Bias-free spin-wave phase shifter for magnonic logic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louis, Steven; Tyberkevych, Vasyl; Slavin, Andrei

2016-06-15

A design of a magnonic phase shifter operating without an external bias magnetic field is proposed. The phase shifter uses a localized collective spin wave mode propagating along a domain wall “waveguide” in a dipolarly-coupled magnetic dot array with a chessboard antiferromagnetic (CAFM) ground state. It is demonstrated numerically that the remagnetization of a single magnetic dot adjacent to the domain wall waveguide introduces a controllable phase shift in the propagating spin wave mode without significant change to the mode amplitude. It is also demonstrated that a logic XOR gate can be realized in the same system.

Coherent Frequency Shifter, Optical Isolator, Lasers on an Integrated Platform for Cold Atom Microsystems

DTIC Science & Technology

2017-10-11

power operation of optical frequency shifter; (7) a new design and theoretical analysis of frequency shifter with larger electro-optical coefficients...integrated laser. 15. SUBJECT TERMS coherent frequency shifter, optical isolation, integrated photonics, 780nm laser design and fabrication 16...coefficient (r33 and r42) ………………………………………………………………… 20 II.3. 780 nm Laser design , fabrication, and testing based on AlGaAs/GaAs Multiple Quantum Wells

A Model for Ferroelectric Phase Shifters

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.; Qureshi, A. Haq

2000-01-01

Novel microwave phase shifters consisting of coupled microstrip lines on thin ferroelectric films have been demonstrated recently. A theoretical model useful for predicting the propagation characteristics (insertion phase shift, dielectric loss, impedance, and bandwidth) is presented here. The model is based on a variational solution for line capacitance and coupled strip transmission line theory.

A compact, low-loss, tunable phase shifter on defect mitigated dielectrics up to 40 GHz

NASA Astrophysics Data System (ADS)

Orloff, Nathan; Long, Christian; Lu, Xifeng; Nair, Hari; Dawley, Natalie; Schlom, Darrell; Booth, James

With the emergence of the internet-of-things and increased connectivity of modern commerce, consumers have driven demand for wireless spectrum beyond current capacity and infrastructure capabilities. One way the telecommunications industry is addressing this problem is by pushing front-end electronics to higher frequencies, introducing carrier aggregation schemes, and developing spectrum-sharing techniques. Some of these solutions require frequency agile components that are vastly different from what is in today's marketplace. Perhaps the most basic and ubiquitous component in front-end electronics is the phase shifter. Phase shifters are particularly important for compact beam-forming antennas that may soon appear in commercial technology. Here, we demonstrate a compact, tunable phase shifter with very low insertion loss up to 40 GHz on a defect mitigated tunable dielectric. We demonstrate performance compared to barium-doped strontium titanate phase shifters. Such phase shifters could potentially meet the stringent size and performance characteristics demanded by telecommunications industry, readily facilitating massive multiple-input multiple-output antennas in the next-generation of mobile handsets.

Q-band 4-state phase shifter in planar technology: Circuit design and performance analysis.

PubMed

Villa, E; Cagigas, J; Aja, B; de la Fuente, L; Artal, E

2016-09-01

A 30% bandwidth phase shifter with four phase states is designed to be integrated in a radio astronomy receiver. The circuit has two 90° out-of-phase microwave phase-shifting branches which are combined by Wilkinson power dividers. Each branch is composed of a 180° phase shifter and a band-pass filter. The 180° phase shifter is made of cascaded hybrid rings with microwave PIN diodes as switching devices. The 90° phase shift is achieved with the two band-pass filters. Experimental characterization has shown significant results, with average phase shift values of -90.7°, -181.7°, and 88.5° within the operation band, 35-47 GHz, and mean insertion loss of 7.4 dB. The performance of its integration in a polarimetric receiver for radio astronomy is analyzed, which validates the use of the presented phase shifter in such type of receiver.

A high-power microwave circular polarizer and its application on phase shifter.

PubMed

Shao, Hao; Hu, Yongmei; Chang, Chao; Guo, Letian

2016-04-01

A high-power waveguide dual circular polarizer was theoretically designed and proof-of-principle was experimentally tested. It consists of two incident rectangular waveguides with a perpendicular H-plane junction, one circular waveguide with a pair of trapezoidal grooves coupled in E-plane at the top, a spherical crown located at the bottom, and an iris at the perpendicular junction of two rectangular waveguides. When wave incidents at one of the two separated rectangular waveguides, it, respectively, generates a left-hand circular polarized wave or a right-hand circular polarized wave in the circular waveguide. By adding a dumbbell-like metal plug driven with a high speed servomotor, a movable short circuit is formed along the circular waveguide to adjust the output RF phase of the rectangular port, realizing a high-speed high-power phase shifter. The C-band high power microwave (HPM) experiments were carried out, and the power capacity of the HPM polarizer and phase shifter was demonstrated to reach gigawatt level.

Advances in Scanning Reflectarray Antennas Based on Ferroelectric Thin Film Phase Shifters for Deep Space Communications

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.

2007-01-01

Though there are a few examples of scanning phased array antennas that have flown successfully in space, the quest for low-cost, high-efficiency, large aperture microwave phased arrays continues. Fixed and mobile applications that may be part of a heterogeneous exploration communication architecture will benefit from the agile (rapid) beam steering and graceful degradation afforded by phased array antennas. The reflectarray promises greater efficiency and economy compared to directly-radiating varieties. Implementing a practical scanning version has proven elusive. The ferroelectric reflectarray, under development and described herein, involves phase shifters based on coupled microstrip patterned on Ba(x)Sr(1-x)TiO3 films, that were laser ablated onto LaAlO3 substrates. These devices outperform their semiconductor counterparts from X- through and K-band frequencies. There are special issues associated with the implementation of a scanning reflectarray antenna, especially one realized with thin film ferroelectric phase shifters. This paper will discuss these issues which include: relevance of phase shifter loss; modulo 2(pi) effects and phase shifter transient effects on bit error rate; scattering from the ground plane; presentation of a novel hybrid ferroelectric-semiconductor phase shifter; and the effect of mild radiation exposure on phase shifter performance.

Ultra-wideband microwave photonic phase shifter with configurable amplitude response.

PubMed

Pagani, M; Marpaung, D; Eggleton, B J

2014-10-15

We introduce a new principle that enables separate control of the amplitude and phase of an optical carrier, simply by controlling the power of two stimulated Brillouin scattering (SBS) pumps. This technique is used to implement a microwave photonic phase shifter with record performance, which solves the bandwidth limitation of previous gain-transparent SBS-based phase shifters, while achieving unprecedented minimum power fluctuations, as a function of phase shift. We demonstrate 360° continuously tunable phase shift, with less than 0.25 dB output power fluctuations, over a frequency band from 1.5 to 31 GHz, limited only by the measurement equipment.

Interference Confocal Microscope Integrated with Spatial Phase Shifter.

PubMed

Wang, Weibo; Gu, Kang; You, Xiaoyu; Tan, Jiubin; Liu, Jian

2016-08-24

We present an interference confocal microscope (ICM) with a new single-body four-step simultaneous phase-shifter device designed to obtain high immunity to vibration. The proposed ICM combines the respective advantages of simultaneous phase shifting interferometry and bipolar differential confocal microscopy to obtain high axis resolution, large dynamic range, and reduce the sensitivity to vibration and reflectance disturbance seamlessly. A compact single body spatial phase shifter is added to capture four phase-shifted interference signals simultaneously without time delay and construct a stable and space-saving simplified interference confocal microscope system. The test result can be obtained by combining the interference phase response and the bipolar property of differential confocal microscopy without phase unwrapping. Experiments prove that the proposed microscope is capable of providing stable measurements with 1 nm of axial depth resolution for either low- or high-numerical aperture objective lenses.

Phase-shifter using submicron silicon waveguide couplers with ultra-small electro-mechanical actuator.

PubMed

Ikeda, Taro; Takahashi, Kazunori; Kanamori, Yoshiaki; Hane, Kazuhiro

2010-03-29

Phase shifter is an important part of optical waveguide circuits as used in interferometer. However, it is not always easy to generate a large phase shift in a small region. Here, a variable phase-shifter operating as delay-line of silicon waveguide was designed and fabricated by silicon micromachining. The proposed phase-shifter consists of a freestanding submicron-wide silicon waveguide with two waveguide couplers and an ultrasmall silicon comb-drive actuator. The position of the freestanding waveguide is moved by the actuator to vary the total optical path. Phase-shift was measured in a Mach-Zehnder interferometer to be 3.0pi at the displacement of 1.0 mum at the voltage of 31 V. The dimension of the fabricated device is 50microm wide and 85microm long.

A Liquid Optical Phase Shifter with an Embedded Electrowetting Actuator

PubMed Central

Ashtiani, Alireza Ousati; Jiang, Hongrui

2017-01-01

We demonstrate an electrowetting-based liquid optical phase shifter. The phase shifter consists of two immiscible liquid layers with different refractive indices. Sandwiched between the two liquids is a rigid membrane that moves freely along the optical axis and supported by a compliant surround. When applied with a pressure, the thicknesses of both liquid layers change, which induces a difference in optical path, resulting in a phase shift. A miniaturized electrowetting-based actuator is used to produce hydraulic pressure. A multi-layered SU8 bonded structure was fabricated. A phase shift of 171° was observed when the device was incorporated in a Mach-Zehnder interferometer and driven with 100 V. PMID:29038640

Figures of merit for microwave photonic phase shifters based on semiconductor optical amplifiers.

PubMed

Sancho, Juan; Lloret, Juan; Gasulla, Ivana; Sales, Salvador; Capmany, José

2012-05-07

We theoretically and experimentally compare the performance of two fully tunable phase shifter structures based on semiconductor optical amplifiers (SOA) by means of several figures of merit common to microwave photonic systems. A single SOA stage followed by a tailored notch filter is compared with a cascaded implementation comprising three SOA-based phase shifter stages. Attention is focused on the assessment of the RF net gain, noise figure and nonlinear distortion. Recommendations on the performance optimization of this sort of approaches are detailed.

Light-driven phase shifter

DOEpatents

Early, James W.

1990-01-01

A light-driven phase shifter is provided for modulating a transmission light beam. A gaseous medium such as argon is provided with electron energy states excited to populate a metastable state. A tunable dye laser is selected with a wavelength effective to deplete the metastable electron state and may be intensity modulated. The dye laser is directed through the gaseous medium to define a first optical path having an index of refraction determined by the gaseous medium having a depleted metastable electron state. A transmission laser beam is also directed through the gaseous medium to define a second optical path at least partially coincident with the first optical path. The intensity of the dye laser beam may then be varied to phase modulate the transmission laser beam.

All-optical phase shifter and switch near 1550nm using tungsten disulfide (WS2) deposited tapered fiber.

PubMed

Wu, Kan; Guo, Chaoshi; Wang, Hao; Zhang, Xiaoyan; Wang, Jun; Chen, Jianping

2017-07-24

All-optical phase shifters and switches play an important role for various all-optical applications including all-optical signal processing, sensing and communication. In this paper, we demonstrate a fiber all-optical phase shifter using few-layer 2D material tungsten disulfide (WS 2 ) deposited on a tapered fiber. WS 2 absorbs injected 980 nm pump (control light) and generates heat, which changes the refractive index of both WS 2 and tapered fiber due to thermo-optic effect and achieves a maximum phase shift of 6.1π near 1550 nm. The device has a loss of 3.7 dB. By constructing a Mach-Zehnder interferometer with WS 2 based phase shifter in one arm, an all-optical switch is also obtained with an extinction ratio of 15 dB and a rise time of 7.3 ms. This all fiber low-cost and compact optical phase shifter and switch demonstrates the potential of 2D transition metal dichalcogenides for all-optical signal processing devices.

A Ku band 5 bit MEMS phase shifter for active electronically steerable phased array applications

NASA Astrophysics Data System (ADS)

Sharma, Anesh K.; Gautam, Ashu K.; Farinelli, Paola; Dutta, Asudeb; Singh, S. G.

2015-03-01

The design, fabrication and measurement of a 5 bit Ku band MEMS phase shifter in different configurations, i.e. a coplanar waveguide and microstrip, are presented in this work. The development architecture is based on the hybrid approach of switched and loaded line topologies. All the switches are monolithically manufactured on a 200 µm high resistivity silicon substrate using 4 inch diameter wafers. The first three bits (180°, 90° and 45°) are realized using switched microstrip lines and series ohmic MEMS switches whereas the fourth and fifth bits (22.5° and 11.25°) consist of microstrip line sections loaded by shunt ohmic MEMS devices. Individual bits are fabricated and evaluated for performance and the monolithic device is a 5 bit Ku band (16-18 GHz) phase shifter with very low average insertion loss of the order of 3.3 dB and a return loss better than 15 dB over the 32 states with a chip area of 44 mm2. A total phase shift of 348.75° with phase accuracy within 3° is achieved over all of the states. The performance of individual bits has been optimized in order to achieve an integrated performance so that they can be implemented into active electronically steerable antennas for phased array applications.

Silicon graphene waveguide tunable broadband microwave photonics phase shifter.

PubMed

Capmany, José; Domenech, David; Muñoz, Pascual

2014-04-07

We propose the use of silicon graphene waveguides to implement a tunable broadband microwave photonics phase shifter based on integrated ring cavities. Numerical computation results show the feasibility for broadband operation over 40 GHz bandwidth and full 360° radiofrequency phase-shift with a modest voltage excursion of 0.12 volt.

A K-Band Low-Power Phase Shifter Based on Injection Locked Oscillator in 0.13 μm CMOS Technology

NASA Astrophysics Data System (ADS)

Qiu, Qi-Lin; Yu, Xiao-Peng; Sui, Wen-Quan

2017-11-01

In this paper, the design challenges of the injection-locked oscillator (ILO)-based phase shifter are reviewed and analyzed. The key design considerations such as the operating frequency, locking range, and linearity of the phase shifters are analysed in detail. It is possible to optimize the phase shifter in certain parameters such as ultra-low power while meeting the requirements of a certain system. As a design example, a K-band phase shifter is implemented using a commercial 0.13 μm CMOS technology, where a conventional LC tank based topology is implemented but optimised with a good balance among power consumption, working range, sensitivity, and silicon area, etc. Measurement results show that the proposed phase shift is able to work at 22-23.4 GHz with a range of 180∘ while consuming 3.14 mW from a 1.2 V supply voltage.

Innovative phase shifter for pulse tube operating below 10 K

NASA Astrophysics Data System (ADS)

Duval, Jean-Marc; Charles, Ivan; Daniel, Christophe; André, Jérôme

2016-09-01

Stirling type pulse tubes are classically based on the use of an inertance phase shifter to optimize their cooling power. The limitations of the phase shifting capabilities of these inertances have been pointed out in various studies. These limitations are particularly critical for low temperature operation, typically below about 50 K. An innovative phase shifter using an inertance tube filled with liquid, or fluid with high density or low viscosity, and separated by a sealed metallic diaphragm has been conceived and tested. This device has been characterized and validated on a dedicated test bench. Operation on a 50-80 K pulse tube cooler and on a low temperature (below 8 K) pulse tube cooler have been demonstrated and have validated the device in operation. These developments open the door for efficient and compact low temperature Stirling type pulse tube coolers. The possibility of long life operation has been experimentally verified and a design for space applications is proposed.

Experimental evaluation of achromatic phase shifters for mid-infrared starlight suppression.

PubMed

Gappinger, Robert O; Diaz, Rosemary T; Ksendzov, Alexander; Lawson, Peter R; Lay, Oliver P; Liewer, Kurt M; Loya, Frank M; Martin, Stefan R; Serabyn, Eugene; Wallace, James K

2009-02-10

Phase shifters are a key component of nulling interferometry, one of the potential routes to enabling the measurement of faint exoplanet spectra. Here, three different achromatic phase shifters are evaluated experimentally in the mid-infrared, where such nulling interferometers may someday operate. The methods evaluated include the use of dispersive glasses, a through-focus field inversion, and field reversals on reflection from antisymmetric flat-mirror periscopes. All three approaches yielded deep, broadband, mid-infrared nulls, but the deepest broadband nulls were obtained with the periscope architecture. In the periscope system, average null depths of 4x10(-5) were obtained with a 25% bandwidth, and 2x10(-5) with a 20% bandwidth, at a central wavelength of 9.5 mum. The best short term nulls at 20% bandwidth were approximately 9x10(-6), in line with error budget predictions and the limits of the current generation of hardware.

Tunable Multifunctional Thermal Metamaterials: Manipulation of Local Heat Flux via Assembly of Unit-Cell Thermal Shifters

PubMed Central

Park, Gwanwoo; Kang, Sunggu; Lee, Howon; Choi, Wonjoon

2017-01-01

Thermal metamaterials, designed by transformation thermodynamics are artificial structures that can actively control heat flux at a continuum scale. However, fabrication of them is very challenging because it requires a continuous change of thermal properties in materials, for one specific function. Herein, we introduce tunable thermal metamaterials that use the assembly of unit-cell thermal shifters for a remarkable enhancement in multifunctionality as well as manufacturability. Similar to the digitization of a two-dimensional image, designed thermal metamaterials by transformation thermodynamics are disassembled as unit-cells thermal shifters in tiny areas, representing discretized heat flux lines in local spots. The programmed-reassembly of thermal shifters inspired by LEGO enable the four significant functions of thermal metamaterials—shield, concentrator, diffuser, and rotator—in both simulation and experimental verification using finite element method and fabricated structures made from copper and PDMS. This work paves the way for overcoming the structural and functional limitations of thermal metamaterials. PMID:28106156

Tunable Multifunctional Thermal Metamaterials: Manipulation of Local Heat Flux via Assembly of Unit-Cell Thermal Shifters

NASA Astrophysics Data System (ADS)

Park, Gwanwoo; Kang, Sunggu; Lee, Howon; Choi, Wonjoon

2017-01-01

Thermal metamaterials, designed by transformation thermodynamics are artificial structures that can actively control heat flux at a continuum scale. However, fabrication of them is very challenging because it requires a continuous change of thermal properties in materials, for one specific function. Herein, we introduce tunable thermal metamaterials that use the assembly of unit-cell thermal shifters for a remarkable enhancement in multifunctionality as well as manufacturability. Similar to the digitization of a two-dimensional image, designed thermal metamaterials by transformation thermodynamics are disassembled as unit-cells thermal shifters in tiny areas, representing discretized heat flux lines in local spots. The programmed-reassembly of thermal shifters inspired by LEGO enable the four significant functions of thermal metamaterials—shield, concentrator, diffuser, and rotator—in both simulation and experimental verification using finite element method and fabricated structures made from copper and PDMS. This work paves the way for overcoming the structural and functional limitations of thermal metamaterials.

Interplay Between Thin Film Ferroelectric Composition, Microstructure and Microwave Phase Shifter Performance

NASA Technical Reports Server (NTRS)

Mueller, Carl H.; VanKeuls, Frederick W.; Romanofsky, Robert R.; Alterovitz, Samuel A.; Miranda, Felix A.

2003-01-01

One of the keys to successfully incorporating ferroelectric films into Ku-band (12 to 18 GHz) phase shifters is to establish the composition, microstructure, and thickness required to meet the tuning needs, and tailor the film properties to meet these needs. Optimal performance is obtained when the film composition and device design are such that the device performance is limited by odd mode dielectric losses, and these losses are minimized as much as possible while still maintaining adequate tunability. The parameters required to maintain device performance will vary slightly depending on composition, but we can conclude that the best tuning-to-loss figures of merit (K-factor) are obtained when there is minimal variation between the in-plane and out-of-plane lattice parameters, and the full-width half maximum values of the BSTO (002) peaks are less than approximately 0.04 deg. We have observed that for phase shifters in which the ferroelectric crystalline quality and thickness are almost identical, higher losses are observed in films with higher BaISr ratios. The best performance was observed in phase shifters with Ba:Sr = 30:70. The superiority of this composition was attributed to several interacting factors: the B a: Sr ratio was such that the Curie temperature (180 K) was far removed from room temperature, the crystalline quality of the film was excellent, and there was virtually no difference between the inplane and out-of-plane lattice parameters of the film.

A Theoretical Model for Thin Film Ferroelectric Coupled Microstripline Phase Shifters

NASA Technical Reports Server (NTRS)

Romanofsky, R. R.; Quereshi, A. H.

2000-01-01

Novel microwave phase shifters consisting of coupled microstriplines on thin ferroelectric films have been demonstrated recently. A theoretical model useful for predicting the propagation characteristics (insertion phase shift, dielectric loss, impedance, and bandwidth) is presented here. The model is based on a variational solution for line capacitance and coupled strip transmission line theory.

Monolithic mm-wave phase shifter using optically activated superconducting switches

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R. (Inventor); Bhasin, Kul B. (Inventor)

1992-01-01

A phase shifter is disclosed having a reference path and a delay path, light sources, and superconductive switches. Each of the superconductive switches is terminated in a virtual short circuit, which may be a radial stub. Switching between the reference path and delayed path is accomplished by illuminating the superconductive switches connected to the desired path, while not illuminating the superconductive switches connected to the other path.

First demonstration of an emulsion multi-stage shifter for accelerator neutrino experiments in J-PARC T60

NASA Astrophysics Data System (ADS)

Yamada, K.; Aoki, S.; Cao, S.; Chikuma, N.; Fukuda, T.; Fukuzawa, Y.; Gonin, M.; Hayashino, T.; Hayato, Y.; Hiramoto, A.; Hosomi, F.; Inoh, T.; Iori, S.; Ishiguro, K.; Kawahara, H.; Kim, H.; Kitagawa, N.; Koga, T.; Komatani, R.; Komatsu, M.; Matsushita, A.; Mikado, S.; Minamino, A.; Mizusawa, H.; Matsumoto, T.; Matsuo, T.; Morimoto, Y.; Morishima, K.; Morishita, M.; Naganawa, N.; Nakamura, K.; Nakamura, M.; Nakamura, Y.; Nakano, T.; Nakatsuka, Y.; Nakaya, T.; Nishio, A.; Ogawa, S.; Oshima, H.; Quilain, B.; Rokujo, H.; Sato, O.; Seiya, Y.; Shibuya, H.; Shiraishi, T.; Suzuki, Y.; Tada, S.; Takahashi, S.; Yokoyama, M.; Yoshimoto, M.

2017-06-01

We describe the first ever implementation of a clock-based, multi-stage emulsion shifter in an accelerator neutrino experiment. The system was installed in the neutrino monitoring building at the Japan Proton Accelerator Research Complex as part of a test experiment, T60, and stable operation was maintained for a total of 126.6 days. By applying time information to emulsion films, various results were obtained. Time resolutions of 5.3-14.7 s were evaluated in an operation spanning 46.9 days (yielding division numbers of 1.4-3.8×105). By using timing and spatial information, reconstruction of coincident events consisting of high-multiplicity and vertex-contained events, including neutrino events, was performed. Emulsion events were matched to events observed by INGRID, one of the on-axis near detectors of the T2K experiment, with high reliability (98.5%), and hybrid analysis of the emulsion and INGRID events was established by means of the multi-stage shifter. The results demonstrate that the multi-stage shifter can feasibly be used in neutrino experiments.

SU-F-T-194: Analyzing the Effect of Range Shifter Air Gap On TPS Dose Modeling Accuracy in Superficial PBS Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shirey, R; Wu, H

2016-06-15

Purpose: Treatment planning systems (TPS) may not accurately model superficial dose distributions of range shifted proton pencil beam scanning (PBS) treatments. Numerous patient-specific QA tests performed on superficially treated PBS plans have shown a consistent overestimate of dose by the TPS. This study quantifies variations between TPS planned dose and measured dose as a function of range shifter air gap and treatment depths up to 5 cm. Methods: PBS treatment plans were created in the TPS to uniformly irradiate a volume of solid water. One plan was created for each range shifter position analyzed, and all plans utilized identical dosemore » optimization parameters. Each optimized plan was analyzed in the TPS to determine the planned dose at varying depths. A PBS proton therapy system with a 3.5 cm lucite range shifter delivered the treatment plans, and a parallel plate chamber embedded in RW3 solid water measured dose at shallow depths for each air gap. Differences between measured and planned doses were plotted and analyzed. Results: The data show that the TPS more accurately models superficial dose as the air gap between the range shifter and patient surface decreases. Air gaps less than 10 cm have an average dose difference of only 1.6%, whereas air gaps between 10 and 20 cm differ by 3.0% and gaps greater than 20 cm differ by 4.4%. Conclusion: This study has shown that the TPS is unable to accurately model superficial dose with a large range shifter air gap. Dose differences greater than 3% will likely cause QA failure, as many institutions analyze patient QA with a 3%/3mm gamma analysis. For superficial PBS therapy, range shifter positions should be chosen to keep the air gap less then 10 cm when patient setup and gantry geometry allow.« less

Enhanced UV light detection using a p-terphenyl wavelength shifter

NASA Astrophysics Data System (ADS)

Joosten, S.; Kaczanowicz, E.; Ungaro, M.; Rehfuss, M.; Johnston, K.; Meziani, Z.-E.

2017-10-01

UV-glass photomultiplier tubes (PMTs) have poor photon detection efficiency for wavelengths below 300 nm due to the opaqueness of the window material. Costly quartz PMTs could be used to enhance the efficiency below 300 nm. A less expensive solution that dramatically improves this efficiency is the application of a thin film of a p-terphenyl (PT) wavelength shifter on UV-glass PMTs. This improvement was quantified for Photonis XP4500B PMTs for wavelengths between 200 nm and 400 nm. The gain factor ranges up to 5 . 4 ± 0 . 5 at a wavelength of 215 nm, with a material load of 110 ± 10 μg /cm2 (894 nm). The wavelength shifter was found to be fully transparent for wavelengths greater than 300 nm. The resulting gain in detection efficiency, when used in a typical C̆erenkov counter, was estimated to be of the order of 40%. Consistent coating quality was assured by a rapid gain testing procedure using narrow-band UV LEDs. Based on these results, 200 Photonis XP4500B PMTs were treated with PT for the upgraded low-threshold C̆erenkov counter (LTCC) to be used in the CEBAF Large Acceptance Spectrometer upgraded detector (CLAS12) at the Thomas Jefferson National Accelerator Facility.

Microwave monolithic filter and phase shifter using magnetic nanostructures

NASA Astrophysics Data System (ADS)

Aslam, Shehreen; Khanna, Manoj; Veenugopal, Veerakumar; Kuanr, Bijoy K.

2018-05-01

Monolithic Microwave Integrated Circuit (MMIC) have major impact on the development of microwave communication technology. Transition metal based ferromagnetic nano-wired (FMNWs) substrate are of special interest in order to fabricate these MMIC devices. Their saturation magnetization is comparatively higher than ferrites which makes them suitable for high frequency (>10 ˜ 40 GHz) operation at zero or a small applied magnetic field. The CoFeB nanowires in anodic alumina templates were synthesized using three-electrode electro-deposition system. After electro-deposition, 1μm thick Cu layer was sputtered on the top surface of FMNW substrate and lithography was done to design microstrip lines. These microstrip transmission lines were tested for band-stop filters and phase shifters based on ferromagnetic resonance (FMR) over a wide applied magnetic field (H) range. It was observed that attenuation and frequency increase with the increase of magnetic field (upto 5.3 kOe). For phase shifter, the influence of magnetic material was studied for two frequency regions: (i) below FMR and (ii) above FMR. These two frequency regions were suitable for many practical device applications as the insertion loss was very less in these regions in comparison to resonance frequency regions. In the high frequency region (at 35 GHz), the optimal differential phase shift increased significantly to ˜ 250 deg/cm and around low frequency region (at 24 GHz), the optimal differential phase shift is ˜175 deg/cm at the highest field (H) value.

Slow-Wave Phase Shifters, Based on Thin Ferroelectric Films, for Reflectarray Antennas. Frequency-Agile Radio: Systems and Technlogies, WMG 139

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.

2006-01-01

We have developed relatively broadband K- and Ka-band phase shifters using synthetic (slow-wave) transmission lines employing coupled microstripline "varactors". The tunable coupled microstripline circuits are based on laser ablated BaSrTiO films on lanthanum aluminate substrates. A model and design criteria for these novel circuits will be presented, along with measured performance including anomalous phase delay characteristics. The critical role of phase shifter loss and transient response in reflectarray antennas will be emphasized.

Enhanced UV light detection using a p-terphenyl wavelength shifter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joosten, Sylvester J.; Kaczanowicz, Ed; Ungaro, Maurizio

Here, UV-glass photomultiplier tubes (PMTs) have poor photon detection efficiency for wavelengths belowmore » $$300\\,\\text{nm}$$ due to the opaqueness of the window material. Costly quartz PMTs could be used to enhance the efficiency below $$300\\,\\text{nm}$$. A less expensive solution that dramatically improves this efficiency is the application of a thin film of a p-terphenyl (PT) wavelength shifter on UV-glass PMTs. This improvement was quantified for Photonis XP4500B PMTs for wavelengths between $$200\\,\\text{nm}$$ and $$400\\,\\text{nm}$$. The gain factor ranges up to 5.4 $$\\pm$$ 0.5 at a wavelength of $$215\\,\\text{nm}$$, with a material load of $$110\\pm10\\,\\mu\\text{g}/\\text{cm}^2$$ ($$894\\,\\text{nm}$$). The wavelength shifter was found to be fully transparent for wavelengths greater than $$300\\,\\text{nm}$$. The resulting gain in detection efficiency, when used in a typical Cherenkov counter, was estimated to be of the order of 40%. Consistent coating quality was assured by a rapid gain testing procedure using narrow-band UV LEDs. Based on these results, 200 Photonis XP4500B PMTs were treated with PT for the upgraded low-threshold Cherenkov counter (LTCC) to be used in the CEBAF Large Acceptance Spectrometer upgraded detector (CLAS12) at the Thomas Jefferson National Accelerator Facility.« less

Enhanced UV light detection using a p-terphenyl wavelength shifter

DOE PAGES

Joosten, Sylvester J.; Kaczanowicz, Ed; Ungaro, Maurizio; ...

2017-07-25

Here, UV-glass photomultiplier tubes (PMTs) have poor photon detection efficiency for wavelengths belowmore » $$300\\,\\text{nm}$$ due to the opaqueness of the window material. Costly quartz PMTs could be used to enhance the efficiency below $$300\\,\\text{nm}$$. A less expensive solution that dramatically improves this efficiency is the application of a thin film of a p-terphenyl (PT) wavelength shifter on UV-glass PMTs. This improvement was quantified for Photonis XP4500B PMTs for wavelengths between $$200\\,\\text{nm}$$ and $$400\\,\\text{nm}$$. The gain factor ranges up to 5.4 $$\\pm$$ 0.5 at a wavelength of $$215\\,\\text{nm}$$, with a material load of $$110\\pm10\\,\\mu\\text{g}/\\text{cm}^2$$ ($$894\\,\\text{nm}$$). The wavelength shifter was found to be fully transparent for wavelengths greater than $$300\\,\\text{nm}$$. The resulting gain in detection efficiency, when used in a typical Cherenkov counter, was estimated to be of the order of 40%. Consistent coating quality was assured by a rapid gain testing procedure using narrow-band UV LEDs. Based on these results, 200 Photonis XP4500B PMTs were treated with PT for the upgraded low-threshold Cherenkov counter (LTCC) to be used in the CEBAF Large Acceptance Spectrometer upgraded detector (CLAS12) at the Thomas Jefferson National Accelerator Facility.« less

Integrated nanophotonic frequency shifter on the silicon-organic hybrid (SOH) platform for laser vibrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lauermann, M.; Weimann, C.; Palmer, R.

2014-05-27

We demonstrate a waveguide-based frequency shifter on the silicon photonic platform, enabling frequency shifts up to 10 GHz. The device is realized by silicon-organic hybrid (SOH) integration. Temporal shaping of the drive signal allows the suppression of spurious side-modes by more than 23 dB.

Reconfigurable, Bi-Directional Flexfet Level Shifter for Low-Power, Rad-Hard Integration

NASA Technical Reports Server (NTRS)

DeGregorio, Kelly; Wilson, Dale G.

2009-01-01

Two prototype Reconfigurable, Bi-directional Flexfet Level Shifters (ReBiLS) have been developed, where one version is a stand-alone component designed to interface between external low voltage and high voltage, and the other version is an embedded integrated circuit (IC) for interface between internal low-voltage logic and external high-voltage components. Targeting stand-alone and embedded circuits separately allows optimization for these distinct applications. Both ReBiLS designs use the commercially available 180-nm Flex fet Independently Double-Gated (IDG) SOI CMOS (silicon on insulator, complementary metal oxide semiconductor) technology. Embedded ReBiLS circuits were integrated with a Reed-Solomon (RS) encoder using CMOS Ultra-Low-Power Radiation Tolerant (CULPRiT) double-gated digital logic circuits. The scope of the project includes: creation of a new high-voltage process, development of ReBiLS circuit designs, and adjustment of the designs to maximize performance through simulation, layout, and manufacture of prototypes. The primary technical objectives were to develop a high-voltage, thick oxide option for the 180-nm Flexfet process, and to develop a stand-alone ReBiLS IC with two 8-channel I/O busses, 1.8 2.5 I/O on the low-voltage pins, 5.0-V-tolerant input and 3.3-V output I/O on the high-voltage pins, and 100-MHz minimum operation with 10-pF external loads. Another objective was to develop an embedded, rad-hard ReBiLS I/O cell with 0.5-V low-voltage operation for interface with core logic, 5.0-V-tolerant input and 3.3-V output I/O pins, and 100-MHz minimum operation with 10- pF external loads. A third objective was to develop a 0.5- V Reed-Solomon Encoder with embedded ReBilS I/O: Transfer the existing CULPRiT RS encoder from a 0.35-micron bulk-CMOS process to the ASI 180-nm Flexfet, rad-hard SOI Process. 0.5-V low-voltage core logic. 5.0-V-tolerant input and 3.3-V output I/O pins. 100-MHz minimum operation with 10- pF external loads. The stand

Fast, optically controlled Kerr phase shifter for digital signal processing.

PubMed

Li, R B; Deng, L; Hagley, E W; Payne, M G; Bienfang, J C; Levine, Z H

2013-05-01

We demonstrate an optically controlled Kerr phase shifter using a room-temperature 85Rb vapor operating in a Raman gain scheme. Phase shifts from zero to π relative to an unshifted reference wave are observed, and gated operations are demonstrated. We further demonstrate the versatile digital manipulation of encoded signal light with an encoded phase-control light field using an unbalanced Mach-Zehnder interferometer. Generalizations of this scheme should be capable of full manipulation of a digitized signal field at high speed, opening the door to future applications.

Light detection and the wavelength shifter deposition in DEAP-3600

NASA Astrophysics Data System (ADS)

Broerman, B.; Retière, F.

2016-02-01

The Dark matter Experiment using Argon Pulse-shape discrimination (DEAP) uses liquid argon as a target medium to perform a direct-detection dark matter search. The 3600 kg liquid argon target volume is housed in a spherical acrylic vessel and viewed by a surrounding array of photomultiplier tubes. Ionizing particles in the argon volume produce scintillation light which must be wavelength shifted to be detected by the photomultiplier tubes. Argon scintillation and wavelength shifting, along with details on the application of the wavelength shifter to the inner surface of the acrylic vessel are presented.

Broadband microwave photonic fully tunable filter using a single heterogeneously integrated III-V/SOI-microdisk-based phase shifter.

PubMed

Lloret, Juan; Morthier, Geert; Ramos, Francisco; Sales, Salvador; Van Thourhout, Dries; Spuesens, Thijs; Olivier, Nicolas; Fédéli, Jean-Marc; Capmany, José

2012-05-07

A broadband microwave photonic phase shifter based on a single III-V microdisk resonator heterogeneously integrated on and coupled to a nanophotonic silicon-on-insulator waveguide is reported. The phase shift tunability is accomplished by modifying the effective index through carrier injection. A comprehensive semi-analytical model aiming at predicting its behavior is formulated and confirmed by measurements. Quasi-linear and continuously tunable 2π phase shifts at radiofrequencies greater than 18 GHz are experimentally demonstrated. The phase shifter performance is also evaluated when used as a key element in tunable filtering schemes. Distortion-free and wideband filtering responses with a tuning range of ~100% over the free spectral range are obtained.

Multi-band phase shifter design using modified slotline configuration

NASA Astrophysics Data System (ADS)

Kulandhaisamy, Indhumathi; Rajendran, Dinesh Babu; Kanagasabai, Malathi; Gurusamy, Gunasekaran; Moorthy, Balaji; George, Jithila V.; Lawrance, Livya

2017-01-01

In this paper, an analog multiband phase shifter using slotline configuration is proposed. To implement the design, a pair of modified Split Ring Resonator (SRR) is employed. The periodic property of SRR provides multiband characteristics, whether the coupling slot gives the phase variations over the bands. The operation is well explained with an equivalent circuit model and its characteristics have been studied both in simulation and measurement. The prototype operates in 1.77-2.16, 3.5-3.97, 5.08-5.33, 6.43-6.93, and 8.01-8.59 GHz frequency bands which can be utilized for GSM, GPS, WLAN, C-band, and X-band applications, respectively.

Terahertz artificial birefringence and tunable phase shifter based on dielectric metasurface with compound lattice.

PubMed

Ji, Yun-Yun; Fan, Fei; Chen, Meng; Yang, Lei; Chang, Sheng-Jiang

2017-05-15

A dielectric metasurface with line-square compound lattice structure has been fabricated and demonstrated in the terahertz (THz) regime by the THz time-domain spectroscopy and numerical simulation. A polarization dependent electromagnetically induced transparency (EIT) effect is achieved in this metasurface due to the mode coupling and interference between the resonance modes in line and square subunits of the metasurface. Accompany with the EIT effect, a large artificial birefringence effect between two orthogonal polarization states is also observed in this compound metasurface, of which birefringence is over 0.6. Furthermore, the liquid crystals are filled on the surface of this dielectric metasurface to fabricate an electrically tunable THz LC phase shifter. The experimental results show that its tunable phase shift under the biased electric field reaches 0.33π, 1.8 times higher than the bare silicon, which confirms the enhancement role of THz microstructure on the LC phase shift in the THz regime. The large birefringence phase shift of this compound metasurface and its LC tunable phase shifter will be of great significance for potential applications in THz polarization and phase devices.

Theoretical modeling on the laser-induced phase deformation of liquid crystal optical phased shifter

NASA Astrophysics Data System (ADS)

Zhou, Zhuangqi; Wang, Xiangru; Zhuo, Rusheng; He, Xiaoxian; Wu, Liang; Wang, Xiaolin; Tan, Qinggui; Qiu, Qi

2018-03-01

To improve the working condition of liquid crystal phase shifter on incident laser power, a theoretical model on laser induced phase distortion is built on the physics of heat deposition and heat transfer. Four typical factors (absorption, heat sink structure, cooling fluid rate, and substrate) are analyzed to evaluate the influence of phase distortion when a relative high-power laser is pumped into the liquid crystal phase shifter. Flow rate of cooling fluid and heat sink structure are the most important two factors on improving the limit of incident laser power. Meanwhile, silicon wafer is suggested to replace the back glass contacting the heat sink, because of its higher heat transfer coefficient. If the device is fabricated on the conditions that: the total absorption is 5% and it has a strong heat sink structure with a flow rate of 0.01 m/s, when the incident laser power is 110W, the laser-induced phase deformation on the center is diminished to be less than 0.06, and the maximum temperature increase on the center is less than 1K degree.

Highly integrated 3×3 silicon thermo-optical switch using a single combined phase shifter for optical interconnects.

PubMed

Wang, Wanjun; Zhou, Haifeng; Yang, Jianyi; Wang, Minghua; Jiang, Xiaoqing

2012-06-15

We report on an experimental 3×3 thermo-optical switch on silicon on insulator. By controlling a single combined phase shifter, light from any input waveguide can be directed to any output waveguide, showing a simple control method and highly integrated structure as compared to the conventional multiway optical switches. Furthermore, the proposed optical switch can be generalized to be a 1×N and N×N optical switch without an extra phase shifter. The switch is fabricated by complementary metal oxide semiconductor technology. By experiment, full 3×3 switching functionality is demonstrated at a wavelength of 1.55 μm, with an average cross talk of -11.1  dB and a power consumption of 97.5 mW.

Evolution of high-level resistance during low-level antibiotic exposure.

PubMed

Wistrand-Yuen, Erik; Knopp, Michael; Hjort, Karin; Koskiniemi, Sanna; Berg, Otto G; Andersson, Dan I

2018-04-23

It has become increasingly clear that low levels of antibiotics present in many environments can select for resistant bacteria, yet the evolutionary pathways for resistance development during exposure to low amounts of antibiotics remain poorly defined. Here we show that Salmonella enterica exposed to sub-MIC levels of streptomycin evolved high-level resistance via novel mechanisms that are different from those observed during lethal selections. During lethal selection only rpsL mutations are found, whereas at sub-MIC selection resistance is generated by several small-effect resistance mutations that combined confer high-level resistance via three different mechanisms: (i) alteration of the ribosomal RNA target (gidB mutations), (ii) reduction in aminoglycoside uptake (cyoB, nuoG, and trkH mutations), and (iii) induction of the aminoglycoside-modifying enzyme AadA (znuA mutations). These results demonstrate how the strength of the selective pressure influences evolutionary trajectories and that even weak selective pressures can cause evolution of high-level resistance.

Ku to V-band 4-bit MEMS phase shifter bank using high isolation SP4T switches and DMTL structures

NASA Astrophysics Data System (ADS)

Dey, Sukomal; Koul, Shiban K.; Poddar, Ajay K.; Rohde, Ulrich L.

2017-10-01

This work presents a micro-electro-mechanical system (MEMS) based on a wide-band 4-bit phase shifter using two back-to-back single-pole-four-throw (SP4T) switches and four different distributed MEMS transmission line (DMTL) structures that are implemented on 635 µm alumina substrate using surface micromachining process. An SP4T switch is designed with a series-shunt configuration and it demonstrates an average return loss of  >17 dB, an insertion loss of  <1.97 dB and maximum isolation of  >28 dB up to 60 GHz. A maximum area of the SP4T switch is ~0.76 mm2. Single-pole-single-throw and SP4T switches are capable of handling 1 W of radio frequency (RF) power up to  >100 million cycles at 25° C; they can even sustained up to  >70 million cycles with 1 W at 85 °C. The proposed wide-band phase shifter works at 17 GHz (Ku-band), 25 GHz (K-band), 35 GHz (Ka-band) and 60 GHz (V-band) frequencies. Finally,a 4-bit phase shifter demonstrates an average insertion loss of  <6 dB, return loss of  >10 dB and maximum phase error of ~3.8° at 60 GHz frequency over 500 MHz bandwidth. Total area of the fabricated device is ~11 mm2. In addition, the proposed device works well up to  >107 cycles with 1 W of RF power. To the best of the author’s knowledge, this is the best reported wide-band MEMS 4-bit phase shifter in the literature that works with a constant resolution.

Stability Formulation for Integrated Opto-mechanic Phase Shifters.

PubMed

Ozer, Yigit; Kocaman, Serdar

2018-01-31

Stability of opto-mechanical phase shifters consisting of waveguides and non-signal carrying control beams is investigated thoroughly and a formula determining the physical limitations has been proposed. Suggested formulation is not only beneficial to determine physical strength of the system but also advantageous to guess the response of the output to the fabrication errors. In the iterative analysis of cantilever and double-clamped beam geometrical configurations, the stability condition is revealed under the strong inter-dependence of the system parameters such as input power, device length and waveguide separation. Numerical calculations involving effective index modifications and opto-mechanic movements show that well-known cantilever beams are unstable and inadequate to generate φ = 180° phase difference, while double-clamped beam structures can be utilized to build functional devices. Ideal operation conditions are also presented in terms of both the device durability and the controllability of phase evolution.

Broadband, Low-Loss Phase Shifters Based on Thin Ferroelectric Films

NASA Technical Reports Server (NTRS)

Romanofsky, Robert

2004-01-01

Several different types of microwave transmission line phase shifters based on thin ferroelectic films have been developed at the NASA Glenn Research Center. These include a series of coupled microstrip lines, slotline incorporating Marchand balms, odd-mode coplanar strips, and hybrid devices incorporating a switch to toggle the output termination between an open and virtual short circuit. A review of the theory of operation of each of these devices will be presented along with measured performance. Also, devices of the first variety have been subjected to total dose (proton) radiation exposure using a 200 MeV beam energy with a total dose up to nearly 1 kRad (Si). Results of these radiation tests will be discussed.

Studies of nitride- and oxide-based materials as absorptive shifters for embedded attenuated phase-shifting mask in 193 nm

NASA Astrophysics Data System (ADS)

Lin, Cheng-ming; Chang, Keh-wen; Lee, Ming-der; Loong, Wen-An

1999-07-01

Abstract-Five materials which are PdSixOy, CrAlxOy, SiNx, TiSixNy, and TiSixOyNz as absorptive shifters for attenuated phase-shifting mask in 193 nm wavelength lithography are presented. PdSixOy films were deposited by dual e-gun evaporation. CrAlxOy, TiSixNy and TiSixOyNz films were formed by plasma sputtering and SiNx films were formed with LPCVD. All of these materials are shown to be capable of achieving 4 percent - 15 percent transmittance in 193 nm with thickness that produce a 180 degrees phase shift. Under BCl3:Cl2 equals 14:70 sccm; chamber pressure 5 mtorr and RF power 1900W, the dry etching selectivity of TiSixNy over DQN positive resist and fused silica, were found to be 2:1 and 4,8:1 respectively. An embedded layer TiSixNy with 0.5 micrometers line/space was successfully patterned.

Novel Electrically Tunable Microwave Solenoid Inductor and Compact Phase Shifter Utilizing Permaloy and PZT Thin Films

DOE PAGES

Wang, Tengxing; Jiang, Wei; Divan, Ralu; ...

2017-08-03

A Permalloy (Py) thin film enabled tunable 3-D solenoid inductor is designed and fabricated. The special configuration of magnetic core is discussed and by selectively patterning Py thin film, the proposed tunable inductor can work at frequency up to several GHz range. The inductance of the solenoid inductor can be electrically tuned by dc current and the tunability is above 10%. Utilizing the implemented Py enabled tunable solenoid inductor and Lead Zirconate Titanate (PZT) thin film enabled metal-insulator-metal (MIM) capacitor, a compact fully electrically tunable lumped elements phase shifter is achieved. The tunable phase shifter has both inductive and capacitivemore » tunability and the dual tunability significantly improves the tuning range and design flexibility. Moreover, the dual tunability is able to retain the equivalent characteristic impedance of the device in the process of the phase being tuned. Here, the phase of the device can be tuned by fully electrical methods and when dc current and dc voltage are provided, the length normalized phase tunability is up to 210°/cm« less

Constant volume gas cell optical phase-shifter

DOEpatents

Phillion, Donald W.

2002-01-01

A constant volume gas cell optical phase-shifter, particularly applicable for phase-shifting interferometry, contains a sealed volume of atmospheric gas at a pressure somewhat different than atmospheric. An optical window is present at each end of the cell, and as the length of the cell is changed, the optical path length of a laser beam traversing the cell changes. The cell comprises movable coaxial tubes with seals and a volume equalizing opening. Because the cell is constant volume, the pressure, temperature, and density of the contained gas do not change as the cell changes length. This produces an exactly linear relationship between the change in the length of the gas cell and the change in optical phase of the laser beam traversing it. Because the refractive index difference between the gas inside and the atmosphere outside is very much the same, a large motion must be made to change the optical phase by the small fraction of a wavelength that is required by phase-shifting interferometry for its phase step. This motion can be made to great fractional accuracy.

MWP phase shifters integrated in PbS-SU8 waveguides.

PubMed

Hervás, Javier; Suárez, Isaac; Pérez, Joaquín; Cantó, Pedro J Rodríguez; Abargues, Rafael; Martínez-Pastor, Juan P; Sales, Salvador; Capmany, José

2015-06-01

We present new kind of microwave phase shifters (MPS) based on dispersion of PbS colloidal quantum dots (QDs) in commercially available photoresist SU8 after a ligand exchange process. Ridge PbS-SU8 waveguides are implemented by integration of the nanocomposite in a silicon platform. When these waveguides are pumped at wavelengths below the band-gap of the PbS QDs, a phase shift in an optically conveyed (at 1550 nm) microwave signal is produced. The strong light confinement produced in the ridge waveguides allows an improvement of the phase shift as compared to the case of planar structures. Moreover, a novel ridge bilayer waveguide composed by a PbS-SU8 nanocomposite and a SU8 passive layer is proposed to decrease the propagation losses of the pump beam and in consequence to improve the microwave phase shift up to 36.5° at 25 GHz. Experimental results are reproduced by a theoretical model based on the slow light effect produced in a semiconductor waveguide due to the coherent population oscillations. The resulting device shows potential benefits respect to the current MPS technologies since it allows a fast tunability of the phase shift and a high level of integration due to its small size.

Quantifying the effect of air gap, depth, and range shifter thickness on TPS dosimetric accuracy in superficial PBS proton therapy.

PubMed

Shirey, Robert J; Wu, Hsinshun Terry

2018-01-01

This study quantifies the dosimetric accuracy of a commercial treatment planning system as functions of treatment depth, air gap, and range shifter thickness for superficial pencil beam scanning proton therapy treatments. The RayStation 6 pencil beam and Monte Carlo dose engines were each used to calculate the dose distributions for a single treatment plan with varying range shifter air gaps. Central axis dose values extracted from each of the calculated plans were compared to dose values measured with a calibrated PTW Markus chamber at various depths in RW3 solid water. Dose was measured at 12 depths, ranging from the surface to 5 cm, for each of the 18 different air gaps, which ranged from 0.5 to 28 cm. TPS dosimetric accuracy, defined as the ratio of calculated dose relative to the measured dose, was plotted as functions of depth and air gap for the pencil beam and Monte Carlo dose algorithms. The accuracy of the TPS pencil beam dose algorithm was found to be clinically unacceptable at depths shallower than 3 cm with air gaps wider than 10 cm, and increased range shifter thickness only added to the dosimetric inaccuracy of the pencil beam algorithm. Each configuration calculated with Monte Carlo was determined to be clinically acceptable. Further comparisons of the Monte Carlo dose algorithm to the measured spread-out Bragg Peaks of multiple fields used during machine commissioning verified the dosimetric accuracy of Monte Carlo in a variety of beam energies and field sizes. Discrepancies between measured and TPS calculated dose values can mainly be attributed to the ability (or lack thereof) of the TPS pencil beam dose algorithm to properly model secondary proton scatter generated in the range shifter. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Optical properties of new wide heterogeneous waveguides with thermo optical shifters.

PubMed

De Leonardis, Francesco; Tsarev, Andrei V; Passaro, Vittorio M

2008-12-22

We present analysis and simulation of novel silicon-on-insulator (SOI) heterogeneous waveguides with thermo-optic phase shifters. New structure design contains a p-n junction on both sides of SOI ridge waveguide with 220 nm x 35 microm silicon core. Strongly mode-dependent optical losses (by additional free charge absorption) provide quasi-singe-mode behavior of wide waveguide with mode size approximately 10 microm. Local heater produces an efficient phase shifting by small temperature increase (DeltaT approximately 2K), switching power (< 40 mW) and switching time (< 10 micros). Mode optical losses are significantly decreased at high heating (DeltaT approximately 120 K).

Ultra-wideband microwave photonic phase shifter with a 360° tunable phase shift based on an erbium-ytterbium co-doped linearly chirped FBG.

PubMed

Liu, Weilin; Yao, Jianping

2014-02-15

A simple photonic approach to implementing an ultra-wideband microwave phase shifter based on an erbium-ytterbium (Er/Yb) co-doped linearly chirped fiber Bragg grating (LCFBG) is proposed and experimentally demonstrated. The LCFBG is designed to have a constant magnitude response over a reflection band, and a phase response that is linear and nonlinear in two sections in the reflection band. When an optical single-sideband with carrier (OSSB+C) signal is sent to the LCFBG, by locating the optical carrier at the section corresponding to the nonlinear phase response and the sideband at the section corresponding to the linear phase response, a phase shift is introduced to the optical carrier, which is then translated to the microwave signal by beating the optical carrier and the sideband at a photodetector. The tuning of the phase shift is realized by optically pumping the Er/Yb co-doped LCFBG by a 980-nm laser diode. The proposed ultra-wideband microwave photonic phase shifter is experimentally demonstrated. A phase shifter with a full 360° phase shift with a bandwidth from 10 to 40 GHz is experimentally demonstrated.

Generation of energetic, picosecond seed pulses for CO2 laser using Raman shifter

NASA Astrophysics Data System (ADS)

Welch, Eric; Tochitsky, Sergei; Joshi, Chan

2017-03-01

We present a new concept for generating 3 ps seed pulses for a high-power CO2 laser amplifier that are multiple orders more energetic than seed pulses generated by slicing from a nanosecond CO2 laser pulse. We propose to send a 1 µm picosecond laser through a C6D6 Raman shifter and mix both the pump and shifted components in a DFG crystal to produce pulses at 10.6 µm. Preliminary results of a proof-of-principle experiment are presented.

A novel IMSL tunable phase shifter for HMSIW-LWA-fed rectangular patches based on nematic liquid crystal

NASA Astrophysics Data System (ADS)

Fu, JiaHui; Raheem, Odai H.

2017-07-01

A novel IMSL tunable phase shifter for HMSIW-LWA-fed rectangular patches based on liquid crystal technology is proposed. Rectangular patches are used as radiators for the opening sidewall of the waveguide and matched section part for a unit cell. The transition structure is added for enhancing the efficiency of HMSIW-LWA due to converting most input power to the leaky mode. The novel IMSL phase shifter is used for investigating the tunable dielectric characteristics of N-LC by applying an electric field to the LC cell, which is controlled by the orientation angle of the LC molecules. Theoretically, the orientation angle is derived and solved numerically with the accurate method. As a result, the HMSIW-LWA can be tuned up to ± 25° for a fixed frequency by tuning the nematic LC with applied voltage from 0 to 20 V. In addition, the realized gain changed from 6 to 9.4 dB for a fixed tuned frequency, and 46° steerable for rest main beams range of the HMSIW-LWA in both forward and backward directions.

A K-Band Linear Phased Array Antenna Based on Ba(0.60)Sr(0.40)TiO3 Thin Film Phase Shifters

NASA Technical Reports Server (NTRS)

Romanofsky, R.; Bernhard, J.; Washington, G.; VanKeuls, F.; Miranda, F.; Cannedy, C.

2000-01-01

This paper summarizes the development of a 23.675 GHz linear 16-element scanning phased array antenna based on thin ferroelectric film coupled microstripline phase shifters and microstrip patch radiators.

Test of SensL SiPM coated with NOL-1 wavelength shifter in liquid xenon

NASA Astrophysics Data System (ADS)

Akimov, D. Yu.; Belov, V. A.; Borshchev, O. V.; Burenkov, A. A.; Grishkin, Yu. L.; Karelin, A. K.; Kuchenkov, A. V.; Martemiyanov, A. N.; Ponomarenko, S. A.; Simakov, G. E.; Stekhanov, V. N.; Surin, N. M.; Timoshin, V. S.; Zeldovich, O. Ya.

2017-05-01

A SensL MicroFC-SMT-60035 6×6 mm2 silicon photo-multiplier coated with a NOL-1 wavelength shifter have been tested in the liquid xenon to detect the 175-nm scintillation light. For comparison, a Hamamatsu vacuum ultraviolet sensitive MPPC VUV3 3×3 mm2 was tested under the same conditions. The photodetection efficiency of 13.1 ± 2.5% and 6.0 ± 1.0%, correspondingly, is obtained.

A wideband photonic microwave phase shifter with 360-degree phase tunable range based on a DP-QPSK modulator

NASA Astrophysics Data System (ADS)

Chen, Yang

2018-03-01

A novel wideband photonic microwave phase shifter with 360-degree phase tunable range is proposed based on a single dual-polarization quadrature phase shift-keying (DP-QPSK) modulator. The two dual-parallel Mach-Zehnder modulators (DP-MZMs) in the DP-QPSK modulator are properly biased to serve as a carrier-suppressed single-sideband (CS-SSB) modulator and an optical phase shifter (OPS), respectively. The microwave signal is applied to the CS-SSB modulator, while a control direct-current (DC) voltage is applied to the OPS. The first-order optical sideband generated from the CS-SSB modulator and the phase tunable optical carrier from the OPS are combined and then detected in a photodetector, where a microwave signal is generated with its phase controlled by the DC voltage applied to the OPS. The proposed technique is theoretically analyzed and experimentally demonstrated. Microwave signals with a carrier frequency from 10 to 23 GHz are continuously phase shifted over 360-degree phase range. The proposed technique features very compact configuration, easy phase tuning and wide operation bandwidth.

Fully tunable 360° microwave photonic phase shifter based on a single semiconductor optical amplifier.

PubMed

Sancho, Juan; Lloret, Juan; Gasulla, Ivana; Sales, Salvador; Capmany, José

2011-08-29

A fully tunable microwave photonic phase shifter involving a single semiconductor optical amplifier (SOA) is proposed and demonstrated. 360° microwave phase shift has been achieved by tuning the carrier wavelength and the optical input power injected in an SOA while properly profiting from the dispersion feature of a conveniently designed notch filter. It is shown that the optical filter can be advantageously employed to switch between positive and negative microwave phase shifts. Numerical calculations corroborate the experimental results showing an excellent agreement.

Novel Phased Array Scanning Employing A Single Feed Without Using Individual Phase Shifters

NASA Technical Reports Server (NTRS)

Host, Nicholas K.; Chen, Chi-Chih; Volakis, John L.; Miranda, Felix A.

2012-01-01

Phased arrays afford many advantages over mechanically steered systems. However, they are also more complex, heavy, and most of all costly. The high cost mainly originates from the complex feeding structure. This paper proposes a novel feeding scheme to eliminate all phase shifters and achieve scanning via one-dimensional motion. Beam scanning is achieved via a series fed array incorporating feeding transmission lines whose wave velocity can be mechanically adjusted. Along with the line design, ideal element impedances to be used in conjunction with the line are derived. Practical designs are shown which achieve scanning to +/-30deg from boresight. Finally, a prototype is fabricated and measured, demonstrating the concept.

Shielding Effects of a Building Structure on the Energy Deposit of Cosmic Rays in a Simple Wavelength Shifter-Based Scintillator

ERIC Educational Resources Information Center

Aiola, Salvatore; La Rocca, Paola; Riggi, Francesco; Riggi, Simone

2012-01-01

An experimental setup, based on a plastic scintillator with an embedded wavelength shifter fibre and photosensors at the two ends, has been used to detect cosmic muons in undergraduate laboratory activities. Time and amplitude information from the two photosensors were measured using the time-over-threshold technique. The distribution of the…

Intermodulation and harmonic distortion in slow light Microwave Photonic phase shifters based on Coherent Population Oscillations in SOAs.

PubMed

Gasulla, Ivana; Sancho, Juan; Capmany, José; Lloret, Juan; Sales, Salvador

2010-12-06

We theoretically and experimentally evaluate the propagation, generation and amplification of signal, harmonic and intermodulation distortion terms inside a Semiconductor Optical Amplifier (SOA) under Coherent Population Oscillation (CPO) regime. For that purpose, we present a general optical field model, valid for any arbitrarily-spaced radiofrequency tones, which is necessary to correctly describe the operation of CPO based slow light Microwave Photonic phase shifters which comprise an electrooptic modulator and a SOA followed by an optical filter and supplements another recently published for true time delay operation based on the propagation of optical intensities. The phase shifter performance has been evaluated in terms of the nonlinear distortion up to 3rd order, for a modulating signal constituted of two tones, in function of the electrooptic modulator input RF power and the SOA input optical power, obtaining a very good agreement between theoretical and experimental results. A complete theoretical spectral analysis is also presented which shows that under small signal operation conditions, the 3rd order intermodulation products at 2Ω1 + Ω2 and 2Ω2 + Ω1 experience a power dip/phase transition characteristic of the fundamental tones phase shifting operation.

Research on a Defects Detection Method in the Ferrite Phase Shifter Cementing Process Based on a Multi-Sensor Prognostic and Health Management (PHM) System.

PubMed

Wan, Bo; Fu, Guicui; Li, Yanruoyue; Zhao, Youhu

2016-08-10

The cementing manufacturing process of ferrite phase shifters has the defect that cementing strength is insufficient and fractures always appear. A detection method of these defects was studied utilizing the multi-sensors Prognostic and Health Management (PHM) theory. Aiming at these process defects, the reasons that lead to defects are analyzed in this paper. In the meanwhile, the key process parameters were determined and Differential Scanning Calorimetry (DSC) tests during the cure process of resin cementing were carried out. At the same time, in order to get data on changing cementing strength, multiple-group cementing process tests of different key process parameters were designed and conducted. A relational model of cementing strength and cure temperature, time and pressure was established, by combining data of DSC and process tests as well as based on the Avrami formula. Through sensitivity analysis for three process parameters, the on-line detection decision criterion and the process parameters which have obvious impact on cementing strength were determined. A PHM system with multiple temperature and pressure sensors was established on this basis, and then, on-line detection, diagnosis and control for ferrite phase shifter cementing process defects were realized. It was verified by subsequent process that the on-line detection system improved the reliability of the ferrite phase shifter cementing process and reduced the incidence of insufficient cementing strength defects.

PPO-ethanol system as wavelength shifter for the Cherenkov counting technique using a liquid scintillation counter

NASA Astrophysics Data System (ADS)

Takiue, Makoto; Fujii, Haruo; Ishikawa, Hiroaki

1984-12-01

2, 5-diphenyloxazole (PPO) has been proposed as a wavelength shifter for Cherenkov counting. Since PPO is not incorporated with water, we have introduced the fluor into water in the form of micelle using a PPO-ethanol system. This technique makes it possible to obtain a high Cherenkov counting efficiency under stable sample conditions, attributed to the proper spectrometric features of the PPO. The 32P Cherenkov counting efficiency (68.4%) obtained from this technique is large as that measured with a conventional Cherenkov technique.

Room Temperature Thin Film Ba(x)Sr(1-x)TiO3 Ku-Band Coupled MicrostripPhase Shifters: Effects of Film Thickness, Doping, Annealing and Substrate Choice

NASA Technical Reports Server (NTRS)

VanKeuls, F. W.; Mueller, C. H.; Miranda, F. A.; Romanofsky, R. R.; Canedy, C. L.; Aggarwal, S.; Venkatesan, T.; Ramesh, R.; Horwitz, S.; Chang, W.

1999-01-01

We report on measurements taken on over twenty Ku-band coupled microstrip phase shifters (CMPS) using thin ferroelectric films of Ba(x)Sr(1-x)TiO3. This CMPS design is a recent innovation designed to take advantage of the high tunability and tolerate the high dielectric constant of ferroelectric films at Ku- and K-band frequencies. These devices are envisioned as a component in low-cost steerable beam phased area antennas, Comparisons are made between devices with differing film thickness, annealed vs unannealed, Mn-doped vs. undoped, and also substrates of LaAlO3 and MgO. A comparison between the CMPS structure and a CPW phase shifter was also made oil the same ferroelectric film.

Performance analysis of fusion nuclear-data benchmark experiments for light to heavy materials in MeV energy region with a neutron spectrum shifter

NASA Astrophysics Data System (ADS)

Murata, Isao; Ohta, Masayuki; Miyamaru, Hiroyuki; Kondo, Keitaro; Yoshida, Shigeo; Iida, Toshiyuki; Ochiai, Kentaro; Konno, Chikara

2011-10-01

Nuclear data are indispensable for development of fusion reactor candidate materials. However, benchmarking of the nuclear data in MeV energy region is not yet adequate. In the present study, benchmark performance in the MeV energy region was investigated theoretically for experiments by using a 14 MeV neutron source. We carried out a systematical analysis for light to heavy materials. As a result, the benchmark performance for the neutron spectrum was confirmed to be acceptable, while for gamma-rays it was not sufficiently accurate. Consequently, a spectrum shifter has to be applied. Beryllium had the best performance as a shifter. Moreover, a preliminary examination of whether it is really acceptable that only the spectrum before the last collision is considered in the benchmark performance analysis. It was pointed out that not only the last collision but also earlier collisions should be considered equally in the benchmark performance analysis.

Wideband 360 degrees microwave photonic phase shifter based on slow light in semiconductor optical amplifiers.

PubMed

Xue, Weiqi; Sales, Salvador; Capmany, José; Mørk, Jesper

2010-03-15

In this work we demonstrate for the first time, to the best of our knowledge, a continuously tunable 360 degrees microwave phase shifter spanning a microwave bandwidth of several tens of GHz (up to 40 GHz). The proposed device exploits the phenomenon of coherent population oscillations, enhanced by optical filtering, in combination with a regeneration stage realized by four-wave mixing effects. This combination provides scalability: three hybrid stages are demonstrated but the technology allows an all-integrated device. The microwave operation frequency limitations of the suggested technique, dictated by the underlying physics, are also analyzed.

On-chip programmable ultra-wideband microwave photonic phase shifter and true time delay unit.

PubMed

Burla, Maurizio; Cortés, Luis Romero; Li, Ming; Wang, Xu; Chrostowski, Lukas; Azaña, José

2014-11-01

We proposed and experimentally demonstrated an ultra-broadband on-chip microwave photonic processor that can operate both as RF phase shifter (PS) and true-time-delay (TTD) line, with continuous tuning. The processor is based on a silicon dual-phase-shifted waveguide Bragg grating (DPS-WBG) realized with a CMOS compatible process. We experimentally demonstrated the generation of delay up to 19.4 ps over 10 GHz instantaneous bandwidth and a phase shift of approximately 160° over the bandwidth 22-29 GHz. The available RF measurement setup ultimately limits the phase shifting demonstration as the device is capable of providing up to 300° phase shift for RF frequencies over a record bandwidth approaching 1 THz.

Complementary frequency shifter based on polarization modulator used for generation of a high-quality frequency-locked multicarrier.

PubMed

Li, Jianping; Yu, Changyuan; Li, Zhaohui

2014-03-15

A novel polarization-modulator-based complementary frequency shifter (PCFS) has been proposed and then used to implement the generation of a frequency-locked multicarrier with single- and dual-recirculating frequency shifting loops, respectively. The transfer functions and output properties of PCFS and PCFS-based multicarrier generator have been studied theoretically. Based on our simulation results through VPItransmissionMaker software, 100 stable carriers have been obtained with acceptable flatness while no DC bias control is required. The results show that the proposed PCFS has the potential to become a commercial product and then used in various scenarios.

Theoretical and experimental study of a gas-coupled two-stage pulse tube cooler with stepped warm displacer as the phase shifter

NASA Astrophysics Data System (ADS)

Pang, Xiaomin; Wang, Xiaotao; Dai, Wei; Li, Haibing; Wu, Yinong; Luo, Ercang

2018-06-01

A compact and high efficiency cooler working at liquid hydrogen temperature has many important applications such as cooling superconductors and mid-infrared sensors. This paper presents a two-stage gas-coupled pulse tube cooler system with a completely co-axial configuration. A stepped warm displacer, working as the phase shifter for both stages, has been studied theoretically and experimentally in this paper. Comparisons with the traditional phase shifter (double inlet) are also made. Compared with the double inlet type, the stepped warm displacer has the advantages of recovering the expansion work from the pulse tube hot end (especially from the first stage) and easily realizing an appropriate phase relationship between the pressure wave and volume flow rate at the pulse tube hot end. Experiments are then carried out to investigate the performance. The pressure ratio at the compression space is maintained at 1.37, for the double inlet type, the system obtains 1.1 W cooling power at 20 K with 390 W acoustic power input and the relative Carnot efficiency is only 3.85%; while for the stepped warm displacer type, the system obtains 1.06 W cooling power at 20 K with only 224 W acoustic power input and the relative Carnot efficiency can reach 6.5%.

Development of high precision digital driver of acoustic-optical frequency shifter for ROG

NASA Astrophysics Data System (ADS)

Zhang, Rong; Kong, Mei; Xu, Yameng

2016-10-01

We develop a high precision digital driver of the acoustic-optical frequency shifter (AOFS) based on the parallel direct digital synthesizer (DDS) technology. We use an atomic clock as the phase-locked loop (PLL) reference clock, and the PLL is realized by a dual digital phase-locked loop. A DDS sampling clock up to 320 MHz with a frequency stability as low as 10-12 Hz is obtained. By constructing the RF signal measurement system, it is measured that the frequency output range of the AOFS-driver is 52-58 MHz, the center frequency of the band-pass filter is 55 MHz, the ripple in the band is less than 1 dB@3MHz, the single channel output power is up to 0.3 W, the frequency stability is 1 ppb (1 hour duration), and the frequency-shift precision is 0.1 Hz. The obtained frequency stability has two orders of improvement compared to that of the analog AOFS-drivers. For the designed binary frequency shift keying (2-FSK) and binary phase shift keying (2-PSK) modulation system, the demodulating frequency of the input TTL synchronous level signal is up to 10 kHz. The designed digital-bus coding/decoding system is compatible with many conventional digital bus protocols. It can interface with the ROG signal detecting software through the integrated drive electronics (IDE) and exchange data with the two DDS frequency-shift channels through the signal detecting software.

An X-Band SOS Resistive Gate-Insulator-Semiconductor /RIS/ switch

NASA Astrophysics Data System (ADS)

Kwok, S. P.

1980-02-01

The new X-Band Resistive Gate-Insulator-Semiconductor (RIS) switch has been fabricated on silicon-on-sapphire, and its equivalent circuit model characterized. An RIS SPST switch with 20-dB on/off isolation, 1.2-dB insertion loss, and power handling capacity in excess of 20-W peak has been achieved at X band. The device switching time is on the order of 600 ns, and it requires negligible control holding current in both on and off states. The device is compatible with monolithic integrated-circuit technology and thus is suitable for integration into low-cost monolithic phase shifters or other microwave integrated circuits.

Electromagnetic characterization of photo-definable ferrite loaded polymers and their applications in micro-rectangular coaxial phase shifters

NASA Astrophysics Data System (ADS)

Sholiyi, Olusegun Samuel

As the demand for smaller size, lighter weight, lower loss and cost of communications transmit and receive (T/R) modules increases, there is an urgent need to focus investigation to the major subsystem or components that can improve these parameters. Phase shifters contribute greatly to the cost of T/R modules, and thus this research investigation examines a new way to reduce the weight and cost by miniaturizing the phaser design. Characterization of hexaferrite powders compatible with the sequential multilayer micro-fabrication technology and numerical simulations of a novel rectangular micro-coaxial phase shifter are investigated. This effort aims to integrate ferrite material into a rectangular micro-coaxial waveguide at Ka-band using electromagnetic finite element numerical tools. The proposed technique exploits rectangular coaxial waveguide with a symmetrically placed inner signal conductor inside an outer conductor connected to the ground. Strontium ferrite-SU8 composite is used as an anisotropic material of choice in the modelled design. Numerical modeling is employed using High Frequency Structure Simulator, HFSS, a 3-D full wave electromagnetic solver for analyzing the performance of the device. Two model structures were designed for reciprocal and non-reciprocal applications. The first model (Model A) produced a tunable phase shift of almost 60 degrees /cm across 0 to 400 kA/m applied field and at 1800 Gauss. In model B, a non-reciprocal phase shift performance of 20 degrees /cm from a reference phase of 24 degrees at 0 A/m was realized at the same saturation magnetization. A return loss better than 20 dB and an insertion loss less than 1.5 dB were obtained for both models.

Levels of eicosapentaenoic acid in obese schoolchildren with and without insulin resistance.

PubMed

Sánchez Meza, Karmina; Tene Pérez, Carlos Enrique; Sánchez Ramírez, Carmen Alicia; Muñiz Valencia, Roberto; Del Toro Equihua, Mario

2014-09-12

Obesity in children is now an increasing health risk worldwide in which the insulin-resistance can be present. Studies have linked a diet rich in n-3 fatty acids with a lower prevalence of insulin-resistance. To compare the levels of eicosapentaenoic acid among obese children with and without insulin-resistance. In 56 randomly school-age children with obesity, insulin-resistance was determined by the homeostasis model assessment for insulin-resistance index and the serum levels of eicosapentaenoic acid were determined by gas chromatography. Insulin-resistance was established when the index was >6.0, non- insulin- resistance when that index was within the range of 1.4-5.9. The serum levels of eicosapentaenoic acid were compared with the Kruskal-Wallis and Mann-Whitney U tests, as needed. No differences in age or sex were identified among the groups studied. The anthropometric parameters were significantly higher in the group of children with insulin-resistance than in the other two groups. The children with insulin- resistance had significantly lower levels of eicosapentaenoic acid than the non- insulin-resistance group [12.4% area under the curve vs. 37.4%, p = 0.031], respectively. Obese primary school-aged children with insulin-resistance had lower plasma levels of eicosapentaenoic acid. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Interferometric space-mode multiplexing based on binary phase plates and refractive phase shifters.

PubMed

Liñares, Jesús; Prieto-Blanco, Xesús; Moreno, Vicente; Montero-Orille, Carlos; Mouriz, Dolores; Nistal, María C; Barral, David

2017-05-15

A Mach-Zehnder interferometer (MZI) that includes in an arm either a reflective image inverter or a Gouy phase shifter (RGPS) can (de)multiplex many types of modes of a few mode fiber without fundamental loss. The use of RGPSs in combination with binary phase plates for multiplexing purposes is studied for the first time, showing that the particular RGPS that shifts π the odd modes only multiplexes accurately low order modes. To overcome such a restriction, we present a new exact refractive image inverter, more compact and flexible than its reflective counterpart. Moreover, we show that these interferometers remove or reduce the crosstalk that the binary phase plates could introduce between the multiplexed modes. Finally, an experimental analysis of a MZI with both an approximated and an exact refractive image inverter is presented for the case of a bimodal multiplexing. Likewise, it is proven experimentally that a RGPS that shifts π/2 demultiplexes two odd modes which can not be achieved by any image inverter.

Genetic Determinants of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus.

PubMed

Pardos de la Gandara, Maria; Borges, Vitor; Chung, Marilyn; Milheiriço, Catarina; Gomes, João Paulo; de Lencastre, Herminia; Tomasz, Alexander

2018-06-01

Methicillin-resistant Staphylococcus aureus (MRSA) strains carry either a mecA - or a mecC -mediated mechanism of resistance to beta-lactam antibiotics, and the phenotypic expression of resistance shows extensive strain-to-strain variation. In recent communications, we identified the genetic determinants associated with the stringent stress response that play a major role in the antibiotic resistant phenotype of the historically earliest "archaic" clone of MRSA and in the mecC -carrying MRSA strain LGA251. Here, we sought to test whether or not the same genetic determinants also contribute to the resistant phenotype of highly and homogeneously resistant (H*R) derivatives of a major contemporary MRSA clone, USA300. We found that the resistance phenotype was linked to six genes ( fruB , gmk , hpt , purB , prsA , and relA ), which were most frequently targeted among the analyzed 20 H*R strains (one mutation per clone in 19 of the 20 H*R strains). Besides the strong parallels with our previous findings (five of the six genes matched), all but one of the repeatedly targeted genes were found to be linked to guanine metabolism, pointing to the key role that this pathway plays in defining the level of antibiotic resistance independent of the clonal type of MRSA. Copyright © 2018 American Society for Microbiology.

Measuring Resistance to Change at the Within-Session Level

PubMed Central

Tonneau, François; Ríos, Américo; Cabrera, Felipe

2006-01-01

Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases more slowly than in another component. A problem with normalization, however, is that it can produce artifactual results if the relation between baseline level and disruption is not multiplicative. One way to address this issue is to fit specific models of disruption to untransformed response rates and evaluate whether or not a multiplicative model accounts for the data. Here we present such a test of resistance to change, using within-session response patterns in rats as a data base for fitting models of disruption. By analyzing response rate at a within-session level, we were able to confirm a central prediction of the resistance-to-change framework while discarding normalization artifacts as a plausible explanation of our results. PMID:16903495

Measuring resistance to change at the within-session level.

PubMed

Tonneau, François; Ríos, Américo; Cabrera, Felipe

2006-07-01

Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases more slowly than in another component. A problem with normalization, however, is that it can produce artifactual results if the relation between baseline level and disruption is not multiplicative. One way to address this issue is to fit specific models of disruption to untransformed response rates and evaluate whether or not a multiplicative model accounts for the data. Here we present such a test of resistance to change, using within-session response patterns in rats as a data base for fitting models of disruption. By analyzing response rate at a within-session level, we were able to confirm a central prediction of the resistance-to-change framework while discarding normalization artifacts as a plausible explanation of our results.

Association between omentin levels and insulin resistance in pregnancy.

PubMed

Aktas, G; Alcelik, A; Ozlu, T; Tosun, M; Tekce, B K; Savli, H; Tekce, H; Dikbas, O

2014-03-01

Omentin is a new adipokine secreted mainly from visceral adipose tissue. Serum omentin is found to be reduced in patients with impaired glucose tolerance, type 2 diabetes mellitus, obesity and insulin resistant states. Despite the fact that pregnancy is also characterized with hyperinsulinemia, literature is lacking about data of omentin levels and its association with insulin resistance in pregnant women. We aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of non-pregnant, non-diabetic women. Uncomplicated pregnant women who admit to our outpatient clinics for routine follow-up were included in the study group. Non-pregnant women without diabetes mellitus were served as control group. Fasting glucose, insulin, omentin levels and HOMA IR were recorded. SPSS 15.0 for Windows was used for statistical analysis. There were 36 pregnant women in the study group and 37 healthy, non-pregnant women in the control group. Serum omentin and fasting glucose levels were significantly decreased and fasting insulin was significantly increased in the study group compared to control group. Omentin might be an indicator of insulin resistance in pregnant women. Larger prospective studies are needed to claim whether omentin can have a clinical use for diagnosis of gestational diabetes mellitus. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Amino acid substitutions in the VanS sensor of the VanA-type vancomycin-resistant Enterococcus strains result in high-level vancomycin resistance and low-level teicoplanin resistance.

PubMed

Hashimoto, Y; Tanimoto, K; Ozawa, Y; Murata, T; Ike, Y

2000-04-15

The vancomycin-resistant enterococci GV1, GV2 and GV3, which were isolated from droppings from broiler farms in Japan have been characterized as VanA-type VRE, which express high-level vancomycin resistance (256 or 512 microg ml(-1), MIC) and low-level teicoplanin resistance (1 or 2 microg ml(-1), MIC). The vancomycin resistances were encoded on plasmids. The vancomycin resistance conjugative plasmid pMG2 was isolated from the GV2 strain. The VanA determinant of pMG2 showed the same genetic organization as that of the VanA genes encoded on the representative transposon Tn1546, which comprises vanRSHAXYZ. The nucleotide sequences of all the genes, except the gene related to the vanS gene on Tn1546, were completely identical to the genes encoded on Tn1546. Three amino acid substitutions in the N-terminal region of the deduced VanS were detected in the nucleotide sequence of vanS encoded on pMG2. There were also three amino acid substitutions in the vanS gene of the GV1 and GV3 strains in the same positions as in the vanS gene of pMG2. Vancomycin induced the increased teicoplanin resistance in these strains.

Characterization of (Ba(0.5)Sr(0.5)) TiO3 Thin Films for Ku-Band Phase Shifters

NASA Technical Reports Server (NTRS)

Mueller, Carl H.; VanKeuls, Fredrick W.; Romanofsky, Robert R.; Miranda, Felix A.; Warner, Joseph D.; Canedy, Chadwick L.; Ramesh, Rammamoorthy

1999-01-01

The microstructural properties of (Ba(0.5)Sr(0.5)TiO3) (BSTO) thin films (300, 700, and 1400 nm thick) deposited on LaAlO3 (LAO) substrates were characterized using high-resolution x-ray diffractometry. Film crystallinity was the parameter that most directly influenced tunability, and we observed that a) the crystalline quality was highest in the thinnest film and progressively degraded with increasing film thickness; and b) strain at the film/substrate interface was completely relieved via dislocation formation. Paraelectric films such as BSTO offer an attractive means of incorporating low-cost phase shifter circuitry into beam-steerable reflectarray antennas.

Measuring Resistance to Change at the Within-Session Level

ERIC Educational Resources Information Center

Tonneau, Francois; Rios, Americo; Cabrera, Felipe

2006-01-01

Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases…

Four-to-one power combiner for 20 GHz phased array antenna using RADC MMIC phase shifters

NASA Technical Reports Server (NTRS)

1991-01-01

The design and microwave simulation of two-to-one microstrip power combiners is described. The power combiners were designed for use in a four element phase array receive antenna subarray at 20 GHz. Four test circuits are described which were designed to enable testing of the power combiner and the four element phased array antenna. Test Circuit 1 enables measurement of the two-to-one power combiner. Test Circuit 2 enables measurement of the four-to-one power combiner. Test Circuit 3 enables measurement of a four element antenna array without phase shifting MMIC's in order to characterize the power combiner with the antenna patch-to-microstrip coaxial feedthroughs. Test circuit 4 is the four element phased array antenna including the RADC MMIC phase shifters and appropriate interconnects to provide bias voltages and control phase bits.

A gallium-arsenide digital phase shifter for clock and control signal distribution in high-speed digital systems

NASA Technical Reports Server (NTRS)

Fouts, Douglas J.

1992-01-01

The design, implementation, testing, and applications of a gallium-arsenide digital phase shifter and fan-out buffer are described. The integrated circuit provides a method for adjusting the phase of high-speed clock and control signals in digital systems, without the need for pruning cables, multiplexing between cables of different lengths, delay lines, or similar techniques. The phase of signals distributed with the described chip can be dynamically adjusted in eight different steps of approximately 60 ps per step. The IC also serves as a fan-out buffer and provides 12 in-phase outputs. The chip is useful for distributing high-speed clock and control signals in synchronous digital systems, especially if components are distributed over a large physical area or if there is a large number of components.

Prediction of Groundwater Level at Slope Areas using Electrical Resistivity Method

NASA Astrophysics Data System (ADS)

Baharuddin, M. F. T.; Hazreek, Z. A. M.; Azman, M. A. A.; Madun, A.

2018-04-01

Groundwater level plays an important role as an agent that triggers landslides. Commonly, the conventional method used to monitor the groundwater level is done by using standpipe piezometer. There were several disadvantages of the conventional method related to cost, time and data coverage. The aim of this study is to determine groundwater level at slope areas using electrical resistivity method and to verify groundwater level of the study area with standpipe piezometer data. The data acquisition was performed using ABEM Terrameter SAS4000. For data analysis and processing, RES2DINV and SURFER were used. The groundwater level was calibrated with reference of standpipe piezometer based on electrical resistivity value (ERV).

Potential effect of exercise in ameliorating insulin resistance at transcriptome level.

PubMed

Hu, Zhigang; Zhou, Lei; He, Tingting

2017-10-24

Insulin resistance can lead to the pathogenesis of type 2 diabetes and exercise can increase insulin sensitivity. And different exercises may have different influences on the mitigation of insulin resistance. It's still unclear how exercise affects inherited insulin resistance at transcriptome level. The purpose of our study was to analyze the potential effects of exercise in ameliorating insulin resistance at transcriptome level. Herein, we analyzed two skeletal muscle transcriptome profiles, including gene profiles between inherited insulin resistant patients and matched healthy controls, and between trained and sedentary subjects (young and old subjects, respectively). Analysis of differentially expressed genes revealed that 12 genes (SGK1, LOC101929876, MYL5, COL6A3, MLF1, LUM, MSTN, COL1A2, COL3A1, IL32, IRS2 and ID1) associated with insulin resistance were reversed by exercise in young subjects, while six genes (MSTN, CFHR1, PFKFB3, IL32, RGCC and NMRK2) were identified in old subjects, suggesting that those genes play potential roles in insulin resistance response to exercise. In addition, we observed that two insulin resistance-related genes, MSTN and IL32, were identified in muscle cells of both young and old subjects, indicating their important roles in the mechanisms behind the beneficial effects of exercise on humans with inherited insulin resistance. Several pathways were also identified, such as "collagen metabolic process", "focal adhesion" and "negative regulation of myoblast differentiation". Taken together, our findings provide novel markers in insulin resistant patients and exercise, and some valuable information for future functional studies on how exercise ameliorating insulin resistance.

Characterization of antimicrobial resistance and quinolone resistance factors in high-level ciprofloxacin-resistant Enterococcus faecalis and Enterococcus faecium isolates obtained from fresh produce and fecal samples of patients.

PubMed

Kim, Min-Chan; Woo, Gun-Jo

2017-07-01

The emergence of fluoroquinolone-resistant enterococci is worldwide. Antimicrobial resistance was characterized and the effect of quinolone-resistance factors was analyzed in high-level ciprofloxacin-resistant (HLCR) Enterococcus faecalis and Enterococcus faecium isolated from fresh produce and fecal samples of patients. Among the 81 ciprofloxacin-resistant Enterococcus isolates, 46 showed high levels of ciprofloxacin resistance, resistance to other quinolone antibiotics, and multidrug resistance profiles. The virulence factors esp and hyl were identified in 27 (58.7%) and 25 (54.3%) of isolates, respectively. Sequence type analysis showed that 35 strains of HLCR E. faecium were clonal complex 17. Eleven strains of HLCR E. faecalis were confirmed as sequence type (ST) 28, ST 64 and ST 125. Quinolone resistance-determining region mutation was identified in HLCR Enterococcus isolates; with serine being changed in gyrA83, gyrA87 and parC80. This result shows that gyrA and parC mutations could be important factors for high-level resistance to fluoroquinolones. No significant differences were observed in antimicrobial resistance patterns and genetic characteristics among the isolates from fresh produce and fecal samples. Therefore, good agricultural practices in farming and continuous monitoring of patients, food and the environment for Enterococcus spp. should be performed to prevent antimicrobial resistance and enable reduction of resistance rates. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Differential Penicillin-Binding Protein 5 (PBP5) Levels in the Enterococcus faecium Clades with Different Levels of Ampicillin Resistance.

PubMed

Montealegre, Maria Camila; Roh, Jung Hyeob; Rae, Meredith; Davlieva, Milya G; Singh, Kavindra V; Shamoo, Yousif; Murray, Barbara E

2017-01-01

Ampicillin resistance in Enterococcus faecium is a serious concern worldwide, complicating the treatment of E. faecium infections. Penicillin-binding protein 5 (PBP5) is considered the main ampicillin resistance determinant in E. faecium The three known E. faecium clades showed sequence variations in the pbp5 gene that are associated with their ampicillin resistance phenotype; however, these changes alone do not explain the array of resistance levels observed among E. faecium clinical strains. We aimed to determine if the levels of PBP5 are differentially regulated between the E. faecium clades, with the hypothesis that variations in PBP5 levels could help account for the spectrum of ampicillin MICs seen in E. faecium We studied pbp5 mRNA levels and PBP5 protein levels as well as the genetic environment upstream of pbp5 in 16 E. faecium strains that belong to the different E. faecium clades and for which the ampicillin MICs covered a wide range. Our results found that pbp5 and PBP5 levels are increased in subclade A1 and A2 ampicillin-resistant strains compared to those in clade B and subclade A2 ampicillin-susceptible strains. Furthermore, we found evidence of major clade-associated rearrangements in the region upstream of pbp5, including large DNA fragment insertions, deletions, and single nucleotide polymorphisms, that may be associated with the differential regulation of PBP5 levels between the E. faecium clades. Overall, these findings highlight the contribution of the clade background to the regulation of PBP5 abundance and point to differences in the region upstream of pbp5 as likely contributors to the differential expression of ampicillin resistance. Copyright © 2016 American Society for Microbiology.

Elevated serum tartrate-resistant acid phosphatase isoform 5a levels in metabolic syndrome.

PubMed

Huang, Yi-Jhih; Huang, Tsai-Wang; Chao, Tsu-Yi; Sun, Yu-Shan; Chen, Shyi-Jou; Chu, Der-Ming; Chen, Wei-Liang; Wu, Li-Wei

2017-09-29

Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 μg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 μg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 μg/L.

High levels of macrolide-resistant Mycoplasma genitalium in Queensland, Australia.

PubMed

Trembizki, Ella; Buckley, Cameron; Bletchly, Cheryl; Nimmo, Graeme R; Whiley, David M

2017-10-01

The macrolide azithromycin is recommended for treatment of Mycoplasma genitalium infection; however, M. genitalium strains possessing macrolide resistance-mediating mutations (MRMMs) are increasingly being reported. Here, we used the SpeeDx ResistancePlus MG kit, which provides simultaneous detection of M. genitalium and MRMMs, to assess MRMM carriage among M. genitalium infections in Queensland, Australia. Performance characteristics of the ResistancePlus MG kit for M. genitalium detection were compared to in-house PCR. Available M. genitalium PCR-positive (n=67) and negative (n=281) samples from the years 2011 to 2017 were tested using the SpeeDx ResistancePlus MG kit. In total, 63.6 % M. genitalium-positive samples were indicated to harbour MRMMs. The ResistancePlus MG method provided sensitivity and specificity of 97 and 99.6 % respectively compared to in-house PCR for M. genitalium detection. Such high levels of macrolide-resistant M. genitalium raise further concerns over future use of azithromycin for treatment of M. genitalium infection.

Thin-Film Ferro Electric-Coupled Microstripline Phase Shifters With Reduced Device Hysteresis

NASA Technical Reports Server (NTRS)

Miranda, Felix A.; Romanofsky, Robert; Mueller, Carl H.; VanKeuls, Frederick

2010-01-01

This work deals with the performance of coupled microstripline phase shifters (CMPS) fabricated using BaxSr 1 -xTiO 3 (BST) ferroelectric thin films. The CMPS were fabricated using commercially available pulsed laser deposition BST films with Ba:Sr ratios of 30:70 and 20:80. Microwave characterization of these CMPS was performed at upper Kuband frequencies, particularly at frequencies near 16 and 18 GHz. X-ray diffraction studies indicate that the 30:70 films exhibit almost a 1:1 ratio between the in-plane and out-of-plane lattice parameters, suggesting that their cubics create strain -free films suitable for producing CMPS devices with reduced hysteresis in the paraelectric state. The quality of performance of the CMPS was studied based on their relative phase shift and insertion loss within the DC bias range of 0 to 400 V (i.e., E-field ranges within 0 to 53 V/micron). The performance of the CMPS was tested as a function of temperature to investigate their operation in the paraelectric, as well as in the ferroelectric, state (i.e., above and below the Curie temperature, respectively). The novel behavior discussed here is based on the experimental observation of the CMPS. This behavior, observed for the aforementioned cation ratio, highlights the relevance of good crystalline structure for high-quality CMPS.

Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

PubMed

Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

2015-09-01

The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=<0.001), glucose (p=<0.001), insulin (p=<0.001) and HOMA IR score (p=<0.0001) in cases of metabolic syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

Broadband tunable microwave photonic phase shifter with low RF power variation in a high-Q AlN microring.

PubMed

Liu, Xianwen; Sun, Changzheng; Xiong, Bing; Wang, Jian; Wang, Lai; Han, Yanjun; Hao, Zhibiao; Li, Hongtao; Luo, Yi; Yan, Jianchang; Wei, Tong Bo; Zhang, Yun; Wang, Junxi

2016-08-01

An all-optically tunable microwave photonic phase shifter is demonstrated based on an epitaxial aluminum nitride (AlN) microring with an intrinsic quality factor of 3.2×10⁶. The microring adopts a pedestal structure, which allows overcoupling with 700 nm gap size and facilitates the fabrication process. A phase shift for broadband signals from 4 to 25 GHz is demonstrated by employing the thermo-optic effect and the separate carrier tuning technique. A phase tuning range of 0°-332° is recorded with a 3 dB radio frequency (RF) power variation and 48 mW optical power consumption. In addition, AlN exhibits intrinsic second-order optical nonlinearity. Thus, our work presents a novel platform with a low propagation loss and the capability of electro-optic modulation for applications in integrated microwave photonics.

Increased plasma FGF21 level as an early biomarker for insulin resistance and metabolic disturbance in obese insulin-resistant rats.

PubMed

Tanajak, Pongpan; Pongkan, Wanpitak; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2018-05-01

Propose: To investigate the temporal relationship between plasma fibroblast growth factor 21 levels, insulin resistance, metabolic dysfunction and cardiac fibroblast growth factor 21 resistance in long-term high-fat diet-induced obese rats. In total, 36 male Wistar rats were fed with either a normal diet or high-fat diet for 12 weeks. Blood was collected from the tail tip, and plasma was used to determine metabolic profiles and fibroblast growth factor 21 levels. Rats were sacrificed at weeks 4, 8 and 12, and the hearts were rapidly removed for the determination of cardiac fibroblast growth factor 21 signalling pathways. Body weight and plasma fibroblast growth factor 21 levels were increased after 4 weeks of consumption of a high-fat diet. At weeks 8 and 12, high-fat diet rats had significantly increased body weight and plasma fibroblast growth factor 21 levels, together with increased plasma insulin, HOMA index, area under the curve of glucose, plasma total cholesterol, plasma low-density lipoprotein cholesterol, serum malondialdehyde and cardiac malondialdehyde levels. However, plasma high-density lipoprotein cholesterol levels and cardiac fibroblast growth factor 21 signalling proteins (p-FGFR1 Tyr 154 , p-ERK1/2 Thr 202 /Tyr 204 and p-Akt Ser 473 ) were decreased, compared with normal diet rats. These findings suggest that plasma fibroblast growth factor 21 levels could be an early predictive biomarker prior to the development of insulin resistance, metabolic disturbance and cardiac fibroblast growth factor 21 resistance.

Microbial cells can cooperate to resist high-level chronic ionizing radiation

PubMed Central

Gaidamakova, Elena K.; Tkavc, Rok; Grichenko, Olga; Klimenkova, Polina; Volpe, Robert P.; Daly, Michael J.

2017-01-01

Understanding chronic ionizing radiation (CIR) effects is of utmost importance to protecting human health and the environment. Diverse bacteria and fungi inhabiting extremely radioactive waste and disaster sites (e.g. Hanford, Chernobyl, Fukushima) represent new targets of CIR research. We show that many microorganisms can grow under intense gamma-CIR dose rates of 13–126 Gy/h, with fungi identified as a particularly CIR-resistant group of eukaryotes: among 145 phylogenetically diverse strains tested, 78 grew under 36 Gy/h. Importantly, we demonstrate that CIR resistance can depend on cell concentration and that certain resistant microbial cells protect their neighbors (not only conspecifics, but even radiosensitive species from a different phylum), from high-level CIR. We apply a mechanistically-motivated mathematical model of CIR effects, based on accumulation/removal kinetics of reactive oxygen species (ROS) and antioxidants, in bacteria (3 Escherichia coli strains and Deinococcus radiodurans) and in fungi (Candida parapsilosis, Kazachstania exigua, Pichia kudriavzevii, Rhodotorula lysinophila, Saccharomyces cerevisiae, and Trichosporon mucoides). We also show that correlations between responses to CIR and acute ionizing radiation (AIR) among studied microorganisms are weak. For example, in D. radiodurans, the best molecular correlate for CIR resistance is the antioxidant enzyme catalase, which is dispensable for AIR resistance; and numerous CIR-resistant fungi are not AIR-resistant. Our experimental findings and quantitative modeling thus demonstrate the importance of investigating CIR responses directly, rather than extrapolating from AIR. Protection of radiosensitive cell-types by radioresistant ones under high-level CIR is a potentially important new tool for bioremediation of radioactive sites and development of CIR-resistant microbiota as radioprotectors. PMID:29261697

Microbial cells can cooperate to resist high-level chronic ionizing radiation.

PubMed

Shuryak, Igor; Matrosova, Vera Y; Gaidamakova, Elena K; Tkavc, Rok; Grichenko, Olga; Klimenkova, Polina; Volpe, Robert P; Daly, Michael J

2017-01-01

Understanding chronic ionizing radiation (CIR) effects is of utmost importance to protecting human health and the environment. Diverse bacteria and fungi inhabiting extremely radioactive waste and disaster sites (e.g. Hanford, Chernobyl, Fukushima) represent new targets of CIR research. We show that many microorganisms can grow under intense gamma-CIR dose rates of 13-126 Gy/h, with fungi identified as a particularly CIR-resistant group of eukaryotes: among 145 phylogenetically diverse strains tested, 78 grew under 36 Gy/h. Importantly, we demonstrate that CIR resistance can depend on cell concentration and that certain resistant microbial cells protect their neighbors (not only conspecifics, but even radiosensitive species from a different phylum), from high-level CIR. We apply a mechanistically-motivated mathematical model of CIR effects, based on accumulation/removal kinetics of reactive oxygen species (ROS) and antioxidants, in bacteria (3 Escherichia coli strains and Deinococcus radiodurans) and in fungi (Candida parapsilosis, Kazachstania exigua, Pichia kudriavzevii, Rhodotorula lysinophila, Saccharomyces cerevisiae, and Trichosporon mucoides). We also show that correlations between responses to CIR and acute ionizing radiation (AIR) among studied microorganisms are weak. For example, in D. radiodurans, the best molecular correlate for CIR resistance is the antioxidant enzyme catalase, which is dispensable for AIR resistance; and numerous CIR-resistant fungi are not AIR-resistant. Our experimental findings and quantitative modeling thus demonstrate the importance of investigating CIR responses directly, rather than extrapolating from AIR. Protection of radiosensitive cell-types by radioresistant ones under high-level CIR is a potentially important new tool for bioremediation of radioactive sites and development of CIR-resistant microbiota as radioprotectors.

An explanation of resisted discoveries based on construal-level theory.

PubMed

Fang, Hui

2015-02-01

New discoveries and theories are crucial for the development of science, but they are often initially resisted by the scientific community. This paper analyses resistance to scientific discoveries that supplement previous research results or conclusions with new phenomena, such as long chains in macromolecules, Alfvén waves, parity nonconservation in weak interactions and quasicrystals. Construal-level theory is used to explain that the probability of new discoveries may be underestimated because of psychological distance. Thus, the insufficiently examined scope of an accepted theory may lead to overstating the suitable scope and underestimating the probability of its undiscovered counter-examples. Therefore, psychological activity can result in people instinctively resisting new discoveries. Direct evidence can help people judge the validity of a hypothesis with rational thinking. The effects of authorities and textbooks on the resistance to discoveries are also discussed. From the results of our analysis, suggestions are provided to reduce resistance to real discoveries, which will benefit the development of science.

Serum AMH levels and insulin resistance in women with PCOS.

PubMed

Sahmay, Sezai; Aydogan Mathyk, Begum; Sofiyeva, Nigar; Atakul, Nil; Azemi, Aslı; Erel, Tamer

2018-05-01

To compare the serum AMH levels between women with and without insulin resistance (IR) in polycystic ovary syndrome (PCOS). 293 women with PCOS according to the Rotterdam criteria were enrolled into our study. Insulin resistance was diagnosed according to the Homeostatic model assessment insulin resistant (HOMA-IR) formula and the cut-off point was set to more than 2.5. Women were grouped according to the presence of insulin resistance (IR) (HOMA-IR ≥ 2.5). Serum AMH and other hormones were compared between the IR (+) and IR (-) groups. Additionally, AMH percentiles were (<25, 25-75, >75) constructed; HOMA-IR and BMI values in women with/without IR were compared in different percentiles. Further, HOMA-IR, BMI and AMH values were measured across different PCOS phenotypes. The prevalence of IR was 45%. The prevalence of IR was 57% in women with BMI ≥ 25. Serum AMH levels were not significantly different among women with and without IR. Also, HOMA-IR values were not significant among different AMH percentiles. However, in each AMH percentile BMI were found to be higher in women with IR than in women without IR. The median HOMA-IR values were the highest in women with BMI ≥ 25 in both IR (+) and IR (-) groups. No significant difference was found among PCOS phenotypes in terms of HOMA-IR and BMI. Positive correlations were found between BMI, free testosterone and HOMA-IR. However, no correlation was found between AMH and HOMA-IR. The serum AMH levels between women with IR and without IR in PCOS were not significantly different. Also, we did not reveal a correlation between serum AMH levels and IR in women with PCOS. IR was not correlated with different PCOS phenotypes either. We found a positive correlation between BMI and IR. IR should be investigated in women with PCOS having a BMI ≥ 25, independent of their phenotype or AMH levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Antibiotic resistance shaping multi-level population biology of bacteria

PubMed Central

Baquero, Fernando; Tedim, Ana P.; Coque, Teresa M.

2013-01-01

Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent “population biologies.” Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of “clinical” antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi-level

Antibiotic resistance shaping multi-level population biology of bacteria.

PubMed

Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

2013-01-01

Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi-level

Contact resistance evolution of highly cycled, lightly loaded micro-contacts

NASA Astrophysics Data System (ADS)

Stilson, Christopher; Coutu, Ronald

2014-03-01

Reliable microelectromechanical systems (MEMS) switches are critical for developing high performance radio frequency circuits like phase shifters. Engineers have attempted to improve reliability and lifecycle performance using novel contact metals, unique mechanical designs and packaging. Various test fixtures including: MEMS devices, atomic force microscopes (AFM) and nanoindentors have been used to collect resistance and contact force data. AFM and nanoindentor test fixtures allow direct contact force measurements but are severely limited by low resonance sensors, and therefore low data collection rates. This paper reports the contact resistance evolution results and fabrication of thin film, sputtered and evaporated gold, micro-contacts dynamically tested up to 3kHz. The upper contact support structure consists of a gold surface micromachined, fix-fix beam designed with sufficient restoring force to overcome adhesion. The hemisphere-upper and planar-lower contacts are mated with a calibrated, external load resulting in approximately 100μN of contact force and are cycled in excess of 106 times or until failure. Contact resistance is measured, in-situ, using a cross-bar configuration and the entire apparatus is isolated from external vibration and housed in an enclosure to minimize contamination due to ambient environment. Additionally, contact cycling and data collection are automated using a computer and LabVIEW. Results include contact resistance measurements of 6 and 8 μm radius contact bumps and lifetime testing up to 323.6 million cycles.

Confirmation of resistance to herbicides and evaluation of resistance levels

USDA-ARS?s Scientific Manuscript database

As cases of resistance to herbicides escalate worldwide, there is increasing demand from growers to test for weed resistance and how to manage it. Scientists have developed resistance testing protocols for numerous herbicides and weed species. Growers need immediate answers and scientists are faced ...

Genotypic and phenotypic characterization of methicillin-resistant Staphylococcus aureus (MRSA) clones with high-level mupirocin resistance.

PubMed

González-Domínguez, María; Seral, Cristina; Potel, Carmen; Sáenz, Yolanda; Álvarez, Maximiliano; Torres, Carmen; Castillo, Francisco Javier

2016-06-01

A high proportion of methicillin-resistant Staphylococcus aureus isolates recovered in one year period showed high-level mupirocin-resistance (HLMUPR-MRSA) in our environment (27.2%). HLMUPR-MRSA isolates were mainly collected from skin and soft tissue samples, and diabetes was the main related comorbidity condition. These isolates were more frequently found in vascular surgery. HLMUPR-MRSA was more resistant to aminoglycosides than mupirocin-susceptible MRSA, linked to the presence of bifunctional and/or nucleotidyltransferase enzymes with/without macrolide resistance associated with the msr(A) gene. Most of HLMUPR-MRSA isolates belonged to ST125/t067. Nine IS257-ileS2 amplification patterns (p3 was the most frequent) were observed in HLMUPR-MRSA isolates, suggesting the presence of several mupirocin-resistance-carrying plasmids in our environment and promoting the emergence of mupirocin resistance. The presence of the same IS257-ileS2 amplification pattern p3 in 65% of HLMUPR-MRSA, all of them ST125/t067, suggests a clonal spread in our hospital and community environment which could explain the high prevalence of HLMUPR-MRSA during the study period. An outbreak situation or an increase in mupirocin consumption was not observed. Copyright © 2016 Elsevier Inc. All rights reserved.

Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli

PubMed Central

Rodríguez-Martínez, José Manuel; Costas, Coloma; Aznar, Javier; Pascual, Álvaro

2016-01-01

Escherichia coli isolates carrying chromosomally encoded low-level-quinolone-resistant (LLQR) determinants are frequently found in urinary tract infections (UTIs). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin (CIP) in E. coli. However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR E. coli strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic E. coli derivatives carrying the most prevalent chromosomal mutations (ΔmarR, gyrA-S83L, gyrA-D87N, and parC-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied became resistant to ciprofloxacin (according to CLSI guidelines) under physiological conditions whereas the control strain lacking LLQR mutations did not. Moreover, the survival of some LLQR E. coli variants increased up to 100-fold after challenge with a high concentration of ciprofloxacin under UTI conditions compared to the results seen with Mueller-Hinton broth. These selective conditions could explain the high prevalence of LLQR mutations in E. coli. Furthermore, our data strongly suggest that recommended methods for MIC determination produce poor estimations of CIP activity against LLQR E. coli in UTIs. PMID:27139482

High Levels of Transmitted HIV Drug Resistance in a Study in Papua New Guinea.

PubMed

Lavu, Evelyn; Kave, Ellan; Mosoro, Euodia; Markby, Jessica; Aleksic, Eman; Gare, Janet; Elsum, Imogen A; Nano, Gideon; Kaima, Petronia; Dala, Nick; Gurung, Anup; Bertagnolio, Silvia; Crowe, Suzanne M; Myatt, Mark; Hearps, Anna C; Jordan, Michael R

2017-01-01

Papua New Guinea is a Pacific Island nation of 7.3 million people with an estimated HIV prevalence of 0.8%. ART initiation and monitoring are guided by clinical staging and CD4 cell counts, when available. Little is known about levels of transmitted HIV drug resistance in recently infected individuals in Papua New Guinea. Surveillance of transmitted HIV drug resistance in a total of 123 individuals recently infected with HIV and aged less than 30 years was implemented in Port Moresby (n = 62) and Mount Hagen (n = 61) during the period May 2013-April 2014. HIV drug resistance testing was performed using dried blood spots. Transmitted HIV drug resistance was defined by the presence of one or more drug resistance mutations as defined by the World Health Organization surveillance drug resistance mutations list. The prevalence of non-nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 16.1% (95% CI 8.8%-27.4%) and 8.2% (95% CI 3.2%-18.2%) in Port Moresby and Mount Hagen, respectively. The prevalence of nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 3.2% (95% CI 0.2%-11.7%) and 3.3% (95% CI 0.2%-11.8%) in Port Moresby and Mount Hagen, respectively. No protease inhibitor transmitted HIV drug resistance was observed. The level of non-nucleoside reverse transcriptase inhibitor drug resistance in antiretroviral drug naïve individuals recently infected with HIV in Port Moresby is amongst the highest reported globally. This alarming level of transmitted HIV drug resistance in a young sexually active population threatens to limit the on-going effective use of NNRTIs as a component of first-line ART in Papua New Guinea. To support the choice of nationally recommended first-line antiretroviral therapy, representative surveillance of HIV drug resistance among antiretroviral therapy initiators in Papua New Guinea should be urgently implemented.

Rapid Induction of High-Level Carbapenem Resistance in Heteroresistant KPC-Producing Klebsiella pneumoniae

PubMed Central

Adams-Sapper, Sheila; Nolen, Shantell; Donzelli, Grace Fox; Lal, Mallika; Chen, Kunihiko; Justo da Silva, Livia Helena; Moreira, Beatriz M.

2015-01-01

Enterobacteriaceae strains producing the Klebsiella pneumoniae carbapenemase (KPC) have disseminated worldwide, causing an urgent threat to public health. KPC-producing strains often exhibit low-level carbapenem resistance, which may be missed by automated clinical detection systems. In this study, eight Klebsiella pneumoniae strains with heterogeneous resistance to imipenem were used to elucidate the factors leading from imipenem susceptibility to high-level resistance as defined by clinical laboratory testing standards. Time-kill analysis with an inoculum as low as 3 × 106 CFU/ml and concentrations of imipenem 8- and 16-fold higher than the MIC resulted in the initial killing of 99.9% of the population. However, full recovery of the population occurred by 20 h of incubation in the same drug concentrations. Population profiles showed that recovery was mediated by a heteroresistant subpopulation at a frequency of 2 × 10−7 to 3 × 10−6. Samples selected 2 h after exposure to imipenem were as susceptible as the unexposed parental strain and produced the major outer membrane porin OmpK36. However, between 4 to 8 h after exposure, OmpK36 became absent, and the imipenem MIC increased at least 32-fold. Individual colonies isolated from cultures after 20 h of exposure revealed both susceptible and resistant subpopulations. Once induced, however, the high-level imipenem resistance was maintained, and OmpK36 remained unexpressed even without continued carbapenem exposure. This study demonstrates the essential coordination between blaKPC and ompK36 expression mediating high-level imipenem resistance from a population of bacteria that initially exhibits a carbapenem-susceptibility phenotype. PMID:25801565

Dietary glycemic factors, insulin resistance, and adiponectin levels in acne vulgaris.

PubMed

Çerman, Aslı Aksu; Aktaş, Ezgi; Altunay, İlknur Kıvanç; Arıcı, Janset Erkul; Tulunay, Aysın; Ozturk, Feyza Yener

2016-07-01

There is increasing evidence to support the relationship between acne vulgaris and diet. The aim of this study was to investigate possible associations among dietary glycemic index, glycemic load, milk consumption, insulin resistance, and adiponectin levels in the pathogenesis of acne vulgaris. The dietary glycemic index, glycemic load, milk consumption, fasting glucose, insulin, insulin-like growth factor)-1, insulin-like growth factor binding protein-3, adiponectin, and homeostasis model assessment of insulin resistance values of 50 patients with acne vulgaris and 36 healthy control subjects were measured. Glycemic index and glycemic load levels were significantly higher (P = .022 and P = .001, respectively) and serum adiponectin levels were significantly lower (P = .015) in patients with acne than in the control subjects. There was an inverse correlation between serum adiponectin concentration and glycemic index (P = .049, r = -0.212). This study used a cross-sectional design and the study population was limited to young, nonobese adults. A high-glycemic-index/-load diet was positively associated with acne vulgaris. Adiponectin may be a pathogenetic cofactor contributing to the development of the disease. Further research on adiponectin levels in patients with acne in terms of development of insulin resistance might be important in this possible relationship. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Combination of all-stage and high-temperature adult-plant resistance QTL confers high-level, durable resistance to stripe rust in winter wheat cultivar Madsen.

PubMed

Liu, L; Wang, M N; Feng, J Y; See, D R; Chao, S M; Chen, X M

2018-05-24

Wheat cultivar Madsen has a new gene on the short arm of chromosome 1A and two QTL for all-stage resistance and three QTL for high-temperature adult-plant resistance that in combination confer high-level, durable resistance to stripe rust. Wheat cultivar Madsen has maintained a high-level resistance to stripe rust over 30 years. To map quantitative trait loci (QTL) underlying the high-level, durable resistance, 156 recombinant inbred lines (RILs) developed from cross Avocet S × Madsen were phenotyped with selected races of Puccinia striiformis f. sp. tritici in the greenhouse seedling tests, and in naturally infected fields during 2015-2017. The RILs were genotyped by SSR and SNP markers from genotyping by sequencing and the 90 K wheat SNP chip. Three QTL for all-stage resistance were mapped on chromosomes 1AS, 1BS and 2AS, and two QTL for high-temperature adult-plant (HTAP) resistance were mapped on 3BS and 6BS. The most effective QTL on 2AS, explaining 8.97-23.10% of the phenotypic variation in seedling tests and 8.60-71.23% in field tests, contained Yr17 for all-stage resistance and an additional gene for HTAP resistance. The 6BS QTL, detected in all field tests, was identified as Yr78. The 1AS QTL, conferring all-stage resistance, was identified as a new gene, which explained 20.45 and 30.23% of variation in resistance to races PSTv-37 and PSTv-40, respectively, and contributed significantly to field resistance at Pullman in 2015-2017, but was not detected at Mount Vernon. The interactions among QTL were mostly additive, and RILs with all five QTL had the highest level of resistance in the field, similar to Madsen. Genotyping 148 US Pacific Northwest wheat cultivars with markers for the 1AS, 2AS and 6BS QTL validated the genes and markers, and indicated their usefulness for marker-assisted selection.

Temperature influences the level of glyphosate resistance in barnyardgrass (Echinochloa colona).

PubMed

Nguyen, Thai Hoan; Malone, Jenna M; Boutsalis, Peter; Shirley, Neil; Preston, Christopher

2016-05-01

Echinochloa colona is an important summer-growing weed species in cropping regions of northern Australia that has evolved resistance to glyphosate owing to intensive use of this herbicide in summer fallow. Pot trials conducted at 20 and 30 °C on six E. colona populations showed a significant increase in the level of glyphosate resistance in resistant populations at 30 °C compared with 20 °C. However, there was no influence of growth temperature on glyphosate susceptibility of the sensitive population. Sequencing of the target-site gene (EPSPS) of the six populations identified a mutation at position 106 leading to a change from proline to serine in the most resistant population A533.1 only. EPSPS gene amplification was not detected in any of the resistant populations examined. Examining (14) C-glyphosate uptake on two resistant and one susceptible population showed a twofold increase at 20 °C; however, few differences in glyphosate translocation occurred from the treated leaf to other plant parts between populations or temperatures. There is reduced efficacy of glyphosate at high temperatures on resistant E. colona populations, making these populations harder to control in summer. © 2015 Society of Chemical Industry.

Temperature dependence of alpha-induced scintillation in the 1,1,4,4-tetraphenyl-1,3-butadiene wavelength shifter

NASA Astrophysics Data System (ADS)

Veloce, L. M.; Kuźniak, M.; Di Stefano, P. C. F.; Noble, A. J.; Boulay, M. G.; Nadeau, P.; Pollmann, T.; Clark, M.; Piquemal, M.; Schreiner, K.

2016-06-01

Liquid noble based particle detectors often use the organic wavelength shifter 1,1,4,4-tetraphenyl-1,3-butadiene (TPB) which shifts UV scintillation light to the visible regime, facilitating its detection, but which also can scintillate on its own. Dark matter searches based on this type of detector commonly rely on pulse-shape discrimination (PSD) for background mitigation. Alpha-induced scintillation therefore represents a possible background source in dark matter searches. The timing characteristics of this scintillation determine whether this background can be mitigated through PSD. We have therefore characterized the pulse shape and light yield of alpha induced TPB scintillation at temperatures ranging from 300 K down to 4 K, with special attention given to liquid noble gas temperatures. We find that the pulse shapes and light yield depend strongly on temperature. In addition, the significant contribution of long time constants above ~50 K provides an avenue for discrimination between alpha decay events in TPB and nuclear-recoil events in noble liquid detectors.

Improvement of multi-level resistive switching characteristics in solution-processed AlO x -based non-volatile resistive memory using microwave irradiation

NASA Astrophysics Data System (ADS)

Kim, Seung-Tae; Cho, Won-Ju

2018-01-01

We fabricated a resistive random access memory (ReRAM) device on a Ti/AlO x /Pt structure with solution-processed AlO x switching layer using microwave irradiation (MWI), and demonstrated multi-level cell (MLC) operation. To investigate the effect of MWI power on the MLC characteristics, post-deposition annealing was performed at 600-3000 W after AlO x switching layer deposition, and the MLC operation was compared with as-deposited (as-dep) and conventional thermally annealing (CTA) treated devices. All solution-processed AlO x -based ReRAM devices exhibited bipolar resistive switching (BRS) behavior. We found that these devices have four-resistance states (2 bits) of MLC operation according to the modulation of the high-resistance state (HRSs) through reset voltage control. Particularly, compared to the as-dep and CTA ReRAM devices, the MWI-treated ReRAM devices showed a significant increase in the memory window and stable endurance for multi-level operation. Moreover, as the MWI power increased, excellent MLC characteristics were exhibited because the resistance ratio between each resistance state was increased. In addition, it exhibited reliable retention characteristics without deterioration at 25 °C and 85 °C for 10 000 s. Finally, the relationship between the chemical characteristics of the solution-processed AlO x switching layer and BRS-based multi-level operation according to the annealing method and MWI power was investigated using x-ray photoelectron spectroscopy.

Paclitaxel-resistant HeLa cells have up-regulated levels of reactive oxygen species and increased expression of taxol resistance gene 1.

PubMed

Bi, Wenxiang; Wang, Yuxia; Sun, Gaoying; Zhang, Xiaojin; Wei, Yongqing; Li, Lu; Wang, Xiaoyuan

2014-07-01

This study is to establish a paclitaxel (PTX)-resistant human cervical carcinoma HeLa cell line (HeLa/PTX) and to investigate its redox characteristics and the expression of taxol resistance gene 1 (Txr1). HeLa cells were treated with PTX and effects of PTX on cell proliferation were detected through cell counting and the MTT assay. Levels of cellular reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG) as well as the ratio of GSH to GSSG were measured by the 2,7-difluorescein diacetate (DCFH-DA) method and the 5,5'dithiobis(2-nitrobenzoic acid) (DTNB) method. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined by the nitrite formation method, the molybdate colorimetric method, and the DTNB colorimetric method, respectively. The level of Txr1 mRNA was determined by real-time PCR. Compared with the regular HeLa cells, HeLa/PTX cells were larger in size and had more cytoplasmic granules. The population doubling time for HeLa/PTX cells was 1.32 times of that of HeLa cells (P<0.01). HeLa/PTX cells showed stronger resistance to PTX than HeLa cells with a resistance index of 122.69. HeLa/PTX cells had higher levels of ROS (P<0.01) and Txr1 mRNA (P<0.01), lower level of GSH (P < 0.05), and lower activities of SOD (P<0.01) and GPx (P < 0.05) than HeLa cells. HeLa/PTX cells, with higher levels of ROS and Txr1 mRNA expression, are more resistant to PTX than HeLa cells.

Effects of Mn2+ Levels on the Resistance Properties of Bacillus cereus Spores

DTIC Science & Technology

2013-01-01

In contrast, Bacillus subtilis spores with over a 200-fold range of protoplast Mn levels exhibited no significant differences in resistance to... Bacillus subtilis . J. Bacteriol. 189:8458-8466. Coleman WH, Zhang P, Li YQ, Setlow P (2010). Mechanism of killing of spores of Bacillus cereus and...Gaidamakova EK, Matrosova VY, Daly MJ, Setlow P (2011). Effects of levels of Mn and Fe on Bacillus subtilis spore resistance, and effects of Mn 2

Ethnic differences in the ability of triglyceride levels to identify insulin resistance.

PubMed

Sumner, Anne E; Cowie, Catherine C

2008-02-01

The Metabolic Syndrome is used to predict the onset of coronary artery disease and Type 2 diabetes. As the predictive value of the Metabolic Syndrome has been challenged, alternative syndromes have been developed. All of these syndromes were developed in populations that were predominantly non-Hispanic white (NHW). They include the Enlarged Waist Elevated Triglyceride Syndrome, the Overweight-Lipid Syndrome and the Hypertriglyceridemic Waist Syndrome. The first applies to postmenopausal women, the second to overweight individuals (BMI> or =25 kg/m(2)), and the third to men. Each syndrome uses hypertriglyceridemia as a criterion. However, the definition of hypertriglyceridemia varies by syndrome i.e. TG> or =128 mg/dL for the Enlarged Waist Elevated Triglyceride Syndrome, TG> or =130 mg/dL for the Overweight-Lipid Syndrome, > or =150 mg/dL for the Metabolic Syndrome, and TG> or =176 mg/dL for the Hypertriglyceridemic Waist Syndrome. Insulin resistance and hypertriglyceridemia are highly correlated. But as insulin resistant non-Hispanic blacks (NHB) often have triglyceride (TG) levels below the thresholds set by these syndromes, the ability of either TG or these syndromes to identify high risk NHB is unknown. Using the National Health and Nutrition Examination Survey (NHANES) 1999-2002, our goals were to determine by ethnicity: (1) the prevalence of each of these syndromes; (2) the ability of fasting TG concentrations to identify insulin resistance at cut-off levels established by these syndromes, specifically 130, 150 and 176 mg/dL. Participants were 2804 adults from NHANES 1999-2002. The cohort was divided into tertiles of homeostasis model assessment. Insulin resistance was defined as the upper tertile (> or =2.73). The prevalence of each syndrome was lower in NHB than NHW or Mexican Americans (MA) (all P<0.05). Mean TG levels in NHB, non-Hispanic Whites (NHW) and Mexican Americans (MA) were: 99, 140 and 144mg/dL, respectively. The mean percents of insulin-resistant

Evaluation of levels of antibiotic resistance in groundwater-derived E. coli isolates in the Midwest of Ireland and elucidation of potential predictors of resistance

NASA Astrophysics Data System (ADS)

O'Dwyer, Jean; Hynds, Paul; Pot, Matthieu; Adley, Catherine C.; Ryan, Michael P.

2017-06-01

Antibiotic-resistant (pathogenic and non-pathogenic) organisms and genes are now acknowledged as significant emerging aquatic contaminants with potentially adverse human and ecological health impacts, and thus require monitoring. This study is the first to investigate levels of resistance among Irish groundwater (private wells) samples; Escherichia coli isolates were examined against a panel of commonly prescribed human and veterinary therapeutic antibiotics, followed by determination of the causative factors of resistance. Overall, 42 confirmed E. coli isolates were recovered from a groundwater-sampling cohort. Resistance to the human panel of antibiotics was moderate; nine (21.4%) E. coli isolates demonstrated resistance to one or more human antibiotics. Conversely, extremely high levels of resistance to veterinary antibiotics were found, with all isolates presenting resistance to one or more veterinary antibiotics. Particularly high levels of resistance (93%) were found with respect to the aminoglycoside class of antibiotics. Results of statistical analysis indicate a significant association between the presence of human (multiple) antibiotic resistance ( p = 0.002-0.011) and both septic tank density and the presence of vulnerable sub-populations (<5 years). For the veterinary antibiotics, results point to a significant relationship ( p = <0.001) between livestock (cattle) density and the prevalence of multiple antibiotic resistant E. coli. Groundwater continues to be an important resource in Ireland, particularly in rural areas; thus, results of this preliminary study offer a valuable insight into the prevalence of antibiotic resistance in the hydrogeological environment and establish a need for further research with a larger geological diversity.

Investigation of glyphosate resistance levels and target-site based resistance (TSR) mechanisms in Conyza canadensis (L.) from apple orchards around areas of Bohai seas and Loess Plateau in China.

PubMed

Mei, Yu; Xu, Yufang; Wang, Shipeng; Qiu, Lihong; Zheng, Mingqi

2018-04-01

The resistance levels to glyphosate and target-site based resistance mechanisms in susceptible (S) and resistant (R) Conyza canadensis (L.) populations, which were collected from apple orchards around areas of Bohai seas and Loess Plateau in China, were investigated. Among forty C. canadensis populations, eighteen populations (45%) were still susceptible; fourteen populations (35%) evolved low resistance levels resistance to glyphosate with resistance index (RI) of 2.02 to 3.90. In contrast, eight populations (20%) evolved medium resistance levels with RI of 4.35 to 8.38. The shikimic acid concentrations in R populations were highly negative relative with the glyphosate resistance levels in C. canadensis, the Pearson correlation coefficient was -0.82 treated by glyphosate at 1.8mg/L. Three 5-enoylpyruvylshikimate 3'-phosphate synthase genes (EPSPS1, EPSPS2 and EPSPS3) were cloned in all S and glyphosate-resistant C. canadensis populations. No amino acid substitution was identified at site of 102 and 106 in three EPSPS genes, which were reported to confer glyphosate resistance in other weed species. The relative expression level of EPSPS mRNA in R populations (SD07, LN05, SHX06 and SD09) was 4.5 to 13.2 times higher than in S biotype. The Pearson correlation coefficient between EPSPS expression levels and RI was 0.79, which indicated the over expression of EPSPS mRNA may cause these R populations evolve higher resistance level to glyphosate. Copyright © 2018 Elsevier Inc. All rights reserved.

Analysis and design of tunable wideband microwave photonics phase shifter based on Fabry-Perot cavity and Bragg mirrors in silicon-on-insulator waveguide.

PubMed

Qu, Pengfei; Zhou, Jingran; Chen, Weiyou; Li, Fumin; Li, Haibin; Liu, Caixia; Ruan, Shengping; Dong, Wei

2010-04-20

We designed a microwave (MW) photonics phase shifter, consisting of a Fabry-Perot filter, a phase modulation region (PMR), and distributed Bragg reflectors, in a silicon-on-insulator rib waveguide. The thermo-optics effect was employed to tune the PMR. It was theoretically demonstrated that the linear MW phase shift of 0-2pi could be achieved by a refractive index variation of 0-9.68x10(-3) in an ultrawideband (about 38?GHz-1.9?THz), and the corresponding tuning resolution was about 6.92 degrees / degrees C. The device had a very compact size. It could be easily integrated in silicon optoelectronic chips and expected to be widely used in the high-frequency MW photonics field.

Multi-level, multi-scale resource selection functions and resistance surfaces for conservation planning: Pumas as a case study

PubMed Central

Vickers, T. Winston; Ernest, Holly B.; Boyce, Walter M.

2017-01-01

The importance of examining multiple hierarchical levels when modeling resource use for wildlife has been acknowledged for decades. Multi-level resource selection functions have recently been promoted as a method to synthesize resource use across nested organizational levels into a single predictive surface. Analyzing multiple scales of selection within each hierarchical level further strengthens multi-level resource selection functions. We extend this multi-level, multi-scale framework to modeling resistance for wildlife by combining multi-scale resistance surfaces from two data types, genetic and movement. Resistance estimation has typically been conducted with one of these data types, or compared between the two. However, we contend it is not an either/or issue and that resistance may be better-modeled using a combination of resistance surfaces that represent processes at different hierarchical levels. Resistance surfaces estimated from genetic data characterize temporally broad-scale dispersal and successful breeding over generations, whereas resistance surfaces estimated from movement data represent fine-scale travel and contextualized movement decisions. We used telemetry and genetic data from a long-term study on pumas (Puma concolor) in a highly developed landscape in southern California to develop a multi-level, multi-scale resource selection function and a multi-level, multi-scale resistance surface. We used these multi-level, multi-scale surfaces to identify resource use patches and resistant kernel corridors. Across levels, we found puma avoided urban, agricultural areas, and roads and preferred riparian areas and more rugged terrain. For other landscape features, selection differed among levels, as did the scales of selection for each feature. With these results, we developed a conservation plan for one of the most isolated puma populations in the U.S. Our approach captured a wide spectrum of ecological relationships for a population, resulted in

Multi-level, multi-scale resource selection functions and resistance surfaces for conservation planning: Pumas as a case study.

PubMed

Zeller, Katherine A; Vickers, T Winston; Ernest, Holly B; Boyce, Walter M

2017-01-01

The importance of examining multiple hierarchical levels when modeling resource use for wildlife has been acknowledged for decades. Multi-level resource selection functions have recently been promoted as a method to synthesize resource use across nested organizational levels into a single predictive surface. Analyzing multiple scales of selection within each hierarchical level further strengthens multi-level resource selection functions. We extend this multi-level, multi-scale framework to modeling resistance for wildlife by combining multi-scale resistance surfaces from two data types, genetic and movement. Resistance estimation has typically been conducted with one of these data types, or compared between the two. However, we contend it is not an either/or issue and that resistance may be better-modeled using a combination of resistance surfaces that represent processes at different hierarchical levels. Resistance surfaces estimated from genetic data characterize temporally broad-scale dispersal and successful breeding over generations, whereas resistance surfaces estimated from movement data represent fine-scale travel and contextualized movement decisions. We used telemetry and genetic data from a long-term study on pumas (Puma concolor) in a highly developed landscape in southern California to develop a multi-level, multi-scale resource selection function and a multi-level, multi-scale resistance surface. We used these multi-level, multi-scale surfaces to identify resource use patches and resistant kernel corridors. Across levels, we found puma avoided urban, agricultural areas, and roads and preferred riparian areas and more rugged terrain. For other landscape features, selection differed among levels, as did the scales of selection for each feature. With these results, we developed a conservation plan for one of the most isolated puma populations in the U.S. Our approach captured a wide spectrum of ecological relationships for a population, resulted in

Carotid baroreceptor influence on forearm vascular resistance during low level lower body negative pressure

NASA Technical Reports Server (NTRS)

Thompson, Cynthia A.; Ludwig, David A.; Convertino, Victor A.

1991-01-01

The degree of forearm vasoconstriction induced by low levels of lower body negative pressure (LBNP) provides a measure of the responsiveness of the cardiopulmonary baroreflex. The validity of this measurement is based on the assumption that this vasoconstriction response is not influenced by unloading of carotid baroreceptors. To test the hypothesis that arterial baroreceptor unloading does not alter the degree of forearm vascular resistance during low levels of LBNP, 12 subjects were exposed to -15 and -20 mm Hg LBNP with and without additional artificial (+ 10 mm Hg neck pressure) unloading of the carotid baroreceptors. There was no measurable influence of carotid unloading on forearm vascular resistance at either level of LBNP. It is concluded that forearm vascular resistance measured during cardiopulmonary baroreceptor unloading is unaffected by carotid baroreceptor unloading within the magnitude encountered during low levels of LBNP.

Serum levels of uncoupling proteins in patients with differential insulin resistance

PubMed Central

Pan, Heng-Chih; Lee, Chin-Chan; Chou, Kuei-Mei; Lu, Shang-Chieh; Sun, Chiao-Yin

2017-01-01

Abstract The uncoupling protein (UCP) belongs to a family of energy-dissipating proteins in mitochondria. Increasing evidences have indicated that UCPs have immense impact on glucose homeostasis and are key proteins in metabolic syndrome. For applying the findings to clinical practice, we designed a study to explore the association between serum UCPs 1–3 and insulin resistance. This investigation prospectively recorded demographical parameter and collected blood samples of 1071 participants from 4 districts in Northeastern Taiwan during the period from August 2013 to July 2014. Propensity score matching by age and sex in patients with top and bottom third homeostasis model assessment of insulin resistance (HOMA-IR) levels was performed, and 326 subjects were enrolled for further studies. The mean age of the patients was 59.4 years and the majority of them (65.5%) were females. The prevalence of metabolic syndrome was 35.5%. Our results demonstrated that serum UCPs 1–3 were significantly associated with differences in HOMA-IR levels. Multiple logistic regression analysis indicated that low UCP 1 and features of metabolic syndrome, namely hypertension, diabetes, body mass index, and high-density lipoprotein, were independent determinants for high HOMA-IR levels. We thus determined that low serum UCP 1 is a predictor for high resistance to insulin. PMID:28984759

Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

PubMed Central

Kawanaka, Miwa; Nishino, Ken; Oka, Takahito; Urata, Noriyo; Nakamura, Jun; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Chiba, Yasutaka; Yamada, Gotaro

2015-01-01

Objective Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. PMID:26082668

Adaptation or Resistance: a classification of responses to sea-level rise

NASA Astrophysics Data System (ADS)

Cooper, J. A.

2016-02-01

Societal responses to sea level rise and associated coastal change are apparently diverse in nature and motivation. Most are commonly referred to as 'adaptation'. Based on a review of current practice, however, it is argued that many of these responses do not involve adaptation, but are rather resisting change. There are several instances where formerly adaptive initiatives involving human adaptability are being replaced by initiatives that resist change. A classification is presented that recognises a continuum of responses ranging from adaptation to resistance, depending upon the willingness to change human activities to accommodate environmental change. In many cases climate change adaptation resources are being used for projects that are purely resistant and which foreclose future adaptation options. It is argued that a more concise definition of adaptation is needed if coastal management is to move beyond the current position of holding the shoreline, other tah n in a few showcase examples.

Identification of katG Mutations Associated with High-Level Isoniazid Resistance in Mycobacterium tuberculosis▿ †

PubMed Central

Ando, Hiroki; Kondo, Yuji; Suetake, Toshinori; Toyota, Emiko; Kato, Seiya; Mori, Toru; Kirikae, Teruo

2010-01-01

Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates. PMID:20211896

Relationship of visfatin level to pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index in overweight women who performed hydraulic resistance exercise.

PubMed

Ha, Chang Ho; Swearingin, Brenda; Jeon, Yong Kyun

2015-09-01

[Purpose] This study aimed to examine the correlation of visfatin level to pancreatic endocrine hormone level, homeostasis model assessment of insulin resistance (HOMA-IR) index, and HOMA β-cell index in hydraulic resistance exercise. Furthermore, it investigated the relationship between visfatin level and other variables affected by exercise in overweight women. [Subjects and Methods] The exercise group trained for 12 weeks, 70 minutes/day, 5 days/week. Visfatin level, pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index were measured before and after the intervention. Based on the blood insulin and glucose concentrations, HOMA-IR index, the indicator of insulin resistance, and HOMA β-cell index, the indicator of insulin secretion level, were assessed. [Results] Interaction effects on visfatin level, insulin level, HOMA-IR index, and HOMA β-cell index were observed. Interaction effects on glucagon and glucose levels were not observed between the intervention groups. The correlations of visfatin level to insulin, glucagon, and glucose levels, and HOMA-IR and HOMA β-cell indexes were not significant for any of the subjects. [Conclusion] Therefore, the 12-week resistance exercise affected body composition, visfatin level, insulin level, HOMA-IR index, and HOMA β-cell index. Finally, visfatin was not related to insulin, glucagon, and glucose levels, and HOMA-IR and HOMA β-cell indexes.

Sampling and Pooling Methods for Capturing Herd Level Antibiotic Resistance in Swine Feces using qPCR and CFU Approaches

PubMed Central

Mellerup, Anders; Ståhl, Marie

2015-01-01

The aim of this article was to define the sampling level and method combination that captures antibiotic resistance at pig herd level utilizing qPCR antibiotic resistance gene quantification and culture-based quantification of antibiotic resistant coliform indicator bacteria. Fourteen qPCR assays for commonly detected antibiotic resistance genes were developed, and used to quantify antibiotic resistance genes in total DNA from swine fecal samples that were obtained using different sampling and pooling methods. In parallel, the number of antibiotic resistant coliform indicator bacteria was determined in the same swine fecal samples. The results showed that the qPCR assays were capable of detecting differences in antibiotic resistance levels in individual animals that the coliform bacteria colony forming units (CFU) could not. Also, the qPCR assays more accurately quantified antibiotic resistance genes when comparing individual sampling and pooling methods. qPCR on pooled samples was found to be a good representative for the general resistance level in a pig herd compared to the coliform CFU counts. It had significantly reduced relative standard deviations compared to coliform CFU counts in the same samples, and therefore differences in antibiotic resistance levels between samples were more readily detected. To our knowledge, this is the first study to describe sampling and pooling methods for qPCR quantification of antibiotic resistance genes in total DNA extracted from swine feces. PMID:26114765

OCCURRENCE OF HIGH-LEVEL AMINOGLYCOSIDE RESISTANCE IN ENVIRONMENTAL ISOLATES OF ENTEROCOCCI

EPA Science Inventory

High-level resistance fo aminoglycosides was observed in environmental isolates of enterococci. Various aquatic habitats, including agricultural runoff, creeks, rivers, wastewater, and wells, were analyzed. Strains of Enterococcus faecalis, e.faecium, E. gallinarum, and other Ent...

Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

PubMed

Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T; Allin, Kristine H; Witte, Daniel R; Jørgensen, Marit E; Grarup, Niels; Pedersen, Oluf; Kilpeläinen, Tuomas O; Hansen, Torben

2017-05-01

Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10 -7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10 -6 , β 0.96 [95% CI 0.45, 1.47] p = 3 × 10 -4 , and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION

Use of Lot Quality Assurance Sampling to Ascertain Levels of Drug Resistant Tuberculosis in Western Kenya

PubMed Central

Cohen, Ted; Zignol, Matteo; Nyakan, Edwin; Hedt-Gauthier, Bethany L.; Gardner, Adrian; Kamle, Lydia; Injera, Wilfred; Carter, E. Jane

2016-01-01

Objective To classify the prevalence of multi-drug resistant tuberculosis (MDR-TB) in two different geographic settings in western Kenya using the Lot Quality Assurance Sampling (LQAS) methodology. Design The prevalence of drug resistance was classified among treatment-naïve smear positive TB patients in two settings, one rural and one urban. These regions were classified as having high or low prevalence of MDR-TB according to a static, two-way LQAS sampling plan selected to classify high resistance regions at greater than 5% resistance and low resistance regions at less than 1% resistance. Results This study classified both the urban and rural settings as having low levels of TB drug resistance. Out of the 105 patients screened in each setting, two patients were diagnosed with MDR-TB in the urban setting and one patient was diagnosed with MDR-TB in the rural setting. An additional 27 patients were diagnosed with a variety of mono- and poly- resistant strains. Conclusion Further drug resistance surveillance using LQAS may help identify the levels and geographical distribution of drug resistance in Kenya and may have applications in other countries in the African Region facing similar resource constraints. PMID:27167381

Use of Lot Quality Assurance Sampling to Ascertain Levels of Drug Resistant Tuberculosis in Western Kenya.

PubMed

Jezmir, Julia; Cohen, Ted; Zignol, Matteo; Nyakan, Edwin; Hedt-Gauthier, Bethany L; Gardner, Adrian; Kamle, Lydia; Injera, Wilfred; Carter, E Jane

2016-01-01

To classify the prevalence of multi-drug resistant tuberculosis (MDR-TB) in two different geographic settings in western Kenya using the Lot Quality Assurance Sampling (LQAS) methodology. The prevalence of drug resistance was classified among treatment-naïve smear positive TB patients in two settings, one rural and one urban. These regions were classified as having high or low prevalence of MDR-TB according to a static, two-way LQAS sampling plan selected to classify high resistance regions at greater than 5% resistance and low resistance regions at less than 1% resistance. This study classified both the urban and rural settings as having low levels of TB drug resistance. Out of the 105 patients screened in each setting, two patients were diagnosed with MDR-TB in the urban setting and one patient was diagnosed with MDR-TB in the rural setting. An additional 27 patients were diagnosed with a variety of mono- and poly- resistant strains. Further drug resistance surveillance using LQAS may help identify the levels and geographical distribution of drug resistance in Kenya and may have applications in other countries in the African Region facing similar resource constraints.

High-level penicillin resistance and penicillin-gentamicin synergy in Enterococcus faecium.

PubMed Central

Torres, C; Tenorio, C; Lantero, M; Gastañares, M J; Baquero, F

1993-01-01

Thirty-seven Enterococcus faecium strains with different levels of penicillin susceptibility were studied in time-kill experiments with a fixed concentration (5 micrograms/ml) of gentamicin combined with different penicillin concentrations (6 to 600 micrograms/ml). Synergy was defined as a relative decrease in counts of greater than 2 log10 CFU per milliliter after 24 h of incubation when the combination of the antibiotics was compared with its most active component alone. The minimal synergistic penicillin concentrations found were 6 micrograms/ml for 16 of 16 strains for which penicillin MICs were < or = 25 micrograms/ml, 20 to 100 micrograms/ml for 14 of 17 strains for which penicillin MICs were 50 to 200 micrograms/ml, and 200 to 500 micrograms/ml for 4 of 4 strains for which MICs penicillin were > 200 micrograms/ml. Penicillin-gentamicin synergy was observed even in high-level penicillin-resistant E. faecium strains at penicillin concentrations close to one-half the penicillin MIC. The possibility of treating infections caused by high-level penicillin-resistant E. faecium strains with penicillin-gentamicin combinations in particular cases may depend on the penicillin levels attainable in vivo. PMID:8285628

Larval development assays reveal the presence of sub-populations showing high- and low-level resistance in a monepantel (Zolvix®)-resistant isolate of Haemonchus contortus.

PubMed

Raza, Ali; Lamb, Jane; Chambers, Michael; Hunt, Peter W; Kotze, Andrew C

2016-04-15

Resistance to the amino-acetonitrile derivative monepantel has been reported in several species of gastrointestinal nematodes over recent years. We were interested in the use of in vitro assays with free-living worm life-stages to detect resistance to this drug. We therefore used larval development and larval migration assays to examine dose response relationships for the drug against two susceptible and one resistant isolate of Haemonchus contortus. The resistant isolate was established by laboratory propagation of the survivors of a field treatment with Zolvix(®) that had originally resulted in a drug efficacy of over 99%. Drug efficacy against this field-derived laboratory-propagated resistant isolate in vivo was approximately 15%. The larval development assay proved able to discriminate between the susceptible and resistant isolates, with larvae of the resistant isolate showing an ability to develop at higher drug concentrations than the two susceptible isolates. The resistant isolate showed the presence of two distinct subpopulations, separated by a plateau in the dose-response curve. Sub-population 1 (approximately 40% of the total population) showed a low level of resistance with an IC50 increased approximately 7-fold compared to the baseline susceptible isolate, while sub-population 2 (the remaining 60% of the total population) showed an IC50 increased over 1000-fold compared to the baseline susceptible isolate. This level of resistance is unusually high for any gastrointestinal nematode species in drug dose-response in vitro assays. In contrast, the migration assay could not discriminate between the three isolates, with migration not reduced to zero at any of the drug concentrations tested. This study demonstrates that a larval development assay is able to detect resistance to monepantel in H. contortus, and that resistance can exist in two distinct forms. This suggests that at least two separate monepantel resistance mechanisms are acting within the worm

MMP-7, sFas and FasL serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer.

PubMed

Szarvas, Tibor; Sevcenco, Sabina; Módos, Orsolya; Keresztes, Dávid; Nyirády, Péter; Csizmarik, Anita; Ristl, Robin; Puhr, Martin; Hoffmann, Michèle J; Niedworok, Christian; Hadaschik, Boris; Maj-Hes, Agnieszka; Shariat, Shahrokh F; Kramer, Gero

2018-05-26

To assess the predictive value of pre-chemotherapy MMP-7, sFas, FasL serum levels as well as their changes during therapy. Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 CRPC patients; 21 docetaxel-resistant who received one single series and 75 docetaxel-sensitive who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. Higher pretreatment serum MMP-7, sFas and PSA levels were significantly associated with both docetaxel-resistance (p=0.007, p=0.001, p<0.001, respectively) and shorter cancer-specific survival (p<0.001, p=0.041, p<0.001, respectively). High MMP-7 remained an independent predictor of both docetaxel resistance (HR: 2.298, 95% CI: 1.354-3.899, p=0.002) and poor cancer-specific survival (HR=2.11, 95%Cl 1.36-3.30, p=0.001) in multivariable analyses. Higher increase of MMP-7 levels in the 2 nd treatment holiday and higher increase of PSA levels in the 1 st and 2 nd holidays were predictive of survival. Pretreatment serum MMP-7 levels may help to select CRPC patients who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 alone or in combination with PSA could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

EPSPS Gene Copy Number and Whole-Plant Glyphosate Resistance Level in Kochia scoparia

PubMed Central

Gaines, Todd A.; Barker, Abigail L.; Patterson, Eric L.; Westra, Philip; Westra, Eric P.; Wilson, Robert G.; Jha, Prashant; Kumar, Vipan

2016-01-01

Glyphosate-resistant (GR) Kochia scoparia has evolved in dryland chemical fallow systems throughout North America and the mechanism of resistance involves 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene duplication. Agricultural fields in four states were surveyed for K. scoparia in 2013 and tested for glyphosate-resistance level and EPSPS gene copy number. Glyphosate resistance was confirmed in K. scoparia populations collected from sugarbeet fields in Colorado, Wyoming, and Nebraska, and Montana. Glyphosate resistance was also confirmed in K. scoparia accessions collected from wheat-fallow fields in Montana. All GR samples had increased EPSPS gene copy number, with median population values up to 11 from sugarbeet fields and up to 13 in Montana wheat-fallow fields. The results indicate that glyphosate susceptibility can be accurately diagnosed using EPSPS gene copy number. PMID:27992501

EPSPS Gene Copy Number and Whole-Plant Glyphosate Resistance Level in Kochia scoparia.

PubMed

Gaines, Todd A; Barker, Abigail L; Patterson, Eric L; Westra, Philip; Westra, Eric P; Wilson, Robert G; Jha, Prashant; Kumar, Vipan; Kniss, Andrew R

2016-01-01

Glyphosate-resistant (GR) Kochia scoparia has evolved in dryland chemical fallow systems throughout North America and the mechanism of resistance involves 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene duplication. Agricultural fields in four states were surveyed for K. scoparia in 2013 and tested for glyphosate-resistance level and EPSPS gene copy number. Glyphosate resistance was confirmed in K. scoparia populations collected from sugarbeet fields in Colorado, Wyoming, and Nebraska, and Montana. Glyphosate resistance was also confirmed in K. scoparia accessions collected from wheat-fallow fields in Montana. All GR samples had increased EPSPS gene copy number, with median population values up to 11 from sugarbeet fields and up to 13 in Montana wheat-fallow fields. The results indicate that glyphosate susceptibility can be accurately diagnosed using EPSPS gene copy number.

Dissemination of high-level mupirocin-resistant CC22-MRSA-IV in Saxony

PubMed Central

Monecke, Stefan; Ruppelt-Lorz, Antje; Müller, Elke; Reissig, Annett; Thürmer, Alexander; Shore, Anna C.; Coleman, David C.; Ehricht, Ralf; Jatzwauk, Lutz

2017-01-01

Mupirocin is used for eradicating methicillin-resistant S. aureus (MRSA) in nasal colonization. A plasmid-borne gene, mupA, is associated with high-level mupirocin resistance. Despite the fact that, among all MRSA from a tertiary care center in the German state of Saxony, the prevalence of mupA, encoding high-level mupirocin resistance, was approximately 1% over a 15-year period from 2000–2015, a sharp increase to nearly 20% was observed in 2016/2017. DNA microarray profiling revealed that this was due to the dissemination of a variant of CC22-MRSA-IV (“Barnim Epidemic Strain” or “UK-EMRSA-15”), which, in addition to mecA, harbors mupA, aacA-aphD, qacA, and – in most isolates – erm(C). In order to prevent therapy failures and a further spread of this strain, the use of mupirocin should be more stringently controlled as well as guided by susceptibility testing. In addition, MRSA decolonization regimens that rely on other substances, such as betaisodona, polyhexanide or octenidine, should be considered. PMID:29184755

Serum betatrophin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome.

PubMed

Qu, Qinglan; Zhao, Dongmei; Zhang, Fengrong; Bao, Hongchu; Yang, Qiuhua

2017-02-01

Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 ± 27.7 vs. 772.6 ± 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.

Development of insulin resistance and endothelin-1 levels in the Zucker fatty rat.

PubMed

Berthiaume, Nathalie; Mika, Amanda K; Zinker, Bradley A

2003-07-01

In order to determine the effects of increasing insulin resistance on endothelin-1 (ET-1) levels, Zucker lean and fatty rats were studied at basal and during a complete nutrient meal tolerance test (MTT) at 7, 12, and 15 weeks of age. The fatty rats were mildly hyperglycemic, severely hyperinsulinemic and glucose-intolerant at all ages versus lean animals and this progressed with age within groups, as previously published. Basal ET-1 levels, at 7 weeks, were significantly increased in fatty versus lean rats (3.2+/-0.5 v 2.0+/-0.3 pg/mL, respectively; P<.05); however, we did not observe any significant basal difference at 12 or 15 weeks. At 7 weeks, ET-1 levels between fatty and lean rats were not different during the MTT (15 minutes: 2.9+/-0.4 v 2.7+/-0.7; 120 minutes: 6.5+/-0.8 v 6.6+/-0.5 pg/mL, fatty v lean, respectively). At 12 weeks, though there was no difference in basal levels, fatty rats had higher ET-1 levels during the MTT compared to lean animals (15 minutes: 6.9+/-1.4 v 1.8+/-0.4; 120 minutes: 9.4+/-1.7 v 3.2+/-0.5 pg/mL, respectively; P<.01). At 15 weeks, ET-1 levels during the MTT receded to levels similar to those observed at 7 weeks, which were significantly higher in fatty versus lean rats 15 minutes following the challenge (3.4+/-0.4 v 2.4+/-0.2 pg/mL, respectively; P<.05). In conclusion, ET-1 levels in the Zucker fatty rat: (1) were increased in the early stages of the progression of insulin resistance at 7 weeks, but were unchanged under basal conditions with age thereafter, and (2) were increased under nutrient challenge conditions with advanced insulin resistance up to 12 weeks, and were still significantly but to a lesser degree increased at 15 weeks of age. The explanation for these results and their relationship to the observed insulin resistance is unclear and will require further investigation.

Pulse width and height modulation for multi-level resistance in bi-layer TaOx based RRAM

NASA Astrophysics Data System (ADS)

Alamgir, Zahiruddin; Beckmann, Karsten; Holt, Joshua; Cady, Nathaniel C.

2017-08-01

Mutli-level switching in resistive memory devices enables a wide range of computational paradigms, including neuromorphic and cognitive computing. To this end, we have developed a bi-layer tantalum oxide based resistive random access memory device using Hf as the oxygen exchange layer. Multiple, discrete resistance levels were achieved by modulating the RESET pulse width and height, ranging from 2 kΩ to several MΩ. For a fixed pulse height, OFF state resistance was found to increase gradually with the increase in the pulse width, whereas for a fixed pulse width, the increase in the pulse height resulted in drastic changes in resistance. Resistive switching in these devices transitioned from Schottky emission in the OFF state to tunneling based conduction in the ON state, based on I-V curve fitting and temperature dependent current measurements. These devices also demonstrated endurance of more than 108 cycles with a satisfactory Roff/Ron ratio and retention greater than 104 s.

Relationship among Periodontal Disease, Insulin Resistance, Salivary Cortisol, and Stress Levels during Pregnancy.

PubMed

Seraphim, Ana Paula Castilho Garcia; Chiba, Fernando Yamamoto; Pereira, Renato Felipe; Mattera, Maria Sara de Lima Coutinho; Moimaz, Suzely Adas Saliba; Sumida, Doris Hissako

2016-01-01

Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother's health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemia (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the

A small amount of dietary carbohydrate can promote the HFD-induced insulin resistance to a maximal level.

PubMed

Mei, Shuang; Yang, Xuefeng; Guo, Huailan; Gu, Haihua; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Bennett, Brian J; He, Ling; Cao, Wenhong

2014-01-01

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1-25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level.

A Small Amount of Dietary Carbohydrate Can Promote the HFD-Induced Insulin Resistance to a Maximal Level

PubMed Central

Guo, Huailan; Gu, Haihua; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Bennett, Brian J.; He, Ling; Cao, Wenhong

2014-01-01

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1–25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level. PMID:25055153

Insulin resistance and serum levels of interleukin-17 and interleukin-18 in normal pregnancy.

PubMed

Jahromi, Abdolreza Sotoodeh; Shojaei, Mohammad; Ghobadifar, Mohamed Amin

2014-06-01

We performed this study to evaluate the role of Interleukin-17 (IL-17) and Interleukin-18 (IL-18) in insulin resistance during normal pregnancy. This descriptive cross sectional study was carried out on 97 healthy pregnant women including 32, 25, and 40 individuals in the first, second, and third trimesters, respectively, and on 28 healthy non pregnant women between the autumn of 2012 and the spring of 2013. We analyzed the serum concentrations of IL-17 and IL-18 by using the enzyme linked immunosorbent assay (ELISA). Insulin resistance was measured by homeostasis model assessment of insulin resistance equation. No significant differences between the demographic data of the pregnant and non pregnant groups were observed. Insulin resistant in pregnant women was significantly higher than the controls (p=0.006). Serum IL-17 concentration was significantly different in non pregnant women and pregnant women in all gestational ages (p<0.05). Serum IL-18 level was significantly lower in subjects with first, second, and third trimesters of pregnancy in compared to non pregnant women (p<0.05). No significant correlations were found between serum IL-17 and IL-18 levels with insulin resistance (r=0.08, p=0.34 vs. r=0.01, p=0.91, respectively). Our data suggested that IL-17 and IL-18 do not appear to attribute greatly to pregnancy deduced insulin resistance during normal pregnancy.

Insulin Resistance and Glucose Levels in Subjects with Subclinical Hypothyroidism.

PubMed

Khan, Sikandar Hayat; Fazal, Nadeem; Ijaz, Aamir; Manzoor, Syed Mohsin; Asif, Naveed; Rafi, Tariq; Yasir, Muhammad; Niazi, Najmusaquib Khan

2017-06-01

To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism. Comparative cross-sectional study. Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2015 to September 2016. Subjects referred for executive screening of apparently healthy population (without any known history of diabetes, hypertension, heart disease or other chronic ailments), were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism. Median (IQR) insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 (n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26, 13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4 (13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2 [p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824). Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1 [111.6 (189.64, p= 0.040)]. Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism.

Insulin resistance and alanine amino transaminase (ALT) levels in first degree relatives of type 2 diabetes mellitus.

PubMed

Kuzhandai velu, V; Jyothirmayi, B; Kumar, J S

2011-01-01

Insulin resistance is established as an independent predictor of a range of disorders such as obesity, hypertension, dyslipidemia, type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. There is an association of hyperinsulinemia with hypertriglycerdemia, low level of HDL and high level of LDL. In nonalcoholic fatty liver disease, there is an elevation of ALT, raising the possibility that the prospective relationship between ALT and type 2 diabetes may reflect cross-sectional associations with insulin resistance or obesity. To find the significance of insulin resistance and alanine aminotransferase level in first degree relatives of type 2 diabetes mellitus. The study included 50 first degree relatives of type 2 diabetes (25 men and 25 women) aged 20-60 years and 30 control of similar age. All cases were taken from SRM Medical College Hospital and Research Centre, Chennai. All the cases were analyzed for HOMA(IR), QUICKI, IR ratio, fasting glucose, insulin (ELISA), lipid profile and alanine aminotransferase. Student's 't' test was applied for statistical analysis. The data show the significance of insulin resistance (HOMA(IR)) (2.76±1.46, 1.35±0.8, p<0.001) in the first degree relatives of type 2 diabetes mellitus when compared with controls respectively and increased level fasting plasma insulin (12.28±6.16, 6.12±3.04, p<0.001). In the lipid profile the total cholesterol and TAG are significant. No statistical significance was found in ALT (24.8±9.84, 20.08±11.02). Results of the study conclude that there is a high prevalence of insulin resistance in the first degree relatives of type 2 diabetes mellitus. ALT levels in the first degree relatives of type 2 diabetes mellitus had increased levels of insulin resistance, the pathogenesis suggesting increase in ALT levels as seen in insulin resistance condition. In our study, ALT was not statistically significant. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

High-level fluoroquinolone resistance in ophthalmic clinical isolates belonging to the species Corynebacterium macginleyi.

PubMed

Eguchi, Hiroshi; Kuwahara, Tomomi; Miyamoto, Tatsuro; Nakayama-Imaohji, Haruyuki; Ichimura, Minoru; Hayashi, Tetsuya; Shiota, Hiroshi

2008-02-01

The clinical importance of nondiphtherial Corynebacterium, a ubiquitous member of the normal human microflora of the skin and mucous membrane, for ocular surface infections has been recognized recently. We performed an antimicrobial susceptibility test with Etest strips for three fluoroquinolones (ciprofloxacin, norfloxacin, and levofloxacin) and a taxonomic analysis on 21 isolates of Corynebacterium from ophthalmic samples. Of these, 16 isolates were identified as C. macginleyi at the species level on the basis of 16S rRNA gene sequence comparisons. The remaining five isolates were determined to be C. mastitidis (four) or C. accolens (one). Eleven of the C. macginleyi isolates showed high levels of resistance to all of the fluoroquinolones tested, and one isolate was resistant to norfloxacin alone. An analysis of the amplified quinolone-resistance-determining regions of the gyrA genes revealed that a single amino acid substitution in position 83 of the gyrA product was sufficient to generate the norfloxacin resistance phenotype, and double mutations leading to amino acid changes in positions 83 and 87 were necessary for high-level resistance against the other fluoroquinolones. We conducted the first example of multilocus sequence typing (MLST) analysis on C. macginleyi. The MLST analysis grouped the majority of C. macginleyi isolates into a single lineage, and another molecular strain typing by random amplified polymorphic DNA fragment patterns supported the finding, indicating that a particular lineage of C. macginleyi is dominant on the human ocular surface. This type of population might be particularly adaptable to the milieu on the human ocular surface.

High-Level Fluoroquinolone Resistance in Ophthalmic Clinical Isolates Belonging to the Species Corynebacterium macginleyi▿

PubMed Central

Eguchi, Hiroshi; Kuwahara, Tomomi; Miyamoto, Tatsuro; Nakayama-Imaohji, Haruyuki; Ichimura, Minoru; Hayashi, Tetsuya; Shiota, Hiroshi

2008-01-01

The clinical importance of nondiphtherial Corynebacterium, a ubiquitous member of the normal human microflora of the skin and mucous membrane, for ocular surface infections has been recognized recently. We performed an antimicrobial susceptibility test with Etest strips for three fluoroquinolones (ciprofloxacin, norfloxacin, and levofloxacin) and a taxonomic analysis on 21 isolates of Corynebacterium from ophthalmic samples. Of these, 16 isolates were identified as C. macginleyi at the species level on the basis of 16S rRNA gene sequence comparisons. The remaining five isolates were determined to be C. mastitidis (four) or C. accolens (one). Eleven of the C. macginleyi isolates showed high levels of resistance to all of the fluoroquinolones tested, and one isolate was resistant to norfloxacin alone. An analysis of the amplified quinolone-resistance-determining regions of the gyrA genes revealed that a single amino acid substitution in position 83 of the gyrA product was sufficient to generate the norfloxacin resistance phenotype, and double mutations leading to amino acid changes in positions 83 and 87 were necessary for high-level resistance against the other fluoroquinolones. We conducted the first example of multilocus sequence typing (MLST) analysis on C. macginleyi. The MLST analysis grouped the majority of C. macginleyi isolates into a single lineage, and another molecular strain typing by random amplified polymorphic DNA fragment patterns supported the finding, indicating that a particular lineage of C. macginleyi is dominant on the human ocular surface. This type of population might be particularly adaptable to the milieu on the human ocular surface. PMID:18077650

High Levels of Resistance in the Common Bed Bug, Cimex lectularius (Hemiptera: Cimicidae), to Neonicotinoid Insecticides.

PubMed

Romero, Alvaro; Anderson, Troy D

2016-05-01

The rapid increase of bed bug populations resistant to pyrethroids demands the development of novel control tactics. Products combining pyrethroids and neonicotinoids have become very popular for bed bug control in the United States, but there are concerns about evolution of resistance to these compounds. Laboratory assays were used to measure the toxicity of topical applications of four neonicotinoids to a susceptible population and three pyrethroid-resistant populations. Activity of esterases, glutathione S-transferases, and cytochrome P450s of all strains was also evaluated. High levels of resistance to four neonicotinoids, acetamiprid, imidacloprid, dinotefuran, and thiamethoxam, relative to the susceptible Fort Dix population, were detected in populations collected from human dwellings in Cincinnati and Michigan. Because activity of detoxifying enzymes was increased in these two populations, our results suggest that these enzymes have some involvement in neonicotinoid resistance, but other resistance mechanisms might be involved as well. Detection of high levels of resistance to neonicotinoids further limits the options for chemical control of bed bugs. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

Different levels of UV-B resistance in Vaccinium corymbosum cultivars reveal distinct backgrounds of phenylpropanoid metabolites.

PubMed

Luengo Escobar, Ana; Magnum de Oliveira Silva, Franklin; Acevedo, Patricio; Nunes-Nesi, Adriano; Alberdi, Miren; Reyes-Díaz, Marjorie

2017-09-01

UV-B radiation induces several physiological and biochemical effects that can influence regulatory plant processes. Vaccinium corymbosum responds differently to UV-B radiation depending on the UV-B resistance of cultivars, according to their physiological and biochemical features. In this work, the effect of two levels of UV-B radiation during long-term exposure on the phenylpropanoid biosynthesis, and the expression of genes associated with flavonoid biosynthesis as well as the absolute quantification of secondary metabolites were studied in two contrasting UV-B-resistant cultivars (Legacy, resistant and Bluegold, sensitive). Multivariate analyses were performed to understand the role of phenylpropanoids in UV-B defense mechanisms. The amount of phenylpropanoid compounds was generally higher in Legacy than in Bluegold. Different expression levels of flavonoid biosynthetic genes for both cultivars were transiently induced, showing that even in longer period of UV-B exposure; plants are still adjusting their phenylpropanoids at the transcription levels. Multivariate analysis in Legacy indicated no significant correlation between gene expression and the levels of the flavonoids and phenolic acids. By contrast, in the Bluegold cultivar higher number of correlations between secondary metabolite and transcript levels was found. Taken together, the results indicated different adjustments between the cultivars for a successful UV-B acclimation. While the sensitive cultivar depends on metabolite adjustments to respond to UV-B exposure, the resistant cultivar also possesses an intrinsically higher antioxidant and UV-B screening capacity. Thus, we conclude that UV-B resistance involves not only metabolite level adjustments during the acclimation period, but also depends on the intrinsic metabolic status of the plant and metabolic features of the phenylpropanoid compounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Rapid emergence of high-level tigecycline resistance in Escherichia coli strains harbouring blaNDM-5 in vivo.

PubMed

Li, Xi; Mu, Xinli; Yang, Yunxing; Hua, Xiaoting; Yang, Qing; Wang, Nanfei; Du, Xiaoxing; Ruan, Zhi; Shen, Xiaoqiang; Yu, Yunsong

2016-04-01

Tigecycline (TIG) resistance is a growing concern because this antibiotic is regarded as one of the last resorts to treat infections caused by multidrug-resistant and extensively drug-resistant (XDR) bacteria. Information regarding TIG-resistant Escherichia coli isolates is scarce. In this study, we report the emergence of high-level TIG resistance in a longitudinal series of XDR E. coli isolates collected during TIG treatment. Whole-genome sequencing was performed for six E. coli strains harbouring bla(NDM-5) and genomic comparison revealed two amino acid substitutions. Mutation in rpsJ could be a significant factor conferring TIG resistance in these isolates. The fitness cost of TIG resistance in resistant strains was evaluated by determining the relative growth rate, indicating that TIG resistance reduced fitness by ca. 7%. This study is the first report to demonstrate high-level TIG resistance in E. coli in vivo. In addition, we report the first treatment-emergent minimum inhibitory concentration (MIC) development of TIG from 1mg/L to 64 mg/L in E. coli. Clinicians should be aware of the risk of an increase in the MIC of TIG under therapy. Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Association between Myeloperoxidase Levels and Risk of Insulin Resistance in Egyptian Obese Women

PubMed Central

Zaki, Moushira; Basha, Walaa; Reyad, Hanaa; Mohamed, Ramy; Hassan, Naglaa; Kholousi, Shams

2018-01-01

BACKGROUND: Myeloperoxidase (MPO) is an enzyme involved in the pathogenesis of several diseases. AIM: The current study aimed to investigate serum MPO levels in obese Egyptian women and assess its relation with insulin resistance (IR) and other biochemical risk parameters. METHODS: The study included 80 obese women and 50 age-and-sex-matched healthy controls. Insulin resistance (IR) was evaluated by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Serum MPO, fasting glucose, insulin and blood lipids and anthropometry were measured. Obese cases were divided into three groups based on MPO tertiles. ROC analysis was performed to obtain the optimal cut-off values of MPO to predicate IR in obese women. RESULTS: The mean serum MPO was significantly higher in obese cases than controls. Cases in the highest MPO tertile had higher HOMA-IR, blood lipids and pressure levels compared with those in the lower tertile. The cutoff point of MPO was > 87.8 (ng/mL) and area under curves was 0.82 (p < 0.01) for diagnosis of IR. MPO levels were higher in obese Egyptian women than healthy controls. CONCLUSION: Elevation of MPO was associated with abnormal metabolic parameters. MPO might be used as an earlier biomarker for IR and metabolic disturbance in obese women. PMID:29731928

TNFα dynamics during the oral glucose tolerance test vary according to the level of insulin resistance in pregnant women.

PubMed

Guillemette, Laetitia; Lacroix, Marilyn; Battista, Marie-Claude; Doyon, Myriam; Moreau, Julie; Ménard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France

2014-05-01

TNFα is suspected to play a role in inflammation and insulin resistance leading to higher risk of metabolic impairment. Controversies exist concerning the role of TNFα in gestational insulin resistance. We investigated the interrelations between TNFα and insulin resistance in a large population-based cohort of pregnant women. Women (n = 756) were followed prospectively at 5-16 weeks and 24-28 weeks of pregnancy. Anthropometric measures and blood samples were collected at both visits. A 75-g oral glucose tolerance test (OGTT) was conducted at the second trimester to assess insulin sensitivity status (homeostasis model of assessment of insulin resistance and Matsuda index). TNFα was measured at the first trimester (nonfasting) and at each time point of the OGTT. Participants were 28.4 ± 4.4 years old and had a mean body mass index of 25.5 ± 5.5 kg/m(2) at first trimester. Median TNFα levels were 1.56 (interquartile range, 1.18-2.06) pg/mL at first trimester and 1.61 (interquartile range, 1.12-2.13) pg/mL at second trimester (1 h after glucose load). At second trimester, higher TNFα levels were associated with higher insulin resistance index levels (r = 0.37 and -0.30 for homeostasis model of assessment of insulin resistance and Matsuda index, respectively; P < .0001), even after adjustment for age, body mass index, triglycerides, and adiponectin. Women with higher insulin resistance showed a continuing decrease in TNFα levels during the OGTT, whereas women who were more insulin sensitive showed an increase in TNFα at hour 1 and a decrease at hour 2 of the test. Higher insulin resistance is associated with higher levels of circulating TNFα at first and second trimesters of pregnancy. TNFα level dynamics during an OGTT at second trimester vary according to insulin-resistance state.

High-level aminoglycoside resistance and virulence characteristics among Enterococci isolated from recreational beaches in Malaysia.

PubMed

Dada, Ayokunle Christopher; Ahmad, Asmat; Usup, Gires; Heng, Lee Yook; Hamid, Rahimi

2013-09-01

We report the first study on the occurrence of high-level aminoglycoside-resistant (HLAR) Enterococci in coastal bathing waters and beach sand in Malaysia. None of the encountered isolates were resistant to high levels of gentamicin (500 μg/mL). However, high-level resistance to kanamycin (2,000 μg/mL) was observed in 14.2 % of tested isolates, the highest proportions observed being among beach sand isolates. High-level resistance to kanamycin was higher among Enterococcus faecalis and Enterococcus faecium than Enterococcus spp. Chi-square analysis showed no significant association between responses to tested antibiotics and the species allocation or source of isolation of all tested Enterococci. The species classification of encountered Enterococci resistance to vancomycin was highest among Enterococcus spp. (5.89 %) followed by E. faecium (4.785) and least among E. faecalis. A total of 160 isolates were also tested for virulence characteristics. On the whole, caseinase production was profoundly highest (15.01 %) while the least prevalent virulence characteristic observed among tested beach Enterococci was haemolysis of rabbit blood (3.65 %). A strong association was observed between the source of isolation and responses for each of caseinase (C = 0.47, V = 0.53) and slime (C = 0.50, V = 0.58) assays. Analysis of obtained spearman's coefficient showed a strong correlation between caseinase and each of the slime production (p = 0.04), gelatinase (p = 0.0035) and haemolytic activity on horse blood (p = 0.004), respectively. Suggestively, these are the main virulent characteristics of the studied beach Enterococci. Our findings suggest that recreational beaches may contribute to the dissemination of Enterococci with HLAR and virulence characteristics.

Insecticide resistance in house flies from the United States: Resistance levels and frequency of pyrethroid resistance alleles

USDA-ARS?s Scientific Manuscript database

Although insecticide resistance is a widespread problem for most insect pests, frequently the assessment of resistance occurs over a limited geographic range. Herein we report the first widespread survey of insecticide resistance ever undertaken for the house fly, Musca domestica, a major pest of a...

The 30-GHz monolithic receive module

NASA Technical Reports Server (NTRS)

Sokolov, V.; Geddes, J.; Bauhahn, P.

1983-01-01

Key requirements for a 30 GHz GaAs monolithic receive module for spaceborne communication antenna feed array applications include an overall receive module noise figure of 5 dB, a 30 dB RF to IF gain with six levels of intermediate gain control, a five-bit phase shifter, and a maximum power consumption of 250 mW. The RF designs for each of the four submodules (low noise amplifier, some gain control, phase shifter, and RF to IF sub-module) are presented. Except for the phase shifter, high frequency, low noise FETs with sub-half micron gate lengths are employed in the submodules. For the gain control, a two stage dual gate FET amplifier is used. The phase shifter is of the passive switched line type and consists of 5-bits. It uses relatively large gate width FETs (with zero drain to source bias) as the switching elements. A 20 GHz local oscillator buffer amplifier, a FET compatible balanced mixer, and a 5-8 GHz IF amplifier constitute the RF/IF sub-module. Phase shifter fabrication using ion implantation and a self-aligned gate technique is described. Preliminary RF results obtained on such phase shifters are included.

C-reactive protein levels and treatment resistance in schizophrenia-A Danish population-based cohort study.

PubMed

Horsdal, Henriette Thisted; Wimberley, Theresa; Benros, Michael Eriksen; Gasse, Christiane

2017-11-01

Schizophrenia is associated with increased levels of inflammatory markers. However, it remains unclear whether inflammatory markers are associated with treatment-resistant schizophrenia. We conducted a population-based follow-up study among individuals with a first-time schizophrenia diagnosis and a baseline C-reactive protein measurement (a commonly available marker of systemic inflammation) from 2000 to 2012. We defined treatment resistance as the earliest observed instance of either clozapine initiation or hospital admission due to schizophrenia after having received at least 2 prior antipsychotic monotherapy trials of adequate duration. We used adjusted Cox regression analysis to calculate hazard ratios. We identified 390 individuals with a C-reactive protein measurement at first-time schizophrenia diagnosis. A nonsignificant higher median C-reactive protein (4.0 vs. 3.1 mg/L, p = .13) was observed among the 52 (13.3%) treatment-resistant individuals. Increased levels of C-reactive protein (above 3 mg/L) at baseline were not associated with treatment resistance (adjusted hazard ratio = 0.99, 95% confidence interval [0.56, 1.73]). C-reactive protein, as a single inflammatory marker, appears insufficient to detect treatment-resistant schizophrenia. Copyright © 2017 John Wiley & Sons, Ltd.

The effects of low-level ionizing radiation and copper exposure on the incidence of antibiotic resistance in lentic biofilm bacteria.

PubMed

McArthur, J Vaun; Dicks, Christian A; Bryan, A Lawrence; Tuckfield, R Cary

2017-09-01

Environmental reservoirs of antibiotic resistant bacteria are poorly understood. Understanding how the environment selects for resistance traits in the absence of antibiotics is critical in developing strategies to mitigate this growing menace. Indirect or co-selection of resistance by environmental pollution has been shown to increase antibiotic resistance. However no attention has been given to the effects of low-level ionizing radiation or the interactions between radiation and heavy metals on the maintenance or selection for antibiotic resistance (AR) traits. Here we explore the effect of radiation and copper on antibiotic resistance. Bacteria were collected from biofilms in two ponds - one impacted by low-level radiocesium and the other an abandoned farm pond. Through laboratory controlled experiments we examined the effects of increasing concentrations of copper on the incidence of antibiotic resistance. Differences were detected in the resistance profiles of the controls from each pond. Low levels (0.01 mM) of copper sulfate increased resistance but 0.5 mM concentrations of copper sulfate depressed the AR response in both ponds. A similar pattern was observed for levels of multiple antibiotic resistance per isolate. The first principal component response of isolate exposure to multiple antibiotics showed significant differences among the six isolate treatment combinations. These differences were clearly visualized through a discriminant function analysis, which showed distinct antibiotic resistance response patterns based on the six treatment groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urban-rural differences explain the association between serum 25-hydroxyvitamin D level and insulin resistance in Korea.

PubMed

Song, Bo Mi; Rhee, Yumie; Kim, Chang Oh; Youm, Yoosik; Kim, Kyoung Min; Lee, Eun Young; Lee, Ju-Mi; Yoon, Young Mi; Kim, Hyeon Chang

2014-12-11

An increasing number of studies report associations between low serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance; however, whether low vitamin D levels directly contribute to increased insulin resistance is unclear. We investigated the impact of residential area on the association between 25(OH)D and insulin resistance in elderly Koreans. Using data from the Korean Urban Rural Elderly study, we conducted cross-sectional analyses in 1628 participants (505 men and 1123 women). Serum 25(OH)D was analyzed as both continuous and categorized variables. Homeostasis model assessment for insulin resistance (HOMA-IR) was calculated using fasting blood glucose and insulin levels. In men, 25(OH)D level was inversely associated with HOMA-IR (standardized β = -0.133, p < 0.001) after adjustment for age, body mass index, waist circumference, smoking, alcohol intake, exercise, and study year. However, we noted significant urban-rural differences in 25(OH)D level (43.4 versus 65.6 nmol/L; p < 0.001) and HOMA-IR (1.2 versus 0.8 mmol · pmol/L2; p < 0.001). When we additionally adjusted for residential area, the association between 25(OH)D and HOMA-IR was attenuated (standardized β = -0.063, p = 0.115). In women, the association between 25(OH)D and HOMA-IR was not significant before or after adjustment for residential area. Environmental or lifestyle differences in urban and rural areas may largely explain the inverse association between serum 25(OH)D and insulin resistance.

[Association between serum zinc level and hypercholesterolemia and insulin resistance in Brazilian children].

PubMed

Albuquerque, Fernanda Martins de; Filgueiras, Mariana De Santis; Rocha, Naruna Pereira; Castro, Ana Paula Pereira; Milagres, Luana Cupertino; Pessoa, Milene Cristine; Fransceschini, Sylvia do Carmo Castro; Novaes, Juliana Farias de

2018-02-05

The objective of the study was to assess the association between serum zinc level and cardiometabolic factors in prepubertal Brazilian children. This was a cross-sectional study in a representative sample of schoolchildren 8 to 9 years of age in public and private urban schools in Viçosa, Minas Gerais State, Brazil. Body composition was assessed with dual-energy x-ray absorptiometry. The study measured serum glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol, triglycerides, apolipoproteins A (Apo A) and B, uric acid, leptin, homocysteine, ultrasenstive C-reactive protein, and serum zinc. Arterial pressure was measured with automatic inflation equipment. Zinc deficiency was observed in 1.3% of the children. Girls showed the worst cardiometabolic profile, with higher prevalence of increased android fat, triglycerides, insulin resistance, leptin, zinc, and Apo A. In the first tertile of serum zinc concentration, prevalence of insulin resistance was 96% higher (PR = 1.96; 95%CI: 1.04-3.66) and hypercholesterolemia was 23% lower (PR = 0.77; 95%CI: 0.61-0.96) than in the reference category (grouped 2nd and 3rd tertiles of serum zinc concentration). Despite the low prevalence of zinc deficiency, insulin resistance was more prevalent in children in the lowest third of serum zinc concentration. It is important to prevent cardiometabolic alterations in childhood, especially insulin resistance, with an emphasis on serum zinc level.

Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS

PubMed Central

Zhang, Ruohan; Qiao, Hongyu; Chen, Suning; Chen, Xu; Dou, Kefeng; Wei, Li; Zhang, Jian

2016-01-01

ABSTRACT Lapatinib, a novel tyrosine kinase inhibitor of HER2/EGFR, is used to treat HER2-positive breast cancer. However, acquired drug resistance has limited the clinical therapeutic efficacy of lapatinib. Our previous study found that inhibition of autophagy can reduce the proliferation, DNA synthesis, and colony-forming capacity of lapatinib-resistant cells. Berberine has attracted extensive attention due to its wide range of biochemical and pharmacological effects in breast cancer treatment. It has been reported that berberine can induce oxidative stress and the mitochondrial-related apoptotic pathway in human breast cancer cells. In our current study, we found that a new combination therapy of berberine with lapatinib overcame lapatinib resistance. Furthermore, we found that berberine induced apoptosis of lapatinib-resistant cells through upregulating the level of ROS. Specially, lapatinib activated both the c-Myc/pro-Nrf2 pathway and GSK-3β signaling to stabilize Nrf2 and maintain a low level of ROS in resistant cells. However, berberine can upset the ROS balance by downregulating c-Myc to reverse the lapatinib resistance. Our finding provides a novel strategy of using berberine to overcome lapatinib resistance. PMID:27416292

Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS.

PubMed

Zhang, Ruohan; Qiao, Hongyu; Chen, Suning; Chen, Xu; Dou, Kefeng; Wei, Li; Zhang, Jian

2016-09-01

Lapatinib, a novel tyrosine kinase inhibitor of HER2/EGFR, is used to treat HER2-positive breast cancer. However, acquired drug resistance has limited the clinical therapeutic efficacy of lapatinib. Our previous study found that inhibition of autophagy can reduce the proliferation, DNA synthesis, and colony-forming capacity of lapatinib-resistant cells. Berberine has attracted extensive attention due to its wide range of biochemical and pharmacological effects in breast cancer treatment. It has been reported that berberine can induce oxidative stress and the mitochondrial-related apoptotic pathway in human breast cancer cells. In our current study, we found that a new combination therapy of berberine with lapatinib overcame lapatinib resistance. Furthermore, we found that berberine induced apoptosis of lapatinib-resistant cells through upregulating the level of ROS. Specially, lapatinib activated both the c-Myc/pro-Nrf2 pathway and GSK-3β signaling to stabilize Nrf2 and maintain a low level of ROS in resistant cells. However, berberine can upset the ROS balance by downregulating c-Myc to reverse the lapatinib resistance. Our finding provides a novel strategy of using berberine to overcome lapatinib resistance.

Parallel Evolution of High-Level Aminoglycoside Resistance in Escherichia coli Under Low and High Mutation Supply Rates.

PubMed

Ibacache-Quiroga, Claudia; Oliveros, Juan C; Couce, Alejandro; Blázquez, Jesus

2018-01-01

Antibiotic resistance is a major concern in public health worldwide, thus there is much interest in characterizing the mutational pathways through which susceptible bacteria evolve resistance. Here we use experimental evolution to explore the mutational pathways toward aminoglycoside resistance, using gentamicin as a model, under low and high mutation supply rates. Our results show that both normo and hypermutable strains of Escherichia coli are able to develop resistance to drug dosages > 1,000-fold higher than the minimal inhibitory concentration for their ancestors. Interestingly, such level of resistance was often associated with changes in susceptibility to other antibiotics, most prominently with increased resistance to fosfomycin. Whole-genome sequencing revealed that all resistant derivatives presented diverse mutations in five common genetic elements: fhuA, fusA and the atpIBEFHAGDC, cyoABCDE , and potABCD operons. Despite the large number of mutations acquired, hypermutable strains did not pay, apparently, fitness cost. In contrast to recent studies, we found that the mutation supply rate mainly affected the speed (tempo) but not the pattern (mode) of evolution: both backgrounds acquired the mutations in the same order, although the hypermutator strain did it faster. This observation is compatible with the adaptive landscape for high-level gentamicin resistance being relatively smooth, with few local maxima; which might be a common feature among antibiotics for which resistance involves multiple loci.

Parallel Evolution of High-Level Aminoglycoside Resistance in Escherichia coli Under Low and High Mutation Supply Rates

PubMed Central

Ibacache-Quiroga, Claudia; Oliveros, Juan C.; Couce, Alejandro; Blázquez, Jesus

2018-01-01

Antibiotic resistance is a major concern in public health worldwide, thus there is much interest in characterizing the mutational pathways through which susceptible bacteria evolve resistance. Here we use experimental evolution to explore the mutational pathways toward aminoglycoside resistance, using gentamicin as a model, under low and high mutation supply rates. Our results show that both normo and hypermutable strains of Escherichia coli are able to develop resistance to drug dosages > 1,000-fold higher than the minimal inhibitory concentration for their ancestors. Interestingly, such level of resistance was often associated with changes in susceptibility to other antibiotics, most prominently with increased resistance to fosfomycin. Whole-genome sequencing revealed that all resistant derivatives presented diverse mutations in five common genetic elements: fhuA, fusA and the atpIBEFHAGDC, cyoABCDE, and potABCD operons. Despite the large number of mutations acquired, hypermutable strains did not pay, apparently, fitness cost. In contrast to recent studies, we found that the mutation supply rate mainly affected the speed (tempo) but not the pattern (mode) of evolution: both backgrounds acquired the mutations in the same order, although the hypermutator strain did it faster. This observation is compatible with the adaptive landscape for high-level gentamicin resistance being relatively smooth, with few local maxima; which might be a common feature among antibiotics for which resistance involves multiple loci. PMID:29615988

RNA-Seq and molecular docking reveal multi-level pesticide resistance in the bed bug

PubMed Central

2012-01-01

Background Bed bugs (Cimex lectularius) are hematophagous nocturnal parasites of humans that have attained high impact status due to their worldwide resurgence. The sudden and rampant resurgence of C. lectularius has been attributed to numerous factors including frequent international travel, narrower pest management practices, and insecticide resistance. Results We performed a next-generation RNA sequencing (RNA-Seq) experiment to find differentially expressed genes between pesticide-resistant (PR) and pesticide-susceptible (PS) strains of C. lectularius. A reference transcriptome database of 51,492 expressed sequence tags (ESTs) was created by combining the databases derived from de novo assembled mRNA-Seq tags (30,404 ESTs) and our previous 454 pyrosequenced database (21,088 ESTs). The two-way GLMseq analysis revealed ~15,000 highly significant differentially expressed ESTs between the PR and PS strains. Among the top 5,000 differentially expressed ESTs, 109 putative defense genes (cuticular proteins, cytochrome P450s, antioxidant genes, ABC transporters, glutathione S-transferases, carboxylesterases and acetyl cholinesterase) involved in penetration resistance and metabolic resistance were identified. Tissue and development-specific expression of P450 CYP3 clan members showed high mRNA levels in the cuticle, Malpighian tubules, and midgut; and in early instar nymphs, respectively. Lastly, molecular modeling and docking of a candidate cytochrome P450 (CYP397A1V2) revealed the flexibility of the deduced protein to metabolize a broad range of insecticide substrates including DDT, deltamethrin, permethrin, and imidacloprid. Conclusions We developed significant molecular resources for C. lectularius putatively involved in metabolic resistance as well as those participating in other modes of insecticide resistance. RNA-Seq profiles of PR strains combined with tissue-specific profiles and molecular docking revealed multi-level insecticide resistance in C. lectularius

Prevalence of carbapenemases among high-level aminoglycoside-resistant Acinetobacter baumannii isolates in a university hospital in China

PubMed Central

Wang, Yanhong; Shen, Min; Yang, Jingni; Dai, Min; Chang, Yaowen; Zhang, Chi; Luan, Guangxin; Ling, Baodong; Jia, Xu

2016-01-01

The prevalence of aminoglycoside resistant enzymes has previously been reported and extended-spectrum β-lactamase among Acinetobacter baumannii. To track the risk of multidrug-resistant A. baumannii, the present study aimed to determine the prevalence of carbapenemases in high-level aminoglycoside resistant A. baumannii over two years. A total of 118 strains of A. baumannii were consecutively collected in the First Affiliated Hospital of Chengdu Medical College, Chengdu, China. These isolates were investigated on the genetic basis of their resistance to aminoglycosides. The results showed that 75 (63.56%) isolates were high-level resistant to aminoglycosides, including gentamicin and amikacin (minimum inhibitory concentration, ≥256 µg/ml). Aminoglycoside-resistant genes ant(2″)-Ia, aac(6′)-Ib, aph(3′)-Ia, aac(3)-Ia, aac(3)-IIa, armA, rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA, and carbapenem-resistant genes blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, blaSIM, blaIMP, blaNDM-1 and blaKPC, were analyzed using polymerase chain reaction. The positive rate of ant(2″)-Ia, aac(6′)-Ib, aph(3′)-Ia, aac(3)-Ia and aac(3)-IIa was 66.95, 69.49, 42.37, 39.83 and 14.41%, respectively. armA was present in 72.0% (54/75) of A. baumannii isolates with high-level resistance to aminoglycosides. The remaining nine 16S ribosomal RNA methlyase genes (rmtA, rmtB, rmtC, rmtD, rmtE, rmtF, rmtG, rmtH and npmA) and aminoglycoside-modifying enzyme gene aac(6′)-Ib-cr were not detected. Among the 54 armA-positive isolates, the prevalence of the carbapenem resistant blaOXA-23 and blaOXA-51 genes was 79.63 and 100%, respectively. armA, ant(2″)-Ia and aac(6′)-Ib were positive in 43 isolates. The results of multilocus sequence typing revealed 31 sequence types (STs) in all clinical strains. Among these STs, the high-level aminoglycoside-resistant A. baumannii ST92, which mostly harbored blaOXA-23, was the predominant clone (29/75). In conclusion, A. baumannii

Antibiosis in Soybean Genotypes and the Resistance Levels to Spodoptera eridania (Cramer) (Lepidoptera: Noctuidae).

PubMed

Souza, B H S; Silva, A G; Janini, J C; Boica Júnior, A L

2014-12-01

The southern armyworm (SAW) Spodoptera eridania (Cramer) is one of the most common armyworm species defoliating soybeans. Preliminary screening trials have indicated that some soybean genotypes exhibit resistance to SAW. Therefore, in this study, we evaluated the development of SAW larvae fed on ten soybean genotypes in order to identify genotypes with antibiosis-type resistance. Neonate SAW larvae were daily fed with young leaves collected from plants at the vegetative growth stages V4-V5. Larval development and survival were recorded. Genotypes PI 227687 and PI 227682 delayed larval, pupal, and larva-adult development and yielded larvae with the lowest weight and survival and pupae with the lowest weight. Genotypes IAC 100 and DM 339 also negatively affected larval and pupal development and larval survival but at a lower level. Based on our results, the soybean lines PI 227687 and PI 227682 could be used as sources of genes for soybean breeding programs aiming to develop high yield, SAW-resistant cultivars. Moreover, further trials must be carried out under field conditions to validate if the commercial cultivars IAC 100 and DM 339, which expressed moderate levels of antibiosis-type resistance in the laboratory, are effective in suppressing SAW larvae populations.

Serum progranulin levels in relation to insulin resistance in childhood obesity.

PubMed

Alissa, Eman M; Sutaih, Rima H; Kamfar, Hayat Z; Alagha, Abdulmoeen E; Marzouki, Zuhair M

2017-11-27

Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases. A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Children were classified into four groups based on quartile for serum progranulin. Anthropometric variables were measured in all study subjects. Fasting blood samples were collected for measurement of blood glucose, insulin and lipid profile. Children within the upper quartile for serum progranulin concentration were heavier, more insulin resistant and had higher concentrations of serum total cholesterol, triglycerides, insulin and high sensitivity C reactive protein compared to those in the lower quartile. On correlation analysis, serum progranulin concentrations were significantly related to general and central adiposity, metabolic parameters, markers of inflammation and insulin resistance. Stepwise multiple regression showed that 26.6% of the variability in serum progranulin could be explained by measures of adiposity. The increased serum progranulin concentrations were closely related to measures of adiposity, metabolic parameters, inflammatory marker and insulin resistance indices, suggesting that progranulin may be an excellent biomarker for obesity in childhood.

Increased levels of antibiotic resistance in urban stream of Jiulongjiang River, China.

PubMed

Ouyang, Wei-Ying; Huang, Fu-Yi; Zhao, Yi; Li, Hu; Su, Jian-Qiang

2015-07-01

The rapid global urbanization and other extensive anthropogenic activities exacerbated the worldwide human health risks induced by antibiotic resistance genes (ARGs). Knowledge of the origins and dissemination of ARGs is essential for understanding modern resistome, while little information is known regarding the overall resistance levels in urban river. In this study, the abundance of multi-resistant bacteria (MRB) and ARGs was investigated using culture-based method and high-throughput qPCR in water samples collected from urban stream and source of Jiulongjiang River, China, respectively. The abundance of MRB (conferring resistance to three combinations of antibiotics and vancomycin) was significantly higher in urban samples. A total of 212 ARGs were detected among all the water samples, which encoded resistance to almost all major classes of antibiotics and encompassed major resistant mechanisms. The total abundance of ARGs in urban samples (ranging from 9.72 × 10(10) to 1.03 × 10(11) copies L(-1)) was over two orders of magnitude higher than that in pristine samples (7.18 × 10(8) copies L(-1)), accompanied with distinct ARGs structures, significantly higher diversity, and enrichment of ARGs. Significant correlations between the abundance of ARGs and mobile genetic elements (MGEs) were observed, implicating the potential of horizontal transfer of ARGs. High abundance and enrichment of diverse ARGs and MGEs detected in urban river provide evidence that anthropogenic activities are responsible for the emergence and dissemination of ARGs to the urban river and management options should be taken into account for minimizing the spread of ARGs.

Association of Tumor Growth Factor-β and Interferon-γ Serum Levels With Insulin Resistance in Normal Pregnancy.

PubMed

Sotoodeh Jahromi, Abdolreza; Sanie, Mohammad Sadegh; Yusefi, Alireza; Zabetian, Hassan; Zareian, Parvin; Hakimelahi, Hossein; Madani, Abdolhossien; Hojjat-Farsangi, Mohammad

2015-09-28

Pregnancy is related to change in glucose metabolism and insulin production. The aim of our study was to determine the association of serum IFN-γ and TGF- β levels with insulin resistance during normal pregnancy. This cross sectional study was carried out on 97 healthy pregnant (in different trimesters) and 28 healthy non-pregnant women. Serum TGF-β and IFN- γ level were measured by ELISA method. Pregnant women had high level TGF-β and low level IFN-γ as compared non-pregnant women. Maternal serum TGF-β concentration significantly increased in third trimester as compared first and second trimester of pregnancy. Maternal serum IFN-γ concentration significantly decreased in third trimester as compared first and second trimester of pregnancy. Pregnant women exhibited higher score of HOMA IR as compared non-pregnant women. There were association between gestational age with body mass index (r=0.28, P=0.005), TGF-β (r=0.45, P<0.001) and IFN-γ (r=-0.50, P<0.001). There was significant association between Insulin resistance and TGF-β (r=0.17, p=0.05). Our findings suggest that changes in maternal cytokine level in healthy pregnant women were anti-inflammatory. Furthermore, Tumor Growth Factor-β appears has a role in induction insulin resistance in healthy pregnant women. However, further studies needed to evaluate role of different cytokines on insulin resistance in normal pregnancy.

Monte Carlo code G3sim for simulation of plastic scintillator detectors with wavelength shifter fiber readout.

PubMed

Mohanty, P K; Dugad, S R; Gupta, S K

2012-04-01

A detailed description of a compact Monte Carlo simulation code "G3sim" for studying the performance of a plastic scintillator detector with wavelength shifter (WLS) fiber readout is presented. G3sim was developed for optimizing the design of new scintillator detectors used in the GRAPES-3 extensive air shower experiment. Propagation of the blue photons produced by the passage of relativistic charged particles in the scintillator is treated by incorporating the absorption, total internal, and diffuse reflections. Capture of blue photons by the WLS fibers and subsequent re-emission of longer wavelength green photons is appropriately treated. The trapping and propagation of green photons inside the WLS fiber is treated using the laws of optics for meridional and skew rays. Propagation time of each photon is taken into account for the generation of the electrical signal at the photomultiplier. A comparison of the results from G3sim with the performance of a prototype scintillator detector showed an excellent agreement between the simulated and measured properties. The simulation results can be parametrized in terms of exponential functions providing a deeper insight into the functioning of these versatile detectors. G3sim can be used to aid the design and optimize the performance of scintillator detectors prior to actual fabrication that may result in a considerable saving of time, labor, and money spent. © 2012 American Institute of Physics

Geometric Morphometrics of Nine Field Isolates of Aedes aegypti with Different Resistance Levels to Lambda-Cyhalothrin and Relative Fitness of One Artificially Selected for Resistance

PubMed Central

Jaramillo-O., Nicolás; Fonseca-González, Idalyd; Chaverra-Rodríguez, Duverney

2014-01-01

Aedes aegypti, a mosquito closely associated with humans, is the principal vector of dengue virus which currently infects about 400 million people worldwide. Because there is no way to prevent infection, public health policies focus on vector control; but insecticide-resistance threatens them. However, most insecticide-resistant mosquito populations exhibit fitness costs in absence of insecticides, although these costs vary. Research on components of fitness that vary with insecticide-resistance can help to develop policies for effective integrated management and control. We investigated the relationships in wing size, wing shape, and natural resistance levels to lambda-cyhalothrin of nine field isolates. Also we chose one of these isolates to select in lab for resistance to the insecticide. The main life-traits parameters were assessed to investigate the possible fitness cost and its association with wing size and shape. We found that wing shape, more than wing size, was strongly correlated with resistance levels to lambda-cyhalothrin in field isolates, but founder effects of culture in the laboratory seem to change wing shape (and also wing size) more easily than artificial selection for resistance to that insecticide. Moreover, significant fitness costs were observed in response to insecticide-resistance as proved by the diminished fecundity and survival of females in the selected line and the reversion to susceptibility in 20 generations of the non-selected line. As a practical consequence, we think, mosquito control programs could benefit from this knowledge in implementing efficient strategies to prevent the evolution of resistance. In particular, the knowledge of reversion to susceptibility is important because it can help in planning better strategies of insecticide use to keep useful the few insecticide-molecules currently available. PMID:24801598

Association of glycosylated hemoglobin (HbA1c) levels with Iinsulin resistance in obese children.

PubMed

Onal, Zehra Esra; Atasayan, Vildan; Gürbüz, Tamay; Hepkaya, Evrim; Nuhoğlu, Cağatay

2014-09-01

We investigated the relationship between insulin resistance reflected by homeostasis model assessment (HOMA-IR) index and serum HbA1c levels of obese children. This study included 70 obese and 60 normal weight healthy children between the ages of 3 and 15. Anthropometric measures and biochemical tests (fasting glucose, fasting insulin, HbA1c) were performed on all subjects. Plasma glucose levels were measured by the glucose oxidase method. Plasma insulin concentrations were measured by radioimmunoassay (RIA). HOMA-IR index was used to estimate insulin resistance. A cut-off HOMA-IR level of ≥2.5 was accepted. The HbA1c analysis was performed using high-pressure liquid chromatography. The statistical analysis was performed using SPSS 5. Student's unpaired t-test and the Mann-Whitney U test were used to determine statistical significance. Gender distribution did not reveal significant difference among the obese (F: 48.6%, M: 51.4%) and the non-obese (F: 46.7%, M: 53.3%) groups. The mean age value was significantly higher in the obese group (10.09 ± 3.09) (p > 0.005) than the non-obese group (8.31 ± 3.14) (p < 0.05). The mean value of body mass index (BMI) was 25.55 ± 4.3 in the obese group and 16.63 ± 2.3 in the non-obese group. The mean HOMA-IR values of obese group (2.84 ± 1.77) was significantly higher than the non-obese group (1.50 ± 0.95) (p < 0.005). Insulin resistance was significantly higher in the obese group. Subjects with HOMA-IR ≥2.5 levels in the obese group had significantly higher HbA1c values than those with HOMA-IR <2.5 levels. High HbA1c levels in obese children can be used as a screening tool to detect insulin sensitivity and resistance at an early stage.

A new low voltage level-shifted FVF current mirror with enhanced bandwidth and output resistance

NASA Astrophysics Data System (ADS)

Aggarwal, Bhawna; Gupta, Maneesha; Gupta, Anil Kumar; Sangal, Ankur

2016-10-01

This paper proposes a new high-performance level-shifted flipped voltage follower (LSFVF) based low-voltage current mirror (CM). The proposed CM utilises the low-supply voltage and low-input resistance characteristics of a flipped voltage follower (FVF) CM. In the proposed CM, level-shifting configuration is used to obtain a wide operating current range and resistive compensation technique is employed to increase the operating bandwidth. The peaking in frequency response is reduced by using an additional large MOSFET. Moreover, a very high output resistance (in GΩ range) along with low-current transfer error is achieved through super-cascode configuration for a wide current range (0-440 µA). Small signal analysis is carried out to show the improvements achieved at each step. The proposed CM is simulated by Mentor Graphics Eldospice in TSMC 0.18 µm CMOS, BSIM3 and Level 53 technology. In the proposed CM, a bandwidth of 6.1799 GHz, 1% settling time of 0.719 ns, input and output resistances of 21.43 Ω and 1.14 GΩ, respectively, are obtained with a single supply voltage of 1 V. The layout of the proposed CM has been designed and post-layout simulation results have been shown. The post-layout simulation results for Monte Carlo and temperature analysis have also been included to show the reliability of the CM against the variations in process parameters and temperature changes.

Resistance Level of Mosquito Species (Diptera: Culicidae) from Shandong Province, China.

PubMed

Liu, Hong-Mei; Yang, Pei-Pei; Cheng, Peng; Wang, Hai-Fang; Liu, Li-Juan; Huang, Xiaodan; Zhao, Yu-Qiang; Wang, Huai-Wei; Zhang, Chong-Xing; Gong, Mao-Qing

2015-01-01

This study describes the aquatic habitats, species composition, and the insecticide resistance level of the mosquito Culex pipiens pallens in Shandong Province, China. A cross-sectional survey of mosquito larval habitats was conducted from May to November 2014 to determine the species composition and larval abundance. Larvae were collected using the standard dipping technique, and a total of four habitat types were sampled. The fourth instar larvae of Cx. pipiens pallens collected in each habitat type were tested for resistance to five insecticides according to a WHO bioassay. A total of 7,281 mosquito larvae were collected, of which 399 (5.48%) were categorized as Anopheles mosquito larvae (An. sinensis), 6636 (91.14%) as culicine larvae (Cx. pipiens pallens, Cx. tritaeniorhynchus, Cx. halifaxii, and Cx. bitaeniorhynchus), 213 (2.93%) as Armigeres larvae, and 33 (0.45%) as Aedes larvae (Aedes albopictus). In addition, a total of 1,149 mosquito pupae were collected. Culex larvae were distributed in all habitats investigated. Tukeys HSD analysis showed that roadside drainages were the most productive habitat type for Culex larvae. Armigeres species were found only in drains, Aedes only in water tanks, and Anopheles in water that was comparatively clear and rich in emergent plants. Bioassay showed that the maximum resistance level of Cx. pipiens pallens was to deltamethrin, while it was lowest to plifenate. The productivity of various mosquitoes in different habitat types is very heterogeneous. It is particularly important to modify human activity and the environment to achieve effective mosquito vector control. For effective larval control, the type of habitat should be considered, and the most productive habitat type should be given priority in mosquito abatement programs.

Cytokines and their association with insulin resistance in obese pregnant women with different levels of physical activity.

PubMed

Nayak, Minakshi; Eekhoff, Marelise E W; Peinhaupt, Miriam; Heinemann, Akos; Desoye, Gernot; van Poppel, Mireille N M

2016-01-01

Cytokines contribute to insulin resistance in pregnancy, but the role of distinct cytokines is not fully understood. To study whether cytokines produced by tissues other than skeletal muscle are associated with glucose and insulin metabolism activity in overweight and obese women and to study whether these associations can be modified by physical activity. A longitudinal study with 44 overweight and obese pregnant women was conducted. Changes in cytokines levels (IFN-γ, IP-10, IL1-α, MIP1-α, adiponectin and leptin) and ICAM1 from early (15wk) to late (32wk) pregnancy were determined. Physical activity was measured objectively with accelerometers. In linear regression models, the associations between (changes in) cytokine levels and fasting glucose, fasting insulin and HOMA-IR were studied. Both IFN-γ and IP-10 levels increased from early to late pregnancy, and adiponectin levels decreased. IFN-γ and IP-10 were positively associated with fasting glucose, whereas IL-1α, ICAM1 and adiponectin were inversely associated with insulin and insulin resistance. The association of IL-1α with insulin and insulin resistance was only found in women with low levels of physical activity. IFN-γ, IP-10, IL1-α, ICAM1, and adiponectin may play a role in glucose and insulin metabolism in pregnancy. The relationship of IL-1α with insulin and insulin resistance might be moderated by levels of physical activity. Further studies are required to confirm the role of these cytokines in glucose and insulin metabolism in obese pregnant women. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mendelian Randomization Studies Do Not Support a Role for Raised Circulating Triglyceride Levels Influencing Type 2 Diabetes, Glucose Levels, or Insulin Resistance

PubMed Central

De Silva, N. Maneka G.; Freathy, Rachel M.; Palmer, Tom M.; Donnelly, Louise A.; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N.; Shields, Beverley; Knight, Beatrice A.; Ward, Kirsten J.; Sandhu, Manjinder S.; Harbord, Roger M.; McCarthy, Mark I.; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T.; Wareham, Nicholas; Lawlor, Debbie A.; Morris, Andrew D.; Palmer, Colin N.A.; Frayling, Timothy M.

2011-01-01

OBJECTIVE The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance. RESEARCH DESIGN AND METHODS We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies. RESULTS Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52–0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97–1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI −0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [−0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log10 triglycerides: 0.61 [95% CI 0.45–0.83]; P = 0.002). CONCLUSIONS Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is

Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.

PubMed

De Silva, N Maneka G; Freathy, Rachel M; Palmer, Tom M; Donnelly, Louise A; Luan, Jian'an; Gaunt, Tom; Langenberg, Claudia; Weedon, Michael N; Shields, Beverley; Knight, Beatrice A; Ward, Kirsten J; Sandhu, Manjinder S; Harbord, Roger M; McCarthy, Mark I; Smith, George Davey; Ebrahim, Shah; Hattersley, Andrew T; Wareham, Nicholas; Lawlor, Debbie A; Morris, Andrew D; Palmer, Colin N A; Frayling, Timothy M

2011-03-01

The causal nature of associations between circulating triglycerides, insulin resistance, and type 2 diabetes is unclear. We aimed to use Mendelian randomization to test the hypothesis that raised circulating triglyceride levels causally influence the risk of type 2 diabetes and raise normal fasting glucose levels and hepatic insulin resistance. We tested 10 common genetic variants robustly associated with circulating triglyceride levels against the type 2 diabetes status in 5,637 case and 6,860 control subjects and four continuous outcomes (reflecting glycemia and hepatic insulin resistance) in 8,271 nondiabetic individuals from four studies. Individuals carrying greater numbers of triglyceride-raising alleles had increased circulating triglyceride levels (SD 0.59 [95% CI 0.52-0.65] difference between the 20% of individuals with the most alleles and the 20% with the fewest alleles). There was no evidence that the carriers of greater numbers of triglyceride-raising alleles were at increased risk of type 2 diabetes (per weighted allele odds ratio [OR] 0.99 [95% CI 0.97-1.01]; P = 0.26). In nondiabetic individuals, there was no evidence that carriers of greater numbers of triglyceride-raising alleles had increased fasting insulin levels (SD 0.00 per weighted allele [95% CI -0.01 to 0.02]; P = 0.72) or increased fasting glucose levels (0.00 [-0.01 to 0.01]; P = 0.88). Instrumental variable analyses confirmed that genetically raised circulating triglyceride levels were not associated with increased diabetes risk, fasting glucose, or fasting insulin and, for diabetes, showed a trend toward a protective association (OR per 1-SD increase in log(10) triglycerides: 0.61 [95% CI 0.45-0.83]; P = 0.002). Genetically raised circulating triglyceride levels do not increase the risk of type 2 diabetes or raise fasting glucose or fasting insulin levels in nondiabetic individuals. One explanation for our results is that raised circulating triglycerides are predominantly secondary to

Relevant role of efflux pumps in high levels of rifaximin resistance in Escherichia coli clinical isolates.

PubMed

Gomes, C; Ruiz, L; Pons, M J; Ochoa, T J; Ruiz, J

2013-09-01

Enteropathogens have shown a high level of resistance against commonly used antibacterial drugs in Peru and it is necessary to explore alternative treatments. The aim of this study was to analyse the in vitro activity of rifaximin against diarrhoeagenic and commensal Escherichia coli in children less than 2 years of age. The minimal inhibitory concentration (MIC) to rifampicin and rifaximin was determined for 210 strains in the presence and absence of phenyl-arginine-β-naphthylamide (PAβN) and the mechanisms of resistance were investigated. The MIC levels ranged between 8 and >256 mg/litre and the predominant mechanism of resistance to rifaximin was the efflux pumps inhibited by PAβN in 95.2% of the isolates. The present MIC values are higher than those observed in other studies. Efflux pumps inhibited by PAβN were the cause of the rifaximin resistance in the majority of cases and suggest the presence of an environmental selective pressure. Consequently, rifaximin should be used with caution in the treatment of diarrhoea in Peru.

Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

PubMed Central

Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

2016-01-01

The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

Evaluation of tumor necrosis factor alpha serum level in obese and lean women with clomiphene citrate-resistant polycystic ovary disease.

PubMed

Seyam, Emaduldin; Hasan, Momen; Khalifa, Eissa M; Ramadan, Ahmad; Hefzy, Enas

2017-11-01

The aim of this work was to investigate the level of the serum level of tumor necrosis factor alpha (TNF-α) as an inflammatory biomarker in lean and obese women with polycystic ovary disease (PCOD), who are resistant to clomiphene citrate (CCR-PCOD). It is a case-controlled study, where 150 (n = 150) PCOD women (study group), who are resistant to clomiphene citrate (CCR-PCOD) had been recruited, in addition to 100 (n = 100) women with PCOD, who are not resistant to clomiphene citrate (NCCR-PCOD) as the first control group, and another 100 women (n = 100) fertile women with normal reproductive health, as the second control group. All the recruited subjects had been divided into subgroups according to the BMI: One obese group with BMI ≥ 27 and the second lean group with BMI < 27. TNF-α had been measured in all women groups recruited, in addition to the other essential, basic and PCOD-relevant biochemical and hormonal tests. TNF-α level was found to be higher in all PCOD women, either the study or control PCOD groups, than the fertile control group (49.93 ± 3.39 versus 35.83 ± 2.47 pg/ml, p < 0.001). The level of TNF-α has come highest in the obese clomiphene citrate-resistant PCOD women (obese CCR-PCOD), while the lowest has come in the lean PCOD women, who are not resistant to clomiphene citrate (NCCR-PCOD). Free Androgen Index (FAI) and androgenic obesity with higher W/H ratio were clearly going with TNF-α pattern and have come higher in all PCOD compared to the fertile control group. Insulin resistance (IR) shows a positive correlation with BMI regardless off PCOD status and androgen level as well. The level of other basic and PCOD-relevant hormones like FSH, TSH and prolactin have never shown statistically significant differences between all the study and control groups, except LH serum level which has shown a nonsignificant higher level in all PCOD women included either resistant to CC or not. TNF-α serum level has

Reliability and clinical relevance of the HIV-1 drug resistance test in patients with low viremia levels.

PubMed

Santoro, Maria Mercedes; Fabeni, Lavinia; Armenia, Daniele; Alteri, Claudia; Di Pinto, Domenico; Forbici, Federica; Bertoli, Ada; Di Carlo, Domenico; Gori, Caterina; Carta, Stefania; Fedele, Valentina; D'Arrigo, Roberta; Berno, Giulia; Ammassari, Adriana; Pinnetti, Carmela; Nicastri, Emanuele; Latini, Alessandra; Tommasi, Chiara; Boumis, Evangelo; Petrosillo, Nicola; D'Offizi, Gianpiero; Andreoni, Massimo; Ceccherini-Silberstein, Francesca; Antinori, Andrea; Perno, Carlo Federico

2014-04-01

We evaluated reliability and clinical usefulness of genotypic resistance testing (GRT) in patients for whom combination antiretroviral therapy (cART) was unsuccessful with viremia levels 50-1000 copies/mL, for whom GRT is generally not recommended by current guidelines. The genotyping success rate was evaluated in 12 828 human immunodeficiency virus type 1 (HIV-1) plasma samples with viremia >50 copies/mL, tested using the commercial ViroSeq HIV-1 Genotyping System or a homemade system. Phylogenetic analysis was performed to test the reliability and reproducibility of the GRT at low-level viremia (LLV). Drug resistance was evaluated in 3895 samples from 2200 patients for whom treatment was unsuccessful (viremia >50 copies/mL) by considering the resistance mutations paneled in the 2013 International Antiviral Society list. Overall, the success rate of amplification/sequencing was 96.4%. Viremia levels of 50-200 and 201-500 copies/mL afforded success rates of 67.2% and 88.1%, respectively, reaching 93.2% at 501-1000 copies/mL and ≥97.3% above 1000 copies/mL. A high homology among sequences belonging to the same subject for 96.4% of patients analyzed was found. The overall resistance prevalence was 74%. Drug resistance was commonly found also at LLV. In particular, by stratifying for different viremia ranges, detection of resistance was as follows: 50-200 copies/mL = 52.8%; 201-500 = 70%; 501-1000 = 74%; 1001-10 000 = 86.1%; 10 001-100 000 = 76.7%; and >100 000 = 63% (P < .001). Similar bell-shaped results were found when the GRT analysis was restricted to 2008-2012, although at a slightly lower prevalence. In patients failing cART with LLV, HIV-1 genotyping provides reliable and reproducible results that are informative about emerging drug resistance.

Accumulation of multiple mutations in linezolid-resistant Staphylococcus epidermidis causing bloodstream infections; in silico analysis of L3 amino acid substitutions that might confer high-level linezolid resistance.

PubMed

Ikonomidis, Alexandros; Grapsa, Anastasia; Pavlioglou, Charikleia; Demiri, Antonia; Batarli, Alexandra; Panopoulou, Maria

2016-12-01

Fifty-six Staphylococcus epidermidis clinical isolates, showing high-level linezolid resistance and causing bacteremia in critically ill patients, were studied. All isolates belonged to ST22 clone and carried the T2504A and C2534T mutations in gene coding for 23SrRNA as well as the C189A, G208A, C209T and G384C missense mutations in L3 protein which resulted in Asp159Tyr, Gly152Asp and Leu94Val substitutions. Other silent mutations were also detected in genes coding for ribosomal proteins L3 and L22. In silico analysis of missense mutations showed that although L3 protein retained the sequence of secondary motifs, the tertiary structure was influenced. The observed alteration in L3 protein folding provides an indication on the putative role of L3-coding gene mutations in high-level linezolid resistance. Furthermore, linezolid pressure in health care settings where linezolid consumption is of high rates might lead to the selection of resistant mutants possessing L3 mutations that might confer high-level linezolid resistance.

Human isolates of Salmonella enterica serovar Typhimurium from Taiwan displayed significantly higher levels of antimicrobial resistance than those from Denmark.

PubMed

Torpdahl, Mia; Lauderdale, Tsai-Ling; Liang, Shiu-Yun; Li, Ishien; Wei, Sung-Hsi; Chiou, Chien-Shun

2013-02-01

Salmonella enterica serovar Typhimurium is a major zoonotic pathogen with a high prevalence of antimicrobial resistance. This pathogen can disseminate across borders and spread far distances via the food trade and international travel. In this study, we compared the genotypes and antimicrobial resistance of 378 S. Typhimurium isolates collected in Taiwan and Denmark between 2009 and 2010. Genotyping revealed that many S. Typhimurium strains were concurrently circulating in Taiwan, Denmark and other countries in 2009 and 2010. When compared to the isolates collected from Denmark, the isolates from Taiwan displayed a significantly higher level of resistance to 11 of the 12 tested antimicrobials. Seven genetic clusters (A-G) were designated for the isolates. A high percentage of the isolates in genetic clusters C, F and G were multidrug-resistant. Of the isolates in cluster C, 79.2% were ASSuT-resistant, characterized by resistance to ampicillin, streptomycin, sulfamethoxazole, and tetracycline. In cluster F, 84.1% of the isolates were ACSSuT-resistant (resistant to ASSuT and chloramphenicol). Cluster G was unique to Taiwan and characterized in most isolates by the absence of three VNTRs (ST20, ST30 and STTR6) as well as a variety of multidrug resistance profiles. This cluster exhibited very high to extremely high levels of resistance to several first-line drugs, and among the seven clusters, it displayed the highest levels of resistance to cefotaxime and ceftazidime, ciprofloxacin and gentamicin. The high prevalence of antimicrobial resistance in S. Typhimurium from Taiwan highlights the necessity to strictly regulate the use of antimicrobials in the agriculture and human health care sectors. Copyright © 2012 Elsevier B.V. All rights reserved.

Pyrethroid-Resistance Level Affects Performance of Larvicides and Adulticides From Different Insecticide Classes in Populations of Listronotus maculicollis (Coleoptera: Curculionidae).

PubMed

Koppenhöfer, Albrecht M; Kostromytska, Olga S; Wu, Shaohui

2018-05-25

The annual bluegrass weevil, Listronotus maculicollis Kirby (Coleoptera: Curculionidae), is a major pest of golf course turf in eastern North America with widespread insecticide resistance. This study examined the effect of pyrethroid-resistance level on the efficacy of adulticides and larvicides from different insecticide classes commonly used for L. maculicollis management through greenhouse and field studies. The tested populations had previously been determined to be susceptible, moderately resistant, resistant, and highly resistant to the pyrethroid bifenthrin. Targeting adults, efficacy was significantly reduced for bifenthrin against the highly resistant population and for the spinosyn spinosad and the oxadizine indoxacarb against the resistant and highly resistant populations. Efficacy of the organophosphate chlorpyrifos was not significantly reduced. No adulticide provided significant control of resistant and highly resistant populations. Targeting larvae, the efficacy of spinosad and the anthranilic diamide cyantraniliprole was marginally reduced against the highly resistant population. Significant reductions in efficacy and no significant control were observed for indoxacarb against the highly resistant population and for the neonicotinoid clothianidin, the anthranilic diamide chlorantraniliprole, and the organophosphate trichlorfon against the resistant and highly resistant populations. Our findings lay the groundwork for management recommendations for populations with different resistance levels. Generally, synthetic insecticide applications should be minimized with greater use of larvicides supplemented with nonchemical control alternatives. The remaining effective larvicides should be rotated using cyantraniliprole, spinosad, and indoxacarb against resistant and cyantraniliprole and spinosad against highly resistant populations.

Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study.

PubMed

Miller, Melissa R; Pereira, Rocio I; Langefeld, Carl D; Lorenzo, Carlos; Rotter, Jerome I; Chen, Yii-Der Ida; Bergman, Richard N; Wagenknecht, Lynne E; Norris, Jill M; Fingerlin, Tasha E

2012-09-01

We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study. In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S(I)); and 3) levels of adiposity and S(I), additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S(I.) After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P = 2.33 × 10(-3); SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S(I) (P = 8.10 × 10(-11)). Increasing BMI, VAT, and SAT were also associated with decreasing S(I) (BMI: P = 4.98 × 10(-71); VAT: P = 1.48 × 10(-64); SAT: P = 4.21 × 10(-62)), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S(I) (P = 0.021). Although levels of circulating FFA are associated both with increasing adiposity and decreasing S(I), they do not appear to mediate the association between levels of adiposity and S(I) in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.

Characteristics of carboxylesterase genes and their expression-level between acaricide-susceptible and resistant Tetranychus cinnabarinus (Boisduval).

PubMed

Wei, Peng; Shi, Li; Shen, Guangmao; Xu, Zhifeng; Liu, Jialu; Pan, Yu; He, Lin

2016-07-01

Carboxylesterases (CarEs) play important roles in metabolism and detoxification of dietary and environmental xenobiotics in insects and mites. On the basis of the Tetranychuscinnabarinus transcriptome dataset, 23 CarE genes (6 genes are full sequence and 17 genes are partial sequence) were identified. Synergist bioassay showed that CarEs were involved in acaricide detoxification and resistance in fenpropathrin- (FeR) and cyflumetofen-resistant (CyR) strains. In order to further reveal the relationship between CarE gene's expression and acaricide-resistance in T. cinnabarinus, we profiled their expression in susceptible (SS) and resistant strains (FeR, and CyR). There were 8 and 4 over-expressed carboxylesterase genes in FeR and CyR, respectively, from which the over-expressions were detected at mRNA level, but not DNA level. Pesticide induction experiment elucidated that 4 of 8 and 2 of 4 up-regulated genes were inducible with significance in FeR and CyR strains, respectively, but they could not be induced in SS strain, which indicated that these genes became more enhanced and effective to withstand the pesticides' stress in resistant T. cinnabarinus. Most expression-changed and all inducible genes possess the Abhydrolase_3 motif, which is a catalytic domain for hydrolyzing. As a whole, these findings in current study provide clues for further elucidating the function and regulation mechanism of these carboxylesterase genes in T. cinnabarinus' resistance formation. Copyright © 2015 Elsevier B.V. All rights reserved.

Dietary Leucine - An Environmental Modifier of Insulin Resistance Acting on Multiple Levels of Metabolism

PubMed Central

Macotela, Yazmin; Emanuelli, Brice; Bång, Anneli M.; Espinoza, Daniel O.; Boucher, Jeremie; Beebe, Kirk; Gall, Walter; Kahn, C. Ronald

2011-01-01

Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor—leucine—can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD). Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance. PMID:21731668

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension.

PubMed

Dudenbostel, Tanja; Ghazi, Lama; Liu, Mingchun; Li, Peng; Oparil, Suzanne; Calhoun, David A

2016-10-01

Prospective studies indicate that hyperaldosteronism is found in 20% of patients with resistant hypertension. A small number of observational studies in normotensive and hypertensive patients suggest a correlation between aldosterone levels and obesity while others could not confirm these findings. The correlation between aldosterone levels and body mass index (BMI) in patients with resistant hypertension has not been previously investigated. Our objective was to determine whether BMI is positively correlated with plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, and 24-hour urinary aldosterone in black and white patients. We performed a cross-sectional analysis of a large diverse cohort (n=2170) with resistant hypertension. The relationship between plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, 24-hour urinary aldosterone, and BMI was investigated for the entire cohort, by sex and race (65.3% white, 40.3% men). We demonstrate that plasma aldosterone concentration and aldosterone:renin ratio were significantly correlated to BMI (P<0.0001) across the first 3 quartiles, but not from the 3rd to 4th quartile of BMI. Plasma renin activity was not correlated with BMI. Twenty-four-hour urinary aldosterone was positively correlated across all quartiles of BMI for the cohort (P<0.0001) and when analyzed by sex (men P<0.0001; women P=0.0013) and race (P<0.05), and stronger for men compared with women (r=0.19, P<0.001 versus r=0.05, P=0.431, P=0.028) regardless of race. In both black and white patients, aldosterone levels were positively correlated to increasing BMI, with the correlation being more pronounced in black and white men. These findings suggest that obesity, particularly the abdominal obesity typical of men, contributes to excess aldosterone in patients with resistant hypertension. © 2016 American Heart Association, Inc.

High-Level Resistance of Staphylococcus aureus to β-Lactam Antibiotics Mediated by Penicillin-Binding Protein 4 (PBP4).

PubMed

Hamilton, Stephanie M; Alexander, J Andrew N; Choo, Eun Ju; Basuino, Li; da Costa, Thaina M; Severin, Anatoly; Chung, Marilyn; Aedo, Sandra; Strynadka, Natalie C J; Tomasz, Alexander; Chatterjee, Som S; Chambers, Henry F

2017-06-01

Penicillin-binding protein 4 (PBP4), a nonessential, low-molecular-weight penicillin-binding protein of Staphylococcus aureus , has been implicated in low-level resistance to β-lactam antibiotics, although the mechanism is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain, CRB, which expresses high-level resistance to β-lactams, including resistance to the new-generation cephalosporins active against methicillin-resistant strains of S. aureus These mutations did not appreciably alter the β-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to that of wild-type PBP4. Compared to the susceptible parent strain, COLnex, the CRB strain produces a highly cross-linked cell wall peptidoglycan, indicative of increased transpeptidase activity. The pbp4 promoter mutation of CRB was associated with greatly increased amounts of PBP4 in membranes compared to those in the COLnex parent. Replacement of the native promoter of COLnex with the mutant promoter of CRB resulted in increased amounts of PBP4 in membranes and a highly cross-linked cell wall. PBP4 can be repurposed to provide essential transpeptidase activity in vivo and confer high-level resistance to β-lactam antibiotics, such as ceftobiprole and ceftaroline. Copyright © 2017 American Society for Microbiology.

High-Level Resistance of Staphylococcus aureus to β-Lactam Antibiotics Mediated by Penicillin-Binding Protein 4 (PBP4)

PubMed Central

Hamilton, Stephanie M.; Alexander, J. Andrew N.; Choo, Eun Ju; Basuino, Li; da Costa, Thaina M.; Severin, Anatoly; Chung, Marilyn; Aedo, Sandra; Strynadka, Natalie C. J.; Tomasz, Alexander; Chatterjee, Som S.

2017-01-01

ABSTRACT Penicillin-binding protein 4 (PBP4), a nonessential, low-molecular-weight penicillin-binding protein of Staphylococcus aureus, has been implicated in low-level resistance to β-lactam antibiotics, although the mechanism is unknown. Mutations in PBP4 and its promoter were identified in a laboratory-generated mutant strain, CRB, which expresses high-level resistance to β-lactams, including resistance to the new-generation cephalosporins active against methicillin-resistant strains of S. aureus. These mutations did not appreciably alter the β-lactam antibiotic binding affinity of purified recombinant mutant PBP4 compared to that of wild-type PBP4. Compared to the susceptible parent strain, COLnex, the CRB strain produces a highly cross-linked cell wall peptidoglycan, indicative of increased transpeptidase activity. The pbp4 promoter mutation of CRB was associated with greatly increased amounts of PBP4 in membranes compared to those in the COLnex parent. Replacement of the native promoter of COLnex with the mutant promoter of CRB resulted in increased amounts of PBP4 in membranes and a highly cross-linked cell wall. PBP4 can be repurposed to provide essential transpeptidase activity in vivo and confer high-level resistance to β-lactam antibiotics, such as ceftobiprole and ceftaroline. PMID:28373193

Biochar amendment changes jasmonic acid levels in two rice varieties and alters their resistance to herbivory

PubMed Central

Shahzad, Raheem; Hamayun, Muhammad; Asaf, Sajjad; Khan, Abdul Latif; Kang, Sang-Mo; Yun, Sopheap; Kim, Kyung-Min; Lee, In-Jung

2018-01-01

Biochar addition to soil not only sequesters carbon for the long-term but enhances agricultural productivity. Several well-known benefits arise from biochar amendment, including constant provision of nutrients, increased soil moisture retention, decreased soil bulk density, and sometimes the induction of systemic resistance against foliar and soil borne plant pathogens. However, no research has investigated the potential of biochar to increase resistance against herbivory. The white-backed plant hopper (WBPH) (Sogatella furcifera Horváth) is a serious agricultural pest that targets rice (Oryza sativa L.), a staple crop that feeds half of the world’s human population. Therefore, we investigated the (1) optimization of biochar amendment levels for two rice varieties (‘Cheongcheong’ and ‘Nagdong’) and (2) subsequent effects of different biochar amendments on resistance and susceptibility of these two varieties to WBPH infestation. Initial screening results for the optimization level revealed that the application of biochar 10% (w/w) to the rooting media significantly improved plant physiological characteristics of both rice varieties. However, levels of biochar amendment, mainly 1, 2, 3, and 20%, resulted in negative effects on plant growth characteristics. Cheongcheong and Nagdong rice plants grown with the optimum biochar level showed contrasting reactions to WBPH infestation. Specifically, biochar application significantly increased plant growth characteristics of Nagdong when exposed to WBPH infestation and significantly decreased these characteristics in Cheongcheong. The amount of WBPH-induced damage to plants was significantly lower and higher in Nagdong and Cheongcheong, respectively, compared to that in the controls. Higher levels of jasmonic acid caused by the biochar priming effect could have accumulated in response to WBPH infestation, resulting in a maladaptive response to stress, negatively affecting growth and resistance to WBPH in

Biochar amendment changes jasmonic acid levels in two rice varieties and alters their resistance to herbivory.

PubMed

Waqas, Muhammad; Shahzad, Raheem; Hamayun, Muhammad; Asaf, Sajjad; Khan, Abdul Latif; Kang, Sang-Mo; Yun, Sopheap; Kim, Kyung-Min; Lee, In-Jung

2018-01-01

Biochar addition to soil not only sequesters carbon for the long-term but enhances agricultural productivity. Several well-known benefits arise from biochar amendment, including constant provision of nutrients, increased soil moisture retention, decreased soil bulk density, and sometimes the induction of systemic resistance against foliar and soil borne plant pathogens. However, no research has investigated the potential of biochar to increase resistance against herbivory. The white-backed plant hopper (WBPH) (Sogatella furcifera Horváth) is a serious agricultural pest that targets rice (Oryza sativa L.), a staple crop that feeds half of the world's human population. Therefore, we investigated the (1) optimization of biochar amendment levels for two rice varieties ('Cheongcheong' and 'Nagdong') and (2) subsequent effects of different biochar amendments on resistance and susceptibility of these two varieties to WBPH infestation. Initial screening results for the optimization level revealed that the application of biochar 10% (w/w) to the rooting media significantly improved plant physiological characteristics of both rice varieties. However, levels of biochar amendment, mainly 1, 2, 3, and 20%, resulted in negative effects on plant growth characteristics. Cheongcheong and Nagdong rice plants grown with the optimum biochar level showed contrasting reactions to WBPH infestation. Specifically, biochar application significantly increased plant growth characteristics of Nagdong when exposed to WBPH infestation and significantly decreased these characteristics in Cheongcheong. The amount of WBPH-induced damage to plants was significantly lower and higher in Nagdong and Cheongcheong, respectively, compared to that in the controls. Higher levels of jasmonic acid caused by the biochar priming effect could have accumulated in response to WBPH infestation, resulting in a maladaptive response to stress, negatively affecting growth and resistance to WBPH in Cheongcheong. This

Modulation in vitro and in vivo of cytotoxicity but not cellular levels of doxorubicin by the calmodulin inhibitor trifluoperazine is dependent on the level of resistance.

PubMed Central

Ganapathi, R.; Schmidt, H.; Grabowski, D.; Melia, M.; Ratliff, N.

1988-01-01

The role of the calmodulin inhibitor trifluoperazine (TFP) in modulating the cellular levels and cytotoxicity in vitro and antitumour effects in vivo of doxorubicin (DOX), was evaluated in progressively DOX-resistant (5- to 40-fold) sublines of B16-BL6 mouse melanoma. In parental-sensitive B16-BL6 cells treated for 3 h, the IC50 of DOX was 0.1 microgram ml-1, and a less than 2-fold enhancement in DOX cell kill in the presence of a noncytotoxic concentration of 5 microM TFP was observed. However, in the DOX-resistant sublines, the IC50 was 0.7 to 5.0 micrograms ml-1 DOX in the absence of 5 microM TFP and 0.3 to 0.7 microgram ml-1 DOX in the presence of 5 microM TFP. The 2- to 7.5-fold decrease in the IC50 of DOX in the presence of 5 microM TFP, was dependent on the level of DOX-resistance in the various sublines. Compared to parental-sensitive cells, a 2-fold decrease in DOX-accumulation was evident only in the 40-fold DOX-resistant subline. Further, maximal enhancement (50%) of cellular DOX accumulation in the presence of 5 microM TFP was observed only in the 40-fold resistant cells treated with 5.0 micrograms ml-1 DOX. Retention of DOX in the 40-fold resistant subline was only 20% lower than similarly treated sensitive cells, and the inclusion of TFP increased DOX retention less than 10-15%. Antitumour studies in mice with experimental pulmonary metastases revealed that although DOX and DOX plus TFP had similar antitumour activity with the parental sensitive B16-BL6 cells, the combination of DOX plus TFP was significantly more effective than DOX alone with the DOX-resistant sublines. No overt toxicity was observed in normal mice treated with doses of TFP, DOX or DOX plus TFP used for in vivo chemotherapy studies. Results from this study suggest that gross cellular DOX levels do not appear to correlate with the magnitude of resistance, and the effects of TFP in modulating DOX resistance is possibly due to mechanisms other than mere alterations in cellular drug

High-Level Fosfomycin Resistance in Vancomycin-Resistant Enterococcus faecium

PubMed Central

Guo, Yan; Tomich, Adam D.; McElheny, Christi L.; Cooper, Vaughn S.; Tait-Kamradt, Amelia; Wang, Minggui; Hu, Fupin; Rice, Louis B.; Sluis-Cremer, Nicolas

2017-01-01

Of 890 vancomycin-resistant Enterococcus faecium isolates obtained by rectal screening from patients in Pittsburgh, Pennsylvania, USA, 4 had MICs >1,024 μg/mL for fosfomycin. These isolates had a Cys119Asp substitution in the active site of UDP-N-acetylglucosamine enolpyruvyl transferase. This substitution increased the fosfomycin MIC >4-fold and rendered this drug inactive in biochemical assays. PMID:29048285

Low levels of PRB3 mRNA are associated with dopamine-agonist resistance and tumor recurrence in prolactinomas.

PubMed

Wang, Fei; Gao, Hua; Li, Chuzhong; Bai, Jiwei; Lu, Runchun; Cao, Lei; Wu, Yongtu; Hong, Lichuan; Wu, Yonggang; Lan, Xiaolei; Zhang, Yazhuo

2014-01-01

Prolactinomas, or prolactin-secreting adenomas, constitute the most common type of hyperfunctioning pituitary adenoma. Dopamine agonists are used as first-line medication for prolactinomas, but the tumors are resistant to the therapy in 5-18 % of patients. To explore potential mechanisms of resistance to bromocriptine (a dopamine agonist), we analyzed six responsive prolactinomas and six resistant prolactinomas by whole-exome sequencing. We identified ten genes with sequence variants that were differentially found in the two groups of tumors. The expression of these genes was then quantified by real-time reverse-transcription PCR (RT-qPCR) in the 12 prolactinomas and in six normal pituitary glands. The mRNA levels of one of the genes, PRB3, were about fourfold lower in resistant prolactinomas than in the responsive tumors (p = 0.02). Furthermore, low PRB3 expression was also associated with tumor recurrence. Our results suggest that low levels of PRB3 mRNA may have a role in dopamine-agonist resistance and tumor recurrence of prolactinomas.

Circulating CTRP9 levels are increased in patients with newly diagnosed type 2 diabetes and correlated with insulin resistance.

PubMed

Jia, Yanjun; Luo, Xiaohe; Ji, Ying; Xie, Jingwen; Jiang, Han; Fu, Mao; Li, Xiaoqiang

2017-09-01

C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has been shown to promote lipid metabolism, enhance insulin sensitivity and protect against cardiovascular disease. However, previous studies in humans have produced controversial results regarding the association between CTRP9 and insulin resistance. The objective of this study was to evaluate the relationships between CTRP9 and insulin resistance in Chinese population. Subjects with normal glucose tolerance (NGT, n=108), impaired glucose tolerance (IGT, n=92), and newly diagnosed type 2 diabetes mellitus (nT2DM, n=106) were recruited to determining the circulating CTRP9 and adiponectin levels by enzyme linked immunosorbent assay. Anthropometric and biochemical measurements related to insulin resistance, adiposity and lipid profile were examined for all participants. Oral glucose tolerance test was performed in healthy subjects (17 male and 17 female). Circulating CTRP9 level was significantly higher in both IGT and nT2DM than in individuals with NGT. Overweight/obese subjects had much higher CTRP9 levels than lean individuals, and in all subjects, females also had higher CTRP9 levels than males. In addition, circulating CTRP9 level was positively correlated with markers of obesity and insulin resistance, including body mass index, fasting blood glucose, insulin, HbA1c, homeostasis model assessment of insulin resistance and low-density lipoprotein-cholesterol, while was inversely correlated with high-density lipoprotein-cholesterol and adiponectin. Moreover, hyperglycemia during an oral glucose challenge increased circulating CTRP9 concentrations. We conclude that CTRP9 was strongly associated with insulin resistance, suggesting that CTRP9 might be important in the development of type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of resistance, cross-resistance, and stability of resistance to new chemistry insecticides in Bemisia tabaci (Homoptera: Aleyrodidae).

PubMed

Basit, Muhammad; Saeed, Shafqat; Saleem, Mushtaq Ahmad; Denholm, Ian; Shah, Maqbool

2013-06-01

Resistance levels in whitefly, Bemisia tabaci (Gennadius) collections from cotton and sunflower (up to four districts) for five neonicotinoids and two insect growth regulators (IGRs) were investigated for two consecutive years. Based on the LC50(s), all collections showed slight to moderate levels of resistance for the tested insecticides compared with the laboratory susceptible population. The data also indicated that cotton and sunflower collections had similar resistance levels. In comparison (four collections), Vehari collections showed higher resistance for acetamiprid, thiacloprid, and nitenpyram compared with those of others. Average resistance ratios for acetamiprid, thiacloprid, and nitenpyram ranged from 5- to 13-, 4- to 8-, and 9- to 13-fold, respectively. Multan and Vehari collections also exhibited moderate levels (9- to 16-fold) of resistance to buprofezin. Furthermore, toxicity of neonicotinoids against immature stages was equal to that of insect growth regulators. The data also suggested that resistance in the field populations was stable. After selection for four generations with bifenthrin (G1 to G4), resistance to bifenthrin increased to 14-fold compared with the laboratory susceptible population. Selection also increased resistance to fenpropathrin, lambdacyhalothrin, imidacloprid, acetamiprid, and diafenthuron. Cross-resistance and stability of resistance in the field populations is of some concern. Rotation of insecticides having no cross-resistance and targeting the control against immature stages may control the resistant insects, simultaneously reducing the selection pressure imposed.

Variation in P450-mediated fenvalerate resistance levels is not correlated with CYP337B3 genotype in Chinese populations of Helicoverpa armigera.

PubMed

Han, Yangchun; Yu, Wanting; Zhang, Weiqing; Yang, Yihua; Walsh, Tom; Oakeshott, John G; Wu, Yidong

2015-06-01

Metabolic resistance to synthetic pyrethroids in Helicoverpa   armigera has recently been associated with the chimeric cytochrome P450 enyzme CYP337B3. One variant of the latter, CYP337B3v1, accounts for 40-50 fold resistance to fenvalerate in an Australian population while a second variant, CYP337B3v2, has been associated with ~7 fold resistance to cypermethrin in a Pakistani population. Here we show that ~250-1200 fold resistance to fenvalerate in populations of the species from northern and northwestern China is largely due to P450-based metabolism, and that CYP337B3v2 is also at high frequency in these populations but absent in a susceptible control strain. However we find little correlation between the level of resistance and CYP337B3v2 frequency, either across the resistant populations studied, or over time within them. While there is variation between populations in the levels of CYP337B3v2 expression, this is not correlated with the level of resistance either. These data suggest that much of the variation in the level of fenvalerate resistance in China is explained by P450s other than CYP337B3. We also find that both the level of resistance and CYP337B3v2 frequency decline in field populations transferred to the laboratory and remained there without fenvalerate exposure, suggesting a fitness cost to both characters in the absence of the pesticide pressure. However the declines in the two characters are not well correlated across populations, again consistent with a large contribution to the variation in resistance levels from factors other than CYP337B3. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative Study of Serum Leptin and Insulin Resistance Levels Between Korean Postmenopausal Vegetarian and Non-vegetarian Women.

PubMed

Kim, Mi-Hyun; Bae, Yun-Jung

2015-07-01

The present study was conducted to compare serum leptin and insulin resistance levels between Korean postmenopausal long-term semi-vegetarians and non-vegetarians. Subjects of this study belonged to either a group of postmenopausal vegetarian women (n = 54), who maintained a semi-vegetarian diet for over 20 years or a group of non-vegetarian controls. Anthropometric characteristics, serum leptin, serum glucose, serum insulin, insulin resistance (HOMA-IR; Homeostasis Model Assessment of Insulin Resistance), and nutrient intake were compared between the two groups. The vegetarians showed significantly lower body weight (p < 0.01), body mass index (p < 0.001), percentage (%) of body fat (p < 0.001), and serum levels of leptin (p < 0.05), glucose (p < 0.001), and insulin (p < 0.01), than the non-vegetarians. The HOMA-IR of the vegetarians was significantly lower than that of the non-vegetarians (p < 0.01) after adjustment for the % of body fat. A long-term vegetarian diet might be related to lower insulin resistance independent of the % of body fat in postmenopausal women.

Comparative Study of Serum Leptin and Insulin Resistance Levels Between Korean Postmenopausal Vegetarian and Non-vegetarian Women

PubMed Central

Kim, Mi-Hyun

2015-01-01

The present study was conducted to compare serum leptin and insulin resistance levels between Korean postmenopausal long-term semi-vegetarians and non-vegetarians. Subjects of this study belonged to either a group of postmenopausal vegetarian women (n = 54), who maintained a semi-vegetarian diet for over 20 years or a group of non-vegetarian controls. Anthropometric characteristics, serum leptin, serum glucose, serum insulin, insulin resistance (HOMA-IR; Homeostasis Model Assessment of Insulin Resistance), and nutrient intake were compared between the two groups. The vegetarians showed significantly lower body weight (p < 0.01), body mass index (p < 0.001), percentage (%) of body fat (p < 0.001), and serum levels of leptin (p < 0.05), glucose (p < 0.001), and insulin (p < 0.01), than the non-vegetarians. The HOMA-IR of the vegetarians was significantly lower than that of the non-vegetarians (p < 0.01) after adjustment for the % of body fat. A long-term vegetarian diet might be related to lower insulin resistance independent of the % of body fat in postmenopausal women. PMID:26251836

Two-level magnetovariational measurements for the determination of underground resistivity distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patella, D.; Siniscalchi, A.

1994-07-01

The authors investigate, from a theoretical point of view, the possibility of performing marine two-level magnetovariational measurements. An apparent resistivity function is defined and calculated after solving the differential equation governing the behavior of the natural magnetic field variations inside a one-dimensional earth. In order to generalize the problem, a frequency-dependent resistivity is assumed to characterize the layers and the distortions caused by the polarization effects are carefully analyzed. The computation of three-layer amplitude and phase diagrams for the apparent resistivity function shows that, in the case of an intermediate polarizable layer, sandwiched between a non-dispersive overburden and substratum, themore » H-type sequence results are the most affected by the dispersion phenomenon as it occurs in magnetotellurics. Finally they consider the problem of the sensitivity of the method, since, in practice, it requires top and bottom sensors separated by a vertical finite distance. It is found that in the higher-frequency range, due to the strong attenuation of the relative components of the field, the depth of the bottom sensor must be small enough to guarantee detectable signals, well above the full-scale resolution of the acquisition system. Conversely, in the lower-frequency range such a depth must be large enough to allow the difference between the top and bottom signals to be above the same recording sensitivity threshold.« less

Sex differences in plasma homovanillic acid levels in schizophrenia and normal controls: relation to neuroleptic resistance.

PubMed

Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

1997-03-01

Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic-resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic-resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis x gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated.

Propagation of resist heating mask error to wafer level

NASA Astrophysics Data System (ADS)

Babin, S. V.; Karklin, Linard

2006-10-01

As technology is approaching 45 nm and below the IC industry is experiencing a severe product yield hit due to rapidly shrinking process windows and unavoidable manufacturing process variations. Current EDA tools are unable by their nature to deliver optimized and process-centered designs that call for 'post design' localized layout optimization DFM tools. To evaluate the impact of different manufacturing process variations on final product it is important to trace and evaluate all errors through design to manufacturing flow. Photo mask is one of the critical parts of this flow, and special attention should be paid to photo mask manufacturing process and especially to mask tight CD control. Electron beam lithography (EBL) is a major technique which is used for fabrication of high-end photo masks. During the writing process, resist heating is one of the sources for mask CD variations. Electron energy is released in the mask body mainly as heat, leading to significant temperature fluctuations in local areas. The temperature fluctuations cause changes in resist sensitivity, which in turn leads to CD variations. These CD variations depend on mask writing speed, order of exposure, pattern density and its distribution. Recent measurements revealed up to 45 nm CD variation on the mask when using ZEP resist. The resist heating problem with CAR resists is significantly smaller compared to other types of resists. This is partially due to higher resist sensitivity and the lower exposure dose required. However, there is no data yet showing CD errors on the wafer induced by CAR resist heating on the mask. This effect can be amplified by high MEEF values and should be carefully evaluated at 45nm and below technology nodes where tight CD control is required. In this paper, we simulated CD variation on the mask due to resist heating; then a mask pattern with the heating error was transferred onto the wafer. So, a CD error on the wafer was evaluated subject to only one term of the

White blood cell counts, insulin resistance, vitamin D levels and sarcopenia in Korean elderly men.

PubMed

Kim, Sang-Hwan; Kwon, Hyun Seok; Hwang, Hee-Jin

2017-05-01

Sarcopenia is a major determinant of frailty, disability and mortality in the elderly. Whether low-grade inflammation, insulin resistance and vitamin D are independently associated with sarcopenia remains unclear. In our study, sarcopenia was defined as an appendicular skeletal muscle mass divided by height squared (ASM/Ht 2 ) that was <2 SD below the normal means for young adults. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index [(insulin (IU/mL) × fasting glucose (mg/dL)/18)/22.5]. Data of white blood cell counts and serum 25-hydroxyvitamin D (25-(OH)D) levels were collected in the second and third year (2008-2009) of Fourth Korean National Health and Nutrition Examination Survey (KNHANES IV). The results showed that the prevalence of sarcopenia in Korean elderly men aged more than 65 years was 11.2%. ASM/Ht 2 were positively associated with vitamin D levels, but negatively associated with white blood cell counts and HOMA-IR by multiple regression analysis. After adjustment for covariables, sarcopenia was associated with the highest quartile of WBC counts (OR = 2.93, 95% CI = 1.21-7.14) and the highest quartile of serum vitamin D levels (OR = 0.38, 95% CI = 0.15-0.95). In conclusion, the study findings suggest that higher WBC counts and lower vitamin D levels are independently associated with the presence of sarcopenia in community-dwelling elderly men. They also provide a basis for further studies of the complex immune-endocrine network in sarcopenia.

Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes.

PubMed Central

Rella, M; Haas, D

1982-01-01

Resistance to high concentrations of nalidixic acid in Pseudomonas aeruginosa PAO was due to mutations in one locus designated nalA, which was mapped by transduction between hex-9001 and leu-10. The nalA mutants were cross-resistant to pipemidic acid, a nalidixic acid analog, at relatively low concentrations. Replicative DNA synthesis was resistant to both drugs in permeabilized cells of nalA mutants. A locus coding for low-level resistance to nalidixic acid, nalB, was cotransducible with pyrB, proC, and met-28. The nalB mutants were also resistant to low levels of pipemidic acid, novobiocin, and beta-lactam antibiotics (e.g., carbenicillin, azlocillin, and cefsulodin), but not to other drugs, such as gentamicin, rifampin, kanamycin, or tetracycline. In nalB mutants, DNA replication showed wild-type sensitivity to nalidixic acid, whereas carbenicillin-induced filamentation required higher drug levels than in the wild-type strain. Thus, nalB mutations appear to decrease cell permeability to some antibiotics. The sensitivity of replicative DNA synthesis to nalidixic acid and novobiocin was very similar in P. aeruginosa and Escherichia coli; by contrast, the concentrations of these drugs needed to inhibit growth of P. aeruginosa were higher than those reported for E. coli by one or two orders of magnitude. PMID:6821455

Variability of cutaneous and nasal population levels between patients colonized and infected by multidrug-resistant bacteria in two Brazilian intensive care units.

PubMed

Damaceno, Quésia; Nicoli, Jacques R; Oliveira, Adriana

2015-01-01

To compare cutaneous and nasal population levels between patients colonized and infected by multidrug-resistant organisms in two intensive care units. A prospective cohort study was performed in adult intensive care units of two hospitals in Belo Horizonte, Brazil (April 2012 to February 2013). Clinical and demographic data were first collected by reviewing patients' charts. Then, samples collected with nasal, groin, and perineum swabs were cultivated in selective media for 48 h at 37°C. After isolation, determination of antimicrobial susceptibility and biochemical identification were performed. A total of 53 cases of colonization were observed by the following bacteria in decreasing frequencies: imipenem-resistant Acinetobacter baumannii (50.9%), vancomycin-resistant Enterococcus faecalis (43.4%), extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (37.7%), imipenem-resistant Pseudomonas aeruginosa (32.1%), oxacillin-resistant Staphylococcus aureus (7.5%), and imipenem-resistant Klebsiella pneumoniae (5.7%). Among these colonization cases, 26 (49.0%) were followed by infection with bacteria phenotypically similar to those of the colonization. A relation between high population levels of colonization by most of the multidrug-resistant organisms at anatomical sites and a subsequent infection was observed. After colonization/infection, bacterial population levels decreased progressively and spontaneously until disappearance by day 45 in all the anatomical sites and for all the multidrug-resistant organisms. There was a correlation between high population levels of colonization by multidrug-resistant organisms at anatomical sites and a subsequent infection. Reduction in multidrug-resistant organism populations after colonization at anatomical sites could be a preventive measure to reduce evolution to infection as well as transmission of these bacteria between patients in intensive care unit.

[Resistance risk, cross-resistance and biochemical resistance mechanism of Laodelphax striatellus to buprofezin].

PubMed

Mao, Xu-lian; Liu, Jin; Li, Xu-ke; Chi, Jia-jia; Liu, Yong-jie

2016-01-01

In order to investigate the resistance development law and biochemical resistance mechanism of Laodelphax striatellus to buprofezin, spraying rice seedlings was used to continuously screen resistant strains of L. striatellus and dipping rice seedlings was applied to determine the toxicity and cross-resistance of L. striatellus to insecticides. After 32-generation screening with buprofezin, L. striatellus developed 168.49 folds resistance and its reality heritability (h2) was 0.11. If the killing rate was 80%-90%, L. striatellus was expected to develop 10-fold resistance to buprofezin only after 5 to 6 generations breeding. Because the actual reality heritability of field populations was usually lower than that of the resistant strains, the production of field populations increasing with 10-fold resistance would need much longer time. The results of cross-resistance showed that resistant strain had high level cross-resistance with thiamethoxam and imidacloprid, low level cross-resistance with acetamiprid, and no cross-resistance with pymetrozine and chlorpyrifos. The activity of detoxification enzymes of different strains and the syergism of synergist were measured. The results showed that cytochrome P450 monooxygenase played a major role in the resistance of L. striatellus to buprofezin, the esterase played a minor role and the GSH-S-transferase had no effect. Therefore, L. striatellus would have high risk to develop resistance to buprofezin when used in the field and might be delayed by using pymetrozine and chlorpyrifos.

Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat.

PubMed

Adamson, Catherine S; Sakalian, Michael; Salzwedel, Karl; Freed, Eric O

2010-04-20

The maturation inhibitor bevirimat (BVM) potently inhibits human immunodeficiency virus type 1 (HIV-1) replication by blocking capsid-spacer peptide 1 (CA-SP1) cleavage. Recent clinical trials demonstrated that a significant proportion of HIV-1-infected patients do not respond to BVM. A patient's failure to respond correlated with baseline polymorphisms at SP1 residues 6-8. In this study, we demonstrate that varying levels of BVM resistance are associated with point mutations at these residues. BVM susceptibility was maintained by SP1-Q6A, -Q6H and -T8A mutations. However, an SP1-V7A mutation conferred high-level BVM resistance, and SP1-V7M and T8Delta mutations conferred intermediate levels of BVM resistance. Future exploitation of the CA-SP1 cleavage site as an antiretroviral drug target will need to overcome the baseline variability in the SP1 region of Gag.

Evolution of antibiotic resistance in biofilm and planktonic P. aeruginosa populations exposed to sub-inhibitory levels of ciprofloxacin.

PubMed

Ahmed, Marwa N; Porse, Andreas; Sommer, Morten Otto Alexander; Høiby, Niels; Ciofu, Oana

2018-05-14

The opportunistic Gram-negative pathogen Pseudomonas aeruginosa , known for its intrinsic and acquired antibiotic resistance, has a notorious ability to form biofilms, which often facilitate chronic infections. The evolutionary paths to antibiotic resistance have mainly been investigated in planktonic cultures and are less studied in biofilms. We experimentally evolved P. aeruginosa PAO1 colony-biofilms and stationary-phase planktonic cultures for seven passages in the presence of sub-inhibitory levels (0.1 mg/L) of ciprofloxacin (CIP) and performed a genotypic (whole bacterial population sequencing) and phenotypic assessment of the populations. We observed a higher proportion of CIP resistance in the CIP-evolved biofilm populations compared to planktonic populations exposed to the same drug concentrations. However, the minimal inhibitory concentrations (MICs) of ciprofloxacin were lower in CIP-resistant isolates selected from biofilm population compared to the MICs of CIP-resistant isolates from the planktonic cultures. We found common evolutionary trajectories between the different lineages, with mutations in known CIP resistance determinants as well as growth condition-dependent adaptations. A general trend towards a reduction in type IV-pili dependent motility (twitching) in CIP-evolved populations, and towards loss of virulence associated traits in the populations evolved in the absence of antibiotic, was observed. In conclusion, our data indicate that biofilms facilitate the development of low-level mutational resistance, probably due to the lower effective drug exposure compared to planktonic cultures. These results provide a framework for the selection process of resistant variants and the evolutionary mechanisms in the two different growth conditions. Copyright © 2018 American Society for Microbiology.

Serum vitamin d level and susceptibility to multidrug-resistant tuberculosis among household contacts

NASA Astrophysics Data System (ADS)

Herlina, N.; Sinaga, B. Y. M.; Siagian, P.; Mutiara, E.

2018-03-01

Low levels of vitamin D is a predisposing factor for Multidrug-resistant tuberculosis. Family members in contact with the patient are also at risk of infection. Currently, there is no study that compares vitamin D levels between MDR-TB patients and household contact. This study aims to identify the association between level vitamin D within MDR-TB occurrence. This was a case-control study, with the number of samples in each group (MDR-TB) patients and household contactswere40 people. Each member of each group was checked for vitamin D levels using enzyme-linked immunosorbent assay (ELISA) technique. Statistical analysis was by using Chi-Square analysis using SPSS. Mean levels of vitamin D in MDR-TB patients were 32.21, household contact 31.7. There was anosignificant association between vitamin D levels and MDR-TB occurrence (p=1.0).No significant associationbetween vitamin D level with theMDR-TB occurrence.

An Upstream Truncation of the furA-katG Operon Confers High-Level Isoniazid Resistance in a Mycobacterium tuberculosis Clinical Isolate with No Known Resistance-Associated Mutations

PubMed Central

Yam, Wing Cheong; Zhang, Ying; Kao, Richard Y. T.

2014-01-01

Although the major causes of isoniazid (INH) resistance in Mycobacterium tuberculosis are confined to structural mutations in katG and promoter mutations in the mabA-inhA operon, a significant proportion of INH-resistant strains have unknown resistance mechanisms. Recently, we identified a high-level INH-resistant M. tuberculosis clinical isolate, GB005, with no known resistance-associated mutations. A comprehensive study was performed to investigate the molecular basis of drug resistance in this strain. Although no mutations were found throughout the katG and furA-katG intergenic region, the katG expression and the catalase activity were greatly diminished compared to those in H37Rv (P < 0.01). Northern blotting revealed that the katG transcript from the isolate was smaller than that of H37Rv. Sequencing analysis of furA and upstream genes discovered a 7.2-kb truncation extended from the 96th base preceding the initiation codon of katG. Complementation of the M. tuberculosis Δ(furA-katG) strain with katG and different portions of the truncated region identified a 134-bp upstream fragment of furA that was essential for full catalase activity and INH susceptibility in M. tuberculosis. The promoter activity of this fragment was also shown to be stronger than that of the furA-katG intergenic region (P < 0.01). Collectively, these findings demonstrate that deletion of the 134-bp furA upstream fragment is responsible for the reduction in katG expression, resulting in INH resistance in GB005. To our knowledge, this is the first report showing that deletion of the upstream region preceding the furA-katG operon causes high-level INH resistance in a clinical isolate of M. tuberculosis. PMID:25092698

Increasing resistance against Phytophthora citrophthora in tangelo Nova fruits by modulating polymethoxyflavones levels.

PubMed

Ortuño, A; Arcas, M C; Botía, J M; Fuster, M D; Del Río, J A

2002-05-08

The effect of 6-benzylaminopurine on polymethoxyflavone levels in tangelo Nova fruits and the possible participation of these secondary metabolites in defense mechanisms against Phytophthora citrophthora are studied. The in vitro study of the inhibitory effect of these compounds on fungal growth reveals that nobiletin is the most active agent followed by sinensetin, heptamethoxyflavone, and tangeretin. Treatment with 100 ppm of 6-benzylaminopurine increased the levels of these polymethoxyflavones in this Citrus hybrid and also enhanced the in vivo resistance of the fruit to the fungus by approximately 60%.

Broadband Achromatic Phase Shifter for a Nulling Interferometer

NASA Technical Reports Server (NTRS)

Bolcar, Matthew R.; Lyon, Richard G.

2011-01-01

Nulling interferometry is a technique for imaging exoplanets in which light from the parent star is suppressed using destructive interference. Light from the star is divided into two beams and a phase shift of radians is introduced into one of the beams. When the beams are recombined, they destructively interfere to produce a deep null. For monochromatic light, this is implemented by introducing an optical path difference (OPD) between the two beams equal to lambda/2, where lambda is the wavelength of the light. For broadband light, however, a different phase shift will be introduced at each wavelength and the two beams will not effectively null when recombined. Various techniques have been devised to introduce an achromatic phase shift a phase shift that is uniform across a particular bandwidth. One popular technique is to use a series of dispersive elements to introduce a wavelength-dependent optical path in one or both of the arms of the interferometer. By intelligently choosing the number, material and thickness of a series of glass plates, a nearly uniform, arbitrary phase shift can be introduced between two arms of an interferometer. There are several constraints that make choosing the number, type, and thickness of materials a difficult problem, such as the size of the bandwidth to be nulled. Several solutions have been found for bandwidths on the order of 20 to 30 percent (Delta(lambda)/lambda(sub c)) in the mid-infrared region. However, uniform phase shifts over a larger bandwidth in the visible regime between 480 to 960 nm (67 percent) remain difficult to obtain at the tolerances necessary for exoplanet detection. A configuration of 10 dispersive glass plates was developed to be used as an achromatic phase shifter in nulling interferometry. Five glass plates were placed in each arm of the interferometer and an additional vacuum distance was also included in the second arm of the interferometer. This configuration creates a phase shift of pi radians with

Effects of soybean resistance on variability in life history traits of the higher trophic level parasitoid Meteorus pulchricornis (Hymenoptera: Braconidae).

PubMed

Li, X; Li, B; Xing, G; Meng, L

2017-02-01

To extrapolate the influence of plant cultivars varying in resistance levels to hosts on parasitoid life history traits, we estimated variation in parasitoid developmental and reproductive performances as a function of resistance in soybean cultivars, which were randomly chosen from a line of resistant genotypes. Our study showed that the parasitoid Meteorus pulchricornis varied widely in offspring survival and lifetime fecundity, but varied slightly in development time and adult body size, in response to the soybean cultivars that varied in resistance to the host Spodoptera litura. Furthermore, the variability in survival and lifetime fecundity was different between attacking the 2nd and the 4th instar host larvae, varying more in survival but less in lifetime fecundity when attacking the 4th than 2nd instar larvae. Our study provides further evidence supporting that plant resistance to herbivorous hosts have variable effects on different life history traits of higher trophic level parasitoids.

Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients.

PubMed

Castillo-Hernandez, Jesus; Maldonado-Cervantes, Martha Imelda; Reyes, Juan Pablo; Patiño-Marin, Nuria; Maldonado-Cervantes, Enrique; Solorzano-Rodriguez, Claudia; de la Cruz Mendoza, Esperanza; Alvarado-Sanchez, Brenda

Systemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. To evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease. Assessments included: body mass index, insulin resistance by Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay. Outstanding results from these studies include: (1) In Rheumatoid arthritis patients, insulin resistance was well correlated with body mass index, but not with levels of serum cytokines. In fact, levels of cytokines were similar in all Rheumatoid arthritis patients, regardless of being obese, overweight or normal weight (2) Insulin resistance was significantly higher in Rheumatoid arthritis with normal weight than in normal weight (3) No significant difference was observed between insulin resistances of Rheumatoid arthritis with obesity and obesity (4) As expected, levels of circulating cytokines were significantly higher in Rheumatoid arthritis patients than in obesity. Obesity appears to be a dominant condition above inflammation to produce IR in RA patients. The dissociation of the inflammation and obesity components to produce IR suggests the need of an independent therapeutic strategy in obese patients with RA. Copyright © 2017. Published by Elsevier Editora Ltda.

Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

PubMed

Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

2014-06-01

In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

Cytokine profiling of docetaxel-resistant castration-resistant prostate cancer.

PubMed

Mahon, K L; Lin, H-M; Castillo, L; Lee, B Y; Lee-Ng, M; Chatfield, M D; Chiam, K; Breit, S N; Brown, D A; Molloy, M P; Marx, G M; Pavlakis, N; Boyer, M J; Stockler, M R; Daly, R J; Henshall, S M; Horvath, L G

2015-04-14

Docetaxel improves symptoms and survival in metastatic castration-resistant prostate cancer (CRPC). However, ∼50% of patients are chemoresistant. This study examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. PC3 cells or their docetaxel-resistant subline (PC3Rx) were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. The circulating levels of 28 cytokines were measured pre-/post cycle 1 of docetaxel from 55 men with CRPC, and compared with prostate-specific antigen (PSA) response. PC3Rx-U937 co-culture expressed more cytokines, chiefly markers of alternative macrophage differentiation, compared with PC3-U937 co-culture. Docetaxel treatment enhanced cytokine production by PC3Rx-U937 co-culture, while reducing cytokine levels in PC3-U937. In patients, changes in the levels of seven circulating cytokines (macrophage inhibitory cytokine 1 (MIC1), interleukin (IL)-1ra, IL-1β, IL-4, IL-6, IL-12 and IFNγ) after cycle 1 of docetaxel were associated with progressive disease (all P<0.05). The combination of changes in MIC1, IL-4 and IL-6 most strongly predicted PSA response (P=0.002). In vitro studies suggest docetaxel resistance is mediated, at least in part, by cytokines induced by the interaction between the docetaxel-resistant tumour cells and macrophages. Early changes in circulating cytokine levels were associated with docetaxel resistance in CRPC patients. When considered together, these data suggest a significant role for the inflammatory response and macrophages in the development of docetaxel resistance in CRPC.

Unraveling the genetic driving forces enabling antibiotic resistance at the single cell level

NASA Astrophysics Data System (ADS)

Bos, Julia

Bacteria are champions at finding ways to quickly respond and adapt to environments like the human gut, known as the epicentre of antibiotic resistance. How do they do it? Combining molecular biology tools to microfluidic and fluorescence microscopy technologies, we monitor the behavior of bacteria at the single cell level in the presence of non-toxic doses of antibiotics. By tracking the chromosome dynamics of Escherichia coli cells upon antibiotic treatment, we examine the changes in the number, localization and content of the chromosome copies within one cell compartment or between adjacent cells. I will discuss how our work pictures the bacterial genomic plasticity as a driving force in evolution and how it provides access to the mechanisms controlling the subtle balance between genetic diversity and stability in the development of antibiotic resistance.

[Resistance mechanisms and cross-resistance of phoxim-resistant Frankliniella occidentalis Pergande population].

PubMed

Wang, Sheng-Yin; Zhou, Xian-Hong; Zhang, An-Sheng; Li, Li-Li; Men, Xing-Yuan; Zhang, Si-Cong; Liu, Yong-Jie; Yu, Yi

2012-07-01

To understand the resistance risks of Frankliniella occidentalis Pergande against phoxim, this paper studied the resistance mechanisms of phoxim-resistant F. occidentalis population against phoxim and the cross-resistance of the population against other insecticides. The phoxim-resistant population had medium level cross-resistance to chlorpyrifos, lambda-cyhalothrin, and methomyl, low level cross-resistance to chlorfenapyr, imidacloprid, emamectin-benzoate, and spinosad, but no cross-resistance to acetamiprid and abamectin. The synergists piperonyl butoxide (PBO), s, s, s-tributyl phosphorotrithioate (DEF), and triphenyl phosphate (TPP) had significant synergism (P < 0.05) on the toxicity of phoxim to the resistant (XK), field (BJ), and susceptible (S) populations, while diethyl maleate (DEM) had no significant synergism to XK and S populations but had significant synergism to BJ population. As compared with S population, the XK and BJ populations had significantly increased activities of mixed-functional oxidases P450 (2.79-fold and 1.48-fold), b, (2.88-fold and 1.88-fold), O-demethylase (2.60-fold and 1.68-fold), and carboxylesterase (2.02-fold and 1.61-fold, respectively), and XK population had a significantly increased acetylcholine esterase activity (3.10-fold). Both XK and BJ population had an increased activity of glutathione S-transferases (1.11-fold and 1.20-fold, respectively), but the increment was not significant. The increased detoxification enzymes activities in F. occidentalis could play an important role in the resistance of the plant against phoxim.

The effect of conventional wastewater treatment on the levels of antimicrobial-resistant bacteria in effluent: a meta-analysis of current studies.

PubMed

Harris, Suvi; Cormican, Martin; Cummins, Enda

2012-12-01

Antimicrobial agents in the environment are a cause for concern. Antimicrobial drug residues and their metabolites reach the aquatic and terrestrial environment primarily through wastewater treatment plants (WWTP). In addition to the potential direct negative health and environmental effects, there is potential for the development of antimicrobial-resistant bacteria. Residue levels below the minimum inhibitory concentration for a bacterial species can be important in selection of resistance. There is uncertainty associated with resistance formation during WWTP processing. A meta-analysis study was carried out to analyse the effect of WWTP processing on the levels of antimicrobial-resistant bacteria within bacterial populations. An analysis of publications relating to multiple antimicrobial-resistant (MAR) bacteria (n = 61), single antimicrobial-resistant (SAR) E. coli (n = 81) and quinolone/fluoroquinolone-resistant (FR) bacteria (n = 19) was carried out. The odds-ratio (OR) of MAR (OR = 1.60, p < 0.01), SAR (OR = 1.33, p < 0.01) and FR (OR = 1.19, p < 0.01) bacteria was determined. The results infer that WWTP processing results in an increase in the proportion of resistant bacteria in effluent, even though the overall bacterial population may have reduced (i.e. a reduction in total bacterial numbers but an increase in the percentage of resistant bacteria). The results support the need for further research into the development of antimicrobial-resistant strains and possible selective pressures operating in WWTPs.

Correlation between plasma component levels of cultured fish and resistance to bacterial infection

USGS Publications Warehouse

Maita, M.; Satoh, K.-I.; Fukuda, Y.; Lee, H.-K.; Winton, J.R.; Okamoto, N.

1998-01-01

Mortalities of yellowtail Seriola quinqueradiata artificially infected with Lactococcus garvieae and of rainbow trout Oncorhynchus mykiss artificially infected with Vibrio anguillarum were compared with the levels of plasma components measured prior to challenge. The levels of plasma total cholesterol, free cholesterol and phospholipid of fish surviving infection were significantly higher in both yellowtail and rainbow trout than those of fish which died during the challenge test. Mortality of yellowtail with plasma total cholesterol levels lower than 250 mg/100 ml was significantly higher than that of fish which had cholesterol levels higher than 275 mg/100 ml (p < 0.05). Rainbow trout whose cholesterol was lower than 520 mg/100 ml suffered a significantly higher mortality due to vibriosis than fish having cholesterol levels higher than 560 mg/100 ml (p < 0.005). These results indicate that low levels of plasma lipid components may be an indicator of lowered disease resistance in cultured fish.

Novel plasmids and resistance phenotypes in Yersinia pestis: unique plasmid inventory of strain Java 9 mediates high levels of arsenic resistance.

PubMed

Eppinger, Mark; Radnedge, Lyndsay; Andersen, Gary; Vietri, Nicholas; Severson, Grant; Mou, Sherry; Ravel, Jacques; Worsham, Patricia L

2012-01-01

Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium.

Novel Plasmids and Resistance Phenotypes in Yersinia pestis: Unique Plasmid Inventory of Strain Java 9 Mediates High Levels of Arsenic Resistance

PubMed Central

Eppinger, Mark; Radnedge, Lyndsay; Andersen, Gary; Vietri, Nicholas; Severson, Grant; Mou, Sherry; Ravel, Jacques; Worsham, Patricia L.

2012-01-01

Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium. PMID:22479347

Calculation of Resistive Loads for Elastic Resistive Exercises.

PubMed

Picha, Kelsey; Uhl, Tim

2018-03-14

What is the correct resistive load to start resistive training with elastic resistance to gain strength? This question is typically answered by the clinician's best estimate and patient's level of discomfort without objective evidence. To determine the average level of resistance to initiate a strengthening routine with elastic resistance following isometric strength testing. Cohort. Clinical. 34 subjects (31 ± 13 y, 73 ± 17 kg, 170 ± 12 cm). The force produced was measured in Newtons (N) with an isometric dynamometer. The force distance was the distance from center of joint to location of force applied was measured in meters to calculate torque that was called "Test Torque" for the purposes of this report. This torque data was converted to "Exercise Load" in pounds based on the location where the resistance was applied, specifically the distance away from the center of rotation of the exercising limb. The average amount of exercise load as percentage of initial Test Torque for each individual for each exercise was recorded to determine what the average level of resistance that could be used for elastic resistance strengthening program. The percentage of initial test torque calculated for the exercise was recorded for each exercise and torque produced was normalized to body weight. The average percentage of maximal isometric force that was used to initiate exercises was 30 ± 7% of test torque. This provides clinicians with an objective target load to start elastic resistance training. Individual variations will occur but utilization of a load cell during elastic resistance provides objective documentation of exercise progression.

Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer.

PubMed

Knappskog, Stian; Chrisanthar, Ranjan; Løkkevik, Erik; Anker, Gun; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Leirvaag, Beryl; Miletic, Hrvoje; Lønning, Per E

2012-03-15

Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy. We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted anthracycline resistance (P-values varying between 0.001 and 0.027 depending on the percentile used to define "low" ATM levels). These results were confirmed in an independent cohort of 109 patients treated with epirubicin monotherapy. In contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or CHEK2 mutations (P > 0.5). Our data indicate loss of function of the ATM-Chk2-p53 cascade to be strongly associated with resistance to anthracycline/mitomycin-containing chemotherapy in breast cancer.

Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer

PubMed Central

2012-01-01

Introduction Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy. Methods We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. Results While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted anthracycline resistance (P-values varying between 0.001 and 0.027 depending on the percentile used to define "low" ATM levels). These results were confirmed in an independent cohort of 109 patients treated with epirubicin monotherapy. In contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or CHEK2 mutations (P > 0.5). Conclusions Our data indicate loss of function of the ATM-Chk2-p53 cascade to be strongly associated with resistance to anthracycline/mitomycin-containing chemotherapy in breast cancer. PMID:22420423

Short term resistance training enhanced plasma apoA-I and FABP4 levels in Streptozotocin-induced diabetic rats.

PubMed

Safarzade, Alireza; Talebi-Garakani, Elahe

2014-03-04

Type 1 diabetes mellitus is associated with a high risk for early atherosclerotic complications. Altered lipids and lipoprotein metabolism in chronic diabetes mellitus is associated with pathogenesis of atherosclerosis and other cardiovascular diseases. The aim of this study was to investigate the effects of 4 weeks resistance training on plasma lipid profile, fatty acid binding protein (FABP) 4 and apolipoprotein (apo) A-I levels in type 1 diabetic rats. Thirty two male Wister rats (12-14 weeks old) were randomly divided into four groups: non-diabetic control; non-diabetic trained; diabetic control; diabetic trained. The rats in training groups were subjected to a resistance training program (3 days/wk, for 4 wk) consisted of climbing a ladder carrying a load suspended from the tail. Diabetic inducing increased plasma apoA-I and decreased FABP4 levels compared with non-diabetic control group (respectively, P = 0.001 & P = 0.041). After 4 weeks' resistance training, plasma levels of apoA-I and FABP4 in the diabetic trained rats were significantly higher compared with the diabetic control group (respectively, P = 0.003 & P = 0.017). Plasma HDL-C level in diabetic trained group was higher than diabetic control group (P = 0.048). Liver triglycerides concentrations were significantly lower in both trained (non-diabetic and diabetic) groups compared with their control groups (respectively, P = 0.041 and P = 0.002). These data indicated that resistance training may be an efficient intervention strategy to increase plasma apoA-I, HDL-C and FABP4 concentrations, along with decreases liver triglycerides in streptozotocin induced diabetic rats. Further research is needed to elucidate physiological significance of circulating FABP4 levels.

Mismatch or cumulative stress: the pathway to depression is conditional on attention style.

PubMed

Nederhof, Esther; Ormel, Johan; Oldehinkel, Albertine J

2014-03-01

In the study reported here, the main question we investigated was whether attention style could be a conditional adaptation. We organized participants of the TRacking Adolescents' Individual Lives Survey (TRAILS; N = 2,230) into shifters, sustainers, and two comparison groups, depending on their performance on a shifting- and a sustained-attention task at age 11 years. Compared with sustainers, shifters reported more pre- and perinatal risk factors and more childhood stress, and they adopted a faster life-history strategy. These differences were not found between the comparison groups, who performed well or poorly on both tasks, which suggests that specialization for either sustained or shifting attention is the key to conditional adaptation. In a subsample (n = 860), we found that stress did not increase depression risk in shifters, whereas a mismatch between early and recent stress predicted depression in sustainers. Cumulative stress predicted depression in the comparison group. These results suggest that shifters retain high levels of plasticity throughout life, whereas sustainers' adapted their phenotype early in life to the expected mature environment.

Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods.

PubMed

Kurtoğlu, Selim; Hatipoğlu, Nihal; Mazıcıoğlu, Mümtaz; Kendirici, Mustafa; Keskin, Mehmet; Kondolot, Meda

2010-01-01

Childhood obesity is associated with an increased risk for insulin resistance. The underlying mechanism for the physiological increase in insulin levels in puberty is not clearly understood. The aim of the present study was to determine the cut-off values for homeostasis model assessment for insulin resistance (HOMA-IR) in obese children and adolescents according to gender and pubertal status. Two hundred and eight obese children and adolescents (141 girls, 127 boys) aged between 5 and 18 years were included in the study. The children were divided into prepubertal and pubertal groups. A standard oral glucose tolerance test (OGTT) was carried out in all children. A total insulin level exceeding 300 μU/mL in the blood samples, collected during the test period, was taken as the insulin resistance criterion. Cut-off values for HOMA-IR were calculated by receiver operating characteristic (ROC) analysis. In the prepubertal period, the rate of insulin resistance was found to be 37% in boys and 27.8% in girls,while in the pubertal period, this rate was 61.7% in boys and 66.7% in girls. HOMA-IR cut-off values for insulin resistance in the prepubertal period were calculated to be 2.67 (sensitivity 88.2%, specificity 65.5%) in boys and 2.22 (sensitivity 100%, specificity 42.3%) in girls, and in the pubertal period, they were 5.22 (sensitivity 56%, specificity 93.3%) in boys and 3.82 (sensitivity 77.1%, specificity 71.4%) in girls. Since gender, obesity and pubertal status are factors affecting insulin resistance, cut-off values which depend on gender and pubertal status, should be used in evaluation of insulin resistance.

High-level tetracycline resistance mediated by efflux pumps Tet(A) and Tet(A)-1 with two start codons.

PubMed

Wang, Weixia; Guo, Qinglan; Xu, Xiaogang; Sheng, Zi-ke; Ye, Xinyu; Wang, Minggui

2014-11-01

Efflux is the most common mechanism of tetracycline resistance. Class A tetracycline efflux pumps, which often have high prevalence in Enterobacteriaceae, are encoded by tet(A) and tet(A)-1 genes. These genes have two potential start codons, GTG and ATG, located upstream of the genes. The purpose of this study was to determine the start codon(s) of the class A tetracycline resistance (tet) determinants tet(A) and tet(A)-1, and the tetracycline resistance level they mediated. Conjugation, transformation and cloning experiments were performed and the genetic environment of tet(A)-1 was analysed. The start codons in class A tet determinants were investigated by site-directed mutagenesis of ATG and GTG, the putative translation initiation codons. High-level tetracycline resistance was transferred from the clinical strain of Klebsiella pneumoniae 10-148 containing tet(A)-1 plasmid pHS27 to Escherichia coli J53 by conjugation. The transformants harbouring recombinant plasmids that carried tet(A) or tet(A)-1 exhibited tetracycline MICs of 256-512 µg ml(-1), with or without tetR(A). Once the ATG was mutated to a non-start codon, the tetracycline MICs were not changed, while the tetracycline MICs decreased from 512 to 64 µg ml(-1) following GTG mutation, and to ≤4 µg ml(-1) following mutation of both GTG and ATG. It was presumed that class A tet determinants had two start codons, which are the primary start codon GTG and secondary start codon ATG. Accordingly, two putative promoters were predicted. In conclusion, class A tet determinants can confer high-level tetracycline resistance and have two start codons. © 2014 The Authors.

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii

PubMed Central

Mahamad Maifiah, Mohd Hafidz; Cheah, Soon-Ee; Johnson, Matthew D.; Han, Mei-Ling; Boyce, John D.; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S.; Hertzog, Paul; Purcell, Anthony W.; Song, Jiangning; Velkov, Tony; Creek, Darren J.; Li, Jian

2016-01-01

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03–149.1 (polymyxin-susceptible) and 03–149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii. PMID:26924392

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii.

PubMed

Maifiah, Mohd Hafidz Mahamad; Cheah, Soon-Ee; Johnson, Matthew D; Han, Mei-Ling; Boyce, John D; Thamlikitkul, Visanu; Forrest, Alan; Kaye, Keith S; Hertzog, Paul; Purcell, Anthony W; Song, Jiangning; Velkov, Tony; Creek, Darren J; Li, Jian

2016-02-29

Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii.

Resistance training inhibits the elevation of skeletal muscle derived-BDNF level concomitant with improvement of muscle strength in zucker diabetic rat

PubMed Central

Kim, Hee-Jae; So, Byunghun; Son, Jun Seok; Song, Han Sol; Oh, Seung Lyul; Seong, Je Kyung; Lee, Hoyoung; Song, Wook

2015-01-01

[Purpose] In the present study, we investigated the effects of 8 weeks of progressive resistance training on the level of skeletal muscle derived BDNF as well as glucose intolerance in Zucker diabetic rats. [Methods] Six week-old male Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were randomly divided into 3 groups: sedentary ZLC (ZLC-Con), sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). Progressive resistance training using a ladder and tail weights was performed for 8 weeks (3 days/week). [Results] After 8 weeks of resistance training, substantial reduction in body weight was observed in ZDF-Ex compared to ZDF-Con. Though the skeletal muscle volume did not change, grip strength grip strength was significantly higher in ZDF-Ex compared to ZDF-Con. In the soleus, the level of BDNF was increased in ZDF-Con, but was significantly decreased (p<0.05) in ZDF-Ex, showing a training effect. Moreover, we found that there was a negative correlation (r=-0.657; p=0.004) between grip strength and BDNF level whereas there was a positive correlation (r=0.612; p=0.008) between plasma glucose level and BDNF level in skeletal muscle. [Conclusion] Based upon our results, we demonstrated that resistance training inhibited the elevation of skeletal muscle derived-BDNF expression concomitant with the improvement of muscle strength in zucker diabetic rats. In addition, muscle-derived BDNF might be a potential mediator for the preventive effect of resistance training on the progress of type 2 diabetes. PMID:27274460

High-level vancomycin resistant Enterococcus faecium related to humans and pigs found in dust from pig breeding facilities.

PubMed

Braga, Teresa M; Pomba, Constança; Lopes, M Fátima Silva

2013-01-25

Environmental dust from animal breeding facilities was never screened for the presence of enterococci, nor of vancomycin-resistant enterococci (VRE), despite the possibility of being a vehicle of transmission of strains and antibiotic resistance genes between food-producing animals and man. Bio-security measures in pig facilities include disinfection with biocides to avoid the dissemination of opportunistic pathogenic bacteria, namely enterococci and in particular VRE. We thus undertook collection of enterococci and VRE in a representative number of breeding pig facilities in Portugal (n=171) and analyzed their susceptibility to benzalkonium chloride (BC) and chlorhexidine (CHX). A prevalence of 15% of VRE was found, with 6% high-level resistance found, and MIC values for CHX and BC were similar to those commonly found among enterococcal isolates from related environments, 8 μg/ml and 4 μg/ml, respectively. Among the isolated high-level vancomycin resistant Enterococcus faecium carrying the vanA genotype, we found multilocus sequence types closely related to pig and human isolates from European countries and Brazil. These results strongly advise constant surveillance of this environment and its inclusion in future epidemiologic studies on VRE. Copyright © 2012 Elsevier B.V. All rights reserved.

High-Level Primary Clarithromycin Resistance of Helicobacter pylori in Algiers, Algeria: A Prospective Multicenter Molecular Study.

PubMed

Djennane-Hadibi, Fazia; Bachtarzi, Mohamed; Layaida, Karim; Ali Arous, Nassima; Nakmouche, Mhamed; Saadi, Berkane; Tazir, Mohamed; Ramdani-Bouguessa, Nadjia; Burucoa, Christophe

2016-04-01

Knowledge of local antibiotic resistance is crucial to adaptation for the choice of the optimal first-line treatment for Helicobacter pylori infection. Clarithromycin is a key component of the standard triple therapy largely used worldwide and, more particularly, in Algeria. Clarithromycin resistance is the main risk factor for treatment failure. The aim of this study was to evaluate, for the first time in Algeria, the prevalence of the primary resistance of H. pylori to clarithromycin. We conducted a prospective study (2008-2014) that included 195 Algerian patients referred for gastroduodenal endoscopy to two University Hospitals, one General Hospital, and several private gastroenterologists in Algiers (Algeria). One gastric biopsy was collected for the molecular detection of H. pylori and the mutations in 23S rRNA genes that confer resistance to clarithromycin with a quadruplex real-time PCR using Scorpion primers. The Scorpion PCR detected H. pylori DNA in 91 biopsies (47%). A mutation conferring resistance to clarithromycin was detected in 32 of the 91 positive patients (35%) and in 29 of the 88 positive patients never previously treated for an H. pylori infection (33%). The prevalence of primary resistance of H. pylori to clarithromycin was 33% in the Algerian population being studied. The high level of primary clarithromycin resistance in the H. pylori strains infecting the Algerian population that we report leads us to recommend the abandonment of the standard clarithromycin-based triple therapy as a first-line treatment in Algeria.

Sunlight-Exposed Biofilm Microbial Communities Are Naturally Resistant to Chernobyl Ionizing-Radiation Levels

PubMed Central

Ragon, Marie; Restoux, Gwendal; Moreira, David; Møller, Anders Pape; López-García, Purificación

2011-01-01

Background The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. Methodology/Principal Findings To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. Conclusions/Significance Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general

Sunlight-exposed biofilm microbial communities are naturally resistant to chernobyl ionizing-radiation levels.

PubMed

Ragon, Marie; Restoux, Gwendal; Moreira, David; Møller, Anders Pape; López-García, Purificación

2011-01-01

The Chernobyl accident represents a long-term experiment on the effects of exposure to ionizing radiation at the ecosystem level. Though studies of these effects on plants and animals are abundant, the study of how Chernobyl radiation levels affect prokaryotic and eukaryotic microbial communities is practically non-existent, except for a few reports on human pathogens or soil microorganisms. Environments enduring extreme desiccation and UV radiation, such as sunlight exposed biofilms could in principle select for organisms highly resistant to ionizing radiation as well. To test this hypothesis, we explored the diversity of microorganisms belonging to the three domains of life by cultivation-independent approaches in biofilms developing on concrete walls or pillars in the Chernobyl area exposed to different levels of radiation, and we compared them with a similar biofilm from a non-irradiated site in Northern Ireland. Actinobacteria, Alphaproteobacteria, Bacteroidetes, Acidobacteria and Deinococcales were the most consistently detected bacterial groups, whereas green algae (Chlorophyta) and ascomycete fungi (Ascomycota) dominated within the eukaryotes. Close relatives to the most radio-resistant organisms known, including Rubrobacter species, Deinococcales and melanized ascomycete fungi were always detected. The diversity of bacteria and eukaryotes found in the most highly irradiated samples was comparable to that of less irradiated Chernobyl sites and Northern Ireland. However, the study of mutation frequencies in non-coding ITS regions versus SSU rRNA genes in members of a same actinobacterial operational taxonomic unit (OTU) present in Chernobyl samples and Northern Ireland showed a positive correlation between increased radiation and mutation rates. Our results show that biofilm microbial communities in the most irradiated samples are comparable to non-irradiated samples in terms of general diversity patterns, despite increased mutation levels at the single

High-level of resistance to spinosad, emamectin benzoate and carbosulfan in populations of Thrips tabaci collected in Israel.

PubMed

Lebedev, Galina; Abo-Moch, Fauzi; Gafni, Guy; Ben-Yakir, David; Ghanim, Murad

2013-02-01

The onion thrips, Thrips tabaci Lindeman, is a major pest of several crop plants in the genus Allium, such as onions, garlic and chives. In Israel, these crops are grown in open fields and in protected housing. This thrips is usually controlled by the application of chemical insecticides. In recent years, spinosad, emamectin benzoate and carbosulfan have been the major insecticides used for the control of the onion thrips. In the last 4 years, growers of chives and green onion from several regions of Israel have reported a significant decrease in the efficacy of insecticides used to control the onion thrips. The susceptibility of 14 populations of the onion thrips, collected mainly from chives between the years 2007 and 2011, to spinosad, emamectin benzoate and carbosulfan was tested using a laboratory bioassay. The majority of the populations showed significant levels of resistance to at least one of the insecticides. LC(50) values calculated for two of the studied populations showed that the resistance factor for spinosad compared with the susceptible population is 21 393, for carbosulfan 54 and for emamectin benzoate 36. Only two populations, collected from organic farms, were susceptible to the insecticides tested. This is the first report of a high resistance level to spinosad, the major insecticide used to control the onion thrips. Resistance cases to spinosad were associated with failures to control the pest. Populations resistant to spinosad also had partial or complete resistance to other insecticides used for controlling the onion thrips. Copyright © 2012 Society of Chemical Industry.

Antimicrobial resistant coliform bacteria in the Gomti river water and determination of their tolerance level.

PubMed

Akhter, Asma; Imran, Mohd; Akhter, Firoz

2014-01-01

The distribution of resistance to ampicillin, chloramphenicol, sulfonamides, tetracycline, and streptomycin among coliform in the Gomti river water samples was investigated. The coliform populations were isolated on Mac Conky and eosin methylene blue (EMB) agar plates supplemented with antibiotics. The incidence of resistance among the coliform population varied considerably in different drug and water sampling sites. Coliform bacteria showed lower drug resistant viable count in sampling site-III (receiving treated wastewater) as compared to more polluted site-I and site-II. Viable count of coliform population obtained on both medium was recorded higher against erythromycin from sampling site-III. Lower viable count of coliforms was recorded against tetracycline in site-II and III. Similar resistance pattern was obtained in the frequency of E. coli and Enterobacter species from all the three sampling sites. Percentage of antibiotic resistant E. coli was observed higher than Enterobacter spp among the total coliforms against all antibiotics tested without Erythromycin and penicillin in site-I and II respectively. Isolates of E. coli and Enterobacter spp. showed their tolerance level (MIC) in the range of 2-100 against the antibiotics tested. Maximum number of isolates of both genus exhibited their MICs at lower concentration range 2-5µg/ml against ciprofloxacin, tetracyclin and amoxycillin. EMB - Eosin methylene blue, IMViC tests - Indole, Methyl Red, Voges Proskauer and Citrate Utilization Tests, MIC - Minimum inhibitory concentration.

Antimicrobial resistant coliform bacteria in the Gomti river water and determination of their tolerance level

PubMed Central

Akhter, Asma; Imran, Mohd; Akhter, Firoz

2014-01-01

The distribution of resistance to ampicillin, chloramphenicol, sulfonamides, tetracycline, and streptomycin among coliform in the Gomti river water samples was investigated. The coliform populations were isolated on Mac Conky and eosin methylene blue (EMB) agar plates supplemented with antibiotics. The incidence of resistance among the coliform population varied considerably in different drug and water sampling sites. Coliform bacteria showed lower drug resistant viable count in sampling site-III (receiving treated wastewater) as compared to more polluted site-I and site-II. Viable count of coliform population obtained on both medium was recorded higher against erythromycin from sampling site-III. Lower viable count of coliforms was recorded against tetracycline in site-II and III. Similar resistance pattern was obtained in the frequency of E. coli and Enterobacter species from all the three sampling sites. Percentage of antibiotic resistant E. coli was observed higher than Enterobacter spp among the total coliforms against all antibiotics tested without Erythromycin and penicillin in site-I and II respectively. Isolates of E. coli and Enterobacter spp. showed their tolerance level (MIC) in the range of 2-100 against the antibiotics tested. Maximum number of isolates of both genus exhibited their MICs at lower concentration range 2-5µg/ml against ciprofloxacin, tetracyclin and amoxycillin. Abbreviations EMB - Eosin methylene blue, IMViC tests - Indole, Methyl Red, Voges Proskauer and Citrate Utilization Tests, MIC - Minimum inhibitory concentration. PMID:24966515

Mono-2-ethylhexyl phthalate associated with insulin resistance and lower testosterone levels in a young population.

PubMed

Chen, Szu-Ying; Hwang, Jing-Shiang; Sung, Fung-Chang; Lin, Chien-Yu; Hsieh, Chia-Jung; Chen, Pau-Chung; Su, Ta-Chen

2017-06-01

Phthalates are commonly used as plasticizers and are reported to associate with testicular dysfunction or insulin resistance in different studies, but the concurrent relationship between phthalate exposure, testosterone levels, and insulin resistance in the young population is not well understood. We recruited 786 subjects aged 12-30 years from a population-based sample of Taiwanese adolescents and young adults from 2006 to 2008. Generalized additive models were used to evaluate glucose homeostasis and testicular function in relation to seven urinary phthalate metabolites among adolescents (aged 12-20) and young adults (aged 20-30) in Taiwan. We observed a trend toward a decrease in male testosterone and an increase in urinary mono-2-ethylhexyl phthalate (MEHP) levels across four quartiles of homeostasis model assessment of insulin resistance (HOMA-IR). After adjusting for potential covariates, generalized additive models further showed that log-transformed insulin and HOMA-IR were raised by 0.055 [95% confidence interval (CI), 0.027-0.082] and 0.056 (95% CI, 0.027-0.084), respectively, with a one-unit increase in log-transformed MEHP in young adults. In male adults (aged 22-30), the log-testosterone levels were reduced by 0.018 (95% CI, 0.001-0.036), with a one-unit of increase in log-transformed MEHP. Such relationships were not observed in adolescents. In conclusion, this study demonstrated age-related associations of urinary MEHP metabolites with impaired metabolic homeostasis of glucose that were only observed in young adults. In addition, MEHP exposure was concurrently associated with lower testosterone levels in young, male adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Herd-level association between antimicrobial use and antimicrobial resistance in bovine mastitis Staphylococcus aureus isolates on Canadian dairy farms.

PubMed

Saini, V; McClure, J T; Scholl, D T; DeVries, T J; Barkema, H W

2012-04-01

Surveillance of antimicrobial use and resistance is needed to manage antimicrobial resistance in bacteria. In this study, data were collected on antimicrobial use and resistance in Staphylococcus aureus (n=562), isolated from intramammary infections and (sub)clinical mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and the Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Dairy producers were asked to deposit empty drug containers into specially provided receptacles, and antimicrobial drug use rate was calculated to quantify antimicrobial use. Minimum inhibitory concentrations were determined using the Sensititer bovine mastitis plate system (TREK Diagnostic Systems Inc., Cleveland, OH), containing antimicrobials commonly used for mastitis treatment and control. Multivariable logistic regression models were built to determine herd-level risk factors of penicillin, ampicillin, pirlimycin, penicillin-novobiocin combination, tetracycline and sulfadimethoxine resistance in Staph. aureus isolates. Intramammary administration of the penicillin-novobiocin combination for dry cow therapy was associated with penicillin and ampicillin resistance [odds ratio (OR): 2.17 and 3.10, respectively]. Systemic administration of penicillin was associated with penicillin resistance (OR: 1.63). Intramammary administration of pirlimycin for lactating cow mastitis treatment was associated with pirlimycin resistance as well (OR: 2.07). Average herd parity was associated with ampicillin and tetracycline resistance (OR: 3.88 and 0.02, respectively). Average herd size was also associated with tetracycline resistance (OR: 1.02). Dairy herds in the Maritime region had higher odds of penicillin and lower odds of ampicillin resistance than dairy herds in Québec (OR: 2.18 and 0.19, respectively). Alberta dairy herds had lower odds of ampicillin and sulfadimethoxine resistance than dairy herds in Québec (OR: 0.04 and 0.08, respectively

Carotid-cardiac baroreflex influence on forearm vascular resistance during low level LBNP

NASA Technical Reports Server (NTRS)

Ludwig, David

1990-01-01

Twelve healthy males were tested at low levels of lower body negative pressure (LBNP) with and without artificial stimulation of the carotid-cardiac baroreceptors. The carotid-cardiac baroreceptors were stimulated by applying a pressure of 10 mmHg to the carotid artery via a pressurized neck chamber. During the procedure, forearm blood flow (FBF) and forearm vascular resistance (FVR) were measured using a Whitney mercury silastic strain gauge technique. FBF decreased while FVR increased with increased intensity of LBNP. Both FBF and FVR were unaffected by carotid-cardiac baroreceptor stimulation.

Country-level operational implementation of the Global Plan for Insecticide Resistance Management

PubMed Central

Hemingway, Janet; Vontas, John; Poupardin, Rodolphe; Raman, Jaishree; Lines, Jo; Schwabe, Chris; Matias, Abrahan; Kleinschmidt, Immo

2013-01-01

Malaria control is reliant on the use of long-lasting pyrethroid-impregnated nets and/or indoor residual spraying (IRS) of insecticide. The rapid selection and spread of operationally significant pyrethroid resistance in African malaria vectors threatens our ability to sustain malaria control. Establishing whether resistance is operationally significant is technically challenging. Routine monitoring by bioassay is inadequate, and there are limited data linking resistance selection with changes in disease transmission. The default is to switch insecticides when resistance is detected, but limited insecticide options and resistance to multiple insecticides in numerous locations make this approach unsustainable. Detailed analysis of the resistance situation in Anopheles gambiae on Bioko Island after pyrethroid resistance was detected in this species in 2004, and the IRS program switched to carbamate bendiocarb, has now been undertaken. The pyrethroid resistance selected is a target-site knock-down resistance kdr-form, on a background of generally elevated metabolic activity, compared with insecticide-susceptible A. gambiae, but the major cytochrome P450-based metabolic pyrethroid resistance mechanisms are not present. The available evidence from bioassays and infection data suggests that the pyrethroid resistance mechanisms in Bioko malaria vectors are not operationally significant, and on this basis, a different, long-lasting pyrethroid formulation is now being reintroduced for IRS in a rotational insecticide resistance management program. This will allow control efforts to be sustained in a cost-effective manner while reducing the selection pressure for resistance to nonpyrethroid insecticides. The methods used provide a template for evidence-based insecticide resistance management by malaria control programs. PMID:23696658

Country-level operational implementation of the Global Plan for Insecticide Resistance Management.

PubMed

Hemingway, Janet; Vontas, John; Poupardin, Rodolphe; Raman, Jaishree; Lines, Jo; Schwabe, Chris; Matias, Abrahan; Kleinschmidt, Immo

2013-06-04

Malaria control is reliant on the use of long-lasting pyrethroid-impregnated nets and/or indoor residual spraying (IRS) of insecticide. The rapid selection and spread of operationally significant pyrethroid resistance in African malaria vectors threatens our ability to sustain malaria control. Establishing whether resistance is operationally significant is technically challenging. Routine monitoring by bioassay is inadequate, and there are limited data linking resistance selection with changes in disease transmission. The default is to switch insecticides when resistance is detected, but limited insecticide options and resistance to multiple insecticides in numerous locations make this approach unsustainable. Detailed analysis of the resistance situation in Anopheles gambiae on Bioko Island after pyrethroid resistance was detected in this species in 2004, and the IRS program switched to carbamate bendiocarb, has now been undertaken. The pyrethroid resistance selected is a target-site knock-down resistance kdr-form, on a background of generally elevated metabolic activity, compared with insecticide-susceptible A. gambiae, but the major cytochrome P450-based metabolic pyrethroid resistance mechanisms are not present. The available evidence from bioassays and infection data suggests that the pyrethroid resistance mechanisms in Bioko malaria vectors are not operationally significant, and on this basis, a different, long-lasting pyrethroid formulation is now being reintroduced for IRS in a rotational insecticide resistance management program. This will allow control efforts to be sustained in a cost-effective manner while reducing the selection pressure for resistance to nonpyrethroid insecticides. The methods used provide a template for evidence-based insecticide resistance management by malaria control programs.

Expression Levels of pvcrt-o and pvmdr-1 Are Associated with Chloroquine Resistance and Severe Plasmodium vivax Malaria in Patients of the Brazilian Amazon

PubMed Central

Melo, Gisely C.; Monteiro, Wuelton M.; Siqueira, André M.; Silva, Siuhelem R.; Magalhães, Belisa M. L.; Alencar, Aline C. C.; Kuehn, Andrea; Portillo, Hernando A. del.; Fernandez-Becerra, Carmen; Lacerda, Marcus V. G.

2014-01-01

Molecular markers associated with the increase of chloroquine resistance and disease severity in Plasmodium vivax are needed. The objective of this study was to evaluate the expression levels of pvcrt-o and pvmdr-1 genes in a group of patients presenting CQRPv and patients who developed severe complications triggered exclusively by P. vivax infection. Two different sets of patients were included to this comprehensive study performed in the Brazilian Amazon: 1) patients with clinically characterized chloroquine-resistant P. vivax compared with patients with susceptible parasites from in vivo studies and 2) patients with severe vivax malaria compared with patients without severity. Quantitative real-time PCR was performed to compare the transcript levels of two main transporters genes, P. vivax chloroquine resistance transporter (pvcrt-o) and the P. vivax multidrug resistance transporter (pvmdr-1). Twelve chloroquine resistant cases and other 15 isolates from susceptible cases were included in the first set of patients. For the second set, seven patients with P. vivax-attributed severe and 10 mild manifestations were included. Parasites from patients with chloroquine resistance presented up to 6.1 (95% CI: 3.8–14.3) and 2.4 (95% CI: 0.53–9.1) fold increase in pvcrt-o and pvmdr-1 expression levels, respectively, compared to the susceptible group. Parasites from the severe vivax group had a 2.9 (95% CI: 1.1–8.3) and 4.9 (95% CI: 2.3–18.8) fold increase in pvcrt-o and pvmdr-1 expression levels as compared to the control group with mild disease. These findings suggest that chloroquine resistance and clinical severity in P. vivax infections are strongly associated with increased expression levels of the pvcrt-o and pvmdr-1 genes likely involved in chloroquine resistance. PMID:25157811

Computing shifts to monitor ATLAS distributed computing infrastructure and operations

NASA Astrophysics Data System (ADS)

Adam, C.; Barberis, D.; Crépé-Renaudin, S.; De, K.; Fassi, F.; Stradling, A.; Svatos, M.; Vartapetian, A.; Wolters, H.

2017-10-01

The ATLAS Distributed Computing (ADC) group established a new Computing Run Coordinator (CRC) shift at the start of LHC Run 2 in 2015. The main goal was to rely on a person with a good overview of the ADC activities to ease the ADC experts’ workload. The CRC shifter keeps track of ADC tasks related to their fields of expertise and responsibility. At the same time, the shifter maintains a global view of the day-to-day operations of the ADC system. During Run 1, this task was accomplished by a person of the expert team called the ADC Manager on Duty (AMOD), a position that was removed during the shutdown period due to the reduced number and availability of ADC experts foreseen for Run 2. The CRC position was proposed to cover some of the AMODs former functions, while allowing more people involved in computing to participate. In this way, CRC shifters help with the training of future ADC experts. The CRC shifters coordinate daily ADC shift operations, including tracking open issues, reporting, and representing ADC in relevant meetings. The CRC also facilitates communication between the ADC experts team and the other ADC shifters. These include the Distributed Analysis Support Team (DAST), which is the first point of contact for addressing all distributed analysis questions, and the ATLAS Distributed Computing Shifters (ADCoS), which check and report problems in central services, sites, Tier-0 export, data transfers and production tasks. Finally, the CRC looks at the level of ADC activities on a weekly or monthly timescale to ensure that ADC resources are used efficiently.

Detection of the High-Level Aminoglycoside Resistance Gene aph(2")-Ib in Enterococcus faecium

PubMed Central

Kao, Susan J.; You, Il; Clewell, Don B.; Donabedian, Susan M.; Zervos, Marcus J.; Petrin, Joanne; Shaw, Karen J.; Chow, Joseph W.

2000-01-01

A new high-level gentamicin resistance gene, designated aph(2")-Ib, was cloned from Enterococcus faecium SF11770. The deduced amino acid sequence of the 897-bp open reading frame of aph(2")-Ib shares homology with the aminoglycoside-modifying enzymes AAC(6′)-APH(2"), APH(2")-Ic, and APH(2")-Id. The observed phosphotransferase activity is designated APH(2")-Ib. PMID:10991878

Study of the optimum level of electrode placement for the evaluation of absolute lung resistivity with the Mk3.5 EIT system.

PubMed

Nebuya, S; Noshiro, M; Yonemoto, A; Tateno, S; Brown, B H; Smallwood, R H; Milnes, P

2006-05-01

Inter-subject variability has caused the majority of previous electrical impedance tomography (EIT) techniques to focus on the derivation of relative or difference measures of in vivo tissue resistivity. Implicit in these techniques is the requirement for a reference or previously defined data set. This study assesses the accuracy and optimum electrode placement strategy for a recently developed method which estimates an absolute value of organ resistivity without recourse to a reference data set. Since this measurement of tissue resistivity is absolute, in Ohm metres, it should be possible to use EIT measurements for the objective diagnosis of lung diseases such as pulmonary oedema and emphysema. However, the stability and reproducibility of the method have not yet been investigated fully. To investigate these problems, this study used a Sheffield Mk3.5 system which was configured to operate with eight measurement electrodes. As a result of this study, the absolute resistivity measurement was found to be insensitive to the electrode level between 4 and 5 cm above the xiphoid process. The level of the electrode plane was varied between 2 cm and 7 cm above the xiphoid process. Absolute lung resistivity in 18 normal subjects (age 22.6 +/- 4.9, height 169.1 +/- 5.7 cm, weight 60.6 +/- 4.5 kg, body mass index 21.2 +/- 1.6: mean +/- standard deviation) was measured during both normal and deep breathing for 1 min. Three sets of measurements were made over a period of several days on each of nine of the normal male subjects. No significant differences in absolute lung resistivity were found, either during normal tidal breathing between the electrode levels of 4 and 5 cm (9.3 +/- 2.4 Omega m, 9.6 +/- 1.9 Omega m at 4 and 5 cm, respectively: mean +/- standard deviation) or during deep breathing between the electrode levels of 4 and 5 cm (10.9 +/- 2.9 Omega m and 11.1 +/- 2.3 Omega m, respectively: mean +/- standard deviation). However, the differences in absolute lung

Plasmid-Mediated High-Level Gentamicin Resistance among Enteric Bacteria Isolated from Pet Turtles in Louisiana

PubMed Central

Díaz, María Alejandra; Cooper, Richard Kent; Cloeckaert, Axel; Siebeling, Ronald John

2006-01-01

The sale of small turtles is banned by the Food and Drug Administration from the U.S. market due to concerns about their excretion of Salmonella spp. To produce a safe pet for the export market, the Louisiana pet turtle industry uses gentamicin sulfate baths (1,000 μg/ml) to eradicate Salmonella spp. from turtle eggs. In 1999, we analyzed bacterial samples recovered from turtle farms and found that strains of Salmonella enterica subsp. arizonae and other bacteria, such as Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were resistant to high concentrations of gentamicin (>2,000 μg/ml) and to other aminoglycosides. The goal of this study was to identify the gene(s) which contributes to the high-level gentamicin resistance phenotype observed in bacteria from environmental samples with turtle farming activity, particularly the salmonellae, and to estimate the incidence of such genes in these bacteria. R plasmids from gentamicin-resistant strains were transferred by conjugation and transformation to naive Escherichia coli cells. Cloning and sequencing of the gentamicin resistance determinants on these plasmids revealed the presence of the aminoglycoside acetyltransferase genes aac(3)-IIa and aac(3)-VIa; the latter was present as a gene cassette of a class 1 integron. Multiplex PCR assays showed that every gentamicin-resistant isolate carried one of these acetyltransferase genes. Pulsed-field gel electrophoresis and restriction enzyme digestion analysis of R plasmids carrying these genes revealed different restriction profiles and sizes, indicating a dissemination of the gentamicin resistance genes through mobile molecular elements. The data presented highlight the need to develop an alternate method for the eradication of Salmonella spp. from turtle eggs. PMID:16391058

Plasmid-mediated high-level gentamicin resistance among enteric bacteria isolated from pet turtles in Louisiana.

PubMed

Díaz, María Alejandra; Cooper, Richard Kent; Cloeckaert, Axel; Siebeling, Ronald John

2006-01-01

The sale of small turtles is banned by the Food and Drug Administration from the U.S. market due to concerns about their excretion of Salmonella spp. To produce a safe pet for the export market, the Louisiana pet turtle industry uses gentamicin sulfate baths (1,000 microg/ml) to eradicate Salmonella spp. from turtle eggs. In 1999, we analyzed bacterial samples recovered from turtle farms and found that strains of Salmonella enterica subsp. arizonae and other bacteria, such as Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were resistant to high concentrations of gentamicin (>2,000 microg/ml) and to other aminoglycosides. The goal of this study was to identify the gene(s) which contributes to the high-level gentamicin resistance phenotype observed in bacteria from environmental samples with turtle farming activity, particularly the salmonellae, and to estimate the incidence of such genes in these bacteria. R plasmids from gentamicin-resistant strains were transferred by conjugation and transformation to naive Escherichia coli cells. Cloning and sequencing of the gentamicin resistance determinants on these plasmids revealed the presence of the aminoglycoside acetyltransferase genes aac(3)-IIa and aac(3)-VIa; the latter was present as a gene cassette of a class 1 integron. Multiplex PCR assays showed that every gentamicin-resistant isolate carried one of these acetyltransferase genes. Pulsed-field gel electrophoresis and restriction enzyme digestion analysis of R plasmids carrying these genes revealed different restriction profiles and sizes, indicating a dissemination of the gentamicin resistance genes through mobile molecular elements. The data presented highlight the need to develop an alternate method for the eradication of Salmonella spp. from turtle eggs.

Plasma levels of lysine, tyrosine, and valine during pregnancy are independent risk factors of insulin resistance and gestational diabetes.

PubMed

Park, Sunmin; Park, Jin Young; Lee, Ju Hong; Kim, Sung-Hoon

2015-03-01

This study compared plasma concentrations of amino acids in pregnant women with and without gestational diabetes mellitus (GDM) and identified the association between plasma amino acid levels and GDM, insulin resistance, and insulin secretion at 24-28 weeks of pregnancy. Circulating amino acid levels were evaluated using high-performance liquid chromatography at 24-28 weeks of pregnancy in 25 non-GDM and 64 GDM women after adjusting for covariates such as maternal age, body mass index (BMI) before pregnancy, BMI and gestational age at screening GDM, and daily caloric intake. Backward stepwise logistic regression analysis was used to identify the predictors of developing GDM, and homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-B). Circulating levels of amino acids except threonine and tyrosine were significantly higher in GDM women than non-GDM women. Along with the intakes of energy, protein, and fat from animal sources, the intakes of each amino acid were significantly higher in the GDM group without a direct correlation to plasma amino acid levels. The variation in GDM development was explained by maternal age, diastolic blood pressure, and plasma lysine levels (R(2)=0.691). Height, BMI before pregnancy, systolic blood pressure, and plasma tyrosine and valine levels accounted for the variation in HOMA-IR (R(2)=0.589). The 53.3% variation of HOMA-B was explained by maternal age, BMI at GDM screening, plasma insulin level at 1 h during the oral glucose tolerance test (OGTT), and plasma valine level. Circulating concentrations of lysine, tyrosine, and valine were independently and positively associated with GDM through modifying insulin resistance and secretion.

Randomized Clinical Trial To Compare The Effects Of Preoperative Oral Carbohydrate Loading Versus Placebo On Insulin Resistance And Cortisol Level After Laparoscopic Cholecystectomy.

PubMed

Pędziwiatr, Michał; Pisarska, Magdalena; Matłok, Maciej; Major, Piotr; Kisielewski, Michał; Wierdak, Mateusz; Natkaniec, Michał; Budzyński, Piotr; Rubinkiewicz, Mateusz; Budzyński, Rzej

2015-08-01

Postoperative insulin resistance, used as a marker of stress response, is clearly an adverse event. It may induce postoperative hyperglycemia, which according to some authors can increase the risk of postoperative complications. One of the elements of modern perioperative care is preoperative administration of oral carbohydrate loading (CHO-loading), which shortens preoperative fasting and reduces insulin resistance. The aim of the study is to establish the influence of CHO-loading on the level of insulin resistance and cortisol in patients undergoing elective laparoscopic cholecystectomy. Patients were randomly allocated to one of 2 groups. The intervention group included 20 patients who received CHO-loading (400 ml Nutricia pre-op®) 2 hours prior surgery. The control group received a placebo (clear water). In every patient blood samples were taken 2 hours prior to surgery, immediately after surgery, and on the 1st postoperative day. Levels and changes in glucose, cortisol and insulin resistance were analyzed in both groups. Although there were differences in the levels of cortisol, insulin, and insulin resistance, no statistically significant differences were observed between groups in every measurement. The length of stay and postoperative complications were comparable in both groups. We believe that CHO-loading is not clinically justified in case of laparoscopic cholecystectomy. No effect on the levels of glucose, insulin resistance and cortisol was observed. Even though such procedure is safe, in our opinion there is no clinical benefit from CHO-loading prior to laparoscopic cholecystectomy.

Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects

PubMed Central

Al Qarni, Ali Ahmed; Joatar, Faris Elbahi; Das, Nagalla; Awad, Mohamed; Eltayeb, Mona; Al-Zubair, Ahmed Gasim; Ali, Muhalab E.; Al Masaud, Abdulaziz; Shire, Abdirashid M.; Gumaa, Khalid

2017-01-01

Background Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM. Methods Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique. Results Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM. Conclusion The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM. PMID:28555463

Increased plasma levels of FABP4 and PTEN is associated with more severe insulin resistance in women with gestational diabetes mellitus.

PubMed

Li, Yuan-yuan; Xiao, Rui; Li, Cai-ping; Huangfu, Jian; Mao, Jiang-feng

2015-02-08

The aim of this study was to investigate the relationship between plasma fatty acid binding protein 4 (FABP4), phosphatase and tensin homolog (PTEN), and insulin resistance in patients with gestational diabetes mellitus (GDM). Plasma FABP4 and PTEN were determined by ELISA in GDM patients (GDM group, n=30) and in euglycemic pregnant women (control group, n=30). The clinical features, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were compared between the 2 groups. The influence of risk factors on insulin resistance, including BMI, lipid profiles, FABP4, and PTEN, were further investigated by multiple-factor stepwise regression analysis. Higher levels of BMI, ΔBMI, triglyceride (TG), fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), fasting insulin, HOMA-IR, FABP4, PTEN, and lower level of high-density lipoprotein cholesterol (HDL-C) were found in the GDM patients than in the controls (all P<0.005). The plasma FABP4 was 1.47±0.25 vs. 0.20±0.07 ng/ml in the GDM and control group, respectively (P<0.0001). Plasma PTEN was 6.46±1.57 vs. 4.72±0.82 ng/ml in the GDM and control group, respectively (P<0.0001). There was a positive relation between plasma FABP4 and PTEN when all blood samples, including GDM and control groups, were analyzed (P<0.05). The multiple-factor regression analysis revealed that plasma FABP4, TG, and PTEN were independent risk factors for increased insulin resistance. GDM patients have more severe insulin resistance compared to euglycemic pregnant women. Higher levels of plasma FABP4 and PTEN are associated with increased insulin resistance and may participate in the pathogenesis of insulin resistance during gestation.

Improvement of Leaching Resistance of Low-level Waste Form in Korea

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, J.Y.; Lee, B.C.; Kim, C.L.

2006-07-01

Low-level liquid concentrate wastes including boric acid have been immobilized with paraffin wax using concentrate waste drying system in Korean nuclear power plants since 1995. Small amount of low density polyethylene (LDPE) was added to increase the leaching resistance of the existing paraffin waste form and the influence of LDPE on the leaching behavior of waste form was investigated. It was observed that the leaching of nuclides immobilized within paraffin waste form remarkably reduced as the content of LDPE increased. The acceptance criteria of paraffin waste form associated with leachability index and compressive strength after the leaching test were successfullymore » satisfied with the help of LDPE. (authors)« less

High-level fluoroquinolone-resistant clinical isolates of Escherichia coli overproduce multidrug efflux protein AcrA.

PubMed

Mazzariol, A; Tokue, Y; Kanegawa, T M; Cornaglia, G; Nikaido, H

2000-12-01

Immunoblotting with antibody against AcrA, an obligatory component of the AcrAB multidrug efflux system, showed that this protein was overexpressed by >/=170% in 9 of 10 clinical isolates of Esherichia coli with high-level ciprofloxacin resistance (MICs, >/=32 microg/ml) but not in any of the 15 isolates for which the MIC was

In vivo transcription of R-plasmid deoxyribonucleic acid in Escherichia coli strains with altered antibiotic resistance levels and/or conjugal proficiency.

PubMed Central

Davis, R; Vapnek, D

1976-01-01

The amounts of plasmid deoxyribonucleic acid (DNA) and the levels of the in vivo transcription of the Escherichia coli plasmids R538-1 (repressed for conjugal transfer) and R538-1drd (derepressed for transfer) were determined by DNA-DNA hybridization and DNA-ribonucleic acid hybridization, respectively. The results demonstrate that the level of plasmid transcription is increased by two-fold in the strain carrying the derepressed plasmid, compared to an isogenic strain carrying the repressed plasmid, whereas the amount of plasmid DNA is approximately the same, suggesting that the transfer genes are under transcriptional control. Levels of plasmid DNA, plasmid DNA transcription, and chloramphenicol acetyltransferase activity were also compared in a mutant strain that carried the R538-1drd plasmid and was resistant to high levels of antibiotics. This strain produces about 13 copies of plasmid DNA per chromosome compared to five copies for the parent strain. The level of transcription of plasmid DNA was found to be twofold higher in the high-level resistant strain, whereas the level of chloramphenition, acetyltransferase activity was increased by 10-fold. In addition the levels of plasmid DNA transcription and chloramphenicol acetyltransferase activity in the high-level resistant strain were found to be further increased by the presence of high levels of chloramphenicol in the growth medium. The amount of plasmid DNA remained constant under these conditions, indicating that high levels of chloramphenicol can stimulate the expression of plasmid genes at the level of transcription in this strain. PMID:767321

Monitoring the ground water level change during the pump test by using the Electric resistivity tomography

NASA Astrophysics Data System (ADS)

Hsu, H.; Chang, P. Y.; Yao, H. J.

2017-12-01

For hydrodynamics study of the unconfined aquifer in gravel formation, a pumping test was established to estimate the hydraulic conductivity in the midstream of Zhoushui River in Taiwan. The hydraulic parameters and the cone of depression could be estimated by monitoring the groundwater drawdown in an observation well which was in a short distance far from the pumping well. In this study we carried out the electric resistivity image monitoring during the whole pumping test. The electric resistivity data was measured with the surface and downhole electrodes which would produce a clear subsurface image of groundwater level through a larger distance than the distance between pumping and observation wells. The 2D electric image could also describe how a cone of depression truly created at subsurface. The continuous records could also show the change of groundwater level during the whole pumping test which could give a larger scale of the hydraulic parameters.

Atrazine Resistance in Chenopodium album

PubMed Central

Bettini, Priscilla; McNally, Sheila; Sevignac, Mireille; Darmency, Henri; Gasquez, Jacques; Dron, Michel

1987-01-01

In Chenopodium album two different levels of atrazine resistance have been found according to following criteria: lethal dose and leaf fluorescence curve. The intermediate (I) phenotype is represented by a low level of resistance and a typical I fluorescence curve. It arose at high frequency, within one generation, after self-pollination of particular plants displaying a susceptible (S) phenotype. The resistance phenotype (Ri) has a high level of resistance and presents a typical resistant fluorescence curve. It appeared after self-pollination of chemically treated I plants. The I, Ri, and also R (resistant plants found in atrazine treated fields) phenotypes contain a serine to glycine mutation at amino acid position 264 in the chloroplast psbA gene product. The steady state level of the psbA gene transcript is not modified between S, I, Ri, and R phenotypes. Images Fig. 4 PMID:16665624

Evolution of a double amino acid substitution in the 5-enolpyruvylshikimate-3-phosphate synthase in Eleusine indica conferring high-level glyphosate resistance.

PubMed

Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R Douglas; Powles, Stephen B

2015-04-01

Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I+P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action. © 2015 American Society of Plant Biologists. All Rights Reserved.

Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain.

PubMed

Cámara, Jordi; Serra, Judit; Ayats, Josefina; Bastida, Teresa; Carnicer-Pont, Dolors; Andreu, Antònia; Ardanuy, Carmen

2012-08-01

The aim of this study was to characterize the first two extended-spectrum cephalosporin-resistant and multidrug-resistant (MDR) Neisseria gonorrhoeae isolates collected from two sexually related patients (men who have sex with men) in Spain. Antimicrobial susceptibility was studied by Etest. Genes involved in quinolone, ceftriaxone and multidrug resistance were amplified by PCR and sequenced in both directions. The isolates were typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST). The two isolates had the same MDR profile, showing resistance to penicillin (MIC 0.094 mg/L; β-lactamase negative), ceftriaxone (MIC 1.5 mg/L), cefixime (MIC 1.5 mg/L), cefotaxime (MIC 1 mg/L), ciprofloxacin (MIC >32 mg/L) and tetracycline (MIC 1.5 mg/L). NG-MAST showed that both isolates belonged to sequence type (ST) 1407 (porB-908 and tbpB-110). Ciprofloxacin resistance was due to amino acid substitutions in GyrA (S91F and D95G) and ParC (S87R). An A deletion in the promoter of the MtrCDE efflux pump (mtrR) was detected. No changes were detected in the pilQ gene. The outer membrane protein PorB showed two substitutions at G120K and A121N. An L421P substitution was observed in the PBP1A (ponA) sequence. The sequence of PBP2 (penA) showed a mosaic structure related to genotype XXXIV with a single additional amino acid substitution (A501P). This genotype was identical to a recently described French isolate (F89). This is the first reported case of high-level extended-spectrum cephalosporin-resistant N. gonorrhoeae transmission. The molecular typing and MDR genotype suggest possible European spread of this strain, highlighting the need for surveillance and the importance of testing the susceptibility of N. gonorrhoeae to extended-spectrum cephalosporins.

Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy.

PubMed

de Castro, J; Sevillano, J; Marciniak, J; Rodriguez, R; González-Martín, C; Viana, M; Eun-suk, O H; de Mouzon, S Hauguel; Herrera, E; Ramos, M P

2011-11-01

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

Implication of Low Level Inflammation in the Insulin Resistance of Adipose Tissue at Late Pregnancy

PubMed Central

de Castro, J.; Sevillano, J.; Marciniak, J.; Rodriguez, R.; González-Martín, C.; Viana, M.; Eun-suk, O. H.; de Mouzon, S. Hauguel; Herrera, E.

2011-01-01

Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance. PMID:21914778

Analysis of the Biceps Brachii Muscle by Varying the Arm Movement Level and Load Resistance Band

PubMed Central

Abdullah, Shahrum Shah; Jali, Mohd Hafiz

2017-01-01

Biceps brachii muscle illness is one of the common physical disabilities that requires rehabilitation exercises in order to build up the strength of the muscle after surgery. It is also important to monitor the condition of the muscle during the rehabilitation exercise through electromyography (EMG) signals. The purpose of this study was to analyse and investigate the selection of the best mother wavelet (MWT) function and depth of the decomposition level in the wavelet denoising EMG signals through the discrete wavelet transform (DWT) method at each decomposition level. In this experimental work, six healthy subjects comprised of males and females (26 ± 3.0 years and BMI of 22 ± 2.0) were selected as a reference for persons with the illness. The experiment was conducted for three sets of resistance band loads, namely, 5 kg, 9 kg, and 16 kg, as a force during the biceps brachii muscle contraction. Each subject was required to perform three levels of the arm angle positions (30°, 90°, and 150°) for each set of resistance band load. The experimental results showed that the Daubechies5 (db5) was the most appropriate DWT method together with a 6-level decomposition with a soft heursure threshold for the biceps brachii EMG signal analysis. PMID:29138687

Analysis of the Biceps Brachii Muscle by Varying the Arm Movement Level and Load Resistance Band.

PubMed

Burhan, Nuradebah; Kasno, Mohammad 'Afif; Ghazali, Rozaimi; Said, Md Radzai; Abdullah, Shahrum Shah; Jali, Mohd Hafiz

2017-01-01

Biceps brachii muscle illness is one of the common physical disabilities that requires rehabilitation exercises in order to build up the strength of the muscle after surgery. It is also important to monitor the condition of the muscle during the rehabilitation exercise through electromyography (EMG) signals. The purpose of this study was to analyse and investigate the selection of the best mother wavelet (MWT) function and depth of the decomposition level in the wavelet denoising EMG signals through the discrete wavelet transform (DWT) method at each decomposition level. In this experimental work, six healthy subjects comprised of males and females (26 ± 3.0 years and BMI of 22 ± 2.0) were selected as a reference for persons with the illness. The experiment was conducted for three sets of resistance band loads, namely, 5 kg, 9 kg, and 16 kg, as a force during the biceps brachii muscle contraction. Each subject was required to perform three levels of the arm angle positions (30°, 90°, and 150°) for each set of resistance band load. The experimental results showed that the Daubechies5 (db5) was the most appropriate DWT method together with a 6-level decomposition with a soft heursure threshold for the biceps brachii EMG signal analysis.

Diversity of plasmids and transmission of high-level mupirocin mupA resistance gene in Staphylococcus haemolyticus.

PubMed

do Carmo Ferreira, Natália; Schuenck, Ricardo P; dos Santos, Kátia Regina Netto; de Freire Bastos, Maria do Carmo; Giambiagi-deMarval, Marcia

2011-03-01

The coagulase-negative staphylococci are known for their ability to acquire resistance genes, which limits the choice of therapeutic options for the treatment of infections caused by these microorganisms. In this study, the diversity of high-level mupirocin resistance plasmids (Mup(R) ) was investigated in four strains of Staphylococcus haemolyticus belonging to different pulsed-field gel electrophoresis (PFGE) types or subtypes, isolated in a Brazilian hospital. These strains harbor the mupA gene in large plasmids. In addition, the presence of IS257 sequences flanking the mupA gene was also shown. Two isolates belonging to two different PFGE types exhibited a similar polymorphism for a fragment of the mupA gene and the closest proximal flanking copies of the IS257, suggesting horizontal transmission of S. haemolyticus mupirocin resistance plasmids in the environment and a role of this species as a reservoir of the mupA gene. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

[Resistance risk and resistance stability of Frankliniella occidentalis to imidacloprid, emamectin benzoate, and phoxim].

PubMed

Wang, Sheng-Yin; Yu, Yi; Liu, Yong-Jie; Ma, Jing-Yu

2012-12-01

In order to effectively control the damage of Frankliniella occidentalis (Pergande), Phaseolus vuglaris was dipped with imidacloprid, phoxim, and emamectin benzoate, respectively to select the resistance populations of F. occidentalis from its susceptible population, and the resistance inheritance and resistance risk were analyzed with the resistance reality heredity. After 32, 32, and 24 generations' selection, the F. occidentalis populations obtained 13.8-fold, 29.4-fold and 39.0-fold resistance to imidacloprid, phoxim, and emamectin benzoate, respectively. The resistance reality heritability to imidacloprid, phoxim, and emamectin benzoate was 0.112, 0.166, and 0.259, respectively. The resistance development rate to emamectin benzoate was the fastest, followed by to phoxim, and to imidacloprid. The higher the resistance levels of the selected populations, the lower the differences between the larva and adult susceptibility to imidacloprid, phoxim, and emamectin benzoate. Stopping selection for 12 continuous generations, the resistance level of the selected resistance populations to imidacloprid, phoxim, and emamectin benzoate had definite decline, but it was difficult to regain the original susceptibility. F. occidentalis had a greater potential to gain high level resistance to imidacloprid, phoxim, and emamectin benzoate. Compared with the resistance of F. occidentalis to phoxim and emamectin benzoate, the resistance to imidacloprid increased slower and decreased faster, and thus, imidacloprid was more appropriate to control F. occidentalis in practice.

Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study.

PubMed

Fifer, Helen; Cole, Michelle; Hughes, Gwenda; Padfield, Simon; Smolarchuk, Christa; Woodford, Neil; Wensley, Adrian; Mustafa, Nazim; Schaefer, Ulf; Myers, Richard; Templeton, Kate; Shepherd, Jill; Underwood, Anthony

2018-05-01

Between Nov 3, 2014, and Feb 24, 2017, 70 cases of high-level azithromycin-resistant (HL-AziR; minimum inhibitory concentration [MIC] ≥256 mg/L) Neisseria gonorrhoeae were reported from across England. Whole-genome sequencing was done to investigate this outbreak to determine whether the ongoing outbreak represented clonal spread of an HL-AziR N gonorrhoeae strain identified in Leeds. We also wanted to elucidate the molecular mechanisms of azithromycin resistance in N gonorrhoeae in the UK. In this observational study, whole-genome sequencing was done on the HL-AziR N gonorrhoeae isolates from England. As comparators, 110 isolates from the UK and Ireland with a range of azithromycin MICs were also sequenced, including eight isolates from Scotland with azithromycin MICs ranging from 0·12 mg/L to 1·00 mg/L that were N gonorrhoeae multi-antigen sequence type 9768 (ST9768), which was the sequence type initially responsible for the outbreak. The presence of mutations or genes associated with azithromycin resistance was also investigated. 37 of the 60 HL-AziR isolates from England belonged to ST9768, and were genetically similar (mean 4·3 single-nucleotide polymorphisms). A 2059A→G mutation was detected in three or all four alleles of the 23S rRNA gene. Five susceptible ST9768 isolates had one mutated 23S rRNA allele and one low-level resistant ST9768 isolate had two mutated alleles. Sustained transmission of a successful HL-AziR clone was seen across England. Mutation 2059A→G was found in isolates with lower azithromycin MICs. Azithromycin exposure might have provided the selection pressure for one or two mutated copies of the 23S rRNA gene to recombine with wild-type copies, leading to three or four mutated copies and the HL-AziR phenotype. HL-AziR could emerge in isolates with low azithromycin MICs and eliminate the effectiveness of azithromycin as part of dual therapy for the treatment of gonorrhoea. Public Health England. Copyright © 2018 Elsevier Ltd. All

High level of resistance to aztreonam and ticarcillin in Pseudomonas aeruginosa isolated from soil of different crops in Brazil.

PubMed

Pitondo-Silva, André; Martins, Vinicius Vicente; Fernandes, Ana Flavia Tonelli; Stehling, Eliana Guedes

2014-03-01

Pseudomonas aeruginosa can be found in water, soil, plants and, human and animal fecal samples. It is an important nosocomial pathogenic agent characterized by an intrinsic resistance to multiple antimicrobial agents and the ability to develop high-level (acquired) multidrug resistance through some mechanisms, among them, by the acquisition of plasmids and integrons, which are mobile genetic elements. In this study, 40 isolates from Brazilian soil were analyzed for antibiotic resistance, presence of integrons and plasmidial profile. The results demonstrated that the vast majority of the isolates have shown resistance for aztreonam (92.5%, n=37) and ticarcillin (85%, n=34), four isolates presented plasmids and eight isolates possess the class 1 integron. These results demonstrated that environmental isolates of P. aeruginosa possess surprising antibiotic resistance profile to aztreonam and ticarcillin, two antimicrobial agents for clinical treatment of cystic fibrosis patients and other infections occurred by P. aeruginosa. Copyright © 2014 Elsevier B.V. All rights reserved.

Evolution of a Double Amino Acid Substitution in the 5-Enolpyruvylshikimate-3-Phosphate Synthase in Eleusine indica Conferring High-Level Glyphosate Resistance1

PubMed Central

Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R. Douglas; Powles, Stephen B.

2015-01-01

Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I + P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action. PMID:25717039

Origins of low resistivity and Ge donor level in Ge ion-implanted ZnO bulk single crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamioka, K.; Oga, T.; Izawa, Y.

2013-12-04

The energy level of Ge in Ge-ion implanted ZnO single crystals is studied by Hall-effect and photoluminescence (PL) methods. The variations in resistivity from ∼10{sup 3} Ωcm for un-implanted samples to ∼10{sup −2} Ωcm for as-implanted ones are observed. The resistivity is further decreased to ∼10{sup −3} Ωcm by annealing. The origins of the low resistivity are attributed to both the zinc interstitial (Zn{sub i}) related defects and the electrical activated Ge donor. An activation energy of Ge donors estimated from the temperature dependence of carrier concentration is 102 meV. In PL studies, the new peak at 372 nm (3.33more » eV) related to the Ge donor is observed in 1000 °C annealed samples.« less

HIV-1 Drug Resistance and Resistance Testing

PubMed Central

Clutter, Dana S; Jordan, Michael R; Bertagnolio, Silvia; Shafer, Robert W

2016-01-01

The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases. PMID:27587334

Cluster of Neisseria gonorrhoeae Isolates With High-level Azithromycin Resistance and Decreased Ceftriaxone Susceptibility, Hawaii, 2016.

PubMed

Katz, Alan R; Komeya, Alan Y; Kirkcaldy, Robert D; Whelen, A Christian; Soge, Olusegun O; Papp, John R; Kersh, Ellen N; Wasserman, Glenn M; O'Connor, Norman P; O'Brien, Pamela S; Sato, Douglas T; Maningas, Eloisa V; Kunimoto, Gail Y; Tomas, Juval E

2017-09-15

The Centers for Disease Control and Prevention (CDC) currently recommends dual therapy with ceftriaxone and azithromycin for gonorrhea to ensure effective treatment and slow emergence of antimicrobial resistance. Since 2013, the prevalence of reduced azithromycin susceptibility increased in the United States; however, these strains were highly susceptible to cephalosporins. We identified a cluster of Neisseria gonorrhoeae isolates with high-level azithromycin resistance, several of which also demonstrated decreased ceftriaxone susceptibility. Eight N. gonorrhoeae isolates collected from 7 patients on Oahu, Hawaii, seen 21 April 2016 through 10 May 2016 underwent routine Etest antimicrobial susceptibility testing by the Hawaii Department of Health. All demonstrated elevated azithromycin minimum inhibitory concentrations (MICs) >256 μg/mL and elevated ceftriaxone MICs (≥0.125 μg/mL). Isolates were sent to the University of Washington and CDC for confirmatory agar dilution testing; sequence data were sent to CDC for analysis. All patients were interviewed and treated, and when possible, partners were interviewed, tested, and treated. All isolates had azithromycin MICs >16 µg/mL and 5 had ceftriaxone MICs = 0.125 µg/mL by agar dilution. All isolates were β-lactamase positive and were resistant to penicillin, tetracycline, and ciprofloxacin. Genomic analysis revealed genetic relatedness. No patients reported recent travel or antibiotic use, and no male patients reported male sex partners. All patients were successfully treated. This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Modified expression of alternative oxidase in transgenic tomato and petunia affects the level of tomato spotted wilt virus resistance.

PubMed

Ma, Hao; Song, Congfeng; Borth, Wayne; Sether, Diane; Melzer, Michael; Hu, John

2011-10-20

Tomato spotted wilt virus (TSWV) has a very wide host range, and is transmitted in a persistent manner by several species of thrips. These characteristics make this virus difficult to control. We show here that the over-expression of the mitochondrial alternative oxidase (AOX) in tomato and petunia is related to TSWV resistance. The open reading frame and full-length sequence of the tomato AOX gene LeAox1au were cloned and introduced into tomato 'Healani' and petunia 'Sheer Madness' using Agrobacterium-mediated transformation. Highly expressed AOX transgenic tomato and petunia plants were selfed and transgenic R1 seedlings from 10 tomato lines and 12 petunia lines were used for bioassay. For each assayed line, 22 to 32 tomato R1 progeny in three replications and 39 to 128 petunia progeny in 13 replications were challenged with TSWV. Enzyme-Linked Immunosorbent Assays showed that the TSWV levels in transgenic tomato line FKT4-1 was significantly lower than that of wild-type controls after challenge with TSWV. In addition, transgenic petunia line FKP10 showed significantly less lesion number and smaller lesion size than non-transgenic controls after inoculation by TSWV. In all assayed transgenic tomato lines, a higher percentage of transgenic progeny had lower TSWV levels than non-transgenic plants after challenge with TSWV, and the significantly increased resistant levels of tomato and petunia lines identified in this study indicate that altered expression levels of AOX in tomato and petunia can affect the levels of TSWV resistance.

Modified expression of alternative oxidase in transgenic tomato and petunia affects the level of tomato spotted wilt virus resistance

PubMed Central

2011-01-01

Background Tomato spotted wilt virus (TSWV) has a very wide host range, and is transmitted in a persistent manner by several species of thrips. These characteristics make this virus difficult to control. We show here that the over-expression of the mitochondrial alternative oxidase (AOX) in tomato and petunia is related to TSWV resistance. Results The open reading frame and full-length sequence of the tomato AOX gene LeAox1au were cloned and introduced into tomato 'Healani' and petunia 'Sheer Madness' using Agrobacterium-mediated transformation. Highly expressed AOX transgenic tomato and petunia plants were selfed and transgenic R1 seedlings from 10 tomato lines and 12 petunia lines were used for bioassay. For each assayed line, 22 to 32 tomato R1 progeny in three replications and 39 to 128 petunia progeny in 13 replications were challenged with TSWV. Enzyme-Linked Immunosorbent Assays showed that the TSWV levels in transgenic tomato line FKT4-1 was significantly lower than that of wild-type controls after challenge with TSWV. In addition, transgenic petunia line FKP10 showed significantly less lesion number and smaller lesion size than non-transgenic controls after inoculation by TSWV. Conclusion In all assayed transgenic tomato lines, a higher percentage of transgenic progeny had lower TSWV levels than non-transgenic plants after challenge with TSWV, and the significantly increased resistant levels of tomato and petunia lines identified in this study indicate that altered expression levels of AOX in tomato and petunia can affect the levels of TSWV resistance. PMID:22014312

High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel penA Mosaic Allele in a Successful International Clone Causes Treatment Failure

PubMed Central

Golparian, Daniel; Nicholas, Robert; Ohnishi, Makoto; Gallay, Anne; Sednaoui, Patrice

2012-01-01

Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefixime and ceftriaxone resistance which was isolated in France and most likely caused a treatment failure with cefixime. F89 was examined using six species-confirmatory tests, antibiograms (33 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of known gonococcal resistance determinants (penA, mtrR, penB, ponA, and pilQ). F89 was assigned to MLST sequence type 1901 (ST1901) and NG-MAST ST1407, which is a successful gonococcal clone that has spread globally. F89 has high-level resistance to cefixime (MIC = 4 μg/ml) and ceftriaxone (MIC = 1 to 2 μg/ml) and resistance to most other antimicrobials examined. A novel penA mosaic allele (penA-CI), which was penA-XXXIV with an additional A501P alteration in penicillin-binding protein 2, was the primary determinant for high-level ESC resistance, as determined by transformation into a set of recipient strains. N. gonorrhoeae appears to be emerging as a superbug, and in certain circumstances and settings, gonorrhea may become untreatable. Investigations of the biological fitness and enhanced understanding and monitoring of the ESC-resistant clones and their international transmission are required. Enhanced disease control activities, antimicrobial resistance control and surveillance worldwide, and public health response plans for global (and national) perspectives are also crucial. Nevertheless, new treatment strategies and/or drugs and, ideally, a vaccine are essential to develop for efficacious gonorrhea management. PMID:22155830

Low levels of vitamin D poorly responsive to daylight exposure in patients with therapy-resistant schizophrenia.

PubMed

Bogers, Jan P.A.M.; Bostoen, Tijmen; Broekman, Theo G.

2016-01-01

Low vitamin D levels are associated with schizophrenia, but the possible association between vitamin D levels and illness severity or duration of exposure to daylight has barely been investigated. To compare vitamin D levels in therapy-refractory severely ill schizophrenia patients and members of staff. To investigate the influence of daylight exposure on vitamin D levels in patients. Vitamin D was measured in patients with therapy-resistant schizophrenia in April, after the winter, and in patients and staff members in June, after an exceptionally sunny spring. Vitamin D levels in April and June were compared in patients, and levels in June were compared in patients and staff. The influence of daylight was taken into account by comparing the time patients spent outdoors during the day with the recommended minimum time for adequate vitamin D synthesis, and by comparing time spent outdoors in patients and staff. Patients had high rates of vitamin D deficiency (79-90%) and lower levels of vitamin D than staff members (p < 0.001), independent of skin pigmentation. In patients, vitamin D levels did not normalize, despite the considerably longer than recommended exposure of the skin to daylight (p < 0.001) and the longer exposure in patients than in staff members (p = 0.003). The vitamin D deficiency of therapy-resistant schizophrenia patients is pronounced and cannot be explained by differences in skin pigmentation or by an inactive, indoor lifestyle on the ward. Even theoretically sufficient exposure of the patients to daylight did not ameliorate the low vitamin D levels. While vitamin D deficiency probably plays a role in somatic health problems, it may also play a role in schizophrenia. Interestingly, exposure to daylight during an unusually sunny spring was not sufficient to correct the vitamin D deficiency seen in the patients. This emphasizes the need to measure and correct vitamin D levels in these patients.

Antibiotic Effects on Methicillin-Resistant Staphylococcus aureus Cytoplasmic Peptidoglycan Intermediate Levels and Evidence for Potential Metabolite Level Regulatory Loops.

PubMed

Vemula, Harika; Ayon, Navid J; Burton, Alloch; Gutheil, William G

2017-06-01

Cytoplasmic peptidoglycan (PG) precursor levels were determined in methicillin-resistant Staphylococcus aureus (MRSA) after exposure to several cell wall-targeting antibiotics. Three experiments were performed: (i) exposure to 4× MIC levels (acute); (ii) exposure to sub-MIC levels (subacute); (iii) a time course experiment of the effect of vancomycin. In acute exposure experiments, fosfomycin increased UDP-GlcNAc, as expected, and resulted in substantially lower levels of total UDP-linked metabolite accumulation relative to other pathway inhibitors, indicating reduced entry into this pathway. Upstream inhibitors (fosfomycin, d-cycloserine, or d-boroalanine) reduced UDP-MurNAc-pentapeptide levels by more than fourfold. Alanine branch inhibitors (d-cycloserine and d-boroalanine) reduced d-Ala-d-Ala levels only modestly (up to 4-fold) but increased UDP-MurNAc-tripeptide levels up to 3,000-fold. Downstream pathway inhibitors (vancomycin, bacitracin, moenomycin, and oxacillin) increased UDP-MurNAc-pentapeptide levels up to 350-fold and UDP-MurNAc-l-Ala levels up to 80-fold, suggesting reduced MurD activity by downstream inhibitor action. Sub-MIC exposures demonstrated effects even at 1/8× MIC which strongly paralleled acute exposure changes. Time course data demonstrated that UDP-linked intermediate levels respond rapidly to vancomycin exposure, with several intermediates increasing three- to sixfold within minutes. UDP-linked intermediate level changes were also multiphasic, with some increasing, some decreasing, and some increasing and then decreasing. The total (summed) UDP-linked intermediate pool increased by 1,475 μM/min during the first 10 min after vancomycin exposure, providing a revised estimate of flux in this pathway during logarithmic growth. These observations outline the complexity of PG precursor response to antibiotic exposure in MRSA and indicate likely sites of regulation (entry and MurD). Copyright © 2017 American Society for Microbiology.

Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis

PubMed Central

Phillips, Andrew N; Cambiano, Valentina; Miners, Alec; Revill, Paul; Pillay, Deenan; Lundgren, Jens D; Bennett, Diane; Raizes, Elliott; Nakagawa, Fumiyo; De Luca, Andrea; Vitoria, Marco; Barcarolo, Jhoney; Perriens, Joseph; Jordan, Michael R; Bertagnolio, Silvia

2016-01-01

Summary Background With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted drug resistance. Methods We created a model of HIV transmission, progression, and the effects of ART, which accounted for resistance generation, transmission, and disappearance of resistance from majority virus in the absence of drug pressure. We simulated 5000 ART programmatic scenarios with different prevalence levels of detectable resistance in people starting ART in 2017 (t0) who had not previously been exposed to antiretroviral drugs. We used the model to predict cost-effectiveness of various potential changes in policy triggered by different prevalence levels of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) measured in the population starting ART. Findings Individual-level resistance testing before ART initiation was not generally a cost-effective option, irrespective of the cost-effectiveness threshold. At a cost-effectiveness threshold of US$500 per quality-adjusted life-year (QALY), no change in policy was cost effective (ie, no change in policy would involve paying less than $500 per QALY gained), irrespective of the prevalence of pretreatment NNRTI resistance, because of the increased cost of the policy alternatives. At thresholds of $1000 or higher, and with the prevalence of pretreatment NNRTI resistance greater than 10%, a policy to measure viral load 6 months after ART initiation became cost effective. The policy option to change the standard first-line treatment to a boosted protease inhibitor regimen became cost effective at a prevalence of NNRTI resistance higher than 15%, for cost-effectiveness thresholds greater than $2000. Interpretation Cost-effectiveness of potential policies to adopt in response

Sublethal Ciprofloxacin Treatment Leads to Rapid Development of High-Level Ciprofloxacin Resistance during Long-Term Experimental Evolution of Pseudomonas aeruginosa

PubMed Central

Jørgensen, Karin Meinike; Wassermann, Tina; Jensen, Peter Østrup; Hengzuang, Wang; Molin, Søren; Høiby, Niels

2013-01-01

The dynamics of occurrence and the genetic basis of ciprofloxacin resistance were studied in a long-term evolution experiment (940 generations) in wild-type, reference strain (PAO1) and hypermutable (PAOΔmutS and PAOMY-Mgm) P. aeruginosa populations continuously exposed to sub-MICs (1/4) of ciprofloxacin. A rapid occurrence of ciprofloxacin-resistant mutants (MIC of ≥12 μg/ml, representing 100 times the MIC of the original population) were observed in all ciprofloxacin-exposed lineages of PAOΔmutS and PAOMY-Mgm populations after 100 and 170 generations, respectively, and in one of the PAO1 lineages after 240 generations. The genetic basis of resistance was mutations in gyrA (C248T and G259T) and gyrB (C1397A). Cross-resistance to beta-lactam antibiotics was observed in the bacterial populations that evolved during exposure to sublethal concentrations of ciprofloxacin. Our study shows that mutants with high-level ciprofloxacin resistance are selected in P. aeruginosa bacterial populations exposed to sub-MICs of ciprofloxacin. This can have implications for the long-term persistence of resistant bacteria and spread of antibiotic resistance by exposure of commensal bacterial flora to low antibiotic concentrations. PMID:23774442

Antimicrobial resistance 1979-2009 at Karolinska hospital, Sweden: normalized resistance interpretation during a 30-year follow-up on Staphylococcus aureus and Escherichia coli resistance development.

PubMed

Kronvall, Göran

2010-09-01

To utilize a material of inhibition zone diameter measurements from disc diffusion susceptibility tests between 1979 and 2009, an objective setting of epidemiological breakpoints was necessary because of methodological changes. Normalized resistance interpretation (NRI) met this need and was applied to zone diameter histograms for Staphylococcus aureus and Escherichia coli isolates. The results confirmed a slow resistance development as seen in Northern countries. The S. aureus resistance levels for erythromycin, clindamycin and fusidic acid in 2009 were 3.2%, 1.8% and 1.4% with denominator correction. A rise in resistance to four antimicrobials in 1983 was probably because of a spread of resistant Methicillin Susceptible Staphylococcus Aureus (MSSA). For E. coli, the denominator-corrected resistance levels in 2009 were 27% for ampicillin, around 3% for third-generation cephalosporins, 0.1% for imipenem, 2.5% for gentamicin, 19% for trimethoprim, 4.5% for co-trimoxazole, 1.2% for nitrofurantoin and 9% for ciprofloxacin. The temporal trends showed a rise in fluoroquinolone resistance from 1993, a parallel increase in gentamicin resistance, a substantial increase in trimethoprim and sulphonamide resistance in spite of decreased consumption, and a steady rise in ampicillin resistance from a constant level before 1989. A short review of global resistance surveillance studies is included.

The Effect of 10 Weeks Resistance Training on Cholesterol and Blood Triglyceride Levels of Patients with Fatty Liver Disease.

PubMed

Valizadeh, Rohollah; Hosseini Askarabadi, Siroos; Karampour, Sedigheh; Abdolhamid Tehrani, Mona

2014-01-01

The present study aims to consider the effect of 10 weeks resistance trainings on cholesterol and blood triglyceride (TG) levels of patients with having fatty liver, aged 50 to 60 in National Iranian South Oil Company (NISOC). This research is practical and its plan has been done experimentally with pretest and post-test on experimental and control groups. In this study, 20 samples from 100 patients who referred to sonography clinic in NISOC with distinction of fatty liver were selected randomly and divided into two groups of control (n = 10) and experimental (n = 10). Cholesterol and blood trigly-ceride were measured as pretest. Test of normality for TG was (p = 0/200) by Kolmogorov-Smirnov and (p = 0/070) for cholesterol by Shapiro-Wilk test. After 10 weeks resistance trainings, the analysis and resolution of data were done by computer and SPSS (16) software as well as the descriptive and statistical methods (t-test). Comparison between these two groups showed that 8 weeks resistance trainings with a ≤ 0.05 causes significant decrease in the amount of TG but did not any significant effect on cholesterol of fatty liver patients. How to cite this article: Valizadeh R, Askarabadi SH, Karampour S, Tehrani MA. The Effect of 10 Weeks Resistance Training on Cholesterol and Blood Triglyceride Levels of Patients with Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2014;4(1):64-65.

Muscle Activity in Upper-Body Single-Joint Resistance Exercises with Elastic Resistance Bands vs. Free Weights

PubMed Central

Bergquist, Ronny; Iversen, Vegard Moe; Mork, Paul J; Fimland, Marius Steiro

2018-01-01

Abstract Elastic resistance bands require little space, are light and portable, but their efficacy has not yet been established for several resistance exercises. The main objective of this study was to compare the muscle activation levels induced by elastic resistance bands versus conventional resistance training equipment (dumbbells) in the upper-body resistance exercises flyes and reverse flyes. The level of muscle activation was measured with surface electromyography in 29 men and women in a cross-over design where resistance loadings with elastic resistance bands and dumbbells were matched using 10-repetition maximum loadings. Elastic resistance bands induced slightly lower muscle activity in the muscles most people aim to activate during flyes and reverse flies, namely pectoralis major and deltoideus posterior, respectively. However, elastic resistance bands increased the muscle activation level substantially in perceived ancillary muscles, that is deltoideus anterior in flyes, and deltoideus medius and trapezius descendens in reverse flyes, possibly due to elastic bands being a more unstable resistance modality. Overall, the results show that elastic resistance bands can be considered a feasible alternative to dumbbells in flyes and reverse flyes. PMID:29599855

High-Level Heat Resistance of Spores of Bacillus amyloliquefaciens and Bacillus licheniformis Results from the Presence of a spoVA Operon in a Tn1546 Transposon

PubMed Central

Berendsen, Erwin M.; Koning, Rosella A.; Boekhorst, Jos; de Jong, Anne; Kuipers, Oscar P.; Wells-Bennik, Marjon H. J.

2016-01-01

Bacterial endospore formers can produce spores that are resistant to many food processing conditions, including heat. Some spores may survive heating processes aimed at production of commercially sterile foods. Recently, it was shown that a spoVA operon, designated spoVA2mob, present on a Tn1546 transposon in Bacillus subtilis, leads to profoundly increased wet heat resistance of B. subtilis spores. Such Tn1546 transposon elements including the spoVA2mob operon were also found in several strains of Bacillus amyloliquefaciens and Bacillus licheniformis, and these strains were shown to produce spores with significantly higher resistances to wet heat than their counterparts lacking this transposon. In this study, the locations and compositions of Tn1546 transposons encompassing the spoVA2mob operons in B. amyloliquefaciens and B. licheniformis were analyzed. Introduction of these spoVA2mob operons into B. subtilis 168 (producing spores that are not highly heat resistant) rendered mutant 168 strains that produced high-level heat resistant spores, demonstrating that these elements in B. amyloliquefaciens and B. licheniformis are responsible for high level heat resistance of spores. Assessment of growth of the nine strains of each species between 5.2°C and 57.7°C showed some differences between strains, especially at lower temperatures, but all strains were able to grow at 57.7°C. Strains of B. amyloliquefaciens and B. licheniformis that contain the Tn1546 elements (and produce high-level heat resistant spores) grew at temperatures similar to those of their Tn1546-negative counterparts that produce low-level heat resistant spores. The findings presented in this study allow for detection of B. amyloliquefaciens and B. licheniformis strains that produce highly heat resistant spores in the food chain. PMID:27994575

Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits

PubMed Central

Acosta-Alvear, Diego; Cho, Min Y; Wild, Thomas; Buchholz, Tonia J; Lerner, Alana G; Simakova, Olga; Hahn, Jamie; Korde, Neha; Landgren, Ola; Maric, Irina; Choudhary, Chunaram; Walter, Peter; Weissman, Jonathan S; Kampmann, Martin

2015-01-01

Hallmarks of cancer, including rapid growth and aneuploidy, can result in non-oncogene addiction to the proteostasis network that can be exploited clinically. The defining example is the exquisite sensitivity of multiple myeloma (MM) to 20S proteasome inhibitors, such as carfilzomib. However, MM patients invariably acquire resistance to these drugs. Using a next-generation shRNA platform, we found that proteostasis factors, including chaperones and stress-response regulators, controlled the response to carfilzomib. Paradoxically, 19S proteasome regulator knockdown induced resistance to carfilzomib in MM and non-MM cells. 19S subunit knockdown did not affect the activity of the 20S subunits targeted by carfilzomib nor their inhibition by the drug, suggesting an alternative mechanism, such as the selective accumulation of protective factors. In MM patients, lower 19S levels predicted a diminished response to carfilzomib-based therapies. Together, our findings suggest that an understanding of network rewiring can inform development of new combination therapies to overcome drug resistance. DOI: http://dx.doi.org/10.7554/eLife.08153.001 PMID:26327694

Genetic Organization of the Chromosome Region Surrounding mecA in Clinical Staphylococcal Strains: Role of IS431-Mediated mecI Deletion in Expression of Resistance in mecA-Carrying, Low-Level Methicillin- Resistant Staphylococcus haemolyticus

PubMed Central

Katayama, Yuki; Ito, Teruyo; Hiramatsu, Keiichi

2001-01-01

We report on the structural diversity of mecA gene complexes carried by 38 methicillin-resistant Staphylococcus aureus and 91 methicillin-resistant coagulase-negative Staphylococcus strains of seven different species with a special reference to its correlation with phenotypic expression of methicillin resistance. The most prevalent and widely disseminated mec complex had the structure mecI-mecR1-mecA-IS431R (or IS431mec), designated the class A mecA gene complex. In contrast, in S. haemolyticus, mecA was bracketed by two copies of IS431, forming the structure IS431L-mecA-IS431R. Of the 38 S. haemolyticus strains, 5 had low-level methicillin resistance (MIC, 1 to 4 mg/liter) and characteristic heterogeneous methicillin resistance as judged by population analysis. In these five strains, IS431L was located to the left of an intact mecI gene, forming the structure IS431L-class A mecA-gene complex. In other S. haemolyticus strains, IS431L was associated with the deletion of mecI and mecR1, forming the structure IS431L-ΔmecR1-mecA-IS431mec, designated the class C mecA gene complex. Mutants with the class C mecA gene complex were obtained in vitro by selecting strain SH621, containing the IS431L-class A mecA gene complex with low concentrations of methicillin (1 and 3 mg/liter). The mutants had intermediate level of methicillin resistance (MIC, 16 to 64 mg/liter). The mecA gene transcription was shown to be derepressed in a representative mutant strain, SH621-37. Our study indicated that the mecI-encoded repressor function is responsible for the low-level methicillin resistance of some S. haemolyticus clinical strains and that the IS431-mediated mecI gene deletion causes the expression of methicillin resistance through the derepression of mecA gene transcription. PMID:11408208

HIV-1 drug resistance and resistance testing.

PubMed

Clutter, Dana S; Jordan, Michael R; Bertagnolio, Silvia; Shafer, Robert W

2016-12-01

The global scale-up of antiretroviral (ARV) therapy (ART) has led to dramatic reductions in HIV-1 mortality and incidence. However, HIV drug resistance (HIVDR) poses a potential threat to the long-term success of ART and is emerging as a threat to the elimination of AIDS as a public health problem by 2030. In this review we describe the genetic mechanisms, epidemiology, and management of HIVDR at both individual and population levels across diverse economic and geographic settings. To describe the genetic mechanisms of HIVDR, we review the genetic barriers to resistance for the most commonly used ARVs and describe the extent of cross-resistance between them. To describe the epidemiology of HIVDR, we summarize the prevalence and patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) in both high-income and low- and middle-income countries (LMICs). We also review to two categories of HIVDR with important public health relevance: (i) pre-treatment drug resistance (PDR), a World Health Organization-recommended HIVDR surveillance metric and (ii) and pre-exposure prophylaxis (PrEP)-related drug resistance, a type of ADR that can impact clinical outcomes if present at the time of treatment initiation. To summarize the implications of HIVDR for patient management, we review the role of genotypic resistance testing and treatment practices in both high-income and LMIC settings. In high-income countries where drug resistance testing is part of routine care, such an understanding can help clinicians prevent virological failure and accumulation of further HIVDR on an individual level by selecting the most efficacious regimens for their patients. Although there is reduced access to diagnostic testing and to many ARVs in LMIC, understanding the scientific basis and clinical implications of HIVDR is useful in all regions in order to shape appropriate surveillance, inform treatment algorithms, and manage difficult cases. Copyright © 2016 Elsevier B

Identification of multiple ear-colonizing insect and disease resistance in CIMMYT maize inbred lines with varying levels of silk maysin.

PubMed

Ni, Xinzhi; Krakowsky, Matthew D; Buntin, G David; Rector, Brian G; Guo, Baozhu; Snook, Maurice E

2008-08-01

Ninety four corn inbred lines selected from International Center for the Improvement of Maize and Wheat (CIMMYT) in Mexico were evaluated for levels of silk maysin in 2001 and 2002. Damage by major ear-feeding insects [i.e., corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae); maize weevil, Sitophilus zeamais (Motschulsky) (Coleoptera: Curculionidae); brown stink bug, Euschistus servus (Say); southern green stink bugs, Nezara viridula (L.) (Heteroptera: Pentatomidae)], and common smut [Ustilago maydis DC (Corda)] infection on these inbred lines were evaluated in 2005 and 2006 under subtropical conditions at Tifton, GA. Ten inbred lines possessing good agronomic traits were also resistant to the corn earworm. The correlation between ear-feeding insect damage or smut infection and three phenotypic traits (silk maysin level, husk extension, and husk tightness of corn ears) was also examined. Corn earworm and stink bug damage was negatively correlated to husk extension, but not to either silk maysin levels or husk tightness. In combination with the best agronomic trait ratings that show the least corn earworm and stink bug damage, lowest smut infection rate, and good insect-resistant phenotypic traits (i.e., high maysin and good husk coverage and husk tightness), 10 best inbred lines (CML90, CML92, CML94, CML99, CML104, CML108, CML114, CML128, CML137, and CML373) were identified from the 94 lines examined. These selected inbred lines will be used for further examination of their resistance mechanisms and development of new corn germplasm that confers multiple ear-colonizing pest resistance.

Herd-level relationship between antimicrobial use and presence or absence of antimicrobial resistance in gram-negative bovine mastitis pathogens on Canadian dairy farms.

PubMed

Saini, Vineet; McClure, J T; Scholl, Daniel T; DeVries, Trevor J; Barkema, Herman W

2013-08-01

Concurrent data on antimicrobial use (AMU) and resistance are needed to contain antimicrobial resistance (AMR) in bacteria. The present study examined a herd-level association between AMU and AMR in Escherichia coli (n=394) and Klebsiella species (n=139) isolated from bovine intramammary infections and mastitis cases on 89 dairy farms in 4 regions of Canada [Alberta, Ontario, Québec, and Maritime Provinces (Prince Edward Island, Nova Scotia, and New Brunswick)]. Antimicrobial use data were collected using inventory of empty antimicrobial containers and antimicrobial drug use rate was calculated to quantify herd-level AMU. Minimum inhibitory concentrations (MIC) were determined using Sensititre National Antimicrobial Resistance Monitoring System (NARMS) gram-negative MIC plate (Trek Diagnostic Systems Inc., Cleveland, OH). Isolates were classified as susceptible, intermediate, or resistant. Intermediate and resistant category isolates were combined to form an AMR category, and multivariable logistic regression models were built to determine herd-level odds of AMR to tetracycline, ampicillin, cefoxitin, chloramphenicol, trimethoprim-sulfamethoxazole combination, sulfisoxazole, streptomycin and kanamycin in E. coli isolates. In the case of Klebsiella species isolates, logistic regression models were built for tetracycline and sulfisoxazole; however, no associations between AMU and AMR in Klebsiella species were observed. Ampicillin-intermediate or -resistant E. coli isolates were associated with herds that used intramammarily administered cloxacillin, penicillin-novobiocin combination, and cephapirin used for dry cow therapy [odds ratios (OR)=26, 32, and 189, respectively], and intramammary ceftiofur administered for lactating cow therapy and systemically administered penicillin (OR=162 and 2.7, respectively). Use of systemically administered penicillin on a dairy farm was associated with tetracycline and streptomycin-intermediate or -resistant E. coli isolates (OR=5

Distributed phased array architecture study

NASA Technical Reports Server (NTRS)

Bourgeois, Brian

1987-01-01

Variations in amplifiers and phase shifters can cause degraded antenna performance, depending also on the environmental conditions and antenna array architecture. The implementation of distributed phased array hardware was studied with the aid of the DISTAR computer program as a simulation tool. This simulation provides guidance in hardware simulation. Both hard and soft failures of the amplifiers in the T/R modules are modeled. Hard failures are catastrophic: no power is transmitted to the antenna elements. Noncatastrophic or soft failures are modeled as a modified Gaussian distribution. The resulting amplitude characteristics then determine the array excitation coefficients. The phase characteristics take on a uniform distribution. Pattern characteristics such as antenna gain, half power beamwidth, mainbeam phase errors, sidelobe levels, and beam pointing errors were studied as functions of amplifier and phase shifter variations. General specifications for amplifier and phase shifter tolerances in various architecture configurations for C band and S band were determined.

Current Status of Thin Film (Ba,Sr) TiO3 Tunable Microwave Components for RF Communications

NASA Technical Reports Server (NTRS)

VanKeuls, F. W.; Romananofsky, R. R.; Mueller, C. H.; Warner, J. D.; Canedy, C. L.; Ramesh, R.; Miranda, F. A.

2000-01-01

The performance of proof-of-concept ferroelectric microwave devices has been moving steadily closer to the level needed for satellite and other rf communications applications. This paper will review recent progress at NASA Glenn in developing thin film Ba(x)Sr(1-x)TiO3 tunable microwave components for these applications. Phase shifters for phased array antennas, tunable filters and tunable oscillators employing microstrip and coupled microstrip configurations will be presented. Tunabilities, maximum dielectric constants, and phase shifter parameters will be discussed (e.g., coupled microstrip phase shifters with phase shift over 200 deg. at 18 GHz and a figure of merit of 74.3 deg./dB). Issues of postannealing, Mn-doping and Ba(x)Sr(1-x)TiO3 growth on sapphire and alumina substrates will be covered. The challenges of incorporating these devices into larger systems, such as yield, variability in phase shift and insertion loss, and protective coatings will also be addressed.

Current Status of Thin Film (Ba,Sr)TiO3 Tunable Microwave Components for RF Communications

NASA Technical Reports Server (NTRS)

VanKeuls, F. W.; Romanofsky, R. R.; Mueller, C. H.; Warner, J. D.; Canedy, C. L.; Ramesh, R.; Miranda, F. A.

2000-01-01

The performance of proof-of-concept ferroelectric microwave devices has been moving steadily closer to the level needed for satellite and other rf communications applications. This paper will review recent progress at NASA Glenn in developing thin film Ba(x)Sr(1-x)TiO3 tunable micro-wave components for these applications. Phase shifters for phased array antennas, tunable filters and tunable oscillators employing microstrip and coupled microstrip configurations will be presented. Tunabilities, maximum dielectric constants, and phase shifter parameters will be discussed (e.g., coupled microstrip phase shifters with phase shift over 200 deg at 18 GHz and a figure of merit of 74.3 deg/dB). Issues of post-annealing, Mn-doping and Ba(x)Sr(1-x) TiO3 growth on sapphire and alumina substrates will be covered. The challenges of incorporating these devices into larger systems, such as yield, variability in phase shift and insertion loss, and protective coatings will also be addressed.

Multilevel Resistance Programming in Conductive Bridge Resistive Memory

NASA Astrophysics Data System (ADS)

Mahalanabis, Debayan

This work focuses on the existence of multiple resistance states in a type of emerging non-volatile resistive memory device known commonly as Programmable Metallization Cell (PMC) or Conductive Bridge Random Access Memory (CBRAM), which can be important for applications such as multi-bit memory as well as non-volatile logic and neuromorphic computing. First, experimental data from small signal, quasi-static and pulsed mode electrical characterization of such devices are presented which clearly demonstrate the inherent multi-level resistance programmability property in CBRAM devices. A physics based analytical CBRAM compact model is then presented which simulates the ion-transport dynamics and filamentary growth mechanism that causes resistance change in such devices. Simulation results from the model are fitted to experimental dynamic resistance switching characteristics. The model designed using Verilog-a language is computation-efficient and can be integrated with industry standard circuit simulation tools for design and analysis of hybrid circuits involving both CMOS and CBRAM devices. Three main circuit applications for CBRAM devices are explored in this work. Firstly, the susceptibility of CBRAM memory arrays to single event induced upsets is analyzed via compact model simulation and experimental heavy ion testing data that show possibility of both high resistance to low resistance and low resistance to high resistance transitions due to ion strikes. Next, a non-volatile sense amplifier based flip-flop architecture is proposed which can help make leakage power consumption negligible by allowing complete shutdown of power supply while retaining its output data in CBRAM devices. Reliability and energy consumption of the flip-flop circuit for different CBRAM low resistance levels and supply voltage values are analyzed and compared to CMOS designs. Possible extension of this architecture for threshold logic function computation using the CBRAM devices as re

The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle.

PubMed

Carroll, Chad C; O'Connor, Devin T; Steinmeyer, Robert; Del Mundo, Jonathon D; McMullan, David R; Whitt, Jamie A; Ramos, Jahir E; Gonzales, Rayna J

2013-07-01

This study evaluated the activity and content of cyclooxygenase (COX)-1 and -2 in response to acute resistance exercise (RE) in human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is the primary COX isoform elevated with resistance exercise in human skeletal muscle. COX activity, however, has not been assessed after resistance exercise in humans. It was hypothesized that RE would increase COX-1 but not COX-2 activity. Muscle biopsies were taken from the vastus lateralis of nine young men (25 ± 1 yr) at baseline (preexercise), 4, and 24 h after a single bout of knee extensor RE (three sets of 10 repetitions at 70% of maximum). Tissue lysate was assayed for COX-1 and COX-2 activity. COX-1 and COX-2 protein levels were measured via Western blot analysis. COX-1 activity increased at 4 h (P < 0.05) compared with preexercise, but returned to baseline at 24 h (PRE: 60 ± 10, 4 h: 106 ± 22, 24 h: 72 ± 8 nmol PGH2·g total protein(-1)·min(-1)). COX-2 activity was elevated at 4 and 24 h after RE (P < 0.05, PRE: 51 ± 7, 4 h: 100 ± 19, 24 h: 98 ± 14 nmol PGH2·g total protein(-1)·min(-1)). The protein level of COX-1 was not altered (P > 0.05) with acute RE. In contrast, COX-2 protein levels were nearly 3-fold greater (P > 0.05) at 4 h and 5-fold greater (P = 0.06) at 24 h, compared with preexercise. In conclusion, COX-1 activity increases transiently with exercise independent of COX-1 protein levels. In contrast, both COX-2 activity and protein levels were elevated with exercise, and this elevation persisted to at least 24 h after RE.

The effect of resistance level and stability demands on recruitment patterns and internal loading of spine in dynamic flexion and extension using a simple trunk model.

PubMed

Zeinali-Davarani, Shahrokh; Shirazi-Adl, Aboulfazl; Dariush, Behzad; Hemami, Hooshang; Parnianpour, Mohamad

2011-07-01

The effects of external resistance on the recruitment of trunk muscles in sagittal movements and the coactivation mechanism to maintain spinal stability were investigated using a simple computational model of iso-resistive spine sagittal movements. Neural excitation of muscles was attained based on inverse dynamics approach along with a stability-based optimisation. The trunk flexion and extension movements between 60° flexion and the upright posture against various resistance levels were simulated. Incorporation of the stability constraint in the optimisation algorithm required higher antagonistic activities for all resistance levels mostly close to the upright position. Extension movements showed higher coactivation with higher resistance, whereas flexion movements demonstrated lower coactivation indicating a greater stability demand in backward extension movements against higher resistance at the neighbourhood of the upright posture. Optimal extension profiles based on minimum jerk, work and power had distinct kinematics profiles which led to recruitment patterns with different timing and amplitude of activation.

SAMPLING OSCILLOSCOPE

DOEpatents

Sugarman, R.M.

1960-08-30

An oscilloscope is designed for displaying transient signal waveforms having random time and amplitude distributions. The oscilloscopc is a sampling device that selects for display a portion of only those waveforms having a particular range of amplitudes. For this purpose a pulse-height analyzer is provided to screen the pulses. A variable voltage-level shifter and a time-scale rampvoltage generator take the pulse height relative to the start of the waveform. The variable voltage shifter produces a voltage level raised one step for each sequential signal waveform to be sampled and this results in an unsmeared record of input signal waveforms. Appropriate delay devices permit each sample waveform to pass its peak amplitude before the circuit selects it for display.

Serum levels of fractalkine are associated with markers of insulin resistance in gestational diabetes.

PubMed

Ebert, T; Hindricks, J; Kralisch, S; Lossner, U; Jessnitzer, B; Richter, J; Blüher, M; Stumvoll, M; Fasshauer, M

2014-08-01

Fractalkine has recently been introduced as an adipokine that improves glucose tolerance. Regulation of fractalkine in gestational diabetes, as well as its association with markers of obesity, glucose and lipid metabolism, inflammation and renal function, has not been elucidated. Circulating fractalkine was quantified by enzyme-linked immunosorbent assay in 74 women with gestational diabetes and 74 healthy, pregnant control subjects matched for age, BMI, and gestational age. Median (interquartile range) levels of fractalkine were not significantly different between the two groups [gestational diabetes: 2.24 (2.16) μg/l; control: 2.45 (1.38) μg/l] (P = 0.461). In multivariate linear regression analysis, fractalkine remained independently associated with homeostasis model assessment of insulin resistance (β = -0.253, P = 0.002) and the proinflammatory adipokine progranulin (β = 0.218, P = 0.007). Circulating fractalkine is not different between women with gestational diabetes and control subjects, but the adipokine is independently associated with markers of insulin resistance and proinflammatory progranulin in pregnancy. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Skeletal Adaptations to Different Levels of Eccentric Resistance Following Eight Weeks of Training

NASA Technical Reports Server (NTRS)

English, Kirk L.; Loehr, James A.; Lee, Stuart M. C.; Maddocks, Mary J.; Laughlin, Mitzi S.; Hagan, R. Donald

2007-01-01

Coupled concentric-eccentric resistive exercise maintains bone mineral density (BMD) during bed rest and aging. PURPOSE: We hypothesized that 8 wks of lower body resistive exercise training with higher ratios of eccentric to concentric loading would enhance hip and lumbar BMD. METHODS: Forty untrained male volunteers (34.9+/-7.0 yrs, 80.9+/-9.8 kg, 178.2+/-7.1 cm; mean+/-SD) were matched for leg press (LP) 1-Repetition Maximum (1-RM) strength and randomly assigned to one of 5 training groups. Concentric load (% 1-RM) was constant across groups, but each group trained with different levels of eccentric load (0, 33, 66, 100, or 138% of concentric) for all training sessions. Subjects performed a periodized supine LP and heel raise (HR) training program 3 d wk-1 for 8 wks using a modified Agaton Fitness System (Agaton Fitness AB, Boden, Sweden). Hip and lumbar BMD (g/sq cm) was measured in triplicate pre- and post-training using DXA (Hologic Discovery ). Pre- and post-training means were compared using the appropriate ANOVA and Tukey's post hoc tests. Within group pre- to post-training BMD was compared using paired t-tests with a Bonferroni adjustment. RESULTS: There was a main effect of training on L1, L2, L3, L4, total lumbar, and greater trochanter BMD, but there were no differences between groups. CONCLUSION: Eights wks of lower body resistive exercise increased greater trochanter and lumbar BMD. Inability to detect group differences may have been influenced by a potentially osteogenic vibration associated with device operation in the 0, 33, and 66% groups.

Instrumentation for investigation of corona discharges from insulated wires

NASA Technical Reports Server (NTRS)

Doreswamy, C. V.; Crowell, C. S.

1975-01-01

A coaxial cylinder configuration is used to investigate the effect of corona impulses on the deterioration of electrical insulation. The corona currents flowing through the resistance develop a voltage which is fed to the measuring set-up. The value of this resistance is made equal to the surge impedance of the coaxial cylinder set up to prevent reflections. This instrumentation includes a phase shifter and Schmidt trigger and is designed to sample, measure, and display corona impulses occurring during any predetermined sampling period of a randomly selectable half cycle of the 60 Hz high voltage wave.

Levels of insecticide resistance to deltamethrin, malathion, and temephos, and associated mechanisms in Aedes aegypti mosquitoes from the Guadeloupe and Saint Martin islands (French West Indies).

PubMed

Goindin, Daniella; Delannay, Christelle; Gelasse, Andric; Ramdini, Cédric; Gaude, Thierry; Faucon, Frédéric; David, Jean-Philippe; Gustave, Joël; Vega-Rua, Anubis; Fouque, Florence

2017-02-10

In the Guadeloupe and Saint Martin islands, Aedes aegypti mosquitoes are the only recognized vectors of dengue, chikungunya, and Zika viruses. For around 40 years, malathion was used as a mosquito adulticide and temephos as a larvicide. Since the European Union banned the use of these two insecticide molecules in the first decade of the 21st century, deltamethrin and Bacillus thuringiensis var. israelensis are the remaining adulticide and larvicide, respectively, used in Guadeloupe. In order to improve the management of vector control activities in Guadeloupe and Saint Martin, we investigated Ae. aegypti resistance to and mechanisms associated with deltamethrin, malathion, and temephos. Ae. aegypti mosquitoes were collected from six different localities of Guadeloupe and Saint Martin. Larvae were used for malathion and temephos bioassays, and adult mosquitoes for deltamethrin bioassays, following World Health Organization recommendations. Knockdown resistance (Kdr) genotyping for V1016I and F1534C mutations, and expression levels of eight enzymes involved in detoxification mechanisms were examined in comparison with the susceptible reference Bora Bora strain. Resistance ratios (RR 50 ) calculated for Ae. aegypti larvae showed high resistance levels to temephos (from 8.9 to 33.1-fold) and low resistance levels to malathion (from 1.7 to 4.4-fold). Adult females displayed moderate resistance levels to deltamethrin regarding the time necessary to affect 50% of individuals, varying from 8.0 to 28.1-fold. Molecular investigations on adult mosquitoes showed high resistant allele frequencies for V1016I and F1534C (from 85 to 96% and from 90 to 98%, respectively), as well as an overexpression of the glutathione S-transferase gene, GSTe2, the carboxylesterase CCEae3a, and the cytochrome genes 014614, CYP6BB2, CYP6M11, and CYP9J23. Ae. aegypti populations from Guadeloupe and Saint Martin exhibit multiple resistance to organophosphates (temephos and malathion), and

Edge effects in phase-shifting masks for 0.25-µm lithography

NASA Astrophysics Data System (ADS)

Wong, Alfred K. K.; Neureuther, Andrew R.

1993-03-01

The impact on image quality of scattering from phase-shifter edges and of interactions between phase-shifter and chrome edges is assessed using rigorous electromagnetic simulation. Effects of edge taper in phase-shift masks, spacing between phase-shifter and chrome edges, small outrigger features with a trench phase-shifter, and of the repair of phase defects by etching to 360 degree(s) are considered. Near field distributions and diffraction efficiencies are examined and images are compared with more approximate results from the commonly used Hopkins' theory of imaging.

Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women.

PubMed

Kim, Mi Joung; Hwang, Jung Hyun; Ko, Hyun Ji; Na, Hye Bock; Kim, Jung Hee

2015-05-01

The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes. Copyright © 2015 Elsevier Inc. All rights reserved.

[Associations of insulin resistance and pancreatic beta-cell function with plasma glucose level in type 2 diabetes].

PubMed

Nian, Xiaoping; Sun, Gaisheng; Dou, Chunmei; Hou, Hongbo; Fan, Xiuping; Yu, Hongmei; Ma, Ling; He, Bingxian

2002-06-10

To investigate the influence of insulin resistance and pancreatic beta-cell function on plasma glucose level in type 2 diabetes so as to provide theoretical basis for reasonable selection of hypoglycemic agents. The plasma non-specific insulin (NSINS), true insulin (TI) and glucose in eight-one type 2 diabetics, 38 males and 43 females, with a mean age of 53 years, were examined 0, 30, 60 and 120 minutes after they had 75 grams of instant noodles. The patients were divided into two groups according to their fasting plasma glucose (FPG): group A (FPG < 8.89 mmol/L) and group B (FPG> = 8.89 mmol/L). The insulin resistance was evaluated by HOMA-IR, the beta-cell function was evaluated by HOMA-beta formula and the formula deltaI(30)/deltaG(30) = (deltaI(30)-deltaI(0))/(deltaG(30)-deltaG(0)). The insulin area under curve (INSAUC) was evaluated by the formula INSAUC=FINS/2+INS(30)+INS(60)+INS(120)/2. The mean FPG was 6.23 mmol/L in group A and 12.6 mmol/L in group B. PG2H was 11.7 mmol/L in group A and 19.2 mmol/L in group B. The TI levels in group B at 0, 30, 60, 120 min during standard meal test were significantly higher than those in group A: 6.15 +/- 1.06 vs 4.77 +/- 1.06, 9.76 +/- 1.1 vs 5.88 +/- 1.1,14.68 +/- 1.11 vs 6.87 +/- 1.1 and 17.13 +/- 1.12 vs 8.0 +/- 1.1 microU/dl (all P< 0.01). The NSINS showed the same trend. The insulin resistance in group B was 1.5 times that in group A. With the insulin resistance adjusted, the beta cell function in group A was 5 to 6 times that in group B. The INSAUC in group A was 1.66 times larger than that in group B, especially the INSAUC for true insulin (2 times larger). The contribution of insulin resistance and beta cell function to PG2H was half by half in group A and 1:8 in group B. beta cell function calculated by insulin (Homa-beta) explained 41% of the plasma glucose changes in group A and 54% of the plasma glucose changes in group B. The contribution of insulin deficiency to plasma glocose was 3.3.times that of insulin

Failure of azithromycin 2.0 g in the treatment of gonococcal urethritis caused by high-level resistance in California.

PubMed

Gose, Severin O; Soge, Olusegun O; Beebe, James L; Nguyen, Duylinh; Stoltey, Juliet E; Bauer, Heidi M

2015-05-01

We report a treatment failure to azithromycin 2.0 g caused by a urethral Neisseria gonorrhoeae isolate with high-level azithromycin resistance in California. This report describes the epidemiological case investigation and phenotypic and genetic characterization of the treatment failure isolate.

Resistance of Feather-Associated Bacteria to Intermediate Levels of Ionizing Radiation near Chernobyl.

PubMed

Ruiz-González, Mario Xavier; Czirják, Gábor Árpád; Genevaux, Pierre; Møller, Anders Pape; Mousseau, Timothy Alexander; Heeb, Philipp

2016-03-15

Ionizing radiation has been shown to produce negative effects on organisms, although little is known about its ecological and evolutionary effects. As a study model, we isolated bacteria associated with feathers from barn swallows Hirundo rustica from three study areas around Chernobyl differing in background ionizing radiation levels and one control study site in Denmark. Each bacterial community was exposed to four different γ radiation doses ranging from 0.46 to 3.96 kGy to test whether chronic exposure to radiation had selected for resistant bacterial strains. Experimental radiation duration had an increasingly overall negative effect on the survival of all bacterial communities. After exposure to γ radiation, bacteria isolated from the site with intermediate background radiation levels survived better and produced more colonies than the bacterial communities from other study sites with higher or lower background radiation levels. Long-term effects of radiation in natural populations might be an important selective pressure on traits of bacteria that facilitate survival in certain environments. Our findings indicate the importance of further studies to understand the proximate mechanisms acting to buffer the negative effects of ionizing radiation in natural populations.

Resistance of Feather-Associated Bacteria to Intermediate Levels of Ionizing Radiation near Chernobyl

PubMed Central

Ruiz-González, Mario Xavier; Czirják, Gábor Árpád; Genevaux, Pierre; Møller, Anders Pape; Mousseau, Timothy Alexander; Heeb, Philipp

2016-01-01

Ionizing radiation has been shown to produce negative effects on organisms, although little is known about its ecological and evolutionary effects. As a study model, we isolated bacteria associated with feathers from barn swallows Hirundo rustica from three study areas around Chernobyl differing in background ionizing radiation levels and one control study site in Denmark. Each bacterial community was exposed to four different γ radiation doses ranging from 0.46 to 3.96 kGy to test whether chronic exposure to radiation had selected for resistant bacterial strains. Experimental radiation duration had an increasingly overall negative effect on the survival of all bacterial communities. After exposure to γ radiation, bacteria isolated from the site with intermediate background radiation levels survived better and produced more colonies than the bacterial communities from other study sites with higher or lower background radiation levels. Long-term effects of radiation in natural populations might be an important selective pressure on traits of bacteria that facilitate survival in certain environments. Our findings indicate the importance of further studies to understand the proximate mechanisms acting to buffer the negative effects of ionizing radiation in natural populations. PMID:26976674

Resistance Responses of Potato to Vesicular-Arbuscular Mycorrhizal Fungi under Varying Abiotic Phosphorus Levels.

PubMed

McArthur, D A; Knowles, N R

1992-09-01

to plant growth decreased and root infection was lower. The in vivo ACC(ox) activity was also greater in roots of plants grown on high levels of P compared with those grown on low levels, although the influence of VAM infection was partially to counteract the nutritional effect of P on ACC(ox) activity. Similar to ACC(ox) activity, extracellular peroxidase activity of roots increased linearly with increasing abiotic P supply, thus indicating a greater potential for resistance to VAM infection. These findings suggest that VAM fungi may alter phenolic metabolism of roots so as to hinder ethylene production and the root's ability to invoke a defense response. Raising the abiotic P supply to plants at least partially restores the capacity of roots to produce ethylene and may, in this way, increase the root's resistance to VAM infection.

Field Level RNAi-Mediated Resistance to Cassava Brown Streak Disease across Multiple Cropping Cycles and Diverse East African Agro-Ecological Locations

PubMed Central

Wagaba, Henry; Beyene, Getu; Aleu, Jude; Odipio, John; Okao-Okuja, Geoffrey; Chauhan, Raj Deepika; Munga, Theresia; Obiero, Hannington; Halsey, Mark E.; Ilyas, Muhammad; Raymond, Peter; Bua, Anton; Taylor, Nigel J.; Miano, Douglas; Alicai, Titus

2017-01-01

Cassava brown streak disease (CBSD) presents a serious threat to cassava production in East and Central Africa. Currently, no cultivars with high levels of resistance to CBSD are available to farmers. Transgenic RNAi technology was employed to combat CBSD by fusing coat protein (CP) sequences from Ugandan cassava brown streak virus (UCBSV) and Cassava brown streak virus (CBSV) to create an inverted repeat construct (p5001) driven by the constitutive Cassava vein mosaic virus promoter. Twenty-five plant lines of cultivar TME 204 expressing varying levels of small interfering RNAs (siRNAs) were established in confined field trials (CFTs) in Uganda and Kenya. Within an initial CFT at Namulonge, Uganda, non-transgenic TME 204 plants developed foliar and storage root CBSD incidences at 96–100% by 12 months after planting. In contrast, 16 of the 25 p5001 transgenic lines showed no foliar symptoms and had less than 8% of their storage roots symptomatic for CBSD. A direct positive correlation was seen between levels of resistance to CBSD and expression of transgenic CP-derived siRNAs. A subsequent CFT was established at Namulonge using stem cuttings from the initial trial. All transgenic lines established remained asymptomatic for CBSD, while 98% of the non-transgenic TME 204 stake-derived plants developed storage roots symptomatic for CBSD. Similarly, very high levels of resistance to CBSD were demonstrated by TME 204 p5001 RNAi lines grown within a CFT over a full cropping cycle at Mtwapa, coastal Kenya. Sequence analysis of CBSD causal viruses present at the trial sites showed that the transgenic lines were exposed to both CBSV and UCBSV, and that the sequenced isolates shared >90% CP identity with transgenic CP sequences expressed by the p5001 inverted repeat expression cassette. These results demonstrate very high levels of field resistance to CBSD conferred by the p5001 RNAi construct at diverse agro-ecological locations, and across the vegetative cropping cycle

New Rice for Africa (NERICA) cultivars exhibit different levels of post-attachment resistance against the parasitic weeds Striga hermonthica and Striga asiatica.

PubMed

Cissoko, Mamadou; Boisnard, Arnaud; Rodenburg, Jonne; Press, Malcolm C; Scholes, Julie D

2011-12-01

Striga hermonthica and S. asiatica are root parasitic weeds that infect the major cereal crops of sub-Saharan Africa causing severe losses in yield. The interspecific upland NEw RICe for Africa (NERICA) cultivars are popular amongst subsistence farmers, but little is known about their post-attachment resistance against Striga. Here, we evaluate the post-attachment resistance levels of the NERICA cultivars and their parents against ecotypes of S. hermonthica and S.asiatica, characterize the phenotype of the resistance mechanisms and determine the effect of Striga on host biomass. Some NERICA cultivars showed good broad-spectrum resistance against several Striga ecotypes, whereas others showed intermediate resistance or were very susceptible. The phenotype of a resistant interaction was often characterized by an inability of the parasite to penetrate the endodermis. Moreover, some parasites formed only a few connections to the host xylem, grew slowly and remained small. The most resistant NERICA cultivars were least damaged by Striga, although even a small number of parasites caused a reduction in above-ground host biomass. The elucidation of the molecular genetic basis of the resistance mechanisms and tolerance would allow the development of cultivars with multiple, durable resistance for use in farmers' fields. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

Resistance to lambda-cyhalothrin in Spanish field populations of Ceratitis capitata and metabolic resistance mediated by P450 in a resistant strain.

PubMed

Arouri, Rabeh; Le Goff, Gaelle; Hemden, Hiethem; Navarro-Llopis, Vicente; M'saad, Mariem; Castañera, Pedro; Feyereisen, René; Hernández-Crespo, Pedro; Ortego, Félix

2015-09-01

The withdrawal of malathion in the European Union in 2009 resulted in a large increase in lambda-cyhalothrin applications for the control of the Mediterranean fruit fly, Ceratitis capitata, in Spanish citrus crops. Spanish field populations of C. capitata have developed resistance to lambda-cyhalothrin (6-14-fold), achieving LC50 values (129-287 ppm) higher than the recommended concentration for field treatments (125 ppm). These results contrast with the high susceptibility to lambda-cyhalothrin found in three Tunisian field populations. We have studied the mechanism of resistance in the laboratory-selected resistant strain W-1Kλ (205-fold resistance). Bioassays with synergists showed that resistance was almost completely suppressed by the P450 inhibitor PBO. The study of the expression of 53 P450 genes belonging to the CYP4, CYP6, CYP9 and CYP12 families in C. capitata revealed that CYP6A51 was overexpressed (13-18-fold) in the resistant strain. The W-1Kλ strain also showed high levels of cross-resistance to etofenprox (240-fold) and deltamethrin (150-fold). Field-evolved resistance to lambda-cyhalothrin has been found in C. capitata. Metabolic resistance mediated by P450 appears to be the main resistance mechanism in the resistant strain W-1Kλ. The levels of cross-resistance found may compromise the effectiveness of other pyrethroids for the control of this species. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

The S230R Integrase Substitution Associated with Viral Rebound during DTG Monotherapy Confers Low Levels INSTI Drug Resistance.

PubMed

Pham, Hanh T; Labrie, Lydia; Wijting, Ingeborg E A; Hassounah, Said; Lok, Ka Yee; Portna, Inna; Goring, Mark; Han, Yingshan; Lungu, Cynthia; van der Ende, Marchina E; Brenner, Bluma G; Boucher, Charles A; Rijnders, Bart J A; van Kampen, Jeroen J A; Mesplède, Thibault; Wainberg, Mark A

2018-03-29

Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI) used for treatment of HIV-infected individuals. Due to its high genetic barrier to resistance, DTG has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virological failure while using DTG monotherapy. We evaluated the effect of S230R substitution in regard to IN enzyme activity, viral infectivity, replicative capacity and susceptibility to different INSTIs by biochemical and cell-based assays. S230R substitution conferred 63% reduction in enzyme efficiency. The S230R virus was 1.29-fold less infectious than wildtype (WT), but could replicate in PM1 cells without significant delay. Resistance levels against DTG, CAB, RAL and EVG in tissue culture were 3.85-, 3.72-, 1.52-, and 1.21-fold, respectively. Our data indicate that the S230R substitution is comparable to the previously reported R263K in some respects. Virological failure under DTG monotherapy can occur through the development of such S230R or R263K mutations without the need for high levels DTG resistance.

Increased Levels of Multiresistant Bacteria and Resistance Genes after Wastewater Treatment and Their Dissemination into Lake Geneva, Switzerland

PubMed Central

Czekalski, Nadine; Berthold, Tom; Caucci, Serena; Egli, Andrea; Bürgmann, Helmut

2012-01-01

At present, very little is known about the fate and persistence of multiresistant bacteria (MRB) and their resistance genes in natural aquatic environments. Treated, but partly also untreated sewage of the city of Lausanne, Switzerland is discharged into Vidy Bay (Lake Geneva) resulting in high levels of contamination in this part of the lake. In the present work we have studied the prevalence of MRB and resistance genes in the wastewater stream of Lausanne. Samples from hospital and municipal raw sewage, treated effluent from Lausanne’s wastewater treatment plant (WTP) as well as lake water and sediment samples obtained close to the WTP outlet pipe and a remote site close to a drinking water pump were evaluated for the prevalence of MRB. Selected isolates were identified (16S rRNA gene fragment sequencing) and characterized with regards to further resistances, resistance genes, and plasmids. Mostly, studies investigating this issue have relied on cultivation-based approaches. However, the limitations of these tools are well known, in particular for environmental microbial communities, and cultivation-independent molecular tools should be applied in parallel in order to take non-culturable organisms into account. Here we directly quantified the sulfonamide resistance genes sul1 and sul2 from environmental DNA extracts using TaqMan real-time quantitative PCR. Hospital sewage contained the highest load of MRB and antibiotic resistance genes (ARGs). Wastewater treatment reduced the total bacterial load up to 78% but evidence for selection of extremely multiresistant strains and accumulation of resistance genes was observed. Our data clearly indicated pollution of sediments with ARGs in the vicinity of the WTP outlet. The potential of lakes as reservoirs of MRB and potential risks are discussed. PMID:22461783

Antimicrobial Use and Resistance in Swine Waste Treatment Systems▿

PubMed Central

Jindal, Archana; Kocherginskaya, Svetlana; Mehboob, Asma; Robert, Matthew; Mackie, Roderick I.; Raskin, Lutgarde; Zilles, Julie L.

2006-01-01

Chlortetracycline and the macrolide tylosin were identified as commonly used antimicrobials for growth promotion and prophylaxis in swine production. Resistance to these antimicrobials was measured throughout the waste treatment processes at five swine farms by culture-based and molecular methods. Conventional farm samples had the highest levels of resistance with both culture-based and molecular methods and had similar levels of resistance despite differences in antimicrobial usage. The levels of resistance in organic farm samples, where no antimicrobials were used, were very low by a culture-based method targeting fecal streptococci. However, when the same samples were analyzed with a molecular method detecting methylation of a specific nucleotide in the 23S rRNA that results in resistance to macrolides, lincosamides, and streptogramin B (MLSB), an unexpectedly high level of resistant rRNA (approximately 50%) was observed, suggesting that the fecal streptococci were not an appropriate target group to evaluate resistance in the overall microbial community and that background levels of MLSB resistance may be substantial. All of the feed samples tested, including those from the organic farm, contained tetracycline resistance genes. Generally, the same tetracycline resistance genes and frequency of detection were found in the manure and lagoon samples for each commercial farm. The levels of tetracycline and MLSB resistance remained high throughout the waste treatment systems, suggesting that the potential impact of land application of treated wastes and waste treatment by-products on environmental levels of resistance should be investigated further. PMID:17041160

Joint-level energetics differentiate isoinertial from speed-power resistance training-a Bayesian analysis.

PubMed

Liew, Bernard X W; Drovandi, Christopher C; Clifford, Samuel; Keogh, Justin W L; Morris, Susan; Netto, Kevin

2018-01-01

There is convincing evidence for the benefits of resistance training on vertical jump improvements, but little evidence to guide optimal training prescription. The inability to detect small between modality effects may partially reflect the use of ANOVA statistics. This study represents the results of a sub-study from a larger project investigating the effects of two resistance training methods on load carriage running energetics. Bayesian statistics were used to compare the effectiveness of isoinertial resistance against speed-power training to change countermovement jump (CMJ) and squat jump (SJ) height, and joint energetics. Active adults were randomly allocated to either a six-week isoinertial ( n  = 16; calf raises, leg press, and lunge), or a speed-power training program ( n  = 14; countermovement jumps, hopping, with hip flexor training to target pre-swing running energetics). Primary outcome variables included jump height and joint power. Bayesian mixed modelling and Functional Data Analysis were used, where significance was determined by a non-zero crossing of the 95% Bayesian Credible Interval (CrI). The gain in CMJ height after isoinertial training was 1.95 cm (95% CrI [0.85-3.04] cm) greater than the gain after speed-power training, but the gain in SJ height was similar between groups. In the CMJ, isoinertial training produced a larger increase in power absorption at the hip by a mean 0.018% (equivalent to 35 W) (95% CrI [0.007-0.03]), knee by 0.014% (equivalent to 27 W) (95% CrI [0.006-0.02]) and foot by 0.011% (equivalent to 21 W) (95% CrI [0.005-0.02]) compared to speed-power training. Short-term isoinertial training improved CMJ height more than speed-power training. The principle adaptive difference between training modalities was at the level of hip, knee and foot power absorption.

Cellular HIV-1 DNA Levels in Drug Sensitive Strains Are Equivalent to Those in Drug Resistant Strains in Newly-Diagnosed Patients in Europe

PubMed Central

Demetriou, Victoria L.; van de Vijver, David A. M. C.; Kousiappa, Ioanna; Balotta, Claudia; Clotet, Bonaventura; Grossman, Zehava; Jørgensen, Louise B.; Lepej, Snjezana Z.; Levy, Itzchak; Nielsen, Claus; Paraskevis, Dimitrios; Poljak, Mario; Roman, Francois; Ruiz, Lidia; Schmidt, Jean-Claude; Vandamme, Anne-Mieke; Van Laethem, Kristel; Vercauteren, Jurgen; Kostrikis, Leondios G.

2010-01-01

Background HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. Methodology/Principal Findings Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log10 HIV-1 copies/106 PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4+ T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. Conclusions/Significance An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA- and DNA

Effect of nitrogen levels and nitrogen ratios on lodging resistance and yield potential of winter wheat (Triticum aestivum L.)

PubMed Central

Wang, Hui; Yi, Yuan; Ding, Jinfeng; Zhu, Min; Li, Chunyan; Guo, Wenshan; Feng, Chaonian; Zhu, Xinkai

2017-01-01

Lodging is one of the constraints that limit wheat yields and quality due to the unexpected bending or breaking stems on wheat (Triticum aestivum L.) production worldwide. In addition to choosing lodging resistance varieties, husbandry practices also have a significant effect on lodging. Nitrogen management is one of the most common and efficient methods. A field experiment with Yangmai 20 as research material (a widely-used variety) was conducted to study the effects of different nitrogen levels and ratios on culm morphological, anatomical characters and chemical components and to explore the nitrogen application techniques for lodging tolerance and high yield. Results showed that some index of basal internodes, such as stem wall thickness, filling degree, lignin content, cellulose content, water-soluble carbohydrate (WSC) and WSC/N ratio, were positively and significantly correlated with culm lodging-resistant index (CLRI). As the increase of nitrogen level and basal nitrogen ratio, the basal internodes became slender and fragile with the thick stem wall, while filling degree, chemical components and the strength of the stem decreased gradually, which significantly increased the lodging risk. The response of grain yield to nitrogen doses was quadratic and grain yield reached the highest at the nitrogen ratio of 50%:10%:20%:20% (the ratio of nitrogen amount applied before sowing, at tillering stage, jointing stage and booting stage respectively, abbreviated as 5:1:2:2). These results suggested that for Yangmai 20, the planting density of 180×104ha-1, nitrogen level of 225 kg ha-1, and the ratio of 5: 1: 2: 2 effectively increased lodging resistance and grain yield. This combination of planting density and nitrogen level and ratio could effectively relieve the contradiction between high-yielding and anti-lodging. PMID:29117250

Effect of nitrogen levels and nitrogen ratios on lodging resistance and yield potential of winter wheat (Triticum aestivum L.).

PubMed

Zhang, Mingwei; Wang, Hui; Yi, Yuan; Ding, Jinfeng; Zhu, Min; Li, Chunyan; Guo, Wenshan; Feng, Chaonian; Zhu, Xinkai

2017-01-01

Lodging is one of the constraints that limit wheat yields and quality due to the unexpected bending or breaking stems on wheat (Triticum aestivum L.) production worldwide. In addition to choosing lodging resistance varieties, husbandry practices also have a significant effect on lodging. Nitrogen management is one of the most common and efficient methods. A field experiment with Yangmai 20 as research material (a widely-used variety) was conducted to study the effects of different nitrogen levels and ratios on culm morphological, anatomical characters and chemical components and to explore the nitrogen application techniques for lodging tolerance and high yield. Results showed that some index of basal internodes, such as stem wall thickness, filling degree, lignin content, cellulose content, water-soluble carbohydrate (WSC) and WSC/N ratio, were positively and significantly correlated with culm lodging-resistant index (CLRI). As the increase of nitrogen level and basal nitrogen ratio, the basal internodes became slender and fragile with the thick stem wall, while filling degree, chemical components and the strength of the stem decreased gradually, which significantly increased the lodging risk. The response of grain yield to nitrogen doses was quadratic and grain yield reached the highest at the nitrogen ratio of 50%:10%:20%:20% (the ratio of nitrogen amount applied before sowing, at tillering stage, jointing stage and booting stage respectively, abbreviated as 5:1:2:2). These results suggested that for Yangmai 20, the planting density of 180×104ha-1, nitrogen level of 225 kg ha-1, and the ratio of 5: 1: 2: 2 effectively increased lodging resistance and grain yield. This combination of planting density and nitrogen level and ratio could effectively relieve the contradiction between high-yielding and anti-lodging.

Hypertension Update: Resistant Hypertension.

PubMed

Viera, Anthony J

2018-06-01

Resistant hypertension is a blood pressure (BP) level that remains above the goal level despite adherence to at least three appropriately dosed antihypertensive drugs of different classes, one of which is a diuretic. Evaluation of suspected resistant hypertension starts with confirming adherence to the drug regimen. White coat hypertension should be ruled out with out-of-office BP level measurements, ideally using 24-hour ambulatory BP monitoring. Obesity, significant alcohol intake, and interfering drugs and other substances can contribute to resistant hypertension. Lifestyle modifications, including exercise and dietary sodium restriction, can be useful in management. Resistant hypertension may be due to secondary etiologies (eg, parenchymal kidney disease, obstructive sleep apnea, hyperaldosteronism). Adequate diuretic treatment is a key part of therapy. In addition to a diuretic, patients with resistant hypertension should take a dihydropyridine calcium channel blocker and an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Spironolactone is an effective fourth drug. Other drug options include a beta blocker, a long-acting nondihydropyridine calcium channel blocker, or clonidine or guanfacine. When the BP level is not controlled despite adherence to a four-drug regimen, referral to a hypertension subspecialist should be considered. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Dose-and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults.

PubMed

Forti, Louis Nuvagah; Van Roie, Evelien; Njemini, Rose; Coudyzer, Walter; Beyer, Ingo; Delecluse, Christophe; Bautmans, Ivan

2015-10-01

BDNF is known to induce neuroplasticity and low circulating levels have been related to neuronal loss in older persons. Physical exercise is thought to trigger BDNF-induced neuroplasticity, but conflicting observations have been reported regarding the effects of resistance training on circulating BDNF in the elderly. These conflicting observations might reflect dose-and gender-specific differences. Fifty-six apparently healthy elderly (68 ± 5 years) participants were randomized to 12 weeks of resistance training (3×/week) at either high-resistance (HIGH, 8 Males, 10 Females, 2 × 10-15 repetitions at 80% 1 RM), low-resistance (LOW, 9 Males, 10 Females, 1 × 80-100 repetitions at 20% 1 RM), or mixed low-resistance (LOW+, 9 Males, 10 Females, 1 × 60 repetitions at 20% 1 RM followed by 1 × 10-20 repetitions at 40% 1 RM). Serum was collected for BDNF assay at baseline and after 12 weeks (24 h-48 h after the last training). 12 weeks of LOW+ exercise significantly increased BDNF levels in male (from 34.9 ± 10.7 ng/mL to 42.9 ± 11.9 ng/mL, time × group interaction p=0.013), but not in female participants. No significant change was observed in HIGH or LOW, neither in male nor female subjects. Our results show that only the mixed-low-resistance training program with a very high number of repetitions at a sufficiently high external resistance was able to increase circulating BDNF in older male participants. Training to volitional fatigue might be necessary to obtain optimal results. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed gender difference. Copyright © 2015 Elsevier Inc. All rights reserved.

Triclosan resistant bacteria in sewage effluent and cross-resistance to antibiotics.

PubMed

Coetzee, I; Bezuidenhout, C C; Bezuidenhout, J J

2017-09-01

The purpose of this study was to identify triclosan tolerant heterotrophic plate count (HPC) bacteria from sewage effluent and to determine cross-resistance to antibiotics. R2 agar supplemented with triclosan was utilised to isolate triclosan resistant bacteria and 16S rRNA gene sequencing was conducted to identify the isolates. Minimum inhibitory concentrations (MICs) of organisms were determined at selected concentrations of triclosan and cross-resistance to various antibiotics was performed. High-performance liquid chromatography was conducted to quantify levels of triclosan in sewage water. Forty-four HPC were isolated and identified as the five main genera, namely, Bacillus, Pseudomonas, Enterococcus, Brevibacillus and Paenibacillus. MIC values of these isolates ranged from 0.125 mg/L to >1 mg/L of triclosan, while combination of antimicrobials indicated synergism or antagonism. Levels of triclosan within the wastewater treatment plant (WWTP) ranged between 0.026 and 1.488 ppb. Triclosan concentrations were reduced by the WWTP, but small concentrations enter receiving freshwater bodies. Results presented indicate that these levels are sufficient to maintain triclosan resistant bacteria under controlled conditions. Further studies are thus needed into the impact of this scenario on such natural receiving water bodies.

Clonal variation in high- and low-level phenotypic and genotypic mupirocin resistance of MRSA isolates in south-east London.

PubMed

Hughes, John; Stabler, Richard; Gaunt, Michael; Karadag, Tacim; Desai, Nergish; Betley, Jason; Ioannou, Avgousta; Aryee, Anna; Hearn, Pasco; Marbach, Helene; Patel, Amita; Otter, Jonathan A; Edgeworth, Jonathan D; Tosas Auguet, Olga

2015-12-01

Both low-level mupirocin resistance (LMR) and high-level mupirocin resistance (HMR) have been identified. The aim of this study was to determine the epidemiology of LMR and HMR in MRSA isolates at five hospitals that have used mupirocin for targeted decolonization as part of successful institutional control programmes. All MRSA identified in three microbiology laboratories serving five central and south-east London hospitals and surrounding communities between November 2011 and February 2012 were included. HMR and LMR were determined by disc diffusion testing. WGS was used to derive multilocus sequence types (MLSTs) and the presence of HMR and LMR resistance determinants. Prevalence of either HMR or LMR amongst first healthcare episode isolates from 795 identified patients was 9.69% (95% CI 7.72-11.96); LMR was 6.29% (95% CI 4.70-8.21) and HMR was 3.40% (95% CI 2.25-4.90). Mupirocin resistance was not significantly different in isolates identified from inpatients at each microbiology laboratory, but was more common in genotypically defined 'hospital' rather than 'community' isolates (OR 3.17, 95% CI 1.36-9.30, P = 0.002). LMR was associated with inpatient stay, previous history of MRSA and age ≥65 years; HMR was associated with age ≥65 years and residential postcode outside London. LMR and HMR varied by clone, with both being low in the dominant UK MRSA clone ST22 compared with ST8, ST36 and ST239/241 for LMR and with ST8 and ST36 for HMR. V588F mutation and mupA carriage had high specificity (>97%) and area under the curve (>83%) to discriminate phenotypic mupirocin resistance, but uncertainty around the sensitivity point estimate was large (95% CI 52.50%-94.44%). Mutations in or near the mupA gene were found in eight isolates that carried mupA but were not HMR. Mupirocin resistance was identified in <10% of patients and varied significantly by clone, implying that changes in clonal epidemiology may have an important role in determining the prevalence of

Oxidative stress, glutathione level and antioxidant response to heavy metals in multi-resistant pathogen, Candida tropicalis.

PubMed

Ilyas, Sidra; Rehman, Abdul

2015-01-01

In this study, we explored the multiple heavy metal-resistant yeast isolated from heavy metal-polluted environment. The isolated yeast showed maximum growth at 30 °C, pH 7.0, and the strain was identified as Candida tropicalis through 18S ribosomal RNA (rRNA) gene sequence analysis. Yeast cells grew well in medium containing different concentrations of heavy metal ions [CdCl₂, Pb(NO₃)₂, NaAsO₂, CuSO₄ and K₂Cr₂O₇]. Minimum inhibitory concentration (MIC) against different metal ions was ranged from 5 to 19 mM, and the metal resistance value against each metal observed by yeast cells was 5 mM (Cr), 10 mM (Cd), 15 mM (As), 14 mM (Cu) and 19 mM (Pb) and increased in the following order: Pb > Cu > As ≥ Cd > Cr. The total cellular glutathione, GSH/GSSG redox couple and metallothioneins like protein (MT) were assayed by growing cultures for 24 h and exposed to 100 mg/L of each heavy metal ion. Remarkable increase in γ-glutamylcysteinylglycine (GSH) level was determined in arsenic and cadmium treatment followed by chromium, lead and copper. Stressed cells had much more oxidized GSH than unstressed cells. GSH/GSSG ratio was significantly increased in cadmium and copper treatment in contrast to chromium, arsenic and lead. Statistical analysis revealed significantly higher cysteine level in all metal-treated samples as compared to control. Antioxidant glutathione transferase activity was not detected in metal-treated and untreated yeast samples. One-dimensional electrophoresis of proteins revealed marked differences in banding pattern of heavy metal-exposed yeast samples. A prominent 20 kDa band was observed in all treated samples suggesting that some differential proteins could be over-expressed during heavy metal treatment and might be involved in cell resistance mechanisms.

Role of the Stringent Stress Response in the Antibiotic Resistance Phenotype of Methicillin-Resistant Staphylococcus aureus

PubMed Central

Aedo, Sandra

2016-01-01

Resistance to beta-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) requires the presence of an acquired genetic determinant, mecA or mecC, which encode penicillin-binding protein PBP2A or PBP2A′, respectively. Although all MRSA strains share a mechanism of resistance, the phenotypic expression of beta-lactam resistance shows considerable strain-to-strain variation. The stringent stress response, a stress response that results from nutrient limitation, was shown to play a key role in determining the resistance level of an MRSA strain. In the present study, we validated the impact of the stringent stress response on transcription and translation of mecA in the MRSA clinical isolate strain N315, which also carries known regulatory genes (mecI/mecR1/mecR2 and blaI/blaR1) for mecA transcription. We showed that the impact of the stringent stress response on the resistance level may be restricted to beta-lactam resistance based on a “foreign” determinant such as mecA, as opposed to resistance based on mutations in the native S. aureus determinant pbpB (encoding PBP2). Our observations demonstrate that high-level resistance mediated by the stringent stress response follows the current model of beta-lactam resistance in which the native PBP2 protein is also essential for expression of the resistance phenotype. We also show that the Staphylococcus sciuri pbpD gene (also called mecAI), the putative evolutionary precursor of mecA, confers oxacillin resistance in an S. aureus strain, generating a heterogeneous phenotype that can be converted to high and homogenous resistance by induction of the stringent stress response in the bacteria. PMID:26833147

Characterization of resistant hypertension: association between resistant hypertension, aldosterone, and persistent intravascular volume expansion.

PubMed

Gaddam, Krishna K; Nishizaka, Mari K; Pratt-Ubunama, Monique N; Pimenta, Eduardo; Aban, Inmaculada; Oparil, Suzanne; Calhoun, David A

2008-06-09

Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage. We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using resistant hypertension vs controls. Of patients with resistant hypertension, men had significantly higher plasma aldosterone (P = .003), aldosterone to renin ratio (P = .02), 24-hour UAldo (P < .001), and urinary cortisol (P < .001) values than women. In univariate linear regression analysis, body mass index (P = .01), serum potassium (P < .001), urinary cortisol (P < .001), urinary sodium (P = .02), and urinary potassium (P < .001) values were correlated with 24-hour UAldo levels. Serum potassium (P = .001), urinary potassium (P < .001), and urinary sodium (P = .03) levels were predictors of 24-hour UAldo levels in multivariate modeling. Aldosterone levels are higher and there is evidence of intravascular volume expansion (higher brain-type and atrial natriuretic peptide levels) in patients with resistant hypertension vs controls. These differences are most pronounced in men. A significant correlation between 24-hour urinary aldosterone levels and cortisol excretion suggests that a common stimulus, such as

Cross-resistance and Inheritance of Resistance to Emamectin Benzoate in Spodoptera exigua (Lepidoptera: Noctuidae).

PubMed

Che, Wunan; Huang, Jianlei; Guan, Fang; Wu, Yidong; Yang, Yihua

2015-08-01

Beet armyworm, Spodoptera exigua (Hübner), is a worldwide pest of many crops. Chemical insecticides are heavily used for its control in China, and serious resistance has been evolved in the field to a variety of insecticides including emamectin benzoate. Through repeated backcrossing to a susceptible strain (WH-S) and selection with emamectin benzoate, the trait conferring resistance to emamectin benzoate in a field-collected population of S. exigua (moderately resistant to emamectin benzoate and strongly resistant to pyrethroids and indoxacarb) was introgressed into WH-S to generate a near-isogenic resistant strain (WH-EB). Compared with WH-S, the WH-EB strain developed a 1,110-fold resistance to emamectin benzoate and a high level of cross-resistance to abamectin (202-fold), with low levels of cross-resistance to cypermethrin (10-fold) and chlorfluazuron (7-fold), but no cross-resistance to representatives of another six different classes of insecticides (chlorantraniliprole, chlorfenapyr, indoxacarb, spinosad, tebufenozide, and chlorpyrifos). Resistance to emamectin benzoate in WH-EB was autosomal, incompletely dominant, and polygenic. Limited cross-resistance in WH-EB indicates that emamectin benzoate can be rotated with other classes of insecticides to which it does not show cross-resistance to delay the evolution of resistance in S. exigua. The incompletely dominant nature of resistance in S. exigua may explain the rapid evolution of resistance to emamectin benzoate in the field, and careful deployment of this chemical within a resistance management program should be considered. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents.

PubMed

Liu, Anne; Fong, Amie; Becket, Elinne; Yuan, Jessica; Tamae, Cindy; Medrano, Leah; Maiz, Maria; Wahba, Christine; Lee, Catherine; Lee, Kim; Tran, Katherine P; Yang, Hanjing; Hoffman, Robert M; Salih, Anya; Miller, Jeffrey H

2011-03-01

Many studies have examined the evolution of bacterial mutants that are resistant to specific antibiotics, and many of these focus on concentrations at and above the MIC. Here we ask for the minimum concentration at which existing resistant mutants can outgrow sensitive wild-type strains in competition experiments at antibiotic levels significantly below the MIC, and we define a minimum selective concentration (MSC) in Escherichia coli for two antibiotics, which is near 1/5 of the MIC for ciprofloxacin and 1/20 of the MIC for tetracycline. Because of the prevalence of resistant mutants already in the human microbiome, allowable levels of antibiotics to which we are exposed should be below the MSC. Since this concentration often corresponds to low or trace levels of antibiotics, it is helpful to have simple tests to detect such trace levels. We describe a simple ultrasensitive test for detecting the presence of antibiotics and genotoxic agents. The test is based on the use of chromogenic proteins as color markers and the use of single and multiple mutants of Escherichia coli that have greatly increased sensitivity to either a wide range of antibiotics or specific antibiotics, antibiotic families, and genotoxic agents. This test can detect ciprofloxacin at 1/75 of the MIC.

Radiation coloration resistant glass

DOEpatents

Tomozawa, M.; Watson, E.B.; Acocella, J.

1986-11-04

A radiation coloration resistant glass is disclosed which is used in a radiation environment sufficient to cause coloration in most forms of glass. The coloration resistant glass includes higher proportions by weight of water and has been found to be extremely resistant to color change when exposed to such radiation levels. The coloration resistant glass is free of cerium oxide and has more than about 0.5% by weight water content. Even when exposed to gamma radiation of more than 10[sup 7] rad, the coloration resistant glass does not lose transparency. 3 figs.

Radiation coloration resistant glass

DOEpatents

Tomozawa, Minoru; Watson, E. Bruce; Acocella, John

1986-01-01

A radiation coloration resistant glass is disclosed which is used in a radiation environment sufficient to cause coloration in most forms of glass. The coloration resistant glass includes higher proportions by weight of water and has been found to be extremely resistant to color change when exposed to such radiation levels. The coloration resistant glass is free of cerium oxide and has more than about 0.5% by weight water content. Even when exposed to gamma radiation of more than 10.sup.7 rad, the coloration resistant glass does not lose transparency.

[Effects of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin-resistant adipocytes].

PubMed

Tu, Jun; Luo, Xin-Xin; Li, Bing-Tao; Li, Yu; Xu, Guo-Liang

2016-06-01

Adipocytokines are closely associated with insulin resistance (IR) in adipose tissues, and they are more and more seriously taken in the study of the development of diabetes. This experiment was mainly to study the effect of berberine on mRNA expression levels of PPARγ and adipocytokines in insulin resistant adipocytes, and investigate the molecular mechanism of berberine in enhancing insulin sensitization and application advantages of droplet digital PCR (ddPCR). ddPCR absolute quantification analysis was taken in this experiment to simply and intuitively determine the appropriate reference genes. ddPCR and quantitative Real-time PCR (qPCR) were used to compare the effect of different doses of berberine (10, 20, 50, 100 μmol•L⁻¹) on mRNA expression levels of PPARγ, adiponectin, resistin and leptin in IR 3T3-L1adipocytes. Antagonist GW9662 was added to study the inherent correlation between PPARγ and adiponectin mRNA expression levels. ddPCR results showed that the expression level of β-actin in adipocytes was stable, and suitable as reference gene for normalization of quantitative PCR data. Both of ddPCR and qPCR results showed that, as compared with IR models, the mRNA expression levels of adiponectin were decreased in the treatment with berberine (10, 20, 50, 100 μmol•L⁻¹) in a dose-dependent manner (P<0.01); the expression of PPARγ was decreased by 20, 50, 100 μmol•L⁻¹ berberine in a dose-dependent manner in qPCR assay (P<0.01) and decreased only by 50 and 100 μmol•L⁻¹ berberine in ddPCR assay (P<0.05). PPARγ specific antagonist GW9662 intervention experiment showed that adiponectin gene expression was directly relevant with PPARγ (P<0.05). ddPCR probe assay showed that various doses of berberine could significantly reduce mRNA expression levels of resistin and leptin (P<0.01) in a dose-dependent manner. In conclusion, berberine enhanced insulin sensitization effect not by up-regulating adiponect in expression of transcriptional

Occurrence, distribution and contamination levels of heat-resistant moulds throughout the processing of pasteurized high-acid fruit products.

PubMed

Santos, Juliana Lane Paixão Dos; Samapundo, Simbarashe; Biyikli, Ayse; Van Impe, Jan; Akkermans, Simen; Höfte, Monica; Abatih, Emmanuel Nji; Sant'Ana, Anderson S; Devlieghere, Frank

2018-05-19

Heat-resistant moulds (HRMs) are well known for their ability to survive pasteurization and spoil high-acid food products, which is of great concern for processors of fruit-based products worldwide. Whilst the majority of the studies on HRMs over the last decades have addressed their inactivation, few data are currently available regarding their contamination levels in fruit and fruit-based products. Thus, this study aimed to quantify and identify heat-resistant fungal ascospores from samples collected throughout the processing of pasteurized high-acid fruit products. In addition, an assessment on the effect of processing on the contamination levels of HRMs in these products was carried out. A total of 332 samples from 111 batches were analyzed from three processing plants (=three processing lines): strawberry puree (n = 88, Belgium), concentrated orange juice (n = 90, Brazil) and apple puree (n = 154, the Netherlands). HRMs were detected in 96.4% (107/111) of the batches and 59.3% (197/332) of the analyzed samples. HRMs were present in 90.9% of the samples from the strawberry puree processing line (1-215 ascospores/100 g), 46.7% of the samples from the orange juice processing line (1-200 ascospores/100 g) and 48.7% of samples from the apple puree processing line (1-84 ascospores/100 g). Despite the high occurrence, the majority (76.8%, 255/332) of the samples were either not contaminated or presented low levels of HRMs (<10 ascospores/100 g). For both strawberry puree and concentrated orange juice, processing had no statistically significant effect on the levels of HRMs (p > 0.05). On the contrary, a significant reduction (p < 0.05) in HRMs levels was observed during the processing of apple puree. Twelve species were identified belonging to four genera - Byssochlamys, Aspergillus with Neosartorya-type ascospores, Talaromyces and Rasamsonia. N. fumigata (23.6%), N. fischeri (19.1%) and B. nivea (5.5%) were the predominant species in

Cross-resistance and biochemical mechanisms of resistance to indoxacarb in the diamondback moth, Plutella xylostella.

PubMed

Zhang, Shuzhen; Zhang, Xiaolei; Shen, Jun; Li, Dongyang; Wan, Hu; You, Hong; Li, Jianhong

2017-08-01

Indoxacarb belongs to a class of insecticides known as oxadiazines and is the first commercialized pyrazoline-type voltage-dependent sodium channel blocker. A moderate level of resistance to indoxacarb has evolved in field populations of Plutella xylostella from Central China. In the present study, cross-resistance, resistance stability and metabolic mechanisms of indoxacarb resistance were investigated in this moth species. A P. xylostella strain with a high level of resistance to indoxacarb was obtained through continuous selection in the laboratory. The strain showed cross-resistance to metaflumizone, beta-cypermethrin and chlorfenapyr, but no resistance to cyantraniliprole, chlorantraniliprole, abamectin, chlorfluazuron, spinosad and diafenthiuron compared with the susceptible strain. Synergism tests revealed that piperonyl butoxide (PBO) (synergistic ratio, SR=7.8) and diethyl maleate (DEF) (SR=3.5) had considerable synergistic effects on indoxacarb toxicity in the resistant strain (F 58 ). Enzyme activity data showed there was an approximate 5.8-fold different in glutathione S-transferase (GST) and a 6.8-fold different in cytochrome P450 monooxygenase between the resistant strain (F 58 ) and susceptible strain, suggesting that the increased activity of these two enzymes is likely the main detoxification mechanism responsible for the species' resistance to indoxacarb. These results will be helpful for insecticide resistance management strategies to delay the development of indoxacarb resistance in fields. Copyright © 2017. Published by Elsevier Inc.

Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated With Increased Insulin Resistance and Higher Risk of Developing Gestational Diabetes Mellitus

PubMed Central

Lacroix, Marilyn; Battista, Marie-Claude; Doyon, Myriam; Ménard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France

2013-01-01

OBJECTIVE To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. RESEARCH DESIGN AND METHODS We performed anthropometric measurements and collected blood samples at 1st (6–13 weeks) and 2nd (24–28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUCinsulin/glucose), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay. RESULTS Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = −0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUCinsulin/glucose. CONCLUSIONS Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements. PMID:23300287

Lower adiponectin levels at first trimester of pregnancy are associated with increased insulin resistance and higher risk of developing gestational diabetes mellitus.

PubMed

Lacroix, Marilyn; Battista, Marie-Claude; Doyon, Myriam; Ménard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France

2013-06-01

To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. We performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC(insulin/glucose)), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay. Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = -0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUC(insulin/glucose). Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.

From multidrug-resistant to extensively drug-resistant tuberculosis in Lisbon, Portugal: the stepwise mode of resistance acquisition.

PubMed

Perdigão, João; Macedo, Rita; Silva, Carla; Machado, Diana; Couto, Isabel; Viveiros, Miguel; Jordao, Luisa; Portugal, Isabel

2013-01-01

The development and transmission of extensively drug-resistant (XDR) tuberculosis (TB) constitutes a serious threat to the effective control of TB in several countries. Here, in an attempt to further elucidate the dynamics of the acquisition of resistance to second-line drugs and investigate an eventual role for eis promoter mutations in aminoglycoside resistance, we have studied a set of multidrug-resistant (MDR)/XDR-TB isolates circulating in Lisbon, Portugal. Forty-four MDR-TB or XDR-TB isolates were genotyped and screened for mutations in genes associated with second-line drug resistance, namely tlyA, gyrA, rrs and eis. The most prevalent mutations found in each gene were Ins755GT in tlyA, A1401G in rrs, G-10A in eis and S91P in gyrA. Additionally, two genetic clusters were found in this study: Lisboa3 and Q1. The characteristic mutational profile found among recent XDR-TB circulating in Lisbon was also found in MDR-TB strains isolated in the 1990s. Also investigated was the resistance level conferred by eis G-10A mutations, revealing that eis G-10A mutations may result in amikacin resistance undetectable by widely used phenotypic assays. The analysis of the distribution of the mutations found by genetic clustering showed that in the Q1 cluster, two mutations, gyrA D94A and rrs A1401G, were enough to ensure development of XDR-TB from an MDR strain. Moreover, in the Lisboa3 cluster it was possible to elaborate a model in which the development of low-level kanamycin resistance was at the origin of the emergence of XDR-TB strains that can be discriminated by tlyA mutations.

Relations between Children's Levels of Responsiveness and Resistance, Maternal Interaction Behaviors, and Children's Social Behaviors with Peers in School

ERIC Educational Resources Information Center

Salinas, Daniela; Neitzel, Carin

2017-01-01

Children's peer relationships have their origins in family relationships. The present study focuses on the relative importance of children's levels of responsiveness and/or resistance during mother-child interactions and tests a model of the direct and indirect relations between mother interaction behaviors and children's social behaviors with…

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

PubMed

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B B; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and

Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

PubMed Central

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B.B.; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing

Architectural-level power estimation and experimentation

NASA Astrophysics Data System (ADS)

Ye, Wu

With the emergence of a plethora of embedded and portable applications and ever increasing integration levels, power dissipation of integrated circuits has moved to the forefront as a design constraint. Recent years have also seen a significant trend towards designs starting at the architectural (or RT) level. Those demand accurate yet fast RT level power estimation methodologies and tools. This thesis addresses issues and experiments associate with architectural level power estimation. An execution driven, cycle-accurate RT level power simulator, SimplePower, was developed using transition-sensitive energy models. It is based on the architecture of a five-stage pipelined RISC datapath for both 0.35mum and 0.8mum technology and can execute the integer subset of the instruction set of SimpleScalar . SimplePower measures the energy consumed in the datapath, memory and on-chip buses. During the development of SimplePower , a partitioning power modeling technique was proposed to model the energy consumed in complex functional units. The accuracy of this technique was validated with HSPICE simulation results for a register file and a shifter. A novel, selectively gated pipeline register optimization technique was proposed to reduce the datapath energy consumption. It uses the decoded control signals to selectively gate the data fields of the pipeline registers. Simulation results show that this technique can reduce the datapath energy consumption by 18--36% for a set of benchmarks. A low-level back-end compiler optimization, register relabeling, was applied to reduce the on-chip instruction cache data bus switch activities. Its impact was evaluated by SimplePower. Results show that it can reduce the energy consumed in the instruction data buses by 3.55--16.90%. A quantitative evaluation was conducted for the impact of six state-of-art high-level compilation techniques on both datapath and memory energy consumption. The experimental results provide a valuable insight for

Important Mutations Contributing to High-Level Penicillin Resistance in Taiwan19F-14, Taiwan23F-15, and Spain23F-1 of Streptococcus pneumoniae Isolated from Taiwan.

PubMed

Liu, Esther Yip-Mei; Chang, Jen-Chang; Lin, Jung-Chung; Chang, Feng-Yee; Fung, Chang-Phone

2016-12-01

Penicillin-resistant Streptococcus pneumoniae is a serious concern worldwide. In this study, we analyzed the cause of β-lactam resistance in pandemic multidrug-resistant clones. A total of 41 penicillin-nonsusceptible clinical isolates were collected from 1996 to 2012. Sero- and molecular typing confirmed that these isolates were clonal types of Taiwan 19F -14, Taiwan 23F -15, and Spain 23F -1. Sero-switching was found in four isolates. All isolates were multidrug resistant. Sequencing analysis of the penicillin binding proteins (PBPs) was performed on PBP1a, 2b, and 2x, and a large number of mutations were identified in comparing to clinical penicillin-susceptible isolates and the recipient strain R6 used for homologous recombination. The T 451 A substitution was the key amino acid in PBP2b that contributed to penicillin resistance. T 338 A in PBP2x played a role in resistance and reached the highest level of resistance when combined with other mutations in PBP2x. High-level penicillin resistance could not be obtained without the combination of mutations in PBP1a with PBP2b and 2x. The amino acid substitutions in PBP1a, 2b, and 2x were the crucial factors for β-lactam resistance.

Direct correlation between serum homocysteine level and insulin resistance index in patients with subclinical hypothyroidism: Does subclinical hypothyroidism increase the risk of diabetes and cardio vascular disease together?

PubMed

Ebrahimpour, Anahita; Vaghari-Tabari, Mostafa; Qujeq, Durdi; Moein, Soheila; Moazezi, Zoleikha

2018-05-05

Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue. Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used. Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients. Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting β-Lactam Resistance Levels in Streptococcus pneumoniae

PubMed Central

Metcalf, Benjamin J.; Chochua, Sopio; Li, Zhongya; Gertz, Robert E.; Walker, Hollis; Hawkins, Paulina A.; Tran, Theresa; Whitney, Cynthia G.; McGee, Lesley; Beall, Bernard W.

2016-01-01

ABSTRACT β-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of β-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking β-lactam resistance could benefit disease surveillance. Here we developed a classification system in which a pneumococcal isolate is assigned to a “PBP type” based on sequence signatures in the transpeptidase domains (TPDs) of the three critical penicillin-binding proteins (PBPs), PBP1a, PBP2b, and PBP2x. We identified 307 unique PBP types from 2,528 invasive pneumococcal isolates, which had known MICs to six β-lactams based on broth microdilution. We found that increased β-lactam MICs strongly correlated with PBP types containing divergent TPD sequences. The PBP type explained 94 to 99% of variation in MICs both before and after accounting for genomic backgrounds defined by multilocus sequence typing, indicating that genomic backgrounds made little independent contribution to β-lactam MICs at the population level. We further developed and evaluated predictive models of MICs based on PBP type. Compared to microdilution MICs, MICs predicted by PBP type showed essential agreement (MICs agree within 1 dilution) of >98%, category agreement (interpretive results agree) of >94%, a major discrepancy (sensitive isolate predicted as resistant) rate of <3%, and a very major discrepancy (resistant isolate predicted as sensitive) rate of <2% for all six β-lactams. Thus, the PBP transpeptidase signatures are robust indicators of MICs to different β-lactam antibiotics in clinical pneumococcal isolates and serve as an accurate alternative to phenotypic susceptibility testing. PMID:27302760

Effect of Insulin Levels on Phosphorylation of Specific Amino Acid Residues in IRS-1: Implications for Burn Induced Insulin Resistance

PubMed Central

Lu, Xiao-Ming; Hamrahi, Victoria F.; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Alterations in the phosphorylation and/or degradation of insulin receptor substrate 1 (IRS-1) produced by burn injury may be responsible, at least in part, for burn-induced insulin resistance. In particular, following burn injury, reductions in glucose uptake by skeletal muscle may be secondary to altered abundance and/or phosphorylation of IRS-1. In this report, we performed in vitro studies with 293 cells transfected with IRS-1. These studies demonstrated that there is a dramatic change in the phosphorylation pattern of Tyr, Ser, and Thr residues in IRS-1 as a function of insulin levels. Specifically, Ser and Thr residues in the C-terminal region were phosphorylated only at high insulin levels. SILAC (stable isotope labeling with amino acids in cell culture) followed by sequencing of C-terminal IRS-1 fragments by tandem mass spectrometry demonstrated that there is significant protein cleavage at these sites. These findings suggest that one of the biological roles of the C-terminal region of IRS-1 may be negative modulation of the finely coordinated insulin signaling system. Clearly, this could represent an important factor in insulin resistance and identification of inhibitors of the kinases that are responsible for the phosphorylation could foster new lines of research for the development of drugs for treating insulin resistance. PMID:19724894

Pyrethroid resistance and cross-resistance in the German cockroach, Blattella germanica (L).

PubMed

Wei, Y; Appel, A G; Moar, W J; Liu, N

2001-11-01

A German cockroach (Blatella germanica (L)) strain, Apyr-R, was collected from Opelika, Alabama after control failures with pyrethroid insecticides. Levels of resistance to permethrin and deltamethrin in Apyr-R (97- and 480-fold, respectively, compared with a susceptible strain, ACY) were partially or mostly suppressed by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF), suggesting that P450 monooxygenases and hydrolases are involved in resistance to these two pyrethroids in Apyr-R. However, incomplete suppression of pyrethroid resistance with PBO and DEF implies that one or more additional mechanisms are involved in resistance. Injection, compared with topical application, resulted in 43- and 48-fold increases in toxicity of permethrin in ACY and Apyr-R, respectively. Similarly, injection increased the toxicity of deltamethrin 27-fold in ACY and 28-fold in Apyr-R. These data indicate that cuticular penetration is one of the obstacles for the effectiveness of pyrethroids against German cockroaches. However, injection did not change the levels of resistance to either permethrin or deltamethrin, suggesting that a decrease in the rate of cuticular penetration may not play an important role in pyrethroid resistance in Apyr-R. Apyr-R showed cross-resistance to imidacloprid, with a resistance ratio of 10. PBO treatment resulted in no significant change in the toxicity of imidacloprid, implying that P450 monooxygenase-mediated detoxication is not the mechanism responsible for cross-resistance. Apyr-R showed no cross-resistance to spinosad, although spinosad had relatively low toxicity to German cockroaches compared with other insecticides tested in this study. This result further confirmed that the mode of action of spinosad to insects is unique. Fipronil, a relatively new insecticide, was highly toxic to German cockroaches, and the multi-resistance mechanisms in Apyr-R did not confer significant cross-resistance to this compound. Thus, we propose

Resistance Responses of Potato to Vesicular-Arbuscular Mycorrhizal Fungi under Varying Abiotic Phosphorus Levels 1

PubMed Central

McArthur, David A. J.; Knowles, N. Richard

1992-01-01

to plant growth decreased and root infection was lower. The in vivo ACCox activity was also greater in roots of plants grown on high levels of P compared with those grown on low levels, although the influence of VAM infection was partially to counteract the nutritional effect of P on ACCox activity. Similar to ACCox activity, extracellular peroxidase activity of roots increased linearly with increasing abiotic P supply, thus indicating a greater potential for resistance to VAM infection. These findings suggest that VAM fungi may alter phenolic metabolism of roots so as to hinder ethylene production and the root's ability to invoke a defense response. Raising the abiotic P supply to plants at least partially restores the capacity of roots to produce ethylene and may, in this way, increase the root's resistance to VAM infection. Images Figure 1 PMID:16652967

Effect of aerobic training and resistance training on circulating irisin level and their association with change of body composition in overweight/obese adults: a pilot study.

PubMed

Kim, H-J; Lee, H-J; So, B; Son, J S; Yoon, D; Song, W

2016-06-20

The novel myokine irisin has been reported as a therapeutic target for metabolic disease. The objective of this study is to reveal the effects of aerobic training (AT) and resistance training (RT) on circulating irisin levels and their associations with change of body composition in overweight/obese adults. Twenty eight overweight/obese adults (BMI>23 kg/m(2)) were included in this study and compared before and after 8 weeks of exercise program (60 min/day, 5 times in a week). The subjects, in both aerobic and resistance training, showed significant improvement in anthropometric parameters and exercise capacities including maximal oxygen uptake and muscle strength. Interestingly, the circulating irisin was significantly increased in resistance training group (p=0.002) but not in aerobic training (p=0.426) compared to control group. In addition, we found the positive correlation between change of the circulating irisin and muscle mass (r=0.432, p=0.022) and the negative correlation between change of the circulating irisin and fat mass (r=-0.407, p=0.031). In the present pilot study, we found that circulating irisin level was increased by 8 weeks of resistance training in overweight/obese adults, suggesting that resistance training could be the efficient exercise type in overweight/obese considering positive change of body composition concomitant with increase of irisin levels.

Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

NASA Astrophysics Data System (ADS)

Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

2006-03-01

Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

Improved multi-level capability in Si3N4-based resistive switching memory using continuous gradual reset switching

NASA Astrophysics Data System (ADS)

Kim, Sungjun; Park, Byung-Gook

2017-01-01

In this letter, we compare three different types of reset switching behavior in a bipolar resistive random-access memory (RRAM) system that is housed in a Ni/Si3N4/Si structure. The abrupt, step-like gradual and continuous gradual reset transitions are largely determined by the low-resistance state (LRS). For abrupt reset switching, the large conducting path shows ohmic behavior or has a weak nonlinear current-voltage (I-V) characteristics in the LRS. For gradual switching, including both the step-like and continuous reset types, trap-assisted direct tunneling is dominant in the low-voltage regime, while trap-assisted Fowler-Nordheim tunneling is dominant in the high-voltage regime, thus causing nonlinear I-V characteristics. More importantly, we evaluate the multi-level capabilities of the two different gradual switching types, including both step-like and continuous reset behavior, using identical and incremental voltage conditions. Finer control of the conductance level with good uniformity is achieved in continuous gradual reset switching when compared to that in step-like gradual reset switching. For continuous reset switching, a single conducting path, which initially has a tunneling gap, gradually responds to pulses with even and identical amplitudes, while for step-like reset switching, the multiple conducting paths only respond to incremental pulses to obtain effective multi-level states.

Plasma visfatin level in lean women with PCOS: relation to proinflammatory markers and insulin resistance.

PubMed

Gen, Ramazan; Akbay, Esen; Muslu, Necati; Sezer, Kerem; Cayan, Filiz

2009-04-01

The present study was undertaken to investigate the association between plasma visfatin concentrations and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP) in company with several metabolic parameters in lean women with polycystic ovary syndrome (PCOS). The study group consisted of 21 lean women with PCOS (BMI 20.74 +/- 1.74 kg/m(2)) and 15 healthy, normally menstruating women (BMI 20.85 +/- 2.08 kg/m(2) control group). PCOS was defined according to the Rotterdam criteria. Visfatin, IL-6, hsCRP, hyperandrogenism markers and metabolic markers were examined in all PCOS and control women. Plasma visfatin level in the PCOS group was higher than that in the control group. Plasma hsCRP and IL-6 levels in PCOS group were similar with the control group. Plasma visfatin levels were positively associated with total cholesterol, high density lipoprotein, hirsutism score, total testosterone and FAI. Plasma visfatin level was negatively associated with SHBG. However, there were no correlation between plasma visfatin level and IL-6 and hsCRP. In multivariate regression analyses, only FAI and high density lipoprotein-cholesterol (HDL-C) showed a significant association with serum visfatin. Our data indicates that plasma visfatin levels are associated with HDL-C and markers of hyperandrogenism, but it is not associated with proinflammatory markers and insulin resistance in lean women with PCOS.

Evaluation of the Xpert MTB/RIF assay for diagnosis of tuberculosis and rifampin resistance in county-level laboratories in Hunan province, China.

PubMed

Hu, Peilei; Bai, Liqiong; Liu, Fengping; Ou, Xichao; Zhang, Zhiying; Yi, Songlin; Chen, Zhongnan; Gong, Daofang; Liu, Binbin; Guo, Jingwei; Tan, Yunhong

2014-01-01

The Xpert MTB/RIF showed high sensitivity and specificity in previous studies carried out in different epidemiological and geographical settings and patient populations in high-burden tuberculosis (TB) countries. However, there were little data obtained by validation or demonstration study of the assay in China. In this study, the performance of Xpert MTB/RIF was investigated in two county-level laboratories in Hunan Province, China. Consecutive patients with suspected pulmonary tuberculosis (PTB) and suspicion for multidrug-resistant tuberculosis (MDR-TB) were enrolled. For each patient suspected to have PTB, three sputum specimens (one spot sputum, one night sputum, and one morning sputum) were collected and each sputum was tested with smear microscopy, Löwenstein-Jensen (LJ) culture, and Xpert MTB/RIF test. For comparison across subgroups and testing methods, 95% confidence intervals were calculated. All analyses were done with SPSS 16.0, and P < 0.05 was regarded as significant. For case detection, the sensitivity of Xpert MTB/RIF was 100% for smear- and culture-positive TB and 88.6% for smear-negative and culture-positive TB; the overall sensitivity was 94.5% for all culture-positive patients. The specificity was 99.8%. The sensitivity of Xpert MTB/RIF assay was 22.0% in clinical TB patients and the specificity reached 100.0% in the group of patients who are infected with nontuberculous mycobacteria. For the detection of rifampin resistance, the sensitivity of MTB/RIF RIF-resistance detection was 92.9%, and the specificity was 98.7%. Of the 26 Xpert MTB/RIF-positive and RIF-resistant patients confirmed by LJ proportion tests, 20 (76.9%) patients were infected by MDR-TB. The Xpert MTB/RIF assay is a highly sensitive and specific method for diagnosis of TB and RIF resistance, which will enable it to have the potential to be used in county-level laboratories and lead to the reduction of the infectious pool and improvements in TB control in China. Further

Sources of diversity of carbapenem resistance levels in Klebsiella pneumoniae carrying blaVIM-1.

PubMed

Loli, A; Tzouvelekis, L S; Tzelepi, E; Carattoli, A; Vatopoulos, A C; Tassios, P T; Miriagou, V

2006-09-01

To elucidate the mechanisms responsible for the diversity of beta-lactam resistance phenotypes among isolates of a VIM-1-producing Klebsiella pneumoniae (VPKP) strain that is endemic in Greek hospitals. Five VPKP clinical isolates were studied. MICs of beta-lactams were determined by agar dilution. PFGE of XbaI-digested genomic DNA was used for typing. Profiles of outer membrane proteins (OMPs) were determined by SDS-PAGE. Selected isolates were transformed with a plasmid encoding the Omp36K porin. beta-Lactamase activities were analysed by IEF and imipenem hydrolysis was assessed by spectrophotometry. VIM-1-encoding, self-transmissible plasmids were characterized by replicon typing, RFLP and hybridization with bla(VIM)- and IS26-specific probes. Characterization of integrons was performed by PCR, cloning and sequencing. Isolates exhibited highly similar PFGE patterns. Imipenem MICs were 2, 4, 16, 32 and 64 mg/L. The isolate with the highest imipenem MIC (Vipm-64) lacked a 36 kDa OMP. Expression of a cloned OmpK36 in this isolate reduced the imipenem MIC to susceptibility levels. Imipenem-hydrolysing activity was significantly higher in Vipm-16 as compared with the other isolates that expressed similar amounts of VIM-1. All isolates transferred beta-lactam resistance to Escherichia coli through conjugative, IncN plasmids that exhibited differences in the RFLP and hybridization patterns with bla(VIM)- and IS26-specific probes. The Vipm-16 plasmid, mediating the higher imipenem MICs among transconjugants, carried two copies of bla(VIM-1). Cloning and sequencing showed In-e541-like integrons truncated at the 5'CS by insertion of IS26 elements at two different positions. A VIM-1-producing strain of K. pneumoniae has evolved through OMP alterations and rearrangements in the bla(VIM-1)-carrying plasmid probably mediated by IS26, generating isolates with imipenem MICs ranging from susceptibility to resistance.

Antimicrobial Drug Use and Resistance in Europe

PubMed Central

van de Sande-Bruinsma, Nienke; Verloo, Didier; Tiemersma, Edine; Monen, Jos; Goossens, Herman; Ferech, Matus

2008-01-01

Our study confronts the use of antimicrobial agents in ambulatory care with the resistance trends of 2 major pathogens, Streptococcus pneumoniae and Escherichia coli, in 21 European countries in 2000–2005 and explores whether the notion that antimicrobial drug use determines resistance can be supported by surveillance data at national aggregation levels. The data obtained from the European Surveillance of Antimicrobial Consumption and the European Antimicrobial Resistance Surveillance System suggest that variation of consumption coincides with the occurrence of resistance at the country level. Linear regression analysis showed that the association between antimicrobial drug use and resistance was specific and robust for 2 of 3 compound pathogen combinations, stable over time, but not sensitive enough to explain all of the observed variations. Ecologic studies based on routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial drug consumption at a national level in Europe. PMID:18976555

Can body fat distribution, adiponectin levels and inflammation explain differences in insulin resistance between ethnic Chinese, Malays and Asian Indians?

PubMed

Gao, H; Salim, A; Lee, J; Tai, E S; van Dam, R M

2012-08-01

Diabetes in Asia constitutes approximately half of the global burden. Although insulin resistance and incidence of type 2 diabetes differ substantially between ethnic groups within Asia, the reasons for these differences are poorly understood. We evaluated to what extent body fatness, adiponectin levels and inflammation mediate the relationship between ethnicity and insulin resistance in an Asian setting. Cross-sectional population-based study. In total, 4136 adult Chinese, Malays and Asian Indians residing in Singapore. Insulin resistance was assessed using homeostasis model assessment (HOMA-IR) and systemic inflammation by C-reactive protein (CRP). Data were analyzed using path analysis. HOMA-IR was highest in Asian Indians, intermediate in Malays and lowest in Chinese (P<0.001). The difference in HOMA-IR between Malays and Chinese disappeared after adjusting for body mass index (BMI). For the comparison of Asian Indians with Chinese, the association between ethnicity and HOMA-IR was mediated by BMI (men: 32.9%; women: 48.5%), BMI-adjusted waist circumference (men: 6.1%; women: 3.5%), and CRP (men: 5.1%; women: 5.6%), and unidentified factors (men: 47.2%; women: 26.5%). Part of the mediating effects of body fatness was indirect through effects of body fatness on CRP and adiponectin concentrations. Mediators of ethnic differences in insulin resistance differed markedly depending on the ethnic groups compared. General adiposity explained the difference in insulin resistance between Chinese and Malays, whereas abdominal fat distribution, inflammation and unexplained factors contributed to excess insulin resistance in Asian Indians as compared with Chinese and Malays. These findings suggest that interventions targeting excess weight gain can reduce ethnic disparities in insulin resistance among Asian Indians, Chinese and Malays.

Inheritance of Cry1F resistance, cross-resistance and frequency of resistant alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae).

PubMed

Vélez, A M; Spencer, T A; Alves, A P; Moellenbeck, D; Meagher, R L; Chirakkal, H; Siegfried, B D

2013-12-01

Transgenic maize, Zea maize L., expressing the Cry1F protein from Bacillus thuringiensis has been registered for Spodoptera frugiperda (J. E. Smith) control since 2003. Unexpected damage to Cry1F maize was reported in 2006 in Puerto Rico and Cry1F resistance in S. frugiperda was documented. The inheritance of Cry1F resistance was characterized in a S. frugiperda resistant strain originating from Puerto Rico, which displayed >289-fold resistance to purified Cry1F. Concentration-response bioassays of reciprocal crosses of resistant and susceptible parental populations indicated that resistance is recessive and autosomal. Bioassays of the backcross of the F1 generation crossed with the resistant parental strain suggest that a single locus is responsible for resistance. In addition, cross-resistance to Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry2Aa and Vip3Aa was assessed in the Cry1F-resistant strain. There was no significant cross-resistance to Cry1Aa, Cry1Ba and Cry2Aa, although only limited effects were observed in the susceptible strain. Vip3Aa was highly effective against susceptible and resistant insects indicating no cross-resistance with Cry1F. In contrast, low levels of cross-resistance were observed for both Cry1Ab and Cry1Ac. Because the resistance is recessive and conferred by a single locus, an F1 screening assay was used to measure the frequency of Cry1F-resistant alleles from populations of Florida and Texas in 2010 and 2011. A total frequency of resistant alleles of 0.13 and 0.02 was found for Florida and Texas populations, respectively, indicating resistant alleles could be found in US populations, although there have been no reports of reduced efficacy of Cry1F-expressing plants.

Changes in insecticide resistance of the rice striped stem borer (Lepidoptera: Crambidae).

PubMed

Su, Jianya; Zhang, Zhenzhen; Wu, Min; Gao, Congfen

2014-02-01

Application of insecticides is the most important method to control Chilo suppressalis (Walker) (Lepidoptera: Crambidae), and continuous use of individual insecticides has driven the rapid development of insecticide resistance in C. suppressalis during the past 30 yr. Monitoring insecticide resistance provides information essential for integrated pest management. Insecticide resistance of field populations to monosultap, triazophos, chlorpyrifos, and abamectin in China was examined in 2010 and 2011. The results indicated that the resistance levels of 14 field populations to four insecticides were significantly different. Four populations showed moderate resistance, and other populations possessed low-level resistance or were susceptible to monosultap. Nine populations displayed an extremely high or a high level of resistance to triazophos, whereas four populations were sensitive to this agent. Five populations exhibited a low level of resistance to abamectin, while the others remained sensitive. When compared with historical data, resistance to monosultap and triazophos decreased significantly, and the percentage of populations with high-level or extremely high-level resistance was obviously reduced. By contrast, the resistance to abamectin increased slightly. The increasing and decreasing resistance levels reported in this study highlight the different evolutionary patterns of insecticide resistance in C. suppressalis. An overreliance on one or two insecticides may promote rapid development of resistance. Slow development of resistance to abamectin, which was used mainly in mixtures with other insecticides, implies that the use of insecticide mixtures may be an effective method to delay the evolution of resistance to insecticides.

Effect from low-level exposure of oxytetracycline on abundance of tetracycline resistance genes in arable soils.

PubMed

Shentu, Jia-Li; Zhang, Kun; Shen, Dong-Sheng; Wang, Mei-Zhen; Feng, Hua-Jun

2015-09-01

To evaluate the effect from low-level exposure of antibiotics on the abundance of antibiotic resistance genes, unpolluted arable soils were treated with oxytetracycline (OTC)-containing manure, with OTC (0, 2, 20, or 70 μg kg(-1)) added every 2 weeks on 10 occasions. Six tetracycline resistance genes [TRGs-tet(A), tet(L), tet(M), tet(Q), tet(O), and tet(W)] and the 16S ribosomal RNA (rRNA) gene were monitored using real-time quantitative polymerase chain reaction. The relative abundance of tet(A), tet(L), tet(M), and tet(Q) genes in soil increased 10-1000 times after application of OTC-containing manure. Tet(A) abundance per unit of residual OTC on day 140 was 1.53-4.42 times higher than that on day 28, while tet(L) abundance was 1.04-1.74 times higher. Treatment with >40 μg kg(-1) OTC significantly increased abundance of tet(A) and tet(L), while tet(M) and tet(Q) abundance was positively correlated (R (2) = 0.965 and 0.932, p < 0.01) with residual OTC concentrations. There was a significant accumulation of TRGs associated with low-level OTC exposure in arable soils. Besides OTC residual, the effects from exposure time and application frequencies should also be considered to limit the increase in abundance of tet(A) and tet(L).

In vitro antibacterial activity of seven Indian spices against high level gentamicin resistant strains of enterococci

PubMed Central

Bipin, Chapagain; Chitra, Pai (Bhat); Minakshi, Bhattacharjee

2015-01-01

Introduction The aim of the study was to explore the in vitro antibacterial activity of seven ethanolic extracts of spices against high level gentamicin resistant (HLGR) enterococci isolated from human clinical samples. Material and methods Two hundred and fifteen enterococcal strains were isolated from clinical samples. High level gentamicin resistance in ethanolic extracts of cumin (Cuminum cyminum), cinnamon (Cinnamomum zeylanicum), ginger (Zingiber officinale), fenugreek (Trigonella foenum-graecum), cloves (Syzygium aromaticum), cardamom (Elettaria cardamomum Maton) and black pepper (Piper nigrum) were prepared using Soxhlet apparatus. The antibacterial effect of the extracts was studied using the well diffusion method. Statistical analysis was carried out by χ2 test using SPSS 17 software. Results Only cinnamon and ginger were found to have activity against all the isolates, whereas cumin and cloves had a variable effect on the strains. Fenugreek, black pepper and cardamom did not show any effect on the isolates. The zone diameter of inhibition obtained for cinnamon, ginger, cloves and cumin was in the range 31–34 mm, 27–30 mm, 25–26 mm and 19–20 mm respectively. Conclusions Cinnamomum zeylanicum and Z. officinale showed the maximum antibacterial activity against the enterococcal isolates followed by S. aromaticum and C. cyminum. The findings of the study show that spices used in the study can contribute to the development of potential antimicrobial agents for inclusion in the anti-enterococcal treatment regimen. PMID:26322099

Environmental Levels of the Antiviral Oseltamivir Induce Development of Resistance Mutation H274Y in Influenza A/H1N1 Virus in Mallards

PubMed Central

Järhult, Josef D.; Söderström, Hanna; Orozovic, Goran; Gunnarsson, Gunnar; Bröjer, Caroline; Latorre-Margalef, Neus; Fick, Jerker; Grabic, Roman; Lennerstrand, Johan; Waldenström, Jonas; Lundkvist, Åke; Olsen, Björn

2011-01-01

Oseltamivir (Tamiflu®) is the most widely used drug against influenza infections and is extensively stockpiled worldwide as part of pandemic preparedness plans. However, resistance is a growing problem and in 2008–2009, seasonal human influenza A/H1N1 virus strains in most parts of the world carried the mutation H274Y in the neuraminidase gene which causes resistance to the drug. The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is poorly degraded in sewage treatment plants and surface water and has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance. To assess if resistance can develop under these circumstances, we infected mallards with influenza A/H1N1 virus and exposed the birds to 80 ng/L, 1 µg/L and 80 µg/L of OC through their sole water source. By sequencing the neuraminidase gene from fecal samples, we found that H274Y occurred at 1 µg/L of OC and rapidly dominated the viral population at 80 µg/L. IC50 for OC was increased from 2–4 nM in wild-type viruses to 400–700 nM in H274Y mutants as measured by a neuraminidase inhibition assay. This is consistent with the decrease in sensitivity to OC that has been noted among human clinical isolates carrying H274Y. Environmental OC levels have been measured to 58–293 ng/L during seasonal outbreaks and are expected to reach µg/L-levels during pandemics. Thus, resistance could be induced in influenza viruses circulating among wild ducks. As influenza viruses can cross species barriers, oseltamivir resistance could spread to human-adapted strains with pandemic potential disabling oseltamivir, a cornerstone in pandemic preparedness planning. We propose surveillance in wild birds as a measure to understand the resistance situation in nature and to monitor it over time. Strategies to lower environmental levels of OC include improved sewage treatment and, more importantly, a prudent use of antivirals. PMID:21931841

The roles of CYP6AY1 and CYP6ER1 in imidacloprid resistance in the brown planthopper: Expression levels and detoxification efficiency.

PubMed

Bao, Haibo; Gao, Hongli; Zhang, Yixi; Fan, Dongzhe; Fang, Jichao; Liu, Zewen

2016-05-01

Two P450 monooxygenase genes, CYP6AY1 and CYP6ER1, were reported to contribute importantly to imidacloprid resistance in the brown planthopper, Nilaparvata lugens. Although recombinant CYP6AY1 could metabolize imidacloprid efficiently, the expression levels of CYP6ER1 gene were higher in most resistant populations. In the present study, three field populations were collected from different countries, and the bioassay, RNAi and imidacloprid metabolism were performed to evaluate the importance of two P450s in imidacloprid resistance. All three populations, DOT (Dongtai) from China, CNA (Chainat) from Thailand and HCM (Ho Chi Minh) from Vietnam, showed high resistance to imidacloprid (57.0-, 102.9- and 89.0-fold). CYP6AY1 and CYP6ER1 were both over expressed in three populations, with highest ratio of 13.2-fold for CYP6ER1 in HCM population. Synergism test and RNAi analysis confirmed the roles of both P450 genes in imidacloprid resistance. However, CYP6AY1 was indicated more important in CNA population, and CYP6AY1 and CYP6ER1 were equal in HCM population, although the expression level of CYP6ER1 (13.2-fold) was much higher than that of CYP6AY1 (4.11-fold) in HCM population. Although the recombinant proteins of both P450 genes could metabolize imidacloprid efficiently, the catalytic activity of CYP6AY1 (Kcat=3.627 pmol/min/pmol P450) was significantly higher than that of CYP6ER1 (Kcat=2.785 pmol/min/pmol P450). It was supposed that both P450 proteins were important for imidacloprid resistance, in which CYP6AY1 metabolized imidacloprid more efficiently and CYP6ER1 gene could be regulated by imidacloprid to a higher level. Copyright © 2015 Elsevier B.V. All rights reserved.

Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine.

PubMed

Yamamori, Hidenaga; Hashimoto, Ryota; Ishima, Tamaki; Kishi, Fukuko; Yasuda, Yuka; Ohi, Kazutaka; Fujimoto, Michiko; Umeda-Yano, Satomi; Ito, Akira; Hashimoto, Kenji; Takeda, Masatoshi

2013-11-27

Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. Peripheral BDNF levels in patients with schizophrenia have been widely reported in the literature. However, it is still controversial whether peripheral levels of BDNF are altered in patients with schizophrenia. The peripheral BDNF levels previously reported in patients with schizophrenia were total BDNF (proBDNF and mature BDNF) as it was unable to specifically measure mature BDNF due to limited BDNF antibody specificity. In this study, we examined whether peripheral levels of mature BDNF were altered in patients with treatment-resistant schizophrenia. Matrix metalloproteinase-9 (MMP-9) levels were also measured, as MMP-9 plays a role in the conversion of proBDNF to mature BDNF. Twenty-two patients with treatment-resistant schizophrenia treated with clozapine and 22 age- and sex-matched healthy controls were enrolled. The plasma levels of mature BDNF and MMP-9 were measured using ELISA kits. No significant difference was observed for mature BDNF however, MMP-9 was significantly increased in patients with schizophrenia. The significant correlation was observed between mature BDNF and MMP-9 plasma levels. Neither mature BDNF nor MMP-9 plasma levels were associated clinical variables. Our results do not support the view that peripheral BDNF levels are associated with schizophrenia. MMP-9 may play a role in the pathophysiology of schizophrenia and serve as a biomarker for schizophrenia. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Unpacking 'Artemisinin Resistance'.

PubMed

Wang, Jigang; Xu, Chengchao; Lun, Zhao-Rong; Meshnick, Steven R

2017-06-01

Artemisinin and its derivatives, in combination with partner drugs, are currently the most effective treatments for malaria parasite infection. Even though artemisinin has been widely used for decades, its mechanism of action had remained controversial until recently. Artemisinin combination therapies (ACTs) have recently been found to be losing efficacy in Southeast Asia. This 'artemisinin resistance', defined by a delayed parasite clearance time, has been associated with several genetic mutations. As with any other drug resistance phenotype, resistance can best be understood based on its mechanism of action. Recently, it was demonstrated that artemisinin attacks multiple parasitic targets, suggesting that mutations in drug targets are unlikely to cause high-level artemisinin resistance. These findings will help us to better understand the mechanisms of artemisinin resistance and suggest protocol modifications that may improve the efficacy of ACTs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of antibiotic prescribing and antimicrobial resistance in urinary tract infections at the municipal level among women in two Nordic regions.

PubMed

Nygaard Jensen, Jette; Melander, Eva; Hedin, Katarina; Bjerrum, Lars; Kornfält Isberg, Helena; Holm, Anne; Neel Jacobsen, Helle; Skovby, Annette; Córdoba Currea, Gloria Cristina; Hyllebusk, Lena; Brogaard, Emma; Arpi, Magnus

2018-05-10

To describe and compare the prescribing of antibiotics used for urinary tract infections and its correlation with resistance in Escherichia coli in urinary samples across two adjacent regions-the Capital Region and the Skaane Region-and their municipalities in Denmark and Sweden. The Capital Region consists of 29 municipalities and 725 960 female inhabitants aged ≥18 years and the Skaane Region consists of 33 municipalities and 515 668 female inhabitants aged ≥18 years. Aggregated data from outpatient care on the prescribing of pivmecillinam, trimethoprim and nitrofurantoin from both regions were analysed. The Department of Clinical Microbiology in both regions provided data on E. coli resistance in urinary samples from women aged ≥18 years. Data were measured as the number of prescriptions/1000 women/year, number of DDDs/1000 women/year and DDDs/prescription. Correlation analyses between antibiotic prescribing and antibiotic resistance rates were performed. Antibiotic prescribing and resistance rates were significantly higher in the Capital Region compared with the Skaane Region. Large variations in prescription and resistance rates were found at the municipal level, but there were no correlations between the antibiotic prescription and resistance rates when each region was analysed separately. Although closely related, there are large differences in antibiotic prescribing and antibiotic resistance. It is suggested that the regional guidelines are an important driver and explanatory factor for the variations; however, further research is needed in this new field and factors such as the influence of cultural aspects should be the target of further research.

Determination, mechanism and monitoring of knockdown resistance in permethrin-resistant human head lice, Pediculus humanus capitis

PubMed Central

Clark, J. Marshall

2009-01-01

Permethrin resistance has been reported worldwide and clinical failures to commercial pediculicides containing permethrin have likewise occurred. Permethrin resistance in head lice populations from the U.S. is widespread but is not yet uniform and the level of resistance is relatively low (~4–8 fold). Permethrin-resistant lice are cross-resistant to pyrethrins, PBO-synergized pyrethrins and to DDT. Nix®, when applied to human hair tufts following manufacture’s instructions, did not provide 100% control when assessed by the hair tuft bioassay in conjunction with the in vitro rearing system. Resistance to permethrin is due to knockdown resistance (kdr), which is the result of three point mutations within the α-subunit gene of the voltage-gated sodium channel that causes amino acid substitutions, leading to nerve insensitivity. A three-tiered resistance monitoring system has been established based on molecular resistance detection techniques. Quantitative sequencing (QS) has been developed to predict the kdr allele frequency in head lice at a population level. The speed, simplicity and accuracy of QS made it an ideal candidate for a routine primary resistance monitoring tool to screen a large number of louse populations as an alternative to conventional bioassay. As a secondary monitoring method, real-time PASA (rtPASA) has been devised for a more precise determination of low resistance allele frequencies. To obtain more detailed information on resistance allele zygosity, as well as allele frequency, serial invasive signal amplification reaction (SISAR) has been developed as an individual genotyping method. Our approach of using three tiers of molecular resistance detection should facilitate large-scale routine resistance monitoring of permethrin resistance in head lice using field-collected samples. PMID:20161186

[Resistance studies: when are they indicated?].

PubMed

Angeles Marcos, M

2011-12-01

Cytomegalovirus (CMV) resistance to antiviral drugs is an emerging problem and is due to selection of mutations in the viral genome. Although ganciclovir resistance is the most common and widely studied, there is resistance to all antiviral agents. Risk factors for the development of resistance are the absence of preexisting immunity to CMV, lung and pancreas transplantation, high viral loads, intense concomitant immunosuppressive therapy and prolonged exposure to ganciclovir or suboptimal levels of this drug. Antiviral resistance should be suspected when, despite adequate treatment exposure for 2 weeks, an increase in viral load, or persistence or clinical progression of CMV disease are detected. However, failure to respond cannot always be attributed to antiviral resistance nor does resistance always lead to poor clinical outcome. When resistance is suspected, phenotypic and genotypic confirmation is required. The most common mutations are those in the UL97 gene, which confers ganciclovir resistance. However, foscarnet and cidofovir can be used. The UL54 mutation is not uncommon, whether alone or in combination with UL97 mutations. The combination of UL54 and UL97 mutations is associated with high-grade and multiple resistance. Early detection of resistance is essential to prevent unfavorable outcome and the development of multi-drug resistance. In patients with a slow response to treatment and without mutations associated with resistance, plasma ganciclovir levels and specific CMV immunity should be investigated. Copyright © 2011 Elsevier España S.L. All rights reserved.

Beta-amyloid deposition in patients with major depressive disorder with differing levels of treatment resistance: a pilot study.

PubMed

Li, Peng; Hsiao, Ing-Tsung; Liu, Chia-Yih; Chen, Chia-Hsiang; Huang, She-Yao; Yen, Tzu-Chen; Wu, Kuan-Yi; Lin, Kun-Ju

2017-12-01

Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using 18 F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33).The standard uptake value ratio (SUVR) of each volume of interest was analysed, and voxel-wise comparisons were made between the MDD patients and HCs. Vascular risk factors, serum homocysteine level, and apolipoprotein E (ApoE) genotype were also determined. The MDD patients with moderate-to-severe treatment resistance had higher 18 F-florbetapir SUVRs than the HCs in the parietal region (P < 0.01). Voxel-wise comparisons further demonstrated elevated SUVRs in MDD patients with moderate-to-severe treatment resistance in the precuneus, parietal, temporal, and occipital regions. The MDD patients with mild treatment resistance were found to have increased 18 F-florbetapir uptake mainly in the left frontal and parietal regions as compared with the HCs. In addition, voxel-to-voxel correlation analysis showed that brain Aβ deposition was correlated positively with MSM score in the occipital region. 18 F-florbetapir SUVRs were correlated negatively with Mini Mental Status Examination (MMSE) score in the sample of all MDD patients (r = -0.355, P = 0.005). This study provided preliminary evidence that region-specific Aβ deposition was present in some (but not all) MDD patients, especially in those with moderate-to-severe treatment resistance, and their depressive symptoms may represent

Plasmid-mediated quinolone resistance: Two decades on.

PubMed

Rodríguez-Martínez, José Manuel; Machuca, Jesús; Cano, María Eliecer; Calvo, Jorge; Martínez-Martínez, Luis; Pascual, Alvaro

2016-11-01

After two decades of the discovery of plasmid-mediated quinolone resistance (PMQR), three different mechanisms have been associated to this phenomenon: target protection (Qnr proteins, including several families with multiple alleles), active efflux pumps (mainly QepA and OqxAB pumps) and drug modification [AAC(6')-Ib-cr acetyltransferase]. PMQR genes are usually associated with mobile or transposable elements on plasmids, and, in the case of qnr genes, are often incorporated into sul1-type integrons. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. Although the three PMQR mechanisms alone cause only low-level resistance to quinolones, they can complement other mechanisms of chromosomal resistance to reach clinical resistance level and facilitate the selection of higher-level resistance, raising a threat to the treatment of infections by microorganisms that host these mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Refractory and Resistant Hypertension: Antihypertensive Treatment Failure versus Treatment Resistance

PubMed Central

2016-01-01

Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension. Risk factors for refractory hypertension include obesity, diabetes, chronic kidney disease, and especially, being of African origin. Patients with refractory are at high cardiovascular risk based on increased rates of known heart disease, prior stroke, and prior episodes of congestive heart failure. Mechanisms of refractory hypertension need exploration, but early studies suggest a possible role of heightened sympathetic tone as evidenced by increased office and ambulatory heart rates and higher urinary excretion of norepinephrine compared to patients with controlled resistant hypertension. Important negative findings argue against refractory hypertension being fluid dependent as is typical of resistant hypertension, including aldosterone levels, dietary sodium intake, and brain natriuretic peptide levels being similar or even less than patients with resistant hypertension and the failure to control blood pressure with use of intensive diuretic therapy, including both a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Further studies, especially longitudinal assessments, are needed to better characterize this extreme phenotype in terms of risk factors and outcomes and hopefully to identify effective treatment strategies. PMID:27721847

Different Levels of Eccentric Resistance during Eight Weeks of Training Affect Muscle Strength and Lean Tissue Mass

NASA Technical Reports Server (NTRS)

English, K. L.; Loehr, J. A.; Lee, S. M. C.; Laughlin, M. S.; Hagan, R. D.

2008-01-01

Coupling concentric and eccentric muscle contractions appears to be important in the development of muscle strength and hypertrophy. The interim Resistive Exercise Device (iRED) currently used aboard the International Space Station does not seem to be as effective as free weight training in ambulatory subjects and has not completely protected against muscular deconditioning due to space flight. The lack of protection during space flight could be caused by iRED's proportionally lower eccentric resistance (60-70%) compared to concentric resistance. PURPOSE: To determine the effects of 8 wks of lower body resistive exercise training using five levels of eccentric resistance on muscle strength and lean tissue mass. METHODS: Forty untrained males (34.9 +/- 7 yrs, 80.9 +/- 9.8 kg, 178.2 +/- 7.1 cm; mean +/- SD) completed three 1-repetition maximum (1-RM) strength tests for both the supine leg press (LP) and supine heel raise (HR) prior to training; subjects were matched for LP strength and randomly assigned to one of five training groups. Concentric load (% 1-RM) was constant across groups during training, but each group trained with different levels of eccentric load (0%, 33%, 66%, 100%, or 138% of concentric). Subjects trained 3 d / wk for 8 wks using a periodized program for LP and HR based on percentages of the highest pre-training 1-RM. LP and HR 1-RM and leg lean mass (LLM; assessed by DEXA) were measured pre- and post-training. A two-way ANOVA was used to analyze all dependent measures. Tukey's post hoc tests were used to test significant main effects. Within group pre- to post-training changes were compared using paired t-tests with a Bonferroni adjustment. Statistical significance was set a priori at p 0.05. All data are expressed as mean +/- SE. RESULTS: LP 1-RM strength increased significantly in all groups pre- to post-training. The 138% group increase (20.1 +/- 3.7%) was significantly greater than the 0% (7.9 +/- 2.8%), 33% (7.7 +/- 4.6%), and 66% (7.5 +/- 4

Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

PubMed

Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

2014-12-01

Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

Mapping insecticide resistance and characterization of resistance mechanisms in Anopheles arabiensis (Diptera: Culicidae) in Ethiopia.

PubMed

Alemayehu, Eba; Asale, Abebe; Eba, Kasahun; Getahun, Kefelegn; Tushune, Kora; Bryon, Astrid; Morou, Evangelia; Vontas, John; Van Leeuwen, Thomas; Duchateau, Luc; Yewhalaw, Delenasaw

2017-09-02

The emergence and spread of insecticide resistance in the major African malaria vectors Anopheles gambiae (s.s.) and An. arabiensis may compromise the current vector control interventions and threatens the global malaria control and elimination efforts. Insecticide resistance was monitored in several study sites in Ethiopia from 2013 to 2015 using papers impregnated with discriminating concentrations of DDT, deltamethrin, bendiocarb, propoxur, malathion, fenitrothion and pirimiphos-methyl, following the WHO insecticide susceptibility test procedure. Mosquitoes sampled from different localities for WHO bioassay were morphologically identified as An. gambiae (s.l.) using standard taxonomic keys. Samples were identified to species using species-specific polymerase chain reaction (PCR) and screened for the presence of target site mutations L1014F, L1014S and N1575Y in the voltage gated sodium channel (VGSC) gene and G119S in the acethylcholinesterase (AChE) gene using allele-specific PCR. Biochemical assays were performed to assess elevated levels of acetylcholinesterases, carboxylcholinesterases, glutathione-S-transferases (GSTs) and cytochrome P450s monooxygenases in wild populations of An. arabiensis, compared to the fully susceptible Sekoru An. arabiensis laboratory strain. Populations of An. arabiensis were resistant to DDT and deltamethrin but were susceptible to fenitrothion in all the study sites. Reduced susceptibility to malathion, pirimiphos-methyl, propoxur and bendiocarb was observed in some of the study sites. Knockdown resistance (kdr L1014F) was detected in all mosquito populations with allele frequency ranging from 42 to 91%. Elevated levels of glutathione-S-transferases (GSTs) were detected in some of the mosquito populations. However, no elevated levels of monooxygenases and esterases were detected in any of the populations assessed. Anopheles arabiensis populations from all surveyed sites in Ethiopia exhibited resistance against DDT and pyrethroids

Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

PubMed Central

Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R.; Taylor, Jonathan; Lemey, Philippe; Varghese, Vici; Hamers, Raph L.; Bertagnolio, Silvia; de Wit, Tobias F. Rinke; Aghokeng, Avelin F.; Albert, Jan; Avi, Radko; Avila-Rios, Santiago; Bessong, Pascal O.; Brooks, James I.; Boucher, Charles A. B.; Brumme, Zabrina L.; Busch, Michael P.; Bussmann, Hermann; Chaix, Marie-Laure; Chin, Bum Sik; D’Aquin, Toni T.; De Gascun, Cillian F.; Derache, Anne; Descamps, Diane; Deshpande, Alaka K.; Djoko, Cyrille F.; Eshleman, Susan H.; Fleury, Herve; Frange, Pierre; Fujisaki, Seiichiro; Harrigan, P. Richard; Hattori, Junko; Holguin, Africa; Hunt, Gillian M.; Ichimura, Hiroshi; Kaleebu, Pontiano; Katzenstein, David; Kiertiburanakul, Sasisopin; Kim, Jerome H.; Kim, Sung Soon; Li, Yanpeng; Lutsar, Irja; Morris, Lynn; Ndembi, Nicaise; NG, Kee Peng; Paranjape, Ramesh S.; Peeters, Martine; Poljak, Mario; Price, Matt A.; Ragonnet-Cronin, Manon L.; Reyes-Terán, Gustavo; Rolland, Morgane; Sirivichayakul, Sunee; Smith, Davey M.; Soares, Marcelo A.; Soriano, Vincent V.; Ssemwanga, Deogratius; Stanojevic, Maja; Stefani, Mariane A.; Sugiura, Wataru; Sungkanuparph, Somnuek; Tanuri, Amilcar; Tee, Kok Keng; Truong, Hong-Ha M.; van de Vijver, David A. M. C.; Vidal, Nicole; Yang, Chunfu; Yang, Rongge; Yebra, Gonzalo; Ioannidis, John P. A.; Vandamme, Anne-Mieke; Shafer, Robert W.

2015-01-01

NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. Conclusions Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen. PMID:25849352

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

PubMed

Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R; Taylor, Jonathan; Lemey, Philippe; Varghese, Vici; Hamers, Raph L; Bertagnolio, Silvia; Rinke de Wit, Tobias F; Aghokeng, Avelin F; Albert, Jan; Avi, Radko; Avila-Rios, Santiago; Bessong, Pascal O; Brooks, James I; Boucher, Charles A B; Brumme, Zabrina L; Busch, Michael P; Bussmann, Hermann; Chaix, Marie-Laure; Chin, Bum Sik; D'Aquin, Toni T; De Gascun, Cillian F; Derache, Anne; Descamps, Diane; Deshpande, Alaka K; Djoko, Cyrille F; Eshleman, Susan H; Fleury, Herve; Frange, Pierre; Fujisaki, Seiichiro; Harrigan, P Richard; Hattori, Junko; Holguin, Africa; Hunt, Gillian M; Ichimura, Hiroshi; Kaleebu, Pontiano; Katzenstein, David; Kiertiburanakul, Sasisopin; Kim, Jerome H; Kim, Sung Soon; Li, Yanpeng; Lutsar, Irja; Morris, Lynn; Ndembi, Nicaise; Ng, Kee Peng; Paranjape, Ramesh S; Peeters, Martine; Poljak, Mario; Price, Matt A; Ragonnet-Cronin, Manon L; Reyes-Terán, Gustavo; Rolland, Morgane; Sirivichayakul, Sunee; Smith, Davey M; Soares, Marcelo A; Soriano, Vincent V; Ssemwanga, Deogratius; Stanojevic, Maja; Stefani, Mariane A; Sugiura, Wataru; Sungkanuparph, Somnuek; Tanuri, Amilcar; Tee, Kok Keng; Truong, Hong-Ha M; van de Vijver, David A M C; Vidal, Nicole; Yang, Chunfu; Yang, Rongge; Yebra, Gonzalo; Ioannidis, John P A; Vandamme, Anne-Mieke; Shafer, Robert W

2015-04-01

��accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Phenotypic and genotypic characterisation of multiple antibiotic-resistant Staphylococcus aureus exposed to subinhibitory levels of oxacillin and levofloxacin.

PubMed

Jo, Ara; Ahn, Juhee

2016-07-29

The emergence and spread of multidrug resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA) has serious health consequences in the presence of sub-MIC antibiotics. Therefore, this study was designed to evaluate β-lactamase activity, efflux activity, biofilm formation, and gene expression pattern in Staphylococcus aureus KACC 10778, S. aureus ATCC 15564, and S. aureus CCARM 3080 exposed to sublethal concentrations of levofloxacin and oxacillin. The decreased MICs were observed in S. aureus KACC and S. aureus ATCC when exposed to levofloxacin and oxacillin, while and S. aureus CCARM remained resistance to streptomycin (512 μg/mL) in the presence of levofloxacin and imipenem (>512 μg/mL) in the presence of oxacillin. The considerable increase in extracellular and membrane-bound β-lactamase activities was observed in S. aureus ATCC exposed to oxacillin (>26 μmol/min/mL). The antibiotic susceptibility of all strains exposed to EPIs (CCCP and PAβN) varied depending on the classes of antibiotics. The relative expression levels of adhesion-related genes (clfA, clfB, fnbA, fnnB, and icaD), efflux-related genes (norB, norC, and qacA/B), and enterotoxin gene (sec) were increased more than 5-fold in S. aureus CCARM. The eno and qacA/B genes were highly overexpressed by more than 12- and 9-folds, respectively, in S. aureus CCARM exposed to levofloxacin. The antibiotic susceptibility, lactamase activity, biofilm-forming ability, efflux activity, and gene expression pattern varied with the intrinsic antibiotic resistance of S. aureus KACC, S. aureus ATCC, and S. aureus CCARM exposed to levofloxacin and oxacillin. This study would provide useful information for better understating of combination therapy related to antibiotic resistance mechanisms and open the door for designing effective antibiotic treatment protocols to prevent excessive use of antibiotics in clinical practice.

Resistance and Resistant Reaction of Gossypium arboreum to the Reniform, Nematode, Rotylenchulus reniformis

PubMed Central

Carter, William W.

1981-01-01

Gossypium arboreum 'Nanking CB 1402' possessed a high level of resistance to Rotylenchulus reniformis. Within 16 h, the nematode penetrated roots of resistant and susceptible cottons equally. After 36 h, significantly fewer nematodes were found in resistant roots. Larvae fed in either an endodermal or pericyclic cell and had no specificity for root tissue of a particular age. In roots of resistant G. arboreum '1402,' wall breakdown of pericyclic cells was evident after 3 d, endodermal and cortical cells collapsed, and the hypertrophied pericyclic cells disintegrated within 12 d. Cell walls immediately adjacent to the nematode's head were thickened and more safranin positive in resistant than in susceptible cotton cultivars. Several other cultivars of G. arboreum were also resistant to R. reniformis, based on nematode fecundity and percent egg reduction. PMID:19300777

Spatial variation in disease resistance: from molecules to metapopulations

PubMed Central

Laine, Anna-Liisa; Burdon, Jeremy J.; Dodds, Peter N.; Thrall, Peter H.

2010-01-01

Summary Variation in disease resistance is a widespread phenomenon in wild plant-pathogen associations. Here, we review current literature on natural plant-pathogen associations to determine how diversity in disease resistance is distributed at different hierarchical levels – within host individuals, within host populations, among host populations at the metapopulation scale and at larger regional scales. We find diversity in resistance across all spatial scales examined. Furthermore, variability seems to be the best counter-defence of plants against their rapidly evolving pathogens. We find that higher diversity of resistance phenotypes also results in higher levels of resistance at the population level. Overall, we find that wild plant populations are more likely to be susceptible than resistant to their pathogens. However, the degree of resistance differs strikingly depending on the origin of the pathogen strains used in experimental inoculation studies. Plant populations are on average 16% more resistant to allopatric pathogen strains than they are to strains that occur within the same population (48 % vs. 32 % respectively). Pathogen dispersal mode affects levels of resistance in natural plant populations with lowest levels detected for hosts of airborne pathogens and highest for waterborne pathogens. Detailed analysis of two model systems, Linum marginale infected by Melampsora lini, and Plantago lanceolata infected by Podosphaera plantaginis, show that the amount of variation in disease resistance declines towards higher spatial scales as we move from individual hosts to metapopulations, but evaluation of multiple spatial scales is needed to fully capture the structure of disease resistance. Synthesis: Variation in disease resistance is ubiquitous in wild plant-pathogen associations. While the debate over whether the resistance structure of plant populations is determined by pathogen-imposed selection versus non-adaptive processes remains unresolved, we do

Changes in whole-body fat distribution, intrahepatic lipids, and insulin resistance of obese adolescents during a low-level lifestyle intervention.

PubMed

Springer, Fabian; Ballweg, Verena; Schweizer, Roland; Schick, Fritz; Ranke, Michael B; Binder, Gerhard; Ehehalt, Stefan

2015-12-01

The aim of this study was to analyze changes in adipose tissue (AT) distribution, intrahepatic lipids (IHL), and insulin resistance (IR) among a group of obese adolescents undergoing a 7-months low-level lifestyle intervention. Thirty-nine obese Caucasian adolescents (mean age 13.9 years, body mass index standard deviation score (BMI-SDSLMS) 2.14) were included. AT and IHL were determined by T1-weighted magnetic resonance (MR) imaging and single-voxel MR spectroscopy; IR was estimated using the homeostatic model assessment (HOMA-IR). The lifestyle intervention led to a reduction of both BMI-SDSLMS (boys 2.27 to 2.17; girls 2.00 to 1.82) and HOMA-IR (boys 6.1 to 4.4 (p = 0.008); girls 6.2 to 4.7 (p = 0.030)). IHL dropped in both genders (boys 7.5 to 4.3 %; girls 4.6 to 3.4 %) positively correlating with HOMA-IR (boys r = 0.52; girls r = 0.68), while in contrast visceral AT did not change significantly. Although the lifestyle intervention only slightly reduced BMI-SDSLMS, insulin sensitivity improved in both genders and came along with a marked reduction of IHL. This suggests that IHL might play the dominant role regarding insulin resistance in the youth, especially if compared to other AT compartments such as visceral AT. • MR imaging/spectroscopy can be used to evaluate body fat distribution and intrahepatic lipids in the youth. • The strength of associations between body fat compartments and insulin resistance is under scientific debate. • The study emphasizes that even a low-level lifestyle intervention has a beneficial effect. • The study suggests that intrahepatic lipids are an important factor in the development of insulin resistance.

Reconceptualizing resistance: sociology and the affective dimension of resistance.

PubMed

Hynes, Maria

2013-12-01

This paper re-examines the sociological study of resistance in light of growing interest in the concept of affect. Recent claims that we are witness to an 'affective turn' and calls for a 'new sociological empiricism' sensitive to affect indicate an emerging paradigm shift in sociology. Yet, mainstream sociological study of resistance tends to have been largely unaffected by this shift. To this end, this paper presents a case for the significance of affect as a lens by which to approach the study of resistance. My claim is not simply that the forms of actions we would normally recognize as resistance have an affective dimension. Rather, it is that the theory of affect broadens 'resistance' beyond the purview of the two dominant modes of analysis in sociology; namely, the study of macropolitical forms, on the one hand, and the micropolitics of everyday resistance on the other. This broadened perspective challenges the persistent assumption that ideological forms of power and resistance are the most pertinent to the contemporary world, suggesting that much power and resistance today is of a more affective nature. In making this argument, it is a Deleuzian reading of affect that is pursued, which opens up to a level of analysis beyond the common understanding of affect as emotion. I argue that an affective approach to resistance would pay attention to those barely perceptible transitions in power and mobilizations of bodily potential that operate below the conscious perceptions and subjective emotions of social actors. These affective transitions constitute a new site at which both power and resistance operate. © London School of Economics and Political Science 2013.

Resistance training alters skeletal muscle structure and function in human heart failure: effects at the tissue, cellular and molecular levels

PubMed Central

Toth, Michael J; Miller, Mark S; VanBuren, Peter; Bedrin, Nicholas G; LeWinter, Martin M; Ades, Philip A; Palmer, Bradley M

2012-01-01

Reduced skeletal muscle function in heart failure (HF) patients may be partially explained by altered myofilament protein content and function. Resistance training increases muscle function, although whether these improvements are achieved by correction of myofilament deficits is not known. To address this question, we examined 10 HF patients and 14 controls prior to and following an 18 week high-intensity resistance training programme. Evaluations of whole muscle size and strength, single muscle fibre size, ultrastructure and tension and myosin–actin cross-bridge mechanics and kinetics were performed. Training improved whole muscle isometric torque in both groups, although there were no alterations in whole muscle size or single fibre cross-sectional area or isometric tension. Unexpectedly, training reduced the myofibril fractional area of muscle fibres in both groups. This structural change manifested functionally as a reduction in the number of strongly bound myosin–actin cross-bridges during Ca2+ activation. When post-training single fibre tension data were corrected for the loss of myofibril fractional area, we observed an increase in tension with resistance training. Additionally, training corrected alterations in cross-bridge kinetics (e.g. myosin attachment time) in HF patients back to levels observed in untrained controls. Collectively, our results indicate that improvements in myofilament function in sedentary elderly with and without HF may contribute to increased whole muscle function with resistance training. More broadly, these data highlight novel cellular and molecular adaptations in muscle structure and function that contribute to the resistance-trained phenotype. PMID:22199163

Muscle activation levels of the gluteus maximus and medius during standing hip-joint strengthening exercises using elastic-tubing resistance.

PubMed

Youdas, James W; Adams, Kady E; Bertucci, John E; Brooks, Koel J; Nelson, Meghan M; Hollman, John H

2014-02-01

No published studies have compared muscle activation levels simultaneously for the gluteus maximus and medius muscles of stance and moving limbs during standing hip-joint strengthening while using elastic-tubing resistance. To quantify activation levels bilaterally of the gluteus maximus and medius during resisted lower-extremity standing exercises using elastic tubing for the cross-over, reverse cross-over, front-pull, and back-pull exercise conditions. Repeated measures. Laboratory. 26 active and healthy people, 13 men (25 ± 3 y) and 13 women (24 ± 1 y). Subjects completed 3 consecutive repetitions of lower-extremity exercises in random order. Surface electromyographic (EMG) signals were normalized to peak activity in the maximum voluntary isometric contraction (MVIC) trial and expressed as a percentage. Magnitudes of EMG recruitment were analyzed with a 2 × 4 repeated-measures ANOVA for each muscle (α = .05). For the gluteus maximus an interaction between exercise and limb factor was significant (F3,75 = 21.5; P < .001). The moving-limb gluteus maximus was activated more than the stance limb's during the back-pull exercise (P < .001), and moving-limb gluteus maximus muscle recruitment was greater for the back-pull exercise than for the cross-over, reverse cross-over, and front-pull exercises (P < .001). For the gluteus medius an interaction between exercise and limb factor was significant (F3,75 = 3.7; P < .03). Gluteus medius muscle recruitment (% MVIC) was greater in the stance limb than moving limb when performing the front-pull exercise (P < .001). Moving-limb gluteus medius muscle recruitment was greater for the reverse cross-over exercise than for the cross-over, front-pull, and back-pull exercises (P < .001). From a clinical standpoint there is no therapeutic benefit to selectively activate the gluteus maximus and gluteus medius muscles on the stance limb by resisting sagittal- and frontal-plane hip movements on the moving limb using resistance

Thinking beyond the Common Candida Species: Need for Species-Level Identification of Candida Due to the Emergence of Multidrug-Resistant Candida auris.

PubMed

Lockhart, Shawn R; Jackson, Brendan R; Vallabhaneni, Snigdha; Ostrosky-Zeichner, Luis; Pappas, Peter G; Chiller, Tom

2017-12-01

Candida species are one of the leading causes of nosocomial infections. Because much of the treatment for Candida infections is empirical, some institutions do not identify Candida to species level. With the worldwide emergence of the multidrug-resistant species Candida auris , identification of Candida to species level has new clinical relevance. Species should be identified for invasive candidiasis isolates, and species-level identification can be considered for selected noninvasive isolates to improve detection of C. auris . Copyright © 2017 American Society for Microbiology.

Predictable Phenotypes of Antibiotic Resistance Mutations.

PubMed

Knopp, M; Andersson, D I

2018-05-15

Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations. IMPORTANCE The spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain