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Sample records for restrained antimicrobial arylamide

  1. Restraining mechanism

    NASA Technical Reports Server (NTRS)

    Hardy, J. C. (Inventor)

    1970-01-01

    A restraining mechanism restraining a pressurized garment so as to limit its ballooning effect is described. A helically wound spring is bonded at its outer periphery to an elongated flat plate which permits the flat plate to bend in a single direction. The flat plate is attached to an inflatable glove to the palm side for restraining the glove from ballooning when inflated.

  2. Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

    PubMed Central

    More, Satish S; Chaitanya, T Krishna; Kumar, Yadla Sateesh; Meruva, Suresh Babu; Rao, L Vaikunta

    2013-01-01

    Summary A highly efficient synthesis of enantiomerically pure (S) and (R)-isomers of N-(2,3-dihydroxypropyl)arylamides has been developed with good overall yields in a two step process. The key step involves the ring opening of the chiral epoxide with a nitrogen heterocyclic carbene (NHC) and further rearrangement to chiral N-(2,3-dihydroxypropyl)arylamides in high yields and enantioselectivity. During the reaction, no erosion in chiral purity was observed. PMID:24204425

  3. Towards Optimization of Arylamides As Novel, Potent, and Brain-Penetrant Antiprion Lead Compounds

    PubMed Central

    2013-01-01

    The prion diseases caused by PrPSc, an alternatively folded form of the cellular prion protein (PrPC), are rapidly progressive, fatal, and untreatable neurodegenerative disorders. We employed HTS ELISA assays to identify compounds that lower the level of PrPSc in prion-infected mouse neuroblastoma (ScN2a-cl3) cells and identified a series of arylamides. Structure–activity relationship (SAR) studies indicated that small amides with one aromatic or heteroaromatic ring on each side of the amide bond are of modest potency. Of note, benzamide (7), with an EC50 of 2200 nM, was one of only a few arylamide hits with a piperazine group on its aniline moiety. The basic piperazine nitrogen can be protonated at physiologic pH, improving solubility, and therefore, we wanted to exploit this feature in our search for a drug candidate. An SAR campaign resulted in several key analogues, including a set with biaryl groups introduced on the carbonyl side for improved potency. Several of these biaryl analogues have submicromolar potency, with the most potent analogue 17 having an EC50 = 22 nM. More importantly, 17 and several biarylamides (20, 24, 26, and 27) were able to traverse the blood–brain barrier (BBB) and displayed excellent drug levels in the brains of mice following oral dosing. These biarylamides may represent good starting points for further lead optimization for the identification of potential drug candidates for the treatment of prion diseases. PMID:23977416

  4. Intramolecular hydrogen bonds: ab initio Car Parrinello simulations of arylamide torsions

    NASA Astrophysics Data System (ADS)

    Doerksen, Robert J.; Chen, Bin; Klein, Michael L.

    2003-10-01

    Gas-phase, room temperature Car-Parrinello molecular dynamics simulations using the HCTH density functional are reported for the arylamides acetanilide ( 1) and ortho-methylthioacetanilide ( 2). The simulations show that in 1, rotation around the ring-amide bond is relatively unrestricted. By contrast, in 2 the methylthio side chain encourages the amide to be directed with N-H pointing toward S, not to flip by 360°, and furthermore to remain close to coplanar with the benzene ring. Because of an intramolecular N-H⋯S hydrogen bond, the N-H stretch frequency of 2 is red-shifted by ˜78 cm -1 compared to that of 1.

  5. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides

    PubMed Central

    He, Xin; Alian, Akram; Ortiz de Montellano, Paul R.

    2007-01-01

    InhA, the enoyl acyl carrier protein reductase (ENR) from Mycobacterium tuberculosis, is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of M. tuberculosis. We report here the discovery, through high-throughput screening, of a series of arylamides as a novel class of potent InhA inhibitors. These direct InhA inhibitors require no mycobacterial enzymatic activation and thus circumvent the resistance mechanism to antitubercular prodrugs such as INH and ETA that is most commonly observed in drug-resistant clinical isolates. The crystal structure of InhA complexed with one representative inhibitor reveals the binding mode of the inhibitor within the InhA active site. Further optimization through a microtiter synthesis strategy followed by in situ activity screening led to the discovery of a potent InhA inhibitor with in vitro IC50 = 90 nM, representing a 34-fold potency improvement over the lead compound. PMID:17723305

  6. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides.

    PubMed

    He, Xin; Alian, Akram; Ortiz de Montellano, Paul R

    2007-11-01

    InhA, the enoyl acyl carrier protein reductase (ENR) from Mycobacterium tuberculosis, is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of M. tuberculosis. We report here the discovery, through high-throughput screening, of a series of arylamides as a novel class of potent InhA inhibitors. These direct InhA inhibitors require no mycobacterial enzymatic activation and thus circumvent the resistance mechanism to antitubercular prodrugs such as INH and ETA that is most commonly observed in drug-resistant clinical isolates. The crystal structure of InhA complexed with one representative inhibitor reveals the binding mode of the inhibitor within the InhA active site. Further optimization through a microtiter synthesis strategy followed by in situ activity screening led to the discovery of a potent InhA inhibitor with in vitro IC(50)=90 nM, representing a 34-fold potency improvement over the lead compound.

  7. Synthesis and properties of azonaphtharylamide pigments having arylamide groups at 2- and 7-positions

    NASA Astrophysics Data System (ADS)

    Otani, Junji; Kikuchi, Takeshi; Higashida, Suguru; Harada, Takashi; Matsumura, Michio

    2015-03-01

    We studied two azonaphtharylamide pigments having arylamide groups at the 2- and 7-positions on the naphthol ring. Presence of the 7-substited amide group distinguishes the pigments from conventional azonaphtharylamide pigments derived from 3-hydroxy-2-naphthoic acid. The 7-substituent caused a hyperchromic effect but did not produce bathochromic shift in the optical absorption spectra in solution compared with the corresponding 7-unsubstituted counterparts. Molecular geometry optimizations through semi-empirical MO calculations showed that extent of the chromophore systems in the pigments with and without the 7-substituent is nearly the same, which is consistent with absence of the bathochromic shift. The MO calculations also showed that the MOs localized in the 7-substituents are involved in the electronic transitions in the longest wavelength bands of the pigments, which is responsible for the hyperchromic effect. The 7-substituted pigments exhibited better resistivity to light and heat than the 7-unsubstituted ones.

  8. Motion restraining device

    NASA Technical Reports Server (NTRS)

    Ford, A. G. (Inventor)

    1977-01-01

    A motion-restraining device for dissipating at a controlled rate the force of a moving body is discussed. The device is characterized by a drive shaft adapted to be driven in rotation by a moving body connected to a tape wound about a reel mounted on the drive shaft, and an elongated pitman link having one end pivotally connected to the crankshaft and the opposite end thereof connected with the mass through an energy dissipating linkage. A shuttle is disposed within a slot and guided by rectilinear motion between a pair of spaced impact surfaces. Reaction forces applied at impact of the shuttle with the impact surfaces include oppositely projected force components angularly related to the direction of the applied impact forces.

  9. [Progress in researches on synthetic antimicrobial macromolecular polymers].

    PubMed

    Wei, Gang; Yang, Lihua; Chu, Liangyin

    2010-08-01

    Broad-spectrum antimicrobial peptides provide a new way to address the urgent growing problem of bacterial resistance. However, the limited natural resources and the high cost of extraction and purification of natural antimicrobial peptides can not meet the requirements of clinical application. In order to solve this problem, researchers have utilized two basic common structural features (amphiphilic and cationic) for designing and preparing synthetic antimicrobial macromolecular polymers. During the last decade, several kinds of amphiphilic polymers, including arylamide oligomers, phenylene ethynylenes, polymethacrylates, polynorbornenes as well as nylon-3 polymers have been synthesized. In this paper, the structures, antibacterial activities and selectivities of these polymers are reviewed, and the effects of molecular size, polarity and ratio of hydrophobic groups, positive charge density on antibacterial activity and selectivity are also summarized.

  10. Vibrations of elastically restrained frames

    NASA Astrophysics Data System (ADS)

    Albarracín, Carlos Marcelo; Grossi, Ricardo Oscar

    2005-07-01

    This paper deals with the determination of eigenfrequencies of a frame which consists of a beam supported by a column and is submitted to intermediate elastic constraints. The ends of the frame are elastically restrained against rotation and translation. The individual members of the frame are assumed to be governed by the transverse and axial vibration theory of an Euler-Bernoulli beam. The boundary and eigenvalue problem which governs the dynamical behavior of the frame structure is derived using the techniques of calculus of variations. Exact values of eigenfrequencies are determined by the application of the separation of variables method. Also, results are obtained by the use of the finite element method. The natural frequencies and mode shapes are presented for a wide range of values of the restraint parameters. Several particular cases are presented and some of these have been compared with those available in the literature.

  11. Design, synthesis, and biological evaluation of new arylamide derivatives possessing sulfonate or sulfamate moieties as steroid sulfatase enzyme inhibitors.

    PubMed

    El-Gamal, Mohammed I; Semreen, Mohammad H; Foster, Paul A; Potter, Barry V L

    2016-06-15

    A series of new arylamide derivatives possessing terminal sulfonate or sulfamate moieties was designed and synthesized. The target compounds were tested for in vitro inhibitory effects against the steroid sulfatase (STS) enzyme in a cell-free assay system. The free sulfamate derivative 1j was the most active. It inhibited the enzymatic activity by 72.0% and 55.7% at 20μM and 10μM, respectively. Compound 1j was further tested for STS inhibition in JEG-3 placental carcinoma cells with high STS enzyme activity. It inhibited 93.9% of the enzyme activity in JEG-3 placental carcinoma cells at 20μM with an efficacy near to that of the well-established drug STX64 as reference. At 10μM, 1j inhibited 86.1% of the STS activity of JEG-3. Its IC50 value against the STS enzyme in JEG-3 cells was 0.421μM. Thus, 1j represents an attractive new non-steroidal lead for further optimization.

  12. Trifluoromethyl arylamides with antileukemia effect and intracellular inhibitory activity over serine/arginine-rich protein kinases (SRPKs).

    PubMed

    Siqueira, Raoni Pais; Barros, Marcus Vinícius de Andrade; Barbosa, Éverton de Almeida Alves; Onofre, Thiago Souza; Gonçalves, Victor Hugo Sousa; Pereira, Higor Sette; Silva Júnior, Abelardo; de Oliveira, Leandro Licursi; Almeida, Márcia Rogéria; Fietto, Juliana Lopes Rangel; Teixeira, Róbson Ricardo; Bressan, Gustavo Costa

    2017-07-07

    The serine/arginine-rich protein kinases (SRPKs) have frequently been found with altered activity in a number of cancers, suggesting they could serve as potential therapeutic targets in oncology. Here we describe the synthesis of a series of twenty-two trifluoromethyl arylamides based on the known SRPKs inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and the evaluation of their antileukemia effects. Some derivatives presented superior cytotoxic effects against myeloid and lymphoid leukemia cell lines compared to SRPIN340. In particular, compounds 24, 30, and 36 presented IC50 values ranging between 6.0 and 35.7 μM. In addition, these three compounds were able to trigger apoptosis and autophagy, and to exhibit synergistic effects with the chemotherapeutic agent vincristine. Furthermore, compound 30 was more efficient than SRPIN340 in impairing the intracellular phosphorylation status of SR proteins as well as the expression of MAP2K1, MAP2K2, VEGF, and RON oncogenic isoforms. Therefore, novel compounds with increased intracellular effects against SRPK activity were obtained, contributing to medicinal chemistry efforts towards the development of new anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Successful restrained eating and trait impulsiveness.

    PubMed

    van Koningsbruggen, Guido M; Stroebe, Wolfgang; Aarts, Henk

    2013-01-01

    Restrained eaters with high scores on the Perceived Self-Regulatory Success in Dieting Scale (PSRS) are more successful than low scorers in regulating their food intake. According to the theory of temptation-elicited goal activation (Fishbach, Friedman, & Kruglanski, 2003), they have become successful because, due to earlier repeated instances of successful self-control, they formed an associative link between temptations and thoughts of dieting. It is unclear, however, why they should have been more successful in earlier attempts at self-control than their unsuccessful counterparts. We examined whether trait impulsiveness plays a role by investigating the associations between dietary restraint, trait impulsiveness, and PSRS. Results showed that the interaction between dietary restraint and impulsiveness predicted dieting success: A lower level of impulsiveness was associated with greater dieting success among restrained eaters. These results suggest that restrained eaters who are less impulsive are more likely to become successful restrained eaters as identified with the PSRS.

  14. Apparatus for restraining and transporting dies

    DOEpatents

    Allison, James W.; LaBarre, Timothy L.

    1994-01-01

    Apparatus for restraining and transporting dies in punch press operations is provided. A floatation platen for supporting a die on the platen's upper surface has a plurality of recessed gas exhaust ports on the platen's lower surface. A source of pressurized gas delivers gas to a platen manifold, for delivery to orifices located in the gas exhaust ports. The flow of gas is controlled by a first valve adjacent the gas source and a second valve adjacent the manifold, with the second valve being used to control the gas flow during movement of the die. In this fashion, a die may be moved on a cushion of air from one workstation to a selected second workstation. A moveable hydraulically operated restraining fixture is also provided, for clamping the die in position during the compacting phase, and for releasing the die after completion of the compacting phase by releasing the hydraulic pressure on the restraining fixture. When pressure in the hydraulic cylinders on the restraining fixture is reversed, the restraining fixture will retract so that there is no contact between the die and the restraining fixture, thereby allowing the die to be removed from a first workstation and moved to a second selected workstation.

  15. Discovery of highly selective CRAF inhibitors, 3-carboxamido-2H-indazole-6-arylamide: In silico FBLD design, synthesis and evaluation.

    PubMed

    Aman, Waqar; Lee, Junghun; Kim, Minjung; Yang, Songyi; Jung, Hoyong; Hah, Jung-Mi

    2016-02-15

    The recent success of vemurafenib shows the importance of selective BRAF V600E inhibition in melanoma. However, paradoxical activation by structurally diverse ATP-competitive RAF kinase inhibitors strongly suggests that selective CRAF inhibitors, not BRAF inhibitors, would be ideal for some Ras mutation cancer treatment. In this respect, we approached designing selective CRAF inhibitors starting from in silico fragment screening and synthesized a 3-carboxamido-2H-indazole-6-arylamide scaffold. Most of the compounds showed potent antiproliferative activity against the WM3629 melanoma cell line and the most promising compound, compound 10d, was found to be a potent and selective CRAF inhibitor with an IC50 value of 38.6 nM, which shows greater than 270-fold selectivity over BRAF kinase (9.45 μM).

  16. Facile synthesis of 1,3,4-benzotriazepines and 1-arylamide-1H-indazoles via palladium-catalyzed cyclization of aryl isocyanates and aryl hydrazones under microwave irradiation.

    PubMed

    Dong, Chune; Xie, Lingli; Mou, Xiaohong; Zhong, Yashan; Su, Wei

    2010-11-07

    A strategy involving palladium-catalyzed cyclization of halo-phenyl hydrazones and aryl isocyanates provides a convenient approach to the synthesis of 1,3,4-benzotriazepines (4) or 1-arylamide-1H-indazoles (5) in good isolated yields. Microwave irradiation was found to afford high reaction efficiency, while the choice of halophenyl hydrazone had an effect on the pathway of the reaction.

  17. Behavior of Restrained Two-Way Slabs.

    DTIC Science & Technology

    1979-02-22

    AC-AGOG "I NEWMARK (NATHAN M) CONSULTING ENGINEERING SERVICES U-ETC F/G 13/13 BEHAVIOR OF RESTRAINED TWO-WAY SLABS. (U) L FEB 79 1 D HALTIWANGER, W J...Building Urbana, Illinois 61801 22 February 1979 Interim Report for Period 1 September 1978-22 February 1979 CONTRACT No. DNA 0O1-78-C-0300 APPROVED FOR...FORM 1 . REPORT NUMBER 2. GOVT ACCESSION NO, 3 HECIPIENT’S CATALOG NUMBER DNA 4959Z ) -,A TYI-t OD 4. TITLE (and Subbiti. 5 rYPE OF REPORT & PERIOD

  18. Prophylaxis of venous thromboembolism in physically restrained psychiatric patients.

    PubMed

    Hilger, Hans; von Beckerath, Olga; Kröger, Knut

    2016-09-01

    We analysed the rate of physical restraint in acute and chronic psychiatric patients and looked at the safety of waiving venous thromboembolic disease (VTE) prophylaxis in the case of restraining of less than 24 h. We did a retrospective analysis of all episodes of restraining in 2012 and 2013, diagnosis of restrained patients, time of restraining and use of low molecular weight heparin (LMWH) for prophylaxis of VTE associated with restraining. Overall, 12 734 patients were hospitalised. The number of episodes of restraining was 1035 and involved 469 (7.4%) patients. Only 79 episodes of restraining lasted more than 24 h and affected only 36 (0.3%) individual patients. The most frequent psychiatric diagnoses were unstable borderline personality in 41 (52%) and schizophrenic or schizoaffective psychosis in 26 (33%) episodes. None of these prolonged restraints and none of the 956 episodes of restraining for less than 24 h were associated with clinical symptoms or signs of VTE that would have required additional diagnostic consequences. The concept of waiving VTE prophylaxis within the first 24 h of restraining seems to be safe. On the other hand, LMWH sufficiently protected the small sample being restrained for more than 24 h.

  19. Temporal attention for visual food stimuli in restrained eaters.

    PubMed

    Neimeijer, Renate A M; de Jong, Peter J; Roefs, Anne

    2013-05-01

    Although restrained eaters try to limit their food intake, they often fail and indulge in exactly those foods that they want to avoid. A possible explanation is a temporal attentional bias for food cues. It could be that for these people food stimuli are processed relatively efficiently and require less attentional resources to enter awareness. Once a food stimulus has captured attention, it may be preferentially processed and granted prioritized access to limited cognitive resources. This might help explain why restrained eaters often fail in their attempts to restrict their food intake. A Rapid Serial Visual Presentation task consisting of dual and single target trials with food and neutral pictures as targets and/or distractors was administered to restrained (n=40) and unrestrained (n=40) eaters to study temporal attentional bias. Results indicated that (1) food cues did not diminish the attentional blink in restrained eaters when presented as second target; (2) specifically restrained eaters showed an interference effect of identifying food targets on the identification of preceding neutral targets; (3) for both restrained and unrestrained eaters, food cues enhanced the attentional blink; (4) specifically in restrained eaters, food distractors elicited an attention blink in the single target trials. In restrained eaters, food cues get prioritized access to limited cognitive resources, even if this processing priority interferes with their current goals. This temporal attentional bias for food stimuli might help explain why restrained eaters typically have difficulties maintaining their diet rules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Adaptively restrained molecular dynamics in LAMMPS

    NASA Astrophysics Data System (ADS)

    Kant Singh, Krishna; Redon, Stephane

    2017-07-01

    Adaptively restrained molecular dynamics (ARMD) is a recently introduced particles simulation method that switches positional degrees of freedom on and off during simulation in order to speed up calculations. In the NVE ensemble, ARMD allows users to trade between precision and speed while, in the NVT ensemble, it makes it possible to compute statistical averages faster. Despite the conceptual simplicity of the approach, however, integrating it in existing molecular dynamics packages is non-trivial, in particular since implemented potentials should a priori be rewritten to take advantage of frozen particles and achieve a speed-up. In this paper, we present novel algorithms for integrating ARMD in LAMMPS, a popular multi-purpose molecular simulation package. In particular, we demonstrate how to enable ARMD in LAMMPS without having to re-implement all available force fields. The proposed algorithms are assessed on four different benchmarks, and show how they allow us to speed up simulations up to one order of magnitude.

  1. Longitudinal relationships between fathers', mothers', and adolescents' restrained eating.

    PubMed

    Snoek, Harriëtte M; van Strien, Tatjana; Janssens, Jan M A M; Engels, Rutger C M E

    2009-04-01

    Family members can exert important direct and indirect influence on the eating behaviours of children; these include modelling, and transmission of preferences, beliefs, and attitudes. Current studies on family similarities in dieting behaviours however show inconsistent results. The present study examines family similarities and reciprocal influences on restrained eating, using data of a longitudinal three-wave full-family study consisting of both parents and two adolescent sibling children (aged 13-16 at time 1) from 404 Dutch families. All family members reported their restrained eating behaviours at three annual waves. Cross-sectional associations were found between parents' and adolescents' restrained eating, but overall no transmission of restrained eating was found between family members over time. Similarities were higher between daughters and mothers compared to sons and mothers. Longitudinally, no differences in the results were found between boys and girls, or between adolescents with high or low quality relationships with their parents.

  2. 49 CFR 1103.22 - Restraining clients from improprieties.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TRANSPORTATION BOARD, DEPARTMENT OF TRANSPORTATION RULES OF PRACTICE PRACTITIONERS Canons of Ethics The Practitioner's Duties and Responsibilities Toward A Client § 1103.22 Restraining clients from improprieties. A...

  3. SIDE DETAIL OF LEFT ENGINE MAINTENANCE. FLAPS ARE RESTRAINED WITH ...

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

    SIDE DETAIL OF LEFT ENGINE MAINTENANCE. FLAPS ARE RESTRAINED WITH LOCKS TO FACILITATE LUBRICATION. ENGINE IDENTIFIED AS #709075, PRATT & WHITNEY 200 JT 8 MODEL. - Greater Buffalo International Airport, Maintenance Hangar, Buffalo, Erie County, NY

  4. Evolving efficiency of restraining bends within wet kaolin analog experiments

    NASA Astrophysics Data System (ADS)

    Hatem, Alexandra E.; Cooke, Michele L.; Madden, Elizabeth H.

    2015-03-01

    Restraining bends along strike-slip fault systems evolve by both propagation of new faults and abandonment of fault segments. Scaled analog modeling using wet kaolin allows for qualitative and quantitative observations of this evolution. To explore how bend geometry affects evolution, we model bends with a variety of initial angles, θ, from θ = 0° for a straight fault to θ = 30°. High-angle restraining bends (θ ≥ 20°) overcome initial inefficiencies by abandoning unfavorably oriented restraining segments and propagating multiple new, inwardly dipping, oblique-slip faults that are well oriented to accommodate convergence within the bend. Restraining bends with 0° < θ ≤ 15° maintain activity along the restraining bend segment and grow a single new oblique slip fault on one side of the bend. In all restraining bends, the first new fault propagates at ~5 mm of accumulated convergence. Particle Image Velocimetry analysis provides a complete velocity field throughout the experiments. From these data, we quantify the strike-slip efficiency of the system as the percentage of applied plate-parallel velocity accommodated as slip in the direction of plate motion along faults within the restraining bend. Bends with small θ initially have higher strike-slip efficiency compared to bends with large θ. Although they have different fault geometries, all systems with a 5 cm bend width reach a steady strike-slip efficiency of 80% after 50 mm of applied plate displacement. These experimental restraining bends resemble crustal faults in their asymmetric fault growth, asymmetric topographic gradient, and strike-slip efficiency.

  5. Genetic and environmental influences on restrained eating behavior

    PubMed Central

    Schur, Ellen; Noonan, Carolyn; Polivy, Janet; Goldberg, Jack; Buchwald, Dedra

    2009-01-01

    Objective We examined the relative contributions of genetic and environmental influences to restrained eating. Methods Restrained eating was assessed by the Restraint Scale in a survey mailed to all twins enrolled in the University of Washington Twin Registry. We used structural equation modeling to estimate genetic and non-genetic contributions to restrained eating. Results 1,196 monozygotic, 456 same-sex dizygotic twins, and 447 opposite-sex twins were included in analyses. Restraint Scale scores were more closely correlated in monozygotic twins (rmale = 0.55, rfemale = 0.55) than in same-sex dizygotic twins (rmale = 0.31, rfemale = 0.19). Based on structural equation modeling, the estimated heritability for restrained eating, adjusted for BMI and sex, was 43% (95% confidence interval 35–50%). There was little evidence for common environmental effects. Conclusion These results indicate an inherited component to restrained eating. Genes could influence restrained eating directly or through inherited mediators such as personality factors or tendencies to gain weight. PMID:19658171

  6. Role of the Conformational Rigidity in the Design of Biomimetic Antimicrobial Compounds

    SciTech Connect

    Ivankin, Andrey; Livne, Liran; Mor, Amram; Caputo, Gregory A.; DeGrado, William F.; Meron, Mati; Lin, Binhua; Gidalevitz, David

    2011-08-16

    A link between structural flexibility of biomimetic antimicrobials and their ability to penetrate into the hydrophobic core and disrupt the integrity of bacterial lipid model membranes has been established using liquid surface X-ray scattering techniques. Results indicate that the modes of interaction of flexible and conformationally restrained antimicrobials with the bacterial membranes are different.

  7. Antimicrobial Stewardship

    PubMed Central

    Doron, Shira; Davidson, Lisa E.

    2011-01-01

    Antimicrobial resistance is increasing; however, antimicrobial drug development is slowing. Now more than ever before, antimicrobial stewardship is of the utmost importance as a way to optimize the use of antimicrobials to prevent the development of resistance and improve patient outcomes. This review describes the why, what, who, how, when, and where of antimicrobial stewardship. Techniques of stewardship are summarized, and a plan for implementation of a stewardship program is outlined. PMID:22033257

  8. Antimicrobials Treatment

    NASA Astrophysics Data System (ADS)

    Drosinos, Eleftherios H.; Skandamis, Panagiotis N.; Mataragas, Marios

    The use of antimicrobials is a common practice for preservation of foods. Incorporation, in a food recipe, of chemical antimicrobials towards inhibition of spoilage and pathogenic micro-organisms results in the compositional modification of food. This treatment is nowadays undesirable for the consumer, who likes natural products. Scientific community reflecting consumers demand for natural antimicrobials has made efforts to investigate the possibility to use natural antimicrobials such us bacteriocins and essential oils of plant origin to inhibit microbial growth.

  9. Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans.

    PubMed

    Hua, J; Yamarthy, R; Felsenstein, S; Scott, R W; Markowitz, K; Diamond, G

    2010-12-01

    Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans but numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (with molecular weight < 1000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-minimum inhibitory concentration levels did not lead to resistant Candida, in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.

  10. Antimicrobial stewardship.

    PubMed

    Allerberger, F; Mittermayer, H

    2008-03-01

    The aim of antimicrobial management or stewardship programmes is to ensure proper use of antimicrobial agents in order to provide the best treatment outcomes, to lessen the risk of adverse effects (including antimicrobial resistance), and to promote cost-effectiveness. Increasingly, long-term sustainability is found to be the major focus of antimicrobial stewardship. Implementing structural measures in healthcare institutions is therefore a major, but not the sole, focus of attention in promoting prudent use of antibiotics. The problem of antimicrobial resistance requires common strategies at all levels--for the prescribers and at ward, departmental, hospital, national and international levels.

  11. Dependence of antimicrobial selectivity and potency on oligomer structure investigated using substrate supported lipid bilayers and sum frequency generation vibrational spectroscopy.

    PubMed

    Avery, Christopher W; Som, Abhigyan; Xu, Yongjiang; Tew, Gregory N; Chen, Zhan

    2009-10-15

    Sum frequency generation (SFG) vibrational spectroscopy was used to study interactions between solid-supported lipid bilayers mimicking microbial and erythrocyte cellular membranes and synthetic antimicrobial arylamide oligomers named 2, 3, and 4, designed with the facial amphiphilicity common to naturally occurring antimicrobial peptides. The three compounds have the same backbone structure but varied side chains. The inherent interfacial sensitivity of SFG allowed for simultaneous monitoring of lipid ordering in the individual bilayer leaflets and orientation of 2, 3, and 4 upon interaction with the bilayer. Critical concentrations at which the inner leaflet is disrupted were determined for each oligomer. Spectral evidence of the oligomers' interaction with the bilayer below the critical concentrations was also found. Oligomers 2 and 3 tilted toward the bilayer surface normal, in agreement with previous experimental and simulation results. These oligomers selectively interact with microbial membrane models over erythrocyte membrane models, correlating well to previously published SFG studies on antimicrobial oligomer 1. It was shown that the oligomers interact with the lipid bilayers differently, indicating their different activity and selectivity. This research further shows that SFG is a particularly useful technique for the investigation of interaction mechanisms between cell membranes and membrane-active molecules. Additionally, SFG provides details of the specific interactions between these novel antimicrobials and lipid bilayers.

  12. Keeping guns out of the hands of abusers: handgun purchases and restraining orders.

    PubMed

    Vittes, Katherine A; Sorenson, Susan B

    2008-05-01

    Persons under certain domestic violence restraining orders are prohibited by federal law from purchasing and possessing a firearm. We used administrative data from California to link 794426 restraining orders with 1388724 handgun purchase applications. We found that restrained persons were not a less law-abiding group in general, but they appeared to be repeatedly or serially abusive to intimate partners, and their handgun purchase rates were highest after their restraining orders expired.

  13. Keeping Guns Out of the Hands of Abusers: Handgun Purchases and Restraining Orders

    PubMed Central

    Vittes, Katherine A.; Sorenson, Susan B.

    2008-01-01

    Persons under certain domestic violence restraining orders are prohibited by federal law from purchasing and possessing a firearm. We used administrative data from California to link 794426 restraining orders with 1388724 handgun purchase applications. We found that restrained persons were not a less law-abiding group in general, but they appeared to be repeatedly or serially abusive to intimate partners, and their handgun purchase rates were highest after their restraining orders expired. PMID:18381985

  14. Are Temporary Restraining Orders More Likely to Be Issued When Applications Mention Firearms?

    ERIC Educational Resources Information Center

    Vittes, Katherine A.; Sorenson, Susan B.

    2006-01-01

    Restraining orders, an important legal intervention for victims of domestic violence, have broad potential for injury prevention. Using data from one of the busiest restraining order clinics in the nation, the authors examined 1,354 applicants' descriptions of abuse. Most (89.2%) applicants were issued a restraining order. A total of 16.0% of…

  15. Are Temporary Restraining Orders More Likely to Be Issued When Applications Mention Firearms?

    ERIC Educational Resources Information Center

    Vittes, Katherine A.; Sorenson, Susan B.

    2006-01-01

    Restraining orders, an important legal intervention for victims of domestic violence, have broad potential for injury prevention. Using data from one of the busiest restraining order clinics in the nation, the authors examined 1,354 applicants' descriptions of abuse. Most (89.2%) applicants were issued a restraining order. A total of 16.0% of…

  16. Emotional, external, restrained eating and overweight in Dutch adolescents.

    PubMed

    Snoek, Harriëtte M; van Strien, Tatjana; Janssens, Jan M A M; Engels, Rutger C M E

    2007-02-01

    The purpose of this study was to determine how emotional, external and restrained eating behavior and other health-related lifestyle factors were associated with being overweight in adolescents. Moreover, demographic and ethnic differences in eating behavior have been examined. The respondents were 10,087 Dutch adolescents aged 11-16 years (M= 13.0, SD= 0.8). Self-reported eating behavior was measured with the DEBQ. Health-related lifestyle was determined by physical activity, breakfasting, fruit consumption and snacking. High restrained, and low external eating were positively associated with being overweight, whereas no significant association between emotional eating and being overweight was found for girls, and a negative association for boys. Adolescents who ate breakfast on a daily basis were less likely to be overweight than those who ate breakfast irregularly or never. Being overweight was positively associated with fruit consumption for girls and negatively with physical activity for boys.

  17. Ulcers in restrained rats: Study of protective substances

    NASA Technical Reports Server (NTRS)

    Buche, L.; Gallaire, D.

    1980-01-01

    The genesis of ulcers in restrained rats is discussed through an investigation of the relationship between the protective effects of nervous system effectual substances examined vis-a-vis ulcers in restrained rats and their elective or secondary pharmacologic effects. The substances used were capable of either peripheral parasympatholytic, sympatholytic, ganglioplegic, spasmolytic effects or central, hypnotic, tranquilizing, neuroleptic, analgesic effects. The regular and considerable protection observed with parasympatholytics (atropine sulfate, benzylonium bromide, dihexyverine, J.L. 1344) and a ganglioplegic (pentamethonium) is a function of their anticholinergic properties. It is of less importance with dibenamine, a sympatholytic action on the adrenergic receptors. Among the central depressive substances tested (hypnotics, tranquilizers, neuroleptics, analgesic), phenobarbital at a nonhypnotic dose, and dextromoramide at a nonanalgesic dose, show antiulcerous effects, which are found with chlorpromazine only at cataleptogenic doses.

  18. Thermal properties of freezing bound water restrained by polysaccharides.

    PubMed

    Hatakeyama, Tatsuko; Tanaka, Masaru; Hatakeyama, Hyoe

    2010-01-01

    This review focuses on the thermal properties of bound water restrained by various kinds of polysaccharides and several synthetic polymers. The characteristic features of freezing bound water which is closely related with biocompatibility of polymers are summarized based on results obtained by differential scanning calorimetry. Glass transition, cold crystallization and melting of water-polysaccharide systems were observed. Three kinds of water, non-freezing, freezing bound and free water, were quantified from the enthalpy of melting of water in the system. Freezing bound water restrained by polysaccharides is in a metastable state. The equilibrium melting temperature of freezing bound water is lower than 0°C and the temperature decreases with decreasing water content. Nucleation and growth rate of freezing bound water were calculated from isothermal crystallization and the values were compared with those of free water.

  19. Social Ultrasonic Vocalization in Awake Head-Restrained Mouse

    PubMed Central

    Weiner, Benjamin; Hertz, Stav; Perets, Nisim; London, Michael

    2016-01-01

    Numerous animal species emit vocalizations in response to various social stimuli. The neural basis of vocal communication has been investigated in monkeys, songbirds, rats, bats, and invertebrates resulting in deep insights into motor control, neural coding, and learning. Mice, which recently became very popular as a model system for mammalian neuroscience, also utilize ultrasonic vocalizations (USVs) during mating behavior. However, our knowledge is lacking of both the behavior and its underlying neural mechanism. We developed a novel method for head-restrained male mice (HRMM) to interact with non-restrained female mice (NRFM) and show that mice can emit USVs in this context. We first recorded USVs in a free arena with non-restrained male mice (NRMM) and NRFM. Of the NRMM, which vocalized in the free arena, the majority could be habituated to also vocalize while head-restrained but only when a female mouse was present in proximity. The USVs emitted by HRMM are similar to the USVs of NRMM in the presence of a female mouse in their spectral structure, inter-syllable interval distribution, and USV sequence length, and therefore are interpreted as social USVs. By analyzing the vocalizations of NRMM, we established criteria to predict which individuals are likely to vocalize while head fixed based on the USV rate and average syllable duration. To characterize the USVs emitted by HRMM, we analyzed the syllable composition of HRMM and NRMM and found that USVs emitted by HRMM have a higher proportion of USVs with complex spectral representation, supporting previous studies showing that mice social USVs are context dependent. Our results suggest a way to study the neural mechanisms of production and control of social vocalization in mice using advanced methods requiring head fixation. PMID:28066202

  20. Dieting and restrained eating as prospective predictors of weight gain.

    PubMed

    Lowe, Michael R; Doshi, Sapna D; Katterman, Shawn N; Feig, Emily H

    2013-09-02

    Research in normal weight individuals paradoxically suggests that measures of attempted eating restriction might represent robust predictors of weight gain. This review examined the extent to which measures of dieting (e.g., self-reported weight loss dieting in the past year) and dietary restraint (e.g., the Cognitive Restraint scale from the Three-Factor Eating Questionnaire) have prospectively predicted weight change. We located and reviewed 25 prospective studies containing 40 relevant comparisons. Studies were limited to those in which participants were non-obese (with a mean BMI between 18.5 and 30) and averaged at least 12 years old. Neither measure predicted future weight loss. Fifteen of the 20 comparisons (75%) that examined measures of dieting significantly predicted future weight gain whereas only 1 of 20 (5%) that examined restrained eating measures did so. Two plausible explanations for these findings are that: (1) dieters and restrained eaters do not differ in terms of an underlying proneness toward weight gain, but restrained eating represents a more effective means of preventing it; and (2) normal weight individuals who diet do so because they are resisting a powerful predisposition toward weight gain which dieting ultimately fails to prevent. Recent dieting in non-obese individuals may be a valuable proxy of susceptibility to weight gain. This easily assessed characteristic could identify individuals for whom obesity prevention interventions would be particularly appropriate.

  1. Antimicrobial Activity.

    PubMed

    2016-01-01

    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  2. Antimicrobial Pesticides

    MedlinePlus

    ... EPA United States Environmental Protection Agency Search Search Pesticides Share Facebook Twitter Google+ Pinterest Contact Us Antimicrobial Pesticides EPA regulates pesticides under the statutory authority of ...

  3. Antimicrobial stewardship

    PubMed Central

    Chung, Gladys W.; Wu, Jia En; Yeo, Chay Leng; Chan, Douglas; Hsu, Li Yang

    2013-01-01

    Antimicrobial stewardship is an emerging field currently defined by a series of strategies and interventions aimed toward improving appropriate prescription of antibiotics in humans in all healthcare settings. The ultimate goal is the preservation of current and future antibiotics against the threat of antimicrobial resistance, although improving patient safety and reducing healthcare costs are important concurrent aims. Prospective audit and feedback interventions are probably the most widely practiced of all antimicrobial stewardship strategies. Although labor-intensive, they are more easily accepted by physicians compared with formulary restriction and preauthorization strategies and have a higher potential for educational opportunities. Objective evaluation of antimicrobial stewardship is critical for determining the success of such programs. Nonetheless, there is controversy over which outcomes to measure and there is a pressing need for novel study designs that can objectively assess antimicrobial stewardship interventions despite the limitations inherent in the structure of most such programs. PMID:23302793

  4. Geomorpho-tectonic evolution of the Jamaican restraining bend

    NASA Astrophysics Data System (ADS)

    Domínguez-González, Leomaris; Andreani, Louis; Stanek, Klaus P.; Gloaguen, Richard

    2015-01-01

    This work applies recent advances in tectonic geomorphology in order to understand the geomorphic evolution of the Jamaican restraining bend located along the Caribbean-Gonâve-North American plate boundary. We propose a classification of landscapes according to their erosional stages. The approach is mainly based on the combination of two DEM-based geomorphic indices: the hypsometric integral which highlights elevated surfaces, and the surface roughness which increases when the relief is incised by the drainage network. River longitudinal profiles were also analyzed as the drainage network responds quickly to base-level change triggered by external forcing such as tectonics. Anomalies in river profiles (knickpoints and convex segments) were mapped using stream length-gradient (SL) and normalized steepness (ksn) indices. The results provide new insights for understanding the complex evolution of the Jamaican restraining bend. Three main morphotectonic regions were identified in Jamaica: (1) the Blue Mountain-Wagwater unit located at the eastern tip of the island, (2) the Jamaican highlands plateau which covers most of the northern and central areas and (3) the tilted block province located along the southern part of Jamaica. Each region has a specific morphological signature which marks a different stage in the Late Miocene to present evolution of the Jamaican restraining bend. The evolution of the bend is mainly associated with the western propagation of major E-trending strike-slip faults and NW-trending thrusts. In the western and central parts of Jamaica the present-day motion between the Caribbean plate and the Gonâve microplate is broadly distributed along several structures, while in the easternmost part of the island this motion seems to be almost completely accommodated along the Blue Mountain range and the Plantain-Garden Fault.

  5. Transverse Vibrations of Single Bellows Expansion Joint Restrained Against Rotation

    SciTech Connect

    Kameswara, Rao C.; Radhakrishna, M.

    2002-07-01

    The paper presents the results of investigation of transverse vibrations of single bellows expansion joint restrained against rotation on either end. A theoretical model is developed based on the Bernoulli-Euler beam theory and includes added mass of the fluid flowing inside the pipe-bellow-pipe assembly. Neglecting effects of shear and rotary inertia an exact frequency equation is derived for the transverse vibrations of single bellows expansion joint including the effects of end elastic restraints against rotation. Numerical results are presented for an example bellow showing the effects of variation of elastic restraints and internal pressure on the first four modes of vibration. (authors)

  6. Transverse Vibrations of Double Bellows Expansion Joint Restrained Against Rotation

    SciTech Connect

    Kameswara, Rao C.; Radhakrishna, M.

    2002-07-01

    The paper presents the results of investigation of transverse vibrations of double bellows expansion joint restrained against rotation on either end. A theoretical model is developed based on the Bernoulli-Euler beam theory and includes added mass of the fluid flowing inside the pipe-bellow-pipe assembly. Neglecting effect of shear, an exact frequency equation is derived for the transverse vibrations of double bellows expansion joint including the effects of end elastic restraints against rotation. Numerical results are presented for an example bellow showing the effects of variation of elastic restraints and internal pressure on the first two modes of vibration. (authors)

  7. Thermal Behavior of Cylindrical Buckling Restrained Braces at Elevated Temperatures

    PubMed Central

    Talebi, Elnaz; Tahir, Mahmood Md.; Yasreen, Airil

    2014-01-01

    The primary focus of this investigation was to analyze sequentially coupled nonlinear thermal stress, using a three-dimensional model. It was meant to shed light on the behavior of Buckling Restraint Brace (BRB) elements with circular cross section, at elevated temperature. Such bracing systems were comprised of a cylindrical steel core encased in a strong concrete-filled steel hollow casing. A debonding agent was rubbed on the core's surface to avoid shear stress transition to the restraining system. The numerical model was verified by the analytical solutions developed by the other researchers. Performance of BRB system under seismic loading at ambient temperature has been well documented. However, its performance in case of fire has yet to be explored. This study showed that the failure of brace may be attributed to material strength reduction and high compressive forces, both due to temperature rise. Furthermore, limiting temperatures in the linear behavior of steel casing and concrete in BRB element for both numerical and analytical simulations were about 196°C and 225°C, respectively. Finally it is concluded that the performance of BRB at elevated temperatures was the same as that seen at room temperature; that is, the steel core yields prior to the restraining system. PMID:24526915

  8. Flavor-nutrient learning in restrained and unrestrained eaters.

    PubMed

    Brunstrom, Jeffrey M; Mitchell, Gemma L

    2007-01-30

    After we consume a novel food an association can form between its sensory characteristics (e.g., taste properties) and the effect it has on the body (rewarding). Associations of this kind underpin much of our everyday dietary behavior because they mediate both the affective quality of food (flavor-preference learning) and the amount that we choose to consume (learning satiation). Notwithstanding this fact, very few studies have successfully demonstrated the process of dietary learning in human adults. In addition, based on evidence from related research, we explored whether learning is less likely to occur in individuals who have high scores on a measure of dietary restraint. Female participants (N = 44) consumed two differently flavored desserts. Each was presented three times on separate days. One was formulated with a high-energy content (1882 kJ) and the other with a low-energy content (226 kJ). After training, we found little evidence for learned satiation. However, we did observe flavor-preference learning. Specifically, participants acquired a greater liking and desire-to-eat the dessert flavor that was paired with a higher energy density during training. Further analysis revealed that this effect on liking is qualified by dietary restraint. As predicted, unrestrained eaters demonstrated greater differential responding to the two desserts than did restrained eaters. These data provide further evidence for flavor-nutrient learning in adults and they highlight a hitherto unexplored and potentially important difference between restrained and unrestrained eaters.

  9. [Differences among chronic restrained eaters: the influence of motivational systems].

    PubMed

    Silva, Jaime R; Livacic-Rojas, Pablo; Slachevsky, Andrea

    2006-06-01

    Restrained eaters (RE) are individuals who restrain their food intake on a regular basis as they are frightened to gain weight. However, they tend to overeat under conditions of anxiety. It has been shown that RE possess a behavioral inhibition system that is more active in tonic terms, which would partially explain their affective vulnerability. Even so, the influence of variations in the activation levels of the emotional systems on the eating behavior of a RE is still unknown. Our hypothesis is that variations of such systems will give place to two types of RE: a successful or a non-successful one. To assess the influence of variations on the activation of motivational systems in food intake of RE. As part of a factorial experimental design, 105 undergraduate university students were part of an experimental test for inducting food intake. Then they reported their levels of dietary restraint and their emotional behavioral preferences. Differences in the activation of motivational systems were significantly related to differences in food intake (F= 7.210; p= 0.001). Additionally, food intake for those RE with a predominant inhibition system tended to be higher than for those with a more active approach system, though the latter did not reach a significant difference (F=0.718; p=0.399). Although more investigations are required, our data suggest that the success of retaining the diet among the RE would depend on their profile of affective reactivity (affective style). There are putative implications for research on anorexia and obesity.

  10. Antimicrobial Polymer

    DOEpatents

    McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

    2004-09-28

    A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The polymeric composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from metals, metal alloys, metal salts, metal complexes and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one example embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl; and the metallic antimicrobial agent is selected from chelated silver ions, silver metal, chelated copper ions, copper metal, chelated zinc ions, zinc metal and mixtures thereof.

  11. Antimicrobial Resistance

    MedlinePlus

    ... spread of antimicrobial resistance. Present situation Resistance in bacteria Antibiotic resistance is present in every country. Patients with infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes ...

  12. Unilateral buckling of elastically restrained rectangular mild steel plates

    NASA Astrophysics Data System (ADS)

    Smith, S. T.; Bradford, M. A.; Oehlers, D. J.

    This paper considers the elastic unilateral buckling of rectangular mild steel plates that are restrained elastically and subjected to bending and axial actions. A variational formulation of the Ritz method using linear combinations of harmonic functions for the buckling deformations is used to establish an eigenproblem to determine the plate local buckling coefficients. The motivation for the study is the retrofit of reinforced concrete beams by gluing and then bolting steel plates to the sides of the beam. Such plates, when acting compositely with the concrete beam, are subjected to predominantly bending and axial actions which may cause unilateral local buckling. Whereas the bolts provide complete restraint against buckling at discrete points, the glue may also inhibit local buckling between these nodal points since it acts as a continuous elastic restraint. The influence of the glue stiffness, support conditions and plate proportions on the unilateral buckling of such plates are assessed.

  13. Blood vessels restrain pancreas branching, differentiation and growth

    PubMed Central

    Magenheim, Judith; Ilovich, Ohad; Lazarus, Alon; Klochendler, Agnes; Ziv, Oren; Werman, Roni; Hija, Ayat; Cleaver, Ondine; Mishani, Eyal; Keshet, Eli; Dor, Yuval

    2011-01-01

    How organ size and form are controlled during development is a major question in biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here, we report that, surprisingly, non-nutritional signals from blood vessels act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells. PMID:21965615

  14. Spatial learning in the restrained American cockroach Periplaneta americana.

    PubMed

    Kwon, Hyung-Wook; Lent, David D; Strausfeld, Nicholas J

    2004-01-01

    Spatial learning abilities were tested in restrained cockroaches by observing antennal projection responses towards the positions of a learned visual cue perceived monocularly by one eye in the context of a second stimulus provided to the contralateral eye. Memory of the position of the conditioning stimulus relative to the contralateral reference stimulus was tested by altering the relative positions of the two stimuli. Memory of the conditioning stimulus is retained if the angle between the conditioning stimulus and the contralateral reference stimulus is maintained. The results suggest that during learning the insect recognizes spatial relationships between the conditioning stimulus and the contralateral reference stimulus. Possible mechanisms, such as retinotopic matching versus angular matching, are discussed.

  15. Estimating the speed-up of adaptively restrained Langevin dynamics

    NASA Astrophysics Data System (ADS)

    Trstanova, Zofia; Redon, Stephane

    2017-05-01

    We consider Adaptively Restrained Langevin dynamics, in which the kinetic energy function vanishes for small velocities. Properly parameterized, this dynamics makes it possible to reduce the computational complexity of updating inter-particle forces, and to accelerate the computation of ergodic averages of molecular simulations. In this paper, we analyze the influence of the method parameters on the total achievable speed-up. In particular, we estimate both the algorithmic speed-up, resulting from incremental force updates, and the influence of the change of the dynamics on the asymptotic variance. This allows us to propose a practical strategy for the parameterization of the method. We validate these theoretical results by representative numerical experiments.

  16. Protein structure refinement with adaptively restrained homologous replicas.

    PubMed

    Della Corte, Dennis; Wildberg, André; Schröder, Gunnar F

    2016-09-01

    A novel protein refinement protocol is presented which utilizes molecular dynamics (MD) simulations of an ensemble of adaptively restrained homologous replicas. This approach adds evolutionary information to the force field and reduces random conformational fluctuations by coupling of several replicas. It is shown that this protocol refines the majority of models from the CASP11 refinement category and that larger conformational changes of the starting structure are possible than with current state of the art methods. The performance of this protocol in the CASP11 experiment is discussed. We found that the quality of the refined model is correlated with the structural variance of the coupled replicas, which therefore provides a good estimator of model quality. Furthermore, some remarkable refinement results are discussed in detail. Proteins 2016; 84(Suppl 1):302-313. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  17. Cyclization improves membrane permeation by antimicrobial peptoids

    DOE PAGES

    Andreev, Konstantin; Martynowycz, Michael W.; Ivankin, Andrey; ...

    2016-10-28

    The peptidomimetic approach has emerged as a powerful tool for overcoming the inherent limitations of natural antimicrobial peptides, where the therapeutic potential can be improved by increasing the selectivity and bioavailability. Restraining the conformational flexibility of a molecule may reduce the entropy loss upon its binding to the membrane. Experimental findings demonstrate that the cyclization of linear antimicrobial peptoids increases their bactericidal activity against Staphylococcus aureus while maintaining high hemolytic concentrations. Surface X-ray scattering shows that macrocyclic peptoids intercalate into Langmuir monolayers of anionic lipids with greater efficacy than for their linear analogues. Lastly, it is suggested that cyclization maymore » increase peptoid activity by allowing the macrocycle to better penetrate the bacterial cell membrane.« less

  18. Cyclization improves membrane permeation by antimicrobial peptoids

    SciTech Connect

    Andreev, Konstantin; Martynowycz, Michael W.; Ivankin, Andrey; Huang, Mia L.; Kuzmenko, Ivan; Meron, Mati; Lin, Binhua; Kirshenbaum, Kent; Gidalevitz, David

    2016-10-28

    The peptidomimetic approach has emerged as a powerful tool for overcoming the inherent limitations of natural antimicrobial peptides, where the therapeutic potential can be improved by increasing the selectivity and bioavailability. Restraining the conformational flexibility of a molecule may reduce the entropy loss upon its binding to the membrane. Experimental findings demonstrate that the cyclization of linear antimicrobial peptoids increases their bactericidal activity against Staphylococcus aureus while maintaining high hemolytic concentrations. Surface X-ray scattering shows that macrocyclic peptoids intercalate into Langmuir monolayers of anionic lipids with greater efficacy than for their linear analogues. Lastly, it is suggested that cyclization may increase peptoid activity by allowing the macrocycle to better penetrate the bacterial cell membrane.

  19. Dynamic modelling of mechanical systems with opposing restrained preloaded stiffnesses

    NASA Astrophysics Data System (ADS)

    Rogers, R. J.; Garland, P.; Oliver, M.

    2004-07-01

    Preloaded springs are used in many mechanical systems such as suspension systems and linkages, as well as household items such as clothing clasps. Usually, the preload has no effect on small amplitude dynamic responses which occur about the mean preloaded position. However if the system has opposing preloaded elastic elements, where unloading is limited by restraints such as central rods which preserve the preload, then the preload has a dramatic effect on a system's dynamic response. When such a system is set into free oscillation, the period of motion steadily decreases as the amplitude diminishes. Until now the authors have not seen this behavior described elsewhere. The present work is motivated by the modelling of joysticks which are used to actuate hydraulic systems in a wide variety of mobile construction and forestry equipment. Their use for long periods of time may lead to repetitive strain injuries in an operator's upper limbs, neck and back. In order to assess the total force required to move a joystick, the stiffness, damping and inertia characteristics must be determined. A mathematical model for joystick dynamics is presented and the effect of restrained spring preloads on the changing period of free vibration is explained. In addition, procedures to estimate the non-symmetric non-linear damping from experimental data are described. By simulating the dynamic response in MATLAB TM, the damping is fine-tuned by comparing the joystick's simulated free oscillation response with its experimental response. Finally, the torque waveform required to perform a simple joystick motion is estimated. The methods developed in this paper could be applied to any lumped-parameter mechanical system where there are opposing restrained preloaded elastic elements.

  20. Altered regional homogeneity and efficient response inhibition in restrained eaters.

    PubMed

    Dong, D; Lei, X; Jackson, T; Wang, Y; Su, Y; Chen, H

    2014-04-25

    Restrained eaters (REs) characterized by less efficient response inhibition are at risk for future onset of binge eating and bulimic pathology. Previous imaging studies investigating REs have been based on task-related functional magnetic resonance imaging (fMRI) and little is known about resting-state neural activity underlying restrained eating. To illuminate this issue, we investigated resting-state fMRI differences between REs (n=22) and unrestrained eaters (UREs) (n=30) using regional homogeneity (ReHo) analysis, which measures the temporal synchronization of spontaneous fluctuations. Samples were equated on body mass index (BMI) and caloric deprivation levels (i.e., 14±2.1h since last evening meal) before undergoing fMRI. Correlation analyses were performed between the ReHo index of identified regions and response inhibition based on stop-signal reaction time (SSRT) within each sample. Compared with UREs, REs showed more ReHo in brain regions associated with food reward (i.e., orbitofrontal cortex (OFC), dorsal-lateral prefrontal cortex (dlPFC)), attention (i.e., lingual gyrus, cuneus, inferior parietal lobule) and somatosensory functioning (i.e., paracentral lobule, anterior insula). In addition, ReHo values for the left dlPFC and left anterior insula, respectively, were negatively and positively correlated with SSRT among REs but not UREs. In concert with previous studies, these results suggest altered local synchronization may help to explain why dieting to maintain or lose weight often fails or increases risk for binge eating among REs. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Restrained eating and self-esteem in premenopausal and postmenopausal women.

    PubMed

    Drobnjak, Suzana; Atsiz, Semra; Ditzen, Beate; Tuschen-Caffier, Brunna; Ehlert, Ulrike

    2014-01-01

    There has been limited research about disordered eating in middle-aged women, and to date, few data exist about restrained eating behavior in postmenopausal women. Therefore, the aim of this study was to examine eating behavior with a specific focus on menopause as an associated factor in restrained eating. Beyond this, we were interested in how postmenopausal status and self-esteem would interact to determine eating patterns in women in middle age. We conducted an online survey in women aged between 40 and 66. Eating behavior was assessed with the Eating Disorder Examination-Questionnaire (EDE-Q) in premenopausal (N = 318) and postmenopausal women (N = 250). All participants rated their self-esteem using the Rosenberg Self-Esteem Scale (RSE) and reported their weight, height, waist circumference, and hip circumference. 15.7% of all participants showed clinically meaningful scores on restrained eating. Postmenopausal women showed significantly higher scores on the EDE-Q subscale of restrained eating as compared to premenopausal women, but when controlling for body mass index, however, this finding was no longer significant. Further exploratory analyses suggest that particularly low or high self-esteem levels are associated with restrained eating. Self-esteem might serve as a mediator between menopausal status and restrained eating, however results of these additional analyses were inconsistent. Restrained eating may appear in middle-aged women. Particularly in postmenopausal women, restrained eating might be associated with lower and higher self-esteem.

  2. Body Dissatisfaction Mediates the Relationship between Self-Esteem and Restrained Eating in Female Undergraduates

    ERIC Educational Resources Information Center

    Gianini, Loren M.; Smith, Jane Ellen

    2008-01-01

    The purpose of the current study was to examine the eating behavior, self-esteem, and social anxiety of restrained and non-restrained eaters exposed to an interpersonal stressor. Sixty female undergraduate students completed questionnaires and took part in a stressor and taste test. Results indicated that self-esteem was not predictive of eating…

  3. Tool and Technique for Restraining Live-Captured American Martens and Fishers

    Treesearch

    Linda Ebel Thomasma; Rolf O. Peterson; Rolf O. Peterson

    1998-01-01

    Restraining live-captured animals poses challenges when working alone, especially in remote field locations. While studying American martens (Marfes americana) and fishers (Martes pennantr) in Michigan, we developed a new tool, trap combs, to restrain a live-captured animal in the trap. The construction and use of trap combs are described.

  4. Antimicrobial polymers.

    PubMed

    Jain, Anjali; Duvvuri, L Sailaja; Farah, Shady; Beyth, Nurit; Domb, Abraham J; Khan, Wahid

    2014-12-01

    Better health is basic requirement of human being, but the rapid growth of harmful pathogens and their serious health effects pose a significant challenge to modern science. Infections by pathogenic microorganisms are of great concern in many fields such as medical devices, drugs, hospital surfaces/furniture, dental restoration, surgery equipment, health care products, and hygienic applications (e.g., water purification systems, textiles, food packaging and storage, major or domestic appliances etc.) Antimicrobial polymers are the materials having the capability to kill/inhibit the growth of microbes on their surface or surrounding environment. Recently, they gained considerable interest for both academic research and industry and were found to be better than their small molecular counterparts in terms of enhanced efficacy, reduced toxicity, minimized environmental problems, resistance, and prolonged lifetime. Hence, efforts have focused on the development of antimicrobial polymers with all desired characters for optimum activity. In this Review, an overview of different antimicrobial polymers, their mechanism of action, factors affecting antimicrobial activity, and application in various fields are given. Recent advances and the current clinical status of these polymers are also discussed.

  5. Antimicrobial Stewardship

    PubMed Central

    King, Sarah; Exley, Josephine; Taylor, Jirka; Kruithof, Kristy; Larkin, Jody; Pardal, Mafalda

    2016-01-01

    Abstract RAND Europe undertook a systematic review of the evidence of effectiveness and cost effectiveness on changing the public's risk related behaviour pertaining to antimicrobial use to inform the development of a NICE public health guideline aimed at delaying antimicrobial resistance (AMR). The review considered educational interventions targeting individuals, communities or the general public delivered via any mode. Specifically, it aimed to address: 1. Which educational interventions are effective and cost-effective in changing the public's behaviour to ensure they only ask for antimicrobials when appropriate and use them correctly? 2. Which educational interventions are effective and cost-effective in changing the public's behaviour to prevent infection and reduce the spread of antimicrobial resistance? Overall, 60 studies met the inclusion criteria; 29 related to research question 1, and 36 related to research question 2 (five studies were applicable to both). The key findings are summarised in “Evidence Statements” in accordance with NICE guidelines. Evidence Statements provide a high level overview of the key features of the evidence including: the number of studies, the quality of evidence, and the direction of the estimated effect followed by a brief summary of each of the supporting studies. Studies are grouped into Evidence Statements by setting and intervention. PMID:28083399

  6. Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice

    PubMed Central

    Li, Yanli; Gao, Rufei; Liu, Xueqing; Chen, Xuemei; Liao, Xinggui; Geng, Yanqing; Ding, Yubin; Wang, Yingxiong; He, Junlin

    2015-01-01

    The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone. PMID:26247969

  7. Stromal response to Hedgehog signaling restrains pancreatic cancer progression.

    PubMed

    Lee, John J; Perera, Rushika M; Wang, Huaijun; Wu, Dai-Chen; Liu, X Shawn; Han, Shiwei; Fitamant, Julien; Jones, Phillip D; Ghanta, Krishna S; Kawano, Sally; Nagle, Julia M; Deshpande, Vikram; Boucher, Yves; Kato, Tomoyo; Chen, James K; Willmann, Jürgen K; Bardeesy, Nabeel; Beachy, Philip A

    2014-07-29

    Pancreatic ductal adenocarcinoma (PDA) is the most lethal of common human malignancies, with no truly effective therapies for advanced disease. Preclinical studies have suggested a therapeutic benefit of targeting the Hedgehog (Hh) signaling pathway, which is activated throughout the course of PDA progression by expression of Hh ligands in the neoplastic epithelium and paracrine response in the stromal fibroblasts. Clinical trials to test this possibility, however, have yielded disappointing results. To further investigate the role of Hh signaling in the formation of PDA and its precursor lesion, pancreatic intraepithelial neoplasia (PanIN), we examined the effects of genetic or pharmacologic inhibition of Hh pathway activity in three distinct genetically engineered mouse models and found that Hh pathway inhibition accelerates rather than delays progression of oncogenic Kras-driven disease. Notably, pharmacologic inhibition of Hh pathway activity affected the balance between epithelial and stromal elements, suppressing stromal desmoplasia but also causing accelerated growth of the PanIN epithelium. In striking contrast, pathway activation using a small molecule agonist caused stromal hyperplasia and reduced epithelial proliferation. These results indicate that stromal response to Hh signaling is protective against PDA and that pharmacologic activation of pathway response can slow tumorigenesis. Our results provide evidence for a restraining role of stroma in PDA progression, suggesting an explanation for the failure of Hh inhibitors in clinical trials and pointing to the possibility of a novel type of therapeutic intervention.

  8. Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice.

    PubMed

    Li, Yanli; Gao, Rufei; Liu, Xueqing; Chen, Xuemei; Liao, Xinggui; Geng, Yanqing; Ding, Yubin; Wang, Yingxiong; He, Junlin

    2015-08-04

    The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone.

  9. Quantum mechanics/molecular mechanics restrained electrostatic potential fitting.

    PubMed

    Burger, Steven K; Schofield, Jeremy; Ayers, Paul W

    2013-12-05

    We present a quantum mechanics/molecular mechanics (QM/MM) method to evaluate the partial charges of amino acid residues for use in MM potentials based on their protein environment. For each residue of interest, the nearby residues are included in the QM system while the rest of the protein is treated at the MM level of theory. After a short structural optimization, the partial charges of the central residue are fit to the electrostatic potential using the restrained electrostatic potential (RESP) method. The resulting charges and electrostatic potential account for the individual environment of the residue, although they lack the transferable nature of library partial charges. To evaluate the quality of the QM/MM RESP charges, thermodynamic integration is used to measure the pKa shift of the aspartic acid residues in three different proteins, turkey egg lysozyme, beta-cryptogein, and Thioredoxin. Compared to the AMBER ff99SB library values, the QM/MM RESP charges show better agreement between the calculated and experimental pK(a) values for almost all of the residues considered.

  10. Buckling and modal analysis of rotationally restrained orthotropic plates

    NASA Astrophysics Data System (ADS)

    Villarreal, Enrique; Abajo, Daniel

    2015-10-01

    This paper describes a theoretical approach for the static buckling, eigenfrequency and vibration buckling analysis of typical orthotropic plates used in aeronautical constructions. The plates are constrained with any combination of simply-supported and rotationally restrained edges, and are subjected to biaxial compressive loads. The derivation of closed-form solutions is discussed, and the results are presented in the form of design charts, where the effect of the restraint stiffness is highlighted. The proposed design charts allow a more accurate initial sizing of typical aerospace structural components, like stiffened panels, where both static and dynamic buckling loads are fundamental for the final design. As compared to classical solutions based on simply-supported and clamped edges, the modeling of the edge constraint as an elastic restraint provides a more refined description of the real stringer-stiffened panel. The results demonstrate that, in contrast to the commonly adopted simply-supported boundary condition, a reduction of the design conservativeness can be achieved if the stiffness of the restraint is accounted for. A novel set of results relative to the vibration buckling is derived, illustrating that the dynamic buckling tends to increase for load frequencies higher than the first natural frequency.

  11. Symmetry-restrained flexible fitting for symmetric EM maps

    PubMed Central

    Chan, Kwok-Yan; Gumbart, James; McGreevy, Ryan; Watermeyer, Jean M.; Sewell, B. Trevor; Schulten, Klaus

    2011-01-01

    Summary Many large biological macromolecules have inherent structural symmetry, being composed of a few distinct subunits, repeated in a symmetric array. These complexes are often not amenable to traditional high-resolution structural determination methods, but can be imaged in functionally relevant states using cryo-electron microscopy (cryo-EM). A number of methods for fitting atomic-scale structures into cryo-EM maps have been developed, including the molecular dynamics flexible fitting (MDFF) method. However, quality and resolution of the cryo-EM map are the major determinants of a method’s success. In order to incorporate knowledge of structural symmetry into the fitting procedure, we developed the symmetry-restrained MDFF method. The new method adds to the cryo-EM map-derived potential further restraints on the allowed conformations of a complex during fitting, thereby improving the quality of the resultant structure. The benefit of using symmetry-based restraints during fitting, particularly for medium to low-resolution data, is demonstrated for three different systems. PMID:21893283

  12. Seismic Energy Demand of Buckling-Restrained Braced Frames

    NASA Astrophysics Data System (ADS)

    Choi, Hyunhoon; Kim, Jinkoo

    2008-07-01

    In this study seismic analyses of steel structures were carried out to examine the effect of ground motion characteristics and structural properties on energy demands using 60 earthquake ground motions recorded in different soil conditions, and the results were compared with those of previous works. Analysis results show that ductility ratios and the site conditions have significant influence on input energy. The ratio of hysteretic to input energy is considerably influenced by the ductility ratio and the strong motion duration. It is also observed that as the predominant periods of the input energy spectra are significantly larger than those of acceleration response spectra used in the strength design, the strength demand on a structure designed based on energy should be checked especially in short period structures. For that reason framed structures with buckling-restrained-braces (BRBs) were designed in such a way that all the input energy was dissipated by the hysteretic energy of the BRBs, and the results were compared with those designed by conventional strength-based design procedure.

  13. Full scale tests of all-steel buckling restrained braces

    NASA Astrophysics Data System (ADS)

    Ma, Ning; Wu, Bin; Li, Hui; Ou, Jinping; Yang, Weibiao

    2009-03-01

    Buckling-restrained braces (BRBs) are widely used seismic response-controlling members with excellent energy dissipation capacity without buckling at design deformation. However, the property of all-steel BRBs with cruciform cross section encased in a square steel tube remains insufficiently studied. In this paper, the properties of this kind of BRBs, which were used in two office buildings in Beijing, were examined by full-scale test. First, initial design was done according to the client's requirement. Then, two full-scale specimens were tested under uniaxial quasi-static cyclic loading. The test results indicate that there should be no welding in yielding portion of the core. Finally, the full-scale subassemblage test was done with an improved BRB and gusset plates installed in a frame. The result shows that the brace exhibited high energy dissipation capacity and stable hysteretic characteristic. According to the results from above tests, some important issues are summarized to provide advices for practical applications.

  14. Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division.

    PubMed

    Adachi, Yoshihiro; Itoh, Kie; Yamada, Tatsuya; Cerveny, Kara L; Suzuki, Takamichi L; Macdonald, Patrick; Frohman, Michael A; Ramachandran, Rajesh; Iijima, Miho; Sesaki, Hiromi

    2016-09-15

    Mitochondria divide to control their size, distribution, turnover, and function. Dynamin-related protein 1 (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the head group and acyl chains of phospholipids. Drp1 recognizes the head group of phosphatidic acid (PA) and two saturated acyl chains of another phospholipid by penetrating into the hydrophobic core of the membrane. The dual phospholipid interactions restrain Drp1 via inhibition of oligomerization-stimulated GTP hydrolysis that promotes membrane constriction. Moreover, a PA-producing phospholipase, MitoPLD, binds Drp1, creating a PA-rich microenvironment in the vicinity of a division apparatus. Thus, PA controls the activation of Drp1 after the formation of the division apparatus.

  15. Antimicrobial Peptides

    PubMed Central

    Bahar, Ali Adem; Ren, Dacheng

    2013-01-01

    The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs), a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes) and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics). PMID:24287494

  16. Acute versus repeated chocolate exposure: effects on intake and cravings in restrained and unrestrained eaters.

    PubMed

    Coelho, Jennifer S; Nederkoorn, Chantal; Jansen, Anita

    2014-04-01

    The cue-reactivity model, which is based on conditioning processes, posits that repeated food exposure (in the absence of consumption) should decrease cue reactivity. To examine whether repeated chocolate exposure attenuates cravings and intake, relative to those exposed to an acute cue, a 2 (repeated vs acute cue) × 2 (restrained vs unrestrained eaters) design was employed. Fifty female participants were recruited. Repeated exposure reduced cravings in unrestrained eaters (relative to acute exposure), but increased cravings in restrained eaters. An interaction between restraint and exposure emerged on intake, such that restrained eaters ate less after acute exposure than did unrestrained eaters.

  17. A circuit processing method for restraining DC drift for Interferometry of micro vibration measurement

    NASA Astrophysics Data System (ADS)

    Hou, Hao; Wang, Xuanze; Zhai, Zhongsheng

    2016-01-01

    A circuit processing method is present to restrain DC drift after analyzing the traditional signal processing method of interferometry for micro vibration measurement. At first, the circuit diagram is designed and its mathematical model is built, then the theoretical equations of the output signal are derived with the practical parameters. By using SIMULINK simulation, the process for restraining DC drift is present on the conditions of the variations of background intensity. The validity of feedback circuit was verified through analyzing the real experiment data. Theoretical predictions match simulation results, showing that this method effectively restrains DC drift for interferometry of micro vibration measurement and it greatly improves the system's stability.

  18. Risk of injury to restrained children from passenger air bags.

    PubMed

    Durbin, Dennis R; Kallan, Michael; Elliott, Michael; Cornejo, Rebecca A; Arbogast, Kristy B; Winston, Flaura K

    2003-03-01

    The objectives of this study were to estimate the prevalence of children's exposure to passenger air bag (PAB) deployments and to determine the relative risk of both minor and more serious nonfatal injuries to restrained children exposed to PABs in frontal impact collisions. Data were collected from 1 December 1998 to 30 November 2001 from a large-scale, child-specific crash surveillance system based on insurance claims, a telephone survey, and on-site crash investigations. Vehicles qualifying for inclusion were State Farm-insured, model year 1990 or newer, and involved in a crash with at least one child occupant < or =15 years of age. Qualifying crashes were limited to those that occurred in 15 states and the District of Columbia. A stratified cluster sample was designed in order to select vehicles (the unit of sampling) for the conduction of a telephone survey with the driver. For cases in which child occupants were seriously injured or killed, in-depth crash investigations were performed. The prevalence of exposure to PABs was calculated as the number of children occupying the right front seat in a PAB deployment crash among all children occupying the right front seat in vehicles equipped with PABs. Complete interview data were obtained on 9,779 vehicles involving 15,341 children. Among PAB-exposed children, 175 (14%) suffered serious injuries versus 41 (7.5%) of those in the comparison group (OR 2.0; 95% CI, 1.1-3.7). The overall risk of any injury (both minor and serious) was 86% among children exposed to PABs, compared to 55% among the comparison group (OR 5.3; 95% CI, 2.1-13.4). Exposure to PABs increased the risk of both minor injuries, including facial and chest abrasions, and more serious injuries, particularly upper extremity fractures.

  19. Immunosuppressive monocytes: possible homeostatic mechanism to restrain chronic intestinal inflammation

    PubMed Central

    Kurmaeva, Elvira; Bhattacharya, Dhruva; Goodman, Wendy; Omenetti, Sara; Merendino, Amber; Berney, Seth; Pizarro, Theresa; Ostanin, Dmitry V.

    2014-01-01

    Chronic colitis is accompanied by extensive myelopoiesis and accumulation of CD11b+Gr-1+ cells in spleens and secondary lymphoid tissues. Although cells with similar phenotype have been described in cancer, chronic infection, or autoimmunity, where they were associated with suppression of T cell responses, little is known regarding how these cells affect CD4 T cell responses in the context of chronic intestinal inflammation. Therefore, we undertook this study to characterize the interplay between colitis-induced myeloid cells and CD4 T cell. Within the CD11b+Gr-1+ population, only monocytes (Ly6GnegLy6Chigh) but not other myeloid cell subsets suppressed proliferation and production of cytokines by CD4 T cells. Suppression was mediated by cell-contact, NO and partially by IFN-γ and PGs. Interestingly, Ly6Chigh MDCs, isolated from colitic colons, showed up-regulation of iNOS and arginase-1 and were more potent suppressors than those isolated from spleen. On a single-cell level, MDCs inhibited Th1 responses but enhanced generation of foxp3+ T cells. MDCs, cocultured with activated/Teffs, isolated from inflamed colons under hypoxic (1% O2) conditions typical for the inflamed intestine, suppressed proliferation but not their production of proinflammatory cytokines and chemokines. Taken together, expansion of monocytes and MDCs and activation of their suppressive properties may represent a homeostatic mechanism aimed at restraining excessive T cell activation during chronic inflammatory settings. The contribution of immunosuppressive monocytes/MDCs to chronic colitis and their role in shaping T cell responses in vivo require further investigation. PMID:24696357

  20. Glucocorticoid receptor alters isovolumetric contraction and restrains cardiac fibrosis

    PubMed Central

    Richardson, Rachel V; Batchen, Emma J; Thomson, Adrian J W; Darroch, Rowan; Pan, Xinlu; Rog-Zielinska, Eva A; Wyrzykowska, Wiktoria; Scullion, Kathleen; Al-Dujaili, Emad A S; Diaz, Mary E; Moran, Carmel M; Kenyon, Christopher J; Gray, Gillian A

    2017-01-01

    Corticosteroids directly affect the heart and vasculature and are implicated in the pathogenesis of heart failure. Attention is focussed upon the role of the mineralocorticoid receptor (MR) in mediating pro-fibrotic and other adverse effects of corticosteroids upon the heart. In contrast, the role of the glucocorticoid receptor (GR) in the heart and vasculature is less well understood. We addressed this in mice with cardiomyocyte and vascular smooth muscle deletion of GR (SMGRKO mice). Survival of SMGRKO mice to weaning was reduced compared with that of littermate controls. Doppler measurements of blood flow across the mitral valve showed an elongated isovolumetric contraction time in surviving adult SMGRKO mice, indicating impairment of the initial left ventricular contractile phase. Although heart weight was elevated in both genders, only male SMGRKO mice showed evidence of pathological cardiomyocyte hypertrophy, associated with increased myosin heavy chain-β expression. Left ventricular fibrosis, evident in both genders, was associated with elevated levels of mRNA encoding MR as well as proteins involved in cardiac remodelling and fibrosis. However, MR antagonism with spironolactone from birth only modestly attenuated the increase in pro-fibrotic gene expression in SMGRKO mice, suggesting that elevated MR signalling is not the primary driver of cardiac fibrosis in SMGRKO mice, and cardiac fibrosis can be dissociated from MR activation. Thus, GR contributes to systolic function and restrains normal cardiac growth, the latter through gender-specific mechanisms. Our findings suggest the GR:MR balance is critical in corticosteroid signalling in specific cardiac cell types. PMID:28057868

  1. Discrimination learning with light stimuli in restrained American lobster.

    PubMed

    Tomina, Yusuke; Takahata, Masakazu

    2012-04-01

    Operant discrimination learning has been extensively utilized in the study on the perceptual ability of animals and their higher order brain functions. We tested in this study whether American lobster Homarus americanus, which was previously found to possess ability of operant learning with claw gripping, could be trained to discriminate light stimuli of different intensities. For the current purpose, we newly developed a PC-controlled operant chamber that allowed the animal under a body-fixed condition to perform operant reward learning with claw gripping. Lobsters were first reinforced when they gripped the sensor bar upon presentation of a light cue. Then they were trained to grip the bar only when the light stimulus of a specific intensity was presented to obtain food reward while the stimuli of three different intensities including the reinforced one were presented in a random order. Finally, they were re-trained to grip the bar only when the light stimulus of another intensity that was not rewarded in the preceding training to obtain food while other intensities including the one that was rewarded previously were not rewarded any more. In these training procedures, the operant behavior occurred more frequently in response to the rewarded cue than to the non-rewarded one. The action latency for the reinforced stimuli showed a significant decrease in the course of training. These data demonstrate that lobsters can be trained with the light cues of different intensity as discriminative stimuli under a restrained condition that would allow application of electrophysiological techniques to the behaving subjects.

  2. 29 CFR 101.37 - Application for temporary relief or restraining orders.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROCEDURES Procedure Under Section 10 (j) and (l) of the Act § 101.37 Application for temporary relief or restraining orders. Whenever it is deemed advisable to seek temporary injunctive relief under section 10(j)...

  3. 29 CFR 101.37 - Application for temporary relief or restraining orders.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROCEDURES Procedure Under Section 10 (j) and (l) of the Act § 101.37 Application for temporary relief or restraining orders. Whenever it is deemed advisable to seek temporary injunctive relief under section 10(j) or...

  4. The influence of air bags and restraining devices on extremity injuries in motor vehicle collisions.

    PubMed

    McGovern, M K; Murphy, R X; Okunski, W J; Wasser, T E

    2000-05-01

    The influence of air bags and other restraining devices on injury after motor vehicle collisions is not well defined. This study examined the relationship between the use of restraining devices and the incidence of extremity injuries in motor vehicle collisions. A retrospective analysis was performed on motor vehicle collision data submitted to the Pennsylvania Trauma Outcome Study database from 1990 through 1995. Criteria for submission included trauma patients who were admitted to the intensive care unit, who died during hospitalization, who were hospitalized for more than 72 hours, or who were transferred in or out of the receiving hospital. A total of 21,875 patients met these criteria. These patients were analyzed for the presence or absence of upper and lower extremity injuries and were compared based on their use of restraining devices. Restraining devices were categorized into four groups: air bag alone, air bag and seat belt, seat belt or carseat without air bag, and no restraining device. Statistical analysis was performed using the chi-squared test of association. For contingency tables with small expected frequencies, Fisher's exact test was used. Study participants included 11,688 men and 10,185 women with a mean age of 38 +/- 20 years. There were 16,033 drivers and 5,842 passengers. Air bags were deployed in 472 instances. In 297 of these cases, additional restraint was provided with a seat belt. In 6,632 cases, air bags were not deployed; however, patients were restrained with either a seat belt or a carseat. In 14,771 cases, patients were not restrained. When comparing restraining devices as a group vs. no restraint, there was a significant decrease in the incidence of upper (p = 0.018) and lower (p < 0.001) extremity injuries. Air bags, however, were associated with an increased incidence of both upper (p = 0.033) and lower (p = 0.002) extremity injuries when compared with no restraint or when compared among patients who were restrained. As a group

  5. Coordinated Control of a Planar Dual-Crane Non-Fully Restrained System

    DTIC Science & Technology

    2008-12-01

    varieties are found; from the basic yard and stay configuration to gantry -types and one of the most common, the wire-luffing jib crane as shown in...CONTROL OF A PLANAR DUAL- CRANE NON-FULLY RESTRAINED SYSTEM by Frank A. Leban December 2008 Dissertation Supervisor: Fotis Papoulias...Dissertation 4. TITLE AND SUBTITLE: Coordinated Control of a Planar Dual Crane Non- Fully Restrained System 6. AUTHOR(S) Frank A. Leban 5

  6. Smoking for weight control: effect of priming for body image in female restrained eaters.

    PubMed

    McKee, Sherry A; Nhean, Siphannay; Hinson, Riley E; Mase, Tricia

    2006-12-01

    Women are more likely than men to believe that smoking helps to control their weight, and this relationship may be more pronounced in those with eating disturbances, such as eating restraint. Restrained eaters have been shown to be more susceptible to media portrayals of idealized body image, like those used in tobacco advertising. The primary aim of this study was to examine the effect of an implicit prime for body image on expectations that smoking can control weight in restrained and non-restrained eaters. Participants were 40 females, who smoked an average of 7.65 (S.D.=4.38) cigarettes per day. Participants were presented with a bogus task of rating slides; either participants viewed 30 slides of nature scenes (neutral prime); or viewed 30 slides depicting fashion models (body image prime). Participants then completed questionnaires that assessed smoking expectancies, smoking history, and eating restraint. As hypothesized, restrained eaters who viewed the slides depicting models had greater likelihood ratings that smoking helps to control appetite and manage weight, in comparison to restrained eaters who viewed the control slides and non-restrained eaters who viewed either type of slides. There were no other group differences across the remaining smoking expectancy factors. Images similar to those used in tobacco advertising targeting women had the ability to elicit stronger beliefs that smoking is beneficial for weight control in a group of women who are at heightened risk for such beliefs.

  7. The control dilemma in eating behavior: influence of temptation cues in restrained versus unrestrained eaters.

    PubMed

    Peláez-Fernández, María Angeles; Extremera, Natalio

    2011-11-01

    The present research explored the effects of pre-exposure to temptation primes and dieting primes on food intake, goal accessibility and explicit automatic evaluations of food-enjoyment and dieting goals among restrained and unrestrained eaters. Participants (n= 166) were randomly assigned to three conditions: food-cue, dieting, or control, in which they were exposed to incidental presentation of gourmet, fashion or geographic magazines, respectively. Words related to the goals of dieting and/or food- enjoyment were presented in a computer decision task following the incidental presentation of gourmet, dieting, and geographic magazine photographs. The computer task and the presentation of food were counterbalanced. Participants' food intake was assessed in a taste-rating task. Restrained eaters ate more than did unrestrained eaters across the three conditions. Restrained eaters who were exposed to food cues ate more than did restrained eaters in the control condition and they evaluated the goal of dieting more negatively compared to restrained eaters in the other two conditions. These findings were inconsistent with 'Counteractive Self-Control Theory' but consistent with previous studies on the effects of food-cue exposure in restrained eaters.

  8. Food Antimicrobials Nanocarriers

    PubMed Central

    Blanco-Padilla, Adriana; Soto, Karen M.; Hernández Iturriaga, Montserrat

    2014-01-01

    Natural food antimicrobials are bioactive compounds that inhibit the growth of microorganisms involved in food spoilage or food-borne illness. However, stability issues result in degradation and loss of antimicrobial activity. Nanoencapsulation allows protection of antimicrobial food agents from unfavorable environmental conditions and incompatibilities. Encapsulation of food antimicrobials control delivery increasing the concentration of the antimicrobials in specific areas and the improvement of passive cellular absorption mechanisms resulted in higher antimicrobial activity. This paper reviews the present state of the art of the nanostructures used as food antimicrobial carriers including nanoemulsions, nanoliposomes, nanoparticles, and nanofibers. PMID:24995363

  9. Antimicrobial AApeptides

    PubMed Central

    Sang, Peng; Shi, Yan; Teng, Peng; Cao, Annie; Xu, Hai; Li, Qi; Cai, Jianfeng

    2017-01-01

    Antibiotic resistance is one of the biggest public concerns in the 21st century. Host-defense peptides (HDPs) can potentially mitigate the problem through bacterial membrane disruption; however, they suffer from moderate activity and low stability. We recently developed a new class of peptidomimetics termed “AApeptides”. This class of peptidomimetics can mimic the mechanism of action of HDPs, and effectively arrest the growth of multidrug resistant Gram-positive and Gram-negative bacteria. As they are built on unnatural backbone, they are resistant to proteolytic degradation. In this review, we summarize the development of this class of antimicrobial peptidomimetics, and discuss the future perspective on how they can move forward on combating antibiotic resistance. PMID:27758686

  10. Successful and unsuccessful restrained eating. Does dispositional self-control matter?

    PubMed

    Keller, Carmen; Siegrist, Michael

    2014-03-01

    In a random sample (N=1078) from the general population, this study examined whether individual differences in dispositional self-control can explain restrained eaters' success in controlling their weight. A regression analysis with body mass index (BMI) as dependent variable revealed a significant negative association between dispositional self-control and BMI, and a significant positive association between dietary restraint and BMI. These effects were qualified by a significant interaction between restraint and self-control. Among restrained eaters, the association between self-control and BMI was significantly more negative than among normal eaters. Furthermore, among female restrained eaters higher dispositional self-control scores were associated with BMIs within the normal-weight range (BMI<25) and lower dispositional self-control scores were associated with BMIs within the overweight range (BMI>25). Among male restrained eaters very high scores on dispositional self-control were associated with BMIs within the normal-weight range, whereas medium or low scores on self-control were associated with BMIs within the overweight range. Results suggest that high dispositional self-control facilitates successful restrained eating.

  11. Neogene development of the Swan Islands restraining-bend complex, Caribbean Sea

    NASA Astrophysics Data System (ADS)

    Mann, Paul; Tyburski, Stacey A.; Rosencrantz, Eric

    1991-08-01

    We present SeaMARC II and multichannel seismic data describing deformation at an active restraining-bend complex formed along a left-lateral strike-slip fault in the western Caribbean Sea. The bend complex consists of three distinct strike- slip fault traces that form two right-stepping "sharp restraining bends" or "push-ups" at its western end and form a right-stepping "gentle restraining bend" at its eastern end. Deformation at the sharp restraining bends is characterized by local folding between overlapping strike-slip faults. Deformation at the much larger gentle restraining bend consists of a large anticline adjacent to a gently curving strike-slip fault. A small, active accretionary wedge forms the northern flank of the bend complex. We speculate that the 30-km-wide, right-stepping bend complex formed as a consequence of southward propagation of the Mid-Cayman spreading center during Oligocene to early Miocene time. Active faults along the southern edge of the bend complex may have formed after the initial uplift and folding of the complex, and may currently serve to straighten the strike-slip fault by "bypassing" the bend complex.

  12. Differential effects of active and passive stress on food intake in restrained and unrestrained eaters.

    PubMed

    Lattimore, Paul; Caswell, Noreen

    2004-04-01

    This study examined the effects of active (AC) and passive coping (PC) stress tasks on food intake in female restrained (n = 20) and unrestrained eaters (n = 20) Participants completed a reaction time task (AC), a cold-pressor test (PC), and a relaxation control condition separated by 1-week intervals. Food intake was assessed after each task. Self-reported anxiety, heart rate and blood pressure (BP) were measured before and after each task. Restraint was measured using the Dutch Eating Behaviour Questionnaire. Significant increases in BP were evident in the AC task only. Stress tasks produced significant increases in self-rated anxiety. Restrained eaters consumed more than unrestrained following the reaction time task, while the opposite was observed following relaxation. The findings of this study show that disinhibited eating of restrained eaters can be triggered by the distracting effects of a cognitively demanding task and may be independent of anxiety experienced.

  13. PARTIAL RESTRAINING FORCE INTRODUCTION METHOD FOR DESIGNING CONSTRUCTION COUNTERMESURE ON ΔB METHOD

    NASA Astrophysics Data System (ADS)

    Nishiyama, Taku; Imanishi, Hajime; Chiba, Noriyuki; Ito, Takao

    Landslide or slope failure is a three-dimensional movement phenomenon, thus a three-dimensional treatment makes it easier to understand stability. The ΔB method (simplified three-dimensional slope stability analysis method) is based on the limit equilibrium method and equals to an approximate three-dimensional slope stability analysis that extends two-dimensional cross-section stability analysis results to assess stability. This analysis can be conducted using conventional spreadsheets or two-dimensional slope stability computational software. This paper describes the concept of the partial restraining force in-troduction method for designing construction countermeasures using the distribution of the restraining force found along survey lines, which is based on the distribution of survey line safety factors derived from the above-stated analysis. This paper also presents the transverse distributive method of restraining force used for planning ground stabilizing on the basis of the example analysis.

  14. Difficult Removal of Retrievable IVC Filters: A Description of the 'Double-Wire Restraining' Technique

    SciTech Connect

    Owens, Charles A. Bui, James T. Knuttinen, M.-Grace Emmanuel, Neelmini Carrillo, Tami C. Gaba, Ron C.

    2011-02-15

    We describe our experience with the use of the 'double-wire restraining' technique to assist in the removal of two retrievable inferior vena cava filters: one had been misplaced in the right brachiocephalic vein with apex perforation of the vessel wall, and the second filter had migrated cephalad to straddle across both renal veins. The 'double-wire restraining' technique consists of two stiff-shaft Glidewires (Terumo, Somerset, NJ) placed through the same introducer sheath and positioned on opposite sides of the filter. Both wires restrain the filter at the tip of the sheath as the sheath is advanced, thus allowing the operator to reposition the filter. This report details how this technique was used to realign two malpositioned filters and reposition the filter apices from their extravascular location, thus exposing them for ensnarement.

  15. Tasting fat: cephalic phase hormonal responses and food intake in restrained and unrestrained eaters.

    PubMed

    Crystal, Susan R; Teff, Karen L

    2006-09-30

    Restrained eaters exhibit strict cognitive control over their food intake, primarily by limiting intake of high-fat foods. Earlier studies indicate a relationship between dietary restraint and cephalic phase insulin release, which is hypothesized to influence hunger and food intake. To compare cephalic phase hormonal responses to high- and low-fat stimuli and determine if the sensory experience of tasting fat alters hormonal responses and influences subsequent food intake in restrained and unrestrained eaters, normal weight women classified as unrestrained (n=11) or restrained (n=11) eaters were tested under 3 conditions: (1) fasting, (2) sham-feeding a non-fat cake, and (3) sham-feeding a high-fat cake. Following an overnight fast, arterialized venous blood was drawn prior to and for 30 min immediately following a 3-min sham feed. Plasma samples were analyzed for insulin, glucose, glucagon and pancreatic polypeptide (PP). Subjects were subsequently given a selection of high-fat and low-fat foods and allowed to select what they wished to eat. Cephalic phase PP was significantly greater following oral sensory stimulation by the high-fat food (205.4+/-83.6) compared to the fasting control (11.1+/-38.8, p=0.04). No significant differences in hormonal responses to the food stimuli were found between restrained and unrestrained eaters but the restrained eaters consumed more food after the high-fat condition (p<0.05) relative to the fasted condition and compared to the unrestrained group (p<0.05). In conclusion, the sensory experience of tasting fat increases food intake in restrained eaters and increases vagal efferent activity compared to a non-fat food in both populations.

  16. Antimicrobial Drugs in Fighting against Antimicrobial Resistance

    PubMed Central

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i.e., mutation and horizontal gene transfer of resistance determinants), the community level resistance (i.e., bilofilms and persisters) is also an issue causing antimicrobial therapy difficulties. Therefore, anti-resistance and antibiofilm strategies have currently become research hotspot to combat antimicrobial resistance. Although metallic nanoparticles can both kill bacteria and inhibit biofilm formation, the toxicity is still a big challenge for their clinical applications. In conclusion, rational use of the existing antimicrobials and combinational use of new strategies fighting against antimicrobial resistance are powerful warranties to preserve potent antimicrobial drugs for both humans and animals. PMID:27092125

  17. Watching food-related television increases caloric intake in restrained eaters.

    PubMed

    Shimizu, Mitsuru; Wansink, Brian

    2011-12-01

    While watching 30-min television (TV) programs that contained either food-related content or non-food-related content, participants were asked to eat two types of candy by explicitly being told that we were interested in how the TV program influenced their taste and therefore they needed to consume some of those candies. The results indicated that there was no overall difference in candy intake based on the TV content; however, the association was moderated by their restrained eating status. Restrained eaters ate more calories while watching a food-related TV program whereas unrestrained eaters were not influenced by the content of the TV program.

  18. Buckling analysis of fully anisotropic plates containing cutouts and elastically restrained edges

    NASA Technical Reports Server (NTRS)

    Jones, Kevin M.; Klang, Eric C.

    1992-01-01

    An analysis is developed which combines the Ritz and collocation methods for the stability solution of an anisotropic plate with a cutout and elastically restrained edges. Results are presented which agree closely with experiment for isotropic and orthotropic materials. Results are also given for restrained anisotropic plates with circular holes loaded in compression and shear. Difference is noted in the critical buckling loads between displacement and stress loaded panels as hole size is increased. Clamping is also seen to affect the trends in buckling associated with hole size.

  19. Antimicrobial Treatments and Efficacy

    EPA Science Inventory

    To limit exposure to indoor biological contamination a risk-management approach which employs various antimicrobial treatments can effectively control contaminants and reduce exposure. Antimicrobial treatment of biological contaminants, especially mold in buildings, it is often n...

  20. Antimicrobial Treatments and Efficacy

    EPA Science Inventory

    To limit exposure to indoor biological contamination a risk-management approach which employs various antimicrobial treatments can effectively control contaminants and reduce exposure. Antimicrobial treatment of biological contaminants, especially mold in buildings, it is often n...

  1. Antimicrobial Acrylic Fiber

    DTIC Science & Technology

    2006-08-01

    other than Government procurement does not in any way obligate the U.S. Government. The fact that the Government formulated or supplied the drawings...rendered antimicrobial. The ability to regenerate the halamines (and the antimicrobial functionality) lasted through 50 home laundry washings. The...antimicrobial. The ability to regenerate the halamines (and the antimicrobial functionality) lasted through 50 home laundry washings. The chlorine

  2. Similar Odor Discrimination Behavior in Head-Restrained and Freely Moving Mice

    PubMed Central

    Abraham, Nixon M.; Guerin, Delphine; Bhaukaurally, Khaleel; Carleton, Alan

    2012-01-01

    A major challenge in neuroscience is relating neuronal activity to animal behavior. In olfaction limited techniques are available for these correlation studies in freely moving animals. To solve this problem, we developed an olfactory behavioral assay in head-restrained mice where we can monitor behavioral responses with high temporal precision. Mice were trained on a go/no-go operant conditioning paradigm to discriminate simple monomolecular odorants, as well as complex odorants such as binary mixtures of monomolecular odorants or natural odorants. Mice learned to discriminate both simple and complex odors in a few hundred trials with high accuracy. We then compared the discrimination performance of head-restrained mice to the performance observed in freely moving mice. Discrimination accuracies were comparable in both behavioral paradigms. In addition, discrimination times were measured while the animals performed well. In both tasks, mice discriminated simple odors in a few hundred milliseconds and took additional time to discriminate the complex mixtures. In conclusion, mice showed similar and efficient discrimination behavior while head-restrained compared with freely moving mice. Therefore, the head-restrained paradigm offers a relevant approach to monitor neuronal activity while animals are actively engaged in olfactory discrimination behaviors. PMID:23272168

  3. Disarming Batterers through Restraining Orders: The Promise and the Reality in California

    ERIC Educational Resources Information Center

    Seave, Paul L.

    2006-01-01

    Laws that prohibit persons under a domestic violence restraining order from purchasing or possessing a firearm are a primary way to keep guns out of the hands of batterers. In July 2005, the California Attorney General's Task Force on the Local Criminal Justice Response to Domestic Violence issued a report called Keeping the Promise: Victim Safety…

  4. Disarming Batterers through Restraining Orders: The Promise and the Reality in California

    ERIC Educational Resources Information Center

    Seave, Paul L.

    2006-01-01

    Laws that prohibit persons under a domestic violence restraining order from purchasing or possessing a firearm are a primary way to keep guns out of the hands of batterers. In July 2005, the California Attorney General's Task Force on the Local Criminal Justice Response to Domestic Violence issued a report called Keeping the Promise: Victim Safety…

  5. High-disinhibition restrained eaters are disinhibited by self-regulatory depletion in the food-related inhibitory control.

    PubMed

    Zhou, Yizhou; Gao, Xiao; Chen, Hong; Kong, Fanchang

    2017-08-01

    Restrained eating for weight control and loss is becoming highly prevalent in many affluent societies, while most of the restrained eaters are rather unsuccessful in the long term. According to the strength model of self-control, the disinhibition effect of restrained eaters may occur after the depletion of self-control resources. However, no work has examined the direct impact of self-control resources on inhibitory control ability of restrained eaters. This study investigated the influences of self-control resources on the food-related inhibitory control among high-restraint/low-disinhibition restrained eaters, high-restraint/high-disinhibition restrained eaters and unrestrained eaters using stop signal task. Results reveal that there's no difference of food-related inhibitory control between three groups when the self-control resources are non-depleted, while high-restraint/high-disinhibition restrained eaters showing a decrease of food-related inhibitory control after ego-depletion. This disinhibition effect only seems to occur in samples of restrained eaters with a high tendency toward overeating. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Kinematics in and around restraining bends in strike-slip faults from numerical models

    NASA Astrophysics Data System (ADS)

    Hilley, G. E.; Gudmundsdottir, M. H.

    2013-12-01

    The kinematics in and around crustal-scale restraining bends in strike-slip faults result from accrued contraction within restraining structures and long-term horizontal advection of material through these features. This contribution examines these kinematics using mechanical models of upper-crustal deformation. Specifically, we use the Gale finite-element model to examine the evolution of uplift within, and structures surrounding restraining bends as a function of the frictional and cohesive properties of each crustal block that is separated by a strike-slip shear zone. The three-dimensional geometry of the model bend was defined by the restraining-bend angle, the step-over width of the restraining bend, and the thickness of the crust. A Drucker-Prager constitutive rule was used to approximate frictional failure within the shear zone and surrounding crustal blocks. Values of friction, cohesion, and strain-weakened cohesion and friction were assigned to each block, while small values of these parameters were used to simulate a weak, narrow (but finite width) strike-slip shear zone. The model was driven by imposing shear and normal velocities along the model sides and ends, respectively, to produce overall right-lateral shear across the model. Dimensional geometric parameters and constitutive properties were non-dimensionalized using the crustal depth as a length-scale, density of crustal material to scale the mass, and the boundary velocities as a time-scale in the model. Model behavior was thus reduced to sixteen dimensionless groups that uniquely define the geometry and constitutive properties of model elements. We varied fault step-over geometry, the thickness of the crust relative to the step-over width, step-over angle, strain-weakening parameters, and relative friction and cohesion values of the two model blocks to examine how these parameters affect the way in which strain is localized around the restraining bend as remote displacements accrue. First, we

  7. Neural correlates of restrained eaters' high susceptibility to food cues: An fMRI study.

    PubMed

    Wang, Yu; Dong, Debo; Todd, Jackson; Du, Jie; Yang, Zhou; Lu, Hui; Chen, Hong

    2016-09-19

    Many studies have reported that specific susceptibility to food cues plays an important role in disordered eating behavior. However, whether restraint status modulates the neural bases of attentional bias to different types of food cues remains unknown. Thus, functional magnetic resonance imaging (fMRI) was conducted in individuals (12 restraint eaters, 12 unrestraint eaters) exposed to high/low-energy food and neutral images while performing a two-choice oddball task. The results indicated that restrained eaters responded more quickly to high-energy food images than to neutral and low-energy food images. More notably, compared with unrestrained eaters, restrained eaters showed faster reaction times, hyper-activation in a much wider array of reward (e.g., insula/orbitofrontal cortex), attention (superior frontal gyrus) and visual processing (e.g., superior temporal gyrus) regions, and hypo-activation in cognitive control areas (e.g., anterior cingulate) in response to high-energy food cues. Furthermore, among restrained eaters, the longest reaction times were found for low-energy food images, and activation of the attention and visual-related cortex (e.g., superior parietal gyrus) in the low-neutral contrast condition was significantly stronger than in unrestrained eaters. These findings contribute to our understanding of susceptibility to food cues: in addition to the special sensitivity (attentional bias) to high-energy food images, restrained eaters may also be more sensitive (allocate more attentional resources) to low-energy food images. These potential neural bases of restrained eaters may help clarify why dieting to lose or maintain weight is so often unsuccessful. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Anti-antimicrobial Peptides

    PubMed Central

    Ryan, Lloyd; Lamarre, Baptiste; Diu, Ting; Ravi, Jascindra; Judge, Peter J.; Temple, Adam; Carr, Matthew; Cerasoli, Eleonora; Su, Bo; Jenkinson, Howard F.; Martyna, Glenn; Crain, Jason; Watts, Anthony; Ryadnov, Maxim G.

    2013-01-01

    Antimicrobial or host defense peptides are innate immune regulators found in all multicellular organisms. Many of them fold into membrane-bound α-helices and function by causing cell wall disruption in microorganisms. Herein we probe the possibility and functional implications of antimicrobial antagonism mediated by complementary coiled-coil interactions between antimicrobial peptides and de novo designed antagonists: anti-antimicrobial peptides. Using sequences from native helical families such as cathelicidins, cecropins, and magainins we demonstrate that designed antagonists can co-fold with antimicrobial peptides into functionally inert helical oligomers. The properties and function of the resulting assemblies were studied in solution, membrane environments, and in bacterial culture by a combination of chiroptical and solid-state NMR spectroscopies, microscopy, bioassays, and molecular dynamics simulations. The findings offer a molecular rationale for anti-antimicrobial responses with potential implications for antimicrobial resistance. PMID:23737519

  9. [Antimicrobial prophylaxis in surgery].

    PubMed

    Cisneros, José Miguel; Rodríguez-Baño, Jesús; Mensa, José; Trilla, Antoni; Cainzos, Miguel

    2002-01-01

    Antimicrobial prophylaxis in surgery refers to a very brief course of an antimicrobial agent initiated just before the start of the procedure. The efficacy of antimicrobials to prevent postoperative infection at the site of surgery (incisional superficial, incisional deep, or organ/space infection) has been demonstrated for many surgical procedures. Nevertheless, the majority of studies centering on the quality of preoperative prophylaxis have found that a high percentage of the antimicrobials used are inappropriate for this purpose. This work discusses the scientific basis for antimicrobial prophylaxis, provides general recommendations for its correct use and specific recommendations for various types of surgery. The guidelines for surgical antimicrobial prophylaxis are based on results from well-designed studies, whenever possible. These guidelines are focussed on reducing the incidence of infection at the surgical site while minimizing the contribution of preoperative administration of antimicrobials to the development of bacterial resistance.

  10. Reworking of structural inheritance at strike-slip restraining-bends: templates from sandbox analogue models

    NASA Astrophysics Data System (ADS)

    Nestola, Yago; Storti, Fabrizio; Cavozzi, Cristian; Magistroni, Corrado; Meda, Marco; Piero Righetti, Fabrizio

    2016-04-01

    Structural inheritance plays a fundamental role during crustal deformation because pre-existing fault and shear zones typically provide weakness zone suitable to fail again when affected by a new regional stress field. Re-activation of structural inheritance is expected to unavoidably increase the complexity of structural architectures, whose geometric and kinematic patterns can significantly deviate from what expected in newly deformed crustal sectors. Availability of templates from analogue models can provide a very effective tool to help unraveling such a structural complexity. For this purpose, we simulated the reworking of a set of basement hosted pre-existing fault zones at strike-slip restraining fault bends. In the models, the mechanical stratigraphy consists of a basement, made of a mixture of dry kaolin and sand to slightly increase cohesion, and a sedimentary cover made by pure dry sand. Inherited fault zones are confined to the basement and coated by a thin veneer of silicone putty. In the experimental programme, the geometry of the left-lateral restraining bend is maintained the same, with a bending angle of 30° of the restraining fault segment. The strike of the inherited fault zones, measured counterclockwise with respect to that of the master strike-slip fault zone outside the restraining bend, was 0°, 30°, and 60° in different experiments, respectively. An end member experiment without inheritance was also run for comparison. Our experimental results show that the angle that the inherited fault zones make with the restraining bend plays a fundamental role in governing the deformation pattern. When structural inheritance is near parallel to the master strike-slip fault zone, synthetic shears form and severely compartmentalize the transpressional pop-up anticline growing on top of the restraining bend. Fault-bounded blocks undergo sinistral escape during transpression. On the other hand, when structural inheritance makes a high angle to the

  11. Investigation on frictional characteristics and drawbead restraining force of steel with/without coating

    NASA Astrophysics Data System (ADS)

    Chen, Lianfeng; Zheng, Tianran; Chen, Qing; Zhang, Jun

    2013-12-01

    Advanced high strength steels (AHSS) are used more and more in automotive industry for increasing crashworthiness and weight reduction. Improving metal flow and reduce friction are important to forming the part and decrease part reject rates of AHSS. The present study focused on friction characteristics and drawbead restraining force of Dual Phase (DP) steels with or without coating, such as DP980, DP780, DP590, DP780+Z, DP780+ZF, DP590+Z, using experimental approach. The effect of material properties, temperature, sliding velocity, surface roughness, dry and lubricant on friction behavior of DP steels is investigated. The contrast of DP steels with mild IF steel is carried out. The restraining force draw through different radius of drawbead is evaluated. This study is benefit to the set up of technique parameters during sheet metal forming simulation.

  12. The danger signal S100B integrates pathogen- and danger-sensing pathways to restrain inflammation.

    PubMed

    Sorci, Guglielmo; Giovannini, Gloria; Riuzzi, Francesca; Bonifazi, Pierluigi; Zelante, Teresa; Zagarella, Silvia; Bistoni, Francesco; Donato, Rosario; Romani, Luigina

    2011-03-01

    Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen- and danger-sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen-induced inflammation and a pathogen-sensing mechanism resolves danger-induced inflammation.

  13. Impact response of restrained PMHS in frontal sled tests: skeletal deformation patterns under seat belt loading.

    PubMed

    Shaw, Greg; Parent, Dan; Purtsezov, Sergey; Lessley, David; Crandall, Jeff; Kent, Richard; Guillemot, Herve; Ridella, Stephen A; Takhounts, Erik; Martin, Peter

    2009-11-01

    This study evaluated the response of restrained post-mortem human subjects (PMHS) in 40 km/h frontal sled tests. Eight male PMHS were restrained on a rigid planar seat by a custom 3-point shoulder and lap belt. A video motion tracking system measured three-dimensional trajectories of multiple skeletal sites on the torso allowing quantification of ribcage deformation. Anterior and superior displacement of the lower ribcage may have contributed to sternal fractures occurring early in the event, at displacement levels below those typically considered injurious, suggesting that fracture risk is not fully described by traditional definitions of chest deformation. The methodology presented here produced novel kinematic data that will be useful in developing biofidelic human models. Additional analysis of the data produced by the reported tests as well as additional tests with a variety of loading conditions are required to fully characterize torso response including ribcage fracture tolerance.

  14. Relationship of dieting and restrained eating to self-reported caloric intake in female college freshmen.

    PubMed

    Goldstein, Stephanie P; Katterman, Shawn N; Lowe, Michael R

    2013-04-01

    Evidence indicates that restrained eaters do not eat less than unrestrained eaters in the natural environment. However, no study has examined caloric intake in those who are currently dieting to lose, or avoid gaining, weight. The current study examined caloric intake using 24-hour food recalls among individuals dieting to lose weight, dieting to avoid weight gain, restrained nondieters, and unrestrained nondieters. Participants were 246 female college students participating in a weight gain prevention trial. The predicted significant difference in caloric intake across the four groups was found for beverage but not for food intake. Results reinforce past literature indicating that dieting/restraint status does not reflect hypo-caloric intake in naturalistic settings.

  15. Block-restraining of residual dipolar couplings to allow fluctuating relative alignments of molecular subdomains.

    PubMed

    Wirz, Lukas N; Allison, Jane R

    2017-02-20

    Residual dipolar couplings (RDCs), unlike most other types of NMR observables, provide orientational information, reporting on the alignment of inter-spin vectors (ISVs) relative to the magnetic field. A great challenge in using experimental RDCs to restrain molecular dynamics (MD) simulations is how to represent this alignment. An alignment tensor is often used to parameterise the contribution of molecular alignment to the angular dependence of RDCs. All ISVs that share the same tensor have fixed relative alignment, i.e. if just one tensor is used, the molecule is internally rigid. Here we propose and illustrate a method for subdividing molecules into individually aligned blocks during MD simulations restrained to fit RDCs. This allows the relative orientation of each block to vary during the simulation, which in turn ensures that the internal structure of each block is more realistically reproduced.

  16. Antimicrobial applications of copper.

    PubMed

    Vincent, Marin; Hartemann, Philippe; Engels-Deutsch, Marc

    2016-10-01

    Copper has long been known to have antimicrobial activity and is used in drinking water treatment and transportation. It has been recognized by the American Environmental Protection Agency as the first metallic antimicrobial agent in 2008. With ongoing waterborne hospital-acquired infections and antibiotic resistance, research on copper as an antimicrobial agent is again very attractive. Many studies have shown that the use of copper surface and copper particles could significantly reduce the environmental bioburden. This review highlights in its first part all the conditions described in the literature to enhance copper antimicrobial activity. Secondly, the different antimicrobial applications of copper in water treatment, hospital care units and public applications are presented. Finally, the future research needs on copper as an antimicrobial agent are discussed. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. Effects of restrained eating behaviour on insulin sensitivity in normal-weight individuals.

    PubMed

    Martins, C; Morgan, L M; Robertson, M D

    2009-03-23

    Restrained eating behaviour has been linked to abnormalities in metabolic and endocrine functions. However, the impact of restraint on fasting insulin and glucose plasma levels and insulin sensitivity remains controversial. Moreover, the few postprandial studies to date are limited by an inappropriate sampling time frame and a low "net" energy and carbohydrate load. The aims of this study are to assess the role of dietary restraint on fasting and postprandial plasma levels of insulin, glucose, triacylglycerol (TAG) and non esterified fatty acids (NEFA) in healthy volunteers with a normal and stable body weight and to determine whether the effect of restraint on the plasma levels of the previous hormones/metabolites is load dependent. Normal-weight participants (21 women and 12 men) were classified as restrained/unrestrained based on the restraint scale of the Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint on the plasma levels of different hormones/metabolites was measured, in response to a 500 kcal and 1000 kcal breakfast, using a randomised crossover design. Restraint was associated with lower fasting insulin plasma levels (P<0.05) and a lower insulin (P<0.015) and glucose (P<0.05) plasma levels in the postprandial state, but did not impact on TAG or NEFA. Moreover, restrained eaters showed a better fasting (P<0.05) and postprandial insulin sensitivity (P<0.01). Restrained eating behaviour has, therefore, a significant impact on both fasting and postprandial glucose metabolism, being associated with increased insulin sensitivity. These findings suggest the need for adjusting for restraint level in studies where glucose metabolism is a major outcome.

  18. Antimicrobials in beekeeping.

    PubMed

    Reybroeck, Wim; Daeseleire, Els; De Brabander, Hubert F; Herman, Lieve

    2012-07-06

    The bee diseases American and European foulbrood and nosemosis can be treated with anti-infectious agents. However, in the EU and the USA the use of these agents in beekeeping is strictly regulated due to the lack of tolerance (e.g. Maximum Residue Limit) for residues of antibiotics and chemotherapeutics in honey. This article reviews the literature dealing with antimicrobials of interest in apiculture, stability of these antimicrobials in honey, and disposition of the antimicrobials in honeybee hives.

  19. In-Situ-measurement of restraining forces during forming of rectangular cups

    NASA Astrophysics Data System (ADS)

    Singer, M.; Liewald, M.

    2016-11-01

    This contribution introduces a new method for evaluating the restraining forces during forming of rectangular cups with the goal of eliminating the disadvantages of the currently used scientifically established measurement procedures. With this method forming forces are measured indirectly by the elastic deformation of die structure caused by locally varying tribological system. Therefore, two sensors were integrated into the punch, which measure the restraining forces during the forming process. Furthermore, it was possible to evaluate the effects of different lubricants showing the time dependent trend as a function of stroke during the forming of the materials DP600 and DC04. A main advantage of this testing method is to get real friction corresponding data out of the physical deep drawing process as well as the measurement of real acting restraining forces at different areas of the deep drawing part by one single test. Measurement results gained by both sensors have been integrated into LS-Dyna simulation in which the coefficient of friction was regarded as a function of time. The simulated and deep drawn parts afterwards are analysed and compared to specific areas with regard to locally measured thickness of part. Results show an improvement of simulation quality when using locally varying, time dependent coefficients of friction compared to commonly used constant values.

  20. 3-D Coupled FE Analysis and Experimental Validation of Restrained Welding to Control Angular Distortion

    NASA Astrophysics Data System (ADS)

    Damale, A. V.; Nandurkar, K. N.

    2012-10-01

    Welding induced distortion is one of the critical defects in the welded structures. Angular distortion is most pronounced which badly affects the welded structures. Non-uniform heating during welding develops this angular distortion. Various methods are available to control/minimize the welding distortions. One of the methods available to control this distortion is restraining, in which clamping pressure is applied on the deforming edges of the plates. In the present study, a 3-dimensional coupled transient thermal analysis is done for simulating the restraining phenomenon of welding. The developed transient thermal heat source was used to simulate the arc welding phenomenon. The element birth and death technique was used for simulating filler material deposition. Thermal model was verified by comparing the macrograph of Finite Element Analysis (FEA) model and the weld and verification of structural model was done by comparing the measured and predicted angular distortions. Experimental and Finite Element (FE) analysis is done for both conventional welding and welding under restraining pressure. Transient thermal and non-linear structural analyses were carried out in order to predict angular distortions. The Finite Element Method analysis and experimental verification is done for manual metal arc welding process.

  1. Restrained eating in overweight children: does eating style run in families?

    PubMed

    Munsch, Simone; Hasenboehler, Kathrin; Michael, Tanja; Meyer, Andrea H; Roth, Binia; Biedert, Esther; Margraf, Juergen

    2007-01-01

    Overweight children show abnormalities in eating style, such as restrained eating and tendency toward overeating (comprising both emotional and external eating). Family surroundings play a major role in developing eating behaviors in children. We tested whether restrained eating and tendency toward overeating predicted the amount of food intake in 41 overweight children (23 girls and 18 boys) and their parents (40 mothers and 11 fathers) after receiving a preload. We further investigated with questionnaires whether there were associations between the parents' and their children's eating behavior and whether mothers' food intake predicted the amount of food consumed by children in an experimental trial. We found that neither children with restrained eating nor their mothers ate more after a preload, but children with a high tendency toward overeating ate somewhat more after receiving a preload. Further analyses showed that children's food intake in the preload paradigm was predicted by mothers' food intake. Our findings point to a familial transmission of eating styles: children eat as their primary caregivers do, even when the caregivers are not present in the laboratory.

  2. Heat capacity and nuclear magnetic relaxation times of non-freezing water restrained by polysaccharides, revisited.

    PubMed

    Hatakeyama, Tatsuko; Hatakeyama, Hyoe

    Calorimetric and nuclear magnetic relaxation studies on non-freezing water restrained by polysaccharide are introduced together with the historical background of this research field. Non-freezing water restrained by the hydrophilic group of polysaccharide shows no first order thermodynamic phase transition. The amount of non-freezing water calculated from the melting enthalpy of water restrained by various kinds of polysaccharides was collected. Molecular motion of polysaccharides is markedly enhanced by the introduction of non-freezing water and glass transition shifts to the ca. 200 K low temperature side. At the same time, molecular chains rearrange to a more stabilized state, which can be observed as the decrease in heat capacities. (1)H nuclear magnetic relaxation studies at a temperature lower than glass transition indicate that a part of the water molecules is closely bound to the backbone proton and is not sufficiently isolated. Calorimetric and nuclear magnetic relaxation studies suggest that non-freezing water inevitably cooperates with matrix polysaccharide molecules.

  3. Experimental Tests of a Real Building Seismically Retrofitted by Special Buckling-Restrained Braces

    SciTech Connect

    D'Aniello, Mario; Della Corte, Gaetano; Mazzolani, Federico M.

    2008-07-08

    Buckling Restrained Braces (BRBs), differently from conventional braces, do not exhibit appreciable difference between the tensile and compression capacity and no strength degradation of brace capacity under compressive and cyclic loading. Since lateral and local buckling behaviour modes are restrained, large inelastic capacities are attainable. Hence, BRBs may represent an efficient and reliable solution for reducing the seismic vulnerability of buildings. Results of experimental tests on the response of a real two-story reinforced concrete (RC) building equipped with BRBs are presented and discussed. The considered BRBs are a special 'only-steel' version of the more common 'unbonded braces'. In particular, two different BRBs have been tested. Both of them are detachable 'only-steel' devices, consisting in a rectangular steel plate and a restraining steel sleeve. The latter is composed by two omega shapes which are bolted together. The main characteristic of the braces consists in the possibility to hide them within the space between the facing and the backing of masonry infill walls commonly used for RC buildings.

  4. Positive fantasies or negative contrasts: the effect of media body ideals on restrained eaters' mood, weight satisfaction, and food intake.

    PubMed

    Boyce, Jessica A; Kuijer, Roeline G; Gleaves, David H

    2013-09-01

    Although viewing media body ideals promotes body dissatisfaction and problematic eating among women (e.g., extreme restraint/overeating), some argue that women only report such negative effects because they think that they are meant to (i.e., demand characteristics). Because restrained eaters are trying to lose weight, they might be vulnerable to such media exposure. However, because of demand characteristics, evidence is mixed. Therefore, we minimized demand characteristics and explored whether media body ideals would trigger restrained eaters to report negative (negative mood, weight dissatisfaction) or positive (positive mood, weight satisfaction) effects. We also hypothesized that this change (negative or positive) would encourage food intake. Restrained and unrestrained eaters (n=107) memorized media or control images. Restrained eaters exposed to media images reported decreased weight satisfaction and increased negative mood, but their food intake was not significantly affected. Perhaps paying advertent attention to the images caused goal-related negative affect, which triggered restraint.

  5. Experimental study of a highway bridge with shape memory alloy restrainers focusing on the mitigation of unseating and pounding

    NASA Astrophysics Data System (ADS)

    Guo, Anxin; Zhao, Qingjie; Li, Hui

    2012-03-01

    This paper presents an experimental study to investigate the performance of shape memory alloy (SMA) restrainers for mitigating the pounding and unseating of highway bridges when subjected to seismic excitations. Mechanical property tests of the SMA wire used in the restrainers are conducted first to understand the pseudo-elastic characteristics of the material. Then, a series of shaking table tests are carried out on a highway bridge model. The structural responses of the highway bridge model equipped with SMA restrainers, installed in the form of deck-deck and deck-pile connections, are analyzed and compared with the uncontrolled structures. The test results of this study indicate that the SMA restrainers are not only effective in preventing unseating but also in suppressing the seismic-induced pounding of the highway bridge model used in this study.

  6. Antimicrobial Peptides in 2014

    PubMed Central

    Wang, Guangshun; Mishra, Biswajit; Lau, Kyle; Lushnikova, Tamara; Golla, Radha; Wang, Xiuqing

    2015-01-01

    This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms. PMID:25806720

  7. Alternative Antimicrobial Approach: Nano-Antimicrobial Materials

    PubMed Central

    Beyth, Nurit; Houri-Haddad, Yael; Domb, Avi; Khan, Wahid; Hazan, Ronen

    2015-01-01

    Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail. PMID:25861355

  8. Antimicrobial prophylaxis in adults.

    PubMed

    Enzler, Mark J; Berbari, Elie; Osmon, Douglas R

    2011-07-01

    Antimicrobial prophylaxis is commonly used by clinicians for the prevention of numerous infectious diseases, including herpes simplex infection, rheumatic fever, recurrent cellulitis, meningococcal disease, recurrent uncomplicated urinary tract infections in women, spontaneous bacterial peritonitis in patients with cirrhosis, influenza, infective endocarditis, pertussis, and acute necrotizing pancreatitis, as well as infections associated with open fractures, recent prosthetic joint placement, and bite wounds. Perioperative antimicrobial prophylaxis is recommended for various surgical procedures to prevent surgical site infections. Optimal antimicrobial agents for prophylaxis should be bactericidal, nontoxic, inexpensive, and active against the typical pathogens that can cause surgical site infection postoperatively. To maximize its effectiveness, intravenous perioperative prophylaxis should be administered within 30 to 60 minutes before the surgical incision. Antimicrobial prophylaxis should be of short duration to decrease toxicity and antimicrobial resistance and to reduce cost.

  9. Denali in a box: analog experiments modeled after a natural setting provide insight on gentle restraining bend deformation

    NASA Astrophysics Data System (ADS)

    Fendick, Anne; Bemis, Sean; Toeneboehn, Kevin; Cooke, Michele; Benowitz, Jeff

    2016-04-01

    Despite restraining bends along strike-slip faults creating zones of focused uplift, the relative contributions from parameters such as fault geometry and scale, obliquity, rheological contrasts, and deformation rates are not well-constrained. Similarities between simple analog models (conducted with homogenous materials) and natural restraining bend systems (typically associated with heterogeneous crust) suggest that there are first-order controls on restraining bend deformation that operate independent of heterogeneity in the upper crust. To investigate these controls we examine the Mount McKinley restraining bend (MMRB) of the Denali fault system in south-central Alaska. The MMRB is associated with an ~18 degree bend in the Denali fault and exhibits strongly asymmetric topography and rock uplift. The viscous relaxation time and the ratio of crustal thickness to the restraining bend stepover distance are scaled within the analog model to that of the MMRB. We compare uplift patterns, localization of deformation, formation of new faults, and displacement fields for the model set up and the natural bend to understand the influence of different variables on the overall system to determine what controls the deformation. As shown in previous analog model studies, asymmetric topography characteristically forms with restraining bend angles of <20°. In our model, a continuous, through-going fault within the restraining bend accompanies a narrow zone of deformation on one side of the bend and a broader zone of deformation the opposite side. However, the active thrust faults of the MMRB are purely dip-slip, whereas the thrust faults formed in the model appear to be oblique-slip. The geometry and slip rates of active faults in the MMRB, as well as preliminary thermochronometric data, suggest that the restraining bend itself is migrating relative to previously deformed deposits. Conventional understanding of restraining bends is that fixed bends produce the highest

  10. Solid-State NMR-Restrained Ensemble Dynamics of a Membrane Protein in Explicit Membranes.

    PubMed

    Cheng, Xi; Jo, Sunhwan; Qi, Yifei; Marassi, Francesca M; Im, Wonpil

    2015-04-21

    Solid-state NMR has been used to determine the structures of membrane proteins in native-like lipid bilayer environments. Most structure calculations based on solid-state NMR observables are performed using simulated annealing with restrained molecular dynamics and an energy function, where all nonbonded interactions are represented by a single, purely repulsive term with no contributions from van der Waals attractive, electrostatic, or solvation energy. To our knowledge, this is the first application of an ensemble dynamics technique performed in explicit membranes that uses experimental solid-state NMR observables to obtain the refined structure of a membrane protein together with information about its dynamics and its interactions with lipids. Using the membrane-bound form of the fd coat protein as a model membrane protein and its experimental solid-state NMR data, we performed restrained ensemble dynamics simulations with different ensemble sizes in explicit membranes. For comparison, a molecular dynamics simulation of fd coat protein was also performed without any restraints. The average orientation of each protein helix is similar to a structure determined by traditional single-conformer approaches. However, their variations are limited in the resulting ensemble of structures with one or two replicas, as they are under the strong influence of solid-state NMR restraints. Although highly consistent with all solid-state NMR observables, the ensembles of more than two replicas show larger orientational variations similar to those observed in the molecular dynamics simulation without restraints. In particular, in these explicit membrane simulations, Lys(40), residing at the C-terminal side of the transmembrane helix, is observed to cause local membrane curvature. Therefore, compared to traditional single-conformer approaches in implicit environments, solid-state NMR restrained ensemble simulations in explicit membranes readily characterize not only protein

  11. Distributed and Localized Deformation Along the Lebanese Restraining Bend from Geomorphic Observations and Modeling

    NASA Astrophysics Data System (ADS)

    Goren, L.; Castelltort, S.; Klinger, Y.

    2014-12-01

    The Dead Sea Fault System changes its orientation across Lebanon and forms a restraining bend. The oblique deformation along the Lebanese restraining bend is characterized by a complex suite of tectonic structures, among which, the Yammouneh Fault (YF), is believed to be the main strand that relays deformation from the southern section to the northern section of the Dead Sea Fault System. However, uncertainties regarding slip rates and strain partitioning in Lebanon still prevail. Here, we use morphometric analysis together with analytical and numerical models to constrain rates and modes of distributed and localized deformation along the Lebanese restraining bend.The rivers that drain the western flank of Mount Lebanon show a consistent counterclockwise rotation with respect to an expected orogen perpendicular orientation. Moreover, a pattern of divide disequilibrium in between these rivers emerges from an application of the χ mapping technique, which aims at estimating the degree of geometrical and topological disequilibrium in river networks. These geometrical patterns are compatible with simulation results using a landscape evolution model, which imposes a distributed velocity field along a domain that represents the western flank of Mount Lebanon. We further develop an analytical model that relates the river orientation to a set of kinematic parameters that represents a combined pure and simple shear strain field, and we find the parameters that best explain the present orientation of the western Lebanon rivers. Our results indicate that distributed deformation to the west of the YF takes as much as 30% of the relative Arabia-Sinai plate velocity since the late Miocene, and that the average slip rate along the YF during the same time interval has been 3.8-4.4 mm/yr. The theoretical model can further explain the inferred rotation from Paleomagnetic measurements.

  12. Antimicrobial Peptides in Reptiles

    PubMed Central

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  13. Column strength of tubes elastically restrained against rotation at the ends

    NASA Technical Reports Server (NTRS)

    Osgood, William R

    1938-01-01

    Report presents the results of a study made of the effects of known end restraint on commercially available round and streamline tubing of chromium-molybdenum steel, duralumin, stainless steel, and heat-treated chromium-molybdenum steel; and a more accurate method than any previously available, but still a practical method, was developed for designing compression members in riveted or welded structures, particularly aircraft. Two hundred specimens were tested as short, medium-length, and long columns with freely supported ends or elastically restrained ends. Tensile and compressive tests were made on each piece of original tubing from which column specimens were cut.

  14. DisVis: quantifying and visualizing accessible interaction space of distance-restrained biomolecular complexes.

    PubMed

    van Zundert, G C P; Bonvin, A M J J

    2015-10-01

    We present DisVis, a Python package and command line tool to calculate the reduced accessible interaction space of distance-restrained binary protein complexes, allowing for direct visualization and quantification of the information content of the distance restraints. The approach is general and can also be used as a knowledge-based distance energy term in FFT-based docking directly during the sampling stage. The source code with documentation is freely available from https://github.com/haddocking/disvis. a.m.j.j.bonvin@uu.nl Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  15. Response to selection for decreased backfat thickness at restrained intramuscular fat content in Duroc pigs.

    PubMed

    Ros-Freixedes, R; Reixach, J; Bosch, L; Tor, M; Estany, J

    2013-08-01

    Intramuscular fat (IMF) content is a relevant trait for the pig industry and consumers. However, selection for IMF has the undesired correlated effect of decreasing lean growth. A selection experiment was performed to investigate the effects of selection against backfat thickness (BT) at restrained IMF. Barrows from a purebred Duroc line were allocated into a selected (n = 165) or a control (n = 185) group based on their litter predicted EBV. Litters in the selected group were selected against BT at 180 d at restrained IMF in gluteus medius (GM) whereas those in the control group were chosen randomly. Realized selection intensities and genetic responses for BT, IMF in GM, and BW were estimated using a 3-trait multivariate animal mixed model under a Bayesian setting. Correlated responses for other traits were estimated similarly but using a 4-trait model, where other traits were added to the previous 3-trait model 1 at a time. Selected pigs had less BT than control pigs [-1.22 mm, with highest posterior density interval at 95% (HPD95; -2.47, -0.75)] with restrained decrease in IMF, both in GM [-0.16%; HPD95 (-0.36, +0.05)] and in LM [-0.15%; HPD95 (-0.37, +0.09)]. However, the realized selection intensity for IMF in GM denotes that the restriction on IMF was incomplete [-0.18; HPD95 (-0.36, +0.02)]. Selection decreased BW [-1.64 kg; HPD95 (-2.47, -0.75)] but increased carcass lean weight [+0.66 kg; HPD95 (+0.14, +1.22)], indicating that the response in BT offsets the unfavorable correlated response in BW. Selected pigs were shorter [-0.50 cm; HPD95 (-0.81, -0.20)] but with similar ham weight and loin depth. These results provide evidence that lean weight can be improved restraining the genetic change in IMF. However, they also stress that a complete restriction on IMF is difficult to achieve unless selection is practiced on a big population where IMF is accurately predicted.

  16. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

    PubMed

    Awasthi, Saurabh; Saraswathi, N T

    2016-06-01

    Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation.

  17. A passive means for eliminating range loss for projectiles with partially restrained internal members

    SciTech Connect

    Hodapp, A.E. Jr.

    1986-11-01

    A theory is developed to investigate offsetting the center of gravity (cg) of a Partially Restrained Internal Member (PRIM) from the projectile spin axis to provide a passive means for eliminating the PRIM induced instabilities that sometimes cause large losses in range and deflection. Results for cylindrical PRIM geometries indicated that, except for large diameter thin PRIM shapes, small PRIM cg offsets, including some that occur randomly within manufacturing tolerances, should be sufficient to reduce the instability induced range and deflection losses to acceptable levels. Experimental results are presented to confirm the stabilizing effect of PRIM cg offset.

  18. Neotectonics of Hispaniola - Plate motion, sedimentation, and seismicity at a restraining bend

    NASA Technical Reports Server (NTRS)

    Mann, P.; Matumoto, T.; Burke, K.

    1984-01-01

    The question as to the extent to which earthquake mechanisms define plate motion is addressed in view of the pattern of Neogene faulting, volcanism, and sedimentation in Hispaniola. The structure of two fault systems that approximately define the northern and southern coasts of the island suggest an east-west trend in relative plate motion, which is consistent with previous findings. The intervening area consists of en echelon mountain ranges thrust up at the restraining bend from the early Miocene. A Pleistocene volcanic province within this area is interpreted as defining a diffuse extensional fault termination of the southern strike-slip fault zone.

  19. Early age stresses and creep-shrinkage interaction of restrained concrete

    NASA Astrophysics Data System (ADS)

    Altoubat, Salah Ahmed

    2000-10-01

    Experimental and numerical analyses were performed to characterize the early age tensile creep and shrinkage behavior of concrete. A uniaxial restrained shrinkage test was developed. The experiment tested two identical specimens: restrained and unrestrained. The test was controlled by computer, and the shrinkage deformation was checked continuously and compared to a threshold value of 5 mum, which when exceeded, triggered an increase in tensile load to recover the shrinkage strain in the restrained specimen. Thus, a restrained condition is achieved and the stress generated by shrinkage mechanisms was measurable. The experiment revealed how shrinkage stresses developed and how creep mechanisms reduced shrinkage strain. The tests revealed that shrinkage stresses in the first days after casting are significant and caused fracture of the concrete. The rate of stress evolution influenced the time and stress of first cracking. The tensile creep of concrete formed a substantial part of the time dependent deformation and reduced the shrinkage stresses by 50%. A method separating drying creep mechanisms of concrete into stress-induced shrinkage and microcracking was developed. The method required measurement of creep and shrinkage of concrete under drying, sealed, and moist curing conditions. The moist-curing test produce the basic creep; the sealed test provided data on basic creep and stress-induced shrinkage, and the drying test provided data on basic creep, stress-induced shrinkage and microcracking. The basic creep results of young concrete indicated a high creep rate in the initial 10--20 hours after loading. Then, the rate decreased and the creep function approached a stable value. The initial rate of creep was sensitive to age at loading in the first two days, and became age-independent after a few days. The analysis revealed stress-induced shrinkage as a major mechanism of drying creep for plain and fiber reinforced concrete (FRC). Microcracking forms a significant

  20. Fast Disinfecting Antimicrobial Surfaces

    PubMed Central

    Madkour, Ahmad E.; Dabkowski, Jeffery M.; Nüsslein, Klaus; Tew, Gregory N.

    2013-01-01

    Silicon wafers and glass surfaces were functionalized with facially amphiphilic antimicrobial copolymers using the “grafting from” technique. Surface initiated atom transfer radical polymerization (ATRP) was used to grow poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces. Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S. aureus and E. coli 100% in less than 5 min. The molecular weight and grafting density of the polymer were controlled by varying the polymerization time and initiator surface density. Antimicrobial studies showed that the killing efficiency of these surfaces was independent of polymer layer thickness or grafting density within the range of surfaces studied. PMID:19177651

  1. Fast disinfecting antimicrobial surfaces.

    PubMed

    Madkour, Ahmad E; Dabkowski, Jeffery M; Nusslein, Klaus; Tew, Gregory N

    2009-01-20

    Silicon wafers and glass surfaces were functionalized with facially amphiphilic antimicrobial copolymers using the "grafting from" technique. Surface-initiated atom transfer radical polymerization (ATRP) was used to grow poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces. Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S. aureus and E. coli 100% in less than 5 min. The molecular weight and grafting density of the polymer were controlled by varying the polymerization time and initiator surface density. Antimicrobial studies showed that the killing efficiency of these surfaces was independent of polymer layer thickness or grafting density within the range of surfaces studied.

  2. A twin study of differences in the response of plasma ghrelin to a milkshake preload in restrained eaters

    PubMed Central

    Myhre, Rachel; Kratz, Mario; Goldberg, Jack; Polivy, Janet; Melhorn, Susan; Buchwald, Dedra; Cummings, David E.; Schur, Ellen A.

    2014-01-01

    Background Genetic, physiological, and psychological factors can affect food intake, but twin studies can distinguish inherited from environmental contributors. We examined the influence of attempted cognitive control of eating (“restrained eating”) on levels of appetite-regulating hormones. Methods Sixteen female, monozygotic twin pairs, discordant for Restraint Scale score (i.e., one twin a restrained eater with score > 15 whereas the co-twin was unrestrained), were selected from the University of Washington Twin Registry. Serial plasma ghrelin concentrations were monitored during meals and a preload study paradigm involving intake of a milkshake followed by an ad libitum ice cream “taste test.” Results Body weight, body mass index, resting energy expenditure, and fasting leptin levels were very similar between restrained and unrestrained twins. In a preload study, twins ate similar amounts of ice cream shortly after drinking identical milkshakes (mean ±SD; restrained 239 ±158 vs. unrestrained 228 ±132 kilocalories; P = 0.83). However, ghrelin concentrations during the preload study were significantly higher (P = 0.03) in restrained twins than in their unrestrained co-twins. Regardless of restraint status, ghrelin levels prior to the preload study were prospectively and positively associated with ice cream intake (P = 0.001). Conclusions Compared to their unrestrained co-twins, restrained twins had higher endogenous ghrelin levels during a preload study, but ate similar amounts. This finding is consistent with exertion of cognitive control relative to the state of physiologic appetite stimulation. Moreover, these findings in twins suggest that higher ghrelin levels result from restrained eating behavior and not from genetic predisposition. PMID:24534168

  3. Pharmacogenomics of antimicrobial agents

    PubMed Central

    Aung, Ar Kar; Haas, David W; Hulgan, Todd; Phillips, Elizabeth J

    2015-01-01

    Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use. PMID:25495412

  4. Pharmacogenomics of antimicrobial agents.

    PubMed

    Aung, Ar Kar; Haas, David W; Hulgan, Todd; Phillips, Elizabeth J

    2014-01-01

    Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use.

  5. What are Antimicrobial Pesticides?

    EPA Pesticide Factsheets

    Antimicrobial pesticides are substances or mixtures of substances used to destroy or suppress the growth of harmful microorganisms such as bacteria, viruses, or fungi on inanimate objects and surfaces.

  6. Head excursion of restrained human volunteers and hybrid III dummies in steady state rollover tests.

    PubMed

    Moffatt, Edward; Hare, Barry; Hughes, Raymond; Lewis, Lance; Iiyama, Hiroshi; Curzon, Anne; Cooper, Eddie

    2003-01-01

    Seatbelts provide substantial benefits in rollover crashes, yet occupants still receive head and neck injuries from contacting the vehicle roof interior when the roof exterior strikes the ground. Prior research has evaluated rollover restraint performance utilizing anthropomorphic test devices (dummies), but little dynamic testing has been done with human volunteers to learn how they move during rollovers. In this study, the vertical excursion of the head of restrained dummies and human subjects was measured in a vehicle being rotated about its longitudinal roll axis at roll rates from 180-to-360 deg/sec and under static inversion conditions. The vehicle's restraint design was the commonly used 3-point seatbelt with continuous loop webbing and a sliding latch plate. This paper presents an analysis of the observed occupant motion and provides a comparison of dummy and human motion under similar test conditions. Thirty-five tests (eighteen static and seventeen dynamic) were completed using two different sizes of dummies and human subjects in both near and far-side roll directions. The research indicates that far-side rollovers cause the restrained test subjects to have greater head excursion than near-side rollovers, and that static inversion testing underestimates head excursion for far-side occupants. Human vertical head excursion of up to 200 mm was found at a roll rate of 220 deg/sec. Humans exhibit greater variability in head excursion in comparison to dummies. Transfer of seatbelt webbing through the latch plate did not correlate directly with differences in head excursion.

  7. Buckling Behavior of Long Anisotropic Plates Subjected to Elastically Restrained Thermal Expansion

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2002-01-01

    An approach for synthesizing buckling results for, and behavior of, thin balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and elastically restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexurally anisotropic plates that are subjected to combined mechanical loads and is based on useful nondimensional parameters. In addition, stiffness-weighted laminate thermal-expansion parameters and compliance coefficients are derived that are used to determine critical temperatures in terms of physically intuitive mechanical-buckling coefficients. The effects of membrane orthotropy and membrane anisotropy are included in the general formulation. Many results are presented for some common laminates that are intended to facilitate a structural designer's transition to the use of generic buckling design curves. Several curves that illustrate the fundamental parameters used in the analysis are presented, for nine contemporary material systems, that provide physical insight into the buckling response in addition to providing useful design data. Examples are presented that demonstrate the use of generic design curves. The analysis approach and generic results indicate the effects and characteristics of elastically restrained laminate thermal expansion or contraction, membrane orthotropy and anisotropy, and flexural orthotropy and anisotropy in a very general and unifying manner.

  8. The effects of emotion regulation on the desire to overeat in restrained eaters.

    PubMed

    Svaldi, Jennifer; Tuschen-Caffier, Brunna; Lackner, Helmut K; Zimmermann, Sabine; Naumann, Eva

    2012-10-01

    The aim of the present study was to test whether emotion regulation (ER) strategies are underlying processes in the link between negative emotions and the desire to overeat (DTE) in high restrained eaters (HR). Forty-eight female HR and 46 female low restrained eaters (LR) watched three sadness inducing film clips. Thereby, participants were randomly assigned to and trained in one of three conditions while watching the first two clips: to suppress upcoming emotions, to accept upcoming emotions or to reappraise the situation. After that, they participated in an experiment in which the learned ER strategy was implemented while watching the third sadness inducing film clip. DTE and sadness were assessed prior to and at the end of each clip. Additionally, physiological measures of the sympathetic and parasympathetic branch were obtained. In the HR group emotion acceptance and suppression lead to a significant increase of the DTE from baseline to post-film, while there was no change in DTE in the reappraisal condition. However, psychophysiological measures were not moderated by ER strategies. The results are discussed in terms of the limited resource model.

  9. Collision-avoidance behaviors of minimally restrained flying locusts to looming stimuli

    PubMed Central

    Chan, R. WM.; Gabbiani, F.

    2013-01-01

    SUMMARY Visually guided collision avoidance is of paramount importance in flight, for instance to allow escape from potential predators. Yet, little is known about the types of collision-avoidance behaviors that may be generated by flying animals in response to an impending visual threat. We studied the behavior of minimally restrained locusts flying in a wind tunnel as they were subjected to looming stimuli presented to the side of the animal, simulating the approach of an object on a collision course. Using high-speed movie recordings, we observed a wide variety of collision-avoidance behaviors including climbs and dives away from – but also towards – the stimulus. In a more restrained setting, we were able to relate kinematic parameters of the flapping wings with yaw changes in the trajectory of the animal. Asymmetric wing flapping was most strongly correlated with changes in yaw, but we also observed a substantial effect of wing deformations. Additionally, the effect of wing deformations on yaw was relatively independent of that of wing asymmetries. Thus, flying locusts exhibit a rich range of collision-avoidance behaviors that depend on several distinct aerodynamic characteristics of wing flapping flight. PMID:23364572

  10. Ductility demands on buckling-restrained braced frames under earthquake loading

    NASA Astrophysics Data System (ADS)

    Fahnestock, Larry A.; Sause, Richard; Ricles, James M.; Lu, Le-Wu

    2003-12-01

    Accurate estimates of ductility demands on buckling-restrained braced frames (BRBFs) are crucial to performance-based design of BRBFs. An analytical study on the seismic behavior of BRBFs has been conducted at the ATLSS Center, Lehigh University to prepare for an upcoming experimental program. The analysis program DRAIN-2DX was used to model a one-bay, four-story prototype BRBF including material and geometric nonlinearities. The buckling-restrained brace (BRB) model incorporates both isotropic and kinematic hardening. Nonlinear static pushover and time-history analyses were performed on the prototype BRBF. Performance objectives for the BRBs were defined and used to evaluate the time-history analysis results. Particular emphasis was placed on global ductility demands and ductility demands on the BRBs. These demands were compared with anticipated ductility capacities. The analysis results, along with results from similar previous studies, are used to evaluate the BRBF design provisions that have been recommended for codification in the United States. The results show that BRB maximum ductility demands can be as high as 20 to 25. These demands significantly exceed those anticipated by the BRBF recommended provisions. Results from the static pushover and time-history analyses are used to demonstrate why the ductility demands exceed those anticipated by the recommended provisions. The BRB qualification testing protocol contained in the BRBF recommended provisions is shown to be inadequate because it requires only a maximum ductility demand of at most 7.5. Modifications to the testing protocol are recommended.

  11. Structural and kinematic evolution of a Miocene to Recent sinistral restraining bend: the Montejunto massif, Portugal

    NASA Astrophysics Data System (ADS)

    Curtis, Michael L.

    1999-01-01

    The Montejunto massif lies in the apex of a large-scale restraining bend at the southern termination of a sinistral transpressive fault system, in the Lusitanian basin of Portugal. Cenozoic deformation within the Montejunto massif initiated with southerly directed thrusting along the southern boundary of the massif, in association with the development of the E-W oriented Montejunto anticline, probably during the Langhian. Deformation switched to the northern boundary of the massif, in association with a change to NW-directed thrusting and continued development of the Montejunto anticline. The youngest set of structures within the massif is related to the sinistral reactivation of the Arieiro fault system, and steeply inclined bedding. This late phase of deformation represents the accommodation of a component of sinistral displacement across the restraining bend along mechanical anisotropies formed during this progressive Cenozoic deformation event. Variation in the kinematic style of the Main Arieiro fault is related to the angle ( α) between the fault plane and the displacement vector. Where α≈20°, abrupt pene-contemporaneous switches in displacement direction are recorded along the fault, whereas strike-slip kinematics predominate where α<20°. The timing of deformation events in the Montejunto massif is uncertain. However, correlation with the established Cenozoic Africa/Europe plate convergence directions may provide potential temporal constraints.

  12. Influence of Nutrition Claims on Appetite Sensations according to Sex, Weight Status, and Restrained Eating

    PubMed Central

    Doucet, Éric; Pomerleau, Sonia

    2016-01-01

    Nutrition claims may help people to adopt healthier eating habits, but little is known about the potential cognitive effects of such claims on appetite sensations. The main purpose of this study was to evaluate the impact of nutrition claims and individual factors on perceived appetite sensations. According to a three (“healthy” versus “diet” (i.e., satiating) versus “hedonic”) by two (restrained or not restrained) by two (normal-weight or overweight/obese) by two (men versus women) factorial design, 164 males and 188 females aged 18–65 were invited to taste an oatmeal-raisin snack in a blinded and ad libitum context. Visual analog scales (150 mm) were used to evaluate appetite sensations before and over 1 h after consumption period. BMI and Restraint Scale were used to categorize participants according to their weight and restraint status. No main condition effect was observed for any of the four appetite sensations. However, subgroups analysis revealed significant differences among specific subgroups. A main effect of sex was also observed for all appetite sensations with men reporting higher levels of desire to eat, hunger and prospective food consumption, and lower levels of fullness than women. These findings highlight the importance of considering individual characteristics in interaction when studying appetite sensations. PMID:27725885

  13. A nonlinear theory for spinning anisotropic beams using restrained warping functions

    NASA Technical Reports Server (NTRS)

    Ie, C. A.; Kosmatka, J. B.

    1993-01-01

    A geometrically nonlinear theory is developed for spinning anisotropic beams having arbitrary cross sections. An assumed displacement field is developed using the standard 3D kinematics relations to describe the global beam behavior supplemented with an additional field that represents the local deformation within the cross section and warping out of the cross section plane. It is assumed that the magnitude of this additional field is directly proportional to the local stress resultants. In order to take into account the effects of boundary conditions, a restraining function is introduced. This function plays the role of reducing the amount of free warping deformation throughout the field due to the restraint of the cross section(s) at the end(s) of the beam, e.g., in the case of a cantilever beam. Using a developed ordering scheme, the nonlinear strains are calculated to the third order. The FEM is developed using the weak form variational formulation. Preliminary interesting numerical results have been obtained that indicate the role of the restraining function in the case of a cantilever beam with circular cross section. These results are for the cases of a tip displacement (static) and free vibration studies for both isotropic and anisotropic materials with varied fiber orientations.

  14. 5-Aminolaevulinic Acid-Based Photodynamic Therapy Restrains Pathological Hyperplasia of Fibroblasts

    PubMed Central

    Wang, Xiaochuan; Cao, Ping; Liu, Jian; Du, Peng; Wang, Zhiqiong; Chen, Wei; Liu, Chang; Wu, Yifei

    2017-01-01

    Background This study aimed to explore whether 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) restrains pathological hyperplasia of fibroblasts from hyperplastic scar tissues, and to investigate the potential mechanism. Material/Methods We used MTT assay, flow cytometry, and terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) to examine the effects of ALA-PDT on proliferation, cell cycle, and apoptosis of fibroblasts isolated from hyperplastic scar tissues. The growth-promoting effect of fibroblasts on vascular endothelial cells was measured by cell co-culture. Real-time PCR and Western blot analysis were performed to detect the expression levels of transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), Collagen I, Collagen III, vascular endothelial growth factor-A (VEGFA), and basic fibroblast growth factor (bFGF). Results ALA-PDT inhibited proliferation delayed cell cycle progress, promoted apoptosis of fibroblasts, and suppressed its growth-promoting effect on vascular endothelial cells, and decreased expression of TGF-β1, α-SMA, Collagen I, Collagen III, VEGFA, and bFGF. Conclusions ALA-PDT effectively restrained pathological hyperplasia of fibroblasts from hyperplastic scar tissues, which may provide a research basis for clinical therapy of hyperplastic scars. PMID:28052053

  15. Emotional, external and restrained eating behaviour and BMI trajectories in adolescence.

    PubMed

    Snoek, Harriëtte M; Engels, Rutger C M E; van Strien, Tatjana; Otten, Roy

    2013-08-01

    Individual differences in eating behaviours might partly explain the variations in development of weight gain and subsequent overweight and obesity. In the current study, identified trajectories of BMI in adolescence and their associations with restrained, emotional and external eating were tested. For the assessment of BMI trajectories growth mixture modelling was used; a method used to identify clusters of individuals within a population that follow distinct developmental trajectories. In total 328 Dutch adolescents (13-15years old at baseline) self-reported their height and weight at five annual waves and their eating behaviour at baseline. Development of BMI was best fitted in five distinct trajectories that showed similar moderate increase of BMI over time; parallel but at a different level. High restrained eaters had a higher chance of being in the higher BMI trajectories. Emotional and external eating were unrelated to the BMI trajectories. In conclusion, adolescents in this study followed very parallel patterns of moderate increases in BMI which suggests that factors acting on individual differences in weight status have had their influence mostly at a - perhaps much - younger age. Restraint eating was related to BMI in early adolescence, but not to an increases or decreases in BMI over the course of adolescence.

  16. Bcl6 Sets a Threshold for Antiviral Signaling by Restraining IRF7 Transcriptional Program.

    PubMed

    Xu, Feng; Kang, Yanhua; Zhuang, Ningtong; Lu, Zhe; Zhang, Hang; Xu, Dakang; Ding, Yina; Yin, Hongping; Shi, Liyun

    2016-01-05

    The coordination of restraining and priming of antiviral signaling constitute a fundamental aspect of immunological functions. However, we currently know little about the molecular events that can translate the pathogenic cues into the appropriate code for antiviral defense. Our present study reports a specific role of B cell lymphoma (Bcl)6 as a checkpoint in the initiation of the host response to cytosolic RNA viruses. Remarkably, Bcl6 specifically binds to the interferon-regulatory factor (IRF)7 loci and restrains its transcription, thereby functioning as a negative regulator for interferon (IFN)-β production and antiviral responses. The signal-controlled turnover of the Bcl6, most likely mediated by microRNA-127, coordinates the antiviral response and inflammatory sequelae. Accordingly, de-repression of Bcl6 resulted in a phenotypic conversion of macrophages into highly potent IFN-producing cells and rendered mice more resistant to pathogenic RNA virus infection. The failure to remove the Bcl6 regulator, however, impedes the antiviral signaling and exaggerates viral pneumonia in mice. We thus reveal a novel key molecular checkpoint to orchestrate antiviral innate immunity.

  17. PTEN inhibits PREX2-catalyzed activation of RAC1 to restrain tumor cell invasion.

    PubMed

    Mense, Sarah M; Barrows, Douglas; Hodakoski, Cindy; Steinbach, Nicole; Schoenfeld, David; Su, William; Hopkins, Benjamin D; Su, Tao; Fine, Barry; Hibshoosh, Hanina; Parsons, Ramon

    2015-03-31

    The tumor suppressor PTEN restrains cell migration and invasion by a mechanism that is independent of inhibition of the PI3K pathway and decreased activation of the kinase AKT. PREX2, a widely distributed GEF that activates the GTPase RAC1, binds to and inhibits PTEN. We used mouse embryonic fibroblasts and breast cancer cell lines to show that PTEN suppresses cell migration and invasion by blocking PREX2 activity. In addition to metabolizing the phosphoinositide PIP₃, PTEN inhibited PREX2-induced invasion by a mechanism that required the tail domain of PTEN, but not its lipid phosphatase activity. Fluorescent nucleotide exchange assays revealed that PTEN inhibited the GEF activity of PREX2 toward RAC1. PREX2 is a frequently mutated GEF in cancer, and examination of human tumor data showed that PREX2 mutation was associated with high PTEN expression. Therefore, we tested whether cancer-derived somatic PREX2 mutants, which accelerate tumor formation of immortalized melanocytes, were inhibited by PTEN. The three stably expressed, somatic PREX2 cancer mutants that we tested were resistant to PTEN-mediated inhibition of invasion but retained the ability to inhibit the lipid phosphatase activity of PTEN. In vitro analysis showed that PTEN did not block the GEF activity of two PREX2 cancer mutants and had a reduced binding affinity for the third. Thus, PTEN antagonized migration and invasion by restraining PREX2 GEF activity, and PREX2 mutants are likely selected in cancer to escape PTEN-mediated inhibition of invasion.

  18. Neurofeedback reduces overeating episodes in female restrained eaters: a randomized controlled pilot-study.

    PubMed

    Schmidt, Jennifer; Martin, Alexandra

    2015-12-01

    Overeating episodes, despite of intentions to control weight, are a common problem among women. Recurring episodes of overeating and dietary failure have been reported to result in higher Body Mass Indexes and to induce severe distress even in non-clinical groups. Based on findings from physiological research on eating behavior and craving, as well as previous biofeedback studies, we derived a cue exposure based EEG neurofeedback protocol to target overeating episodes. The treatment was evaluated in a randomized controlled trial, comparing a neurofeedback group (NFG; n = 14) with a waiting list control group (WLG; n = 13) in a sub-clinical sample of female restrained eaters. At post-treatment, the number of weekly overeating episodes and subsequent distress were significantly reduced in the NFG compared to the WLG (p < .01; r > .50). In a 3 month follow-up, effects in the NFG remained stable. As secondary outcomes, perceived dieting success was enhanced after the treatment. At follow-up, additional beneficial effects on trait food craving were observed. Altogether, we found preliminary evidence for the cue exposure neurofeedback against overeating episodes in female restrained eaters, although specific effects and underlying mechanisms still have to be explored in future research.

  19. Novel antimicrobial textiles

    NASA Astrophysics Data System (ADS)

    Cho, Unchin

    2003-10-01

    Many microorganisms can survive, and perhaps proliferate on textiles, generating adverse effects such as: disease transmission, odor generation, pH changes, staining, discoloration and loss of performance. These adverse effects may threaten users' health, deteriorate textile properties and degrade service quality. It may, therefore, be desirable to incorporate antimicrobials on textiles for controlling the growth of microorganisms. This dissertation focuses on the development of antimicrobial fibers and fabrics by integration of antimicrobials with these textiles. The applications of hydantoin-based halamines were mainly investigated in the research. The typical process is that hydantoin containing compounds are grafted onto textiles and transformed to halamine by chlorination. Hydantoin-based halamines are usually chloramines that release chlorine (Cl+) via cleavage of the -NCl functional group which attacks and kills microbes. The antimicrobial behavior is rechargeable many times by rinsing the fiber or fabric with chlorine-containing solution. Some quaternary ammonium type antimicrobials were also investigated in this research. The choice of integrating techniques is dependant on both the textile and antimicrobial compounds. In this dissertation, the nine approaches were studied for incorporating antimicrobial with various textiles: (1) co-extrusion of fibers with halamine precursor additive; (2) grafting of the quaternary ammonium compounds onto ethylene-co-acrylic acid fiber for creating quaternary ammonium type antimicrobial fiber; (3) entrapment of the additives in thermally bonded bicomponent nonwoven fabrics; (4) attaching antimicrobial additives to surfaces with latex adhesive coating; (5) grafting of antimicrobial compounds onto rubber latex via UV exposure; (6) reaction of halamine with needle-punched melamine formaldehyde nonwoven fabric and laminates; (7) coating melamine resin onto tent fabrics and laminates; (8) synthesis of super absorbent polymer

  20. Antimicrobial compounds in tears.

    PubMed

    McDermott, Alison M

    2013-12-01

    The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Antimicrobial Compounds in Tears

    PubMed Central

    McDermott, Alison M.

    2013-01-01

    The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here. PMID:23880529

  2. Responsiveness to healthy advertisements in adults: An experiment assessing beyond brand snack selection and the impact of restrained eating.

    PubMed

    Dovey, Terence M; Torab, Tina; Yen, Dorothy; Boyland, E J; Halford, Jason C G

    2017-05-01

    The objective of this study was to explore the impact of different advertising messages on adults' snack choice. Eighty participants (18-24 years old) were offered the choice between two snack packs following exposure to one of three advertising conditions. The snack packs contained either healthy or high fat, sugar or salt (HFSS) foods. Participants were exposed to commercials containing either non-food products, healthy food products or HFSS food products and their subsequent choice of snack pack was recorded. The Dutch Eating Behaviour Questionnaire (DEBQ) was used to assess the impact of external, restrained and emotional eating behaviour on snack pack selection following exposure to advertisements. The majority of unrestrained participants preferentially choose the HFSS snack pack irrespective of advertisement condition. In contrast, high restrained individuals exposed to the healthy eating advertisement condition preferentially selected the healthy snack pack while those in other advertisement conditions refused to take either snack pack. The healthy eating message, when distributed through mass media, resonated with restrained eaters only. Exposure to healthy food adverts provoked restrained eaters into choosing a snack pack; while exposure to other messages results in restrained eaters refusing to take any foods. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. [Antimicrobial agents in eyedrops].

    PubMed

    Sklubalová, Z

    2004-05-01

    Microbial contamination of ophthalmic drops means a risk of serious injury to the eye. Ophthalmic drops must therefore comply with sterility requirements. Protection of multiple-dose drops against secondary contamination is ensured by an addition of an antimicrobial agent. Selection of a suitable antimicrobial agent is conditioned by many factors, such as the spectrum of effect, properties of the preparation, compatibility with the components of the preparation and the container, and the technology of manufacture. Although the added antimicrobial substance ensures the safety of the preparation, on the other hand it can produce a number of negative effects in the eye tissue. The present paper summarizes pharmacopoeial requirements for microbial quality of ophthalmic drops, outlining the properties and efficacy of antimicrobial substances commonly used in ophthalmic drops (benzalkonium chloride BAC, cetrimide CTM, phenyl mercuric salts PHg, thiomersal TM, chlorobutanol ChB, benzyl alcohol BA, phenyl ethyl alcohol PEA, chlorohexidin ChX, parabens PB), their typical concentrations and combinations, including the parameters of formulation and the interactions which affect their activity. It deals with the toxicity of these antimicrobial substances, side effects on the eye tissue, and alternatives to the use of antimicrobial agents.

  4. Inhibition ability of food cues between successful and unsuccessful restrained eaters: a two-choice oddball task.

    PubMed

    Kong, Fanchang; Zhang, Yan; Chen, Hong

    2015-01-01

    Previous studies have presented mixed findings on the inhibition ability in restrained eaters (REs) due to the limited amount of neural evidence and limitations of behavioral measures. The current study explores the neural correlations of the specific inhibition ability among successful restrained eaters (S-REs), unsuccessful restrained eaters (US-REs), and unrestrained eaters (UREs). Three groups of females (with 13 participants in each group) completed a two-choice Oddball task, while the event-related potentials (ERPs) are recorded synchronously. Results indicate that S-REs showed inhibition deficit in processing high-energy food cues whereas US-REs show inhibition deficit in processing both low- and high-energy food cues. Results indicate that S-REs and US-REs differ in terms of specific inhibition ability and that enhanced inhibition is essential to a successful diet.

  5. The effect of brand and caloric information on flavor perception and food consumption in restrained and unrestrained eaters.

    PubMed

    Cavanagh, Kevin V; Kruja, Blina; Forestell, Catherine A

    2014-11-01

    The goal of the current study was to determine whether provision of brand and caloric information affects sensory perception and consumption of a food in restrained (n=84) and unrestrained eaters (n=104). Using a between-subjects 2 × 2 × 3 design, female restrained and unrestrained eaters were asked to taste and rate a cookie that was labeled with a brand associated with healthful eating (Kashi(®)) or one associated with unhealthful eating (Nabisco(®)). Additionally, some participants were presented with a nutrition label alongside the brand name indicating that one serving contained 130 calories (Low-Calorie Condition), or 260 calories (High-Calorie Condition). The remaining participants were not shown a nutrition label (No Label Condition). Results indicated that those in the No Label or the High-Calorie Condition perceived the healthful branded cookie to have a better flavor than those who received the unhealthful branded cookie regardless of their restraint status. However, restrained eaters in the No Label Condition consumed more of the healthful than the unhealthful branded cookie, whereas those in the Low-Calorie Condition consumed more of the unhealthful than the healthful branded cookie. In contrast, unrestrained eaters ate more of the healthful branded cookie regardless of the caloric information provided. Thus, although restrained and unrestrained eaters' perceptions are similarly affected by branding and caloric information, brands and caloric information interact to affect restrained eaters' consumption. This study reveals that labeling foods as low calorie may create a halo effect which may lead to over-consumption of these foods in restrained eaters.

  6. Removing guns from batterers: findings from a pilot survey of domestic violence restraining order recipients in California.

    PubMed

    Vittes, Katherine A; Webster, Daniel W; Frattaroli, Shannon; Claire, Barbara E; Wintemute, Garen J

    2013-05-01

    Persons under certain domestic violence restraining orders in California are required to surrender any firearms in their possession within 24 hours of service. The California Department of Justice funded a pilot program in which Sheriff's Offices in two counties developed a system for better enforcing the firearm surrender requirement. As part of a larger process evaluation, 17 restraining order recipients were interviewed about their experiences with and feelings about the removal of firearms from their abusers. Most women surveyed wanted firearms removed and felt safer as a result of their removal. Implications of the findings are discussed.

  7. Body image and restrained eating in blind and sighted women: A preliminary study.

    PubMed

    Ashikali, Eleni-Marina; Dittmar, Helga

    2010-03-01

    Sociocultural theory attributes the high levels of body image concerns and disordered eating in Western women to the promotion of an unrealistically thin body ideal. This study investigated body dissatisfaction, restrained eating, and attitudes toward appearance in visually impaired and sighted women. There were 21 congenitally blind, 11 blinded later in life, and 60 sighted. Blind women were more satisfied with their body and dieted less than sighted women. Appearance attitudes, particularly thin-ideal internalization, accounted for differences in body dissatisfaction and dieting among the three groups of women. Possible explanations for our findings are considered, including the importance of visual exposure to the media's thin ideal, as well as the usefulness of future research on blind women. Copyright 2010 Elsevier Ltd. All rights reserved.

  8. Restrained torsional dynamics of nuclear DNA in living proliferative mammalian cells.

    PubMed Central

    Tramier, M; Kemnitz, K; Durieux, C; Coppey, J; Denjean, P; Pansu, R B; Coppey-Moisan, M

    2000-01-01

    Physical parameters, describing the state of chromatinized DNA in living mammalian cells, were revealed by in situ fluorescence dynamic properties of ethidium in its free and intercalated states. The lifetimes and anisotropy decays of this cationic chromophore were measured within the nuclear domain, by using the ultra-sensitive time-correlated single-photon counting technique, confocal microscopy, and ultra-low probe concentrations. We found that, in living cells: 1) free ethidium molecules equilibrate between extracellular milieu and nucleus, demonstrating that the cation is naturally transported into the nucleus; 2) the intercalation of ethidium into chromatinized DNA is strongly inhibited, with relaxation of the inhibition after mild (digitonin) cell treatment; 3) intercalation sites are likely to be located in chromatin DNA; and 4) the fluorescence anisotropy relaxation of intercalated molecules is very slow. The combination of fluorescence kinetic and fluorescence anisotropy dynamics indicates that the torsional dynamics of nuclear DNA is highly restrained in living cells. PMID:10777758

  9. Effect of selective monoamine oxidase inhibitors on the morphine-induced hypothermia in restrained rats.

    PubMed

    Milanés, M V; Cremades, A; Vargas, M L; Arnaldos, J D

    1987-01-01

    Morphine (30 mg/kg i.p.) produced a hypothermic effect in restrained rats which was antagonized by naloxone pretreatment (10 mg/kg s.c.). This hypothermia was inhibited by deprenyl pretreatment (5 mg/kg i.p.) and by beta-phenylethylamine treatment (25 mg/kg i.p.). However, the effect of morphine was partially potentiated when a higher dose of deprenyl (10 mg/kg i.p.) was administered. Pretreatment with clorgyline (1 mg/kg i.p.) potentiated the morphine-induced hypothermia. In contrast, the effect of morphine was antagonized when a higher dose of clorgyline was used (5 mg/kg i.p.). Based on these results, a possible role of brain serotonin and dopamine in the thermoregulatory effects of morphine is proposed in this paper.

  10. Buckling Behavior of Long Anisotropic Plates Subjected to Elastically Restrained Thermal Expansion and Contraction

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2004-01-01

    An approach for synthesizing buckling results for thin balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and elastically restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexural anisotropic plates that are subjected to combined mechanical loads. In addition, stiffness-weighted laminate thermal-expansion parameters and compliance coefficients are derived that are used to determine critical temperatures in terms of physically intuitive mechanical-buckling coefficients. Many results are presented for some common laminates that are intended to facilitate a structural designer s transition to the use of the generic buckling design curves. Several curves that illustrate the fundamental parameters used in the analysis are presented, for nine contemporary material systems, that provide physical insight into the buckling response in addition to providing useful design data. Examples are presented that demonstrate the use of the generic design curves.

  11. "Conditional Restraints": Restraining the Free Atoms in ARP/wARP.

    PubMed

    Mooij, Wijnand T M; Cohen, Serge X; Joosten, Krista; Murshudov, Garib N; Perrakis, Anastassis

    2009-02-13

    The automated building of a protein model into an electron density map remains a challenging problem. In the ARP/wARP approach, model building is facilitated by initially interpreting a density map with free atoms of unknown chemical identity; all structural information for such chemically unassigned atoms is discarded. Here, this is remedied by applying restraints between free atoms, and between free atoms and a partial protein model. These are based on geometric considerations of protein structure and tentative (conditional) assignments for the free atoms. Restraints are applied in the REFMAC5 refinement program and are generated on an ad hoc basis, allowing them to fluctuate from step to step. A large set of experimentally phased and molecular replacement structures showcases individual structures where automated building is improved drastically by the conditional restraints. The concept and implementation we present can also find application in restraining geometries, such as hydrogen bonds, in low-resolution refinement.

  12. “Conditional Restraints”: Restraining the Free Atoms in ARP/wARP

    PubMed Central

    Mooij, Wijnand T.M.; Cohen, Serge X.; Joosten, Krista; Murshudov, Garib N.; Perrakis, Anastassis

    2009-01-01

    Summary The automated building of a protein model into an electron density map remains a challenging problem. In the ARP/wARP approach, model building is facilitated by initially interpreting a density map with free atoms of unknown chemical identity; all structural information for such chemically unassigned atoms is discarded. Here, this is remedied by applying restraints between free atoms, and between free atoms and a partial protein model. These are based on geometric considerations of protein structure and tentative (conditional) assignments for the free atoms. Restraints are applied in the REFMAC5 refinement program and are generated on an ad hoc basis, allowing them to fluctuate from step to step. A large set of experimentally phased and molecular replacement structures showcases individual structures where automated building is improved drastically by the conditional restraints. The concept and implementation we present can also find application in restraining geometries, such as hydrogen bonds, in low-resolution refinement. PMID:19217389

  13. Size-dependent thermal buckling of heated nanowires with ends axially restrained

    NASA Astrophysics Data System (ADS)

    Wang, Yu; Wang, Zhi-Qiao; Lv, Jian-Guo

    2014-02-01

    Nanowires (NWs) are being actively explored for applications as nanoscale building blocks of sensors, actuators and nanoelectromechanical systems (NEMS). Temperature changes can induce an axial force within NWs due to the thermal expansion and may lead to buckling. The thermal buckling behaviors of ends-axially-restrained nanowires, subjected to a uniform temperature rise, are studied based on Bernoulli-Euler beam theory including the surface thermoelastic effects. Besides the surface elastic modulus, the influences of surface thermal expansion coefficient are incorporated into the model presented herein to describe size-dependent thermoelastic behaviors of nanowires. The results show that the critical buckling temperature and postbuckling deflection are significantly affected by surface thermoelastic effects and the influences become more prominent as the thickness of nanowire decreases. The corresponding influences of the slenderness ratio are also discussed. This research is helpful not only in understanding the thermal buckling properties of nanowires but also in designing the nanowire-based sensor and thermal actuator.

  14. On the characterization of claw-free graphs with given total restrained domination number.

    PubMed

    Pi, Xiaoming

    2016-01-01

    A set S of vertices in graph [Formula: see text] is a [Formula: see text], abbreviated TRDS, of G if every vertex of G is adjacent to a vertex in S and every vertex of [Formula: see text] is adjacent to a vertex in [Formula: see text]. The [Formula: see text] of G, denoted by [Formula: see text], is the minimum cardinality of a TRDS of G. Jiang and Kang (J Comb Optim. 19:60-68, 2010) characterized the connected claw-free graph G of order n with [Formula: see text]. This paper studies the total restrained domination number of claw-free graphs and characterizes the connected claw-free graph G of order n with [Formula: see text].

  15. Sugar-sweetened and artificially sweetened soft drinks in association to restrained, external and emotional eating.

    PubMed

    Elfhag, K; Tynelius, P; Rasmussen, F

    2007-06-08

    We studied sugar-sweetened soft drinks and light soft drinks in their associations to psychological constructs of eating behavior and demographic data for adults and children. Soft drink intakes were assessed by consumption of soft drinks in number of days the last week, and eating behavior was measured by the Dutch Eating Behaviour Questionnaire (DEBQ). The sample included 3265 men and women, and their 12-year old children, originating from Swedish national databases. Associations to younger age and lower education in adults were in particular apparent for sugar-sweetened soft drinks. Consumption of sugar-sweetened soft drinks was further associated to less restrained and more external eating in adults. In contrast, light soft drinks were associated with higher BMI, more restrained eating and also more emotional eating in adults. For the children these associations were generally weaker. Sugar-sweetened soft drinks are consumed by persons with a lower education, who furthermore are less prone to attempt to restrict their calorie intake, and by some of those who are sensitive to external stimuli of foods. Light soft drinks are rather chosen by the more heavy persons who try to restrict their energy intake perhaps in order to control the body weight, and more unexpectedly, by adults who eat for comfort. Being more sensitive to an external stimulus of food such as taste seems to imply proneness to consume sugar-sweetened soft drinks instead of the light versions. Light soft drinks may be perceived as an adequate substitute in the use of foods for comfort, meaning the sweet taste may be sufficient for this purpose.

  16. Head Excursion of Restrained Human Volunteers and Hybrid III Dummies in Steady State Rollover Tests

    PubMed Central

    Moffatt, Edward; Hare, Barry; Hughes, Raymond; Lewis, Lance; Iiyama, Hiroshi; Curzon, Anne; Cooper, Eddie

    2003-01-01

    Seatbelts provide substantial benefits in rollover crashes, yet occupants still receive head and neck injuries from contacting the vehicle roof interior when the roof exterior strikes the ground. Prior research has evaluated rollover restraint performance utilizing anthropomorphic test devices (dummies), but little dynamic testing has been done with human volunteers to learn how they move during rollovers. In this study, the vertical excursion of the head of restrained dummies and human subjects was measured in a vehicle being rotated about its longitudinal roll axis at roll rates from 180-to-360 deg/sec and under static inversion conditions. The vehicle’s restraint design was the commonly used 3-point seatbelt with continuous loop webbing and a sliding latch plate. This paper presents an analysis of the observed occupant motion and provides a comparison of dummy and human motion under similar test conditions. Thirty-five tests (eighteen static and seventeen dynamic) were completed using two different sizes of dummies and human subjects in both near and far-side roll directions. The research indicates that far-side rollovers cause the restrained test subjects to have greater head excursion than near-side rollovers, and that static inversion testing underestimates head excursion for far-side occupants. Human vertical head excursion of up to 200 mm was found at a roll rate of 220 deg/sec. Humans exhibit greater variability in head excursion in comparison to dummies. Transfer of seatbelt webbing through the latch plate did not correlate directly with differences in head excursion. PMID:12941241

  17. PTEN inhibits PREX2-catalyzed activation of RAC1 to restrain tumor cell invasion

    PubMed Central

    Mense, Sarah M.; Barrows, Douglas; Hodakoski, Cindy; Steinbach, Nicole; Schoenfeld, David; Su, William; Hopkins, Benjamin D.; Su, Tao; Fine, Barry; Hibshoosh, Hanina; Parsons, Ramon

    2016-01-01

    The tumor suppressor PTEN restrains cell migration and invasion by a mechanism that is independent of inhibition of the PI3K pathway and decreased activation of the kinase AKT. PREX2, a widely distributed GEF that activates the GTPase RAC1, binds to and inhibits PTEN. We used mouse embryonic fibroblasts and breast cancer cell lines to show that PTEN suppresses cell migration and invasion by blocking PREX2 activity. In addition to metabolizing the phosphoinositide PIP3, PTEN inhibited PREX2-induced invasion by a mechanism that required the tail domain of PTEN, but not its lipid phosphatase activity. Fluorescent nucleotide exchange assays revealed that PTEN inhibited the GEF activity of PREX2 toward RAC1. PREX2 is a frequently mutated GEF in cancer, and examination of human tumor data showed that PREX2 mutation was associated with high PTEN expression. Therefore, we tested whether cancer-derived somatic PREX2 mutants, which accelerate tumor formation of immortalized melanocytes, were inhibited by PTEN. The three stably expressed, somatic PREX2 cancer mutants that we tested were resistant to PTEN-mediated inhibition of invasion but retained the ability to inhibit the lipid phosphatase activity of PTEN. In vitro analysis showed that PTEN did not block the GEF activity of two PREX2 cancer mutants and had a reduced binding affinity for the third. Thus, PTEN antagonized migration and invasion by restraining PREX2 GEF activity, and PREX2 mutants are likely selected in cancer to escape PTEN-mediated inhibition of invasion. PMID:25829446

  18. Restrained Ion Population Transfer: A Novel Ion Transfer Method for Mass Spectrometry.

    SciTech Connect

    Kaiser, Nathan K.; Skulason, Gunnar; Weisbrod, Chad R.; Wu, Si; Zhang, Kai; Prior, David C.; Buschbach, Michael A.; Anderson, Gordon A.; Bruce, James E.

    2008-06-30

    With modern Fourier transform ion cyclotron resonance (ICR) mass spectrometers, ions are created and accumulated exterior to the mass analyzer. The ion accumulation event takes place in a region of higher pressure which allows ions to be thermally cooled before being given kinetic energy and accelerated toward the ICR cell where they are to be decelerated and re-trapped. When gated trapping is used to collect ions in the ICR cell for analysis, mass discrimination can occur due to time-of-flight effects. Also, trapping ions with large axial kinetic energy can decrease the performance of the ICR instrument when compared to the analysis of thermally-cooled ions located at the trap center. Therefore, it is desirable to limit the energy imparted in the ions within the ICR cell as well as minimize time-of-flight effects. The approach presented here for ion transfer called restrained ion population transfer or RIPT provides complete axial control of an ion population throughout the entire transfer sequence from the accumulation region to the ICR cell. This is accomplished by utilization of a number of quadrupole segments arranged in series with independent control of the dc bias voltage applied to each segment of the quadrupole ion guide. This approach circumvents problems associated with time-of-flight effects and minimizes the energy imparted to the ions allowing transfer of the cooled ion packet from the ion accumulation region to the ICR cell. Initial data are presented to illustrate feasibility of restrained ion population transfer. RIPT was also modeled with SIMION 7.0 and simulation results that support our feasibility studies of the ions transfer process are presented.

  19. Differences in Thoracic Injury Causation Patterns Between Seat Belt Restrained Children and Adults

    PubMed Central

    Arbogast, Kristy B.; Locey, Caitlin M.; Zonfrillo, Mark R.

    2012-01-01

    The objective of this research was to delineate age-based differences in specific thoracic injury diagnoses for seat belt restrained rear seat occupants and describe the associated injury causation in order to provide insight into how the load of the seat belt is transferred to occupants of various sizes. Using data from the Crash Investigation Research and Engineering Network (CIREN), 20 cases of rear seated, lap and shoulder belt restrained occupants with AIS2+ thoracic injuries in frontal crashes were reviewed. Seven were children and adolescents age 8–15 years, 5 were 16–24 years, 3 were 25–54 years, and 5 were 55+ years. Six of the seven 8–15 year olds sustained injuries to the lung in the form of pulmonary contusion or pneumothorax. Only three of the seven sustained a skeletal (sternum or rib) fracture; only one of these three involved multiple ribs bilaterally. In contrast, four of the five 16–24 year olds sustained at least one rib fracture - often multiple and bilateral. The adult cohort (25+ years) was involved in predominantly more minor crashes; however they all sustained complex rib fractures – seven of the eight involved multiple ribs, four of the eight were also bilateral. Belt compression – either from the shoulder belt or the lap belt – was identified as the primary cause of the thoracic injuries. Often, there was clear evidence of the location of belt loading from AIS 1 chest contusions or abrasions. These findings have implications for age-based thoracic injury criteria suggesting that that different metrics may be needed for different age groups. PMID:23169131

  20. General principles of antimicrobial therapy.

    PubMed

    Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

    2011-02-01

    Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.

  1. [Antimicrobial susceptibility cumulative reports].

    PubMed

    Canut-Blasco, Andrés; Calvo, Jorge; Rodríguez-Díaz, Juan Carlos; Martínez-Martínez, Luis

    2016-10-01

    Cumulative reports on antimicrobial susceptibility tests data are important for selecting empirical treatments, as an educational tool in programs on antimicrobial use, and for establishing breakpoints defining clinical categories. These reports should be based on data validated by clinical microbiologists using diagnostic samples (not surveillance samples). In order to avoid a bias derived from including several isolates obtained from the same patient, it is recommended that, for a defined period, only the first isolate is counted. A minimal number of isolates per species should be presented: a figure of >=30 isolates is statistically acceptable. The report is usually presented in a table format where, for each cell, information on clinically relevant microorganisms-antimicrobial agents is presented. Depending on particular needs, multiple tables showing data related to patients, samples, services or special pathogens can be prepared.

  2. Antimicrobial Peptides from Fish

    PubMed Central

    Masso-Silva, Jorge A.; Diamond, Gill

    2014-01-01

    Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

  3. Antimicrobial activity of spices.

    PubMed

    Arora, D S; Kaur, J

    1999-08-01

    Spices have been shown to possess medicinal value, in particular, antimicrobial activity. This study compares the sensitivity of some human pathogenic bacteria and yeasts to various spice extracts and commonly employed chemotherapeutic substances. Of the different spices tested only garlic and clove were found to possess antimicrobial activity. The bactericidal effect of garlic extract was apparent within 1 h of incubation and 93% killing of Staphylococcus epidermidis and Salmonella typhi was achieved within 3 h. Yeasts were totally killed in 1 h by garlic extract but in 5 h with clove. Some bacteria showing resistance to certain antibiotics were sensitive to extracts of both garlic and clove. Greater anti-candidal activity was shown by garlic than by nystatin. Spices might have a great potential to be used as antimicrobial agents.

  4. Antimicrobial drug resistance.

    PubMed

    Martinez, Marilyn; Silley, Peter

    2010-01-01

    This chapter provides an overview of our current understanding of the mechanisms associated with the development of antimicrobial drug resistance, international differences in definitions of resistance, ongoing efforts to track shifts in drug susceptibility, and factors that can influence the selection of therapeutic intervention. The latter presents a matrix of complex variables that includes the mechanism of drug action, the pharmacokinetics (PK) of the antimicrobial agent in the targeted patient population, the pharmacodynamics (PD) of the bacterial response to the antimicrobial agent, the PK/PD relationship that will influence dose selection, and the integrity of the host immune system. Finally, the differences between bacterial tolerance and bacterial resistance are considered, and the potential for non-traditional anti-infective therapies is discussed.

  5. Peptide Antimicrobial Agents

    PubMed Central

    Jenssen, Håvard; Hamill, Pamela; Hancock, Robert E. W.

    2006-01-01

    Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents. PMID:16847082

  6. Polyphenols as antimicrobial agents.

    PubMed

    Daglia, Maria

    2012-04-01

    Polyphenols are secondary metabolites produced by higher plants, which play multiple essential roles in plant physiology and have potential healthy properties on human organism, mainly as antioxidants, anti-allergic, anti-inflammatory, anticancer, antihypertensive, and antimicrobial agents. In the present review the antibacterial, antiviral, and antifungal activities of the most active polyphenol classes are reported, highlighting, where investigated, the mechanisms of action and the structure-activity relationship. Moreover, considering that the microbial resistance has become an increasing global problem, and there is a compulsory need to find out new potent antimicrobial agents as accessories to antibiotic therapy, the synergistic effect of polyphenols in combination with conventional antimicrobial agents against clinical multidrug-resistant microorganisms is discussed.

  7. Critical Compressive Stress for Flat Rectangular Plates Supported Along All Edges and Elastically Restrained Against Rotation along the Unloaded Edges

    NASA Technical Reports Server (NTRS)

    Lundquist, Eugene E; Stowell, Elbridge Z

    1942-01-01

    A chart is presented for the values of the coefficient in the formula for the critical compressive stress at which buckling may be expected to occur in flat rectangular plates supported along all edges and, in addition, elastically restrained against rotation along the unloaded edges. The mathematical derivations of the formulas required in the construction of the chart are given.

  8. Radial anisotropy beneath northeast Tibet, implications for lithosphere deformation at a restraining bend in the Kunlun fault and its vicinity

    NASA Astrophysics Data System (ADS)

    Li, Lun; Li, Aibing; Murphy, Michael A.; Fu, Yuanyuan V.

    2016-09-01

    Three-dimensional shear wave velocity and radial anisotropy models of the crust and upper mantle beneath the NE Tibetan plateau are constructed from new measurements of Love wave dispersions (20-77s) and previously obtained Rayleigh wave dispersions (20-87s) using a two-plane-wave method. The mid-lower crust is characterized with positive anisotropy (VSH > VSV) with large strength beneath the Qinling and Qilian Mountains and small values beneath the Anyemaqen Mountain. The large positive anisotropy can be explained by horizontal alignment of anisotropic minerals in the mid-lower crust due to crustal flow. The mantle lithosphere above 90 km is largely isotropic while weak positive anisotropy appears beneath 90 km, which probably marks the lithosphere-asthenosphere boundary (LAB). A low shear wave velocity anomaly and relatively negative radial anisotropy are imaged in the entire lithosphere beneath the restraining bend in the eastern Kunlun fault, consistent with a weak lithosphere experiencing vertical thickening under horizontal compression. The asthenosphere at the restraining bend is characterized by significant low velocity and positive radial anisotropy, reflecting that the asthenosphere here is probably hotter, has more melts, and deforms more easily than the surrounding region. We propose that the lithosphere at the restraining bend was vertically thickened and subsequently delaminated locally, and induced asthenosphere upwelling. This model explains the observations of velocity and anisotropy anomalies in the lithosphere and asthenosphere as well as geological observations of rapid rock uplift at the restraining bend of the Kunlun fault.

  9. Antimicrobial resistance challenged with metal-based antimicrobial macromolecules.

    PubMed

    Abd-El-Aziz, Alaa S; Agatemor, Christian; Etkin, Nola

    2017-02-01

    Antimicrobial resistance threatens the achievements of science and medicine, as it deactivates conventional antimicrobial therapeutics. Scientists respond to the threat by developing new antimicrobial platforms to prevent and treat infections from these resistant strains. Metal-based antimicrobial macromolecules are emerging as an alternative to conventional platforms because they combine multiple mechanisms of action into one platform due to the distinctive properties of metals. For example, metals interact with intracellular proteins and enzymes, and catalyse various intracellular processes. The macromolecular architecture offers a means to enhance antimicrobial activity since several antimicrobial moieties can be conjugated to the scaffold. Further, these macromolecules can be fabricated into antimicrobial materials for contact-killing medical implants, fabrics, and devices. As volatilization or leaching out of the antimicrobial moieties from the macromolecular scaffold is reduced, these medical implants, fabrics, and devices can retain their antimicrobial activity over an extended period. Recent advances demonstrate the potential of metal-based antimicrobial macromolecules as effective platforms that prevent and treat infections from resistant strains. In this review these advances are thoroughly discussed within the context of examples of metal-based antimicrobial macromolecules, their mechanisms of action and biocompatibility.

  10. Antimicrobial potential of consolidation polymers loaded with biological copper nanoparticles.

    PubMed

    Essa, Ashraf M M; Khallaf, Mohamed K

    2016-07-11

    Biodeterioration of historic monuments and stone works by microorganisms takes place as a result of biofilm production and secretion of organic compounds that negatively affect on the stone matrix. Copper nanoparticles (CuNPs) were prepared biologically using the headspace gases generated by the bacterial culture Escherichia coli Z1. The antimicrobial activity of CuNPs was evaluated against the bacterial strains Bacillus subtilis, Micrococcus luteus, Streptomyces parvulus, Escherichia coli, Pseudomonas aeruginosa as well as some fungal strains Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum, Fusarium solani and Alternaria solani. Biological CuNPs demonstrated antibacterial and antifungal activities higher than those of the untreated copper sulfate. At the same time, limestone and sandstone blocks treated with consolidation polymers functionalized with CuNPs recorded apparent antimicrobial activity against E. coli, S. parvulus and B. subtilis in addition to an improvement in the physical and mechanical characters of the treated stones. Furthermore, the elemental composition of CuNPs was elucidated using electron dispersive x-ray system connected with the scanning electron microscope. Consolidation polymers impregnated with CuNPs could be used to restrain microbial deterioration in addition to the refinement of physico-mechanical behavior of the historic stones.

  11. A nudge in a healthier direction: How environmental cues help restrained eaters pursue their weight-control goal.

    PubMed

    Stämpfli, Aline E; Stöckli, Sabrina; Brunner, Thomas A

    2017-03-01

    Losing weight is a goal for many people, but it is hard to pursue. However, dieting cues in the environment hold promise for improving individuals' eating behavior. For example, exposure to thin, human-like sculptures by the artist Alberto Giacometti has been found to promote healthy snack choices at a vending machine. Whether health- or weight-related processes drive such effects has not yet been determined. However, a detailed understanding of the content-related drivers of environmental cues' effects provides the first indications regarding a cue's possible use. Therefore, two laboratory studies were conducted. They examined the Giacometti sculptures' effects on unhealthy and healthy food intake (Study 1) and on the completion of weight- and health-related fragmented words (Study 2). Study 1 indicated that the sculptures are weight-related by showing that they reduced food intake independent of food healthiness. Furthermore, the "Giacometti effect" was moderated by restrained eating. Restrained eaters, who are known for their weight-control goal, ate less after having been exposed to the thin sculptures. The results of Study 2 pointed in the same direction. Restrained eaters completed more weight-related words after being exposed to the sculptures. Overall, these studies suggest that the thin sculptures are primarily weight-related cues and particularly helpful for restrained eaters. Environmental weight-control cues such as the Giacometti sculptures could act as a counterforce to our obesogenic environment and help restrained eaters pursue their weight-control goal. In this way, they could nudge food decisions in a healthier direction.

  12. Antimicrobial Tolerance in Biofilms

    PubMed Central

    Stewart, Philip S.

    2015-01-01

    The tolerance of microorganisms in biofilms to antimicrobial agents is examined through a meta-analysis of literature data. A numerical tolerance factor comparing the rates of killing in the planktonic and biofilm states is defined to provide a quantitative basis for the analysis. Tolerance factors for biocides and antibiotics range over three orders of magnitude. This variation is not explained by taking into account the molecular weight of the agent, the chemistry of the agent, the substratum material, or the speciation of the microorganisms. Tolerance factors do depend on the areal cell density of the biofilm at the time of treatment and on the age of the biofilm as grown in a particular experimental system. This suggests that there is something that happens during biofilm maturation, either physical or physiological, that is essential for full biofilm tolerance. Experimental measurements of antimicrobial penetration times in biofilms range over orders of magnitude, with slower penetration (>12 min) observed for reactive oxidants and cationic molecules. These agents are retarded through the interaction of reaction, sorption, and diffusion. The specific physiological status of microbial cells in a biofilm contributes to antimicrobial tolerance. A conceptual framework for categorizing physiological cell states is discussed in the context of antimicrobial susceptibility. It is likely that biofilms harbor cells in multiple states simultaneously (e.g., growing, stress-adapted, dormant, inactive) and that this physiological heterogeneity is an important factor in the tolerance of the biofilm state. PMID:26185072

  13. Pediatric Antimicrobial Stewardship Programs

    PubMed Central

    Nichols, Kristen; Stoffella, Sylvia; Meyers, Rachel; Girotto, Jennifer

    2017-01-01

    The frequent use of antimicrobials in pediatric patients has led to a significant increase in multidrug-resistant bacterial infections among children. Antimicrobial stewardship programs have been created in many hospitals in an effort to curtail and optimize the use of antibiotics. Pediatric-focused programs are necessary because of the differences in antimicrobial need and use among this patient population, unique considerations and dosing, vulnerability for resistance due to a lifetime of antibiotic exposure, and the increased risk of adverse events. This paper serves as a position statement of the Pediatric Pharmacy Advocacy Group (PPAG) who supports the implementation of antimicrobial stewardship programs for all pediatric patients. PPAG also believes that a pediatric pharmacy specialist should be included as part of that program and that services be covered by managed care organizations and government insurance entities. PPAG also recommends that states create legislation similar to that in existence in California and Missouri and that a federal Task Force for Combating Antibiotic-Resistant Bacteria be permanently established. PPAG also supports post-doctoral pharmacy training programs in antibiotic stewardship.

  14. Multifactorial antimicrobial wood protectants

    Treesearch

    Robert D. Coleman; Carol A. Clausen

    2008-01-01

    It is unlikely that a single antimicrobial compound, whether synthetic or natural, will provide the ‘magic bullet’ for eliminating multiple biological agents affecting wood products. Development of synergistic combinations of selected compounds, especially those derived from natural sources, is recognized as a promising approach to improved wood protection. Recent...

  15. Multidimensional signatures in antimicrobial peptides

    PubMed Central

    Yount, Nannette Y.; Yeaman, Michael R.

    2004-01-01

    Conventional analyses distinguish between antimicrobial peptides by differences in amino acid sequence. Yet structural paradigms common to broader classes of these molecules have not been established. The current analyses examined the potential conservation of structural themes in antimicrobial peptides from evolutionarily diverse organisms. Using proteomics, an antimicrobial peptide signature was discovered to integrate stereospecific sequence patterns and a hallmark three-dimensional motif. This striking multidimensional signature is conserved among disulfide-containing antimicrobial peptides spanning biological kingdoms, and it transcends motifs previously limited to defined peptide subclasses. Experimental data validating this model enabled the identification of previously unrecognized antimicrobial activity in peptides of known identity. The multidimensional signature model provides a unifying structural theme in broad classes of antimicrobial peptides, will facilitate discovery of antimicrobial peptides as yet unknown, and offers insights into the evolution of molecular determinants in these and related host defense effector molecules. PMID:15118082

  16. Triclosan antimicrobial polymers

    PubMed Central

    Petersen, Richard C.

    2016-01-01

    Triclosan antimicrobial molecular fluctuating energies of nonbonding electron pairs for the oxygen atom by ether bond rotations are reviewed with conformational computational chemistry analyses. Subsequent understanding of triclosan alternating ether bond rotations is able to help explain several material properties in Polymer Science. Unique bond rotation entanglements between triclosan and the polymer chains increase both the mechanical properties of polymer toughness and strength that are enhanced even better through secondary bonding relationships. Further, polymer blend compatibilization is considered due to similar molecular relationships and polarities. With compatibilization of triclosan in polymers a more uniform stability for nonpolar triclosan in the polymer solid state is retained by the antimicrobial for extremely low release with minimum solubility into aqueous solution. As a result, triclosan is projected for long extended lifetimes as an antimicrobial polymer additive. Further, triclosan rapid alternating ether bond rotations disrupt secondary bonding between chain monomers in the resin state to reduce viscosity and enhance polymer blending. Thus, triclosan is considered for a polymer additive with multiple properties to be an antimicrobial with additional benefits as a nonpolar toughening agent and a hydrophobic wetting agent. The triclosan material relationships with alternating ether bond rotations are described through a complete different form of medium by comparisons with known antimicrobial properties that upset bacterial cell membranes through rapid fluctuating mechanomolecular energies. Also, triclosan bond entanglements with secondary bonding can produce structural defects in weak bacterial lipid membranes requiring pliability that can then interfere with cell division. Regarding applications with polymers, triclosan can be incorporated by mixing into a resin system before cure, melt mixed with thermoplastic polymers that set on cooling

  17. Assessment of Prone Positioning of Restrained, Seated Crewmembers in a Post Landing Stable 2 Orion Configuration

    NASA Technical Reports Server (NTRS)

    Barr, Yael; Fogarty, Jennifer

    2010-01-01

    During the Orion landing and recovery subsystem design review, June 2009, it was noted that the human system and various vehicle systems, the environmental control and life support (ECLSS) and guidance, navigation and control (GN&C) systems for example, are negatively affected by Orion assuming a stable 2 (upside down; Figure A) configuration post landing. The stable 2 configuration is predicted to occur about 50% of the time based on Apollo landing data and modeling of the current capsule. The stable 2 configuration will be countered by an active up-righting system (crew module up-righting system; CMUS). Post landing balloons will deploy and inflate causing the vehicle to assume or maintain the stable 1 (up-right; Figure B) configuration. During the design review it was proposed that the up-righting system could be capable of righting the vehicle within 60 seconds. However, this time limit posed a series of constraints on the design which made it less robust than desired. The landing and recovery subsystem team requested an analysis of Orion vehicle systems as well as the human system with regard to the effect of stable 2 in order to determine if an up-righting response time greater than 60 seconds could be tolerated. The following report focuses on the assessment of the human system in the posture assumed when Orion is in the stable 2 configuration. Stable 2 will place suited, seated, and restrained crewmembers in a prone (facedown), head-up position for a period of time dependent on the functionality of the up-righting systems, ability of the crew to release themselves from the seat and restraints, and/or time to arrival of rescue forces. Given that the Orion seat and restraint system design is not complete and therefore, not available for evaluation, Space Medicine assessed how long a healthy but deconditioned crewmember could stay in this prone, restrained position and the physiological consequences of this posture by researching terrestrial analogs and

  18. Fluid-structure interaction of a rolling restrained body of revolution at high angles of attack

    NASA Astrophysics Data System (ADS)

    Degani, D.; Ishay, M.; Gottlieb, O.

    2017-03-01

    The current work investigates numerically rolling instabilities of a free-to-roll slender rigid-body of revolution placed in a wind tunnel at a high angle of attack. The resistance to the roll moment is represented by a linear torsion spring and equivalent linear damping representing friction in the bearings of a simulated wind tunnel model. The body is subjected to a three-dimensional, compressible, laminar flow. The full Navier-Stokes equations are solved using the second-order implicit finite difference Beam-Warming scheme, adapted to a curvilinear coordinate system, whereas the coupled structural second order equation of motion for roll is solved by a fourth-order Runge-Kutta method. The body consists of a 3.5-diameter tangent ogive forebody with a 7.0-diameter long cylindrical afterbody extending aft of the nose-body junction to x/D = 10.5. We describe in detail the investigation of three angles of attack 20°, 40°, and 65°, at a Reynolds number of 30 000 (based on body diameter) and a Mach number of 0.2. Three distinct configurations are investigated as follows: a fixed body, a free-to-roll body with a weak torsion spring, and a free-to-roll body with a strong torsion spring. For each angle of attack the free-to-roll configuration portrays a distinct and different behavior pattern, including bi-stable limit-cycle oscillations. The bifurcation structure incorporates both large and small amplitude periodic roll oscillations where the latter lose their periodicity with increasing stiffness of the restraining spring culminating with distinct quasiperiodic oscillations. We note that removal of an applied upstream disturbance for a restrained body does not change the magnitude or complexity of the oscillations or of the flow patterns along the body. Depending on structure characteristics and flow conditions even a small rolling moment coefficient at the relatively low angle of attack of 20° may lead to large amplitude resonant roll oscillations.

  19. Starch-based Antimicrobial Films Incorporated with Lauric Acid and Chitosan

    NASA Astrophysics Data System (ADS)

    Salleh, E.; Muhamad, I. I.

    2010-03-01

    Antimicrobial (AM) packaging is one of the most promising active packaging systems. Starch-based film is considered an economical material for antimicrobial packaging. This study aimed at the development of food packaging based on wheat starch incorporated with lauric acid and chitosan as antimicrobial agents. The purpose is to restrain or inhibit the growth of spoilage and/or pathogenic microorganisms that are contaminating foods. The antimicrobial effect was tested on B. substilis and E. coli. Inhibition of bacterial growth was examined using two methods, i.e. zone of inhibition test on solid media and liquid culture test (optical density measurements). The control and AM films (incorporated with chitosan and lauric acid) were produced by casting method. From the observations, AM films exhibited inhibitory zones. Interestingly, a wide clear zone on solid media was observed for B. substilis growth inhibition whereas inhibition for E. coli was not as effective as B. substilis. From the liquid culture test, the AM films clearly demonstrated a better inhibition against B. substilis than E. coli.

  20. Early age damage quantification of actively restrained concrete using inverse analysis

    NASA Astrophysics Data System (ADS)

    Albanna, Ali

    Early-age cracking can be a significant problem in concrete pavements, floors, and bridge decks. Cracking occurs when the volumetric changes associated with drying, hydration, and temperature reduction are prevented. Good knowledge about the characteristics of early age concrete is necessary to achieve reliable crack control. Volumetric changes due to shrinkage depend on the type of concrete and its components. It has been found that light weight aggregates can work as internal reservoir to supply the concrete matrix with water that is needed during the early age; this process is called internal curing. Also fibers can give more ductility to the concrete and produce less shrinkage. There is a need to better understand the effects of early age uniaxial restraint on long term concrete mechanical performance. In this study, two types of concrete were studied (high performance fiber reinforced concrete and ordinary concrete) under actively restrained loading conditions to assess the effect on the long term fracture toughness and energy. Single edge notched specimens having dimensions of 250 mm x 150 mm x 75 mm and a notch to depth ratio of 0.33 were caste and used in both direct tension and three point bending. The direct tension tests were carried out on a direct tension loading frame constructed in house that was supplied with two mechanical jacks and load cell.

  1. Megakaryocytes possess a functional intrinsic apoptosis pathway that must be restrained to survive and produce platelets

    PubMed Central

    Josefsson, Emma C.; James, Chloé; Henley, Katya J.; Debrincat, Marlyse A.; Rogers, Kelly L.; Dowling, Mark R.; White, Michael J.; Kruse, Elizabeth A.; Lane, Rachael M.; Ellis, Sarah; Nurden, Paquita; Mason, Kylie D.; O’Reilly, Lorraine A.; Roberts, Andrew W.; Metcalf, Donald; Huang, David C.S.

    2011-01-01

    It is believed that megakaryocytes undergo a specialized form of apoptosis to shed platelets. Conversely, a range of pathophysiological insults, including chemotherapy, are thought to cause thrombocytopenia by inducing the apoptotic death of megakaryocytes and their progenitors. To resolve this paradox, we generated mice with hematopoietic- or megakaryocyte-specific deletions of the essential mediators of apoptosis, Bak and Bax. We found that platelet production was unperturbed. In stark contrast, deletion of the prosurvival protein Bcl-xL resulted in megakaryocyte apoptosis and a failure of platelet shedding. This could be rescued by deletion of Bak and Bax. We examined the effect on megakaryocytes of three agents that activate the intrinsic apoptosis pathway in other cell types: etoposide, staurosporine, and the BH3 mimetic ABT-737. All three triggered mitochondrial damage, caspase activation, and cell death. Deletion of Bak and Bax rendered megakaryocytes resistant to etoposide and ABT-737. In vivo, mice with a Bak−/− Bax−/− hematopoietic system were protected against thrombocytopenia induced by the chemotherapeutic agent carboplatin. Thus, megakaryocytes do not activate the intrinsic pathway to generate platelets; rather, the opposite is true: they must restrain it to survive and progress safely through proplatelet formation and platelet shedding. PMID:21911424

  2. Parametric vibrations of a restrained beam with an end mass under displacement excitation

    NASA Astrophysics Data System (ADS)

    Gürgöze, M.

    1986-07-01

    This paper is concerned with the stability and the steady state response of the main parametric resonance vibrations of a simply supported vertical beam. The beam carries a concentrated mass and is restrained at one end and subjected to a periodic axial displacement excitation at the other end. This system can be looked upon as a dynamic model of the vibrations of an engine valve mechanism. Non-linear terms arising from moderately large curvatures, longitudinal inertia of the beam elements and concentrated mass are included in the equation of motion. By using the one mode approximation and applying Galerkin's method, the governing partial differential equation is reduced to a non-linear ordinary differential equation with a periodic coefficient. The boundaries of the main parametric instability region of the linearized equation are obtained. The harmonic balance method is applied to solve the equation and an analytical expression for the dynamic response in the vicinity of the main parametric resonance is derived. The effects of various parameters on the boundaries of the instability region and the dynamic response are investigated.

  3. YY1 restrained cell senescence through repressing the transcription of p16.

    PubMed

    Wang, Xiuli; Feng, Yunpeng; Xu, Liang; Chen, Yuli; Zhang, Yu; Su, Dongmei; Ren, Guoling; Lu, Jun; Huang, Baiqu

    2008-10-01

    The transcription factor YY1 has been implicated to play a role in cell growth control. In this report, we demonstrate that YY1 was able to suppress NCI-H460 cell senescence through regulating the expression of p16(INK4a), a cyclin-dependent kinase inhibitor. We also show that YY1 participated in the repression of p16(INK4a) expression in 293T cells through an epigenetic mechanism involving histone acetylation modification. Specifically, HDAC3 and HDAC4 inhibited the p16(INK4a) promoter activity. The chromatin immunoprecipitation (ChIP) assays verified that HDAC3 and HDAC4 were recruited to p16(INK4a) promoter by YY1. Moreover, co-immunoprecipitation assays revealed that these three protein factors formed a complex. Furthermore, knockdown of these factors induced cell enlargement and flattened morphology and significantly increased the SA-beta-gal activity, a biochemical marker of cell senescence. Overall, data from this study suggest that YY1, HDAC3 and HDAC4 restrained cell senescence by repressing p16(INK4a) expression through an epigenetic modification of histones.

  4. E3 Ubiquitin Ligase RLIM Negatively Regulates c-Myc Transcriptional Activity and Restrains Cell Proliferation

    PubMed Central

    Wang, Lan; Cai, Hao; Zhu, Jingjing; Yu, Long

    2016-01-01

    RNF12/RLIM is a RING domain-containing E3 ubiquitin ligase whose function has only begun to be elucidated recently. Although RLIM was reported to play important roles in some biological processes such as imprinted X-chromosome inactivation and regulation of TGF-β pathway etc., other functions of RLIM are largely unknown. Here, we identified RLIM as a novel E3 ubiquitin ligase for c-Myc, one of the most frequently deregulated oncoproteins in human cancers. RLIM associates with c-Myc in vivo and in vitro independently of the E3 ligase activity of RLIM. Moreover, RLIM promotes the polyubiquitination of c-Myc protein independently of Ser62 and Thr58 phosphorylation of c-Myc. However, RLIM-mediated ubiquitination does not affect c-Myc stability. Instead, RLIM inhibits the transcriptional activity of c-Myc through which RLIM restrains cell proliferation. Our results suggest that RLIM may function as a tumor suppressor by controlling the activity of c-Myc oncoprotein. PMID:27684546

  5. Ischemia Reperfusion Unveils Impaired Capacity of Older Adults to Restrain Oxidative Insult

    PubMed Central

    Davies, Sean S.; Traustadóttir, Tinna; Stock, Anthoney A.; Ye, Fei; Shyr, Yu; Harman, S. Mitchell; Roberts, L. Jackson

    2009-01-01

    Age independently predicts poor outcome in a variety of medical settings including sepsis, trauma, severe burns, and surgery. Since these conditions are associated with oxidative stress, we hypothesized that the capacity to constrain oxidative insult diminishes with age, leading to more extensive oxidative damage during trauma. To test this hypothesis, we used supra-systolic inflation of an arm blood pressure cuff to safely induce localized forearm ischemia/reperfusion (I/R) and quantified plasma F2-isoprostane (IsoP) levels in serial blood samples. Prior to I/R, IsoP levels were similar in young (20-33 yrs) and older adults (62-81 yrs). After I/R challenge, the magnitude and duration of increased IsoP levels was significantly greater in older adults. Because aging is associated with declining levels of sex hormones that contribute to regulation of antioxidant enzyme expression, we then examined the response to I/R in older women receiving hormone replacement therapy, and found these women did not manifest the amplified IsoP response found in untreated older women. These finding demonstrate that aging impairs the ability to restrain oxidative damage after an acute insult, which may contribute to the increased vulnerability of older adults to traumatic conditions, and establishes a useful method to identify effective interventions to ameliorate this deficiency. PMID:19596063

  6. Occurring mechanism and restraining method research of numerical noise signal in penetration simulation

    NASA Astrophysics Data System (ADS)

    Wang, Chen; Wang, Yabin

    2016-09-01

    In hard target penetration simulation, the existing researches of the convergence of results are mainly concentrating in the corresponding relationship between penetration depth and mesh scales. However, the influence of the mesh difference on the penetration resistance and acceleration signals are seldom refer to. This paper presents the occurring mechanism and restraining method of numerical noise signal in penetration simulation. First, the concept of the noise signal izs proposed. By taking a 3D penetration simulation as example, the influence of the noise signal on the penetration resistance in different mesh scales and impact velocity is studied. To ensure the convergence of the computational results, the grid scale of the target is encrypted to 1:1:8. In addition, modern spectrum analysis method is introduced to further analyze the penetration resistance signal. The research results presented is useful to improve the computational accuracy of high speed projectile penetration simulation, and provide important reference for carrying out structural design and optimization of fuze system.

  7. Effects of chewing gum on short-term appetite regulation in moderately restrained eaters.

    PubMed

    Hetherington, Marion M; Regan, Martin F

    2011-10-01

    Orosensory stimulation is an important contributing factor to the development of satiation. Providing orosensory stimulation with few calories may satisfy appetite and help to suppress cravings for high energy snacks. This may be a useful strategy for those motivated to lose or maintain weight. The present study tested the hypothesis that chewing sweetened gum will reduce subjective appetite and subsequent snack intake in moderately restrained eaters. Within-subjects, repeated measures study, sixty healthy participants (53 women; body mass index, in kg/m(2): 26.2±4.5) came to the laboratory 4 times for a standard lunch. Immediately after this meal, participants rated hunger, appetite and cravings for sweet and salty snacks every hour until they returned to the laboratory 3 h later for snack. On two occasions during this 3 h period participants chewed gum for at least 15 min at hourly intervals (45 min) and on two occasions no gum was chewed. On two occasions salty snacks were offered and on two occasions sweet snacks were provided. A small but significant reduction in snack intake was observed, chewing gum reduced weight of snack consumed by 10% compared to no gum (p<0.05). Overall, chewing gum for at least 45 min significantly suppressed rated hunger, appetite and cravings for snacks and promoted fullness (p<0.05). This study demonstrated some benefit of chewing gum which could be of utility to those seeking an aid to appetite control.

  8. Quorum sensing restrains growth and is rapidly inactivated during domestication of Sinorhizobium meliloti.

    PubMed

    Charoenpanich, Pornsri; Soto, Maria J; Becker, Anke; McIntosh, Matthew

    2015-04-01

    Microbial cooperative behaviours, such as quorum sensing (QS), improve survival and this explains their prevalence throughout the microbial world. However, relatively little is known about the mechanisms by which cooperation promotes survival. Furthermore, cooperation typically requires costly contributions, e.g. exopolysaccharides, which are produced from limited resources. Inevitably, cooperation is vulnerable to damaging mutations which results in mutants that are relieved of the burden of contributing but nonetheless benefit from the contributions of their parent. Unless somehow prevented, such mutants may outcompete and replace the parent. The bacterium Sinorhizobium meliloti uses QS to activate the production of copious levels of exopolysaccharide (EPS). Domestication of this bacterium is typified by the appearance of spontaneous mutants incapable of EPS production, which take advantage of EPS production by the parent and outcompete the parent. We found that all of the mutants were defect in QS, implying that loss of QS is a typical consequence of the domestication of this bacterium. This instability was traced to several QS-regulated processes, including a QS-dependent restraint of growth, providing the mutant with a significant growth advantage. A model is proposed whereby QS restrains population growth to prevent overcrowding and prepares the population for the survival of severe conditions.

  9. Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation.

    PubMed

    Lettieri Barbato, D; Aquilano, K; Baldelli, S; Cannata, S M; Bernardini, S; Rotilio, G; Ciriolo, M R

    2014-01-01

    The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-α, peroxisome proliferator-activated receptor-γ coactivator-1α), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders.

  10. An oligodeoxynucleotide with CCT repeats restrains CpG ODN-induced TLR9 trafficking.

    PubMed

    Zhang, Xiaoling; Sun, Wei; Wu, Xiuli; Wang, Hua; Yan, Youyou; Guo, Sheng; Song, Dandan; Li, Hainan; Gao, Shuang; Wang, Luowei; Yu, Yongli; Wang, Liying

    2014-01-01

    Toll-like receptor 9 (TLR9) can sense pathogen DNA and CpG ODN or even self-DNA by trafficking assisted by Unc93B1, an endoplasmic reticulum (ER) transmembrane protein, from ER to endolysosomes or cell surface. In previous study, we found that an oligodeoxynucleotide with CCT repeats (SAT05f) could selectively inhibit TLR7/9 activation. However, the mechanism for the inhibitory activity of SAT05f is still unknown. In present research, it was found that SAT05f could inhibit CpG ODN-induced the intracellular trafficking of TLR9 and Unc93B1 with feedback the responses of decreased surface TLR9 and enhanced TLR9 mRNA expression but not influence TLR9 protein level by using human plasmacytoid dendritic cell line CAL-1 cells, suggesting that SAT05f inhibits TLR9 activation by restraining TLR9 trafficking. Since the mitochondrial DNA released from injured tissue can cause systemic inflammatory response syndrome (SIRS), this study may provide valuable data for prevention and treatment of SIRS and rescue severe trauma patients.

  11. Intimate Partner Violence Victims Seeking a Temporary Restraining Order: Social Support and Resilience Attenuating Psychological Distress.

    PubMed

    Jose, Rupa; Novaco, Raymond W

    2016-12-01

    Social support has been found in many studies to be a protective factor for those exposed to intimate partner violence (IPV), but personal resilience has received far less attention. The present study concerns 136 female IPV victims seeking a temporary restraining order (TRO) from a Family Justice Center (FJC). The relationships between IPV victimization, social support, resilience, and psychological distress were examined. Hierarchical regressions found that both perceived social support and self-reported resilience were inversely associated with distress symptoms. Higher social support was associated with lower trauma symptoms, controlling for abuse history, demographics, and resilience. Higher resilience was associated with lower mood symptoms and lower perceived stress, controlling for abuse history, demographics, and social support. No significant associations were recorded for anger symptoms. These findings suggest that fostering resilience can have important health benefits for IPV victims, above and beyond the well-known benefits of social support. Ways that resilience might be cultivated in this population and other implications for practice are discussed.

  12. Neuropharmacological Manipulation of Restrained and Free-flying Honey Bees, Apis mellifera.

    PubMed

    Søvik, Eirik; Plath, Jenny A; Devaud, Jean-Marc; Barron, Andrew B

    2016-11-26

    Honey bees demonstrate astonishing learning abilities and advanced social behavior and communication. In addition, their brain is small, easy to visualize and to study. Therefore, bees have long been a favored model amongst neurobiologists and neuroethologists for studying the neural basis of social and natural behavior. It is important, however, that the experimental techniques used to study bees do not interfere with the behaviors being studied. Because of this, it has been necessary to develop a range of techniques for pharmacological manipulation of honey bees. In this paper we demonstrate methods for treating restrained or free-flying honey bees with a wide range of pharmacological agents. These include both noninvasive methods such as oral and topical treatments, as well as more invasive methods that allow for precise drug delivery in either systemic or localized fashion. Finally, we discuss the advantages and disadvantages of each method and describe common hurdles and how to best overcome them. We conclude with a discussion on the importance of adapting the experimental method to the biological questions rather than the other way around.

  13. Buckling Of Long Compression-Loaded Anisotropic Plates Restrained Against Inplane Lateral and Shear Deformations

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2003-01-01

    An approach for synthesizing buckling results and behavior for thin balanced and unbalanced symmetric laminates that are subjected to uniform axial compression loads and elastically restrained against inplane expansion, contraction, and shear deformation is presented. This approach uses a nondimensional analysis for infinitely long, flexurally anisotropic plates (coupling between bending and twisting) that are subjected to combined mechanical loads and is based on nondimensional parameters. In addition, nondimensional loading parameters are derived that account for the effects of the elastic inplane deformation restraints, membrane orthotropy, and membrane anisotropy on the induced prebuckling stress state. The loading parameters are used to determine buckling coefficients that include the effects of flexural orthotropy and flexural anisotropy. Many results are presented, for some selected laminates, that are intended to facilitate a structural designer's transition to the use of the generic buckling design curves that are presented and discussed in the paper. Several buckling response curves are presented that provide physical insight into the behavior for combined loads, in addition to providing useful design data. An example is presented that demonstrates the use of the generic design curves, which are applicable to a wide range of laminate constructions. The analysis approach and generic results indicate the effects and characteristics of laminate orthotropy and anisotropy in a very general and unifying manner.

  14. Gun Violence Restraining Orders: Alternative or Adjunct to Mental Health-Based Restrictions on Firearms?

    PubMed

    Frattaroli, Shannon; McGinty, Emma E; Barnhorst, Amy; Greenberg, Sheldon

    2015-06-01

    The gun violence restraining order (GVRO) is a new tool for preventing gun violence. Unlike traditional approaches to prohibiting gun purchase and possession, which rely on a high threshold (adjudication by criminal justice or mental health systems) before intervening, the GVRO allows family members and intimate partners who observe a relative's dangerous behavior and believe it may be a precursor to violence to request a GVRO through the civil justice system. Once issued by the court, a GVRO authorizes law enforcement to remove any guns in the respondent's possession and prohibits the respondent from purchasing new guns. In September 2014, California's governor signed AB1014 into law, making California the first U.S. state to enact a GVRO law. This article describes the GVRO and the rationale behind the concept, considers case examples to assess the potential impact of the GVRO as a strategy for preventing gun violence, and reviews the content of the California law. Copyright © 2015 John Wiley & Sons, Ltd.

  15. Parallel helix bundles and ion channels: molecular modeling via simulated annealing and restrained molecular dynamics.

    PubMed Central

    Kerr, I D; Sankararamakrishnan, R; Smart, O S; Sansom, M S

    1994-01-01

    A parallel bundle of transmembrane (TM) alpha-helices surrounding a central pore is present in several classes of ion channel, including the nicotinic acetylcholine receptor (nAChR). We have modeled bundles of hydrophobic and of amphipathic helices using simulated annealing via restrained molecular dynamics. Bundles of Ala20 helices, with N = 4, 5, or 6 helices/bundle were generated. For all three N values the helices formed left-handed coiled coils, with pitches ranging from 160 A (N = 4) to 240 A (N = 6). Pore radius profiles revealed constrictions at residues 3, 6, 10, 13, and 17. A left-handed coiled coil and a similar pattern of pore constrictions were observed for N = 5 bundles of Leu20. In contrast, N = 5 bundles of Ile20 formed right-handed coiled coils, reflecting loosened packing of helices containing beta-branched side chains. Bundles formed by each of two classes of amphipathic helices were examined: (a) M2a, M2b, and M2c derived from sequences of M2 helices of nAChR; and (b) (LSSLLSL)3, a synthetic channel-forming peptide. Both classes of amphipathic helix formed left-handed coiled coils. For (LSSLLSL)3 the pitch of the coil increased as N increased from 4 to 6. The M2c N = 5 helix bundle is discussed in the context of possible models of the pore domain of nAChR. Images FIGURE 1 FIGURE 3 PMID:7529585

  16. Apoptosis repressor with a CARD domain (ARC) restrains Bax-mediated pathogenesis in dystrophic skeletal muscle.

    PubMed

    Davis, Jennifer; Kwong, Jennifer Q; Kitsis, Richard N; Molkentin, Jeffery D

    2013-01-01

    Myofiber wasting in muscular dystrophy has largely been ascribed to necrotic cell death, despite reports identifying apoptotic markers in dystrophic muscle. Here we set out to identify the contribution of canonical apoptotic pathways to skeletal muscle degeneration in muscular dystrophy by genetically deleting a known inhibitor of apoptosis, apoptosis repressor with a card domain (Arc), in dystrophic mouse models. Nol3 (Arc protein) genetic deletion in the dystrophic Sgcd or Lama2 null backgrounds showed exacerbated skeletal muscle pathology with decreased muscle performance compared with single null dystrophic littermate controls. The enhanced severity of the dystrophic phenotype associated with Nol3 deletion was caspase independent but dependent on the mitochondria permeability transition pore (MPTP), as the inhibitor Debio-025 partially rescued skeletal muscle pathology in Nol3 (-/-) Sgcd (-/-) double targeted mice. Mechanistically, Nol3 (-/-) Sgcd (-/-) mice showed elevated total and mitochondrial Bax protein levels, as well as greater mitochondrial swelling, suggesting that Arc normally restrains the cell death effects of Bax in skeletal muscle. Indeed, knockdown of Arc in mouse embryonic fibroblasts caused an increased sensitivity to cell death that was fully blocked in Bax Bak1 (genes encoding Bax and Bak) double null fibroblasts. Thus Arc deficiency in dystrophic muscle exacerbates disease pathogenesis due to a Bax-mediated sensitization of mitochondria-dependent death mechanisms.

  17. Brain activation in restrained and unrestrained eaters: an fMRI study.

    PubMed

    Coletta, Maria; Platek, Steven; Mohamed, Feroze B; van Steenburgh, J Jason; Green, Deborah; Lowe, Michael R

    2009-08-01

    Restraint theory has been used to model the process that produces binge eating. However, there is no satisfactory explanation for the tendency of restrained eaters (REs) to engage in counterregulatory eating, an ostensible analogue of binge eating. Using functional magnetic resonance imaging (fMRI), the authors investigated brain activation of normal weight REs (N = 9) and unrestrained eaters (UREs; N = 10) when fasted and fed and viewing pictures of highly and moderately palatable foods and neutral objects. When fasted and viewing highly palatable foods, UREs showed widespread bilateral activation in areas associated with hunger and motivation, whereas REs showed activation only in the cerebellum, an area previously implicated in low-level processing of appetitive stimuli. When fed and viewing high palatability foods, UREs showed activation in areas related to satiation and memory, whereas REs showed activation in areas implicated in desire, expectation of reward, and goal-defined behavior. These findings parallel those from behavioral research. The authors propose that the counterintuitive findings from preload studies and the present study are due to the fact that REs are less hungry than UREs when fasted and find palatable food more appealing than UREs when fed.

  18. Buckling Behavior of Long Anisotropic Plates Subjected to Fully Restrained Thermal Expansion

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2003-01-01

    An approach for synthesizing buckling results and behavior for thin, balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and which are fully-restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexurally anisotropic plates that are subjected to combined mechanical loads and is based on useful nondimensional parameters. In addition, stiffness-weighted laminate thermal-expansion parameters are derived and used to determine critical temperature changes in terms of physically intuitive mechanical buckling coefficients. The effects of membrane orthotropy and anisotropy are included. Many results are presented for some common laminates that are intended to facilitate a structural designer's transition to the use of the generic buckling design curves that are presented in the paper. Several generic buckling design curves are presented that provide physical insight into buckling response and provide useful design data. Examples are presented that demonstrate the use of generic design curves. The analysis approach and generic results indicate the effects and characteristics of laminate thermal expansion, membrane orthotropy and anisotropy, and flexural orthotropy and anisotropy in a very general, unifying manner.

  19. Buckling Behavior of Long Anisotropic Plates Subjected to Fully Restrained Thermal Expansion

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2001-01-01

    An approach for synthesizing buckling results and behavior for thin balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and fully restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexurally anisotropic plates that are subjected to combined mechanical loads and is based on useful nondimensional parameters. In addition, stiffness-weighted laminate thermal-expansion parameters are derived that are used to determine critical temperatures in terms of physically intuitive mechanical buckling coefficients, and the effects of membrane orthotropy and membrane anisotropy are included. Many results are presented for some common laminates that are intended to facilitate a structural designer's transition to the use of the generic buckling design curves that are presented in the paper. Several generic buckling design curves are presented that provide physical insight into the buckling response in addition to providing useful design data. Examples are presented that demonstrate the use of the generic design curves. The analysis approach and generic results indicate the effects and characteristics of laminate thermal expansion, membrane orthotropy and anisotropy, and flexural orthotropy and anisotropy in a very general and unifying manner.

  20. Klar ensures thermal robustness of oskar localization by restraining RNP motility

    PubMed Central

    Gaspar, Imre; Yu, Yanxun V.; Cotton, Sean L.; Kim, Dae-Hwan

    2014-01-01

    Communication usually applies feedback loop–based filters and amplifiers to ensure undistorted delivery of messages. Such an amplifier acts during Drosophila melanogaster midoogenesis, when oskar messenger ribonucleic acid (mRNA) anchoring depends on its own locally translated protein product. We find that the motor regulator Klar β mediates a gain-control process that prevents saturation-based distortions in this positive feedback loop. We demonstrate that, like oskar mRNA, Klar β localizes to the posterior pole of oocytes in a kinesin-1–dependent manner. By live imaging and semiquantitative fluorescent in situ hybridization, we show that Klar β restrains oskar ribonucleoprotein motility and decreases the posterior-ward translocation of oskar mRNA, thereby adapting the rate of oskar delivery to the output of the anchoring machinery. This negative regulatory effect of Klar is particularly important for overriding temperature-induced changes in motility. We conclude that by preventing defects in oskar anchoring, this mechanism contributes to the developmental robustness of a poikilothermic organism living in a variable temperature environment. PMID:25049271

  1. DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination

    PubMed Central

    Zamudio, Natasha; Barau, Joan; Teissandier, Aurélie; Walter, Marius; Borsos, Maté; Servant, Nicolas; Bourc'his, Déborah

    2015-01-01

    DNA methylation is essential for protecting the mammalian germline against transposons. When DNA methylation-based transposon control is defective, meiotic chromosome pairing is consistently impaired during spermatogenesis: How and why meiosis is vulnerable to transposon activity is unknown. Using two DNA methylation-deficient backgrounds, the Dnmt3L and Miwi2 mutant mice, we reveal that DNA methylation is largely dispensable for silencing transposons before meiosis onset. After this, it becomes crucial to back up to a developmentally programmed H3K9me2 loss. Massive retrotransposition does not occur following transposon derepression, but the meiotic chromatin landscape is profoundly affected. Indeed, H3K4me3 marks gained over transcriptionally active transposons correlate with formation of SPO11-dependent double-strand breaks and recruitment of the DMC1 repair enzyme in Dnmt3L−/− meiotic cells, whereas these features are normally exclusive to meiotic recombination hot spots. Here, we demonstrate that DNA methylation restrains transposons from adopting chromatin characteristics amenable to meiotic recombination, which we propose prevents the occurrence of erratic chromosomal events. PMID:26109049

  2. FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy

    PubMed Central

    Lexmond, Willem S.; Goettel, Jeremy A.; Lyons, Jonathan J.; Jacobse, Justin; Deken, Marion M.; Lawrence, Monica G.; DiMaggio, Thomas H.; Kotlarz, Daniel; Garabedian, Elizabeth; Sackstein, Paul; Nelson, Celeste C.; Jones, Nina; Stone, Kelly D.; Rings, Edmond H.H.M.; Thrasher, Adrian J.; Milner, Joshua D.; Snapper, Scott B.; Fiebiger, Edda

    2016-01-01

    In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE. Here, we have shown that WAS patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen–free as well as germ-free housing conditions. Conditional deletion of Was in FOXP3+ Tregs resulted in more severe Th2-type intestinal inflammation than that observed in mice with global WASP deficiency, indicating that allergic responses to food allergens are dependent upon loss of WASP expression in this immune compartment. While WASP-deficient Tregs efficiently contained Th1- and Th17-type effector differentiation in vivo, they failed to restrain Th2 effector responses that drive allergic intestinal inflammation. Loss of WASP was phenotypically associated with increased GATA3 expression in effector memory FOXP3+ Tregs, but not in naive-like FOXP3+ Tregs, an effect that occurred independently of increased IL-4 signaling. Our results reveal a Treg-specific role for WASP that is required for prevention of Th2 effector cell differentiation and allergic sensitization to dietary antigens. PMID:27643438

  3. Knee injuries in restrained car drivers in German road traffic accidents.

    PubMed

    Haasper, Carl; Otte, Dietmar; Knobloch, Karsten; Probst, Christian; Board, Timothy N; Krettek, Christian; Richter, Martinus

    2008-07-01

    The purpose of this study was to estimate the prevalence of knee injuries in real world car crashes in Germany. Restrained car drivers (RCD) were included in a medical and technical analysis to create a basis for preventive measures. Technical and medical data were collected at the scene, shortly after the crash. Two time periods (group A, 1985-1993; group B, 1995-2003) were compared focusing on knee injuries [abbreviated injury scale (AISKnee)]. Technical analysis included type of collision, impact angle, and relative velocity. Medical analysis included injury pattern and severity (AIS, maximum AIS). About 5,972 RCD were included in this study from a total of 22,804 victims involved in 16,563 crashes. In total, severe injuries (AISKnee 2/3) occurred in 1.2% (82 patients) of all RCD. The knee injury prevalence significantly decreased over time (group A vs. B, p < 0.0001). A so-called dashboard injury was registered in 5.8% (n = 5). The overall prevalence for knee injuries in RCD involved in road traffic accidents was low and decreased over time. Higher loads were necessary to cause ligamentous injuries of the knee than fractures in the knee region. Because direct impact caused most of the injuries, modifications of the interior and exterior design should reduce the incidence of these injuries. A dashboard injury was very rare.

  4. A Novel Restraining Device for Small Animal Imaging Exams: Validation in Rabbits.

    PubMed

    Barbosa, Carlos Henrique; Carvalho, Antonio Carlos; de Souza, Sérgio; Machado, Fernanda; Guedes, Fábio; Monteiro, André; Schanaider, Alberto

    2015-01-01

    To develop, validate, and patent a Restraining Device for Small Animal Imaging Exams (RDSAIE) that allows exams to be comfortably conducted without risks to animals and professionals. A RDSAIE with a mobile cover and shelf was built with transparent acrylic material. A total of six anesthetized rabbits were used to perform the following imaging exams of the skull: Cone Beam Computed Tomography, Magnetic Resonance Imaging, and Scintigraphy. The device showed great functionality and full visibility of the animal behavior, which remained fully stabilized and immobilized in either the horizontal or vertical position without the need for a person to remain in the test room to assist them. The procedures were performed without difficulty, and images of good resolution and without artifacts were obtained. The RDSAIE is comfortable, safe, efficient, and ergonomic. It allows the easy placement of animals in different body positions, including the vertical, the maintenance of postural stability, and full visibility. It may be constructed for animals heavier than 4 kg and it is adaptable for translational studies in anima nobile.

  5. A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation.

    PubMed

    Atianand, Maninjay K; Hu, Wenqian; Satpathy, Ansuman T; Shen, Ying; Ricci, Emiliano P; Alvarez-Dominguez, Juan R; Bhatta, Ankit; Schattgen, Stefan A; McGowan, Jason D; Blin, Juliana; Braun, Joerg E; Gandhi, Pallavi; Moore, Melissa J; Chang, Howard Y; Lodish, Harvey F; Caffrey, Daniel R; Fitzgerald, Katherine A

    2016-06-16

    Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS localizes at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3' end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses, highlighting the importance of lincRNAs in the immune system. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination.

    PubMed

    Zamudio, Natasha; Barau, Joan; Teissandier, Aurélie; Walter, Marius; Borsos, Maté; Servant, Nicolas; Bourc'his, Déborah

    2015-06-15

    DNA methylation is essential for protecting the mammalian germline against transposons. When DNA methylation-based transposon control is defective, meiotic chromosome pairing is consistently impaired during spermatogenesis: How and why meiosis is vulnerable to transposon activity is unknown. Using two DNA methylation-deficient backgrounds, the Dnmt3L and Miwi2 mutant mice, we reveal that DNA methylation is largely dispensable for silencing transposons before meiosis onset. After this, it becomes crucial to back up to a developmentally programmed H3K9me2 loss. Massive retrotransposition does not occur following transposon derepression, but the meiotic chromatin landscape is profoundly affected. Indeed, H3K4me3 marks gained over transcriptionally active transposons correlate with formation of SPO11-dependent double-strand breaks and recruitment of the DMC1 repair enzyme in Dnmt3L(-/-) meiotic cells, whereas these features are normally exclusive to meiotic recombination hot spots. Here, we demonstrate that DNA methylation restrains transposons from adopting chromatin characteristics amenable to meiotic recombination, which we propose prevents the occurrence of erratic chromosomal events.

  7. Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10

    PubMed Central

    Xie, Luokun; Choudhury, Gourav Roy; Winters, Ali; Yang, Shao-Hua; Jin, Kunlin

    2014-01-01

    Forkhead box P3 (Foxp3)+ regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the central nervous system under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ+CD4+Foxp3+ T-cell population (cerebral Treg cells) in the normal rat cerebrum, constituting more than 15% of the cerebral CD4+ T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the normal rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state. PMID:25329858

  8. Design of focused and restrained subsets from extremely large virtual libraries.

    PubMed

    Jamois, Eric A; Lin, Chien T; Waldman, Marvin

    2003-11-01

    With the current and ever-growing offering of reagents along with the vast palette of organic reactions, virtual libraries accessible to combinatorial chemists can reach sizes of billions of compounds or more. Extracting practical size subsets for experimentation has remained an essential step in the design of combinatorial libraries. A typical approach to computational library design involves enumeration of structures and properties for the entire virtual library, which may be unpractical for such large libraries. This study describes a new approach termed as on the fly optimization (OTFO) where descriptors are computed as needed within the subset optimization cycle and without intermediate enumeration of structures. Results reported herein highlight the advantages of coupling an ultra-fast descriptor calculation engine to subset optimization capabilities. We also show that enumeration of properties for the entire virtual library may not only be unpractical but also wasteful. Successful design of focused and restrained subsets can be achieved while sampling only a small fraction of the virtual library. We also investigate the stability of the method and compare results obtained from simulated annealing (SA) and genetic algorithms (GA).

  9. A Novel Restraining Device for Small Animal Imaging Exams: Validation in Rabbits

    PubMed Central

    Barbosa, Carlos Henrique; Carvalho, Antonio Carlos; de Souza, Sérgio; Machado, Fernanda; Guedes, Fábio; Monteiro, André; Schanaider, Alberto

    2015-01-01

    Objective. To develop, validate, and patent a Restraining Device for Small Animal Imaging Exams (RDSAIE) that allows exams to be comfortably conducted without risks to animals and professionals. Methods. A RDSAIE with a mobile cover and shelf was built with transparent acrylic material. A total of six anesthetized rabbits were used to perform the following imaging exams of the skull: Cone Beam Computed Tomography, Magnetic Resonance Imaging, and Scintigraphy. Results. The device showed great functionality and full visibility of the animal behavior, which remained fully stabilized and immobilized in either the horizontal or vertical position without the need for a person to remain in the test room to assist them. The procedures were performed without difficulty, and images of good resolution and without artifacts were obtained. Conclusion. The RDSAIE is comfortable, safe, efficient, and ergonomic. It allows the easy placement of animals in different body positions, including the vertical, the maintenance of postural stability, and full visibility. It may be constructed for animals heavier than 4 kg and it is adaptable for translational studies in anima nobile. PMID:26114109

  10. A constrained theory for single crystal shape memory wires with application to restrained recovery

    NASA Astrophysics Data System (ADS)

    Rizzoni, Raffaella

    2011-07-01

    The theory of thin wires developed in Dret and Meunier (Comptes Rendus de l'Académie des Sciences. Série I. Mathématique 337:143-147, 2003) is adapted to phase-transforming materials with large elastic moduli in the sense discussed in James and Rizzoni (J Elast 59:399-436, 2000). The result is a one-dimensional constitutive model for shape memory wires, characterized by a small number of material constants. The model is used to analyze self-accommodated and detwinned microstructures and to study superelasticity. It also turns out that the model successfully reproduces the behavior of shape memory wires in experiments of restrained recovery (Tsoi et al. in Mater Sci Eng A 368:299-310, 2004; Tsoi in 50:3535-3544, 2002; S̆ittner et al. in Mater Sci Eng A 286:298-311, 2000; vokoun in Smart Mater Struct 12:680-685, 2003; Zheng and Cui in Intermetallics 12:1305-1309, 2004; Zheng et al. in J Mater Sci Technol 20(4):390-394, 2004). In particular, the model is able to predict the shift to higher transformation temperatures on heating. The model also captures the effect of prestraining on the evolution of the recovery stress and of the martensite volume fraction.

  11. Apigenin Restrains Colon Cancer Cell Proliferation via Targeted Blocking of Pyruvate Kinase M2-Dependent Glycolysis.

    PubMed

    Shan, Shuhua; Shi, Jiangying; Yang, Peng; Jia, Bin; Wu, Haili; Zhang, Xiaoli; Li, Zhuoyu

    2017-09-20

    Apigenin (AP), as an anticancer agent, has been widely explored. However, the molecular targets of apigenin on tumor metabolism are unclear. Herein, we found that AP could block cellular glycolysis through restraining the tumor-specific pyruvate kinase M2 (PKM2) activity and expression and further significantly induce anti-colon cancer effects. The IC50 values of AP against HCT116, HT29, and DLD1 cells were 27.9 ± 2.45, 48.2 ± 3.01 and 89.5 ± 4.89 μM, respectively. Fluorescence spectra and solid-phase AP extraction assays proved that AP could directly bind to PKM2 and markedly inhibit PKM2 activity in vitro and in HCT116 cells. Interestingly, in the presence of d-fructose-1,6-diphosphate (FBP), the inhibitory effect of AP on PKM2 was not reversed, which suggests that AP is a new allosteric inhibitor of PKM2. RT-PCR and Western blot assays showed that AP could ensure a low PKM2/PKM1 ratio in HCT116 cells via blocking the β-catenin/c-Myc/PTBP1 signal pathway. Hence, PKM2 represents a novel potential target of AP against colon cancer.

  12. Arabidopsis cryptochrome-1 restrains lateral roots growth by inhibiting auxin transport.

    PubMed

    Zeng, Jianxin; Wang, Qiming; Lin, Jianzhong; Deng, Keqin; Zhao, Xiaoying; Tang, Dongying; Liu, Xuanming

    2010-05-15

    Cryptochromes are blue-light photoreceptors that control many aspects of plant development. In this study, cryptochrome mutants of Arabidopsis were examined to assess the role of cryptchrome-1 (CRY1) in lateral roots growth. When grown in blue light for 12d, mutant seedlings (cry1) showed increased growth of lateral roots, while CRY1-overexpressing transgenic seedlings (CRY1ox) exhibited a marked decrease. Lateral roots growth of CRY1ox could be stimulated by auxin, but expression of PIN1 (efflux carrier of polar auxin transport) was strongly reduced. Contrary, the cry1 mutation showed the opposite effect, indicating that blue light and the auxin-signaling pathway interact in lateral roots growth of Arabidopsis. The free IAA content in CRY1ox roots was half of that in wild type and cry1 mutant roots. Moreover, the content of flavonoids (quercetin, kaempferol, isorhamnetin), which act as endogenous negative regulators of auxin transport, increased in CRY1ox seedlings. Taken together, these results suggest that Arabidopsis CRY1 restrains lateral roots growth by inhibiting auxin transport. (c) 2010 Elsevier GmbH. All rights reserved.

  13. Is beauty in the eye of the beholder? Effects of weight and shape on attractiveness ratings of female line drawings by restrained and nonrestrained eaters.

    PubMed

    Forestell, Catherine A; Humphrey, Tara M; Stewart, Sherry H

    2004-05-01

    This study tested the differences between restrained and nonrestrained eaters' attractiveness perceptions of female line drawings, of their own figures, and the ideal female figure. Female line drawings varied systematically in body weight and in waist and hip circumference. Forty-six female undergraduate students, 23 nonrestrainers and 23 restrainers, rated stimuli in attractiveness, identified the figure which best represented their own body type (PAF), and the ideal body figure (IF) according to the Restraint Scale [RS; Herman, C. P., & Polivy, J. (1980). Restrained eating. In: A. Stunkard (Ed.), Obesity (pp. 208-225). Philadelphia, PA: Saunders]. Restrainers did not generally differ from nonrestrainers in attractiveness ratings or in their choice of IF. However, differences between IF and PAF were larger in restrainers than in nonrestrainers because restrainers chose PAFs with larger hips than nonrestrainers did. This difference between the restraint groups was independent of between-group differences in hip size. This discrepancy between IF and PAF may contribute to the restrainers' motivation to diet.

  14. Antimicrobial Resistance in Agriculture.

    PubMed

    Thanner, Sophie; Drissner, David; Walsh, Fiona

    2016-04-19

    In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans. Copyright © 2016 Thanner et al.

  15. Antimicrobial Resistance in Agriculture

    PubMed Central

    Thanner, Sophie; Drissner, David

    2016-01-01

    ABSTRACT In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans. PMID:27094336

  16. Reconnaissance Observations of Newly Identified Active Faults and Their Relationship to Evolution of the Mount McKinley Restraining Bend, Denali National Park, Alaska

    NASA Astrophysics Data System (ADS)

    Bemis, S. P.; Benowitz, J.

    2012-12-01

    The processes of restraining bend formation and evolution along strike-slip faults remain poorly understood. Although connections between exhumation, fault displacement, and structural geometry are difficult to establish, long-lived active faults contribute to rock uplift, partition strain, and provide insight into the crustal stresses that result from the complex geometry of a restraining bend. The highest topography in North America, Mount McKinley (also known as Denali), is closely associated with an ~17 degree bend in the Denali fault and the region exhibits structural, geomorphic, and thermochronologic constraints on the late Cenozoic evolution of the Mount McKinley restraining bend. As a component of our investigation into the initiation and growth of this restraining bend, we are mapping the bedrock and surficial geology along the north side of the restraining bend to document evidence for Quaternary-active faults. Previous workers only document one active fault, the East Fork fault, north of the Denali fault. The lack of active faults is surprising due to the high rate of regional seismicity. Our initial studies recognize several previously undocumented faults that offset late Pleistocene glacial moraines and fluvial/alluvial surfaces, indicating active deformation is more widely spread than previously recognized and illustrating distinct patterns of strain accommodation. The East Fork fault and nearby structures occur east of the apex of the restraining bend and are sub-vertical with characteristically south-side-down displacements. Faults occurring adjacent to, and west of, the restraining bend apex are all south-side-up thrust faults and appear to have accommodated a significant component of the modern topographic development on the north side of the Denali fault. Future work will target the structural geometry and slip rates of these faults in order to determine how this restraining bend has evolved to the present configuration, and these results will

  17. Antimicrobials and QT prolongation.

    PubMed

    Mason, Jay W

    2017-05-01

    Solithromycin, a ketolide/macrolide antibiotic, has recently been reported to be free of the expected QT-prolonging effect of macrolides. It appears that its keto substitution provides a structural basis for this observation, as the other two tested ketolides also have minimal QT effect.Among non-cardiovascular therapies, antimicrobials probably carry the greatest potential to cause cardiac arrhythmias. This is a result of their propensity to bind to the delayed rectifier potassium channel, IKr, inducing QT prolongation and risk of torsades de pointes ventricular tachycardia, their frequent interference with the metabolism of other QT prolongers and their susceptibility to metabolic inhibition by numerous commonly used drugs.Unfortunately, there is evidence that medical practitioners do not take account of the QT/arrhythmia risk of antimicrobials in their prescribing practices. Education on this topic is sorely needed. When a macrolide is indicated, a ketolide should be considered in patients with a QT risk. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Antimicrobial Peptides and Colitis

    PubMed Central

    Ho, Samantha; Pothoulakis, Charalabos; Koon, Hon Wai

    2013-01-01

    Antimicrobial peptides (AMPs) are important components of innate immunity. They are often expressed in response to colonic inflammation and infection. Over the last several years, the roles of several antimicrobial peptides have been explored. Gene expression of many AMPs (beta defensin HBD2-4 and cathelicidin) is induced in response to invasion of gut microbes into the mucosal barrier. Some AMPs are expressed in a constitutive manner (alpha defensin HD 5-6 and beta defensin HBD1), while others (defensin and bactericidal/permeability increasing protein BPI) are particularly associated with Inflammatory Bowel Disease (IBD) due to altered defensin expression or development of autoantibodies against Bactericidal/permeability increasing protein (BPI). Various AMPs have different spectrum and strength of antimicrobial effects. Some may play important roles in modulating the colitis (cathelicidin) while others (lactoferrin, hepcidin) may represent biomarkers of disease activity. The use of AMPs for therapeutic purposes is still at an early stage of development. A few natural AMPs were shown to be able to modulate colitis when delivered intravenously or intracolonically (cathelicidin, elafin and SLPI) in mouse colitis models. New AMPs (synthetic or artificial non-human peptides) are being developed and may represent new therapeutic approaches against colitis. This review discusses the latest research developments in the AMP field with emphasis in innate immunity and pathophysiology of colitis. PMID:22950497

  19. [Neruda and antimicrobial resistance].

    PubMed

    Cotera, Alejandro

    2011-07-01

    Antimicrobial resistance has been a problem in medicine, since their incorporation to clinical practice. Numerous papers have been written on the subject. The analysis of two poems by Pablo Neruda "How much does a man live" and "Larynx", included in the volume "Estravagario" and published for the first time in 1957 and 1958, give us an incredible revelation about the concept of resistance. In these poems aureomycin, the first antimicrobial of the family of tetracyclines, was included as a poetic figure and the therapeutic action of antimicrobials was described. "Never so much bugs died I tons of them fell I but the few that remained olive I manifested their perversity". These writings incorporated novel concepts, even for physicians of that time and described the closeness of death that a patient may perceive during the course of a given disease. The capacity of Pablo Neruda to extract the essence of situations and to anticipate to conditions that only years later became clinically relevant problems, is noteworthy.

  20. [Antimicrobial mechanisms of action].

    PubMed

    Calvo, Jorge; Martínez-Martínez, Luis

    2009-01-01

    A large number of families and groups of antimicrobial agents are of clinical interest. The mechanisms by which compounds with antibacterial activity inhibit growth or cause bacterial death are varied and depend on the affected targets. The bacterial cell wall-a unique structure in most bacteria that is absent in eukaryotic cells-can be affected in several ways: at different stages of synthesis (fosfomycin, cycloserine) or transport (bacitracin, mureidomycins) of its metabolic precursors, or by a direct action on its structural organization (beta-lactams, glycopeptides). The main drugs affecting the cytoplasmic membrane are polymyxins and daptomycin. Protein synthesis can be blocked by a large variety of compounds that affect any of the phases of this process, including activation (mupirocin), initiation (oxazolidinones, aminoglycosides), binding of the tRNA amino acid complex to ribosomes (tetracyclines, glycylcyclines) and elongation (amphenicols, lincosamides, macrolides, ketolides, streptogramins, fusidic acid). The metabolism of nucleic acids can be altered at the DNA-dependent RNA polymerase or in the process of DNA coiling (quinolones); some compounds affect DNA directly (nitroimidazoles, nitrofurans). Trimethoprim and sulfamides (often used in combination) are examples of antimicrobial agents that block bacterial metabolic pathways. Some compounds are unable to inhibit or kill bacteria in themselves, but can block bacterial mechanisms of resistance, enhancing the activity of other antimicrobials administered in combination. Among this group of agents, only certain beta-lactamase inhibitors are currently in clinical use.

  1. Substandard/Counterfeit Antimicrobial Drugs

    PubMed Central

    Kelesidis, Theodoros

    2015-01-01

    SUMMARY Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue. PMID:25788516

  2. Regional Gray Matter Volume Is Associated with Restrained Eating in Healthy Chinese Young Adults: Evidence from Voxel-Based Morphometry

    PubMed Central

    Su, Yanhua; Jackson, Todd; Wei, Dongtao; Qiu, Jiang; Chen, Hong

    2017-01-01

    Highlight Participants were non-clinical young adults with different restrained eating levels.We assessed relations of restrained eating (RE) with regional gray matter volume (rGMV).High RE scores were related to larger GMV in specific areas related to reward.High RE scores were also linked to less GMV in regions related to response inhibition. Objective: Dieting is a popular method of weight control. However, few dieters are able to maintain initial weight losses over an extended period of time. Why do most restrained dieters fail to lose weight? Alterations in brain structures associated with restrained eating (RE) represent one potentially important mechanism that contributes to difficulties in maintaining weight loss within this group. To evaluate this contention, we investigated associations between intentional, sustained restriction of food intake to lose or maintain body weight, and regional gray matter volume (rGMV) within a large non-clinical young adult, sample. Methods: Participants (150 women, 108 men) completed measures of RE and demographics prior to undergoing an MRI scan. Voxel-based morphometry (VBM) evaluated strengths of association between RE scores and rGMV. Results: Higher RE levels corresponded to more rGMV in regions linked to risk of overeating and binge-eating including the left insula and orbitofrontal cortex (OFC). Conversely, RE had significant negative correlations with rGMV in the left and right posterior cingulum gyrus, regions linked to inhibitory control and potential risk for future weight gain. Conclusions: Together, findings suggested individual differences in RE among young adults correspond to GMV variability in regions linked to overweight and obesity risk. PMID:28396646

  3. Smoking as alternative to eating among restrained eaters: effect of food prime on young adult female smokers.

    PubMed

    Kovacs, Michelle A; Correa, John B; Brandon, Thomas H

    2014-10-01

    Restrained eaters attempt to employ cognitive control over decisions to eat, which leaves them prone to eat in a disinhibited manner. This eating style is associated with elevated rates of smoking compared to the general population. The current study merged smoking and eating research methodology to investigate a mechanism that may underlie this association by testing whether a food prime, which has been found to elicit disinhibited eating in restrained eaters, could also motivate smoking as an alternative to eating. Using a randomized, 2-arm (Prime/No-Prime) between-subjects design, it was hypothesized that young adult female smokers who endorsed elevated dietary restraint and received a food prime would smoke more when given the option, compared to smokers who did not receive the food prime. As predicted, restraint score moderated the effect of the food prime upon smoking behavior (latency to first puff, β = 1, t = 3.8, df = 123, p < .001) and cigarette craving (β = -.79, t = -2.9, df = 127, p < .005), suggesting that after a food prime, restrained-eating smokers may opt to smoke to prevent further food intake. This study identified a pathway, namely violation of dietary restraint, linking eating and smoking behaviors that may contribute to the population-based covariance between disordered eating and tobacco use.

  4. Stress and eating: the effects of ego-threat and cognitive demand on food intake in restrained and emotional eaters.

    PubMed

    Wallis, D J; Hetherington, M M

    2004-08-01

    Restrained and emotional eaters overeat in response to stress. To compare differential effects of cognitive demand and ego-threatening stressors on subsequent chocolate intake, 38 females completed a neutral (control), an ego threatening and an incongruent Stroop colour-naming task on three separate occasions. Participants were assigned to four groups based on median-split scores on the restrained and emotional eating scales of the Dutch Eating Behaviour Questionnaire-high restraint/high emotional, high restraint/low emotional, low restraint/high emotional and low restraint/low emotional. Higher response latencies were observed in the incongruent task, confirming its greater cognitive (attentional) demand. Overall intake was enhanced by 23% after ego-threat and 15% after the incongruent Stroop task relative to control. Restraint was associated with greater intake after both ego-threat and the incongruent task than in the control condition. In contrast, emotional eating was associated with greater intake after only the ego-threat, relative to control. A positive association between reaction time and subsequent intake in all conditions for high restraint/low emotional eaters provided support for the limited capacity hypothesis. Enhanced intake in emotional eaters is proposed to relate to escape from self-awareness. These findings demonstrate differential effects of threat and demand on stress-related eating in restrained and emotional eaters.

  5. Structural refinement of membrane proteins by restrained molecular dynamics and solvent accessibility data.

    PubMed

    Sompornpisut, Pornthep; Roux, Benoît; Perozo, Eduardo

    2008-12-01

    We present an approach for incorporating solvent accessibility data from electron paramagnetic resonance experiments in the structural refinement of membrane proteins through restrained molecular dynamics simulations. The restraints have been parameterized from oxygen (PiO(2)) and nickel-ethylenediaminediacetic acid (PiNiEdda) collision frequencies, as indicators of lipid or aqueous exposed spin-label sites. These are enforced through interactions between a pseudoatom representation of the covalently attached Nitroxide spin-label and virtual "solvent" particles corresponding to O(2) and NiEdda in the surrounding environment. Interactions were computed using an empirical potential function, where the parameters have been optimized to account for the different accessibilities of the spin-label pseudoatoms to the surrounding environment. This approach, "pseudoatom-driven solvent accessibility refinement", was validated by refolding distorted conformations of the Streptomyces lividans potassium channel (KcsA), corresponding to a range of 2-30 A root mean-square deviations away from the native structure. Molecular dynamics simulations based on up to 58 electron paramagnetic resonance restraints derived from spin-label mutants were able to converge toward the native structure within 1-3 A root mean-square deviations with minimal computational cost. The use of energy-based ranking and structure similarity clustering as selection criteria helped in the convergence and identification of correctly folded structures from a large number of simulations. This approach can be applied to a variety of integral membrane protein systems, regardless of oligomeric state, and should be particularly useful in calculating conformational changes from a known reference crystal structure.

  6. Administration of Simvastatin after Kainic Acid-Induced Status Epilepticus Restrains Chronic Temporal Lobe Epilepsy

    PubMed Central

    Qiao, Weidong; Lu, Dunyue; Wei, Lanlan; Na, Meng; Song, Yuanyuan; Hou, Xiaohua; Lin, Zhiguo

    2011-01-01

    In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP) staining and neuron loss using Nissl staining in hippocampus at 4–6 months after KA-lesion. We found that simvastatin suppressed reactive astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar (DH). We next assessed aberrant mossy fiber sprouting (MFS) that is known to contribute to recurrence of spontaneous seizure in epileptic brain. In contrast to the robust MFS observed in saline-treated animals, the extent of MFS was restrained by simvastatin in epileptic rats. Attenuated MFS was related to decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying decreased hippocampal susceptibility in animal treated with simvastatin. Electronic encephalography (EEG) was recorded during 4 to 6 months after KA-lesion. The frequency of abnormal spikes in rats with simvastatin-treatment decreased significantly compared to the saline group. In summary, simvastatin treatment suppressed cytokines expression and reactive astrocytosis and decreased the frequency of discharges of epileptic brain, which might be due to the inhibition of MFS in DH. Our study suggests that simvastatin administration might be a possible intervention and promising strategy for preventing SE exacerbating to chronic epilepsy. PMID:21949812

  7. The adaptive immune system restrains Alzheimer's disease pathogenesis by modulating microglial function.

    PubMed

    Marsh, Samuel E; Abud, Edsel M; Lakatos, Anita; Karimzadeh, Alborz; Yeung, Stephen T; Davtyan, Hayk; Fote, Gianna M; Lau, Lydia; Weinger, Jason G; Lane, Thomas E; Inlay, Matthew A; Poon, Wayne W; Blurton-Jones, Mathew

    2016-03-01

    The innate immune system is strongly implicated in the pathogenesis of Alzheimer's disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting "Rag-5xfAD" mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive-innate immunity cross talk and accelerated disease progression.

  8. [Metal ions restrain the elimination of 4-tert-octylphenol by delta-MnO2].

    PubMed

    Li, Fei-Li; Mou, Hua-Qian

    2013-06-01

    The effect of metal ions on elimination of 4-t-OP by synthetic delta-MnO2 suspension at pH 4.0 was studied. Experiments indicated that the removal of 4-t-OP by delta-MnO2 achieved 100% at reaction time of 150 min. However, the removal of 4-t-OP by delta-MnO2 was restrained when metal ions were added, and the higher concentration of metal ion was, the stronger the inhibition produced. Additionally, there were apparent differences among the inhibitory effect of the tested metal ions. Firstly, Pb2+ and Mn2+ had the strongest effect at pH 4.0, followed by the transition metal ions, then the alkaline earth ions, while the alkali metal ions had little influence on the removal of 4-t-OP by delta-MnO2. Also comparing the adsorption results of metal ions by delta-MnO2, Pb2+ showed the greatest attraction with delta-MnO2, and among the other metal ions, transition metal ions were adsorbed a little more strongly on delta-MnO2 than alkaline earth metal ions. Consequences showed that the inhibitory effects of metal ions were due to their occupying reactive sites on delta-MnO2 surface, which competed with 4-t-OP. Moreover, the dissimilar suppressions were contributed by the different adsorption capacities, surface structure change of MnO2 and the difference of free metal ion percentage in solution as well as metal ions radii.

  9. Firing properties of anatomically identified neurons in the medial septum of anesthetized and unanesthetized restrained rats.

    PubMed

    Simon, Axelle Pascale; Poindessous-Jazat, Frédérique; Dutar, Patrick; Epelbaum, Jacques; Bassant, Marie-Hélène

    2006-08-30

    Cholinergic and GABAergic neurons in the medial septum-diagonal band of Broca (MS-DB) project to the hippocampus where they are involved in generating theta rhythmicity. So far, the functional properties of neurochemically identified MS-DB neurons are not fully characterized. In this study, MS-DB neurons recorded in urethane anesthetized rats and in unanesthetized restrained rats were labeled with neurobiotin and processed for immunohistochemistry against glutamic acid decarboxylase (GAD), parvalbumin (PV), and choline acetyltransferase (ChAT). The majority of the 90 labeled neurons (75.5%) were GAD+. Among them, 34.0% were also PV+, but none were ChAT+. Only 8.8% of the labeled neurons were found ChAT+. Remaining neurons (15.5%) were not identified. In anesthetized rats, all of the PV/GAD+ and 65% of GAD+ neurons exhibited burst-firing activity at the theta frequency. PV/GAD+ neurons displayed higher discharge rate and longer burst duration compared with GAD+ neurons. At variance, all of the ChAT+ neurons were slow-firing. Cluster-firing and tonic-firing were observed in GAD+ and unidentified neurons. In unanesthetized rats, during wakefulness or rapid eye movement sleep with hippocampal theta, the bursting neurons were PV/GAD+ or GAD+, whereas all of the ChAT+ neurons were slow-firing. Across the sleep-wake cycle, the GABAergic component of the septohippocampal pathway was always more active than the cholinergic one. The fact that cholinergic MS-DB neurons do not display theta-related bursting or tonic activity but have a very low firing rate questions how acetylcholine exerts its activating role in the septohippocampal system.

  10. Head injuries to restrained occupants in single-vehicle pure rollover crashes.

    PubMed

    Mattos, G A; Grzebieta, R H; Bambach, M R; McIntosh, A S

    2013-01-01

    Studies performed previously of seat-belted occupants in real-world passenger vehicle rollover-only crashes have identified the head as one of the body regions most often seriously injured. However, there have been few studies investigating how these head injuries occur in any detail. This study aims to investigate the characteristics and patterns of head injury to seat-belted occupants in real-world rollover-only crashes and to identify possible biomechanical mechanisms responsible for head injury to aid in the development of a dynamic rollover test protocol. National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) data were used to generate summary statistics and perform logistic regression analysis of restrained and contained occupants in U.S. pure trip-over rollover crashes. Specific information from selected CDS cases focused on identifying potential mechanisms and patterns of serious head injury and the rollover conditions under which the injury occurred are also presented. Twenty-one percent of seriously injured occupants in pure trip-over rollovers had a serious head injury. On average, occupants seated on the far side of the rollover sustained serious head injuries more frequently and were more likely to receive injuries to the inboard side of the head than near-side occupants. Serious head injuries appear to be decoupled from serious injuries to other body regions except for a relationship found between basal skull fractures and cervical spine fractures. Serious head injuries were sustained by some occupants who had less than 15 cm of roof crush above their seated position. Serious brain injuries appear to occur frequently as a result of loading to the periphery of the head from contact with the roof assembly. Two mechanisms of injury for basal skull fractures in rollover crashes were identified. The injury patterns and locations of contact to the head are sensitive to the seated position of the occupant.

  11. Matching the Oculomotor Drive During Head-Restrained and Head-Unrestrained Gaze Shifts in Monkey

    PubMed Central

    Bechara, Bernard P.

    2010-01-01

    High-frequency burst neurons in the pons provide the eye velocity command (equivalently, the primary oculomotor drive) to the abducens nucleus for generation of the horizontal component of both head-restrained (HR) and head-unrestrained (HU) gaze shifts. We sought to characterize how gaze and its eye-in-head component differ when an “identical” oculomotor drive is used to produce HR and HU movements. To address this objective, the activities of pontine burst neurons were recorded during horizontal HR and HU gaze shifts. The burst profile recorded on each HU trial was compared with the burst waveform of every HR trial obtained for the same neuron. The oculomotor drive was assumed to be comparable for the pair yielding the lowest root-mean-squared error. For matched pairs of HR and HU trials, the peak eye-in-head velocity was substantially smaller in the HU condition, and the reduction was usually greater than the peak head velocity of the HU trial. A time-varying attenuation index, defined as the difference in HR and HU eye velocity waveforms divided by head velocity [α = (Ḣhr − Ėhu)/Ḣ] was computed. The index was variable at the onset of the gaze shift, but it settled at values several times greater than 1. The index then decreased gradually during the movement and stabilized at 1 around the end of gaze shift. These results imply that substantial attenuation in eye velocity occurs, at least partially, downstream of the burst neurons. We speculate on the potential roles of burst-tonic neurons in the neural integrator and various cell types in the vestibular nuclei in mediating the attenuation in eye velocity in the presence of head movements. PMID:20505131

  12. Tobacco use and exposure to tobacco promoting and restraining factors among adolescents in a developing country.

    PubMed

    Doku, D; Koivusilta, L; Raisamo, S; Rimpelä, A

    2012-08-01

    With a long history of tobacco cultivation, adolescents in Ghana are at relatively high risk of the emerging tobacco epidemic in developing countries. This study explored exposure to tobacco promoting/restraining factors and their associations with smoking and tawa (traditional smokeless tobacco) use among 13-18-year-old Ghanaians. School-based representative data were collected in 2008 (n = 1165). Prevalence rates of tobacco use, smoking and tawa use were 9.1% (11.5% boys and 6.4% girls), 6.6% (8.0% boys and 4.7% girls) and 5.7% (7.3% boys and 3.9% girls), respectively. Four percent of the respondents attended schools without a smoking ban, 66% had been taught about the harmful effects of smoking in the current school year, and 53% had been exposed to tobacco advertising. Fifty-three percent of adolescents who had tried to purchase tobacco products were not refused because of their age. Multivariate analyses found that attendance at a school where smoking was allowed, not having been taught about the harmful effects of smoking, exposure to tobacco advertising and parental smoking were positively associated with tobacco use, and knowledge that smoking is harmful to health and difficult to quit were negatively associated with tobacco use. Both smoking and tawa use were relatively low among Ghanaian adolescents. Exposure to tobacco advertising was high. There is no tobacco legislation in Ghana, but societal norms or cultural values seem to restrict smoking in schools and access to tobacco products. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  13. Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments

    PubMed Central

    Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M.; Schulten, Klaus; Roux, Benoît

    2015-01-01

    The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with

  14. Bromodomain and Extra-terminal (BET) Protein Inhibitors Suppress Chondrocyte Differentiation and Restrain Bone Growth.

    PubMed

    Niu, Ningning; Shao, Rui; Yan, Guang; Zou, Weiguo

    2016-12-23

    Small molecule inhibitors for bromodomain and extra-terminal (BET) proteins have recently emerged as potential therapeutic agents in clinical trials for various cancers. However, to date, it is unknown whether these inhibitors have side effects on bone structures. Here, we report that inhibition of BET bromodomain proteins may suppress chondrocyte differentiation and restrain bone growth. We generated a luciferase reporter system using the chondrogenic cell line ATDC5 in which the luciferase gene was driven by the promoter of Col2a1, an elementary collagen of the chondrocyte. The Col2a1-luciferase ATDC5 system was used for rapidly screening both activators and repressors of human collagen Col2a1 gene expression, and we found that BET bromodomain inhibitors reduce the Col2a1-luciferase. Consistent with the luciferase assay, BET inhibitors decrease the expression of Col2a1 Furthermore, we constructed a zebrafish line in which the enhanced green fluorescent protein (EGFP) expression was driven by col2a1 promoter. The transgenic (col2a1-EGFP) zebrafish line demonstrated that BET inhibitors I-BET151 and (+)-JQ1 may affect EGFP expression in zebrafish. Furthermore, we found that I-BET151 and (+)-JQ1 may affect chondrocyte differentiation in vitro and inhibit zebrafish growth in vivo Mechanistic analysis revealed that BET inhibitors influenced the depletion of RNA polymerase II from the Col2a1 promoter. Collectively, these results suggest that BET bromodomain inhibition may have side effects on skeletal bone structures. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Ensemble MD simulations restrained via crystallographic data: Accurate structure leads to accurate dynamics

    PubMed Central

    Xue, Yi; Skrynnikov, Nikolai R

    2014-01-01

    Currently, the best existing molecular dynamics (MD) force fields cannot accurately reproduce the global free-energy minimum which realizes the experimental protein structure. As a result, long MD trajectories tend to drift away from the starting coordinates (e.g., crystallographic structures). To address this problem, we have devised a new simulation strategy aimed at protein crystals. An MD simulation of protein crystal is essentially an ensemble simulation involving multiple protein molecules in a crystal unit cell (or a block of unit cells). To ensure that average protein coordinates remain correct during the simulation, we introduced crystallography-based restraints into the MD protocol. Because these restraints are aimed at the ensemble-average structure, they have only minimal impact on conformational dynamics of the individual protein molecules. So long as the average structure remains reasonable, the proteins move in a native-like fashion as dictated by the original force field. To validate this approach, we have used the data from solid-state NMR spectroscopy, which is the orthogonal experimental technique uniquely sensitive to protein local dynamics. The new method has been tested on the well-established model protein, ubiquitin. The ensemble-restrained MD simulations produced lower crystallographic R factors than conventional simulations; they also led to more accurate predictions for crystallographic temperature factors, solid-state chemical shifts, and backbone order parameters. The predictions for 15N R1 relaxation rates are at least as accurate as those obtained from conventional simulations. Taken together, these results suggest that the presented trajectories may be among the most realistic protein MD simulations ever reported. In this context, the ensemble restraints based on high-resolution crystallographic data can be viewed as protein-specific empirical corrections to the standard force fields. PMID:24452989

  16. Dendritic cell-bound IgE functions to restrain allergic inflammation at mucosal sites

    PubMed Central

    Platzer, Barbara; Baker, Kristi; Vera, Miguel Pinilla; Singer, Kathleen; Panduro, Marisella; Lexmond, Willem S.; Turner, Devin; Vargas, Sara O.; Kinet, Jean-Pierre; Maurer, Dieter; Baron, Rebecca M.; Blumberg, Richard S.; Fiebiger, Edda

    2014-01-01

    Antigen-mediated crosslinking of Immunoglobulin E (IgE) bound to mast cells/basophils via FcεRI, the high affinity IgE Fc-receptor, is a well-known trigger of allergy. In humans, but not mice, dendritic cells (DCs) also express FcεRI that is constitutively occupied with IgE. In contrast to mast cells/basophils, the consequences of IgE/FcεRI signals for DC function remain poorly understood. We show that humanized mice that express FcεRI on DCs carry IgE like non-allergic humans and do not develop spontaneous allergies. Antigen-specific IgE/FcεRI crosslinking fails to induce maturation or production of inflammatory mediators in human DCs and FcεRI-humanized DCs. Furthermore, conferring expression of FcεRI to DCs decreases the severity of food allergy and asthma in disease-relevant models suggesting anti-inflammatory IgE/FcεRI signals. Consistent with the improved clinical parameters in vivo, antigen-specific IgE/FcεRI crosslinking on papain or LPS-stimulated DCs inhibits the production of pro-inflammatory cytokines and chemokines. Migration assays confirm that the IgE-dependent decrease in cytokine production results in diminished recruitment of mast cell progenitors; providing a mechanistic explanation for the reduced mast cell-dependent allergic phenotype observed in FcεRI-humanized mice. Our study demonstrates a novel immune regulatory function of IgE and proposes that DC-intrinsic IgE signals serve as a feedback mechanism to restrain allergic tissue inflammation. PMID:25227985

  17. The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function

    PubMed Central

    Abud, Edsel M.; Lakatos, Anita; Karimzadeh, Alborz; Yeung, Stephen T.; Davtyan, Hayk; Fote, Gianna M.; Lau, Lydia; Weinger, Jason G.; Lane, Thomas E.; Inlay, Matthew A.; Poon, Wayne W.; Blurton-Jones, Mathew

    2016-01-01

    The innate immune system is strongly implicated in the pathogenesis of Alzheimer’s disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting “Rag-5xfAD” mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive–innate immunity cross talk and accelerated disease progression. PMID:26884167

  18. Cyclooxygenase-derived vasoconstriction restrains hypoxia-mediated cerebral vasodilation in young adults with metabolic syndrome.

    PubMed

    Harrell, John W; Schrage, William G

    2014-01-15

    Poor cerebrovascular function in metabolic syndrome (MetSyn) likely contributes to elevated risk of cerebrovascular disease in this growing clinical population. Younger MetSyn adults without clinical evidence of cerebrovascular disease exhibit preserved hypercapnic vasodilation yet markedly impaired hypoxic vasodilation, but the mechanisms behind reduced hypoxic vasodilation are unknown. Based on data from rats, we tested the hypothesis that younger adults with MetSyn exhibit reduced cerebral hypoxic vasodilation due to loss of vasodilating prostaglandins. Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in adults with MetSyn (n = 13, 33 ± 3 yr) and healthy controls (n = 15, 31 ± 2 yr). Isocapnic hypoxia was induced by titrating inspired oxygen to lower arterial saturation to 90% and 80% for 5 min each. Separately, hypercapnia was induced by increasing end-tidal CO2 10 mmHg above baseline levels. Cyclooxygenase inhibition (100 mg indomethacin) was conducted in a randomized double-blind, placebo controlled design. MCAv was normalized for group differences in blood pressure (healthy: 89 ± 2 mmHg vs. MetSyn: 102 ± 2 mmHg) as cerebrovascular conductance index (CVCi), and used to assess cerebral vasodilation. Hypoxia increased CVCi in both groups; however, vasodilation was ∼55% lower in MetSyn at SpO2 = 80% (P < 0.05). Indomethacin tended to decrease hypoxic vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P < 0.05). In contrast to hypoxia, hypercapnia-mediated vasodilation was similar between groups, as was the decrease in vasodilation with indomethacin. These data indicate increased production of vasoconstrictor prostaglandins restrains hypoxic cerebral vasodilation in MetSyn, preventing them from responding appropriately to this important physiological stressor.

  19. Cyclooxygenase-derived vasoconstriction restrains hypoxia-mediated cerebral vasodilation in young adults with metabolic syndrome

    PubMed Central

    Harrell, John W.

    2013-01-01

    Poor cerebrovascular function in metabolic syndrome (MetSyn) likely contributes to elevated risk of cerebrovascular disease in this growing clinical population. Younger MetSyn adults without clinical evidence of cerebrovascular disease exhibit preserved hypercapnic vasodilation yet markedly impaired hypoxic vasodilation, but the mechanisms behind reduced hypoxic vasodilation are unknown. Based on data from rats, we tested the hypothesis that younger adults with MetSyn exhibit reduced cerebral hypoxic vasodilation due to loss of vasodilating prostaglandins. Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in adults with MetSyn (n = 13, 33 ± 3 yr) and healthy controls (n = 15, 31 ± 2 yr). Isocapnic hypoxia was induced by titrating inspired oxygen to lower arterial saturation to 90% and 80% for 5 min each. Separately, hypercapnia was induced by increasing end-tidal CO2 10 mmHg above baseline levels. Cyclooxygenase inhibition (100 mg indomethacin) was conducted in a randomized double-blind, placebo controlled design. MCAv was normalized for group differences in blood pressure (healthy: 89 ± 2 mmHg vs. MetSyn: 102 ± 2 mmHg) as cerebrovascular conductance index (CVCi), and used to assess cerebral vasodilation. Hypoxia increased CVCi in both groups; however, vasodilation was ∼55% lower in MetSyn at SpO2 = 80% (P < 0.05). Indomethacin tended to decrease hypoxic vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P < 0.05). In contrast to hypoxia, hypercapnia-mediated vasodilation was similar between groups, as was the decrease in vasodilation with indomethacin. These data indicate increased production of vasoconstrictor prostaglandins restrains hypoxic cerebral vasodilation in MetSyn, preventing them from responding appropriately to this important physiological stressor. PMID:24213610

  20. Perceived parental control of food intake is related to external, restrained and emotional eating in 7-12-year-old boys and girls.

    PubMed

    van Strien, Tatjana; Bazelier, Francien G

    2007-11-01

    This study examined the prevalence of external, restrained and emotional eating and the relationship of these disturbed types of eating behaviours with perceived parental control of food intake (pressure to eat and restriction) in a group of 7- to 12-year-old boys and girls (n = 596). External eating turned out to be the most prevalent disturbed eating behaviour for boys and girls, followed by restrained eating and emotional eating. Sex differences were found in external and restrained eating. For the boys, perceived pressure to eat was positively related to emotional and external eating. For both sexes, perceived restriction to eat was negatively related to emotional and external eating and positively related to restrained eating. This led to the conclusion that perceived pressure to eat has a disruptive effect on a child's self-regulating mechanism of food intake, particularly so for boys, whereas perceived restriction can also have a positive effect.

  1. Plant antimicrobial peptides.

    PubMed

    Nawrot, Robert; Barylski, Jakub; Nowicki, Grzegorz; Broniarczyk, Justyna; Buchwald, Waldemar; Goździcka-Józefiak, Anna

    2014-05-01

    Plant antimicrobial peptides (AMPs) are a component of barrier defense system of plants. They have been isolated from roots, seeds, flowers, stems, and leaves of a wide variety of species and have activities towards phytopathogens, as well as against bacteria pathogenic to humans. Thus, plant AMPs are considered as promising antibiotic compounds with important biotechnological applications. Plant AMPs are grouped into several families and share general features such as positive charge, the presence of disulfide bonds (which stabilize the structure), and the mechanism of action targeting outer membrane structures.

  2. Engineering Antimicrobials Refractory to Resistance

    USDA-ARS?s Scientific Manuscript database

    Multi-drug resistant superbugs are a persistent problem in modern health care, demonstrating the need for a new class of antimicrobials that can address this concern. Triple-acting peptidoglycan hydrolase fusions are a novel class of antimicrobials which have qualities well suited to avoiding resis...

  3. Use of Antimicrobials during Pregnancy

    PubMed Central

    Nicolle, L.E.

    1987-01-01

    The use of any drug during pregnancy is complicated by concerns of adverse effects, not only on the pregnant woman, but also on the fetus. This paper provides an overview of the use of antimicrobials in pregnancy, based on current knowledge of fetal development and on available documented experience. The author also discusses the use of specific antimicrobial agents during pregnancy. PMID:21263935

  4. Antimicrobial stewardship: philosophy versus practice.

    PubMed

    Dodds Ashley, Elizabeth S; Kaye, Keith S; DePestel, Daryl D; Hermsen, Elizabeth D

    2014-10-15

    To promote the judicious use of antimicrobials and preserve their usefulness in the setting of growing resistance, a number of policy-making bodies and professional societies have advocated the development of antimicrobial stewardship programs. Although these programs have been implemented at many institutions in the United States, their impact has been difficult to measure. Current recommendations advocate the use of both outcome and process measures as metrics for antimicrobial stewardship. Although patient outcome metrics have the greatest impact on the quality of care, the literature shows that antimicrobial use and costs are the indicators measured most frequently by institutions to justify the effectiveness of antimicrobial stewardship programs. The measurement of more meaningful outcomes has been constrained by difficulties inherent to these measures, lack of funding and resources, and inadequate study designs. Antimicrobial stewardship can be made more credible by refocusing the antimicrobial review process to target specific disease states, reassessing the usefulness of current metrics, and integrating antimicrobial stewardship program initiatives into institutional quality and safety efforts. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Absorbent silver (I) antimicrobial fabrics

    USDA-ARS?s Scientific Manuscript database

    In recent years, silver in form of silver ions, has been gaining importance in the wound management as an effective broad-spectrum antimicrobial agent. Silver has a long history as an antimicrobial agent, especially in the treatment of wounds. Alginates and carboxymethyl (CM) cotton contain carboxyl...

  6. How to fight antimicrobial resistance.

    PubMed

    Foucault, Cédric; Brouqui, Philippe

    2007-03-01

    Antimicrobial misuse results in the development of resistance and superbugs. Over recent decades, resistance has been increasing despite continuing efforts to control it, resulting in increased mortality and cost. Many authorities have proposed local, regional and national guidelines to fight against this phenomenon, and the usefulness of these programmes has been evaluated. Multifaceted intervention seems to be the most efficient method to control antimicrobial resistance. Monitoring of bacterial resistance and antibiotic use is essential, and the methodology has now been homogenized. The implementation of guidelines and infection control measures does not control antimicrobial resistance and needs to be reinforced by associated measures. Educational programmes and rotation policies have not been evaluated sufficiently in the literature. Combination antimicrobial therapy is inefficient in controlling antimicrobial resistance.

  7. Antimicrobial dyes and mechanosensitive channels.

    PubMed

    Boulos, Ramiz A

    2013-08-01

    The search for new and effective antimicrobial agents has never been as important; however, since the discovery of antibiotics, exploring the antimicrobial activity of dyes has been forgotten. Antimicrobial dyes are an untapped resource and have the ability to potentially combat the spread of drug-resistant bacteria either alone or as antimicrobial adjuvants. The mechanosensitive ion channel of large conductance (MscL) is highly conserved and ubiquitous in bacterial species. There is evidence to suggest that at least one triphenylmethane dye acts through the highly conserved MscL channel and combining the two approaches of exploring the mechanism of action of other triphenylmethane dyes or antimicrobial dyes in general and the novel MscL target provides a new opportunity for further exploration.

  8. Antimicrobial mechanism of monocaprylate.

    PubMed

    Hyldgaard, Morten; Sutherland, Duncan S; Sundh, Maria; Mygind, Tina; Meyer, Rikke Louise

    2012-04-01

    Monoglyceride esters of fatty acids occur naturally and encompass a broad spectrum of antimicrobial activity. Monocaprylate is generally regarded as safe (GRAS) and can function both as an emulsifier and as a preservative in food. However, knowledge about its mode of action is lacking. The aim of this study was therefore to elucidate the mechanism behind monocaprylate's antimicrobial effect. The cause of cell death in Escherichia coli, Staphylococcus xylosus, and Zygosaccharomyces bailii was investigated by examining monocaprylate's effect on cell structure, membrane integrity, and its interaction with model membranes. Changes in cell structure were visible by atomic force microscopy (AFM), and propidium iodide staining showed membrane disruption, indicating the membrane as a site of action. This indication was confirmed by measuring calcein leakage from membrane vesicles exposed to monocaprylate. AFM imaging of supported lipid bilayers visualized the integration of monocaprylate into the liquid disordered, and not the solid ordered, phase of the membrane. The integration of monocaprylate was confirmed by quartz crystal microbalance measurements, showing an abrupt increase in mass and hydration of the membrane after exposure to monocaprylate above a threshold concentration. We hypothesize that monocaprylate destabilizes membranes by increasing membrane fluidity and the number of phase boundary defects. The sensitivity of cells to monocaprylate will therefore depend on the lipid composition, fluidity, and curvature of the membrane.

  9. Antimicrobial resistance in Canada

    PubMed Central

    Conly, John

    2002-01-01

    Antibiotic resistance has increased rapidly during the last decade, creating a serious threat to the treatment of infectious diseases. Canada is no exception to this worldwide phenomenon. Data from the Canadian Nosocomial Infection Surveillance Program have revealed that the incidence of methicillin-resistant Staphylococcus aureus, as a proportion of S. aureus isolates, increased from 1% in 1995 to 8% by the end of 2000, and vancomycin-resistant enterococcus has been documented in all 10 provinces since the first reported outbreak in 1995. The prevalence of nonsusceptible Streptococcus pneumoniae in Canada in 2000 was found to be 12%. Human antimicrobial prescriptions, adjusted for differences in the population, declined 11% based on the total number of prescriptions dispensed between 1995 and 2000. There was also a 21% decrease in β-lactam prescriptions during this same period. These data suggest that systematic efforts to reduce unnecessary prescribing of antimicrobials to outpatients in Canada, beginning after a national consensus conference in 1997, may be having an impact. There is, however, still a need for continued concerted efforts on a national, provincial and regional level to quell the rising tide of antibiotic resistance. PMID:12406948

  10. Antimicrobial Mechanism of Monocaprylate

    PubMed Central

    Hyldgaard, Morten; Sutherland, Duncan S.; Sundh, Maria; Mygind, Tina

    2012-01-01

    Monoglyceride esters of fatty acids occur naturally and encompass a broad spectrum of antimicrobial activity. Monocaprylate is generally regarded as safe (GRAS) and can function both as an emulsifier and as a preservative in food. However, knowledge about its mode of action is lacking. The aim of this study was therefore to elucidate the mechanism behind monocaprylate's antimicrobial effect. The cause of cell death in Escherichia coli, Staphylococcus xylosus, and Zygosaccharomyces bailii was investigated by examining monocaprylate's effect on cell structure, membrane integrity, and its interaction with model membranes. Changes in cell structure were visible by atomic force microscopy (AFM), and propidium iodide staining showed membrane disruption, indicating the membrane as a site of action. This indication was confirmed by measuring calcein leakage from membrane vesicles exposed to monocaprylate. AFM imaging of supported lipid bilayers visualized the integration of monocaprylate into the liquid disordered, and not the solid ordered, phase of the membrane. The integration of monocaprylate was confirmed by quartz crystal microbalance measurements, showing an abrupt increase in mass and hydration of the membrane after exposure to monocaprylate above a threshold concentration. We hypothesize that monocaprylate destabilizes membranes by increasing membrane fluidity and the number of phase boundary defects. The sensitivity of cells to monocaprylate will therefore depend on the lipid composition, fluidity, and curvature of the membrane. PMID:22344642

  11. Force Measurement Using Non-Restrained Models In A Shock Tunnel

    NASA Astrophysics Data System (ADS)

    Tanno, Hideyuki; Sato, Kazuo; Komuro, Tomoyuki; Takahashi, Massahiro; Itoh, Katsuhiro; Fujita, Kazuhisa; Laurence, Stuart; Hannemann, Klaus

    2011-05-01

    A novel force measurement technique has been developed at the impulsive facility HIEST, in which the test model is completely non-restrained for the duration of the test, so it experiences free-flight conditions for a period on the order of milliseconds. This technique was demonstrated with a three-component aerodynamic force measurement with a blunted cone of total length 318 mm and a total mass of 22 kg. At the beginning of the wind tunnel test, the blunted cone test model was suspended from electromagnets fixed on the test-section ceiling. The model was released when a triggering signal arrived from the tunnel start signal. The model then fell so that it met the hypersonic test flow just as it arrived in the test section, and made a soft landing on a model catcher with four hydraulic shock absorbers. A miniature model-onboard data-logger, which was a key technology for this technique, was also developed in order to store the measured data. The data-logger was designed to be small enough to be instrumented in test models, with an overall size of 50 mm x 70 mm x 50 mm, including batteries. Since the logger was designed to measure force and pressure, it includes six piezoelectric amplifiers and four piezoresistive amplifiers, as well as high-speed analog-digital converters, which digitize the measured data with 16-bit resolution. The logger’s sampling rate and sample size are 500 kHz and 200 ms, respectively. The logger waits for a trigger signal (accelerometer output) and then starts to take measurements. The trigger threshold and pre-trigger delay time can be adjusted arbitrarily. Measured data is stored to static memory for transfer to a PC via a USB interface after a wind tunnel test. To demonstrate the entire measurement system, wind tunnel experiments were conducted in HIEST. In the present wind tunnel test campaign, records of pressure and axial force were obtained under conditions of H0 = 4 MJ/kg, P0 = 14 MPa. This demonstrated that the system worked

  12. Adsorption characteristics of sulfur powder by bamboo charcoal to restrain sulfur allergies.

    PubMed

    Peng, Wanxi; Ge, Shengbo; Liu, Zhenling; Furuta, Yuzo

    2017-01-01

    Exposures to particulate matter with a diameter of 2.5 μm or less (PM2.5) may influence the risk of birth defects and make you allergic, which causes serious harm to human health. Bamboo charcoal can adsorb harmful substances,that was of benefitto people's health. In order to figure out the optimal adsorbtion condition and the intrinsic change of bamboo charcoal, five chemicals were adsorbed by bamboo charcoal and were analyzed by FT-IR. The optimal blast time was 80 min of Na2SO3, 100 min of Na2S2O8, 20 min of Na2SO4, 120 min of Fe2(SO4)3 and 60 min or 100 min of S. FT-IR spectra showed that bamboo charcoal had five characteristic peaks of S-S stretch, H2O stretch, O-H stretch, C 000000000000 000000000000 000000000000 111111111111 000000000000 111111111111 000000000000 000000000000 000000000000 O stretch or CC stretch, and NO2 stretch at 3850 cm(-1), 3740 cm(-1), 3430 cm(-1), 1630 cm(-1) and 1530 cm(-1), respectively. For Na2SO3, the peaks at 3850 cm(-1), 3740 cm(-1), 3430 cm(-1), 1630 cm(-1) and 1530 cm(-1) achieved the maximum at 20 min. For Na2S2O8, the peaks at 3850 cm(-1), 3740 cm(-1), 3430 cm(-1) and 1530 cm(-1) achieved the maximum at 40 min. For Na2SO4, the peaks at 3850 cm(-1), 3740 cm(-1) and 1530 cm(-1) achieved the maximum at 40 min. For Fe2(SO4)3, the peaks at 3850 cm(-1), 3740 cm(-1), 1630 cm(-1) and 1530 cm(-1) achieved the maximum at 120 min. For S, the peaks at 3850 cm(-1) and 3740 cm(-1) achieved the maximum at 40 min, the peaks at 1630 cm(-1) and 1530 cm(-1) achieved the maximum at 40 min. It proved that bamboo charcoal could remove sulfur powder from air to restrain sulfur allergies.

  13. HDAC1 and HDAC2 Restrain the Intestinal Inflammatory Response by Regulating Intestinal Epithelial Cell Differentiation

    PubMed Central

    Turgeon, Naomie; Blais, Mylène; Gagné, Julie-Moore; Tardif, Véronique; Boudreau, François; Perreault, Nathalie; Asselin, Claude

    2013-01-01

    , epithelial HDAC1 and HDAC2 restrain the intestinal inflammatory response, by regulating intestinal epithelial cell proliferation and differentiation. PMID:24040068

  14. Restrained tibial rotation may prevent ACL injury during landing at different flexion angles.

    PubMed

    Mokhtarzadeh, Hossein; Ng, Andrew; Yeow, Chen Hua; Oetomo, Denny; Malekipour, Fatemeh; Lee, Peter Vee Sin

    2015-01-01

    Internal tibial rotation is a risk factor for anterior cruciate ligament (ACL) injury. The effect of restraining tibial rotation (RTR) to prevent ACL injury during single-leg landing is not well understood. We aimed to investigate the effect of impact load and RTR on ACL injury with respect to flexion angle. We hypothesized that RTR could protect the knee from ACL injury compared to free tibial rotation (FTR) regardless of flexion angle and create a safety zone to protect the ACL. Thirty porcine specimens were potted in a rig manufactured to replicate single-leg landing maneuvers. A mechanical testing machine was used to apply external forces in the direction of the tibial long axis. A 3D displacement sensor measured anterior tibial translation (ATT). The specimens were divided into 3 groups of 10 specimens and tested at flexion angles of 22 ± 1°, 37 ± 1° and 52 ± 1° (five RTR and five FTR) through a consecutive range of actuator displacements until ACL failure. After dissection, damage to the joint was visually recorded. Two-way ANOVA were utilized in order to compare compressive forces, torques and A/P displacements with respect to flexion angle. The largest difference between peak axial compressive forces (~3.4 kN) causing ACL injury between RTR and FTR was reported at a flexion angle of 22°. Tibial torques with RTR was in the same range and < 20 Nm at the instance and just before ACL failure, compared to a significant reduction when cartilage/bone damage (no ACL failure) was reported. Isolated ACL injuries were observed in ten of the 15 FTR specimens. Injuries to bone and cartilage were more common with RTR. RTR increases the threshold for ACL injury by elevating the compressive impact load required at lower flexion angles. These findings may contribute to neuromuscular training programs or brace designs used to avoid excessive internal/external tibial rotation. Caution must be exercised as bone/cartilage damage may result. Copyright © 2014 Elsevier B

  15. Associations between Restrained Eating and the Size and Frequency of Overall Intake, Meal, Snack and Drink Occasions in the UK Adult National Diet and Nutrition Survey

    PubMed Central

    Olea López, Ana Lorena; Johnson, Laura

    2016-01-01

    Obesity is a global public health priority. Restrained eating is related to obesity and total energy intake but associations with the eating patterns are unclear. We examined the associations of restrained eating with the size and frequency of intake occasions among 1213 British adult (19–64 y) participants in a cross-sectional analysis of the UK National Diet and Nutrition Survey 2000. The Dutch Eating Behaviour Questionnaire assessed restrained eating. Overall intake occasions were all energy consumed in a 60 min period. A food-based classification separated intake occasions into meals, snacks, or drinks from seven-day weighed food diaries. Average daily frequency and size (kcal) of overall intake, meal, snack and drink occasions were calculated and associations with restrained eating were modelled using multiple linear regression including under-reporting of energy intake, age, gender, BMI, emotional eating, external eating and physical activity as covariates. Restrained eating was very weakly positively correlated with overall intake (r = 0.08, p<0.05) and meal frequency (r = 0.10, p<0.05) but not snack or drink frequency (r = 0.02 and -0.02 respectively). Adjusted regressions showed a one-point change in restrained eating was associated with 0.07 (95% CI 0.03, 0.11) more meal occasions/day and 0.13 (95% CI 0.01, 0.25) extra overall intake occasions/day. Overall intake occasion size was weakly negatively correlated with restrained eating regardless of type (r = -0.16 to -0.20, all p<0.0001). Adjusted regressions showed each one-point increase in restrained eating was associated with lower-energy meals (-15 kcal 95% CI -5.9, -24.2) and drinks (-4 kcal 95%CI -0.1, -8), but not snacks or overall intake occasions. Among a national sample of UK adults, greater restrained eating was associated with smaller and slightly more frequent eating, suggesting that restrained eaters restrict their energy intake by reducing meal/drink size rather than skipping snacks. PMID

  16. Structure and geometry of the Aksay restraining double bend along the Altyn Tagh Fault, northern Tibet, imaged using magnetotelluric method

    NASA Astrophysics Data System (ADS)

    Xiao, Qibin; Yu, Guo; Liu-Zeng, Jing; Oskin, Michael E.; Shao, Guihang

    2017-05-01

    Large restraining bends along active strike-slip faults locally enhance the accumulation of clamping tectonic normal stresses that may limit the size of major earthquakes. In such settings, uncertain fault geometry at depth limits understanding of how effectively a bend arrests earthquake ruptures. Here we demonstrate fault imaging within a major restraining bend along the Altyn Tagh Fault of western China using the magnetotelluric (MT) method. The new MT data were collected along two profiles across the Aksay restraining double bend, which is bounded by two subparallel strands of the Altyn Tagh Fault: Northern (NATF) and Southern (SATF). Both two-dimensional (2-D) and three-dimensional (3-D) inversion models show that the Aksay bend may be the center of a positive flower structure, imaged as a high-resistivity body extending to an 40 km depth and bounded by subvertical resistivity discontinuities corresponding to the NATF and SATF. In the western section of the Aksay bend, both the NATF and SATF show similar low-resistivity structure, whereas in the eastern part of the bend, the low-resistivity anomaly below the SATF is wider and more prominent than that below the NATF. This observation indicates that the SATF shear zone may be wider and host more fluid than the NATF, lending structural support to the contention that fault slip at depth is asymmetrically focused on the SATF, even though surface slip is focused on the NATF. A south dipping, low-resistivity interface branching upward from the SATF toward the NATF indicates a fault link between these strands at depth.

  17. Study Under AC Stimulation on Excitement Properties of Weighted Small-World Biological Neural Networks with Side-Restrain Mechanism

    NASA Astrophysics Data System (ADS)

    Yuan, Wu-Jie; Luo, Xiao-Shu; Jiang, Pin-Qun

    2007-02-01

    In this paper, we propose a new model of weighted small-world biological neural networks based on biophysical Hodgkin-Huxley neurons with side-restrain mechanism. Then we study excitement properties of the model under alternating current (AC) stimulation. The study shows that the excitement properties in the networks are preferably consistent with the behavior properties of a brain nervous system under different AC stimuli, such as refractory period and the brain neural excitement response induced by different intensities of noise and coupling. The results of the study have reference worthiness for the brain nerve electrophysiology and epistemological science.

  18. Transcranial Two-Photon Imaging of Synaptic Structures in the Cortex of Awake Head-Restrained Mice

    PubMed Central

    Yang, Guang; Pan, Feng; Chang, Paul C.; Gooden, Frank; Gan, Wen-Biao

    2013-01-01

    Transcranial two-photon microscopy allows long-term imaging of neurons, glia, and vasculature in the intact cortex of living animals. So far, this technique has been primarily used to acquire images in anesthetized animals. Here, we describe a detailed protocol for high-resolution two-photon imaging of neuronal structures in the cortex of awake head-restrained mice. Surgery is done within 1 h in anesthetized mice. After animals recover from anesthesia, two-photon imaging can be performed multiple times over minutes to days, allowing longitudinal studies of synaptic plasticity and pathology without the complication induced by anesthesia reagents. PMID:23754217

  19. Cone restraining and head-only electrical stunning in broilers: effects on physiological responses and meat quality.

    PubMed

    Lambooij, E; Reimert, H G M; Verhoeven, M T W; Hindle, V A

    2014-03-01

    Two experiments were conducted to evaluate a new electrical stunning system for broilers. The objective of the first experiment was to evaluate the behavioral, neural, and physiological responses of 27 broilers after head-only electrical stunning while their bodies were restrained in cone-shaped holders. In the second experiment, quality of meat from 30 broilers after head-only electrical stunning in a cone-shaped restrainer was compared with that from 30 broilers stunned in a conventional water bath. Broilers were restrained in the cone with their heads positioned to facilitate a correct stun, followed by a neck cut by hand. After stunning, each broiler displayed a tonic phase, followed by minimal brain activity during bleeding. On average, heart rate was 258 ± 51 beats/min before stunning. The heart was observed to malfunction after cutting. According to the correlation dimension analyses, the score remained low. Within a confidence limit of 95%, taking into account the number of birds with a reliable electroencephalogram (n = 27), the chance of an effective stun and exsanguination with all broilers lies between 0.90 and 1.00 using a sinusoidal AC current of 264 ± 29 mA (∼130 V). After a brief learning period, operators were able to easily position the broilers in the cone in a commercial setting. The pH after chilling was 0.5 units lower (P < 0.05) in the head-only stunned group compared with the group stunned in a conventional water bath. After head-only stunning, 60% of breast fillets showed no blood splashes and 3% showed severe blood splashes compared with 20 and 27% after conventional water bath stunning. No differences in temperature and color were observed between the 2 groups. It is concluded that broilers could be restrained in a cone, followed by correct head-only stunning, neck-cutting, and unconscious shackling afterward under laboratory and commercial slaughterhouse conditions. When this procedure was used, meat quality was better compared with

  20. Novel Formulations for Antimicrobial Peptides

    PubMed Central

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  1. [Antimicrobial susceptibility in Chile 2012].

    PubMed

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  2. Novel formulations for antimicrobial peptides.

    PubMed

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2014-10-09

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  3. Antimicrobial peptides: therapeutic potentials.

    PubMed

    Kang, Su-Jin; Park, Sung Jean; Mishig-Ochir, Tsogbadrakh; Lee, Bong-Jin

    2014-12-01

    The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.

  4. [Antimicrobial prophylaxis in surgery].

    PubMed

    Shinagawa, Nagao

    2004-02-01

    Antimicrobial prophylaxis is widely performed in any surgical procedures to prevent postoperative infections. However, we have neither double-blind placebo-controlled studies nor sufficient surveillance of postoperative infections that are common in Europe and the United States, and therefore there is little convincing scientific basis accounting for the validity of this therapy. In addition, prophylactic agent is still uncovered by medical insurance despite the persistent arguments as to its necessity. To establish the guidelines in our own country, a greater deal of evidence needs to be accumulated. Strategies for antimicrobial prophylaxis should be determined based on the types of possible postoperative infections and the classifications of operations according to contamination levels in individual operative fields. This process may involve the precise selection of prophylactic agents for suspected contaminating bacterial species in each operative organ and their administration regimens suitable for the individual surgery. Upon selection of prophylactic agents for postoperative infections, various conditions should be considered: e.g., susceptibility, resistance, blood concentrations, urinary excretion, transition into body fluid and tissues, and adverse reactions. The first and second generations of cephem and cephamycin derivatives can be the first choice, but the use of various other antibacterial agents may be necessary for resistant bacterial strains such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP). Cyclic therapy based on penicillins (including mixtures), cephems (including cephamycins) and phosphomycins also seems useful for such resistant strains. At present, there is only limited evidence supporting the importance of prophylactic agents. Controlled trials employing well-designed protocols that endure scientific criticism must be done with due consideration for medical economics.

  5. Focusing on media body ideal images triggers food intake among restrained eaters: a test of restraint theory and the elaboration likelihood model.

    PubMed

    Boyce, Jessica A; Kuijer, Roeline G

    2014-04-01

    Although research consistently shows that images of thin women in the media (media body ideals) affect women negatively (e.g., increased weight dissatisfaction and food intake), this effect is less clear among restrained eaters. The majority of experiments demonstrate that restrained eaters - identified with the Restraint Scale - consume more food than do other participants after viewing media body ideal images; whereas a minority of experiments suggest that such images trigger restrained eaters' dietary restraint. Weight satisfaction and mood results are just as variable. One reason for these inconsistent results might be that different methods of image exposure (e.g., slideshow vs. film) afford varying levels of attention. Therefore, we manipulated attention levels and measured participants' weight satisfaction and food intake. We based our hypotheses on the elaboration likelihood model and on restraint theory. We hypothesised that advertent (i.e., processing the images via central routes of persuasion) and inadvertent (i.e., processing the images via peripheral routes of persuasion) exposure would trigger differing degrees of weight dissatisfaction and dietary disinhibition among restrained eaters (cf. restraint theory). Participants (N = 174) were assigned to one of four conditions: advertent or inadvertent exposure to media or control images. The dependent variables were measured in a supposedly unrelated study. Although restrained eaters' weight satisfaction was not significantly affected by either media exposure condition, advertent (but not inadvertent) media exposure triggered restrained eaters' eating. These results suggest that teaching restrained eaters how to pay less attention to media body ideal images might be an effective strategy in media-literary interventions.

  6. Crash characteristics and injury patterns of restrained front seat occupants in far-side impacts.

    PubMed

    Yoganandan, Narayan; Arun, Mike W J; Halloway, Dale E; Pintar, Frank A; Maiman, Dennis J; Szabo, Aniko; Rudd, Rodney W

    2014-01-01

    The study was conducted to determine the association between vehicle-, crash-, and demographic-related factors and injuries to front seat far-side occupants in modern environments. Field data were obtained from the NASS-CDS database for the years 2009-2012. Inclusion factors included the following: adult restrained front outboard-seated occupants, no ejection or rollovers, and vehicle model years less than 10 years old at the time of crash. Far-side crashes were determined by using collision deformation classification. Injuries were scored using the Abbreviated Injury Scale (AIS). Injuries (MAIS 2+, MAIS 3+, M denotes maximum score) were examined based on demographics, change in velocity, vehicle type, direction of force, extent zone, collision partner, and presence of another occupant in the front seat. Only weighted data were used in the analysis. Injuries to the head and face, thorax, abdomen, pelvis, and upper and lower extremity regions were studied. Odds ratios and upper and lower confidence intervals were estimated from multivariate analysis. Out of 519,195 far-side occupants, 17,715 were MAIS 2+ and 4,387 were MAIS 3+ level injured occupants. The mean age, stature, total body mass, and body mass index (BMI) were 40.7 years, 1.7 m, 77.2 kg, and 26.8 kg/m2, respectively. Of occupants with MAIS 2+ injuries, 51% had head and 19% had thorax injuries. Of occupants with MAIS 3+ injuries, 50% had head and 69% had thorax injuries. The cumulative distribution of changes in velocities at the 50th percentile for the struck vehicle for all occupants and occupants with MAIS 2+ and MAIS 3+ injuries were 19, 34, and 42 km/h, respectively. Furthermore, 73% of MAIS 2+ injuries and 86% of MAIS 3+ injuries occurred at a change in velocity of 24 km/h or greater. Odds of sustaining MAIS 2+ and MAIS 3+ injuries increased with each unit increase in change in velocity, stature, and age, with one exception. Odds of sustaining injuries were higher with the presence of an occupant in

  7. Crash characteristics and injury patterns of restrained front seat occupants in far-side impacts

    PubMed Central

    Yoganandan, Narayan; Arun, Mike W. J.; Halloway, Dale E.; Pintar, Frank A.; Maiman, Dennis J.; Szabo, Aniko; Rudd, Rodney W.

    2015-01-01

    STRUCTURED ABSTRACT Objective The study was conducted to determine the association between vehicle-, crash- and demographic-related factors and injuries to front seat far-side occupants in modern environments. Methods Field data were obtained from the United States (US) National Automotive Sampling System – Crashworthiness Data System (NASS-CDS) database, for the years 2009–2012. Inclusion factors: adult restrained front outboard seated occupants, no ejection or rollovers, and vehicle model years less than 10 years old at the time of crash. Far-side crashes were determined by using collision deformation classification. Injuries were scored using the Abbreviated Injury Scale (AIS). Injuries (MAIS2+, MAIS3+, M denotes maximum score) were examined based on demographics, change in velocity, vehicle type, direction of force, extent zone, collision partner and presence of another occupant in the front seat. Only weighted data were used in the analysis. Injuries to the head and face, thorax, abdomen, pelvis, upper extremity and lower extremity regions were studied. Odds ratios and upper and lower confidence intervals were estimated from multivariate analysis. Results Out of 519,195 far-side occupants, 17,715 were MAIS2+ and 4,387 were MAIS3+ level injured occupants. The mean age, stature, total body mass, and BMI were 40.7 years, 1.7 m, 77.2 kg, and 26.8 kg/m2, respectively. Of occupants with MAIS2+ injuries, 51% had head and 19% had thorax injuries. Of occupants with MAIS 3+ injuries, 50% had head and 69% had thorax injuries. The cumulative distribution of changes in velocities at the 50th percent level for the struck vehicle for all occupants and, MAIS2+ and MAIS3+ occupants were 19, 34 and 42 km/h, respectively. Furthermore, 73% of MAIS2+ injuries and 86% of MAIS3+ injuries occurred at a change in velocity of 24 km/h or greater. Odds of sustaining MAIS2+ and MAIS3+ injuries increased with unit increase in change in velocity, stature and age, with one exception

  8. Antimicrobial Pesticide Use Site Index

    EPA Pesticide Factsheets

    This Use Site Index provides guidance to assist applicants for antimicrobial pesticide registration by helping them identify the data requirements necessary to register a pesticide or support their product registrations.

  9. Antimicrobial seafood packaging: a review.

    PubMed

    Singh, Suman; Ho Lee, Myung; Park, Lnsik; Shin, Yangjai; Lee, Youn Suk

    2016-06-01

    Microorganisms are the major cause of spoilage in most seafood products; however, only few microbes, called the specific spoilage organisms (SSOs), contribute to the offensive off-flavors associated with seafood spoilage. In food, microbial degradation manifests itself as spoilage, or changes in the sensory properties of a food product, rendering it unsuitable for human consumption. The use of antimicrobial substances can control the general microflora as well as specific microorganisms related to spoilage to provide products with higher safety and better quality. Many antimicrobial compounds have been evaluated in film structures for use in seafood, especially organic acids and their salts, enzymes, bacteriocins; some studies have considered inorganic compounds such as AgSiO2, zinc oxide, silver zeolite, and titanium oxide. The characteristics of some organic antimicrobial packaging systems for seafood and their antimicrobial efficiency in film structures are reviewed in this article.

  10. Antimicrobial resistance in Burkholderia pseudomallei.

    PubMed

    Vorachit, M; Chongtrakool, P; Arkomsean, S; Boonsong, S

    2000-02-05

    Four strains of Burkholderia pseudomallei were used to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves with 13 single antimicrobial agents: ceftazidime, piperacillin, imipenem, amoxicillin/clavulanic acid, doxycycline, cotrimoxazole, kanamycin, rifampicin, ciprofloxacin, trovafloxacin, clarithromycin, azithromycin and meropenem. The time-kill studies were also performed with 33 pairs of combinations of the above antimicrobial agents: 15 combinations which would be expected to be used for acute therapy and 18 combinations for maintenance therapy. The results show that the single and combination antimicrobial agents with bactericidal effects against the four strains of B. pseudomallei which should be used for clinical trials in acute melioidosis are: imipenem, meropenem, and imipenem + azithromycin. The combination antimicrobial agents which should be further studied for the ability to eliminate biofilm and intracellular killing effect are ciprofloxacin + clarithromycin, ciprofloxacin + azithromycin, and imipenem + azithromycin.

  11. Automation of antimicrobial activity screening.

    PubMed

    Forry, Samuel P; Madonna, Megan C; López-Pérez, Daneli; Lin, Nancy J; Pasco, Madeleine D

    2016-03-01

    Manual and automated methods were compared for routine screening of compounds for antimicrobial activity. Automation generally accelerated assays and required less user intervention while producing comparable results. Automated protocols were validated for planktonic, biofilm, and agar cultures of the oral microbe Streptococcus mutans that is commonly associated with tooth decay. Toxicity assays for the known antimicrobial compound cetylpyridinium chloride (CPC) were validated against planktonic, biofilm forming, and 24 h biofilm culture conditions, and several commonly reported toxicity/antimicrobial activity measures were evaluated: the 50 % inhibitory concentration (IC50), the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC). Using automated methods, three halide salts of cetylpyridinium (CPC, CPB, CPI) were rapidly screened with no detectable effect of the counter ion on antimicrobial activity.

  12. Antimicrobial peptides: properties and applicability.

    PubMed

    van 't Hof, W; Veerman, E C; Helmerhorst, E J; Amerongen, A V

    2001-04-01

    All organisms need protection against microorganisms, e. g. bacteria, viruses and fungi. For many years, attention has been focused on adaptive immunity as the main antimicrobial defense system. However, the adaptive immune system, with its network of humoral and cellular responses is only found in higher animals, while innate immunity is encountered in all living creatures. The turning point in the appreciation of the innate immunity was the discovery of antimicrobial peptides in the early eighties. In general these peptides act by disrupting the structural integrity of the microbial membranes. It has become clear that membrane-active peptides and proteins play a crucial role in both the innate and the adaptive immune system as antimicrobial agents. This review is focused on the functional and structural features of the naturally occurring antimicrobial peptides, and discusses their potential as therapeutics.

  13. Chloroplast downsizing under nitrate nutrition restrained mesophyll conductance and photosynthesis in rice (Oryza sativa L.) under drought conditions.

    PubMed

    Li, Yong; Ren, Binbin; Yang, Xiuxia; Xu, Guohua; Shen, Qirong; Guo, Shiwei

    2012-05-01

    The phenomenon whereby ammonium enhances the tolerance of rice seedlings (Oryza sativa L., cv. 'Shanyou 63' hybrid indica China) to water stress has been reported in previous studies. To study the intrinsic mechanism of biomass synthesis related to photosynthesis, hydroponic experiments supplying different nitrogen (N) forms were conducted; water stress was simulated by the addition of polyethylene glycol. Water stress decreased leaf water potential (Ψ(leaf)) under nitrate nutrition, while it had no negative effect under ammonium nutrition. The decreased Ψ(leaf) under nitrate nutrition resulted in chloroplast downsizing and subsequently decreased mesophyll conductance to CO(2) (g(m)). The decreased g(m) and stomatal conductance (g(s)) under nitrate nutrition with water stress restrained the CO(2) supply to the chloroplast and Rubisco. The relatively higher distribution of leaf N to Rubisco under ammonium nutrition might also be of benefit for photosynthesis under water stress. In conclusion, chloroplast downsizing induced a decline in g(m), a relatively higher decrease in g(s) under nitrate nutrition with water stress, restrained the CO(2) supply to Rubisco and finally decreased the photosynthetic rate.

  14. The posteromedial corner revisited. An anatomical description of the passive restraining structures of the medial aspect of the human knee.

    PubMed

    Robinson, J R; Sanchez-Ballester, J; Bull, A M J; Thomas, R de W M; Amis, A A

    2004-07-01

    We have reviewed the literature on the anatomy of the posteromedial peripheral ligamentous structures of the knee and found differing descriptions. Our aim was to clarify the differing descriptions with a simplified interpretation of the anatomy and its contribution to the stability of the knee. We dissected 20 fresh-frozen cadaver knees and the anatomy was recorded using video and still digital photography. The anatomy was described by dividing the medial collateral ligament (MCL) complex into thirds, from anterior to posterior and into superficial and deep layers. The main passive restraining structures of the posteromedial aspect of the knee were found to be superficial MCL (parallel, longitudinal fibres), the deep MCL and the posteromedial capsule (PMC). In the posterior third, the superficial and deep layers blend. Although there are oblique fibres (capsular condensations) running posterodistally from femur to tibia, no discrete ligament was seen. In extension, the PMC appears to be an important functional unit in restraining tibial internal rotation and valgus. Our aim was to clarify and possibly simplify the anatomy of the posteromedial structures. The information would serve as the basis for future biomechanical studies to investigate the contribution of the posteromedial structures to joint stability.

  15. Identifying Armed Respondents to Domestic Violence Restraining Orders and Recovering Their Firearms: Process Evaluation of an Initiative in California

    PubMed Central

    Frattaroli, Shannon; Claire, Barbara E.; Vittes, Katherine A.; Webster, Daniel W.

    2014-01-01

    Objectives. We evaluated a law enforcement initiative to screen respondents to domestic violence restraining orders for firearm ownership or possession and recover their firearms. Methods. The initiative was implemented in San Mateo and Butte counties in California from 2007 through 2010. We used descriptive methods to evaluate the screening process and recovery effort in each county, relying on records for individual cases. Results. Screening relied on an archive of firearm transactions, court records, and petitioner interviews; no single source was adequate. Screening linked 525 respondents (17.7%) in San Mateo County to firearms; 405 firearms were recovered from 119 (22.7%) of them. In Butte County, 88 (31.1%) respondents were linked to firearms; 260 firearms were recovered from 45 (51.1%) of them. Nonrecovery occurred most often when orders were never served or respondents denied having firearms. There were no reports of serious violence or injury. Conclusions. Recovering firearms from persons subject to domestic violence restraining orders is possible. We have identified design and implementation changes that may improve the screening process and the yield from recovery efforts. Larger implementation trials are needed. PMID:24328660

  16. Identifying armed respondents to domestic violence restraining orders and recovering their firearms: process evaluation of an initiative in California.

    PubMed

    Wintemute, Garen J; Frattaroli, Shannon; Claire, Barbara E; Vittes, Katherine A; Webster, Daniel W

    2014-02-01

    We evaluated a law enforcement initiative to screen respondents to domestic violence restraining orders for firearm ownership or possession and recover their firearms. The initiative was implemented in San Mateo and Butte counties in California from 2007 through 2010. We used descriptive methods to evaluate the screening process and recovery effort in each county, relying on records for individual cases. Screening relied on an archive of firearm transactions, court records, and petitioner interviews; no single source was adequate. Screening linked 525 respondents (17.7%) in San Mateo County to firearms; 405 firearms were recovered from 119 (22.7%) of them. In Butte County, 88 (31.1%) respondents were linked to firearms; 260 firearms were recovered from 45 (51.1%) of them. Nonrecovery occurred most often when orders were never served or respondents denied having firearms. There were no reports of serious violence or injury. Recovering firearms from persons subject to domestic violence restraining orders is possible. We have identified design and implementation changes that may improve the screening process and the yield from recovery efforts. Larger implementation trials are needed.

  17. Assessment of buckling-restrained braced frame reliability using an experimental limit-state model and stochastic dynamic analysis

    NASA Astrophysics Data System (ADS)

    Andrews, Blake M.; Song, Junho; Fahnestock, Larry A.

    2009-09-01

    Buckling-restrained braces (BRBs) have recently become popular in the United States for use as primary members of seismic lateral-force-resisting systems. A BRB is a steel brace that does not buckle in compression but instead yields in both tension and compression. Although design guidelines for BRB applications have been developed, systematic procedures for assessing performance and quantifying reliability are still needed. This paper presents an analytical framework for assessing buckling-restrained braced frame (BRBF) reliability when subjected to seismic loads. This framework efficiently quantifies the risk of BRB failure due to low-cycle fatigue fracture of the BRB core. The procedure includes a series of components that: (1) quantify BRB demand in terms of BRB core deformation histories generated through stochastic dynamic analyses; (2) quantify the limit-state of a BRB in terms of its remaining cumulative plastic ductility capacity based on an experimental database; and (3) evaluate the probability of BRB failure, given the quantified demand and capacity, through structural reliability analyses. Parametric studies were conducted to investigate the effects of the seismic load, and characteristics of the BRB and BRBF on the probability of brace failure. In addition, fragility curves (i.e., conditional probabilities of brace failure given ground shaking intensity parameters) were created by the proposed framework. While the framework presented in this paper is applied to the assessment of BRBFs, the modular nature of the framework components allows for application to other structural components and systems.

  18. Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation

    PubMed Central

    Mishra, Vikas; Shuai, Bing; Kodali, Maheedhar; Shetty, Geetha A.; Hattiangady, Bharathi; Rao, Xiaolan; Shetty, Ashok K.

    2015-01-01

    Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy. PMID:26639668

  19. Study: ED providers could be doing more to prevent injuries, deaths related to improperly restrained child passengers.

    PubMed

    2013-07-01

    Researchers from the University of Michigan's CS Mott Children's Hospital in Ann Arbor, MI, report that both general and pediatric-trained emergency providers are missing opportunities to get critical information about the proper use of child restraints out to the families of children when they are brought to the ED following motor vehicle crashes. In a survey sent to a random sample of 1200 emergency physicians across the country, fewer than one-half of the responding physicians indicated that the parents of a 2-year-old being discharged from their ED following a motor vehicle crash would be supplied with discharge instructions that include advice about the proper use of car seats. The study notes that 20% of 1 to 3-year-olds and about one-half of 4 to 7-year-olds are typically not restrained in the recommended restraint for their age. Child passenger injuries in crashes are the leading cause of death for children who are older than age 3 years in the United States, and they are the second leading cause of death among children aged 1 to 4. Researchers recommend that resources on child passenger safety be highlighted in discharge instructions, and that emergency providers tap into their own experiences when speaking with families about the importance of properly restraining child passengers.

  20. Crash analysis of lower extremity injuries in children restrained in forward-facing car seats during front and rear impacts.

    PubMed

    Bennett, Tellen D; Kaufman, Robert; Schiff, Melissa; Mock, Charles; Quan, Linda

    2006-09-01

    The mechanism, crash characteristics, and spectrum of lower extremity injuries in children restrained in forward-facing car seats during front and rear impacts have not been described. We identified in two databases children who sustained lower extremity injuries while restrained in forward-facing car seats. To identify the mechanism, we analyzed crash reconstructions from three frontal-impact cases from the Crash Injury Research and Engineering Network. To further describe the crash and injury characteristics we evaluated children between 1 and 4 years of age with lower extremity injuries from front or rear impacts in the National Automotive Sampling System (NASS) Crashworthiness Data System (CDS) database. Crash reconstruction data demonstrated that the likely mechanism of lower extremity injury was contact between the legs and the front seatbacks. In the CDS database, we identified 15 children with lower extremity injuries in a forward-facing child seat, usually (13 out of 15) placed in the rear seat, incurred in frontal impacts (11 out of 15). Several (5 out of 15) children were in unbelted or improperly secured forward-facing car seats. Injury Severity Scores varied widely (5-50). Children in forward-facing car seats involved in severe front or rear crashes may incur a range of lower extremity injury from impact with the car interior component in front of them. Crash scene photography can provide useful information about anatomic sites at risk for injury and alert emergency department providers to possible subtle injury.

  1. [Antimicrobial resistance in developing countries].

    PubMed

    Blomberg, Bjørn

    2008-11-06

    While bacterial infections are one of the most important causes of disease and death in developing countries, the prevalence and consequences of antimicrobial resistance are not well known. This is a review article based on literature retrieved from a non-systematic review and own experience from research on the topic. Research on antimicrobial resistance is increasing in developing countries, but most of the data are obtained from referral hospitals in capitals and major cities. Multiresistant Gram-negative bacteria, including ESBL-(extended-spectrum beta-lactamase) producing bacteria have been documented in several countries and are associated with increased lethality. The most serious resistance problems in developing countries are associated with Gram-negative bacteria and tuberculosis and may result in increased risk of death. Developing countries have a much higher overall burden of infectious diseases than the rich western countries and also poor access to newer antibiotics, which can be lifesaving when treating infections caused by resistant bacteria. To combat overuse and misuse of antibiotics, the diagnosis of infectious diseases must be strengthened and antimicrobial resistance must be emphasized in education of health professionals and the general public. There is a need for improved surveillance of antimicrobial resistance and strengthened quality control of antimicrobial drugs. In the long-term perspective, poverty reduction, improved living conditions and hygiene, safe water supplies and access to quality health care (including vaccination and HIV care), may contribute to prevent emerging antimicrobial resistance.

  2. Antimicrobial activity of flavonoids.

    PubMed

    Cushnie, T P Tim; Lamb, Andrew J

    2005-11-01

    Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (-)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2'-trihydroxy-5'-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

  3. Antimicrobial Peptides from Plants

    PubMed Central

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  4. Peptides and Peptidomimetics for Antimicrobial Drug Design

    PubMed Central

    Mojsoska, Biljana; Jenssen, Håvard

    2015-01-01

    The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics. PMID:26184232

  5. Editorial of the Special Issue Antimicrobial Polymers

    PubMed Central

    Piozzi, Antonella; Francolini, Iolanda

    2013-01-01

    The special issue “Antimicrobial Polymers” includes research and review papers concerning the recent advances on preparation of antimicrobial polymers and their relevance to industrial settings and biomedical field. Antimicrobial polymers have recently emerged as promising candidates to fight microbial contamination onto surfaces thanks to their interesting properties. In this special issue, the main strategies pursued for developing antimicrobial polymers, including polymer impregnation with antimicrobial agents or synthesis of polymers bearing antimicrobial moieties, were discussed. The future application of these polymers either in industrial or healthcare settings could result in an extremely positive impact not only at the economic level but also for the improvement of quality of life. PMID:24005863

  6. Purification of antimicrobial peptide from Antarctic Krill ( Euphausia superba) and its function mechanism

    NASA Astrophysics Data System (ADS)

    Zhao, Ling; Yin, Bangzhong; Liu, Qi; Cao, Rong

    2013-09-01

    The preliminary purification and antimicrobial mechanism of antimicrobial peptide from Antarctic Krill were studied in this paper. The results showed that the molecular weight range of antimicrobial polypeptide (CMCC-1) obtained by cation exchange chromatography was between 245-709D as detected by molecular sieve chromatography, and the minimum inhibition concentration (MIC) of CMCC-1 against Staphylococcus aureus was 5.0 mg mL-1. The antimicrobial mechanism of CMCC-1 was studied with S. aureus as indicator bacterium. Compared with control group, the results of the experimental group in which S. aureus was treated with CMCC-1 were as follows: 1) CMCC-1 could inhibit cell division at logarithmic phase. 2) The protein and reducing sugar content, and the conductivity of culture medium increased, and the activity of alkaline phosphatase and β-galactosidase could be detected in the culture medium. 3) Observation under scanning electron microscope revealed that somatic morphology became irregular, and then somatic surface became coarse. The cell became much smaller, and most somatic cells gathered. The boundary between cells became dim and finally fused as a whole. 4) Observation under transmission electron microscope showed that the surface of S. aureus became rough and the reproducing ability was restrained. The cell wall became thin and the cytoplasm shrunk. Substances inside cell leaked out, which caused cells death. 5) SDS-PAGE analysis showed that some bands disappeared, and the residual bands became vague. 6) The genomic DNA electrophoresis results showed that the genomic DNA bands of S. aureus were not degraded but the brightness significantly reduced. Thus, it is supposed that CMCC-1 could destroy the cell wall and membrane of S. aureu, increase the cell membrane permeability and the leaking-out of intracellular substances, and thus cause the death of S. aureu.

  7. Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance.

    PubMed

    Maddox, T W; Clegg, P D; Williams, N J; Pinchbeck, G L

    2015-11-01

    Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin-resistant Staphylococcus aureus has been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin-resistant Staphylococcus aureus strains either to be predominantly of types associated with horses or of sequence type ST398. Antimicrobial-resistant Escherichia coli (including multidrug-resistant and extended spectrum β-lactamase-producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci, Salmonella, Acinetobacter and Pseudomonas species. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.

  8. Antimicrobial anxiety: the impact of stress on antimicrobial immunity

    PubMed Central

    Radek, Katherine A.

    2010-01-01

    Leukocytes and epithelial cells are fundamental to antimicrobial immunity. Their antimicrobial responses are an evolutionarily conserved component of the innate immune system and are influenced by the host’s response to external stimuli. The efficacy of host defense via antimicrobial responses derives from the ability of AMPs to rapidly identify and eradicate foreign microbes and activate proinflammatory pathways, and from the capacity of later innate and adaptive immune responses to amplify protection through distinct biochemical mechanisms. Recent advances in neuroimmunology have identified a direct link between the neuroendocrine and immune systems, where environmental stimuli are generally believed to promote a transient effect on the immune system in response to environmental challenges and are presumably brought back to baseline levels via neuroendocrine pathways. Stress is an environmental stimulus that flares from a variety of circumstances and has become engrained in human society. Small bouts of stress are believed to enhance the host’s immune response; however, prolonged periods of stress can be detrimental through excess production of neuroendocrine-derived mediators that dampen immune responses to invasive pathogens. Elucidation of the mechanisms behind stress-induced immune modulation of antimicrobial responses will ultimately lead to the development of more effective therapeutic interventions for pathologic conditions. It is the intent of this review to broaden the existing paradigm of how stress-related molecules dampen immune responses through suppression of antimicrobial mechanisms, and to emphasize that bacteria can use these factors to enhance microbial pathogenesis during stress. PMID:20442225

  9. "Restrained eating" vs "trying to lose weight": how are they associated with body weight and tendency to overeat among postmenopausal women?

    PubMed

    Rideout, Candice A; Barr, Susan I

    2009-05-01

    In an effort to control body weight, many women diet or adopt a restrained approach to eating. Although common, dieting and dietary restraint remain poorly understood. Clarification of their association with health-related factors, such as body weight and overeating, is required. In this study, we explored how dieting and dietary restraint were associated with body mass index (BMI; calculated as kg/m2) and disinhibition (tendency to overeat) in a sample of 1,071 postmenopausal women aged 45 to 75 years. In a survey of dietary attitudes and body image, we asked about current dieting status and measured restrained eating and disinhibition. Self-reported height and weight were used to calculate BMI, which was confirmed in a subset. Participants were classified by dieting status (yes/no) and level of dietary restraint (high/low by median split).We examined the independent effects of dieting and restrained eating on BMI and disinhibition. More than half of the sample (53%) reported current dieting. Dieting and dietary restraint showed opposite associations with BMI. Among dieters, BMI was 4.1 higher (95% confidence interval: 3.6 to 4.6) than among nondieters. In contrast, BMI of restrained eaters was 1.0 lower (95% confidence interval: -1.6 to -0.5) than unrestrained eaters. Dieters had higher scores for disinhibition, but disinhibition scores of restrained eaters did not differ from those of unrestrained eaters. Our results suggest that dieting and dietary restraint are not equivalent. Finding that dietary restraint is associated with lower BMI (when considered independently of dieting) suggests that restrained eating, rather than dieting, may contribute to successful weight management.

  10. The Association of Restrained Eating With Weight Change Over Time in a Community-Based Sample of Twins

    PubMed Central

    Schur, Ellen A.; Heckbert, Susan R.; Goldberg, Jack H.

    2013-01-01

    We investigated the association of restrained eating with BMI and weight gain while controlling for the influence of genes and shared environment. Participants were 1,587 twins enrolled in the University of Washington Twin Registry (UWTR). Restrained eating was assessed by the Herman and Polivy Restraint Scale. Height and weight were self-reported on two occasions. Analyses used generalized estimating equations or multiple linear regression techniques. Restraint Scale scores were positively associated with both BMI (adjusted β = 0.39 kg/m2; 95% confidence interval (CI) = 0.34–0.44; P < 0.001) and weight gain (adjusted β = 0.33 pounds; 95% CI = 0.17–0.49; P < 0.001). High Restraint Scale scorers had an adjusted mean BMI of 27.9 kg/m2 (95% CI = 27.4–28.4) as compared to intermediate (mean = 25.5 kg/m2; 95% CI = 25.2–25.8) and low scorers (mean = 23.0 kg/m2; 95% CI = 22.7–23.3). In within-pair analyses among 598 same-sex twin pairs, the adjusted association between Restraint Scale scores and BMI persisted even when genetic and shared environmental factors were controlled for (adjusted β = 0.18; 95% CI = 0.12–0.24; P < 0.001), as did the association with weight gain (adjusted β = 0.37; 95% CI = 0.13–0.61; P = 0.003). In stratified analyses, dizygotic (DZ) twins differed more in BMI for a given difference in the Restraint Scale score than monozygotic (MZ) twins, for whom genetics are 100% controlled (adjusted β = 0.32; 95% CI = 0.20–0.44 vs. adjusted β = 0.10; 95% CI = 0.04–0.16; P = 0.001 for test of interaction). These data demonstrate that observed relationships between BMI, weight gain, and restrained eating, as assessed by the Restraint Scale, have a strong environmental influence and are not solely due to shared genetic factors. PMID:20111024

  11. Antimicrobial resistance in Scandinavia after ban of antimicrobial growth promoters.

    PubMed

    Bengtsson, Björn; Wierup, Martin

    2006-01-01

    The banned use of antimicrobial growth promoters resulted in a considerably decreased use of antimicrobials in food animal production in Sweden (65%), Denmark (47%), Norway (40%) and Finland (27%). The current prevalence of antimicrobial resistance in animal bacterial populations is also considerably lower than in some other countries in the EU. In the swine production, no or limited effect was found in the finisher production (>25 to 30 kg). Temporary negative effects occurred during the post weaning period (7-30 kg). In Denmark, the cost of production from birth to slaughter per pig produced increased by approximately 1.0 euro with a high variability between pig producers. In the broiler production the termination had no significant negative effect on animal health and welfare or on production economy.

  12. Comparative study of choleretic agents in anesthetized rats as well as in restrained and and unrestrained rats, with or without compensation for biliary loss

    NASA Technical Reports Server (NTRS)

    Labrid, C.; Dureng, G.; Tachon, J.; Duchene-Marullaz, P.

    1980-01-01

    Tests were conducted on Wistar rats by using 3 control choleretic agents: 1-phenyl-1-hydroxy n-pentane, dehydrocholic acid, and phenyl-dimethylacetic acid. The effects of these agents were compared in different experimental conditions. The comparative study of choleretic agents in anesthetized rats, in restrained and unrestrained rats, with or without compensation for biliary loss by the biliary secretion of restrained or unrestrained rats does not show, in systematic pharmecodynamic investigations, an obvious superiority over the methods based on the simple technique.

  13. Novel histone-derived antimicrobial peptides use different antimicrobial mechanisms.

    PubMed

    Pavia, Kathryn E; Spinella, Sara A; Elmore, Donald E

    2012-03-01

    The increase in multidrug resistant bacteria has sparked an interest in the development of novel antibiotics. Antimicrobial peptides that operate by crossing the cell membrane may also have the potential to deliver drugs to intracellular targets. Buforin 2 (BF2) is an antimicrobial peptide that shares sequence identity with a fragment of histone subunit H2A and whose bactericidal mechanism depends on membrane translocation and DNA binding. Previously, novel histone-derived antimicrobial peptides (HDAPs) were designed based on properties of BF2, and DesHDAP1 and DesHDAP3 showed significant antibacterial activity. In this study, their DNA binding, permeabilization, and translocation abilities were assessed independently and compared to antibacterial activity to determine whether they share a mechanism with BF2. To investigate the importance of proline in determining the peptides' mechanisms of action, proline to alanine mutants of the novel peptides were generated. DesHDAP1, which shows significant similarities to BF2 in terms of secondary structure, translocates effectively across lipid vesicle and bacterial membranes, while the DesHDAP1 proline mutant shows reduced translocation abilities and antimicrobial potency. In contrast, both DesHDAP3 and its proline mutant translocate poorly, though the DesHDAP3 proline mutant is more potent. Our findings suggest that a proline hinge can promote membrane translocation in some peptides, but that the extent of its effect on permeabilization depends on the peptide's amphipathic properties. Our results also highlight the different antimicrobial mechanisms exhibited by histone-derived peptides and suggest that histones may serve as a source of novel antimicrobial peptides with varied properties.

  14. Ruthenium complexes as antimicrobial agents.

    PubMed

    Li, Fangfei; Collins, J Grant; Keene, F Richard

    2015-04-21

    One of the major advances in medical science has been the development of antimicrobials; however, a consequence of their widespread use has been the emergence of drug-resistant populations of microorganisms. There is clearly a need for the development of new antimicrobials--but more importantly, there is the need for the development of new classes of antimicrobials, rather than drugs based upon analogues of known scaffolds. Due to the success of the platinum anticancer agents, there has been considerable interest in the development of therapeutic agents based upon other transition metals--and in particular ruthenium(II/III) complexes, due to their well known interaction with DNA. There have been many studies of the anticancer properties and cellular localisation of a range of ruthenium complexes in eukaryotic cells over the last decade. However, only very recently has there been significant interest in their antimicrobial properties. This review highlights the types of ruthenium complexes that have exhibited significant antimicrobial activity and discusses the relationship between chemical structure and biological processing--including site(s) of intracellular accumulation--of the ruthenium complexes in both bacterial and eukaryotic cells.

  15. Antimicrobial resistance mechanisms among Campylobacter.

    PubMed

    Wieczorek, Kinga; Osek, Jacek

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

  16. Antimicrobial Resistance Mechanisms among Campylobacter

    PubMed Central

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  17. Antimicrobial implications of vitamin D

    PubMed Central

    Youssef, Dima A; Miller, Christopher WT; El-Abbassi, Adel M; Cutchins, Della C; Cutchins, Coleman; Grant, William B

    2011-01-01

    Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections. PMID:22259647

  18. Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice

    PubMed Central

    González-Sánchez, Carlos; Fraile, Juan-Carlos; Pérez-Turiel, Javier; Damm, Ellen; Schneider, Jochen G.; Zimmermann, Heiko; Schmitt, Daniel; Ihmig, Frank R.

    2016-01-01

    Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC) sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram). First experimental results are shown. PMID:27399713

  19. The nature and source of the head injuries sustained by restrained front-seat car occupants in frontal collisions.

    PubMed

    Thomas, P; Bradford, M

    1995-08-01

    The paper examines the types of head injury sustained by restrained front-seat car occupants in frontal collisions. Injuries are classified into soft tissue, diffuse and focal brain injuries and facial bone or skull fractures. Survivors seldom sustain focal injuries although these are common amongst fatalities. The contact sources within the car are described. Intruding structures and high crash severities are typically associated with high rates of the more severe injuries from steering wheel contact, although some are sustained with intrusion below 11 cm. Low-speed impact testing on nondeployed airbag-equipped wheels is suggested. Toughened glass windscreens are overrepresented amongst those sustaining injuries from glazing materials. Test procedures to reduce injuries from pillar contacts should take account of the dynamic effects of an intruding pillar. Contacts with objects outside the car caused higher rates of severe fractures and brain injury; however, the total numbers are greater from interior contacts.

  20. Effect of Increased Rear Row Occupancy on Injury to Seat Belt Restrained Children in Side Impact Crashes

    PubMed Central

    Maltese, Matthew R.; Chen, Irene G.; Arbogast, Kristy B.

    2005-01-01

    Previous work identified a similar risk of injury for children seated on the struck side and center rear in side impact crashes in passenger cars. In order to further explain this finding, we investigated the effect of sharing the rear row with other occupants on injury risk and delineated differences in injury patterns among the seat positions. These analyses, conducted from a large child specific crash surveillance system, included: children 4–15 years old, rear seated, seat belt restrained, in a passenger car, and in a side impact crash. Injury risk was compared among each rear seat position stratified by the presence of other occupants on the rear row. Occupants are at an increased risk of injury if they sit alone on their row as compared to sitting with other occupants. Patterns of injuries distinct to each seat position were delineated. PMID:16179151

  1. Restrained and external-emotional eating patterns in young overweight children-results of the Ulm Birth Cohort Study.

    PubMed

    Hirsch, Oliver; Kluckner, Viktoria J; Brandt, Stephanie; Moss, Anja; Weck, Melanie; Florath, Ines; Wabitsch, Martin; Hebebrand, Johannes; Schimmelmann, Benno G; Christiansen, Hanna

    2014-01-01

    Childhood obesity is one of the greatest public health challenges in Western countries. Abnormal eating behavior is thought to be a developmental trajectory to obesity. The Eating Pattern Inventory for Children (EPI-C) has not been used for children as young as eight years, and possible associations with body weight have not yet been established. Five hundred and twenty-one children of the Ulm Birth Cohort Study (UBCS; age eight) filled out the EPI-C and BMI was assessed. Adequacy of the scales was tested with confirmatory factor analysis and a MANOVA and cluster analysis established associations between eating patterns and BMI. The factor structure of the EPI-C was confirmed (GFI = .968) and abnormal eating behavior was associated with overweight (χ(2)(8) =79.29, p<.001). The EPI-C is a valid assessment tool in this young age group. Overweight children consciously restrain their eating.

  2. Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice.

    PubMed

    González-Sánchez, Carlos; Fraile, Juan-Carlos; Pérez-Turiel, Javier; Damm, Ellen; Schneider, Jochen G; Zimmermann, Heiko; Schmitt, Daniel; Ihmig, Frank R

    2016-07-07

    Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC) sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram). First experimental results are shown.

  3. Targeted Conformational Search with Map-Restrained Self-Guided Langevin Dynamics: Application to Flexible Fitting of Electron Microscopy Images

    PubMed Central

    Wu, Xiongwu; Subramaniam, Sriram; Case, David A.; Wu, Katherine W.; Brooks, Bernard R.

    2013-01-01

    We present a map-restrained self-guided Langevin dynamics (MapSGLD) simulation method for efficient targeted conformational search. The targeted conformational search represents simulations under restraints defined by experimental observations and/or by user specified structural requirements. Through map-restraints, this method provides an efficient way to maintain substructures and to set structure targets during conformational searching. With an enhanced conformational searching ability of self-guided Langevin dynamics, this approach is suitable for simulating large-scale conformational changes, such as the formation of macromolecular assemblies and transitions between different conformational states. Using several examples, we illustrate the application of this method in flexible fitting of atomic structures into density maps from cryo-electron microscopy. PMID:23876978

  4. Restraining forces in various designs of knee ankle orthoses: their placement and effect on the anatomical knee joint.

    PubMed

    Lehmann, J F; Warren, C G

    1976-09-01

    A biochemical evaluation was conducted on double upright knee ankle orthoses, which were instrumented with strain gauge transducers to determine the magnitudes of the restraining forces exerted on the leg. Measurements were made on six commonly used designs of orthoses worn by spinal cord injured persons ambulating with a swing-through gait. The measurements were used to determine distribution of forces on the limb as well as their effect on anatomical knee shear. Based on the experimental data, the following basic principles of optimal orthosis design were identified: The forces required to stabilize the knee should be minimized by applying the stabilizing force as close as possible to the knee center, and by maintaining the anatomical knee as straight as possible. When the major portion of the knee stabilizing force is applied below the knee, the shear on the anatomical knee structures is markedly reduced. Further, the stabilizing forces should be well distributed over tolerant areas.

  5. Solution structures of psoralen monoadducted and cross-linked DNA oligomers by NMR spectroscopy and restrained molecular dynamics

    SciTech Connect

    Spielmann, H.P.; Dwyer, T.J.; Hearst, J.E. |

    1995-10-10

    We have used two-dimensional {sup 1}H NMR spectroscopy to determine the solution structures of the 4,5{prime}, 8-trimethylpsoralen (HMT) furanside monoadducted (MAf) and the photoisomeric HMT interstrand cross-linked (XL) DNA oligonucleotide d(t{prime}-GCGTACGC-3{prime}){sub 2}. The determination of the structure was based on total relaxation matrix analysis of the NOESY cross-peak intensities using the program MARDIGRAS. Improved procedures to consider the experimental {open_quotes}noise{close_quotes} in NOESY spectra during these calculations have been employed. The NOE-derived distance restraints were applied in restrained molecular dynamics calculations. Twenty final structures each were generated for both the MAf and XL from both A-form and B-form dsDNA starting structures. 80 refs., 7 figs., 6 tabs.

  6. Nanoscale organization and dynamics of the siglec CD22 cooperate with the cytoskeleton in restraining BCR signalling.

    PubMed

    Gasparrini, Francesca; Feest, Christoph; Bruckbauer, Andreas; Mattila, Pieta K; Müller, Jennifer; Nitschke, Lars; Bray, Dennis; Batista, Facundo D

    2016-02-01

    Receptor organization and dynamics at the cell membrane are important factors of signal transduction regulation. Using super-resolution microscopy and single-particle tracking, we show how the negative coreceptor CD22 works with the cortical cytoskeleton in restraining BCR signalling. In naïve B cells, we found endogenous CD22 to be highly mobile and organized into nanodomains. The landscape of CD22 and its lateral diffusion were perturbed either in the absence of CD45 or when the CD22 lectin domain was mutated. To understand how a relatively low number of CD22 molecules can keep BCR signalling in check, we generated Brownian dynamic simulations and supported them with ex vivo experiments. This combined approach suggests that the inhibitory function of CD22 is influenced by its nanoscale organization and is ensured by its fast diffusion enabling a "global BCR surveillance" at the plasma membrane. © 2015 The Authors.

  7. An alternative discourse of productive aging: A self-restrained approach in older Chinese people in Hong Kong.

    PubMed

    Luo, Minxia; Chui, Ernest Wing-Tak

    2016-08-01

    While Western discourses regarding productive aging emphasize individuals' contributions to economic productivity, the Confucian cultural heritage of the Chinese community may provide an alternative perspective. This qualitative study explores interpretations of what constitutes productive aging, based on a series of in-depth interviews with older Chinese people in Hong Kong. It shows that some of these individuals adopted a passive and indirect interpretation of productive aging, distinct from that found in Western countries. The Confucianism-based, collectivist, normative order underpinning Hong Kong society disposed these older people to adopting a self-restrained attitude with the aim of avoiding becoming a burden to others, especially family members. Such a tendency toward self-restraint or avoidance also encompassed a compromise between ideals and reality, with the older people opting to compromise their expectations of the younger generation as a whole, their adult children in particular, in terms of respect and reciprocity. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Simulated annealing with restrained molecular dynamics using a flexible restraint potential: theory and evaluation with simulated NMR constraints.

    PubMed Central

    Bassolino-Klimas, D.; Tejero, R.; Krystek, S. R.; Metzler, W. J.; Montelione, G. T.; Bruccoleri, R. E.

    1996-01-01

    A new functional representation of NMR-derived distance constraints, the flexible restraint potential, has been implemented in the program CONGEN (Bruccoleri RE, Karplus M, 1987, Biopolymers 26:137-168) for molecular structure generation. In addition, flat-bottomed restraint potentials for representing dihedral angle and vicinal scalar coupling constraints have been introduced into CONGEN. An effective simulated annealing (SA) protocol that combines both weight annealing and temperature annealing is described. Calculations have been performed using ideal simulated NMR constraints, in order to evaluate the use of restrained molecular dynamics (MD) with these target functions as implemented in CONGEN. In this benchmark study, internuclear distance, dihedral angle, and vicinal coupling constant constraints were calculated from the energy-minimized X-ray crystal structure of the 46-amino acid polypeptide crambin (ICRN). Three-dimensional structures of crambin that satisfy these simulated NMR constraints were generated using restrained MD and SA. Polypeptide structures with extended backbone and side-chain conformations were used as starting conformations. Dynamical annealing calculations using extended starting conformations and assignments of initial velocities taken randomly from a Maxwellian distribution were found to adequately sample the conformational space consistent with the constraints. These calculations also show that loosened internuclear constraints can allow molecules to overcome local minima in the search for a global minimum with respect to both the NMR-derived constraints and conformational energy. This protocol and the modified version of the CONGEN program described here are shown to be reliable and robust, and are applicable generally for protein structure determination by dynamical simulated annealing using NMR data. PMID:8845749

  9. Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1

    PubMed Central

    Kang, Hui; Yan, Yufei; Jia, Peng; Yang, Kai; Guo, Changjun; Chen, Hao; Qi, Jin; Qian, Niandong; Xu, Xing; Wang, Fei; Li, Changwei; Guo, Lei; Deng, Lianfu

    2016-01-01

    As wear particles-induced osteolysis still remains the leading cause of early implant loosening in endoprosthetic surgery, and promotion of osteoclastogenesis by wear particles has been confirmed to be responsible for osteolysis. Therapeutic agents targeting osteoclasts formation are considered for the treatment of wear particles-induced osteolysis. In the present study, we demonstrated for the first time that desferrioxamine (DFO), a powerful iron chelator, could significantly alleviate osteolysis in an ultrahigh-molecular-weight polyethylene (UHMWPE) particles-induced mice calvaria osteolysis model. Furthermore, DFO attenuated calvaria osteolysis by restraining enhanced inflammatory osteoclastogenesis induced by UHMWPE particles. Consistent with the in vivo results, we found DFO was also able to inhibit osteoclastogenesis in a dose-dependent manner in vitro, as evidenced by reduction of osteoclasts formation and suppression of osteoclast specific genes expression. In addition, DFO dampened osteoclasts differentiation and formation at early stage but not at late stage. Mechanistically, the reduction of osteoclastogenesis by DFO was due to increased heme oxygenase-1 (HO-1) expression, as decreased osteoclasts formation induced by DFO was significantly restored after HO-1 was silenced by siRNA, while HO-1 agonist COPP treatment enhanced DFO-induced osteoclastogenesis inhibition. In addition, blocking of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway promoted DFO-induced HO-1 expression, implicating that p38 signaling pathway was involved in DFO-mediated HO-1 expression. Taken together, our results suggested that DFO inhibited UHMWPE particles-induced osteolysis by restraining inflammatory osteoclastogenesis through upregulation of HO-1 via p38MAPK pathway. Thus, DFO might be used as an innovative and safe therapeutic alternative for treating wear particles-induced aseptic loosening. PMID:27787522

  10. CHK2-BRCA1 tumor-suppressor axis restrains oncogenic Aurora-A kinase to ensure proper mitotic microtubule assembly.

    PubMed

    Ertych, Norman; Stolz, Ailine; Valerius, Oliver; Braus, Gerhard H; Bastians, Holger

    2016-02-16

    BRCA1 (breast cancer type 1 susceptibility protein) is a multifunctional tumor suppressor involved in DNA damage response, DNA repair, chromatin regulation, and mitotic chromosome segregation. Although the nuclear functions of BRCA1 have been investigated in detail, its role during mitosis is little understood. It is clear, however, that loss of BRCA1 in human cancer cells leads to chromosomal instability (CIN), which is defined as a perpetual gain or loss of whole chromosomes during mitosis. Moreover, our recent work has revealed that the mitotic function of BRCA1 depends on its phosphorylation by the tumor-suppressor kinase Chk2 (checkpoint kinase 2) and that this regulation is required to ensure normal microtubule plus end assembly rates within mitotic spindles. Intriguingly, loss of the positive regulation of BRCA1 leads to increased oncogenic Aurora-A activity, which acts as a mediator for abnormal mitotic microtubule assembly resulting in chromosome missegregation and CIN. However, how the CHK2-BRCA1 tumor suppressor axis restrains oncogenic Aurora-A during mitosis to ensure karyotype stability remained an open question. Here we uncover a dual molecular mechanism by which the CHK2-BRCA1 axis restrains oncogenic Aurora-A activity during mitosis and identify BRCA1 itself as a target for Aurora-A relevant for CIN. In fact, Chk2-mediated phosphorylation of BRCA1 is required to recruit the PP6C-SAPS3 phosphatase, which acts as a T-loop phosphatase inhibiting Aurora-A bound to BRCA1. Consequently, loss of CHK2 or PP6C-SAPS3 promotes Aurora-A activity associated with BRCA1 in mitosis. Aurora-A, in turn, then phosphorylates BRCA1 itself, thereby inhibiting the mitotic function of BRCA1 and promoting mitotic microtubule assembly, chromosome missegregation, and CIN.

  11. ACVIM consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance.

    PubMed

    Weese, J S; Giguère, S; Guardabassi, L; Morley, P S; Papich, M; Ricciuto, D R; Sykes, J E

    2015-01-01

    The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.

  12. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  13. Antimicrobial Properties of Titanium Nanoparticles

    NASA Astrophysics Data System (ADS)

    Erdural, B. K.; Yurum, A.; Bakir, U.; Karakas, G.

    In the present study, nanostructured titania particles were synthesized using hydrothermal processing and their photocatalytic antimicrobial activities were characterized. Sol-gel synthesized TiO2 samples were treated with a two step hydrothermal treatment. The first stage treatment was the alkaline treatment with 10 M of NaOH for 48 h at 130°C, followed with the second step which applied with distilled water for 48 h at 200°C. Scanning Electron Microscope (SEM) images showed that alkaline treatment yields lamellar structure particles from the sol-gel synthesized anatase. Further treatment of nanoplates with distilled water results in crystal growth and the formation of nano structured thorn like particles. The photocatalytic antimicrobial activities of samples were determined against Escherichia coli under solar irradiation for 4 h. It was observed that the samples treated under alkaline conditions have higher antimicrobial activity than the untreated samples.

  14. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  15. Antimicrobial resistance in staphylococci in small animals.

    PubMed

    Cain, Christine L

    2013-01-01

    Staphylococcal antimicrobial resistance presents an emerging challenge for both human and veterinary medical professionals. Infections associated with methicillin- and multidrug-resistant staphylococci are increasingly encountered by veterinarians and are frequently associated with empiric therapeutic failures and limited systemic antimicrobial options. This article addresses mechanisms of antimicrobial resistance in common staphylococcal pathogens and implications for clinical practice, including indications for culture and susceptibility testing, rational antimicrobial selection, and potential for zoonotic transmission. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Uses of antimicrobial genes from microbial genome

    DOEpatents

    Sorek, Rotem; Rubin, Edward M.

    2013-08-20

    We describe a method for mining microbial genomes to discover antimicrobial genes and proteins having broad spectrum of activity. Also described are antimicrobial genes and their expression products from various microbial genomes that were found using this method. The products of such genes can be used as antimicrobial agents or as tools for molecular biology.

  17. Antimicrobials for bacterial bioterrorism agents.

    PubMed

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future. © 2011 Future Medicine Ltd

  18. Antimicrobial therapy for skin infections.

    PubMed

    Hirschmann, Jan V

    2007-06-01

    The most common skin infections are caused by Staphylococcus aureus, group A streptococci (Streptococcus pyogenes), or the normal skin flora. An antistaphylococcal oral antibiotic is the preferred treatment for nonbullous and bullous impetigo, and a therapeutic agent that is effective against both S aureus and streptococci is appropriate for most cases of cellulitis. For furuncles, carbuncles, cutaneous abscesses, and inflamed epidermal cysts, the most important therapy is incision and drainage, and in most cases there is no need for antimicrobial therapy. Patients with venous ulcers and atopic eczema do not benefit from systemic antimicrobial therapy unless obvious infection is present, as indicated by clinical features such as fever, cellulitis, and lymphangitis.

  19. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

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

  20. Antimicrobial drugs for treating cholera.

    PubMed

    Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

    2014-06-19

    Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43.51 to -30.03, 19 trials, 1013 participants, moderate quality evidence). Antimicrobial therapy also

  1. Refinement of the solution structure of the ribonucleotide 5'r(GCAUGC)/sub 2/: combined use of nuclear magnetic resonance and restrained molecular dynamics

    SciTech Connect

    Happ, C.S.; Happ, E.; Nilges, M.; Gronenborn, A.M.; Clore, G.M.

    1988-03-08

    The solution structure of the self-complementary hexamer 5'r(GCAUGC)/sub 2/ is investigated by means of nuclear magnetic resonance spectroscopy and restrained molecular dynamics. The proton resonances are assigned in a sequential manner, and a set of 110 approximate interproton distance restraints are derived from the two-dimensional nuclear Overhauser enhancement spectra. These distances are used as the basis of a structure refinement by restrained molecular dynamics in which the experimental restraints are incorporated into the total energy function of the system in the form of effective potentials. Eight restrained molecular dynamics simulations are carried out, four starting from a structure with regular A-type geometry and four from one with regular B-type geometry. These results suggest that the restrained dynamics structures represent good approximations of the solution structure. The converged structures exhibit clear sequence-dependent variation in some of the helical parameters, in particular helix twist, roll, slide, and propellor twist. The variation in roll follows that predicted by Dickerson, whereas those for helix twist and propellor twist follow the opposite trend to the predicted one.

  2. Determination of the conformation of d(GGAAATTTCC) sub 2 in solution by use of sup 1 H NMR and restrained molecular dynamics

    SciTech Connect

    Katahira, Masato; Sugeta, Hiromu; Kyogoku, Yoshimasa; Fujii, S. )

    1990-08-07

    The conformation of the putative bent DNA d(GGAAATTTCC){sub 2} in solution was studied by use of {sup 1}H NMR and restrained molecular dynamics. Most of the resonances were assigned sequentially. A total of 182 interproton distance restraints were determined from two-dimensional nuclear Overhauser effect spectra with short mixing times. Torsion angle restraints for each sugar moiety were determined by qualitative analysis of a two-dimensional correlated spectrum. Restrained molecular dynamics was carried out with the interproton distances and torsion angles incorporated into the total energy function of the system in the form of effective potential terms. On the other hand, the conformations obtained by use of molecular dynamics without experimental restraints or restrained energy minimization depended heavily on the initial conformations, and convergence to a similar conformation was not attained. The conformation obtained by use of restrained molecular dynamics exhibits a few remarkable features. The second G residue takes on the BII conformation rather than the standard BI conformation. There is discontinuity of the sugar puckering between the eight T and ninth C. The minor groove of the oligo(dA) tract is rather compressed. As a result, d(GGAAATTTCC){sub 2} is bent.

  3. Critical Compressive Stress for Flat Rectangular Plates Supported Along all Edges and Elastically Restrained Against Rotation Along the Unloaded Edges, Special Report 189

    NASA Technical Reports Server (NTRS)

    Lundquist, Eugene E.; Stowell, Eldbridge Z.

    1941-01-01

    A chart is presented for the values of the coefficient in the formula for the critical compressive stress at which buckling may be expected to occur in flat rectangular plates supported along all edges and, in addition, elastically restrained against rotation along the unloaded edges. The mathematical derivations of the formulas required in the construction of the chart are given.

  4. Endotoxin reduces muscle protein synthesis and restrains translation initiation by decreasing eIF4G phosphorylation in neonatal and young pigs

    USDA-ARS?s Scientific Manuscript database

    Endotoxin (LPS) reduces muscle protein synthesis by restraining translation in the presence of fed levels of insulin and amino acids. "In vivo" effects of LPS on translation initiation in muscle during basal fasting insulin and amino acid conditions have not been determined in neonates, whose muscle...

  5. Does self-affirmation following ego depletion moderate restrained eaters' explicit preferences for, and implicit associations with, high-calorie foods?

    PubMed

    Storr, Scarlett Marie; Sparks, Paul

    2016-07-01

    The difficulty for chronic dieters (i.e. restrained eaters) in regulating their food intake is a conflict between two apparently incompatible goals: eating enjoyment and weight control. The latter goal consistently relies on the deployment of cognitive resources, and very often on a significant amount of self-control. This study investigated whether self-affirmation might counteract the effect of ego depletion on restrained eaters' motivation to consume high-calorie foods. Participants (N = 183) were assigned to one of four conditions in a 2 × 2 (Ego depletion × Self-Affirmation) experimental design and were subsequently exposed to images of high- and low-calorie foods. Participants completed tasks assessing their implicit and explicit preferences for high vs. low-calorie foods, along with a measure of the perceived self-control required to resist foods. Results indicated that, following ego depletion, self-affirmation facilitated restrained eaters' perceptions of self-control and led to lower explicit preferences for high-calorie foods. This pattern was not apparent for implicit preferences. Self-affirmation interventions may be capable of restoring self-control resources among restrained eaters. Pointers for future research and practical applications are discussed.

  6. Antimicrobial food packaging in meat industry.

    PubMed

    Quintavalla, Stefania; Vicini, Loredana

    2002-11-01

    Antimicrobial packaging, an active packaging concept, can be considered an extremely challenging technology that could have a significant impact on shelf-life extension and food safety of meat and meat products. Use of antimicrobial substances can control the microbial population and target specific microorganisms to provide higher safety and quality products. Many classes of antimicrobial compounds have been evaluated in film structures, both synthetic polymers and edible films: organic acids and their salts, enzymes, bacteriocins, and miscellaneous compounds such as triclosan, silver zeolites, and fungicides. The characteristics of some antimicrobial packaging systems are reviewed in this article. The regulatory status of antimicrobial packaging in EU is also examined.

  7. Antimicrobial Activity and Resistance: Influencing Factors

    PubMed Central

    Li, Jun; Xie, Shuyu; Ahmed, Saeed; Wang, Funan; Gu, Yufeng; Zhang, Chaonan; Chai, Ximan; Wu, Yalan; Cai, Jinxia; Cheng, Guyue

    2017-01-01

    Rational use of antibiotic is the key approach to improve the antibiotic performance and tackling of the antimicrobial resistance. The efficacy of antimicrobials are influenced by many factors: (1) bacterial status (susceptibility and resistance, tolerance, persistence, biofilm) and inoculum size; (2) antimicrobial concentrations [mutant selection window (MSW) and sub-inhibitory concentration]; (3) host factors (serum effect and impact on gut micro-biota). Additional understandings regarding the linkage between antimicrobial usages, bacterial status and host response offers us new insights and encourage the struggle for the designing of antimicrobial treatment regimens that reaching better clinical outcome and minimizing the emergence of resistance at the same time. PMID:28659799

  8. Antimicrobial susceptibilities of Erysipelothrix rhusiopathiae.

    PubMed Central

    Venditti, M; Gelfusa, V; Tarasi, A; Brandimarte, C; Serra, P

    1990-01-01

    The in vitro susceptibilities of 10 isolates of Erysipelothrix rhusiopathiae to 16 antimicrobial agents were determined. Penicillin and imipenem were the most active agents, followed by piperacillin, cefotaxime, ciprofloxacin, pefloxacin, and clindamycin. Some resistance was observed with erythromycin, tetracycline, and chloramphenicol. Activity was poor or absent with vancomycin, teicoplanin, daptomycin, trimethoprim-sulfamethoxazole, gentamicin, and netilmicin. PMID:2291674

  9. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  10. Helical Antimicrobial Sulfono- {gamma} -AApeptides

    SciTech Connect

    Li, Yaqiong; Wu, Haifan; Teng, Peng; Bai, Ge; Lin, Xiaoyang; Zuo, Xiaobing; Cao, Chuanhai; Cai, Jianfeng

    2015-06-11

    Host-defense peptides (HDPs) such as magainin 2 have emerged as potential therapeutic agents combating antibiotic resistance. Inspired by their structures and mechanism of action, herein we report the fi rst example of antimicrobial helical sulfono- γ - AApeptide foldamers. The lead molecule displays broad-spectrum and potent antimicrobial activity against multi-drug-resistant Gram- positive and Gram-negative bacterial pathogens. Time-kill studies and fl uorescence microscopy suggest that sulfono- γ -AApeptides eradicate bacteria by taking a mode of action analogous to that of HDPs. Clear structure - function relationships exist in the studied sequences. Longer sequences, presumably adopting more-de fi ned helical structures, are more potent than shorter ones. Interestingly, the sequence with less helical propensity in solution could be more selective than the stronger helix-forming sequences. Moreover, this class of antimicrobial agents are resistant to proteolytic degradation. These results may lead to the development of a new class of antimicrobial foldamers combating emerging antibiotic-resistant pathogens.

  11. Molecular Detection of Antimicrobial Resistance

    PubMed Central

    Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

    2001-01-01

    The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

  12. Antimicrobial Polymers with Metal Nanoparticles

    PubMed Central

    Palza, Humberto

    2015-01-01

    Metals, such as copper and silver, can be extremely toxic to bacteria at exceptionally low concentrations. Because of this biocidal activity, metals have been widely used as antimicrobial agents in a multitude of applications related with agriculture, healthcare, and the industry in general. Unlike other antimicrobial agents, metals are stable under conditions currently found in the industry allowing their use as additives. Today these metal based additives are found as: particles, ions absorbed/exchanged in different carriers, salts, hybrid structures, etc. One recent route to further extend the antimicrobial applications of these metals is by their incorporation as nanoparticles into polymer matrices. These polymer/metal nanocomposites can be prepared by several routes such as in situ synthesis of the nanoparticle within a hydrogel or direct addition of the metal nanofiller into a thermoplastic matrix. The objective of the present review is to show examples of polymer/metal composites designed to have antimicrobial activities, with a special focus on copper and silver metal nanoparticles and their mechanisms. PMID:25607734

  13. Antimicrobial resistance: a global response.

    PubMed Central

    Smith, Richard D.; Coast, Joanna

    2002-01-01

    Resistance to antimicrobial therapies reduces the effectiveness of these drugs, leading to increased morbidity, mortality, and health care expenditure. Because globalization increases the vulnerability of any country to diseases occurring in other countries, resistance presents a major threat to global public health, and no country acting on its own can adequately protect the health of its population against it. International collective action is therefore essential. Nevertheless, responsibility for health remains predominantly national. Consequently, there is a potentially significant disparity between the problems and solutions related to antimicrobial resistance and the institutions and mechanisms that are available to deal with them. This paper considers the capacity of national and international institutions and mechanisms to generate a collective response to antimicrobial resistance. Strategies for containing resistance are outlined, with particular reference to globally coordinated activities of countries. The adequacy of national and international responses to resistance is assessed, and the actions that international bodies could take to solve difficulties associated with present responses are highlighted. Approaches are suggested for securing international collective action for the containment of antimicrobial resistance. PMID:11953791

  14. Antimicrobial polymers with metal nanoparticles.

    PubMed

    Palza, Humberto

    2015-01-19

    Metals, such as copper and silver, can be extremely toxic to bacteria at exceptionally low concentrations. Because of this biocidal activity, metals have been widely used as antimicrobial agents in a multitude of applications related with agriculture, healthcare, and the industry in general. Unlike other antimicrobial agents, metals are stable under conditions currently found in the industry allowing their use as additives. Today these metal based additives are found as: particles, ions absorbed/exchanged in different carriers, salts, hybrid structures, etc. One recent route to further extend the antimicrobial applications of these metals is by their incorporation as nanoparticles into polymer matrices. These polymer/metal nanocomposites can be prepared by several routes such as in situ synthesis of the nanoparticle within a hydrogel or direct addition of the metal nanofiller into a thermoplastic matrix. The objective of the present review is to show examples of polymer/metal composites designed to have antimicrobial activities, with a special focus on copper and silver metal nanoparticles and their mechanisms.

  15. Antimicrobial activity of Securidaca longipedunculata.

    PubMed

    Ajali, U; Chukwurah, B K C

    2004-11-01

    The folk herbal uses of Securidaca longipedunculata in the treatment of diarrhea, boils, gonorrhea, and cough prompted phytochemical analyses and antimicrobial activity screening of extracts of the root. Some flavonoids isolated showed activity against many micro-organisms. These flavonoids were isolated using chromatographic methods.

  16. An Antimicrobial Susceptibility Management System

    PubMed Central

    Farmer, James J.; O'Donnell, Edward D.

    1981-01-01

    A computerized system is described which is used to store, manipulate and retrieve antimicrobial susceptibility data in the clinical microbiology lab. Features include facilitated input of susceptibility data, rapid generation of reports, realtime access to data, and enhanced retrieval of information for Infection Control.

  17. ANTIMICROBIAL EFFECT OF INTRACANAL SUBSTANCES

    PubMed Central

    Carreira, Cláudia de Moura; dos Santos, Silvana Soléo Ferreira; Jorge, Antônio Olavo Cardoso; Lage-Marques, José Luiz

    2007-01-01

    In some situations, endodontic infections do not respond to therapeutic protocol. In these cases, it is suggested the administration of an alternative intracanal medication that presents a wide spectrum of action and has an in-depth effect on the root canal system. The purpose of this study was to assess the antimicrobial action of ciprofloxacin, metronidazole and polyethylene glycol and natrosol vehicles with different associations and concentrations. The minimum inhibitory concentration (MIC) was determined by using the agar dilution method. The culture media (Müller-Hinton agar) were prepared containing antimicrobial agents at multiple two-fold dilutions of 0.25 to 16 µg/mL, and with the vehicles at the concentrations of 50, 45, 40, 35, 30 and 25%. Twenty-three microbial strains were selected for the study. Metronidazole was not capable of eliminating any of the tested microorganisms. The association of ciprofloxacin with metronidazole resulted in a reduction of the MIC. The vehicle polyethylene glycol inhibited the growth of 100% of the tested strains, while natrosol inhibited 18% of the strains. Ciprofloxacin formulations with polyethylene glycol presented better effects than those of formulations to which metronidazole was added. It was possible to conclude that ciprofloxacin presented antimicrobial action against all tested bacterial strains, and its association with metronidazole was synergic. The vehicle polyethylene glycol showed antimicrobial effect and the ciprofloxacin/polyethylene glycol association was the most effective combination for reducing the tested bacteria and yeasts. PMID:19089178

  18. Antimicrobial activity of Bryum argenteum.

    PubMed

    Sabovljevic, Aneta; Sokovic, Marina; Sabovljevic, Marko; Grubisic, Dragoljub

    2006-02-01

    The antimicrobial activity of Bryum argenteum ethanol extracts was evaluated by microdilution method against four bacterial (Escherichia coli, Bacillus subtilis, Micrococcus luteus and Staphilococcus aureus) and four fungal species (Aspergillus niger, Penicillium ochrochloron, Candida albicans and Trichophyton mentagrophyes). All the investigated ethanol extracts have been proved to be active against all bacteria and fungi tested.

  19. Combating Antimicrobial Resistance in Foodborne Microorganisms.

    PubMed

    Lai, Edward P C; Iqbal, Zafar; Avis, Tyler J

    2016-02-01

    This review addresses an important public health hazard affecting food safety. Antimicrobial agents are used in foods to reduce or eliminate microorganisms that cause disease. Many traditional organic compounds, novel synthetic organic agents, natural products, peptides, and proteins have been extensively studied for their effectiveness as antimicrobial agents against foodborne Campylobacter spp., Escherichia coli, Listeria spp. and Salmonella. However, antimicrobial resistance can develop in microorganisms, enhancing their ability to withstand the inhibiting or killing action of antimicrobial agents. Knowledge gaps still exist with regard to the actual chemical and microbiological mechanisms that must be identified to facilitate the search for new antimicrobial agents. Technical implementation of antimicrobial active packing films and coatings against target microorganisms must also be improved for extended product shelf life. Recent advances in antimicrobial susceptibility testing can provide researchers with new momentum to pursue their quest for a resistance panacea.

  20. Access to effective antimicrobials: a worldwide challenge.

    PubMed

    Laxminarayan, Ramanan; Matsoso, Precious; Pant, Suraj; Brower, Charles; Røttingen, John-Arne; Klugman, Keith; Davies, Sally

    2016-01-09

    Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.

  1. Structural perspectives on antimicrobial chemokines

    PubMed Central

    Nguyen, Leonard T.; Vogel, Hans J.

    2012-01-01

    Chemokines are best known as signaling proteins in the immune system. Recently however, a large number of human chemokines have been shown to exert direct antimicrobial activity. This moonlighting activity appears to be related to the net high positive charge of these immune signaling proteins. Chemokines can be divided into distinct structural elements and some of these have been studied as isolated peptide fragments that can have their own antimicrobial activity. Such peptides often encompass the α-helical region found at the C-terminal end of the parent chemokines, which, similar to other antimicrobial peptides, adopt a well-defined membrane-bound amphipathic structure. Because of their relatively small size, intact chemokines can be studied effectively by NMR spectroscopy to examine their structures in solution. In addition, NMR relaxation experiments of intact chemokines can provide detailed information about the intrinsic dynamic behavior; such analyses have helped for example to understand the activity of TC-1, an antimicrobial variant of CXCL7/NAP-2. With chemokine dimerization and oligomerization influencing their functional properties, the use of NMR diffusion experiments can provide information about monomer-dimer equilibria in solution. Furthermore, NMR chemical shift perturbation experiments can be used to map out the interface between self-associating subunits. Moreover, the unusual case of XCL1/lymphotactin presents a chemokine that can interconvert between two distinct folds in solution, both of which have been elucidated. Finally, recent advances have allowed for the determination of the structures of chemokines in complex with glycosaminoglycans, a process that could interfere with their antimicrobial activity. Taken together, these studies highlight several different structural facets that contribute to the way in which chemokines exert their direct microbicidal actions. PMID:23293636

  2. Temporin-SHf, a New Type of Phe-rich and Hydrophobic Ultrashort Antimicrobial Peptide*

    PubMed Central

    Abbassi, Feten; Lequin, Olivier; Piesse, Christophe; Goasdoué, Nicole; Foulon, Thierry; Nicolas, Pierre; Ladram, Ali

    2010-01-01

    Because issues of cost and bioavailability have hampered the development of gene-encoded antimicrobial peptides to combat infectious diseases, short linear peptides with high microbial cell selectivity have been recently considered as antibiotic substitutes. A new type of short antimicrobial peptide, designated temporin-SHf, was isolated and cloned from the skin of the frog Pelophylax saharica. Temporin-SHf has a highly hydrophobic sequence (FFFLSRIFa) and possesses the highest percentage of Phe residues of any known peptide or protein. Moreover, it is the smallest natural linear antimicrobial peptide found to date, with only eight residues. Despite its small size and hydrophobicity, temporin-SHf has broad-spectrum microbicidal activity against Gram-positive and Gram-negative bacteria and yeasts, with no hemolytic activity. CD and NMR spectroscopy combined with restrained molecular dynamics calculations showed that the peptide adopts a well defined non-amphipathic α-helical structure from residue 3 to 8, when bound to zwitterionic dodecyl phosphocholine or anionic SDS micelles. Relaxation enhancement caused by paramagnetic probes showed that the peptide adopts nearly parallel orientations to the micelle surface and that the helical structure is stabilized by a compact hydrophobic core on one face that penetrates into the micelle interior. Differential scanning calorimetry on multilamellar vesicles combined with membrane permeabilization assays on bacterial cells indicated that temporin-SHf disrupts the acyl chain packing of anionic lipid bilayers, thereby triggering local cracks and microbial membrane disintegration through a detergent-like effect probably via the carpet mechanism. The short length, compositional simplicity, and broad-spectrum activity of temporin-SHf make it an attractive candidate to develop new antibiotic agents. PMID:20308076

  3. Antimicrobial activity of Nigerian medicinal plants

    PubMed Central

    Anyanwu, Madubuike Umunna; Okoye, Rosemary Chinazam

    2017-01-01

    Antimicrobial resistance (AMR) is currently one of the major threats facing mankind. The emergence and rapid spread of multi- and pan-drug-resistant organisms (such as vancomycin-, methicillin-, extended-spectrum β-lactam-, carbapenem- and colistin-resistant organisms) has put the world in a dilemma. The health and economic burden associated with AMR on a global scale are dreadful. Available antimicrobials have been misused and are almost ineffective with some of these drugs associated with dangerous side effects in some individuals. Development of new, effective, and safe antimicrobials is one of the ways by which AMR burden can be reduced. The rate at which microorganisms develop AMR mechanisms outpaces the rate at which new antimicrobials are being developed. Medicinal plants are potential sources of new antimicrobial molecules. There is renewed interest in antimicrobial activities of phytochemicals. Nigeria boasts of a huge heritage of medicinal plants and there is avalanche of researches that have been undertaken to screen antimicrobial activities of these plants. Scientific compilation of these studies could provide useful information on the antimicrobial properties of the plants. This information can be useful in the development of new antimicrobial drugs. This paper reviews antimicrobial researches that have been undertaken on Nigerian medicinal plants. PMID:28512606

  4. Antimicrobial Stewardship and Urinary Tract Infections

    PubMed Central

    Abbo, Lilian M.; Hooton, Thomas M.

    2014-01-01

    Urinary tract infections are the most common bacterial infections encountered in ambulatory and long-term care settings in the United States. Urine samples are the largest single category of specimens received by most microbiology laboratories and many such cultures are collected from patients who have no or questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed inappropriately in such patients. Antimicrobial use, whether appropriate or inappropriate, is associated with the selection for antimicrobial-resistant organisms colonizing or infecting the urinary tract. Infections caused by antimicrobial-resistant organisms are associated with higher rates of treatment failures, prolonged hospitalizations, increased costs and mortality. Antimicrobial stewardship consists of avoidance of antimicrobials when appropriate and, when antimicrobials are indicated, use of strategies to optimize the selection, dosing, route of administration, duration and timing of antimicrobial therapy to maximize clinical cure while limiting the unintended consequences of antimicrobial use, including toxicity and selection of resistant microorganisms. This article reviews successful antimicrobial stewardship strategies in the diagnosis and treatment of urinary tract infections. PMID:27025743

  5. Three-dimensional structure of phoratoxin in solution: combined use of nuclear magnetic resonance, distance geometry, and restrained molecular dynamics

    SciTech Connect

    Clore, G.M.; Sukumaran, D.K.; Nilges, M.; Gronenborn, A.M.

    1987-03-24

    The solution conformation of phoratoxin, a 46-residue plant protein, has been investigated by /sup 1/H nuclear magnetic resonance (NMR) spectroscopy. The spectrum is assigned in a sequential manner by a combination of two-dimensional NMR techniques to demonstrate through-bond and through-space (< 5 A) connectivities. A set of 331 approximate interproton distance restraints and six phi backbone torsion angle restraints is derived from the two-dimensional nuclear Overhauser enhancement and double quantum filtered homonuclear correlated spectra, respectively. These restraints are used as the basis of a structure determination with a metric matrix distance geometry algorithm. A total of eight structures are computed in this manner and subjected to refinement by restrained molecular dynamics in which the experimental restraints are incorporated into the total energy function of the system in the form of square well effective potentials. The overall shape of phoratoxin is that of the capital letter L, similar to that of crambin and ..cap alpha../sub 1/-purothionin, with the longer arm comprising two ..cap alpha..-helices at an angle of approx. 140/sup 0/ to each other and the shorter arm a mini-antiparallel ..beta..-sheet and a loop made up of two turns and a strand.

  6. Mnin restraining stepover - evidence of significant Cretaceous-Cenozoic dextral strike-slip faulting along the Teisseyre-Tornquist Zone?

    NASA Astrophysics Data System (ADS)

    Konon, Andrzej; Ostrowski, Szymon; Rybak-Ostrowska, Barbara; Ludwiniak, Mirosław; Śmigielski, Michał; Wyglądała, Michał; Uroda, Joanna; Kowalczyk, Sebastian; Mieszkowski, Radosław; Kłopotowska, Agnieszka

    2016-09-01

    A newly recognized Mnin restraining stepover is identified in the Permo-Mesozoic cover of the western part of the Late Palaeozoic Holy Cross Mountains Fold Belt (Poland), within a fault pattern consisting of dextral strike-slip faults. The formation of a large contractional structure at the Late Cretaceous - Cenozoic transition displays the significant role of strike-slip faulting along the western border of the Teisseyre-Tornquist Zone, in the foreland of the Polish part of the Carpathian Orogen. Theoretical relationships between the maximum fault offsets/ mean step length, as well as between the maximum fault offsets/mean step width allowed the estimation of the values of possible offsets along the Snochowice and Mieczyn faults forming the Mnin stepover. The estimated values suggest displacements of as much as several tens of kilometres. The observed offset along the Tokarnia Fault and theoretical calculations suggest that the strike-slip faults west of the Late Palaeozoic Holy Cross Mountains Fold Belt belong to a large strike-slip fault system. We postulate that the observed significant refraction of the faults forming the anastomosing fault pattern is related also to the interaction of the NW-SE-striking faults formed along the western border of the Teisseyre- Tornquist Zone and the reactivated WNW-ESE-striking faults belonging to the fault systems of the northern margin of the Tethys Ocean.

  7. Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

    SciTech Connect

    Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

    2005-03-03

    Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

  8. IL-33 regulates the IgA-microbiota axis to restrain IL-1α–dependent colitis and tumorigenesis

    PubMed Central

    Malik, Ankit; Zhu, Qifan; Karki, Rajendra; Guy, Clifford S.

    2016-01-01

    Inflammatory bowel diseases (IBD) affect over 5 million individuals in the industrialized world, with an increasing incidence rate worldwide. IBD also predisposes affected individuals to development of colorectal cancer, which is a leading cause of cancer-related deaths in adults. Mutations in genes encoding molecules in the IL-33 signaling pathway are associated with colitis and colitis-associated cancer (CAC), but how IL-33 modulates gut homeostasis is unclear. Here, we have shown that Il33-deficient mice are highly susceptible to colitis and CAC. Mechanistically, we observed that IL-33 promoted IgA production from B cells, which is important for maintaining microbial homeostasis in the intestine. Il33-deficient mice developed a dysbiotic microbiota that was characterized by increased levels of mucolytic and colitogenic bacteria. In response to chemically induced colitis, this microbial landscape promoted the release of IL-1α, which acted as a critical driver of colitis and CAC. Consequently, reconstitution of symbiotic microbiota or IL-1α ablation markedly ameliorated colitis susceptibility in Il33-deficient animals. Our results demonstrate that IL-33 promotes IgA production to maintain gut microbial homoeostasis and restrain IL-1α–dependent colitis and CAC. This study therefore highlights modulation of IL-33, IgA, IL-1α, and the microbiota as a potential therapeutic approach in the treatment of IBD and CAC. PMID:27775548

  9. Manganese-containing cellulose nanocomposites: the restrain effect of cellulose treated with NaOH/urea aqueous solutions.

    PubMed

    Ma, Ming-Guo; Deng, Fu; Yao, Ke

    2014-10-13

    In this article, the manganese-containing cellulose nanocomposites were obtained using microcrystalline cellulose and Mn(CH3COO)2 · 4H2O in the NaOH/urea aqueous solutions by a efficient microwave-assisted method. The effects of the heating time and Mn(CH3COO)2 · 4H2O concentration on the cellulose nanocomposites were investigated. It was found that the microcrystalline cellulose pretreated with NaOH/urea aqueous solutions played an important role in the phase, shape, and thermal stability of manganese-containing cellulose nanocomposites. Well-crystalline phases of manganese oxides were not observed in the manganese-containing cellulose nanocomposites. Furthermore, well-crystalline phases of manganese oxides were not also observed by thermal treatment of the manganese-containing cellulose nanocomposites at 600 °C for 3h. These results could be attributed to the restrain effect of cellulose treated with NaOH/urea aqueous solutions. It was supposed the possible mechanism during the phase transformation of cellulose nanocomposites.

  10. Restrained Proton Indicator in Combined Quantum-Mechanics/Molecular-Mechanics Dynamics Simulations of Proton Transfer through a Carbon Nanotube.

    PubMed

    Duster, Adam W; Lin, Hai

    2017-09-14

    Recently, a collective variable "proton indicator" was purposed for tracking an excess proton solvated in bulk water in molecular dynamics simulations. In this work, we demonstrate the feasibility of utilizing the position of this proton indicator as a reaction coordinate to model an excess proton migrating through a hydrophobic carbon nanotube in combined quantum-mechanics/molecular-mechanics simulations. Our results indicate that applying a harmonic restraint to the proton indicator in the bulk solvent near the nanotube pore entrance leads to the recruitment of water molecules into the pore. This is consistent with an earlier study that employed a multistate empirical valence bond potential and a different representation (center of excess charge) of the proton. We attribute this water recruitment to the delocalized nature of the solvated proton, which prefers to be in high-dielectric bulk solvent. While water recruitment into the pore is considered an artifact in the present simulations (because of the artificially imposed restraint on the proton), if the proton were naturally restrained, it could assist in building water wires prior to proton transfer through the pore. The potential of mean force for a proton translocation through the water-filled pore was computed by umbrella sampling, where the bias potentials were applied to the proton indicator. The free energy curve and barrier heights agree reasonably with those in the literature. The results suggest that the proton indicator can be used as a reaction coordinate in simulations of proton transport in confined environments.

  11. Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1.

    PubMed

    Ben-David, Moshe; Sussman, Joel L; Maxwell, Christopher I; Szeler, Klaudia; Kamerlin, Shina C L; Tawfik, Dan S

    2015-03-27

    Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, combined with empirical valence bond simulations, reveal a network of hydrogen bonds that connect HDL binding residues with Asn168--a key catalytic residue residing >15Å from the HDL contacting interface. This network ensures precise alignment of N168, which, in turn, ligates PON1's catalytic calcium and aligns the lactone substrate for catalysis. HDL binding restrains the overall motion of the active site and particularly of N168, thus reducing the catalytic activation energy barrier. We demonstrate herein that disturbance of this network, even at its most far-reaching periphery, undermines PON1's activity. Membrane binding thus immobilizes long-range interactions via second- and third-shell residues that reduce the active site's floppiness and pre-organize the catalytic residues. Although this network is critical for efficient catalysis, as demonstrated here, unraveling these long-rage interaction networks is challenging, let alone their implementation in artificial enzyme design. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Proteins in the Nutrient-Sensing and DNA Damage Checkpoint Pathways Cooperate to Restrain Mitotic Progression following DNA Damage

    PubMed Central

    Searle, Jennifer S.; Wood, Matthew D.; Kaur, Mandeep; Tobin, David V.; Sanchez, Yolanda

    2011-01-01

    Checkpoint pathways regulate genomic integrity in part by blocking anaphase until all chromosomes have been completely replicated, repaired, and correctly aligned on the spindle. In Saccharomyces cerevisiae, DNA damage and mono-oriented or unattached kinetochores trigger checkpoint pathways that bifurcate to regulate both the metaphase to anaphase transition and mitotic exit. The sensor-associated kinase, Mec1, phosphorylates two downstream kinases, Chk1 and Rad53. Activation of Chk1 and Rad53 prevents anaphase and causes inhibition of the mitotic exit network. We have previously shown that the PKA pathway plays a role in blocking securin and Clb2 destruction following DNA damage. Here we show that the Mec1 DNA damage checkpoint regulates phosphorylation of the regulatory (R) subunit of PKA following DNA damage and that the phosphorylated R subunit has a role in restraining mitosis following DNA damage. In addition we found that proteins known to regulate PKA in response to nutrients and stress either by phosphorylation of the R subunit or regulating levels of cAMP are required for the role of PKA in the DNA damage checkpoint. Our data indicate that there is cross-talk between the DNA damage checkpoint and the proteins that integrate nutrient and stress signals to regulate PKA. PMID:21779180

  13. Rear seat occupant safety: kinematics and injury of PMHS restrained by a standard 3-point belt in frontal crashes.

    PubMed

    Michaelson, Jarett; Forman, Jason; Kent, Richard; Kuppa, Shashi

    2008-11-01

    Very little experimental research has focused on the kinematics, dynamics, and injuries of rear-seated occupants. This study seeks to develop a baseline response for rear-seated post mortem human surrogates (PMHS) in frontal crashes. Three PMHS sled tests were performed in a sled buck designed to represent the interior rear-seat compartment of a contemporary mid-sized sedan. All occupants were positioned in the right-rear passenger seat and subjected to simulated frontal crashes with an impact speed of 48 km/h. The subjects were restrained by a standard, rear seat, 3-point seat belt. The response of each subject was evaluated in terms of whole-body kinematics, dynamics, and injury. All the PMHS experienced excessive forward translation of the pelvis resulting in a backward rotation of the torso at the time of maximum forward excursion. The three subjects experienced maximum normalized chest deflections of 30%, 45%, and 30%, respectively, and maximum 3 ms clip resultant chest accelerations of 50, 42, and 52 g, respectively. Additionally, each PMHS received at least 13 rib fractures (maximum of 29 fractures), and flexion-tension induced neck injuries initiating in the lower cervical spine (C4-T1). The neck trauma ranged from ligament damage (AIS 1) to complete cervical spine transection (AIS 5).

  14. REV1 restrains DNA polymerase zeta to ensure frame fidelity during translesion synthesis of UV photoproducts in vivo.

    PubMed

    Szüts, Dávid; Marcus, Adam P; Himoto, Masayuki; Iwai, Shigenori; Sale, Julian E

    2008-12-01

    Exposure to ultraviolet light induces a number of forms of damage in DNA, of which (6-4) photoproducts present the most formidable challenge to DNA replication. No single DNA polymerase has been shown to bypass these lesions efficiently in vitro suggesting that the coordinate use of a number of different enzymes is required in vivo. To further understand the mechanisms and control of lesion bypass in vivo, we have devised a plasmid-based system to study the replication of site-specific T-T(6-4) photoproducts in chicken DT40 cells. We show that DNA polymerase zeta is absolutely required for translesion synthesis (TLS) of this lesion, while loss of DNA polymerase eta has no detectable effect. We also show that either the polymerase-binding domain of REV1 or ubiquitinated PCNA is required for the recruitment of Polzeta as the catalytic TLS polymerase. Finally, we demonstrate a previously unappreciated role for REV1 in ensuring bypass synthesis remains in frame with the template. Our data therefore suggest that REV1 not only helps to coordinate the delivery of DNA polymerase zeta to a stalled primer terminus but also restrains its activity to ensure that nucleotides are incorporated in register with the template strand.

  15. Biofilm Formation Restrained by Subinhibitory Concentrations of Tigecyclin in Acinetobacter baumannii Is Associated with Downregulation of Efflux Pumps.

    PubMed

    Chen, Huale; Cao, Jianming; Zhou, Cui; Liu, Haiyang; Zhang, Xiaoxiao; Zhou, Tieli

    2017-01-01

    Tigecycline, one of the few therapeutic options against multidrug-resistant Acinetobacter baumannii, reaches subinhibitory serum concentrations only with cautious clinical dosing and pharmacokinetics. Subinhibitory concentrations of tigecycline might induce an A. baumannii biofilm. Biofilm formation was assessed via the crystal violet staining method. We further analyzed the main biofilm components with NaIO4, proteinase K, and DNase. Real-time RT-PCR was applied for quantitative detection of biofilm potential-associated genes. In this study, A. baumannii proved to be a strong biofilm producer, and we found that proteins and extracellular DNA are crucial components of the A. baumannii biofilm. Quantitative real-time RT-PCR revealed positive correlations between biofilm formation restrained by subinhibitory concentrations of tigecycline and the expression of biofilm potential-associated genes, especially the AdeFGH efflux pump gene. Our results suggest that downregulation of efflux pumps, especially the AdeFGH efflux pump, is probably responsible for the decline in biofilm formation in A. baumannii treated with subinhibitory concentrations of tigecyclin. © 2016 S. Karger AG, Basel.

  16. Use of restrained molecular dynamics to predict the conformations of phosphorylated receiver domains in two‐component signaling systems

    PubMed Central

    Foster, Clay A.

    2016-01-01

    ABSTRACT Two‐component signaling (TCS) is the primary means by which bacteria, as well as certain plants and fungi, respond to external stimuli. Signal transduction involves stimulus‐dependent autophosphorylation of a sensor histidine kinase and phosphoryl transfer to the receiver domain of a downstream response regulator. Phosphorylation acts as an allosteric switch, inducing structural and functional changes in the pathway's components. Due to their transient nature, phosphorylated receiver domains are challenging to characterize structurally. In this work, we provide a methodology for simulating receiver domain phosphorylation to predict conformations that are nearly identical to experimental structures. Using restrained molecular dynamics, phosphorylated conformations of receiver domains can be reliably sampled on nanosecond timescales. These simulations also provide data on conformational dynamics that can be used to identify regions of functional significance related to phosphorylation. We first validated this approach on several well‐characterized receiver domains and then used it to compare the upstream and downstream components of the fungal Sln1 phosphorelay. Our results demonstrate that this technique provides structural insight, obtained in the absence of crystallographic or NMR information, regarding phosphorylation‐induced conformational changes in receiver domains that regulate the output of their associated signaling pathway. To our knowledge, this is the first time such a protocol has been described that can be broadly applied to TCS proteins for predictive purposes. Proteins 2016; 85:155–176. © 2016 Wiley Periodicals, Inc. PMID:27802580

  17. Restrain of bone growth by estrogen-mimetic peptide-1 (EMP-1): a micro-computed tomographic study.

    PubMed

    Kasher, Roni; Bajayo, Alon; Gabet, Yankel; Nevo, Nava; Fridkin, Mati; Katchalski-Katzir, Ephraim; Kohen, Fortune; Bab, Itai

    2009-06-01

    Estrogen has a key role in the regulation of skeletal growth and maintenance of bone mass. Recently, we developed peptides having estrogen-like activity as potential estrogen-based new drugs. The aim of the present study was to evaluate the influence of long-term administration of the most efficacious of these peptides, the hexapeptide EMP-1 (VSWFFE), on bone mass and development. EMP-1 was injected daily to ovariectomized (OVX) and intact young, sexually mature female mice for 10 weeks. Whole femora, including the cartilaginous growth plates were analyzed by micro-computed tomography (microCT). We found that peptide EMP-1 restrains bone growth in OVX mice: it inhibited dramatically bone longitudinal growth (40%), and decreased femoral diaphyseal diameter. Peptide EMP-1 had no effect on bone growth in normal mice, and did not influence the OVX-induced bone loss. We then developed a new microCT methodology to evaluate uncalcified and calcified growth plate parameters. In the OVX mice, peptide EMP-1 reduced volume and thickness of the uncalcified growth plate, a possible cause for the inhibition of bone longitudinal growth. Peptide EMP-1 may be used as a lead compound for the development of drugs to treat acromegalic patients.

  18. IL-33 regulates the IgA-microbiota axis to restrain IL-1α-dependent colitis and tumorigenesis.

    PubMed

    Malik, Ankit; Sharma, Deepika; Zhu, Qifan; Karki, Rajendra; Guy, Clifford S; Vogel, Peter; Kanneganti, Thirumala-Devi

    2016-12-01

    Inflammatory bowel diseases (IBD) affect over 5 million individuals in the industrialized world, with an increasing incidence rate worldwide. IBD also predisposes affected individuals to development of colorectal cancer, which is a leading cause of cancer-related deaths in adults. Mutations in genes encoding molecules in the IL-33 signaling pathway are associated with colitis and colitis-associated cancer (CAC), but how IL-33 modulates gut homeostasis is unclear. Here, we have shown that Il33-deficient mice are highly susceptible to colitis and CAC. Mechanistically, we observed that IL-33 promoted IgA production from B cells, which is important for maintaining microbial homeostasis in the intestine. Il33-deficient mice developed a dysbiotic microbiota that was characterized by increased levels of mucolytic and colitogenic bacteria. In response to chemically induced colitis, this microbial landscape promoted the release of IL-1α, which acted as a critical driver of colitis and CAC. Consequently, reconstitution of symbiotic microbiota or IL-1α ablation markedly ameliorated colitis susceptibility in Il33-deficient animals. Our results demonstrate that IL-33 promotes IgA production to maintain gut microbial homoeostasis and restrain IL-1α-dependent colitis and CAC. This study therefore highlights modulation of IL-33, IgA, IL-1α, and the microbiota as a potential therapeutic approach in the treatment of IBD and CAC.

  19. Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function

    PubMed Central

    2015-01-01

    The nucleus tractus solitarii (nTS) is the initial central termination site for visceral afferents and is important for modulation and integration of multiple reflexes including cardiorespiratory reflexes. Glutamate is the primary excitatory neurotransmitter in the nTS and is removed from the extracellular milieu by excitatory amino acid transporters (EAATs). The goal of this study was to elucidate the role of EAATs in the nTS on basal synaptic and neuronal function and cardiorespiratory regulation. The majority of glutamate clearance in the central nervous system is believed to be mediated by astrocytic EAAT 1 and 2. We confirmed the presence of EAAT 1 and 2 within the nTS and their colocalization with astrocytic markers. EAAT blockade with dl-threo-β-benzyloxyaspartic acid (TBOA) produced a concentration-related depolarization, increased spontaneous excitatory postsynaptic current (EPSC) frequency, and enhanced action potential discharge in nTS neurons. Solitary tract-evoked EPSCs were significantly reduced by EAAT blockade. Microinjection of TBOA into the nTS of anesthetized rats induced apneic, sympathoinhibitory, depressor, and bradycardic responses. These effects mimicked the response to microinjection of exogenous glutamate, and glutamate responses were enhanced by EAAT blockade. Together these data indicate that EAATs tonically restrain nTS excitability to modulate cardiorespiratory function. PMID:26719090

  20. The Rho-GTPase Rnd1 Suppresses Mammary Tumorigenesis and EMT by Restraining Ras-MAPK signaling

    PubMed Central

    Okada, Tomoyo; Sinha, Surajit; Esposito, Ilaria; Schiavon, Gaia; López-Lago, Miguel A.; Su, Wenjing; Pratilas, Christine A.; Abele, Cristina; Hernandez, Jonathan M.; Ohara, Masahiro; Okada, Morihito; Viale, Agnes; Heguy, Adriana; Socci, Nicholas D.; Sapino, Anna; Seshan, Venkatraman E.; Long, Stephen; Inghirami, Giorgio; Rosen, Neal; Giancotti, Filippo G.

    2015-01-01

    SUMMARY We identified the Rho-GTPase Rnd1 as a candidate metastasis suppressor through bioinformatics analysis and showed that its depletion disrupt epithelial adhesion and polarity, induced Epithelial-to-Mesenchymal Transition (EMT), and cooperated with deregulated expression of c-Myc or loss of p53 to cause neoplastic conversion. Mechanistic studies revealed that Rnd1 suppresses Ras signalling by activating the GAP domain of Plexin B1, which inhibits Rap1. Rap1 inhibition in turn led to derepression of p120-RasGAP, which was able to inhibit Ras. Inactivation of Rnd1 in mammary epithelial cells induced highly undifferentiated and invasive tumors in mice. Conversely, Rnd1 expression inhibited spontaneous and experimental lung colonization in mouse models of metastasis. Genomic studies indicated that gene deletion in combination with epigenetic silencing or, more rarely, point mutation inactivates RND1 in human breast cancer. These results reveal a previously unappreciated mechanism through which Rnd1 restrains activation of Ras-MAPK signaling and breast tumor initiation and progression. PMID:25531777

  1. Disulphide bond restrains the C-terminal region of thermostable direct hemolysin during folding to promote oligomerization.

    PubMed

    Kundu, Nidhi; Tichkule, Swapnil; Pandit, Shashi Bhushan; Chattopadhyay, Kausik

    2017-01-15

    Pore-forming toxins (PFTs) are typically produced as water-soluble monomers, which upon interacting with target cells assemble into transmembrane oligomeric pores. Vibrio parahaemolyticus thermostable direct hemolysin (TDH) is an atypical PFT that exists as a tetramer in solution, prior to membrane binding. The TDH structure highlights a core β-sandwich domain similar to those found in the eukaryotic actinoporin family of PFTs. However, the TDH structure harbors an extended C-terminal region (CTR) that is not documented in the actinoporins. This CTR remains tethered to the β-sandwich domain through an intra-molecular disulphide bond. Part of the CTR is positioned at the inter-protomer interface in the TDH tetramer. Here we show that the truncation, as well as mutation, of the CTR compromise tetrameric assembly, and the membrane-damaging activity of TDH. Our study also reveals that intra-protomer disulphide bond formation during the folding/assembly process of TDH restrains the CTR to mediate its participation in the formation of inter-protomer contact, thus facilitating TDH oligomerization. However, once tetramerization is achieved, disruption of the disulphide bond does not affect oligomeric assembly. Our study provides critical insights regarding the regulation of the oligomerization mechanism of TDH, which has not been previously documented in the PFT family.

  2. Thrombospondin-1 restrains neutrophil granule serine protease function and regulates the innate immune response during Klebsiella pneumoniae infection

    PubMed Central

    Zhao, Yani; Olonisakin, Tolani F.; Xiong, Zeyu; Hulver, Mei; Sayeed, Sameera; Yu, Min Ting; Gregory, Alyssa D.; Kochman, Elizabeth J.; Chen, Bill B.; Mallampalli, Rama K.; Sun, Ming; Silverstein, Roy L.; Stolz, Donna B.; Shapiro, Steve D.; Ray, Anuradha; Ray, Prabir; Lee, Janet S.

    2014-01-01

    Neutrophil elastase (NE) and cathepsin G (CG) contribute to intracellular microbial killing but, if left unchecked and released extracellularly, promotes tissue damage. Conversely, mechanisms that constrain neutrophil serine protease activity protect against tissue damage but may have the untoward effect of disabling the microbial killing arsenal. The host elaborates thrombospondin-1 (TSP-1), a matricellular protein released during inflammation, but its role during neutrophil activation following microbial pathogen challenge remains uncertain. Mice deficient in thrombospondin-1 (thbs1−/−) showed enhanced lung bacterial clearance, reduced splenic dissemination, and increased survival compared with WT controls during intrapulmonary Klebsiella pneumoniae infection. More effective pathogen containment was associated with reduced burden of inflammation in thbs1−/− mouse lungs compared with WT controls. Lung NE activity was increased in thbs1−/− mice following Klebsiella pneumoniae challenge, and thbs1−/− neutrophils showed enhanced intracellular microbial killing that was abrogated with recombinant TSP-1 administration or WT serum. Thbs1−/− neutrophils exhibited enhanced NE and CG enzymatic activity and a peptide corresponding to amino acid residues 793–801 within the type 3 repeats domain of TSP-1 bridled neutrophil proteolytic function and microbial killing in vitro. Thus, TSP-1 restrains proteolytic action during neutrophilic inflammation elicited by Klebsiella pneumoniae, providing a mechanism that may regulate the microbial killing arsenal. PMID:25492474

  3. Antimicrobial resistance of mastitis pathogens.

    PubMed

    Oliver, Stephen P; Murinda, Shelton E

    2012-07-01

    Antibiotics are used extensively in the dairy industry to combat disease and to improve animal performance. Antibiotics such as penicillin, cephalosporin, streptomycin, and tetracycline are used for the treatment and prevention of diseases affecting dairy cows caused by a variety of gram-positive and gram-negative bacteria. Antibiotics are often administrated routinely to entire herds to prevent mastitis during the dry period. An increase in the incidence of disease in a herd generally results in increased use of antimicrobials, which in turn increases the potential for antibiotic residues in milk and the potential for increased bacterial resistance to antimicrobials. Continued use of antibiotics in the treatment and prevention of diseases of dairy cows will continue to be scrutinized. It is clear that strategies employing the prudent use of antimicrobials are needed. This clearly illustrates the importance of effective herd disease prevention and control programs. Based on studies published to date, scientific evidence does not support widespread, emerging resistance among mastitis pathogens to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in dairy cows can contribute to increased antimicrobial resistance. While antimicrobial resistance does occur, we are of the opinion that the advantages of using antibiotics for the treatment of mastitis far outweigh the disadvantages. The clinical consequences of antimicrobial resistance of dairy pathogens affecting humans appear small. Antimicrobial resistance among dairy pathogens, particularly those found in milk, is likely not a human health concern as long as the milk is pasteurized. However, there are an increasing number of people who choose to consume raw milk. Transmission of an antimicrobial-resistant mastitis pathogen and/or foodborne pathogen to humans could occur

  4. Antimicrobial peptides interact with peptidoglycan

    NASA Astrophysics Data System (ADS)

    Neelay, Om P.; Peterson, Christian A.; Snavely, Mary E.; Brown, Taylor C.; TecleMariam, Ariam F.; Campbell, Jennifer A.; Blake, Allison M.; Schneider, Sydney C.; Cremeens, Matthew E.

    2017-10-01

    Traditional therapeutics are losing effectiveness as bacterial resistance increases, and antimicrobial peptides (AMPs) can serve as an alternative source for antimicrobial agents. Their mode of action is commonly hypothesized to involve pore formation in the lipid membrane, thereby leading to cell death. However, bacterial cell walls are much more complex than just the lipid membrane. A large portion of the wall is comprised of peptidoglycan, yet we did not find any report of AMP-peptidoglycan interactions. Consequently, this work evaluated AMP-peptidoglycan and AMP-phospholipid (multilamellar vesicles) interactions through tryptophan fluorescence. Given that peptidoglycan is insoluble and vesicles are large particles, we took advantage of the unique properties of Trp-fluorescence to use one technique for two very different systems. Interestingly, melittin and cecropin A interacted with peptidoglycan to a degree similar to vancomycin, a positive control. Whether these AMP-peptidoglycan interactions relate to a killing mode of action requires further study.

  5. Antimicrobial resistance in Rhodococcus equi.

    PubMed

    Cisek, Agata A; Rzewuska, Magdalena; Witkowski, Lucjan; Binek, Marian

    2014-01-01

    Rhodococcus equi is an important etiologic agent of respiratory- and non-respiratory tract infections, diseases of animals and humans. Therapy includes the use of various group of chemotherapeutic agents, however resistance acquirement is quite common. To date there is no preferred treatment protocol for infections caused by isolates resistant to macrolides and rifampicin. The resistance acquirement is a result of many molecular mechanisms, some of which include alterations in the cell envelope composition and structure, activity of the efflux pumps, enzymatic destruction or inactivation of antibiotics, and changes in the target site. This paper contains an overview of antimicrobial susceptibility of R. equi, and explains the possible molecular mechanisms responsible for antimicrobial resistance in this particular microorganism.

  6. Bacteriophage endolysins as novel antimicrobials

    PubMed Central

    Schmelcher, Mathias; Donovan, David M; Loessner, Martin J

    2013-01-01

    Endolysins are enzymes used by bacteriophages at the end of their replication cycle to degrade the peptidoglycan of the bacterial host from within, resulting in cell lysis and release of progeny virions. Due to the absence of an outer membrane in the Gram-positive bacterial cell wall, endolysins can access the peptidoglycan and destroy these organisms when applied externally, making them interesting antimicrobial candidates, particularly in light of increasing bacterial drug resistance. This article reviews the modular structure of these enzymes, in which cell wall binding and catalytic functions are separated, as well as their mechanism of action, lytic activity and potential as antimicrobials. It particularly focuses on molecular engineering as a means of optimizing endolysins for specific applications, highlights new developments that may render these proteins active against Gram-negative and intracellular pathogens and summarizes the most recent applications of endolysins in the fields of medicine, food safety, agriculture and biotechnology. PMID:23030422

  7. Antimicrobial Peptides from Marine Proteobacteria

    PubMed Central

    Desriac, Florie; Jégou, Camille; Balnois, Eric; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

    2013-01-01

    After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs. PMID:24084784

  8. Antimicrobial peptides from marine proteobacteria.

    PubMed

    Desriac, Florie; Jégou, Camille; Balnois, Eric; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

    2013-09-30

    After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of "classical" antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs.

  9. Antimicrobial Activity of Commercial Nanoparticles

    NASA Astrophysics Data System (ADS)

    Gajjar, Priyanka; Pettee, Brian; Britt, David W.; Huang, Wenjie; Johnson, William P.; Anderson, Anne J.

    2009-07-01

    Engineered nanoparticles are finding increased use in applications ranging from biosensors to prophylactic antimicrobials embedded in socks. The release of heavy metal-containing nanoparticles (NP) into the environment may be harmful to the efficacy of beneficial microbes that function in element cycling, pollutant degradation, and plant growth. Antimicrobial activity of commercial NP of Ag, CuO, and ZnO is demonstrated here against the beneficial soil microbe, Pseudomonas putida KT2440, which was modified to serve as a bioluminescent sentinel organism. "As manufactured" preparations of nano- Ag, -CuO, and -ZnO caused rapid, dose dependent loss of light output in the biosensor. Bulk equivalents of these products showed no inhibitory activity, indicating that particle size was determinant in activity.

  10. Antimicrobial proteins of murine macrophages.

    PubMed Central

    Hiemstra, P S; Eisenhauer, P B; Harwig, S S; van den Barselaar, M T; van Furth, R; Lehrer, R I

    1993-01-01

    Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an H1 histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized. Images PMID:8514411

  11. Plant Products as Antimicrobial Agents

    PubMed Central

    Cowan, Marjorie Murphy

    1999-01-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations. PMID:10515903

  12. Antimicrobial mechanisms of fish leukocytes.

    PubMed

    Rieger, Aja M; Barreda, Daniel R

    2011-12-01

    Early activation and coordination of innate defenses are critical for effective responses against infiltrating pathogens. Rapid engagement of immune cells provides a critical first line of defense soon after pathogen infiltration. Activation leads to a well-orchestrated set of events that sees the induction and regulation of intracellular and extracellular antimicrobial defenses. An array of regulatory mediators, highly toxic soluble molecules, degradative enzymes and antimicrobial peptides provides maximal protection against a wide range of pathogens while limiting endogenous damage to host tissues. In this review we highlight recent advances in our understanding of innate cellular antimicrobial responses of teleost fish and discuss their implications to cell survival, immunomodulation and death. The evolutionary conservation of these responses is a testament to their effectiveness against pathogen infiltration and their commitment to effective maintenance of host homeostasis. Importantly, recent developments in teleost fish systems have identified novel host defense strategies that may be unique to this lower vertebrate group or may point to previously unknown innate mechanisms that also play a significant role in higher vertebrate host immunity.

  13. Antimicrobial Properties of Amyloid Peptides

    PubMed Central

    Kagan, Bruce L.; Jang, Hyunbum; Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh; Nussinov, Ruth

    2011-01-01

    More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-β structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape β-strand-turn-β-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids are not only toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function. PMID:22081976

  14. Antimicrobial compounds of porcine mucosa

    NASA Astrophysics Data System (ADS)

    Kotenkova, E. A.; Lukinova, E. A.; Fedulova, L. V.

    2017-09-01

    The aim of the study was to investigate porcine oral cavity mucosa (OCM), nasal cavity mucosa (NCM), rectal mucosa (RM) and tongue mucosa (TM) as sources of antimicrobial compounds. Ultrafiltrates with MW >30 kDa, MW 5-30 kDa and MW <5 kDa were obtained. All ultrafiltrates had antimicrobial activity against Escherichia coli and Proteus vulgaris. NCM ultrafiltrates revealed the highest antibacterial activity in respect to negative control: for the fraction with MW >30 kDa, the zone of microbial growth inhibition was 7.5 mm, for the MW<5 kDa fraction, it was 7 mm, and for MW 5-30 kDa fraction, it was 4.5 mm. No significant differences were found in high molecular weight proteomic profile, while qualitative and quantitative differences were observed in the medium and low molecular weight areas, especially in OCM and NCM. HPLC showed 221 tissue-specific peptides in OCM, 156 in NCM, 225 in RM, but only 5 in TM. The results observed confirmed porcine mucous tissues as a good source of antimicrobial compounds, which could be an actual alternative for reduction of microbial spoilage of foods.

  15. Antimicrobial Peptides Under Clinical Trials.

    PubMed

    Greber, Katarzyna E; Dawgul, Małgorzata

    2017-01-01

    Today microbial drug resistance has become a serious problem not only within inpatient setting but also within outpatient setting. Repeated intake and unnecessary usage of antibiotics as well as the transfer of resistance genes are the most important factors that make the microorganisms resistant to conventional antibiotics. A large number of antimicrobials successfully used for prophylaxis and therapeutic purposes have now become ineffective [1, 2]. Therefore, new molecules are being studied to be used in the treatment of various diseases. Some of these molecules are structural compounds based on a combination of peptides, for example, naturally occurring endogenous peptide antibiotics and their synthetic analogues or molecules designed de novo using QSAR (quantitative structureproperty relationships)-based methods [3]. Trying to exploit numerous advantages of antimicrobial peptides such as high potency and selectivity, broad range of targets, potentially low toxicity and low accumulation in tissues, pharmaceutical industry aims to develop them as commercially available drugs and appropriate clinical trials are being conducted [4]. In this paper we define clinical trials steps and describe current status of several antimicrobial peptides under clinical development as well as briefly depict peptide drug formulation.

  16. Antimicrobial Stewardship in Laboratory Animal Facilities

    PubMed Central

    Narver, Heather L

    2017-01-01

    Bacterial resistance to antimicrobial drugs has become a global health crisis. Physicians and veterinarians are embracing the concept of ‘antimicrobial stewardship’ (AMS) to preserve the efficacy of antibiotics for future generations. Antimicrobials are used in laboratory animals to treat clinical disease, to protect populations that may be vulnerable to infection, and in research projects including studies of the microbiome and to influence expression in genetically engineered animals. This overview provides a critical look at the use of antimicrobials in contemporary vivaria, with special attention to rodents because they are the most commonly used species in research and because antimicrobial use in rodents is not straightforward. Improvements in antibiotic use are encouraged with the goal of decreasing bacterial resistance while continuing to provide quality clinical care and research support. Suggestions are framed by using the 5 Rs: Reduce, Refine, Replace, and Review antimicrobial use in the vivarium, and take Responsibility for the judicious use of antibiotics in research animals. PMID:28905709

  17. Antimicrobial hydrogels for the treatment of infection

    PubMed Central

    Veiga, Ana Salomé; Schneider, Joel P.

    2014-01-01

    The increasing prevalence of microbial infections, especially those associated with impaired wound healing and biomedical implant failure has spurred the development of new materials having antimicrobial activity. Hydrogels are a class of highly hydrated material finding use in diverse medical applications such as drug delivery, tissue engineering, as wound fillers and as implant coatings, to name a few. The biocompatible nature of many gels make them a convenient starting platform to develop selectively active antimicrobial materials. Hydrogels with antimicrobial properties can be obtained through the encapsulation or covalent immobilization of known antimicrobial agents, or the material itself can be designed to possess inherent antimicrobial activity. In this review we present an overview of antimicrobial hydrogels that have recently been developed and when possible provide a discussion relevant to their mechanism of action. PMID:24122459

  18. Comparison of Thoracic Injury Risk in Frontal Car Crashes for Occupant Restrained without Belt Load Limiters and Those Restrained with 6 kN and 4 kN Belt Load Limiters.

    PubMed

    Foret-Bruno, J Y; Trosseille, X; Page, Y; Huère, J F; Le Coz, J Y; Bendjellal, F; Diboine, A; Phalempin, T; Villeforceix, D; Baudrit, P; Guillemot, H; Coltat, J C

    2001-11-01

    In France, as in other countries, accident research studies show that a large proportion of restrained occupants who sustain severe or fatal injuries are involved in frontal impacts (65% and 50%, respectively). In severe frontal impacts with restrained occupants and where intrusion is not preponderant, the oldest occupants very often sustain severe thoracic injuries due to the conventional seat belt. As we have been observing over the last years, we will expect in the coming years developments which include more solidly-built cars, as offset crash test procedures are widely used to evaluate the passive safety of production vehicles. The reduction of intrusion for the most severe frontal impacts, through optimization of car deformation, usually translates into an increase in restraint forces and hence thoracic injury risk with a conventional retractor seat belt for a given impact severity. It is, therefore essential to limit the restraint forces exerted by the seat belt on the thorax in order to reduce the number of road casualties. In order to address thoracic injury risk in frontal impact, Renault cars have been equipped with the Programmed Restraint System (PRS) since 1995. The PRS is a restraint system that combines belt load limitation and pyrotechnic belt pretension. In an initial design of the Programmed Restraint System (PRS1), the belt load limiter was a steel component designed to shear at a given shoulder force, namely 6 kN. It was mounted between the retractor and the lower anchorage point of the belt. The design of the PRS was modified in 1998 (PRS2), but the principle of load limitation was maintained. The threshold was decreased to 4 kN and this lower belt belt-force limiter has been combined with a specially designed airbag. This paper reports on 347 real-world frontal accidents where the EES (Equivalent Energy Speed) ranged from 35 to 75 km/h. One hundred and ninety-eight (198) of these accidents involved cars equipped with the 6 kN load limiter

  19. Antimicrobial technology in orthopedic and spinal implants

    PubMed Central

    Eltorai, Adam EM; Haglin, Jack; Perera, Sudheesha; Brea, Bielinsky A; Ruttiman, Roy; Garcia, Dioscaris R; Born, Christopher T; Daniels, Alan H

    2016-01-01

    Infections can hinder orthopedic implant function and retention. Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion. Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems, material science, immunology, and polymer chemistry are in development and early clinical use. This review outlines orthopedic implant antimicrobial technology, its current applications and supporting evidence, and clinically promising future directions. PMID:27335811

  20. Correlations between Income Inequality and Antimicrobial Resistance

    PubMed Central

    Kirby, Andrew; Herbert, Annie

    2013-01-01

    Objectives The aim of this study is to investigate if correlations exist between income inequality and antimicrobial resistance. This study’s hypothesis is that income inequality at the national level is positively correlated with antimicrobial resistance within developed countries. Data collection and analysis Income inequality data were obtained from the Standardized World Income Inequality Database. Antimicrobial resistance data were obtained from the European antimicrobial Resistance Surveillance Network and outpatient antimicrobial consumption data, measured by Defined daily Doses per 1000 inhabitants per day, from the European Surveillance of antimicrobial Consumption group. Spearman’s correlation coefficient (r) defined strengths of correlations of: > 0.8 as strong, > 0.5 as moderate and > 0.2 as weak. Confidence intervals and p values were defined for all r values. Correlations were calculated for the time period 2003-10, for 15 European countries. Results Income inequality and antimicrobial resistance correlations which were moderate or strong, with 95% confidence intervals > 0, included the following. Enterococcus faecalis resistance to aminopenicillins, vancomycin and high level gentamicin was moderately associated with income inequality (r= ≥0.54 for all three antimicrobials). Escherichia coli resistance to aminoglycosides, aminopenicillins, third generation cephalosporins and fluoroquinolones was moderately-strongly associated with income inequality (r= ≥0.7 for all four antimicrobials). Klebsiella pneumoniae resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones was moderately associated with income inequality (r= ≥0.5 for all three antimicrobials). Staphylococcus aureus methicillin resistance and income inequality were strongly associated (r=0.87). Conclusion As income inequality increases in European countries so do the rates of antimicrobial resistance for bacteria including E. faecalis, E. coli, K. pneumoniae

  1. Insect inducible antimicrobial peptides and their applications.

    PubMed

    Ezzati-Tabrizi, Reyhaneh; Farrokhi, Naser; Talaei-Hassanloui, Reza; Alavi, Seyed Mehdi; Hosseininaveh, Vahid

    2013-12-01

    Antimicrobial peptides (AMPs) are found as important components of the innate immune system (host defense) of all invertebrates. These peptides can be constitutively expressed or induced in response to microbial infections. Indeed, they vary in their amino acid sequences, potency and antimicrobial activity spectra. The smaller AMPs act greatly by disrupting the structure or function of microbial cell membranes. Here, the insect innate immune system with emphasis on inducible antimicrobial peptide properties against microbial invaders has been discussed.

  2. Antimicrobial technology in orthopedic and spinal implants.

    PubMed

    Eltorai, Adam Em; Haglin, Jack; Perera, Sudheesha; Brea, Bielinsky A; Ruttiman, Roy; Garcia, Dioscaris R; Born, Christopher T; Daniels, Alan H

    2016-06-18

    Infections can hinder orthopedic implant function and retention. Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion. Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems, material science, immunology, and polymer chemistry are in development and early clinical use. This review outlines orthopedic implant antimicrobial technology, its current applications and supporting evidence, and clinically promising future directions.

  3. Antimicrobial polymer films for food packaging

    NASA Astrophysics Data System (ADS)

    Concilio, S.; Piotto, S.; Sessa, L.; Iannelli, P.; Porta, A.; Calabrese, E. C.; Galdi, M. R.; Incarnato, L.

    2012-07-01

    New antimicrobial polymeric systems were realized introducing new antimicrobial azo compounds in PP and LDPE matrices. The polymeric materials containing different percentage of azo compounds were mold-casted and the obtained film were tested in vitro against Gram+ and Gram- bacteria and fungi. These results hold promise for the fabrication of bacteria-resistant polymer films by means of simple melt processing with antimicrobial azo-dyes.

  4. Interviewer BMI effects on under- and over-reporting of restrained eating: evidence from a national Dutch face-to-face survey and a postal follow-up.

    PubMed

    Eisinga, Rob; te Grotenhuis, Manfred; Larsen, Junilla K; Pelzer, Ben

    2012-06-01

    To determine the effect of interviewer BMI on self-reported restrained eating in a face-to-face survey and to examine under- and over-reporting using the face-to face study and a postal follow-up. A sample of 1,212 Dutch adults was assigned to 98 interviewers with different BMI who administered an eating questionnaire. To further evaluate misreporting a mail follow-up was conducted among 504 participants. Data were analyzed using two-level hierarchical models. Interviewer BMI had a positive effect on restrained eating. Normal weight and pre-obese interviewers obtained valid responses, underweight interviewers stimulated under-reporting whereas obese interviewers triggered over-reporting. In face-to-face interviews self-reported dietary restraint is distorted by interviewer BMI. This result has implications for public health surveys, the more so given the expanding obesity epidemic.

  5. Equivalent Stabilizing Force of the Simply Supported Roof Girders Including the Longitudinal Variability of the Compression Force Acting in the Restrained Chord

    NASA Astrophysics Data System (ADS)

    Biegus, Antoni; Czepiżak, Dariusz

    2017-06-01

    In the calculation model of the equivalent stabilizing force qd for bracing system consistent with EN 1993-1-1 it has been conservatively assumed that the member to be restrained is uniformly compressed within its length by an axial force. This assumption is incorrect owing to the actual distribution of the axial force which is non-uniform in the shape of parabola. Thus a different imperfection force is generated in comparison with this given in EN 1993-1-1. In the paper the equivalent stabilizing force qd of simply supported roof girders has been analyzed. The formulas for an equivalent stabilizing forces of restrained roof girders with parabolic variability of axial force, have been proposed. Obtained results have been discussed and illustrated with examples.

  6. Antimicrobial use in food and companion animals.

    PubMed

    Prescott, John F

    2008-12-01

    The vast literature on antimicrobial drug use in animals has expanded considerably recently as the antimicrobial resistance (AMR) crisis in human medicine leads to questions about all usage of antimicrobial drugs, including long-term usage in intensively managed food animals for growth promotion and disease prevention. Attention is also increasingly focusing on antimicrobial use and on bacterial resistance in companion animals, which are in intimate contact with the human population. They may share resistant bacteria with their owners, amplify resistant bacteria acquired from their owners, and act as a reservoir for human infection. Considerable effort is being made to describe the basis of AMR in bacterial pathogens of animals. Documentation of many aspects of use of antimicrobials in animals is, however, generally less developed and only a few countries can describe quantities of drugs used in animals to kg levels annually. In recent years, many national veterinary associations have produced 'prudent use guidelines' to try to improve antimicrobial drug use and decrease resistance, but the impact of guidelines is unknown. Within the evolving global movement for 'antimicrobial stewardship', there is considerable scope to improve many aspects of antimicrobial use in animals, including infection control and reduction of use, with a view to reducing resistance and its spread, and to preserving antimicrobial drugs for the future.

  7. Antimicrobial Stewardship in the Management of Sepsis.

    PubMed

    Pulia, Michael S; Redwood, Robert; Sharp, Brian

    2017-02-01

    Sepsis represents a unique clinical dilemma with regard to antimicrobial stewardship. The standard approach to suspected sepsis in the emergency department centers on fluid resuscitation and timely broad-spectrum antimicrobials. The lack of gold standard diagnostics and evolving definitions for sepsis introduce a significant degree of diagnostic uncertainty that may raise the potential for inappropriate antimicrobial prescribing. Intervention bundles that combine traditional quality improvement strategies with emerging electronic health record-based clinical decision support tools and rapid molecular diagnostics represent the most promising approach to enhancing antimicrobial stewardship in the management of suspected sepsis in the emergency department.

  8. The Potential of Antimicrobial Peptides as Biocides

    PubMed Central

    Laverty, Garry; Gorman, Sean P.; Gilmore, Brendan F.

    2011-01-01

    Antimicrobial peptides constitute a diverse class of naturally occurring antimicrobial molecules which have activity against a wide range of pathogenic microorganisms. Antimicrobial peptides are exciting leads in the development of novel biocidal agents at a time when classical antibiotics are under intense pressure from emerging resistance, and the global industry in antibiotic research and development stagnates. This review will examine the potential of antimicrobial peptides, both natural and synthetic, as novel biocidal agents in the battle against multi-drug resistant pathogen infections. PMID:22072905

  9. Antimicrobial activity of Gymnema sylvestre leaf extract.

    PubMed

    Satdive, R K; Abhilash, P; Fulzele, Devanand P

    2003-12-01

    The ethanolic extract of Gymnema sylvestre leaves demonstrated antimicrobial activity against Bacillus pumilis, B. subtilis, Pseudomonas aeruginosa and Staphylococcus aureus and inactivity against Proteus vulgaris and Escherichia coli.

  10. Antimicrobial peptides: clinical relevance and therapeutic implications.

    PubMed

    Pinheiro da Silva, Fabiano; Machado, Marcel Cerqueira César

    2012-08-01

    Antimicrobial peptides (AMPs) are molecules that provide protection against environmental pathogens, acting against a large number of microorganisms, including bacteria, fungi, yeast, virus and others. Two major groups of antimicrobial peptides are found in humans: cathelicidins and defensins. Recently, several studies have furnished information that besides their role in infection diseases, antimicrobial peptides play a role in diseases as diverse as inflammatory disorders, autoimmunity and cancer. Here, we discuss the role of antimicrobial peptides and vitamin D have in such complex diseases and propose their use should be more explored in the diagnosis and treatment of such conditions.

  11. Antimicrobial drugs for treating cholera

    PubMed Central

    Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

    2014-01-01

    Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. Objectives To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Selection criteria Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Data collection and analysis Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Main results Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43

  12. Promoting antimicrobial stewardship: using video tools for junior doctors' induction.

    PubMed

    Hadjiphilippou, Savvas; Odogwu, Sarah-Elizabeth; Jeyaratnam, Dakshika

    2014-02-01

    Antimicrobial prescribing is linked to key issues in infection control and patient safety. This article presents a novel video tool for junior doctors promoting antimicrobial stewardship, and thus safe antimicrobial prescribing, through improved awareness of local information technology systems.

  13. Inspiration or deflation? Feeling similar or dissimilar to slim and plus-size models affects self-evaluation of restrained eaters.

    PubMed

    Papies, Esther K; Nicolaije, Kim A H

    2012-01-01

    The present studies examined the effect of perceiving images of slim and plus-size models on restrained eaters' self-evaluation. While previous research has found that such images can lead to either inspiration or deflation, we argue that these inconsistencies can be explained by differences in perceived similarity with the presented model. The results of two studies (ns=52 and 99) confirmed this and revealed that restrained eaters with high (low) perceived similarity to the model showed more positive (negative) self-evaluations when they viewed a slim model, compared to a plus-size model. In addition, Study 2 showed that inducing in participants a similarities mindset led to more positive self-evaluations after viewing a slim compared to a plus-size model, but only among restrained eaters with a relatively high BMI. These results are discussed in the context of research on social comparison processes and with regard to interventions for protection against the possible detrimental effects of media images.

  14. To eat or not to eat red meat. A closer look at the relationship between restrained eating and vegetarianism in college females.

    PubMed

    Forestell, Catherine A; Spaeth, Andrea M; Kane, Stephanie A

    2012-02-01

    Previous research has suggested that vegetarianism may serve as a mask for restrained eating. The purpose of this study was to compare the dietary habits and lifestyle behaviors of vegetarians (n=55), pesco-vegetarians (n=28), semi-vegetarians (n=29), and flexitarians (n=37), to omnivores (n=91), who do not restrict animal products from their diets. A convenience sample of college-age females completed questionnaires about their eating habits, food choice motivations, and personality characteristics. Results indicated that while vegetarians and pesco-vegetarians were more open to new experiences and less food neophobic, they were not more restrained than omnivores. Rather semi-vegetarians; those who restricted only red meat from their diet, and flexitarians; those who occasionally eat red meat, were significantly more restrained than omnivores. Whereas food choices of semi-vegetarians and flexitarians were motivated by weight control, vegetarians and pesco-vegetarians' food choices were motivated by ethical concerns. By focusing specifically on semi-vegetarian and flexitarian subgroups, more effective approaches can be developed to ensure that their concerns about weight loss do not lead to unhealthful or disordered eating patterns. Published by Elsevier Ltd.

  15. Worry or craving? A selective review of evidence for food-related attention biases in obese individuals, eating-disorder patients, restrained eaters and healthy samples.

    PubMed

    Werthmann, Jessica; Jansen, Anita; Roefs, Anne

    2015-05-01

    Living in an 'obesogenic' environment poses a serious challenge for weight maintenance. However, many people are able to maintain a healthy weight indicating that not everybody is equally susceptible to the temptations of this food environment. The way in which someone perceives and reacts to food cues, that is, cognitive processes, could underlie differences in susceptibility. An attention bias for food could be such a cognitive factor that contributes to overeating. However, an attention bias for food has also been implicated with restrained eating and eating-disorder symptomatology. The primary aim of the present review was to determine whether an attention bias for food is specifically related to obesity while also reviewing evidence for attention biases in eating-disorder patients, restrained eaters and healthy-weight individuals. Another aim was to systematically examine how selective attention for food relates (causally) to eating behaviour. Current empirical evidence on attention bias for food within obese samples, eating-disorder patients, and, even though to a lesser extent, in restrained eaters is contradictory. However, present experimental studies provide relatively consistent evidence that an attention bias for food contributes to subsequent food intake. This review highlights the need to distinguish not only between different (temporal) attention bias components, but also to take different motivations (craving v. worry) and their impact on attentional processing into account. Overall, the current state of research suggests that biased attention could be one important cognitive mechanism by which the food environment tempts us into overeating.

  16. Diurnal, seasonal, and sex patterns of heart rate in grip-restrained African giant rats (Cricetomys gambianus, Waterhouse).

    PubMed

    Dzenda, Tavershima; Ayo, Joseph O; Sinkalu, Victor O; Yaqub, Lukuman S

    2015-10-01

    This study was carried out to determine heart rate (HR) values, including diurnal, seasonal, and sex patterns, in the African giant rat (Cricetomys gambianus, Waterhouse). HR was measured using stethoscope in grip-restrained African giant rats of either sex (103 bucks and 98 does), live-trapped from a tropical Savannah, and caged individually in the laboratory during the harmattan (cold-dry), hot-dry, and rainy seasons over a 3-year period. The HR fluctuated between 90 and 210 beats per minute (bpm) throughout the study period. Diurnal changes in HR (mean ± SEM) during the hot-dry and rainy seasons were nonsignificant (P > 0.05), but the morning and afternoon values differed (P < 0.01) during the cold-dry season. The HR varied (P < 0.05) among seasons, with peak, nadir, and moderate values recorded during the cold-dry (165.8 ± 0.51 bpm), hot-dry (153.1 ± 0.74 bpm), and rainy (163.4 ± 0.70 bpm) seasons, respectively. Mean HR of bucks was lower than that of does during the cold-dry (P < 0.0001) and hot-dry (P < 0.01) seasons, but sex difference during the rainy season was insignificant (P > 0.05). Overall, mean HR was lower (P < 0.0001) in bucks (158.8 ± 0.53 bpm) than in does (164.8 ± 0.53 bpm). In conclusion, values of HR in African giant rats are shown for the first time. Season, sex, and daytime influenced the HR, and should be considered during clinical evaluations of the rats.

  17. PED/PEA-15 regulates glucose-induced insulin secretion by restraining potassium channel expression in pancreatic beta-cells.

    PubMed

    Miele, Claudia; Raciti, Gregory Alexander; Cassese, Angela; Romano, Chiara; Giacco, Ferdinando; Oriente, Francesco; Paturzo, Flora; Andreozzi, Francesco; Zabatta, Assunta; Troncone, Giancarlo; Bosch, Fatima; Pujol, Anna; Chneiweiss, Hervé; Formisano, Pietro; Beguinot, Francesco

    2007-03-01

    The phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (ped/pea-15) gene is overexpressed in human diabetes and causes this abnormality in mice. Transgenic mice with beta-cell-specific overexpression of ped/pea-15 (beta-tg) exhibited decreased glucose tolerance but were not insulin resistant. However, they showed impaired insulin response to hyperglycemia. Islets from the beta-tg also exhibited little response to glucose. mRNAs encoding the Sur1 and Kir6.2 potassium channel subunits and their upstream regulator Foxa2 were specifically reduced in these islets. Overexpression of PED/PEA-15 inhibited the induction of the atypical protein kinase C (PKC)-zeta by glucose in mouse islets and in beta-cells of the MIN-6 and INS-1 lines. Rescue of PKC-zeta activity elicited recovery of the expression of the Sur1, Kir6.2, and Foxa2 genes and of glucose-induced insulin secretion in PED/PEA-15-overexpressing beta-cells. Islets from ped/pea-15-null mice exhibited a twofold increased activation of PKC-zeta by glucose; increased abundance of the Sur1, Kir6.2, and Foxa2 mRNAs; and enhanced glucose effect on insulin secretion. In conclusion, PED/PEA-15 is an endogenous regulator of glucose-induced insulin secretion, which restrains potassium channel expression in pancreatic beta-cells. Overexpression of PED/PEA-15 dysregulates beta-cell function and is sufficient to impair glucose tolerance in mice.

  18. Vascular Smooth Muscle LRP6 Limits Arteriosclerotic Calcification in Diabetic LDLR-/- Mice by Restraining Noncanonical Wnt Signals

    PubMed Central

    Cheng, Su-Li; Ramachandran, Bindu; Behrmann, Abraham; Shao, Jian-Su; Mead, Megan; Smith, Carolyn; Krchma, Karen; Arredondo, Yoanna Bello; Kovacs, Attila; Kapoor, Kapil; Brill, Laurence M.; Perera, Ranjan; Williams, Bart O.; Towler, Dwight A.

    2015-01-01

    Rationale Wnt signaling regulates key aspects of diabetic vascular disease. Objective We generated SM22-Cre;LRP6(fl/fl);LDLR-/- mice to determine contributions of Wnt co-receptor LRP6 in the vascular smooth muscle lineage (VSM) of male LDLR-null mice, a background susceptible to diet (HFD) - induced diabetic arteriosclerosis. Methods and Results As compared to LRP6(fl/fl);LDLR-/- controls, SM22-Cre;LRP6(fl/fl);LDLR-/- (LRP6-VKO) siblings exhibited increased aortic calcification on HFD without changes in fasting glucose, lipids, or body composition. Pulse wave velocity (index of arterial stiffness) was also increased. Vascular calcification paralleled enhanced aortic osteochondrogenic programs and circulating osteopontin (OPN), a matricellular regulator of arteriosclerosis. Survey of ligands and Frizzled (Fzd) receptor profiles in LRP6-VKO revealed upregulation of canonical and noncanonical Wnts alongside Fzd10. Fzd10 stimulated noncanonical signaling and OPN promoter activity via an USF-activated cognate inhibited by LRP6. RNAi revealed that USF1 but not USF2 supports OPN expression in LRP6-VKO VSM, and immunoprecipitation confirmed increased USF1 association with OPN chromatin. ML141, an antagonist of cdc42/Rac1 noncanonical signaling, inhibited USF1 activation, osteochondrogenic programs, alkaline phosphatase, and VSM calcification. Mass spectrometry identified LRP6 binding to protein arginine methyltransferase (PRMT) - 1, and nuclear asymmetric dimethylarginine modification was increased with LRP6-VKO. RNAi demonstrated that PRMT1 inhibits OPN and TNAP while PRMT4 supports expression. USF1 complexes containing the H3R17Me2a signature of PRMT4 are increased with LRP6-VKO. Jmjd6, a demethylase downregulated with LRP6 deficiency, inhibits OPN and TNAP expression, USF1:H3R17Me2a complex formation and transactivation. Conclusions LRP6 restrains VSM noncanonical signals that promote osteochondrogenic differentiation, mediated in part via USF1- and arginine methylation

  19. A Simple and Accurate Method To Calculate Free Energy Profiles and Reaction Rates from Restrained Molecular Simulations of Diffusive Processes.

    PubMed

    Ovchinnikov, Victor; Nam, Kwangho; Karplus, Martin

    2016-08-25

    A method is developed to obtain simultaneously free energy profiles and diffusion constants from restrained molecular simulations in diffusive systems. The method is based on low-order expansions of the free energy and diffusivity as functions of the reaction coordinate. These expansions lead to simple analytical relationships between simulation statistics and model parameters. The method is tested on 1D and 2D model systems; its accuracy is found to be comparable to or better than that of the existing alternatives, which are briefly discussed. An important aspect of the method is that the free energy is constructed by integrating its derivatives, which can be computed without need for overlapping sampling windows. The implementation of the method in any molecular simulation program that supports external umbrella potentials (e.g., CHARMM) requires modification of only a few lines of code. As a demonstration of its applicability to realistic biomolecular systems, the method is applied to model the α-helix ↔ β-sheet transition in a 16-residue peptide in implicit solvent, with the reaction coordinate provided by the string method. Possible modifications of the method are briefly discussed; they include generalization to multidimensional reaction coordinates [in the spirit of the model of Ermak and McCammon (Ermak, D. L.; McCammon, J. A. J. Chem. Phys. 1978, 69, 1352-1360)], a higher-order expansion of the free energy surface, applicability in nonequilibrium systems, and a simple test for Markovianity. In view of the small overhead of the method relative to standard umbrella sampling, we suggest its routine application in the cases where umbrella potential simulations are appropriate.

  20. Fermentable fibers do not affect satiety or food intake by women who do not practice restrained eating.

    PubMed

    Karalus, Melinda; Clark, Michelle; Greaves, Kathryn A; Thomas, William; Vickers, Zata; Kuyama, Megumi; Slavin, Joanne

    2012-09-01

    Fiber is thought to enhance satiety, although not all fibers are equally effective. Colonic fermentation may influence satiety and food intake. To test the satiating properties of four isolated fibers added to chocolate crisp bars. Within-subject preload design with repeated measures. Each participant completed five conditions, presented in random order. Participants were 22 adult women who do not practice restrained eating (body mass index 18 to 29). The experimental conditions were four fiber treatments: 10 g oligofructose, inulin, soluble corn fiber, or resistant wheat starch in chocolate crisp bars. A no-added-fiber bar was evaluated as the control. The night before each treatment, participants consumed a dinner bar containing 10 g of the same fiber given the next morning. Repeated ratings of feelings related to hunger and fullness at the lunch meal were the main measures. Secondary outcomes included breath hydrogen and methane, gastrointestinal symptoms, energy consumed at an ad libitum lunch, and energy from 24-hour dietary recall. Mixed-effect linear models with random intercept for participants to model within-subject correlation. All treatments were well tolerated. No differences were found in subjective satiety during the morning or food intake at lunch or over 24 hours. The oligofructose bar produced the greatest increase in breath hydrogen, and the most bloating and flatulence symptoms. Functional fibers incorporated into chocolate bars at high fiber doses produce greater gastrointestinal symptoms than control, but do not alter satiety, hunger, or food intake compared with control in the short term. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  1. Analysis of the Efficiency of Fugitive Dust Restrain Methods on Bare Land of Da-an River

    NASA Astrophysics Data System (ADS)

    CHEN, H.

    2013-12-01

    Nowadays due to the increasing severity of season fugitive dust at estuary area, the public agencies of government gradually pay more attention to various refrain works. However, it is difficult to evaluate the efficiency of various refrain methods because of lacking of appropriate quantitative index. As a consequence, the only way to understand the fundamentals and efficiency of various refrain works at current stage is to implement the constructions directly on the bare land of riverbed and perform a series of field monitoring. In this study, incorporating with construction cost a FDRE (Fugitive Dust Restrain Efficiency) value was defined to evaluate the cost/refrain-efficiency of various refrain works. Moreover, two case histories of fugitive dust emission at the estuary of Da-An river during Ka-Maegi and Fung-Wong typhoons of 2008 were used for FDRE and cost/refrain-efficiency analyses. Firstly, numerical simulations of fugitive dust emission were performed for the estuary area of Da-An river to calculate the concentration of PM2.5 and PM10 with and without installation of fugitive dust refrain works and the corresponding FDRE values. Subsequently, considering the construction cost and FDRE value one can determine the FDRB values for various refrain works. Meanwhile, the simulations of fugitive dust concentrations were converted into PSI (Pollutant Standard Index) value to evaluate the air quality during fugitive dust emission at the estuary. According to the analyses, without considering the construction cost, the water curtain method (or sprinkling method) is capable of providing the highest FDRE value and best refrain effect to fugitive dust. On the contrary, the vein-type watering covering has the highest FDRB value and is the most economic method to fugitive dust refrain. Construction layout of vein-type water covering method on bare land of riverbed sites of FDRE monitoring stations (P1~P7) and PSI evaluating central point (Q1)

  2. Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance.

    PubMed

    Holman, Devin B; Chénier, Martin R

    2015-11-01

    Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gut microbiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gut microbiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gut microbiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gut microbiota and on antimicrobial resistance determinants in the gut microbiota.

  3. Antimicrobial edible films and coatings.

    PubMed

    Cagri, Arzu; Ustunol, Zeynep; Ryser, Elliot T

    2004-04-01

    Increasing consumer demand for microbiologically safer foods, greater convenience, smaller packages, and longer product shelf life is forcing the industry to develop new food-processing, cooking, handling, and packaging strategies. Nonfluid ready-to-eat foods are frequently exposed to postprocess surface contamination, leading to a reduction in shelf life. The food industry has at its disposal a wide range of nonedible polypropylene- and polyethylene-based packaging materials and various biodegradable protein- and polysaccharide-based edible films that can potentially serve as packaging materials. Research on the use of edible films as packaging materials continues because of the potential for these films to enhance food quality, food safety, and product shelf life. Besides acting as a barrier against mass diffusion (moisture, gases, and volatiles), edible films can serve as carriers for a wide range of food additives, including flavoring agents, antioxidants, vitamins, and colorants. When antimicrobial agents such as benzoic acid, sorbic acid, propionic acid, lactic acid, nisin, and lysozyme have been incorporated into edible films, such films retarded surface growth of bacteria, yeasts, and molds on a wide range of products, including meats and cheeses. Various antimicrobial edible films have been developed to minimize growth of spoilage and pathogenic microorganisms, including Listeria monocytogenes, which may contaminate the surface of cooked ready-to-eat foods after processing. Here, we review the various types of protein-based (wheat gluten, collagen, corn zein, soy, casein, and whey protein), polysaccharide-based (cellulose, chitosan, alginate, starch, pectin, and dextrin), and lipid-based (waxes, acylglycerols, and fatty acids) edible films and a wide range of antimicrobial agents that have been or could potentially be incorporated into such films during manufacture to enhance the safety and shelf life of ready-to-eat foods.

  4. Antimicrobial and biofilm inhibiting diketopiperazines.

    PubMed

    de Carvalho, M P; Abraham, W-R

    2012-01-01

    Diketopiperazines are the smallest cyclic peptides known. 90% of Gram-negative bacteria produce diketopiperazines and they have also been isolated from Gram-positive bacteria, fungi and higher organisms. Biosynthesis of cyclodipeptides can be achieved by dedicated nonribosomal peptide synthetases or by a novel type of synthetases named cyclopeptide synthases. Since the first report in 1924 a large number of bioactive diketopiperazines was discovered spanning activities as antitumor, antiviral, antifungal, antibacterial, antiprion, antihyperglycemic or glycosidase inhibitor agents. As infections are of increasing concern for human health and resistances against existing antibiotics are growing this review focuses on the antimicrobial activities of diketopiperazines. The antibiotic bicyclomycin is a diketopiperazine and structure activity studies revealed the unique nature of this compound which was finally developed for clinical applications. The antimicrobial activities of a number of other diketopiperazines along with structure activity relationships are discussed. Here a special focus is on the activity-toxicity problem of many compounds setting tight limitations to their application as drugs. Not only these classical antimicrobial activities but also proposed action in modulating bacterial communication as a new target to control biofilms will be evaluated. Pathogens organized in biofilms are difficult to eradicate because of the increase of their tolerance for antibiotics for several orders. Diketopiperazines were reported to modulate LuxR-mediated quorum-sensing systems of bacteria, and they are considered to influence cell-cell signaling offering alternative ways of biofilm control by interfering with microbial communication. Concluding the review we will finally discuss the potential of diketopiperazines in the clinic to erase biofilm infections.

  5. Evaluation of Persistent Antimicrobial Effects of an Antimicrobial Formulation

    PubMed Central

    Ferrara, Michael S.; Courson, Ron; Paulson, Daryl S.

    2011-01-01

    Context: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is becoming more prevalent in healthy athletic populations. Various preventive measures have been proposed, but few researchers have evaluated the protective effects of a prophylactic application of a commercially available product. Objective: To compare the persistent antimicrobial properties of a commercially available antimicrobial product containing 4% chlorhexidine gluconate (Hibiclens) with those of a mild, nonmedicated soap (Dr. Bronner's Magic Soap). Design: Cross-sectional study. Setting: Microbiology laboratory, contract research organization. Patients or Other Participants: Twenty healthy human volunteers. Intervention(s): The test and control products were randomly assigned and applied to both forearms of each participant. Each forearm was washed for 2 minutes with the test or control product, rinsed, and dried. At, 1, 2, and 4 hours after application, each forearm was exposed to MRSA for approximately 30 minutes. Main Outcome Measure(s): Differences in numbers of MRSA recovered from each forearm, test and control, at each postapplication time point were compared. Results: Fewer MRSA (P < .0001) were recovered from the forearms treated with the test product (4% chlorhexidine gluconate) than from the forearms treated with the control product (nonmedicated soap). Conclusions: The 4% chlorhexidine gluconate product demonstrated persistent bactericidal activity versus MRSA for up to 4 hours after application. PMID:22488188

  6. Antimicrobial terpenoids from Pterocarpus indicus.

    PubMed

    Ragasa, Consolacion Y; De Luna, Roderick D; Hofilena, Joy G

    2005-06-01

    A mixture of loliolide 1 (> 85%) and paniculatadiol 2 (< 15%) was obtained from the ethyl acetate leaf extract of Pterocarpus indicus by silica gel chromatography, while the air-dried flowers afforded lupeol 3 and phytol esters 4. The structures of 1-4 were determined by NMR spectroscopy. Antimicrobial tests on a mixture of 1 and 2 indicated that it has moderate activity against Candida albicans and low activity against Pseudomonas aeruginosa, Escherichia coli, and Aspergillus niger. It was found inactive against Staphylococcus aureus, Bacillus subtilis, and Trichophyton mentagrophytes.

  7. TESTING ANTIMICROBIAL EFFICACY ON POROUS MATERIALS

    EPA Science Inventory

    The efficacy of antimicrobial treatments to eliminate or control biological growth in the indoor environment can easily be tested on nonporous surfaces. However, the testing of antimicrobial efficacy on porous surfaces, such as those found in the indoor environment [i.e., gypsum ...

  8. Cationic Antimicrobial Polymers and Their Assemblies

    PubMed Central

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2013-01-01

    Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

  9. TESTING ANTIMICROBIAL EFFICACY ON POROUS MATERIALS

    EPA Science Inventory

    The efficacy of antimicrobial treatments to eliminate or control biological growth in the indoor environment can easily be tested on nonporous surfaces. However, the testing of antimicrobial efficacy on porous surfaces, such as those found in the indoor environment [i.e., gypsum ...

  10. [Antimicrobial activity of Calendula L. plants].

    PubMed

    Radioza, S A; Iurchak, L D

    2007-01-01

    The sap of different organs of genus Calendula plant species has been studied for antimicrobial activity. The sap of racemes demonstrated the most expressed antimicrobial effect while that of the roots - the least one. Calendula species inhibited all tested pathogenic microorganisms, especially Pseudomonas syringae, P. fluorescens, Xanthomonas campestris, Agrobacterium tumefaciens. Calendula suffruticosa was the most active to all investigated microorganisms.

  11. Antimicrobial food packaging: potential and pitfalls

    PubMed Central

    Malhotra, Bhanu; Keshwani, Anu; Kharkwal, Harsha

    2015-01-01

    Nowadays food preservation, quality maintenance, and safety are major growing concerns of the food industry. It is evident that over time consumers’ demand for natural and safe food products with stringent regulations to prevent food-borne infectious diseases. Antimicrobial packaging which is thought to be a subset of active packaging and controlled release packaging is one such promising technology which effectively impregnates the antimicrobial into the food packaging film material and subsequently delivers it over the stipulated period of time to kill the pathogenic microorganisms affecting food products thereby increasing the shelf life to severe folds. This paper presents a picture of the recent research on antimicrobial agents that are aimed at enhancing and improving food quality and safety by reduction of pathogen growth and extension of shelf life, in a form of a comprehensive review. Examination of the available antimicrobial packaging technologies is also presented along with their significant impact on food safety. This article entails various antimicrobial agents for commercial applications, as well as the difference between the use of antimicrobials under laboratory scale and real time applications. Development of resistance amongst microorganisms is considered as a future implication of antimicrobials with an aim to come up with actual efficacies in extension of shelf life as well as reduction in bacterial growth through the upcoming and promising use of antimicrobials in food packaging for the forthcoming research down the line. PMID:26136740

  12. Antimicrobial resistance issues in beef production

    USDA-ARS?s Scientific Manuscript database

    Antimicrobial resistance threats to human health as identified have been recognized as a critical global public health concern. Linkage of some threats to beef production is discussed. The relevance to beef production of recent government actions will be examined. Prominent antimicrobial resistance ...

  13. Antimicrobial Activities of Clove and Thyme Extracts

    PubMed Central

    Nzeako, B C; Al-Kharousi, Zahra S N; Al-Mahrooqui, Zahra

    2006-01-01

    Objective: It has been postulated that geographical locations of the herbs affect the constituents of their essential oils and thus the degree of their antimicrobial action. This study examine two samples of clove obtained from Sri Lanka and Zanzibar and two samples of thyme from Iran and Oman to determine the antimicrobial potential of their extracted oils. Method: The active agents in each plant were extracted by steam distillation and by boiling. The antimicrobial activities of the extracts were determined at neat and by two-fold dilutions in well agar diffusion technique using Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pyogenes, Corynebacterium species, Salmonella species, Bacteroides fragilis and Candida albicans. Results: All oil extracts possessed antimicrobial activity against all bacteria and yeast tested. Their water extracts exhibited lower antimicrobial activity, though thyme aqueous extract was active only against S. aureus. The lowest concentration of antimicrobial activity (0.1% i.e., 1:1024) was obtained with thyme oil extract using Candida albicans. There was no significant difference in antimicrobial activity between clove obtained from Sri Lanka or Zanzibar or thyme obtained from Iran or Oman. Conclusion: Our experiment showed that the country of origin of the herbs has no effect on their antimicrobial activity. However, further work is necessary to ascertain why Candida albicans displayed remarkable degree of sensitivity with the extracts than all the other organisms test. PMID:21748125

  14. National Antimicrobial Resistance Monitoring System (NARMS) Program

    USDA-ARS?s Scientific Manuscript database

    The National Antimicrobial Resistance Monitoring System (NARMS) – Enteric Bacteria is a national public health surveillance system in the United States that tracks changes in the susceptibility of certain enteric bacteria to antimicrobial agents of human and veterinary medical importance. The NARMS ...

  15. Methods of Antimicrobial Coating of Diverse Materials

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of coating diverse substrate materials with antimicrobial agents have been developed. Originally intended to reduce health risks to astronauts posed by pathogenic microorganisms that can grow on surfaces in spacecraft, these methods could also be used on Earth for example, to ensure sterility of surgical inserts and other medical equipment. The methods involve, generally, chemical preparation of substrate surfaces to enable attachment of antimicrobial molecules to the substrate surfaces via covalent bonds. Substrate materials that have been treated successfully include aluminum, glass, a corrosion-resistant nickel alloy, stainless steel, titanium, and poly(tetrafluoroethylene). Antimicrobial agents that have been successfully immobilized include antibiotics, enzymes, bacteriocins, bactericides, and fungicides. A variety of linkage chem istries were employed. Activity of antimicrobial coatings against gram-positive bacteria, gram-negative bacteria, and fungi was demonstrated. Results of investigations indicate that the most suitable combination of antimicrobial agent, substrate, and coating method depends upon the intended application.

  16. Antimicrobial peptides: an alternative for innovative medicines?

    PubMed

    da Costa, João Pinto; Cova, Marta; Ferreira, Rita; Vitorino, Rui

    2015-03-01

    Antimicrobial peptides are small molecules with activity against bacteria, yeasts, fungi, viruses, bacteria, and even tumor cells that make these molecules attractive as therapeutic agents. Due to the alarming increase of antimicrobial resistance, interest in alternative antimicrobial agents has led to the exploitation of antimicrobial peptides, both synthetic and from natural sources. Thus, many peptide-based drugs are currently commercially available for the treatment of numerous ailments, such as hepatitis C, myeloma, skin infections, and diabetes. Initial barriers are being increasingly overcome with the development of cost-effective, more stable peptides. Herein, we review the available strategies for their synthesis, bioinformatics tools for the rational design of antimicrobial peptides with enhanced therapeutic indices, hurdles and shortcomings limiting the large-scale production of AMPs, as well as the challenges that the pharmaceutical industry faces on their use as therapeutic agents.

  17. Application of natural antimicrobials for food preservation.

    PubMed

    Tiwari, Brijesh K; Valdramidis, Vasilis P; O'Donnell, Colm P; Muthukumarappan, Kasiviswanathan; Bourke, Paula; Cullen, P J

    2009-07-22

    In this review, antimicrobials from a range of plant, animal, and microbial sources are reviewed along with their potential applications in food systems. Chemical and biochemical antimicrobial compounds derived from these natural sources and their activity against a range of pathogenic and spoilage microorganisms pertinent to food, together with their effects on food organoleptic properties, are outlined. Factors influencing the antimicrobial activity of such agents are discussed including extraction methods, molecular weight, and agent origin. These issues are considered in conjunction with the latest developments in the quantification of the minimum inhibitory (and noninhibitory) concentration of antimicrobials and/or their components. Natural antimicrobials can be used alone or in combination with other novel preservation technologies to facilitate the replacement of traditional approaches. Research priorities and future trends focusing on the impact of product formulation, intrinsic product parameters, and extrinsic storage parameters on the design of efficient food preservation systems are also presented.

  18. Developing Novel Antimicrobial and Antiviral Textile Products.

    PubMed

    Iyigundogdu, Zeynep Ustaoglu; Demir, Okan; Asutay, Ayla Burcin; Sahin, Fikrettin

    2017-03-01

    In conjunction with an increasing public awareness of infectious diseases, the textile industry and scientists are developing hygienic fabrics by the addition of various antimicrobial and antiviral compounds. In the current study, sodium pentaborate pentahydrate and triclosan are applied to cotton fabrics in order to gain antimicrobial and antiviral properties for the first time. The antimicrobial activity of textiles treated with 3 % sodium pentaborate pentahydrate, 0.03 % triclosan, and 7 % Glucapon has been investigated against a broad range of microorganisms including bacteria, yeast, and fungi. Moreover, modified cotton fabrics were tested against adenovirus type 5 and poliovirus type 1. According to the test results, the modified textile goods attained very good antimicrobial and antiviral properties. Thus, the results of the present study clearly suggest that sodium pentaborate pentahydrate and triclosan solution-treated textiles can be considered in the development of antimicrobial and antiviral textile finishes.

  19. Antimicrobial defense systems in saliva.

    PubMed

    van 't Hof, Wim; Veerman, Enno C I; Nieuw Amerongen, Arie V; Ligtenberg, Antoon J M

    2014-01-01

    The oral cavity is one of the most heavily colonized parts of our body. The warm, nutrient-rich and moist environment promotes the growth of a diverse microflora. One of the factors responsible for the ecological equilibrium in the mouth is saliva, which in several ways affects the colonization and growth of bacteria. In this paper, we discuss the various mechanisms by which the composition of the oral microflora is modulated by saliva. Saliva covers the oral hard and soft tissues with a conditioning film which governs the initial attachment of microorganisms, a crucial step in the setup of the oral microflora. It furthermore contains proteins which in the soluble phase bind to bacteria, blocking their adherence to surfaces. When the supply of nutrients is diminished, bacteria use salivary glycoproteins, especially high-molecular-weight mucins, as a source of complex carbohydrates, requiring a consortium of microorganisms for breakdown. In this way saliva promotes the complexity of the oral microflora, which in itself protects against overgrowth by few pathogenic species. Finally, saliva harbors a large panel of antimicrobial proteins which directly and indirectly inhibit uncontrolled outgrowth of bacteria. These include lactoferrin, lactoperoxidase, lysozyme and antimicrobial peptides. Under pathological conditions serum leakage occurs, and saliva mobilizes the humoral and cellular defense mechanisms in the blood. In sum, saliva favors the establishment of a highly diverse microflora, rather than a semisterile environment.

  20. Animal venoms as antimicrobial agents.

    PubMed

    Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

    2017-06-15

    Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Bacterial sensing of antimicrobial peptides.

    PubMed

    Otto, Michael

    2009-01-01

    Antimicrobial peptides (AMPs) form a crucial part of human innate host defense, especially in neutrophil phagosomes and on epithelial surfaces. Bacteria have a variety of efficient resistance mechanisms to human AMPs, such as efflux pumps, secreted proteases, and alterations of the bacterial cell surface that are aimed to minimize attraction of the typically cationic AMPs. In addition, bacteria have specific sensors that activate AMP resistance mechanisms when AMPs are present. The prototypical Gram-negative PhoP/PhoQ and the Gram-positive Aps AMP-sensing systems were first described and investigated in Salmonella typhimurium and Staphylococcus epidermidis, respectively. Both include a classical bacterial two-component sensor/regulator system, but show many structural, mechanistic, and functional differences. The PhoP/PhoQ regulon controls a variety of genes not necessarily limited to AMP resistance mechanisms, but apparently aimed to combat innate host defense on a broad scale. In contrast, the staphylococcal Aps system predominantly upregulates AMP resistance mechanisms, namely the D-alanylation of teichoic acids, inclusion of lysyl-phosphati-dylglycerol in the cytoplasmic membrane, and expression of the putative VraFG AMP efflux pump. Notably, both systems are crucial for virulence and represent possible targets for antimicrobial therapy. Copyright (c) 2009 S. Karger AG, Basel.

  2. Antimicrobial Peptides: Versatile Biological Properties

    PubMed Central

    Pushpanathan, Muthuirulan; Rajendhran, Jeyaprakash

    2013-01-01

    Antimicrobial peptides are diverse group of biologically active molecules with multidimensional properties. In recent past, a wide variety of AMPs with diverse structures have been reported from different sources such as plants, animals, mammals, and microorganisms. The presence of unusual amino acids and structural motifs in AMPs confers unique structural properties to the peptide that attribute for their specific mode of action. The ability of these active AMPs to act as multifunctional effector molecules such as signalling molecule, immune modulators, mitogen, antitumor, and contraceptive agent makes it an interesting candidate to study every aspect of their structural and biological properties for prophylactic and therapeutic applications. In addition, easy cloning and recombinant expression of AMPs in heterologous plant host systems provided a pipeline for production of disease resistant transgenic plants. Besides these properties, AMPs were also used as drug delivery vectors to deliver cell impermeable drugs to cell interior. The present review focuses on the diversity and broad spectrum antimicrobial activity of AMPs along with its multidimensional properties that could be exploited for the application of these bioactive peptides as a potential and promising drug candidate in pharmaceutical industries. PMID:23935642

  3. Antimicrobial peptide action on parasites.

    PubMed

    Torrent, Marc; Pulido, David; Rivas, Luis; Andreu, David

    2012-08-01

    Diseases caused by protozoan parasites can pose a severe thread to human health and are behind some serious neglected tropical diseases like malaria and leishmaniasis. Though several different drugs have been developed in order to eradicate these diseases, a successful candidate has not yet been discovered. Among the most active compounds tested, antimicrobial peptides (AMPs) are particularly appealing because of their wide spectrum of action. AMPs have been described to perturb protozoan homeostasis by disrupting the cellular membranes but also by interfering with key processes in the parasite metabolism. In this review we describe the diverse mechanisms of action of AMPs on protozoan targets and how they can be exploited to treat diseases. Moreover, we describe with detail the antimicrobial action of AMPs on two major parasitical infections: leishmaniasis and malaria. All the features reviewed here show that AMPs are promising drugs to target protozoan parasites and that further understanding of the mechanism of action of these compounds will lead to improved drugs that could be worth to test in a clinical phase.

  4. Antimicrobial outcomes in plasma medicine

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas P.; Stalder, Kenneth R.; Woloszko, Jean

    2015-03-01

    Plasma is referred to as the fourth state of matter and is frequently generated in the environment of a strong electric field. The result consists of highly reactive species--ions, electrons, reactive atoms and molecules, and UV radiation. Plasma Medicine unites a number of fields, including Physics, Plasma Chemistry, Cell Biology, Biochemistry, and Medicine. The treatment modality utilizes Cold Atmospheric Plasma (CAP), which is able to sterilize and treat microbes in a nonthermal manner. These gas-based plasma systems operate at close to room temperature and atmospheric pressure, making them very practical for a range of potential treatments and are highly portable for clinical use throughout the health care system. The hypothesis is that gas based plasma kills bacteria, fungus, and viruses but spares mammalian cells. This paper will review systematic work which shows examples of systems and performance in regards to antimicrobial effects and the sparing of mammalian cells. The mechanism of action will be discussed, as well as dosing for the treatment of microbial targets, including sterilization processes, another important healthcare need. In addition, commercial systems will be overviewed and compared, along with evidence-based, patient results. The range of treatments cover wound treatment and biofilms, as well as antimicrobial treatment, with little chance for resistance and tolerance, as in drug regimens. Current clinical studies include applications in dentistry, food treatment, cancer treatment, wound treatment for bacteria and biofilms, and systems to combat health care related infections.

  5. Mechanical Analysis of an SM 2 Blk IV restrained firing within a concentric canister launcher test unit

    SciTech Connect

    Kassner, M C; Kennedy, T C; Puttapitukporn, T; Rosen, R S

    1999-03-01

    The Office of Naval Research (ONR) and PMS512 have undertaken a program to develop a new Vertical Launching System (VLS) for future generation ships, such as the DD-21 Destroyer. The Naval Sea Systems Command Combat Weapons Program (NAVSEA 05K) and Naval Surface Warfare Center Dahlgren Division (NSWCDD) are working jointly with industry and universities to develop one such launcher design, the Concentric Canister Launcher (CCL). The basic CCL design consists of a tube made of two concentric cylinders; one end is open, the other is sealed with a hemispherical end cap. During firing, the missile exhaust gas is turned 180 degrees by the hemispherical end cap and flows through the annular space between inner and outer cylinders. Depending on the missile utilized and the particular service environment of the CCL, maximum temperatures within the cylinder material have been calculated to exceed 2000 F. In an earlier study [1], the authors determined the high temperature mechanical properties of several candidate alloys being considered for fabrication of the CCL. This study [1] found that, of these candidate materials, titanium alloys exhibit higher yield stresses than that of 316L stainless steel at temperatures up to about 1000 F; above 1500 F, the yield stress of 316L stainless steel is comparable to those of the titanium alloys. The 316L stainless steel was found to strain harden (increase its flow stress with increasing strain) at temperatures up to about 1800 F. The ability of the 316L stainless steel to strain harden at high temperatures may provide an added margin of safety for engineering design of the CCL. The objective of the current study was to perform a computer simulation of the structural response of a CCL during a restrained firing, one in which a SM-2 Blk IV missile would fail to exit the canister. A finite element model of the inner cylinder, outer cylinder, end rings (mounting brackets), and lateral restraints in the uptake was constructed. An elastic

  6. Heterogeneous Exhumation of Mid-crustal Rocks along the Hayes Restraining Bend of the Central Denali Fault

    NASA Astrophysics Data System (ADS)

    Tait, L.; Roeske, S.; Mookerjee, M.; Benowitz, J.; Huff, C. J.

    2016-12-01

    The Denali fault has been continuously active as a dextral-oblique thrust fault since 25-27 Ma, which has resulted locally in rocks being exhumed from below the brittle-ductile transition. The youngest 40Ar/39Ar cooling ages (as young as 15 Ma for mica and 6 Ma for K-feldspar) occur in the eastern Alaska Range, within a narrow zone on the north side of the Hayes restraining bend. This pattern of maximum exhumation (> 11 km) near the apex of the bend supports the idea that rocks to the north of the fault have been relatively fixed with respect to the bend since the early Miocene, and the strain history should record exhumation in a dextral transpressive system. Vorticity analyses provide an opportunity to better understand the mechanisms for exhumation along this section of the Denali fault and were carried out on samples of both orthogneiss and quartz-rich metasedimentary rock from sites around the bend. The kinematic vorticity number (Wk) for each sample was determined using the Vorticity Diagram method and the EBSD-based Lattice Preferred Orientation method. Most of the rocks in this area display subvertical to steeply N-dipping foliations subparallel to the Denali fault with W to NW trending, moderately plunging mineral lineations. In contrast, the long axis of the strain ellipsoids determined for these samples trend overall to the NE. This suggests that lineations in this region are not indicative of the maximum stretching direction recorded by the strain ellipsoid. Preliminary vorticity results suggest that there are no systematic differences around the bend or between rock types and that deformation in this section of the fault is generally dominated by pure shear (Wk < 0.71). C-axis pole figures generated from EBSD yield predominantly single girdle patterns, which indicate that some component of simple shear is also preserved. Girdles from samples east of the bend are consistent with dextral motion on the Denali fault, but girdles from samples to the west

  7. A dark past, a restrained present, and an apocalyptic future: time perspective, personality, and life satisfaction among anorexia nervosa patients.

    PubMed

    Garcia, Danilo; Granjard, Alexandre; Lundblad, Suzanna; Archer, Trevor

    2017-01-01

    time dimensions predicted life satisfaction among patients. Anorexia patients were less satisfied with life despite being more conscientious, social, and agreeable than controls. Moreover, compared to controls, patients had an unbalanced time perspective: a dark view of the past (i.e., high past negative), a restrained present (i.e., low present hedonistic) and an apocalyptic view of the future (i.e., high present fatalistic). It is plausible to suggest that, therapeutic interventions should focus on empowering patients to cultivate a sentimental and positive view of the past (i.e., high past positive) and the desire to experience pleasure without concern for future consequences (i.e., high present hedonistic) so that they can make self-directed and flexible choices for their own well-being. Such interventions might have effects on life satisfaction beyond the patients' temperamental disposition.

  8. A dark past, a restrained present, and an apocalyptic future: time perspective, personality, and life satisfaction among anorexia nervosa patients

    PubMed Central

    Granjard, Alexandre; Lundblad, Suzanna; Archer, Trevor

    2017-01-01

    positive and present hedonistic time dimensions predicted life satisfaction among patients. Conclusion Anorexia patients were less satisfied with life despite being more conscientious, social, and agreeable than controls. Moreover, compared to controls, patients had an unbalanced time perspective: a dark view of the past (i.e., high past negative), a restrained present (i.e., low present hedonistic) and an apocalyptic view of the future (i.e., high present fatalistic). It is plausible to suggest that, therapeutic interventions should focus on empowering patients to cultivate a sentimental and positive view of the past (i.e., high past positive) and the desire to experience pleasure without concern for future consequences (i.e., high present hedonistic) so that they can make self-directed and flexible choices for their own well-being. Such interventions might have effects on life satisfaction beyond the patients’ temperamental disposition. PMID:28929023

  9. Experimental determination of optimal root-mean-square deviations of macromolecular bond lengths and angles from their restrained ideal values.

    PubMed

    Tickle, Ian J

    2007-12-01

    A number of inconsistencies are apparent in the recent research paper by Jaskolski et al. [(2007), Acta Cryst. D63, 611-620] concerning their recommendations for the values of the magnitude and resolution-dependence of the root-mean-square deviations (RMSDs) of bond lengths and angles from their restrained ideal values in macromolecular refinement, as well as their suggestions for the use of variable standard uncertainties dependent on atomic displacement parameters (ADPs) and occupancies. Whilst many of the comments and suggestions in the paper regarding updates for the ideal geometry values proposed by Engh and Huber are entirely reasonable and supported by the experimental evidence, the recommendations concerning the optimal values of RMSDs appear to be in conflict with previous experimental and theoretical work in this area [Tickle et al. (1998), Acta Cryst. D54, 243-252] and indeed appear to be based on a misunderstanding of the distinction between RMSD and standard uncertainty (SU). In contrast, it is proposed here that the optimal values of all desired weighting parameters, in particular the weighting parameters for the ADP differences and for the diffraction terms, be estimated by the purely objective procedure of maximizing the experiment-based log(free likelihood). In principle, this allows all weighting parameters that are not known accurately a priori to be scaled globally, relative to those that are known accurately, for an optimal refinement. The RMS Z score (RMSZ) is recommended as a more satisfactory statistic than the RMSD to assess the extent to which the geometry deviates from the ideal values and a theoretical rationale for the results obtained is presented in which the optimal RMSZ is identified as the calculated versus true Z-score correlation coefficient, the latter being a monotonic function of the resolution cutoff of the data. Regarding the proposal to use variable standard uncertainties, it is suggested that any departure from the current

  10. An Interprofessional Curriculum on Antimicrobial Stewardship Improves Knowledge and Attitudes Toward Appropriate Antimicrobial Use and Collaboration.

    PubMed

    MacDougall, Conan; Schwartz, Brian S; Kim, Lisa; Nanamori, Mari; Shekarchian, Sharmin; Chin-Hong, Peter V

    2017-01-01

    Inappropriate antimicrobial use can threaten patient safety and is the focus of collaborative physician and pharmacist antimicrobial stewardship teams. However, antimicrobial stewardship is not comprehensively taught in medical or pharmacy school curricula. Addressing this deficiency can teach an important concept as well as model interprofessional healthcare. We created an antimicrobial stewardship curriculum consisting of an online learning module and workshop session that combined medical and pharmacy students, with faculty from both professions. Learners worked through interactive, branched-logic clinical cases relating to appropriate antimicrobial use. We surveyed participants before and after the curriculum using validated questions to assess knowledge and attitudes regarding antimicrobial stewardship and interprofessional collaboration. Results were analyzed using paired χ(2) and t tests and mixed-effects logistic regression. Analysis was performed with the 745 students (425 medical students, 320 pharmacy students) who completed both pre- and postcurriculum surveys over 3 years. After completing the curriculum, significantly more students perceived that they were able to describe the role of each profession in appropriate antimicrobial use (34% vs 82%, P < .001), communicate in a manner that engaged the interprofessional team (75% vs 94%, P < .001), and describe collaborative approaches to appropriate antimicrobial use (49% vs 92%, P < .001). Student favorability ratings were high for the online learning module (85%) and small group workshop (93%). A curriculum on antimicrobial stewardship consisting of independent learning and an interprofessional workshop significantly increased knowledge and attitudes towards collaborative antimicrobial stewardship among preclinical medical and pharmacy students.

  11. An Interprofessional Curriculum on Antimicrobial Stewardship Improves Knowledge and Attitudes Toward Appropriate Antimicrobial Use and Collaboration

    PubMed Central

    Schwartz, Brian S.; Kim, Lisa; Nanamori, Mari; Shekarchian, Sharmin; Chin-Hong, Peter V.

    2017-01-01

    Abstract Background. Inappropriate antimicrobial use can threaten patient safety and is the focus of collaborative physician and pharmacist antimicrobial stewardship teams. However, antimicrobial stewardship is not comprehensively taught in medical or pharmacy school curricula. Addressing this deficiency can teach an important concept as well as model interprofessional healthcare. Methods. We created an antimicrobial stewardship curriculum consisting of an online learning module and workshop session that combined medical and pharmacy students, with faculty from both professions. Learners worked through interactive, branched-logic clinical cases relating to appropriate antimicrobial use. We surveyed participants before and after the curriculum using validated questions to assess knowledge and attitudes regarding antimicrobial stewardship and interprofessional collaboration. Results were analyzed using paired χ2 and t tests and mixed-effects logistic regression. Results. Analysis was performed with the 745 students (425 medical students, 320 pharmacy students) who completed both pre- and postcurriculum surveys over 3 years. After completing the curriculum, significantly more students perceived that they were able to describe the role of each profession in appropriate antimicrobial use (34% vs 82%, P < .001), communicate in a manner that engaged the interprofessional team (75% vs 94%, P < .001), and describe collaborative approaches to appropriate antimicrobial use (49% vs 92%, P < .001). Student favorability ratings were high for the online learning module (85%) and small group workshop (93%). Conclusions. A curriculum on antimicrobial stewardship consisting of independent learning and an interprofessional workshop significantly increased knowledge and attitudes towards collaborative antimicrobial stewardship among preclinical medical and pharmacy students. PMID:28480231

  12. Antimicrobial use and antimicrobial resistance in nosocomial pathogens at a tertiary care hospital in Pune

    PubMed Central

    Nair, Velu; Sharma, Dinesh; Sahni, A.K.; Grover, Naveen; Shankar, S.; Jaiswal, S.S.; Dalal, S.S.; Basannar, D.R.; Phutane, Vivek S.; Kotwal, Atul; Gopal Rao, G.; Batura, Deepak; Venkatesh, M.D.; Sinha, Tapan; Kumar, Sushil; Joshi, D.P.

    2015-01-01

    Background Resistance to antimicrobial agents is emerging in wide variety of nosocomial and community acquired pathogens. Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance. This study was conducted to gain insight into the prevalent antimicrobial prescribing practices, and antimicrobial resistance pattern in nosocomial pathogens at a tertiary care hospital in Pune, India. Methods Series of one day cross sectional point prevalence surveys were carried out on four days between March and August 2014. All eligible in patients were included in the study. A structured data entry form was used to collect the data for each patient. Relevant samples were collected for microbiological examination from all the clinically identified hospital acquired infection cases. Results 41.73% of the eligible patients (95% CI: 39.52–43.97) had been prescribed at least one antimicrobial during their stay in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%). Majority of the organisms isolated from Hospital acquired infection (HAI cases) were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams. Conclusion There is need to have regular antimicrobial susceptibility surveillance and dissemination of this information to the clinicians. In addition, emphasis on the rational use of antimicrobials, antimicrobial rotation and strict adherence to the standard treatment guidelines is very essential. PMID:25859071

  13. Antimicrobial use and antimicrobial resistance in nosocomial pathogens at a tertiary care hospital in Pune.

    PubMed

    Nair, Velu; Sharma, Dinesh; Sahni, A K; Grover, Naveen; Shankar, S; Jaiswal, S S; Dalal, S S; Basannar, D R; Phutane, Vivek S; Kotwal, Atul; Gopal Rao, G; Batura, Deepak; Venkatesh, M D; Sinha, Tapan; Kumar, Sushil; Joshi, D P

    2015-04-01

    Resistance to antimicrobial agents is emerging in wide variety of nosocomial and community acquired pathogens. Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance. This study was conducted to gain insight into the prevalent antimicrobial prescribing practices, and antimicrobial resistance pattern in nosocomial pathogens at a tertiary care hospital in Pune, India. Series of one day cross sectional point prevalence surveys were carried out on four days between March and August 2014. All eligible in patients were included in the study. A structured data entry form was used to collect the data for each patient. Relevant samples were collected for microbiological examination from all the clinically identified hospital acquired infection cases. 41.73% of the eligible patients (95% CI: 39.52-43.97) had been prescribed at least one antimicrobial during their stay in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%). Majority of the organisms isolated from Hospital acquired infection (HAI cases) were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams. There is need to have regular antimicrobial susceptibility surveillance and dissemination of this information to the clinicians. In addition, emphasis on the rational use of antimicrobials, antimicrobial rotation and strict adherence to the standard treatment guidelines is very essential.

  14. Clinical and Antibiofilm Efficacy of Antimicrobial Hydrogels.

    PubMed

    Finnegan, Simon; Percival, Steven L

    2015-07-01

    Significance: Hydrogels have been shown to have a significant role to play in wound healing. Hydrogels are used to assist in the management of dry, sloughy, or necrotic wounds. However, recent scientific evidence has shown that biofilms delay wound healing and increase a wound propensity to infection. It is therefore essential that hydrogels incorporating antimicrobials demonstrate efficacy on biofilms. Consequently, it is the aim of this article to review the efficacy of hydrogels, incorporating antimicrobials, on wounds with specific reference to their efficacy on biofilms. Recent Advances: Technologies being developed for the management of wounds are rapidly expanding. In particularly next-generation hydrogels, incorporating copolymers, have been reported to enable the smart release of antimicrobials. This has led to the development of a more tailored patient-specific antimicrobial hydrogel therapy. Critical Issues: Evidence relating to the efficacy of hydrogels, incorporating antimicrobials, on biofilms within both the in vitro and in vivo environments is lacking. Future Direction: Studies that investigate the efficacy of antimicrobial hydrogel wound dressings on both in vivo and in vitro biofilms are important. However, there is a significant need for better and more reproducible in vivo biofilm models. Until this is possible, data generated from appropriate and representative in vitro models will help to assist researchers and clinicians in evaluating antimicrobial and antibiofilm hydrogel technology for the extrapolation of efficacy data relevant to biofilms present in the in vivo environment.

  15. Clinical and Antibiofilm Efficacy of Antimicrobial Hydrogels

    PubMed Central

    Finnegan, Simon; Percival, Steven L.

    2015-01-01

    Significance: Hydrogels have been shown to have a significant role to play in wound healing. Hydrogels are used to assist in the management of dry, sloughy, or necrotic wounds. However, recent scientific evidence has shown that biofilms delay wound healing and increase a wound propensity to infection. It is therefore essential that hydrogels incorporating antimicrobials demonstrate efficacy on biofilms. Consequently, it is the aim of this article to review the efficacy of hydrogels, incorporating antimicrobials, on wounds with specific reference to their efficacy on biofilms. Recent Advances: Technologies being developed for the management of wounds are rapidly expanding. In particularly next-generation hydrogels, incorporating copolymers, have been reported to enable the smart release of antimicrobials. This has led to the development of a more tailored patient-specific antimicrobial hydrogel therapy. Critical Issues: Evidence relating to the efficacy of hydrogels, incorporating antimicrobials, on biofilms within both the in vitro and in vivo environments is lacking. Future Direction: Studies that investigate the efficacy of antimicrobial hydrogel wound dressings on both in vivo and in vitro biofilms are important. However, there is a significant need for better and more reproducible in vivo biofilm models. Until this is possible, data generated from appropriate and representative in vitro models will help to assist researchers and clinicians in evaluating antimicrobial and antibiofilm hydrogel technology for the extrapolation of efficacy data relevant to biofilms present in the in vivo environment. PMID:26155382

  16. The role of poverty in antimicrobial resistance.

    PubMed

    Planta, Margaret B

    2007-01-01

    Antimicrobial resistance is a worldwide problem that has deleterious long-term effects as the development of drug resistance outpaces the development of new drugs. Poverty has been cited by the World Health Organization as a major force driving the development of antimicrobial resistance. In developing countries, factors such as inadequate access to effective drugs, unregulated dispensing and manufacture of antimicrobials, and truncated antimicrobial therapy because of cost are contributing to the development of multidrug-resistant organisms. Within the United States, poverty-driven practices such as medication-sharing, use of "leftover" antibiotics, and the purchase and use of foreign-made drugs of questionable quality are likely contributing to antimicrobial resistance. However, there is currently a dearth of studies in the United States analyzing the socioeconomic and behavioral factors behind antimicrobial resistance in United States communities. Further studies of these factors, with an emphasis on poverty-driven practices, need to be undertaken in order to fully understand the problem of antimicrobial resistance in the United States and to develop effective intervention to combat this problem.

  17. Antimicrobial Dose in Obese Patient

    PubMed Central

    Kassab, Sawsan; Syed Sulaiman, Syed Azhar; Abdul Aziz, Noorizan

    2007-01-01

    Introduction Obesity is a chronic disease that has become one of major public health issue in Malaysia because of its association with other disease states including cardiovascular disease and diabetes. Despite continuous efforts to educate the public about the health risks associated with obesity, prevalence of the disease continues to increase. Dosing of many medications are based on weight, limited data are available on how antimicrobial agents should be dosed in obesity. The aim of this case presentation is to discuss dose of antibiotic in obese patient. Case report: Patient: GMN, Malay, Female, 45 year old, 150kg, transferred from medical ward to ICU with problems of fever, orthopnea, sepsis secondary to nosocomial pneumonia. She was admitted to hospital a week ago for SOB on exertion, cyanosis, mildly dyspneic, somasthenia, bilateral ankle swelling. There was no fever, cough, chest pain, clubbing, flapping tremor. Her grand father has pre-morbid history of obesity, HPT, DM and asthma. She was non alcoholic, smoker, and not on diet control. The diagnosis Pickwickian syndrome was made. Patient was treated with IV Dopamine 11mcg/kg/min, IV Morphine 4mg/h. IV GTN 15mcg/min, IV Ca gluconate 10g/24h for 3/7, IV Zantac 50mg tds, IV Augmentin 1.2g tds, IV Lasix 40mg od, IV Plasil 10mg tds, S.c heparin 5000IU bd. patient become stable and moved to medical ward to continue her treatment. Discussion: The altered physiologic function seen in obese patients is a concern in patients receiving antimicrobial agents because therapeutic outcomes depend on achieving a minimum inhibitory concentration (MIC). The therapeutic effect of any drug can be altered when any of the 4 pharmacokinetic processes (absorption, distribution, metabolism, or elimination) are altered. Decreased blood flow rates and increased renal clearance in obese patients can affect drug distribution and elimination. Changes in serum protein levels can change the metabolism and distribution of drugs that are

  18. Human Antimicrobial Peptides and Proteins

    PubMed Central

    Wang, Guangshun

    2014-01-01

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to

  19. Recent Advances in Antimicrobial Polymers: A Mini-Review

    PubMed Central

    Huang, Keng-Shiang; Yang, Chih-Hui; Huang, Shu-Ling; Chen, Cheng-You; Lu, Yuan-Yi; Lin, Yung-Sheng

    2016-01-01

    Human safety and well-being is threatened by microbes causing numerous infectious diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising antimicrobial strategy for fighting pathogens and have received considerable attention in both academic and industrial research. This mini-review presents the advances made in antimicrobial polymers since 2013. Antimicrobial mechanisms exhibiting either passive or active action and polymer material types containing bound or leaching antimicrobials are introduced. This article also addresses the applications of these antimicrobial polymers in the medical, food, and textile industries. PMID:27657043

  20. Recent Advances in Antimicrobial Polymers: A Mini-Review.

    PubMed

    Huang, Keng-Shiang; Yang, Chih-Hui; Huang, Shu-Ling; Chen, Cheng-You; Lu, Yuan-Yi; Lin, Yung-Sheng

    2016-09-20

    Human safety and well-being is threatened by microbes causing numerous infectious diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising antimicrobial strategy for fighting pathogens and have received considerable attention in both academic and industrial research. This mini-review presents the advances made in antimicrobial polymers since 2013. Antimicrobial mechanisms exhibiting either passive or active action and polymer material types containing bound or leaching antimicrobials are introduced. This article also addresses the applications of these antimicrobial polymers in the medical, food, and textile industries.

  1. Nanostructures for delivery of natural antimicrobials in food.

    PubMed

    Lopes, Nathalie Almeida; Brandelli, Adriano

    2017-04-10

    Natural antimicrobial compounds are a topic of utmost interest in food science due to the increased demand for safe and high-quality foods with minimal processing. The use of nanostructures is an interesting alternative to protect and delivery antimicrobials in food, also providing controlled release of natural compounds such as bacteriocins and antimicrobial proteins, and also for delivery of plant derived antimicrobials. A diversity of nanostructures are capable of trapping natural antimicrobials maintaining the stability of substances that are frequently sensitive to food processing and storage conditions. This article provides an overview on natural antimicrobials incorporated in nanostructures, showing an effective antimicrobial activity on a diversity of food spoilage and pathogenic microorganisms.

  2. De Novo Design of Potent Antimicrobial Peptides

    PubMed Central

    Frecer, V.; Ho, B.; Ding, J. L.

    2004-01-01

    Lipopolysaccharide (LPS), shed by gram-negative bacteria during infection and antimicrobial therapy, may lead to lethal endotoxic shock syndrome. A rational design strategy based on the presumed mechanism of antibacterial effect was adopted to design cationic antimicrobial peptides capable of binding to LPS through tandemly repeated sequences of alternating cationic and nonpolar residues. The peptides were designed to achieve enhanced antimicrobial potency due to initial bacterial membrane binding with a reduced risk of endotoxic shock. The peptides designed displayed binding affinities to LPS and lipid A (LA) in the low micromolar range and by molecular modeling were predicted to form amphipathic β-hairpin-like structures when they bind to LPS or LA. They also exhibited strong effects against gram-negative bacteria, with MICs in the nanomolar range, and low cytotoxic and hemolytic activities at concentrations significantly exceeding their MICs. Quantitative structure-activity relationship (QSAR) analysis of peptide sequences and their antimicrobial, cytotoxic, and hemolytic activities revealed that site-directed substitutions of residues in the hydrophobic face of the amphipathic peptides with less lipophilic residues selectively decrease the hemolytic effect without significantly affecting the antimicrobial or cytotoxic activity. On the other hand, the antimicrobial effect can be enhanced by substitutions in the polar face with more polar residues, which increase the amphipathicity of the peptide. On the basis of the QSARs, new analogs that have strong antimicrobial effects but that lack hemolytic activity can be proposed. The findings highlight the importance of peptide amphipathicity and allow a rational method that can be used to dissociate the antimicrobial and hemolytic effects of cationic peptides, which have potent antimicrobial properties, to be proposed. PMID:15328096

  3. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats

    PubMed Central

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H.; Desai, S.D.

    2016-01-01

    Introduction Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. Aim To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. Materials and Methods Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. Results Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. Conclusion Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels. PMID:27656428

  4. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats.

    PubMed

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H; Desai, S D; Das, Kusal Kanti

    2016-08-01

    Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels.

  5. The undue influence of shape and weight on self-evaluation in anorexia nervosa, bulimia nervosa and restrained eaters: a combined ERP and behavioral study.

    PubMed

    Blechert, J; Ansorge, U; Beckmann, S; Tuschen-Caffier, B

    2011-01-01

    Current theories and nosology assume that the self-evaluation (SE) of individuals with eating disorders (EDs) is unduly influenced by body shape and weight. However, experimental data supporting this link are scarce, and it is not specified which subdomains of SE might be affected. We studied patients with anorexia nervosa (AN), bulimia nervosa (BN) and healthy controls (HC) with an affective priming (AP) procedure (Study 1) to unveil explicit and implicit associations between shape/weight and SE. We used weight/shape-related prime sentences, complemented by affectively congruent and incongruent target words from two SE domains. AP effects were assessed by event-related potentials (ERPs), reaction times (RTs) and subjective ratings. The ratings were also assessed (Study 2) in undergraduate restrained (RES) and unrestrained eaters (UNRES). Study 1 demonstrated stronger AP effects in both ED groups compared to HC on RTs and subjective ratings. ERPs showed AP effects only in the BN group. Restrained eaters showed similar, albeit less pronounced, priming effects on subjective ratings. ED patients associate shape/weight concerns with the non-appearance-related SE domains of interpersonal relationships and achievement/performance. These associations seem to be encoded deeper in BN patients relative to the other groups. Links between shape/weight and SE explain how body dissatisfaction impacts on self-esteem and mood in ED. The existence of similar associations in restrained eaters supports a continuum model according to which increasing associations between shape/weight and SE go along with increasing levels of ED symptoms.

  6. Antimicrobial properties of nitric oxide and its application in antimicrobial formulations and medical devices.

    PubMed

    Jones, Mitchell Lawrence; Ganopolsky, Jorge Gabriel; Labbé, Alain; Wahl, Christopher; Prakash, Satya

    2010-09-01

    This review describes the antimicrobial properties of nitric oxide (NO) and its application as an antimicrobial agent in different formulations and medical devices. We depict the eukaryotic biosynthesis of NO and its physiologic functions as a cell messenger and as an antimicrobial agent of the cell-mediated immune response. We analyze the antimicrobial activity of NO and the eukaryotic protective mechanisms against NO for the purpose of delineating the therapeutic NO dosage range required for an efficacious and safe antimicrobial activity. We also examine the role of NO produced by virulent bacteria in lessening the efficacy of traditional antimicrobials. In addition, we discuss the efficacy of NO in the healing of infected wounds, describing different NO-producing devices by category, analyzing therapeutic levels, duration of NO production, as well as commercial considerations. Finally, we provide current and future prospects for the design and use of NO-producing devices.

  7. Naturally occurring antimicrobials for minimally processed foods.

    PubMed

    Davidson, P Michael; Critzer, Faith J; Taylor, T Matthew

    2013-01-01

    Natural antimicrobials are gaining increased interest from researchers and food manufacturers alike seeking to discover label-friendly alternatives to the widely implemented synthetic compounds. Naturally occurring antimicrobials can be applied directly to food to protect food quality, extend food shelf life by inhibiting or inactivating spoilage microorganisms, and improve food safety by inhibiting or inactivating food-borne pathogens. There are a great number of natural antimicrobials derived from animal, plant, and microbial sources. This manuscript reviews their efficacy against spoilage and pathogenic organisms, their methods of evaluation, and their application in various foods as well as the development of novel delivery systems and incorporation with other hurdles.

  8. [Antimicrobial peptide in dentisty. Literature review].

    PubMed

    Sato, F Simain; Rompen, E; Heinen, E

    2009-12-01

    The use of antimicrobial substances has contributed to the development of multiple antimicrobial resistances (1), challenging the pharmaceutical industry to develop with new, innovative, and effective molecules. Discovered around 1980, molecules called natural antimicrobial peptides (AMPs) appear to hold great potential for the treatment of infections. These cationic peptides are able to stop the bacterial development and to control infections. The purpose of this review is to help improve the understanding of the way AMPs operate in the context of the development of new cures against viruses, bacteria, and mushrooms found in the human body in general and in the oral cavity in particular.

  9. Comparative evaluation of antimicrobials for textile applications.

    PubMed

    Windler, Lena; Height, Murray; Nowack, Bernd

    2013-03-01

    Many antimicrobial technologies are available for textiles. They may be used in many different textile applications to prevent the growth of microorganisms. Due to the biological activity of the antimicrobial compounds, the assessment of the safety of these substances is an ongoing subject of research and regulatory scrutiny. This review aims to give an overview on the main compounds used today for antimicrobial textile functionalization. Based on an evaluation of scientific publications, market data as well as regulatory documents, the potential effects of antimicrobials on the environment and on human health were considered and also life cycle perspectives were taken into account. The characteristics of each compound were summarized according to technical, environmental and human health criteria. Triclosan, silane quaternary ammonium compounds, zinc pyrithione and silver-based compounds are the main antimicrobials used in textiles. The synthetic organic compounds dominate the antimicrobials market on a weight basis. On the technical side the application rates of the antimicrobials used to functionalize a textile product are an important parameter with treatments requiring lower dosage rates offering clear benefits in terms of less active substance required to achieve the functionality. The durability of the antimicrobial treatment has a strong influence on the potential for release and subsequent environmental effects. In terms of environmental criteria, all compounds were rated similarly in effective removal in wastewater treatment processes. The extent of published information about environmental behavior for each compound varies, limiting the possibility for an in-depth comparison of all textile-relevant parameters across the antimicrobials. Nevertheless the comparative evaluation showed that each antimicrobial technology has specific risks and benefits that should be taken into account in evaluating the suitability of different antimicrobial products. The

  10. Antimicrobial resistance of enteric bacteria among ceftiofur treated and non-antimicrobial treated co-mingled pasture beef cows

    USDA-ARS?s Scientific Manuscript database

    Concerns have been raised that antimicrobial use in food animal production considerably increases antimicrobial resistance in bacteria. Due to their longevity, pasture beef cows are likely to be exposed to different antimicrobials that may create favorable conditions for antimicrobial resistant bact...

  11. Antimicrobial peptides of multicellular organisms

    NASA Astrophysics Data System (ADS)

    Zasloff, Michael

    2002-01-01

    Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

  12. Signal restoration method for restraining the range walk error of Geiger-mode avalanche photodiode lidar in acquiring a merged three-dimensional image.

    PubMed

    Xu, Lu; Zhang, Yu; Zhang, Yong; Wu, Long; Yang, Chenghua; Yang, Xu; Zhang, Zijing; Zhao, Yuan

    2017-04-10

    The fluctuation in the number of signal photoelectrons will cause a range walk error in a Geiger-mode avalanche photodiode (Gm-APD) lidar, which significantly depends on the target intensity. For a nanosecond-pulsed laser, the range walk error of traditional time-of-flight will cause deterioration. A new signal restoration method, based on the Poisson probability response model and the center-of-mass algorithm, is proposed to restrain the range walk error. We obtain a high-precision depth and intensity merged 3D image using this method. The range accuracy is 0.6 cm, and the intensity error is less than 3%.

  13. Optimizing Antimicrobial Susceptibility Test Reporting

    PubMed Central

    Schreckenberger, Paul C.; Binnicker, Matthew J.

    2011-01-01

    A meeting of clinical microbiologists, representing a diverse group of practice settings, together with representatives from industry partners, discussed the pitfalls of current practices for testing and reporting antimicrobial susceptibility test results. The participants in this session identified several needs. Regarding what antibiotics to test, the discussants noted that the CLSI M100 documents must be readily accessible to all those who need them and presented in a way that is easily understood. Engineering controls (e.g., software programs) are needed that incorporate intrinsic resistance and susceptibility information and contain pathways that would allow the reporting of antibiotics for only those body locations where the antibiotic reaches therapeutic concentrations. These programs should be linked with the patient electronic medical record (EMR) and flag the physician or clinical pharmacist using an active alert messenger when testing reveals that the antibiotic(s) that the patient is receiving may not be optimal or de-escalation of the antibiotic treatment regimen is indicated. Guidelines for the practice of cascade reporting are needed and should be developed to assist laboratories in the identification and reporting of therapeutic and cost-effective antimicrobials. Personalized antibiotic reporting (PAR) software programs are needed that would deduce the optimal antibiotic for each individual patient based on a number of clinical and laboratory features. These would include the following: (i) organism identification; (ii) MIC; (iii) patient-specific factors such as weight, immune status, allergies, creatinine clearance, and albumin level; (iv) site of infection; (v) desired method of dosing (bolus versus continuous infusion); (vi) patient convenience (oral versus intravenous); (vii) drug interactions; and (viii) cost.

  14. Antimicrobial Peptides in Human Sepsis

    PubMed Central

    Martin, Lukas; van Meegern, Anne; Doemming, Sabine; Schuerholz, Tobias

    2015-01-01

    Nearly 100 years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1–3 and human beta-defensins (HBDs) 1–3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1–3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1–3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1–11 (hLF 1–11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections

  15. Availability and estimates of veterinary antimicrobial use in British Columbia

    PubMed Central

    2004-01-01

    Abstract The amount of antimicrobial use is a significant selection pressure that alters the frequency of antimicrobial resistance. This paper summarizes attempts to estimate the weight of antimicrobial purchases in British Columbia for use in animals. The data reported here do not capture all sources of veterinary antimicrobial use in British Columbia. This paper highlights how information deficits on veterinary drug use complicate the development of an evidence-based policy framework for combating antimicrobial resistance. PMID:15144102

  16. Antimicrobial activity of human islet amyloid polypeptides: an insight into amyloid peptides' connection with antimicrobial peptides.

    PubMed

    Wang, Lan; Liu, Qian; Chen, Jin-Chun; Cui, Yi-Xian; Zhou, Bing; Chen, Yong-Xiang; Zhao, Yu-Fen; Li, Yan-Mei

    2012-07-01

    Human islet amyloid polypeptide (hIAPP) shows an antimicrobial activity towards two types of clinically relevant bacteria. The potency of hIAPP varies with its aggregation states. Circular dichroism was employed to determine the interaction between hIAPP and bacteria lipid membrane mimic. The antimicrobial activity of each aggregate species is associated with their ability to induce membrane disruption. Our findings provide new evidence revealing the antimicrobial activity of amyloid peptide, which suggest a possible connection between amyloid peptides and antimicrobial peptides.

  17. Notification: Evaluation of the Antimicrobial Testing Program

    EPA Pesticide Factsheets

    Project #OPE-FY16-0001, August 26, 2015. The OIG’s objective is to determine whether the Antimicrobial Testing Program ensures the efficacy of EPA-registered hospital sterilants, disinfectants and tuberculocides.

  18. Antimicrobial-Coated Granules for Disinfecting Water

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

  19. Antimicrobial preservative effectiveness of natural peptide antibiotics.

    PubMed

    Kamysz, Wojciech; Turecka, Katarzyna

    2005-01-01

    The constantly growing resistance of microbes to drugs and other substances which fight microbial infections leads to search for new antimicrobial substances. Among substances which attract the scientists attention are antimicrobial peptides. Such compounds are quite common in nature and belong to the most important elements of the innate immune system of all living organisms. Numerous antimicrobial peptides have been isolated from insects, amphibians, mammals, plants and bacterial species. In this study we investigated the in vitro activity of two animal peptides, citropin 1.1 and protegrin 1 alone and in combination against microbial strains proposed for the evaluation of preservatives: Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 10231, and Aspergillus niger ATCC 16404. The results of the antimicrobial preservative effectiveness were compared to the values received for benzalkonium chloride, popular preservative of medicines and cosmetics.

  20. Antimicrobial Testing Methods & Procedures: MB-31

    EPA Pesticide Factsheets

    Information about ATMP - SOP Quantitative Disk Carrier Test Method (QCT-2) Modified for Testing Antimicrobial Products Against Spores of Clostridium difficile (ATCC 43598) on Inanimate, Hard, Non-porous Surfaces - MB-31-Final

  1. Membrane disruption mechanism of antimicrobial peptides

    NASA Astrophysics Data System (ADS)

    Lee, Ka Yee

    2012-04-01

    Largely distributed among living organisms, antimicrobial peptides are a class of small (<100 residues) host defense peptides that induce selective membrane lytic activity against microbial pathogens. The permeabilizing behavior of these diverse peptides has been commonly attributed to the formation of pores, and such pore formation has been categorized as barrel-stave, toroidal, or carpet-like. With the continuing discovery of new peptide species, many are uncharacterized and the exact mechanism is unknown. Through the use of atomic force microscopy, the disruption of supported lipid bilayer patches by protegrin-1 is concentration-dependent. The intercalation of antimicrobial peptide into the bilayer results in structures beyond that of pore formation, but with the formation of worm-like micelles at high peptide concentration. Our results suggest that antimicrobial peptide acts to lower the interfacial energy of the bilayer in a way similar to detergents. Antimicrobial peptides with structural differences, magainin-1 and aurein 1.1, exhibit a mechanistic commonality.

  2. Antimicrobial activity of extractives of Solidago microglossa.

    PubMed

    Morel, A F; Dias, G O; Porto, C; Simionatto, E; Stuker, C Z; Dalcol, I I

    2006-09-01

    The antimicrobial activity of the methanol extract from Solidago microglossa roots, essential oil from its aerial part and some isolated compounds was investigated. The oil exhibited concentration-dependent activity against all the tested bacteria and yeasts.

  3. Synthetic biology platform technologies for antimicrobial applications.

    PubMed

    Braff, Dana; Shis, David; Collins, James J

    2016-10-01

    The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels.

  4. The First Salamander Defensin Antimicrobial Peptide

    PubMed Central

    Jiang, Ke; Rong, Mingqiang; Lai, Ren

    2013-01-01

    Antimicrobial peptides have been widely identified from amphibian skins except salamanders. A novel antimicrobial peptide (CFBD) was isolated and characterized from skin secretions of the salamander, Cynops fudingensis. The cDNA encoding CFBD precursor was cloned from the skin cDNA library of C. fudingensis. The precursor was composed of three domains: signal peptide of 17 residues, mature peptide of 41 residues and intervening propeptide of 3 residues. There are six cysteines in the sequence of mature CFBD peptide, which possibly form three disulfide-bridges. CFBD showed antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli. This peptide could be classified into family of β-defensin based on its seqeuence similarity with β-defensins from other vertebrates. Evolution analysis indicated that CFBD was close to fish β-defensin. As far as we know, CFBD is the first β-defensin antimicrobial peptide from salamanders. PMID:24386139

  5. Thioridazine: resurrection as an antimicrobial agent?

    PubMed Central

    Thanacoody, H K R

    2007-01-01

    The emergence of multiresistant bacterial strains and the continuing burden of infectious disease globally point to the urgent need for novel affordable antimicrobial drugs. Thioridazine is a phenothiazine antipsychotic drug with well-recognized antimicrobial activity, but this property has not been harnessed for clinical use as a result of its central nervous system and cardiac side-effects. The cardiotoxicity of thioridazine has recently been shown to be structurally specific at a molecular level, whereas its antimicrobial properties are shared by a number of phenothiazine analogues. This raises the possibility that its enantiomers or its inactive metabolite, the ring sulphoxide, may act as a lead compound in the future development of antimicrobial drugs to face the new challenges in infectious disease. PMID:17764469

  6. Antimicrobial dispensing by Ontario dairy veterinarians

    PubMed Central

    Léger, David F.; Newby, Nathalie C.; Reid-Smith, Richard; Anderson, Neil; Pearl, David L.; Lissemore, Kerry D.; Kelton, David F.

    2015-01-01

    This questionnaire-based cross-sectional study was designed to capture the demographics of dairy practitioners in Ontario and to describe aspects of antimicrobial dispensing on-farm and over-the-counter by these veterinarians. The information collected revealed that the prescription status of a drug and the level of veterinary-client-patient relationship were important elements of dispensing policies. Over-the-counter dispensing records were incomplete, while only a small proportion of on-farm dispensing records contained pertinent information and directions as required by the Veterinarians Act. While respondents recognized that antimicrobial use in dairy herds could lead to resistance in cattle, few indicated that this was a significant public health issue. Veterinarians can play a key role in antimicrobial stewardship, part of which is the provision of complete written dispensing instructions to producers for antimicrobial use in dairy cattle. PMID:26130834

  7. Guideline for Antimicrobial Prophylaxis in Breast Surgery

    PubMed Central

    Bağhaki, Sema; Soybir, Gürsel Remzi; Soran, Atilla

    2014-01-01

    The American Society of Health-System Pharmacists (ASHP) published the 2012/2013 edition of the book entitled “Best Practices for Hospital & Health-System Pharmacy: Position and Guidance Documents of ASHP” with Bruce Hawkins as the editor. (ISSN: 15558975). Pages 582–667 of this book contain the section: “Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery”. This section includes current clinical developments, evidence and recommendations on the application of standard and effective antimicrobial prophylaxis in adult and pediatric patients, and has significant differences compared to the previous 1999 edition. On pages 632–633, antimicrobial prophylaxis in breast and plastic surgery practice is addressed in detail. This article contains a summary of the recommendations made in ASHP 2012/2013 Report regarding the antimicrobial prophylaxis in breast and plastic surgery applications.

  8. Antimicrobial silver: An unprecedented anion effect

    NASA Astrophysics Data System (ADS)

    Swathy, J. R.; Sankar, M. Udhaya; Chaudhary, Amrita; Aigal, Sahaja; Anshup; Pradeep, T.

    2014-11-01

    Silver is an indispensable metal but its use has to be minimised for sustainable growth. Much of the silver lost during use is unrecoverable; an example being its use as an antimicrobial agent, a property known since ages. While developing methods to create an affordable drinking water purifier especially for the developing world, we discovered that 50 parts per billion (ppb) of Ag+ released continuously from silver nanoparticles confined in nanoscale cages is enough to cause antimicrobial activity in conditions of normal water. Here we show that the antibacterial and antiviral activities of Ag+ can be enhanced ~1,000 fold, selectively, in presence of carbonate ions whose concentration was maintained below the drinking water norms. The protective layers of the organisms were affected during the carbonate-assisted antimicrobial activity. It is estimated that ~1,300 tons of silver can be saved annually using this new way to enhance its antimicrobial activity.

  9. Antimicrobial silver: An unprecedented anion effect

    PubMed Central

    Swathy, J. R.; Sankar, M. Udhaya; Chaudhary, Amrita; Aigal, Sahaja; Anshup; Pradeep, T.

    2014-01-01

    Silver is an indispensable metal but its use has to be minimised for sustainable growth. Much of the silver lost during use is unrecoverable; an example being its use as an antimicrobial agent, a property known since ages. While developing methods to create an affordable drinking water purifier especially for the developing world, we discovered that 50 parts per billion (ppb) of Ag+ released continuously from silver nanoparticles confined in nanoscale cages is enough to cause antimicrobial activity in conditions of normal water. Here we show that the antibacterial and antiviral activities of Ag+ can be enhanced ~1,000 fold, selectively, in presence of carbonate ions whose concentration was maintained below the drinking water norms. The protective layers of the organisms were affected during the carbonate-assisted antimicrobial activity. It is estimated that ~1,300 tons of silver can be saved annually using this new way to enhance its antimicrobial activity. PMID:25418185

  10. The first salamander defensin antimicrobial peptide.

    PubMed

    Meng, Ping; Yang, Shilong; Shen, Chuanbin; Jiang, Ke; Rong, Mingqiang; Lai, Ren

    2013-01-01

    Antimicrobial peptides have been widely identified from amphibian skins except salamanders. A novel antimicrobial peptide (CFBD) was isolated and characterized from skin secretions of the salamander, Cynops fudingensis. The cDNA encoding CFBD precursor was cloned from the skin cDNA library of C. fudingensis. The precursor was composed of three domains: signal peptide of 17 residues, mature peptide of 41 residues and intervening propeptide of 3 residues. There are six cysteines in the sequence of mature CFBD peptide, which possibly form three disulfide-bridges. CFBD showed antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Candida albicans and Escherichia coli. This peptide could be classified into family of β-defensin based on its sequence similarity with β-defensins from other vertebrates. Evolution analysis indicated that CFBD was close to fish β-defensin. As far as we know, CFBD is the first β-defensin antimicrobial peptide from salamanders.

  11. Topical antimicrobial agents for burn wounds.

    PubMed

    Greenhalgh, David G

    2009-10-01

    Because burns destroy the barrier against invading bacteria, topical antimicrobial agents have been developed to minimize the proliferation of bacteria and other microorganisms. The topical treatment depends on the depth of burns. The goal for superficial burns is to optimize re-epithelialization. For deep burns, topical antimicrobial agents should be used to minimize microbial growth until the wound is grafted. This article introduces a strategy for the rational use of these agents.

  12. Antimicrobial prophylaxis in caesarean section delivery

    PubMed Central

    Liu, Ronghua; Lin, Lin; Wang, Dujuan

    2016-01-01

    Antimicrobial prophylaxis is used routinely for pre-, intra- and post-operative caesarean section. One of the most important risk factors for postpartum infection is caesarean delivery. Caesarean section shows a higher incidence of infection than vaginal delivery. It is complicated by surgical site infections, endometritis or urinary tract infection. The aim of the present study was to assess the usage of antimicrobials in women undergoing caesarean section at a Tertiary Care Hospital. A prospective study was conducted in 100 women during the period of February 2013 to August 2013 in the inpatient Department of Gynaecology and Obstetrics. Data collected included the age of the patient, gravidity, and type of caesarean section, which was analyzed for the nature and number of antimicrobials prescribed, duration of treatment, polypharmacy, fixed-dose combinations, generic/brand names used and failure of prophylaxis. Antimicrobial prophylaxis was administered to the patients. The most commonly prescribed antimicrobial was a combination of ceftriaxone and sulbactam. Of 100 patients, 87% were aged 20–35 years. The highest proportion of patients were primigravida 72%. Elective procedure was carried out in 38%, the remaining were emergency C-section in whom intra- and post-operative antimicrobial prophylaxis was given for a duration of 7 days. In total, 27% of patients were reported with infection even after the antimicrobial prophylaxis. In conclusion, pre-operative prophylaxis was given in the early rupture of membranes. Fixed-dose combinations were preferred. Incidence of infection even after antimicrobial prophylaxis was reported due to pre-existing infection, debilitating disease or prolonged rupture of membranes. Patients with recurrent infection were shifted to amoxicillin and clavulinic acid combination. Drugs were prescribed only by brand names which is of concern. PMID:27446303

  13. Antimicrobial Actions of Reactive Oxygen Species

    PubMed Central

    Fang, Ferric C.

    2011-01-01

    ABSTRACT Everything should be as simple as it can be, but not simpler.—Attributed to Albert Einstein (1) Reactive oxygen species (ROS) are produced by host phagocytes and exert antimicrobial actions against a broad range of pathogens. The observable antimicrobial actions of ROS are highly dependent on experimental conditions. This perspective reviews recent controversies regarding ROS in Salmonella-phagocyte interactions and attempts to reconcile conflicting observations from different laboratories. PMID:21896680

  14. Report: Antimicrobial activity of Kalanchoe laciniata.

    PubMed

    Manan, Maria; Hussain, Liaqat; Ijaz, Hira; Qadir, Muhammad Imran

    2016-07-01

    This study was conducted to identify antimicrobial potential of Kalanchoe laciniata. The plants were extracted with 30-70% aqueous-methanol and n-hexane. The antimicrobial activities were examined using agar well diffusion method against bacteria (Staphylococcus aureus, Escherichia coli) and fungi (Candidaalbicans). Results showed that E. coli were more sensitive than Staphylococcus aureus and Candida albicans. The largest zone of inhibition (52 mm) was recorded against E. coli with the n-hexane extract of Kalanchoe laciniata.

  15. Optimizing antimicrobial therapy in critically ill patients

    PubMed Central

    Vitrat, Virginie; Hautefeuille, Serge; Janssen, Cécile; Bougon, David; Sirodot, Michel; Pagani, Leonardo

    2014-01-01

    Critically ill patients with infection in the intensive care unit (ICU) would certainly benefit from timely bacterial identification and effective antimicrobial treatment. Diagnostic techniques have clearly improved in the last years and allow earlier identification of bacterial strains in some cases, but these techniques are still quite expensive and not readily available in all institutions. Moreover, the ever increasing rates of resistance to antimicrobials, especially in Gram-negative pathogens, are threatening the outcome for such patients because of the lack of effective medical treatment; ICU physicians are therefore resorting to combination therapies to overcome resistance, with the direct consequence of promoting further resistance. A more appropriate use of available antimicrobials in the ICU should be pursued, and adjustments in doses and dosing through pharmacokinetics and pharmacodynamics have recently shown promising results in improving outcomes and reducing antimicrobial resistance. The aim of multidisciplinary antimicrobial stewardship programs is to improve antimicrobial prescription, and in this review we analyze the available experiences of such programs carried out in ICUs, with emphasis on results, challenges, and pitfalls. Any effective intervention aimed at improving antibiotic usage in ICUs must be brought about at the present time; otherwise, we will face the challenge of intractable infections in critically ill patients in the near future. PMID:25349478

  16. Topical antimicrobials in pediatric burn wound management.

    PubMed

    Patel, Priti P; Vasquez, Sylvia A; Granick, Mark S; Rhee, Samuel T

    2008-07-01

    Burn trauma continues to injure an estimated 1 million children each year in the United States alone, with many more injuries suffered worldwide. Several decades ago, advances in acute burn wound management, including development of topical antimicrobials, dramatically improved outcomes in pediatric burn injuries. However, infection remains the leading cause of burn wound mortality. With increasing antibiotic resistance in many medical centers, precise selection of topical antimicrobial therapy has grown in importance for pediatric burn management. Effective choice and application of topical antimicrobials require correct classification of burn wounds, appropriate understanding of the process of burn wound sepsis, and accurate identification of pathogens for individual patients as well as for their surrounding environment. This article examines the current and evolving role of topical antimicrobials in pediatric burn wound management. Burn wound classification, the biologic process of burn wound sepsis, wound cultures with pathogen profiling, and evaluations of commonly used topical antimicrobials are reviewed. Newer biologically active occlusive (bio-occlusive) and hybrid products are examined in the context of topical antimicrobial therapy and their increasing role in pediatric burn wound management.

  17. Antimicrobial Protection of Marsupial Pouch Young

    PubMed Central

    Cheng, Yuanyuan; Belov, Katherine

    2017-01-01

    Marsupials diverged from eutherian mammals about 148 million years ago and represent a unique lineage of mammals with distinctive morphological and reproductive characteristics. Marsupials have significantly shorter gestation periods than eutherians. Pregnancy typically ranges from 15 to 35 days, with young being born at a very early developmental stage and lacking differentiated lymphoid tissues and mature effector cells. Recent microbiome studies of the marsupial pouch revealed that marsupial young can face intense microbial challenges after birth, as the pouch contains a broad range of Gram-positive and Gram-negative bacteria. Antimicrobials are believed to play a significant role in the immune protection of marsupial newborns during their pouch life. The skin of the post-reproductive pouch secretes antimicrobial lysozyme and dermcidin, which may contribute to the decreased density of certain bacteria in the pouch. A range of antimicrobial agents, such as immunoglobulins, lysozyme, transferrin, and cathelicidins, have been identified in marsupial milk. Antimicrobial assays have revealed that marsupial cathelicidins have broad-spectrum activity against a variety of bacteria and fungi, including several multi-drug resistant strains. In this article, we will review the action mechanisms of these antimicrobial compounds and discuss how they protect marsupial newborns from potentially pathogenic bacteria inside the pouch. We will also discuss the potential of marsupial antimicrobial compounds as a source of novel antibiotics. PMID:28326070

  18. The antimicrobial possibilities of green tea

    PubMed Central

    Reygaert, Wanda C.

    2014-01-01

    Green tea is a popular drink, especially in Asian countries, although its popularity continues to spread across the globe. The health benefits of green tea, derived from the leaves of the Camellia sinensis plant, have been studied for many years. Fairly recently, researchers have begun to look at the possibility of using green tea in antimicrobial therapy, and the potential prevention of infections. The particular properties of catechins found in the tea have shown promise for having antimicrobial effects. There are four main catechins (polyphenols) found in green tea: (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin-3-gallate (EGCG). Three of these, ECG, EGC, and EGCG have been shown to have antimicrobial effects against a variety of organisms. These catechins have exhibited a variety of antimicrobial mechanisms. The results of studies on the antimicrobial effects of green tea have shown that the potential for preventive and therapeutic purposes is present. Further data collection on studies performed with human consumption during the course of infections, and studies on the occurrence of infections in populations that consume regular amounts of green tea will be necessary to complete the picture of its antimicrobial possibilities. PMID:25191312

  19. Derivation of Reliable Geometries in QM Calculations of DNA Structures: Explicit Solvent QM/MM and Restrained Implicit Solvent QM Optimizations of G-Quadruplexes.

    PubMed

    Gkionis, Konstantinos; Kruse, Holger; Šponer, Jiří

    2016-04-12

    Modern dispersion-corrected DFT methods have made it possible to perform reliable QM studies on complete nucleic acid (NA) building blocks having hundreds of atoms. Such calculations, although still limited to investigations of potential energy surfaces, enhance the portfolio of computational methods applicable to NAs and offer considerably more accurate intrinsic descriptions of NAs than standard MM. However, in practice such calculations are hampered by the use of implicit solvent environments and truncation of the systems. Conventional QM optimizations are spoiled by spurious intramolecular interactions and severe structural deformations. Here we compare two approaches designed to suppress such artifacts: partially restrained continuum solvent QM and explicit solvent QM/MM optimizations. We report geometry relaxations of a set of diverse double-quartet guanine quadruplex (GQ) DNA stems. Both methods provide neat structures without major artifacts. However, each one also has distinct weaknesses. In restrained optimizations, all errors in the target geometries (i.e., low-resolution X-ray and NMR structures) are transferred to the optimized geometries. In QM/MM, the initial solvent configuration causes some heterogeneity in the geometries. Nevertheless, both approaches represent a decisive step forward compared to conventional optimizations. We refine earlier computations that revealed sizable differences in the relative energies of GQ stems computed with AMBER MM and QM. We also explore the dependence of the QM/MM results on the applied computational protocol.

  20. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    PubMed

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.