed microbiological resistant breakpoints are as follows (in micrograms per milliliter): gatifloxacin, >0.25; gemifloxacin, >0.03; levofloxacin, >1; and moxifloxacin, >0.12. Monte Carlo simulations of the once daily 400-mg doses of gatifloxacin and 750-mg doses levofloxacin demonstrated a high level of target attainment (free-drug area under the concentration-time curve from 0 to 24 h/MIC ratio of 30) by using these new genetically derived breakpoints. PMID:15328145

  10. Resistance of Stenotrophomonas maltophilia to Fluoroquinolones: Prevalence in a University Hospital and Possible Mechanisms

    PubMed Central

    Jia, Wei; Wang, Jiayuan; Xu, Haotong; Li, Gang

    2015-01-01

    Objective: The purpose of this study was to investigate the clinical distribution and genotyping of Stenotrophomonas maltophilia, its resistance to antimicrobial agents, and the possible mechanisms of this drug resistance. Methods: S. maltophilia isolates were collected from clinical specimens in a university hospital in Northwestern China during the period between 2010 and 2012, and were identified to the species level with a fully automated microbiological system. Antimicrobial susceptibility testing was performed for S. maltophilia with the Kirby-Bauer disc diffusion method. The minimal inhibitory concentrations (MICs) of norfloxacin, ofloxacin, chloramphenicol, minocycline, ceftazidime, levofloxacin and ciprofloxacin against S. maltophilia were assessed using the agar dilution method, and changes in the MIC of norfloxacin, ciprofloxacin and ofloxacin were observed after the addition of reserpine, an efflux pump inhibitor. Fluoroquinolone resistance genes were detected in S. maltophilia using a polymerase chain reaction (PCR) assay, and the expression of efflux pump smeD and smeF genes was determined using a quantitative fluorescent (QF)-PCR assay. Pulsed-field gel electrophoresis (PFGE) was employed to genotype identified S. maltophilia isolates. Results: A total of 426 S. maltophilia strains were isolated from the university hospital from 2010 to 2012, consisting of 10.1% of total non-fermentative bacteria. The prevalence of norfloxacin, ciprofloxacin and ofloxacin resistance was 32.4%, 21.9% and 13.2% in the 114 S. maltophilia isolates collected from 2012, respectively. Following reserpine treatment, 19 S. maltophilia isolates positive for efflux pump were identified, and high expression of smeD and smeF genes was detected in two resistant isolates. gyrA, parC, smeD, smeE and smeF genes were detected in all 114 S. maltophilia isolates, while smqnr gene was found in 25.4% of total isolates. Glu-Lys mutation (GAA-AAA) was detected at the 151th amino acid of the

  11. Environmental photochemistry of fluoroquinolones in soil and in aqueous soil suspensions under solar light.

    PubMed

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Pretali, Luca; Profumo, Antonella; Fasani, Elisa; Albini, Angelo

    2014-12-01

    The photodegradation fate of widely used fluoroquinolone (FQ) drugs has been studied both at the water-soil interface and in soil at actual concentrations (500 ng g(-1)) under natural solar light. Both human and veterinary drugs have been examined, namely ciprofloxacin, danofloxacin, enrofloxacin, levofloxacin, marbofloxacin and moxifloxacin. After spiking and irradiation, samples were submitted to microwave-assisted extraction and analyzed by high-performance liquid chromatography coupled to fluorescence detection (HPLC-FD). FQs degradation was faster in aqueous soil suspension than in neat soil (but lower than in "clean" water). A number of byproducts were identified by HPLC electrospray ionization tandem mass spectrometry after a post-extraction cleanup based on a molecularly imprinted polymer phase, for a more accurate detection. The distribution in the suspension was intermediate between those observed in soils and in aqueous solutions. PMID:24026207

  12. Persistence of the fluoroquinolone antibiotic difloxacin in soil and lacking effects on nitrogen turnover.

    PubMed

    Rosendahl, Ingrid; Siemens, Jan; Kindler, Reimo; Groeneweg, Joost; Zimmermann, Judith; Czerwinski, Sonja; Lamshöft, Marc; Laabs, Volker; Wilke, Berndt-Michael; Vereecken, Harry; Amelung, Wulf

    2012-01-01

    The environmental risks caused by the use of fluoroquinolone antibiotics in human therapeutics and animal husbandry are associated with their persistence and (bio)accessibility in soil. To assess these aspects, we administered difloxacin to pigs and applied the contaminated manure to soil. We then evaluated the dissipation and sequestration of difloxacin in soil in the absence and presence of plants within a laboratory trial, a mesocosm trial, and a field trial. A sequential extraction yielded antibiotic fractions of differing binding strength. We also assessed the antibiotic's effects on nitrogen turnover in soil (potential nitrification and denitrification). Difloxacin was hardly (bio)accessible and was very persistent under all conditions studied (dissipation half-life in bulk soil, >217 d), rapidly forming nonextractable residues. Although varying environmental conditions did not affect persistence, dissipation was accelerated in soil surrounding plant roots. Effects on nitrogen turnover were limited due to the compound's strong binding and small (bio)accessibility despite its persistence. PMID:22751072

  13. Fluoroquinolone-resistant Escherichia coli carriage in long-term care facility.

    PubMed

    Maslow, Joel N; Lee, Betsy; Lautenbach, Ebbing

    2005-06-01

    We conducted a cross-sectional study to determine the prevalence of, and risk factors for, colonization with fluoroquinolone (FQ)-resistant Escherichia coli in residents in a long-term care facility. FQ-resistant E. coli were identified from rectal swabs for 25 (51%) of 49 participants at study entry. On multivariable analyses, prior FQ use was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures in the previous 3, 6, 9, or 12 months. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified clonal spread of 1 strain among 16 residents. Loss (6 residents) or acquisition (7 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. Unlike the case in the hospital setting, FQ-resistant E. coli carriage in long-term care facilities is associated with clonal spread. PMID:15963284

  14. Reduced fluoroquinolone susceptibility in Salmonella enterica serotypes in travelers returning from Southeast Asia.

    PubMed

    Hakanen, A; Kotilainen, P; Huovinen, P; Helenius, H; Siitonen, A

    2001-01-01

    During 1995 to 1999, we collected 1,210 Salmonella isolates; 629 were from Finnish travelers returning from abroad. These isolates were tested for susceptibility by determining MICs to ciprofloxacin, nalidixic acid, and seven additional antimicrobial agents. From 1995 to 1999, the annual proportion of reduced ciprofloxacin susceptibility (MIC > 0.125 microg/mL) among all travelers' isolates increased from 3.9% to 23.5% (p<0.001). The increasing trend was outstanding among the isolates from Southeast Asia; isolates from Thailand alone increased from 5.6% to 50.0% (p<0.001). The reduced fluoroquinolone susceptibility was nonclonal in character and significantly associated with multidrug resistance. A point mutation in the quinolone resistance-determining region of gyrA was present in all isolates with reduced susceptibility. These data provide further evidence for the rapid spread of multidrug-resistant pathogens from one continent to another. PMID:11747728

  15. Fluoroquinolone-resistant Escherichia coli Carriage in Long-Term Care Facility

    PubMed Central

    Lee, Betsy; Lautenbach, Ebbing

    2005-01-01

    We conducted a cross-sectional study to determine the prevalence of, and risk factors for, colonization with fluoroquinolone (FQ)-resistant Escherichia coli in residents in a long-term care facility. FQ-resistant E. coli were identified from rectal swabs for 25 (51%) of 49 participants at study entry. On multivariable analyses, prior FQ use was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures in the previous 3, 6, 9, or 12 months. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified clonal spread of 1 strain among 16 residents. Loss (6 residents) or acquisition (7 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. Unlike the case in the hospital setting, FQ-resistant E. coli carriage in long-term care facilities is associated with clonal spread. PMID:15963284

  16. Spectrometric studies on the interaction of fluoroquinolones and bovine serum albumin

    NASA Astrophysics Data System (ADS)

    Ni, Yongnian; Su, Shaojing; Kokot, Serge

    2010-02-01

    The interaction between fluoroquinolones (FQs), ofloxacin and enrofloxacin, and bovine serum albumin (BSA) was investigated by fluorescence and UV-vis spectroscopy. It was demonstrated that the fluorescence quenching of BSA by FQ is a result of the formation of the FQ-BSA complex stabilized, in the main, by hydrogen bonds and van der Waals forces. The Stern-Volmer quenching constant, KSV, and the corresponding thermodynamic parameters, Δ H, Δ S and Δ G, were estimated. The distance, r, between the donor, BSA, and the acceptor, FQ, was estimated from fluorescence resonance energy transfer (FRET). The effect of FQ on the conformation of BSA was analyzed with the aid of UV-vis absorbance spectra and synchronous fluorescence spectroscopy. Spectral analysis showed that the two FQs affected the conformation of the BSA but in a different manner. Thus, with ofloxacin, the polarity around the tryptophan residues decreased and the hydrophobicity increased, while for enrofloxacin, the opposite effect was observed.

  17. Pleiotropic Effects of Levofloxacin, Fluoroquinolone Antibiotics, against Influenza Virus-Induced Lung Injury.

    PubMed

    Enoki, Yuki; Ishima, Yu; Tanaka, Ryota; Sato, Keizo; Kimachi, Kazuhiko; Shirai, Tatsuya; Watanabe, Hiroshi; Chuang, Victor T G; Fujiwara, Yukio; Takeya, Motohiro; Otagiri, Masaki; Maruyama, Toru

    2015-01-01

    Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-γ in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs. PMID:26086073

  18. Pleiotropic Effects of Levofloxacin, Fluoroquinolone Antibiotics, against Influenza Virus-Induced Lung Injury

    PubMed Central

    Enoki, Yuki; Ishima, Yu; Tanaka, Ryota; Sato, Keizo; Kimachi, Kazuhiko; Shirai, Tatsuya; Watanabe, Hiroshi; Chuang, Victor T. G.; Fujiwara, Yukio; Takeya, Motohiro; Otagiri, Masaki; Maruyama, Toru

    2015-01-01

    Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2’-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-γ in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs. PMID:26086073

  19. Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae.

    PubMed

    Ferrándiz, M J; Martín-Galiano, A J; Arnanz, C; Zimmerman, T; de la Campa, A G

    2016-01-01

    We studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction. PMID:26525786

  20. Embryo lethality and teratogenicity of a new fluoroquinolone antibacterial DW-116 in rats.

    PubMed

    Kim, J C; Yun, H I; Shin, H C; Han, S S; Chung, M K

    2000-04-01

    DW-116, 1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-l-piperazinyl)-1, 4-dihydro-4-oxoquinolone-3-carboxylic acid hydrochloride, is a newly developed fluoroquinolone antibacterial. The potential of DW-116 to induce developmental toxicity was, investigated in Sprague-Dawley rats. DW-116 was administered by gavage to pregnant rats from days 6 to 16 of gestation at dose levels of 0, 31.3, 125, and 500 mg/kg per day. All dams were subjected to caesarean section on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. At 500 mg/kg, toxic effects including clinical signs of toxicity, suppressed body weight and decreased food intake were found in dams. An increase in the resorption rate, a decrease in the litter size, a reduction in the fetal weight, and a decrease in the placental weight were also seen. In addition, various types of external, visceral, and skeletal malformations occurred at an incidence of 17.9, 74.2 and 8.3%, respectively. Characteristic malformations included oedema, cleft palate, dilated cerebral ventricle, hypoplasia of lung and ventricular septum defect. A dramatic increase in the incidence of skeletal variations (55.6%) and retardations (94.4%) and a decrease in the number of ossification centres of sternebra, metacarpals, metatarsals and sacrocaudal vertebra were also observed. At 125 mg/kg, a reduction in the placental weight and an increase in the incidence of skeletal variations were found. There were no signs of maternal toxicity or embryotoxicity at 31.3 mg/kg. These results indicate that the fluoroquinolone antibacterial DW-116 is embryotoxic and teratogenic at minimally maternally toxic dose and is minimally embryotoxic at nonmaternally toxic dose in rats. PMID:10839480

  1. Reactive Oxygen Species Contribute to the Bactericidal Effects of the Fluoroquinolone Moxifloxacin in Streptococcus pneumoniae

    PubMed Central

    Ferrándiz, M. J.; Martín-Galiano, A. J.; Arnanz, C.; Zimmerman, T.

    2015-01-01

    We studied the transcriptomic response of Streptococcus pneumoniae to the fluoroquinolone moxifloxacin at a concentration that inhibits DNA gyrase. Treatment of the wild-type strain R6, at a concentration of 10× the MIC, triggered a response involving 132 genes after 30 min of treatment. Genes from several metabolic pathways involved in the production of pyruvate were upregulated. These included 3 glycolytic enzymes, which ultimately convert fructose 6-phosphate to pyruvate, and 2 enzymes that funnel phosphate sugars into the glycolytic pathway. In addition, acetyl coenzyme A (acetyl-CoA) carboxylase was downregulated, likely leading to an increase in acetyl-CoA. When coupled with an upregulation in formate acetyltransferase, an increase in acetyl-CoA would raise the production of pyruvate. Since pyruvate is converted by pyruvate oxidase (SpxB) into hydrogen peroxide (H2O2), an increase in pyruvate would augment intracellular H2O2. Here, we confirm a 21-fold increase in the production of H2O2 and a 55-fold increase in the amount of hydroxyl radical in cultures treated during 4 h with moxifloxacin. This increase in hydroxyl radical through the Fenton reaction would damage DNA, lipids, and proteins. These reactive oxygen species contributed to the lethality of the drug, a conclusion supported by the observed protective effects of an SpxB deletion. These results support the model whereby fluoroquinolones cause redox alterations. The transcriptional response of S. pneumoniae to moxifloxacin is compared with the response to levofloxacin, an inhibitor of topoisomerase IV. Levofloxacin triggers the transcriptional activation of iron transport genes and also enhances the Fenton reaction. PMID:26525786

  2. Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change.

    PubMed

    Zhu, Linyan; Santiago-Schübel, Beatrix; Xiao, Hongxia; Hollert, Henner; Kueppers, Stephan

    2016-10-01

    In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium. It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test (Desmodesmus subspicatus). The median effective concentration (EC50) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes. PMID:27318447

  3. Relationships among antibacterial activity, inhibition of DNA gyrase, and intracellular accumulation of 11 fluoroquinolones.

    PubMed Central

    Bazile, S; Moreau, N; Bouzard, D; Essiz, M

    1992-01-01

    A series of 11 fluoroquinolone antibacterial agents, including 8 newly synthesized molecules and 3 reference compounds (pefloxacin, ciprofloxacin, and sparfloxacin), were tested for their MICs against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The intracellular accumulation of fluoroquinolones by these microorganisms was measured by centrifugation through silicone oil and a fluorescence assay. The minimal effective dose (MED) was determined for all agents in a supercoiling assay with E. coli DNA gyrase. The hydrophobicities of the quinolones were determined and expressed as the logarithm of the coefficient of distribution (log D) between 1-octanol and phosphate buffer (pH 7.2). No correlation was found between MICs and cell accumulation for the quinolones studied. A correlation was found between log D and accumulation by S. aureus (r = 0.71, n = 11), and an inverse correlation was found between log D and accumulation by E. coli (r = 0.73, n = 11) and P. aeruginosa (r = 0.64, n = 10). The correlation coefficients between MICs and MED for E. coli, which were 0.60, 0.64, and 0.74 (n = 11) for E. coli, P. aeruginosa, and S. aureus, respectively, rose to 0.85, 0.74, and 0.74 (n = 11) for the same microorganisms, respectively, when the accumulation of the drug by the cell was taken into account. It was concluded that the inhibitory activity against DNA gyrase remains the most important parameter for quinolone potency, but that intracellular accumulation must be taken into account, since, for a given organism, both parameters are under the control of the physicochemical properties of the quinolones. PMID:1336340

  4. A Kinesthetic Learning Approach to Earth Science for 3rd and 4th Grade Students on the Pajarito Plateau, Los Alamos, NM

    NASA Astrophysics Data System (ADS)

    Wershow, H. N.; Green, M.; Stocker, A.; Staires, D.

    2010-12-01

    Current efforts towards Earth Science literacy in New Mexico are guided by the New Mexico Science Benchmarks [1]. We are geoscience professionals in Los Alamos, NM who believe there is an important role for non-traditional educators utilizing innovative teaching methods. We propose to further Earth Science literacy for local 3rd and 4th grade students using a kinesthetic learning approach, with the goal of fostering an interactive relationship between the students and their geologic environment. We will be working in partnership with the Pajarito Environmental Education Center (PEEC), which teaches the natural heritage of the Pajarito Plateau to 3rd and 4th grade students from the surrounding area, as well as the Family YMCA’s Adventure Programs Director. The Pajarito Plateau provides a remarkable geologic classroom because minimal structural features complicate the stratigraphy and dramatic volcanic and erosional processes are plainly on display and easily accessible. Our methodology consists of two approaches. First, we will build an interpretive display of the local geology at PEEC that will highlight prominent rock formations and geologic processes seen on a daily basis. It will include a simplified stratigraphic section with field specimens and a map linked to each specimen’s location to encourage further exploration. Second, we will develop and implement a kinesthetic curriculum for an exploratory field class. Active engagement with geologic phenomena will take place in many forms, such as a scavenger hunt for precipitated crystals in the vesicles of basalt flows and a search for progressively smaller rhyodacite clasts scattered along an actively eroding canyon. We believe students will be more receptive to origin explanations when they possess a piece of the story. Students will be provided with field books to make drawings of geologic features. This will encourage independent assessment of phenomena and introduce the skill of scientific observation. We

  5. Multiresidue determination of quinolone and fluoroquinolone antibiotics in fish and shrimp by liquid chromatography/tandem mass spectrometry.

    PubMed

    Dufresne, Guy; Fouquet, Andre; Forsyth, Don; Tittlemier, Sheryl A

    2007-01-01

    A multiresidue method was developed to measure low levels of 8 fluoroquinolones (norfloxacin, ofloxacin, danofloxacin, ciprofloxacin, desethylene ciprofloxacin, enrofloxacin, sarafloxacin, and difloxacin) and 4 quinolones (oxolinic acid, flumequine, nalidixic acid, and piromidic acid). Method detection limits range from 0.1 ng/g for quinolones to 0.4 ng/g for fluoroquinolones. Average recoveries range from 57 to 96%, depending on analyte and commodity; relative standard deviations are all less than 18%. The drugs are extracted from tissues using a mixture of ethanol and 1% acetic acid, diluted in aqueous HCI, and defatted by extraction with hexane. The compounds are further isolated using cation-exchange solid-phase extraction and measured using liquid chromatography with electrospray tandem mass spectrometry detection. The method has been evaluated and applied to the analysis of salmon, trout, and shrimp. Detectable residues were observed in 10 out of 73 samples, at concentrations ranging from 0.28 to 16 ng/g. PMID:17474531

  6. Occurrence and sorption of fluoroquinolones in poultry litters and soils from São Paulo State, Brazil.

    PubMed

    Leal, Rafael Marques Pereira; Figueira, Rafael Fernandes; Tornisielo, Valdemar Luiz; Regitano, Jussara Borges

    2012-08-15

    Animal production is one of the most expressive sectors of Brazilian agro-economy. Although antibiotics are routinely used in this activity, their occurrence, fate, and potential impacts to the local environment are largely unknown. This research evaluated sorption-desorption and occurrence of four commonly used fluoroquinolones (norfloxacin, ciprofloxacin, danofloxacin, and enrofloxacin) in poultry litter and soil samples from São Paulo State, Brazil. The sorption-desorption studies involved batch equilibration technique and followed the OECD guideline for pesticides. All compounds were analyzed by HPLC, using fluorescence detector. Fluoroquinolones' sorption potential to the poultry litters (K(d) ≤65 L kg(-1)) was lower than to the soil (K(d) ~40,000 L kg(-1)), but was always high (≥69% of applied amount) indicating a higher specificity of fluoroquinolones interaction with soils. The addition of poultry litter (5%) to the soil had not affected sorption or desorption of these compounds. Desorption was negligible in the soil (≤0.5% of sorbed amount), but not in the poultry litters (up to 42% of sorbed amount). Fluoroquinolones' mean concentrations found in the poultry litters (1.37 to 6.68 mg kg(-1)) and soils (22.93 μg kg(-1)) were compatible to those found elsewhere (Austria, China, and Turkey). Enrofloxacin was the most often detected compound (30% of poultry litters and 27% of soils) at the highest mean concentrations (6.68 mg kg(-1) for poultry litters and 22.93 μg kg(-1) for soils). These results show that antibiotics are routinely used in poultry production and might represent one potential source of pollution to the environment that has been largely ignored and should be further investigated in Brazil. PMID:22750180

  7. Surface interactions and degradation of a fluoroquinolone antibiotic in the dark in aqueous TiO2 suspensions

    SciTech Connect

    Peterson, Jonathan W.; Gu, Baohua; Seymour, Michael D.

    2015-06-15

    Fluoroquinolone antibiotics (FQs) are important drugs used in human and veterinary medicine. Their detection in natural waters and waste water treatment plants, along with increased resistance to FQs among some bacteria, have generated an increased interest in the fate of these drugs in the environment. Partitioning of FQs between an aqueous solution and attendant substrates depends, in part, on the surface reactivity of the adsorbent, commonly a function of particle size, surface charge, and functional groups. In this paper, this study investigated the surface interactions between the FQ drug ofloxacin (OFL) and titanium oxide (TiO2), a common catalyst and widely-observed constituent in many consumer products. Raman and fluorescence spectroscopic techniques, as well as LC/MS, were used to determine the OFL moieties present on TiO2 surfaces and in attendant solutions. Raman spectra indicate that the C==O (ketone) group of the quinolone core, the NH+ of the piperazinyl ring, and CH3 of benzoxazine core are the most active in sorption onto the TiO2 surface. Raman spectra also show that the sorbed benzoxazine–quinolone core and piperazinyl moieties are readily desorbed from the surface by re-suspending samples in water. Importantly, we found that OFL could be degraded by reacting with TiO2 even in the dark. Complementary LC/MS analysis of the attendant supernatants indicates the presence of de-piperazinylated and de-carboxylated OFL breakdown products in supernatant solutions. Together, both Raman and LC/MS analyses indicate that TiO2 breaks the compound into piperazinyl and carboxylate groups which attach to the surface, whereas de-carboxylated and hydroxylated quinolone moieties remain in solution. Finally, the present study thus identifies the sorption mechanisms and breakdown products of OFL during dark reactions with TiO2, which is critically important for understanding the

  8. Surface interactions and degradation of a fluoroquinolone antibiotic in the dark in aqueous TiO2 suspensions

    DOE PAGESBeta

    Peterson, Jonathan W.; Gu, Baohua; Seymour, Michael D.

    2015-06-15

    Fluoroquinolone antibiotics (FQs) are important drugs used in human and veterinary medicine. Their detection in natural waters and waste water treatment plants, along with increased resistance to FQs among some bacteria, have generated an increased interest in the fate of these drugs in the environment. Partitioning of FQs between an aqueous solution and attendant substrates depends, in part, on the surface reactivity of the adsorbent, commonly a function of particle size, surface charge, and functional groups. In this paper, this study investigated the surface interactions between the FQ drug ofloxacin (OFL) and titanium oxide (TiO2), a common catalyst and widely-observedmore » constituent in many consumer products. Raman and fluorescence spectroscopic techniques, as well as LC/MS, were used to determine the OFL moieties present on TiO2 surfaces and in attendant solutions. Raman spectra indicate that the C==O (ketone) group of the quinolone core, the NH+ of the piperazinyl ring, and CH3 of benzoxazine core are the most active in sorption onto the TiO2 surface. Raman spectra also show that the sorbed benzoxazine–quinolone core and piperazinyl moieties are readily desorbed from the surface by re-suspending samples in water. Importantly, we found that OFL could be degraded by reacting with TiO2 even in the dark. Complementary LC/MS analysis of the attendant supernatants indicates the presence of de-piperazinylated and de-carboxylated OFL breakdown products in supernatant solutions. Together, both Raman and LC/MS analyses indicate that TiO2 breaks the compound into piperazinyl and carboxylate groups which attach to the surface, whereas de-carboxylated and hydroxylated quinolone moieties remain in solution. Finally, the present study thus identifies the sorption mechanisms and breakdown products of OFL during dark reactions with TiO2, which is critically important for understanding the fate and transport of OFL as it enters the soil and aquatic environment.« less

  9. Evaluation of the current trend of nalidixic acid susceptibility in typhoidal Salmonellae; a marker of therapeutic failure for the fluoroquinolones

    PubMed Central

    Abbasi, S; Imtiaz, A; Usman, J; Kaleem, F; Hassan, A

    2011-01-01

    Background and Objectives Typhoid is a major health problem faced by the developing countries like Pakistan. More than 20 million cases are reported annually worldwide. Currently fluoroquinolones are the drugs of choice to treat typhoid fever. In vivo resistance to fluoroquinolones leading to therapeutic failure is developing rapidly and is becoming a major concern for the clinicians. The objective of this study was to determine the sensitivity pattern of Nalidixic acid over the last four years Material and Methods A descriptive cross sectional study was carried out at the Microbiology Department of the Army Medical College, National University of Sciences and Technology, Rawalpindi from January 2006 to December 2009. All the isolates were dealt with standard microbiological procedures. The antimicrobial sensitivity of Nalidixic acid and Ciprofloxacin was determined using Kirby-Bauer disc diffusion method as per the guidelines of Clinical and Laboratory Standard Institute (CLSI). Results Out of 240 isolates, 111 were Salmonella typhi and 129 were Salmonella paratyphi A. The resistance of the typhoidal Salmonella to Nalidixic acid has reached significant levels and it seems only a matter of time when hundred percent resistance will be encountered. All isolates were sensitive to Ciprofloxacin on disc diffusion method. Conclusion Resistance to Nalidixic acid predicting therapeutic failure with fluoroquinolones is on a steady rise. PMID:22347587

  10. Opportunities and Limitation of Hyporheic Restoration in a 4th Order Semi-Arid Floodplain: a Case Study of Meacham Creek, Oregon

    NASA Astrophysics Data System (ADS)

    O'Daniel, S. J.; Amerson, B. E.; Lambert, M. B.

    2014-12-01

    Persistent societal interest in improving water quality and recovering imperiled, native, aquatic species has expanded the scope of stream restoration to include the hyporheic zone as a focus. Despite the lack of detailed studies, hyporheic restoration is often invoked as a means to achieve multiple objectives including moderation of water temperature, delay of seasonal flows and increasing the localized volume of floodplain water. We present interim results from an ongoing case study that monitors the changes as a result of stream restoration of the hyporheic zone of a 4th order, alluvial floodplain in northeast Oregon, USA, Meacham Creek. Active and passive restoration of 2.5 km of Meacham Creek has altered the creek from a single-threaded, incised and bedrock-dominated channel to a perched, alluvial channel that seasonally exchanges overbank flows with the surrounding floodplain. Our results suggest that the stream restoration effort on Meacham Creek has increased the volume of annual hyporheic storage and created a more diverse distribution of flowpath lengths within the restoration site. Furthermore, our monitoring indicates that hyporheic process response to stream restoration, analogous to other geomorphic processes, conforms to a systematic hierarchy where nested flow paths range in length and residence time from meters and hours at the habitat scale to tens of meters and months at the floodplain scale. We assert that scale-explicit and measurement-focused restoration planning has a greater likelihood of meeting the stated objectives and result in improved water quality and encourage recovery of many native aquatic species.

  11. Status and Trend of Regal Fritillary (Speyeria idalia) (Lepidoptera: Nymphalidae) in the 4th of July Butterfly Count Program in 1977-2014.

    PubMed

    Swengel, Scott R; Swengel, Ann B

    2016-01-01

    Regal Fritillary (Speyeria idalia) primarily inhabits prairie, a native grassland of central North America, and occurs rarely in nonprairie grasslands further east. This butterfly has experienced widespread decline and marked range contraction. We analyze Regal Fritillary incidence and abundance during 1977-2014 in 4th of July Butterfly Counts, an annual census of butterflies in North America. Volunteers count within the same 24 km diameter circle each year. Only 6% of counts in range reported a Regal, while 18% of counts in core range in the Midwest and Great Plains did. 99.9% of Regal individuals occurred in core range. Only four circles east of core range reported this species, and only during the first half of the study period. All individuals reported west of its main range occurred in two circles in Colorado in the second half of the study. The number of counts per year and survey effort per count increased during the study. During 1991-2014, >31 counts occurred per year in core Regal range, compared to 0-23 during 1975-1990. During 1991-2014, all measures of Regal presence and abundance declined, most significantly. These results agree with other sources that Regal Fritillary has contracted its range and declined in abundance. PMID:27239370

  12. Evidence of human-induced morphodynamic changes along the Campania coastal areas (southern Italy) since the 3rd-4th cent. AD

    NASA Astrophysics Data System (ADS)

    Russo Ermolli, Elda; Romano, Paola; Liuzza, Viviana; Amato, Vincenzo; Ruello, Maria Rosaria; Di Donato, Valentino

    2014-05-01

    Campania has always offered suitable climatic and physiographic conditions for human settlements since prehistoric times. In particular, many Graeco-Roman towns developed along its coasts starting from the 7th-6th cent. BC. In the last decade, geoarchaelogical surveys have been carried out in the archaeological excavations of Neapolis, Paestum and Elea-Velia allowing the main steps of the landscape evolution around these towns to be defined in detail. The greek town of Neapolis rose in the late 6th cent. BC [1] on a terrace overlooking a low-relief rocky coast surrounded by volcanic hills. Port activities developed in a protected bay facing the town from the 4th-2nd cent. BC up to the 4th cent. AD, as testified by the discovery of structures and shipwrecks [2, 3, 4]. Starting from the 3rd cent. AD a spit bar formed at the bay entrance causing the progressive establishment of a lagoon which was gradually filled up by alluvial inputs and completely closed in the 5th cent. AD. During the same period, episodes of increased alluvial inputs were also recorded further west along the coast, where a narrow sandy beach formed at the cliff toe. The greek town of Poseidonia, renamed Paestum by the Romans, was founded in the 540 BC on a travertine terrace facing the sandy littoral of a prograding coastal plain [5]. In front of the main town door, a coastal lagoon developed thanks to the growth of a dune ridge and was probably used for harbor activities [5]. After this period the shoreline shifted seawards, another dune ridge formed and the back-ridge depression was filled with fluvial-marshy deposits, slowly drying up. Phases of travertine deposition, which characterized the SE sector of the plain all along the Holocene, were recorded in the northern and southern quarters of the town in historical times and were connected to the abandonment of the town in the early Medieval times. The greek colony of Elea-Velia was located on top of a siliciclastic promontory where the ruins of

  13. Status and Trend of Regal Fritillary (Speyeria idalia) (Lepidoptera: Nymphalidae) in the 4th of July Butterfly Count Program in 1977–2014

    PubMed Central

    2016-01-01

    Regal Fritillary (Speyeria idalia) primarily inhabits prairie, a native grassland of central North America, and occurs rarely in nonprairie grasslands further east. This butterfly has experienced widespread decline and marked range contraction. We analyze Regal Fritillary incidence and abundance during 1977–2014 in 4th of July Butterfly Counts, an annual census of butterflies in North America. Volunteers count within the same 24 km diameter circle each year. Only 6% of counts in range reported a Regal, while 18% of counts in core range in the Midwest and Great Plains did. 99.9% of Regal individuals occurred in core range. Only four circles east of core range reported this species, and only during the first half of the study period. All individuals reported west of its main range occurred in two circles in Colorado in the second half of the study. The number of counts per year and survey effort per count increased during the study. During 1991–2014, >31 counts occurred per year in core Regal range, compared to 0–23 during 1975–1990. During 1991–2014, all measures of Regal presence and abundance declined, most significantly. These results agree with other sources that Regal Fritillary has contracted its range and declined in abundance. PMID:27239370

  14. Future perspectives in melanoma research. Meeting report from the “Melanoma Bridge. Napoli, December 2nd-4th 2012”

    PubMed Central

    2013-01-01

    Recent insights into the genetic and somatic aberrations have initiated a new era of rapidly evolving targeted and immune-based treatments for melanoma. After decades of unsuccessful attempts to finding a more effective cure in the treatment of melanoma now we have several drugs active in melanoma. The possibility to use these drugs in combination to improve responses to overcome the resistance, to potentiate the action of immune system with the new immunomodulating antibodies, and identification of biomarkers that can predict the response to a particular therapy represent new concepts and approaches in the clinical management of melanoma. The third “Melanoma Research: “A bridge from Naples to the World” meeting, shortened as “Bridge Melanoma Meeting” took place in Naples, December 2 to 4th, 2012. The four topics of discussion at this meeting were: advances in molecular profiling and novel biomarkers, combination therapies, novel concepts toward integrating biomarkers and therapies into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage, and the knowledge gained from the biology of tumor microenvironment across different tumors as a bridge to impact on prognosis and response to therapy in melanoma. This international congress gathered more than 30 international faculty members who in an interactive atmosphere which stimulated discussion and exchange of their experience regarding the most recent advances in research and clinical management of melanoma patients. PMID:23731854

  15. Dynamics of the properties of steppe paleosols of the Sarmatian time (2nd century BC-4th century AD) in relation to secular variations in climatic humidity

    NASA Astrophysics Data System (ADS)

    Demkin, V. A.; Zolotareva, B. N.; Demkina, T. S.; Khomutova, T. E.; Kashirskaya, N. N.; El'Tsov, M. V.; Udal'Tsov, S. N.

    2012-02-01

    Paleosols buried under kurgans of the Early (2nd-1st centuries BC), Middle (1st-2nd centuries AD) and Late (2nd-IV centuries AD) Sarmatian epochs were studied in dry steppes and desert steppes of the Lower Volga region (the Privolzhskaya and Ergeni Uplands and the Caspian Lowland). It was found that temporal variations in the morphological, chemical, microbiological, and magnetic properties of the paleosols in the interval of 2200-1600 BP were characterized by the cyclic pattern related to secular dynamics of climatic humidity with changes in the mean annual precipitation of ±30-50 mm. These climate changes did not transform chestnut paleosols and paleosolonetzes at the type or subtype taxonomic levels. However, they led to certain changes in the humus, carbonate, and salt profiles of the soils; in the character of solonetzic horizon B1; and in the state of microbial communities. According to these data, the Sarmatian time was characterized by alternation of micropluvial and microarid stages lasting fro about 100-200 years. In particular, the stages of humidization were observed in the 1st century BC-1st century AD and in the 4th century AD; the most arid conditions were observed in the second half of the 2nd and the first half of the 3rd century AD.

  16. Integrating data and mashup concepts in Hydro-Meteorological Research: the torrential rainfall event in Genoa (4th November 2011) case study.

    NASA Astrophysics Data System (ADS)

    Bedrina, T.; Parodi, A.; Quarati, A.; Clematis, A.; Rebora, N.; Laiosa, D.

    2012-04-01

    One of the critical issues in Hydro-Meteorological Research (HMR) is a better exploitation of data archives according to a multidisciplinary perspective. Different Earth science databases offer a huge amount of observational data, which often need to be assembled, processed, combined accordingly HM scientists needs. The cooperation between scientists active in HMR and Information and Communication Technologies (ICT) is essential in the development of innovative tools and applications for manipulating, aggregating and re-arranging heterogeneous information in flexible way. In this paper it is described an application devoted to the collection and integration of HM datasets, originated by public or private sources, freely exposed via Web services API. This application uses the mashup, recently become very popular in many fields, (Chow S.-W., 2007) technology concepts. Such methodology means combination of data and/or programs published by external online sources into an integrated experience. Mashup seems to be a promising methodology to respond to the multiple data-related activities into which HM researchers are daily involved (e.g. finding and retrieving high volume data; learning formats and developing readers; extracting parameters; performing filtering and mask; developing analysis and visualization tools). The specific case study of the recent extreme rainfall event, occurred over Genoa in Italy on the 4th November 2011 is shown through the integration of semi-professional weather observational networks as free available data source in addition to official weather networks.

  17. Activity of faropenem tested against Neisseria gonorrhoeae isolates including fluoroquinolone-resistant strains.

    PubMed

    Jones, Ronald N; Critchley, Ian A; Whittington, William L H; Janjic, Nebojsa; Pottumarthy, Sudha

    2005-12-01

    We evaluated the anti-gonococcal potency of faropenem along with 7 comparator reference antimicrobials against a preselected collection of clinical isolates. The 265 isolates were inclusive of 2 subsets: 1) 76 well-characterized resistant phenotypes of gonococcal strains (53 quinolone-resistant strains--31 with documented quinolone resistance-determining region changes from Japan, 15 strains resistant to penicillin and tetracycline, and 8 strains with intermediate susceptibility to penicillin) and 2) 189 recent isolates from clinical specimens in 2004 from 6 states across the United States where quinolone resistance is prevalent. Activity of faropenem was adversely affected by l-cysteine hydrochloride in IsoVitaleX (4-fold increase in [minimal inhibitory concentration] MIC50; 0.06 versus 0.25 microg/mL). The rank order of potency of the antimicrobials for the entire collection was ceftriaxone (MIC90, 0.06 microg/mL) > faropenem (0.25 microg/mL) > azithromycin (0.5 microg/mL) > cefuroxime (1 microg/mL) > tetracycline (2 microg/mL) > penicillin = ciprofloxacin = levofloxacin (4 microg/mL). Using MIC90 for comparison, faropenem was 4-fold more potent than cefuroxime (0.25 versus 1 microg/mL), but was 4-fold less active than ceftriaxone (0.25 versus 0.06 microg/mL). Although the activity of faropenem was not affected by either penicillinase production (MIC90, 0.12 microg/mL, penicillinase-positive) or increasing ciprofloxacin MIC (0.25 microg/mL, ciprofloxacin-resistant), increasing penicillin MIC was associated with an increase in MIC90 values (0.016 microg/mL for penicillin-susceptible to 0.25 microg/mL for penicillin-resistant strains). Among the recent (2004) clinical gonococcal isolates tested, reduced susceptibility to penicillins, tetracycline, and fluoroquinolones was high (28.0-94.2%). Geographic distribution of the endemic resistance rates of gonococci varied considerably, with 16.7-66.7% of the gonococcal isolates being ciprofloxacin-resistant in Oregon

  18. Frequency and Geographic Distribution of gyrA and gyrB Mutations Associated with Fluoroquinolone Resistance in Clinical Mycobacterium Tuberculosis Isolates: A Systematic Review

    PubMed Central

    Avalos, Elisea; Catanzaro, Donald; Catanzaro, Antonino; Ganiats, Theodore; Brodine, Stephanie; Alcaraz, John; Rodwell, Timothy

    2015-01-01

    Background The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance. Methods In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution. Results Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21–32% for D94G and 13–20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay. Conclusions Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88–94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular

  19. Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway.

    PubMed

    Theodore, Alyssa; Lewis, Kim; Vulic, Marin

    2013-12-01

    Bacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive without becoming genetically resistant. Survival of these phenotypically resistant cells, commonly called "persisters," depends on the SOS gene network. We have examined mutants in all known SOS-regulated genes to identify functions essential for tolerance in Escherichia coli. The absence of DinG and UvrD helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a decrease in survival. Analysis of the respective mutants indicates that, in addition to repair of double-strand breaks, tolerance depends on the repair of collapsed replication forks and stalled transcription complexes. Mutation in recF results in increased survival, which identifies RecAF recombination as a poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of SOS promoting its induction, whereas RuvAB participates in repair only. UvrD directly promotes all repair processes initiated by FQ-induced damage and prevents RecAF-dependent misrepair, making it one of the crucial SOS functions required for tolerance. PMID:24077306

  20. Improved extraction of fluoroquinolones with recyclable ionic-liquid-based aqueous biphasic systems†

    PubMed Central

    Almeida, Hugo F. D.; Freire, Mara G.; Marrucho, Isabel M.

    2016-01-01

    In the past few years, the improvement of advanced analytical tools allowed to confirm the presence of trace amounts of metabolized and unchanged active pharmaceutical ingredients (APIs) in wastewater treatment plants (WWTPs) as well as in freshwater surfaces. It is known that the continuous contact with APIs, even at very low concentrations (ng L−1–μg L−1), leads to serious human health problems. In this context, this work shows the feasibility of using ionic-liquid-based aqueous biphasic systems (IL-based ABS) in the extraction of quinolones present in aqueous media. In particular, ABS composed of imidazolium- and phosphonium-based ILs and aluminium-based salts (already used in water treatment plants) were evaluated in one-step extractions of six fluoroquinolones (FQs), namely ciprofloxacin, enrofloxacin, moxifloxacin, norfloxacin, ofloxacin and sarafloxacin, and extraction efficiencies up to 98% were obtained. Despite the large interest devoted to IL-based ABS as extractive systems of outstanding performance, their recyclability/reusability has seldomly been studied. An efficient extraction/cleaning process of the IL-rich phase is here proposed by FQs induced precipitation. The recycling of the IL and its further reuse without losses in the ABS extractive performance for FQs were established, as confirmed by the four consecutive removal/extraction cycles evaluated. This novel recycling strategy supports IL-based ABS as sustainable and cost-efficient extraction platforms.

  1. The occurrence and removal of selected fluoroquinolones in urban drinking water treatment plants.

    PubMed

    Xu, Yongpeng; Chen, Ting; Wang, Yuan; Tao, Hui; Liu, Shiyao; Shi, Wenxin

    2015-12-01

    Fluoroquinolones (FQs) are a widely prescribed group of antibiotics. They enter the aqueous environment, where they are frequently detected, and can lead to a threat to human health. Drinking water treatment plants (DWTPs) play a key role in removing FQs from potable water. This study investigated the occurrence and removal of four selected FQs (norfloxacin (NOR), ciprofloxacin (CIP), enrofloxacin (ENR), and ofloxacin (OFL)) in three urban DWTPs in China. The treatment efficacy for each system was simultaneously evaluated. Two of the examined DWTPs used conventional treatment processes. The third used conventional processes followed by additional treatment processes (ozonation-biologically activated carbon (ozonation-BAC) and membrane technology). The average concentrations of the four FQs in the source water and the finished water ranged from 51 to 248 ng/L and from <5 to 46 ng/L, respectively. Based on residual concentrations, the conventional treatment system had a low removal of FQs. In contrast, the addition of advanced treatment processes such as the ozonation-BAC and membranes, substantially improved the removal of FQs. The finding of this study has important implications: even though coagulation-sedimentation and chlorination treatment processes can remove most target FQs, the typical practice of advanced treatment processes is necessary for the further removal. PMID:26545373

  2. Salmonella Typhi in the Democratic Republic of the Congo: Fluoroquinolone Decreased Susceptibility on the Rise

    PubMed Central

    Lunguya, Octavie; Lejon, Veerle; Phoba, Marie-France; Bertrand, Sophie; Vanhoof, Raymond; Verhaegen, Jan; Smith, Anthony Marius; Keddy, Karen Helena; Muyembe-Tamfum, Jean-Jacques; Jacobs, Jan

    2012-01-01

    Background Drug resistance of Salmonella enterica serovar Typhi (Salmonella Typhi) to first-line antibiotics is emerging in Central Africa. Although increased use of fluoroquinolones is associated with spread of resistance, Salmonella Typhi with decreased ciprofloxacin susceptibility (DCS) has rarely been reported in Central Africa. Methodology/Principal Findings As part of a microbiological surveillance study in the Democratic Republic of the Congo (DR Congo), Salmonella Typhi isolates from bloodstream infections were collected prospectively between 2007 and 2011. The genetic relationship of the Salmonella Typhi isolates was assessed by pulsed-field gel electrophoresis (PFGE). The antimicrobial resistance profile of the isolates was determined and mutations associated with DCS were studied. In total, 201 Salmonella Typhi isolates were collected. More than half of the Salmonella Typhi isolates originated from children and young adults aged 5–19. Thirty different PFGE profiles were identified, with 72% of the isolates showing a single profile. Multidrug resistance, DCS and azithromycin resistance were 30.3%, 15.4% and 1.0%, respectively. DCS was associated with point mutations in the gyrA gene at codons 83 and 87. Conclusions/Significance Our study describes the first report of widespread multidrug resistance and DCS among Salmonella Typhi isolates from DR Congo. Our findings highlight the need for increased microbiological diagnosis and surveillance in DR Congo, being a prerequisite for rational use of antimicrobials and the development of standard treatment guidelines. PMID:23166855

  3. Photodegradation of fluoroquinolones in surface water and antimicrobial activity of the photoproducts.

    PubMed

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Pretali, Luca; Profumo, Antonella; Fasani, Elisa; Albini, Angelo; Migliavacca, Roberta; Nucleo, Elisabetta

    2012-11-01

    The widespread presence of fluoroquinolone antibiotics (FQs) in natural ecosystems is a health hazard for humans and other living organisms. The role of sunlight in degrading FQs present in environmental waters has been studied. In particular, the photodegradation of four largely employed FQs, viz. Ciprofloxacin (CIP), Danofloxacin (DAN), Levofloxacin (LEV) and Moxifloxacin (MOX) has been studied in not tampered river water. Degradation rates have been investigated at ppb levels (20-50 μg L(-1)) under solar light, and the results have been commented critically. The products distribution has been studied by HPLC-ESI-MS/MS analysis and structures have been attributed on the basis of their mass fragmentation spectra. Importantly from the environmental point of view, the (potentially toxic) FQ nucleus remained intact over the early stages of the degradation. Indeed, the photoproducts were proved to possess residual antibacterial activity, as shown from in vitro antibacterial activity tests against different well characterized human and environmental bacterial strains, carried out on the above FQs, as well as for Enrofloxacin (ENR) and Marbofloxacin (MAR). PMID:22901305

  4. Selective sample pretreatment by molecularly imprinted polymer monolith for the analysis of fluoroquinolones from milk samples.

    PubMed

    Zheng, Ming-Ming; Gong, Rui; Zhao, Xing; Feng, Yu-Qi

    2010-04-01

    Water-compatible pefloxacin-imprinted monoliths synthesized in a water-containing system were used for the selective extraction of fluoroquinolones (FQs). The MIP monolith was synthesized by using methacrylic acid as the functional monomer, di(ethylene glycol) dimethacrylate as a cross-linker and methanol-water (10:3, v/v) as the porogenic solvent. The ability of the derivated MIP for selective recognition of FQs (ciprofloxacin, difloxacin, danofloxacin and enrofloxacin) and quinolones (flumequine, and oxolinic acid) was evaluated. The derivated monolith showed high selectivity and was able to distinguish between FQs and quinolones. A simple rapid and sensitive method using polymer monolith microextraction (PMME) based on the MIP monolith combined with HPLC with fluorescence detection was developed for the determination of four FQs from milk samples. Owing to the unique porous structure and flow-through channels in the network skeleton of the MIP monolith, phosphate buffer diluted milk samples were directly supplied to PMME; allowing non-specific bound proteins and other biological matrix to be washed out, and FQs to be selectively enriched. The limit of detection of the method was 0.4-1.6ng/mL and recovery was 92.4-98.2% with relative standard deviations less than 5.9%. PMID:20189184

  5. Rapid determination of fluoroquinolone residues in honey by a microbiological screening method and liquid chromatography.

    PubMed

    Kanda, Maki; Kusano, Tomoto; Kanai, Setsuko; Hayashi, Hiroshi; Matushima, Yoko; Nakajima, Takayuki; Takeba, Kazue; Sasamoto, Takeo; Nagayma, Toshijiro

    2010-01-01

    A rapid and efficient method was developed for the simultaneous determination of seven fluoroquinolone (FQ) residues: norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, orbifloxacin, sarafloxacin, and difloxacin in honey. The samples were first screened with a microbiological method by using test plates made from metal-free purified agar seeded with Bacillus subtilis BGA. When a sample was found to contain FQ residues by using the microbiological method, it was analyzed by LC with fluorescence detection (LC/FL). FQs were extracted with Na2EDTA-McIlvaine buffer and purified by a dual SPE method in which a cation-exchange cartridge was connected to an anion-exchange cartridge. The overall recoveries of the seven FQs ranged from 70.0 to 92.1%. The intra-assay and interassay CVs were < or = 7.8 and < or = 5.1%, respectively. For the microbiological method, the LOD values ranged from 2 to 9 microg/kg. For LC/FL, the LOQ values ranged from 2 to 7 microg/kg. The developed method was used to analyze 70 honey samples. In 14 samples in which the microbiological method detected the presence of FQ residues, norfloxacin, ciprofloxacin, and enrofloxacin were identified by LC/FL. PMID:20922969

  6. Systematic optimization of an SPE with HPLC-FLD method for fluoroquinolone detection in wastewater.

    PubMed

    He, Ke; Blaney, Lee

    2015-01-23

    This paper describes a selective and ultra-sensitive analytical method for simultaneous determination of 11 fluoroquinolone (FQ) antibiotics in environmental and wastewater samples. The method employs offline solid-phase extraction (SPE) and reversed-phase high performance liquid chromatography with fluorescence detection (HPLC-FLD). A weak cation exchange SPE protocol was developed with a novel loading volume optimization algorithm and a methanol cleanup step to remove background organic matter. Various parameters were optimized to recover FQs from water/wastewater and analyte recovery was generally greater than 80%. Chromatographic separation of the 11 FQs was achieved on a 150 mm pentafluorophenyl column using a gradient elution scheme with methanol, acetonitrile, and 20mM phosphate buffer (pH=2.4). Excitation and emission wavelengths were individually optimized for each FQ using fluorescence spectroscopy; the excitation and emission wavelengths were 276-296 nm and 444-506 nm, respectively. Instrumental quantitation limits were 20-100 pg of mass injected. Of the 11 FQs investigated, seven (i.e., ciprofloxacin, difloxacin, enrofloxacin, fleroxacin, norfloxacin, moxifloxacin, and ofloxacin) were detected during a four-month sampling campaign of wastewater and wastewater-impacted surface water. Concentrations of FQs in raw wastewater, wastewater effluent, and wastewater-impacted surface water were 5-1292, 2-504, and 4-187ng/L, respectively. PMID:25200119

  7. Aquatic photochemistry of fluoroquinolone antibiotics: kinetics, pathways, and multivariate effects of main water constituents.

    PubMed

    Ge, Linke; Chen, Jingwen; Wei, Xiaoxuan; Zhang, Siyu; Qiao, Xianliang; Cai, Xiyun; Xie, Qing

    2010-04-01

    The ubiquity of fluoroquinolone antibiotics (FQs) in surface waters urges insights into their fate in the aqueous euphotic zone. In this study, eight FQs (ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin, enrofloxacin, gatifloxacin, and balofloxacin) were exposed to simulated sunlight, and their photodegradation was observed to follow apparent first-order kinetics. Based on the determined photolytic quantum yields, solar photodegradation half-lives for the FQs in pure water and at 45 degrees N latitude were calculated to range from 1.25 min for enrofloxacin to 58.0 min for balofloxacin, suggesting that FQs would intrinsically photodegrade fast in sunlit surface waters. However, we found freshwater and seawater constituents inhibited their photodegradation. The inhibition was further explored by a central composite design using sarafloxacin and gatifloxacin as representatives. Humic acids (HA), Fe(III), NO(3)(-), and HA-Cl(-) interaction inhibited the photodegradation, as they mainly acted as radiation filters and/or scavengers for reactive oxygen species. The photodegradation product identification and ROS scavenging experiments indicated that the FQs underwent both direct photolysis and self-sensitized photo-oxidation via *OH and (1)O(2). Piperazinyl N(4)-dealkylation was primary for N(4)-alkylated FQs, whereas decarboxylation and defluorination were comparatively important for the other FQs. These results are of importance toward the goal of assessing the persistence of FQs in surface waters. PMID:20205456

  8. Isolation of a non-genomic origin fluoroquinolone responsive regulatory element using a combinatorial bioengineering approach

    PubMed Central

    Srivastava, Santosh Kumar; Iyer, V. Rajesh; Ghosh, Tamoghna; Lambadi, Paramesh Ramulu; Pathania, Ranjana; Navani, Naveen Kumar

    2016-01-01

    Advances in chemical biology have led to selection of synthetic functional nucleic acids for in vivo applications. Discovery of synthetic nucleic acid regulatory elements has been a long-standing goal of chemical biologists. Availability of vast genome level genetic resources has motivated efforts for discovery and understanding of inducible synthetic genetic regulatory elements. Such elements can lead to custom-design of switches and sensors, oscillators, digital logic evaluators and cell–cell communicators. Here, we describe a simple, robust and universally applicable module for discovery of inducible gene regulatory elements. The distinguishing feature is the use of a toxic peptide as a reporter to suppress the background of unwanted bacterial recombinants. Using this strategy, we show that it is possible to isolate genetic elements of non-genomic origin which specifically get activated in the presence of DNA gyrase A inhibitors belonging to fluoroquinolone (FQ) group of chemicals. Further, using a system level genetic resource, we prove that the genetic regulation is exerted through histone-like nucleoid structuring (H-NS) repressor protein. Till date, there are no reports of in vivo selection of non-genomic origin inducible regulatory promoter like elements. Our strategy opens an uncharted route to discover inducible synthetic regulatory elements from biologically-inspired nucleic acid sequences. PMID:26837578

  9. Isolation of a non-genomic origin fluoroquinolone responsive regulatory element using a combinatorial bioengineering approach.

    PubMed

    Srivastava, Santosh Kumar; Iyer, V Rajesh; Ghosh, Tamoghna; Lambadi, Paramesh Ramulu; Pathania, Ranjana; Navani, Naveen Kumar

    2016-03-18

    Advances in chemical biology have led to selection of synthetic functional nucleic acids for in vivo applications. Discovery of synthetic nucleic acid regulatory elements has been a long-standing goal of chemical biologists. Availability of vast genome level genetic resources has motivated efforts for discovery and understanding of inducible synthetic genetic regulatory elements. Such elements can lead to custom-design of switches and sensors, oscillators, digital logic evaluators and cell-cell communicators. Here, we describe a simple, robust and universally applicable module for discovery of inducible gene regulatory elements. The distinguishing feature is the use of a toxic peptide as a reporter to suppress the background of unwanted bacterial recombinants. Using this strategy, we show that it is possible to isolate genetic elements of non-genomic origin which specifically get activated in the presence of DNA gyrase A inhibitors belonging to fluoroquinolone (FQ) group of chemicals. Further, using a system level genetic resource, we prove that the genetic regulation is exerted through histone-like nucleoid structuring (H-NS) repressor protein. Till date, there are no reports of in vivo selection of non-genomic origin inducible regulatory promoter like elements. Our strategy opens an uncharted route to discover inducible synthetic regulatory elements from biologically-inspired nucleic acid sequences. PMID:26837578

  10. Fluoroquinolones as chemical tools to define a strategy for photogenotoxicity in vitro assessment.

    PubMed

    Marrot, L; Belaidi, J P; Chaubo, C; Meunier, J R; Perez, P; Agapakis-Causse, C

    2001-04-01

    Today's lifestyle is often associated with frequent exposure to sunlight, but some xenobiotics used in drugs, cosmetics or food chemicals can produce adverse biological effects when irradiated. In particular, they can increase the risk of photogenotoxicity already due to UV radiation itself. There is thus a need to design appropriate approaches in order to obtain relevant data at the molecular and cellular level in this field. For ethical and practical reasons, in vitro models can be very convenient at least for first evaluation tests. Here, we propose a strategy based on complementary experiments to study the photogenotoxic potential of a compound. The fluoroquinolones BAYy3118 and lomefloxacin were used as standards to demonstrate the performance of each test: photoinduced interaction with supercoiled circular DNA, photomutagenicity in the yeast Saccharomyces cerevisae, induction of DNA photodamage in cultured human skin cells as revealed by comet assay, and finally induction of specific phototoxic stress responses such as p53 activation or melanogenesis stimulation. Such a strategy should help to ensure the safety of products likely to undergo environmental sunlight exposure. PMID:11287172

  11. Membrane localization and topology of the DnpA protein control fluoroquinolone tolerance in Pseudomonas aeruginosa.

    PubMed

    Liebens, Veerle; Frangipani, Emanuela; Van der Leyden, Annelies; Fauvart, Maarten; Visca, Paolo; Michiels, Jan

    2016-09-01

    DnpA, a putative de-N-acetylase of the PIG-L superfamily, is required for antibiotic tolerance in Pseudomonas aeruginosa Exactly how dnpA (gene locus PA5002) directs the formation of antibiotic-tolerant persister cells is currently unknown. Previous research provided evidence for a role in surface-associated process(es), possibly in lipopolysaccharide biosynthesis. In silico sequence analysis of DnpA predicts a single transmembrane domain and Nin/Cout orientation of DnpA. In contrast, we here show that DnpA is an integral inner membrane protein containing two transmembrane domains, with the major C-terminal part located at the cytoplasmic face. Correct insertion into the inner membrane is necessary for DnpA to promote fluoroquinolone tolerance. The membrane localization of DnpA further supports its role in cell envelope-associated process(es). In addition to shedding light on the biological role of DnpA, this study highlights the risks of overreliance on the predictive value of bioinformatics tools and the importance of rigorous experimental validation of in silico predictions. PMID:27481702

  12. Risk assessment of three fluoroquinolone antibiotics in the groundwater recharge system.

    PubMed

    Chen, Guoli; Liu, Xiang; Tartakevosky, Daniel; Li, Miao

    2016-11-01

    Three fluoroquinolone antibiotics agents (FQs) in groundwater and reclaimed water have been investigated in Changzhou and Beijing, China. The occurrence of ofloxacin (OFL), enrofloxacin (ENR) and norfloxacin (NOR) is in nanograms per liter and has 100% frequency. The concentration order of FQs in reclaimed water is NOR>OFL>ENR, whilst the order in groundwater is NOR>ENR>OFL. And then the single and mixture adsorption-desorption have been studied and showed that (i) silty clay loam has higher sorption capacity than loamy sand, (ii) competitive adsorption exists when the three selected FQs coexist, (iii) ENR has a significantly priority sorption to NOR, whilst OFL has a least sorption among the mixture, (iv) there is no significant difference between the desorption results of mixture and the indivdual compound in relatively low concentration, (v) the formed chemical bonds and the irreversible combination of adsorption point are the significant influential factors for explaining desorption hysteresis of the selected FQs. Based on the above study, transport model and risk quotient have been performed, and the calculated risk quotient reveals that: (i) the selected FQs risk order in reclaimed water is OFL>ENR>NOR, (ii) in groundwater, OFL and ENR pose a higher risk than NOR no matter whether considering the long time groundwater recharge. This study will help policy makers to decide which FQs need to be covered in the priority substance lists defined in legislative frameworks. PMID:27400060

  13. [Clinical contribution of the newer fluoroquinolones in acute bacterial exacerbation of chronic bronchitis].

    PubMed

    Niederman, M S

    1999-01-01

    Acute exacerbations occur frequently in patients with chronic bronchitis and the majority of these patients benefit from antimicrobial therapy. The ideal antimicrobial agent for the management of acute exacerbations of chronic bronchitis (AECB) should have good activity against the common bacterial pathogens associated with these exacerbations (non-typable Haemophilus influenzae, Moraxella catarrhalis and pneumococci); it should be resistant to bacterial betalactamases; penetrate well into pulmonary tissues and secretions; kill bacteria without inducing excessive airway inflammation; be easy to take (given once or twice a day) in order to ensure high patient compliance, and be cost-effective. Fluoroquinolone antibiotics have demonstrated efficacy in the treatment of AECB, but because of the limited activity of certain older agents in this class when administered in standard doses against Streptococcus pneumoniae, they have not be extensively used for this indication. Newer agents including levofloxacin, grepafloxacin, sparfloxacin and trovafloxacin have excellent activity against both Gram positive and Gram negative pathogens likely to be involved in AECB. These agents can be administered once daily, making patient compliance and a successful therapeutic outcome more likely. The new quinolones offer promising alternatives for antimicrobial therapy in outpatients with AECB, particularly those with underlying co-morbidity and severe obstruction. PMID:10436551

  14. Design of a portable fluoroquinolone analyzer based on terbium-sensitized luminescence

    NASA Astrophysics Data System (ADS)

    Chen, Guoying

    2007-09-01

    A portable fluoroquinolone (FQ) analyzer is designed and prototyped based on terbium-sensitized luminescence (TSL). The excitation source is a 327-nm light emitting diode (LED) operated in pulsed mode; and the luminescence signal is detected by a photomultiplier tube (PMT). In comparison to a conventional xenon flashlamp, an LED is small, light, robust, and energy efficient. More importantly, its narrow emission bandwidth and low residual radiation reduce background signal. In pulse mode, an LED operates at a current 1-2 orders of magnitude lower than that of a xenon flashlamp, thus minimizing electromagnetic interference (EMI) to the detector circuitry. The PMT is gated to minimize its response to the light source. These measures lead to reduced background noise in time domain. To overcome pulse-to-pulse variation signal normalization is implemented based on individual pulse energy. Instrument operation and data processing are controlled by a computer running a custom LabVIEW program. Enrofloxacin (ENRO) is used as a model analyte to evaluate instrument performance. The integrated TSL intensity reveals a linear dependence up to 2 ppm. A 1.1-ppb limit of detection (LOD) is achieved with relative standard deviation (RSD) averaged at 5.1%. The background noise corresponds to ~5 ppb. At 19 lbs, this portable analyzer is field deployable for agriculture, environmental and clinical analyses.

  15. Adsorptive Removal and Adsorption Kinetics of Fluoroquinolone by Nano-Hydroxyapatite

    PubMed Central

    Chen, Yajun; Lan, Tao; Duan, Lunchao; Wang, Fenghe; Zhao, Bin; Zhang, Shengtian; Wei, Wei

    2015-01-01

    Various kinds of antibiotics, especially fluoroquinolone antibiotics (FQs) have been widely used for the therapy of infectious diseases in human and livestock. For their poorly absorbed by living organisms, large-scale misuse or abuse of FQs will foster drug resistance among pathogenic bacteria, as well as a variety of environmental problems when they were released in the environment. In this work, the adsorption properties of two FQs, namely norfloxacin (NOR) and ciprofloxacin (CIP), by nano-hydroxyapatite (n-HAP) were studied by batch adsorption experiments. The adsorption curves of FQs by n-HAP were simulated by Langmuir and Freundlich isotherms. The results shown that NOR and CIP can be adsorbed effectively by the adsorbent of n-HAP, and the adsorption capacity of FQs increase with increasing dosage of n-HAP. The optimum dosage of n-HAP for FQs removal was 20 g·L-1, in which the removal efficiencies is 51.6% and 47.3%, and an adsorption equilibrium time is 20 min. The maximum removal efficiency occurred when pH is 6 for both FQs. The adsorption isotherm of FQs fits well for both Langmuir and Freundlich equations. The adsorption of both FQs by n-HAP follows second-order kinetics. PMID:26698573

  16. Mutant prevention concentrations of fluoroquinolones against Campylobacter jejuni isolated from chicken.

    PubMed

    Wang, Liping; Yuanshu, Zhang; Yuhan, Zhang; Yaojie; Yingxia, Li

    2010-08-26

    The mutant prevention concentration (MPC) and mutant selection window (MSW) concepts have been used to evaluate antibiotic concentration ranges that prevent the emergence of antibiotic resistant mutants. Campylobacter jejuni is highly mutable to fluoroquinolone (FQ) antibiotics, but it is unknown if the MPC concept can be used to prevent mutant emergence. In this study, the MPCs of three FQs including enrofloxacin, norfloxacin and ciprofloxacin were determined using 13 C. jejuni isolates. Also, first- and second-step FQ-resistant mutants were selected and the mutations in gyrA and gyrB as well as the contribution of efflux pump to FQ resistance were investigated. The MICs of all selected mutants were determined in the presence or absence of the efflux pump inhibitors carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and reserpine. Our results revealed that the three tested FQs had different MPC ranges and the MPC order was norfloxacin > ciprofloxacin > enrofloxacin, suggesting a better in vitro efficacy of enrofloxacin over ciprofloxacin and norfloxacin in reducing the emergence of C. jejuni mutants. The results also confirmed the single-step mechanism of acquired FQs resistance in C. jejuni mutants. Both point mutations (Thr-86-Ile and Asp-90-Asn) in the gyrA gene and the function of efflux pumps contributed to the acquired resistance to ciprofloxacin and norfloxacin, while gyrA mutations (Thr-86-Ile and Asp-90-Asn) were the main mechanism for enrofloxacin resistance. These findings provide new insights into the development and mechanisms of FQ resistance in Campylobacter. PMID:20226601

  17. Using robust Bayesian network to estimate the residuals of fluoroquinolone antibiotic in soil.

    PubMed

    Li, Xuewen; Xie, Yunfeng; Li, Lianfa; Yang, Xunfeng; Wang, Ning; Wang, Jinfeng

    2015-11-01

    Prediction of antibiotic pollution and its consequences is difficult, due to the uncertainties and complexities associated with multiple related factors. This article employed domain knowledge and spatial data to construct a Bayesian network (BN) model to assess fluoroquinolone antibiotic (FQs) pollution in the soil of an intensive vegetable cultivation area. The results show: (1) The relationships between FQs pollution and contributory factors: Three factors (cultivation methods, crop rotations, and chicken manure types) were consistently identified as predictors in the topological structures of three FQs, indicating their importance in FQs pollution; deduced with domain knowledge, the cultivation methods are determined by the crop rotations, which require different nutrients (derived from the manure) according to different plant biomass. (2) The performance of BN model: The integrative robust Bayesian network model achieved the highest detection probability (pd) of high-risk and receiver operating characteristic (ROC) area, since it incorporates domain knowledge and model uncertainty. Our encouraging findings have implications for the use of BN as a robust approach to assessment of FQs pollution and for informing decisions on appropriate remedial measures. PMID:26141975

  18. Bridging the US and China together to conquer cancer: report of the 4th annual meeting of the US Chinese Anti-Cancer Association (USCACA)

    PubMed Central

    Yang, Wancai; Guan, Lingjie

    2012-01-01

    A global collaborative effort is pivotal to conquer cancer. Themed “Emerging role of China in global clinical development of novel anti-cancer drugs”, the US Chinese Anti-Cancer Association (USCACA) held its 4th annual meeting in Chicago on June 2, 2012, in conjunction with the American Society of Clinical Oncology (ASCO) annual meeting to further bridge the US and China together to outsmart cancer. Although a young organization, USCACA has made significant contributions to this goal in the 3 years since its inception through extensive collaboration with academic organizations, the pharmaceutical industry, and governmental agencies. USCACA has engaged various stakeholders in developing translational and personalized medical strategies to facilitate new anti-cancer drug development and clinical trials in China. USCACA has initiated and implemented the USCACA-National Foundation for Cancer Research (NFCR) scholarship to encourage overseas returnees to continue cancer research in China. USCACA announced the Hengrui-USCACA scholarship to fund clinical trial staff from China to conduct the observation of early oncologic clinical trials in the US. During the annual meeting, distinguished panelists and the audience discussed the following critical topics: (1) oncologic translational research and early development capabilities in China; (2) novel chemical entity development and partnership with Chinese companies; and (3) Chinese participation in global anti-cancer drug development. USCACA will continue to promote collaborations among cancer researchers and clinicians in the US and China by engaging in more frequent communications and joint efforts across fields, disciplines, and countries, diligently working together toward curing and eliminating cancers. PMID:22739264

  19. Changes in the regional prevalence of child obesity in 4th, 8th, and 11th grade students in Texas from 2000-2002 to 2004-2005.

    PubMed

    Hoelscher, Deanna M; Kelder, Steven H; Pérez, Adriana; Day, R Sue; Benoit, Julia S; Frankowski, Ralph F; Walker, Joey L; Lee, Eun S

    2010-07-01

    Although national and state estimates of child obesity are available, data at these levels are insufficient to monitor effects of local obesity prevention initiatives. The purpose of this study was to examine regional changes in the prevalence of obesity due to statewide policies and programs among children in grades 4, 8, and 11 in Texas Health Services Regions (HSRs) between 2000-2002 and 2004-2005, and nine selected counties in 2004-2005. A cross-sectional, probability-based sample of 23,190 Texas students in grades 4, 8, and 11 were weighed and measured to obtain BMI. Obesity was >95th percentile for BMI by age/sex using Centers for Disease Control and Prevention growth charts. Child obesity prevalence significantly decreased between 2000-2002 and 2004-2005 for 4th grade students in the El Paso HSR (-7.0%, P = 0.005). A leveling off in the prevalence of obesity was noted for all other regions for grades 4, 8, and 11. County-level data supported the statistically significant decreases noted in the El Paso region. The reduction of child obesity levels observed in the El Paso area is one of the few examples of effective programs and policies based on a population-wide survey: in this region, a local foundation funded extensive regional implementation of community programs for obesity prevention, including an evidence-based elementary school-based health promotion program, adult nutrition and physical activity programs, and a radio and television advertising campaign. Results emphasize the need for sustained school, community, and policy efforts, and that these efforts can result in decreases in child obesity at the population level. PMID:19798066

  20. Cardiovascular screening in adolescents and young adults: a prospective study comparing the Pre-participation Physical Evaluation Monograph 4th Edition and ECG

    PubMed Central

    Fudge, Jessie; Harmon, Kimberly G; Owens, David S; Prutkin, Jordan M; Salerno, Jack C; Asif, Irfan M; Haruta, Alison; Pelto, Hank; Rao, Ashwin L; Toresdahl, Brett G; Drezner, Jonathan A

    2015-01-01

    Background This study compares the accuracy of cardiovascular screening in active adolescents and young adults using a standardised history, physical examination and resting 12-lead ECG. Methods Participants were prospectively screened using a standardised questionnaire based on the Pre-participation Physical Evaluation Monograph 4th Edition (PPE-4), physical examination and ECG interpreted using modern standards. Participants with abnormal findings had focused echocardiography and further evaluation. Primary outcomes included disorders associated with sudden cardiac arrest (SCA). Results From September 2010 to July 2011, 1339 participants underwent screening: age 13–24 (mean 16) years, 49% male, 68% Caucasian, 17% African-American and 1071 (80%) participating in organised sports. Abnormal history responses were reported on 916 (68%) questionnaires. After physician review, 495/ 916 (54%) participants with positive questionnaires were thought to have non-cardiac symptoms and/or a benign family history and did not warrant additional evaluation. Physical examination was abnormal in 124 (9.3%) participants, and 72 (5.4%) had ECG abnormalities. Echocardiograms were performed in 586 (44%) participants for abnormal history (31%), physical examination (8%) or ECG (5%). Five participants (0.4%) were identified with a disorder associated with SCA, all with ECG-detected Wolff-Parkinson-White. The false-positive rates for history, physical examination and ECG were 31.3%, 9.3% and 5%, respectively. Conclusions A standardised history and physical examination using the PPE-4 yields a high false-positive rate in a young active population with limited sensitivity to identify those at risk for SCA. ECG screening has a low false-positive rate using modern interpretation standards and improves detection of primary electrical disease at risk of SCA. PMID:24948082

  1. Image transformation into device-dependent color printer description using 4th-order polynomial regression and object-oriented programming development of image processing modules

    NASA Astrophysics Data System (ADS)

    Mongeon, Michael C.

    1996-03-01

    This paper investigates the development of printer device profiles used in color document printing system environments when devices with intrinsically different gamut capabilities communicate with one another in a common (CIELAB) color space. While the main thrust of this activity focuses on the output printer, namely the Xerox 5760 printer, and its rendition of some device independent image description, characterizations are provided which investigate relative areas of photographic, monitor, and printer gamuts using a visual hue leaf comparison between devices. The printer is modeled using 4th-order polynomial regression which maps the device independent CIELAB image representation into device dependent printer CMYK. This technique results in 1.89 AEEavg over the training data set. Some key properties of the proposed calibration method are as follows: (1) Linearized CMYK tone reproduction curves with respect to AEEpaper to improve the distribution of calibration data in color space. (2) Application of GCR strategy and linearization to the calibration target prior to the regression on the measured CIELAB and original CMY values. Each strategy employs a K addition/No CMY removal method which maximizes printer gamut and relies on the regression to determine the appropriate CMY removal. The following GCR strategies are explored: CMY only (0% K addition), 50% K addition, 100% K addition, and non-linear K addition. A library of image processing algorithms is included, using LabView object oriented programming, which provides a modular approach for key color processing tasks. In the user interface, an image is selected with appropriate GCR strategy, and the program operates on the image. In general, the pictorial image quality is excellent for each GCR strategy with subtle differences between GCR approaches. Quantitative analysis of Q60 color matching performance is included.

  2. Relationship between Long Working Hours and Suicidal Thoughts: Nationwide Data from the 4th and 5th Korean National Health and Nutrition Examination Survey

    PubMed Central

    Yoon, Jin-Ha; Jung, Pil Kyun; Roh, Jaehoon; Seok, Hongdeok; Won, Jong-Uk

    2015-01-01

    Background Long working hours are a worldwide problem and may increase the risk of various health issues. However, the health effects of long working hours on suicidal thoughts have not been frequently studied. Our goal was to investigate the relationship between long working hours and suicidal thoughts in the rapidly developing country of Korea. Methods Data from 12,076 participants (7,164 men, 4,912 women) from the 4th and 5th Korean National Health and Nutrition Examination Surveys were used for the current analysis. Multivariate logistic regression models were used to estimate odds ratios and 95% confidence intervals for suicidal thoughts. Combined effects of long working hours and lower socioeconomic status or sleep disturbance were also estimated. Results Compared to groups who worked less than 52 hours per week, odds ratios (95% confidence intervals) for suicidal thoughts in groups who worked 60 hours or more per week were 1.36 (1.09–1.70) for males and 1.38 (1.11–1.72) for females, even after controlling for household income, marital status, history of hypertension or diabetes mellitus, health-related behaviors, and past two weeks’ experience of injury, intoxication, or acute or chronic diseases, as well as type of work. The combined effects of long working hours with lower socioeconomic status, or with sleep disturbance, were also significantly higher compared to participants who worked less than 52 hours per week with higher socioeconomic status, or with 6–8 hours of nighttime sleep. Conclusion In this study, long working hours were linked to suicidal thoughts for both genders. Additionally, the odds of those suicidal thoughts were higher for lower socioeconomic groups. To prevent adverse psychological health problems such as suicidal thoughts, a strategy regarding long working hours should be investigated. PMID:26080022

  3. Student learning of key concepts and skills in inquiry science: A longitudinal study of 4th and 6th grade students

    NASA Astrophysics Data System (ADS)

    Davison, Reeny De Vos

    This study arose out of the need to measure the validity of the hands-on, inquiry-based approach to science learning, as articulated in the National Science Education Standards. It addressed the question of whether the use of hands-on, inquiry-based curriculum promotes improved student understanding of science content and problem-solving and scientific reasoning skills. It measured 4th and 6th grade student learning in five skills (comparing, graphing, investigating, measuring, predicting) and five concepts (objects in the sky, properties, variables, units of measure, life cycle). Data were collected in 1997 and 1999 from two elementary schools in one suburban Pittsburgh school district, where hands-on curriculum units were implemented starting in 1997. A performance-based assessment instrument was devised. Findings were compared by school and by year and showed significant improvement in student learning over the two years. Students improved significantly in the skills of comparing and measuring and in the concepts of objects in the sky, variables, and the life cycle. Additionally, in the repeated measures group, significant improvement was also indicated in the skill of graphing and the concepts of properties and units of measure. No significant differences were found in the skills of investigating and predicting. Student scores in the school with somewhat lower socio-economic status increased more significantly. The study supports the key principles that guided the development of the National Science Education Standards and comprehensive science education programs aligned with them. The results support including the elements of systemic reform, i.e., hands-on curriculum materials, ongoing professional development, centralized materials support, assessment, and community involvement, in all schools.

  4. High prevalence of Fluoroquinolone- and Methicillin-resistant Staphylococcus pseudintermedius isolates from canine pyoderma and otitis externa in veterinary teaching hospital.

    PubMed

    Yoo, Jong-Hyun; Yoon, Jang W; Lee, So-Young; Park, Hee-Myung

    2010-04-01

    Recently, a total of 74 Staphylococcus pseudintermedius isolates were collected from clinical cases of canine pyoderma and otitis externa in Korea. In this study, we examined in vitro fluoroquinolone resistance among those isolates using a standard disk diffusion technique. The results demonstrated that approximately 18.9% to 27.0% of the isolates possessed bacterial resistance to both veterinary- and human-licensed fluoroquinolones except one isolate, including moxifloxacin (18.9% resistance), levofloxacin (20.3% resistance), ofloxacin (24.3% resistance), ciprofloxacin (25.7% resistance), and enrofloxacin (27.0% resistance). Most surprisingly, 14 out of 74 (18.9%) isolates were resistant to all the five fluoroquinolones evaluated. Moreover, a PCR detection of the methicillin resistance gene (mecA) among the 74 isolates revealed that 13 out of 25 (52.0%) mecA-positive isolates, but only 7 out of 49 (14.3%) mecA-negative isolates, were resistant to one or more fluoroquinones. Taken together, our results imply that bacterial resistance to both veterinary- and human-use fluoroquinolones becomes prevalent among the S. pseudintermedius isolates from canine pyoderma and otitis externa in Korea as well as that the high prevalence of the mecA-positive S. pseudintermedius isolates carrying multiple fluoroquinolone resistance could be a potential public health problem. PMID:20467256

  5. The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients.

    PubMed

    Kandemir, Özlem; Bozlu, Murat; Efesoy, Ozan; Güntekin, Onur; Tek, Mesut; Akbay, Erdem

    2016-08-01

    We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P = 0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization. PMID:25630553

  6. Resistance Mutations in gyrA and parC are Common in Escherichia Communities of both Fluoroquinolone-Polluted and Uncontaminated Aquatic Environments

    PubMed Central

    Johnning, Anna; Kristiansson, Erik; Fick, Jerker; Weijdegård, Birgitta; Larsson, D. G. Joakim

    2015-01-01

    Alterations in the target proteins of fluoroquinolones, especially in GyrA and ParC, are known to cause resistance. Here, we investigated environmental Escherichia communities to explore the possible link between the abundance of mutations, and the exposure to fluoroquinolones. Sediment samples were collected from a relatively pristine lake, up and downstream from a sewage treatment plant, and from several industrially polluted sites. The quinolone resistance-determining regions of gyrA and parC were analyzed using amplicon sequencing of metagenomic DNA. Five non-synonymous substitutions were present in all samples, and all of these mutations have been previously linked to fluoroquinolone resistance in Escherichia coli. In GyrA, substitutions S83L and D87N were on average detected at frequencies of 86 and 32%, respectively, and 31% of all amplicons encoded both substitutions. In ParC, substitutions S80I, E84G, and E84V were detected in 42, 0.9, and 6.0% of the amplicons, respectively, and 6.5% encoded double substitutions. There was no significant correlation between the level of fluoroquinolone pollution and the relative abundance of resistance mutations, with the exception of the most polluted site, which showed the highest abundance of said substitutions in both genes. Our results demonstrate that resistance mutations can be common in environmental Escherichia, even in the absence of a fluoroquinolone selective pressure. PMID:26696975

  7. How Do 4th, 5th, and 6th Grade Students' Categories of Cognitive Reflections in Interviews on Derivational Morphology Compare to Their Upper Level Spelling Inventory Orthographic Knowledge?

    ERIC Educational Resources Information Center

    Smith, Darcie D.

    2012-01-01

    Eighty-seven 4th, 5th and 6th grade students were administered the "Derivational Relatedness Interview" (DRI) (Templeton, Smith, Moloney, Van Pelt, & Ives, 2009). The purpose of this instrument is to explore students' understanding of derivational morphology. During the same week, the subjects were also administered an Upper…

  8. Fluoroquinolone-mediated inhibition of cell growth, S-G2/M cell cycle arrest, and apoptosis in canine osteosarcoma cell lines.

    PubMed

    Seo, Kyoung won; Holt, Roseline; Jung, Yong-Sam; Rodriguez, Carlos O; Chen, Xinbin; Rebhun, Robert B

    2012-01-01

    Despite significant advancements in osteosarcoma research, the overall survival of canine and human osteosarcoma patients has remained essentially static over the past 2 decades. Post-operative limb-spare infection has been associated with improved survival in both species, yet a mechanism for improved survival has not been clearly established. Given that the majority of canine osteosarcoma patients experiencing post-operative infections were treated with fluoroquinolone antibiotics, we hypothesized that fluoroquinolone antibiotics might directly inhibit the survival and proliferation of canine osteosarcoma cells. Ciprofloxacin or enrofloxacin were found to inhibit p21(WAF1) expression resulting in decreased proliferation and increased S-G(2)/M accumulation. Furthermore, fluoroquinolone exposure induced apoptosis of canine osteosarcoma cells as demonstrated by cleavage of caspase-3 and PARP, and activation of caspase-3/7. These results support further studies examining the potential impact of quinolones on survival and proliferation of osteosarcoma. PMID:22927942

  9. Fluoroquinolone-Mediated Inhibition of Cell Growth, S-G2/M Cell Cycle Arrest, and Apoptosis in Canine Osteosarcoma Cell Lines

    PubMed Central

    Seo, Kyoung won; Holt, Roseline; Jung, Yong-Sam; Rodriguez, Carlos O.; Chen, Xinbin; Rebhun, Robert B.

    2012-01-01

    Despite significant advancements in osteosarcoma research, the overall survival of canine and human osteosarcoma patients has remained essentially static over the past 2 decades. Post-operative limb-spare infection has been associated with improved survival in both species, yet a mechanism for improved survival has not been clearly established. Given that the majority of canine osteosarcoma patients experiencing post-operative infections were treated with fluoroquinolone antibiotics, we hypothesized that fluoroquinolone antibiotics might directly inhibit the survival and proliferation of canine osteosarcoma cells. Ciprofloxacin or enrofloxacin were found to inhibit p21WAF1 expression resulting in decreased proliferation and increased S-G2/M accumulation. Furthermore, fluoroquinolone exposure induced apoptosis of canine osteosarcoma cells as demonstrated by cleavage of caspase-3 and PARP, and activation of caspase-3/7. These results support further studies examining the potential impact of quinolones on survival and proliferation of osteosarcoma. PMID:22927942

  10. Proarrhythmic effects of fluoroquinolone antibacterial agents: in vivo effects as physiologic substrate for torsades.

    PubMed

    Chiba, K; Sugiyama, A; Satoh, Y; Shiina, H; Hashimoto, K

    2000-11-15

    Drug-induced prolongation of the QT interval is often associated with the onset of Torsades de Pointes (TdP) resulting in a life-threatening ventricular arrhythmia. The potential of the proarrhythmic effects of the new fluoroquinolone antibacterial agents, levofloxacin and sparfloxacin, was examined in the chronic complete atrioventricular block dogs with stable idioventricular automaticity using Holter ECG monitoring in conscious state (Experiment 1). Next, to better analyze the mechanisms of the proarrhythmic property, the cardiovascular effects of these two drugs were compared in the halothane-anesthetized dogs under the monitoring of ECG, His bundle electrogram, systemic and left ventricular pressure, monophasic action potential, cardiac output, and effective refractory period (Experiment 2). In Experiment 1, oral administration of 6 mg/kg (n = 4) as well as 60 mg/kg (n = 4) of levofloxacin did not induce any ventricular premature depolarization. On the other hand, oral administration of 60 mg/kg of sparfloxacin (n = 4) induced TdP leading to ventricular fibrillation in all animals within 24 h, while 6 mg/kg of sparfloxacin (n = 4) did not induce any ventricular premature depolarization. In Experiment 2, intravenous administration of 0.3 mg/kg as well as 3.0 mg/kg of levofloxacin slightly increased cardiac output, but no significant changes were detected in the other parameters (n = 6). On the other hand, intravenous administration of 0.3 mg/kg of sparfloxacin prolonged the effective refractory period. Additional administration of 3.0 mg/kg of sparfloxacin decreased the heart rate and prolonged the effective refractory period and ventricular repolarization phase in a similar extent, but no significant changes were detected in the other parameters (n = 6). These results suggest that backward shift of the relative repolarization period in a cardiac cycle may be the mechanism responsible for the torsadegenic effect of sparfloxacin. PMID:11076691

  11. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia

    PubMed Central

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18–24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID:27405358

  12. Comprehensive evaluation of formulation factors for ocular penetration of fluoroquinolones in rabbits using cassette dosing technique

    PubMed Central

    Sharma, Charu; Biswas, Nihar R; Ojha, Shreesh; Velpandian, Thirumurthy

    2016-01-01

    Objective Corneal permeability of drugs is an important factor used to assess the efficacy of topical preparations. Transcorneal penetration of drugs from aqueous formulation is governed by various physiological, physiochemical, and formulation factors. In the present study, we investigated the effect of formulation factors like concentration, pH, and volume of instillation across the cornea using cassette dosing technique for ophthalmic fluoroquinolones (FQs). Materials and methods Sterile cocktail formulations were prepared using four congeneric ophthalmic FQs (ofloxacin, sparfloxacin, pefloxacin mesylate, and gatifloxacin) at concentrations of 0.025%, 0.5%, and 0.1%. Each formulation was adjusted to different pH ranges (4.5, 7.0, and 8.0) and assessed for transcorneal penetration in vivo in rabbit’s cornea (n=4 eyes) at three different volumes (12.5, 25, and 50 μL). Aqueous humor was aspirated through paracentesis after applying local anesthesia at 0, 5, 15, 30, 60, 120, and 240 minutes postdosing. The biosamples collected from a total of 27 groups were analyzed using liquid chromatography–tandem mass spectroscopy to determine transcorneal permeability of all four FQs individually. Results Increase in concentration showed an increase in penetration up to 0.05%; thereafter, the effect of concentration was found to be dependent on volume of instillation as we observed a decrease in transcorneal penetration. The highest transcorneal penetration of all FQs was observed at pH 7.0 at concentration 0.05% followed by 0.025% at pH 4.5. Lastly, increasing the volume of instillation from 12.5 to 50 μL showed a significant fall in transcorneal penetration. Conclusion The study concludes that formulation factors showed discernible effect on transcorneal permeation; therefore, due emphasis should be given on drug development and design of ophthalmic formulation. PMID:26955263

  13. Antimicrobial resistance and genetic characterization of fluoroquinolone resistance of Pseudomonas aeruginosa isolated from canine infections.

    PubMed

    Rubin, J; Walker, R D; Blickenstaff, K; Bodeis-Jones, S; Zhao, S

    2008-09-18

    Infections with antimicrobial-resistant bacteria are a great challenge in both human and veterinary medicine. The purpose of this study was to determine antimicrobial susceptibility of 106 strains of Pseudomonas aeruginosa isolated from dogs with otitis and pyoderma from 2003 to 2006 in the United States. Three antimicrobial panels, including 6 classes and 32 antimicrobial agents, were used. A wide range of susceptibility patterns were noted with some isolates being resistant to between 8 and 28 (mean 16) of the antimicrobials tested. Among the beta-lactams, all isolates were resistant to ampicillin, cefoxitin, cefpodoxime, cephalothin and cefazolin followed by amoxicillin/clavulanic acid (99%), ceftiofur (97%), ceftriaxone (39%), cefotaxime (26%), and cefotaxime/clavulanic acid (20%), whereas less than 7% of isolates were resistant to ceftazidime/clavulanic acid, ceftazidime, piperacillin/tazobactam or cefepime. Two isolates were resistant to the carbapenems. Among the quinolones and fluoroquinolones, the most isolates were resistant to naladixic acid (96%), followed by orbifloxacin (52%), difloxacin (43%), enrofloxacin (31%), marbofloxacin (27%), gatifloxacin (23%), levofloxacin (21%), and ciprofloxacin (16%). Among the aminoglycosides, the most resistance was seen to kanamycin (90%), followed by streptomycin (69%), gentamicin (7%), and amikacin (3%). Of the remaining antimicrobials 100% of the isolates were resistant to chloramphenicol followed by tetracycline (98%), trimethoprim/sulfamethoxazole (57%), and sulfisoxazole (51%). Point mutations were present in gyrA, gyrB, parC, and/or parE genes among 34 of the 102 naladixic acid-resistant isolates. Two isolates contained class 1 integrons carrying aadA gene conferring streptomycin and spectinomycin resistance. The findings suggest that many antimicrobial agents commonly used in companion animals may not constitute appropriate therapy for canine pseudomonas infections. PMID:18395369

  14. Fluoroquinolones and Tetracycline Antibiotics in a Portuguese Aquaculture System and Aquatic Surroundings: Occurrence and Environmental Impact.

    PubMed

    Pereira, André M P T; Silva, Liliana J G; Meisel, Leonor M; Pena, Angelina

    2015-01-01

    The growth of aquaculture over the past few years is widely recognized as one of the main sources of antibiotics, mainly fluoroquinolones (FQ) and tetracyclines (TC), in the aquatic environment, consequently, increasing the risk of the emergence of antibiotic bacterial resistance and promoting the spread of resistant genes. This study aimed to (1) develop and validate a multiresidue method for determination and quantification of ciprofloxacin (CIP), difloxacin (DIFL), enrofloxacin (ENR), norfloxacin (NOR), sarafloxacin (SARA), and oxytetracycline (OXY) in aquaculture waters and surrounding water bodies and (2) provide the first Portuguese data to utilize in assessment of risk of adverse effects. In addition, the potential environmental impact posed by these antibiotics to aquatic organisms, belonging to different trophic levels, when exposed to the studied aquaculture waters was also assessed. The analytical strategy comprised of solid-phase extraction (SPE) through Oasis HLB cartridges, and detection and quantification by liquid chromatography with tandem mass spectrometry (LC/MS(n)). Method detection limits (MDL) and method quantification limits (MQL) were in the range of 0.7-3 ng/L and 2.4-10 ng/L, respectively. Recoveries varied between 57.4 and 122.8%. The method was applied to 31 water samples collected from an aquaculture and surrounding water bodies located in north of Portugal. Residues of all antibiotics, except SARA and DIFL, were detected at concentrations ranging from 3 to 75.1 ng/L. Norfloxacin was the antibiotic present at highest frequency and concentration. Regarding the environmental impact assessment (EIA), a risk quotient higher than 1 was observed for NOR. PMID:26262440

  15. Degradation of fluoroquinolone antibiotics by ferrate(VI): Effects of water constituents and oxidized products.

    PubMed

    Feng, Mingbao; Wang, Xinghao; Chen, Jing; Qu, Ruijuan; Sui, Yunxia; Cizmas, Leslie; Wang, Zunyao; Sharma, Virender K

    2016-10-15

    The degradation of five fluoroquinolone (FQ) antibiotics (flumequine (FLU), enrofloxacin (ENR), norfloxacin (NOR), ofloxacin (OFL) and marbofloxacin (MAR)) by ferrate(VI) (Fe(VI)O4(2-), Fe(VI)) was examined to demonstrate the potential of this iron-based chemical oxidant to treat antibiotics in water. Experiments were conducted at different molar ratios of Fe(VI) to FQs at pH 7.0. All FQs, except FLU, were degraded within 2 min at [Fe(VI)]:[FQ] ≤ 20.0. Multiple additions of Fe(VI) improved the degradation efficiency, and provided greater degradation than a single addition of Fe(VI). The effects of anions, cations, and humic acid (HA), usually present in source waters and wastewaters, on the removal of FLU were investigated. Anions (Cl(-), SO4(2-), NO3(-), and HCO3(-)) and monovalent cations (Na(+) and K(+)) had no influence on the removal of FLU. However, multivalent cations (Ca(2+), Mg(2+), Cu(2+), and Fe(3+)) in water decreased the efficiency of FLU removal by Fe(VI). An increase in the ionic strength of the solution, and the presence of HA in the water, also decreased the percentage of FLU removed by Fe(VI). Experiments on the removal of selected FQs, present as co-existing antibiotics in pure water, river water, synthetic water and wastewater, were also conducted to demonstrate the practical application of Fe(VI) to remove the antibiotics during water treatment. The seventeen oxidized products (OPs) of FLU were identified using solid phase extraction-liquid chromatography-high-resolution mass spectrometry. The reaction pathways are proposed, and are theoretically confirmed by molecular orbital calculations. PMID:27429354

  16. Mechanism of hERG K+ channel blockade by the fluoroquinolone antibiotic moxifloxacin

    PubMed Central

    Alexandrou, Ari J; Duncan, Rona S; Sullivan, Anneli; Hancox, Jules C; Leishman, Derek J; Witchel, Harry J; Leaney, Joanne L

    2006-01-01

    The fluoroquinolone antibiotic moxifloxacin has been associated with the acquired long QT syndrome and is used as a positive control in the evaluation of the QT-interval prolonging potential of new drugs. In common with other QT-prolonging agents, moxifloxacin is known to inhibit the hERG potassium K+ channel, but at present there is little mechanistic information available on this action. This study was conducted in order to characterise the inhibition of hERG current (IhERG) by moxifloxacin, and to determine the role in drug binding of the S6 aromatic amino-acid residues Tyr652 and Phe656. hERG currents were studied using whole-cell patch clamp (at room temperature and at 35–37°C) in an HEK293 cell line stably expressing hERG channels. Moxifloxacin reversibly inhibited currents in a dose-dependent manner. We investigated the effects of different voltage commands to elicit hERG currents on moxifloxacin potency. Using a ‘step-ramp' protocol, the IC50 was 65 μM at room temperature and 29 μM at 35°C. When a ventricular action potential waveform was used to elicit currents, the IC50 was 114 μM. Block of hERG by moxifloxacin was found to be voltage-dependent, occurred rapidly and was independent of stimulation frequency. Mutagenesis of the S6 helix residue Phe656 to Ala failed to eliminate or reduce the moxifloxacin-mediated block whereas mutation of Tyr652 to Ala reduced moxifloxacin block by ∼66%. Our data demonstrate that moxifloxacin blocks the hERG channel with a preference for the activated channel state. The Tyr652 but not Phe656 S6 residue is involved in moxifloxacin block of hERG, concordant with an interaction in the channel inner cavity. PMID:16474415

  17. A prescription event monitoring study on the utility of garenoxacin, a newer fluoroquinolone in India

    PubMed Central

    Hajare, Anoop; Gupta, Amandeep; Patil, Saiprasad; Krishnaprasad, K; Bhargava, Amit

    2015-01-01

    Background: Prescription event monitoring (PEM) study is conducted worldwide. The main objective of such study is to monitor the adverse events when a drug is being prescribed in “real life clinical” settings. PEM studies are being looked upon as an essential observational tool of postmarketing surveillance. Garenoxacin, a newer fluoroquinolone offers an excellent spectrum of antimicrobial coverage, which includes Gram-positive, Gram-negative, anaerobes and atypical microorganism. This broad spectrum of activity is attributed to its unique structure. Aim: The aim was to assess the safety profile of garenoxacin in Indian settings. Materials and Methods: A total of 400 doctors across the country participated in the study. Data from 12,498 patients was obtained. Monitoring of each patient was done for any adverse events. Results: As an initial line of therapy garenoxacin was preferred in majority of cases of community-acquired pneumonia (CAP) and acute exacerbations of chronic bronchitis. Adverse events were reported in 159 patients which included 0.5% cases with nausea/vomiting, 0.1% cases with diarrhea. Central nervous system side-effects like drowsiness or dizziness was reported in 0.02% of the cases. All the adverse events were of mild to moderate severity and did not require hospitalization. Conclusion: Garenoxacin a novel desfluoroquinolone appears to be an ideal antimicrobial agent for the treatment of various respiratory tract infections including CAP. With superior safety profile, excellent antimicrobial coverage and a convenient once a day dosing garenoxacin appears to improve the patient compliance. PMID:26097813

  18. Revisit of fluoroquinolone and azithromycin susceptibility breakpoints for Salmonella enterica serovar Typhi.

    PubMed

    Das, Surojit; Ray, Ujjwayini; Dutta, Shanta

    2016-07-01

    In recent years, increase in occurrence of fluoroquinolone (FQ)-resistant S almonella Typhi isolates has caused considerable inconvenience in selecting appropriate antimicrobials for treatment of typhoid. The World Health Organization (WHO) recommends azithromycin for the empirical treatment option of uncomplicated typhoid. The CLSI updated the breakpoints of disc diffusion (DD) and MIC results of FQs and azithromycin for Salmonella Typhi in 2015, but DD breakpoints of ofloxacin and levofloxacin were not included. In this study, the inhibition zone diameters and MICs of nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin and azithromycin were determined in Salmonella Typhi Kolkata isolates (n =146) over a 16-year period (1998 to 2013) and the data were compared with the available CLSI breakpoints. Very major error and major error (ME) of FQs were not observed in the study isolates, but the minor error of ciprofloxacin (15.8 %) and ME of azithromycin (3.5 %) exceeded the acceptable limit. A positive correlation between MICs of FQ and mutations in the quinolone-resistance-determining region (QRDR) showed the reliability of MIC results to determine FQ susceptibility of Salmonella Typhi (n =74). Isolates showing decreased ciprofloxacin susceptibility (MIC 0.125-0.5 µg  ml-1) were likely to have at least one mutation in the QRDR region. The results on DD breakpoints of ofloxacin (resistant, ≤15 mm; intermediate, 16-24 mm, and susceptible, ≥25 mm) and levofloxacin (resistant, ≤18 mm; intermediate, 19-27 mm, and susceptible, ≥28 mm) corroborated those of earlier studies. In view of the emerging FQ- and azithromycin-resistant Salmonella Typhi isolates, DD and MIC breakpoints of those antimicrobials should be revisited routinely. PMID:27221661

  19. Spectroscopic studies on the lanthanide sensitized luminescence and chemiluminescence properties of fluoroquinolone with different structure.

    PubMed

    Sun, Chunyan; Ping, Hong; Zhang, Minwei; Li, Hongkun; Guan, Fengrui

    2011-11-01

    Lanthanide sensitized luminescence and chemiluminescence (CL) are of great importance because of the unique spectral properties, such as long lifetime, large Stokes shifts, and narrow emission bands characteristic to lanthanide ions (Ln(3+)). With the fluoroquinolone (FQ) compounds including enoxacin (ENX), norfloxacin (NFLX), lomefloxacin (LMFX), fleroxacin (FLRX), ofloxacin (OFLX), rufloxacin (RFX), gatifloxacin (GFLX) and sparfloxacin (SPFX), the luminescence and CL properties of Tb(3+)-FQ and Eu(3+)-FQ complexes have been investigated in this contribution. Ce(4+)-SO(3)(2-) in acidic conditions was taken as the CL system and sensitized CL intensities of Tb(3+)-FQ and Eu(3+)-FQ complexes were determined by flow-injection analysis. The luminescence and CL spectra of Tb(3+)-FQ complexes show characteristic peaks of Tb(3+) at 490 nm, 545 nm, 585 nm and 620 nm. Complexes of Tb(3+)-ENX, Tb(3+)-NFLX, Tb(3+)-LMFX and Tb(3+)-FLRX display relatively strong emission intensity compared with Tb(3+)-OFLX, Tb(3+)-RFX, Tb(3+)-GFLX and Tb(3+)-SPFX. Quite weak peaks with unique characters of Eu(3+) at 590 nm and 617 nm appear in the luminescence and CL spectra of Eu(3+)-ENX, but no notable sensitized luminescence and CL of Eu(3+) could be observed when Eu(3+) is added into other FQ. The distinct differences on emission intensity of Tb(3+)-FQ and Eu(3+)-FQ might originate from the different energy gap between the triplet levels of FQ and the excited levels of the Ln(3+). The different sensitized luminescence and CL signals among Tb(3+)-FQ complexes could be attributed to different optical properties and substituents of these FQ compounds. The detailed mechanism involved in the luminescence and CL properties of Tb(3+)-FQ and Eu(3+)-FQ complexes has been investigated by analyzing the luminescence and CL spectra, quantum yields, and theoretical calculation results. PMID:21821467

  20. Effects of Fluoroquinolones and Azithromycin on Biofilm Formation of Stenotrophomonas maltophilia.

    PubMed

    Wang, Aihua; Wang, Qinqin; Kudinha, Timothy; Xiao, Shunian; Zhuo, Chao

    2016-01-01

    Stenotrophomonas maltophilia is an opportunistic pathogen that causes respiratory and urinary tract infections, as well as wound infections in immunocompromised patients. This pathogen is difficult to treat due to increased resistance to many antimicrobial agents. We investigated the in vitro biofilm formation of S. maltophilia, including effects of fluoroquinolones (FQs) and azithromycin on biofilm formation. The organism initiated attachment to polystyrene surfaces after a 4 h incubation period, and reached maximal growth at 18-24 h. In the presence of FQs (moxifloxacin, levofloxacin or ciprofloxacin), the biofilm biomass was significantly reduced (P < 0.05). A lower concentration of moxifloxacin (10 μg/mL) exhibited a better inhibiting effect on biofilm formation than 100 μg/mL (P < 0.01), but with no difference in effect compared to the 50 μg/mL concentration (P > 0.05). However, the inhibitory effects of 10 μg/mL of levofloxacin or ciprofloxacin were slightly less pronounced than those of the higher concentrations. A combination of azithromycin and FQs significantly reduced the biofilm inhibiting effect on S. maltophilia preformed biofilms compared to azithromycin or FQs alone. We conclude that early use of clinically acceptable concentrations of FQs, especially moxifloxacin (10 μg/mL), may possibly inhibit biofilm formation by S. maltophilia. Our study provides an experimental basis for a possible optimal treatment strategy for S. maltophilia biofilm-related infections. PMID:27405358

  1. Spectroscopic studies on the lanthanide sensitized luminescence and chemiluminescence properties of fluoroquinolone with different structure

    NASA Astrophysics Data System (ADS)

    Sun, Chunyan; Ping, Hong; Zhang, Minwei; Li, Hongkun; Guan, Fengrui

    2011-11-01

    Lanthanide sensitized luminescence and chemiluminescence (CL) are of great importance because of the unique spectral properties, such as long lifetime, large Stokes shifts, and narrow emission bands characteristic to lanthanide ions (Ln 3+). With the fluoroquinolone (FQ) compounds including enoxacin (ENX), norfloxacin (NFLX), lomefloxacin (LMFX), fleroxacin (FLRX), ofloxacin (OFLX), rufloxacin (RFX), gatifloxacin (GFLX) and sparfloxacin (SPFX), the luminescence and CL properties of Tb 3+-FQ and Eu 3+-FQ complexes have been investigated in this contribution. Ce 4+-SO 32- in acidic conditions was taken as the CL system and sensitized CL intensities of Tb 3+-FQ and Eu 3+-FQ complexes were determined by flow-injection analysis. The luminescence and CL spectra of Tb 3+-FQ complexes show characteristic peaks of Tb 3+ at 490 nm, 545 nm, 585 nm and 620 nm. Complexes of Tb 3+-ENX, Tb 3+-NFLX, Tb 3+-LMFX and Tb 3+-FLRX display relatively strong emission intensity compared with Tb 3+-OFLX, Tb 3+-RFX, Tb 3+-GFLX and Tb 3+-SPFX. Quite weak peaks with unique characters of Eu 3+ at 590 nm and 617 nm appear in the luminescence and CL spectra of Eu 3+-ENX, but no notable sensitized luminescence and CL of Eu 3+ could be observed when Eu 3+ is added into other FQ. The distinct differences on emission intensity of Tb 3+-FQ and Eu 3+-FQ might originate from the different energy gap between the triplet levels of FQ and the excited levels of the Ln 3+. The different sensitized luminescence and CL signals among Tb 3+-FQ complexes could be attributed to different optical properties and substituents of these FQ compounds. The detailed mechanism involved in the luminescence and CL properties of Tb 3+-FQ and Eu 3+-FQ complexes has been investigated by analyzing the luminescence and CL spectra, quantum yields, and theoretical calculation results.

  2. Removal of fluoroquinolone contaminants from environmental waters on sepiolite and its photo-induced regeneration.

    PubMed

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Profumo, Antonella; Tarantino, Serena; Gualtieri, Alessandro F; Zema, Michele

    2016-05-01

    Sepiolite is studied as sorbent for removal of Fluoroquinolone (FQ) contaminants from water. Marbofloxacin (MAR) and Enrofloxacin (ENR) were chosen as model FQs since they are the two most commonly employed veterinary FQs in livestock farming in northern Italy. Adsorption experiments on two sepiolites (SP-1 and SSE16) were carried out in tap water at pH 7.5 to better mimic real conditions. The sorption experimental data were fitted by Freundlich, Langmuir and S-Logistic1 models. The latter better described MAR and ENR adsorptions. Adsorption capacities of SP-1 and SSE16, respectively, were 132 mg g(-1) and 121 mg g(-1) for MAR, and 112 mg g(-1) and 93 mg g(-1) for ENR. X-ray powder diffraction, performed on clay samples enriched with each FQ and on the pristine clays, showed no substantial differences between the two sepiolites and evidenced no significant structural changes after FQs uptake, as also verified by infrared spectroscopy. This indicates that adsorption occurs only on the external surface of the mineral and not in the intracrystalline microporosity, likely due to the interaction between the FQ carboxylic group and the sepiolite surface. For the first time solid-state photodegradation of the adsorbed FQs was investigated for regenerating the sorbent. Results showed that the adsorbed drugs are effectively photodegraded by solar light, thus allowing sepiolite to be reused. The efficiency of this material for remediation of contaminated water was proved on ditch water, collected downstream a swine farm, containing some tens of ng L(-1) of MAR and ENR. PMID:26796589

  3. Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

    PubMed

    Pettigrew, Melinda M; Tsuji, Brian T; Gent, Janneane F; Kong, Yong; Holden, Patricia N; Sethi, Sanjay; Murphy, Timothy F

    2016-07-01

    Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. Five of 27 (19%) strains developed 4-fold increases in azithromycin MICs and reached or exceeded the susceptibility breakpoint (≤4 μg/ml) during exposure. H. influenzae isolates were uniformly susceptible to ciprofloxacin, levofloxacin, and moxifloxacin (MIC90s of 0.015, 0.015, and 0.06, respectively); there were no mutations in quinolone resistance-determining regions. Fluoroquinolone administration was associated with increased H. influenzae eradication compared to macrolides (odds ratio [OR], 16.67; 95% confidence interval [CI], 2.67 to 104.09). There was no difference in H. influenzae eradication when comparing macrolide administration to no antibiotic (OR, 1.89; 95% CI, 0.43 to 8.30). Fluoroquinolones are effective in eradicating H. influenzae in individuals with COPD. Macrolides are ineffective in eradicating H. influenzae, and their use in COPD patients may lead to decreased macrolide susceptibility and resistance. PMID:27139476

  4. Antimicrobial activity of prulifloxacin in comparison with other fluoroquinolones against community-acquired urinary and respiratory pathogens isolated in Greece.

    PubMed

    Karageorgopoulos, D E; Maraki, S; Vatopoulos, A C; Samonis, G; Schito, G C; Falagas, M E

    2013-11-01

    Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum fluoroquinolone rather recently introduced in certain European countries. We compared the antimicrobial potency of ulifloxacin with that of other fluoroquinolones against common urinary and respiratory bacterial pathogens. The microbial isolates were prospectively collected between January 2007 and May 2008 from patients with community-acquired infections in Greece. Minimum inhibitory concentrations (MICs) were determined for ciprofloxacin, levofloxacin, moxifloxacin (for respiratory isolates only), and ulifloxacin using the E-test method. The binary logarithms of the MICs [log2(MICs)] were compared by using the Wilcoxon signed-ranks test. A total of 409 isolates were studied. Ulifloxacin had the lowest geometric mean MIC for the 161 Escherichia coli, 59 Proteus mirabilis, and 22 Staphylococcus saprophyticus urinary isolates, the second lowest geometric mean MIC for the 38 Streptococcus pyogenes respiratory isolates (after moxifloxacin), and the third lowest geometric mean MIC for the 114 Haemophilus influenzae and the 15 Moraxella catarrhalis respiratory isolates (after ciprofloxacin and moxifloxacin). Compared with levofloxacin, ulifloxacin had lower log2(MICs) against E. coli (p < 0.001), P. mirabilis (p < 0.001), S. saprophyticus (p < 0.001), and S. pyogenes (p < 0.001). Compared with ciprofloxacin, ulifloxacin had lower log2(MICs) against P. mirabilis (p < 0.001), S. saprophyticus (p = 0.008), and S. pyogenes (p < 0.001), but higher log2(MICs) against H. influenzae (p < 0.001) and M. catarrhalis (p = 0.001). In comparison with other clinically relevant fluoroquinolones, ulifloxacin had the most potent antimicrobial activity against the community-acquired urinary isolates studied and very good activity against the respiratory isolates. PMID:23686506

  5. EDITORIAL: Instrumentation and Methods for Neutron Scattering—papers from the 4th European Conference on Neutron Scattering in Lund, Sweden, June 2007

    NASA Astrophysics Data System (ADS)

    Rennie, Adrian R.

    2008-03-01

    Neutron scattering is used as a tool to study problems in disciplines that include chemistry, materials science, biology and condensed matter physics as well as problems from neighbouring disciplines such as geology, environmental sciences and archaeology. Equipment for these studies is found at laboratories with research reactors or spallation neutron sources and there are many recent or current developments with new instruments and even entirely new facilities such as the Spallation Neutron Source at Oak Ridge, USA, the OPAL reactor at Lucas Heights, Australia and the second target station at the ISIS facility in the UK. Design and optimization of the instruments at these facilities involves work with many research laboratories and groups in universities. Every four years the European Conference on Neutron Scattering (ECNS) brings together both the specialists in neutron instrumentation and the community of users (in intervening years there are International and American conferences). In June 2007 about 700 delegates came to the 4th ECNS that was held in Lund, Sweden. There were more than 600 presentations as talks and posters. The opportunity to publish papers in Measurement Science and Technology that relate to neutron scattering instrumentation and method development was offered to the participants, and the papers that follow describe some of the recent activity in this field. Accounts of work on condensed matter science and the applications of neutron scattering appear separately in Journal of Physics: Condensed Matter. There are, of course, many features of neutron instrumentation that are specific to this particular field of measurement. However, there are also many elements of apparatus and experiment design that can usefully be shared with a broader community. It is hoped that this issue with papers from ECNS will find a broad community of interest. Apart from descriptions of overall design of diffractometers and spectrometers there are accounts of new

  6. New Wisdom to Defy an Old Enemy: Summary from a scientific symposium at the 4th Influenza Vaccines for the World (IVW) 2012 Congress, 11 October, Valencia, Spain.

    PubMed

    Poland, Gregory A; Fleming, Douglas M; Treanor, John J; Maraskovsky, Eugene; Luke, Thomas C; Ball, Emma M A; Poland, Caroline M

    2013-04-17

    Both seasonal and pandemic influenza cause considerable morbidity and mortality globally. In addition, the ongoing threat of new, unpredictable influenza pandemics from emerging variant strains cannot be underestimated. Recently bioCSL (previously known as CSL Biotherapies) sponsored a symposium 'New Wisdom to Defy an Old Enemy' at the 4th Influenza Vaccines for the World Congress in Valencia, Spain. This symposium brought together a renowned faculty of experts to discuss lessons from past experience, novel influenza vaccine developments, and new methods to increase vaccine acceptance and coverage. Specific topics reviewed and discussed included new vaccine development efforts focused on improving efficacy via alternative administration routes, dose modifications, improved adjuvants, and the use of master donor viruses. Improved safety was also discussed, particularly the new finding of an excess of febrile reactions isolated to children who received the 2010 Southern Hemisphere (SH) trivalent inactivated influenza vaccine (TIV). Significant work has been done to both identify the cause and minimize the risk of febrile reactions in children. Other novel prophylactic and therapeutic advances were discussed including immunotherapy. Standard IVIg and hIVIg have been used in ferret studies and human case reports with promising results. New adjuvants, such as ISCOMATRIX™ adjuvant, were noted to provide single-dose, prolonged protection with seasonal vaccine after lethal H5N1 virus challenge in a ferret model of human influenza disease. The data suggest that adjuvanted seasonal influenza vaccines may provide broader protection than unadjuvanted vaccines. The use of an antigen-formulated vaccine to induce broad protection between pandemics that could bridge the gap between pandemic declaration and the production of a homologous vaccine was also discussed. Finally, despite the availability of effective vaccines, most current efforts to increase influenza vaccine coverage

  7. Quantitative Estimates of Temporal Mixing across a 4th-order Depositional Sequence: Variation in Time-averaging along the Holocene Marine Succession of the Po Plain, Italy

    NASA Astrophysics Data System (ADS)

    Scarponi, D.; Kaufman, D.; Bright, J.; Kowalewski, M.

    2009-04-01

    Single fossiliferous beds contain biotic remnants that commonly vary in age over a time span of hundreds to thousands of years. Multiple recent studies suggest that such temporal mixing is a widespread phenomenon in marine depositional systems. This research focuses on quantitative estimates of temporal mixing obtained by direct dating of individual corbulid bivalve shells (Lentidium mediterraneum and Corbula gibba) from Po plain marine units of the Holocene 4th-order depositional sequence, including Transgressive Systems Tract [TST] and Highstand Systems Tract [HST]. These units displays a distinctive succession of facies consisting of brackish to marginal marine retrogradational deposits, (early TST), overlain by fully marine fine to coarse gray sands (late TST), and capped with progradational deltaic clays and sands (HST). More than 300 corbulid specimens, representing 19 shell-rich horizons evenly distributed along the depositional sequence and sampled from 9 cores, have been dated by means of aspartic acid racemization calibrated using 23 AMS-radiocarbon dates (14 dates for Lentidium mediterraneum and 9 dates for Corbula gibba, respectively). The results indicate that the scale of time-averaging is comparable when similar depositional environments from the same systems tract are compared across cores. However, time averaging is notably different when similar depositional environments from TST and HST segments of the sequence are compared. Specifically, late HST horizons (n=8) display relatively low levels of time-averaging: the mean within-horizon range of shell ages is 537 years and standard deviation averages 165 years. In contrast, late TST horizons (n=7) are dramatically more time-averaged: mean range of 5104 years and mean standard deviations of 1420 years. Thus, late TST horizons experience a 1 order of magnitude higher time-averaging than environmentally comparable late HST horizons. In conclusion the HST and TST systems tracts of the Po Plain display

  8. Effectiveness of rifaximin and fluoroquinolones in preventing travelers’ diarrhea (TD): a systematic review and meta-analysis

    PubMed Central

    2012-01-01

    Background Recent developments related to a safe and effective nonabsorbable antibiotic, rifaximin, and identification of postinfectious irritable bowel syndrome as a frequent sequela call for a need to reconsider the value of primary prevention of traveler’s diarrhea (TD) with antibiotics. Methods Randomized, placebo-controlled, double-blind studies evaluating the effectiveness and safety of rifaximin or a fluoroquinolone chemoprophylaxis against TD were pooled using a random effects model and assessed for heterogeneity. Results The nine studies (four rifaximin and five fluoroquinolone) included resulted in pooled relative risk estimates of 0.33 (95% CI = 0.24–0.45, I2 = 3.1%) and 0.12 (95% CI = 0.07–0.20, I2 =0.0%), respectively. Similar rates of treatment emergent adverse events were found between antibiotic and placebo groups. Conclusions This meta-analysis supports the effectiveness of antibiotics in preventing TD. However, further studies that include prevention of secondary chronic health outcomes among travelers to different geographic regions, and a formal risk-benefit analysis for antibiotic chemoprophylaxis, are needed. PMID:22929178

  9. Fluoroquinolone and Ovariectomy in the Bitch: Physiology of the Immune System as to CD56 and CD16 Expression.

    PubMed

    Albrizio, Maria; Rizzo, Annalisa; Pantaleo, Marianna; Pampurini, Fabrizio; Piccinno, Mariagrazia; Sciorsci, Raffaele Luigi

    2015-01-01

    Natural killer (NK) cells are innate lymphoid cells which act against a variety of pathogens and tumours. Phenotypically they are characterized by surface markers named cluster designation (CD) antigens. CD56 and CD16 are recognized as specific NK markers in the dogs as well as in humans. Surgical interventions suppress NK cells both in rats and humans. In this direction, it has been shown that an antibiotic regimen (amoxicillin, benzylpenicillin/dihydrostreptomycin, sulfametazine/sulfamerazine/ sulfathiazole, enrofloxacin, lincomycin/spectinomycin) administered only twice is effective in preventing infections after laparatomic ovariectomy, in the bitch. On these grounds, this research will show that the administration of a fluoroquinolone (5 mg/kg of enrofloxacin, Baytril®, Bayer, Milan, Italy) one hour before and at the end of ovariectomy is able to increase CD56 and CD16 expression levels. Moreover, the antibiotic administration modifies the relative expression levels of the two CD; thus suggesting that the fluoroquinolone employed enhances the activation of a specific subset of NK cells mainly involved in body recovering during the post operative period as already observed in humans. PMID:25512196

  10. Prevalence and Subtypes of Ciprofloxacin-Resistant Campylobacter spp. in Commercial Poultry Flocks before, during, and after Treatment with Fluoroquinolones

    PubMed Central

    Humphrey, Tom J.; Jørgensen, Frieda; Frost, Jennifer A.; Wadda, Haddy; Domingue, Gil; Elviss, Nicola C.; Griggs, Deborah J.; Piddock, Laura J. V.

    2005-01-01

    Five commercial broiler chicken flocks were treated with either difloxacin or enrofloxacin for a clinically relevant infection, as instructed by a veterinarian. Campylobacters were isolated from individual fecal samples and from samples associated with the broiler environment before, during, and after treatment. Ciprofloxacin-resistant Campylobacter jejuni and/or C. coli strains were detected pretreatment in four flocks, but they constituted a very small proportion of the campylobacters present. When the broilers were treated with a fluoroquinolone, a rapid increase in the proportion of ciprofloxacin-resistant campylobacters was observed. During treatment nearly 100% of campylobacters were resistant, and in some flocks a high proportion of resistant strains persisted for up to 4 weeks after treatment. Prior to treatment a variety of campylobacter subtypes were present. During and after treatment considerable changes in both species and subtype prevalence were observed, but no single fluoroquinolone-resistant clone became dominant. Instead, resistant C. coli strains or a mixture of resistant C. coli and C. jejuni strains became dominant, whereas susceptible C. jejuni strains had usually been dominant prior to treatment. The resistant subtypes which emerged and became dominant were not always the same as those detected pretreatment. The persistence of resistant strains for up to 4 weeks posttreatment has important implications for any strategy designed to avoid the introduction of such strains into the food chain. PMID:15673753

  11. Single-step extraction followed by LC for determination of (fluoro)quinolone drug residues in muscle, eggs, and milk.

    PubMed

    Cho, Hee-Jung; Yi, Hee; Cho, Soo Min; Lee, Dong Goo; Cho, Kyul; Abd el-Aty, A M; Shim, Jae-Han; Lee, Soon-Ho; Jeong, Ji-Yoon; Shin, Ho-Chul

    2010-04-01

    In this study, a simplified method for the extraction and determination of seven fluoroquinolone residues (danofloxacin, difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, ofloxacin, and sarafloxacin) and three quinolones (oxolinic acid, flumequine, and nalidixic acid), in porcine muscle, table eggs, and commercial whole milk, which required no cleanup step, was devised. This procedure involves the extraction of analytes from the samples via liquid-phase extraction, and the subsequent quantitative determination was accomplished via LC-fluorescence detection. Analyte separation was successfully conducted on an XBridge-C(18) column, with a linear gradient mobile phase composed of acetonitrile and 0.01 M oxalic acid buffer at pH=3.5. The one-step liquid-liquid extraction method evidenced good selectivity, precision (RSDs=0.26-15.07%), and recovery of the extractable analytes, ranging from 61.12 to 115.93% in matrices. The LOQs ranged from 0.3 to 25 microg/kg. A survey of ten samples purchased from local markets was conducted, and none of the samples harbored fluoroquinolone residues. This method is an improvement over existing methodologies, since no additional cleanup was necessary. PMID:20175091

  12. Quantitation of fluoroquinolones in honey using tandem mass spectrometry (LC-MS/MS): nested validation with two mass spectrometers.

    PubMed

    Durden, David A; Fernandes, Gwen

    2010-01-01

    A number of drugs in the quinolone and fluoroquinolone families, approved for veterinary treatment of food animals by various countries, may be used to treat bee diseases and thereby contaminate honey. An LC-MS/MS method has been developed for the quantification of the quinolones: flumequine, nalidixic acid, oxolinic acid, and pipemidic acid; and the fluoroquinolones ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, norfloxacin, ofloxacin, orbifloxacin, marbofloxacin, sarafloxacin, and sparfloxacin. A method-matched calibration curve is used with several internal standards, i.e., ciprofloxacin-d8, Iomefloxacin, and cinoxacin, to correct for the various types of honey matrices: white, light, medium, and dark colors. Enoxacin is added as an external recovery standard. The LOD values range from 0.05 microg/kg (ofloxacin) to 0.4 microg/kg (flumequine). The compounds are verified by LC-MS/MS retention times and ion ratios. Method uncertainty was determined using two separate analytical systems. The method has successfully measured the presence of norfloxacin in several samples of honey imported into Canada. PMID:21140677

  13. Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis.

    PubMed

    Peterson, Johnny W; Moen, Scott T; Healy, Daniel; Pawlik, Jennifer E; Taormina, Joanna; Hardcastle, Jason; Thomas, John M; Lawrence, William S; Ponce, Cindy; Chatuev, Bagram M; Gnade, Bryan T; Foltz, Sheri M; Agar, Stacy L; Sha, Jian; Klimpel, Gary R; Kirtley, Michelle L; Eaves-Pyles, Tonyia; Chopra, Ashok K

    2010-01-01

    Successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. Bacillus anthracis Ames, Yersinia pestis CO92, and Francisella tularensis SCHU S4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited information is available regarding in vivo susceptibility of these infectious agents to the fluoroquinolone antibiotics in small animal models. Mice, guinea pig, and rabbit models have been developed to evaluate the protective efficacy of antibiotic therapy against these life-threatening infections. Our results indicated that doses of ciprofloxacin and levofloxacin required to protect mice against inhalation anthrax were approximately 18-fold higher than the doses of levofloxacin required to protect against pneumonic plague and tularemia. Further, the critical period following aerosol exposure of mice to either B. anthracis spores or Y. pestis was 24 h, while mice challenged with F. tularensis could be effectively protected when treatment was delayed for as long as 72 h postchallenge. In addition, it was apparent that prolonged antibiotic treatment was important in the effective treatment of inhalation anthrax in mice, but short-term treatment of mice with pneumonic plague or tularemia infections were usually successful. These results provide effective antibiotic dosages in mice, guinea pigs, and rabbits and lay the foundation for the development and evaluation of combinational treatment modalities. PMID:21127743

  14. Protection Afforded by Fluoroquinolones in Animal Models of Respiratory Infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis

    PubMed Central

    Peterson, Johnny W; Moen, Scott T; Healy, Daniel; Pawlik, Jennifer E; Taormina, Joanna; Hardcastle, Jason; Thomas, John M; Lawrence, William S; Ponce, Cindy; Chatuev, Bagram M; Gnade, Bryan T; Foltz, Sheri M; Agar, Stacy L; Sha, Jian; Klimpel, Gary R; Kirtley, Michelle L; Eaves-Pyles, Tonyia; Chopra, Ashok K

    2010-01-01

    Successful treatment of inhalation anthrax, pneumonic plague and tularemia can be achieved with fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, and initiation of treatment is most effective when administered as soon as possible following exposure. Bacillus anthracis Ames, Yersinia pestis CO92, and Francisella tularensis SCHU S4 have equivalent susceptibility in vitro to ciprofloxacin and levofloxacin (minimal inhibitory concentration is 0.03 μg/ml); however, limited information is available regarding in vivo susceptibility of these infectious agents to the fluoroquinolone antibiotics in small animal models. Mice, guinea pig, and rabbit models have been developed to evaluate the protective efficacy of antibiotic therapy against these life-threatening infections. Our results indicated that doses of ciprofloxacin and levofloxacin required to protect mice against inhalation anthrax were approximately 18-fold higher than the doses of levofloxacin required to protect against pneumonic plague and tularemia. Further, the critical period following aerosol exposure of mice to either B. anthracis spores or Y. pestis was 24 h, while mice challenged with F. tularensis could be effectively protected when treatment was delayed for as long as 72 h postchallenge. In addition, it was apparent that prolonged antibiotic treatment was important in the effective treatment of inhalation anthrax in mice, but short-term treatment of mice with pneumonic plague or tularemia infections were usually successful. These results provide effective antibiotic dosages in mice, guinea pigs, and rabbits and lay the foundation for the development and evaluation of combinational treatment modalities. PMID:21127743

  15. High performance liquid chromatography coupled with resonance Rayleigh scattering for the detection of three fluoroquinolones and mechanism study

    NASA Astrophysics Data System (ADS)

    Zhou, Mingqiong; Peng, Jingdong; He, Rongxing; He, Yuting; Zhang, Jing; Li, Aiping

    2015-02-01

    A reliable and versatile high performance liquid chromatography coupled with resonance Rayleigh scattering method was established for the determination of three fluoroquinolones, including levofloxacin, norfloxacin and enrofloxacin in water sample and human urine sample. In pH 4.4-4.6 Britton-Robinson buffer medium, the fluoroquinolones separated by high performance liquid chromatography could react with erythrosine to form 1:1 ion-association complexes, which could make contributions to the great enhancement of RRS. The resonance Rayleigh scattering signal was recorded at λex = λem = 330 nm. The resonance Rayleigh scattering spectral characteristics of the drugs and the experimental conditions such as pH, detection wavelength, erythrosine concentration, flow rate, the length of reaction tube were studied. Quantum chemistry calculation, Fourier transform infrared spectroscopy and absorption spectroscopy were used to discuss the reaction mechanism. The recoveries of samples added standard ranged from 97.53% to 102.00%, and the relative standard deviation was below 4.64%. The limit of detection (S/N = 3) of 0.05-0.12 μg mL-1 was reached, and the linear regression coefficients were all above 0.999. The proposed method was proved as a simple, low cost and high sensitivity method.

  16. Impact of Fluoroquinolone Exposure Prior to Tuberculosis Diagnosis on Clinical Outcomes in Immunocompromised Patients.

    PubMed

    Lee, Ju Young; Lee, Hyun Jung; Kim, Yong Kyun; Yu, Shinae; Jung, Jiwon; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Shim, Tae Sun; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

    2016-07-01

    There have been concerns about an association of fluoroquinolone (FQ) use prior to tuberculosis (TB) diagnosis with adverse outcomes. However, FQ use might prevent clinical deterioration in missed TB patients, especially in those who are immunocompromised, until they receive definitive anti-TB treatment. All adult immunocompromised patients with smear-negative and culture-positive TB at a tertiary care hospital in Korea over a 2-year period were included in this study. Long-term FQ (≥7 days) use was defined as exposure to FQ for at least 7 days prior to TB diagnosis. A total of 194 patients were identified: 33 (17%) in the long-term FQ group and 161 (83%) in the comparator, including a short-term FQ group (n = 23), non-FQ group (n = 78), and a group receiving no antibiotics (n = 60). Patients in the long-term FQ group presented with atypical chest radiologic pattern more frequently than those in the comparator (77% [24/31] versus 46% [63/138]; P = 0.001). The median time from mycobacterial test to positive mycobacterial culture appeared to be longer in the long-term FQ group (8.1 weeks versus 7.7 weeks; P = 0.09), although the difference was not statistically significant. Patients in the long-term FQ group were less likely to receive empirical anti-TB treatment (55% versus 74%; P = 0.03). The median time from mycobacterial test to anti-TB therapy was longer in the long-term FQ group (4.6 weeks versus 2.2 weeks; P < 0.001), but there was no significant difference in FQ resistance (0% versus 3%; P > 0.99) or in the 30-day (6% versus 6%; P > 0.99) or 90-day (12% versus 12%; P > 0.99) mortality rate between the two groups. FQ exposure (≥7 days) prior to TB diagnosis in immunocompromised patients appears not to be associated with adverse outcomes. PMID:27090178

  17. Toxicity assessment of combined fluoroquinolone and tetracycline exposure in zebrafish (Danio rerio).

    PubMed

    Zhang, Yuna; Wang, Xuedong; Yin, Xiaohan; Shi, Mengru; Dahlgren, Randy Alan; Wang, Huili

    2016-06-01

    Fluoroquinolones (FQs) and tetracyclines (TCs), the two β-diketone antibiotics (DKAs), are two frequently detected pollutants in the environment; however, little data are available on their combined toxicity to zebrafish (Danio rerio). This study reports that toxicologic effects of combined DKA (FQs-TCs) exposure on zebrafish were comparable with or slightly less than those of TCs alone, showing that TCs played a major toxicologic role in the mixtures. The effects of FQs, TCs, and DKAs on malformation rates of zebrafish were dose dependent, with EC50 values of 481.3, 16.4, and 135.1 mg/L, respectively. According to the combined effects of DKAs on zebrafish hatching, mortality, and malformation rates, the interaction between FQs and TCs was shown to be antagonistic based on three assessment methods: Toxic Unit, Additional Index, and Mixture Toxic Index. The 1.56 mg/L TC and 9.38 mg/L DKA treatments resulted in higher zebrafish basal swimming rate compared with the control group at 120 hours postfertilization (hpf). in both light and light-to-dark photoperiod experiments. Under conditions of no obvious abnormality in cardiac development, the heart beats were decreased significantly because of DKA exposure, such as decreasing by ∼20% at 150 mg/L DKAs. Transmission electron microscopy observation of myocytes from DKA-exposed hearts displayed prominent interruptions and myofibrillar disorganization of the normal parallel alignment of thick and thin filaments, and partial edematous and dissolved membranes of cell nuclear tissues. At 90 mg/L DKAs, the transcriptional levels of the acta1a, myl7, and gle1b genes, related to heart development and skeletal muscle formation, were significantly changed. This is consistent with the swimming behavior and histopathologic results obtained by transmission electron microscopy. In summary, the toxicity of the combined DKAs to zebrafish was comparable with or less than that of TCs alone and had the ability to impair individual

  18. Respiratory failure and acalculous cholecystitis in a patient with AIDS and disseminated tuberculosis: masking effect of fluoroquinolone monotherapy and immune restoration syndrome.

    PubMed

    Chen, Po-Lin; Lee, Hsin-Chun; Shan, Yan-Shen; Ko, Nai-Ying; Lee, Nan-Yao; Chang, Chia-Ming; Wu, Chi-Jung; Lee, Ching-Chi; Ko, Wen-Chien

    2009-07-01

    The clinical presentation of Mycobacterium tuberculosis infection varies in patients with AIDS. We report a case of disseminated tuberculosis in an AIDS patient. The initial manifestation was masked by fluoroquinolone monotherapy, and subsequently complicated by acalculous cholecystitis and immune restoration syndrome after antiretroviral therapy. PMID:19008140

  19. New Real-Time PCR Assay Using Locked Nucleic Acid Probes To Assess Prevalence of ParC Mutations in Fluoroquinolone-Susceptible Streptococcus pneumoniae Isolates from France

    PubMed Central

    Decousser, Jean-Winoc; Methlouthi, Imen; Pina, Patrick; Collignon, Anne; Allouch, Pierre

    2006-01-01

    A real-time PCR assay with locked nucleic acid probes was developed to screen mutations at codons 79 and 83 of the Streptococcus pneumoniae parC gene. Only silent mutations were detected among 236 French invasive fluoroquinolone-susceptible strains. This test could be useful for some high-risk patients or in national surveys. PMID:16569894

  20. Evaluation of Serum as a Potential Matrix for Multiresidue Determiantion of Fluoroquinolone Antibiotics in Chicken using Liquid Chromatography-Fluorescence-Mass Spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An efficient multiresidue method was developed for the determination of fluoroquinolones (FQs) in chicken serum, as well as muscle. In this method, FQs are extracted from matrix with ammoniacal acetonitrile, the extracts are defatted and then evaporated. After addition of basic phosphate buffer an...

  1. Simultaneous determination of 13 fluoroquinolone and 22 sulfonamide residues in milk by a dual-colorimetric enzyme-linked immunosorbent assay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enzyme-linked immunosorbent assays (ELISAs) usually focus on the detection of a single analyte or a single group of analytes, e.g., fluoroquinolones or sulfonamides. However, it is often necessary to simultaneously monitor the two classes of antimicrobial residues in different food matrices. In th...

  2. Computer-Generated Geometry Instruction: A Preliminary Study

    ERIC Educational Resources Information Center

    Kang, Helen W.; Zentall, Sydney S.

    2011-01-01

    This study hypothesized that increased intensity of graphic information, presented in computer-generated instruction, could be differentially beneficial for students with hyperactivity and inattention by improving their ability to sustain attention and hold information in-mind. To this purpose, 18 2nd-4th grade students, recruited from general…

  3. Molecular Epidemiology and Genetic Diversity of Fluoroquinolone-Resistant Escherichia coli Isolates from Patients with Community-Onset Infections in 30 Chinese County Hospitals

    PubMed Central

    Zhao, Lina; Zhang, Jing; Zheng, Beiwen; Wei, Zeqing; Shen, Ping; Li, Sujuan; Li, Lanjuan

    2014-01-01

    The high frequency of fluoroquinolone resistance in Escherichia coli is a feature of clinical bacteriology in China, where the molecular epidemiology and genetic characteristics of this resistance in county hospitals remain unclear. A total of 590 nonduplicate E. coli isolates from 30 county hospitals located across seven Chinese regions were examined for plasmid-mediated quinolone resistance (PMQR) genes and mutations in quinolone resistance-determining regions (QRDRs). Multilocus sequence typing (MLST) and phylogenetic analysis of fluoroquinolone-resistant isolates were used to determine their genetic relatedness. The ciprofloxacin resistance rate of community-onset E. coli was 51.2%, and at least one PMQR gene was carried by 220 (37.3%) isolates. These included qnr (3.7%), aac(6′)-Ib-cr (19.7%), qepA (14.4%), and oqxAB (3.8%). Two novel oqxB mutants were identified and named oqxB20 and oqxB29. From 60 sequence types (STs) isolated, 5 novel STs (ST4499 to ST4503) were identified. ST1193 (7.9%) was the second most abundant ST among fluoroquinolone-resistant isolates (ST131 was the most common, with 14.6%), and this is the first report of it in China. This is also the first report of ST2115 and ST3014 isolates from human samples. Ciprofloxacin-resistant E. coli isolates fell mainly into phylogroups B2 and D. The rates of fluoroquinolone resistance and the prevalence of PMQR genes in community-onset E. coli isolates from Chinese county hospitals were high. The wide-ranging molecular epidemiology of E. coli isolates from scattered locations across China indicates that fluoroquinolone resistance evolved from different sources. PMID:25520451

  4. Prevalence of plasmid-mediated multidrug resistance determinants in fluoroquinolone-resistant bacteria isolated from sewage and surface water.

    PubMed

    Osińska, Adriana; Harnisz, Monika; Korzeniewska, Ewa

    2016-06-01

    Fluoroquinolones (FQs) are fully synthetic broad-spectrum antibacterial agents that are becoming increasingly popular in the treatment of clinical and veterinary infections. Being excreted during treatment, mostly as active compounds, their biological action is not limited to the therapeutic site, but it is moved further as resistance selection pressure into the environment. Water environment is an ideal medium for the aggregation and dissemination of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic resistance genes (ARGs), which can pose a serious threat to human health. Because of this, the aim of this study was to determine the number of fluoroquinolone-resistant bacteria (FQRB) and their share in total heterotrophic plate counts (HPC) in treated wastewater (TWW), and upstream and downstream river water (URW, DRW) samples where TWW is discharged. The spread of plasmid-mediated quinolone resistance (PMQR) determinants and the presence/absence of resistance genes to other most popular antibiotic groups (against tetracyclines and beta-lactams) in selected 116 multiresistant isolates were investigated. The share of FQRB in total HPC in all samples was rather small and ranged from 0.7 % in URW samples to 7.5 % in TWW. Bacteria from Escherichia (25.0 %), Acinetobacter (25.0 %), and Aeromonas (6.9 %) genera were predominant in the FQRB group. Fluoroquinolone resistance was mostly caused by the presence of the gene aac(6')-1b-cr (91.4 %). More rarely reported was the occurrence of qnrS, qnrD, as well as oqxA, but qnrA, qnrB, qepA, and oqxB were extremely rarely or never noted in FQRB. The most prevalent bacterial genes connected with beta-lactams' resistance in FQRB were bla TEM, bla OXA, and bla CTX-M. The bla SHV was less common in the community of FQRB. The occurrence of bla genes was reported in almost 29.3 % of FQRB. The most abundant tet genes in FQRB were tet(A), tet(L), tet(K), and tet(S). The prevalence of tet genes was observed in 41.4

  5. Determination of fluoroquinolone antibiotics via ionic-liquid-based, salt-induced, dual microextraction in swine feed.

    PubMed

    Wang, Huili; Gao, Ming; Gao, Jiajia; Yu, Nana; Huang, Hong; Yu, Qing; Wang, Xuedong

    2016-09-01

    In conventional microextraction procedures, the disperser (organic solvent or ionic liquid) is left in the aqueous phase and discarded after finishing the microextraction process. Because the disperser is water-soluble, it results in low extraction recovery for polar compounds. In this investigation, an ionic-liquid-based microextraction (ILBME) was integrated with salting-out assisted liquid-liquid microextraction (SALLME) to build an ionic-liquid-based, salt-induced, dual microextraction (ILSDME) for isolation of five fluoroquinolone antibiotics (FQs) with high polarity (log P, -1.0 to 1.0). The proposed ILSDME method incorporates a dual microextraction by converting the disperser in the ILBME to the extractor in the SALLME. Optimization of key factors was conducted by integrating single-factor experiments and central composite design. The optimized experimental parameters were 80 μL [C8MIM][PF6] as extractor, 505 μL acetone as disperser, pH = 2.0, 4.1 min extraction time, and 4.2 g of Na2SO4. Under optimized conditions, high ERs (90.6-103.2 %) and low LODs (0.07-0.61 μg kg(-1)) were determined for five FQs in swine feed. Experimental precision based on RSDs was 1.4-5.2 % for intra-day and 2.4-6.9 % for inter-day analyses. The combination of ILBME with SALLME increased FQ recoveries by 15-20 % as compared with SALLME, demonstrating that the ILSDME method can enhance extraction efficiency for polar compounds compared to single-step microextraction. Therefore, the ILSDME method developed in this study has wide application for pretreatment of moderately to highly polar pollutants in complex matrices. Graphical Abstract A dual microextraction was developed by integrating ionic-liquid-based microextraction with salting-out assisted liquid-liquid microextraction for isolation of five fluoroquinolone antibiotics (FQs) with high polarity (log P = -1.0 to 1.0). The principle of dual microextraction is based on converting the remaining disperser from

  6. Pharmacodynamics of the New Fluoroquinolone Gatifloxacin in Murine Thigh and Lung Infection Models

    PubMed Central

    Andes, D.; Craig, W. A.

    2002-01-01

    Gatifloxacin is a new 8-methoxy fluoroquinolone with enhanced activity against gram-positive cocci. We used the neutropenic murine thigh infection model to characterize the time course of antimicrobial activity of gatifloxacin and determine which pharmacokinetic (PK)-pharmacodynamic (PD) parameter best correlated with efficacy. The thighs of mice were infected with 106.5 to 107.4 CFU of strains of Staphylococcus aureus, Streptococcus pneumoniae, or Escherichia coli, and the mice were then treated for 24 h with 0.29 to 600 mg of gatifloxacin per kg of body weight per day, with the dose fractionated for dosing every 3, 6, 12, and 24 h. Levels in serum were measured by microbiologic assay. In vivo postantibiotic effects (PAEs) were calculated from serial values of the log10 numbers of CFU per thigh 2 to 4 h after the administration of doses of 8 and 32 mg/kg. Nonlinear regression analysis was used to determine which PK-PD parameter best correlated with the numbers of CFU per thigh at 24 h. Pharmacokinetic studies revealed peak/dose values of 0.23 to 0.32, area under the concentration-time curve (AUC)/dose values of 0.47 to 0.62, and half-lives of 0.6 to 1.1 h. Gatifloxacin produced in vivo PAEs of 0.2 to 3.1 h for S. pneumoniae and 0.4 to 2.3 h for S. aureus. The 24-h AUC/MIC was the PK-PD parameter that best correlated with efficacy (R2 = 90 to 94% for the three organisms, whereas R2 = 70 to 81% for peak level/MIC and R2 = 48 to 73% for the time that the concentration in serum was greater than the MIC). There was some reduced activity when dosing every 24 h was used due to the short half-life of gatifloxacin in mice. In subsequent studies we used the neutropenic and nonneutropenic murine thigh and lung infection models to determine if the magnitude of the AUC/MIC needed for the efficacy of gatifloxacin varied among pathogens (including resistant strains) and infection sites. The mice were infected with 106.5 to 107.4 CFU of four isolates of S. aureus (one methicillin

  7. Role of nitric oxide in the convulsive seizures induced by fluoroquinolones coadministered with 4-biphenyl acetic acid.

    PubMed

    Kohno, K; Niwa, M; Nozaki, M; Uematsu, T; Fujimura, H

    1997-11-01

    1. Contribution of nitric oxide to the convulsive seizures induced by fluoroquinolones (FQs) coadministered with 4-biphenyl acetic acid (BPAA), the active metabolite of fenbufen, was assessed in mice. 2. Enoxacin + 4-biphenyl acetic acid caused clonic seizures in all treated mice, followed by tonic seizures and death. These events were associated with a significant increase in intracerebellar cyclic GMP. 3. Pretreatment with the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methylester (L-NAME), but not with D-NAME, significantly reduced the incidence of convulsions and lethality, as well as the increase in cyclic GMP. 4. Pretreatment with N-methyl-D-aspartic acid (NMDA)-receptor antagonist, MK-801, inhibited only the transition of clonic seizure to tonic seizure without affecting the incidence of clonic seizure and lethality. 5. These findings suggest that FQs + BPAA exert convulsions by activating NOS partly through the mediation of the NMDA receptor in the brain cells. PMID:9347323

  8. Synthesis and in vitro antibacterial activity of 7-(3-alkoxyimino-4-amino-4-methylpiperidin-1-yl) fluoroquinolone derivatives.

    PubMed

    Wang, Ju-Xian; Zhang, Yi-Bin; Liu, Ming-Liang; Wang, Bo; Chai, Yun; Li, Su-Jie; Guo, Hui-Yuan

    2011-06-01

    A series of novel 7-(3-alkoxyimino-4-amino-4-methylpiperidin-1-yl)fluoroquinolone derivatives were designed, synthesized and evaluated for their in vitro antibacterial activity and cytotoxicity. All of the target compounds have potent antibacterial activity against the tested Gram-positive and Gram-negative strains, and exhibit good potency in inhibiting the growth of Staphylococcus aureus including MRSA, Staphylococcus epidermidis including MRSE and Streptococcus pneumoniae (MICs: 0.125-4 μg/mL). Compound 22, with the best activity against Gram-positive strains, is 4-16 fold more potent than gemifloxacin, gatifloxacin and levofloxacin against Enterococcus faecalis, and 16- and 4-fold more potent than levofloxacin against S. epidermidis 09-6 and S. pneumoniae 08-4, respectively. PMID:21481984

  9. Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

    PubMed Central

    Bolhuis, Mathieu S.; Panday, Prashant N.; Pranger, Arianna D.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2011-01-01

    Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs. PMID:24309312

  10. Emergence of fluoroquinolone-resistant Stenotrophomonas maltophilia in blood isolates causing bacteremia: molecular epidemiology and microbiologic characteristics.

    PubMed

    Cha, Min Kyeong; Kang, Cheol-In; Kim, So Hyun; Cho, Sun Young; Ha, Young Eun; Chung, Doo Ryeon; Peck, Kyong Ran; Song, Jae-Hoon

    2016-06-01

    Among 127 Stenotrophomonas maltophilia isolates causing bacteremia, 41 (32.3%) were nonsusceptible to levofloxacin, in which four sequence types and 24 diverse allelic profiles were detected. The most prevalent ST was ST77 (n = 8, 19.5%), followed by ST28 (n = 3, 7.3%). Amino acid substitutions were found in the gyrB and parC genes of 10 and 1 isolates, respectively. No amino acid substitutions were identified in gyrA. Twenty-three (56.1%) isolates showed amino acid substitutions in the parE gene. These results suggest that quinolone resistance-determining regions of parE may not be the primary targets, but an important determining factor of high levels of fluoroquinolone resistance. PMID:27117514

  11. Susceptibility of canine and feline bacterial pathogens to pradofloxacin and comparison with other fluoroquinolones approved for companion animals.

    PubMed

    Schink, Anne-Kathrin; Kadlec, Kristina; Hauschild, Tomasz; Brenner Michael, Geovana; Dörner, Julia C; Ludwig, Carolin; Werckenthin, Christiane; Hehnen, Hans-Robert; Stephan, Bernd; Schwarz, Stefan

    2013-02-22

    In this study, 908 bacterial pathogens from defined infections of dogs and cats were tested for their susceptibility to the novel fluoroquinolone pradofloxacin, which was approved in 2011 for use in cats and dogs. Most of the bacteria tested (Staphylococcus aureus, Staphylococcus pseudintermedius, Escherichia coli, β-haemolytic streptococci, Pasteurella multocida and Bordetella bronchiseptica) exhibited low pradofloxacin MIC(90) values of ≤ 0.25 μg/ml. Solely Proteus spp. and Pseudomonas aeruginosa had higher MIC(90) values of ≥ 4 μg/ml. Only six (3.4%) of 177 S. pseudintermedius and 12 (5.3%) of 227 E. coli isolates showed pradofloxacin MICs of ≥ 2 μg/ml. Analysis of the quinolone resistance determining regions of the target genes identified double mutations in GyrA that resulted in amino acid exchanges S83L+D87N or S83L+D87Y and single or double mutations in ParC that resulted in amino acid exchanges S80I or S80I+E84G in all 12 E. coli isolates. The six S. pseudintermedius isolates exhibited amino acid exchanges S84L or E88K in GyrA and S80I in GrlA. Comparative analysis of the MICs of pradofloxacin and the MICs determined for enrofloxacin and its main metabolite ciprofloxacin, but also marbofloxacin, orbifloxacin, difloxacin and ibafloxacin was conducted for the target pathogens S. pseudintermedius, E. coli and P. multocida. This comparison confirmed that pradofloxacin MICs were significantly lower than those of the other tested fluoroquinolones. PMID:22939523

  12. In vitro susceptibilities to fluoroquinolones in current and archived Mycoplasma gallisepticum and Mycoplasma synoviae isolates from meat-type turkeys.

    PubMed

    Gerchman, Irina; Lysnyansky, Inna; Perk, Shimon; Levisohn, Sharon

    2008-10-15

    Monitoring of susceptibility to antibiotics in field isolates of pathogenic avian mycoplasmas is important for appropriate choice of treatment. Our study compared in vitro susceptibility to enrofloxacin and difloxacin in recent (2005-2006) isolates of Mycoplasma gallisepticum and Mycoplasma synoviae from meat-type turkey flocks with archived (1997-2003) isolates and reference strains. Comparison of minimal inhibitory concentration (MIC) values determined by microtest, agar dilution and commercial Etest showed good agreement, but underscored the need for standardized methods for testing. Notably, while the commercial Etest was convenient and accurate for determining MICs for enrofloxacin in the range 0.002-0.094microg/ml, the endpoint of inhibition for M. gallisepticum and M. synoviae strains with MIC values > or =1.0microg/ml could not be determined. A decrease in susceptibility to both fluoroquinolones was detected in archived strains but to a greater degree in recent isolates, most of which had MICs above the NCCLS susceptibility breakpoint for these antibiotics (< or =0.5microg/ml). In contrast, except for one flock, M. synoviae isolates were susceptible, although intrinsically less susceptible than M. gallisepticum. Overall for the 88 strains tested (45 M. gallisepticum, 43 M. synoviae), the MIC50 for both enrofloxacin and difloxacin was 0.5microg/ml. The isolation of fluoroquinolone-resistant M. gallisepticum isolates from breeder and broiler flocks as well as from meat-type turkeys suggests that these strains have become established in Israel, necessitating a reevaluation of antibiotic therapy. Periodic survey of MICs in field isolates of avian mycoplasmas to monitor for the possible appearance of resistant strains is recommended. PMID:18534788

  13. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014).

    PubMed

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995-2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  14. Molecular Analysis of Rising Fluoroquinolone Resistance in Belgian Non-Invasive Streptococcus pneumoniae Isolates (1995-2014)

    PubMed Central

    Ceyssens, Pieter-Jan; Van Bambeke, Françoise; Mattheus, Wesley; Bertrand, Sophie; Fux, Frédéric; Van Bossuyt, Eddie; Damée, Sabrina; Nyssen, Henry-Jean; De Craeye, Stéphane; Verhaegen, Jan; Tulkens, Paul M.; Vanhoof, Raymond

    2016-01-01

    We present the results of a longitudinal surveillance study (1995–2014) on fluoroquinolone resistance (FQ-R) among Belgian non-invasive Streptococcus pneumoniae isolates (n = 5,602). For many years, the switch to respiratory fluoroquinolones for the treatment of (a)typical pneumonia had no impact on FQ-R levels. However, since 2011 we observed a significant decrease in susceptibility towards ciprofloxacin, ofloxacin and levofloxacin with peaks of 9.0%, 6.6% and 3.1% resistant isolates, respectively. Resistance to moxifloxacin arised sporadically, and remained <1% throughout the entire study period. We observed classical topoisomerase mutations in gyrA (n = 25), parC (n = 46) and parE (n = 3) in varying combinations, arguing against clonal expansion of FQ-R. The impact of recombination with co-habiting commensal streptococci on FQ-R remains marginal (10.4%). Notably, we observed that a rare combination of DNA Gyrase mutations (GyrA_S81L/GyrB_P454S) suffices for high-level moxifloxacin resistance, contrasting current model. Interestingly, 85/422 pneumococcal strains display MICCIP values which were lowered by at least four dilutions by reserpine, pointing at involvement of efflux pumps in FQ-R. In contrast to susceptible strains, isolates resistant to ciprofloxacin significantly overexpressed the ABC pump PatAB in comparison to reference strain S. pneumoniae ATCC 49619, but this could only be linked to disruptive terminator mutations in a fraction of these. Conversely, no difference in expression of the Major Facilitator PmrA, unaffected by reserpine, was noted between susceptible and resistant S. pneumoniae strains. Finally, we observed that four isolates displayed intermediate to high-level ciprofloxacin resistance without any known molecular resistance mechanism. Focusing future molecular studies on these isolates, which are also commonly found in other studies, might greatly assist in the battle against rising pneumococcal drug resistance. PMID:27227336

  15. Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5.

    PubMed

    Arakawa, Hiroshi; Shirasaka, Yoshiyuki; Haga, Makoto; Nakanishi, Takeo; Tamai, Ikumi

    2012-09-01

    Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K(m) value of 140 µm, and naringin inhibited the uptake with an IC(50) value of 18 µm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC(50) value of 7.5 µm by the Ussing-type chamber method. The estimated IC(50) values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp. PMID:22899169

  16. A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis.

    PubMed Central

    Kern, W V; Hay, B; Kern, P; Marre, R; Arnold, R

    1994-01-01

    Fluoroquinolone prophylaxis in patients with profound neutropenia may be useful for preventing gram-negative bacterial infection, but it is ineffective against gram-positive bacterial infections in the bloodstream, particularly those caused by streptococci and coagulase-negative staphylococci, which appear to have emerged as significant causes of morbidity, decreased treatment efficacy, and the increased costs of empiric antimicrobial therapy. In a prospective, randomized, open trial, we evaluated the efficacy and safety of oral roxithromycin (150 mg twice daily) as additional antibacterial prophylaxis in 131 adult patients with acute leukemia and bone marrow transplant recipients receiving oral ofloxacin. In comparison with patients given ofloxacin alone, fewer patients receiving ofloxacin plus roxithromycin developed bacteremia caused by viridans group streptococci (incidence, 9 versus 0%; P = 0.03), while the incidence of bacteremia caused by other organisms, the incidence of febrile episodes from any cause, the risk of infection-associated complications (including prolonged or secondary fever, pneumonia, septic shock, need for mechanical ventilation, and/or infection-related death), and antimicrobial usage for therapy were comparable between both groups. Adverse events possibly related to the study drugs were slightly more common among the patients receiving the combination treatment (P = 0.05). Although effective for the prevention of streptococcal bacteremia, the addition of roxithromycin to a fluoroquinolone should not be used routinely as a prophylactic regimen in patients with profound neutropenia, but it might be considered and may be useful for cancer patients with a particularly high risk of streptococcal infection and related complications. PMID:8203838

  17. Nuclear Science Symposium, 4th, and Nuclear Power Systems Symposium, 9th, San Francisco, Calif., October 19-21, 1977, Proceedings

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Consideration is given to the following types of high energy physics instrumentation: drift chambers, multiwire proportional chambers, calorimeters, optical detectors, ionization and scintillation detectors, solid state detectors, and electronic and digital subsystems. Attention is also paid to reactor instrumentation, nuclear medicine instrumentation, data acquisition systems for nuclear instrumentation, microprocessor applications in nuclear science, environmental instrumentation, control and instrumentation of nuclear power generating stations, and radiation monitoring. Papers are also presented on instrumentation for the High Energy Astronomy Observatory.

  18. Feasibility Study of Supercritical Light Water Cooled Fast Reactors for Actinide Burning and Electric Power Production, Progress Report for Work Through September 2002, 4th Quarterly Report

    SciTech Connect

    Mac Donald, Philip Elsworth

    2002-09-01

    The use of light water at supercritical pressures as the coolant in a nuclear reactor offers the potential for considerable plant simplification and consequent capital and O&M cost reduction compared with current light water reactor (LWR) designs. Also, given the thermodynamic conditions of the coolant at the core outlet (i.e. temperature and pressure beyond the water critical point), very high thermal efficiencies of the power conversion cycle are possible (i.e. up to about 45%). Because no change of phase occurs in the core, the need for steam separators and dryers as well as for BWR-type re-circulation pumps is eliminated, which, for a given reactor power, results in a substantially shorter reactor vessel and smaller containment building than the current BWRs. Furthermore, in a direct cycle the steam generators are not needed. If no additional moderator is added to the fuel rod lattice, it is possible to attain fast neutron energy spectrum conditions in a supercritical water-cooled reactor (SCWR). This type of core can make use of either fertile or fertile-free fuel and retain a hard spectrum to effectively burn plutonium and minor actinides from LWR spent fuel while efficiently generating electricity. One can also add moderation and design a thermal spectrum SCWR. The Generation IV Roadmap effort has identified the thermal spectrum SCWR (followed by the fast spectrum SCWR) as one of the advanced concepts that should be developed for future use. Therefore, the work in this NERI project is addressing both types of SCWRs.

  19. Delafloxacin, a non-zwitterionic fluoroquinolone in Phase III of clinical development: evaluation of its pharmacology, pharmacokinetics, pharmacodynamics and clinical efficacy.

    PubMed

    Van Bambeke, Françoise

    2015-01-01

    Delafloxacin is a fluoroquinolone lacking a basic substituent in position 7. It shows MICs remarkably low against Gram-positive organisms and anaerobes and similar to those of ciprofloxacin against Gram-negative bacteria. It remains active against most fluoroquinolone-resistant strains, except enterococci. Its potency is further increased in acidic environments (found in many infection sites). Delafloxacin is active on staphylococci growing intracellularly or in biofilms. It is currently evaluated as an intravenous and intravenous/oral stepdown therapy in Phase III trials for the treatment of complicated skin/skin structure infections. It was also granted as Qualified Infectious Disease Product for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, due to its high activity on pneumococci and atypical pathogens. PMID:26119479

  20. Magnetic mixed hemimicelles solid-phase extraction coupled with high-performance liquid chromatography for the extraction and rapid determination of six fluoroquinolones in environmental water samples.

    PubMed

    Wang, Li; Yuan, Qiuxiang; Liang, Guoxi; Shi, Longbiao; Zhan, Qian

    2015-03-01

    In this study, a mixed hemimicelle solid-phase extraction method based on Fe3 O4 nanoparticles coated with sodium dodecyl sulfate was applied for the preconcentration and fast isolation of six fluoroquinolones in environmental water samples before high-performance liquid chromatography determination. The main factors affecting the extraction efficiency of the analytes, such as amount of surfactant, amount of Fe3 O4 nanoparticles, extraction time, sample volume, sample pH, ionic strength, and desorption conditions, were investigated and optimized. The method has detection limits from 0.05 to 0.1 ng/mL and good linearity (r ≥ 09948) in the range 0.1-200 ng/mL depending on the fluoroquinolone. The enrichment factor is ∼200. The recoveries (at spiked levels of 1, 5, and 50 ng/mL) are in the range of 79-120%. PMID:25581496