Science.gov

Sample records for 4th generation fluoroquinolones

  1. Plasma-Based Studies on 4th Generation Light Sources

    SciTech Connect

    Lee, R W; Baldis, H A; Cauble, R C; Landen, O L; Wark, J S; Ng, A; Rose, S J; Lewis, C; Riley, D; Gauthier, J-C; Audebert, P

    2000-11-28

    The construction of a short pulse tunable x-ray laser source will be a watershed for plasma-based and warm dense matter research. The areas we will discuss below can be separated broadly into warn dense matter (WDM) research, laser probing of near solid density plasmas, and laser-plasma spectroscopy of ions in plasmas. The area of WDM refers to that part of the density-temperature phase space where the standard theories of condensed matter physics and/or plasma statistical physics are invalid. Warm dense matter, therefore, defines a region between solids and plasmas, a regime that is found in planetary interiors, cool dense stars, and in every plasma device where one starts from a solid, e.g., laser-solid matter produced plasma as well as all inertial fusion schemes. The study of dense plasmas has been severely hampered by the fact that laser-based methods have been unavailable. The single most useful diagnostic of local plasma conditions, e.g., the temperature (T{sub e}), the density (n{sub e}), and the ionization (Z), has been Thomson scattering. However, due to the fact that visible light will not propagate at electron densities, n{sub e}, {ge} 10{sup 22} cm{sup -3} implies dense plasmas can not be probed. The 4th generation sources, LCLS and Tesla will remove these restrictions. Laser-based plasma spectroscopic techniques have been used with great success to determine the line shapes of atomic transitions in plasmas, study the population kinetics of atomic systems embedded in plasmas, and look at redistribution of radiation. However. the possibilities end for plasmas with n{sub e} {ge} 10{sup 22} since light propagation through the medium is severely altered by the plasma. The entire field of high Z plasma kinetics from laser produced plasma will then be available to study with the tunable source.

  2. 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.

  3. Fluoroquinolone susceptibility in Mycobacterium tuberculosis after pre-diagnosis exposure to older- versus newer-generation fluoroquinolones.

    PubMed

    van der Heijden, Yuri F; Maruri, Fernanda; Blackman, Amondrea; Mitchel, Ed; Bian, Aihua; Shintani, Ayumi K; Eden, Svetlana; Warkentin, Jon V; Sterling, Timothy R

    2013-09-01

    Fluoroquinolone exposure before tuberculosis (TB) diagnosis is common. We anticipated that exposure to older-generation fluoroquinolones is associated with greater fluoroquinolone MICs in Mycobacterium tuberculosis than exposure to newer agents. A nested case-control study was performed among newly diagnosed TB patients reported to the Tennessee Department of Health (January 2002-December 2009). Each fluoroquinolone-resistant case (n=25) was matched to two fluoroquinolone-susceptible controls (n=50). Ciprofloxacin and ofloxacin were classified as older-generation fluoroquinolones; levofloxacin, moxifloxacin and gatifloxacin were considered newer agents. There was no difference between median ofloxacin MIC for isolates from 9 patients exposed only to older fluoroquinolones, 25 exposed only to newer fluoroquinolones, 6 exposed to both and 35 fluoroquinolone-unexposed patients (Kruskal-Wallis, P=0.35). Using multivariate proportional odds logistic regression adjusting for age and sex, duration of exposure to newer fluoroquinolones was independently associated with higher MIC (OR=1.79, 95% CI 1.22-2.64), but duration of exposure to older fluoroquinolones was not (OR=0.94, 95% CI 0.50-1.78). Isolates from patients exposed only to newer fluoroquinolones tended to have mutations at gyrA codons 90, 91 or 94 more frequently than those exposed only to older fluoroquinolones (44% vs. 11%). We were surprised to find that duration of exposure to newer fluoroquinolones, but not older ones, was independently associated with higher ofloxacin MIC. This suggests that the mutant selection window lower boundary is likely to have clinical relevance; caution is warranted when newer fluoroquinolones are prescribed to patients with TB risk factors.

  4. 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.

  5. [Analysis of the 4th generation outer space bred Angelica dahurica by FTIR spectroscopy].

    PubMed

    Zhu, Yan-ying; Wu, Peng-le; Liu, Mei-yi; Wang, Zhi-zhou; Guo, Xi-hua; Guan, Ying

    2012-03-01

    The major components of the 4th generation outer space bred angelica and the ground group were determined and analyzed by Fourier transform infrared spectroscopy (FTIR) and second derivative spectrum, considering the large mutation of the plants with space mutagenesis. The results show that the content of the coumarin (1741 cm(-1)), which is the main active components of the space angelica dahurica increased, and the content of the protein (1 459, 1 419 cm(-1)) and the fat (930 cm(-1)) increased slightly, whereas the content of the starch and the dietary fiber reduced drastically. There are obvious differences between the peak values of the second derivative spectra of the plants, revealing that the outer space angelica dahurica contained amine component at 1 279 cm(-1). Space mutation breeding is favor of breeding angelica with better idiosyncrasy.

  6. 4th generation of the 1st level surface detector trigger in the Pierre Auger Observator

    NASA Astrophysics Data System (ADS)

    Szadkowski, Z.

    The proposal of a new 4th generation of the Front-End with the advanced 1st level triggers for the Infill Array of the Pierre Auger Observatory and for the Auger North is described. Newest FPGA chips offer much higher capacity of logic registers and memories, as well as DSP blocks. The calibration channel, previously supported by an external dual-port RAM, has been fully implemented into FPGA chip, through a large internal memory. In turn DSP blocks allowed on implementation of much more sophisticated spectral trigger algorithms. A single chip simplified board design, newer architecture of FPGA reduced resouces utilization and power consumption. Higher sampling in the new Front- End in comparison with previous 40 MHz designs as well as free resources for new detection algotithms can be a good platform for CR radio detection technique at Auger enhancing a duty cycle for the detection of UHECR’s.

  7. 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

  8. Reliability of a new 4th generation FloTrac algorithm to track cardiac output changes in patients receiving phenylephrine.

    PubMed

    Ji, Fuhai; Li, Jian; Fleming, Neal; Rose, David; Liu, Hong

    2015-08-01

    Phenylephrine is often used to treat intra-operative hypotension. Previous studies have shown that the FloTrac cardiac monitor may overestimate cardiac output (CO) changes following phenylephrine administration. A new algorithm (4th generation) has been developed to improve performance in this setting. We performed a prospective observational study to assess the effects of phenylephrine administration on CO values measured by the 3rd and 4th generation FloTrac algorithms. 54 patients were enrolled in this study. We used the Nexfin, a pulse contour method shown to be insensitive to vasopressor administration, as the reference method. Radial arterial pressures were recorded continuously in patients undergoing surgery. Phenylephrine administration times were documented. Arterial pressure recordings were subsequently analyzed offline using three different pulse contour analysis algorithms: FloTrac 3rd generation (G3), FloTrac 4th generation (G4), and Nexfin (nf). One minute of hemodynamic measurements was analyzed immediately before phenylephrine administration and then repeated when the mean arterial pressure peaked. A total of 157 (4.6 ± 3.2 per patient, range 1-15) paired sets of hemodynamic recordings were analyzed. Phenylephrine induced a significant increase in stroke volume (SV) and CO with the FloTrac G3, but not with FloTrac G4 or Nexfin algorithms. Agreement between FloTrac G3 and Nexfin was: 0.23 ± 1.19 l/min and concordance was 51.1%. In contrast, agreement between FloTrac G4 and Nexfin was: 0.19 ± 0.86 l/min and concordance was 87.2%. In conclusion, the pulse contour method of measuring CO, as implemented in FloTrac 4th generation algorithm, has significantly improved its ability to track the changes in CO induced by phenylephrine.

  9. 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.

  10. Fourth-generation fluoroquinolone-resistant mycobacterial keratitis after laser in situ keratomileusis.

    PubMed

    Moshirfar, Majid; Meyer, Jay J; Espandar, Ladan

    2007-11-01

    We report a case of mycobacterial keratitis resistant to fourth-generation fluoroquinolones after laser in situ keratomileusis (LASIK) with fourth-generation fluoroquinolone prophylaxis. While receiving moxifloxacin post LASIK, the patient was diagnosed with moxifloxacin-resistant Mycobacterium chelonae keratitis. Culture susceptibilities revealed isolates resistant to moxifloxacin and gatifloxacin, and treatment with topical amikacin and clarithromycin with oral doxycycline and clarithromycin along with flap amputation was necessary to control the infection. This case demonstrates the potential limitations in the coverage of these antibiotic agents.

  11. Characterization of γ and γ' phases in 2nd and 4th generation single crystal nickel-base superalloys

    NASA Astrophysics Data System (ADS)

    Zietara, Maciej; Neumeier, Steffen; Göken, Mathias; Czyrska-Filemonowicz, Aleksandra

    2017-01-01

    A Ni based single crystal superalloy from the 2nd generation, PWA 1484, and one from the 4th generation, PWA 1497, were comparatively studied by scanning electron microscopy, energy dispersive X-ray spectroscopy and nanoindentation technique in an atomic force microscope (NI-AFM) after high temperature creep deformation. During primary creep of both generations of superalloys, γ' precipitates start to coalesce and grow directionally. Further creep deformation leads to the topological inversion and coarsening of the rafted microstructure. The NI-AFM technique was used for measurements of the hardness of the γ and γ' phases in as-received and creep deformed samples in various conditions. The g matrix of the PWA 1497 superalloy is on average 0.8 GPa harder than that of PWA 1484 that can be explained by higher content of Re and Ru, since they partition predominantly to the matrix phase.

  12. 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.

  13. 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.

  14. Battling the "Hydra": Changing Operational Factors in 4th Generation War

    DTIC Science & Technology

    2007-11-02

    challenging us to change current doctrine and attempts to reduce war to algebraic formulae. Current Operational Doctrine Operational art, as advanced...over terrain -- the image and concept of ’classic’ war. A- 2 Armies turned to ’science," relying upon mathematical probabilities and algebraic formulae...Jominian war of algebraic formula and mathematical probabilities, vice accepting the 3d generation premise to cause and thrive within chaos. Lacking

  15. Development of partially-coherent wavefront propagation simulation methods for 3rd and 4th generation synchrotron radiation sources

    NASA Astrophysics Data System (ADS)

    Chubar, Oleg; Berman, Lonny; Chu, Yong S.; Fluerasu, Andrei; Hulbert, Steve; Idir, Mourad; Kaznatcheev, Konstantine; Shapiro, David; Shen, Qun; Baltser, Jana

    2011-09-01

    Partially-coherent wavefront propagation calculations have proven to be feasible and very beneficial in the design of beamlines for 3rd and 4th generation Synchrotron Radiation (SR) sources. These types of calculations use the framework of classical electrodynamics for the description, on the same accuracy level, of the emission by relativistic electrons moving in magnetic fields of accelerators, and the propagation of the emitted radiation wavefronts through beamline optical elements. This enables accurate prediction of performance characteristics for beamlines exploiting high SR brightness and/or high spectral flux. Detailed analysis of radiation degree of coherence, offered by the partially-coherent wavefront propagation method, is of paramount importance for modern storage-ring based SR sources, which, thanks to extremely small sub-nanometer-level electron beam emittances, produce substantial portions of coherent flux in X-ray spectral range. We describe the general approach to partially-coherent SR wavefront propagation simulations and present examples of such simulations performed using "Synchrotron Radiation Workshop" (SRW) code for the parameters of hard X-ray undulator based beamlines at the National Synchrotron Light Source II (NSLS-II), Brookhaven National Laboratory. These examples illustrate general characteristics of partially-coherent undulator radiation beams in low-emittance SR sources, and demonstrate advantages of applying high-accuracy physical-optics simulations to the optimization and performance prediction of X-ray optical beamlines in these new sources.

  16. 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…

  17. 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

    2008-02-04

    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%.

  18. 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 Central

    Bidell, Monique R.; Palchak, Melissa; Mohr, John

    2016-01-01

    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

  19. 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.

  20. Organization of the Topical Meeting on Short Wavelength Coherent Radiation: Generation and Applications (4th) Held in North Falmouth, Massachusetts

    DTIC Science & Technology

    1989-03-01

    spectrometer using coherent VUV generated by four -wave 8:30 AM (Invited Paper) sum mixing has been used to study autoionization in NO and MAI The A. C...tween n = 5, 4, and 3 excited levels are observed in a 100- ps TuC13 Capillary Discharge Plasmas as Extreme Ultraviolet laser-produced heliumlike Al plasma...Interference in Four -Wave TuC28 Gain Measurement on a 18.2-nm Carbon Recombin- Mixing, K. G. H. Baldwin. Australian National U. Constructive ation Laser

  1. 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

  2. Probing ultra-fast processes with high dynamic range at 4th-generation light sources: Arrival time and intensity binning at unprecedented repetition rates

    PubMed Central

    Kovalev, S.; Green, B.; Golz, T.; Maehrlein, S.; Stojanovic, N.; Fisher, A. S.; Kampfrath, T.; Gensch, M.

    2017-01-01

    Understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systems and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession. PMID:28382317

  3. Probing ultra-fast processes with high dynamic range at 4th-generation light sources: Arrival time and intensity binning at unprecedented repetition rates.

    PubMed

    Kovalev, S; Green, B; Golz, T; Maehrlein, S; Stojanovic, N; Fisher, A S; Kampfrath, T; Gensch, M

    2017-03-01

    Understanding dynamics on ultrafast timescales enables unique and new insights into important processes in the materials and life sciences. In this respect, the fundamental pump-probe approach based on ultra-short photon pulses aims at the creation of stroboscopic movies. Performing such experiments at one of the many recently established accelerator-based 4th-generation light sources such as free-electron lasers or superradiant THz sources allows an enormous widening of the accessible parameter space for the excitation and/or probing light pulses. Compared to table-top devices, critical issues of this type of experiment are fluctuations of the timing between the accelerator and external laser systems and intensity instabilities of the accelerator-based photon sources. Existing solutions have so far been only demonstrated at low repetition rates and/or achieved a limited dynamic range in comparison to table-top experiments, while the 4th generation of accelerator-based light sources is based on superconducting radio-frequency technology, which enables operation at MHz or even GHz repetition rates. In this article, we present the successful demonstration of ultra-fast accelerator-laser pump-probe experiments performed at an unprecedentedly high repetition rate in the few-hundred-kHz regime and with a currently achievable optimal time resolution of 13 fs (rms). Our scheme, based on the pulse-resolved detection of multiple beam parameters relevant for the experiment, allows us to achieve an excellent sensitivity in real-world ultra-fast experiments, as demonstrated for the example of THz-field-driven coherent spin precession.

  4. Second-generation surveillance for HIV/AIDS in Pakistan: results from the 4th round of Integrated Behavior and Biological Survey 2011–2012

    PubMed Central

    Emmanuel, Faran; Salim, Momina; Akhtar, Naeem; Arshad, Salwa; Reza, Tahira Ezra

    2013-01-01

    Objectives In an effort to fully analyse and understand the HIV situation and its epidemiology in Pakistan, a bilateral collaboration between the National AIDS Control Program and the Canadian International Development Agency resulted in the establishment of an effective second-generation surveillance (SGS) system for HIV/AIDS between 2004 and 2012 in accordance with the published guidelines. This paper presents findings from the 4th round of SGS. Methods A mapping exercise was initially conducted for size estimations of the key vulnerable populations: people who inject drugs (PWIDs), male sex workers (MSWs), hijra sex workers (HSWs), and female sex workers (FSWs), followed by an Integrated Behavioral and Biological Surveillance in 20 selected cities across Pakistan. Results The estimated sizes of the four key populations mapped in the 20 cities were 89 178 FSWs, 46 351 PWIDs, 23 317 HSWs and 19 119 MSWs. The HIV sero-prevalence among PWIDs was the highest among all key populations surveyed at 37.8% (CI 37.3 to 38.3) nationally, followed by a prevalence of 7.2% (CI 6.8 to 7.5) among HSWs, 3.1% (CI 2.8 to 3.4) among MSWs and 0.8% (CI 0.4 to 1.0) for FSWs. Various key risk behaviours, that is, sharing of syringes by PWIDs and inconsistent use of condoms by sex workers, were documented. Conclusions Pakistan's HIV epidemic that once was characterised primarily by transmission among PWIDs is now increasingly characterised by significant sexual transmission, and all types of sex workers (male, hijra and female) exhibit epidemiological proportions of infection. There is a need to develop concrete strategic plans for each vulnerable subpopulation, initially focusing prevention resources on those with a higher risk or vulnerability. PMID:23912818

  5. [Treatment of drug resistant destructive pulmonary tuberculosis: gemifloxacin and other fluoroquinolones clinical efficiency and tolerance at the end of initial phase of treatment].

    PubMed

    Petrenko, V I; Radysh, H V

    2013-12-01

    Gemifloxacin efficiency and tolerance in comparison to the ofloxacin, levofloxacin and gatifloxacin during the intensive phase of the antituberculosis therapy for drug resistant cases was evaluated. 156 drug resistant TB patients were examined in the open, prospective, randomized research, being divided into 2 groups with similar drug resistance profile. The 1st group received gemifloxacin, the 2nd--other fluoroquinolones. Gemifloxacin efficiency in the treatment regimen for the drug resistant TB patients did not differ from the efficiency of the use of other fluoroquinolones of the 4th generation and was significantly higher in comparison to ofloxacin. At the same time the identical level of side effects was registered in the course of treatment with mentioned drugs. Gemifloxacin is effective and safe at treatment of tuberculosis in comparison to other fluoroquinolones that allows considering it as the drug of choice among fluoroquinolones for treatment of drug resistant TB, including multidrug-resistant TB.

  6. 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.

  7. [Fluoroquinolones: Non-antibacterial properties].

    PubMed

    Leyva-Ramos, S; Hernández-López, H

    2017-02-01

    Fluoroquinolones are a class of well-established chemotherapeutic agents with a potent biological activity being the structure of 4-quinolone-3-carboxilic acids privileged because it contains different sites for functionalization allowing expand its use in clinical practice for their antifungal, antiviral and anticancer activities. Quinolones structural changes have resulted in a first, second, third and fourth generation of drugs so it is advisable to continue modifying existing structures in new ways to generate compounds with desirable biological and pharmacological properties.

  8. The Leap into 4th Grade

    ERIC Educational Resources Information Center

    Anderson, Mike

    2011-01-01

    Fourth grade is a pivotal year, in which students commonly face increased academic demands. According to Anderson, teachers can help students make a smooth transition to 4th grade by introducing these new challenges in ways that are in line with 4th graders' common developmental characteristics: incredible energy and emotion, industriousness and…

  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. 166. GENERAL VIEW DOWN 4TH AVENUE. VIEW NORTHEAST DOWN 4TH ...

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

    166. GENERAL VIEW DOWN 4TH AVENUE. VIEW NORTHEAST DOWN 4TH AVE. FROM BUILDING 44 SHOWING, FROM LEFT TO RIGHT, BUILDING 46, 48, 55, AND 50 (PART OF ENLISTED BARRACKS COMPLEX), AND BUILDINGS 17, 16, 484, 483, 374, AND 375 (IN THE WAREHOUSE COMPLEX). - Quonset Point Naval Air Station, Roger Williams Way, North Kingstown, Washington County, RI

  11. Peer Review Handbook 4th Edition, 2015

    EPA Pesticide Factsheets

    The 4th edition of EPA's Peer Review Handbook, 2015 is the most up to date version. It was prepared for the U.S. Environmental Protection Agency by Members of the Peer Review Advisory Group under the direction of EPA’s Science and Technology Policy Council

  12. Kids & Family Reading Report™. 4th Edition

    ERIC Educational Resources Information Center

    Scholastic Inc., 2013

    2013-01-01

    This report presents the 4th Edition of Scholastic's biannual study of children's and parents' attitudes and behaviors about reading. Much has changed since the first "Kids & Family Reading Report" was issued in 2006, but literacy remains the critical skill needed for school success. Today's children are growing up in a world full of…

  13. Combinatorially-generated library of 6-fluoroquinolone analogs as potential novel antitubercular agents: a chemometric and molecular modeling assessment.

    PubMed

    Minovski, Nikola; Perdih, Andrej; Solmajer, Tom

    2012-05-01

    The virtual combinatorial chemistry approach as a methodology for generating chemical libraries of structurally-similar analogs in a virtual environment was employed for building a general mixed virtual combinatorial library with a total of 53.871 6-FQ structural analogs, introducing the real synthetic pathways of three well known 6-FQ inhibitors. The druggability properties of the generated combinatorial 6-FQs were assessed using an in-house developed drug-likeness filter integrating the Lipinski/Veber rule-sets. The compounds recognized as drug-like were used as an external set for prediction of the biological activity values using a neural-networks (NN) model based on an experimentally-determined set of active 6-FQs. Furthermore, a subset of compounds was extracted from the pool of drug-like 6-FQs, with predicted biological activity, and subsequently used in virtual screening (VS) campaign combining pharmacophore modeling and molecular docking studies. This complex scheme, a powerful combination of chemometric and molecular modeling approaches provided novel QSAR guidelines that could aid in the further lead development of 6-FQs agents.

  14. Low prevalence of fluoroquinolone resistant strains and resistance precursor strains in Streptococcus pneumoniae from patients with community-acquired pneumonia despite high fluoroquinolone usage.

    PubMed

    Pletz, Mathias W; van der Linden, Mark; von Baum, Heike; Duesberg, Christoph B; Klugman, Keith P; Welte, Tobias

    2011-01-01

    We investigated the usage of fluoroquinolones and the prevalence of fluoroquinolone resistant pneumococci and their precursors (first step mutants and efflux expressing isolates) in patients with community-acquired pneumonia, who were enroled into the German CAPNETZ surveillance study from 2002 to 2006 before the introduction of the pneumococcal conjugate vaccine (n=5780). Thirty-eight percent of all outpatients received fluoroquinolones. Moxifloxacin accounted for 70%, levofloxacin for 19% and ciprofloxacin for 9% of all fluoroquinolone prescriptions. One hundred and sixty-three pneumococcal isolates from 556 patients with pneumococcal pneumonia were analyzed for fluoroquinolone resistance, efflux phenotype, prevalence of mutations within the quinolone-resistance determining regions and clonality. None of the isolates exhibited fluoroquinolone resistance, 1.2% of the isolates contained a first step mutation and 6.7% exhibited an efflux phenotype. There was no clonal relationship among these strains at increased risk for fluoroquinolone resistance. The absence of fluoroquinolone resistance in the context of high fluoroquinolone usage might be explained by the high proportion of third-generation fluoroquinolones with enhanced activity against pneumococci.

  15. 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

  16. Hypersensitivity reactions to fluoroquinolones.

    PubMed

    Scherer, Kathrin; Bircher, Andreas J

    2005-01-01

    Fluoroquinolone antibiotics cause immediate and delayed hypersensitivity reactions, and may also affect internal organs and circulating blood cells. The underlying pathomechanisms are only partly understood. The extent of cross-reactivity among different quinolones depends on the type of clinical manifestation and its underlying mechanism. Despite recent advances, reliable diagnostic tests are still lacking. Recent studies have shown quinolone-specific IgE in vitro in more than 50% of patients with immediate-type reactions and a considerable cross-reactivity with related compounds. In maculopapular drug exanthems from ciprofloxacin, specific T-cell clones were identified, and cross-reactivity to related compounds was detected in approximately 50% of the clones. From re-exposure studies in patients with exanthems, cross-reactivity appears to be lower. Cellular tests such as lymphocyte transformation tests are currently not very useful. For prick and intradermal skin tests, widely divergent nonirritant test concentrations have been recommended. Desensitization may be possible in selected patients.

  17. ACSPRI 2014 4th International Social Science Methodology Conference Report

    DTIC Science & Technology

    2015-04-01

    behaviour (Ackland, 2014). Big Data and in particular, social media data, present both methodological challenges and opportunities in empirical social ...UNCLASSIFIED UNCLASSIFIED ACSPRI 2014 4th International Social Science Methodology Conference Report Elena Mazourenko Joint...interest to the Technology Forecasting and Futures (TFF) Group of JOAD presented at the ACSPRI 4th International Social Science Methodology conference

  18. Venezuela as an Exporter of 4th Generation Warfare Instability

    DTIC Science & Technology

    2012-12-01

    Bolivia, Cuba, Ecuador, Nicaragua, and, possibly, Argentina ; 2) Iran and Russia; and, 3) at the very least, this alliance offers material and political...destabilize bourgeois regimes. Consequently, the CCB is reported to be active in, at the least, Argentina , Bolivia, Brazil, Chile, Cuba, the Dominican...Chavista populism in Venezuela”), in La democracia defraudada, Buenos Aires, Argentina : Grito Sagrado, 2005, pp. 115-139; Julio Alblert Cirino, “La Revo

  19. Fluoroquinolone-associated tendinopathy.

    PubMed

    Tsai, Wen-Chung; Yang, Yun-Ming

    2011-01-01

    The fluoroquinolones (FQs) are used to treat a wide range of infections because of their excellent gastrointestinal absorption, superior tissue penetration and broad-spectrum activity. Recently, FQ-associated tendinopathy and tendon rupture have been reported, especially in the elderly and patients with diabetes and renal failure. However, these adverse effects do not appear to be widely known among physicians. Because of the frequent use of FQs in clinical practice, physicians should be aware of their potential for severe disability from tendon rupture. Achilles tendinopathy or rupture is among the most serious side effects associated with FQ use, with reports markedly increasing, especially with the use of ciprofloxacin. The histopathologic findings include degenerative lesions, fissures, interstitial edema without cellular infiltration, necrosis and neovascularization. There are possible molecular mechanisms accounting for FQ-associated tendinopathy. First, ciprofloxacin mediates inhibition of cell proliferation and G2/M cell cycle arrest in tendon cells by down-regulation of cyclin B and cyclin-dependent kinase 1. Second, ciprofloxacin inhibits the spead and migration of tenocytes by down-regulation of focal adhesion kinase phosphorylation. Third, ciprofloxacin enhances the enzymatic activity of matrix metalloproteinase-2 with degradation of type I collagen. Management of FQ-associated tendinopathy includes immediate discontinuation of FQs, rest, non-steroidal anti-inflammatory drugs, physical modalities and eccentric strengthening exercise. Tendon rupture may require surgical intervention.

  20. [Salmonella of Indian origin: pseudo-susceptibility to fluoroquinolones].

    PubMed

    Denes, E; Gondran, G; Bezanahary, H; Genet, C; Rogez, J P; Weinbreck, P; Martin, C

    2005-04-01

    We report the case of a patient presenting with typhoid fever after returning from a stay in India. This infection was not cured with a course of ciprofloxacin, due to a reduced susceptibility of the bacteria to the drug. This decreased susceptibility to fluoroquinolones was not detected by the antibiogram, but the MIC for nalidixic acid was greater than 32 mg/l. This case suggests using a third generation cephalosporin instead of a quinolone, for people coming from a high-risk zone. It also suggests that the MIC for nalidixic acid and for norfloxacin can be used as the first clue for a reduced susceptibility to fluoroquinolones.

  1. 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

  2. The use of systemic and topical fluoroquinolones.

    PubMed

    Bradley, John S; Jackson, Mary Anne

    2011-10-01

    Appropriate prescribing practices for fluoroquinolones are essential as evolving resistance patterns are considered, additional treatment indications are identified, and the toxicity profile of fluoroquinolones in children becomes better defined. Earlier recommendations for systemic therapy remain; expanded uses of fluoroquinolones for the treatment of certain infections are outlined in this report. Although fluoroquinolones are reasonably safe in children, clinicians should be aware of the specific adverse reactions. Use of fluoroquinolones in children should continue to be limited to treatment of infections for which no safe and effective alternative exists.

  3. 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

  4. 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".

  5. 4(th) HUPO Brain Proteome Project Workshop in Munich, Germany.

    PubMed

    Hamacher, Michael; Stephan, Christian; Palacios Bustamante, Nadine; van Hall, Andre; Marcus, Katrin; Meyer, Helmut E

    2006-01-01

    More than 70 interested colleagues attended the 4(th) Workshop of HUPO's Brain Proteome Project. The project was presented within nine talks mainly focusing on two running pilot studies as well as on data re-processing. A bioinformatics jamboree in Hinxton, UK, and the 5th Workshop taking place in Dublin next February were announced.

  6. 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.

  7. Summary of the 4th Nordic Symposium on Digital Pathology

    PubMed Central

    Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

    2017-01-01

    The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange across stakeholders in health care, industry, and academia. In 2016, the 4th NDP installment took place in Linköping, Sweden, promoting development and collaboration in digital pathology for the benefit of routine care advances. This article summarizes the symposium, gathering 170 attendees from 13 countries. This summary also contains results from a survey on integrated diagnostics aspects, in particular radiology-pathology collaboration. PMID:28382222

  8. 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.

  9. Report of the 4th European Zebrafish Principal Investigator Meeting.

    PubMed

    Lopes, Susana S; Distel, Martin; Linker, Claudia; Fior, Rita; Monteiro, Rui; Bianco, Isaac H; Portugues, Ruben; Strähle, Uwe; Saúde, Leonor

    2016-12-01

    The European Zebrafish Principal Investigator Meeting (EZPM) is an ideal forum for group leaders using this fantastic animal model not only to discuss science but also to strengthen their interactions, to push forward technological advances, and to define guidelines for the use of this fish in research. The city of Lisbon (Portugal) was voted by the European group leaders to be the setting for the 4th EZPM, and the organizing committee, composed by Leonor Saúde (iMM Lisboa, PT), Susana Lopes (CEDOC, PT), Michael Orger (Champalimaud Foundation, PT), Rui Oliveira (ISPA, PT), and António Jacinto (CEDOC, PT), was very enthusiastic to organize a productive event. The 4th EZPM took place from March 15 to 19 at Pavilhão do Conhecimento, a Science Museum and Educational Center winner of The Great Prize FAD of Arquitecture 1999 and The Society for Environmental Graphic Design Award 2011. Over 5 days, 135 group leaders (89 men and 46 women) coming from 19 different European countries and also from the United States, Turkey, Israel, Chile, and Singapore presented and discussed their recent research achievements. In addition to the scientific oral and poster presentations, the group leaders gathered in very lively community sessions on morphants versus mutants (chaired by Didier Stainier, Max Planck Institute for Heart and Lung Research, DE), funding issues (chaired by Uwe Strahle, KIT-ITG, DE), and gender equality (chaired by Corinne Houart, KCL, United Kingdom). One of the highlights of the 4th EZPM was the guided visit to Oceanário de Lisboa, an international award-winning place that celebrates life with a stunning display of living aquatic creatures.

  10. 4TH Marine Division Operation Plan Number 49-44

    DTIC Science & Technology

    1944-12-26

    I / i i -4- A. o. o o o 3 4-’ 4TH MARINE DIVISION 54 OPERATION PLAN NO. 49-44 DECLASSIFIED IAW CLIASSIFICATION $4...INTO ENEMY HANDS. LUISrAR! UNCLASS0FIDo .-O UNCLASSIFIED ri LL!n .. I . 155 - - o.- sr Report Documentation Page Form ApprovedOMB No. 0704-0188 Public...the remainder of O-1 within Z, repared or further OPN PLAN 49-44 - 1 - O1 :?’:¢ . ... ~·~:~ I I - I --" , I %,"_’,: A I 1-W_ , - I I ---. -

  11. Rate of Missing Socioeconomic Factors in the 4th KNHANES.

    PubMed

    Park, Hyun Ah

    2012-11-01

    This study is to assess how missing values in socioeconomic status (SES) variables were handled in the Korean Journal of Family Medicine (KJFM) article using the Korea National Health and Nutrition Examination Survey (KNHANES) data and to estimate the rate of missing SES variables from the 4th KNHANES. We searched all original articles published in the KJFM from 2007 to 2011 and identified those that used KNHANES as their primary source of data. None of the 11 articles which presented KNHANES SES variables took into account of omitions in the analysis. The estimated rate of missing data on education, household income, marital status, and occupation data of the 4th KNHANES was 0.3 (0.05)%, 2.7 (0.2)%, 0.5 (0.1)%, and 9.4 (0.9)%, respectively. When all four variables were used simultaneously, the rates increased to 11.8 (0.9)%. Respondents with missing household income tended to be older (P < 0.001), less educated (P < 0.001), and more likely to be unemployed (P < 0.001), and widowed (P < 0.001). A similar relationship was shown for missing occupation data. Omissions in SES variables in KNHANES were related to certain characteristics of study participants. Researchers using KNHANES data should keep in mind the possible bias which can be introduced by missing SES values.

  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. [Allergies and adverse events associated with fluoroquinolones].

    PubMed

    Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D

    2015-04-08

    The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

  14. 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...

  15. 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

  16. Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India

    PubMed Central

    Banerjee, Tuhina; Anupurba, Shampa

    2016-01-01

    Background & objectives: Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. Methods: A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. Results: A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Interpretation & conclusions: Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance. PMID:28256471

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

    PubMed Central

    Yassien, M.A.M.; Elfaky, M.A.

    2015-01-01

    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

  18. 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.

  19. The 4th Concept Detector for the ILC

    NASA Astrophysics Data System (ADS)

    Mazzacane, A.

    2010-05-01

    The 4th Concept Detector is designed for high precision measurements of Physics processes accessible at ILC. It consists of four basic subsystems: a pixel vertex detector for high precision vertex definitions, impact parameter tagging and near-beam occupancy reduction; a cluster-counting low-mass drift chamber for robust pattern recognition with over 100 three-dimensional space-points each with about 55 μm resolution, 3.5% specific ionization measurement; a high precision dual-readout fiber calorimeter, complemented with an EM dual-readout crystal calorimeter, both with time-history readout, for the energy measurement of hadrons, jets, electrons, photons, missing momentum, and the tagging of muons; and, an iron-free dual-solenoid to return the flux and provide a second field region for the inverse direction bending of muons in a gas volume to achieve high acceptance and good muon momentum resolution. All four subsystems separately achieve the important scientific goal to be 2-to-10 times better than the already excellent LEP detectors, Aleph, Delphi, L3, and Opal. All four sub-detector will be described along with their performance and Physics capabilities obtained with full simulation studies.

  20. 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.

  1. 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) ...

  2. 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....

  3. 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

  4. 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

  5. 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...

  6. 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 Fireworks Display Berkeley, CA AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast... Berkeley Pier, Berkeley, CA in support of the 4th of July Festival Berkeley Marina Fireworks...

  7. 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…

  8. 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...

  9. 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…

  10. DNA repair inhibition by UVA photoactivated fluoroquinolones and vemurafenib

    PubMed Central

    Peacock, Matthew; Brem, Reto; Macpherson, Peter; Karran, Peter

    2014-01-01

    Cutaneous photosensitization is a common side effect of drug treatment and can be associated with an increased skin cancer risk. The immunosuppressant azathioprine, the fluoroquinolone antibiotics and vemurafenib—a BRAF inhibitor used to treat metastatic melanoma—are all recognized clinical photosensitizers. We have compared the effects of UVA radiation on cultured human cells treated with 6-thioguanine (6-TG, a DNA-embedded azathioprine surrogate), the fluoroquinolones ciprofloxacin and ofloxacin and vemurafenib. Despite widely different structures and modes of action, each of these drugs potentiated UVA cytotoxicity. UVA photoactivation of 6-TG, ciprofloxacin and ofloxacin was associated with the generation of singlet oxygen that caused extensive protein oxidation. In particular, these treatments were associated with damage to DNA repair proteins that reduced the efficiency of nucleotide excision repair. Although vemurafenib was also highly phototoxic to cultured cells, its effects were less dependent on singlet oxygen. Highly toxic combinations of vemurafenib and UVA caused little protein carbonylation but were nevertheless inhibitory to nucleotide excision repair. Thus, for three different classes of drugs, photosensitization by at least two distinct mechanisms is associated with reduced protection against potentially mutagenic and carcinogenic DNA damage. PMID:25414333

  11. 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.

  12. [Pharmacodynamic and pharmacokinetic evaluation of respiratory fluoroquinolones. Guideline to selection of the most appropriate fluoroquinolone].

    PubMed

    Parra-Ruiz, Jorge; Hernández-Quero, José

    2012-12-01

    Since its approval, fluoroquinolones have become one of the most prescribed antibacterial agents. Because of its widespread use, serious concerns about the emergence of resistance in Streptococcus pneumoniae, Pseudomonas spp, and entrobacteriaceae, has arisen, especially because of cross-resistance between fluoroquinolones. Huge efforts has been done to identify pharmacokinetic (PK) parameters like maximum serum concentration (Cmax), area under the curve of serum concentrations (AUC) and pharmacodynamic (PD) parameters like the minimum inhibitory concentration (MIC) or the mutant prevention concentration (MPC), to optimize the use of the new fluoroquinolones, especially against these difficult to treat microorganisms. The new fluoroquinolones commercially available in Spain, levofloxacin and moxifloxacin, have significant differences in their PK (Cmax, half-life, volume of distribution, etc), PD (MIC, MPC,) and in their PK/PD parameters (AUC/MIC; AUC/MPC) that allow clinicians to establish clear preference for the utilization of one of them. Proper use of these new fluoroquinolones according to these PK/PD parameters will result in better management of respiratory infections with a reduction in the emergence of resistance. Based on data reviewed in this paper moxifloxacin use, with best PK/PD characteristics, should be preferred over levofloxacin. Should levofloxacin be used, alternative dosing strategies would be recommended to avoid selection of resistant variants.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Qualification of the 4th stage propulsor of the Brazilian launcher. SLV: A new sounding rocket

    NASA Astrophysics Data System (ADS)

    Boscov, Jayme; Toyama, Wilson Katsumi

    1989-06-01

    The development of the Satellite Launcher Vehicle (SLV) is presented. In particular, the attention is focused on the acquisition of the propulsion parameters of the 4th stage propulsor. The device feasibility analysis is considered. The system consists of a two staged sounding rocket. Its second stage contains the SVL, which can be launched by the 4th stage propulsor to a height range of about 50 to 60 km.

  18. Susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada.

    PubMed

    Patel, Samir N; McGeer, Allison; Melano, Roberto; Tyrrell, Gregory J; Green, Karen; Pillai, Dylan R; Low, Donald E

    2011-08-01

    Ciprofloxacin, the first fluoroquinolone to be used to treat lower respiratory tract infections (LRTI), demonstrates poor potency against Streptococcus pneumoniae, and its use has been associated with the emergence of resistance. During the last decade, fluoroquinolones with enhanced in vitro activity against S. pneumoniae have replaced ciprofloxacin for the treatment of LRTI. Here, we analyzed the impact of more active fluoroquinolone usage on pneumococci by examining the fluoroquinolone usage, prevalence of fluoroquinolone resistance, and mutations in the genes that encode the major target sites for the fluoroquinolones (gyrA and parC) in pneumococcal isolates collected in Canada-wide surveillance. A total of 26,081 isolates were collected between 1998 and 2009. During this time period, total per capita outpatient use of fluoroquinolones increased from 64 to 96 prescriptions per 1,000 persons per year. The proportion of prescriptions for respiratory tract infection that were for fluoroquinolones increased from 5.9% to 10.7%, but the distribution changed: the proportion of prescriptions for ciprofloxacin decreased from 5.3% to 0.5%, and those for levofloxacin or moxifloxacin increased from 1.5% in 1999 to 5.9% in 2009. The prevalence of ciprofloxacin resistance (MIC ≥ 4 μg/ml), levofloxacin resistance, and moxifloxacin resistance remained unchanged at <2%. Multivariable analyses showed that prevalence of mutations known to be associated with reduced susceptibility to fluoroquinolones did not change during the surveillance period. If fluoroquinolone therapy is required, the preferential use of fluoroquinolones with enhanced pneumococcal activity to treat pneumococcal infections may slow the emergence of resistance in S. pneumoniae.

  19. 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

  20. 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

  1. 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.

  2. Fluoroquinolone-resistant mutants of Burkholderia cepacia.

    PubMed

    Pope, C F; Gillespie, S H; Pratten, J R; McHugh, T D

    2008-03-01

    Fluoroquinolone-resistant Burkholderia cepacia mutants were selected on ciprofloxacin. The rate of mutation in gyrA was estimated to be 9.6 x 10(-11) mutations per division. Mutations in gyrA conferred 12- to 64-fold increases in MIC, and an additional parC mutation conferred a large increase in MIC (>256-fold). Growth rate, biofilm formation, and survival in water and during drying were not impaired in strains containing single gyrA mutations. Double mutants were impaired only in growth rate (0.85, relative to the susceptible parent).

  3. Support for the 4th Pan-American Congress on Plants and Bioenergy

    SciTech Connect

    Carpita, Nicholas C.

    2016-01-25

    Intellectual Merit: Following the success of the first three Pan-American Congresses on Plants and BioEnergy held biennially, the 4th congress will be held at the University of Guelph, Canada June 4-7, 2014. We aim to continue a tradition of showcasing major advances in energy crop improvement yet keep in perspective the realities of the economic drivers and pressures that govern the translation of scientific success into a commercial success. The congress is endorsed by the American Society of Plant Biologists and the Canadian Society of Plant Biologists. The program will cover a range of disciplines, including algal and plant systems for bioenergy, plant genetics and genomics, gene discovery for improvement of bioenergy production and quality, regulatory mechanisms of synthesis and degradation, strategies for 3rd generation biofuel production and the promise of synthetic biology in production of biofuels and bio-based products, cropping systems and productivity for biomass production, and mitigation of environmental impacts of bioenergy production. Broader Impacts: We are requesting support to generate stipends for domestic and permanent-resident students, post-doctorals, and pre-tenured faculty members to attend and benefit from the outstanding program. The stipends will be limited to registration and on-site lodging costs, with partial support for travel in instances of great need. So that as great a number can benefit as possible, airfare costs will be provided for only applicants with great need. ASPB has endorsed this meeting and will assist in advertising and promoting the meeting. ASPB has a long-standing commitment to increase participation and advance the careers in plant biology of women, minorities and underrepresented scientists, and they will assist us in identifying worthy candidates.

  4. Fluoroquinolones for the treatment of tuberculosis in children.

    PubMed

    Thee, S; Garcia-Prats, A J; Donald, P R; Hesseling, A C; Schaaf, H S

    2015-05-01

    The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens as well as in the prevention of drug-resistant TB. The objective of this review was to identify existing evidence for the use of the fluoroquinolones ofloxacin, levofloxacin and moxifloxacin in the treatment of TB in children. Existing data from in vitro, animal and human studies consistently demonstrate the efficacy of the fluoroquinolones against Mycobacterium tuberculosis, with superiority of levofloxacin and moxifloxacin compared to ofloxacin. In vitro and murine studies demonstrated the potential of moxifloxacin to shorten drug-susceptible TB treatment, but in multiple randomized controlled trials shortened fluoroquinolone-containing regimens have not been non-inferior compared to standard therapy. Resistance occurs frequently via mutations in the gyrA gene, and emerges rapidly depending on the fluoroquinolone concentration, with newer more potent fluoroquinolones less likely to develop resistance. Emerging data from paediatric studies underlines the importance of fluoroquinolones in the treatment of MDR-TB in children. There is a paucity of pharmacokinetic data especially in children <5 years of age and HIV-infected children; existing studies show substantially lower serum concentrations in children compared to adults at currently recommended doses, probably due to faster elimination. This has implications for optimizing paediatric treatment and for the development of resistance. Fluoroquinolone use has been restricted in children due to concerns about drug-induced arthropathy. The available data does not demonstrate any serious arthropathy or other severe toxicity in children. Although there is limited paediatric safety data for the prolonged treatment of MDR-TB, extended administration of fluoroquinolones in adults with MDR-TB does not show serious adverse effects and there is no evidence

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Mechanisms of clinical resistance to fluoroquinolones in Enterococcus faecalis.

    PubMed Central

    Nakanishi, N; Yoshida, S; Wakebe, H; Inoue, M; Mitsuhashi, S

    1991-01-01

    About 10% of 100 clinical isolates of Enterococcus faecalis were resistant to greater than or equal to 25 micrograms of norfloxacin, ofloxacin, ciprofloxacin, and temafloxacin per ml. In this study, the DNA gyrase of E. faecalis was purified from a fluoroquinolone-susceptible strain (ATCC 19433) and two resistant isolates, MS16968 and MS16996. Strains MS16968 and MS16996 were 64- to 128-fold and 16- to 32-fold less susceptible, respectively, to fluoroquinolones than was ATCC 19433; MICs of nonquinolone antibacterial agents for these strains were almost equal. The DNA gyrase from ATCC 19433 had two subunits, designated A and B, with properties similar to those of DNA gyrase from other gram-positive bacteria such as Bacillus subtilis and Micrococcus luteus. Inhibition of the supercoiling activity of the enzyme from ATCC 19433 by the fluoroquinolones correlated with their antibacterial activities. In contrast, preparations of DNA gyrase from MS16968 and MS16996 were at least 30-fold less sensitive to inhibition of supercoiling by the fluoroquinolones than the gyrase from ATCC 19433 was. Experiments that combined heterologous gyrase subunits showed that the A subunit from either of the resistant isolates conferred resistance to fluoroquinolones. These findings indicate that an alteration in the gyrase A subunit is the major contributor to fluoroquinolone resistance in E. faecalis clinical isolates. A difference in drug uptake may also contribute to the level of fluoroquinolone resistance in these isolates. Images PMID:1656852

  10. Seismically induced liquefaction structures in La Magdalena archaeological site, the 4th century AD Roman Complutum (Madrid, Spain)

    NASA Astrophysics Data System (ADS)

    Rodríguez-Pascua, M. A.; Silva, P. G.; Perucha, M. A.; Giner-Robles, J. L.; Heras, C.; Bastida, A. B.; Carrasco, P.; Roquero, E.; Lario, J.; Bardaji, T.; Pérez-López, R.; Elez, J.

    2016-10-01

    The ancient Roman city of Complutum (Alcalá de Henares, Madrid), founded in the 1st century AD, was one of the most important cities of Hispania. The old Roman city was destroyed, abruptly abandoned, relocated close by and rebuilt during the late 4th century AD. Destruction of the city and its relocation has not yet been explained by archaeologists. In this paper, with our multidisciplinary approach, we identify and characterize earthquake archaeological effects (EAEs) affecting the archaeological site, the La Magdalena, an agricultural holding 4 km from the core of Complutum. The most important EAEs in the site are liquefactions (sand dikes and explosive sand-gravel craters) affecting Roman structures, such as water tanks (cisterns), houses and graves. Ground liquefaction generated significant ground cracks, explosive craters and folds in foundations of buildings. Several other Roman sites throughout the valley were also abandoned abruptly during the 4th century AD, in some cases with EAEs of similar origin. This suggests the occurrence of a 5.0-6.6 Mw seismic event in the zone, in accordance with the minimum empirical limit of seismically-induced liquefaction and the maximum surface rupture length of the Henares fault.

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

    PubMed Central

    2012-01-01

    Fluoroquinolones are commonly used to treat lung infections in those with cystic fibrosis. Patients with cystic fibrosis are susceptible to lung infection with common bacteria such as Staphylococcus aureus and Haemophilus influenzae, but also are prone to infection by opportunistic bacteria, including Pseudomonas aeruginosa. The good oral bioavailability and broad antimicrobial spectrum of activity, including anti-pseudomonal 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 is also discussed. PMID:22968160

  12. 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.

  13. 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.

  14. Improving the Attitudes of 4th Graders toward Older People through a Multidimensional Intergenerational Program

    ERIC Educational Resources Information Center

    Lynott, Patricia P.; Merola, Pamela R.

    2007-01-01

    The purpose of this study was to examine the effects of an intergenerational program on children's attitudes toward older people. Four 4th grade classes, one each during the years 2002 through 2005, participated in the study. The elders and school children engaged in meaningful activities over a 5 month period, including the performance of a play…

  15. 75 FR 34639 - Safety Zone; Reedville July 4th Celebration, Cockrell's Creek, Reedville, VA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Reedville July 4th Celebration, Cockrell's... establishing a temporary safety zone on Cockrell's Creek in the vicinity of Reedville, Virginia in support of... impracticable. Delaying the effective date would be contrary to the safety zone's intended objectives...

  16. 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...

  17. 77 FR 39408 - Safety Zone; Buffalo July 4th Fireworks, Lake Erie, Buffalo, NY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... 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 is establishing a temporary safety zone on Lake Erie, Buffalo, NY. This safety zone is intended to...

  18. 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

  19. 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...

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

  3. 33 CFR 165.166 - Safety Zone: Macy's July 4th Fireworks, East River, NY.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Fireworks, East River, NY. 165.166 Section 165.166 Navigation and Navigable Waters COAST GUARD, DEPARTMENT... § 165.166 Safety Zone: Macy's July 4th Fireworks, East River, NY. (a) Regulated area. The following area...) in length, carrying persons for the purpose of viewing the fireworks, may take position in an...

  5. 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...

  6. 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

  7. 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…

  8. 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

  9. Quantitative Contributions of Target Alteration and Decreased Drug Accumulation to Pseudomonas aeruginosa Fluoroquinolone Resistance

    PubMed Central

    Bruchmann, Sebastian; Dötsch, Andreas; Nouri, Bianka; Chaberny, Iris F.

    2013-01-01

    Quinolone antibiotics constitute a clinically successful and widely used class of broad-spectrum antibiotics; however, the emergence and spread of resistance increasingly limits the use of fluoroquinolones in the treatment and management of microbial disease. In this study, we evaluated the quantitative contributions of quinolone target alteration and efflux pump expression to fluoroquinolone resistance in Pseudomonas aeruginosa. We generated isogenic mutations in hot spots of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, and parC and inactivated the efflux regulator genes so as to overexpress the corresponding multidrug resistance (MDR) efflux pumps. We then introduced the respective mutations into the reference strain PA14 singly and in various combinations. Whereas the combined inactivation of two efflux regulator-encoding genes did not lead to resistance levels higher than those obtained by inactivation of only one efflux regulator-encoding gene, the combination of mutations leading to increased efflux and target alteration clearly exhibited an additive effect. This combination of target alteration and overexpression of efflux pumps was commonly observed in clinical P. aeruginosa isolates; however, these two mechanisms were frequently found not to be sufficient to explain the level of fluoroquinolone resistance. Our results suggest that there are additional mechanisms, independent of the expression of the MexAB-OprM, MexCD-OprJ, MexEF-OprN, and/or MexXY-OprM efflux pump, that increase ciprofloxacin resistance in isolates with mutations in the QRDRs. PMID:23274661

  10. Insight into Prodrugs of Quinolones and Fluoroquinolones.

    PubMed

    Sharma, Prabodh Chander; Piplani, Mona; Mittal, Monika; Pahwa, Rakesh

    2016-01-01

    Quinolones and fluoroquinolones are principal weapons against variety of bacterial infections and exert their antibacterial potential by interfering the activities of bacterial enzymes. As these agents are associated with some limitations, an important approach to overcome these major constraints is to prepare covalent derivatives, i.e. prodrugs. Prodrug design has been employed to improve the limitations of these drugs such as less aqueous solubility, poor absorption and distribution, toxicity, disagreeable taste, poor lipophilicity etc and for improving their pharmacological profile. This paper highlights the utility of various prodrug strategies in optimizing the therapeutic index of these antibacterial agents and their recent patents. Some of their prodrugs being utilized at preclinical and clinical levels have also been discussed. Hence, this paper has been prepared to present the significant findings of various research papers that would be helpful in motivating scientific researchers to forward the research in direction of utilization of prodrugs in clinical therapy.

  11. The first steps towards fluoroquinolone resistance in Hungarian pneumococci.

    PubMed

    Dobay, O; Rozgonyi, F; Ghidán, A; Matuz, M; Nagy, K; Amyes, S G B

    2006-12-01

    The incidence of fluoroquinolone resistance among Hungarian routine laboratory Streptococcus pneumoniae isolates, collected in 2000-2002, in common with other European countries, was very low; only 5/304 strains (1.64%) were resistant to ciprofloxacin (MIC = 4 microg/ml), and the other fluoroquinolones showed full efficacy. However, we could identify the Lys-137-Asp amino acid change, caused by a point mutation in the QRDR of the parC gene, in five strains. Additionally, we observed a definite shift in the minimum inhibitory concentrations (MICs) of all fluoroquinolones towards higher values throughout the study period. These two findings, coupled with the increasing consumption figures of fluoroquinolones, suggest that pneumococcal resistance looks poised to develop in Hungary.

  12. In vitro-selected resistance to fluoroquinolones in two Brucella strains associated with mutational changes in gyrA.

    PubMed

    Turkmani, Aun; Psaroulaki, Anna; Christidou, Athanasia; Chochlakis, Dimosthenis; Tabaa, Darem; Tselentis, Yannis

    2008-09-01

    In the present study, Brucella melitensis biovar Abortus 2308 and Brucella abortus 3196 biotype 5 reference strains, which are susceptible to fluoroquinolones, became in vitro-resistant to fluoroquinolones by culture in trypticase soy agar. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes of the two reference strains were analysed by polymerase chain reaction sequencing analysis to obtain the wild-type sequence. These sequences were then compared with the corresponding sequences of four in vitro-selected fluoroquinolone-resistant mutants to characterise mutations associated with resistance. Sequencing of the ofloxacin-selected resistant mutant 2308 revealed a transition of GAT to AAT (corresponding to position 87 of Escherichia coli gyrA), leading to substitution of Asp91-->Asn, whilst at the same position the ciprofloxacin-selected resistant mutant 2308 revealed a transition of GAT to TAT (corresponding to the same position of E. coli as above), leading to substitution of Asp91-->Tyr. The ofloxacin-selected resistant mutant 3196 had a transition of GCT to GTT, generating an amino acid change of Ala87-->Val. Amino acid changes were detected in the portion of the Brucella gyrA gene (Ala71 to Gln110) corresponding to the E. coli gyrA QRDR region (Ala67 to Gln110). Amino acid changes were also detected in Ser83, corresponding to the region where fluoroquinolone-associated amino acid changes are most commonly found in other bacterial species.

  13. Direct Photolysis of Fluoroquinolone Antibiotics at 253.7 nm: Specific Reaction Kinetics and Formation of Equally Potent Fluoroquinolone Antibiotics.

    PubMed

    Snowberger, Sebastian; Adejumo, Hollie; He, Ke; Mangalgiri, Kiranmayi P; Hopanna, Mamatha; Soares, Ana Dulce; Blaney, Lee

    2016-09-06

    Three fluoroquinolone-to-fluoroquinolone antibiotic transformations were monitored during UV-C irradiation processes. In particular, the following reactions were observed: enrofloxacin-to-ciprofloxacin, difloxacin-to-sarafloxacin, and pefloxacin-to-norfloxacin. The apparent molar absorptivity and fluence-based pseudo-first-order rate constants for transformation of the six fluoroquinolones by direct photolysis at 253.7 nm were determined for the pH 2-12 range. These parameters were deconvoluted to calculate specific molar absorptivity and fluence-based rate constants for cationic, zwitterionic, and anionic fluoroquinolone species. For a typical disinfection fluence of 40 mJ/cm(2), the apparent transformation efficiencies were inflated by 2-8% when fluoroquinolone products were not considered; moreover, the overall transformation efficiencies at 400 mJ/cm(2) varied by up to 40% depending on pH. The three product antibiotics, namely ciprofloxacin, sarafloxacin, and norfloxacin, were found to be equally or more potent than the parent fluoroquinolones using an Escherichia coli-based assay. UV treatment of a solution containing difloxacin was found to increase antimicrobial activity due to formation of sarafloxacin. These results highlight the importance of considering antibiotic-to-antibiotic transformations in UV-based processes.

  14. Effects of Public Preschool Expenditures on the Test Scores of 4th Graders: Evidence from TIMSS

    PubMed Central

    Waldfogel, Jane; Zhai, Fuhua

    2011-01-01

    This study examines the effects of public preschool expenditures on the math and science scores of 4th graders, holding constant child, family, and school characteristics, other relevant social expenditures, and country and year effects, in seven Organization for Economic Co-operation and Development (OECD) countries -- Australia, Japan, Netherlands, New Zealand, Norway, U.K., and U.S -- using data from the 1995 and 2003 Trends in International Mathematics and Science Study (TIMSS). Our results indicate that there are small but significant positive effects of public preschool expenditures on the math and science scores of 4th graders and preschool expenditures reduce the risk of children scoring at the low level of proficiency. We also find some evidence that children from low-resource homes and homes where the test language is not always spoken may tend to gain more from increased public preschool expenditures than other children,. PMID:21442008

  15. A Generalized 4th-Order Runge-Kutta Method for the Gross-Pitaevskii Equation

    NASA Astrophysics Data System (ADS)

    Kandes, Martin

    2015-04-01

    We present the implementation of a method-of-lines approach for numerically approximating solutions of the time-dependent Gross-Pitaevksii equation in non-uniformly rotating reference frames. Implemented in parallel using a hybrid MPI + OpenMP framework, which will allow for scalable, high-resolution numerical simulations, we utilize an explicit, generalized 4th-order Runge-Kutta time-integration scheme with 2nd- and 4th-order central differences to approximate the spatial derivatives in the equation. The principal objective of this project is to model the effect(s) of inertial forces on quantized vortices within weakly-interacting dilute atomic gas Bose-Einstein condensates in the mean-field limit of the Gross-Pitaevskii equation. Here, we discuss our work-to-date and preliminary results.

  16. 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

  17. LESSONS LEARNED, HEADQUARTERS, 4TH BATTALION (AW)(SP), 60TH ARTILLERY

    DTIC Science & Technology

    The 4th Battalion (AW)(SP) 60th Artillery with attached Battery E (MG), 41st Artillery, remained assigned to I Field Force Vietnam, attached to I ...Battalion (AW)(SP), 60th Artillery, with attached Battery E (MG), 41st Artillery, was detached from 41st Artillery Group and fully attached to I Field Force...States and Free World Military Assistance Forces throughout the II Corps Tactical Zone and the I Corps Tactical Zone.

  18. 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

  19. 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

    2016-03-17

    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.

  20. 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

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Crescent City 4th of July Fireworks; Crescent City Harbor, Crescent City, CA AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking... Crescent City, CA in support of the Crescent City 4th of July Fireworks on July 4, 2013. This safety...

  1. 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

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Redwood City 4th of July Fireworks Show; Port of Redwood City, Redwood City, CA AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking... of Redwood City near Redwood City, CA in support of the Redwood City 4th of July Fireworks Show...

  2. 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.

  3. Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells.

    PubMed

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

    2015-09-04

    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.

  4. 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

  5. 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.

  6. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates.

    PubMed

    Meng, Dong-Ya; Sun, Chang-Jian; Yu, Jing-Bo; Ma, Jun; Xue, Wen-Cheng

    2014-01-01

    To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  7. The role of fluoroquinolones in the management of urinary tract infections in areas with high rates of fluoroquinolone-resistant uropathogens.

    PubMed

    Chen, Y-H; Ko, W-C; Hsueh, P-R

    2012-08-01

    Fluoroquinolones have been recommended as the drugs of choice for the empirical treatment of uncomplicated and complicated urinary tract infections (UTIs) caused by trimethoprim-sulfamethoxazole-resistant uropathogens. However, because of the increased use of both oral and parenteral fluoroquinolones for other kinds of infections, increasing rates of resistance to fluoroquinolones among the most common uropathogens have challenged this recommendation, particularly in the Asia-Pacific region. The current interpretative criteria for the in vitro susceptibility of uropathogens to some fluoroquinolones, such as levofloxacin and ciprofloxacin, are set according to their therapeutic efficacy for bloodstream infections, and are not specific to UTIs. Fluoroquinolones exhibit concentration-dependent antibacterial activity, high renal excretion, and relatively early and prolonged urinary bactericidal titers. Whether or not current interpretative criteria for the in vitro susceptibility of uropathogens to fluoroquinolones predict clinical failure in treating UTIs is still controversial. The Clinical and Laboratory Standards Institute (CLSI) has established UTI-specific breakpoints for resistance to a few fluoroquinolones. However, the application of high-dose fluoroquinolone therapy for the treatment of mild to moderate UTIs caused by isolates with higher minimum inhibitory concentrations (MICs) of several fluoroquinolones needs to be re-validated based on more relevant clinical studies, prudent pharmacokinetic/pharmacodynamic (PK/PD) considerations, and thorough study of the mutant prevention concentration of fluoroquinolones in the treatment of UTI.

  8. Fluoroquinolones in community-acquired pneumonia: guide to selection and appropriate use.

    PubMed

    Frei, Christopher R; Labreche, Matthew J; Attridge, Russell T

    2011-04-16

    Fluoroquinolone use has dramatically increased since the introduction of the first respiratory fluoroquinolone in the late 1990s. Over a relatively brief period of time, the respiratory fluoroquinolones have supplanted other first-line options as the predominant community-acquired pneumonia (CAP) therapy in hospitals. This article discusses the rise of the fluoroquinolone era, debates the comparative effectiveness of fluoroquinolones for CAP therapy, examines fluoroquinolone resistance and adverse drug reactions, and discusses new trends in pneumonia epidemiology and outcomes assessment. Overall, published data suggest that fluoroquinolone monotherapy is associated with improved patient survival compared with β-lactam monotherapy and similar survival to β-lactam plus macrolide combination therapy. Fluoroquinolone monotherapy may be associated with shorter hospital length of stay compared with β-lactam plus macrolide combination therapy, particularly in severe pneumonia or with high-dose therapy. There is insufficient evidence to conclude that any individual fluoroquinolone therapy is better than another with regards to patient mortality. Fluoroquinolones are generally well tolerated and Streptococcus pneumoniae resistance remains low; however, rare but serious adverse effects have been reported. Some members of the fluoroquinolone class have been removed from the market amidst safety concerns. Pneumonia classifications have changed and antipseudomonal fluoroquinolones may have a role in healthcare-associated pneumonia when administered in combination with other antipseudomonal and anti-methicillin-resistant Staphylococcus aureus therapies.

  9. Insight view on possible role of fluoroquinolones in cancer therapy.

    PubMed

    Sharma, Prabodh C; Chaudhary, Monika; Sharma, Archana; Piplani, Mona; Rajak, Harish; Prakash, Om

    2013-08-01

    Cancer is a disease without limits turning out to be prime cause for raising death toll around the world. Several treatment strategies including chemotherapy, surgery and radiotherapy are being employed worldwide to combat this disease. Due to the unwanted effects of currently available therapies, scientific community is immensely interested in exploring newer alternative pathways. Fluoroquinolones have been employed as potent anti-microbial agents for last few decades and now being looked up as potential therapeutic agents in the other ailments also. Several research endeavours are carried out in different parts of the world to focus on the prospective role of fluoroquinolones in carcinogenesis and mutagenesis. This article is an earnest attempt to present recent research work carried out on fluoroquinolones in the context to cancer treatment therapies.

  10. Fluoroquinolone-resistant Streptococcus agalactiae isolates from Argentina.

    PubMed

    Faccone, D; Guerriero, L; Méndez, E; Errecalde, L; Cano, H; Yoyas, N; Togneri, A; Romanowski, V; Galas, M; Whonet, Red; Corso, A

    2010-01-01

    Fluoroquinolone resistance is a growing problem that has only recently emerged in S. agalactiae. Between 2005-2007, WHONET--Argentina network evaluated levofloxacin susceptibility in 1128 clinical S. agalactiae isolates, 10 (0.9%) of which proved to be resistant. Nine of them had come from 5 hospitals (in Buenos Aires City and 4 Argentinean provinces) and recovered from urine (n=7) and vaginal screening cultures (n=2). Three strains were also resistant to macrolides, lincosamides and B streptogramins due to the ermA gene. All nine fluoroquinolone-resistant isolates bore the same two mutations, Ser79Phe in ParC and Ser81Leu in GyrA proteins. Genetic relationships were analyzed by Apal-PFGE and two clones were determined, A (n=6) and B (n=3). To our knowledge, these are the first fluoroquinolone-resistant S. agalactiae isolates detected in Latin America.

  11. 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.

  12. 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.

  13. Spectrofluorimetric determination of fluoroquinolones in pharmaceutical preparations.

    PubMed

    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.

  14. Appropriate use of fluoroquinolones in children.

    PubMed

    Principi, Nicola; Esposito, Susanna

    2015-04-01

    With the increasing resistance to antibiotics among common bacterial pathogens, challenges associated with the use of fluoroquinolones (FQs) in paediatrics have emerged. The majority of FQs have favourable pharmacokinetic properties, although these properties can differ in children compared with adults. Moreover, all FQs have broad antimicrobial activity both against Gram-positive and Gram-negative bacteria. However, only some FQs for which adequate studies are available have been approved for use in children in a limited number of clinical situations owing to the supposed risk of development of severe musculoskeletal disorders, as demonstrated in juvenile animals. Recent short- and long-term evaluations appear to indicate that, at least for levofloxacin, this risk, if present at all, is marginal. This marginal risk could lead to more frequent use of FQs in children, even to treat diseases for which several other drugs with documented efficacy, safety and tolerability are considered the first-line antibiotics. However, for most of the FQs, adequate long-term studies of safety are not available. This indicates that the use of FQs should be limited to selected respiratory infections (including tuberculosis), exacerbation of lung disease in cystic fibrosis, central nervous system infections, enteric infections, febrile neutropenia, as well as serious infections attributable to FQ-susceptible pathogen(s) in children with life-threatening allergies to alternative agents. When considering diseases that could benefit from the use of FQs, particular attention must be paid to the choice of drug and its dosage, considering that not all of the FQs have been evaluated in different diseases.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. [Global Health. Information for change. 4th report of the Italian Observatory on Global Health].

    PubMed

    2011-01-01

    Global Health. Information for change. 4th report of the Italian Observatory on Global Health. InformAzione (InformAction) is the title of the last OISG report (Italian observatory on Global Health), dedicated to information and education, the essential bases for a conscious action aimed at decreasing inequalities. Increasing the investments in information, education and interventions oriented to global health may broaden the number of aware and informed citizens, able to start a dialogue, to make pressures to increase the interventions in favor of those in need.

  20. [Fluoroquinolones in ophthalmology: mechanisms of action and resistance].

    PubMed

    Labetoulle, M; Chiquet, C

    2008-10-01

    The arrival of fluoroquinolones in the 1980s aroused enormous enthusiasm in the medical community, justified by the spectrum of antibacterial activity, good tolerance, and wide distribution in tissues, even after oral administration. However, the extensive use of these new antibiotiques finally ended in emerging resistance, which limits the efficiency of all the molecules in the class, including those that have appeared in the last few years. Ocular diseases also benefited from the emergence of fluoroquinolones, notably for topical treatments. It is now mandatory to adapt the prescriptions to the best indications, in order to protect the vast therapeutic potential of these molecules.

  1. Control of fluoroquinolone resistance through successful regulation, Australia.

    PubMed

    Cheng, Allen C; Turnidge, John; Collignon, Peter; Looke, David; Barton, Mary; Gottlieb, Thomas

    2012-09-01

    Fluoroquinolone antimicrobial drugs are highly bioavailable, broad-spectrum agents with activity against gram-negative pathogens, especially those resistant to other classes of antimicrobial drugs. Australia has restricted the use of quinolones in humans through its national pharmaceutical subsidy scheme; and, through regulation, has not permitted the use of quinolones in food-producing animals. As a consequence, resistance to fluoroquinolones in the community has been slow to emerge and has remained at low levels in key pathogens, such as Escherichia coli. In contrast to policies in most other countries, this policy has successfully preserved the utility of this class of antimicrobial drugs for treatment of most infections.

  2. Cotrimoxazole treats fluoroquinolone-resistant Salmonella typhi H58 infection.

    PubMed

    Karki, Manan; Pandit, Sarbagya; Baker, Stephen; Basnyat, Buddha

    2016-10-26

    A woman aged 20 years presented with fever and no localising signs. She was treated with cotrimoxazole and the subsequent blood culture was positive for Salmonella typhi (S. typhi), which was resistant to fluoroquinolones but susceptible to cotrimoxazole. Genotyping identified an FQ-R subclade of H58 S. typhi Fever clearance time was 4 days after starting the antibiotics, and no relapses were noted on 2 months of follow-up. This inexpensive, well-known and easily available antimicrobial could be suitably redeployed for fluoroquinolone-resistant enteric fever in South Asia.

  3. Anionic fluoroquinolones as antibacterials against biofilm-producing Pseudomonas aeruginosa.

    PubMed

    Long, Timothy E; Keding, Lexie C; Lewis, Demetria D; Anstead, Michael I; Withers, T Ryan; Yu, Hongwei D

    2016-02-15

    Pseudomonas aeruginosa is a common biofilm-forming bacterial pathogen implicated in diseases of the lungs. The extracellular polymeric substances (EPS) of respiratory Pseudomonas biofilms are largely comprised of anionic molecules such as rhamnolipids and alginate that promote a mucoid phenotype. In this Letter, we examine the ability of negatively-charged fluoroquinolones to transverse the EPS and inhibit the growth of mucoid P. aeruginosa. Anionic fluoroquinolones were further compared with standard antibiotics via a novel microdiffusion assay to evaluate drug penetration through pseudomonal alginate and respiratory mucus from a patient with cystic fibrosis.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Call for the international adoption of microbiological breakpoints for fluoroquinolones and Streptococcus pneumoniae.

    PubMed

    Schurek, Kristen N; Adam, Heather J; Hoban, Daryl J; Zhanel, George G

    2006-09-01

    The use of current Clinical and Laboratory Standards Institute levofloxacin breakpoints for assessing fluoroquinolone resistance in Streptococcus pneumoniae is inadequate for detecting isolates possessing first-step parC mutations. Consequently, the risk for development of fluoroquinolone resistance is greatly underestimated. Adopting microbiological breakpoints for fluoroquinolones and S. pneumoniae, where parC mutations are rare in susceptible isolates, more accurately describes the emergence of resistance and may help to prevent a number of future fluoroquinolone treatment failures. Additionally, we propose that the use of a second fluoroquinolone marker, such as ciprofloxacin, offers the best prediction for detecting an isolate possessing a first-step parC mutation.

  9. [Giant cell tumor of the 4th metacarpal bone of the left hand. Apropos of a case].

    PubMed

    Kamel, E J; Pinto, J A; Potenza, L; Michelena, A; Perez Signini, F; Fuenmayor, A

    1983-01-01

    He is a 46 year old patient that consults on a tumor that deforms the back of his left hand. The X-ray examination shows a bone osteolytic tumor with complete dis appearance of the 4th metacarpal. Surgical removal of the tumor was practiced with immediate reconstruction of the 4th metacarpal by an oseo-iliac graft. Anatomopathological examination. It is an ovoid tumor 6.5 long and irregular surface.

  10. In vitro selection of fluoroquinolone resistance in Brucella melitensis.

    PubMed

    Ravanel, N; Gestin, B; Maurin, M

    2009-07-01

    Moxifloxacin-resistant mutants of Brucella melitensis 16M [moxifloxacin minimum inhibitory concentration (MIC)=1mg/L] were selected in order to characterise fluoroquinolone resistance mechanisms in this species. Eight independent mutants were obtained, with moxifloxacin MICs of 16-32mg/L. The mutants displayed variable cross-resistance levels to other fluoroquinolone compounds, but no increased resistance to aminoglycosides, tetracycline, rifampicin, macrolides or co-trimoxazole. Sequencing of type II topoisomerase-encoding genes (gyrA, gyrB, parC and parE), which are natural targets for fluoroquinolones, revealed a gyrA mutation leading to the amino acid substitution Ala83Val (Escherichia coli numbering system) in five mutants with a moxifloxacin MIC of 32mg/L, whereas no mutation was found in the remaining three mutants with a MIC of 16mg/L. Phenylalanine-arginine-beta-naphthylamide dihydrochloride, an efflux pump inhibitor, reduced moxifloxacin MICs by a factor of two to eight in all resistant mutants. In B. melitensis, fluoroquinolone resistance may arise from gyrA mutation and efflux pump overexpression mechanisms.

  11. 1:1 Ground-track resonance in a uniformly rotating 4th degree and order gravitational field

    NASA Astrophysics Data System (ADS)

    Feng, Jinglang; Noomen, Ron; Hou, Xiyun; Visser, Pieter; Yuan, Jianping

    2017-01-01

    Using a gravitational field truncated at the 4th degree and order, the 1:1 ground-track resonance is studied. To address the main properties of this resonance, a 1-degree of freedom (1-DOF) system is firstly studied. Equilibrium points (EPs), stability and resonance width are obtained. Different from previous studies, the inclusion of non-spherical terms higher than degree and order 2 introduces new phenomena. For a further study about this resonance, a 2-DOF model which includes a main resonance term (the 1-DOF system) and a perturbing resonance term is studied. With the aid of Poincaré sections, the generation of chaos in the phase space is studied in detail by addressing the overlap process of these two resonances with arbitrary combinations of eccentricity ( e) and inclination ( i). Retrograde orbits, near circular orbits and near polar orbits are found to have better stability against the perturbation of the second resonance. The situations of complete chaos are estimated in the e-i plane. By applying the maximum Lyapunov Characteristic Exponent (LCE), chaos is characterized quantitatively and similar conclusions can be achieved. This study is applied to three asteroids 1996 HW1, Vesta and Betulia, but the conclusions are not restricted to them.

  12. STO-2: Support for 4th Year Operations, Recovery, and Science ASU Co-I

    NASA Astrophysics Data System (ADS)

    Groppi, Christopher

    This is a Co-Investigator proposal for "STO-2: Support for 4th Year Operations, Recovery, and Science" with Prof. Christopher K. Walker (University of Arizona) as PI. As a participant in the STO-2 mission, ASU will participate in instrument design and construction, mission I&T, flight operations and data analysis. ASU has unique capabilities in the field of direct metal micromachining, which it will bring to bear on the STO-2 cold optical assembly, flight mixers and LO hardware. In addition, our extensive experience with receiver integration and test will supplement the capabilities of the PI institution during the I&T phase at the University of Arizona, CSBF (Palestine, TX) and in Antarctica. Both the ASU PI and student will also participate in data analysis and publication after the flight.

  13. The 4th Bologna Winter School: Hot Topics in Structural Genomics

    PubMed Central

    2003-01-01

    The 4th Bologna Winter School on Biotechnologies was held on 9–15 February 2003 at the University of Bologna, Italy, with the specific aim of discussing recent developments in bioinformatics. The school provided an opportunity for students and scientists to debate current problems in computational biology and possible solutions. The course, co-supported (as last year) by the European Science Foundation program on Functional Genomics, focused mainly on hot topics in structural genomics, including recent CASP and CAPRI results, recent and promising genomewide predictions, protein–protein and protein–DNA interaction predictions and genome functional annotation. The topics were organized into four main sections (http://www.biocomp.unibo.it). PMID:18629078

  14. Beyond the genomics blueprint: the 4th Human Variome Project Meeting, UNESCO, Paris, 2012.

    PubMed

    Kohonen-Corish, Maija R J; Smith, Timothy D; Robinson, Helen M

    2013-07-01

    The 4th Biennial Meeting of the Human Variome Project Consortium was held at the headquarters of the United Nations Educational, Scientific and Cultural Organization (UNESCO) in Paris, 11-15 June 2012. The Human Variome Project, a nongovernmental organization and an official partner of UNESCO, enables the routine collection, curation, interpretation, and sharing of information on all human genetic variation. This meeting was attended by more than 180 delegates from 39 countries and continued the theme of addressing issues of implementation in this unique project. The meeting was structured around the four main themes of the Human Variome Project strategic plan, "Project Roadmap 2012-2016": setting normative function, behaving ethically, sharing knowledge, and building capacity. During the meeting, the members held extensive discussions to formulate an action plan in the key areas of the Human Variome Project. The actions agreed on were promulgated at the Project's two Advisory Council and Scientific Advisory Committee postconference meetings.

  15. Giant viruses in the oceans: the 4th Algal Virus Workshop.

    PubMed

    Claverie, Jean-Michel

    2005-06-20

    Giant double-stranded DNA viruses (such as record breaking Acanthamoeba polyphaga Mimivirus), with particle sizes of 0.2 to 0.6 microm, genomes of 300 kbp to 1.200 kbp, and commensurate complex gene contents, constitute an evolutionary mystery. They challenge the common vision of viruses, traditionally seen as highly streamlined genomes optimally fitted to the smallest possible--filterable--package. Such giant viruses are now discovered in increasing numbers through the systematic sampling of ocean waters as well as freshwater aquatic environments, where they play a significant role in controlling phyto- and bacterio- plankton populations. The 4th Algal Virus Workshop showed that the study of these ecologically important viruses is now massively entering the genomic era, promising a better understanding of their diversity and, hopefully, some insights on their origin and the evolutionary forces that shaped their genomes.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Fluoroquinolone resistance in atypical pneumococci and oral streptococci: evidence of horizontal gene transfer of fluoroquinolone resistance determinants from Streptococcus pneumoniae.

    PubMed

    Ip, Margaret; Chau, Shirley S L; Chi, Fang; Tang, Julian; Chan, Paul K

    2007-08-01

    Atypical strains, presumed to be pneumococcus, with ciprofloxacin MICs of > or =4.0 microg/ml and unique sequence variations within the quinolone resistance-determining regions (QRDRs) of the gyrase and topoisomerase genes in comparison with the Streptococcus pneumoniae R6 strain, were examined. These strains were reidentified using phenotypic methods, including detection of optochin susceptibility, bile solubility, and agglutination by serotype-specific antisera, and genotypic methods, including detection of pneumolysin and autolysin genes by PCR, 16S rRNA sequencing, and multilocus sequence typing (MLST). The analysis based on concatenated sequences of the six MLST loci distinguished the "atypical" strains from pneumococci, and these strains clustered closely with S. mitis. However, all these strains and five of nine strains from the viridans streptococcal group possessed one to three gyrA, gyrB, parC, and parE genes whose QRDR sequences clustered with those of S. pneumoniae, providing evidence of horizontal transfer of the QRDRs of the gyrase and topoisomerase genes from pneumococci into viridans streptococci. These genes also conferred fluoroquinolone resistance to viridans streptococci. In addition, the fluoroquinolone resistance determinants of 32 well-characterized Streptococcus mitis and Streptococcus oralis strains from bacteremic patients were also compared. These strains have unique amino acid substitutions in GyrA and ParC that were distinguishable from those in fluoroquinolone-resistant pneumococci and the "atypical" isolates. Both recombinational events and de novo mutations play an important role in the development of fluoroquinolone resistance.

  2. 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.

  3. 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

  4. EDITORIAL: Special issue containing papers presented at the 4th IAEA Technical Meeting on the Theory of Plasma Instabilities Special issue containing papers presented at the 4th IAEA Technical Meeting on the Theory of Plasma Instabilities

    NASA Astrophysics Data System (ADS)

    Itoh, K.; Wilson, H. R.

    2010-05-01

    The 4th IAEA technical meeting (TM) on the Theory of Plasma Instabilities was held in Kyoto, May 18th--20th 2009, following the first (Seeon), second (Trieste) and third (York) meetings in this series. This IAEA-TM was motivated by the recent advances in theoretical methodology, the rapid progress in observations of laboratory and astrophysical plasmas and the evolution of fusion research as we approach the ITER era. The international advisory committee (IAC) and local organizing committee (LOC), the members of which are listed below, collaborated to define the scope and the content of the scientific programme. Young scientists were actively encouraged to participate in this TM to help stimulate their future research careers and raise their international profiles. Through these young scientists, the IAEA-TM planned to identify the future directions of research. About 90 researchers, from 13 countries and the IAEA, participated in this IAEA-TM, with 72 scientific presentations. The talks and posters generated enthusiastic discussions, contributing to the vibrancy of the meeting. This special issue of Nuclear Fusion consists of a cluster of papers, reporting some of the main contributions to the IAEA-TM. The articles in this cluster are representative of the scientific width of presentations at the meeting, spanning topics from micro-turbulence to large-scale MHD dynamics and from transport to detailed analysis of diagnostics. They demonstrate the quality and depth of the research presented at the conference. List of IAC (alphabetical order): B. Breizman (USA), S. Guenter (Germany), T. S. Hahm (USA), K. Itoh (Japan, Chair of 2009), Ya. I. Kolesnichenko (Ukraine), A. G. Peeters (UK), H. Wilson (UK) List of LOC (alphabetical order): A. Fukuyama, R. Horiuchi, S.-I. Itoh, N. Kasuya, Y. Kishimoto (co-chair), K. Kusano, J. Li, K. Mima, S. Murakami, H. Naitou, N. Nakajima, Y. Nakamura, H. Ohtani, S. Okamura, T. Ozeki, S. Sudo (co-chair), H. Sugama, Y. Todo, S. Tokuda, S

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. The relationship between snack intake and its availability of 4th-6th graders in Taiwan.

    PubMed

    Hang, Chi-Ming; Lin, Wei; Yang, Hsiao-Chi; Pan, Wen-Harn

    2007-01-01

    The purpose of this study was to examine the relationship between the snack intake and snack availability of elementary school children. Data analyzed were from 722 4th to 6th graders' food availability and food intake questionnaires collected in the Nutrition and Health Survey in Taiwan Elementary School Children 2001-2002. The snacks commonly eaten were divided into two groups. Healthy snacks included dairy products, 100% fruit juice and fresh fruits. Unhealthy snacks included high fat/sugar snacks, cookies, candy, carbonated/sugared beverages and fast food. Structural equating modeling was used to test the models that describe the availability and intake of two snack groups. Results indicated that parents' intake and children's preference were major predictors of children intake of both healthy and unhealthy snacks. Other than that, the intake of unhealthy snacks was positively associated with "purchase by children themselves" but not the intake of healthy snacks, which was influenced predominantly by "present in home". The results support the perception that a positive family food environment is important for improving children's diet quality. To build a healthy family food environment, parents have to not only provide healthy snacks but also limit the unhealthy snacks in home. In addition to that, the role modeling of parents as eating healthy snacks instead of unhealthy snacks themselves may help children to develop similar behaviors.

  11. 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.

  12. A 4th-order reconfigurable analog baseband filter for software-defined radio applications

    NASA Astrophysics Data System (ADS)

    Weiwei, Wang; Xuegui, Chang; Xiao, Wang; Kefeng, Han; Xi, Tan; Na, Yan; Hao, Min

    2011-04-01

    This paper presents a 4th-order reconfigurable analog baseband filter for software-defined radios. The design exploits an active-RC low pass filter (LPF) structure with digital assistant, which is flexible for tunability of filter characteristics, such as cut-off frequency, selectivity, type, noise, gain and power. A novel reconfigurable operational amplifier is proposed to realize the optimization of noise and scalability of power dissipation. The chip was fabricated in an SMIC 0.13 μm CMOS process. The main filter and frequency calibration circuit occupy 1.8 × 0.8 mm2 and 0.48 × 0.25 mm2 areas, respectively. The measurement results indicate that the filter provides Butterworth and Chebyshev responses with a wide frequency tuning range from 280 kHz to 15 MHz and a gain range from 0 to 18 dB. An IIP3 of 29 dBm is achieved under a 1.2 V power supply. The input inferred noise density varies from 41 to 133 according to a given standard, and the power consumptions are 5.46 mW for low band (from 280 kHz to 3 MHz) and 8.74 mW for high band (from 3 to 15 MHz) mode.

  13. Putting agent-based modeling to work: results of the 4th International Project Albert Workshop

    NASA Astrophysics Data System (ADS)

    Horne, Gary E.; Bjorkman, Eileen A.; Colton, Trevor

    2002-07-01

    Project Albert is an initiative of the US Marine Corps which uses a series of new models and tools, multidisciplinary teams, and the scientific method to explore questions of interest to military planners. Project Albert attempts to address key areas that traditional modeling and simulation techniques often do not capture satisfactorily and uses two data management concepts, data farming and data mining, to assist in identifying areas of interest. The current suite of models used by Project Albert includes four agent-based models that allow agents to interact with each other and produce emergent behaviors. The 4th International Project Albert Workshop was held 6-9 August 2001 in Australia. Workshop participants split into five groups, each of which attempted to apply various combinations of the Project Albert models to answer a series of questions in five areas: Control Operations; Reconnaissance, Surveillance, and Intelligence Force Mix; Precision Maneuver; Mission Area Analysis; and Peace Support Operations. This paper focuses on the methodology used during the workshop, the results of the workshop, and a summary of follow-on work since the workshop.

  14. 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."

  15. CD4(+) Th2 cells are directly regulated by IL-10 during allergic airway inflammation.

    PubMed

    Coomes, S M; Kannan, Y; Pelly, V S; Entwistle, L J; Guidi, R; Perez-Lloret, J; Nikolov, N; Müller, W; Wilson, M S

    2017-01-01

    Interleukin-10 (IL-10) is an important regulatory cytokine required to control allergy and asthma. IL-10-mediated regulation of T cell-mediated responses was previously thought to occur indirectly via antigen-presenting cells. However, IL-10 can act directly on regulatory T cells and T helper type 17 (Th17) cells. In the context of allergy, it is therefore unclear whether IL-10 can directly regulate T helper type 2 (Th2) cells and whether this is an important regulatory axis during allergic responses. We sought to determine whether IL-10 signaling in CD4(+) Th2 cells was an important mechanism of immune regulation during airway allergy. We demonstrate that IL-10 directly limits Th2 cell differentiation and survival in vitro and in vivo. Ablation of IL-10 signaling in Th2 cells led to enhanced Th2 cell survival and exacerbated pulmonary inflammation in a murine model of house dust mite allergy. Mechanistically, IL-10R signaling regulated the expression of several genes in Th2 cells, including granzyme B. Indeed, IL-10 increased granzyme B expression in Th2 cells and led to increased Th2 cell death, identifying an IL-10-regulated granzyme B axis in Th2 cells controlling Th2 cell survival. This study provides clear evidence that IL-10 exerts direct effects on Th2 cells, regulating the survival of Th2 cells and severity of Th2-mediated allergic airway inflammation.

  16. 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.

  17. 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.

  18. 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).

  19. 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

    2014-05-02

    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.

  20. Effect of fluoroquinolones on mitochondrial function in pancreatic beta cells.

    PubMed

    Ghaly, Hany; Jörns, Anne; Rustenbeck, Ingo

    2014-02-14

    Hyper- and hypoglycaemias are known side effects of fluoroquinolone antibiotics, resulting in a number of fatalities. Fluoroquinolone-induced hypoglycaemias are due to stimulated insulin release by the inhibition of the KATP channel activity of the beta cell. Recently, it was found that fluoroquinolones were much less effective on metabolically intact beta cells than on open cell preparations. Thus the intracellular effects of gatifloxacin, moxifloxacin and ciprofloxacin were investigated by measuring NAD(P)H- and FAD-autofluorescence, the mitochondrial membrane potential, and the adenine nucleotide content of isolated pancreatic islets and beta cells. 100 μM of moxifloxacin abolished the NAD(P)H increase elicited by 20mM glucose, while gatifloxacin diminished it and ciprofloxacin had no significant effect. This pattern was also seen with islets from SUR1 Ko mice, which have no functional KATP channels. Moxifloxacin also diminished the glucose-induced decrease of FAD-fluorescence, which reflects the intramitochondrial production of reducing equivalents. Moxifloxacin, but not ciprofloxacin or gatifloxacin significantly reduced the effect of 20mM glucose on the ATP/ADP ratio. The mitochondrial hyperpolarization caused by 20mM glucose was partially antagonized by moxifloxacin, but not by ciprofloxacin or gatifloxacin. Ultrastructural analyses after 20 h tissue culture showed that all three compounds (at 10 and 100 μM) diminished the number of insulin secretory granules and that gatifloxacin and ciprofloxacin, but not moxifloxacin induced fission/fusion configurations of the beta cell mitochondria. In conclusion, fluoroquinolones affect the function of the mitochondria in pancreatic beta cells which may diminish the insulinotropic effect of KATP channel closure and contribute to the hyperglycaemic episodes.

  1. First Characterization of Fluoroquinolone Resistance in Streptococcus suis▿

    PubMed Central

    Escudero, Jose Antonio; San Millan, Alvaro; Catalan, Ana; de la Campa, Adela G.; Rivero, Estefania; Lopez, Gema; Dominguez, Lucas; Moreno, Miguel Angel; Gonzalez-Zorn, Bruno

    2007-01-01

    We have identified and sequenced the genes encoding the quinolone-resistance determining region (QRDR) of ParC and GyrA in fluoroquinolone-susceptible and -resistant Streptococcus suis clinical isolates. Resistance is the consequence of single point mutations in the QRDRs of ParC and GyrA and is not due to clonal spread of resistant strains or horizontal gene transfer with other bacteria. PMID:17116660

  2. Lessons Learned in Antibiotic Stewardship: Fluoroquinolone Use in Pediatrics.

    PubMed

    Hersh, Adam L; Gerber, Jeffrey S; Hicks, Lauri A; Pavia, Andrew T

    2015-03-01

    The use of fluoroquinolones differs dramatically between adult and pediatric patients. For adults, they are the leading class of antibiotics prescribed in ambulatory care visits whereas in children, they are the least frequently prescribed class. The reasons for this difference in practice likely relate to perceptions of their potential for harm. This highlights the impact of physicians' perception of direct patient harm in antibiotic decision making which has implications for antibiotic stewardship.

  3. Comparative Killing Rates of Fluoroquinolones and Cell Wall-Active Agents

    PubMed Central

    Fung-Tomc, Joan C.; Gradelski, Elizabeth; Valera, Lourdes; Kolek, Benjamin; Bonner, Daniel P.

    2000-01-01

    Killing rates of fluoroquinolones, β-lactams, and vancomycin were compared against Enterobacteriaceae, Staphylococcus aureus, pneumococci, streptococci, and Enterococcus faecalis. The times required for fluoroquinolones to decrease viability by 3 log10 were 1.5 h for Enterobacteriaceae, 4 to 6 h for staphylococci, and ≥6 h for streptococci and enterococci. Thus, the rate of killing by fluoroquinolones is organism group dependent; overall, they killed more rapidly than β-lactams and vancomycin. PMID:10770784

  4. Intractable Acute Pain Related to Fluoroquinolone-Induced Peripheral Neuropathy.

    PubMed

    Danesh, Arash; Onyima, Chiemeka; Dukewich, Matthew; Gupta, Anita

    2017-03-30

    Fluoroquinolones are widely prescribed antibiotics, used for various infectious etiologies. These antibiotics carry the possibility of the serious adverse effect of peripheral neuropathy, with a true incidence not known owing to its rare existence. Recently, the Food and Drug Administration (FDA) has required alterations to drug labels to highlight this adverse effect of fluoroquinolones. This is a case report of a single patient at an inpatient neurology service at an urban academic medical center in the United States. The patient is a 20-year-old male, with well-controlled type 1 diabetes mellitus, presenting with a short duration of bilateral lower extremity pain following a 10-day course of levofloxacin for suspected epididymitis. The patient was initially diagnosed with complex regional pain syndrome and treated with a variety of pain medications, including lidocaine infusions, hydromorphone, methadone, and ketamine infusions. After review of the patient's history and limited response to medical management, the patient's condition was reclassified as an adverse effect from fluoroquinolone treatment. Pain of unknown etiology can be perplexing, both for the physician and the patient. Reporting of similar incidents attributed to medication adverse effects will increase the awareness of this type of neuropathy, avoid future cases of misdiagnosis, and enable early detection and treatment.

  5. Consumption patterns and in vitro resistance of Streptococcus pneumoniae to fluoroquinolones.

    PubMed

    Simoens, Steven; Verhaegen, Jan; van Bleyenbergh, Pascal; Peetermans, Willy E; Decramer, Marc

    2011-06-01

    This article analyzes patterns of consumption of fluoroquinolones and documents the in vitro resistances of Streptococcus pneumoniae isolates to fluoroquinolones in the ambulatory care setting in Belgium over time. The volume of fluoroquinolone consumption has fallen consistently since 2003. Fluoroquinolones were used primarily for their registered indications (i.e., urinary tract infections and lower respiratory tract infections). The MIC distributions of moxifloxacin and levofloxacin in S. pneumoniae isolates remained stable during 2004 to 2009, and the level of resistance to moxifloxacin and levofloxacin was low (≤1%).

  6. Occurrence of fluoroquinolones and fluoroquinolone-resistance genes in the aquatic environment.

    PubMed

    Adachi, Fumie; Yamamoto, Atsushi; Takakura, Koh-Ichi; Kawahara, Ryuji

    2013-02-01

    Fluoroquinolones (FQs) have been detected in aquatic environments in several countries. Long-term exposure to low levels of antimicrobial agents provides selective pressure, which might alter the sensitivity of bacteria to antimicrobial agents in the environment. Here, we examined FQ levels and the resistance of Escherichia coli (E. coli) to FQs by phenotyping and genotyping. In the aquatic environment in Osaka, Japan, ciprofloxacin, enoxacin, enfloxacin, lomefloxacin, norfloxacin, and ofloxacin were detected in concentrations ranging from 0.1 to 570 ng L(-1). FQ-resistant E. coli were also found. Although no obvious correlation was detected between the concentration of FQs and the presence of FQ-resistant E. coli, FQ-resistant E. coli were detected in samples along with FQs, particularly ciprofloxacin and ofloxacin. Most FQ-resistant E. coli carried mutations in gyrA, parC, and parE in quinolone resistance-determining regions. No mutations in gyrB were detected in any isolates. Amino acid changes in these isolates were quite similar to those in clinical isolates. Six strains carried the plasmid-mediated quinolone resistance determinant qnrS1 and expressed low susceptibility to ciprofloxacin and nalidixic acid: the minimum inhibitory concentrations ranged from 0.25 μg mL(-1) for ciprofloxacin, and from 8 to 16 μg mL(-1) for nalidixic acid. This finding confirmed that plasmids containing qnr genes themselves did not confer full resistance to quinolones. Because plasmids are responsible for much of the horizontal gene transfer, these genes may transfer and spread in the environment. To our knowledge, this is the first report of plasmid-mediated quinolone resistance determinant qnrS1 in the aquatic environment, and this investigation provides baseline data on antimicrobial resistance profiles in the Osaka area.

  7. 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.

  8. Seeking to shed some light on the binding of fluoroquinolones to albumins.

    PubMed

    Bosca, Francisco

    2012-03-22

    Interactions between serum albumins (HSA, human, and BSA, bovine) and fluoroquinolones (FQs), such as enoxacin, norfloxacin, ciprofloxacin, and ofloxacin, have been studied using the laser flash photolysis technique. Lifetimes and quantum yields of FQs triplet excited states ((3)FQs) are not affected by the presence of albumins, however, the quenching of (3)FQs by tryptophan and tyrosine and the subsequent generation of FQs radical anions and tyrosyl or tryptophanyl radicals were detected. These results, besides agreeing with association constants (K(a)) for FQs binding to albumins lower than 6 × 10(2) M(-1), are highly relevant to understanding the process of photohapten formation, the first event in the onset of photoallergy. The emission of tryptophan within albumin is not affected by the presence of FQs when the inner filter effects (IFE) of these drugs are taken into account, which explains the discrepancies reported in the literature about K(a) of FQs with albumins.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. PREFACE: CYGNUS 2013: 4th Workshop on Directional Detection of Dark Matter

    NASA Astrophysics Data System (ADS)

    Naka, Tatsuhiro; Miuchi, Kentaro

    2013-12-01

    It is a great pleasure to publish the proceedings of the 4th Workshop on Directional Detection of Dark Matter held in Toyama, Japan on 10-12 June 2013 (CYGNUS 2013). These proceedings contain written versions of the presentations made at CYGNUS 2013 as scientific outputs of the directional detection of dark matter. The GYGNUS workshop started in 2007 at Boulby Underground Laboratory (UK), followed by CYGNUS 2009 (MIT in Cambridge, Massachusetts, USA) and CYGNUS 2011 (AUSSOIS, France). CYGNUS 2013 was held by the combination of a two and a half days of scientific program and a half day visit to the underground laboratory (Kamioka Observatory) as a 'tradition' of CYGNUS workshops. The name 'CYGNUS' came from the fact that the 'dark matter wind' is expected to come from the direction of the constellation Cygnus due to the motion of the Solar system in the galaxy. A general aim of these CYGNUS workshops is to bring together the theoretical and experimental studies on the directional dark matter detection. Directional detection of dark matter is a promising approach to a 'clear detection' and also to 'further investigations' of galactic dark matter, or Weakly Interacting Massive Particles (WIMPs). Directional detection requires the simultaneous detection of the energy and track of low energy recoils. Among many technological challenges for the requirement above, three of them, namely size, background, and directionality (angular resolution and head-tail detection), are most important to demonstrate and improve the quality as a dark matter detector. In the workshop, up-to-date activities by the international reserchers are discussed. The workshop was a great success thanks to the oral contributions and fruitful discussions held throughout the workshop period. We hope that readers will remember and share the great enthusiasm shown during the CYGNUS 2013 workshop. The Editors Tatsuhiro Naka and Kentaro Miuchi

  16. 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."

  17. 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

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zones; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing two temporary safety zones on Lake Michigan near Chicago, Illinois....

  18. 75 FR 22330 - Safety Zone; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-28

    ... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; City of Chicago's July 4th Celebration Fireworks, Lake Michigan, Chicago, IL AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard proposes to establish a safety zone on Lake Michigan near Chicago, Illinois....

  19. 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…

  20. 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…

  1. Comparative analysis of 1st, 2nd, and 4th year MD students' attitudes toward Complementary Alternative Medicine (CAM)

    PubMed Central

    Riccard, Christopher P; Skelton, Michele

    2008-01-01

    Background To identify and report the attitudes and beliefs of 1st, 2nd, and 4th year medical students toward complementary alternative medicine (CAM). Methods The previously validated and reliability tested CHBQ was administered to medical students attending the University of South Florida School of Medicine. Results Significant changes were found between both 1st (46.0 ± 7.7) and 4th (37.8 ± 15.7) year students and 2nd (48.3 ± 7.8) and 4th (37.8 ± 15.7) year students. No significant difference was found between 1st (46.0 ± 7.7) and 2nd (48.3 ± 7.8) year students. When comparing scores based on gender, a significant difference was present between males (41.2 ± 12.2) and females (46.1 ± 11.0). Conclusion CHBQ scores were significantly more positive in both 1st and 2nd year medical students in comparison with 4th year student's scores. These findings suggest that as student exposure to allopathic techniques and procedures increases during the last year of medical school, their attitudes toward CAM decrease. Females were also significantly more likely to have stronger positive attitudes toward CAM than males, though both genders represented an overall positive attitude toward CAM. PMID:18799010

  2. 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 Huron, Mackinac Island, MI AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone on Lake Huron, Mackinac Island, Michigan. This zone...

  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. 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…

  5. 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…

  6. 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...

  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. Analysis of Lexical Quality and Its Relation to Writing Quality for 4th Grade, Primary School Students in Chile

    ERIC Educational Resources Information Center

    Gómez Vera, Gabriela; Sotomayor, Carmen; Bedwell, Percy; Domínguez, Ana María; Jéldrez, Elvira

    2016-01-01

    Few studies have addressed vocabulary quality in developing writing skill in Spanish. Even less addressed it within the Chilean educational system. The specific objective of this study was to characterize, using a comprehensive set of indicators, the quality of the vocabulary produced by Chilean 4th grade students. Based on a national writing…

  9. 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…

  10. 4th Rare Disease South Eastern Europe (See) Meeting Skopje, Macedonia (November 14th, 2015).

    PubMed

    Gucev, Zoran; Tasic, Velibor; Polenakovic, Momir

    2015-01-01

    The 4th meeting on rare diseases in South Eastern Europe (SEE) was held in Skopje, at the Macedonian Academy of Sciences and Arts (MASA) on the 14(th) of November 2015. The focuses were metabolic, rare brain diseases as well as the rare dysmorphic syndrome. The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. The talk on an iminosugar-based pharmacological chaperone compound as a drug candidate for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B) was enlightening. To date, there is no treatment available to be offered to patients, but chaperones lead mutated proteins to adopt a native-like conformation and to successfully traffic to their normal cellular destination. DORPHAN is developing an iminosugar-based pharmacological chaperone compound for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB. A talk on recent developments in the laboratory diagnosis of mucopolysaccharidoses (MPS) was particularly interesting, covering the laboratory diagnosis of the MPS diseases by a strategy of clinical examination, biochemical analysis of urine samples, enzyme tests and genetic characterization of underlying mutations. New techniques were developed, including analysis of urinary glycosaminoglycans with tandem mass spectrometry, miniaturized enzyme tests or novel synthetic substrates for enzyme assays using mass spectrometry detection of products using dried blood spots. Feasibility and cost-effectiveness of these methods in newborn screening programs have been demonstrated. Neuromuscular RDs, and especially familial amyloid polyneuropathy (FAP) were a topic of the Bulgarian colleagues. Diagnosis, screening and the role of microglia were also topics of particular interest. In summary, this year RD meeting was exciting and productive on a wide range of diseases and on a novel insights on

  11. 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

  12. 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

  13. Colonization with extraintestinal pathogenic Escherichia coli among nursing home residents and its relationship to fluoroquinolone resistance.

    PubMed

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

    2004-09-01

    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.

  14. 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...

  15. 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

  16. The Effect of Primer Application Modifications on the Bond Strength of 4th Generation Adhesive Bonding Agents

    DTIC Science & Technology

    2012-03-30

    dentin. Methods: The coronal enamel of 120 extracted human third molars was removed with a low-speed saw. The teeth were mounted in PVC pipe with dental...LITERATURE REVIEW A. Background 1. Acid Etching in Dentistry. Buonocore demonstrated in 1955 that the preparation of dental enamel with an...The influence of deviations from the manufacturer’s instructions for the use of six adhesive systems on the bond strengths to enamel and dentin

  17. 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.

  18. Proceedings of the Biennial EO/EEO Research Symposium (4th) Held in Cocoa Beach, Florida on December 5-7, 2001

    DTIC Science & Technology

    2003-01-01

    PROCEEDINGS 4th Biennial EO/EEO Research Symposium December 5-7, 2001 Cocoa Beach, Florida Published January 2003 DEOMI Research Report 03-01...distribution unlimited 13. SUPPLEMENTARY NOTES Proceedings 4th Biennial EO/EEO Research Symposium, Held in Cocoa Beach, Florida on December 5-7...Prescribed by ANSI Std Z39-18 ii Proceedings 4th Biennial EO/EEO Research Symposium December 5-7, 2001 Cocoa Beach, Florida Sponsored

  19. 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.

  20. [Resistance to fluoroquinolones in 2013: what are the consequences in internal medicine?].

    PubMed

    de Lastours, V; Fantin, B

    2014-09-01

    Because of their important qualities, fluoroquinolones are amongst the most prescribed antibiotics in the world. The corollary of this success is the rapid increase in resistance to fluoroquinolones, responsible for treatment failures. Moreover, fluoroquinolone-resistance is often accompanied by resistance to other classes of antibiotics. Currently, significant levels of resistance are found both in hospitals and in community settings, severely limiting possibilities for empirical use of fluoroquinolones. A major mechanism explaining the rapid emergence of resistance to fluoroquinolones is their specific impact on human microbiota and the selection of resistant strains in the microbiota, which seems to be an unavoidable ecological side effect. In order to preserve the efficiency of this important class of antibiotics, limiting their use and respecting good practice recommendations are essential.

  1. Fluoroquinolone-induced serious, persistent, multisymptom adverse effects.

    PubMed

    Golomb, Beatrice Alexandra; Koslik, Hayley Jean; Redd, Alan J

    2015-10-05

    We present a case series of four previously healthy, employed adults without significant prior medical history in each of whom symptoms developed while on fluoroquinolones (FQs), with progression that continued following discontinuation evolving to a severe, disabling multisymptom profile variably involving tendinopathy, muscle weakness, peripheral neuropathy, autonomic dysfunction, sleep disorder, cognitive dysfunction and psychiatric disturbance. Physicians and patients should be alert to the potential for FQ-induced severe disabling multisymptom pathology that may persist and progress following FQ use. Known induction by FQs of delayed mitochondrial toxicity provides a compatible mechanism, with symptom profiles (and documented mechanisms of FQ toxicity) compatible with the hypothesis of an exposure-induced mitochondrial neurogastrointestinal encephalomyopathy.

  2. Shortening Tuberculosis Treatment With Fluoroquinolones: Lost in Translation?

    PubMed

    Lanoix, Jean-Philippe; Chaisson, Richard E; Nuermberger, Eric L

    2016-02-15

    The disappointing recent failure of fluoroquinolone-containing regimens to shorten the duration of tuberculosis treatment in costly phase 3 trials has raised serious questions about the reliability of preclinical tuberculosis models, especially mice, and the current paradigm of regimen development. Therefore we re-examined data from murine models and early-stage clinical trials on which the pivotal trials were based, concluding that phase 3 trial results were in line with preceding studies. Finally, we offer suggestions for a more efficient and integrated preclinical and clinical regimen development program where quantitative pharmacokinetic and pharmacodynamic models more predictive of curative treatment durations are set forth.

  3. Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections.

    PubMed

    Shah, Ansal; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2017-02-13

    The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived in patients with gram-negative bloodstream infections based on fluoroquinolone use within the past 6 months among other clinical and healthcare exposure criteria. This study aims to examine the utility of the FQRS in complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA from April 1, 2015 through July 31, 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 151 (63%) were women and 137 (58%) had cUTI due to Escherichia coli Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR] 23.4, 95% confidence intervals [CI]: 8.2-76.8, p<0.001) and within 3-12 months (aOR 13.2, 95% CI: 3.1-68.4, p<0.001) was independently associated with fluoroquinolone resistance as compared to no prior use. Area under receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRS ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI based on predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis.

  4. STO-2: Support for 4th Year Operations, Recovery, and Science (JPL co-I)

    NASA Astrophysics Data System (ADS)

    Kawamura, Jonathan

    Here we propose "STO-2: Support for 4th Year Operations, Recovery, and Science," a project being led by Dr. Christopher Walker of the University of Arizona. The Stratospheric TeraHertz Observatory was ready for its second Antarctic flight (STO-2) in the 2015-2016 austral summer. However, due to the late establishment of the stratospheric anti-cyclone and poor surface conditions, STO-2 was unable to launch. The decision was made to winter-over the STO-2 payload in its hangar for launch during the 2016-2017 Antarctic campaign. Funds to cover preparations and deployment of key members of the instrument team in support of the campaign are being provided by NASA under the existing grant. However, these funds are only sufficient to cover expenses up to December 31st, 2016. Here, we request resources for calendar year 2017 to support mission operations, payload recovery, and science operations. These elements will enable the team to deliver fully on STO-2's science mission, and maximize NASA's demonstrated investment in STO-2's success. STO-2 addresses a key problem in modern astrophysics: understanding the Life Cycle of the Interstellar Medium (ISM). STO-2 will survey approximately ˜ of the Southern Galactic Plane in the dominant interstellar cooling line [CII] (158 μm) and the important star formation tracer [NII] (205 μm). In addition, STO-2 will perform path finding observations of the 63 μm [OI] line toward selected regions. With 1 arcminute angular resolution, STO-2 will spatially resolve atomic, ionic and molecular clouds out to 10 kpc. The STO-2 survey will be conducted at unparalleled sensitivity levels. STO-2 will uniquely probe the pivotal formative and disruptive stages in the life cycle of interstellar clouds and the relationship between global star formation rates and the properties of the ISM. Combined with previous HI and CO surveys, STO-2 will create 3- dimensional maps of the structure, dynamics, turbulence, energy balance, and pressure of the Milky

  5. 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

  6. 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

  7. Campylobacter and fluoroquinolones: a bias data set?

    PubMed

    Silley, Peter

    2003-04-01

    always been the case for isolation of Campylobacter spp., however, we know that the antibiotic cocktails used in media over the last 10 years have changed and indeed there was a time when the filtration protocol which didn't use antibiotics was more widely used. As most reports in the literature do not state what methods were used to isolate Campylobacter spp. it is not possible to quantify any relationship between antibiotics used in the isolation media and susceptibility data. An approved method for Campylobacter susceptibility testing was not available until May 2002, all data generated prior to this date will have been generated using non-standard methods. As tremendous variability in the reproducibility data for Campylobacter spp. was observed during the development of the standard agar dilution susceptibility method, data generated with disk diffusion and broth microdilution methods must be considered with caution. It has been shown that, compared with the conventional agar dilution method, the E-test tends to give rise to lower minimal inhibitory concentrations (MICs) for sensitive strains and higher MICs for resistant strains. There are no recommended antibiotic breakpoint concentrations for Campylobacter spp. A breakpoint is used to separate sensitive from resistant strains of bacteria and is thus crucial to any discussion of antibiotic resistance. This discussion is further complicated by introduction of the terms microbiological and clinical breakpoints. While a microbiological breakpoint can be a useful parameter with regard to identifying resistance factors it cannot on its own be used to predict whether that bacteria will respond to treatment from an appropriate antibiotic. Predicting clinical response is a function of the clinical breakpoint which considers the pharmacokinetic profile of the antimicrobial compound, i.e. the concentration of the antimicrobial compound in the body and the MIC. The National Committee for Clinical Laboratory Standards (NCCLS

  8. R&W Club Frederick Hosts 4th Annual Golf Tournament Benefiting The Children’s Inn at NIH | Poster

    Cancer.gov

    The R&W Club Frederick’s 4th Annual Golf Tournament to benefit the Children’s Inn at NIH teed off on time despite cloudy weather and scattered showers. Employees from NCI at Frederick, the main NIH campus, and Leidos Biomed, along with family and friends, came to enjoy an afternoon at the beautiful Maryland National Golf Club in Middletown and to support a wonderful charity.

  9. Working Group on Ice Forces (4th) State-of-the-Art Report Held in Iowa City, Iowa in 1986.

    DTIC Science & Technology

    1989-02-01

    OTTAWA OF CANADA CANADA HYDRAULICS LABORATORY Preface The following papers comprise the contributions to the 4 th State-of-the-Art Report on Ice Forces...in developing an understanding of ice interacting with offshore structures. : Odes iili/or AjA Jordaan and McKenna follow with a description of the...and Moore follow with a more detailed look at ice impact loads on ship hulls. This review is based on full scale trials of several icebreaking vessels

  10. Impact of Antibiotic Use during Hospitalization on the Development of Gastrointestinal Colonization with Escherichia coli with Reduced Fluoroquinolone Susceptibility

    PubMed Central

    Han, Jennifer H.; Bilker, Warren B.; Nachamkin, Irving; Tolomeo, Pam; Mao, Xiangqun; Fishman, Neil O.; Lautenbach, Ebbing

    2014-01-01

    OBJECTIVE Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization. DESIGN A prospective cohort study was conducted from 2002 to 2004 within a university health system. METHODS Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates. RESULTS Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1–1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21–0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10–1.29]; P < .001) or cefepime (HR, 1.05 [95% CI, 1.00–1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization. CONCLUSIONS The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC. PMID:24018924

  11. Fluoroquinolone susceptibility testing of Salmonella enterica: detection of acquired resistance and selection of zone diameter breakpoints for levofloxacin and ofloxacin.

    PubMed

    Sjölund-Karlsson, Maria; Howie, Rebecca L; Crump, John A; Whichard, Jean M

    2014-03-01

    Fluoroquinolones (e.g., ciprofloxacin) have become a mainstay for treating severe Salmonella infections in adults. Fluoroquinolone resistance in Salmonella is mostly due to mutations in the topoisomerase genes, but plasmid-mediated quinolone resistance (PMQR) mechanisms have also been described. In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised the ciprofloxacin interpretive criteria (breakpoints) for disk diffusion and MIC test methods for Salmonella. In 2013, the CLSI published MIC breakpoints for Salmonella to levofloxacin and ofloxacin, but breakpoints for assigning disk diffusion results to susceptible (S), intermediate (I), and resistant (R) categories are still needed. In this study, the MICs and inhibition zone diameters for nalidixic acid, ciprofloxacin, levofloxacin, and ofloxacin were determined for 100 clinical isolates of nontyphi Salmonella with or without resistance mechanisms. We confirmed that the new levofloxacin MIC breakpoints resulted in the highest category agreement (94%) when plotted against the ciprofloxacin MICs and that the new ofloxacin MIC breakpoints resulted in 92% category agreement between ofloxacin and ciprofloxacin. By applying the new MIC breakpoints in the MIC zone scattergrams for levofloxacin and ofloxacin, the following disk diffusion breakpoints generated the least number of errors: ≥28 mm (S), 19 to 27 mm (I), and ≤18 mm (R) for levofloxacin and ≥25 mm (S), 16 to 24 mm (I), and ≤15 mm (R) for ofloxacin. Neither the levofloxacin nor the ofloxacin disk yielded good separation of isolates with and without resistance mechanisms. Further studies will be needed to develop a disk diffusion assay that efficiently detects all isolates with acquired resistance to fluoroquinolones.

  12. Effect of magnesium complexation by fluoroquinolones on their antibacterial properties.

    PubMed

    Lecomte, S; Baron, M H; Chenon, M T; Coupry, C; Moreau, N J

    1994-12-01

    By using infrared and 19F nuclear magnetic resonance spectroscopies, we localized the binding site and measured the affinity of magnesium for six fluoroquinolones. It was proven that magnesium is situated between the ketone and the carboxylate groups. We determined the binding constants for the 1:1 Mg(2+)-drug complex in solution. Sparfloxacin and pefloxacin, with affinity constants (Ka) of (10.1 +/- 0.6) x 10(2) M-1 and (21 +/- 1) x 10(2) M-1, respectively, were the least and the most bound, respectively. The trend of the affinities of the assayed fluoroquinolones for magnesium was correlated with their antimicrobial activities against four bacteria and with their accumulation by these bacteria. The reference strain, Escherichia coli KL16, and two resistant mutants, NalA (gyrase mutation) and NalB (uptake defect), plus Staphylococcus aureus 209P were used. It appeared that, in every case, an impairment of accumulation is responsible for the increase in the MICs observed upon the addition of magnesium.

  13. Effect of magnesium complexation by fluoroquinolones on their antibacterial properties.

    PubMed Central

    Lecomte, S; Baron, M H; Chenon, M T; Coupry, C; Moreau, N J

    1994-01-01

    By using infrared and 19F nuclear magnetic resonance spectroscopies, we localized the binding site and measured the affinity of magnesium for six fluoroquinolones. It was proven that magnesium is situated between the ketone and the carboxylate groups. We determined the binding constants for the 1:1 Mg(2+)-drug complex in solution. Sparfloxacin and pefloxacin, with affinity constants (Ka) of (10.1 +/- 0.6) x 10(2) M-1 and (21 +/- 1) x 10(2) M-1, respectively, were the least and the most bound, respectively. The trend of the affinities of the assayed fluoroquinolones for magnesium was correlated with their antimicrobial activities against four bacteria and with their accumulation by these bacteria. The reference strain, Escherichia coli KL16, and two resistant mutants, NalA (gyrase mutation) and NalB (uptake defect), plus Staphylococcus aureus 209P were used. It appeared that, in every case, an impairment of accumulation is responsible for the increase in the MICs observed upon the addition of magnesium. Images PMID:7695267

  14. Fluoroquinolone resistance in Streptococcus pneumoniae from a university hospital, Thailand.

    PubMed

    Srifuengfung, Somporn; Tribuddharat, Chanwit; Chokephaibulkit, Kulkanya; Comerungsee, Sopita

    2010-11-01

    The most frequent markers of fluoroquinolone resistance in S. pneumoniae are chromosomal mutations in the quinolone-resistance-determining regions of DNA gyrase and topoisomerase IV encoding for the gyrA, gyrB and parC, parE genes. In 2008, 6.5% of the Streptococcus pneumoniae isolates in a Bangkok university hospital were resistant to ofloxacin. Using PCR and DNA sequencing, we identified mutations in both the gyrA and parC genes of four ofloxacin- and ciprofloxacin-resistant S. pneumoniae isolates (minimum inhibitory concentrations > 32 microg/ml). Mutations were found in the gyrA gene at positions Ser81Phe, Glu85Gly, Glu85Lys and in the parC gene at position Ser79Tyr. Three isolates had mutations in both genes. Two of the isolates were serotype 6B and two were serotypes not contained in currently licensed pneumococcal vaccines. This is the first report of the mechanisms of fluoroquinolone resistance in S. pneumoniae in Thailand.

  15. A comparison of interview methods to ascertain fluoroquinolone exposure before tuberculosis diagnosis.

    PubMed

    Van Der Heijden, Y F; Maruri, F; Holt, E; Mitchel, E; Warkentin, J; Sterling, T R

    2015-04-01

    SUMMARY Fluoroquinolone use before tuberculosis (TB) diagnosis delays the time to diagnosis and treatment, and increases the risk of fluoroquinolone-resistant TB and death. Ascertainment of fluoroquinolone exposure could identify such high-risk patients. We compared four methods of ascertaining fluoroquinolone exposure in the 6 months prior to TB diagnosis in culture-confirmed TB patients in Tennessee from January 2007 to December 2009. The four methods included a simple questionnaire administered to all TB suspects by health department personnel (FQ-Form), an in-home interview conducted by research staff, outpatient and inpatient medical record review, and TennCare pharmacy database review. Of 177 TB patients included, 72 (41%) received fluoroquinolones during the 6 months before TB diagnosis. Fluoroquinolone exposure determined by review of inpatient and outpatient medical records was considered the gold standard for comparison. The FQ-Form had 61% [95% confidence interval (CI) 48-73] sensitivity and 93% (95% CI 85-98) specificity (agreement 79%, kappa = 0.56) while the in-home interview had 28% (95% CI 18-40) sensitivity and 99% (94-100%) specificity (agreement 68%, kappa = 0.29). A simple questionnaire administered by health department personnel identified fluoroquinolone exposure before TB diagnosis with moderate reliability.

  16. Key Role of Mfd in the Development of Fluoroquinolone Resistance in Campylobacter jejuni

    PubMed Central

    Han, Jing; Sahin, Orhan; Barton, Yi-Wen; Zhang, Qijing

    2008-01-01

    Campylobacter jejuni is a major food-borne pathogen and a common causative agent of human enterocolitis. Fluoroquinolones are a key class of antibiotics prescribed for clinical treatment of enteric infections including campylobacteriosis, but fluoroquinolone-resistant Campylobacter readily emerges under the antibiotic selection pressure. To understand the mechanisms involved in the development of fluoroquinolone-resistant Campylobacter, we compared the gene expression profiles of C. jejuni in the presence and absence of ciprofloxacin using DNA microarray. Our analysis revealed that multiple genes showed significant changes in expression in the presence of a suprainhibitory concentration of ciprofloxacin. Most importantly, ciprofloxacin induced the expression of mfd, which encodes a transcription-repair coupling factor involved in strand-specific DNA repair. Mutation of the mfd gene resulted in an approximately 100-fold reduction in the rate of spontaneous mutation to ciprofloxacin resistance, while overexpression of mfd elevated the mutation frequency. In addition, loss of mfd in C. jejuni significantly reduced the development of fluoroquinolone-resistant Campylobacter in culture media or chickens treated with fluoroquinolones. These findings indicate that Mfd is important for the development of fluoroquinolone resistance in Campylobacter, reveal a previously unrecognized function of Mfd in promoting mutation frequencies, and identify a potential molecular target for reducing the emergence of fluoroquinolone-resistant Campylobacter. PMID:18535657

  17. Use of the respiratory fluoroquinolones for the outpatient management of community-acquired pneumonia

    PubMed Central

    Liu, Hans H.

    2004-01-01

    Background Approximately 4 million cases of community-acquired pneumonia (CAP) occur in the United States each year, with the majority treated on an outpatient basis. The first fluoroquinolones (eg, ciprofloxacin) were used with caution for respiratory tract infections due to limited in vitro activity against common gram-positive pathogens. With the availability of levofloxacin, followed by gatifloxacin and moxifloxacin hydrochloride, which exhibited increased activity against gram-positive organisms, the fluoroquinolones have become a practical choice for the treatment of CAP. Objective The aim of this review was to compare the respiratory fluoroquinolones in the outpatient management of CAP. Methods We conducted a search for English-language articles (key terms: fluoroquinolone, levofloxacin, gatifloxacin, moxifloxacin, and pneumonia; years: 1996–2004). Data from published literature were reviewed regarding clinical and microbiologic efficacy and tolerability; pharmacokinetic and pharmacodynamic properties; and drug costs of levofloxacin, gatifloxacin, and moxifloxacin. Results The 3 fluoroquinolones reviewed showed comparable clinical and microbiologic efficacy for the treatment of CAP. In general, the fluoroquinolones were well tolerated, although some differences have been reported, including higher rates of gastrointestinal and other adverse events for gatifloxacin and moxifloxacin. Gatifloxacin and moxifloxacin exhibited greater in vitro potency than levofloxacin against Streptococcus pneumoniae. However, levofloxacin achieved a higher serum drug concentration than the other agents, allowing similar attainment of pharmacokinetic and pharmacodynamic targets required for effective treatment. Conclusions The respiratory fluoroquinolones provided appropriate first line treatment in select patients with CAP on the basis of their microbiologic and clinical efficacy and their safety profiles. PMID:24764589

  18. 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

  19. 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

  20. 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.

  1. Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.

    PubMed

    Perucca, Paola; Savio, Monica; Cazzalini, Ornella; Mocchi, Roberto; Maccario, Cristina; Sommatis, Sabrina; Ferraro, Daniela; Pizzala, Roberto; Pretali, Luca; Fasani, Elisa; Albini, Angelo; Stivala, Lucia Anna

    2014-11-01

    The photobehavior of ciprofloxacin, lomefloxacin and ofloxacin fluoroquinolones was investigated using several in vitro methods to assess their cytotoxic, antiproliferative, and genotoxic potential against two human cancer cell lines. We focused our attention on the possible relationship between their chemical structure, O₂ partial pressure and photobiological activity on cancer cells. The three molecules share the main features of most fluoroquinolones, a fluorine in 6 and a piperazino group in 7, but differ at the key position 8, unsubstituted in ciprofloxacin, a fluorine in lomefloxacin and an alkoxy group in ofloxacin. Studies in solution show that ofloxacin has a low photoreactivity; lomefloxacin reacts via aryl cation, ciprofloxacin reacts but not via the cation. In our experiments, ciprofloxacin and lomefloxacin showed a high and comparable potential for photodamaging cells and DNA. Lomefloxacin appeared the most efficient molecule in hypoxia, acting mainly against tumour cell proliferation and generating DNA plasmid photocleavage. Although our results do not directly provide evidence that a carbocation is involved in photodamage induced by lomefloxacin, our data strongly support this hypothesis. This may lead to new and more efficient anti-tumour drugs involving a cation in their mechanism of action. This latter acting independently of oxygen, can target hypoxic tumour tissue.

  2. 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

  3. Characterization of fluoroquinolone-resistant Escherichia coli causing septicemic colibacillosis in calves in Italy: emergence of a multiresistant O78 clonal group.

    PubMed

    Marchese, Anna; Coppo, Erika; Barbieri, Ramona; Zoppi, Simona; Pruzzo, Carla; Rossi, Francesca; Bergagna, Stefania; Dondo, Alessandro; Debbia, Eugenio

    2012-02-01

    An increased incidence of enrofloxacin-resistant Escherichia coli associated with septicemic colibacillosis in calves was observed recently in northern Italy. The aim of this study was to investigate this phenomenon. A total of 47 consecutive E. coli isolates exhibiting reduced susceptibility to enrofloxacin (intermediately resistant or resistant) causing septicemic colibacillosis in calves from 45 large-scale farms during 2006-2008, were studied. Phylogenetic group, antimicrobial agents susceptibility, and O serogroup were determined with randomly amplified polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) typing, providing additional discrimination. All of the microorganisms carried resistance to two or more additional drugs, with the pattern fluoroquinolone-ampicillin-co-trimoxazole-tetracycline-gentamicin-thiamphenicol being the most represented (18/47; 38.3%). Plasmid-mediated extended-spectrum and AmpC β-lactamases and plasmid-mediated fluoroquinolone resistance genetic determinants were not detected. Third-generation cephalosporins emerged as the most active antimicrobial agents tested (97.9% of susceptible strains). Overall, 37 different RAPD profiles and 18 different O serogroups could be distinguished among the typeable strains, indicating a substantial heterogeneity and suggesting the occurrence of several independent selection events. However, approximately one-fourth (11/47) of the strains belonged to serogroup O78, and PFGE revealed that the great majority (7/11) of these were clonally related, indicating the selection of a O78 clonal group. This is the first report investigating the molecular epidemiology of fluoroquinolone-resistant E. coli in calves and describing the emergence of a fluoroquinolone-resistant E. coli clonal group in these animals.

  4. 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.

  5. International Symposium on Stratified Flows (4th) Held in Grenoble, France on June 29-July 2, 1994. Volume 3

    DTIC Science & Technology

    1994-10-10

    differential geometry aproach to geophysical flows " - to be published in Phys.Letters A 9 The structure of the turbulent wake and the random internal wave field... flows , the Sc effects should come into play especially when Re drop to values of the order of [(cX/tX2 ,n(Sc) -2; such low Reynolds numbers are not...proceedings 29 June - 2 July 1994 4. Title & subtitle 5a. Contract or Grant # 4th International Symposium on Stratified Flows N00014-94-J-9018 5b

  6. Synapses as Therapeutic Targets for Autism Spectrum Disorders: An International Symposium Held in Pavia on July 4th, 2014

    PubMed Central

    Curatolo, Paolo; Ben-Ari, Yehezkel; Bozzi, Yuri; Catania, Maria Vincenza; D’Angelo, Egidio; Mapelli, Lisa; Oberman, Lindsay M.; Rosenmund, Christian; Cherubini, Enrico

    2014-01-01

    New progresses into the molecular and cellular mechanisms of autism spectrum disorders (ASDs) have been discussed in 1 day international symposium held in Pavia (Italy) on July 4th, 2014 entitled “synapses as therapeutic targets for autism spectrum disorders” (satellite of the FENS Forum for Neuroscience, Milan, 2014). In particular, world experts in the field have highlighted how animal models of ASDs have greatly advanced our understanding of the molecular pathways involved in synaptic dysfunction leading sometimes to “synaptic clinical trials” in children. PMID:25324723

  7. 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.

  8. Synapses as therapeutic targets for autism spectrum disorders: an international symposium held in pavia on july 4th, 2014.

    PubMed

    Curatolo, Paolo; Ben-Ari, Yehezkel; Bozzi, Yuri; Catania, Maria Vincenza; D'Angelo, Egidio; Mapelli, Lisa; Oberman, Lindsay M; Rosenmund, Christian; Cherubini, Enrico

    2014-01-01

    New progresses into the molecular and cellular mechanisms of autism spectrum disorders (ASDs) have been discussed in 1 day international symposium held in Pavia (Italy) on July 4th, 2014 entitled "synapses as therapeutic targets for autism spectrum disorders" (satellite of the FENS Forum for Neuroscience, Milan, 2014). In particular, world experts in the field have highlighted how animal models of ASDs have greatly advanced our understanding of the molecular pathways involved in synaptic dysfunction leading sometimes to "synaptic clinical trials" in children.

  9. Report on the 4'th scientific meeting of the "Verein zur Förderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Nov. 2'nd - Nov. 4'th, 2012.

    PubMed

    Linker, Ralf A; Meuth, Sven G; Magnus, Tim; Korn, Thomas; Kleinschnitz, Christoph

    2012-11-22

    From November 2nd - 4th 2012, the 4th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Again more than 60 participants, predominantly at the doctoral student or postdoc level, gathered to share their latest findings in the fields of neurovascular research, neurodegeneration and neuroinflammation. Like in the previous years, the symposium provided an excellent platform for scientific exchange and the presentation of innovative projects in the stimulating surroundings of the Brandenburg outback. This year's keynote lecture on the pathophysiological relevance of neuronal networks was given by Christian Gerloff, Head of the Department of Neurology at the University Clinic of Hamburg-Eppendorf. Another highlight of the meeting was the awarding of the NEUROWIND e.V. prize for young scientists working in the field of experimental neurology. The award is donated by the Merck Serono GmbH, Darmstadt, Germany and is endowed with 20.000 Euro. This year the jury decided unanimously to adjudge the award to Michael Gliem from the Department of Neurology at the University Clinic of Düsseldorf (group of Sebastian Jander), Germany, for his outstanding work on different macrophage subsets in the pathogenesis of ischemic stroke published in the Annals of Neurology in 2012.

  10. 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.

  11. 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).

  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. 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

  14. 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.

  15. Observational cohort study of pregnancy outcome after first-trimester exposure to fluoroquinolones.

    PubMed

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

    2014-08-01

    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 [OR(adj)], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HR(adj)], 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 [OR(crude)], 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 (HR(adj), 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.

  16. Molecular characterization of fluoroquinolone resistance in nontypeable Haemophilus influenzae clinical isolates.

    PubMed

    Puig, Carmen; Tirado-Vélez, José Manuel; Calatayud, Laura; Tubau, Fe; Garmendia, Junkal; Ardanuy, Carmen; Marti, Sara; de la Campa, Adela G; Liñares, Josefina

    2015-01-01

    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.

  17. 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.

  18. 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

  19. 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.

  20. Insights into the Enhanced in vivo Fitness of Neisseria gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase

    DTIC Science & Technology

    2015-02-05

    Insights into the Enhanced in vivo Fitness of Neisseria gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase...gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase" Name of Candidate: MAJ Jonathan D’ Ambrozio Doctor of Philosophy Degree...gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase" is appropriately acknowledged and, bey9nd brief excerpts, is with

  1. 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

  2. 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.

  3. 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

  4. Preliminary Study on LiF4-ThF4-PuF4 Utilization as Fuel Salt of miniFUJI Molten Salt Reactor

    NASA Astrophysics Data System (ADS)

    Waris, Abdul; Aji, Indarta K.; Pramuditya, Syeilendra; Widayani; Irwanto, Dwi

    2016-08-01

    miniFUJI reactor is molten salt reactor (MSR) which is one type of the Generation IV nuclear energy systems. The original miniFUJI reactor design uses LiF-BeF2-ThF4-233UF4 as a fuel salt. In the present study, the use of LiF4-ThF4-PuF4 as fuel salt instead of LiF-BeF2-ThF4-UF4 will be discussed. The neutronics cell calculation has been performed by using PIJ (collision probability method code) routine of SRAC 2006 code, with the nuclear data library is JENDL-4.0. The results reveal that the reactor can attain the criticality condition with the plutonium concentration in the fuel salt is equal to 9.16% or more. The conversion ratio diminishes with the enlarging of plutonium concentration in the fuel. The neutron spectrum of miniFUJI MSR with plutonium fuel becomes harder compared to that of the 233U fuel.

  5. DNA topoisomerase targets of the fluoroquinolones: A strategy for avoiding bacterial resistance

    PubMed Central

    Zhao, Xilin; Xu, Chen; Domagala, John; Drlica, Karl

    1997-01-01

    Fluoroquinolones are antibacterial agents that attack DNA gyrase and topoisomerase IV on chromosomal DNA. The existence of two fluoroquinolone targets and stepwise accumulation of resistance suggested that new quinolones could be found that would require cells to obtain two topoisomerase mutations to display resistance. For wild-type cells to become resistant, the two mutations must be acquired concomitantly. That is expected to occur infrequently. To identify such compounds, fluoroquinolones were tested for the ability to kill a moderately resistant gyrase mutant. Compounds containing a C8-methoxyl group were particularly lethal, and incubation of wild-type cultures on agar containing C8-methoxyl fluoroquinolones produced no resistant mutant, whereas thousands arose during comparable treatment with control compounds lacking the C8 substituent. When the test strain contained a preexisting topoisomerase IV mutation, which by itself conferred no resistance, equally high numbers of resistant mutants were obtained for C8-methoxyl and control compounds. Thus C8-methoxyl fluoroquinolones required two mutations for expression of resistance. Although highly lethal, C8-methoxyl fluoroquinolones were not more effective than C8-H controls at blocking bacterial growth. Consequently, quinolone action involves two events, which we envision as formation of drug–enzyme–DNA complexes followed by release of lethal double-strand DNA breaks. Release of DNA breaks, which must occur less frequently than complex formation, is probably the process stimulated by the C8-methoxyl group. Understanding this stimulation should provide insight into intracellular quinolone action and contribute to development of fluoroquinolones that prevent selection of resistant bacteria. PMID:9391140

  6. The mechanisms of insulin secretion and calcium signaling in pancreatic β-cells exposed to fluoroquinolones.

    PubMed

    Bito, Motoki; Tomita, Takashi; Komori, Mika; Taogoshi, Takanori; Kimura, Yasuhiro; Kihira, Kenji

    2013-01-01

    Fluoroquinolones reportedly induce hypoglycemia through stimulation of insulin secretion from pancreatic β-cells via inhibition of K(ATP) channels and activation of L-type voltage-dependent Ca(2+) channels. In physiological condition, the cytosolic Ca(2+) concentration ([Ca(2+)](c)) is also regulated by release of Ca(2+) from intracellular Ca(2+) stores. In this study, we investigated the mechanism of insulin secretion induced by fluoroquinolones, with respect to intracellular Ca(2+) stores. Even where the absence of supplemental extracellular Ca(2+), insulin secretion and [Ca(2+)](c) were increased by gatifloxacin, levofloxacin or tolbutamide. Insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones were reduced by depleting of Ca(2+) in endoplasmic reticumum (ER) by thapsigargin, and inhibiting ryanodine receptor of ER by dantrolene. Inhibition of inositol 1,4,5-triphosphate receptor of ER by xestospongin C suppressed insulin secretion induced by fluoroquinolones, whereas it did not affect [Ca(2+)](c). Destruction of acidic Ca(2+) stores such as lysosome and lysosome-related organelles by glycyl-L-phenylalanine-2-nephthylamide (GPN) did not affect insulin secretion and the rise of [Ca(2+)](c) induced by fluoroquinolones. The increase in insulin and [Ca(2+)](c) induced by tolbutamide were reduced by thapsigargin, dantrolene, and GPN but not by xestospongin C. In conclusion, fluoroquinolones induces Ca(2+) release from ER mediated by the ryanodine receptor, and the reaction might involve in insulin secretion. Sulfonylureas induce Ca(2+) release from GPN-sensitive acidic Ca(2+) stores, but fluoroquinolones did not.

  7. STO-2: Support for 4th Year Operations, Recovery, and Science: Smithsonian Astrophysical Observatory Co-I

    NASA Astrophysics Data System (ADS)

    Stark, Antony

    The Lead Proposal for this investigation originates from the University of Arizona, Steward Observatory under Principal Investigator Dr. Christopher K. Walker. The Smithsonian Astrophysical Observatory (SAO) is pleased to submit this subsidiary proposal for engineering and scientific collaboration on the reflight of the Stratospheric TeraHertz Observatory (STO-2). This proposal covers Support for 4th Year Operations, Recovery, and Science as a result of the failure to launch due to weather in the 2015-2016 season. The Institutional Principal Investigator for the SAO effort is Antony A. Stark, and scientific Co-Investigators Gary Melnick, Volker Tolls, and Matthew Ashby. SAO will provide pre-flight engineering and flight monitoring support for the second Long Duration Flight (LDF) from McMurdo Sound in Antarctica. Subsequent to the flight, SAO Co-Is will contribute to data management and analysis, scientific interpretation, publication of results, and public distribution of data.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. Fluoroquinolone-induced tendinopathy: etiology and preventive measures.

    PubMed

    Kaleagasioglu, Ferda; Olcay, Ercan

    2012-01-01

    Tendinopathy is a serious health problem and its etiology is not fully elucidated. Among intrinsic and extrinsic predisposing factors of tendinopathy, the impact of therapeutic agents, especially fluoroquinolone (FQ) group antibiotics, is recently being recognized. FQs are potent bactericidal agents widely used in various infectious diseases, including community acquired pneumonia and bronchitis, chronic osteomyelitis, traveler's diarrhea, typhoid fever, shigellosis, chronic bacterial prostatitis, uncomplicated cervical and urethral gonorrhea and prophylaxis of anthrax. FQs have an acceptable tolerability range. However, many lines of evidence for developing tendinitis and tendon rupture during FQ use have resulted in the addition of a warning in patient information leaflets. FQ-induced tendinopathy presents a challenge for the clinician because healing response is poor due to low metabolic rate in mature tendon tissue and tendinopathy is more likely to develop in patients who are already at high risk, such as elderly, solid organ transplant recipients and concomitant corticosteroid users. FQs become photo-activated under exposure to ultraviolet light, and this process results in formation and accumulation of intracellular reactive oxygen species (ROS). The subsequent FQ-related oxidative stress disturbs mitochondrial functions, leading to apoptosis. ROS overproduction also has direct cytotoxic effects on extracellular matrix components. Understanding the mechanisms of the FQ-associated tendinopathy may enable designing safer therapeutic strategies, hence optimization of clinical response. In this review, we evaluate multi-factorial etiology of the FQ-induced tendinopathy and discuss proposed preventive measures such as antioxidant use and protection from natural sunlight and artificial ultraviolet exposure.

  14. Fluoroquinolone Resistance in Penicillin-resistant Streptococcus pneumoniae Clones, Spain

    PubMed Central

    Balsalobre, Luz; Ardanuy, Carmen; Fenoll, Asunción; Pérez-Trallero, Emilio; Liñares, Josefina

    2004-01-01

    Among 2,882 Streptococcus pneumoniae sent to the Spanish Reference Laboratory during 2002, 75 (2.6%) were ciprofloxacin-resistant. Resistance was associated with older patients (3.9% in adults and 7.2% in patients >65 years of age), with isolation from noninvasive sites (4.3% vs. 1.0%), and with penicillin and macrolide resistance. Among 14 low-level resistant (MIC 4–8 µg/mL) strains, 1 had a fluoroquinolone efflux phenotype, and 13 showed single ParC changes. The 61 high-level ciprofloxacin-resistant (MIC >16 µg/mL) strains showed either two or three changes at ParC, ParE, and GyrA. Resistance was acquired either by point mutation (70 strains) or by recombination with viridans streptococci (4 strains) at the topoisomerase II genes. Although 36 pulsed-field gel electrophoresis patterns were observed, 5 international multiresistant clones (Spain23F-1, Spain6B-2, Spain9V-3, Spain14-5 and Sweden15A-25) accounted for 35 (46.7%) of the ciprofloxacin-resistant strains. Continuous surveillance is needed to prevent the dissemination of these clones. PMID:15504260

  15. Characterization of Recombinant Fluoroquinolone-Resistant Pneumococcus-Like Isolates

    PubMed Central

    Ortega, Montserrat; de la Campa, Adela G.

    2013-01-01

    Fourteen fluoroquinolone-resistant streptococcal isolates with recombinant DNA topoisomerase genes, preliminarily identified as pneumococci, were further characterized using phenotypic and genotypic approaches. Phenotypic tests classified them as atypical pneumococci. Phylogenetic relationships were analyzed by using the sequences of seven housekeeping alleles from these isolates and from isolates of Streptococcus pneumoniae, Streptococcus mitis, Streptococcus oralis, and Streptococcus pseudopneumoniae. Four isolates grouped with S. pneumoniae, seven grouped with S. pseudopneumoniae, and three grouped with S. mitis. These results generally agreed with those obtained with an optochin susceptibility test and with the organization of the atp operon chromosomal region, encoding the FoF1 H+-ATPase (the target of optochin). All seven isolates grouping with S. pseudopneumoniae share the same spr1368-atpC-atpA gene order; all four grouping with S. pneumoniae share the spr1368-IS1239-atpC-atpA order, and two out of the three grouping with S. mitis share the spr1284-atpC-atpA order. In addition, evidence for recombination within the seven housekeeping alleles of the S. pseudopneumoniae population was provided by several methods: the index of association (0.4598, P < 0.001), the pairwise homoplasy index, and the split-decomposition method. This study confirms the existence of pneumococci among the alpha-hemolytic streptococci with DNA topoisomerase genes showing a mosaic structure and reveals a close relationship between atypical pneumococci and S. pseudopneumoniae. PMID:23114769

  16. Impact of Intervention by an Antimicrobial Stewardship Team on Conversion from Intravenous to Oral Fluoroquinolones

    PubMed Central

    Jeong, Young Mi; Lee, Jung Hwa; Lee, Eunsook

    2017-01-01

    Background Early conversion from intravenous to oral antibiotics plays an important role in lowering the risk of catheter-associated infections, reducing the workload of nurses, decreasing direct and indirect costs, and shortening hospital stays. In August 2015, an antimicrobial stewardship program (ASP) was implemented to facilitate conversion from intravenous to oral administration of fluoroquinolones in our institute. This study evaluated the clinical and economic impact of the intervention. Materials and Methods Data were retrospectively collected by reviewing electronic medical records. All hospitalized patients aged 18 and older who met the study inclusion criteria for the conversion were included between August and November 2015. We computed the physicians' adherence rate to the ASP recommendations. We also measured the total use of fluoroquinolones, length of hospital stay, and medication costs. Results During 4 months, 129 cases were enrolled in the study. The adherence rate was 79.8%. The average total prescription volume of intravenous fluoroquinolones, the length of hospital stay, and the total cost of the fluoroquinolones statistically significantly decreased in the intervention-adherent group. Conclusion Intervention to facilitate conversion from intravenous to oral administration has reduced excess use of intravenous fluoroquinolones and length of hospital stay. With these findings, further implementations of the ASP extending to other antibiotics may be warranted. PMID:28332344

  17. Ribavirin exerts differential effects on functions of Cd4+ Th1, Th2, and regulatory T cell clones in hepatitis C.

    PubMed

    Langhans, Bettina; Nischalke, Hans Dieter; Arndt, Simone; Braunschweiger, Ingrid; Nattermann, Jacob; Sauerbruch, Tilman; Spengler, Ulrich

    2012-01-01

    Ribavirin improves outcomes of therapy in chronic hepatitis C but its mode of action has still remained unclear. Since ribavirin has been proposed to modulate the host's T cell responses, we studied its direct effects on CD4(+) T cell clones with diverse functional polarization which had been generated from patients with chronic hepatitis C. We analysed in vitro proliferation ([(3)H] thymidine uptake) and cytokine responses (IL-10, IFN-gamma) at varying concentrations of ribavirin (0-10 µg/ml) in 8, 9 and 7 CD4(+) TH1, TH2 and regulatory T cell (Treg) clones, respectively. In co-culture experiments, we further determined effects of ribarivin on inhibition of TH1 and TH2 effector cells by Treg clones. All clones had been generated from peripheral blood of patients with chronic hepatitis C in the presence of HCV core protein. Ribavirin enhanced proliferation of T effector cells and increased production of IFN-gamma in TH1 clones, but had only little effect on IL-10 secretion in TH2 clones. However, ribavirin markedly inhibited IL-10 release in Treg clones in a dose dependent fashion. These Treg clones suppressed proliferation of T effector clones by their IL-10 secretion, and in co-culture assays ribavirin reversed Treg-mediated suppression of T effector cells. Our in vitro data suggest that--in addition to its immunostimulatory effects on TH1 cells--ribavirin can inhibit functions of HCV-specific Tregs and thus reverses Treg-mediated suppression of T effector cells in chronic hepatitis C.

  18. Effects of fluoroquinolone treatment and group housing of pigs on the selection and spread of fluoroquinolone-resistant Campylobacter.

    PubMed

    Usui, Masaru; Sakemi, Yoko; Uchida, Ikuo; Tamura, Yutaka

    2014-06-04

    There are concerns that the use of fluoroquinolones (FQs) and group housing of food animals may contribute to the development of bacterial FQ resistance. Here, we studied the effects of administering FQ to pigs on the selection of FQ-resistant Campylobacter. Fifteen pigs were randomly allocated to either a group treated with FQs (enrofloxacin or norfloxacin), or an untreated control group. The number of FQ-resistant Campylobacter in feces was determined using appropriate selective agar containing enrofloxacin. FQ-resistant Campylobacter from samples of both groups were observed on days 3 and 4. These bacteria persisted for up to 21 days after treatment was discontinued. To evaluate the effect of group housing on the transmission of FQ-resistant Campylobacter, five pigs infected with FQ-sensitive Campylobacter pigs and one pig infected with FQ-resistant Campylobacter were housed together. On day 3, FQ-resistant Campylobacter were isolated from all six pigs. Moreover, FQ-resistant Campylobacter were isolated from environmental samples from the pen. These results indicate that the treatment of pigs with FQs selects for and spreads FQ-resistant Campylobacter among the pen. Therefore, responsible and prudent use of FQs at pig farms is required to prevent the emergence and transmission of FQ-resistant Campylobacter.

  19. Effects of exposure of Clostridium difficile PCR ribotypes 027 and 001 to fluoroquinolones in a human gut model.

    PubMed

    Saxton, Katie; Baines, Simon D; Freeman, Jane; O'Connor, Rachael; Wilcox, Mark H

    2009-02-01

    The incidence of Clostridium difficile infection is increasing, with reports implicating fluoroquinolone use. A three-stage chemostat gut model was used to study the effects of three fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) on the gut microbiota and two epidemic C. difficile strains, strains of PCR ribotypes 027 and 001, in separate experiments. C. difficile total viable counts, spore counts, and cytotoxin titers were determined. The emergence of C. difficile isolates with reduced antibiotic susceptibility was monitored with fluoroquinolone-containing medium, and molecular analysis of the quinolone resistance-determining region was performed. C. difficile spores were quiescent in the absence of fluoroquinolones. Instillation of each fluoroquinolone led to C. difficile spore germination and high-level cytotoxin production. High-level toxin production occurred after detectable spore germination in all experiments except those with C. difficile PCR ribotype 027 and moxifloxacin, in which marked cytotoxin production preceded detectable germination, which coincided with isolate recovery on fluoroquinolone-containing medium. Three C. difficile PCR ribotype 027 isolates and one C. difficile PCR ribotype 001 isolate from fluoroquinolone-containing medium exhibited elevated MICs (80 to > or =180 mg/liter) and possessed mutations in gyrA or gyrB. These in vitro results suggest that all fluoroquinolones have the propensity to induce C. difficile infection, regardless of their antianaerobe activities. Resistant mutants were seen only following moxifloxacin exposure.

  20. Novel dummy molecularly imprinted polymers for matrix solid-phase dispersion extraction of eight fluoroquinolones from fish samples.

    PubMed

    Sun, Xiaoli; Wang, Jincheng; Li, Yun; Yang, Jiajia; Jin, Jing; Shah, Syed Mazhar; Chen, Jiping

    2014-09-12

    A series of novel dummy molecularly imprinted polymers (DMIPs) were prepared as highly class-selective sorbents for fluoroquinolones. A non-poisonous dummy template, daidzein, was used for the first time to create specific molecular recognition sites for fluoroquinolones in the synthesized polymers. The influence of porogen polarity on dummy molecular imprinting effect was studied. The DMIP prepared using dimethylsulfoxide-acetonitrile (1:1.8, v/v) as porogen achieved the highest imprinting factors (IF) for fluoroquinolones over a range of IF 13.4-84.0. This DMIP was then used for selective extraction of eight fluoroquinolones (fleroxacin, ofloxacin, norfloxacin, pefloxacin, ciprofloxacin, lomefloxacin, enrofloxacin and gatifloxacin) from fish samples based on dummy molecularly imprinted matrix solid-phase dispersion (DMI-MSPD). The extracted fluoroquinolones were subsequently analyzed by high-performance liquid chromatography (HPLC) equipped with a fluorescence detector (FLD). The developed method had acceptable recoveries (64.4-102.7%) and precision (RSDs: 1.7-8.5%, n=5) for determination of fluoroquinolones in fish samples fortified at levels of 10 and 100ngg(-1). The limits of detection (LODs) for identification of eight fluoroquinolones ranged between 0.06 and 0.22ngg(-1). The results demonstrated great potential of the optimized method for sample preparation in routine analysis of trace fluoroquinolones in fish samples.

  1. [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

  2. Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection.

    PubMed

    Snell, Laura M; Osokine, Ivan; Yamada, Douglas H; De la Fuente, Justin Rafael; Elsaesser, Heidi J; Brooks, David G

    2016-09-20

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection.

  3. Synthesis and antitubercular activity of palladium and platinum complexes with fluoroquinolones.

    PubMed

    Vieira, Lígia Maria M; de Almeida, Mauro V; Lourenço, Maria Cristina S; Bezerra, Flávio Augusto F M; Fontes, Ana Paula S

    2009-10-01

    The fluoroquinolones are an important family of synthetic antimicrobial agents being clinically used over the past thirty years. In addition, some fluoroquinolones have been used in the development of anticancer drugs, and others have demonstrated anti-HIV activity. Furthermore, there has been some additional work investigating the effect of metal ions on biological activity. Aiming to obtain novel palladium(II) and platinum(II) complexes that exhibit biological activity, we have synthesized complexes using fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, and gatifloxacin) as ligands. The compounds were characterized using IR and NMR spectroscopy, thermogravimetric and elemental analyses. The complexes show activity against Mycobacterium tuberculosis strain H(37)Rv. The minimal inhibitory concentration (MIC) of the complexes was determined.

  4. Adjuvants Based on Hybrid Antibiotics Overcome Resistance in Pseudomonas aeruginosa and Enhance Fluoroquinolone Efficacy.

    PubMed

    Gorityala, Bala Kishan; Guchhait, Goutam; Fernando, Dinesh M; Deo, Soumya; McKenna, Sean A; Zhanel, George G; Kumar, Ayush; Schweizer, Frank

    2016-01-11

    The use of adjuvants that rescue antibiotics against multidrug-resistant (MDR) pathogens is a promising combination strategy for overcoming bacterial resistance. While the combination of β-lactam antibiotics and β-lactamase inhibitors has been successful in restoring antibacterial efficacy in MDR bacteria, the use of adjuvants to restore fluoroquinolone efficacy in MDR Gram-negative pathogens has been challenging. We describe tobramycin-ciprofloxacin hybrid adjuvants that rescue the activity of fluoroquinolone antibiotics against MDR and extremely drug-resistant Pseudomonas aeruginosa isolates in vitro and enhance fluoroquinolone efficacy in vivo. Structure-activity studies reveal that the presence of both tobramycin and ciprofloxacin, which are separated by a C12 tether, is critical for the function of the adjuvant. Mechanistic studies indicate that the antibacterial modes of ciprofloxacin are retained while the role of tobramycin is limited to destabilization of the outer membrane in the hybrid.

  5. 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.

  6. Fluoroquinolones in the management of community-acquired pneumonia in primary care.

    PubMed

    Wispelwey, Brian; Schafer, Katherine R

    2010-11-01

    A literature search was conducted to evaluate the pharmacokinetic and pharmacodynamic profile of the respiratory fluoroquinolones (gemifloxacin, levofloxacin and moxifloxacin) and their efficacy and safety in the management of community-acquired pneumonia (CAP). Data show that CAP is a common presentation in primary care practice, and is associated with high rates of morbidity and mortality, particularly in the elderly. Although the causative pathogens differ depending on treatment setting and patient factors, Streptococcus pneumoniae is the primary pathogen in all treatment settings. As a class, the respiratory fluoroquinolones have a very favorable pharmacokinetic and pharmacodynamic profile. Pharmacodynamic criteria suggest that moxifloxacin and gemifloxacin are more potent against S. pneumoniae, which may have the added benefit of reducing resistance selection and enhancing bacterial eradication. The respiratory fluoroquinolones are also generally well tolerated, and are first-line options for outpatient treatment of CAP in patients with comorbidities or previous antibiotic use.

  7. 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

  8. Apparent involvement of a multidrug transporter in the fluoroquinolone resistance of Streptococcus pneumoniae.

    PubMed Central

    Baranova, N N; Neyfakh, A A

    1997-01-01

    A Streptococcus pneumoniae strain selected for resistance to ethidium bromide demonstrated enhanced energy-dependent efflux of this toxic dye. Both the ethidium resistance and the ethidium efflux could be inhibited by the plant alkaloid reserpine. The ethidium-selected cells demonstrated cross-resistance to the fluoroquinolones norfloxacin and ciprofloxacin; this resistance could also be completely reversed by reserpine. Furthermore, reserpine potentiated the susceptibility of wild-type S. pneumoniae to fluoroquinolones and ethidium. The most plausible explanation for these results is that S. pneumoniae, like some other gram-positive bacteria, expresses a reserpine-sensitive multidrug transporter, which may play an important role in both intrinsic and acquired resistances of this pathogen to fluoroquinolone therapy. PMID:9174208

  9. Efflux pump induction by quaternary ammonium compounds and fluoroquinolone resistance in bacteria.

    PubMed

    Buffet-Bataillon, Sylvie; Tattevin, Pierre; Maillard, Jean-Yves; Bonnaure-Mallet, Martine; Jolivet-Gougeon, Anne

    2016-01-01

    Biocides, primarily those containing quaternary ammonium compounds (QAC), are heavily used in hospital environments and various industries (e.g., food, water, cosmetic). To date, little attention has been paid to potential implications of QAC use in the emergence of antibiotic resistance, especially fluoroquinolone-resistant bacteria in patients and in the environment. QAC-induced overexpression of efflux pumps can lead to: cross resistance with fluoroquinolones mediated by multidrug efflux pumps; stress response facilitating mutation in the Quinolone Resistance Determining Region; and biofilm formation increasing the risk of transfer of mobile genetic elements carrying fluoroquinolone or QAC resistance determinants. By following the European Biocidal Product Regulation, manufacturers of QAC are required to ensure that their QAC-based biocidal products are safe and will not contribute to emerging bacterial resistance.

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

    PubMed

    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

    2015-04-24

    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.

  11. Allogeneic hematopoietic cell transplantation without fluconazole and fluoroquinolone prophylaxis.

    PubMed

    Heidenreich, D; Kreil, S; Nolte, F; Reinwald, M; Hofmann, W-K; Klein, S A

    2016-01-01

    Fluoroquinolone (FQ) and fluconazole prophylaxis is recommended for patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). However, due to an uncertain scientific basis and the increasing emergence of resistant germs, this policy should be questioned. Therefore, FQ and fluconazole prophylaxis was omitted in alloHCT at our center. In this retrospective analysis, all consecutive patients (n = 63) who underwent first alloHCT at our institution from September 2010 to September 2013 were included. Patients neither received FQ nor fluconazole prophylaxis. Day 100 mortality, incidence of febrile neutropenia, bacterial infections, and invasive fungal diseases (IFD) were assessed. Sixteen patients who started conditioning under antimicrobial treatment/prophylaxis due to pre-existing neutropenia (3/16), IFD (12/16), or aortic valve replacement (1/16) were excluded from the analysis. Finally, 47 patients were transplanted without prophylaxis as intended. Day 100 mortality was 9 %. Febrile neutropenia occurred in 62 % (29/47); 17/47 patients (36 %) experienced a blood stream infection (BSI) with detection of Gram-positive bacteria in 14 patients, Gram-negative bacteria in five patients, and candida in one patient, respectively. Coagulase-negative staphylococci were the most frequently isolated Gram-positive bacteria; 12/21 isolated Gram-positive and 3/6 Gram-negative bacteria were FQ resistant. In 21 % (10/47) of the patients, IFD (1x proven, 1x probable, and 8x possible) were diagnosed. To conclude, all three criteria, day 100 mortality, the incidence of IFD, and BSI, are in the range of published data for patients transplanted with FQ and fluconazole prophylaxis. These data demonstrate that alloHCT is feasible without FQ and fluconazole prophylaxis.

  12. Primary photophysical properties of moxifloxacin--a fluoroquinolone antibiotic.

    PubMed

    Lorenzo, Fernando; Navaratnam, Suppiah; Edge, Ruth; Allen, Norman S

    2008-01-01

    The photophysical properties of the fluoroquinolone antibiotic moxifloxacin (MOX) were investigated in aqueous media. MOX in water, at pH 7.4, shows two intense absorption bands at 287 and 338 nm (epsilon = 44,000 and 17,000 dm(3) mol(-1) cm(-1), respectively). The absorption and emission properties of MOX are pH-dependent, pK(a) values for the protonation equilibria of both the ground (6.1 and 9.6) and excited singlet states (6.8 and 9.1) of MOX were determined spectroscopically. MOX fluoresces weakly, the quantum yield for fluorescence emission being maximum (0.07) at pH 8. Phosphorescence from the excited triplet state in frozen ethanol solution has a quantum yield of 0.046. Laser flash photolysis and pulse radiolysis studies have been carried out to characterize the transient species of MOX in aqueous solution. On laser excitation, MOX undergoes monophotonic photoionization with a quantum yield of 0.14. This leads to the formation of a long-lived cation radical whose absorption is maximum at 470 nm (epsilon(470) = 3400 dm(3) mol(-1) cm(-1)). The photoionization process releases hydrated electron which rapidly reacts (k = 2.8 x 10(10) dm(3) mol(-1) s(-1)) with ground state MOX, yielding a long-lived anion radical with maximum absorption at 390 nm (epsilon(390) = 2400 dm(3) mol(-1) cm(-1)). The cation radical of MOX is able to oxidize protein components tryptophan and tyrosine. The bimolecular rate constants for these reactions are 2.3 x 10(8) dm(3) mol(-1) s(-1) and 1.3 x 10(8) dm(3) mol(-1) s(-1), respectively. Singlet oxygen sensitized by the MOX triplet state was also detected only in oxygen-saturated D(2)O solutions, with a quantum yield of 0.075.

  13. Mass spectrometic study of speciation in aluminium-fluoroquinolone solutions.

    PubMed

    Cvijovic, Mirjana; Di Marco, Valerio; Traldi, Pietro; Stankov, Milena J; Djurdjevic, Predrag

    2012-01-01

    Fluoroquinolones (FQLs) are synthetic antibacterial agents containing a 4-oxo-1,4-dihydroquinoline skeleton. When concomintantly administered with other drugs which may contain metal ions, particularly Al(3+) (antacids, phosphate binders, vaccines etc) they may form metal-drug complexes. Pharmacokinetic studies showed that aluminium-quinolone interactions lead to reduced bio- availability and altered activity of the drug with possible development of the toxic effects of aluminum ion. Reliable speciation in Al(3+) - quinolone systems at micromolar concentration level is needed to better understand pharmaco- and toxicokinetics of the FQLs in the presence of Al. In this work, the speciation in solutions containing Al(3+) and FQL family members (fleroxacin, moxifloxacin and ciprofloxacin) was studied by electrospray mass spectrometry (ESI-MS), ESI-MS/MS, and laser desorption ionization (LDI) MS. The dominating species identified in all the three Al(3+)-FQL solutions, at ca 30-50 µmol L(-1) total Al concentration and 2:1 to 1:3 metal-to-ligand ratio in the pH range 3.0- 6.0, were the ions related to the complexes AlL(2+), AlL(2)(+) and AlL(3)(0) (L = ligand in the monodeprotonated form). Mixed protonated and hydroxo complexes were also formed at lower and higher pH values respectively and, as expected, dimeric and polymeric species were not observed in ESI spectra. LDI measurements confirmed the existence of the mononuclear complexes found by ESI, and indicated the formation of polymeric species. The ion [2Al(3+) +5(-)](+) was identified with all three FQLs. This ionic species most probably arises from Al(2)L(2) by clustering with free ligand anions. Comparison of literature potentiometric data with mass spectral data indicated good agreement between speciation schemes. The obtained results suggest the presence of strong interaction between FQLs and Al(3+) which may be important in affecting absorption of these drugs in the gastrointestinal tract.

  14. Amino acid substitutions at position 95 in GyrA can add fluoroquinolone resistance to Mycobacterium leprae.

    PubMed

    Yokoyama, Kazumasa; Kim, Hyun; Mukai, Tetsu; Matsuoka, Masanori; Nakajima, Chie; Suzuki, Yasuhiko

    2012-02-01

    Amino acid substitutions at position 89 or 91 in GyrA of fluoroquinolone-resistant Mycobacterium leprae clinical isolates have been reported. In contrast, those at position 94 in M. tuberculosis, equivalent to position 95 in M. leprae, have been identified most frequently. To verify the possible contribution of amino acid substitutions at position 95 in M. leprae to fluoroquinolone resistance, we conducted an in vitro assay using wild-type and mutant recombinant DNA gyrases. Fluoroquinolone-mediated supercoiling activity inhibition assay and DNA cleavage assay revealed the potent contribution of an amino acid substitution of Asp to Gly or Asn at position 95 to fluoroquinolone resistance. These results suggested the possible future emergence of quinolone-resistant M. leprae isolates with these amino acid substitutions and the usefulness of detecting these mutations for the rapid identification of fluoroquinolone resistance in leprosy.

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

    PubMed

    Bearson, Bradley L; Brunelle, Brian W

    2015-08-01

    Fluoroquinolones are broad-spectrum antibiotics that inhibit bacterial DNA gyrase and topoisomerase activity, which can cause DNA damage and result in bacterial cell death. In response to DNA damage, bacteria induce an SOS response to stimulate DNA repair. However, the SOS response may also induce prophage with production of infectious virions. Salmonella strains typically contain multiple prophages, and certain strains including phage types DT120 and DT104 contain prophage that upon induction are capable of generalised transduction. In this study, strains of multidrug-resistant (MDR) Salmonella enterica serovar Typhimurium DT120 and DT104 were exposed to fluoroquinolones important for use in human and veterinary disease therapy to determine whether prophage(s) are induced that could facilitate phage-mediated gene transfer. Cultures of MDR S. Typhimurium DT120 and DT104 containing a kanamycin resistance plasmid were lysed after exposure to fluoroquinolones (ciprofloxacin, enrofloxacin and danofloxacin). Bacterial cell lysates were able to transfer the plasmid to a recipient kanamycin-susceptible Salmonella strain by generalised transduction. In addition, exposure of DT120 to ciprofloxacin induced the recA gene of the bacterial SOS response and genes encoded in a P22-like generalised transducing prophage. This research indicates that fluoroquinolone exposure of MDR Salmonella can facilitate horizontal gene transfer, suggesting that fluoroquinolone usage in human and veterinary medicine may have unintended consequences, including the induction of phage-mediated gene transfer from MDR Salmonella. Stimulation of gene transfer following bacterial exposure to fluoroquinolones should be considered an adverse effect, and clinical decisions regarding antibiotic selection for infectious disease therapy should include this potential risk.

  16. 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

  17. Effect of urinary excretion on the bladder tissue distribution of fluoroquinolones in rats.

    PubMed

    Izawa, Shigeru; Yamaoka, Makiko; Deguchi, Takashi

    2015-04-01

    The purpose of this study was to evaluate which of blood or urine has the greater effect on bladder tissue concentrations of fluoroquinolones important for the treatment of urinary tract infections by measuring concentrations of fluoroquinolones in the vesical tissue (chemically and immunohistochemically) and intravesical space (chemically). Thirty-minute incubation of isolated rat bladders with fluoroquinolones showed only a 1.9-fold difference in transferability among norfloxacin, levofloxacin, ciprofloxacin and sparfloxacin. Intravesical instillation of norfloxacin and sparfloxacin in rats yielded similar vesical tissue distributions. Thus, there were no large differences in vesical tissue transfer among the four fluoroquinolones. The bladder tissue/plasma concentration ratios of norfloxacin (high urinary excretion-type) and sparfloxacin (low urinary excretion-type) at 1 h after a single oral dose (10 mg/kg) to rats were 15.4 and 1.3, respectively. The bladder tissue/plasma concentration ratios of norfloxacin after an intravenous injection (10 mg/kg) to ureter-catheterized and sham-operated rats were 1.36 and 57.8. Thus the bladder tissue distribution was significantly higher in the urine-exposed bladder. Immunohistochemical examination of the vesical tissue localization of norfloxacin in rats given a single intravenous dose revealed the presence of the drug-positive image in the cytoplasm of surface layer cells (both in umbrella and cover cells) of the bladder transitional epithelium. In conclusion, the results suggest that norfloxacin and other fluoroquinolones are excreted into urine and then transferred to the surface layer of the bladder transitional epithelium. Therefore, the urine levels have a greater effect on the vesicle tissue distribution of fluoroquinolones than the plasma levels in rats.

  18. Molecular characterization of clinical Streptococcus pneumoniae isolates with reduced susceptibility to fluoroquinolones emerging in Italy.

    PubMed

    Montanari, Maria Pia; Tili, Emily; Cochetti, Ileana; Mingoia, Marina; Manzin, Aldo; Varaldo, Pietro Emanuele

    2004-01-01

    Fifteen Streptococcus pneumoniae clinical isolates with reduced fluoroquinolone susceptibility (defined as a ciprofloxacin MIC of > or = 4 microg/ml), all collected in Italy in 2000-2003, were typed and subjected to extensive molecular characterization to define the contribution of drug target alterations and efflux mechanisms to their resistance. Serotyping and pulsed-field gel electrophoresis analysis indicated substantial genetic unrelatedness among the 15 isolates, suggesting that the new resistance traits arise in multiple indigenous strains rather than through clonal dissemination. Sequencing of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE demonstrated that point mutations producing single amino acid changes were more frequent in topoisomerase IV (parC mutations in 14 isolates and parE mutations in 13) than in DNA gyrase subunits (gyrA mutations in 7 isolates and no gyrB mutations observed). No isolate displayed a quinolone efflux system susceptible to carbonyl cyanide m-chlorophenylhydrazone; conversely, four-fold or greater MIC reductions in the presence of reserpine were observed in all 15 isolates with ethidium bromide, in 13 with ulifloxacin, in 9 with ciprofloxacin, in 5 with norfloxacin, and in none with five other fluoroquinolones. The effect of efflux pump activity on the level and profile of fluoroquinolone resistance in our strains was minor compared with that of target site modifications. DNA mutations and/or efflux systems other than those established so far might contribute to the fluoroquinolone resistance expressed by our strains. Susceptibility profiles to nonquinolone class antibiotics and resistance-associated phenotypic and genotypic characteristics were also determined and correlated with fluoroquinolone resistance. A unique penicillin-binding protein profile was observed in all five penicillin-resistant isolates, whereas the same PBP profile as S. pneumoniae R6 was exhibited by all six penicillin

  19. 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.

  20. Detection of Helicobacter pylori resistance to clarithromycin and fluoroquinolones in Brazil: A national survey

    PubMed Central

    Sanches, Bruno Squarcio; Martins, Gustavo Miranda; Lima, Karine; Cota, Bianca; Moretzsohn, Luciana Dias; Ribeiro, Laercio Tenorio; Breyer, Helenice P; Maguilnik, Ismael; Maia, Aline Bessa; Rezende-Filho, Joffre; Meira, Ana Carolina; Pinto, Henrique; Alves, Edson; Mascarenhas, Ramiro; Passos, Raissa; de Souza, Julia Duarte; Trindade, Osmar Reni; Coelho, Luiz Gonzaga

    2016-01-01

    AIM To evaluate bacterial resistance to clarithromycin and fluoroquinolones in Brazil using molecular methods. METHODS The primary antibiotic resistance rates of Helicobacter pylori (H. pylori) were determined from November 2012 to March 2015 in the Southern, South-Eastern, Northern, North-Eastern, and Central-Western regions of Brazil. Four hundred ninety H. pylori patients [66% female, mean age 43 years (range: 18-79)] who had never been previously treated for this infection were enrolled. All patients underwent gastroscopy with antrum and corpus biopsies and molecular testing using GenoType HelicoDR (Hain Life Science, Germany). This test was performed to detect the presence of H. pylori and to identify point mutations in the genes responsible for clarithromycin and fluoroquinolone resistance. The molecular procedure was divided into three steps: DNA extraction from the biopsies, multiplex amplification, and reverse hybridization. RESULTS Clarithromycin resistance was found in 83 (16.9%) patients, and fluoroquinolone resistance was found in 66 (13.5%) patients. There was no statistical difference in resistance to either clarithromycin or fluoroquinolones (P = 0.55 and P = 0.06, respectively) among the different regions of Brazil. Dual resistance to clarithromycin and fluoroquinolones was found in 4.3% (21/490) of patients. The A2147G mutation was present in 90.4% (75/83), A2146G in 16.9% (14/83) and A2146C in 3.6% (3/83) of clarithromycin-resistant patients. In 10.8% (9/83) of clarithromycin-resistant samples, more than 01 mutation in the 23S rRNA gene was noticed. In fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. D91N mutation was observed in 34.8% (23/66), D91G in 18.1% (12/66), N87K in 16.6% (11/66) and D91Y in 13.6% (9/66) of cases. Among fluoroquinolone-resistant samples, 37.9% (25/66) showed mutations not specified by the GenoType HelicoDR test. CONCLUSION The H. pylori clarithromycin

  1. In-vitro activity of grepafloxacin, a new fluoroquinolone, against mycoplasmas.

    PubMed

    Bébéar, C M; Renaudin, H; Schaeverbeke, T; Leblanc, F; Bébéar, C

    1999-05-01

    The in-vitro activity of grepafloxacin, a new oral fluoroquinolone antibiotic, was compared with those of three other fluoroquinolones and two unrelated antimicrobials, doxycycline and erythromycin, against various Mycoplasma spp. For 65 mycoplasma and 42 ureaplasma strains, grepafloxacin (MIC range 0.03-2 mg/L) was some two to 16 times more active than ofloxacin and ciprofloxacin, showing similar activity to that of sparfloxacin. MBCs of grepafloxacin increased two- to 16-fold when compared with MICs and were comparable to those of sparfloxacin, and lower than those of ofloxacin and ciprofloxacin.

  2. Bug on the back: vertebral osteomyelitis secondary to fluoroquinolone resistant Salmonella typhi in an immunocompetent patient.

    PubMed

    Shrestha, Pragya; Mohan, Sachin; Roy, Satyajeet

    2015-11-27

    Although Salmonella osteomyelitis is commonly seen in immunocompromised patients, it may occasionally affect an immunocompetent host. Symptoms are usually non-specific, such as fever, abdominal or back pain; hence it should be considered in the differential diagnosis of patients with a history of travel to endemic regions. Fluoroquinolone resistance is rising and non-responsive patients should be treated with ampicillin, trimethoprim-sulfamethoxazole and ceftriaxone. We present a case of acute T8-T11 osteomyelitis with cord compression caused by a fluoroquinolone resistant strain of Salmonella typhi.

  3. Persistence and complex evolution of fluoroquinolone-resistant Streptococcus pneumoniae clone.

    PubMed

    Ben-David, Debby; Schwaber, Mitchell J; Adler, Amos; Masarwa, Samira; Edgar, Rotem; Navon-Venezia, Shiri; Schwartz, David; Porat, Nurith; Kotlovsky, Tali; Polivkin, Nikolay; Weinberg, Irina; Lazary, Avraham; Ohana, Nissim; Dagan, Ron

    2014-05-01

    Prolonged outbreaks of multidrug-resistant Streptococcus pneumoniae in health care facilities are uncommon. We found persistent transmission of a fluroquinolone-resistant S. pneumoniae clone during 2006-2011 in a post-acute care facility in Israel, despite mandatory vaccination and fluoroquinolone restriction. Capsular switch and multiple antimicrobial nonsusceptibility mutations occurred within this single clone. The persistent transmission of fluoroquinolone-resistant S. pneumoniae during a 5-year period underscores the importance of long-term care facilities as potential reservoirs of multidrug-resistant streptococci.

  4. Metalloantibiotics: synthesis, characterization and antimicrobial evaluation of bismuth-fluoroquinolone complexes against Helicobacter pylori.

    PubMed

    Shaikh, Anwar R; Giridhar, Rajani; Megraud, Francis; Yadav, Mange Ram

    2009-09-01

    Novel organometallic compounds have been prepared by complexing the fluoroquinolones, norfloxacin, ofloxacin, ciprofloxacin, sparfloxacin, lomefloxacin, pefloxacin and gatifloxacin, with bismuth. The complexes were characterized by UV, IR, atomic absorption spectroscopy, elemental analysis, differential scanning calorimetry, thermogravimetric analysis and mass spectrometry. Their antibacterial potential against Helicobacter pylori and other microorganisms was investigated. These compounds were found to possess strong activity against Helicobacter pylori with a minimum inhibitory concentration of 0.5 mg L-1. They also exhibited moderate activity against Escherichia coli, Staphylococcus aureus, Bacillus pumilus and Staphylococcus epidermidis. These bismuth-fluoroquinolone complexes have the potential to be developed as drugs against H. pylori related ailments.

  5. SatR Is a Repressor of Fluoroquinolone Efflux Pump SatAB

    PubMed Central

    Escudero, Jose Antonio; San Millan, Alvaro; Montero, Natalia; Gutierrez, Belen; Ovejero, Cristina Martinez; Carrilero, Laura

    2013-01-01

    Streptococcus suis is an emerging zoonotic agent responsible for high-mortality outbreaks among the human population in China. In this species, the ABC transporter SatAB mediates fluoroquinolone resistance when overexpressed. Here, we describe and characterize satR, an open reading frame (ORF) encoding a MarR superfamily regulator that acts as a repressor of satAB. satR is cotranscribed with satAB, and its interruption entails the overexpression of the pump, leading to a clinically relevant increase in resistance to fluoroquinolones. PMID:23650171

  6. The St. Jude Cancer Education for Children Program Pilot Study: Determining the Knowledge Acquisition and Retention of 4th-Grade Students.

    PubMed

    Ayers, Katherine; Villalobos, Aubrey Van Kirk; Li, Zhenghong; Krasin, Matthew

    2016-03-01

    In 2006, St. Jude Children's Research Hospital began developing a school-based outreach program known as the St. Jude Cancer Education for Children Program (SJCECP). The program aimed to teach children about cancer and healthy habits that can prevent the formation of cancers into adulthood. During the 2010-2011 academic years, we conducted a pilot evaluation of the SJCECP curriculum, with the primary objective of evaluating the impact of the intervention on knowledge acquisition and retention among 4th-grade students participating in the program. Seven local schools and 481 students from the Memphis area participated in the program evaluation. The results of this study show that 4th-grade students are able to acquire gains in knowledge related to cells, cancer, and healthy living after receiving the SJCECP intervention. We conclude that the program can be a useful tool for improving knowledge of cancer concepts at the 4th-grade level.

  7. 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

  8. 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.

  9. 4th International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis. Various uses for DNA variations.

    PubMed

    Brookes, Anthony J

    2002-02-01

    At the 4th International Meeting on Single Nucleotide Polymorphism and Complex Genome Analysis (Stockholm, Sweden, 10th-14th October 2001), approximately 100 scientists from more than 20 nations undertook a probing review of latest developments in the field. Despite impressive and still ongoing activities towards SNP discovery and validation, plus efforts towards haplotype exploitation, it was clear that supporting technologies for genotyping are way behind where they need to be. Innate complexity and large variances in aspects of genome function together pose immense challenges that are difficult to surmount in the human situation. In contrast, studies in simpler organisms and population/evolutionary genetics studies are yielding important new insights. Breakthroughs that are being made in understanding the genetic etiology of complex disease tend to involve genes of larger effect or extremely well merited candidates. Linkage studies and proximal phenotypes are being recommended, though the best way forward is still hotly debated. Consequently, many diverse and ambitious projects are underway, from which the data itself will eventually show what is and is not possible.

  10. 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.

  11. [Experience with percutaneous endoscopic gastrostomy in the nutrition of a patient with 3rd and 4th degree facial burns].

    PubMed

    Halmy, C; Szücs, A; Gyökeres, T; Dékány, K; Mezeine, T I; Kertész, E

    1998-05-17

    Recovery after thermal injury depends in great proportion on nutrition. A major problem is accounted in patients with facial burn, because they can not be nourished per vias naturales. Eliminating disadvantages of parenteral nutrition, but utilizing the advantages of enteral nutrition, we have tried a new method of treatment in a patient whose case is presented. On the second day after injury a percutaneous endoscopic gastrostomy was made. On the 7th day after injury and on the 4th day from the beginning of enteral nutrition complete intake of food and liquid was assured through the percutaneous endoscopic gastrostoma. We had no complication related to the gastrostoma. Nutrition through the percutaneous endoscopic gastrostoma at our patient provided a "natural" route to assure liquid, electrolite and energy balance, prevented atrophy of intestinal mucosa and its metabolic and immunologic complications. With the use of percutaneous endoscopic gastrostoma the possible complications of central line catheter were omitted. Our opinion is that percutaneous endoscopic gastrostomy is a safe and effective method for the clinical nutrition of burned patients.

  12. 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

  13. Occurrence of (fluoro)quinolones and (fluoro)quinolone resistance in soil receiving swine manure for 11 years.

    PubMed

    Xu, Yonggang; Yu, Wantai; Ma, Qiang; Zhou, Hua

    2015-10-15

    Because of the widespread use of antibiotics in animal breeding, the agricultural application of animal manure can lead to the introduction of antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes to the soil and surrounding environment, which may pose a threat to public health. In this study, we investigated the status of (fluoro)quinolone (FQ) residues and FQ resistance levels in soil with and without receiving long-term swine manure. Six FQs (pipemidic acid, lomefloxacin, enrofloxacin, norfloxacin, ciprofloxacin, and ofloxacin) were only detected in manured soil, with individual concentrations ranging from below the detection limit to 27.2 μg kg(-1) and increasing with the increase in swine manure application rates. Higher load rates of swine manure yielded a higher number of ciprofloxacin-resistant (CIPr) bacteria after spreading. A total of 24 CIPr bacterial isolates were obtained from the tested soil, which belonged to four phyla (Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes) or were related to nine different genera. Only 18 isolates from manured soil were positive for five plasmid-mediated quinolone resistance (PMQR) genes (aac(6')-Ib-cr, qnrD, qepA, oqxA, and oqxB). To our knowledge, this study is the first to examine the occurrence of PMQR genes in FQ-resistant bacteria from the soil environment. A similar result was observed for the total DNA from soil, with the exception of aac(6')-Ib being detected in the control sample. The absolute and relative abundances of total PMQR genes also increased with fertilization quantity. Significant correlations were observed between FQ resistance levels and FQ concentrations. These results indicated that the agricultural application of swine manure led to FQ residues and enhanced FQ resistance. This investigation provides baseline data on FQ resistance profiles in soils receiving long-term swine manure.

  14. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors.

    PubMed

    Wright, John M; Vered, Marilena

    2017-03-01

    The 4th edition of the World Health Organization's Classification of Head and Neck Tumours was published in January of 2017. This article provides a summary of the changes to Chapter 4 Tumours of the oral cavity and mobile tongue and Chapter 8 Odontogenic and maxillofacial bone tumours. Odontogenic cysts which were eliminated from the 3rd 2005 edition were included in the 4th edition as well as other unique allied conditons of the jaws. Many new tumors published since 2005 have been included in the 2017 classification.

  15. Genomic Analysis of the Evolution of Fluoroquinolone Resistance in Mycobacterium tuberculosis Prior to Tuberculosis Diagnosis.

    PubMed

    Zhang, Danfeng; Gomez, James E; Chien, Jung-Yien; Haseley, Nathan; Desjardins, Christopher A; Earl, Ashlee M; Hsueh, Po-Ren; Hung, Deborah T

    2016-11-01

    Fluoroquinolones (FQs) are effective second-line drugs for treating antibiotic-resistant tuberculosis (TB) and are being considered for use as first-line agents. Because FQs are used to treat a range of infections, in a setting of undiagnosed TB, there is potential to select for drug-resistant Mycobacterium tuberculosis mutants during FQ-based treatment of other infections, including pneumonia. Here we present a detailed characterization of ofloxacin-resistant M. tuberculosis samples isolated directly from patients in Taiwan, which demonstrates that selection for FQ resistance can occur within patients who have not received FQs for the treatment of TB. Several of these samples showed no mutations in gyrA or gyrB based on PCR-based molecular assays, but genome-wide next-generation sequencing (NGS) revealed minority populations of gyrA and/or gyrB mutants. In other samples with PCR-detectable gyrA mutations, NGS revealed subpopulations containing alternative resistance-associated genotypes. Isolation of individual clones from these apparently heterogeneous samples confirmed the presence of the minority drug-resistant variants suggested by the NGS data. Further NGS of these purified clones established evolutionary links between FQ-sensitive and -resistant clones derived from the same patient, suggesting de novo emergence of FQ-resistant TB. Importantly, most of these samples were isolated from patients without a history of FQ treatment for TB. Thus, selective pressure applied by FQ monotherapy in the setting of undiagnosed TB infection appears to be able to drive the full or partial emergence of FQ-resistant M. tuberculosis, which has the potential to confound diagnostic tests for antibiotic susceptibility and limit the effectiveness of FQs in TB treatment.

  16. 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.

  17. [Level of smoking of 3rd and 4th grade students studying health and related factors: follow-up study].

    PubMed

    Göktalay, Tuğba; Cengiz Özyurt, Beyhan; Sakar Coşkun, Ayşin; Celik, Pinar

    2011-01-01

    The levels of smoking of 1st and 2nd year students at Faculty of Medicine and Manisa School of Health at Celal Bayar University were investigated in 2006-2007. This study is carried out in order to see if there is a change in the same students' level of smoking while they are in 3rd and 4th year. In addition, the study aimed to examine the factors affecting the level of use and attitudes towards the law effectuated in July 19, 2009. This is a follow-up study with 80.42% return rate. A 26-item structured questionnaire was administered. The participants filled out the questionnaires under supervision of the researchers in their classrooms. The University Institutional Review Board approved the study. The total of participants (263) of the follow-up study included 189 female and 74 male. The rate of experimenting with smoking was 49% with the mean age of 15.7 (SD= 4.01 years). The mean age of experimenting with smoking was the earliest on male students studying at faculty of medicine. The level of smoking was found to be the most on females, studying at faculty of medicine and staying at the dormitory, with smoking parents (p< 0.05). The most important reason to begin smoking was curiosity (55.2%) while bad breath and yellowing of teeth were the reasons to quit (91.7%). 83.3% of the students thought that the law will be effective on quit smoking. The level of both experimenting and use of smoking has been increased over time. It is suggested that medical students' awareness about the danger of smoking should be raised at earlier grades. In addition, lectures should be offered to students at School of Health and they should be encouraged to unite in order to fight with smoking.

  18. 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.

  19. 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

  20. Role of Efflux Pumps and Topoisomerase Mutations in Fluoroquinolone Resistance in Campylobacter jejuni and Campylobacter coli

    PubMed Central

    Ge, Beilei; McDermott, Patrick F.; White, David G.; Meng, Jianghong

    2005-01-01

    Point mutations in the topoisomerase (DNA gyrase A) gene are known to be associated with fluoroquinolone resistance in Campylobacter. Recent studies have shown that an efflux pump encoded by cmeABC is also involved in decreased susceptibilities to fluoroquinolones, as well as other antimicrobials. Genome analysis suggests that Campylobacter jejuni contains at least nine other putative efflux pumps. Using insertional inactivation and site-directed mutagenesis, we investigated the potential contributions of these pumps to susceptibilities to chloramphenicol, ciprofloxacin, erythromycin, and tetracycline in C. jejuni and Campylobacter coli. Insertional inactivation of cmeB resulted in 4- to 256-fold decreases in the MICs of chloramphenicol, ciprofloxacin, erythromycin, and tetracycline, with erythromycin being the most significantly affected. In contrast, inactivation of all other putative efflux pumps had no effect on susceptibility to any of the four antimicrobials tested. Mutation of gyrA at codon 86 (Thr-Ile) caused 128- and 64-fold increases in the MICs of ciprofloxacin and nalidixic acid, respectively. The replacement of the mutated gyrA with a wild-type gyrA allele resulted in a 32-fold decrease in the ciprofloxacin MIC and no change in the nalidixic acid MIC. Our findings indicate that CmeABC is the only efflux pump among those tested that influences antimicrobial resistance in Campylobacter and that a point mutation (Thr-86-Ile) in gyrA directly causes fluoroquinolone resistance in Campylobacter. These two mechanisms work synergistically in acquiring and maintaining fluoroquinolone resistance in Campylobacter species. PMID:16048946

  1. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 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.

  6. 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.

  7. Draft Genome Sequences of Streptococcus pneumoniae with High-Level Resistance to Respiratory Fluoroquinolones.

    PubMed

    Keness, Yoram; Bisharat, Naiel

    2016-03-31

    Streptococcus pneumoniaeis the leading cause of community-acquired pneumonia. Levofloxacin is a fluoroquinolone used for treatment of severe community-acquired pneumonia. Here, we describe the draft genome sequences ofS. pneumoniaewith emerging resistance to levofloxacin, resulting in failure of treatment of pneumococcal pneumonia.

  8. 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...

  9. The Attitude of the Students towards the Value of "Paying Attention to Being Healthy" in 4th Grade Elementary Social Sciences Course

    ERIC Educational Resources Information Center

    Tahiroglu, Mustafa; Cetin, Turhan

    2012-01-01

    This study was aimed to define the teaching of the value of "Paying Attention to Being Healthy" in 4th grade elementary Social Sciences course and to determine the students' attitude towards this value. To reach this goal, activities to teach the value of paying attention to being healthy were prepared and conducted. The effect of these…

  10. 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…

  11. 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…

  12. 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%;…

  13. 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…

  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…

  15. 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…

  16. Correlation Between Virulence Genotype and Fluoroquinolone Resistance in Carbapenem-Resistant Pseudomonas aeruginosa

    PubMed Central

    Cho, Hye Hyun; Kwon, Kye Chul; Kim, Semi

    2014-01-01

    Background Pseudomonas aeruginosa is a clinically important pathogen that causes opportunistic infections and nosocomial outbreaks. Recently, the type III secretion system (TTSS) has been shown to play an important role in the virulence of P. aeruginosa. ExoU, in particular, has the greatest impact on disease severity. We examined the relationship among the TTSS effector genotype (exoS and exoU), fluoroquinolone resistance, and target site mutations in 66 carbapenem-resistant P. aeruginosa strains. Methods Sixty-six carbapenem-resistant P. aeruginosa strains were collected from patients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Minimum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to determine the TTSS effector genotype and quinolone resistance-determining regions (QRDRs) of the respective target genes gyrA, gyrB, parC, and parE. Results A higher proportion of exoU+ strains were fluoroquinolone-resistant than exoS+ strains (93.2%, 41/44 vs. 45.0%, 9/20; P≤0.0001). Additionally, exoU+ strains were more likely to carry combined mutations than exoS+ strains (97.6%, 40/41 vs. 70%, 7/10; P=0.021), and MIC increased as the number of active mutations increased. Conclusions The recent overuse of fluoroquinolone has led to both increased resistance and enhanced virulence of carbapenem-resistant P. aeruginosa. These data indicate a specific relationship among exoU genotype, fluoroquinolone resistance, and resistance-conferring mutations. PMID:24982833

  17. Introduction and establishment of fluoroquinolone-resistant Shigella sonnei into Bhutan

    PubMed Central

    Chung The, Hao; Rabaa, Maia A.; Thanh, Duy Pham; Ruekit, Sirigade; Wangchuk, Sonam; Dorji, Tshering; Tshering, Kinzang Pem; Nguyen, To Nguyen Thi; Vinh, Phat Voong; Thanh, Tuyen Ha; Minh, Chau Nguyen Ngoc; Turner, Paul; Sar, Poda; Thwaites, Guy; Holt, Kathryn E.; Thomson, Nicholas R.; Bodhidatta, Ladaporn; Jeffries Mason, Carl; Baker, Stephen

    2015-01-01

    Shigella sonnei is a major contributor to the global burden of diarrhoeal disease, generally associated with dysenteric diarrhoea in developed countries but also emerging in developing countries. The reason for the recent success of S. sonnei is unknown, but is likely catalysed by its ability to acquire resistance against multiple antimicrobials. Between 2011 and 2013, S. sonnei exhibiting resistance to fluoroquinolones, the first-line treatment recommended for shigellosis, emerged in Bhutan. Aiming to reconstruct the introduction and establishment of fluoroquinolone-resistant S. sonnei populations in Bhutan, we performed whole-genome sequencing on 71 S. sonnei samples isolated in Bhutan between 2011 and 2013.We found that these strains represented an expansion of a clade within the previously described lineage III, found specifically in Central Asia. Temporal phylogenetic reconstruction demonstrated that all of the sequenced Bhutanese S. sonnei diverged from a single ancestor that was introduced into Bhutan around 2006. Our data additionally predicted that fluoroquinolone resistance, conferred by mutations in gyrA and parC, arose prior to the introduction of the founder strain into Bhutan. Once established in Bhutan, these S. sonnei had access to a broad gene pool, as indicated by the acquisition of extended-spectrum β-lactamase-encoding plasmids and genes encoding type IV pili. The data presented here outline a model for the introduction and maintenance of fluoroquinolone-resistant S. sonnei in a new setting. Given the current circulation of fluoroquinolone-resistant S. sonnei in Asia, we speculate that this pattern of introduction is being recapitulated across the region and beyond. PMID:28348825

  18. 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

  19. 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

    2016-02-09

    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

  20. 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

  1. 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

  2. Intensity and Mechanisms of Fluoroquinolone Resistance within the H30 and H30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli

    PubMed Central

    Johnston, Brian; Kuskowski, Michael A.; Sokurenko, Evgeni V.; Tchesnokova, Veronika

    2015-01-01

    The recent expansion of the H30 subclone of Escherichia coli sequence type 131 (ST131) and its CTX-M-15-associated H30Rx subset remains unexplained. Although ST131 H30 typically exhibits fluoroquinolone resistance, so do multiple other E. coli lineages that have not expanded similarly. To determine whether H30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistant E. coli isolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistant E. coli isolates (48 non-H30 and 41 H30 [23 H30Rx and 18 H30 non-Rx]). We compared the MICs with the H30 and H30Rx status, the presence/number of nonsynonymous mutations in gyrA, parC, and parE, the presence of aac(6′)-1b-cr (an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recent E. coli clinical isolates, ST131 H30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-H30 isolates, H30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations in gyrA, parC, and parE (specifically gyrA D87N, parC E84V, and parE I529L), and a numerically higher prevalence of (H30Rx-associated) aac(6′)-1b-cr but lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [for aac(6′)-1b-cr: ciprofloxacin and norfloxacin only]. parC D87N corresponded with ST131 H30 and parE I529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131 H30, especially H30Rx [if aac(6′)-1b-cr positive], with subtle fitness advantages over other fluoroquinolone-resistant E. coli strains. This urges both parsimonious

  3. Intensity and Mechanisms of Fluoroquinolone Resistance within the H30 and H30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli.

    PubMed

    Johnson, James R; Johnston, Brian; Kuskowski, Michael A; Sokurenko, Evgeni V; Tchesnokova, Veronika

    2015-08-01

    The recent expansion of the H30 subclone of Escherichia coli sequence type 131 (ST131) and its CTX-M-15-associated H30Rx subset remains unexplained. Although ST131 H30 typically exhibits fluoroquinolone resistance, so do multiple other E. coli lineages that have not expanded similarly. To determine whether H30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistant E. coli isolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistant E. coli isolates (48 non-H30 and 41 H30 [23 H30Rx and 18 H30 non-Rx]). We compared the MICs with the H30 and H30Rx status, the presence/number of nonsynonymous mutations in gyrA, parC, and parE, the presence of aac(6')-1b-cr (an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recent E. coli clinical isolates, ST131 H30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-H30 isolates, H30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations in gyrA, parC, and parE (specifically gyrA D87N, parC E84V, and parE I529L), and a numerically higher prevalence of (H30Rx-associated) aac(6')-1b-cr but lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [for aac(6')-1b-cr: ciprofloxacin and norfloxacin only]. parC D87N corresponded with ST131 H30 and parE I529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131 H30, especially H30Rx [if aac(6')-1b-cr positive], with subtle fitness advantages over other fluoroquinolone-resistant E. coli strains. This urges both parsimonious fluoroquinolone

  4. Synthesis and biological activity of fluoroquinolone-pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

    PubMed

    Kamal, Ahmed; Devaiah, V; Reddy, K Laxma; Kumar, M Shiva

    2005-03-15

    Fluoroquinolones have been synthesized and linked to DC-81 at C8 position through different alkyl chain spacers. These PBD conjugates have exhibited good DNA binding affinity, and a representative compound shows promising in vitro anticancer activity.

  5. Prediction of Fluoroquinolone Resistance in Gram-Negative Bacteria Causing Bloodstream Infections.

    PubMed

    Dan, Seejil; Shah, Ansal; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2016-04-01

    Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve (AUC). Among 824 patients with Gram-negative BSI, 143 (17%) had BSI due to fluoroquinolone-nonsusceptible Gram-negative bacilli. Independent risk factors for FQ-R and point allocation in FQRS included male sex (adjusted odds ratio [aOR], 1.97; 95% confidence intervals [CI], 1.36 to 2.98; 1 point), diabetes mellitus (aOR, 1.54; 95% CI, 1.03 to 2.28; 1 point), residence at a skilled nursing facility (aOR, 2.28; 95% CI, 1.42 to 3.63; 2 points), outpatient procedure within 30 days (aOR, 3.68; 95% CI, 1.96 to 6.78; 3 points), prior fluoroquinolone use within 90 days (aOR, 7.87; 95% CI, 4.53 to 13.74; 5 points), or prior fluoroquinolone use within 91 to 180 days of BSI (aOR, 2.77; 95% CI, 1.17 to 6.16; 3 points). The AUC for both final logistic regression and FQRS models was 0.73. Patients with an FQRS of 0, 3, 5, or 8 had predicted probabilities of FQ-R of 6%, 22%, 39%, or 69%, respectively. The estimation of patient-specific risk of antimicrobial resistance using FQRS may improve empirical antimicrobial therapy and fluoroquinolone utilization in Gram-negative BSI.

  6. Evaluation of (99m)Tc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection.

    PubMed

    Nayak, Dipak Kumar; Baishya, Rinku; Halder, Kamal Krishna; Sen, Tuhinadri; Sarkar, Bharat R; Ganguly, Shantanu; Das, M K; Debnath, Mita Chatterjee

    2012-11-01

    The aim of this study was to develop (99m)Tc(CO)(3)-labeled fluoroquinolones as novel SPECT radiopharmaceuticals for imaging bacterial infection. Fluoroquinolones, e.g., ofloxacin (OFX), levofloxacin (LVX), lomefloxacin (LMX) and norfloxacin (NFX) were labeled with a fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor. The radiochemical purity of the radiopharmaceuticals exceeded 97% as determined by thin layer chromatography and HPLC. No further purification was necessary before injection. The Re(CO)(3) complex of one of the fluoroquinolones (levofloxacin) was synthesized using [Re(CO)(3)(H(2)O)(3)]OTf and Re(CO)(5)Br precursors in separate experiments and characterized by IR, NMR and mass spectroscopic analysis. These studies revealed the formation of a single species in which the piperazinyl nitrogen and the -COOH group attached to the benzoxazine ring system of quinolone were involved in co-ordination to the Re(CO)(3) core. The HPLC elution pattern and retention time of the Re(CO)(3)-LVX complex were comparable to those of the corresponding (99m)Tc(CO)(3)-complex proving their similarity. When incubated in isotonic saline and serum up to 24 h (99m)Tc(CO)(3)-labeled fluoroquinolones exhibited good in vitro stability. Biodistribution studies performed at different time points on rats intramuscularly infected with S. aureus as well as on rats with sterile inflammation revealed a higher uptake in the infected area than the turpentine induced inflamed area. The uptake in infected thigh was significant with (99m)Tc(CO)(3)-OFX followed by (99m)Tc(CO)(3)-LVX. The mean ratios of the uptake in infected/non-infected thighs were 4.75 and 4.27 at 8 h and 24 h, respectively, for (99m)Tc(CO)(3)-OFX and 4.42 and 4.18 at 24 h and 8 h, respectively, for (99m)Tc(CO)(3)-LVX. The above abscess to muscle ratios were higher than reported for (99m)Tc-ciprofloxacin and other (99m)Tc-labeled fluoroquinolones. Scintigraphy studies also showed a significant uptake in the infectious lesions

  7. Prediction of Fluoroquinolone Resistance in Gram-Negative Bacteria Causing Bloodstream Infections

    PubMed Central

    Dan, Seejil; Shah, Ansal; Justo, Julie Ann; Bookstaver, P. Brandon; Kohn, Joseph; Albrecht, Helmut

    2016-01-01

    Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve (AUC). Among 824 patients with Gram-negative BSI, 143 (17%) had BSI due to fluoroquinolone-nonsusceptible Gram-negative bacilli. Independent risk factors for FQ-R and point allocation in FQRS included male sex (adjusted odds ratio [aOR], 1.97; 95% confidence intervals [CI], 1.36 to 2.98; 1 point), diabetes mellitus (aOR, 1.54; 95% CI, 1.03 to 2.28; 1 point), residence at a skilled nursing facility (aOR, 2.28; 95% CI, 1.42 to 3.63; 2 points), outpatient procedure within 30 days (aOR, 3.68; 95% CI, 1.96 to 6.78; 3 points), prior fluoroquinolone use within 90 days (aOR, 7.87; 95% CI, 4.53 to 13.74; 5 points), or prior fluoroquinolone use within 91 to 180 days of BSI (aOR, 2.77; 95% CI, 1.17 to 6.16; 3 points). The AUC for both final logistic regression and FQRS models was 0.73. Patients with an FQRS of 0, 3, 5, or 8 had predicted probabilities of FQ-R of 6%, 22%, 39%, or 69%, respectively. The estimation of patient-specific risk of antimicrobial resistance using FQRS may improve empirical antimicrobial therapy and fluoroquinolone utilization in Gram-negative BSI. PMID:26833166

  8. 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

  9. Association between fluoroquinolone usage and a dramatic rise in ciprofloxacin-resistant Streptococcus pneumoniae in Canada, 1997-2006.

    PubMed

    Adam, Heather J; Hoban, Daryl J; Gin, Alfred S; Zhanel, George G

    2009-07-01

    This study evaluated the prevalence of fluoroquinolone usage and investigated the association between usage and resistance in respiratory isolates of Streptococcus pneumoniae in Canada. Fluoroquinolone susceptibility testing was conducted on S. pneumoniae collected from 25 medical centres across Canada over nine study years. Fluoroquinolone prescriptions and consumption figures were derived from data in the IMS Health, Canada CompuScript Audit. Between 1997 and 2006, 11825 S. pneumoniae isolates were collected. Ciprofloxacin resistance rates increased significantly (P<0.01) during the study from 0% to 4.5% in children (0-15 years), from 0.2% to 5.4% in adults (16-64 years) and from 1.4% to 11.6% in the elderly (> or = 65 years). Outpatient ciprofloxacin and respiratory fluoroquinolone prescriptions increased by 55.6% (38.2 prescriptions/1000 population to 59.4 prescriptions/1000 population; P<0.01) and 416.2% (5.3 prescriptions/1000 to 27.4 prescriptions/1000; P<0.01), respectively. Ciprofloxacin and respiratory fluoroquinolone consumption increased by 10.6% [1.1 defined daily doses (DDDs)/1000/day to 1.2 DDDs/1000/day; P=0.02] and 38.2% (0.5 to 0.7 DDDs/1000/day; P=0.02), respectively, from 2001 to 2006. A strong association between ciprofloxacin use and resistance (R(2)=0.89) was identified. Fluoroquinolone resistance in S. pneumoniae increased significantly in Canada from 1997 to 2006 in conjunction with increased ciprofloxacin and respiratory fluoroquinolone consumption. Ciprofloxacin usage appears to be the biggest driver of resistance; however, total fluoroquinolone usage is also important.

  10. STO-2: Support for 4th Year Operations, Recovery, and Science JHU/APL Co-I

    NASA Astrophysics Data System (ADS)

    Bernasconi, Pietro

    This is a collaboration Co-I Institution proposal for the proposal "STO-2: Support for 4th Year Operations, Recovery, and Science" whose lead proposal is submitted by the University of Arizona with Dr. Christofer Walker as PI. STO-2 was flight-ready in the 2015-2016 austral summer. However, due to the late establishment of the stratospheric anti-cyclone and poor surface conditions, STO-2 was unable to launch. The decision was made to winter-over the STO-2 payload in its hangar for launch during the 2016-2017 Antarctic campaign. Funds to cover preparations and deployment of key members of the instrument team in support of the campaign are being provided by NASA under the existing grant. However, these funds are only sufficient to cover expenses up to approximately December 31st. Here we request supplemental funds to cover costs associated with STO-2 operations and recovery beyond this date. STO-2 will address a key problem in modern astrophysics, understanding the Life Cycle of the Interstellar Medium (ISM). STO-2 will survey approximately 1/4 of the Southern Galactic Plane in the dominant interstellar cooling line [CII] (158 μm) and the important star formation tracer [NII] (205 μm). In addition, STO-2 will perform path finding observations of the 63 μm [OI] line toward selected regions. With 1 arcminute angular resolution, STO-2 will spatially resolve atomic, ionic and molecular clouds out to 10 kpc. The STO-2 survey will be conducted at unparalleled sensitivity levels. STO-2 will uniquely probe the pivotal formative and disruptive stages in the life cycle of interstellar clouds and the relationship between global star formation rates and the properties of the ISM. Combined with previous HI and CO surveys, STO-2 will create 3-dimensional maps of the structure, dynamics, turbulence, energy balance, and pressure of the Milky Way's ISM, as well as the star formation rate. Once we gain an understanding of the relationship between ISM properties and star formation

  11. 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

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

    PubMed

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

    2015-11-02

    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.

  13. Fluoroquinolone resistance mechanisms in an Escherichia coli isolate, HUE1, without quinolone resistance-determining region mutations

    PubMed Central

    Sato, Toyotaka; Yokota, Shin-ichi; Uchida, Ikuo; Okubo, Torahiko; Usui, Masaru; Kusumoto, Masahiro; Akiba, Masato; Fujii, Nobuhiro; Tamura, Yutaka

    2013-01-01

    Fluoroquinolone resistance can cause major clinical problems. Here, we investigated fluoroquinolone resistance mechanisms in a clinical Escherichia coli isolate, HUE1, which had no mutations quinolone resistance-determining regions (QRDRs) of DNA gyrase and topoisomerase IV. HUE1 demonstrated MICs that exceeded the breakpoints for ciprofloxacin, levofloxacin, and norfloxacin. HUE1 harbored oqxAB and qnrS1 on distinct plasmids. In addition, it exhibited lower intracellular ciprofloxacin concentrations and higher mRNA expression levels of efflux pumps and their global activators than did reference strains. The genes encoding AcrR (local AcrAB repressor) and MarR (MarA repressor) were disrupted by insertion of the transposon IS3-IS629 and a frameshift mutation, respectively. A series of mutants derived from HUE1 were obtained by plasmid curing and gene knockout using homologous recombination. Compared to the MICs of the parent strain HUE1, the fluoroquinolone MICs of these mutants indicated that qnrS1, oqxAB, acrAB, acrF, acrD, mdtK, mdfA, and tolC contributed to the reduced susceptibility to fluoroquinolone in HUE1. Therefore, fluoroquinolone resistance in HUE1 is caused by concomitant acquisition of QnrS1 and OqxAB and overexpression of AcrAB–TolC and other chromosome-encoded efflux pumps. Thus, we have demonstrated that QRDR mutations are not absolutely necessary for acquiring fluoroquinolone resistance in E. coli. PMID:23745120

  14. A global perspective for managing obesity and improving health: conventional treatment and surgical options: 4th Annual Obesity Summit, London, April 2016

    PubMed Central

    Ahmad, Adeel Nazir; Edwards, Kimberley L

    2016-01-01

    4th Annual Obesity Summit, London, 12–14 April 2016 There are more than 1.9 billion overweight people worldwide, culminating in high rates of Type 2 diabetes; and cardiovascular, digestive and other health problems. This makes obesity a startling phenomenon and a significant global health epidemic. To address this, The 2016 Obesity Summit, 4th in the series of obesity-related annual events organized by EuroSciCon, was held from 12 to 14 April 2016 at Cineworld, The O2 in London. This conference set the stage for three days of stimulating high-quality presentations on the advancements in obesity in an informal academic setting. Approximately 156 delegates including students, researchers, healthcare professionals and scientists from 36 countries around the world attended the event. This meeting report summarizes some of the most outstanding presentations. PMID:28116126

  15. A global perspective for managing obesity and improving health: conventional treatment and surgical options: 4th Annual Obesity Summit, London, April 2016.

    PubMed

    Ahmad, Adeel Nazir; Edwards, Kimberley L

    2016-12-01

    4th Annual Obesity Summit, London, 12-14 April 2016 There are more than 1.9 billion overweight people worldwide, culminating in high rates of Type 2 diabetes; and cardiovascular, digestive and other health problems. This makes obesity a startling phenomenon and a significant global health epidemic. To address this, The 2016 Obesity Summit, 4th in the series of obesity-related annual events organized by EuroSciCon, was held from 12 to 14 April 2016 at Cineworld, The O2 in London. This conference set the stage for three days of stimulating high-quality presentations on the advancements in obesity in an informal academic setting. Approximately 156 delegates including students, researchers, healthcare professionals and scientists from 36 countries around the world attended the event. This meeting report summarizes some of the most outstanding presentations.

  16. Biological Damage Threshold Induced by Ultrashort Fundamental, 2nd, and 4th Harmonic Light Pulses from a Mode-Locked Nd: Glass Laser.

    DTIC Science & Technology

    1980-12-01

    BY ULTRASHORT FUNDAMENTAL, 2ND, AND 4TH HARMONIC LIGHT PULSES 00 , FROM A MODE-LOCKED Nd:GLASS LASER C Adam P. Bruckner, Ph.D. J. Michael Schurr, Ph.D...Medicine, Aerospace Medical Division, AFSC, Brooks Air Force Base, Texas. Dr. Taboada (USAFSAM/RZL) was the Laboratory Project Scientist-in-Charge. When... TABOADA , Ph.D. /AONN E. PICKERING, M.S. Project Scientist Chief, Radiation Sciences Division ROY L. DEHART Colonel, USAF, MC Commander UNCLASSIFIED S

  17. Ovarian and adipose tissue dysfunction in polycystic ovary syndrome: report of the 4th special scientific meeting of the Androgen Excess and PCOS Society

    PubMed Central

    Yildiz, Bulent O.; Azziz, Ricardo

    2013-01-01

    Significant advances have been made in our understanding of ovarian dysfunction in polycystic ovary syndrome (PCOS), and alterations in adipose tissue function are likely to play an important role in its pathophysiology. This review highlights the principal novel concepts presented at the 4th special scientific meeting of the Androgen Excess and PCOS Society, “Ovarian and Adipose Tissue Dysfunction: Potential Roles in Polycystic Ovary Syndrome,” which occurred on June 6, 2008 in San Francisco, California. PMID:19394000

  18. Short communication: Fluoroquinolone susceptibility of Staphylococcus aureus strains isolated from caprine clinical mastitis in southeast Spain.

    PubMed

    Marín, P; Escudero, E; Fernández-Varón, E; Cárceles, C M; Corrales, J C; Gómez-Martín, A; Martínez, I

    2010-11-01

    The antibiotic susceptibility of 32 strains of Staphylococcus aureus isolated from the mastitic milk of dairy goats was evaluated. The antibiotics tested were 3 fluoroquinolones that have been developed especially for use in veterinary medicine: danofloxacin, marbofloxacin, and orbifloxacin. Minimum inhibitory concentration (MIC) tests were performed according to the microdilution broth method. The MIC(90) (concentration at which 90% inhibition is achieved) values obtained were 0.5, 1, and 1 mg/L for danofloxacin, marbofloxacin, and orbifloxacin, respectively. Danofloxacin was the most active fluoroquinolone tested against Staph. aureus strains isolated from milk; however, specific testing is required before using these drugs as therapy for the control of clinical mammary infections in goats.

  19. Design, synthesis, and evaluation of novel fluoroquinolone-aminoglycoside hybrid antibiotics.

    PubMed

    Pokrovskaya, Varvara; Belakhov, Valery; Hainrichson, Mariana; Yaron, Sima; Baasov, Timor

    2009-04-23

    A series of new hybrid structures containing fluoroquinolone (ciprofloxacin) and aminoglycoside (neomycin) antibiotics linked via 1,2,3-triazole moiety were designed and synthesized, and their antibacterial activities were determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The nature of spacers in both the ciprofloxacin and neomycin parts greatly influenced the antibacterial activity. The majority of hybrids was significantly more potent than the parent neomycin and overcame most prevalent types of resistance associated with aminoglycosides. Selected hybrids inhibited bacterial protein synthesis with the potencies similar to or better than that of neomycin and were up to 32-fold more potent inhibitors than ciprofloxacin for the fluoroquinolone targets, DNA gyrase and toposiomerase IV, indicating a balanced dual mode of action. Significant delay of resistance formation was observed in both E. coli and B. subtilis to the treatment with ciprofloxacin-neomycin hybrid in comparison to that of each drug separately or their 1:1 mixture.

  20. Chemiluminescence determination of fluoroquinolones using Fenton system in the presence of terbium(iii) ions.

    PubMed

    Kaczmarek, Małgorzata; Lis, Stefan

    2011-06-21

    A simple new chemiluminescent, CL, method is described for the determination of fluoroquinolones such as: ciprofloxacin (CF), norfloxacin (NF), and ofloxacin (OF). This method is based on the measurement of terbium(iii) emission. This emission follows an energy transfer to the uncomplexed terbium(iii) ions from the excited products of fluoroquinolone oxidations. Under optimum conditions, calibration graphs were obtained for 2 × 10(-8)-2 × 10(-6) mol L(-1) of NF; 3 × 10(-8)-2 × 10(-6) mol L(-1) of CF and 4 × 10(-7)-5 × 10(-5) mol L(-1) of OF. The detection limits are 7 × 10(-9) mol L(-1) norfloxacin, 1 × 10(-8) mol L(-1) ciprofloxacin and 1.5 × 10(-7) mol L(-1) ofloxacin. The method was successfully applied to the determination of these drugs in pharmaceutical formulations.

  1. Antimicrobial activity and a comparison of published pharmacodynamics of gemifloxacin and eight fluoroquinolones against Streptococcus pneumoniae.

    PubMed

    Saravolatz, Louis; Manzor, Odette; Pawlak, Joan; Belian, Bradley

    2005-07-01

    Gemifloxacin was evaluated for its in vitro activity and was compared with eight fluoroquinolones. Pharmacodynamic comparisons were made based on published pharmacokinetic information. Gemifloxacin demonstrated excellent in vitro activity (minimum inhibitory concentration necessary to inhibit 90% of the strains tested, MIC90 = 0.03 mg/L (range 0.0019-0.03 mg/L)) against 199 strains of Streptococcus pneumoniae. Its activity was not influenced by penicillin or ciprofloxacin non-susceptibility. Gemifloxacin demonstrated excellent pharmacodynamic parameters, with a Cmax/MIC90 of 67 (where Cmax is the peak serum level) and an AUC/MIC90 of 297 (where AUC is the area under the curve). Compared with the other eight fluoroquinolones tested, gemifloxacin demonstrated the best in vitro activity and Cmax/MIC90.

  2. New hydroxamic acid derivatives of fluoroquinolones: synthesis and evaluation of antibacterial and anticancer properties.

    PubMed

    Rajulu, Gavara Govinda; Bhojya Naik, Halehatty Seephya; Viswanadhan, Abhilash; Thiruvengadam, Jayaraman; Rajesh, Kondodiyil; Ganesh, Sambasivam; Jagadheshan, Hiriyan; Kesavan, Poonimangadu Koppolu

    2014-01-01

    A series of new hydroxamic acid derivatives (6a-f) at C-3 position of fluoroquinolones were designed and synthesized through multistep synthesis. The design concept involved replacement of the 3-carboxylic acid in fluoquinolones with hydroxamic acid as an acid mimicking group. The synthetic work employed in this work provides a good example for the synthesis of pure hydroxamic acid based fluoroquinolones. The synthesized compounds were characterized by (1)H-NMR, electrospray ionization (ESI)-MS and IR. The new compounds were tested for their in vitro antimicrobial and anti-proliferative activity. Out of the six derivatives, compound 6e exhibited moderate antibacterial activity by inhibiting the growth of Escherichia coli and Klebsiella pneumoniae (MIC: 4.00-8.00 µg/mL). Compounds 6b and 6f displayed good growth inhibition against A549 Lung adenocarcinoma and HCT-116 Colon carcinoma cell lines.

  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. The antifungal caspofungin increases fluoroquinolone activity against Staphylococcus aureus biofilms by inhibiting N-acetylglucosamine transferase

    PubMed Central

    Siala, Wafi; Kucharíková, Soňa; Braem, Annabel; Vleugels, Jef; Tulkens, Paul M; Mingeot-Leclercq, Marie-Paule; Van Dijck, Patrick; Van Bambeke, Françoise

    2016-01-01

    Biofilms play a major role in Staphylococcus aureus pathogenicity but respond poorly to antibiotics. Here, we show that the antifungal caspofungin improves the activity of fluoroquinolones (moxifloxacin, delafloxacin) against S. aureus biofilms grown in vitro (96-well plates or catheters) and in vivo (murine model of implanted catheters). The degree of synergy among different clinical isolates is inversely proportional to the expression level of ica operon, the products of which synthesize poly-N-acetyl-glucosamine polymers, a major constituent of biofilm matrix. In vitro, caspofungin inhibits the activity of IcaA, which shares homology with β-1-3-glucan synthase (caspofungin's pharmacological target in fungi). This inhibition destructures the matrix, reduces the concentration and polymerization of exopolysaccharides in biofilms, and increases fluoroquinolone penetration inside biofilms. Our study identifies a bacterial target for caspofungin and indicates that IcaA inhibitors could potentially be useful in the treatment of biofilm-related infections. PMID:27808087

  5. The battle against emerging antibiotic resistance: should fluoroquinolones be used to treat children?

    PubMed

    Mandell, Lionel A; Peterson, Lance R; Wise, Richard; Hooper, David; Low, Donald E; Schaad, Urs B; Klugman, Keith P; Courvalin, Patrice

    2002-09-15

    Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adults.

  6. Impact of fluoroquinolone resistance in Gram-negative bloodstream infections on healthcare utilization.

    PubMed

    Brigmon, M M; Bookstaver, P Brandon; Kohn, J; Albrecht, H; Al-Hasan, M N

    2015-09-01

    There has been a concerning increase in fluoroquinolone resistance among Gram-negative bloodstream isolates. This retrospective cohort study examines the implications of fluoroquinolone resistance on use of healthcare resources in patients with Gram-negative bloodstream infections (BSI). Hospitalized adults with first episodes of community-onset Gram-negative BSI from 2010 to 2012 at Palmetto Health Hospitals in Columbia, SC, USA were identified. Multivariate linear regression was used to examine risk factors for prolonged hospital length of stay (HLOS) in survivors of Gram-negative BSI. Among 474 unique patients, 384 (81%) and 90 (19%) had BSI due to fluoroquinolone-susceptible (FQ-S) and fluoroquinolone non-susceptible (FQ-NS) Gram-negative bacilli, respectively. The FQ-NS bloodstream isolates, particularly Escherichia coli, were more likely than FQ-S isolates to be multi-drug resistant (56% versus 6%, p < 0.001). Compared with patients with BSI due to FQ-S bloodstream isolates, those with FQ-NS isolates were more likely to receive inappropriate empirical antimicrobial therapy (26% versus 3%, p < 0.001), have longer mean HLOS (11.6 versus 9.3 days, p 0.03) and treatment duration with intravenous antibiotics during hospitalization (9.1 versus 7.1 days, p 0.001), and use outpatient intravenous antibiotics at hospital discharge (15% versus 8%, p 0.05). After adjustments in the multivariate model, inappropriate empirical antimicrobial therapy was an independent risk factor for prolonged HLOS in survivors of Gram-negative BSI (parameter estimate 3.65 days, 95% CI 0.43-6.86). Multi-drug resistance among FQ-NS bloodstream isolates limits both empirical and definitive antimicrobial treatment options and poses excessive burdens on the healthcare system.

  7. Interactions of fluoroquinolone antibacterial agents with aqueous chlorine: reaction kinetics, mechanisms, and transformation pathways.

    PubMed

    Dodd, Michael C; Shah, Amisha D; von Gunten, Urs; Huang, Ching-Hua

    2005-09-15

    Kinetics, products, and mechanistic aspects of reactions between free available chlorine (HOCl/OCl-), ciprofloxacin (CF), and enrofloxacin (EF) were extensively investigated to elucidate the behavior of fluoroquinolone antibacterial agents during water chlorination processes. Although the molecular structures of these two substrates differ only with respect to degree of N(4) amine alkylation, CF and EF exhibit markedly different HOCl reaction kinetics and transformation pathways. HOCI reacts very rapidly at CF's secondary N(4) amine, forming a chloramine intermediate that spontaneously decays in aqueous solution by concerted piperazine fragmentation. In contrast, HOCl reacts relatively slowly at EF's tertiary N(4) amine, apparently forming a highly reactive chlorammonium intermediate (R3N-(4)Cl+) that can catalytically halogenate EF or other substrates present in solution. Flumequine, a fluoroquinolone that lacks the characteristic piperazine ring, exhibits no apparent reactivity toward HOCI but appears to undergo facile halodecarboxylation in the presence of R3N(4)-Cl+ species derived from EF. Measured reaction kinetics were validated in real water matrixes by modeling CF and EF losses in the presence of free chlorine residuals. Combined chlorine (CC) kinetics were determined under selected conditions to evaluate the potential significance of reactions with chloramines. CF's rapid kinetics in direct reactions with HOCl, and relatively high reactivity toward CC, indicate that secondary amine-containing fluoroquinolones should be readily transformed during chlorination of real waters, whether applied chlorine doses are present as free or combined residuals. However, EF's slower HOCl reaction kinetics, recalcitrance toward CC, and participation in the catalytic halogenation cycle described herein suggest that tertiary amine-containing fluoroquinolones will be comparatively stable during most full-scale water chlorination processes.

  8. Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase.

    PubMed

    Aldred, Katie J; Blower, Tim R; Kerns, Robert J; Berger, James M; Osheroff, Neil

    2016-02-16

    Mycobacterium tuberculosis is a significant source of global morbidity and mortality. Moxifloxacin and other fluoroquinolones are important therapeutic agents for the treatment of tuberculosis, particularly multidrug-resistant infections. To guide the development of new quinolone-based agents, it is critical to understand the basis of drug action against M. tuberculosis gyrase and how mutations in the enzyme cause resistance. Therefore, we characterized interactions of fluoroquinolones and related drugs with WT gyrase and enzymes carrying mutations at GyrA(A90) and GyrA(D94). M. tuberculosis gyrase lacks a conserved serine that anchors a water-metal ion bridge that is critical for quinolone interactions with other bacterial type II topoisomerases. Despite the fact that the serine is replaced by an alanine (i.e., GyrA(A90)) in M. tuberculosis gyrase, the bridge still forms and plays a functional role in mediating quinolone-gyrase interactions. Clinically relevant mutations at GyrA(A90) and GyrA(D94) cause quinolone resistance by disrupting the bridge-enzyme interaction, thereby decreasing drug affinity. Fluoroquinolone activity against WT and resistant enzymes is enhanced by the introduction of specific groups at the C7 and C8 positions. By dissecting fluoroquinolone-enzyme interactions, we determined that an 8-methyl-moxifloxacin derivative induces high levels of stable cleavage complexes with WT gyrase and two common resistant enzymes, GyrA(A90V) and GyrA(D94G). 8-Methyl-moxifloxacin was more potent than moxifloxacin against WT M. tuberculosis gyrase and displayed higher activity against the mutant enzymes than moxifloxacin did against WT gyrase. This chemical biology approach to defining drug-enzyme interactions has the potential to identify novel drugs with improved activity against tuberculosis.

  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.

  10. Application of two methods to determine killing of Streptococcus pneumoniae by various fluoroquinolones.

    PubMed

    Blondeau, J M; Blondeau, L D; Hesje, C; Borsos, S

    2006-08-01

    Minimum inhibitory concentration (MIC) testing measures the lowest drug concentration that prevents microbial growth using an inoculum of 10(5) colony forming units/ml (cfu/ml) whereas the mutant prevention concentration (MPC) (inoculum approximately 10(10) cells) defines the antimicrobial drug concentration threshold that would require an organism to possess two simultaneous mutations for continued growth in the presence of the drug. The rates at which multidrug-resistant Streptococcus pneumoniae [MDRSP] were killed by the respiratory fluoroquinolones, gatifloxacin, gemfloxacin, levofloxacin and moxifloxacin, were compared based on the MIC and MPC drug concentrations and at inocula ranging from 10(6)-10(9) cfu/ml. The MIC drug concentration failed to eradicate all viable cells whereas the MPC drug concentration resulted in 99.9% to 100% cellular reduction following 12-24 hours of drug exposure. MPC values against S. pneumoniae were different for each fluoroquinolone. The MPC drug concentration prevents the selection of multidrug-resistant or fluoroquinolone-resistant S. pneumoniae. The value of dosing of antimicrobial agents based on MPC thresholds results in a rapid reduction in viable cells--even at higher inocula which are more reflective of organism burden in pneumonia. The rapid reduction in viable cells observed at MPC drug concentrations may not only have an impact on preventing the selection of resistant mutants but may also help explain the rapid symptom resolution seen with new fluoroquinolones since these agents lead to little or low release of cell contents which are known to drive the inflammatory response.

  11. Emergence of a Streptococcus pneumoniae clinical isolate highly resistant to telithromycin and fluoroquinolones.

    PubMed

    Faccone, Diego; Andres, Patricia; Galas, Marcelo; Tokumoto, Marta; Rosato, Adriana; Corso, Alejandra

    2005-11-01

    Streptococcus pneumoniae is a major pathogen causing community-acquired pneumonia and acute bronchitis. Macrolides, fluoroquinolones (FQs), and, recently, telithromycin (TEL) constitute primary therapeutic options, and rare cases of resistance have been reported. In this report, we describe the emergence of an S. pneumoniae clinical isolate with high-level TEL resistance (MIC, 256 microg/ml) and simultaneous resistance to FQs. Ongoing studies are oriented to elucidate the precise mechanism of resistance to TEL.

  12. 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

  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 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.

  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. 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

  16. Trihydroxamate siderophore-fluoroquinolone conjugates are selective sideromycin antibiotics that target Staphylococcus aureus.

    PubMed

    Wencewicz, Timothy A; Long, Timothy E; Möllmann, Ute; Miller, Marvin J

    2013-03-20

    Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a "Trojan horse" fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a β-lactam carbacepholosporin, Lorabid, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic toward Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 μM for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents.

  17. Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.

    PubMed

    Ascierto, Paolo A; Agarwala, Sanjiv; Botti, Gerardo; Cesano, Alessandra; Ciliberto, Gennaro; Davies, Michael A; Demaria, Sandra; Dummer, Reinhard; Eggermont, Alexander M; Ferrone, Soldano; Fu, Yang Xin; Gajewski, Thomas F; Garbe, Claus; Huber, Veronica; Khleif, Samir; Krauthammer, Michael; Lo, Roger S; Masucci, Giuseppe; Palmieri, Giuseppe; Postow, Michael; Puzanov, Igor; Silk, Ann; Spranger, Stefani; Stroncek, David F; Tarhini, Ahmad; Taube, Janis M; Testori, Alessandro; Wang, Ena; Wargo, Jennifer A; Yee, Cassian; Zarour, Hassane; Zitvogel, Laurence; Fox, Bernard A; Mozzillo, Nicola; Marincola, Francesco M; Thurin, Magdalena

    2016-11-15

    The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease. Specifically, many clinical successes have been using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death-1 (PD-1) and its ligand PD-L1. Despite demonstrated successes, responses to immunotherapy interventions occur only in a minority of patients. Attempts are being made to improve responses to immunotherapy by developing biomarkers. Optimizing biomarkers for immunotherapy could help properly select patients for treatment and help to monitor response, progression and resistance that are critical challenges for the immuno-oncology (IO) field. Importantly, biomarkers could help to design rational combination therapies. In addition, biomarkers may help to define mechanism of action of different agents, dose selection and to sequence drug combinations. However, biomarkers and assays development to guide cancer immunotherapy is highly challenging for several reasons: (i) multiplicity of immunotherapy agents with different mechanisms of action including immunotherapies that target activating and inhibitory T cell receptors (e.g., CTLA-4, PD-1, etc.); adoptive T cell therapies that include tissue infiltrating lymphocytes (TILs), chimeric antigen receptors (CARs), and

  18. 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

  19. TaqMan real-time quantitative PCR assay for detection of fluoroquinolone-resistant Neisseria gonorrhoeae.

    PubMed

    Zhao, LiHong; Zhao, ShuPing

    2012-12-01

    It is noted that more than 99 % of fluoroquinolone resistance in Neisseria gonorrhoeae (QRNG) specimens have been shown to have the mutation of Ser91/Phe in the gyrA gene. In order to detect QRNG isolates as quickly as possible, the real-time TaqMan quantitative PCR assay was established for detection of the point mutation of Ser91/Phe in gyrA gene. The standard curve was generated automatically on ABI Prism PE7500. The correlation coefficient (r) of the standard curve was -0.9984 (R(2) = 0.9968), indicating a quietly precise log-linear relationship between the concentration of target DNA and the Ct value. Presently, correlated, cultured antimicrobial susceptibility testing of N. gonorrhoeae isolates continues to be the gold standard method for the detection of antimicrobial resistance. Comparison to the correlated, cultured antimicrobial susceptibility testing, the sensitivity and specificity of the established TaqMan assay for the detection of the QRNG specimens were 100 and 99 %, respectively. The TaqMan assay also allows for rapid detection of QRNG isolates without complex laboratory techniques. Therefore, real-time TaqMan quantitative PCR assay is a rapid, simple, highly sensitive, highly specific, and easy-to-perform method for the detection of the QRNG specimens. It can be applied as a quick screening method for QRNG isolates to help clinical determination of optimal treatment prescription.

  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. Proceedings of the 1980 IPMAAC Conference on Public Personnel Assessment (4th, Boston, Massachusetts, July 6-10, 1980).

    ERIC Educational Resources Information Center

    International Personnel Management Association, Washington, DC.

    The International Personnel Management Association Assessment Council (IPMAAC) contains over 500 psychometric specialists, personnel psychologists, and personnel staffing specialists dedicated to the improvement of public personnel assessment in such fields as selection and performance evaluation. Author-generated summaries/outlines of papers…

  2. Supercomputing '91; Proceedings of the 4th Annual Conference on High Performance Computing, Albuquerque, NM, Nov. 18-22, 1991

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Various papers on supercomputing are presented. The general topics addressed include: program analysis/data dependence, memory access, distributed memory code generation, numerical algorithms, supercomputer benchmarks, latency tolerance, parallel programming, applications, processor design, networks, performance tools, mapping and scheduling, characterization affecting performance, parallelism packaging, computing climate change, combinatorial algorithms, hardware and software performance issues, system issues. (No individual items are abstracted in this volume)

  3. An Analysis of the Implementation of the Standard Accounting, Budgeting and Reporting System (SABRS) in the 4th Marine Division.

    DTIC Science & Technology

    1980-12-01

    request, itemized shopping list for General Services Administration (GSA), Direct Supply Support Control ( DSSC ), Serve Mart, or Mili- tary Standard...a Marine Corps DSSC are listed on a mechanized Daily Stock Fund Expense Listing resulting in a credit in the same total amount of the list- ing on...These documents may be generated by fund administra- tors, DSSC , purchasing and contracting, or disbursing. Validations and edits will be performed

  4. Fluoroquinolone Efflux in Streptococcus suis Is Mediated by SatAB and Not by SmrA ▿

    PubMed Central

    Escudero, Jose Antonio; San Millan, Alvaro; Gutierrez, Belen; Hidalgo, Laura; La Ragione, Roberto M.; AbuOun, Manal; Galimand, Marc; Ferrándiz, María José; Domínguez, Lucas; de la Campa, Adela G.; Gonzalez-Zorn, Bruno

    2011-01-01

    Streptococcus suis is an emerging zoonotic pathogen. With the lack of an effective vaccine, antibiotics remain the main tool to fight infections caused by this pathogen. We have previously observed a reserpine-sensitive fluoroquinolone (FQ) efflux phenotype in this species. Here, SatAB and SmrA, two pumps belonging to the ATP binding cassette (ABC) and the major facilitator superfamily (MFS), respectively, have been analyzed in the fluoroquinolone-resistant clinical isolate BB1013. Genes encoding these pumps were overexpressed either constitutively or in the presence of ciprofloxacin in this strain. These genes could not be cloned in plasmids in Escherichia coli despite strong expression repression. Finally, site-directed insertion of smrA and satAB in the amy locus of the Bacillus subtilis chromosome using ligated PCR amplicons allowed for the functional expression and study of both pumps. Results showed that SatAB is a narrow-spectrum fluoroquinolone exporter (norfloxacin and ciprofloxacin), susceptible to reserpine, whereas SmrA was not involved in fluoroquinolone resistance. Chromosomal integration in Bacillus is a novel method for studying efflux pumps from Gram-positive bacteria, which enabled us to demonstrate the possible role of SatAB, and not SmrA, in fluoroquinolone efflux in S. suis. PMID:21930876

  5. Effect of olfactory and visual stimuli on the orientation of the 4th instar larvae of the stem borer Chilo partellus swinhoe (Lepidoptera: Pyralidae).

    PubMed

    Tokro, P G; Saxena, K N

    1991-01-01

    The orientational responses of 4th instar larvae of Chilo partellus to different sources of stimuli being artificial diet, leaves and stems of maize and sorghum were tested, under free choice and no-choice situations. Larvae were attracted to maize and sorghum in a moderate to high degree dependent on what choice they were given. The orientational preference of the larvae, offered a choice between the visual and the odour sources, depended upon their stimulating capacities which were represented by the percentages of individuals responding to the sources of stimuli. Odour played a greater role than visual stimuli in this close range attraction when the two competed with each other.

  6. [Tumors of the 4th ventricle and the craniospinal transitional zone. Review of patients of the Neurosurgical Clinic of the Department of Medicine of the Karl Marx University].

    PubMed

    Niebeling, H G; Fried, H; Goldhahn, W E; Skrzypczak, J; Brachmann, J; Eichler, I

    1983-01-01

    From a total of 1,028 infratentorial tumours operated on at the Neurosurgical Hospital of the Section Medicine of the Karl-Marx University Leipzig in the last 30 years, 167 tumours in the region of the 4th ventrical have been selected. Their statistical processing was carried out with respect to specific localisation, average age, kind of tumour, sex, clinical findings, duration of case history, application of instrumental diagnostic procedures and radicality of operation, success and failure. Some fundamental conclussions are drawn. A subdivision in detail will be contained in the following articles based on this material.

  7. Global challenges in the management of congenital cataract: proceedings of the 4th International Congenital Cataract Symposium held on March 7, 2014, New York, New York.

    PubMed

    Lenhart, Phoebe D; Courtright, Paul; Wilson, M Edward; Lewallen, Susan; Taylor, David Samuel; Ventura, Marcelo C; Bowman, Richard; Woodward, Lee; Ditta, Lauren C; Kruger, Stacey; Haddad, Danny; El Shakankiri, Nihal; Rai, Salma Kc; Bailey, Tehara; Lambert, Scott R

    2015-04-01

    Childhood cataracts have become a leading cause of preventable childhood blindness in many areas of the world. Here we summarize regional focus group discussions from the 4th Annual International Congenital Cataract Symposium on the current situation, challenges, and recommendations for the management of congenital cataracts in sub-Saharan Africa, the Middle East and North Africa, South Asia, Central America, South America, and developed nations. Strategies for managing congenital cataracts must be adapted and developed according to regional conditions. A basic framework for acceptable outcomes must focus on developing systems to address the critical components of education, access, quality care, and good follow-up.

  8. Fluoroquinolone resistance mechanisms in urinary tract pathogenic Escherichia coli isolated during rapidly increasing fluoroquinolone consumption in a low-use country.

    PubMed

    Christiansen, Nina; Nielsen, Lene; Jakobsen, Lotte; Stegger, Marc; Hansen, Lars Hestbjerg; Frimodt-Møller, Niels

    2011-09-01

    Resistance to ciprofloxacin in Escherichia coli from urinary tract infections (UTI) in Denmark is increasing parallel to increased use of fluoroquinolones both in Denmark and in other European countries. The objective was to investigate the occurrence of ciprofloxacin resistance mechanisms, phenotypic coresistance, and if ciprofloxacin resistance was caused by clonal spread or to individual mutational events in a collection of consecutively obtained E. coli submitted to a clinical microbiology department at a Danish hospital. One hundred four UTI-related E. coli resistant toward nalidixic acid by disc diffusion were typed by Pulsed Field Gel Electrophoresis (PFGE) with XbaI. One isolate representing each PFGE type and only one patient (n = 77) were investigated for point mutations in sequenced PCR amplicons of the four topoisomerase genes; qnr genes by use of PCR; aac(6')-Ib-cr by BtsCI restriction of PCR products; and efflux using efflux pump inhibitors in a broth dilution assay. Minimal inhibitory concentration (MIC) was determined for 21 antibacterial agents, including ciprofloxacin. Of the 77 isolates, the majority were resistant to ciprofloxacin (91%) and multiresistant (resistant to ≥ 3 antimicrobial classes, 83%). Ciprofloxacin-resistant isolates showed at least one target mutation. A significant, positive correlation was found regarding MIC of ciprofloxacin and the number of target mutations. Efflux was found as a resistance mechanism in 77% of isolates tested (n = 60). The aac(6')-Ib-cr gene was detected on plasmids from five isolates showing ciprofloxacin MICs >512 mg/L. No overall clonal relationship among isolates was found according to PFGE. Target modification is the dominating fluoroquinolone resistance mechanism often found in combination with efflux and sometimes aac(6')-Ib-cr. In Denmark, increasing ciprofloxacin resistance in E. coli is mainly due to mutational events and not to spread of clones.

  9. 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.

  10. Magnetic graphene dispersive solid phase extraction combining high performance liquid chromatography for determination of fluoroquinolones in foods.

    PubMed

    He, Xin; Wang, Geng Nan; Yang, Kun; Liu, Hui Zhi; Wu, Xia Jun; Wang, Jian Ping

    2017-04-15

    In this study, a magnetic graphene-based dispersive solid phase extraction method was developed that was combined with high performance liquid chromatography to determine the residues of fluoroquinolone drugs in foods of animal origin. During the experiments, several parameters possible influencing the extraction performance were optimized (amount of magnetic graphene, sample pH, extraction time and elution solution). This extraction method showed high absorption capacities (>6800ng) and high enrichment factors (68-79-fold) for seven fluoroquinolones. Furthermore, this absorbent could be reused for at least 40 times. The limits of detection were in the range of 0.05-0.3ng/g, and the recoveries from the standards fortified blank samples (bovine milk, chicken muscle and egg) were in the range of 82.4-108.5%. Therefore, this method could be used as a simple and sensitive tool to determine the residues of fluoroquinolones in foods of animal origin.

  11. Absence of tmRNA Has a Protective Effect against Fluoroquinolones in Streptococcus pneumoniae.

    PubMed

    Brito, Liliana; Wilton, Joana; Ferrándiz, María J; Gómez-Sanz, Alicia; de la Campa, Adela G; Amblar, Mónica

    2016-01-01

    The transfer messenger RNA (tmRNA), encoded by the ssrA gene, is a small non-coding RNA involved in trans-translation that contributes to the recycling of ribosomes stalled on aberrant mRNAs. In most bacteria, its inactivation has been related to a decreased ability to respond to and recover from a variety of stress conditions. In this report, we investigated the role of tmRNA in stress adaptation in the human pathogen Streptococcus pneumoniae. We constructed a tmRNA deletion mutant and analyzed its response to several lethal stresses. The ΔssrA strain grew slower than the wild type, indicating that, although not essential, tmRNA is important for normal pneumococcal growth. Moreover, deletion of tmRNA increased susceptibility to UV irradiation, to exogenous hydrogen peroxide and to antibiotics that inhibit protein synthesis and transcription. However, the ΔssrA strain was more resistant to fluoroquinolones, showing twofold higher MIC values and up to 1000-fold higher survival rates than the wild type. Deletion of SmpB, the other partner in trans-translation, also reduced survival to levofloxacin in a similar extent. Accumulation of intracellular reactive oxygen species associated to moxifloxacin and levofloxacin treatment was also highly reduced (∼100-fold). Nevertheless, the ΔssrA strain showed higher intracellular accumulation of ethidium bromide and levofloxacin than the wild type, suggesting that tmRNA deficiency protects pneumococcal cells from fluoroquinolone-mediated killing. In fact, analysis of chromosome integrity revealed that deletion of tmRNA prevented the fragmentation of the chromosome associated to levofloxacin treatment. Moreover, such protective effect appears to relay mainly on inhibition of protein synthesis, since a similar effect was observed with antibiotics that inhibit that process. The emergence and spread of drug-resistant pneumococci is a matter of concern and these results contribute to a better comprehension of the mechanisms

  12. Fluoroquinolone interactions with Mycobacterium tuberculosis gyrase: Enhancing drug activity against wild-type and resistant gyrase

    PubMed Central

    Aldred, Katie J.; Kerns, Robert J.; Berger, James M.; Osheroff, Neil

    2016-01-01

    Mycobacterium tuberculosis is a significant source of global morbidity and mortality. Moxifloxacin and other fluoroquinolones are important therapeutic agents for the treatment of tuberculosis, particularly multidrug-resistant infections. To guide the development of new quinolone-based agents, it is critical to understand the basis of drug action against M. tuberculosis gyrase and how mutations in the enzyme cause resistance. Therefore, we characterized interactions of fluoroquinolones and related drugs with WT gyrase and enzymes carrying mutations at GyrAA90 and GyrAD94. M. tuberculosis gyrase lacks a conserved serine that anchors a water–metal ion bridge that is critical for quinolone interactions with other bacterial type II topoisomerases. Despite the fact that the serine is replaced by an alanine (i.e., GyrAA90) in M. tuberculosis gyrase, the bridge still forms and plays a functional role in mediating quinolone–gyrase interactions. Clinically relevant mutations at GyrAA90 and GyrAD94 cause quinolone resistance by disrupting the bridge–enzyme interaction, thereby decreasing drug affinity. Fluoroquinolone activity against WT and resistant enzymes is enhanced by the introduction of specific groups at the C7 and C8 positions. By dissecting fluoroquinolone–enzyme interactions, we determined that an 8-methyl-moxifloxacin derivative induces high levels of stable cleavage complexes with WT gyrase and two common resistant enzymes, GyrAA90V and GyrAD94G. 8-Methyl-moxifloxacin was more potent than moxifloxacin against WT M. tuberculosis gyrase and displayed higher activity against the mutant enzymes than moxifloxacin did against WT gyrase. This chemical biology approach to defining drug–enzyme interactions has the potential to identify novel drugs with improved activity against tuberculosis. PMID:26792518

  13. Absence of tmRNA Has a Protective Effect against Fluoroquinolones in Streptococcus pneumoniae

    PubMed Central

    Brito, Liliana; Wilton, Joana; Ferrándiz, María J.; Gómez-Sanz, Alicia; de la Campa, Adela G.; Amblar, Mónica

    2017-01-01

    The transfer messenger RNA (tmRNA), encoded by the ssrA gene, is a small non-coding RNA involved in trans-translation that contributes to the recycling of ribosomes stalled on aberrant mRNAs. In most bacteria, its inactivation has been related to a decreased ability to respond to and recover from a variety of stress conditions. In this report, we investigated the role of tmRNA in stress adaptation in the human pathogen Streptococcus pneumoniae. We constructed a tmRNA deletion mutant and analyzed its response to several lethal stresses. The ΔssrA strain grew slower than the wild type, indicating that, although not essential, tmRNA is important for normal pneumococcal growth. Moreover, deletion of tmRNA increased susceptibility to UV irradiation, to exogenous hydrogen peroxide and to antibiotics that inhibit protein synthesis and transcription. However, the ΔssrA strain was more resistant to fluoroquinolones, showing twofold higher MIC values and up to 1000-fold higher survival rates than the wild type. Deletion of SmpB, the other partner in trans-translation, also reduced survival to levofloxacin in a similar extent. Accumulation of intracellular reactive oxygen species associated to moxifloxacin and levofloxacin treatment was also highly reduced (∼100-fold). Nevertheless, the ΔssrA strain showed higher intracellular accumulation of ethidium bromide and levofloxacin than the wild type, suggesting that tmRNA deficiency protects pneumococcal cells from fluoroquinolone-mediated killing. In fact, analysis of chromosome integrity revealed that deletion of tmRNA prevented the fragmentation of the chromosome associated to levofloxacin treatment. Moreover, such protective effect appears to relay mainly on inhibition of protein synthesis, since a similar effect was observed with antibiotics that inhibit that process. The emergence and spread of drug-resistant pneumococci is a matter of concern and these results contribute to a better comprehension of the mechanisms

  14. In vitro activity of older and newer fluoroquinolones against efflux-mediated high-level ciprofloxacin-resistant Streptococcus pneumoniae.

    PubMed

    Daporta, Matilde Trigo; Muñoz Bellido, Juan Luis; Guirao, Genoveva Yagüe; Hernández, Manuel Segovia; García-Rodríguez, José Angel

    2004-08-01

    The effect of high-level efflux activity on the MICs of fluoroquinolones against Streptococcus pneumoniae in the absence of topoisomerase mutations leading to fluoroquinolones resistance was investigated. A S. pneumoniae ATCC 46619-derived strain with high-level efflux activity was obtained (SP-25A). Both the parent and obtained strains were tested against efflux substrates acriflavine (Acr) and ethidium bromide (EtBr), and against norfloxacin (NFX), ciprofloxacin (CFX), levofloxacin (LFX), moxifloxacin (MFX), trovafloxacin (TVX) and sitafloxacin (SFX), in presence and absence of the efflux pump inhibitor reserpine. gyrA, gyrB, parC and parE QRDR genes were amplified by PCR and sequenced. MICs of NFX and CFX against SP-25A were 64-fold higher than parent strain MICs (256 mg/L versus 4 mg/L and 64 mg/L versus 1mg/L, respectively). MIC of LFX increased from 1 to 4 mg/L and MICs of MFX, TVX and SFX remained virtually unchanged (0.1-0.2 mg/L). MICs of Acr and EtBr against SP-25A were 8- and 16-fold higher than against parent strains. In both cases, reserpine reverted MICs to the parent strain values (1 and 0.2 mg/L). Only parE showed two mutations leading to a Pro(454) --> Ser and Glu(443) changes, which have previously been shown not to lead to significant fluoroquinolones MIC increases. SP-25A showed a significant increase of MICs of the hydrophilic fluoroquinolones, apparently derived only from efflux activity. Efflux activity, at these high levels, can lead to high-level resistance to older hydrophilic fluoroquinolones, but does affect newer fluoroquinolones such as moxifloxacin, trovafloxacin and sitafloxacin.

  15. Further Increases in Carbapenem-, Amikacin-, and Fluoroquinolone-Resistant Isolates of Acinetobacter spp. and P. aeruginosa in Korea: KONSAR Study 2009

    PubMed Central

    Lee, Kyungwon; Kim, Mi-Na; Kim, Jae-Seok; Hong, Hye Lim; Kang, Jung Oak; Shin, Jong Hee; Park, Yeon-Joon; Yong, Dongeun; Jeong, Seok Hoon

    2011-01-01

    Purpose The increasing prevalence of antimicrobial resistant bacteria has become a serious worldwide problem. The aim of this study was to analyze antimicrobial resistance data generated in 2009 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program. Materials and Methods Susceptibility data were collected from 24 hospitals and two commercial laboratories. In the analysis, resistance did not include intermediate susceptibility. Duplicate isolates were excluded from the analysis of hospital isolates, but not from the commercial laboratory isolates. Results Among the hospital isolates, methicillin-resistant Staphylococcus aureus, penicillin G-non-susceptible Streptococcus pneumoniae based on meningitis breakpoint, and ampicillin-resistant Enterococcus faecium remained highly prevalent. The proportion of vancomycin-resistant E. faecium gradually increased to 29%. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae increased to 17% and 33%, respectively, and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa increased to 33%, 67% and 39%, respectively. Amikacin-resistant Acinetobacter spp. increased to 48%. Imipenem-resistant Acinetobacter spp. and P. aeruginosa increased to 51% and 26%, respectively. Higher resistance rates were observed in intensive care unit (ICU) isolates than in non-ICU isolates among the isolates from hospitals. Resistance rates were higher in hospital isolates than in clinic isolates among the isolates from commercial laboratories. Conclusion Among the hospital isolates, ceftazidime-resistant K. pneumoniae and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp., and P. aeruginosa further increased. The increase in imipenem resistance was slight in P. aeruginosa, but drastic in Acinetobacter spp. The problematic antimicrobial-organism combinations were much more prevalent among ICU isolates. PMID:21786445

  16. Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra.

    PubMed Central

    Kocagöz, T; Hackbarth, C J; Unsal, I; Rosenberg, E Y; Nikaido, H; Chambers, H F

    1996-01-01

    To characterize mechanisms of resistance to fluoroquinolones by Mycobacterium tuberculosis, mutants of strain H37Ra were selected in vitro with ofloxacin. Their quinolone resistance-determining regions for gyrA and gyrB were amplified and sequenced to identify mutations in gyrase A or B. Three types of mutants were obtained: (i) one mutant (TKp1) had no mutations in gyrA or gyrB; (ii) mutants that had single missense mutations in gyrA, and (iii) mutants that had two missense mutations resulting in either two altered gyrase A residues or an altered residue in both gyrases A and B. The TKp1 mutant had slightly reduced levels of uptake of [14C]norfloxacin, which was associated with two- to fourfold increases in the MICs of ofloxacin, ciprofloxacin, and sparfloxacin. Gyrase mutations caused a much greater increase in the MICs of fluoroquinolones. For mutants with single gyrA mutations, the increases in the MICs were 4- to 16-fold, and for mutants with double gyrase mutations, the MICs were increased 32-fold or more compared with those for the parent. A gyrA mutation in TKp1 secondary mutants was associated with 32- to 128-fold increases in the MICs of ofloxacin and ciprofloxacin compared with the MICs for H37Ra and an eight-fold increase in the MIC of sparfloxacin. Sparfloxacin was the most active fluoroquinolone tested. No sparfloxacin-resistant single-step mutants were selected at concentrations of > 2.5 micrograms/ml, and high-level resistance (i.e., MIC, > and = 5 micrograms/ml) was associated with two gyrase mutations. Mutations in gyrB and possibly altered levels of intracellular accumulation of drug are two additional mechanisms that may be used by M. tuberculosis in the development of fluoroquinolone resistance. Because sparfloxacin is more active in vitro and selection of resistance appears to be less likely to occur, it may have important advantage over ofloxacin or ciprofloxacin for the treatment of tuberculosis. PMID:8843279

  17. 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.

  18. Combined CD4+ Th1 effect and lymphotactin transgene expression enhance CD8+ Tc1 tumor localization and therapy.

    PubMed

    Huang, H; Bi, X G; Yuan, J Y; Xu, S L; Guo, X L; Xiang, J

    2005-06-01

    Type 1 T cells are the major components in antitumor immunity. The lack of efficient CD8(+) cytotoxic T (Tc) cell infiltration of tumors is a major obstacle to adoptive Tc-cell therapy. We have previously demonstrated that adenovirus (AdV)-mediated transgene lymphotactin (Lptn) expression by intratumoral AdVLptn injection and intravenous CD4(+) helper T (Th) cell transfer can enhance Tc-cell tumor infiltration and eradication of early stage tumors (5 mm in diameter). In this study, we generated ovalbumin (OVA)-specific Tc1 and Th1 cells in vitro by incubation of OVA-pulsed dendritic cells with naive T cells from T-cell receptor (TCR) transgenic OT I and OT II mice. We then investigated the potential synergy of Th1 help effect and Lptn transgene expression in Tc1-cell therapy of well-established OVA-expressing EG7 solid tumors (7 mm in diameter). Our data showed that a combined adoptive T-cell therapy of Th1 (2.5 x 10(6) cells per mouse) and Tc1 (5 x 10(6) cells per mouse) resulted in regression of all eight (100%) transgene Lptn expressed EG7 tumors, which is significantly higher than four from eight (50%) in AdVLptn/Tc1 group and two from eight (25%) in Tc1/Th1 group (P < 0.05). The amount of transferred Tc1 cells detected in Lptn-expressed tumors with Th1 treatment is 0.72%, which is significantly higher than those of AdVLptn (0.22%), Th1 (0.41%) and the control AdVpLpA (0.09%) treatment groups (P < 0.05). Enhanced Tc1 tumor localization may be derived from the chemotactic effect of Lptn and the proliferative effect of Th1 and Lptn. This novel therapeutic strategy with enhancement of Tc1 tumor localization in the therapy of well-established tumors may become a tool of considerable conceptual interest in the implementation of future clinical objectives.

  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. 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.

  1. Effects of β-Lactam Antibiotics and Fluoroquinolones on Human Gut Microbiota in Relation to Clostridium difficile Associated Diarrhea

    PubMed Central

    Heinsen, Femke Anouska; Knecht, Carolin; Schilhabel, Anke; Schmitz, Ruth A.; Zimmermann, Alexandra; dos Santos, Vitor Martins; Ferrer, Manuel; Rosenstiel, Philip C.; Schreiber, Stefan; Friedrichs, Anette K.; Ott, Stephan J.

    2014-01-01

    Clostridium difficile infections are an emerging health problem in the modern hospital environment. Severe alterations of the gut microbiome with loss of resistance to colonization against C. difficile are thought to be the major trigger, but there is no clear concept of how C. difficile infection evolves and which microbiological factors are involved. We sequenced 16S rRNA amplicons generated from DNA and RNA/cDNA of fecal samples from three groups of individuals by FLX technology: (i) healthy controls (no antibiotic therapy); (ii) individuals receiving antibiotic therapy (Ampicillin/Sulbactam, cephalosporins, and fluoroquinolones with subsequent development of C. difficile infection or (iii) individuals receiving antibiotic therapy without C. difficile infection. We compared the effects of the three different antibiotic classes on the intestinal microbiome and the effects of alterations of the gut microbiome on C. difficile infection at the DNA (total microbiota) and rRNA (potentially active) levels. A comparison of antibiotic classes showed significant differences at DNA level, but not at RNA level. Among individuals that developed or did not develop a C. difficile infection under antibiotics we found no significant differences. We identified single species that were up- or down regulated in individuals receiving antibiotics who developed the infection compared to non-infected individuals. We found no significant differences in the global composition of the transcriptionally active gut microbiome associated with C. difficile infections. We suggest that up- and down regulation of specific bacterial species may be involved in colonization resistance against C. difficile providing a potential therapeutic approach through specific manipulation of the intestinal microbiome. PMID:24586762

  2. [Mutation window for the "pneumococcus-fluoroquinolone" couple. Contribution of experimental models].

    PubMed

    Chavanet, P; Croisier, D

    2006-01-01

    Low-level resistance to fluoroquinolones (in vitro susceptible but with topoisomerase mutation, parC) is currently rare among pneumococci in France. However, this resistance is more frequently observed in previously exposed patients and therapeutic failure has been reported. These issues were investigated by using a humanized model of experimental pneumonia induced by pneumococci exhibiting this low-level resistance profile. The results are as follows: 1) when the pneumonia is due to a wild type pneumococcus, humanized ciprofloxacin treatment is not effective because of resistant mutants with parC mutation; moreover, levoflaxin treatment is less bactericidal than gatiflo- or moxifloxacin (-4 vs -6 log CFU/g); 2) when an efflux strain is used, levo-treatment is not efficient but there are no mutants, a gatiflo-treatment is combined when mutants appear and moxiflo-treatment is effective; 3) when the pneumonia is induced with susceptible parC strains, treatment with either levo, or gati, or moxifloxacin is completely ineffective because resistant mutants appear (acquisition of another gyrA mutation). Measure of the mutation prevention concentration (MPC) allows anticipating these results since the mutation window can be determined. These results stress the necessity to identify patients with such pneumococcal strains in order to avoid therapeutic failure and the emergence of fluoroquinolone resistant mutants.

  3. Gemifloxacin, a fluoroquinolone antimicrobial drug, inhibits migration and invasion of human colon cancer cells.

    PubMed

    Kan, Jung-Yu; Hsu, Ya-Ling; Chen, Yen-Hsu; Chen, Tun-Chieh; Wang, Jaw-Yuan; Kuo, Po-Lin

    2013-01-01

    Gemifloxacin (GMF) is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT). In addition, GMF suppresses the activation of NF- κ B and cell migration and invasion induced by TNF- α and inhibits the TAK1/TAB2 interaction, resulting in decreased I κ B phosphorylation and NF- κ B nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

  4. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds.

    PubMed

    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.

  5. Effectiveness of two fluoroquinolones for the treatment of chronic respiratory disease outbreak in broilers.

    PubMed

    Sumano, L H; Ocampo, C L; Brumbaugh, G W; Lizarraga, R E

    1998-03-01

    1. Chronic respiratory disease (CRD) caused by Mycoplasma synoviae in association with Escherichia coli is the disease most frequently encountered in poultry in Mexico. 2. Differences of antimycoplasmal activity, pharmacokinetics and cost among fluoroquinolones were the impetus for this clinical evaluation of efficacy of enrofloxacin and norfloxacin-nicotinate in broilers with CRD. 3. A total of 99,600 broilers, naturally infected with M. synoviae and E. coli, were treated with enrofloxacin (10 mg/kg/d for 3 d) (n = 49,800) or norfloxacin-nicotinate (20 mg/kg/d for 3 d) (n = 49,800). 4. Based on survivor analysis, there were no significant differences of efficacy of the 2 drugs. Survivor probabilities were above 0.99. 5. These results indicate that enrofloxacin and norfloxacin-nicotinate are efficacious for treatment of CRD. Questions remaining to be answered by other studies include: public health concern about the use of fluoroquinolones for the treatment of CRD; clinical superiority of one of these drugs on the basis of an attribute other than antimicrobial activity, such as cost:benefit ratio or ability to prevent bacterial resistance. 6. Clinical efficacy is not a relevant variable in assessing whether norfloxacin-nicotinate or enrofloxacin should be used for the treatment of CRD associated with E. coli in broilers.

  6. Degradation of two fluoroquinolone antibiotics photoinduced by Fe(III)-microalgae suspension in an aqueous solution.

    PubMed

    Ge, Liyun; Deng, Huanhuan

    2015-04-01

    The widespread presence of fluoroquinolone antibiotics (FQs) in natural ecosystems is a health hazard for humans and other living organisms. In this work, the photochemical degradation process of two antibiotics in the presence of Fe(III) and marine microalgae has been studied. Two fluoroquinolone (FQ) antibiotics, enrofloxacin (ENR) and ciprofloxacin hydrochloride (CIP), and two marine microalgae, Platymonas subcordiformis and Isochrysis galbana, were investigated under irradiation with a high-pressure mercury lamp (HPML) in a laboratory-scale experiment. The effects of the initial concentration of antibiotics on the degradation of these two FQs in Fe(III)-algae suspensions were also investigated. On the basis of the information in this study, compared to other systems, the efficiency of photo-degradation of the two FQs is better at lower FQ concentrations in the Fe(III)-algae system. Moreover, the low initial concentration of antibiotics benefits the photochemical process of antibiotics. This work demonstrated that the Fe(III)-algae system is an interesting and valuable research area and could be considered as a promising photochemical system for seawater remediation.

  7. Fitness benefits in fluoroquinolone-resistant Salmonella Typhi in the absence of antimicrobial pressure.

    PubMed

    Baker, Stephen; Duy, Pham Thanh; Nga, Tran Vu Thieu; Dung, Tran Thi Ngoc; Phat, Voong Vinh; Chau, Tran Thuy; Turner, A Keith; Farrar, Jeremy; Boni, Maciej F

    2013-12-10

    Fluoroquinolones (FQ) are the recommended antimicrobial treatment for typhoid, a severe systemic infection caused by the bacterium Salmonella enterica serovar Typhi. FQ-resistance mutations in S. Typhi have become common, hindering treatment and control efforts. Using in vitro competition experiments, we assayed the fitness of eleven isogenic S. Typhi strains with resistance mutations in the FQ target genes, gyrA and parC. In the absence of antimicrobial pressure, 6 out of 11 mutants carried a selective advantage over the antimicrobial-sensitive parent strain, indicating that FQ resistance in S. Typhi is not typically associated with fitness costs. Double-mutants exhibited higher than expected fitness as a result of synergistic epistasis, signifying that epistasis may be a critical factor in the evolution and molecular epidemiology of S. Typhi. Our findings have important implications for the management of drug-resistant S. Typhi, suggesting that FQ-resistant strains would be naturally maintained even if fluoroquinolone use were reduced. DOI: http://dx.doi.org/10.7554/eLife.01229.001.

  8. Temporal Changes in Resistance Mechanisms in Colonizing Escherichia coli Isolates with Reduced Susceptibility to Fluoroquinolones

    PubMed Central

    Han, Jennifer H.; Nachamkin, Irving; Tolomeo, Pam; Mao, Xiangqun; Bilker, Warren B.; Lautenbach, Ebbing

    2013-01-01

    The objective of this study was to characterize the temporal variability of fluoroquinolone resistance mechanisms among Escherichia coli colonizing the gastrointestinal tract of hospitalized patients. Patients with new fluoroquinolone-resistant E. coli (FQREC) colonization were followed with serial fecal sampling until discharge or death. Genetic mechanism(s) of resistance for all FQREC isolates were characterized, including mutations in gyrA and parC and efflux pump overexpression. Of 451 subjects, 73 (16.2%) became newly colonized with FQREC. There was significant variability in regard to temporal changes in resistance mechanisms and levofloxacin MICs among isolates from individual patients. Compared to patients with transient colonization, patients with persistent colonization were more likely to have a urinary catheter (P=0.04), diarrhea (P=0.04), and a longer duration of hospitalization (22 and 9.0 mean days, respectively; P=0.01) prior to sampling. Our data demonstrate the significant variability of resistance mechanisms in colonizing E. coli isolates among hospitalized patients. PMID:23719087

  9. 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

  10. Mechanisms of Resistance and Clinical Relevance of Resistance to β-Lactams, Glycopeptides, and Fluoroquinolones

    PubMed Central

    Rice, Louis B.

    2012-01-01

    The widespread use of antibiotics has resulted in a growing problem of antimicrobial resistance in the community and hospital settings. Antimicrobial classes for which resistance has become a major problem include the β-lactams, the glycopeptides, and the fluoroquinolones. In gram-positive bacteria, β-lactam resistance most commonly results from expression of intrinsic low-affinity penicillin-binding proteins. In gram-negative bacteria, expression of acquired β-lactamases presents a particular challenge owing to some natural spectra that include virtually all β-lactam classes. Glycopeptide resistance has been largely restricted to nosocomial Enterococcus faecium strains, the spread of which is promoted by ineffective infection control mechanisms for fecal organisms and the widespread use of colonization-promoting antimicrobials (especially cephalosporins and antianaerobic antibiotics). Fluoroquinolone resistance in community-associated strains of Escherichia coli, many of which also express β-lactamases that confer cephalosporin resistance, is increasingly prevalent. Economic and regulatory forces have served to discourage large pharmaceutical companies from developing new antibiotics, suggesting that the antibiotics currently on the market may be all that will be available for the coming decade. As such, it is critical that we devise, test, and implement antimicrobial stewardship strategies that are effective at constraining and, ideally, reducing resistance in human pathogenic bacteria. PMID:22305032

  11. 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

  12. Fitness cost of fluoroquinolone resistance in Campylobacter coli and Campylobacter jejuni.

    PubMed

    Zeitouni, Salman; Kempf, Isabelle

    2011-06-01

    In this study, the fitness cost of fluoroquinolone resistance was evaluated in vitro, on food matrices, and in vivo, using Campylobacter coli and Campylobacter jejuni in vitro selected mutants. In vitro, the growth rate of the susceptible (wild type) and resistant (mutant) strains did not differ when cultured separately. However, by conducting sequential passages of mixed cultures, the ratio of the resistant mutant to the susceptible strain decreased for C. coli but not for C. jejuni. When the wild type and the mutant were co-inoculated on food matrices, mutants were no longer detectable 3 to 5 days after artificial contamination, but the wild-type strains remained detectable for over 13 days. In mono-inoculated animals, no difference was observed between wild-type and mutant fecal titers. When co-inoculated into chickens, the susceptible strain outcompeted the resistant mutant for C. coli and for C. jejuni. However, for C. coli, if the resistant strain was already present in animals, it could persist at high titers in the digestive tract even in the presence of the wild-type strain. Together, these findings suggest that, depending on strain and study conditions, fluoroquinolone resistance can impose a fitness cost on Campylobacter.

  13. Comparison of the Richmond HRR 4th edition and Farnsworth-Munsell 100 Hue Test for quantitative assessment of tritan color deficiencies.

    PubMed

    Foote, Katharina G; Neitz, Maureen; Neitz, Jay

    2014-04-01

    Drugs and environmental factors can induce tritan deficiencies. The Farnsworth-Munsell (FM) 100 Hue Test has become the gold standard in measuring these acquired defects. However, the test is time consuming, and color discrimination is confounded by concentration and patience. Here, we describe a test that compares six tritan plates from the HRR Pseudoisochromatic Plates 4th edition to 16 FM 100 Hue tritan caps. CIE Standard Illuminant C was reduced over five light intensities to simulate the effects of acquired losses in the S-cone pathway. Both tests showed quantitative differences in error rates with all light levels; thus they could serve equally well for assessing acquired deficiencies. However, compared to the FM 100, the HRR took subjects about 20-40 s per trial, making it more practical.

  14. 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.

  15. 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

  16. Development of a low-noise, 4th-order readout ASIC for CdZnTe detectors in gamma spectrometer applications

    NASA Astrophysics Data System (ADS)

    Wang, Jia; Su, Lin; Wei, Xiaomin; Zheng, Ran; Hu, Yann

    2016-09-01

    This paper presents an ASIC readout circuit development, which aims to achieve low noise. In order to compensate the leakage current and improve gain, a dual-stage CSA has been utilized. A 4th-order high-linearity shaper is proposed to obtain a Semi-Gaussian wave and further decrease the noise induced by the leakage current. The ASIC has been designed and fabricated in a standard commercial 2P4M 0.35 μm CMOS process. Die area of one channel is about 1190 μm×147 μm. The input charge range is 1.8 fC. The peaking time can be adjusted from 1 μs to 3 μs. Measured ENC is about 55e- (rms) at input capacitor of 0 F. The gain is 271 mV/fC at the peaking time of 1 μs.

  17. 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

  18. 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

  19. 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...

  20. 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

    2016-03-11

    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.

  1. 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.

  2. The 4th R: Reasoning.

    ERIC Educational Resources Information Center

    Miles, Curtis

    1983-01-01

    Reviews sources of information on materials for teaching reasoning with a microcomputer. Suggests microcomputer magazines, catalogs of commercial materials, CONDUIT (a nonprofit organization devoted to educational computer use), and local microcomputer users groups. Lists Apple II software for strategy games with reasoning applications. (DMM)

  3. Modern Physics, 4th edition

    NASA Astrophysics Data System (ADS)

    Tipler, Paul A.; Llewellyn, Ralph

    The new edition of the classic text for the intermediate-level modern physics course, revised and updated to take students to the forefront of contemporary research and applications across the full spectrum of science and technology."

  4. Installation Contracting Course (4th)

    DTIC Science & Technology

    1991-09-27

    increasingly having to cope with the presence of endangered species (e.g., the desert tortoise at Fort Irwin and the red cockaded woodpecker at Fort Bragg). 3...the ears." Robert Burton Anatomy of Melancholy "Democritus to the Reader" I. INTRODUCTION. A. References. 1. FAR SUBPART 33.2; DFARS 33.232; AFARS

  5. Molecularly imprinted pipette-tip solid phase extraction for selective determination of fluoroquinolones in human urine using HPLC-DAD.

    PubMed

    de Oliveira, Hanna Leijoto; da Silva Anacleto, Sara; da Silva, Anny Talita Maria; Pereira, Arnaldo César; de Souza Borges, Warley; Figueiredo, Eduardo Costa; Borges, Keyller Bastos

    2016-10-15

    A simple method using HPLC-DAD was developed for the determination of fluoroquinolones in human urine including ciprofloxacin (CIPRO), enrofloxacino (ENRO), marbofloxacino (MARBO) and norfloxacin (NOR). In addition, it was studied the extraction of fluoroquinolones in human urine samples using pipette tip-based molecularly imprinted polymers solid phase extraction (PT-MIPs-SPE). With the goal of finding the best procedure for extraction of four fluoroquinolones in human urine, several parameters that are likely to affect the efficiency of extraction during sample preparation, including the washing solvent, type and volume of eluent, amount of material, the volume of the sample, pH and the ionic strength were systematically optimized. Chromatographic separations of fluoroquinolones were hit within 10min using a Synergi(®) C18 (250×4.6mm, 4μm) column and mobile phase consisting of water (10mM of phosphoric acid, the pH adjusted at 3.29 with triethylamine) : acetonitrile (85.7: 14.3, v/v) at a flow rate of 1.5mLmin(-1). Detection was performed at 290nm. The average extraction recoveries/standard deviation relative to ENRO, CIPRO, NOR and MARBO were 96.40±5.51%, 42.47±4.81%, 41.82±7.99% and 87.49±4.70, respectively. The method was liner from 39 to 1260ngmL(-1) for each fluoroquinolone with correlation coefficient of 0.9904, 0.9910, 0.9914 and 0.9919, to ENRO, CIPRO, NOR and MARBO, respectively. The assays of within-day and between-day precision and accuracy for all analytes were studied at three concentration levels and were lower than 15%. The method was successfully employed in a preliminary cumulative urinary excretion study after administration of CIPRO to a healthy volunteer.

  6. 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

  7. Spontaneous mutation frequency and molecular mechanisms of Shigella flexneri fluoroquinolone resistance under antibiotic selective stress.

    PubMed

    Pu, Xiao-Ying; Zhang, Qijing; Pan, Jing-Cao; Shen, Zhangqi; Zhang, Wei

    2013-02-01

    The incidence of fluoroquinolone-resistant Shigella strains has risen rapidly, presumably in response to ciprofloxacin antibiotic stress. Understanding the molecular mechanisms underlying this resistance phenotype is critical to developing novel and effective therapeutic strategies. In this study, the frequency of ciprofloxacin-induced mutation was measured in antibiotic resistance genes (gyrA, gyrB, parC, parE, marOR, and marA) of Shigella flexneri. The S. flexneri 2a strain 301 was cultured on Luria-Bertani agar plates containing one of seven different ciprofloxacin concentrations (range: 0.03125-2 μg mL(-1)). Resistant colonies were selected for gene-targeted sequencing analysis; the identified point mutations were subsequently confirmed by insertion into antibiotic cassette plasmids and growth under ciprofloxacin stress. The results demonstrated that the seven different ciprofloxacin concentrations produced dose-dependent frequencies of spontaneous mutations: 10(-8) (0.03125 and 0.0625 μg mL(-1)), 10(-9) (0.125 μg mL(-1)), and <10(-9) (0.25, 0.5, 1, 2 μg mL(-1)). PCR sequencing of the ten randomly selected resistant colonies (minimum inhibitory concentrations (MICs) of 0.125 μg mL(-1), n = 5 and 0.25 μg mL(-1), n = 5) revealed that all colonies had mutations in the gyrA gene at either codon 83 (Ser83 → Leu) or 87 (Asp87 → Tyr or → Gly), both of which were confirmed at MIC of 0.125 μg mL(-1). None of the spontaneous mutation colonies exhibited gyrB, parC, parE, marOR, or marA mutations. In conclusion, S. flexneri is normomutable under ciprofloxacin antibiotic stress and fluoroquinolone resistance by spontaneous mutation occurs at a low rate. Codon mutations gyrA 83 and/or gyrA 87 cause a 4-fold increase in the ciprofloxacin MIC, and may represent the natural mechanism of fluoroquinolone resistance.

  8. 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

  9. 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

  10. 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.

  11. Impact of fluoroquinolones on human microbiota. Focus on the emergence of antibiotic resistance.

    PubMed

    de Lastours, Victoire; Fantin, Bruno

    2015-01-01

    The aggregate of microorganisms residing on the surface of the skin, in the oropharynx and in the GI tract, known as the human microbiota, play a major role as natural reservoirs for bacterial resistance to antibiotics. Fluoroquinolones (FQ) are among the most prescribed antibiotics and a major increase in FQ resistance is occurring worldwide. High concentrations of FQ are found in microbial ecosystems explaining their profound effect on the clinically relevant bacteria that compose them. Yet, because of different local pharmacokinetics, distinct selective pressures occur in the different microbiota. Here we review the qualitative and quantitative impact of FQ on the three main human microbiota and their consequences, particularly in terms of emergence of antibiotic resistance. Finally, we review potential actions that could decrease the impact of FQs on microbiota.

  12. 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.

  13. Predicting the minimal inhibitory concentration of fluoroquinolones for Escherichia coli using an accumulation model.

    PubMed

    Zhang, Wen; Wang, Chenyin; Tam, Kin Y

    2014-01-01

    The objective of this study is to evaluate whether the accumulation model developed by Zarfl et al. (2008) could be used to predict the minimal inhibitory concentration (MIC) of a group of antibacterial fluoroquinolones (FQs) for Escherichia coli (E. coli). Our model, which is based on the "Fick-Nernst-Planck" equation and the permeability of the neutral and charged species as well as the physicochemical parameters of the FQs, could predict 1/MIC90 using a linear function. It is envisaged that in the drug development projects of new FQs, the accumulation model described in this study could be utilized as an effective tool to enable early assessment of MIC value using physiochemical parameters.

  14. Simultaneous Raising of Rabbit Monoclonal Antibodies to Fluoroquinolones with Diverse Recognition Functionalities via Single Mixture Immunization.

    PubMed

    Liu, Na; Zhao, Zhiyong; Tan, Yanglan; Lu, Lei; Wang, Lin; Liao, Yucai; Beloglazova, Natalia; De Saeger, Sarah; Zheng, Xiaodong; Wu, Aibo

    2016-01-19

    Highly specific monoclonal and polyclonal antibodies are the key components in a diverse set of immunoassay applications, from research work to routine monitoring and analysis. In the current manuscript, combinatorial strategies for a single mixture immunization, screening and rabbit hybridoma cell technology were described. Fluoroquinolones (FQs) drugs were chosen as representative analytes. Six FQs were conjugated with bovine serum albumin and used as immunogens for subsequent immunization, while a mixture of all was injected for coimmunization. The hybridomas obtained against the individual and multiple FQs were used for the production of diverse varieties of rabbit monoclonal antibodies (RabMAbs) against the target analytes. As was proven by indirect competitive ELISA and quantitative lateral flow immunoassay, this approach opens a new way for simultaneously obtaining functional monoclonal antibodies which are capable of recognizing both individual and multiple analytes in a single preparation circle. This addresses various needs of different monitoring regulations as analytical methodology advances.

  15. 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

  16. Immunochemical determination of fluoroquinolone antibiotics in cattle hair: a strategy to ensure food safety.

    PubMed

    Fernández, Fátima; Pinacho, Daniel G; Gratacós-Cubarsí, Marta; García-Regueiro, José-Antonio; Castellari, Massimo; Sánchez-Baeza, Francisco; Marco, M-Pilar

    2014-08-15

    Enrofloxacin (ERFX) is a synthetic antibiotic of the fluoroquinolone (FQ) family, which is commonly administered in veterinary medicine. ERFX and its metabolite, ciprofloxacin (CPFX), have been reported to accumulate in hair of treated animals. Therefore, hair analysis is an attractive non-invasive alternative to control misuse of such antibiotic and to ensure food safety by preventing such food derived products arrive to the consumer. In this context, an immunochemical analytical protocol has been established to detect ERFX and CPFX residues in cattle hair samples. Unpigmented and pigmented hair were collected from ERFX-treated and non-treated calves, and the aqueous NH4OH extracts were directly analyzed by ELISA, being possible to achieve limits of detection in the range of 10-30 μg kg(-1). A good concordance between HPLC and ELISA measurements was observed. The results demonstrate the potential of the immunochemical procedure reported here to rapidly screen and quantitate FQ residues in hair samples.

  17. Novel organic salts based on fluoroquinolone drugs: synthesis, bioavailability and toxicological profiles.

    PubMed

    Florindo, Catarina; Costa, Alexandra; Matos, Carla; Nunes, Sara L; Matias, Ana N; Duarte, Catarina M M; Rebelo, Luís Paulo N; Branco, Luís C; Marrucho, Isabel M

    2014-07-20

    In order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), novel organic salts containing fluoroquinolones (e.g. ciprofloxacin and norfloxacin) were prepared, using an optimized synthetic procedure based on direct protonation, with different biocompatible counter ions such as mesylate, gluconate and glycolate. All the prepared organic salts were characterized by spectroscopic techniques, mass spectrometry and thermal analysis. Solubility studies in water and simulated biological fluids at 25°C and 37°C were also performed. Additionally, octanol-water and phospholipid-water partition coefficients were measured at 25°C. The cytotoxicity and anti-inflammatory efficacy using an human cell model of intestinal epithelia (Caco-2 cells) were also evaluated and compared to those of the parent APIs. The adequate selection of the biocompatible anions allows the tuning of important physical, thermal and toxicological properties.

  18. 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

    2015-11-02

    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.

  19. 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

  20. 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.

  1. Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action?

    PubMed

    Dalhoff, A

    2015-04-01

    This review summarizes evidence that commercially available fluoroquinolones used for the treatment of bacterial infections are active against other non-bacterial infectious agents as well. Any of these fluoroquinolones exerts, in parallel to its antibacterial action, antiviral, antifungal, and antiparasitic actions at clinically achievable concentrations. This broad range of anti-infective activities is due to one common mode of action, i.e., the inhibition of type II topoisomerases or inhibition of viral helicases, thus maintaining the selective toxicity of fluoroquinolones inhibiting microbial topoisomerases at low concentrations but mammalian topoisomerases at much higher concentrations. Evidence suggests that standard doses of the fluoroquinolones studied are clinically effective against viral and parasitic infections, whereas higher doses administered topically were active against Candida spp. causing ophthalmological infections. Well-designed clinical studies should be performed to substantiate these findings.

  2. Effect of a Healthcare-system Respiratory Fluoroquinolone Restriction Program to Alter Utilization and Impact Rates of C. difficile Infection.

    PubMed

    Shea, Katherine M; Hobbs, Athena L V; Jaso, Theresa C; Bissett, Jack D; Cruz, Christopher M; Douglass, Elizabeth T; Garey, Kevin W

    2017-03-27

    Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a healthcare-system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. Following implementation, respiratory fluoroquinolone utilization decreased from a monthly mean (SD) of 41.0 (4.4) days of therapy per 1000 patient days (DOT/1000 PD) pre-intervention to 21.5 (6.4) DOT/1000 PD and 4.8 (3.6) DOT/1000 PD post-education and restriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1000 PD per month decrease; p=0.023) and restriction (24.5 DOT/1000 PD per month decrease; p<0.0001) were associated with decreased utilization. Additionally, CDI rates decreased significantly (p=0.044) from pre-intervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean (SD) monthly CDI cases/10,000 PD decreased from 4.0 (2.1) pre-intervention to 2.2 (1.35) post-restriction. A significant increase in appropriate respiratory fluoroquinolone use was experienced post-restriction vs. pre-intervention in patients administered at least 1 dose [74/232 (32%) vs. 74/130 (57%); p<0.001] as well as those receiving 2 or more doses [47/65 (72%) vs. 67/191 (35%); p<0.001]. A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was found post-restriction compared to pre-intervention within the healthcare-system ($123,882 vs. $12,273; p=0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a healthcare-system.

  3. [MALDI-ToF mass-spectrometry in analysis of genetically determined resistance of Streptococcus pneumoniae to fluoroquinolones].

    PubMed

    Malakhova, M V; Vereshchagin, V A; Il'ina, E N; Govorun, V M; Filimonova, O Iu; Grudinina, S A; Sidorenko, S V

    2007-01-01

    New fluoroquinolones with higher antipneumococcal activity are considered promising in the treatment of respiratory tract infections. Still, their wide use in clinical practice is connected with possible selection and rapid distribution of the resistance, requiring constant monitoring. Development of resistance to fluoroquinolones results from step-wise accumulation of mutations in the genes of DNA-gyrase and topoisomerase IV, the mutations of the first step being not always accompanied by a significant increase of the MIC of the new fluoroquinolones. Therefore, to detect the first signs of the resistance development, it is necessary not only to detect the susceptibility of the circulating Streptococcus pneumoniae strains phenotypically, but also to detect the genetic changes. In the present study the minisequent reaction followed by detection of the reaction products by MALD-ToF mass-spectrometry was used to reveal the mutations in the genes of the fluoroquinolone targets of 38 S. pneumoniae strains with different levels of the resistance to ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin. In the strains with high resistance to all the three fluoroquinolones (MIC 4-16 mcg/ml) there were detected mutations in GyrA (Ser81Tyr or Glu85Zys) and as well in ParC (Ser79Phe or Ser79Tyr). In the strains resistant to ofloxacin and ciprofloxacin (MIC 4-8 mcg/ml) with preserved susceptibility to levofloxacin and moxifloxacin, the mutations were detected only in GyrA (Ser114Gly). In the moderately resistant strains (MICs 4 and 2-4 mcg/ml respectively for ofloxacin and ciprofloxacin) there were detected the known mutations in ParC (Ser79Tyr or Ser79Phe or Asp83Tyr) and in GyrB (Glu475Lys) as well as the earlier not described mutations in ParE (ins Asn381a) and in Gyr B (Thr329Ala or Va1355Ile). The described method can be used in mass screening of S. pneumoniae strains for the presence of mutations in the genes of the fluoroquinolone targets.

  4. Fluoroquinolones stimulate the DNA cleavage activity of topoisomerase IV by promoting the binding of Mg2+ to the second metal binding site

    PubMed Central

    Oppegard, Lisa M.; Schwanz, Heidi A.; Towle, Tyrell R.; Kerns, Robert J.; Hiasa, Hiroshi

    2016-01-01

    Background Fluoroquinolones target bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV (Topo IV). Fluoroquinolones trap a topoisomerase-DNA covalent complex as a topoisomerase-fluoroquinolone-DNA ternary complex and ternary complex formation is critical for their cytotoxicity. A divalent metal ion is required for type IIA topoisomerase-catalyzed strand breakage and religation reactions. Recent studies have suggested that type IIA topoisomerases use two metal ions, one structural and one catalytic, to carry out the strand breakage reaction. Methods We conducted a series of DNA cleavage assays to examine the effects of fluoroquinolones and quinazolinediones on Mg2+-, Mn2+-, or Ca2+-supported DNA cleavage activity of Esherichia coli Topo IV. Results In the absence of any drug, 20–30 mM Mg2+ was required for the maximum levels of the DNA cleavage activity of Topo IV, whereas approximately 1 mM of either Mn2+ or Ca2+ was sufficient to support the maximum levels of the DNA cleavage activity of Topo IV. Fluoroquinolones promoted the Topo IV-catalyzed strand breakage reaction at low Mg2+ concentrations where Topo IV alone could not efficiently cleave DNA. Conclusions and General Significance At low Mg2+ concentrations, fluoroquinolones may stimulate the Topo IV-catalyzed strand breakage reaction by promoting Mg2+ binding to metal binding site B through the structural distortion in DNA. As Mg2+ concentration increases, fluoroquinolones may inhibit the religation reaction by either stabilizing Mg2+ at site B or inhibition the binding of Mg2+ to site A. This study provides a molecular basis of how fluoroquinolones stimulate the Topo IV-catalyzed strand breakage reaction by modulating Mg2+ binding. PMID:26723176

  5. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia.

    PubMed

    Averbuch, Diana; Orasch, Christina; Cordonnier, Catherine; Livermore, David M; Mikulska, Malgorzata; Viscoli, Claudio; Gyssens, Inge C; Kern, Winfried V; Klyasova, Galina; Marchetti, Oscar; Engelhard, Dan; Akova, Murat

    2013-12-01

    Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4(th) European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient's risk factors for resistant bacteria and for a complicated clinical course. An 'escalation' approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A 'de-escalation' approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72-96 h should be based on the patient's clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance.

  6. 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

  7. A 4th-order band-pass filter using differential readout of two in-phase actuated contour-mode resonators

    NASA Astrophysics Data System (ADS)

    Yagubizade, Hadi; Darvishi, Milad; Elwenspoek, Miko C.; Tas, Niels R.

    2013-10-01

    A 4th-order band-pass filter (BPF) based on the subtraction of two 2nd-order contour-mode Lamb-wave resonators is presented. The resonators have slightly different resonance frequencies around 380 MHz. Each resonator consists of a 500 nm pulsed-laser deposited lead zirconate titanate (PZT) thin-film on top of a 3 μm silicon (PZT-on-Si). The resonators are actuated in-phase, and their outputs are subtracted. Utilizing this technique, the feed-through signals are eliminated while the outputs of the resonators are added up constructively, due to the phase difference between the two output signals. The BPF is presented using 50 Ω termination with a bandwidth of approximately 3.9 MHz and 43 dB stopband rejection. This technique provides further opportunities for MEMS filter design in addition to existing methods, i.e., mechanical and/or electrical coupling. It also resolves the design issue associated with high feed-through when exploiting piezoelectric materials with high-dielectric constant like PZT.

  8. 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.

  9. 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

  10. [Report of the World Federation of Neurosurgical Societies (WFNS) international course and Cameroon Neurosurgery Society Congress (CNS) Yaoundé (Cameroon), 1st--4th October 2007].

    PubMed

    Eyenga, V C; Ndoumbe, A; Eloundou, N J

    2008-04-01

    Neurosurgery remains a very marginal activity in sub-Saharan Africa. In this part of the world which counts nearly 40 countries, some do not have a single neurosurgeon, some have one to five, the number of ten neurosurgeons per country remaining an exception! In its concern of popularizing and of developing neurosurgery worldwide, the WFNS organized an international course in Africa, October 2007 2nd-3rd in Yaoundé (Cameroon). The Cameroon Neurosurgery Society (CNS) took this opportunity to organize its very first congress in the presence of the WFNS delegation from October 1st to 4th, 2007. The joint meeting with the WFNS was baptized the "African Week of Neurosurgery". This special event was a first in sub-Saharan Africa. The delegation of the WFNS, led by Professor J. Brotchi (Belgium) President of the WFNS, was made up of Professors A. Sousa (Brazil), Mr. Choux (France), N. Tribolet (Swiss), M. Arraez (Spain), A. Bricolo (Italy), A. Kamlichi (Morocco), G. Dechambenoit (France), K. Kalangu (Zimbabwe). Twenty three neurosurgeons coming from nine African countries (Cameroon, Nigeria, Gabon, Congo, Niger, Burkina Faso, Ivory Coast, Senegal, and Guinea) took an active part in work. The scientific success of this event led to the creation of the "Association of Neurological Surgeons of Africa (ANSA)" which will be the WFNS-Africa interface in order to insure the development of neurosurgery in Africa.

  11. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland.

    PubMed

    Seethala, Raja R; Stenman, Göran

    2017-03-01

    The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of "Other epithelial lesions," for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.

  12. The structure of Diagnostic and Statistical Manual of Mental Disorders (4th edition, text revision) personality disorder symptoms in a large national sample.

    PubMed

    Trull, Timothy J; Vergés, Alvaro; Wood, Phillip K; Jahng, Seungmin; Sher, Kenneth J

    2012-10-01

    We examined the latent structure underlying the criteria for DSM-IV-TR (American Psychiatric Association, 2000, Diagnostic and statistical manual of mental disorders (4th ed., text revision). Washington, DC: Author.) personality disorders in a large nationally representative sample of U.S. adults. Personality disorder symptom data were collected using a structured diagnostic interview from approximately 35,000 adults assessed over two waves of data collection in the National Epidemiologic Survey on Alcohol and Related Conditions. Our analyses suggested that a seven-factor solution provided the best fit for the data, and these factors were marked primarily by one or at most two personality disorder criteria sets. A series of regression analyses that used external validators tapping Axis I psychopathology, treatment for mental health problems, functioning scores, interpersonal conflict, and suicidal ideation and behavior provided support for the seven-factor solution. We discuss these findings in the context of previous studies that have examined the structure underlying the personality disorder criteria as well as the current proposals for DSM-5 personality disorders.

  13. European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia

    PubMed Central

    Averbuch, Diana; Orasch, Christina; Cordonnier, Catherine; Livermore, David M.; Mikulska, Małgorzata; Viscoli, Claudio; Gyssens, Inge C.; Kern, Winfried V.; Klyasova, Galina; Marchetti, Oscar; Engelhard, Dan; Akova, Murat

    2013-01-01

    Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4th European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient’s risk factors for resistant bacteria and for a complicated clinical course. An ‘escalation’ approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A ‘de-escalation’ approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72–96 h should be based on the patient’s clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance. PMID:24323983

  14. Frequency Drift Rate Investigation of Solar Radio Burst Type II Due to Coronal Mass Ejections Occurrence on 4th November 2015 Captured by CALLISTO at Sumedang-Indonesia

    NASA Astrophysics Data System (ADS)

    Batubara, M.; Manik, T.; Suryana, R.; Lathif, M.; Sitompul, P.; Zamzam, M.; Mumtahana, F.

    2017-03-01

    The formations type of solar radio bursts can be known base on the frequency range that is detected. The CALLISTO system works with a wide band of the frequency making it possible to detect several types of solar burst. Indonesia exactly at Sumedang, CALLISTO system detected the formation of solar radio bursts forms of type II for the first time on 5 November 2014. On the other side, CALLISTO spectrometer detects and traces the phenomenon of CME (Coronal Mass Ejections) which causes the solar radio burst type II occurrence. In this paper will be calculated frequency drift rate during the occurrence of solar radio bursts of type II phenomenon on 4th November 2015 at 03:30 UT. The results of these calculations will be discussed as a related study of drift rate during the phenomenon of burst type II radio bursts associated with CME. The obtained drift rate during the solar radio bursts events above 2.8 MHz / s with low drift rate so that the speed of the CME that occurred only about 790 km / s as shown from LASCO.

  15. Does empirical treatment of community-acquired pneumonia with fluoroquinolones delay tuberculosis treatment and result in fluoroquinolone resistance in Mycobacterium tuberculosis? Controversies and solutions.

    PubMed

    Shen, Gwan-Han; Tsao, Thomas Chang-Yao; Kao, Shang-Jyh; Lee, Jen-Jyh; Chen, Yen-Hsu; Hsieh, Wei-Chung; Hsu, Gwo-Jong; Hsu, Yen-Tao; Huang, Ching-Tai; Lau, Yeu-Jun; Tsao, Shih-Ming; Hsueh, Po-Ren

    2012-03-01

    The role of fluoroquinolones (FQs) as empirical therapy for community-acquired pneumonia (CAP) remains controversial in countries with high tuberculosis (TB) endemicity owing to the possibility of delayed TB diagnosis and treatment and the emergence of FQ resistance in Mycobacterium tuberculosis. Although the rates of macrolide-resistant Streptococcus pneumoniae and amoxicillin/clavulanic acid-resistant Haemophilus influenzae have risen to alarming levels, the rates of respiratory FQ (RFQ) resistance amongst these isolates remain relatively low. It is reported that ca. 1-7% of CAP cases are re-diagnosed as pulmonary TB in Asian countries. A longer duration (≥ 7 days) of symptoms, a history of night sweats, lack of fever (> 38 °C), infection involving the upper lobe, presence of cavitary infiltrates, opacity in the lower lung without the presence of air, low total white blood cell count and the presence of lymphopenia are predictive of pulmonary TB. Amongst patients with CAP who reside in TB-endemic countries who are suspected of having TB, imaging studies as well as aggressive microbiological investigations need to be performed early on. Previous exposure to a FQ for >10 days in patients with TB is associated with the emergence of FQ-resistant M. tuberculosis isolates. However, rates of M. tuberculosis isolates with FQ resistance are significantly higher amongst multidrug-resistant M. tuberculosis isolates than amongst susceptible isolates. Consequently, in Taiwan and also in other countries with TB endemicity, a short-course (5-day) regimen of a RFQ is still recommended for empirical therapy for CAP patients if the patient is at low risk for TB.

  16. CD4+ Th1 cells promote CD8+ Tc1 cell survival, memory response, tumor localization and therapy by targeted delivery of interleukin 2 via acquired pMHC I complexes.

    PubMed

    Huang, Hui; Hao, Siguo; Li, Fang; Ye, Zhenmin; Yang, Junbao; Xiang, Jim

    2007-02-01

    The cooperative role of CD4+ helper T (Th) cells has been reported for CD8+ cytotoxic T (Tc) cells in tumor eradication. However, its molecular mechanisms have not been well elucidated. We have recently demonstrated that CD4+ Th cells can acquire major histocompatibility complex/peptide I (pMHC I) complexes and costimulatory molecules by dendritic cell (DC) activation, and further stimulate naïve CD8+ T cell proliferation and activation. In this study, we used CD4+ Th1 and CD8+ Tc1 cells derived from ovalbumin (OVA)-specific T cell receptor (TCR) transgenic OT II and OT I mice to study CD4+ Th1 cell's help effects on active CD8+ Tc1 cells and the molecular mechanisms involved in CD8+ Tc1-cell immunotherapy of OVA-expressing EG7 tumors. Our data showed that CD4+ Th1 cells with acquired pMHC I by OVA-pulsed DC (DCOVA) stimulation are capable of prolonging survival and reducing apoptosis formation of active CD8+ Tc1 cells in vitro, and promoting CD8+ Tc1 cell tumor localization and memory responses in vivo by 3-folds. A combined adoptive T-cell therapy of CD8+ Tc1 with CD4+ Th1 cells resulted in regression of well-established EG7 tumors (5 mm in diameter) in all 10/10 mice. The CD4+ Th1's help effect is mediated via the helper cytokine IL-2 specifically targeted to CD8+ Tc1 cells in vivo by acquired pMHC I complexes. Taken together, these results will have important implications for designing adoptive T-cell immunotherapy protocols in treatment of solid tumors.

  17. TARGETed surveillance: susceptibility of Streptococcus pneumoniae isolated from community-acquired respiratory tract infections in 2003 to fluoroquinolones and other agents.

    PubMed

    Morrissey, I; Colclough, A; Northwood, J

    2007-10-01

    We assessed antibiotic resistance in Streptococcus pneumoniae collected worldwide in 2003. Resistance to clarithromycin was the highest overall (34.1%) followed by penicillin G (22.1%). Patient age and/or country of origin had the greatest effect on susceptibility. Resistance was highest in children<6 years of age and in patients from South Africa or France. Resistance to penicillin or amoxicillin/clavulanic acid decreased in adults and was low in Germany. Fluoroquinolone resistance was very low overall, but 3.0% levofloxacin resistance (2.6% gatifloxacin and 0.4% moxifloxacin) was observed in Italy. Interestingly, many isolates with minimum inhibitory concentrations (MICs) at the top of the fluoroquinolone susceptibility breakpoints possessed single quinolone resistance-determining region (QRDR) mutations. Care should be taken when treating fluoroquinolone-susceptible isolates with a higher MIC, which are likely to harbour QRDR mutations and may become fully resistant and cause treatment failure. We concur with the conclusions of other recent studies that suggest fluoroquinolone breakpoints should be lowered to ensure these isolates are categorised as resistant. Fluoroquinolones would still remain an important alternative treatment for respiratory tract infections (albeit for adults only), with moxifloxacin being the most potent fluoroquinolone tested in this study.

  18. 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.

  19. Design, synthesis, and evaluation of novel fluoroquinolone-flavonoid hybrids as potent antibiotics against drug-resistant microorganisms.

    PubMed

    Xiao, Zhu-Ping; Wang, Xu-Dong; Wang, Peng-Fei; Zhou, Yin; Zhang, Jing-Wen; Zhang, Lei; Zhou, Jiao; Zhou, Sha-Sha; Ouyang, Hui; Lin, Xiao-Yi; Mustapa, Manzira; Reyinbaike, Asaimuguli; Zhu, Hai-Liang

    2014-06-10

    Based on a rationally conceived pharmacophore model to build a multi-target bacterial topoisomerase inhibitor, twenty-one fluoroquinolone-flavonoid hybrids were synthesized. Some obtained hybrids show excellent antibacterial activity against drug-resistant microorganisms with narigenin-ciprofloxacin being the most active, showing 8, 43, 23 and 88 times better activity than ciprofloxacin against Escherichia coli ATCC 35218, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 90873, respectively. Drug accumulation and DNA supercoiling assays of two active analogues revealed potent inhibition of both the DNA gyrase and efflux pump, confirming the desired dual mode of action. Molecular docking study disclosed that the introduced flavonoid moiety not only provides several additional interactions but also does not disturb the binding mode of the floxacin moiety. Our data also demonstrated that development of antifungals is possible from fluoroquinolones modified at C-7 position.

  20. Surface interactions and degradation of a fluoroquinolone antibiotic in the dark in aqueous TiO2 suspensions

    DOE PAGES

    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

  1. 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

  2. Surface-coated wooden-tip electrospray ionization mass spectrometry for determination of trace fluoroquinolone and macrolide antibiotics in water.

    PubMed

    Deng, Jiewei; Yu, Tiantian; Yao, Yao; Peng, Qi; Luo, Lijuan; Chen, Baowei; Wang, Xiaowei; Yang, Yunyun; Luan, Tiangang

    2017-02-15

    In this study, a surface-coated wooden-tip electrospray ionization mass spectrometry (SCWT-ESI-MS) method was developed for rapid and sensitive analysis of trace fluoroquinolone and macrolide antibiotics in water. First, a SCWT solid-phase microextration (SPME) probe was prepared, via silanization and sulfonation for modification of a layer of adsorbent containing both C8-chain and sulfo group on the surface of wooden tips. Then, the SCWT-SPME probe was applied for extraction of trace fluoroquinolone and macrolide antibiotics in water. The specially designed adsorbent gave the probe desirable enrichment capacity towards fluoroquinolone and macrolide antibiotics, with enrichment factors of approximately 100-500 folds for six target analytes. After extraction, the loaded SCWT-SPME probe was directly applied for ambient MS analysis. With the application of a high voltage and some spray solvent on the SCWT-SPME probe, analytes enriched on the probe was desorbed and ionized for mass spectrometric analysis under ambient and open-air conditions. The method was sensitive, with limits of detection and quantification of 1.8-4.5 ng/L and 5.9-15.1 ng/L, respectively. The method also showed good linearity, with correlation coefficient values (r(2)) of no less than 0.9940 for six target analytes. The developed method was successfully applied for the analysis of six fluoroquinolone and macrolide antibiotics in tap and river water samples, and no antibiotic was found in tap water but some antibiotics were detected in river water with concentrations at dozens to hundreds nanogram-per-liter level. Standard addition experiments were also performed, and the obtained recoveries were 89-102% for tap waters and 82-92% for river waters, respectively. All the experimental results demonstrated that our proposed SCWT-ESI-MS method was rapid, sensitive, and reliable for analyzing trace antibiotics in water.

  3. Repression of Invasion Genes and Decreased Invasion in a High-Level Fluoroquinolone-Resistant Salmonella Typhimurium Mutant

    PubMed Central

    Fàbrega, Anna; du Merle, Laurence; Le Bouguénec, Chantal; Jiménez de Anta, M. Teresa; Vila, Jordi

    2009-01-01

    Background Nalidixic acid resistance among Salmonella Typhimurium clinical isolates has steadily increased, whereas the level of ciprofloxacin resistance remains low. The main objective of this study was to characterize the fluoroquinolone resistance mechanisms acquired in a S. Typhimurium mutant selected with ciprofloxacin from a susceptible isolate and to investigate its invasion ability. Methodology/Principal Findings Three different amino acid substitutions were detected in the quinolone target proteins of the resistant mutant (MIC of ciprofloxacin, 64 µg/ml): D87G and G81C in GyrA, and a novel mutation, E470K, in ParE. A protein analysis revealed an increased expression of AcrAB/TolC and decreased expression of OmpC. Sequencing of the marRAB, soxRS, ramR and acrR operons did not show any mutation and neither did their expression levels in a microarray analysis. A decreased percentage of invasion ability was detected when compared with the susceptible clinical isolate in a gentamicin protection assay. The microarray results revealed a decreased expression of genes which play a role during the invasion process, such as hilA, invF and the flhDC operon. Of note was the impaired growth detected in the resistant strain. A strain with a reverted phenotype (mainly concerning the resistance phenotype) was obtained from the resistant mutant. Conclusions/Significance In conclusion, a possible link between fluoroquinolone resistance and decreased cell invasion ability may exist explaining the low prevalence of fluoroquinolone-resistant S. Typhimurium clinical isolates. The impaired growth may appear as a consequence of fluoroquinolone resistance acquisition and down-regulate the expression of the invasion genes. PMID:19946377

  4. Mechanistic considerations for the advanced oxidation treatment of fluoroquinolone pharmaceutical compounds using TiO(2) heterogeneous catalysis.

    PubMed

    An, Taicheng; Yang, Hai; Song, Weihua; Li, Guiying; Luo, Haiying; Cooper, William J

    2010-02-25

    Pharmaceutical compounds and metabolites are being found in surface and ground waters which is indicative of inefficient removal by conventional wastewater treatment technologies. Advanced oxidation processes (AOPs), which utilize free-radical reactions to degrade chemical contaminates, are an alternative to traditional water treatment. Three fluoroquinolone pharmaceutical compounds were studied and the absolute rate constants for hydroxyl radical (*OH) and hydrated electron (e(-)(aq)) are reported. For norfloxacin, levofloxacin, and lomefloxacin, the bimolecular reaction rate constants with *OH were determined as (6.18 +/- 0.18) x 10(9), (7.59 +/- 0.16) x 10(9) and (8.04 +/- 0.62) x 10(9) M(-1) s(-1), and with e(-)(aq) were (1.18 +/- 0.10) x 10(10), (2.46 +/- 0.05) x 10(10) and (2.79 +/- 0.05) x 10(10) M(-1) s(-1), respectively. To provide insights into the chemistry of destruction of these three target pharmaceuticals, transient spectra were obtained for the reaction of hydroxyl radicals with the three compounds. Photocatalysis was chosen as a representative advanced oxidation technology to degrade these three fluoroquinolones and their degradation pathways were proposed. Elimination of piperazynilic ring in fluoroquinolone molecules, addition of hydroxyl radical to quinolone ring, and ipso attack at the F atoms on the aromatic ring by hydroxyl radicals occurred. These results indicate that AOPs involving production of *OH radicals are efficiently alternative treatment technologies for degradation of fluoroquinolones in aqueous solution.

  5. Comparison of charcoal- and starch-based media for testing susceptibilities of Legionella species to macrolides, azalides, and fluoroquinolones.

    PubMed Central

    Pendland, S L; Martin, S J; Chen, C; Schreckenberger, P C; Danziger, L H

    1997-01-01

    We compared growth characteristics of 46 Legionella strains grown on buffered charcoal yeast extract alpha (BCYE alpha) agar and buffered starch yeast extract (BSYE) agar and MICs of macrolides, azalides, and fluoroquinolones for these organisms. Growth was poor and not reproducible on BSYE agar. Growth was excellent on BCYE alpha, and MICs were easy to interpret. BCYE alpha is superior to BSYE for testing susceptibilities of Legionella species by agar dilution. PMID:9350781

  6. Prevalence of resistance to aminoglycosides and fluoroquinolones among Pseudomonas aeruginosa strains in a University Hospital in Northeastern Poland.

    PubMed

    Michalska, Anna Diana; Sacha, Pawel Tomasz; Ojdana, Dominika; Wieczorek, Anna; Tryniszewska, Elzbieta

    2014-01-01

    The present study was conducted to investigate the prevalence of genes encoding resistance to aminoglycosides and fluoroquinolones among twenty-five Pseudomonas aeruginosa isolated between 2002 and 2009. In PCR, following genes were detected: ant(2″)-Ia in 9 (36.0%), aac(6')-Ib in 7 (28.0%), qnrB in 5 (20.0%), aph(3″)-Ib in 2 (8.0%) of isolates.

  7. 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.

  8. In vitro susceptibility of six fluoroquinolones against invasive Streptococcus pneumoniae isolated from 1996 to 2001 in Taiwan.

    PubMed

    Chen, J Y; Fung, C P; Wang, C C; Chu, M L; Siu, L K

    2003-01-01

    A total of 331 invasive nonduplicated Streptococcus pneumoniae isolates from three sampling periods during 1996 to 2001 were tested for susceptibility to recently developed fluoroquinolones. Five major serotypes, 23F, 6B, 14, 19F, and 3, were frequently encountered in this collection. Penicillin nonsusceptible isolates constituted 52.9% from 1996 to 1997, 61.6% from 1998 to 1999, and 60.0% from 2000 to 2001. Fifty-seven percent of the isolates were susceptible to cefotaxime, 56.5% to ceftriaxone, 54.1% to cefepime, and 52.6% to cefuroxime. Macrolide-susceptible isolates constituted less than 14% of the total sample, and no vancomycin-resistant isolates were detected. For fluoroquinolones, MIC90 was lowest for gemifloxacin (MIC90 = < or = 0.12 microg/ml), followed by moxifloxacin (MIC90 = 0.25 microg/ml), gatifloxacin (MIC90 = 0.5 microg/ml), sparfloxacin (MIC90 = 0.5 microg/ml), levofloxacin (MIC90 = 1 microg/ml), and ciprofloxacin (MIC90 = 2 microg/ml). All isolates were susceptible to sparfloxacin, levofloxacin, gatifloxacin, and gemifloxacin apart from one isolate (0.3%), which was simultaneously resistant to sparfloxacin, levofloxacin, and gatifloxacin. Mutations at the positions S81F of GyrA and D435N and I460V of ParC were detected for this multiple drug resistant isolate. The in vitro results suggest that recently developed fluoroquinolones are very effective against invasive S. pneumoniae isolates in Taiwan. Nevertheless, emerging fluoroquinolone resistance should be acknowledged and clinicians alerted. Surveillance should be carried out to monitor any changes in antibiotic resistance of S. pneumoniae.

  9. 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.

  10. Salicylate functions as an efflux pump inducer and promotes the emergence of fluoroquinolone-resistant Campylobacter jejuni mutants.

    PubMed

    Shen, Zhangqi; Pu, Xiao-Ying; Zhang, Qijing

    2011-10-01

    Salicylate, a nonsteroidal anti-inflammatory compound, has been shown to increase the resistance of Campylobacter to antimicrobials. However, the molecular mechanism underlying salicylate-induced resistance has not yet been established. In this study, we determined how salicylate increases antibiotic resistance and evaluated its impact on the development of fluoroquinolone-resistant Campylobacter mutants. Transcriptional fusion assays, real-time quantitative reverse transcription-PCR (RT-PCR), and immunoblotting assays consistently demonstrated the induction of the CmeABC multidrug efflux pump by salicylate. Electrophoretic mobility shift assays further showed that salicylate inhibits the binding of CmeR (a transcriptional repressor of the TetR family) to the promoter DNA of cmeABC, suggesting that salicylate inhibits the function of CmeR. The presence of salicylate in the culture medium not only decreased the susceptibility of Campylobacter to ciprofloxacin but also resulted in an approximately 70-fold increase in the observed frequency of emergence of fluoroquinolone-resistant mutants under selection with ciprofloxacin. Together, these results indicate that in Campylobacter, salicylate inhibits the binding of CmeR to the promoter DNA and induces expression of cmeABC, resulting in decreased susceptibility to antibiotics and in increased emergence of fluoroquinolone-resistant mutants under selection pressure.

  11. The selection of resistance to and the mutagenicity of different fluoroquinolones in Staphylococcus aureus and Streptococcus pneumoniae.

    PubMed

    Sierra, J M; Cabeza, J G; Ruiz Chaler, M; Montero, T; Hernandez, J; Mensa, J; Llagostera, M; Vila, J

    2005-09-01

    Two quinolone-susceptible Staphylococcus aureus and five quinolone-susceptible Streptococcus pneumoniae isolates were used to obtain in-vitro quinolone-resistant mutants in a multistep resistance selection process. The fluoroquinolones used were ciprofloxacin, moxifloxacin, levofloxacin, gemifloxacin, trovafloxacin and clinafloxacin. The mutagenicity of these quinolones was determined by the Salmonella and the Escherichia coli retromutation assays. All quinolone-resistant Staph. aureus mutants had at least one mutation in the grlA gene, while 86.6% of quinolone-resistant Strep. pneumoniae mutants had mutations in either or both the gyrA and parC genes. Moxifloxacin and levofloxacin selected resistant mutants later than the other quinolones, but this difference was more obvious in Staph. aureus. Accumulation of the fluoroquinolones by Staph. aureus did not explain these differences, since levofloxacin and moxifloxacin accumulated inside bacteria to the same extent as clinafloxacin and trovafloxacin. The results also showed that moxifloxacin and levofloxacin had less mutagenic potency in both mutagenicity assays, suggesting a possible relationship between the selection of resistance to quinolones and the mutagenic potency of the molecule. Furthermore, gemifloxacin selected efflux mutants more frequently than the other quinolones used. Thus, the risk of developing quinolone resistance may depend on the density of the microorganism at the infection site and the concentration of the fluoroquinolone, and also on the mutagenicity of the quinolone used, with moxifloxacin and levofloxacin being the least mutagenic.

  12. Prevalence of Ile-460-Val/ParE substitution in clinical Streptococcus pneumoniae isolates that were less susceptible to fluoroquinolones.

    PubMed

    Kawamura-Sato, Kumiko; Hasegawa, Tadao; Torii, Keizo; Ito, Hideo; Ohta, Michio

    2005-07-01

    A total of 73 clinical isolates of Streptococcus pneumoniae were measured for susceptibilities to nine fluoroquinolones, and nucleotide sequences of the quinolone resistance-determining regions (QRDRs) were determined. MIC90s of sparfloxacin, tosufloxacin, grepafloxacin, and gatifloxacin were less than 0.5 mg/L and the MIC90 of ciprofloxacin was 2 mg/L, although MIC values of some isolates to ciprofloxacin were more than 2 mg/L. We found that 60 of 73 isolates had only Ile-460-Val/ParE substitution and two isolates had an additional substitution of Ser-114-Gly/GyrA, while none of the isolates had any other substitutions in QRDRs of either ParC/E or GyrA/B. The isolates carrying Ile-460-Val/ParE substitution were more resistant to the fluoroquinolones norfloxacin and ciprofloxacin than the isolates with no amino acid substitution and the differences in MIC values were significant, suggesting that Ile-460-Val/ParE substitution in recent clinical S. pneumoniae isolates should be involved in the low-level fluoroquinolone resistance.

  13. 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…

  14. Impact of preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria on the incidence of sepsis following transrectal ultrasound guided prostate biopsy

    PubMed Central

    Farrell, John J; Hicks, Jennifer L; Wallace, Stephanie E; Seftel, Allen D

    2017-01-01

    With the universal adoption of antibiotic prophylaxis prior to prostate biopsy, the current risk of post-biopsy infection (including sepsis) is <2%. Preoperative prophylactic antibiotic regimens can vary, and although fluoroquinolones have emerged as the standard of care, there is no universally agreed upon preoperative antibiotic regimen. Recently, an increase in the proportion of postoperative infections caused by fluoroquinolone-resistant Escherichia coli (as well as other Enterobacteriaceae) has led to the exploration of simple, practical, and cost-effective methods to minimize this postoperative infection risk. We performed a prospective, nonrandomized, controlled study of preoperative rectal cultures to screen for rectal colonization with fluoroquinolone-resistant bacteria using ciprofloxacin-supplemented MacConkey agar culture media. To evaluate the feasibility and practicality of this test, one provider used the results of rectal swab cultures collected during the preoperative outpatient evaluation to adjust each patient’s preoperative antibiotic prophylaxis when fluoroquinolone-resistant enteric bacteria were detected, whereas two other providers continued usual preoperative care and empiric antimicrobial prophylaxis. Rectal colonization with fluoroquinolone-resistant bacteria was detected in 19/152 (12.5%) of patients. In our intention-to-treat analysis (N=268), the rate of post-biopsy sepsis was 3.6% lower in the group that was screened for rectal colonization with fluoroquinolone-resistant bacteria prior to transrectal prostate biopsy. The observed risk reduction in the rectal screening group trended toward, but did not achieve, statistical significance. We suggest that preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria may be a useful step toward mitigating post-prostate biopsy sepsis. PMID:28280717

  15. Highly sensitive detection of five typical fluoroquinolones in low-fat milk by field-enhanced sample injection-based CE in bubble cell capillary.

    PubMed

    Deng, Yan; Gasilova, Natalia; Qiao, Liang; Zhou, Ying-Lin; Zhang, Xin-Xiang; Girault, Hubert H

    2014-12-01

    Fluoroquinolones are a group of synthetic antibiotics with a broad activity spectrum against mycoplasma, Gram-positive, and Gram-negative bacteria. Due to the extensive use of fluoroquinolones in farming and veterinary science, there is a constant need in the analytical methods able to efficiently monitor their residues in food products of animal origin, regulated by Commission Regulation (European Union) no. 37/2010. Herein, field-enhanced sample injection for sample stacking prior the CZE separation was developed inside a bubble cell capillary for highly sensitive detection of five typical fluoroquinolones in bovine milk. Ethylenediamine was proposed as the main component of BGE for the antibiotics separation. The effect of BGE composition, injection parameters, and water plug length on the field-enhanced sample injection-based CE with UV detection was investigated. Under the optimized conditions, described field-enhanced sample injection-based CE-UV analysis of fluoroquinolones provides LODs varying from 0.4 to 1.3 ng/mL. These LOD values are much lower (from 460 to 1500 times) than those obtained by a conventional CE in a standard capillary without bubble cell. The developed method was finally applied for the analysis of fluoroquinolones in low-fat milk from a Swiss supermarket. Sample recovery values from 93.6 to 106.0% for different fluoroquinolones, and LODs from 0.7 to 2.5 μg/kg, were achieved. Moreover, the proposed ethylenediamine-based BGE as volatile and compatible with MS system, enabled the coupling of the field-enhanced sample injection-based CE with a recently introduced electrostatic spray ionization MS via an iontophoretic fraction collection interface for qualitative fluoroquinolones identification.

  16. Detection and prevention of ocular phototoxicity of ciprofloxacin and other fluoroquinolone antibiotics.

    PubMed

    Zhao, Baozhong; Chignell, Colin F; Rammal, Mustapha; Smith, Frank; Hamilton, Mary G; Andley, Usha P; Roberts, Joan E

    2010-01-01

    Fluoroquinolone (FLQ) drugs are a potent family of antibiotics used to treat infections including ocular infections. To determine if these antibiotics may be phototoxic to the eye, we exposed human lens epithelial cells to 0.125-1 mm FLQs (ciprofloxacin [Cipro], lomefloxacin [Lome], norfloxacin [Nor] and ofloxacin [Ofl]), the precursor quinolone nalidixic acid (Nalid) and UVA radiation (2.5 J cm(-2)). Based on fluorescence confocal microscopy, FLQs are diffused throughout the cytoplasm and preferentially located in the lysosomes of lens epithelial cells. Neither FLQ exposure alone nor UVA exposure alone reduced cell viability. However, with exposure to UVA radiation the FLQs studied (Cipro, Nor, Lome and Ofl) induced a phototoxic reaction that included necrosis, apoptosis, loss of cell viability as measured by MTS, and membrane damage as determined by the lactate dehydrogenase assay. Both Nalid and all FLQs studied (Cipro, Nor, Lome and Ofl) photopolymerized the lens protein alpha-crystallin. Phototoxic damage to lens epithelial cells and/or alpha-crystallin will lead to a loss of transparency of the human lens. However, if precautions are taken to filter all UV radiation from the eye while taking these antibiotics, eye damage may be prevented.

  17. Environmental exposure assessment of fluoroquinolone antibacterial agents from sewage to soil.

    PubMed

    Golet, Eva M; Xifra, Irene; Siegrist, Hansruedi; Alder, Alfredo C; Giger, Walter

    2003-08-01

    The behavior of fluoroquinolone antibacterial agents (FQs) during mechanical-biological wastewater treatment was studied by mass flow analysis. In addition, the fate of FQs in agricultural soils after sludge application was investigated. Concentrations of FQs in filtered wastewater (raw sewage, primary, secondary, and tertiary effluents) were determined using solid-phase extraction with mixed phase cation exchange disk cartridges and reversed-phase liquid chromatography with fluorescence detection. FQs in suspended solids, sewage sludge (raw, excess, and anaerobically digested sludge), and sludge-treated soils were determined as described for the aqueous samples but preceded by accelerated solvent extraction. Wastewater treatment resulted in a reduction of the FQ mass flow of 88-92%, mainly due to sorption on sewage sludge. A sludge-wastewater partition coefficient (log Kd approximately 4) was calculated in the activated sludge reactors with a hydraulic residence time of about 8 h. No significant removal of FQs occurred under methanogenic conditions of the sludge digesters. These results suggest sewage sludge as the main reservoir of FQ residues and outline the importance of sludge management strategies to determine whether most of the human-excreted FQs enter the environment. Field experiments of sludge-application to agricultural land confirmed the long-term persistence of trace amounts of FQs in sludge-treated soils and indicated a limited mobility of FQs into the subsoil.

  18. Assessment of the genotoxicity of quinolone and fluoroquinolones contaminated soil with the Vicia faba micronucleus test.

    PubMed

    Khadra, A; Pinelli, E; Lacroix, M Z; Bousquet-Melou, A; Hamdi, H; Merlina, G; Guiresse, M; Hafidi, M

    2012-02-01

    The genotoxicity of quinolone and fluroquinolones was assessed using the micronucleus (MN) test on Vicia faba roots by direct contact exposure to a solid matrix. Plants were exposed to quinolones (nalidixic acid) and fluoroquinolones (ciprofloxacin and enrofloxacin) alone or mixed with artificially contaminated soils. Four different concentrations of each of these antibiotics were tested (0.01, 0.1, 1 and 10 mg/Kg) for nalidixic acid and (0.005, 0.05, 0.5 and 5 mg/Kg) for ciprofloxacin and enrofloxacin. These antibiotics were also used in mixture. Exposure of Vicia faba plants to each antibiotic at the highest two concentrations showed significant MN induction. The lowest two concentrations had no significant genotoxic effect. The mixture of the three compounds induced a significant MN induction whatever the mixture tested, from 0.02 to 20 mg/Kg. The results indicated that a similar genotoxic effect was obtained with the mixture at 0.2 mg/Kg in comparison with each molecule alone at 5-10 mg/Kg. Data revealed a clear synergism of these molecules on Vicia faba genotoxicity.

  19. Adsorptive Removal and Adsorption Kinetics of Fluoroquinolone by Nano-Hydroxyapatite.

    PubMed

    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.

  20. 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.

  1. Effect of protein on the detection of fluoroquinolone residues in fish meat.

    PubMed

    Li, Huifang; Yin, Jungang; Liu, Yongming; Shang, Jian

    2012-02-22

    Using fish serum albumin (FSA) as the model protein, molecular fluorescence spectrometry and high-performance liquid chromatography (HPLC) were applied to study the effect of protein on the extraction of fluoroquinolone (FQ) residues in fish meat. There was a strong interaction between FQs and protein through hydrogen bonds, which could be broken as protein degenerated with 60-100% (v/v) acetonitrile acid solution, and FQs bound with protein were released in various degrees. On the basis of the results, a novel sample preparation procedure loosely based on QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) methodology was developed for the determination of FQ residues in fish muscle samples, using 90% (v/v) acetonitrile acid solution as the extractant, combined with a dispersive solid-phase extraction (DSPE) cleanup step. Mean recoveries of four FQs from spiked samples at a concentration range of 50-200 ng g(-1) were 73.3-95.9% with relative standard deviations (RSD) lower than 10.7%.

  2. Improved extraction of fluoroquinolones with recyclable ionic-liquid-based aqueous biphasic systems.

    PubMed

    Almeida, Hugo F D; Freire, Mara G; Marrucho, Isabel M

    2016-05-07

    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.

  3. Fluoroquinolone-resistant Campylobacter isolates from conventional and antibiotic-free chicken products.

    PubMed

    Price, Lance B; Johnson, Elizabeth; Vailes, Rocio; Silbergeld, Ellen

    2005-05-01

    The use of fluoroquinolones (FQs) in poultry production is an important issue in public health today. In February 2002, two prominent U.S. poultry companies pledged to stop using FQs for flock-wide treatment. One year later, we began a survey of Campylobacter isolates on chicken products from these two companies and from two producers claiming total abstention from antibiotic use. Using both standard isolation methods and new methods modified to enhance detection of FQ-resistant Campylobacter, we compared rates of FQ-resistant Campylobacter among these products. Four major findings were drawn from this study: a) antibiotic-free brands were not more likely to be contaminated with Campylobacter; b) a high percentage of products from the two conventional brands were contaminated with FQ-resistant Campylobacter (43 and 96%); c) these conventional brands had significantly higher odds of carrying resistant strains compared with antibiotic-free products; and d) supplementing media with FQs increased the sensitivity of detecting FQ-resistant strains among mixed populations of Campylobacter, thus reducing a bias toward underestimating the prevalence of FQ-resistant Campylobacter on samples. These results suggest that FQ resistance may persist in the commercial poultry environment in the absence of FQ-selective pressure and that these strains contaminate a larger proportion of foods than reported previously.

  4. Occurrence of class 1 integrons in uropathogenic fluoroquinolone-resistant clinical Escherichia coli isolates from Jamaica.

    PubMed

    Stephenson, Stacy A M; Brown, Paul D

    2013-03-01

    Quinolone resistance is generally caused by chromosomal mutations, but has been more recently found associated with the plasmid-mediated qnr genes. The objective of this study was to screen and analyse polymorphisms of integrons in clinical isolates of Escherichia coli in Jamaica. Previous studies in Jamaica identified fluoroquinolone resistance in predominantly uropathogenic E. coli clinical isolates: 45% harbouring qnrA, qnrB and/or qnrS, and 17% were (Extended-spectrum beta-lactamase) ESBL-producers. These isolates were analysed for the presence and variation of class 1 and 2 integrase genes, 5'- and 3'- conserved segments and the Orf513 recombinase gene by primer-specific polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP). Results indicated integron-encoded integrases in 93% of isolates primarily harbouring class 1 integrase genes; four of 58 isolates carried both classes. The Orf513 and 5'- and 3'-conserved segment (CS) regions were identified in 83% and 55% of the isolates respectively. RFLP evaluation of the 5'- and 3'-CS regions in int1-positive strains yielded two main types. The reduced diversity, but wide dispersion of class 1 integrons harbouring qnr genes may give rise to the conservation of the mobile genetic elements in which they are carried.

  5. 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.

  6. Fluoroquinolones: A micro-species equilibrium in the protonation of amphoteric compounds.

    PubMed

    Nurchi, Valeria M; Crisponi, Guido; Lachowicz, Joanna I; Zoroddu, Maria Antonietta; Peana, Massimiliano; Medici, Serenella; Veclani, Daniele; Tolazzi, Marilena; Melchior, Andrea

    2016-10-10

    The knowledge of the speciation of fluoroquinolones is of great actuality for the implications on the activity, bioavailability and pharmacokinetics. Literature reports a number of contrasting evaluations on the existence of tautomeric forms of mono-protonated species, described by a set of protonation micro-constants. Here the protonation sequence and the related protonation constants of four representative molecules are evaluated by a combined potentiometric-spectrophotometric method. The experimental observations necessary to differentiate between a protonation scheme represented by macro-constants alone, and the one that requires the introduction of a micro-protonation scheme, are clearly delineated based on a careful analysis of experimental data and of simulated models. The role of the medium was investigated and UV-vis spectra in water- methanol solution were analyzed. The existence of the zwitterionic species alone at physiological pH in water, and an increase of the relative amount of the neutral species with the lipophilicity of the medium were remarked. This surely affects the bioavailability of FQs, with the increase of the neutral species when the molecules approach the local lipophilic environment close to the cellular membranes. NMR studies allowed the attribution of the protonation sites of the different forms. Quantum chemical evaluation of all the possible existent forms with different protonation degrees and in different sites strongly substantiates the experimental results. The study of the relevant frontier molecular orbitals completed the detailed theoretical characterization of the species.

  7. 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

  8. MALDI MSI and LC-MS/MS: Towards preclinical determination of the neurotoxic potential of fluoroquinolones.

    PubMed

    Shobo, Adeola; Baijnath, Sooraj; Bratkowska, Dominika; Naiker, Suhashni; Somboro, Anou M; Bester, Linda A; Singh, Sanil D; Naicker, Tricia; Kruger, Hendrik G; Govender, Thavendran

    2016-08-01

    Fluoroquinolones are broad-spectrum antibiotics with efficacy against a wide range of pathogenic microbes associated with respiratory and meningeal infections. The potential toxicity of this class of chemical agents is a source of major concern and is becoming a global issue. The aim of this study was to develop a method for the brain distribution and the pharmacokinetic profile of gatifloxacin in healthy Sprague-Dawley rats, via Multicenter matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) and quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed a sensitive LC-MS/MS method to quantify gatifloxacin in plasma, lung, and brain homogenates. A pharmacokinetic profile was observed where there is a double peak pattern; a sharp initial increase in the concentration soon after dosing followed by a steady decline until another increase in concentration after a longer period post dosing in all three biological samples was observed. The imaging results showed the drug gradually entering the brain via the blood brain barrier and into the cortical regions from 15 to 240 min post dose. As time elapses, the drug leaves the brain following the same path as it followed on its entry and finally concentrates at the cortex. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi--Metabolites, enzymes and residual antibacterial activity.

    PubMed

    Čvančarová, Monika; Moeder, Monika; Filipová, Alena; Cajthaml, Tomáš

    2015-10-01

    A group of white rot fungi (Irpex lacteus, Panus tigrinus, Dichomitus squalens, Trametes versicolor and Pleurotus ostreatus) was investigated for the biodegradation of norfloxacin (NOR), ofloxacin (OF) and ciprofloxacin (CIP). The selected fluoroquinolones were readily degraded almost completely by I. lacteus and T. versicolor within 10 and 14 d of incubation in liquid medium, respectively. The biodegradation products were identified by liquid chromatography-mass spectrometry. The analyses indicated that the fungi use similar mechanisms to degrade structurally related antibiotics. The piperazine ring of the molecules is preferably attacked via either substitution or/and decomposition. In addition to the degradation efficiency, attention was devoted to the residual antibiotic activities estimated using Gram-positive and Gram-negative bacteria. Only I. lacteus was able to remove the antibiotic activity during the course of the degradation of NOR and OF. The product-effect correlations evaluated by Principal Component Analysis (PCA) enabled elucidation of the participation of the individual metabolites in the residual antibacterial activity. Most of the metabolites correlated with the antibacterial activity, explaining the rather high residual activity remaining after the biodegradation. PCA of ligninolytic enzyme activities indicated that manganese peroxidase might participate in the degradation.

  10. [Contamination characteristics of fluoroquinolones in different kinds of soil profiles in Southeast suburb of Beijing].

    PubMed

    Su, Si-Hui; He, Jiang-Tao; Yang, Lei; Qiao, Xiao-Cui; Cui, Ya-Feng

    2014-11-01

    Eighty-six soil samples were collected using Geoprobe soil sampler from 11 borehole profiles of Beijing Southeast suburb. The sampling sites could be divided into 8 kinds of landuse. Physical and chemical properties of samples were analyzed. The concentrations of 5 fluoroquinolones (FQs) were analyzed by the high-performance liquid chromatography. Results show that the average value of total concentrations of 5 FQs is 46.1 μg x kg(-1). Ofloxacin (OFL) is the predominant among them, and then is norfloxacin (NOR). Last comes to enrofloxacin (ENR), ciprofloxacin (CIP) and lomefloxacin (LOM). There are significant differences in FQs concentrations and kinds among the 8 land use types of soil profiles. The average value of total concentrations of 5 FQs decrease with an increasing of soil depth. The average concentration of OFL, NOR, LOM and ENR decrease with an increasing of soil depth. But CIP has the opposite result. Based on FQs concentrations from 42 soil samples with a depth among 0 to 3 meters, contamination characteristics of FQs were analyzed by fuzzy hierarchial clustering. Sampling sites of vegetable greenhouse, woods, sewage irrigation zone, groundwater irrigation zone, livestock and poultry farm, sediments from sewage river have similar components and contents of FQs, with less kinds and low concentration. In contrast, sampling sites of pharmaceutical enterprises and refuse landfill have more kinds and medium concentration of FQs.

  11. 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.

  12. 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.

  13. Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia

    PubMed Central

    Abera, Bayeh; Kibret, Mulugeta

    2014-01-01

    Aim: To determine profiles of non-chlamydia conjunctival bacteria and their antimicrobial susceptibility from adults who underwent trachomatous trichiasis surgery in rural areas of Ethiopia. Materials and Methods: A cross-sectional study was conducted in rural districts in West Gojjam administrative zone. Conjunctival swabs were collected during surgery and transported using Stuart transport broth (Oxoid, UK). Antibiotic susceptibility of conjunctival isolates was determined using the Kirby-Bauer disc-diffusion method. Results: Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31%) participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G), Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4%) were observed to ceftriaxone, tetracycline and cotrimoxazole. Conclusion: Fluoroquinolones that have activity against the majority of bacterial isolates were potent at in vitro. However, unacceptably high levels of resistance to azithromycin and chloramphenicol in rural community indicated a need for further study and antimicrobial resistance surveillance. PMID:23571246

  14. 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

  15. 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.

  16. Comparative evaluation of antiproliferative activity and induction of apoptosis by some fluoroquinolones with a human non-small cell lung cancer cell line in culture.

    PubMed

    Mondal, E R; Das, S K; Mukherjee, P

    2004-01-01

    Lung cancer is the leading cause of cancer- related death in the world today. Since the effective management of drug resistant lung cancer, and particularly non-small cell lung carcinomas is a major problem, attempts need to be made to identify new potential anticancer drugs that can kill non-small cell lung cancer cells efficiently. In the present study, a human non-small cell lung carcinoma NCI-H460 cell line was used to evaluate the antiproliferative activity of Fluoroquinolones like Enoxacin, Norfloxacin, Ciprofloxacin and Levofloxacin. As determined by Sulphorodhamine B assay (SRB assay), all Fluoroquinolones caused cellular growth inhibition in a concentration and time-dependent manner. Enoxacin was found to be the most effective Fluoroquinolone followed by Norfloxacin, Ciprofloxacin and Levofloxacin. Growth inhibitory effects were also found to be independent of the concentrations of serum growth factors in culture medium or variation of initial cell seeding density and proved to be irreversible in nature. Appearance of rounded cells with altered morphology and cell surface blebbing indicated cell killing by apoptosis. Cell shrinkage, nuclear condensation & fragmentation, and cytoplasmic blebbing as indicated by MGG staining confirmed this to be the case. Thus, this investigation clearly demonstrated that the NCI-H460 human non-small cell lung carcinoma cell line is highly sensitive to Fluoroquinolone treatment. The Fluoroquinolones used in this study which are clinically used as antibacterial agents, can also inhibit tumor cell growth suggesting their potential use in a strategy for cancer treatment which might help in controlling cancer.

  17. Overexpression of patA and patB, which encode ABC transporters, is associated with fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae.

    PubMed

    Garvey, Mark I; Baylay, Alison J; Wong, Ryan L; Piddock, Laura J V

    2011-01-01

    Fifty-seven clinical isolates of Streptococcus pneumoniae were divided into four groups based on their susceptibilities to the fluoroquinolones ciprofloxacin and norfloxacin and the dyes ethidium bromide and acriflavine. Comparative reverse transcription-PCR was used to determine the level of expression of the genes patA and patB, which encode putative ABC transporters. Overexpression was observed in 14 of the 15 isolates that were resistant to both fluoroquinolones and dyes and in only 3 of 24 of those resistant to fluoroquinolones only. Isolates overexpressing patA and patB accumulated significantly less of the fluorescent dye Hoechst 33342 than wild-type isolates, suggesting that PatA and PatB are involved in efflux. Inactivation of patA and patB by in vitro mariner mutagenesis conferred hypersusceptibility to ethidium bromide and acriflavine in all isolates tested and lowered the MICs of ciprofloxacin in the patAB-overproducing and/or fluoroquinolone-resistant isolates. These data represent the first observation of overexpression of patA and patB in clinical isolates and show that PatA and PatB play a clinically relevant role in fluoroquinolone resistance.

  18. 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.

  19. 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…

  20. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones.

    PubMed

    Li, Qiming; Xie, Longxiang; Long, Quanxin; Mao, Jinxiao; Li, Hui; Zhou, Mingliang; Xie, Jianping

    2015-07-03

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics.