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Sample records for systemic acquired resistance

  1. Next-generation systemic acquired resistance.

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    Luna, Estrella; Bruce, Toby J A; Roberts, Michael R; Flors, Victor; Ton, Jurriaan

    2012-02-01

    Systemic acquired resistance (SAR) is a plant immune response to pathogen attack. Recent evidence suggests that plant immunity involves regulation by chromatin remodeling and DNA methylation. We investigated whether SAR can be inherited epigenetically following disease pressure by Pseudomonas syringae pv tomato DC3000 (PstDC3000). Compared to progeny from control-treated Arabidopsis (Arabidopsis thaliana; C(1)), progeny from PstDC3000-inoculated Arabidopsis (P(1)) were primed to activate salicylic acid (SA)-inducible defense genes and were more resistant to the (hemi)biotrophic pathogens Hyaloperonospora arabidopsidis and PstDC3000. This transgenerational SAR was sustained over one stress-free generation, indicating an epigenetic basis of the phenomenon. Furthermore, P(1) progeny displayed reduced responsiveness of jasmonic acid (JA)-inducible genes and enhanced susceptibility to the necrotrophic fungus Alternaria brassicicola. This shift in SA- and JA-dependent gene responsiveness was not associated with changes in corresponding hormone levels. Instead, chromatin immunoprecipitation analyses revealed that SA-inducible promoters of PATHOGENESIS-RELATED GENE1, WRKY6, and WRKY53 in P(1) plants are enriched with acetylated histone H3 at lysine 9, a chromatin mark associated with a permissive state of transcription. Conversely, the JA-inducible promoter of PLANT DEFENSIN1.2 showed increased H3 triple methylation at lysine 27, a mark related to repressed gene transcription. P(1) progeny from the defense regulatory mutant non expressor of PR1 (npr1)-1 failed to develop transgenerational defense phenotypes, demonstrating a critical role for NPR1 in expression of transgenerational SAR. Furthermore, the drm1drm2cmt3 mutant that is affected in non-CpG DNA methylation mimicked the transgenerational SAR phenotype. Since PstDC3000 induces DNA hypomethylation in Arabidopsis, our results suggest that transgenerational SAR is transmitted by hypomethylated genes that direct priming

  2. Arabidopsis MAP kinase 4 negatively regulates systemic acquired resistance

    DEFF Research Database (Denmark)

    Petersen, M.; Brodersen, P.; Naested, H.

    2000-01-01

    Transposon inactivation of Arabidopsis MAP kinase 4 produced the mpk4 mutant exhibiting constitutive systemic acquired resistance (SAR) including elevated salicylic acid (SA) revels, increased resistance to virulent pathogens, and constitutive pathogenesis-related gene expression shown by Northern...... of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression....

  3. Foliar application of systemic acquired resistance (SAR) inducers for ...

    African Journals Online (AJOL)

    nbuensanteai

    2013-08-14

    Aug 14, 2013 ... induced by chitosan and BTH were involved in defense mechanism, reflecting the strong direct positive effect that chitosan ... to control plant diseases based on the systemic acquired resistance ... salicylic acid (SA) as a signal molecule and is associated ... treated plants for SAR relating chemical analyses.

  4. Monoterpenes Support Systemic Acquired Resistance within and between Plants.

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    Riedlmeier, Marlies; Ghirardo, Andrea; Wenig, Marion; Knappe, Claudia; Koch, Kerstin; Georgii, Elisabeth; Dey, Sanjukta; Parker, Jane E; Schnitzler, Jörg-Peter; Vlot, A Corina

    2017-06-01

    This study investigates the role of volatile organic compounds in systemic acquired resistance (SAR), a salicylic acid (SA)-associated, broad-spectrum immune response in systemic, healthy tissues of locally infected plants. Gas chromatography coupled to mass spectrometry analyses of SAR-related emissions of wild-type and non-SAR-signal-producing mutant plants associated SAR with monoterpene emissions. Headspace exposure of Arabidopsis thaliana to a mixture of the bicyclic monoterpenes α-pinene and β-pinene induced defense, accumulation of reactive oxygen species, and expression of SA- and SAR-related genes, including the SAR regulatory AZELAIC ACID INDUCED1 ( AZI1 ) gene and three of its paralogs. Pinene-induced resistance was dependent on SA biosynthesis and signaling and on AZI1 Arabidopsis geranylgeranyl reductase1 mutants with reduced monoterpene biosynthesis were SAR-defective but mounted normal local resistance and methyl salicylate-induced defense responses, suggesting that monoterpenes act in parallel with SA The volatile emissions from SAR signal-emitting plants induced defense in neighboring plants, and this was associated with the presence of α-pinene, β-pinene, and camphene in the emissions of the "sender" plants. Our data suggest that monoterpenes, particularly pinenes, promote SAR, acting through ROS and AZI1 , and likely function as infochemicals in plant-to-plant signaling, thus allowing defense signal propagation between neighboring plants. © 2017 American Society of Plant Biologists. All rights reserved.

  5. A critical role for Arabidopsis MILDEW RESISTANCE LOCUS O2 in systemic acquired resistance.

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    Gruner, Katrin; Zeier, Tatyana; Aretz, Christina; Zeier, Jürgen

    2018-04-16

    Members of the MILDEW RESISTANCE LOCUS O (MLO) gene family confer susceptibility to powdery mildews in different plant species, and their existence therefore seems to be disadvantageous for the plant. We recognized that expression of the Arabidopsis MLO2 gene is induced after inoculation with the bacterial pathogen Pseudomonas syringae, promoted by salicylic acid (SA) signaling, and systemically enhanced in the foliage of plants exhibiting systemic acquired resistance (SAR). Importantly, distinct mlo2 mutant lines were unable to systemically increase resistance to bacterial infection after inoculation with P. syringae, indicating that the function of MLO2 is necessary for biologically-induced SAR in Arabidopsis. Our data also suggest that the close homolog MLO6 has a supportive but less critical role in SAR. In contrast to SAR, basal resistance to bacterial infection was not affected in mlo2. Remarkably, SAR-defective mlo2 mutants were still competent in systemically increasing the levels of the SAR-activating metabolites pipecolic acid (Pip) and SA after inoculation, and to enhance SAR-related gene expression in distal plant parts. Furthermore, although MLO2 was not required for SA- or Pip-inducible defense gene expression, it was essential for the proper induction of disease resistance by both SAR signals. We conclude that MLO2 acts as a critical downstream component in the execution of SAR to bacterial infection, being required for the translation of elevated defense responses into disease resistance. Moreover, our data suggest a function for MLO2 in the activation of plant defense priming during a P. syringae challenge. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Involvement of ethylene in lesion development and systemic acquired resistance in tobacco during the hypersensitive reaction to tobacco mosaic virus

    NARCIS (Netherlands)

    Knoester, M.; Linthorst, H.J.M.; Bol, J.F.; Loon, L.C. van

    2001-01-01

    Different approaches were taken to investigate the significance of ethylene in lesion development and systemic acquired resistance (SAR) in tobacco (Nicotiana tabacum) reacting hypersensitively to tobacco mosaic virus (TMV). Gaseous ethylene, the ethylene precursor 1-aminocyclopropane-1-carboxylic

  7. The spatiotemporal system dynamics of acquired resistance in an engineered microecology.

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    Datla, Udaya Sree; Mather, William H; Chen, Sheng; Shoultz, Isaac W; Täuber, Uwe C; Jones, Caroline N; Butzin, Nicholas C

    2017-11-22

    Great strides have been made in the understanding of complex networks; however, our understanding of natural microecologies is limited. Modelling of complex natural ecological systems has allowed for new findings, but these models typically ignore the constant evolution of species. Due to the complexity of natural systems, unanticipated interactions may lead to erroneous conclusions concerning the role of specific molecular components. To address this, we use a synthetic system to understand the spatiotemporal dynamics of growth and to study acquired resistance in vivo. Our system differs from earlier synthetic systems in that it focuses on the evolution of a microecology from a killer-prey relationship to coexistence using two different non-motile Escherichia coli strains. Using empirical data, we developed the first ecological model emphasising the concept of the constant evolution of species, where the survival of the prey species is dependent on location (distance from the killer) or the evolution of resistance. Our simple model, when expanded to complex microecological association studies under varied spatial and nutrient backgrounds may help to understand the complex relationships between multiple species in intricate natural ecological networks. This type of microecological study has become increasingly important, especially with the emergence of antibiotic-resistant pathogens.

  8. Mono- and Digalactosyldiacylglycerol Lipids Function Nonredundantly to Regulate Systemic Acquired Resistance in Plants

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    Qing-ming Gao

    2014-12-01

    Full Text Available Summary: The plant galactolipids monogalactosyldiacylglycerol (MGDG and digalactosyldiacylglycerol (DGDG have been linked to the anti-inflammatory and cancer benefits of a green leafy vegetable diet in humans due to their ability to regulate the levels of free radicals like nitric oxide (NO. Here, we show that DGDG contributes to plant NO as well as salicylic acid biosynthesis and is required for the induction of systemic acquired resistance (SAR. In contrast, MGDG regulates the biosynthesis of the SAR signals azelaic acid (AzA and glycerol-3-phosphate (G3P that function downstream of NO. Interestingly, DGDG is also required for AzA-induced SAR, but MGDG is not. Notably, transgenic expression of a bacterial glucosyltransferase is unable to restore SAR in dgd1 plants even though it does rescue their morphological and fatty acid phenotypes. These results suggest that MGDG and DGDG are required at distinct steps and function exclusively in their individual roles during the induction of SAR. : The galactolipids monogalactosyldiacylglycerol (MGDG and digalactosyldiacylglycerol (DGDG constitute ∼80% of total membrane lipids in plants. Gao et al. now show that these galactolipids function nonredundantly to regulate systemic acquired resistance (SAR. Furthermore, they show that the terminal galactose on the α-galactose-β-galactose head group of DGDG is critical for SAR.

  9. Interconnection between flowering time control and activation of systemic acquired resistance

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    Zeeshan Zahoor Banday

    2015-03-01

    Full Text Available The ability to avoid or neutralize pathogens is inherent to all higher organisms including plants. Plants recognize pathogens through receptors, and mount resistance against the intruders, with the help of well-elaborated defense arsenal. In response to some local infections, plants develop systemic acquired resistance (SAR, which provides heightened resistance during subsequent infections. Infected tissues generate mobile signalling molecules that travel to the systemic tissues, where they epigenetically modify expression of a set of genes to initiate the manifestation of SAR in distant tissues. Immune responses are largely regulated at transcriptional level. Flowering is a developmental transition that occurs as a result of the coordinated action of large numbers of transcription factors that respond to intrinsic signals and environmental conditions. The plant hormone salicylic acid (SA which is required for SAR activation positively regulates flowering. Certain components of chromatin remodelling complexes that are recruited for suppression of precocious flowering are also involved in suppression of SAR in healthy plants. FLOWERING LOCUS D (FLD, a putative histone demethylase positively regulates SAR manifestation and flowering transition in Arabidopsis. Similarly, incorporation of histone variant H2A.Z in nucleosomes mediated by PHOTOPERIOD-INDEPENDENT EARLY FLOWERING 1 (PIE1, an orthologue of yeast chromatin remodelling complex SWR1, concomitantly influences SAR and flowering time. SUMO conjugation and deconjugation mechanisms also similarly affect SAR and flowering in an SA-dependent manner. The evidences suggest a common underlying regulatory mechanism for activation of SAR and flowering in plants.

  10. Methyl salicylate is a critical mobile signal for plant systemic acquired resistance.

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    Park, Sang-Wook; Kaimoyo, Evans; Kumar, Dhirendra; Mosher, Stephen; Klessig, Daniel F

    2007-10-05

    In plants, the mobile signal for systemic acquired resistance (SAR), an organism-wide state of enhanced defense to subsequent infections, has been elusive. By stimulating immune responses in mosaic tobacco plants created by grafting different genetic backgrounds, we showed that the methyl salicylate (MeSA) esterase activity of salicylic acid-binding protein 2 (SABP2), which converts MeSA into salicylic acid (SA), is required for SAR signal perception in systemic tissue, the tissue that does not receive the primary (initial) infection. Moreover, in plants expressing mutant SABP2 with unregulated MeSA esterase activity in SAR signal-generating, primary infected leaves, SAR was compromised and the associated increase in MeSA levels was suppressed in primary infected leaves, their phloem exudates, and systemic leaves. SAR was also blocked when SA methyl transferase (which converts SA to MeSA) was silenced in primary infected leaves, and MeSA treatment of lower leaves induced SAR in upper untreated leaves. Therefore, we conclude that MeSA is a SAR signal in tobacco.

  11. Systemic acquired resistance in soybean is regulated by two proteins, Orthologous to Arabidopsis NPR1

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    Sandhu Devinder

    2009-08-01

    Full Text Available Abstract Background Systemic acquired resistance (SAR is induced in non-inoculated leaves following infection with certain pathogenic strains. SAR is effective against many pathogens. Salicylic acid (SA is a signaling molecule of the SAR pathway. The development of SAR is associated with the induction of pathogenesis related (PR genes. Arabidopsis non-expressor of PR1 (NPR1 is a regulatory gene of the SA signal pathway 123. SAR in soybean was first reported following infection with Colletotrichum trancatum that causes anthracnose disease. We investigated if SAR in soybean is regulated by a pathway, similar to the one characterized in Arabidopsis. Results Pathogenesis-related gene GmPR1 is induced following treatment of soybean plants with the SAR inducer, 2,6-dichloroisonicotinic acid (INA or infection with the oomycete pathogen, Phytophthora sojae. In P. sojae-infected plants, SAR was induced against the bacterial pathogen, Pseudomonas syringae pv. glycinea. Soybean GmNPR1-1 and GmNPR1-2 genes showed high identities to Arabidopsis NPR1. They showed similar expression patterns among the organs, studied in this investigation. GmNPR1-1 and GmNPR1-2 are the only soybean homologues of NPR1and are located in homoeologous regions. In GmNPR1-1 and GmNPR1-2 transformed Arabidopsis npr1-1 mutant plants, SAR markers: (i PR-1 was induced following INA treatment and (ii BGL2 following infection with Pseudomonas syringae pv. tomato (Pst, and SAR was induced following Pst infection. Of the five cysteine residues, Cys82, Cys150, Cys155, Cys160, and Cys216 involved in oligomer-monomer transition in NPR1, Cys216 in GmNPR1-1 and GmNPR1-2 proteins was substituted to Ser and Leu, respectively. Conclusion Complementation analyses in Arabidopsis npr1-1 mutants revealed that homoeologous GmNPR1-1 and GmNPR1-2 genes are orthologous to Arabidopsis NPR1. Therefore, SAR pathway in soybean is most likely regulated by GmNPR1 genes. Substitution of Cys216 residue, essential

  12. Systemic acquired resistance in soybean is regulated by two proteins, Orthologous to Arabidopsis NPR1.

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    Sandhu, Devinder; Tasma, I Made; Frasch, Ryan; Bhattacharyya, Madan K

    2009-08-05

    Systemic acquired resistance (SAR) is induced in non-inoculated leaves following infection with certain pathogenic strains. SAR is effective against many pathogens. Salicylic acid (SA) is a signaling molecule of the SAR pathway. The development of SAR is associated with the induction of pathogenesis related (PR) genes. Arabidopsis non-expressor of PR1 (NPR1) is a regulatory gene of the SA signal pathway 123. SAR in soybean was first reported following infection with Colletotrichum trancatum that causes anthracnose disease. We investigated if SAR in soybean is regulated by a pathway, similar to the one characterized in Arabidopsis. Pathogenesis-related gene GmPR1 is induced following treatment of soybean plants with the SAR inducer, 2,6-dichloroisonicotinic acid (INA) or infection with the oomycete pathogen, Phytophthora sojae. In P. sojae-infected plants, SAR was induced against the bacterial pathogen, Pseudomonas syringae pv. glycinea. Soybean GmNPR1-1 and GmNPR1-2 genes showed high identities to Arabidopsis NPR1. They showed similar expression patterns among the organs, studied in this investigation. GmNPR1-1 and GmNPR1-2 are the only soybean homologues of NPR1and are located in homoeologous regions. In GmNPR1-1 and GmNPR1-2 transformed Arabidopsis npr1-1 mutant plants, SAR markers: (i) PR-1 was induced following INA treatment and (ii) BGL2 following infection with Pseudomonas syringae pv. tomato (Pst), and SAR was induced following Pst infection. Of the five cysteine residues, Cys82, Cys150, Cys155, Cys160, and Cys216 involved in oligomer-monomer transition in NPR1, Cys216 in GmNPR1-1 and GmNPR1-2 proteins was substituted to Ser and Leu, respectively. Complementation analyses in Arabidopsis npr1-1 mutants revealed that homoeologous GmNPR1-1 and GmNPR1-2 genes are orthologous to Arabidopsis NPR1. Therefore, SAR pathway in soybean is most likely regulated by GmNPR1 genes. Substitution of Cys216 residue, essential for oligomer-monomer transition of Arabidopsis NPR1

  13. Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

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    Male, C; Mitchell, L; Julian, J; Vegh, P; Joshua, P; Adams, M; David, M; Andrew, M E

    2001-02-15

    Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)

  14. Glycerol-3-phosphate metabolism in wheat contributes to systemic acquired resistance against Puccinia striiformis f. sp. tritici.

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    Yuheng Yang

    Full Text Available Glycerol-3-phosphate (G3P is a proposed regulator of plant defense signaling in basal resistance and systemic acquired resistance (SAR. The GLY1-encoded glycerol-3-phosphate dehydrogenase (G3PDH and GLI1-encoded glycerol kinase (GK are two key enzymes involved in the G3P biosynthesis in plants. However, their physiological importance in wheat defense against pathogens remains unclear. In this study, quantification analysis revealed that G3P levels were significantly induced in wheat leaves challenged by the avirulent Puccinia striiformis f. sp. tritici (Pst race CYR23. The transcriptional levels of TaGLY1 and TaGLI1 were likewise significantly induced by avirulent Pst infection. Furthermore, knocking down TaGLY1 and TaGLI1 individually or simultaneously with barley stripe mosaic virus-induced gene silencing (BSMV-VIGS inhibited G3P accumulation and compromised the resistance in the wheat cultivar Suwon 11, whereas the accumulation of salicylic acid (SA and the expression of the SA-induced marker gene TaPR1 in plant leaves were altered significantly after gene silencing. These results suggested that G3P contributes to wheat systemic acquired resistance (SAR against stripe rust, and provided evidence that the G3P function as a signaling molecule is conserved in dicots and monocots. Meanwhile, the simultaneous co-silencing of multiple genes by the VIGS system proved to be a powerful tool for multi-gene functional analysis in plants.

  15. Characterization of Taurine Transporting Systems During Acquirement of Resistance to Platinum(II)-based, Chemotherapeutic Drugs

    DEFF Research Database (Denmark)

    Sørensen, Belinda Halling

    Although, cisplatin is one of the most effective broad-spectrum anticancer drugs, prolonged cisplatin treatment often results in development of chemoresistance and subsequent therapeutic failure. Dysregulation of the taurine transporting systems i.e., the taurine transporter (TauT) and volume....... Cisplatin resistance correlates with a reduction in the volume regulated anion current and taurine release mediated by VRACs, as well as an improved cellular accumulation of taurine through TauT. In human ovarian A2780 cancer cells, for instance, cisplatin resistance is associated with an absent swelling......-induced taurine release and inability to volume regulate. The dismissed taurine release was due to an almost absent leucin-rich-repeat containing 8A (LRRC8A) total protein expression. LRRC8A is an important component of VRACs. Cellular taurine contributes to the intracellular pool of organic osmolytes. Moreover...

  16. [Relationship between phenomenon of acquired activated protein C resistance and antiphospholipid antibodies in patients with systemic lupus erythematosus].

    Science.gov (United States)

    Hu, Y Q; Chen, F P; Xie, Q Z

    2001-10-28

    To determine the occurrence of activated protein C resistance (APCR), to identify APCR is associated with thrombotic events (TEs), and acquired APCR is associated with the presence of antiphospholipid antibodies (APLAs) in 30 patients with systemic lupus erythematosus (SLE). Laboratory tests included dilute Russell's viper venom time assay for LA (dRVVT-LA), ELISA assay for ACL, APC sensitivity ratio, and factor V Leiden were detected by PCR-Mnl/I digestion. Acquired APCR was presented in 14(46.67%) of 30 patients. Factor V Leiden was not found in any patients. The incidence of TEs in the APCR-positive patients was significantly higher than that in the APCR-negative patients (42.85% vs 6.25%, P TEs in the LA-positive patients was also significantly higher than that in the LA-negative patients (50% vs 11.1%, P TEs (P TEs. Acquired APCR may not reflect the interference of LAs with the protein C pathway which may represent a mechanism of LA-associated TEs.

  17. Pipecolic Acid Orchestrates Plant Systemic Acquired Resistance and Defense Priming via Salicylic Acid-Dependent and -Independent Pathways.

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    Bernsdorff, Friederike; Döring, Anne-Christin; Gruner, Katrin; Schuck, Stefan; Bräutigam, Andrea; Zeier, Jürgen

    2016-01-01

    We investigated the relationships of the two immune-regulatory plant metabolites, salicylic acid (SA) and pipecolic acid (Pip), in the establishment of plant systemic acquired resistance (SAR), SAR-associated defense priming, and basal immunity. Using SA-deficient sid2, Pip-deficient ald1, and sid2 ald1 plants deficient in both SA and Pip, we show that SA and Pip act both independently from each other and synergistically in Arabidopsis thaliana basal immunity to Pseudomonas syringae. Transcriptome analyses reveal that SAR establishment in Arabidopsis is characterized by a strong transcriptional response systemically induced in the foliage that prepares plants for future pathogen attack by preactivating multiple stages of defense signaling and that SA accumulation upon SAR activation leads to the downregulation of photosynthesis and attenuated jasmonate responses systemically within the plant. Whereas systemic Pip elevations are indispensable for SAR and necessary for virtually the whole transcriptional SAR response, a moderate but significant SA-independent component of SAR activation and SAR gene expression is revealed. During SAR, Pip orchestrates SA-dependent and SA-independent priming of pathogen responses in a FLAVIN-DEPENDENT-MONOOXYGENASE1 (FMO1)-dependent manner. We conclude that a Pip/FMO1 signaling module acts as an indispensable switch for the activation of SAR and associated defense priming events and that SA amplifies Pip-triggered responses to different degrees in the distal tissue of SAR-activated plants. © 2016 American Society of Plant Biologists. All rights reserved.

  18. : acquired resistance in mice by implantation of young irradiated worms into the portal system

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    Paulo Marcos Z. Coelho

    1989-02-01

    Full Text Available In two distinct experiments, immature S. mansoni worms (LE strain, Belo Horizonte, Brazil, aged 20 days, obtained from the portal system of white outbred mice, were irradiated with 14 and 4 Krad, respectively. Afterwards, the worms were directly inoculated into the portal vein of normal mice. Inoculation was performed with 20 irradiated worms per animal. Fifty days after inoculation, the mice that received 4 and 14 Krad-irradiated worms and their respective controls were infected with S. mansoni cercariae (LE strain, by transcutaneous route. Twenty days after this challenge infection, the animals were sacrificed and perfused for mature irradiated (90-day-old and immature (20-day-old worm counts. Analysis of the results showed that statistically significant protection against cercariae occurred in both groups with irradiated worms.

  19. A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants.

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    Dong Wang

    2006-11-01

    Full Text Available Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given system. Systemic acquired resistance (SAR is an inducible plant defense response involving a cascade of transcriptional events induced by salicylic acid through the transcription cofactor NPR1. To identify additional regulatory nodes in the SAR network, we performed microarray analysis on Arabidopsis plants expressing the NPR1-GR (glucocorticoid receptor fusion protein. Since nuclear translocation of NPR1-GR requires dexamethasone, we were able to control NPR1-dependent transcription and identify direct transcriptional targets of NPR1. We show that NPR1 directly upregulates the expression of eight WRKY transcription factor genes. This large family of 74 transcription factors has been implicated in various defense responses, but no specific WRKY factor has been placed in the SAR network. Identification of NPR1-regulated WRKY factors allowed us to perform in-depth genetic analysis on a small number of WRKY factors and test well-defined phenotypes of single and double mutants associated with NPR1. Among these WRKY factors we found both positive and negative regulators of SAR. This genomics-directed approach unambiguously positioned five WRKY factors in the complex transcriptional regulatory network of SAR. Our work not only discovered new transcription regulatory components in the signaling network of SAR but also demonstrated that functional studies of large gene families have to take into consideration sequence similarity as well as the expression patterns of the candidates.

  20. Identification of acquired antimicrobial resistance genes

    DEFF Research Database (Denmark)

    Zankari, Ea; Hasman, Henrik; Cosentino, Salvatore

    2012-01-01

    ObjectivesIdentification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic laborato......ObjectivesIdentification of antimicrobial resistance genes is important for understanding the underlying mechanisms and the epidemiology of antimicrobial resistance. As the costs of whole-genome sequencing (WGS) continue to decline, it becomes increasingly available in routine diagnostic...... laboratories and is anticipated to substitute traditional methods for resistance gene identification. Thus, the current challenge is to extract the relevant information from the large amount of generated data.MethodsWe developed a web-based method, ResFinder that uses BLAST for identification of acquired...... antimicrobial resistance genes in whole-genome data. As input, the method can use both pre-assembled, complete or partial genomes, and short sequence reads from four different sequencing platforms. The method was evaluated on 1862 GenBank files containing 1411 different resistance genes, as well as on 23 de...

  1. SABP2, a methyl salicylate esterase is required for the systemic acquired resistance induced by acibenzolar-S-methyl in plants.

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    Tripathi, Diwaker; Jiang, Yu-Lin; Kumar, Dhirendra

    2010-08-04

    Tobacco SABP2, a 29kDa protein catalyzes the conversion of methyl salicylic acid (MeSA) into salicylic acid (SA) to induce SAR. Pretreatment of plants with acibenzolar-S-methyl (ASM), a functional analog of salicylic acid induces systemic acquired resistance (SAR). Data presented in this paper suggest that SABP2 catalyzes the conversion of ASM into acibenzolar to induce SAR. Transgenic SABP2-silenced tobacco plants when treated with ASM, fail to express PR-1 proteins and do not induce robust SAR expression. When treated with acibenzolar, full SAR is induced in SABP2-silenced plants. These results show that functional SABP2 is required for ASM-mediated induction of resistance. Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. Orthology Analysis and In Vivo Complementation Studies to Elucidate the Role of DIR1 during Systemic Acquired Resistance in Arabidopsis thaliana and Cucumis sativus

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    Marisa Isaacs

    2016-05-01

    Full Text Available AtDIR1 (Defective in Induced Resistance1 is an acidic lipid transfer protein essential for systemic acquired resistance (SAR in Arabidopsis thaliana. Upon SAR induction, DIR1 moves from locally infected to distant uninfected leaves to activate defense priming; however, a molecular function for DIR1 has not been elucidated. Bioinformatic analysis and in silico homology modeling identified putative AtDIR1 orthologs in crop species, revealing conserved protein motifs within and outside of DIR1’s central hydrophobic cavity. In vitro assays to compare the capacity of recombinant AtDIR1 and targeted AtDIR1-variant proteins to bind the lipophilic probe TNS (6,P-toluidinylnaphthalene-2-sulfonate provided evidence that conserved leucine 43 and aspartic acid 39 contribute to the size of the DIR1 hydrophobic cavity and possibly hydrophobic ligand binding. An Arabidopsis–cucumber SAR model was developed to investigate the conservation of DIR1 function in cucumber (Cucumis sativus, and we demonstrated that phloem exudates from SAR-induced cucumber rescued the SAR defect in the Arabidopsis dir1-1 mutant. Additionally, an AtDIR1 antibody detected a protein of the same size as AtDIR1 in SAR-induced cucumber phloem exudates, providing evidence that DIR1 function during SAR is conserved in Arabidopsis and cucumber. In vitro TNS displacement assays demonstrated that recombinant AtDIR1 did not bind the SAR signals azelaic acid (AzA, glycerol-3-phosphate or pipecolic acid. However, recombinant CsDIR1 and CsDIR2 interacted weakly with AzA and pipecolic acid. Bioinformatic and functional analyses using the Arabidopsis–cucumber SAR model provide evidence that DIR1 orthologs exist in tobacco, tomato, cucumber, and soybean, and that DIR1-mediated SAR signaling is conserved in Arabidopsis and cucumber.

  3. Molecular dissection of the response of the rice Systemic Acquired Resistance Deficient 1 (SARD1) gene to different types of ionizing radiation.

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    Jung, In Jung; Hwang, Jung Eun; Han, Sung Min; Kim, Dong Sub; Ahn, Joon-Woo; Choi, Hong-Il; Kwon, Soon-Jae; Kang, Si-Yong; Kim, Jin-Baek

    2017-07-01

    Exposure to ionizing radiation induces plant defenses by regulating the expression of response genes. The systemic acquired resistance deficient 1 (SARD1) is a key gene in plant defense response. In this study, the function of Oryza sativa SARD1 (OsSARD1) was investigated after exposure of seeds/plants to ionizing radiation, jasmonic acid (JA) or salicylic acid (SA). Rice seeds exposed to two types of ionizing radiations (gamma ray [GR] and ion beam [IB]) were analyzed by quantitative reverse transcription PCR (qRT-PCR) to identify the genes that are altered in response to ionizing radiation. Then, OsSARD1-overexpressing homozygous Arabidopsis plants were generated to assess the effects of OsSARD1 in the response to irradiation. The phenotypes of these transgenic plants, as well as control plants, were monitored after GR irradiation at doses of 200 and 300 Gray (Gy). The OsSARD1 transcript was strongly downregulated after exposure to GR and IB irradiation. Previous phylogenetic analysis showed that the Arabidopsis SARD1 (AtSARD1) protein is closely related to Arabidopsis calmodulin-binding protein 60g (AtCBP60g), which is known to be required for activation of SA biosynthesis. In this study, phylogenetic analysis showed that OsSARD1 was grouped with AtSARD1. The OsSARD1 gene was induced after exposure to SA and JA. The biological phenotype of OsSARD1-overexpressing Arabidopsis plants was examined. OsSARD1-overexpressing plants displayed resistance to GR; in comparison with wild-type plants, the height and weight of OsSARD1-overexpressing plants were significantly greater after GR irradiation. In addition, OsSARD1 protein was abundantly accumulated in the nucleus. The results indicate that OsSARD1 plays an important role in the regulation of the defense responses to GR and IB irradiation and exhibits phytohormone induced expression.

  4. Cancer resistance as an acquired and inheritable trait

    DEFF Research Database (Denmark)

    Koch, Janne; Hau, Jann; Jensen, Henrik Elvang

    2014-01-01

    AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer c...... of the resistance is unknown but may involve epigenetic mechanisms. Other examples of inheritability of acquired phenotypic changes exist but, to our knowledge, this is the first demonstration of acquired, inherited cancer resistance.......AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer...... cells in BALB/c mice was induced by immunization with inactivated S180 cancer cells. The immunization was performed by either frozen/thawed or irradiated cancer cells or cell-free ascitic fluid (CFAF). RESULTS: In all instances the induced resistance was demonstrated to be inheritable. The phenotype...

  5. The Extent to Which Methyl Salicylate Is Required for Signaling Systemic Acquired Resistance Is Dependent on Exposure to Light after Infection1[OA

    Science.gov (United States)

    Liu, Po-Pu; von Dahl, Caroline C.; Klessig, Daniel F.

    2011-01-01

    Systemic acquired resistance (SAR) is a state of heightened defense to a broad spectrum of pathogens that is activated throughout a plant following local infection. Development of SAR requires the translocation of one or more mobile signals from the site of infection through the vascular system to distal (systemic) tissues. The first such signal identified was methyl salicylate (MeSA) in tobacco (Nicotiana tabacum). Subsequent studies demonstrated that MeSA also serves as a SAR signal in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum). By contrast, another study suggested that MeSA is not required for SAR in Arabidopsis and raised questions regarding its signaling role in tobacco. Differences in experimental design, including the developmental age of the plants, the light intensity, and/or the strain of bacterial pathogen, were proposed to explain these conflicting results. Here, we demonstrate that the length of light exposure that plants receive after the primary infection determines the extent to which MeSA is required for SAR signaling. When the primary infection occurred late in the day and as a result infected plants received very little light exposure before entering the night/dark period, MeSA and its metabolizing enzymes were essential for SAR development. In contrast, when infection was done in the morning followed by 3.5 h or more of exposure to light, SAR developed in the absence of MeSA. However, MeSA was generally required for optimal SAR development. In addition to resolving the conflicting results concerning MeSA and SAR, this study underscores the importance of environmental factors on the plant’s response to infection. PMID:22021417

  6. The extent to which methyl salicylate is required for signaling systemic acquired resistance is dependent on exposure to light after infection.

    Science.gov (United States)

    Liu, Po-Pu; von Dahl, Caroline C; Klessig, Daniel F

    2011-12-01

    Systemic acquired resistance (SAR) is a state of heightened defense to a broad spectrum of pathogens that is activated throughout a plant following local infection. Development of SAR requires the translocation of one or more mobile signals from the site of infection through the vascular system to distal (systemic) tissues. The first such signal identified was methyl salicylate (MeSA) in tobacco (Nicotiana tabacum). Subsequent studies demonstrated that MeSA also serves as a SAR signal in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum). By contrast, another study suggested that MeSA is not required for SAR in Arabidopsis and raised questions regarding its signaling role in tobacco. Differences in experimental design, including the developmental age of the plants, the light intensity, and/or the strain of bacterial pathogen, were proposed to explain these conflicting results. Here, we demonstrate that the length of light exposure that plants receive after the primary infection determines the extent to which MeSA is required for SAR signaling. When the primary infection occurred late in the day and as a result infected plants received very little light exposure before entering the night/dark period, MeSA and its metabolizing enzymes were essential for SAR development. In contrast, when infection was done in the morning followed by 3.5 h or more of exposure to light, SAR developed in the absence of MeSA. However, MeSA was generally required for optimal SAR development. In addition to resolving the conflicting results concerning MeSA and SAR, this study underscores the importance of environmental factors on the plant's response to infection.

  7. Electrical Signaling, Photosynthesis and Systemic Acquired Acclimation

    Directory of Open Access Journals (Sweden)

    Magdalena Szechyńska-Hebda

    2017-09-01

    Full Text Available Electrical signaling in higher plants is required for the appropriate intracellular and intercellular communication, stress responses, growth and development. In this review, we have focus on recent findings regarding the electrical signaling, as a major regulator of the systemic acquired acclimation (SAA and the systemic acquired resistance (SAR. The electric signaling on its own cannot confer the required specificity of information to trigger SAA and SAR, therefore, we have also discussed a number of other mechanisms and signaling systems that can operate in combination with electric signaling. We have emphasized the interrelation between ionic mechanism of electrical activity and regulation of photosynthesis, which is intrinsic to a proper induction of SAA and SAR. In a special way, we have summarized the role of non-photochemical quenching and its regulator PsbS. Further, redox status of the cell, calcium and hydraulic waves, hormonal circuits and stomatal aperture regulation have been considered as components of the signaling. Finally, a model of light-dependent mechanisms of electrical signaling propagation has been presented together with the systemic regulation of light-responsive genes encoding both, ion channels and proteins involved in regulation of their activity. Due to space limitations, we have not addressed many other important aspects of hormonal and ROS signaling, which were presented in a number of recent excellent reviews.

  8. Induction of Systemic acquired resistance in Mungbean against Mungbean Yellow Mosaic Begomovirus by the exogenous application of Salicylic acid and Benzothiadiazole.

    OpenAIRE

    Muhammad Farooq; Naila Ilyas; Kaleem Kakar; Iltaf Khan; Abdul Saboor; Nabeela Ilyas; Shoaib Khan; Abdul Qayum; Naqeeb Ullah; Muhammad Bakhtiar

    2018-01-01

    Abstract— The diseases caused by bipartite Begomoviruses have emerged as overwhelming problem in various cropping systems of Pakistan. The study was conducted to evaluate the potential of induced resistance in mungbean to Mungbean yellow mosaic virus (MYMV) disease. In this work, resistance to MYMV infection was induced in mungbean plants by activating the Salicylic acid (SA) pathway using SA and Benzothiadiazole (BTH) as treatments. The resistance was characterized by evaluating symptom appe...

  9. Association between Mycobacterium tuberculosis complex phylogenetic lineage and acquired drug resistance.

    Directory of Open Access Journals (Sweden)

    Courtney M Yuen

    Full Text Available BACKGROUND: Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. METHODS: We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. RESULTS: M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14 adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90 adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83. CONCLUSIONS: We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management.

  10. Systemic resistance induced by rhizosphere bacteria

    NARCIS (Netherlands)

    Loon, L.C. van; Bakker, P.A.H.M.; Pieterse, C.M.J.

    1998-01-01

    Nonpathogenic rhizobacteria can induce a systemic resistance in plants that is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). Rhizobacteria-mediated induced systemic resistance (ISR) has been demonstrated against fungi, bacteria, and viruses in Arabidopsis, bean,

  11. Antibiotic resistance patterns of pediatric community-acquired urinary infections

    Directory of Open Access Journals (Sweden)

    Eliana Biondi Medeiros Guidoni

    Full Text Available Knowledge about antimicrobial resistance patterns of the etiological agents of urinary tract infections (UTIs is essential for appropriate therapy. Urinary isolates from symptomatic UTI cases attended at Santa Casa University Hospital of São Paulo from August 1986 to December 1989 and August 2004 to December 2005 were identified by conventional methods. Antimicrobial resistance testing was performed by Kirby Bauer's disc diffusion method. Among the 257 children, E. coli was found in 77%. A high prevalence of resistance was observed against ampicillin and TMP/SMX (55% and 51%. The antibiotic resistance rates for E. coli were: nitrofurantoin (6%, nalidixic acid (14%, 1st generation cephalosporin (13%, 3rd generation cephalosporins (5%, aminoglycosides (2%, norfloxacin (9% and ciprofloxacin (4%. We found that E. coli was the predominant bacterial pathogen of community-acquired UTIs. We also detected increasing resistance to TMP/SMX among UTI pathogens in this population.

  12. Acquired resistance to EGFR inhibitors: mechanisms and prevention strategies

    International Nuclear Information System (INIS)

    Viloria-Petit, Alicia M.; Kerbel, Robert S.

    2004-01-01

    Potent and specific, or relatively specific, inhibitors of epidermal growth factor receptor (EGFR) signaling, including monoclonal antibodies and small molecular weight compounds, have been successfully developed. Both types of agent have been found to have significant antitumor activity, especially when used in combination with radio- hormone- and chemotherapy in preclinical studies. Because of the potentiation of the conventional drug activity in these combination settings, inhibitors of EGFR signaling have often been referred to as sensitizers for chemotherapy or radiation, as well as drug resistance reversal agents. Phase II clinical trials in head-and-neck as well as lung cancer suggested this concept of chemosensitization might translate into the clinic, but this remains to be definitively proven in randomized, double-blind Phase III trials. Given the extensive preclinical literature on EGFR blocking drugs and the advanced clinical development of such agents, it is surprising that the possibility of development of acquired resistance to the EGFR inhibitors themselves, a common clinical problem with virtually all other currently used anticancer drugs, remains a largely unexplored subject of investigation. Here we summarize some of the possible mechanisms that can result in acquired resistance to EGFR-targeting drugs. Alternative combination therapies to circumvent and delay this problem are suggested

  13. The Genomic Basis of Intrinsic and Acquired Antibiotic Resistance in the Genus Serratia

    Science.gov (United States)

    Sandner-Miranda, Luisa; Vinuesa, Pablo; Cravioto, Alejandro; Morales-Espinosa, Rosario

    2018-01-01

    Serratia marcescens, a member of the Enterobacteriaceae family, was long thought to be a non-pathogenic bacterium prevalent in environmental habitats. Together with other members of this genus, it has emerged in recent years as an opportunistic nosocomial pathogen causing various types of infections. One important feature of pathogens belonging to this genus is their intrinsic and acquired resistance to a variety of antibiotic families, including β-lactam, aminoglycosides, quinolones and polypeptide antibiotics. The aim of this study was to elucidate which genes participate in the intrinsic and acquired antibiotic resistance of this genus in order to determine the Serratia genus resistome. We performed phylogenomic and comparative genomic analyses using 32 Serratia spp. genomes deposited in the NCBI GenBank from strains isolated from different ecological niches and different lifestyles. S. marcescens strain SmUNAM836, which was previously isolated from a Mexican adult with obstructive pulmonary disease, was included in this study. The results show that most of the antibiotic resistance genes (ARGs) were found on the chromosome, and to a lesser degree, on plasmids and transposons acquired through horizontal gene transfer. Four strains contained the gyrA point mutation in codon Ser83 that confers quinolone resistance. Pathogenic and environmental isolates presented a high number of ARGs, especially genes associated with efflux systems. Pathogenic strains, specifically nosocomial strains, presented more acquired resistance genes than environmental isolates. We may conclude that the environment provides a natural reservoir for antibiotic resistance, which has been underestimated in the medical field.

  14. Primary and acquired resistance to biologic therapies in gastrointestinal cancers.

    Science.gov (United States)

    Lubner, Sam J; Uboha, Nataliya V; Deming, Dustin A

    2017-06-01

    Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds. Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways.

  15. Prospective Genotyping of Hospital-Acquired Methicillin-Resistant Staphylococcus aureus Isolates by Use of a Novel, Highly Discriminatory Binary Typing System

    Science.gov (United States)

    Zhou, Fei; Sintchenko, Vitali; Gilbert, Gwendolyn L.

    2012-01-01

    In settings of high methicillin-resistant Staphylococcus aureus (MRSA) prevalence, detection of nosocomial transmission events can be difficult without strain typing. Prospective typing of all MRSA isolates could potentially identify transmission in a timely fashion, making infection control responses to outbreaks more effective. We describe the development and evaluation of a novel 19-target binary typing system for MRSA using the multiplex-PCR/reverse line blot hybridization platform. Pulse-field gel electrophoresis (PFGE), spa typing, and phage-derived open reading frame (PDORF) typing were performed for comparison. The system was utilized to identify transmission events in three general surgical wards over a 12-month period. Initial MRSA isolates from 273 patients were differentiated into 55 unique binary types. One or more potential contacts colonized with the same MRSA strain were identified in 69 of 87 cases (79%) in which definite or possible nosocomial MRSA acquisition had occurred. The discriminatory power of the typing system was similar to that of PFGE (Simpson's index of diversity [D] = 0.994, versus 0.987) and higher than that of spa typing (D = 0.926). Strain typing reduced the total number of potential MRSA-colonized source contacts from 859 to 212 and revealed temporal clustering of transmission events. Prospective MRSA typing using this novel binary typing method can rapidly identify nosocomial transmission events, even in high-prevalence settings, which allows timely infection control interventions. The system is rapid, inexpensive, discriminatory, and suitable for routine, high-throughput use in the hospital microbiology laboratory. PMID:22895043

  16. A mechanism of acquired resistance to complement-mediated lysis by Entamoeba histolytica.

    Science.gov (United States)

    Gutiérrez-Kobeh, L; Cabrera, N; Pérez-Montfort, R

    1997-04-01

    Some Entamoeba histolytica strains resist complement-mediated lysis by serum. Susceptible and resistant strains activate the complement system equivalently, but resistant amebas evade killing by membrane attack complexes. Our objective was to determine the mechanism by which trophozoites of E. histolytica resist lysis by human serum. Amebas were made resistant to lysis by incubation with increasing concentrations of normal human serum. The possibility that resistant cells ingest membrane attack complexes was explored by subcellular fractionation of susceptible and resistant trophozoites treated with sublytic concentrations of human serum containing radiolabeled C9. In both cases, most of the label was in the fractions containing plasma membrane. The susceptible strain consistently showed more label associated with these fractions than the resistant strain. Thus, the possibility that the membrane attack complexes were released to the medium was explored. Both resistant and susceptible trophozoites release to the medium similar amounts of material excluded by Sepharose CL-2B in the presence or absence of normal human serum. Labeled C9 elutes together with the main bulk of proteins from the medium: this indicates that it is not in vesicles or high molecular weight aggregates. Coincubation of susceptible amebas with lysates of resistant trophozoites confers resistance to susceptible cells within 30 min. Resistance to lysis by serum can also be acquired by susceptible amebas after coincubation with lysates from human erythrocytes or after feeding them with whole human red blood cells. Resistant but not susceptible trophozoites show intense immunofluorescent staining on their surface with anti-human erythrocytic membrane antibody. These results suggest that amebas acquire resistance to lysis by serum by incorporating into their membranes complement regulatory proteins.

  17. System Acquires Data On Reactivities Of Foams

    Science.gov (United States)

    Walls, Joe T.

    1994-01-01

    Data-acquisition and -plotting system, called DAPS(TM), developed enabling accurate and objective determination of physical properties related to reactivities of polyurethane and polyisocyanurate foams. Automated, computer-controlled test apparatus that acquires data on rates of rise, rise profiles, exothermic temperatures, and internal pressures of foams prepared from both manual and machine-mixed batches. Data used to determine minute differences between reaction kinetics and exothermic profiles of foam formulations, properties of end products which are statistically undifferentiated.

  18. The Genomic Basis of Intrinsic and Acquired Antibiotic Resistance in the Genus Serratia

    Directory of Open Access Journals (Sweden)

    Luisa Sandner-Miranda

    2018-05-01

    Full Text Available Serratia marcescens, a member of the Enterobacteriaceae family, was long thought to be a non-pathogenic bacterium prevalent in environmental habitats. Together with other members of this genus, it has emerged in recent years as an opportunistic nosocomial pathogen causing various types of infections. One important feature of pathogens belonging to this genus is their intrinsic and acquired resistance to a variety of antibiotic families, including β-lactam, aminoglycosides, quinolones and polypeptide antibiotics. The aim of this study was to elucidate which genes participate in the intrinsic and acquired antibiotic resistance of this genus in order to determine the Serratia genus resistome. We performed phylogenomic and comparative genomic analyses using 32 Serratia spp. genomes deposited in the NCBI GenBank from strains isolated from different ecological niches and different lifestyles. S. marcescens strain SmUNAM836, which was previously isolated from a Mexican adult with obstructive pulmonary disease, was included in this study. The results show that most of the antibiotic resistance genes (ARGs were found on the chromosome, and to a lesser degree, on plasmids and transposons acquired through horizontal gene transfer. Four strains contained the gyrA point mutation in codon Ser83 that confers quinolone resistance. Pathogenic and environmental isolates presented a high number of ARGs, especially genes associated with efflux systems. Pathogenic strains, specifically nosocomial strains, presented more acquired resistance genes than environmental isolates. We may conclude that the environment provides a natural reservoir for antibiotic resistance, which has been underestimated in the medical field.

  19. Antibiotic resistance in community-acquired urinary tract infections

    African Journals Online (AJOL)

    the treatment of other infections would inevitably lead to the development of resistance. S Afr Med J 1994; 84: 600-602. Antibiotic resistance is a major problem in developing countries.' There are many reasons for this, including antibiotic use in animal feeds, inappropriate prescribing and poor sanitation. Resistance rates in ...

  20. Antibiotic resistance in community-acquired urinary tract infections

    African Journals Online (AJOL)

    of community-acquired UTI organisms to amoxycillin and co-trimoxazole was .... Treatment of uncomplicated urinary tract infection in non-pregnant women. Postgrad ... Single-dose antibiotic treatment for symptomatic uri- nary tract infections in ...

  1. Antibiotic resistance patterns of pediatric community-acquired urinary infections

    OpenAIRE

    Guidoni, Eliana Biondi Medeiros; Berezin, Eitan N.; Nigro, Stanley; Santiago, Nataly A; Benini, Vanda; Toporovski, Julio

    2008-01-01

    Knowledge about antimicrobial resistance patterns of the etiological agents of urinary tract infections (UTIs) is essential for appropriate therapy. Urinary isolates from symptomatic UTI cases attended at Santa Casa University Hospital of São Paulo from August 1986 to December 1989 and August 2004 to December 2005 were identified by conventional methods. Antimicrobial resistance testing was performed by Kirby Bauer's disc diffusion method. Among the 257 children, E. coli was found in 77%. A h...

  2. Community-acquired methicillin-resistant Staphylococcus aureus: community transmission, pathogenesis, and drug resistance.

    Science.gov (United States)

    Yamamoto, Tatsuo; Nishiyama, Akihito; Takano, Tomomi; Yabe, Shizuka; Higuchi, Wataru; Razvina, Olga; Shi, Da

    2010-08-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is able to persist not only in hospitals (with a high level of antimicrobial agent use) but also in the community (with a low level of antimicrobial agent use). The former is called hospital-acquired MRSA (HA-MRSA) and the latter community-acquired MRSA (CA-MRSA). It is believed MRSA clones are generated from S. aureus through insertion of the staphylococcal cassette chromosome mec (SCCmec), and outbreaks occur as they spread. Several worldwide and regional clones have been identified, and their epidemiological, clinical, and genetic characteristics have been described. CA-MRSA is likely able to survive in the community because of suitable SCCmec types (type IV or V), a clone-specific colonization/infection nature, toxin profiles (including Pantone-Valentine leucocidin, PVL), and narrow drug resistance patterns. CA-MRSA infections are generally seen in healthy children or young athletes, with unexpected cases of diseases, and also in elderly inpatients, occasionally surprising clinicians used to HA-MRSA infections. CA-MRSA spreads within families and close-contact groups or even through public transport, demonstrating transmission cores. Re-infection (including multifocal infection) frequently occurs, if the cores are not sought out and properly eradicated. Recently, attention has been given to CA-MRSA (USA300), which originated in the US, and is growing as HA-MRSA and also as a worldwide clone. CA-MRSA infection in influenza season has increasingly been noted as well. MRSA is also found in farm and companion animals, and has occasionally transferred to humans. As such, the epidemiological, clinical, and genetic behavior of CA-MRSA, a growing threat, is focused on in this study.

  3. Molecular Basis for Necitumumab Inhibition of EGFR Variants Associated with Acquired Cetuximab Resistance.

    Science.gov (United States)

    Bagchi, Atrish; Haidar, Jaafar N; Eastman, Scott W; Vieth, Michal; Topper, Michael; Iacolina, Michelle D; Walker, Jason M; Forest, Amelie; Shen, Yang; Novosiadly, Ruslan D; Ferguson, Kathryn M

    2018-02-01

    Acquired resistance to cetuximab, an antibody that targets the EGFR, impacts clinical benefit in head and neck, and colorectal cancers. One of the mechanisms of resistance to cetuximab is the acquisition of mutations that map to the cetuximab epitope on EGFR and prevent drug binding. We find that necitumumab, another FDA-approved EGFR antibody, can bind to EGFR that harbors the most common cetuximab-resistant substitution, S468R (or S492R, depending on the amino acid numbering system). We determined an X-ray crystal structure to 2.8 Å resolution of the necitumumab Fab bound to an S468R variant of EGFR domain III. The arginine is accommodated in a large, preexisting cavity in the necitumumab paratope. We predict that this paratope shape will be permissive to other epitope substitutions, and show that necitumumab binds to most cetuximab- and panitumumab-resistant EGFR variants. We find that a simple computational approach can predict with high success which EGFR epitope substitutions abrogate antibody binding. This computational method will be valuable to determine whether necitumumab will bind to EGFR as new epitope resistance variants are identified. This method could also be useful for rapid evaluation of the effect on binding of alterations in other antibody/antigen interfaces. Together, these data suggest that necitumumab may be active in patients who are resistant to cetuximab or panitumumab through EGFR epitope mutation. Furthermore, our analysis leads us to speculate that antibodies with large paratope cavities may be less susceptible to resistance due to mutations mapping to the antigen epitope. Mol Cancer Ther; 17(2); 521-31. ©2017 AACR . ©2017 American Association for Cancer Research.

  4. Antimicrobial resistance patterns in community acquired urinary tract infections

    International Nuclear Information System (INIS)

    Gilani, S.Y.H; Ahmad, N.; Shah, S.R.A.

    2016-01-01

    Urinary tract infection (UTI) is the most frequent disease for which patients seek medical care. The antimicrobial agents causing UTI and their sensitivity patterns have remarkably changed throughout the world over the past few years. Hence, the present study was designed to explore the uropathogens and their susceptibility to various molecules in our region. Methods: This descriptive cross sectional study was conducted at Medical C Unit of Ayub Teaching Hospital, Abbottabad from January 2015 to January 2016. Patients with clinical features of UTI were evaluated using Urine R/E and Urine culture and sensitivity. Ten antibiotics were checked for susceptibility. Results were analysed using SPSS 17. Results: A total of 630 patients presented with urinary complaints. Of these, 236 patients had more than 8-10 pus cells on urine R/E. They were further evaluated using culture and sensitivity and positive culture was obtained in 75 patients. Of these 34 (45.3%) were males and 41 (54.7%) were females. E Coli was the predominant isolate being present in 49 (65.3%) patients. This was followed by Klebsiella in 9 (12%) patients. Tazobactam-piperacillin and cefoperazone-sulbactam were the most sensitive drugs having overall sensitivity of 96% and 93.3% respectively. The isolates were highly resistant to Fluoroquinolones 77.3% followed by Penicillins 72% and TMP-SMX 69.3%.Conclusion: Antibiotic sensitivity patterns have enormously changed over the past decade. Newer agents are quite efficacious but their use should be highly judicious to prevent the development of resistance to these molecules. (author)

  5. Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Bertran-Alamillo, Jordi; Molina, Miguel Angel

    2017-01-01

    Non-small-cell lung cancer patients with activating epidermal growth factor receptor (EGFR) mutations typically benefit from EGFR tyrosine kinase inhibitor treatment. However, virtually all patients succumb to acquired EGFR tyrosine kinase inhibitor resistance that occurs via diverse mechanisms....... The diversity and unpredictability of EGFR tyrosine kinase inhibitor resistance mechanisms presents a challenge for developing new treatments to overcome EGFR tyrosine kinase inhibitor resistance. Here, we show that Akt activation is a convergent feature of acquired EGFR tyrosine kinase inhibitor resistance......, across a spectrum of diverse, established upstream resistance mechanisms. Combined treatment with an EGFR tyrosine kinase inhibitor and Akt inhibitor causes apoptosis and synergistic growth inhibition in multiple EGFR tyrosine kinase inhibitor-resistant non-small-cell lung cancer models. Moreover...

  6. Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

    Science.gov (United States)

    Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

    2011-01-01

    The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

  7. Individual’s Resistance to Social Crises is Acquired in Childhood

    Directory of Open Access Journals (Sweden)

    Burvytė Sigita

    2011-12-01

    Full Text Available Objective: the development of person’s resistance to crises. The aim of the study is to revealthe importance of childhood experience to the person, by acquiring resistance to crises; theneed of pedagogical help in overcoming adaptation difficulties of the first-year pupil at school.The analysis of pedagogical, psychological, philosophical literature; the analysis of empiricalresearch and statistic data; as well as the method of observation were used in the current study.Though 60 percent of preparation possibilities for life are realised until the beginning of the firstgrade, the analysis of various authors’ research, quantitative analysis and observation of firstyearpupils in the schools of Vilnius, allow us to conclude that the main reason for a difficultadaptation of first-year pupils is the prevailing belief, that individuals’ preparation for life beginsat school. Educational system is based on rendering of the knowledge rather than the developmentof thinking ability and universal recognition of the environment. Inactivated brain during infancyand early childhood reduces the possibility of mastering information provided at school, andusing it in life. Family is the basis, which provides the feeling of safety, which instils real values,which creates the conditions of developing resistance to social changes, and various adaptationalskills, which are particularly necessary in the contemporary changing society. Extra attentionshould be paid to the education of parents and preparation for responsible parenthood.

  8. Absence of death receptor translocation into lipid rafts in acquired TRAIL-resistant NSCLC cells.

    Science.gov (United States)

    Ouyang, Wen; Yang, Chunxu; Zhang, Simin; Liu, Yu; Yang, Bo; Zhang, Junhong; Zhou, Fuxiang; Zhou, Yunfeng; Xie, Conghua

    2013-02-01

    Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a major limitation for its clinical use. The mechanisms of TRAIL resistance have been mostly studied in the context of cell lines that are intrinsically resistant to TRAIL. However, little is known about the molecular alterations that contribute to the development of acquired resistance during treatment with TRAIL. In this study, we established H460R, an isogenic cell line with acquired TRAIL resistance, from the TRAIL‑sensitive human lung cancer cell line H460 to investigate the mechanisms of acquired resistance. The acquired TRAIL‑resistant H460R cells remained sensitive to cisplatin. The mRNA and protein expression levels of death receptor 4 (DR4) and death receptor 5 (DR5) were not altered in either of the TRAIL-treated cell lines. Nevertheless, tests in which the DR4 or DR5 gene was overexpressed or silenced suggest that death receptor expression is necessary but not sufficient for TRAIL‑induced apoptosis. Compared with parental TRAIL-sensitive H460 cells, H460R cells showed a decreased TRAIL-induced translocation of DR4/DR5 into lipid rafts. Further studies showed that nystatin partially prevented lipid raft aggregation and DR4 and DR5 clustering and reduced apoptosis in H460 cells again. Analysis of apoptotic molecules showed that more pro-caspase-8, FADD, caspase-3 and Bid, but less cFLIP in H460 cells than in H460R cells. Our findings suggest that the lack of death receptor redistribution negatively impacts DISC assembly in lipid rafts, which at least partially leads to the development of acquired resistance to TRAIL in H460R cells.

  9. Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells.

    Science.gov (United States)

    Gaspar, Nathalie; Sharp, Swee Y; Pacey, Simon; Jones, Chris; Walton, Michael; Vassal, Gilles; Eccles, Suzanne; Pearson, Andrew; Workman, Paul

    2009-03-01

    Heat shock protein 90 (HSP90) inhibitors, such as 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), which is currently in phase II/phase III clinical trials, are promising new anticancer agents. Here, we explored acquired resistance to HSP90 inhibitors in glioblastoma (GB), a primary brain tumor with poor prognosis. GB cells were exposed continuously to increased 17-AAG concentrations. Four 17-AAG-resistant GB cell lines were generated. High-resistance levels with resistance indices (RI = resistant line IC(50)/parental line IC(50)) of 20 to 137 were obtained rapidly (2-8 weeks). After cessation of 17-AAG exposure, RI decreased and then stabilized. Cross-resistance was found with other ansamycin benzoquinones but not with the structurally unrelated HSP90 inhibitors, radicicol, the purine BIIB021, and the resorcinylic pyrazole/isoxazole amide compounds VER-49009, VER-50589, and NVP-AUY922. An inverse correlation between NAD(P)H/quinone oxidoreductase 1 (NQO1) expression/activity and 17-AAG IC(50) was observed in the resistant lines. The NQO1 inhibitor ES936 abrogated the differential effects of 17-AAG sensitivity between the parental and resistant lines. NQO1 mRNA levels and NQO1 DNA polymorphism analysis indicated different underlying mechanisms: reduced expression and selection of the inactive NQO1*2 polymorphism. Decreased NQO1 expression was also observed in a melanoma line with acquired resistance to 17-AAG. No resistance was generated with VER-50589 and NVP-AUY922. In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in GB, melanoma, and, possibly, other tumor types. Such resistance can be overcome with novel HSP90 inhibitors.

  10. Tracking acquired antibiotic resistance in commensal bacteria of Galápagos land iguanas: no man, no resistance.

    Science.gov (United States)

    Thaller, Maria Cristina; Migliore, Luciana; Marquez, Cruz; Tapia, Washington; Cedeño, Virna; Rossolini, Gian Maria; Gentile, Gabriele

    2010-02-01

    Antibiotic resistance, evolving and spreading among bacterial pathogens, poses a serious threat to human health. Antibiotic use for clinical, veterinary and agricultural practices provides the major selective pressure for emergence and persistence of acquired resistance determinants. However, resistance has also been found in the absence of antibiotic exposure, such as in bacteria from wildlife, raising a question about the mechanisms of emergence and persistence of resistant strains under similar conditions, and the implications for resistance control strategies. Since previous studies yielded some contrasting results, possibly due to differences in the ecological landscapes of the studied wildlife, we further investigated this issue in wildlife from a remote setting of the Galapagos archipelago. Screening for acquired antibiotic resistance was carried out in commensal enterobacteria from Conolophus pallidus, the terrestrial iguana of Isla Santa Fe, where: i) the abiotic conditions ensure to microbes good survival possibilities in the environment; ii) the animal density and their habits favour microbial circulation between individuals; and iii) there is no history of antibiotic exposure and the impact of humans and introduced animal species is minimal except for restricted areas. Results revealed that acquired antibiotic resistance traits were exceedingly rare among bacteria, occurring only as non-dominant strains from an area of minor human impact. Where both the exposure to antibiotics and the anthropic pressure are minimal, acquired antibiotic resistance traits are not normally found in bacteria from wildlife, even if the ecological landscape is highly favourable to bacterial circulation among animals. Monitoring antibiotic resistance in wildlife from remote areas could also be a useful tool to evaluate the impact of anthropic pressure.

  11. Tracking acquired antibiotic resistance in commensal bacteria of Galápagos land iguanas: no man, no resistance.

    Directory of Open Access Journals (Sweden)

    Maria Cristina Thaller

    Full Text Available BACKGROUND: Antibiotic resistance, evolving and spreading among bacterial pathogens, poses a serious threat to human health. Antibiotic use for clinical, veterinary and agricultural practices provides the major selective pressure for emergence and persistence of acquired resistance determinants. However, resistance has also been found in the absence of antibiotic exposure, such as in bacteria from wildlife, raising a question about the mechanisms of emergence and persistence of resistant strains under similar conditions, and the implications for resistance control strategies. Since previous studies yielded some contrasting results, possibly due to differences in the ecological landscapes of the studied wildlife, we further investigated this issue in wildlife from a remote setting of the Galapagos archipelago. METHODOLOGY/PRINCIPAL FINDINGS: Screening for acquired antibiotic resistance was carried out in commensal enterobacteria from Conolophus pallidus, the terrestrial iguana of Isla Santa Fe, where: i the abiotic conditions ensure to microbes good survival possibilities in the environment; ii the animal density and their habits favour microbial circulation between individuals; and iii there is no history of antibiotic exposure and the impact of humans and introduced animal species is minimal except for restricted areas. Results revealed that acquired antibiotic resistance traits were exceedingly rare among bacteria, occurring only as non-dominant strains from an area of minor human impact. CONCLUSIONS/SIGNIFICANCE: Where both the exposure to antibiotics and the anthropic pressure are minimal, acquired antibiotic resistance traits are not normally found in bacteria from wildlife, even if the ecological landscape is highly favourable to bacterial circulation among animals. Monitoring antibiotic resistance in wildlife from remote areas could also be a useful tool to evaluate the impact of anthropic pressure.

  12. Pattern of secondary acquired drug resistance to antituberculosis drug in Mumbai, India--1991-1995.

    Science.gov (United States)

    Chowgule, R V; Deodhar, L

    1998-01-01

    A retrospective observational study was conducted to find out whether secondary acquired drug resistance to isoniazid and ethambutol is high and to rifamycin and pyrazinamide is low, as is commonly believed in India. There were 2033 patients, whose sputum samples (6099) were reviewed from a specimen registry of the microbiology laboratory for the years 1991 to 1995. Of these, 521 (25.6%) patients [335 males and 186 females; age ranged from 11 to 75 years] had sputum positive culture and sensitivity for acid-fast bacilli (AFB). The drug resistance patterns in our study were: isoniazid (H) 15%, rifamycin (R) 66.8%, pyrazinamide (Z) 72.2%, ethambutol (E) 8.4%, streptomycin (S) 53.6%, cycloserine (C) 39.2% kanamycin (K) 25.1% and ethionamide (Eth) 65.3%. The resistance to streptomycin showed a significant fall over a year while there was a rise in resistance to cycloserine and kanamycin which is significant. The rate of secondary acquired resistance of isoniazid and ethambutol was low, and the rate of secondary acquired resistance to rifamycin and pyrazinamide was high, which is contarary to the common belief regarding these drugs in India. This implies that isoniazid is still a valuable drug in the treatment of multidrug resistance in India.

  13. RESISTENCIA SISTÉMICA ADQUIRIDA MEDIADA POR EL ÁCIDO SALICÍLICO RESISTÊNCIA SISTÊMICA ADQUIRIDA MEDIADA POR O ÁCIDO SALICÍLICO SYSTEMIC ACQUIRED RESISTANCE INDUCED BY SALICYLIC ACID

    Directory of Open Access Journals (Sweden)

    LUZ NELLY DIAZ-PUENTES

    2012-12-01

    , poderiam ser responsáveis pela indução de RSA no tecido sistêmico. Durante RSA há uma estreita interação entre o AS, o AJ, as auxinas, o etileno e as proteínas NPR1 e PR1. Esta revisão descreve o que mais recentemente se conhece sobre a sinalização molecular para induzir RSA através do AS.Systemic Acquired Resistance (SAR confers long-lasting protection against a secondary infection by biotrophic, necrotrophic and hemibiotrophic pathogens. SAR is a two steps process. Firstly, the plant recognizes the pathogen and induces a local plant response through a signal cascade that ends in an intracellular Salicylic Acid (SA accumulation. This accumulation induces an increase in Reactive Oxygen Species (ROS and expression of pathogenesis related (pr genes. Secondly, this local response induces a long distant resistance to pathogens in uninfected tissue. It has been postulated that molecules such as Methyl Salicylate (MeSa, some MAPKs and Nitric Oxide (NO, among others, could be responsible for the induction of SAR in the systemic tissue. During SAR there is a big interaction among SA, JA, auxins, ethylene and NPR1 and PR1 proteins. This review describes the last understanding about the molecular signalling to induce SAR trough SA.

  14. Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis.

    Directory of Open Access Journals (Sweden)

    David Quinto-Alemany

    Full Text Available Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP, giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC, 600 (C. albicans -5-FC or 1000 (S. cerevisiae--CSP fold higher than the spontaneous mutation frequency, the experimental data for C. albicans -5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.

  15. Intrinsic, adaptive and acquired antimicrobial resistance in Gram-negative bacteria.

    Science.gov (United States)

    Arzanlou, Mohsen; Chai, Wern Chern; Venter, Henrietta

    2017-02-28

    Gram-negative bacteria are responsible for a large proportion of antimicrobial-resistant infections in humans and animals. Among this class of bacteria are also some of the most successful environmental organisms. Part of this success is their adaptability to a variety of different niches, their intrinsic resistance to antimicrobial drugs and their ability to rapidly acquire resistance mechanisms. These mechanisms of resistance are not exclusive and the interplay of several mechanisms causes high levels of resistance. In this review, we explore the molecular mechanisms underlying resistance in Gram-negative organisms and how these different mechanisms enable them to survive many different stress conditions. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  16. Inhibition of BMP signaling overcomes acquired resistance to cetuximab in oral squamous cell carcinomas.

    Science.gov (United States)

    Yin, Jinlong; Jung, Ji-Eun; Choi, Sun Il; Kim, Sung Soo; Oh, Young Taek; Kim, Tae-Hoon; Choi, Eunji; Lee, Sun Joo; Kim, Hana; Kim, Eun Ok; Lee, Yu Sun; Chang, Hee Jin; Park, Joo Yong; Kim, Yeejeong; Yun, Tak; Heo, Kyun; Kim, Youn-Jae; Kim, Hyunggee; Kim, Yun-Hee; Park, Jong Bae; Choi, Sung Weon

    2018-02-01

    Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that bone morphogenic protein-7-phosphorylated Smad-1, -5, -8 (BMP7-p-Smad1/5/8) signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of p-Smad1/5/8. Treatment with the bone morphogenic protein receptor type 1 (BMPRI) inhibitor, DMH1 significantly reduced cetuximab-resistant OSCC tumor growth, and combined treatment of DMH1 and cetuximab remarkably reduced relapsed tumor growth in vivo. Importantly, p-Smad1/5/8 level was elevated in cetuximab-resistant patients and this correlated with poor prognosis. Collectively, our results indicate that the BMP7-p-Smad1/5/8 signaling is a key pathway to acquired cetuximab resistance, and demonstrate that combination therapy of cetuximab and a BMP signaling inhibitor as potentially a new therapeutic strategy for overcoming acquired resistance to cetuximab in OSCC. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer

    DEFF Research Database (Denmark)

    Jacobsen, Kirstine; Bertran-Alamillo, Jordi; Molina, Miguel Angel

    2017-01-01

    Non-small-cell lung cancer patients with activating epidermal growth factor receptor (EGFR) mutations typically benefit from EGFR tyrosine kinase inhibitor treatment. However, virtually all patients succumb to acquired EGFR tyrosine kinase inhibitor resistance that occurs via diverse mechanisms....

  18. Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells.

    Science.gov (United States)

    Li, Guangmin; Guo, Jun; Shen, Ben-Quan; Bumbaca Yadav, Daniela; Sliwkowski, Mark X; Crocker, Lisa M; Lacap, Jennifer A; Lewis Phillips, Gail D

    2018-04-25

    The receptor tyrosine kinase HER2 is overexpressed in approximately 20% of breast cancer, and its amplification is associated with reduced survival. Trastuzumab emtansine (Kadcyla®, T-DM1), an antibody-drug conjugate that is comprised of trastuzumab covalently linked to the anti-mitotic agent DM1 through a stable linker, was designed to selectively deliver DM1 to HER2-overexpressing tumor cells. T-DM1 is approved for the treatment of patients with HER2-positive metastatic breast cancer following progression on trastuzumab and a taxane. Despite the improvement in clinical outcome, many patients who initially respond to T-DM1 treatment eventually develop progressive disease. The mechanisms that contribute to T-DM1 resistance are not fully understood. To this end, we developed T-DM1-resistant in vitro models to examine the mechanisms of acquired T-DM1 resistance. We demonstrate that decreased HER2 and up-regulation of MDR1 contribute to T-DM1 resistance in KPL-4 T-DM1 resistant cells. In contrast, both loss of SLC46A3 and PTEN deficiency play a role in conferring resistance in BT-474M1 T-DM1 resistant cells. Our data suggest that these two cell lines acquire resistance through distinct mechanisms. Furthermore, we show that the KPL-4 T-DM1 resistance can be overcome by treatment with an inhibitor of MDR1, whereas a PI3K inhibitor can rescue PTEN loss-induced resistance in T-DM1-resistant BT-474M1 cells. Our results provide a rationale for developing therapeutic strategies to enhance T-DM1 clinical efficacy by combining T-DM1 and other inhibitors that target signaling transduction or resistance pathways. Copyright ©2018, American Association for Cancer Research.

  19. Prevalence of methicillin-resistant Staphylococcus aureus (MRSA in community-acquired primary pyoderma

    Directory of Open Access Journals (Sweden)

    Patil Rahul

    2006-01-01

    Full Text Available Background: Although prevalence of MRSA strains is reported to be increasing, there are no studies of their prevalence in community-acquired primary pyodermas in western India. Aims: This study aimed at determining the prevalence of MRSA infection in community-acquired primary pyodermas. Methods: Open, prospective survey carried out in a tertiary care hospital in Mumbai. Materials and Methods: Eighty-six patients with primary pyoderma, visiting the dermatology outpatient, were studied clinically and microbiologically. Sensitivity testing was done for vancomycin, sisomycin, gentamicin, framycetin, erythromycin, methicillin, cefazolin, cefuroxime, penicillin G and ciprofloxacin. Phage typing was done for MRSA positive strains. Results : The culture positivity rate was 83.7%. Staphylococcus aureus was isolated in all cases except two. Barring one, all strains of Staphylococcus were sensitive to methicillin. Conclusions: Methicillin resistance is uncommon in community-acquired primary pyodermas in Mumbai. Treatment with antibacterials active against MRSA is probably unwarranted for community-acquired primary pyodermas.

  20. Bacterial viruses enable their host to acquire antibiotic resistance genes from neighbouring cells

    DEFF Research Database (Denmark)

    Haaber, Jakob Krause; Leisner, Jørgen; Cohn, Marianne Thorup

    2016-01-01

    Prophages are quiescent viruses located in the chromosomes of bacteria. In the human pathogen, Staphylococcus aureus, prophages are omnipresent and are believed to be responsible for the spread of some antibiotic resistance genes. Here we demonstrate that release of phages from a subpopulation of S....... aureus cells enables the intact, prophage-containing population to acquire beneficial genes from competing, phage-susceptible strains present in the same environment. Phage infection kills competitor cells and bits of their DNA are occasionally captured in viral transducing particles. Return...... of such particles to the prophage-containing population can drive the transfer of genes encoding potentially useful traits such as antibiotic resistance. This process, which can be viewed as ‘auto-transduction’, allows S. aureus to efficiently acquire antibiotic resistance both in vitro and in an in vivo virulence...

  1. Mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitor in Korean patients with lung cancer

    International Nuclear Information System (INIS)

    Ji, Wonjun; Lee, Dae Ho; Lee, Jae Cheol; Choi, Chang-Min; Rho, Jin Kyung; Jang, Se Jin; Park, Young Soo; Chun, Sung-Min; Kim, Woo Sung; Lee, Jung-Shin; Kim, Sang-We

    2013-01-01

    Despite an initial good response to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), resistance to treatment eventually develops. Although several resistance mechanisms have been discovered, little data exist regarding Asian patient populations. Among patients at a tertiary referral hospital in Korea who initially responded well to gefitinib and later acquired resistance to treatment, we selected those with enough tissues obtained before EGFR-TKI treatment and after the onset of resistance to examine mutations by mass spectrometric genotyping technology (Asan-Panel), MET amplification by fluorescence in situ hybridization (FISH), and analysis of AXL status, epithelial-to-mesenchymal transition (EMT) and neuroendocrine markers by immunohistochemistry. Twenty-six patients were enrolled, all of whom were diagnosed with adenocarcinoma with EGFR mutations (19del: 16, L858R: 10) except one (squamous cell carcinoma with 19del). Secondary T790M mutation was detected in 11 subjects (42.3%) and four of these patients had other co-existing resistance mechanisms; increased AXL expression was observed in 5/26 patients (19.2%), MET gene amplification was noted in 3/26 (11.5%), and one patient acquired a mutation in the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) gene. None of the patients exhibited EMT; however, increased CD56 expression suggesting neuroendocrine differentiation was observed in two patients. Interestingly, conversion from L858R-mutant to wild-type EGFR occurred in one patient. Seven patients (26.9%) did not exhibit any known resistance mechanisms. Patients with a T790M mutation showed a more favorable prognosis. The mechanisms and frequency of acquired EGFR-TKI resistance in Koreans are comparable to those observed in Western populations; however, more data regarding the mechanisms that drive EGFR-TKI resistance are necessary

  2. P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

    International Nuclear Information System (INIS)

    Kim, Hee Joung; Lee, Kye Young; Kim, Young Whan; Choi, Yun Jung; Lee, Jung-Eun; Choi, Chang Min; Baek, In-Jeoung; Rho, Jin Kyung; Lee, Jae Cheol

    2015-01-01

    Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement. The online

  3. Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit

    Directory of Open Access Journals (Sweden)

    Heiko Löhr

    2018-05-01

    Full Text Available Summary: Anorexigenic pro-opiomelanocortin (Pomc/alpha-melanocyte stimulating hormone (αMSH neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful. : The melanocortin system controls energy homeostasis and somatic growth, but the underlying mechanisms are elusive. Löhr et al. identify a functional neural circuit in which Pomc neurons stimulate hypothalamic somatostatin neurons, thereby inhibiting hypophyseal growth hormone production. Excessive feeding and acquired leptin resistance attenuate this pathway, allowing faster somatic growth when food resources are rich. Keywords: Pomc neuron, somatostatin neuron, somatic growth, growth hormone, melanocortin system, high-fat diet, obesity, leptin resistance, zebrafish, mouse

  4. Prevalence and resistance pattern of Moraxella catarrhalis in community-acquired lower respiratory tract infections

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    Shaikh SBU

    2015-07-01

    Full Text Available Safia Bader Uddin Shaikh, Zafar Ahmed, Syed Ali Arsalan, Sana Shafiq Department of Pulmonology, Liaquat National Hospital, Karachi, Pakistan Introduction: Moraxella catarrhalis previously considered as commensal of upper respiratory tract has gained importance as a pathogen responsible for respiratory tract infections. Its beta-lactamase-producing ability draws even more attention toward its varying patterns of resistance. Methods: This was an observational study conducted to evaluate the prevalence and resistance pattern of M. catarrhalis. Patients aged 20–80 years admitted in the Department of Chest Medicine of Liaquat National Hospital from March 2012 to December 2012 were included in the study. Respiratory samples of sputum, tracheal secretions, and bronchoalveolar lavage were included, and their cultures were followed. Results: Out of 110 respiratory samples, 22 showed positive cultures for M. catarrhalis in which 14 were males and eight were females. Ten samples out of 22 showed resistance to clarithromycin, and 13 samples out of 22 displayed resistance to erythromycin, whereas 13 showed resistance to levofloxacin. Hence, 45% of the cultures showed resistance to macrolides so far and 59% showed resistance to quinolones. Conclusion: Our study shows that in our environment, M. catarrhalis may be resistant to macrolides and quinolones; hence, these should not be recommended as an alternative treatment in community-acquired lower respiratory tract infections caused by M. catarrhalis. However, a study of larger sample size should be conducted to determine if the recommendations are required to be changed. Keywords: community-acquired lower respiratory tract infections or pneumonia, M. catarrhalis, antibiotic resistance, gram-negative diplococcic, Pakistan

  5. Technical Equivalency Documentation for a Newly Acquired Alpha Spectroscopy System

    International Nuclear Information System (INIS)

    Hickman, D P; Fisher, S K; Hann, P R; Hume, R

    2007-01-01

    The response of a recently acquired Canberra(trademark) Alpha Analyst 'Blue' system (Chamber Number's 173-208) used by the Hazards Control, Radiation Safety Section, WBC/Spectroscopy Team has been studied with respect to an existing Canberra system. The existing Canberra system consists of thirty Alpha Analyst dual chambers Model XXXX comprising a total of sixty detectors (Chambers Number's 101-124 and 137-172). The existing chambers were previously compared to an older system consisting of thirty-six Model 7401 alpha spectrometry chambers (Chamber Number's 1-36) Chambers 101-124 and 137-172 are DOELAP accredited. The older system was previously DOELAP accredited for the routine Alpha Spectroscopy program used in LLNL's in vitro bioassay program. The newly acquired Alpha Analyst system operates on a network with software that controls and performs analysis of the current Alpha Analyst system (Chamber Number's 101-124 and 137-172). This exact same software is used for the current system and the newly acquired system and is DOELAP accredited. This document compares results from the existing Alpha System with the newer Alpha Analyst system

  6. Acquired resistance to chlorhexidine - is it time to establish an 'antiseptic stewardship' initiative?

    Science.gov (United States)

    Kampf, G

    2016-11-01

    Chlorhexidine digluconate (CHG) is an antimicrobial agent used for different types of applications in hand hygiene, skin antisepsis, oral care, and patient washing. Increasing use raises concern regarding development of acquired bacterial resistance. Published data from clinical isolates with CHG minimum inhibitory concentrations (MICs) were reviewed and compared to epidemiological cut-off values to determine resistance. CHG resistance is rarely found in Escherichia coli, Salmonella spp., Staphylococcus aureus or coagulase-negative staphylococci. In Enterobacter spp., Pseudomonas spp., Proteus spp., Providencia spp. and Enterococcus spp., however, isolates are more often CHG resistant. CHG resistance may be detected in multi-resistant isolates such as extremely drug-resistant Klebsiella pneumoniae. Isolates with a higher MIC are often less susceptible to CHG for disinfection. Although cross-resistance to antibiotics remains controversial, some studies indicate that the overall exposure to CHG increases the risk for resistance to some antibiotic agents. Resistance to CHG has resulted in numerous outbreaks and healthcare-associated infections. On an average intensive care unit, most of the CHG exposure would be explained by hand hygiene agents when liquid soaps or alcohol-based hand rubs contain CHG. Exposure to sub-lethal CHG concentration may enhance resistance in Acinetobacter spp., K. pneumoniae, and Pseudomonas spp., all species well known for emerging antibiotic resistance. In order to reduce additional selection pressure in nosocomial pathogens it seems to make sense to restrict the valuable agent CHG to those indications with a clear patient benefit and to eliminate it from applications without any benefit or with a doubtful benefit. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  7. Naturally occurring dominant drug resistance mutations occur infrequently in the setting of recently acquired hepatitis C.

    Science.gov (United States)

    Applegate, Tanya L; Gaudieri, Silvana; Plauzolles, Anne; Chopra, Abha; Grebely, Jason; Lucas, Michaela; Hellard, Margaret; Luciani, Fabio; Dore, Gregory J; Matthews, Gail V

    2015-01-01

    Direct-acting antivirals (DAAs) are predicted to transform hepatitis C therapy, yet little is known about the prevalence of naturally occurring resistance mutations in recently acquired HCV. This study aimed to determine the prevalence and frequency of drug resistance mutations in the viral quasispecies among HIV-positive and -negative individuals with recent HCV. The NS3 protease, NS5A and NS5B polymerase genes were amplified from 50 genotype 1a participants of the Australian Trial in Acute Hepatitis C. Amino acid variations at sites known to be associated with possible drug resistance were analysed by ultra-deep pyrosequencing. A total of 12% of individuals harboured dominant resistance mutations, while 36% demonstrated non-dominant resistant variants below that detectable by bulk sequencing (that is, Resistance variants (resistance from all classes, with the exception of sofosbuvir. Dominant resistant mutations were uncommonly observed in the setting of recent HCV. However, low-level mutations to all DAA classes were observed by deep sequencing at the majority of sites and in most individuals. The significance of these variants and impact on future treatment options remains to be determined. Clinicaltrials.gov NCT00192569.

  8. School Reentry for Children with Acquired Central Nervous Systems Injuries

    Science.gov (United States)

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

  9. Disseminated cryptococcosis and fluconazole resistant oral candidiasis in a patient with acquired immunodeficiency syndrome (AIDS).

    Science.gov (United States)

    Kothavade, Rajendra J; Oberai, Chetan M; Valand, Arvind G; Panthaki, Mehroo H

    2010-10-28

    Disseminated cryptococcosis and recurrent oral candidiasis was presented in a-heterosexual AIDS patient. Candida tropicalis (C.tropicalis) was isolated from the oral pseudomembranous plaques and Cryptococcus neoformans (C. neoformans) was isolated from maculopapular lesions on body parts (face, hands and chest) and body fluids (urine, expectorated sputum, and cerebrospinal fluid). In vitro drug susceptibility testing on the yeast isolates demonstrated resistance to fluconazole acquired by C. tropicalis which was a suggestive possible root cause of recurrent oral candidiasis in this patient.

  10. Drug resistance in community-acquired respiratory tract infections: role for an emerging antibacterial

    Directory of Open Access Journals (Sweden)

    Lorenzo Aguilar

    2010-06-01

    Full Text Available Lorenzo Aguilar1, María-José Giménez1, José Barberán21Microbiology Department, School of Medicine, University Complutense, Madrid; 2Infectious Diseases Department, Hospital Central de la Defensa Gomez Ulla, Madrid, SpainAbstract: The nasopharynx is the ecological niche where evolution towards resistance occurs in respiratory tract isolates. Dynamics of different bacterial populations in antibiotic-free multibacterial niches are the baseline that antibiotic treatments can alter by shifting the competitive balance in favor of resistant populations. For this reason, antibiotic resistance is increasingly being considered to be an ecological problem. Traditionally, resistance has implied the need for development of new antibiotics for which basic efficacy and safety data are required prior to licensing. Antibiotic development is mainly focused on demonstrating clinical efficacy and setting susceptibility breakpoints for efficacy prediction. However, additional information on pharmacodynamic data predicting absence of selection of resistance and of resistant subpopulations, and specific surveillance on resistance to core antibiotics (to detect emerging resistances and its link with antibiotic consumption in the community are valuable data in defining the role of a new antibiotic, not only from the perspective of its therapeutic potential but also from the ecologic perspective (countering resistances to core antibiotics in the community. The documented information on cefditoren gleaned from published studies in recent years is an example of the role for an emerging oral antibacterial facing current antibiotic resistance in community-acquired respiratory tract infections.Keywords: respiratory tract infection, antibiotic resistance, cefditoren, community

  11. Radiation response of human lung cancer cells with inherent and acquired resistance to cisplatin

    International Nuclear Information System (INIS)

    Twentyman, P.R.; Wright, K.A.; Rhodes, T.

    1991-01-01

    We have derived sublines of three human lung cancer cell lines with acquired resistance to cisplatin. The cisplatin resistant sublines of NCI-H69 (small cell), COR-L23 (large cell), and MOR (adenocarcinoma) show 5.3 fold, 3.1 fold, and 3.8 fold resistance, respectively, determined in a 6-day MTT assay. Although the parent lines show a wide range of glutathione content per cell, the sublines each show similar values to their corresponding parent line. Radiation response curves have been obtained using a soft agar clonogenic assay. Values obtained for the parent lines (95% CL in parentheses) were: NCI-H69: Do = 0.99 Gy (0.87-1.16), n = 2.9 (1.6-5.2), GSH = 14 ng/10(4) cells; COR-L23: Do = 1.23 Gy (1.05-1.49), n = 1.3 (0.7-2.2), GSH = 47 ng/10(4) cells; MOR: Do = 1.66 Gy (1.48-1.88), n = 3.0 (1.9-4.8), GSH = 86 ng/10(4) cells. The cisplatin resistant variants of NCI-H69 and COR-L23 showed 31% and 63% increases, respectively, in Do compared to their parent lines, whereas no change in radiation response was seen in MOR. In this panel of lines, therefore, although there is a correlation between glutathione content and radiosensitivity of the parent cell lines, acquired resistance to cisplatin is not accompanied by increased glutathione content. However, two of the three cisplatin resistant lines do show a significantly reduced radiosensitivity

  12. Sym004, a Novel EGFR Antibody Mixture, Can Overcome Acquired Resistance to Cetuximab1

    Science.gov (United States)

    Iida, Mari; Brand, Toni M; Starr, Megan M; Li, Chunrong; Huppert, Evan J; Luthar, Neha; Pedersen, Mikkel W; Horak, Ivan D; Kragh, Michael; Wheeler, Deric L

    2013-01-01

    The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in a variety of human cancers. Cetuximab is an anti-EGFR monoclonal antibody that has been approved for head and neck and colorectal cancer treatment, but many patients treated with cetuximab don't respond or eventually acquire resistance. To determine how tumor cells acquire resistance to cetuximab, we previously developed a model of acquired resistance using the non-small cell lung cancer line NCI-H226. These cetuximab-resistant (CtxR) cells exhibit increased steady-state EGFR expression secondary to alterations in EGFR trafficking and degradation and, further, retained dependence on EGFR signaling for enhanced growth potential. Here, we examined Sym004, a novel mixture of antibodies directed against distinct epitopes on the extracellular domain of EGFR, as an alternative therapy for CtxR tumor cells. Sym004 treatment of CtxR clones resulted in rapid EGFR degradation, followed by robust inhibition of cell proliferation and down-regulation of several mitogen-activated protein kinase pathways. To determine whether Sym004 could have therapeutic benefit in vivo, we established de novo CtxR NCI-H226 mouse xenografts and subsequently treated CtxR tumors with Sym004. Sym004 treatment of mice harboring CtxR tumors resulted in growth delay compared to mice continued on cetuximab. Levels of total and phospho-EGFR were robustly decreased in CtxR tumors treated with Sym004. Immunohistochemical analysis of these Sym004-treated xenograft tumors further demonstrated decreased expression of Ki67, and phospho-rpS6, as well as a modest increase in cleaved caspase-3. These results indicate that Sym004 may be an effective targeted therapy for CtxR tumors. PMID:24204198

  13. Update on HIV-1 acquired and transmitted drug resistance in Africa.

    Science.gov (United States)

    Ssemwanga, Deogratius; Lihana, Raphael W; Ugoji, Chinenye; Abimiku, Alash'le; Nkengasong, John; Dakum, Patrick; Ndembi, Nicaise

    2015-01-01

    The last ten years have witnessed a significant scale-up and access to antiretroviral therapy in Africa, which has improved patient quality of life and survival. One major challenge associated with increased access to antiretroviral therapy is the development of antiretroviral resistance due to inconsistent drug supply and/or poor patient adherence. We review the current state of both acquired and transmitted drug resistance in Africa over the past ten years (2001-2011) to identify drug resistance associated with the different drug regimens used on the continent and to help guide affordable strategies for drug resistance surveillance. A total of 161 references (153 articles, six reports and two conference abstracts) were reviewed. Antiretroviral resistance data was available for 40 of 53 African countries. A total of 5,541 adult patients from 99 studies in Africa were included in this analysis. The pooled prevalence of drug resistance mutations in Africa was 10.6%, and Central Africa had the highest prevalence of 54.9%. The highest prevalence of nucleoside reverse transcriptase inhibitor mutations was in the west (55.3%) and central (54.8%) areas; nonnucleoside reverse transcriptase inhibitor mutations were highest in East Africa (57.0%) and protease inhibitors mutations highest in Southern Africa (16.3%). The major nucleoside reverse transcriptase inhibitor mutation in all four African regions was M184V. Major nonnucleoside reverse transcriptase inhibitor as well as protease inhibitor mutations varied by region. The prevalence of drug resistance has remained low in several African countries although the emergence of drug resistance mutations varied across countries. Continued surveillance of antiretroviral therapy resistance remains crucial in gauging the effectiveness of country antiretroviral therapy programs and strategizing on effective and affordable strategies for successful treatment.

  14. Antibacterial resistance patterns of pediatric community-acquired urinary infection: Overview.

    Science.gov (United States)

    Konca, Capan; Tekin, Mehmet; Uckardes, Fatih; Akgun, Sadik; Almis, Habip; Bucak, Ibrahim Hakan; Genc, Yeliz; Turgut, Mehmet

    2017-03-01

    Urinary tract infection (UTI) is common in children. The aim of this study was therefor to construct a guide for the empirical antibiotic treatment of community-acquired UTI by investigating the etiology and antimicrobial resistance patterns of uropathogens and analyzing the epidemiological and clinical patient characteristics. A total of 158 children with positive urine culture were included in the study. Antibiotic susceptibility testing was performed with Vitek 2 Compact for 28 commonly used antimicrobials. Mean age was 3.36 ± 3.38 years (range, 45 days-15 years). Escherichia coli (60.1%), and Klebsiella spp. (16.5%) were the most common uropathogens. For all Gram-negative isolates, a high level of resistance was found against ampicillin/sulbactam (60.1%), trimethoprim/sulfamethoxazole (44.2%), cefazolin (36.2%), cefuroxime sodium (33.5%), and amoxicillin/clavulanate (31.5%). A low level of resistance was noted against cefepime (8.7%), ertapenem (4.6%), norfloxacin (1.3%), and meropenem (0.7%). There was no resistance against amikacin. There is high antibiotic resistance in children with UTI. The patterns of uropathogen antimicrobial resistance vary in susceptibility to antimicrobials depending on region and time. Thus, the trends of antibiotic susceptibility patterns should be analyzed periodically to select the appropriate regimen for UTI treatment. © 2016 Japan Pediatric Society.

  15. Identification of Systemic Acquired Resistance–Related Volatile Organic Compounds and their Role in Plant Immunity

    OpenAIRE

    Bichlmeier, Marlies

    2017-01-01

    Systemic acquired resistance (SAR) is an inducible immune response that depends on ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), which is essential for SAR signalling. In contrast to SAR, local resistance remains intact in Arabidopsis (Arabidopsis thaliana) eds1-2 mutant plants in response to Pseudomonas syringae delivering the effector protein AvrRpm1. I utilized the SAR-specific phenotype of the eds1-2 mutant to identify volatile organic compounds (VOCs) related to SAR. To this end, SAR was indu...

  16. Selinexor is effective in acquired resistance to ibrutinib and synergizes with ibrutinib in chronic lymphocytic leukemia.

    Science.gov (United States)

    Hing, Zachary A; Mantel, Rose; Beckwith, Kyle A; Guinn, Daphne; Williams, Erich; Smith, Lisa L; Williams, Katie; Johnson, Amy J; Lehman, Amy M; Byrd, John C; Woyach, Jennifer A; Lapalombella, Rosa

    2015-05-14

    Despite the therapeutic efficacy of ibrutinib in chronic lymphocytic leukemia (CLL), complete responses are infrequent, and acquired resistance to Bruton agammaglobulinemia tyrosine kinase (BTK) inhibition is being observed in an increasing number of patients. Combination regimens that increase frequency of complete remissions, accelerate time to remission, and overcome single agent resistance are of considerable interest. We previously showed that the XPO1 inhibitor selinexor is proapoptotic in CLL cells and disrupts B-cell receptor signaling via BTK depletion. Herein we show the combination of selinexor and ibrutinib elicits a synergistic cytotoxic effect in primary CLL cells and increases overall survival compared with ibrutinib alone in a mouse model of CLL. Selinexor is effective in cells isolated from patients with prolonged lymphocytosis following ibrutinib therapy. Finally, selinexor is effective in ibrutinib-refractory mice and in a cell line harboring the BTK C481S mutation. This is the first report describing the combined activity of ibrutinib and selinexor in CLL, which represents a new treatment paradigm and warrants further evaluation in clinical trials of CLL patients including those with acquired ibrutinib resistance. © 2015 by The American Society of Hematology.

  17. The changing face of community-acquired methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    P Kale

    2016-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA is an important cause of infection, both in hospitalised patients with significant healthcare exposure and in patients without healthcare risk factors. Community-acquired methicillin-resistant S. aureus (CA-MRSA are known for their rapid community transmission and propensity to cause aggressive skin and soft tissue infections and community-acquired pneumonia. The distinction between the healthcare-associated (HA-MRSA and CA-MRSA is gradually fading owing to the acquisition of multiple virulence factors and genetic elements. The movement of CA-MRSA strains into the nosocomial setting limits the utility of using clinical risk factors alone to designate community or HA status. Identification of unique genetic characteristics and genotyping are valuable tools for MRSA epidemiological studies. Although the optimum pharmacotherapy for CA-MRSA infections has not been determined, many CA-MRSA strains remain broadly susceptible to several non-β-lactam antibacterial agents. This review aimed at illuminating the characteristic features of CA-MRSA, virulence factors, changing clinical settings and molecular epidemiology, insurgence into the hospital settings and therapy with drug resistance.

  18. Prevalence of Methicillin Resistant Staphylococcus aureus in pyogenic community and hospital acquired skin and soft tissues infections

    International Nuclear Information System (INIS)

    Ahmad, M. K.; Asrar, A.

    2014-01-01

    Objective: To determine the percentage and frequency of Methicillin Resistant Staphylococcus aureus in community and hospital-acquired pyogenic skin and soft tissue infections. Methods: The descriptive cross-sectional study was conducted at the Dermatology Department of Combined Military Hospital, Abbottabad, from June 2009 to March 2010, and comprised 144 community-acquired and 54 hospital-acquired skin and soft tissue infections. Pus swabs from the infected lesions one from each individual were sent to laboratory for culture and sensitivity tests. Methicillin resistance was detected by 1 (mu) g oxacillin disk. Organisms were labelled methicillin-resistant once the inhibition zone for oxocillin was less than 10 mm. Data analysis was done by using SPSS 20. Results: Of the 198 patients in the study, 98(49.5%) were males and 100(50.5%) were females, with an overall mean age of 33.7+-14.8144 years. There were 144(72.72%) community-acquired infections and 54(27.27%) had hospital-acquired infections. Community-acquired Methicillin Resistant Staphylococcus aureus numbered 40(27.8%) and hospital-acquired ones numbered 26(48.1%). Conclusion: Prevalence of Methicillin Resistant Staphylococcus aureus in community and hospital-acquired pyogenic skin and soft tissue infections was high. (author)

  19. Surveillance for Travel and Domestically Acquired Multidrug-Resistant Human Shigella Infections-Pennsylvania, 2006-2014.

    Science.gov (United States)

    Li, Yu Lung; Tewari, Deepanker; Yealy, Courtney C; Fardig, David; M'ikanatha, Nkuchia M

    2016-01-01

    Shigellosis is a leading cause of enteric infections in the United States. We compared antimicrobial resistance in Shigella infections related to overseas travel (travel-associated) and in those acquired domestically by analyzing antimicrobial resistance patterns, geographic distributions, and pulsed-field gel electrophoresis (PFGE) patterns. We tested samples (n = 204) from a collection of isolates recovered from patients in Pennsylvania between 2006 and 2014. Isolates were grouped into travel- and non-travel-associated categories. Eighty-one (79.4%) of the Shigella isolates acquired during international travel were resistant to multiple antibiotics compared to 53 (52.1%) of the infections transmitted in domestic settings. A majority (79.4%) of isolates associated with international travel demonstrated resistance to aminoglycosides and tetracyclines, whereas 47 (46.1%) of the infections acquired domestically were resistant to tetracycline. Almost all isolates (92.2%) transmitted in domestic settings were resistant to aminoglycosides, and 5 isolates from adult male patients were resistant to azithromycin, a drug often used for empiric treatment of severe shigellosis. Twenty (19.6%) isolates associated with illnesses acquired during overseas travel in 4 countries were resistant to quinolones. One S. sonnei PFGE pattern was traced to a multidrug-resistant isolate acquired overseas that had caused a multistate outbreak of shigellosis, suggesting global dissemination of a drug-resistant species. Resistance to certain drugs-for example, tetracycline-increased in both overseas- and domestic-acquired infections during the study period. The prevalence of resistance to macrolides (azithromycin) and third-generation cephalosporins (ceftriaxone) was less than 1%; however, efforts to better monitor changes in drug resistance over time combined with increased antimicrobial stewardship are essential at the local, national, and global levels.

  20. Identification of genes differentially expressed in association with acquired cisplatin resistance

    Science.gov (United States)

    Johnsson, A; Zeelenberg, I; Min, Y; Hilinski, J; Berry, C; Howell, S B; Los, G

    2000-01-01

    The goal of this study was to identify genes whose mRNA levels are differentially expressed in human cells with acquired cisplatin (cDDP) resistance. Using the parental UMSCC10b head and neck carcinoma cell line and the 5.9-fold cDDP-resistant subline, UMSCC10b/Pt-S15, two suppressive subtraction hybridization (SSH) cDNA libraries were prepared. One library represented mRNAs whose levels were increased in the cDDP resistant variant (the UP library), the other one represented mRNAs whose levels were decreased in the resistant cells (the DOWN library). Arrays constructed with inserts recovered from these libraries were hybridized with SSH products to identify truly differentially expressed elements. A total of 51 cDNA fragments present in the UP library and 16 in the DOWN library met the criteria established for differential expression. The sequences of 87% of these cDNA fragments were identified in Genbank. Among the mRNAs in the UP library that were frequently isolated and that showed high levels of differential expression were cytochrome oxidase I, ribosomal protein 28S, elongation factor 1α, α-enolase, stathmin, and HSP70. The approach taken in this study permitted identification of many genes never before linked to the cDDP-resistant phenotype. © 2000 Cancer Research Campaign PMID:10993653

  1. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

    International Nuclear Information System (INIS)

    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

    1987-01-01

    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni

  2. Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition.

    Science.gov (United States)

    Gao, Xuejin; Tian, Feng; Wang, Xinying; Zhao, Jie; Wan, Xiao; Zhang, Li; Wu, Chao; Li, Ning; Li, Jieshou

    2015-01-01

    Protein-energy malnutrition (PEM) can lead to growth hormone (GH) resistance. Leucine supplementation diets have been shown to increase protein synthesis in muscles. Our study aimed at investigating if long-term leucine supplementation could modulate GH-insulin-like growth factor (IGF)-1 system function and mammalian target of rapamycin (mTOR)-related signal transduction in skeletal muscles in a rat model of severe malnutrition. Male Sprague-Dawley rats (n = 50; weight, 302 ± 5 g) were divided into 5 treatment groups, including 2 control groups (a normal control group that was fed chow and ad libitum water [CON, n = 10] and a malnourished control group [MC, n = 10] that was fed a 50% chow diet). After undergoing a weight loss stage for 4 weeks, rats received either the chow diet (MC-CON, n = 10), the chow diet supplemented with low-dose leucine (MC-L, n = 10), or the chow diet supplemented with high-dose leucine (MC-H, n = 10) for 2 weeks. The muscle masses of the gastrocnemius, soleus, and extensor digitorum longus were significantly reduced in the MC group. Re-feeding increased muscle mass, especially in the MC-L and MC-H groups. In the MC group, serum IGF-1, IGF-binding protein (IGFBP)-3, and hepatic growth hormone receptor (GHR) levels were significantly decreased and phosphorylation of the downstream anabolic signaling effectors protein kinase B (Akt), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were significantly lower than in other groups. However, serum IGF-1 and IGF binding protein (IGFBP)-3 concentrations and hepatic growth hormone receptor (GHR) levels were significantly higher in the MC-L and MC-H groups than in the MC-CON group, and serum IGFBP-1 levels was significantly reduced in the MC-L and MC-H groups. These changes were consistent with those observed for hepatic mRNA expression levels. Phosphorylation of the downstream anabolic signaling effectors Akt, mTOR, and S6K1 were also significantly higher in the MC-L and MC-H groups than in the MC

  3. Presence and mechanisms of acquired antimicrobial resistance in Belgian Brachyspira hyodysenteriae isolates belonging to different clonal complexes.

    Science.gov (United States)

    Mahu, M; Pasmans, F; Vranckx, K; De Pauw, N; Vande Maele, L; Vyt, Philip; Vandersmissen, Tamara; Martel, A; Haesebrouck, F; Boyen, F

    2017-08-01

    Swine dysentery (SD) is an economically important disease for which antimicrobial treatment still occupies an important place to control outbreaks. However, acquired antimicrobial resistance is increasingly observed in Brachyspira hyodysenteriae. In this study, the Minimal Inhibitory Concentrations (MIC) of six antimicrobial compounds for 30 recent Belgian B. hyodysenteriae isolates were determined using a broth microdilution method. In addition, relevant regions of the 16S rRNA, 23S rRNA and the L3 protein encoding genes were sequenced to reveal mutations associated with acquired resistance. Finally, a phylogeny was reconstructed using minimal spanning tree analysis of multi locus sequence typing of the isolates. For lincomycin, doxycycline, tylosin and tylvalosin, at least 70% of the isolates did not belong to the wild-type population and were considered to have acquired resistance. For valnemulin and tiamulin, this was over 50%. In all isolates with acquired resistance to doxycycline, the G1058C mutation was present in their 16S rRNA gene. All isolates showing acquired resistance to lincomycin and both macrolides displayed the A2058T mutation in their 23S rRNA gene. Other mutations in this gene and the N148S mutation in the L3 protein were present in both wild-type isolates and isolates considered to have acquired resistance. Multi locus sequence analysis revealed a previously undescribed clonal complex, with 4 novel sequence types in which the majority of isolates showed acquired resistance to all tested antimicrobial products. In conclusion, acquired antimicrobial resistance is widespread among Belgian B. hyodysenteriae isolates. The emergence of multi-resistant clonal complexes can pose a threat to swine industry. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Long-term persistence of acquired resistance to 5-fluorouracil in the colon cancer cell line SW620

    Energy Technology Data Exchange (ETDEWEB)

    Tentes, I.K., E-mail: itentes@med.duth.gr [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Schmidt, W.M. [Center for Anatomy and Cell Biology, Waehringer Strasse 13, 1090 Vienna (Austria); Krupitza, G. [Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Steger, G.G.; Mikulits, W. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Kortsaris, A. [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Mader, R.M. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2010-11-15

    Treatment resistance to antineoplastic drugs represents a major clinical problem. Here, we investigated the long-term stability of acquired resistance to 5-fluorouracil (FU) in an in vitro colon cancer model, using four sub-clones characterised by increasing FU-resistance derived from the cell line SW620. The resistance phenotype was preserved after FU withdrawal for 15 weeks ({approx} 100 cell divisions) independent of the established level of drug resistance and of epigenetic silencing. Remarkably, resistant clones tolerated serum deprivation, adopted a CD133{sup +} CD44{sup -} phenotype, and further exhibited loss of membrane-bound E-cadherin together with predominant nuclear {beta}-catenin localisation. Thus, we provide evidence for a long-term memory of acquired drug resistance, driven by multiple cellular strategies (epithelial-mesenchymal transition and selective propagation of CD133{sup +} cells). These resistance phenomena, in turn, accentuate the malignant phenotype.

  5. Proliferation resistance assessment of nuclear systems

    International Nuclear Information System (INIS)

    1978-09-01

    The paper focuses on examining the degree to which nuclear systems could be used to acquire nuclear weapons material. It establishes a framework for proliferation resistance assessment and illustrates its applicability through an analysis of reference systems for once-through cycles, breeder cycles and thermal recycle. On a more tentative basis, the approach is applied to various alternative technical and institutional measures. This paper was also submitted to Working Groups 5 and 8

  6. Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Neesha Rockwood

    Full Text Available Studies looking at acquired drug resistance (ADR are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies.Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1 HIV and 2 baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies.Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I2 58%, 95% CI 26 to 76%. Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11; there was considerable heterogeneity amongst these studies (I2 81%, 95% CI 64 to 90%. Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST was 0.1% (5th to 95th percentile 0.07 to 3.2%.Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely

  7. Design of two molecular methodologies for the rapid identification of Colombian community-acquired methicillin-resistant Staphylococcus aureus isolates

    OpenAIRE

    Escobar, Javier Antonio; Gómez, Ingrid Tatiana; Murillo, Martha Johanna; Castro, Betsy Esperanza; Chavarro, Bibiana; Márquez, Ricaurte Alejandro; Vanegas, Natasha

    2012-01-01

    Introduction. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are found with increasing the frequency, both in healthy individuals in the community and in hospitalized patients. In Colombia and the Andean region, CA-MRSA isolates have a genetic background that is related to the pandemic USA300 clone. Objective. Two molecular methods are designed and standardized for the rapid differentiation of Colombian community-acquired and hospital-acquired methicillin-...

  8. Cutaneous community-acquired methicillin-resistant Staphylococcus aureus infection in participants of athletic activities.

    Science.gov (United States)

    Cohen, Philip R

    2005-06-01

    Cutaneous community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA) has been identified in otherwise healthy individuals either with or without methicillin-resistant S. aureus (MRSA)-associated risk factors who participate in athletic activities. The purpose of this study was to describe the clinical features of CAMRSA skin infection that occurred in university student athletes, evaluate the potential mechanisms for the transmission of MRSA infection of the skin in participants of athletic activities, and review the measures for preventing the spread of cutaneous CAMRSA infection in athletes. A retrospective chart review of the student athletes from the University of Houston whose skin lesions were evaluated at the Health Center and grew MRSA was performed. The clinical characteristics and the postulated mechanisms of cutaneous MRSA infection in the athletes were compared with those previously published in reports of CAMRSA skin infection outbreaks in other sports participants. Cutaneous CAMRSA infection occurred in seven student athletes (four women and three men) who were either weight lifters (three students) or members of a varsity sports team: volleyball (two women), basketball (one woman), and football (one man). The MRSA skin infection presented as solitary or multiple, tender, erythematous, fluctuant abscesses with surrounding cellulitis. The lesions were most frequently located in the axillary region (three weight lifters), on the buttocks (two women), or on the thighs (two women). The drainage from all of the skin lesions grew MRSA, which was susceptible to clindamycin, gentamicin, rifampin, trimethoprim/sulfamethoxazole, and vancomycin; five of the isolates were also susceptible to ciprofloxacin and levofloxacin. All of the bacterial strains were resistant to erythromycin, oxacillin, and penicillin. The cutaneous MRSA infections persisted or worsened in the six athletes who were empirically treated for methicillin-sensitive S. aureus at

  9. Histological transformation after acquired resistance to epidermal growth factor tyrosine kinase inhibitors.

    Science.gov (United States)

    Shao, Yi; Zhong, Dian-Sheng

    2018-04-01

    Non-small-cell lung cancer patients with sensitive epidermal growth factor receptor mutations generally respond well to tyrosine kinase inhibitors (TKIs). However, acquired resistance will eventually develop place after 8-16 months. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification, epithelial mesenchymal transformation and PIK3CA mutation; however, histological transformation is a rare mechanism. The patterns and mechanisms underlying histological transformation need to be explored. We searched PubMed, EMBASE and search engines Google Scholar, Medical Matrix for literature related to histological transformation. Case reports, cases series, and clinical and basic medical research articles were reviewed. Sixty-one articles were included in this review. Cases of transformation to small-cell lung cancer, squamous cell carcinoma, large-cell neuroendocrine carcinoma and sarcoma after TKI resistance have all been reported. As the clinical course differed dramatically between cases, a new treatment scheme needs to be recruited. The mechanisms underlying histological transformation have not been fully elucidated and probably relate to cancer stem cells, driver genetic alterations under selective pressure or the heterogeneity of the tumor. When TKI resistance develops, we recommend that patients undergo a second biopsy to determine the reason, guide the next treatment and predict the prognosis.

  10. The impact of nosocomially-acquired resistant Pseudomonas aeruginosa infection in a burn unit.

    Science.gov (United States)

    Armour, Alexis D; Shankowsky, Heather A; Swanson, Todd; Lee, Jonathan; Tredget, Edward E

    2007-07-01

    Nosocomially-acquired Pseudomonas aeruginosa remains a serious cause of infection and septic mortality in burn patients. This study was conducted to quantify the impact of nosocomially-transmitted resistant P. aeruginosa in a burn population. Using a TRACS burn database, 48 patients with P. aeruginosa resistant to gentamicin were identified (Pseudomonas group). Thirty-nine were case-matched to controls without resistant P. aeruginosa cultures (control group) for age, total body surface area, admission year, and presence of inhalation injury. Mortality and various morbidity endpoints were examined, as well as antibiotic costs. There was a significantly higher mortality rate in the Pseudomonas group (33% vs. 8%, p products used (packed cells 51.1 +/- 8.0 vs. 21.1 +/- 3.4, p < 0.01; platelets 11.9 +/- 3.0 vs. 1.4 +/- 0.7, p < 0.01) were all significantly higher in the Pseudomonas group. Cost of antibiotics was also significantly higher ($2,658.52 +/- $647.93 vs. $829.22 +/- $152.82, p < 0.01). Nosocomial colonization or infection, or both, of burn patients with aminoglycoside-resistant P. aeruginosa is associated with significantly higher morbidity, mortality, and cost of care. Increased resource consumption did not prevent significantly higher mortality rates when compared with that of control patients. Thus, prevention, identification, and eradication of nosocomial Pseudomonas contamination are critical for cost-effective, successful burn care.

  11. The human microbiota: novel targets for hospital-acquired infections and antibiotic resistance.

    Science.gov (United States)

    Pettigrew, Melinda M; Johnson, J Kristie; Harris, Anthony D

    2016-05-01

    Hospital-acquired infections are increasing in frequency due to multidrug resistant organisms (MDROs), and the spread of MDROs has eroded our ability to treat infections. Health care professionals cannot rely solely on traditional infection control measures and antimicrobial stewardship to prevent MDRO transmission. We review research on the microbiota as a target for infection control interventions. We performed a literature review of key research findings related to the microbiota as a target for infection control interventions. These data are summarized and used to outline challenges, opportunities, and unanswered questions in the field. The healthy microbiota provides protective functions including colonization resistance, which refers to the microbiota's ability to prevent colonization and/or expansion of pathogens. Antibiotic use and other exposures in hospitalized patients are associated with disruptions of the microbiota that may reduce colonization resistance and select for antibiotic resistance. Novel methods to exploit protective mechanisms provided by an intact microbiota may provide the key to preventing the spread of MDROs in the health care setting. Research on the microbiota as a target for infection control has been limited. Epidemiologic studies will facilitate progress toward the goal of manipulating the microbiota for control of MDROs in the health care setting. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Nasopharyngeal bacterial carriage and antimicrobial resistance in underfive children with community acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Cissy B. Kartasasmita

    2001-12-01

    Full Text Available Lung puncture is the best way to determine the etiology of pneumonia since it yields the highest rate of positive cultures. However, this procedure is difficult, especially for a study in the community. According to WHO, isolates to be tested for antimicrobial resistance in the community should be obtained from nasopharyngeal (NP swabs. Previous studies support the use of NP isolates to determine antimicrobial resistance patterns of isolates from children with pneumonia. The aim of our study was to know the bacterial patterns of the nasopharynx in underfive children with community acquired pneumonia and their antimicrobial resistance. The study was carried out in 4 Primary Health Clinics in Majalaya sub-district, Bandung, Indonesia. All underfives with cough or difficult breathing and classified as having non-severe pneumonia (WHO guidelines, were included in the study. Nasopharyngeal swabs (CDC/WHO Manual were obtained by the doctor, the swabs were placed in Amies transport medium and stored in a sterile jar before taken to the laboratory in the same day. All children were treated with co-trimoxazole. During the nine month study, 698 children with clinical signs of non-severe pneumonia were enrolled. About 25% of the nasopharyngeal specimens yielded bacterial isolates; the two most frequently found were S. pneumoniae and S. epidermidis. The antimicrobial resistance test to co-trimoxazole showed 48.2% S. pneumoniae strain had full resistance and 32.7% showed intermediate resistance to co-trimoxazole. This result is almost similar to other studies from Asian countries. It seems that H. influenzae is not a problem in the study area; however, further studies are needed.

  13. Nasopharyngeal bacterial carriage and antimicrobial resistance in underfive children with community acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Cissy B. Kartasasmita

    2002-09-01

    Full Text Available Pathogens in nasopharynx is a significant risk factor of pneumonia. According to WHO, isolates to be tested for antimicrobial resistance in the community should be obtained from nasopharyngeal (NP swabs. The aim of this study is to know the bacterial patterns of the nasopharynx and cotrimoxazole resistance in under five-year old children with community acquired pneumonia. The study was carried out in 4 primary health clinic (Puskesmas in Majalaya sub-district, Bandung, West Java, Indonesia. All underfive children with cough and/or difficult breathing and classified as having non-severe pneumonia (WHO guidelines were placed in Amies transport medium and stored in a sterile jar, before taken to the laboratory for further examination, in the same day. During this nine month study, 698 children with clinical signs of non-severe pneumonia were enrolled. About 25.4% (177/698 of the nasopharyngeal specimens yielded bacterial isolates; i.e. 120 (67.8% were positive for S pneumoniae, 21 for S epidermidis and alpha streptococcus, 6 for Hafnia alvei, 5 for S aureus, 2 for B catarrhalis, and 1(0.6% for H influenza and Klebsiella, respectively. The antimicrobial resistance test to cotrimoxazole showed that 48.2% of S pneumoniae strain had full resistance and 32.7% showed intermediate resistance to cotrimoxazole. This result is almost similar to the other studies from Asian countries. It seems that H influenza is not a problem in the study area, however, a further study is needed. (Med J Indones 2002; 11: 164-8 Keywords: nasopharyngeal swab, S pneumoniae, cotrimoxazole

  14. [Acquiring Science English: A Plan and System Are Needed].

    Science.gov (United States)

    Foong, Foo Wah

    2018-01-01

     Literary English is different from science English (SE) and pharmaceutical science English (PSE). Therefore, a totally new approach was adopted for students to learn PSE at Kyoto Pharmaceutical University (KPU). In 2012, a 4-year program for teaching PSE was proposed, and a stepwise-stepup tertiary science English education (SSTSEE) system was introduced at KPU. The system provides a novel form of PSE teaching that stretches from year 1 to 4, where the PSE level progresses to higher levels of learning with each passing academic year. With the launch of the SSTSEE system, relevant science-educated staff were provided with training and were also requested to study the syllabi of the respective academic years to write textbooks with the appropriate PSE content for their respective levels. From 2012 to 2015, textbooks and curricula for 4 year academic levels were developed and published to meet the needs for PSE learning at each academic level. Based on results of the SSTSEE system, year 1 students acquired the SE basics, and year 2 students applied the SE basics acquired. In years 3 and 4, students further pursued and developed their PSE ability. Additionally, students participated actively in developing skills in the reading, listening, writing, and speaking of SE/PSE. Active-plus-deep learning prompted students in developing those skills using illustrations, posters, and power-point slideshow presentations. By year 4, average achievers had established an independent level of competency in reading, listening, speaking, and writing PSE. Moreover, the SSTSEE system accommodated students timely in developing communication skills for practical fieldwork (clerkships) at pharmacies/hospitals in year 5 and for their future endeavors.

  15. Circumvention of inherent or acquired cytotoxic drug resistance in vitro using combinations of modulating agents.

    Science.gov (United States)

    Cadagan, David; Merry, Stephen

    2013-10-01

    Modulating agents are used to circumvent drug resistance in the clinical setting. However achievable serum concentrations are often lower than those which are optimal in vitro. Combination of modulating agents with non-overlapping toxicities may overcome this obstacle. We have investigated combinations of three modulating agents (quinine, verapamil, and cinnarizine) to circumvent inherent or acquired resistance to the cytotoxic drugs doxorubicin, vincristine and paclitaxel. Dose-response curves to cytotoxic drugs in the presence/absence of modulating agents were determined using colony formation and cell proliferation assays. Doxorubicin accumulation into cell monolayers was measured by fluorescence spectrophotometry. Greater (1.9-fold) sensitisation to particular cytotoxic drugs was observed for certain combinations of modulating agents compared to individual effects. The most effective combination was quinine-plus-verapamil with the cytotoxic drug doxorubicin. This increase in sensitivity was associated with increased doxorubicin accumulation. Such enhanced activity was, however, not observed for all combinations of modulating agents or for all studied cytotoxic drugs. The findings of the present study suggest certain combinations of modulating agents to have a clinical role in circumventing drug resistance. Particular combinations of modulating agents must be carefully chosen to suit particular cytotoxic drug treatments.

  16. Cholesterol-producing transgenic Caenorhabditis elegans lives longer due to newly acquired enhanced stress resistance

    International Nuclear Information System (INIS)

    Lee, Eun-Young; Shim, Yhong-Hee; Chitwood, David J.; Hwang, Soon Baek; Lee, Junho; Paik, Young-Ki

    2005-01-01

    Because Caenorhabditis elegans lacks several components of the de novo sterol biosynthetic pathway, it requires sterol as an essential nutrient. Supplemented cholesterol undergoes extensive enzymatic modification in C. elegans to form other sterols of unknown function. 7-Dehydrocholesterol reductase (DHCR) catalyzes the reduction of the Δ 7 double bond of sterols and is suspected to be defective in C. elegans, in which the major endogenous sterol is 7-dehydrocholesterol (7DHC). We microinjected a human DHCR expression vector into C. elegans, which was then incorporated into chromosome by γ-radiation. This transgenic C. elegans was named cholegans, i.e., cholesterol-producing C. elegans, because it was able to convert 7DHC into cholesterol. We investigated the effects of changes in sterol composition on longevity and stress resistance by examining brood size, mean life span, UV resistance, and thermotolerance. Cholegans contained 80% more cholesterol than the wild-type control. The brood size of cholegans was reduced by 40% compared to the wild-type control, although the growth rate was not significantly changed. The mean life span of cholegans was increased up to 131% in sterol-deficient medium as compared to wild-type. The biochemical basis for life span extension of cholegans appears to partly result from its acquired resistance against both UV irradiation and thermal stress

  17. Congenital and acquired mitochondrial disorders of the central nervous system

    Directory of Open Access Journals (Sweden)

    V. V. Nikitina

    2014-01-01

    Full Text Available Clinical presentations of disorders of the nervous system manifest in young and middle-aged patients with congenital and acquired mitochondrial dysfunctions and cognitive disorders manifest in patients with mitochondrial diseases more often. Nowadays the effective methods of initial diagnosing of these conditions are neurological and neuropsychological examination of patients, using of biochemical markers of mitochondrial diseases: the indices of lactate, total homocysteine in plasma and liquor. Neuro-visual study (Magnetic resonance imaging of the brain, MR spectroscopy, tractography, diffusion-weighted magnetic resonance imaging of the brain, mitochondrial DNA typing is actually used for the differential diagnosing of mitochondrial diseases with other disorders that are accompanied by demyelinating disorders.

  18. Community-Acquired Methicillin-Resistant Staphylococcus aureus: The New Face of an Old Foe?

    Science.gov (United States)

    Udo, Edet E.

    2013-01-01

    The burden of infections caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasing among different patient populations globally. As CA-MRSA has become established in healthcare facilities, the range of infections caused by them has also increased. Molecular characterization of CA-MRSA isolates obtained from different centers has revealed significant diversity in their genetic backgrounds. Although many CA-MRSA strains are still susceptible to non-β-lactam antibiotics, multiresistance to non-β-lactam agents has emerged in some clones, posing substantial problems for empirical and directed therapy of infections caused by these strains. Some CA-MRSA clones have acquired the capacity to spread locally and internationally. CA-MRSA belonging to ST80-MRSA-IV and ST30-MRSA-IV appear to be the dominant clones in the countries of the Gulf Cooperation Council (GCC). The emergence of pandemic CA-MRSA clones not only limits therapeutic options but also presents significant challenges for infection control. Continued monitoring of global epidemiology and emerging drug resistance data is critical for the effective management of these infections. PMID:24051949

  19. High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome

    Directory of Open Access Journals (Sweden)

    Sehgal S

    2008-01-01

    Full Text Available In north India the number of paediatric cases with acquired immunodeficiency syndrome (AIDS is on the rise. Most drug combinations used for treatment of AIDS incorporate nevirapine, resistance to which develops very fast if given singly or because of unplanned interruptions. This paper investigates presence of mutations at codon 103 and codon 215 of the HIV pol gene causing resistance to nevirapine and zidovudine (AZT respectively in 25 children with AIDS. Mutations T215Y and K103N were detected by a nested cum amplification refractory mutation system polymerase chain reaction (ARMS PCR and the results were confirmed by direct sequencing in five randomly selected cases. Nineteen patients had received nevirapine containing regimen and six were drug naive. Mutation K103N was observed in 56% (14/25 of the children while mutation T215Y was found in none. Two of the six drug naοve children also showed K103N mutation. Thus, Indian children drug naοve or treated with nevirapine containing regimens show a high rate of mutation conferring resistance to nevirapine which calls for a judicious use of nevirapine both in antenatal and postnatal setting.

  20. TV-acquired optical diagnostics systems on ATA

    International Nuclear Information System (INIS)

    Kalibjian, R.; Chong, Y.P.; Cornish, J.P.; Jackson, C.H.; Fessenden, T.J.

    1984-06-01

    The purpose of this paper is to report on optical system developments on the ATA and their applications to ATA beam characterization. Television (TV)-acquired optical diagnostics data provide spatial and temporal properties of the ATA beam that complements recorded information from other types of sensors, such as, beam-wall current monitors, x-ray probes, and rf probes. The ATA beam operates: (1) in the normal mode at 50-MeV, 10-kA at a 1-Hz rate; and (2) in the 1-KHz burst mode (for 10-pulses) at a 0.5 Hz rate. The beam has a 70-ns pulse width in vacuum propagation; however, beam-head erosion will occur in atmospheric propagation, thus limiting the pulse width to less than 50-ns. Various optical systems are used for ATA diagnostics. Optical-imaging provides a convenient measurement in a single pulse of the 2-dimensional profile of the beam intensity. It can also provide multiple 2-D framing in a single pulse. In some studies it may be desirable to study optical events with temporal resolution less than 100-ps with 1-dimensional streak cameras. Spatially integrated data from phototube cameras can also be used for background measurement applications as well as for single pixel monitoring. The optical line-of-sight (LOS) configurations have been made versatile to accommodate a large number of options for the various optical systems

  1. Vorinostat-induced autophagy switches from a death-promoting to a cytoprotective signal to drive acquired resistance.

    Science.gov (United States)

    Dupéré-Richer, D; Kinal, M; Ménasché, V; Nielsen, T H; Del Rincon, S; Pettersson, F; Miller, W H

    2013-02-07

    Histone deacetylase inhibitors (HDACi) have shown promising activity against hematological malignancies in clinical trials and have led to the approval of vorinostat for the treatment of cutaneous T-cell lymphoma. However, de novo or acquired resistance to HDACi therapy is inevitable, and their molecular mechanisms are still unclear. To gain insight into HDACi resistance, we developed vorinostat-resistant clones from the hematological cell lines U937 and SUDHL6. Although cross-resistant to some but not all HDACi, the resistant cell lines exhibit dramatically increased sensitivity toward chloroquine, an inhibitor of autophagy. Consistent with this, resistant cells growing in vorinostat show increased autophagy. Inhibition of autophagy in vorinostat-resistant U937 cells by knockdown of Beclin-1 or Lamp-2 (lysosome-associated membrane protein 2) restores sensitivity to vorinostat. Interestingly, autophagy is also activated in parental U937 cells by de novo treatment with vorinostat. However, in contrast to the resistant cells, inhibition of autophagy decreases sensitivity to vorinostat. These results indicate that autophagy can switch from a proapoptotic signal to a prosurvival function driving acquired resistance. Moreover, inducers of autophagy (such as mammalian target of rapamycin inhibitors) synergize with vorinostat to induce cell death in parental cells, whereas the resistant cells remain insensitive. These data highlight the complexity of the design of combination strategies using modulators of autophagy and HDACi for the treatment of hematological malignancies.

  2. A novel system to tackle hospital acquired pressure ulcers.

    Science.gov (United States)

    Renganathan, B S; Preejith, S P; Nagaiyan, Sridhar; Joseph, Jayaraj; Sivaprakasam, Mohanasankar

    2016-08-01

    Hospital acquired pressure ulcers (HAPUs) is a major problem that affects around one in twenty patients who are admitted in hospital with sudden illness. These ulcers often occur when patients have limited mobility and cannot change positions in bed on their own. Traditionally, the occurrence of HAPUs has been minimized by turning the patient every 2 hours to alternating lateral and supine positions, and by using pressure redistributing mattresses. In many healthcare facilities, such a patient repositioning schedule is not always maintained owing to low caregiver compliance to turning protocols. Difficulty in monitoring patient position continuously, lack of turn reminders/alerts and suboptimal caregiver staffing ratio increases the occurrence of HAPUs. A novel method to address the need for improved pressure ulcer prevention is presented. The proposed method consists of a wearable device which continuously monitors the patient's position and communicates wirelessly with a tablet which enables alerts to be sent to the caregiver when a patient turn is due in accordance with the protocol adopted by the hospital. The patient's position is continuously monitored and the turning procedure carried out is logged and updated on the hospital's cloud system, thereby enabling centralized monitoring. Under a controlled setting, system was able to continuously monitor patient's position and can accurately detect standard patient positions.

  3. Acquire: an open-source comprehensive cancer biobanking system.

    Science.gov (United States)

    Dowst, Heidi; Pew, Benjamin; Watkins, Chris; McOwiti, Apollo; Barney, Jonathan; Qu, Shijing; Becnel, Lauren B

    2015-05-15

    The probability of effective treatment of cancer with a targeted therapeutic can be improved for patients with defined genotypes containing actionable mutations. To this end, many human cancer biobanks are integrating more tightly with genomic sequencing facilities and with those creating and maintaining patient-derived xenografts (PDX) and cell lines to provide renewable resources for translational research. To support the complex data management needs and workflows of several such biobanks, we developed Acquire. It is a robust, secure, web-based, database-backed open-source system that supports all major needs of a modern cancer biobank. Its modules allow for i) up-to-the-minute 'scoreboard' and graphical reporting of collections; ii) end user roles and permissions; iii) specimen inventory through caTissue Suite; iv) shipping forms for distribution of specimens to pathology, genomic analysis and PDX/cell line creation facilities; v) robust ad hoc querying; vi) molecular and cellular quality control metrics to track specimens' progress and quality; vii) public researcher request; viii) resource allocation committee distribution request review and oversight and ix) linkage to available derivatives of specimen. © The Author 2015. Published by Oxford University Press.

  4. Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Sara Taveras Alam

    2014-01-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT with severely decreased levels of von Willebrand factor (VWF measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

  5. New Fks hot spot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species.

    Science.gov (United States)

    Johnson, Michael E; Katiyar, Santosh K; Edlind, Thomas D

    2011-08-01

    Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two "hot spot" regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new "hot spot 3" in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES.

  6. Community-acquired methicillin-resistant Staphylococcus aureus: an emerging pathogen in orthopaedics.

    Science.gov (United States)

    Marcotte, Anthony L; Trzeciak, Marc A

    2008-02-01

    Staphylococcus aureus (S aureus) remains one of the most common pathogens for skin and soft-tissue infections encountered by the orthopaedic surgeon. Community-acquired methicillin-resistant S aureus (CA-MRSA) has become increasingly prevalent, particularly among athletes, children in day care, homeless persons, intravenous drug users, men who have sex with men, military recruits, certain minorities (ie, Alaskan Natives, Native Americans, Pacific Islanders), and prison inmates. Risk factors include antibiotic use within the preceding year, crowded living conditions, compromised skin integrity, contaminated surfaces, frequent skin-to-skin contact, shared items, and suboptimal cleanliness. When a patient presents with a skin or soft-tissue infection, the clinician should determine whether an abscess or other infection needs to be surgically incised and drained. Cultures should be performed. When the patient is a member of an at-risk group or has any of the risk factors for CA-MRSA, beta-lactam antibiotics (eg, methicillin) are no longer a reasonable choice for treatment. Empiric treatment should consist of non-beta-lactam antibiotics active against CA-MRSA.

  7. Investigating the effects of ABC transporter-based acquired drug resistance mechanisms at the cellular and tissue scale.

    Science.gov (United States)

    Liu, Cong; Krishnan, J; Xu, Xiao Yun

    2013-03-01

    In this paper we systematically investigate the effects of acquired drug resistance at the cellular and tissue scale, with a specific focus on ATP-binding cassette (ABC) transporter-based mechanisms and contrast this with other representative intracellular resistance mechanisms. This is done by developing in silico models wherein the drug resistance mechanism is overlaid on a coarse-grained description of apoptosis; these cellular models are coupled with interstitial drug transport, allowing for a transparent examination of the effect of acquired drug resistances at the tissue level. While ABC transporter-mediated resistance mechanisms counteract drug effect at the cellular level, its tissue-level effect is more complicated, revealing unexpected trends in tissue response as drug stimuli are systematically varied. Qualitatively different behaviour is observed in other drug resistance mechanisms. Overall the paper (i) provides insight into the tissue level functioning of a particular resistance mechanism, (ii) shows that this is very different from other resistance mechanisms of an apparently similar type, and (iii) demonstrates a concrete instance of how the functioning of a negative feedback based cellular adaptive mechanism can have unexpected higher scale effects.

  8. Impact of amoxicillin therapy on resistance selection in patients with community-acquired lower respiratory tract infections

    DEFF Research Database (Denmark)

    Malhotra-Kumar, Surbhi; Van Heirstraeten, Liesbet; Coenen, Samuel

    2016-01-01

    OBJECTIVES: To determine the effect of amoxicillin treatment on resistance selection in patients with community-acquired lower respiratory tract infections in a randomized, placebo-controlled trial. METHODS: Patients were prescribed amoxicillin 1 g, three times daily (n = 52) or placebo (n = 50) ...

  9. Meta-Analysis of Clinical Studies Supports the Pharmacokinetic Variability Hypothesis for Acquired Drug Resistance and Failure of Antituberculosis Therapy

    OpenAIRE

    Pasipanodya, Jotam G.; Srivastava, Shashikant; Gumbo, Tawanda

    2012-01-01

    Laboratory studies have questioned nonadherence as a cause of antituberculosis drug failure and propose that between-patient pharmacokinetic variability may be the cause. This meta-analysis provides clinical evidence that pharmacokinetic variability of isoniazid alone leads to worse microbiological failure, relapse, and acquired drug resistance.

  10. Loss of activating EGFR mutant gene contributes to acquired resistance to EGFR tyrosine kinase inhibitors in lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Keisuke Tabara

    Full Text Available Non-small-cell lung cancer harboring epidermal growth factor receptor (EGFR mutations attains a meaningful response to EGFR-tyrosine kinase inhibitors (TKIs. However, acquired resistance to EGFR-TKIs could affect long-term outcome in almost all patients. To identify the potential mechanisms of resistance, we established cell lines resistant to EGFR-TKIs from the human lung cancer cell lines PC9 and11-18, which harbored activating EGFR mutations. One erlotinib-resistant cell line from PC9 and two erlotinib-resistant cell lines and two gefitinib-resistant cell lines from 11-18 were independently established. Almost complete loss of mutant delE746-A750 EGFR gene was observed in the erlotinib-resistant cells isolated from PC9, and partial loss of the mutant L858R EGFR gene copy was specifically observed in the erlotinib- and gefitinib-resistant cells from 11-18. However, constitutive activation of EGFR downstream signaling, PI3K/Akt, was observed even after loss of the mutated EGFR gene in all resistant cell lines even in the presence of the drug. In the erlotinib-resistant cells from PC9, constitutive PI3K/Akt activation was effectively inhibited by lapatinib (a dual TKI of EGFR and HER2 or BIBW2992 (pan-TKI of EGFR family proteins. Furthermore, erlotinib with either HER2 or HER3 knockdown by their cognate siRNAs also inhibited PI3K/Akt activation. Transfection of activating mutant EGFR complementary DNA restored drug sensitivity in the erlotinib-resistant cell line. Our study indicates that loss of addiction to mutant EGFR resulted in gain of addiction to both HER2/HER3 and PI3K/Akt signaling to acquire EGFR-TKI resistance.

  11. Toxic shock syndrome due to community-acquired methicillin-resistant Staphylococcus aureus infection: Two case reports and a literature review in Japan

    OpenAIRE

    Sada, Ryuichi; Fukuda, Saori; Ishimaru, Hiroyasu

    2017-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus has been spreading worldwide, including in Japan. However, few cases of toxic shock syndrome caused by Community-acquired methicillin-resistant Staphylococcus aureus have been reported in Japan. We report 2 cases, in middle-aged women, of toxic shock syndrome due to Community-acquired methicillin-resistant Staphylococcus aureus via a vaginal portal of entry. The first patient had used a tampon and the second patient had vaginitis ...

  12. New Real-Time PCR Assays for Detection of Inducible and Acquired Clarithromycin Resistance in the Mycobacterium abscessus Group.

    Science.gov (United States)

    Shallom, Shamira J; Moura, Natalia S; Olivier, Kenneth N; Sampaio, Elizabeth P; Holland, Steven M; Zelazny, Adrian M

    2015-11-01

    Members of the Mycobacterium abscessus group (MAG) cause lung, soft tissue, and disseminated infections. The oral macrolides clarithromycin and azithromycin are commonly used for treatment. MAG can display clarithromycin resistance through the inducible erm(41) gene or via acquired mutations in the rrl (23S rRNA) gene. Strains harboring a truncation or a T28C substitution in erm(41) lose the inducible resistance trait. Phenotypic detection of clarithromycin resistance requires extended incubation (14 days), highlighting the need for faster methods to detect resistance. Two real-time PCR-based assays were developed to assess inducible and acquired clarithromycin resistance and tested on a total of 90 clinical and reference strains. A SYBR green assay was designed to distinguish between a full-length and truncated erm(41) gene by temperature shift in melting curve analysis. Single nucleotide polymorphism (SNP) allele discrimination assays were developed to distinguish T or C at position 28 of erm(41) and 23S rRNA rrl gene mutations at position 2058 and/or 2059. Truncated and full-size erm(41) genes were detected in 21/90 and 69/90 strains, respectively, with 64/69 displaying T at nucleotide position 28 and 5/69 containing C at that position. Fifteen isolates showed rrl mutations conferring clarithromycin resistance, including A2058G (11 isolates), A2058C (3 isolates), and A2059G (1 isolate). Targeted sequencing and phenotypic assessment of resistance concurred with molecular assay results. Interestingly, we also noted cooccurring strains harboring an active erm(41), inactive erm(41), and/or acquired mutational resistance, as well as slowly growing MAG strains and also strains displaying an inducible resistance phenotype within 5 days, long before the recommended 14-day extended incubation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. New Fks Hot Spot for Acquired Echinocandin Resistance in Saccharomyces cerevisiae and Its Contribution to Intrinsic Resistance of Scedosporium Species▿

    Science.gov (United States)

    Johnson, Michael E.; Katiyar, Santosh K.; Edlind, Thomas D.

    2011-01-01

    Echinocandins represent a new antifungal group with potent activity against Candida species. These lipopeptides inhibit the synthesis of β-1,3-glucan, the major cell wall polysaccharide. Acquired resistance or reduced echinocandin susceptibility (RES) is rare and associated with mutations in two “hot spot” regions of Fks1 or Fks2, the probable β-1,3-glucan synthases. In contrast, many fungi demonstrate intrinsic RES for reasons that remain unclear. We are using Saccharomyces cerevisiae to understand the basis for RES by modeling echinocandin-Fks interaction. Previously characterized mutations confer cross-RES; we screened for mutations conferring differential RES, implying direct interaction of that Fks residue with a variable echinocandin side chain. One mutant (in an fks1Δ background) exhibited ≥16-fold micafungin and anidulafungin versus caspofungin RES. Sequencing identified a novel Fks2 mutation, W714L/Y715N. Equivalent W695L/Y696N and related W695L/F/C mutations in Fks1 generated by site-directed mutagenesis and the isolation of a W695L-equivalent mutation in Candida glabrata confirmed the role of the new “hot spot 3” in RES. Further mutagenesis expanded hot spot 3 to Fks1 residues 690 to 700, yielding phenotypes ranging from cross-RES to differential hypersusceptibility. Fks1 sequences from intrinsically RES Scedosporium species revealed W695F-equivalent substitutions; Fks1 hybrids expressing Scedosporium prolificans hot spot 3 confirmed that this substitution imparts RES. PMID:21576441

  14. Origin and evolution of European community-acquired methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Stegger, Marc; Wirth, Thierry; Andersen, Paal S; Skov, Robert L; De Grassi, Anna; Simões, Patricia Martins; Tristan, Anne; Petersen, Andreas; Aziz, Maliha; Kiil, Kristoffer; Cirković, Ivana; Udo, Edet E; del Campo, Rosa; Vuopio-Varkila, Jaana; Ahmad, Norazah; Tokajian, Sima; Peters, Georg; Schaumburg, Frieder; Olsson-Liljequist, Barbro; Givskov, Michael; Driebe, Elizabeth E; Vigh, Henrik E; Shittu, Adebayo; Ramdani-Bougessa, Nadjia; Rasigade, Jean-Philippe; Price, Lance B; Vandenesch, Francois; Larsen, Anders R; Laurent, Frederic

    2014-08-26

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection

  15. NH4+ protects tomato plants against Pseudomonas syringae by activation of systemic acquired acclimation.

    Science.gov (United States)

    Fernández-Crespo, Emma; Scalschi, Loredana; Llorens, Eugenio; García-Agustín, Pilar; Camañes, Gemma

    2015-11-01

    NH4 (+) nutrition provokes mild toxicity by enhancing H2O2 accumulation, which acts as a signal activating systemic acquired acclimation (SAA). Until now, induced resistance mechanisms in response to an abiotic stimulus and related to SAA were only reported for exposure to a subsequent abiotic stress. Herein, the first evidence is provided that this acclimation to an abiotic stimulus induces resistance to later pathogen infection, since NH4 (+) nutrition (N-NH4 (+))-induced resistance (NH4 (+)-IR) against Pseudomonas syringae pv tomato DC3000 (Pst) in tomato plants was demonstrated. N-NH4 (+) plants displayed basal H2O2, abscisic acid (ABA), and putrescine (Put) accumulation. H2O2 accumulation acted as a signal to induce ABA-dependent signalling pathways required to prevent NH4 (+) toxicity. This acclimatory event provoked an increase in resistance against later pathogen infection. N-NH4 (+) plants displayed basal stomatal closure produced by H2O2 derived from enhanced CuAO and rboh1 activity that may reduce the entry of bacteria into the mesophyll, diminishing the disease symptoms as well as strongly inducing the oxidative burst upon Pst infection, favouring NH4 (+)-IR. Experiments with inhibitors of Put accumulation and the ABA-deficient mutant flacca demonstrated that Put and ABA downstream signalling pathways are required to complete NH4 (+)-IR. The metabolic profile revealed that infected N-NH4 (+) plants showed greater ferulic acid accumulation compared with control plants. Although classical salicylic acid (SA)-dependent responses against biotrophic pathogens were not found, the important role of Put in the resistance of tomato against Pst was demonstrated. Moreover, this work revealed the cross-talk between abiotic stress acclimation (NH4 (+) nutrition) and resistance to subsequent Pst infection. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  16. A trade-off between natural and acquired antibody production in a reptile: implications for long-term resistance to disease

    Directory of Open Access Journals (Sweden)

    Franziska C. Sandmeier

    2012-08-01

    Vertebrate immune systems are understood to be complex and dynamic, with trade-offs among different physiological components (e.g., innate and adaptive immunity within individuals and among taxonomic lineages. Desert tortoises (Gopherus agassizii immunised with ovalbumin (OVA showed a clear trade-off between levels of natural antibodies (NAbs; innate immune function and the production of acquired antibodies (adaptive immune function. Once initiated, acquired antibody responses included a long-term elevation in antibodies persisting for more than one year. The occurrence of either (a high levels of NAbs or (b long-term elevations of acquired antibodies in individual tortoises suggests that long-term humoral resistance to pathogens may be especially important in this species, as well as in other vertebrates with slow metabolic rates, concomitantly slow primary adaptive immune responses, and long life-spans.

  17. Emergence of community-acquired methicillin-resistant Staphylococcus aureus in an Iranian referral paediatric hospital.

    Science.gov (United States)

    Mamishi, S; Mahmoudi, S; Bahador, A; Matini, H; Movahedi, Z; Sadeghi, R H; Pourakbari, B

    2015-01-01

    The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals has been changed in recent years due to the arrival of community-associated MRSA (CA-MRSA) strains into healthcare settings. The aim of this study is to investigate the distribution of staphylococcal cassette chromosome mec (SCCmec) type V as well as SCCmec IV subtypes, which have been associated with community-acquired infection among healthcare-associated MRSA (HA-MRSA) isolates. Antimicrobial susceptibility, SCCmec type, spa type and the presence of Panton-Valentine leukocidin (PVL) genes were determined for all HA-MRSA isolates in an Iranian referral hospital. In this study of 48 HA-MRSA isolates, 13 (27%), three (6.2%), five (10.4%) and one (2%) belonged to SCCmec subtypes IVa, IVb, IVc and IVd, respectively. Only two isolates (4.2%) belonged to SCCmec types V Notably, one isolate was found to harbour concurrent SCCmec subtypes IVb and IVd. MRSA containing SCCmec subtype IVb, IVc and IVd as well as type V isolates were all susceptible to chloramphenicol, clindamycin and rifampicin, while the sensitivity to these antibiotics was lower among MRSA containing SCCmec subtype IVa. The most frequently observed spa ttype was t037, accounting for 88% (22/25). Three other spa type was t002, t1816 and t4478. Large reservoirs of MRSA containing type IV subtypes and type V now exist in patients in this Iranian hospital. Therefore, effective infection control management in order to control the spread of CA-MRSA is highly recommended.

  18. Prevalence and invasiveness of community-acquired methicillin-resistant Staphylococcus aureus: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Shipeng Li

    2014-01-01

    Full Text Available Background: Reports suggest that the prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA has increased, and that CA-MRSA is more virulent than healthcare-associated (HA-MRSA. Aims: The aim of this study is to gain a better understanding of the invasiveness and prevalence of CA-MRSA in patients; we systematically reviewed the literature by conducting a meta-analysis. Materials and Methods: We searched the MEDLINE and PUBMED databases from the year these databases were established to January 2013. Results: The pooled CA-MRSA prevalence among 50,737 patients from 33 studies was 39.0% (range, 30.8-47.8%. The pooled CA-MRSA prevalence rates among pediatric and adult patients with MRSA infection were 50.2% (range, 37.5-62.8% and 42.3% (range, 16.4-73.3%, respectively. The pooled CA-MRSA prevalence rates of MRSA-infected patients in Asia, Europe, and North America were 23.1% (range, 12.0-39.8%, 37.4% (range, 21.1-56.4%, and 47.4% (range, 35.8-59.4%, respectively. Using the random effects model, we determined that the pooled odds ratio of invasive infections in CA- and HA-MRSA was 0.30 (95% confidence interval: 0.08-1.10; P = 0.07, test for heterogeneity P < 0.00001. Conclusions: The prevalence of CA-MRSA in MRSA infection varied with area and population. No difference in the ability to cause invasive infections was found between CA- and HA-MRSA. This finding challenges the view that CA-MRSA is more virulent than HA-MRSA.

  19. Proliferation resistance assessment of thermal recycle systems

    International Nuclear Information System (INIS)

    1979-02-01

    This paper examines the major proliferation aspects of thermal recycle systems and the extent to which technical or institutional measures could increase the difficulty or detectability of misuse of the system by would-be proliferators. It does this by examining the various activities necessary to acquire weapons-usable material using a series of assessment factors; resources required, time required, detectability. It is concluded that resistance to proliferation could be improved substantially by collecting reprocessing, conversion and fuel fabrication plants under multi national control and instituting new measures to protect fresh MOX fuel. Resistance to theft at sub-national level could be improved by co-location of sensitive facilities high levels of physical protection at plants and during transportation and possibly by adding a radiation barrier to MOX prior to shipment

  20. Mechanisms of Acquired Resistance to ALK Inhibitors and the Rationale for Treating ALK-positive Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Isozaki, Hideko [Department of Clinical Pharmaceutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Takigawa, Nagio, E-mail: ntakigaw@gmail.com [Department of General Internal Medicine 4, Kawasaki Medical School, Okayama 700-8505 (Japan); Kiura, Katsuyuki [Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama 700-8558 (Japan)

    2015-04-30

    The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib. Some second-generation ALK tyrosine kinase inhibitors (TKIs), which might be more potent than crizotinib or effective on crizotinib-resistant patients, have been developed. Although these ALK-TKIs show an excellent response initially, most patients eventually acquire resistance. Therefore, careful consideration of the resistance mechanisms might lead to superior therapeutic strategies. Here, we summarize the history of ALK-TKIs and their underlying resistance mechanisms in both the preclinical and clinical settings. In addition, we discuss potential future treatment strategies in ALK-TKI-naïve and -resistant patients with lung cancer harboring the EML4-ALK fusion gene.

  1. A horizontally gene transferred copper resistance locus confers hyper‐resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages

    Science.gov (United States)

    Purves, Joanne; Thomas, Jamie; Riboldi, Gustavo P.; Zapotoczna, Marta; Tarrant, Emma; Andrew, Peter W.; Londoño, Alejandra; Planet, Paul J.; Geoghegan, Joan A.; Waldron, Kevin J.

    2018-01-01

    Summary Excess copper is highly toxic and forms part of the host innate immune system's antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. We show for the first time that a novel, horizontally gene transferred copper resistance locus (copXL), uniquely associated with the SCCmec elements of the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus (CA‐MRSA) USA300, confers copper hyper‐resistance. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S. aureus lineages, but are increasingly identified in emerging pathogenic isolates. Our data show that CopX, a putative P1B‐3‐ATPase efflux transporter, and CopL, a novel lipoprotein, confer copper hyper‐resistance compared to typical S. aureus strains. The copXL genes form an operon that is tightly repressed in low copper environments by the copper regulator CsoR. Significantly, CopX and CopL are important for S. aureus USA300 intracellular survival within macrophages. Therefore, the emergence of new S. aureus clones with the copXL locus has significant implications for public health because these genes confer increased resistance to antibacterial copper toxicity, enhancing bacterial fitness by altering S. aureus interaction with innate immunity. PMID:29521441

  2. Microsoft Acquired Nokia in Unipolar Operating System Market

    Directory of Open Access Journals (Sweden)

    Netra Pal Singh

    2014-09-01

    Full Text Available The recent big tickets include Microsoft acquiring part of Nokia for US$ 7.2 billion, Verizon buy 45% stake in Vodafone for US$130 billion, Google acquiring Motorola for 12.5 billion. These buyouts are analyzed and commented by experts of the industry. This research paper attempted to collate their view in the context of Microsoft and Nokia deal on six parameters. These parameters are (i reasons for the downfall of the Nokia market share, (ii general comments of the experts, (iii similarities / dissimilarities of past and business models of the smartphone business, (iv reasons for Microsoft to buy out Nokia, (vi impact of buyout on Microsoft, Nokia, consumers and markets.

  3. Transcriptomics and knockout mutant analysis of rhizobacteria-mediated induced systemic resistance in Arabidopsis

    NARCIS (Netherlands)

    Verhagen, B.W.M.

    2004-01-01

    A classic example of induced resistance is triggered after infection by a necrotizing pathogen, rendering uninfected,distal parts more resistant to subsequent pathogen attack, and is often referred to as systemic acquired resistance (SAR). A phenotypically comparable type of induced resistance is

  4. The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer

    International Nuclear Information System (INIS)

    Loh, Yan Ni; Hedditch, Ellen L; Baker, Laura A; Jary, Eve; Ward, Robyn L; Ford, Caroline E

    2013-01-01

    Acquired resistance to Tamoxifen remains a critical problem in breast cancer patient treatment, yet the underlying causes of resistance have not been fully elucidated. Abberations in the Wnt signalling pathway have been linked to many human cancers, including breast cancer, and appear to be associated with more metastatic and aggressive types of cancer. Here, our aim was to investigate if this key pathway was involved in acquired Tamoxifen resistance, and could be targeted therapeutically. An in vitro model of acquired Tamoxifen resistance (named TamR) was generated by growing the estrogen receptor alpha (ER) positive MCF7 breast cancer cell line in increasing concentrations of Tamoxifen (up to 5 uM). Alterations in the Wnt signalling pathway and epithelial to mesenchymal transition (EMT) in response to Tamoxifen and treatment with the Wnt inhibitor, IWP-2 were measured via quantitative RT-PCR (qPCR) and TOP/FOP Wnt reporter assays. Resistance to Tamoxifen, and effects of IWP-2 treatment were determined by MTT proliferation assays. TamR cells exhibited increased Wnt signalling as measured via the TOP/FOP Wnt luciferase reporter assays. Genes associated with both the β-catenin dependent (AXIN2, MYC, CSNK1A1) and independent arms (ROR2, JUN), as well as general Wnt secretion (PORCN) of the Wnt signalling pathway were upregulated in the TamR cells compared to the parental MCF7 cell line. Treatment of the TamR cell line with human recombinant Wnt3a (rWnt3a) further increased the resistance of both MCF7 and TamR cells to the anti-proliferative effects of Tamoxifen treatment. TamR cells demonstrated increased expression of EMT markers (VIM, TWIST1, SNAI2) and decreased CDH1, which may contribute to their resistance to Tamoxifen. Treatment with the Wnt inhibitor, IWP-2 inhibited cell proliferation and markers of EMT. These data support the role of the Wnt signalling pathway in acquired resistance to Tamoxifen. Further research into the mechanism by which activated Wnt

  5. Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

    Science.gov (United States)

    Xia, Pinghui; Cao, Jinlin; Lv, Xiayi; Wang, Luming; Lv, Wang; Hu, Jian

    2018-05-01

    Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  6. Involvement of p38 mitogen-activated protein kinase in acquired gemcitabine-resistant human urothelial carcinoma sublines

    Directory of Open Access Journals (Sweden)

    Yu-Ting Kao

    2014-07-01

    Full Text Available Resistance to chemotherapeutic drugs is one of the major challenges in the treatment of cancer. A better understanding of how resistance arises and what molecular alterations correlate with resistance is the key to developing novel effective therapeutic strategies. To investigate the underlying mechanisms of gemcitabine (Gem resistance and provide possible therapeutic options, three Gem-resistant urothelial carcinoma sublines were established (NG0.6, NG0.8, and NG1.0. These cells were cross-resistant to arabinofuranosyl cytidine and cisplatin, but sensitive to 5-fluorouracil. The resistant cells expressed lower values of [hENT1 × dCK/RRM1 × RRM2] mRNA ratio. Two adenosine triphosphate-binding cassette proteins ABCD1 as well as multidrug resistance protein 1 were elevated. Moreover, cyclin D1, cyclin-dependent kinases 2 and 4 were upregulated, whereas extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase (MAPK activity were repressed significantly. Administration of p38 MAPK inhibitor significantly reduced the Gem sensitivity in NTUB1 cells, whereas that of an extracellular signal-regulated kinase MAPK inhibitor did not. Furthermore, the Gem-resistant sublines also exhibited higher migration ability. Forced expression of p38 MAPK impaired the cell migration activity and augmented Gem sensitivity in NG1.0 cells. Taken together, these results demonstrate that complex mechanisms were merged in acquiring Gem resistance and provide information that can be important for developing therapeutic targets for treating Gem-resistant tumors.

  7. Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

    International Nuclear Information System (INIS)

    Němcová-Fürstová, Vlasta; Kopperová, Dana; Balušíková, Kamila; Ehrlichová, Marie; Brynychová, Veronika; Václavíková, Radka; Daniel, Petr; Souček, Pavel; Kovář, Jan

    2016-01-01

    Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100 nM and 300 nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype. Interestingly, resistance in both paclitaxel-resistant sublines is circumvented by the second-generation taxane SB-T-1216. Moreover, we demonstrated that it was not possible to establish sublines of SK-BR-3 and MCF-7 cells resistant to this taxane. It means that at least the tested breast cancer cells are unable to develop resistance to some taxanes. Employing mRNA expression profiling of all known human ABC transporters and subsequent Western blot analysis of the expression of selected transporters, we demonstrated that only the ABCB1/PgP and ABCC3/MRP3 proteins were up-regulated in both paclitaxel-resistant sublines. We found up-regulation of ABCG2/BCRP and ABCC4 proteins only in paclitaxel-resistant SK-BR-3 cells. In paclitaxel-resistant MCF-7 cells, ABCB4/MDR3 and ABCC2/MRP2 proteins were up-regulated. Silencing of ABCB1 expression using specific siRNA increased significantly, but did not completely restore full sensitivity to both paclitaxel and doxorubicin. Thus we showed a key, but not exclusive, role for ABCB1 in mechanisms of paclitaxel resistance. It suggests the involvement of multiple mechanisms in paclitaxel resistance in tested breast cancer cells. - Highlights: • Expression of all ABC transporters in paclitaxel-resistant sublines of SK-BR-3 and MCF-7 cells was analyzed. • SK-BR-3 and MCF-7 cells are unable to develop resistance to some taxanes. • Some taxanes are able to overcome developed resistance to

  8. Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

    Energy Technology Data Exchange (ETDEWEB)

    Němcová-Fürstová, Vlasta, E-mail: vlasta.furstova@lf3.cuni.cz [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Kopperová, Dana; Balušíková, Kamila [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Ehrlichová, Marie; Brynychová, Veronika; Václavíková, Radka [Toxicogenomics Unit, National Institute of Public Health, Prague (Czech Republic); Daniel, Petr [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic); Souček, Pavel [Toxicogenomics Unit, National Institute of Public Health, Prague (Czech Republic); Kovář, Jan [Division of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague (Czech Republic)

    2016-11-01

    Development of taxane resistance has become clinically very important issue. The molecular mechanisms underlying the resistance are still unclear. To address this issue, we established paclitaxel-resistant sublines of the SK-BR-3 and MCF-7 breast cancer cell lines that are capable of long-term proliferation in 100 nM and 300 nM paclitaxel, respectively. Application of these concentrations leads to cell death in the original counterpart cells. Both sublines are cross-resistant to doxorubicin, indicating the presence of the MDR phenotype. Interestingly, resistance in both paclitaxel-resistant sublines is circumvented by the second-generation taxane SB-T-1216. Moreover, we demonstrated that it was not possible to establish sublines of SK-BR-3 and MCF-7 cells resistant to this taxane. It means that at least the tested breast cancer cells are unable to develop resistance to some taxanes. Employing mRNA expression profiling of all known human ABC transporters and subsequent Western blot analysis of the expression of selected transporters, we demonstrated that only the ABCB1/PgP and ABCC3/MRP3 proteins were up-regulated in both paclitaxel-resistant sublines. We found up-regulation of ABCG2/BCRP and ABCC4 proteins only in paclitaxel-resistant SK-BR-3 cells. In paclitaxel-resistant MCF-7 cells, ABCB4/MDR3 and ABCC2/MRP2 proteins were up-regulated. Silencing of ABCB1 expression using specific siRNA increased significantly, but did not completely restore full sensitivity to both paclitaxel and doxorubicin. Thus we showed a key, but not exclusive, role for ABCB1 in mechanisms of paclitaxel resistance. It suggests the involvement of multiple mechanisms in paclitaxel resistance in tested breast cancer cells. - Highlights: • Expression of all ABC transporters in paclitaxel-resistant sublines of SK-BR-3 and MCF-7 cells was analyzed. • SK-BR-3 and MCF-7 cells are unable to develop resistance to some taxanes. • Some taxanes are able to overcome developed resistance to

  9. Increasing trend of community-acquired methicillin-resistant: Staphylococcal carriers: An alarming bell for urgent measures

    Directory of Open Access Journals (Sweden)

    Poongodi Lakshmi Santhana Kumarasamy

    2015-01-01

    Full Text Available Background: An increase in the incidence of infections caused by community-associated-methicillin resistant Staphylococcus aureus (MRSA has been reported. Hence, the knowledge of resistance pattern of these isolates is a precondition for alleviating emerging antibiotic resistance and devising better treatment strategies Aim: To find out the prevalence of community-acquired methicillin-resistant staphylococcal strains from nasal carriers. Materials and Methods: A total of 352 nasal swabs collected during routine health checkup were analyzed. Results: Of the 58 (16% staphylococci isolated, 32 (55% were S. aureus and 26 (45% were coagulase-negative staphylococci (CoNS. Methicillin resistance was observed in 7 (22% of staphylococci aureus and 11 (42% of CoNS. "D test" was positive in 1 (14% MRSA, 2 (8% methicillin-susceptible S. aureus and 2 (8% methicillin resistant-CoNS. Conclusion: Effective implementation of the antibiotic policy along with measures like hand wash, isolation of patients will reduce the incidence of resistance.

  10. Acquired multi-azole resistance in Candida tropicalis during persistent urinary tract infection in a dog

    Directory of Open Access Journals (Sweden)

    Sergio Álvarez-Pérez

    2016-03-01

    Full Text Available Multi-azole resistance acquisition by Candida tropicalis after prolonged antifungal therapy in a dog with urinary candidiasis is reported. Pre- and post-azole treatment isolates were clonally related and had identical silent mutations in the ERG11 gene, but the latter displayed increased azole minimum inhibitory concentrations. A novel frameshift mutation in ERG3 was found in some isolates recovered after resistance development, so it appears unlikely that this mutation is responsible for multi-azole resistance.

  11. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E

    2007-01-01

    Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for...

  12. Nuclear HER4 mediates acquired resistance to trastuzumab and is associated with poor outcome in HER2 positive breast cancer

    Science.gov (United States)

    Nafi, Siti Norasikin Mohd; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Haider, Syed; Li, Ji-Liang; Bridges, Esther; Capala, Jacek; Ioannis, Roxanis; Harris, Adrian L; Kong, Anthony

    2014-01-01

    The role of HER4 in breast cancer is controversial and its role in relation to trastuzumab resistance remains unclear. We showed that trastuzumab treatment and its acquired resistance induced HER4 upregulation, cleavage and nuclear translocation. However, knockdown of HER4 by specific siRNAs increased trastuzumab sensitivity and reversed its resistance in HER2 positive breast cancer cells. Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased trastuzumab-induced HER4 nuclear translocation and enhanced trastuzumab response. There was also increased nuclear HER4 staining in the tumours from BT474 xenograft mice and human patients treated with trastuzumab. Furthermore, nuclear HER4 predicted poor clinical response to trastuzumab monotherapy in patients undergoing a window study and was shown to be an independent poor prognostic factor in HER2 positive breast cancer. Our data suggest that HER4 plays a key role in relation to trastuzumab resistance in HER2 positive breast cancer. Therefore, our study provides novel findings that HER4 activation, cleavage and nuclear translocation influence trastuzumab sensitivity and resistance in HER2 positive breast cancer. Nuclear HER4 could be a potential prognostic and predictive biomarker and understanding the role of HER4 may provide strategies to overcome trastuzumab resistance in HER2 positive breast cancer. PMID:25153719

  13. Community acquired pneumonia: genetic variants influencing systemic inflammation.

    Science.gov (United States)

    Ferrer Agüero, J M; Millán, S; Rodríguez de Castro, F; Martín-Loeches, I; Solé Violán, J

    2014-01-01

    The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also on the balance between inflammatory and antiinflammatory response. Several studies have presented evidence of the importance of genetic factors in severe infections. The innate immune response prevents the invasion and spread of pathogens during the first hours after infection. Each of the different processes involved in innate immunity may be affected by genetic polymorphisms, which can result in susceptibility or resistance to infection. The results obtained in the different studies do not irrefutably prove the role or function of a gene in the pathogenesis of respiratory infections. However, they can generate new hypotheses, suggest new candidate genes based on their role in the inflammatory response, and constitute a first step in understanding the underlying genetic factors. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  14. Circumvention of acquired resistance to doxorubicin in K562 human leukemia cells by oxatomide.

    Science.gov (United States)

    Ishikawa, M; Fujita, R; Furusawa, S; Takayanagi, M; Sasaki, K; Satoh, S

    2001-10-01

    We studied the effect of oxatomide, an antiallergic drug, on the resistance of K562 cells to doxorubicin. Oxatomide synergistically potentiated the cytotoxicity of doxorubicin in doxorubicin-resistant K562 cells (K562/DXR) at a concentration of 1-10 microM, but had hardly any synergistic effect on the parental cell line (K562) at the same concentration. Oxatomide inhibit P-glycoprotein pump-efflux activity and the binding of [3H]-azidopine to the cell-surface protein P-glycoprotein, in a dose-related manner. These results indicate that oxatomide reverses the multidrug-resistance phenotype through direct interaction with P-glycoprotein.

  15. Risk factors for hospital-acquired bacteremia due to carbapenem-resistant Pseudomonas aeruginosa in a Colombian hospital.

    Science.gov (United States)

    Valderrama, Sandra Liliana; González, Pedro Felipe; Caro, María Alejandra; Ardila, Natalia; Ariza, Beatriz; Gil, Fabián; Álvarez, Carlos

    2016-02-23

    Bacteremia due to Pseudomonas aeruginosa resistant to carbapenems is a public health problem due to the limitations it places on therapeutic options, as well as the increased time patients must spend in hospital, costs and the risk of mortality.  To evaluate the risk factors for presentation of bacteremia due to carbapenem-resistant P. aeruginosa acquired in the Hospital Universitario San Ignacio between January 2008 and June 2014.  This was a case control study in which the case patients presented bacteremia due to P. aeruginosa resistant to carbapenems and the control group included patients with P. aeruginosa susceptible to this group of antibiotics. Variables such as the previous use of meropenem and ertapenem, immunosuppression and neoplasia were measured. Mortality and duration of hospital were also described.  In all, 168 patients were evaluated, of which 42 were cases and 126 controls. Using a multivariate model, the risk factors related to bacteremia due to carbapenem-resistant P. aeruginosa acquired in hospital were the following: use of parenteral nutrition (OR=8.28; 95% CI: 2.56-26.79; p=0); use of meropenem (OR=1.15; 95% CI: 1.03-1.28; p=0.01); and use of ciprofloxacin (OR=81.99; 95% CI: 1.14-5884; p=0.043).  In order to prevent the emergence of carbapenem-resistant P. aeruginosa, antimicrobial control programs should be strengthened by promoting the prudent administration of carbapenems and quinolones. The correct use of parenteral nutrition should also be monitored.

  16. Multidrug-Resistant CTX-M-(15, 9, 2)- and KPC-2-Producing Enterobacter hormaechei and Enterobacter asburiae Isolates Possessed a Set of Acquired Heavy Metal Tolerance Genes Including a Chromosomal sil Operon (for Acquired Silver Resistance).

    Science.gov (United States)

    Andrade, Leonardo N; Siqueira, Thiago E S; Martinez, Roberto; Darini, Ana Lucia C

    2018-01-01

    Bacterial resistance to antibiotics is concern in healthcare-associated infections. On the other hand, bacterial tolerance to other antimicrobials, like heavy metals, has been neglected and underestimated in hospital pathogens. Silver has long been used as an antimicrobial agent and it seems to be an important indicator of heavy metal tolerance. To explore this perspective, we searched for the presence of acquired silver resistance genes ( sil operon: silE, silS, silR, silC, silF, silB, silA , and silP ) and acquired extended-spectrum cephalosporin and carbapenem resistance genes ( bla CTX-M and bla KPC ) in Enterobacter cloacae Complex (EcC) ( n = 27) and Enterobacter aerogenes ( n = 8) isolated from inpatients at a general hospital. Moreover, the genetic background of the silA (silver-efflux pump) and the presence of other acquired heavy metal tolerance genes, pcoD (copper-efflux pump), arsB (arsenite-efflux pump), terF (tellurite resistance protein), and merA (mercuric reductase) were also investigated. Outstandingly, 21/27 (78%) EcC isolates harbored silA gene located in the chromosome. Complete sil operon was found in 19/21 silA -positive EcC isolates. Interestingly, 8/20 (40%) E. hormaechei and 5/6 (83%) E. asburiae co-harbored silA/pcoD genes and bla CTX-M-(15,2,or9) and/or bla KPC-2 genes. Frequent occurrences of arsB, terF , and merA genes were detected, especially in silA/pcoD -positive, multidrug-resistant (MDR) and/or CTX-M-producing isolates. Our study showed co-presence of antibiotic and heavy metal tolerance genes in MDR EcC isolates. In our viewpoint, there are few studies regarding to bacterial heavy metal tolerance and we call attention for more investigations and discussion about this issue in different hospital pathogens.

  17. Multidrug-Resistant CTX-M-(15, 9, 2- and KPC-2-Producing Enterobacter hormaechei and Enterobacter asburiae Isolates Possessed a Set of Acquired Heavy Metal Tolerance Genes Including a Chromosomal sil Operon (for Acquired Silver Resistance

    Directory of Open Access Journals (Sweden)

    Leonardo N. Andrade

    2018-03-01

    Full Text Available Bacterial resistance to antibiotics is concern in healthcare-associated infections. On the other hand, bacterial tolerance to other antimicrobials, like heavy metals, has been neglected and underestimated in hospital pathogens. Silver has long been used as an antimicrobial agent and it seems to be an important indicator of heavy metal tolerance. To explore this perspective, we searched for the presence of acquired silver resistance genes (sil operon: silE, silS, silR, silC, silF, silB, silA, and silP and acquired extended-spectrum cephalosporin and carbapenem resistance genes (blaCTX−M and blaKPC in Enterobacter cloacae Complex (EcC (n = 27 and Enterobacter aerogenes (n = 8 isolated from inpatients at a general hospital. Moreover, the genetic background of the silA (silver-efflux pump and the presence of other acquired heavy metal tolerance genes, pcoD (copper-efflux pump, arsB (arsenite-efflux pump, terF (tellurite resistance protein, and merA (mercuric reductase were also investigated. Outstandingly, 21/27 (78% EcC isolates harbored silA gene located in the chromosome. Complete sil operon was found in 19/21 silA-positive EcC isolates. Interestingly, 8/20 (40% E. hormaechei and 5/6 (83% E. asburiae co-harbored silA/pcoD genes and blaCTX−M−(15,2,or9 and/or blaKPC−2 genes. Frequent occurrences of arsB, terF, and merA genes were detected, especially in silA/pcoD-positive, multidrug-resistant (MDR and/or CTX-M-producing isolates. Our study showed co-presence of antibiotic and heavy metal tolerance genes in MDR EcC isolates. In our viewpoint, there are few studies regarding to bacterial heavy metal tolerance and we call attention for more investigations and discussion about this issue in different hospital pathogens.

  18. Acquired IFNγ resistance impairs anti-tumor immunity and gives rise to T-cell-resistant melanoma lesions

    Science.gov (United States)

    Sucker, Antje; Zhao, Fang; Pieper, Natalia; Heeke, Christina; Maltaner, Raffaela; Stadtler, Nadine; Real, Birgit; Bielefeld, Nicola; Howe, Sebastian; Weide, Benjamin; Gutzmer, Ralf; Utikal, Jochen; Loquai, Carmen; Gogas, Helen; Klein-Hitpass, Ludger; Zeschnigk, Michael; Westendorf, Astrid M.; Trilling, Mirko; Horn, Susanne; Schilling, Bastian; Schadendorf, Dirk; Griewank, Klaus G.; Paschen, Annette

    2017-01-01

    Melanoma treatment has been revolutionized by antibody-based immunotherapies. IFNγ secretion by CD8+ T cells is critical for therapy efficacy having anti-proliferative and pro-apoptotic effects on tumour cells. Our study demonstrates a genetic evolution of IFNγ resistance in different melanoma patient models. Chromosomal alterations and subsequent inactivating mutations in genes of the IFNγ signalling cascade, most often JAK1 or JAK2, protect melanoma cells from anti-tumour IFNγ activity. JAK1/2 mutants further evolve into T-cell-resistant HLA class I-negative lesions with genes involved in antigen presentation silenced and no longer inducible by IFNγ. Allelic JAK1/2 losses predisposing to IFNγ resistance development are frequent in melanoma. Subclones harbouring inactivating mutations emerge under various immunotherapies but are also detectable in pre-treatment biopsies. Our data demonstrate that JAK1/2 deficiency protects melanoma from anti-tumour IFNγ activity and results in T-cell-resistant HLA class I-negative lesions. Screening for mechanisms of IFNγ resistance should be considered in therapeutic decision-making. PMID:28561041

  19. Bacterial Etiology and Antibiotic Resistance Profile of Community-Acquired Urinary Tract Infections in a Cameroonian City.

    Science.gov (United States)

    Nzalie, Rolf Nyah-Tuku; Gonsu, Hortense Kamga; Koulla-Shiro, Sinata

    2016-01-01

    Introduction. Community-acquired urinary tract infections (CAUTIs) are usually treated empirically. Geographical variations in etiologic agents and their antibiotic sensitivity patterns are common. Knowledge of antibiotic resistance trends is important for improving evidence-based recommendations for empirical treatment of UTIs. Our aim was to determine the major bacterial etiologies of CAUTIs and their antibiotic resistance patterns in a cosmopolitan area of Cameroon for comparison with prescription practices of local physicians. Methods. We performed a cross-sectional descriptive study at two main hospitals in Yaoundé, collecting a clean-catch mid-stream urine sample from 92 patients having a clinical diagnosis of UTI. The empirical antibiotherapy was noted, and identification of bacterial species was done on CLED agar; antibiotic susceptibility testing was performed using the Kirby-Bauer disc diffusion method. Results. A total of 55 patients had samples positive for a UTI. Ciprofloxacin and amoxicillin/clavulanic acid were the most empirically prescribed antibiotics (30.9% and 23.6%, resp.); bacterial isolates showed high prevalence of resistance to both compounds. Escherichia coli (50.9%) was the most common pathogen, followed by Klebsiella pneumoniae (16.4%). Prevalence of resistance for ciprofloxacin was higher compared to newer quinolones. Conclusions. E. coli and K. pneumoniae were the predominant bacterial etiologies; the prevalence of resistance to commonly prescribed antibiotics was high.

  20. Bacterial Etiology and Antibiotic Resistance Profile of Community-Acquired Urinary Tract Infections in a Cameroonian City

    Directory of Open Access Journals (Sweden)

    Rolf Nyah-tuku Nzalie

    2016-01-01

    Full Text Available Introduction. Community-acquired urinary tract infections (CAUTIs are usually treated empirically. Geographical variations in etiologic agents and their antibiotic sensitivity patterns are common. Knowledge of antibiotic resistance trends is important for improving evidence-based recommendations for empirical treatment of UTIs. Our aim was to determine the major bacterial etiologies of CAUTIs and their antibiotic resistance patterns in a cosmopolitan area of Cameroon for comparison with prescription practices of local physicians. Methods. We performed a cross-sectional descriptive study at two main hospitals in Yaoundé, collecting a clean-catch mid-stream urine sample from 92 patients having a clinical diagnosis of UTI. The empirical antibiotherapy was noted, and identification of bacterial species was done on CLED agar; antibiotic susceptibility testing was performed using the Kirby-Bauer disc diffusion method. Results. A total of 55 patients had samples positive for a UTI. Ciprofloxacin and amoxicillin/clavulanic acid were the most empirically prescribed antibiotics (30.9% and 23.6%, resp.; bacterial isolates showed high prevalence of resistance to both compounds. Escherichia coli (50.9% was the most common pathogen, followed by Klebsiella pneumoniae (16.4%. Prevalence of resistance for ciprofloxacin was higher compared to newer quinolones. Conclusions. E. coli and K. pneumoniae were the predominant bacterial etiologies; the prevalence of resistance to commonly prescribed antibiotics was high.

  1. Interpretation of deep directional resistivity measurements acquired in high-angle and horizontal wells using 3-D inversion

    Science.gov (United States)

    Puzyrev, Vladimir; Torres-Verdín, Carlos; Calo, Victor

    2018-05-01

    The interpretation of resistivity measurements acquired in high-angle and horizontal wells is a critical technical problem in formation evaluation. We develop an efficient parallel 3-D inversion method to estimate the spatial distribution of electrical resistivity in the neighbourhood of a well from deep directional electromagnetic induction measurements. The methodology places no restriction on the spatial distribution of the electrical resistivity around arbitrary well trajectories. The fast forward modelling of triaxial induction measurements performed with multiple transmitter-receiver configurations employs a parallel direct solver. The inversion uses a pre-conditioned gradient-based method whose accuracy is improved using the Wolfe conditions to estimate optimal step lengths at each iteration. The large transmitter-receiver offsets, used in the latest generation of commercial directional resistivity tools, improve the depth of investigation to over 30 m from the wellbore. Several challenging synthetic examples confirm the feasibility of the full 3-D inversion-based interpretations for these distances, hence enabling the integration of resistivity measurements with seismic amplitude data to improve the forecast of the petrophysical and fluid properties. Employing parallel direct solvers for the triaxial induction problems allows for large reductions in computational effort, thereby opening the possibility to invert multiposition 3-D data in practical CPU times.

  2. Acquired resistance of malarial parasites against artemisinin-based drugs: social and economic impacts

    Directory of Open Access Journals (Sweden)

    Johanna M Porter-Kelley

    2010-08-01

    Full Text Available Johanna M Porter-Kelley1, Joann Cofie2, Sophonie Jean2, Mark E Brooks1, Mia Lassiter1, DC Ghislaine Mayer21Life Sciences Department, ­Winston-Salem State University, Winston Salem, NC, USA; 2Department of Biology, Virginia Commonwealth University, Richmond, VA, USAAbstract: Malaria, a disease of poverty and high morbidity and mortality in the tropical world, has led to a worldwide search for control measures. To that end, good antimalarial chemotherapies have been difficult to find in the global market and those that seem to be most effective are rapidly becoming ineffective due to the emergence and spread of drug resistance. Artemisinin, a very effective yet expensive antimalarial, has quickly become the recommended drug of choice when all other possibilities fail. However, for all its promise as the next great antimalarial, the outlook is bleak. Resistance is developing to artemisinin while another effective antimalarial is not in sight. Malaria endemic areas which are mostly in developing countries must deal with the multifaceted process of changing and implementing new national malaria treatment guidelines. This requires complex interactions between several sectors of the affected society which in some cases take place within the context of political instability. Moreover, the cost associated with preventing and containing the spread of antimalarial resistance is detrimental to economic progress. This review addresses the impact of artemisinin resistance on the socioeconomic structure of malaria endemic countries.Keywords: artemisinin-based drugs, social, economic, malarial parasite resistance

  3. Identification and Determination of Drug Resistant of Candida species isolated from Hospital Acquired Infections

    Directory of Open Access Journals (Sweden)

    Kambiz Diba

    2015-01-01

    Full Text Available Background & aim: Currently, the use of antifungal azole group and yeasts resistant to these drugs is increasing. The aim of this study was to isolate and identify the yeasts obtained from candidiasis patients and furthermore determining thier antifungal resistance. Methods: In the present descriptive study, infections samples were collected from 256 patients with suspected nosocomial candidiasis, then direct exam and culture were performed. Yeast colonies were identified using phenotypic methods, polymerase chain reaction method and enzyme digestion. Data were analyzed using Descriptive statistical tests. Results: Of sixty isolated yeast, thirty-seven cases of Candida albicans (61.6%, seven cases of C. krusei and C. glabrata (11.6% each, five cases of C. dubliniensis (8.3% and four cases of C. tropicalis (6.6% were indicated. The study showed that the sensitivity of C. albicans and C. cruise species to amphotericin B was negligible in disk diffusion and very sensitve in microdilution. Conclusion: Inspite of the results of antifungal susceptibility test of strains studied did not show high resistance, but screening for drug-resistant Candida isolates in Candida infection by disk diffusion and microdilution methods for new cases of drug resistance is reasonable.

  4. The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.

    Science.gov (United States)

    Agostino, Jason W; Ferguson, John K; Eastwood, Keith; Kirk, Martyn D

    2017-11-06

    To identify groups at risk of methicillin-resistant Staphylococcus aureus (MRSA) infection, patterns of antimicrobial resistance, and the proportion of patients with MRSA infections but no history of recent hospitalisation. Case series of 39 231 patients with S. aureus isolates from specimens processed by the Hunter New England Local Health District (HNELHD) public pathology provider during 2008-2014. Proportion of MRSA infections among people with S. aureus isolates; antimicrobial susceptibility of MRSA isolates; origin of MRSA infections (community- or health care-associated); demographic factors associated with community-associated MRSA infections. There were 71 736 S. aureus-positive specimens during the study period and MRSA was isolated from 19.3% of first positive specimens. Most patients (56.9%) from whom MRSA was isolated had not been admitted to a public hospital in the past year. Multiple regression identified that patients with community-associated MRSA were more likely to be younger (under 40), Indigenous Australians (odds ratio [OR], 2.6; 95% CI, 2.3-2.8), or a resident of an aged care facility (OR, 4.7; 95% CI, 3.8-5.8). The proportion of MRSA isolates that included the dominant multi-resistant strain (AUS-2/3-like) declined from 29.6% to 3.4% during the study period (P resistant strain decreased, new strategies for controlling infections in the community are needed to reduce the prevalence of non-multi-resistant strains.

  5. Community-acquired carbapenem-resistant Acinetobacter baumannii urinary tract infection just after marriage in a renal transplant recipient.

    Science.gov (United States)

    Solak, Y; Atalay, H; Turkmen, K; Biyik, Z; Genc, N; Yeksan, M

    2011-12-01

    Urinary tract infection (UTI) is common in renal transplant recipients and may worsen allograft and patient survival. Many risk factors such as age, female gender, immunosuppression, comorbidity, deceased-donor kidney transplantation, and uretheral catheterization are involved in development of UTI. Acinetobacter baumannii has rarely been reported as a causative agent for development of UTI. Here, we present an unusual case of a renal transplant recipient who developed community-acquired carbapenem-resistent A. baumannii UTI. © 2011 John Wiley & Sons A/S.

  6. Acquired MET expression confers resistance to EGFR inhibition in a mouse model of glioblastoma multiforme.

    Science.gov (United States)

    Jun, H J; Acquaviva, J; Chi, D; Lessard, J; Zhu, H; Woolfenden, S; Bronson, R T; Pfannl, R; White, F; Housman, D E; Iyer, L; Whittaker, C A; Boskovitz, A; Raval, A; Charest, A

    2012-06-21

    Glioblastoma multiforme (GBM) is an aggressive brain tumor for which there is no cure. Overexpression of wild-type epidermal growth factor receptor (EGFR) and loss of the tumor suppressor genes Ink4a/Arf and PTEN are salient features of this deadly cancer. Surprisingly, targeted inhibition of EGFR has been clinically disappointing, demonstrating an innate ability for GBM to develop resistance. Efforts at modeling GBM in mice using wild-type EGFR have proven unsuccessful to date, hampering endeavors at understanding molecular mechanisms of therapeutic resistance. Here, we describe a unique genetically engineered mouse model of EGFR-driven gliomagenesis that uses a somatic conditional overexpression and chronic activation of wild-type EGFR in cooperation with deletions in the Ink4a/Arf and PTEN genes in adult brains. Using this model, we establish that chronic activation of wild-type EGFR with a ligand is necessary for generating tumors with histopathological and molecular characteristics of GBMs. We show that these GBMs are resistant to EGFR kinase inhibition and we define this resistance molecularly. Inhibition of EGFR kinase activity using tyrosine kinase inhibitors in GBM tumor cells generates a cytostatic response characterized by a cell cycle arrest, which is accompanied by a substantial change in global gene expression levels. We demonstrate that an important component of this pattern is the transcriptional activation of the MET receptor tyrosine kinase and that pharmacological inhibition of MET overcomes the resistance to EGFR inhibition in these cells. These findings provide important new insights into mechanisms of resistance to EGFR inhibition and suggest that inhibition of multiple targets will be necessary to provide therapeutic benefit for GBM patients.

  7. Streamlining the Process of Acquiring Secure Open Architecture Software Systems

    Science.gov (United States)

    2013-10-08

    Microsoft.NET, Enterprise Java Beans, GNU Lesser General Public License (LGPL) libraries, and data communication protocols like the Hypertext Transfer...NetBeans development environments),  customer relationship management (SugarCRM),  database management systems (PostgreSQL, MySQL ),  operating

  8. Understanding The Resistance to Health Information Systems

    OpenAIRE

    David Ackah; Angelito E Alvarado; Heru Santoso Wahito Nugroho; Sanglar Polnok; Wiwin Martiningsih

    2017-01-01

    User resistance is users’ opposition to system implementation. Resistance often occurs as a result of a mismatch between management goals and employee preferences. There are two types of resistance to health iformation system namely active resistance and passive resistance. The manifestation of active resistance are being critical,  blaming/accusing, blocking, fault finding, sabotaging, undermining, ridiculing, intimidating/threatening, starting rumors, appealing to fear, manipulating arguing...

  9. Identification of genes involved in rhizobacteria-mediated induced systemic resistance in Arabidopsis

    NARCIS (Netherlands)

    Léon-Kloosterziel, K.M.; Verhagen, B.W.M.; Keurentjes, J.J.B.; Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    Different forms of biologically induced disease resistance have been identified in plants. Following attack by a necrotizing pathogen systemic acquired resistance (SAR) is induced, leading to a broad-spectrum disease resistance that is associated with an increase in salicylic acid (SA) levels

  10. Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation--diversity, ductility, and destiny.

    Science.gov (United States)

    Suda, Kenichi; Mizuuchi, Hiroshi; Maehara, Yoshihiko; Mitsudomi, Tetsuya

    2012-12-01

    Lung cancers that harbor somatic activating mutations in the gene for the epidermal growth factor receptor (EGFR) depend on mutant EGFR for their proliferation and survival; therefore, lung cancer patients with EGFR mutations often dramatically respond to orally available EGFR tyrosine kinase inhibitors (TKIs). However, emergence of acquired resistance is virtually inevitable, thus limiting improvement in patient outcomes. To elucidate and overcome this acquired resistance, multidisciplinary basic and clinical investigational approaches have been applied, using in vitro cell line models or samples obtained from lung cancer patients treated with EGFR-TKIs. These efforts have revealed several acquired resistance mechanisms and candidates, including EGFR secondary mutations (T790M and other rare mutations), MET amplification, PTEN downregulation, CRKL amplification, high-level HGF expression, FAS-NFκB pathway activation, epithelial-mesenchymal transition, and conversion to small cell lung cancer. Interestingly, cancer cells harbor potential destiny and ductility together in acquiring resistance to EGFR-TKIs, as shown in in vitro acquired resistance models. Molecular mechanisms of "reversible EGFR-TKI tolerance" that occur in early phase EGFR-TKI exposure have been identified in cell line models. Furthermore, others have reported molecular markers that can predict response to EGFR-TKIs in clinical settings. Deeper understanding of acquired resistance mechanisms to EGFR-TKIs, followed by the development of molecular target drugs that can overcome the resistance, might turn this fatal disease into a chronic disorder.

  11. Trade-offs with stability modulate innate and mutationally acquired drug-resistance in bacterial dihydrofolate reductase enzymes.

    Science.gov (United States)

    Matange, Nishad; Bodkhe, Swapnil; Patel, Maitri; Shah, Pooja

    2018-06-05

    Structural stability is a major constraint on the evolution of protein sequences. However, under strong directional selection, mutations that confer novel phenotypes but compromise structural stability of proteins may be permissible. During the evolution of antibiotic resistance, mutations that confer drug resistance often have pleiotropic effects on the structure and function of antibiotic-target proteins, usually essential metabolic enzymes. In this study, we show that trimethoprim-resistant alleles of dihydrofolate reductase from Escherichia coli (EcDHFR) harbouring the Trp30Gly, Trp30Arg or Trp30Cys mutations are significantly less stable than the wild type making them prone to aggregation and proteolysis. This destabilization is associated with lower expression level resulting in a fitness cost and negative epistasis with other TMP-resistant mutations in EcDHFR. Using structure-based mutational analysis we show that perturbation of critical stabilizing hydrophobic interactions in wild type EcDHFR enzyme explains the phenotypes of Trp30 mutants. Surprisingly, though crucial for the stability of EcDHFR, significant sequence variation is found at this site among bacterial DHFRs. Mutational and computational analyses in EcDHFR as well as in DHFR enzymes from Staphylococcus aureus and Mycobacterium tuberculosis demonstrate that natural variation at this site and its interacting hydrophobic residues, modulates TMP-resistance in other bacterial DHFRs as well, and may explain the different susceptibilities of bacterial pathogens to trimethoprim. Our study demonstrates that trade-offs between structural stability and function can influence innate drug resistance as well as the potential for mutationally acquired drug resistance of an enzyme. ©2018 The Author(s).

  12. HOW ROMANIAN FINANCIAL AND INTERNAL AUDITORS ACQUIRE ACCOUNTING INFORMATION SYSTEMS KNOWLEDGE AND COMPETENCES?

    OpenAIRE

    Cardos Vasile - Daniel

    2011-01-01

    Research theme - in this article we investigate how Romanian financial and internal auditors acquire accounting information systems knowledge and competences and how they use this knowledge to improve their activity in order to fulfill their mission as required by the professional standards. Objectives - our main purpose is to establish through what type of courses Romanian financial and internal auditors acquiring accounting information systems knowledge and competences and how useful these ...

  13. Radiation-resistant control system

    International Nuclear Information System (INIS)

    Cable, T.C.; Jones, S.

    1995-01-01

    REMOTEC has developed a open-quotes radiation resistanceclose quotes control system under a U.S. Department of Energy Small Business Innovative Research (SBIR) contract with assistance from the University of Florida. The SBIR goal was to develop a radiation resistant mobile robot from the ANDROS family of hazardous duty mobile robots that REMOTEC manufactures. See Refs. 1 and 2 for additional SBIR results. The control system, as well as the entire ANDROS robot, was redesigned, where necessary, to withstand radiation doses in excess of 10 6 rad. Those components of the robot that could not be purchased as open-quotes radiation hardenedclose quotes were tested under standard operating conditions for determination of their open-quotes radiation resistance.close quotes The entire ANDROS robot was then assembled with these new components and tested to > 10 6 rad

  14. Community-acquired multidrug-resistant Gram-negative bacterial infective endocarditis.

    Science.gov (United States)

    Naha, Sowjanya; Naha, Kushal; Acharya, Vasudev; Hande, H Manjunath; Vivek, G

    2014-08-05

    We describe two cases of bacterial endocarditis secondary to multidrug-resistant Gram-negative organisms. In both cases, the diagnosis was made in accordance with the modified Duke's criteria and confirmed by histopathological analysis. Furthermore, in both instances there were no identifiable sources of bacteraemia and no history of contact with hospital or other medical services prior to the onset of symptoms. The patients were managed in similar fashion with prolonged broad-spectrum antibiotic therapy and surgical intervention and made complete recoveries. These cases highlight Gram-negative organisms as potential agents for endocarditis, as well as expose the dissemination of such multidrug-resistant bacteria into the community. The application of an integrated medical and surgical approach and therapeutic dilemmas encountered in managing these cases are described. 2014 BMJ Publishing Group Ltd.

  15. Risk of resistance related to antibiotic use before admission in patients with community-acquired bacteraemia

    DEFF Research Database (Denmark)

    Pedersen, Gitte; Schønheyder, Henrik Carl; Steffensen, Flemming Hald

    1999-01-01

    %), Streptococcus pneumoniae (23%) Staphylococcus aureus (10%). Of the 575 isolates of E. coli, 425 (74%), 432 (75%) and 518 (90%) were susceptible to ampicillin, sulphonamides and trimethoprim, respectively. Previous antibiotic prescriptions were strongly associated with resistance to ampicillin, sulphonamides...... and trimethoprim in E. coli. The association was less pronounced for S. aureus and enteric rods other than E. coli. Antibiotic prescriptions within the last 3 months predicted antibiotic resistance, and this should be taken into account when selecting empirical antibiotic therapy of severe community...... admission and to 37% during the 6 months. The most frequently prescribed antibiotics within 30 days were ampicillin (28%), penicillin G (27%), sulphonamides and/or trimethoprim (16%) and macrolides (14%). The most frequent blood isolates were Escherichia coli (33%), other Enterobacteriaceae 8...

  16. Impact resistant battery enclosure systems

    Science.gov (United States)

    Tsutsui, Waterloo; Feng, Yuezhong; Chen, Weinong Wayne; Siegmund, Thomas Heinrich

    2017-10-31

    Battery enclosure arrangements for a vehicular battery system. The arrangements, capable of impact resistance include plurality of battery cells and a plurality of kinetic energy absorbing elements. The arrangements further include a frame configured to encase the plurality of the kinetic energy absorbing elements and the battery cells. In some arrangements the frame and/or the kinetic energy absorbing elements can be made of topologically interlocked materials.

  17. Travel to Asia and traveller's diarrhoea with antibiotic treatment are independent risk factors for acquiring ciprofloxacin-resistant and extended spectrum β-lactamase-producing Enterobacteriaceae-a prospective cohort study.

    Science.gov (United States)

    Reuland, E A; Sonder, G J B; Stolte, I; Al Naiemi, N; Koek, A; Linde, G B; van de Laar, T J W; Vandenbroucke-Grauls, C M J E; van Dam, A P

    2016-08-01

    Travel to (sub)tropical countries is a well-known risk factor for acquiring resistant bacterial strains, which is especially of significance for travellers from countries with low resistance rates. In this study we investigated the rate of and risk factors for travel-related acquisition of extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E), ciprofloxacin-resistant Enterobacteriaceae (CIPR-E) and carbapenem-resistant Enterobacteriaceae. Data before and after travel were collected from 445 participants. Swabs were cultured with an enrichment broth and sub-cultured on selective agar plates for ESBL detection, and on plates with a ciprofloxacin disc. ESBL production was confirmed with the double-disc synergy test. Species identification and susceptibility testing were performed with the Vitek-2 system. All isolates were subjected to ertapenem Etest. ESBL and carbapenemase genes were characterized by PCR and sequencing. Twenty-seven out of 445 travellers (6.1%) already had ESBL-producing strains and 45 of 445 (10.1%) travellers had strains resistant to ciprofloxacin before travel. Ninety-eight out of 418 (23.4%) travellers acquired ESBL-E and 130 of 400 (32.5%) travellers acquired a ciprofloxacin-resistant strain. Of the 98 ESBL-E, predominantly Escherichia coli and predominantly blaCTX-M-15, 56% (55/98) were resistant to gentamicin, ciprofloxacin and co-trimoxazole. Multivariate analysis showed that Asia was a high-risk area for ESBL-E as well as CIPR-E acquisition. Travellers with diarrhoea combined with antimicrobial use were significantly at higher risk for acquisition of resistant strains. Only one carbapenemase-producing isolate was acquired, isolated from a participant after visiting Egypt. In conclusion, travelling to Asia and diarrhoea combined with antimicrobial use are important risk factors for acquiring ESBL-E and CIPR-E. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All

  18. Role of major histocompatibility complex class II in resistance of mice to naturally acquired infection with Syphacia obvelata

    Science.gov (United States)

    Stewart, Patricia W.; Chapes, Stephen K.

    2003-01-01

    Genetics plays a substantial role in host resistance in many host-parasite interactions. We examined the prevalence of naturally acquired infection with Syphacia obvelata in a number of mouse strains housed in a non-barrier facility. These mice, which included cross-bred and congenic, inbred strains on various genetic backgrounds, differ in the loci for the immune function genes--major histocompatibility complex class II (MHCII), toll-like receptor 4 (Tlr4), and solute carrier family 11, member 1 (Slc11a1)--which allowed comparisons of the impact of these genes on resistance to pinworm infection. Male and female mice of various ages were sampled over an 18-month period; infection was determined by use of the cellophane tape test. Results indicated that mice that were MHCII+/+ had a significantly lower prevalence of infection than did mice that were MHCII-/-. Differences were not seen between male and female mice. Although MHCII+/+ mice had an age-associated decrease in infection prevalence, such decrease was not seen in MHCII-/- mice. In contrast, infection prevalence in mice with the normal Tlr4 gene (Tlr4(LPS-n/LPS-n)) gene did not differ significantly compared with that in mice that were homozygous for either the point mutation (Tlr4(LPS-d/LPS-d)) or deletion (Tlr4(LPS-del/LPS-del)) of that gene. Likewise, the presence (Sle11a1r/r) or absence (Slc11a1s/s) of functional alleles for Slc11a1 had no effect on the prevalence of infection with S. obvelata. In conclusion, presence of MHCII, but not Tlr4 or Slc11a1 significantly influences prevalence of naturally acquired infection with S. obvelata. These data justify further comprehensive analyses of the immune components that are involved in pinworm resistance.

  19. Genetic control of acquired resistance to gastrointestinal nematode parasites in sheep

    International Nuclear Information System (INIS)

    Windon, R.G.; Wagland, B.M.; Dineen, J.K.

    1988-01-01

    A radiation attenuated larval vaccine has been used to evaluate the role of genetic components of the immune response in the control of Trichostrongylus colubriformis in sheep. Through selection based on age dependent responsiveness, lines of sheep have been established in which lambs are either high or low responders to vaccination and challenge infection. The estimated and realized heritabilities for the selected trait are 0.35-0.41. Significant interline differences were demonstrated and, within the lines, ewe lambs were consistently more responsive than rams or wethers. The effect of selection was not antigenically specific, since high responsiveness to T. colubriformis was associated with increased responsiveness to other related (T. rugatus) and unrelated parasites (Ostertagia circumcincta and Haemonchus contortus). In addition, high responders had a more vigorous reaction against naturally acquired infections than low responders. The general immunological competence was also increased in high responders; this was shown by the levels of serum complement fixing antibody to larval antigens after vaccination and challenge, in vitro blastogenic responses stimulated by larval antigens and the phagocytic function of peripheral leucocytes. No production penalty (weight gain and wool growth) was associated with heightened responsiveness. (author). 10 refs, 1 fig

  20. The comparative development of elevated resistance to macrolides in community-acquired pneumonia caused by Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Yayan J

    2014-10-01

    Full Text Available Josef Yayan Department of Internal Medicine, Division of Pulmonary, Allergy and Sleep Medicine, Saarland University Medical Center, Homburg/Saar, Germany Background: Community-acquired pneumonia (CAP is an acute inflammation of the lungs, which is often caused by Streptococcus pneumoniae. CAP is the leading cause of death by infectious disease in industrialized countries. Therefore, an immediate and effective antibiotic therapy is of great importance for the nonfatal outcome of the disease. The literature contains increasing data about the development of resistance to antibiotics that are used for the treatment of CAP caused by S. pneumoniae; this article also examines the possible development of resistance to antibiotics in S. pneumoniae in recent years.Methods: Within the study period of 2004–2014, all hospital charts from patients with CAP caused by S. pneumoniae were collected from the Department of Internal Medicine, Saarland University Medical Center, Homburg/Saar, Germany. The tracheal secretions of S. pneumoniae in CAP patients were obtained by bronchoalveolar lavage; bronchial aspirates were obtained through flexible bronchoscopy and directly from sputum, and blood cultures were examined microbiologically for microorganisms.Results: From a total of 100 patients with CAP caused by S. pneumoniae, 23 (53.49% [34.78% female], 95% confidence interval, 38.58–68.4 patients with a mean age of 59.78±15.77 years met the inclusion criteria of this investigation. These patients were compared to a total of 20 (46.51% [35% female], 95% confidence interval, 31.6–61.42 patients with a mean age of 58.9±13.36 years with CAP who were infested with S. pneumoniae. In the latter group, the streptococcal antigen was detected in pulmonary aspirations by bronchoscopy or in urine using polymerase chain reaction and a rapid pneumococcal test. Penicillin G and vancomycin had a high rate of sensitivity on the antibiogram for S. pneumoniae, which was

  1. Hospital-Acquired Methicillin-resistant Staphylococcus aureus Bacteremia Related to Medicare Antibiotic Prescriptions: A State-Level Analysis.

    Science.gov (United States)

    Fukunaga, Bryce T; Sumida, Wesley K; Taira, Deborah A; Davis, James W; Seto, Todd B

    2016-10-01

    Methicillin-resistant Staphylococcus aureus (MRSA) results in almost half of all deaths caused by antibiotic resistant organisms. Current evidence suggests that MRSA infections are associated with antibiotic use. This study examined state-level data to determine whether outpatient antibiotic use was associated with hospital-acquired MRSA (HA-MRSA) infections. The 2013 Centers for Disease Control and Prevention (CDC) Healthcare-Associated Infections Progress Report was used to obtain HA-MRSA infection rates. Data on the number of antibiotic prescriptions with activity towards methicillin-sensitive Staphylococcus aureus (MSSA) at the state level were obtained from the 2013 Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use File. Pearson's correlation coefficient was used to analyze the relationship between the number of antibiotic prescriptions and HA-MRSA infection rates. The average number of HA-MRSA infections was 0.026 per 1000 persons with the highest rates concentrated in Southeastern and Northeastern states. The average number of outpatient prescriptions per capita was 0.74 with the highest rates in Southeastern states. A significant correlation (ρ = 0.64, P resistance.

  2. Effect of nutritional rehabilitation on acquired growth hormone resistance in malnourished children using radioisotopic technique

    International Nuclear Information System (INIS)

    El-Nabarawy, F.S.; Nour Eldin, A.M.

    2003-01-01

    The present study was undertaken to clarify the influence of nutrition on growth hormone resistance in children who were suffering from prologed protein energy malnutrition (PEM). The plasma levels of glucose and serum levels of insulin, free triiodothyronine (FT 3 ), free teraiodothyronine (FT 4 ), thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin like growth factor binding protein-3 (IGFBP-3) were analyzed by radioisotopic techniques in 7 children with marasmus (mean age 5.29 1.01) and 14 children with unexplained short stature (stunted) (mean age 6.21 1.72) before and after nutritional rehabilitation. At the basal condition of laboratory investigations, the GH level was significantly higher in the two malnourished groups compared to control (P< 0.01), whereas, plasma glucose levels and insulin concentrations did not differ significantly between the two malnourished groups and the control

  3. How active resisters and organizational constipators affect health care-acquired infection prevention efforts.

    Science.gov (United States)

    Saint, Sanjay; Kowalski, Christine P; Banaszak-Holl, Jane; Forman, Jane; Damschroder, Laura; Krein, Sarah L

    2009-05-01

    As of October 2008, hospitals in the United States no longer receive Medicare reimbursement for certain types of health care-associated infection (HAI), thereby heightening the need for effective prevention efforts. The mere existence of evidence-based practices, however, does not always result in the use of such practices because of the complexities inherent in translating evidence into practice. A qualitative study was conducted to determine the barriers to implementing evidence-based practices to prevent HAI, with a specific focus on the role played by hospital personnel. In-depth phone and in-person interviews were conducted between October 2006 and September 2007 with 86 participants (31 physicians) including chief executive officers, chiefs of staff, hospital epidemiologists, infection control professionals, intensive care unit directors, nurse managers, and frontline physicians and nurses, in 14 hospitals. Active resistance to evidence-based practice change was pervasive. Successful efforts to overcome active resisters included benchmarking infection rates, identifying effective champions, and participating in collaborative efforts. Organizational constipators-mid- to high-level executives who act as insidious barriers to change-also increased the difficulty in implementing change. Recognizing the presence of constipators is often the first step in addressing the problem but can be followed with including the organizational constipator early in group discussions to improve communication and obtain buy-in, working around the individual, and terminating the constipator's employment. Two types of personnel-active resistors and organizational constipators-impeded HAI prevention activities, and several approaches were used to overcome those barriers. Hospital administrators and patient safety leaders can use the findings to more successfully structure activities that prevent HAI in their hospitals.

  4. Molecular characterization of acquired enrofloxacin resistance in Mycoplasma synoviae field isolates.

    Science.gov (United States)

    Lysnyansky, I; Gerchman, I; Mikula, I; Gobbo, F; Catania, S; Levisohn, S

    2013-07-01

    The in vitro activity of enrofloxacin against 73 Mycoplasma synoviae field strains isolated in Israel and Europe was determined by broth microdilution. Decreased susceptibility to enrofloxacin was identified in 59% of strains, with the MICs ranging from 1 to >16 μg/ml. The estimated MIC50 and MIC90 values for enrofloxacin were 2 and 8 μg/ml, respectively. Moreover, this study showed that 92% of recent Israeli field isolates (2009 to 2011) of M. synoviae have MICs of ≥ 2 μg/ml to enrofloxacin. Comparison of the quinolone resistance-determining regions (QRDRs) in M. synoviae isolates revealed a clear correlation between the presence of one of the amino acid substitutions Asp79-Asn, Thr80-Ala/Ile, Ser81-Pro, and Asp84-Asn/Tyr/His of the ParC QRDR and decreased susceptibility to enrofloxacin (MIC, ≥ 1 μg/ml). Amino acid substitutions at positions GyrA 87, GyrB 401/402, and ParE 420/454 were also identified, but there was no clear-cut correlation with susceptibility to enrofloxacin. Comparison of vlhA molecular profiles revealed the presence of 9 different genotypes in the Israeli M. synoviae field isolates and 10 genotypes in the European isolates; only one vlhA genotype (type 4) was identified in both cohorts. Based on results of vlhA molecular typing, several mechanisms for emergence and dissemination of Israeli enrofloxacin-resistant M. synoviae isolates are suggested.

  5. Stethoscopes as a source of hospital-acquired methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Russell, Abigail; Secrest, Janet; Schreeder, Carolyn

    2012-04-01

    Stethoscopes are potential vectors of methicillin-resistant Staphylococcus aureus (MRSA). The purpose of this project was to determine the presence of MRSA on the diaphragms of personal and unit stethoscopes within a hospital setting before and after cleaning with alcohol prep pads. The sample consisted of 141 personal and unit stethoscopes in adult medical-surgical and intensive care units of a large university hospital in the Southeast. Each stethoscope was cultured once before cleaning and once after cleaning. Cultures were obtained using sterile swabs and inoculated on a selective medium for MRSA. Bacterial growth was noted in the precleaning group, but no MRSA colonies were detected. The postcleaning group had no bacterial growth. There was not enough data to statistically support that isopropyl alcohol is effective in decreasing bacterial counts; however, these findings suggest that current disinfection guidelines are effective in preventing MRSA colonization on stethoscopes in this setting. Copyright © 2012 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  6. Update on the prevention and control of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA).

    Science.gov (United States)

    Skov, Robert; Christiansen, Keryn; Dancer, Stephanie J; Daum, Robert S; Dryden, Matthew; Huang, Yhu-Chering; Lowy, Franklin D

    2012-03-01

    The rapid dissemination of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) since the early 2000s and the appearance of new successful lineages is a matter of concern. The burden of these infections varies widely between different groups of individuals and in different regions of the world. Estimating the total burden of disease is therefore problematic. Skin and soft-tissue infections, often in otherwise healthy young individuals, are the most common clinical manifestation of these infections. The antibiotic susceptibilities of these strains also vary, although they are often more susceptible to 'traditional' antibiotics than related hospital-acquired strains. Preventing the dissemination of these organisms throughout the general population requires a multifaceted approach, including screening and decolonisation, general hygiene and cleaning measures, antibiotic stewardship programmes and, in the future, vaccination. The current evidence on the prevention and control of CA-MRSA is appraised and summarised in this review. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  7. Hand hygiene noncompliance and the cost of hospital-acquired methicillin-resistant Staphylococcus aureus infection.

    Science.gov (United States)

    Cummings, Keith L; Anderson, Deverick J; Kaye, Keith S

    2010-04-01

    Hand hygiene noncompliance is a major cause of nosocomial infection. Nosocomial infection cost data exist, but the effect of hand hygiene noncompliance is unknown. To estimate methicillin-resistant Staphylococcus aureus (MRSA)-related cost of an incident of hand hygiene noncompliance by a healthcare worker during patient care. Two models were created to simulate sequential patient contacts by a hand hygiene-noncompliant healthcare worker. Model 1 involved encounters with patients of unknown MRSA status. Model 2 involved an encounter with an MRSA-colonized patient followed by an encounter with a patient of unknown MRSA status. The probability of new MRSA infection for the second patient was calculated using published data. A simulation of 1 million noncompliant events was performed. Total costs of resulting infections were aggregated and amortized over all events. Duke University Medical Center, a 750-bed tertiary medical center in Durham, North Carolina. Model 1 was associated with 42 MRSA infections (infection rate, 0.0042%). Mean infection cost was $47,092 (95% confidence interval [CI], $26,040-$68,146); mean cost per noncompliant event was $1.98 (95% CI, $0.91-$3.04). Model 2 was associated with 980 MRSA infections (0.098%). Mean infection cost was $53,598 (95% CI, $50,098-$57,097); mean cost per noncompliant event was $52.53 (95% CI, $47.73-$57.32). A 200-bed hospital incurs $1,779,283 in annual MRSA infection-related expenses attributable to hand hygiene noncompliance. A 1.0% increase in hand hygiene compliance resulted in annual savings of $39,650 to a 200-bed hospital. Hand hygiene noncompliance is associated with significant attributable hospital costs. Minimal improvements in compliance lead to substantial savings.

  8. Community-acquired pneumonia in older patients: does age influence systemic cytokine levels in community-acquired pneumonia?

    LENUS (Irish Health Repository)

    Kelly, Emer

    2009-03-01

    Community-acquired pneumonia (CAP) is a major cause of death in the elderly. The age-related increase in comorbid illnesses plays a part but the effect of aging on the immune response may be equally important. We aimed to evaluate patients with CAP for evidence of a muted response to infection in elderly patients admitted to hospital compared with a younger patient group.

  9. When Unbiased Probabilistic Learning Is Not Enough: Acquiring a Parametric System of Metrical Phonology

    Science.gov (United States)

    Pearl, Lisa S.

    2011-01-01

    Parametric systems have been proposed as models of how humans represent knowledge about language, motivated in part as a way to explain children's rapid acquisition of linguistic knowledge. Given this, it seems reasonable to examine if children with knowledge of parameters could in fact acquire the adult system from the data available to them.…

  10. 12 CFR 617.7620 - What should the System institution do when it decides to sell acquired agricultural real estate...

    Science.gov (United States)

    2010-01-01

    ... decides to sell acquired agricultural real estate at a public auction? 617.7620 Section 617.7620 Banks and... What should the System institution do when it decides to sell acquired agricultural real estate at a public auction? System institutions electing to sell or lease acquired agricultural real estate or a...

  11. Toxic shock syndrome due to community-acquired methicillin-resistant Staphylococcus aureus infection: Two case reports and a literature review in Japan.

    Science.gov (United States)

    Sada, Ryuichi; Fukuda, Saori; Ishimaru, Hiroyasu

    2017-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus has been spreading worldwide, including in Japan. However, few cases of toxic shock syndrome caused by Community-acquired methicillin-resistant Staphylococcus aureus have been reported in Japan. We report 2 cases, in middle-aged women, of toxic shock syndrome due to Community-acquired methicillin-resistant Staphylococcus aureus via a vaginal portal of entry. The first patient had used a tampon and the second patient had vaginitis due to a cleft narrowing associated with vulvar lichen sclerosus. Both patients were admitted to our hospital with septic shock and severe acute kidney injury and subsequently recovered with appropriate antibiotic treatment. In our review of the literature, 8 cases of toxic shock syndrome caused by Community-acquired methicillin-resistant Staphylococcus aureus were reported in Japan. In these 8 cases, the main portals of entry were the skin and respiratory tract; however, the portal of entry of Community-acquired methicillin-resistant Staphylococcus aureus from a vaginal lesion has not been reported in Japan previously.

  12. HOW ROMANIAN FINANCIAL AND INTERNAL AUDITORS ACQUIRE ACCOUNTING INFORMATION SYSTEMS KNOWLEDGE AND COMPETENCES?

    Directory of Open Access Journals (Sweden)

    Cardos Vasile - Daniel

    2011-07-01

    Full Text Available Research theme in this article we investigate how Romanian financial and internal auditors acquire accounting information systems knowledge and competences and how they use this knowledge to improve their activity in order to fulfill their mission as required by the professional standards. Objectives our main purpose is to establish through what type of courses Romanian financial and internal auditors acquiring accounting information systems knowledge and competences and how useful these courses are perceived by the auditors. Prior work audit professional organizations prescribed that auditors must acquire, maintain and develop their knowledge and competences. Information technology and information systems are considered to be a main knowledge component of professional development programs. The scientific literature indicates that auditors have to enhance their information systems knowledge in order to cope with the increasing complexity of the client's entities accounting information systems. We consider that our article embraces Curtis et al. (2009 call for research on how auditors obtain information systems knowledge. Methodology an electronic questionnaire was created and sent to Romanian financial and internal auditors, which were required to indicate the number of accounting information systems course they attended and how the knowledge gained improved their activity. Results We concluded that financial auditors acquire accounting information systems knowledge mainly by attending the courses organized by the Chamber of Financial Auditors of Romanian, while internal auditors by attending the course organized by the companies they are working with. Implications - The results of this study might be used by Romanian professional audit organizations in reconsidering their priorities regarding the accounting information systems knowledge and competence needs of their constituents. Originality/Contribution Our study is the first one to

  13. High Prevalence of Multidrug-Resistant Community-Acquired Methicillin-Resistant Staphylococcus aureus at the Largest Veterinary Teaching Hospital in Costa Rica.

    Science.gov (United States)

    Rojas, Irene; Barquero-Calvo, Elías; van Balen, Joany C; Rojas, Norman; Muñoz-Vargas, Lohendy; Hoet, Armando E

    2017-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen associated with severe infections in companion animals present in the community, and it is diagnosed in animals admitted to veterinary hospitals. However, reports that describe the circulation of MRSA in animal populations and veterinary settings in Latin America are scarce. Therefore, the objective of this study was to determine the prevalence and investigate the molecular epidemiology of MRSA in the environment of the largest veterinary teaching hospital in Costa Rica. Preselected contact surfaces were sampled twice within a 6-week period. Antimicrobial resistance, SCCmec type, Panton-Valentine leukocidin screening, USA type, and clonality were assessed in all recovered isolates. Overall, MRSA was isolated from 26.5% (27/102) of the surfaces sampled, with doors, desks, and examination tables most frequently contaminated. Molecular analysis demonstrated a variety of surfaces from different sections of the hospital contaminated by three highly related clones/pulsotypes. All, but one of the isolates were characterized as multidrug-resistant SCCmec type IV-USA700, a strain sporadically described in other countries and often classified as community acquired. The detection and frequency of this unique strain in this veterinary setting suggest Costa Rica has a distinctive MRSA ecology when compared with other countries/regions. The high level of environmental contamination highlights the necessity to establish and enforce standard cleaning and disinfection protocols to minimize further spread of this pathogen and reduce the risk of nosocomial and/or occupational transmission of MRSA.

  14. Detection of T790M, the acquired resistance EGFR mutation, by tumor biopsy versus noninvasive blood-based analyses

    Science.gov (United States)

    Sundaresan, Tilak K.; Sequist, Lecia V.; Heymach, John V.; Riely, Gregory J.; Jänne, Pasi A.; Koch, Walter H.; Sullivan, James P.; Fox, Douglas B.; Maher, Robert; Muzikansky, Alona; Webb, Andrew; Tran, Hai T.; Giri, Uma; Fleisher, Martin; Yu, Helena A.; Wei, Wen; Johnson, Bruce E.; Barber, Thomas A.; Walsh, John R.; Engelman, Jeffrey A.; Stott, Shannon L.; Kapur, Ravi; Maheswaran, Shyamala; Toner, Mehmet

    2015-01-01

    Purpose The T790M gatekeeper mutation in the Epidermal Growth Factor Receptor (EGFR) is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKIs). As third generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management. Experimental Design As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Results T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47–50% of patients using each of the genotyping assays, with concordance among them ranging from 57–74%. While CTC- and ctDNA-based genotyping were each unsuccessful in 20–30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate. Conclusion Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient’s cancer, which should be validated in predicting response to T790M-targeted inhibitors. PMID:26446944

  15. Automated surveillance system for hospital-acquired urinary tract infections in Denmark

    DEFF Research Database (Denmark)

    Condell, Orla; Gubbels, Sophie; Nielsen, J

    2016-01-01

    BACKGROUND: The Danish Hospital-Acquired Infections Database (HAIBA) is an automated surveillance system using hospital administrative, microbiological, and antibiotic medication data. AIM: To define and evaluate the case definition for hospital-acquired urinary tract infection (HA-UTI) and to de......BACKGROUND: The Danish Hospital-Acquired Infections Database (HAIBA) is an automated surveillance system using hospital administrative, microbiological, and antibiotic medication data. AIM: To define and evaluate the case definition for hospital-acquired urinary tract infection (HA-UTI......) and to describe surveillance data from 2010 to 2014. METHODS: The HA-UTI algorithm defined a laboratory-diagnosed UTI as a urine culture positive for no more than two micro-organisms with at least one at ≥10(4)cfu/mL, and a probable UTI as a negative urine culture and a relevant diagnosis code or antibiotic...... treatment. UTI was considered hospital-acquired if a urine sample was collected ≥48h after admission and UTI was calculated per 10,000 risk-days. For validation, prevalence was calculated for each day and compared to point prevalence survey (PPS) data. FINDINGS: HAIBA...

  16. Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tyler, Andreas, E-mail: andreas.tyler@medbio.umu.se [Department of Medical Biosciences, Umeå University, S-901 85 Umea (Sweden); Johansson, Anders [Department of Odontology, Umeå University, S-901 85 Umea (Sweden); Karlsson, Terese [Department of Radiation Sciences, Oncology, S-901 85 Umea (Sweden); Gudey, Shyam Kumar; Brännström, Thomas; Grankvist, Kjell; Behnam-Motlagh, Parviz [Department of Medical Biosciences, Umeå University, S-901 85 Umea (Sweden)

    2015-08-01

    Background: Acquired resistance to cisplatin treatment is a caveat when treating patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. However, a tumour stress activation of glucosylceramide synthase (GCS) follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1. Ceramide elimination enhances cell proliferation and apoptosis blockade, thus stimulating tumor progression. GSLs transactivate multidrug resistance 1/P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1) expression which further prevents ceramide accumulation and stimulates drug efflux. We investigated the expression of Gb3, MDR1 and MRP1 in NSCLC and MPM cells with acquired cisplatin resistance, and if GCS activity or MDR1 pump inhibitors would reduce their expression and reverse cisplatin-resistance. Methods: Cell surface expression of Gb3, MDR1 and MRP1 and intracellular expression of MDR1 and MRP1 was analyzed by flow cytometry and confocal microscopy on P31 MPM and H1299 NSCLC cells and subline cells with acquired cisplatin resistance. The effect of GCS inhibitor PPMP and MDR1 pump inhibitor cyclosporin A for 72 h on expression and cisplatin cytotoxicity was tested. Results: The cisplatin-resistant cells expressed increased cell surface Gb3. Cell surface Gb3 expression of resistant cells was annihilated by PPMP whereas cyclosporin A decreased Gb3 and MDR1 expression in H1299 cells. No decrease of MDR1 by PPMP was noted in using flow cytometry, whereas a decrease of MDR1 in H1299 and H1299res was indicated with confocal microscopy. No certain co-localization of Gb3 and MDR1 was noted. PPMP, but not cyclosporin A, potentiated cisplatin cytotoxicity in all cells. Conclusions: Cell surface Gb3 expression is a likely tumour biomarker for acquired cisplatin

  17. The burden and epidemiology of community-acquired central nervous system infections

    DEFF Research Database (Denmark)

    Erdem, H; Inan, A; Guven, E

    2017-01-01

    Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012...

  18. Community-acquired necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus ST30-SCCmecIVc-spat019-PVL positive in San Antonio de Areco, Argentina

    Directory of Open Access Journals (Sweden)

    Silvina Fernández

    2015-03-01

    Full Text Available Community-acquired methicillin-resistant Staphylococcus aureus is the first cause of skin and soft tissue infections, but can also produce severe diseases such as bacteremia, osteomyelitis and necrotizing pneumonia. Some S. aureus lineages have been described in cases of necrotizing pneumonia worldwide, usually in young, previously healthy patients. In this work, we describe a fatal case of necrotizing pneumonia due to community-acquired methicillin-resistant S. aureus clone ST30-SCCmecIVc-spat019-PVL positive in an immunocompetent adult patient.

  19. Community-acquired necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus ST30-SCCmecIVc-spat019-PVL positive in San Antonio de Areco, Argentina.

    Science.gov (United States)

    Fernandez, Silvina; Murzicato, Sofía; Sandoval, Orlando; Fernández-Canigia, Liliana; Mollerach, Marta

    2015-01-01

    Community-acquired methicillin-resistant Staphylococcus aureus is the first cause of skin and soft tissue infections, but can also produce severe diseases such as bacteremia, osteomyelitis and necrotizing pneumonia. Some S. aureus lineages have been described in cases of necrotizing pneumonia worldwide, usually in young, previously healthy patients. In this work, we describe a fatal case of necrotizing pneumonia due to community-acquired methicillin-resistant S. aureus clone ST30-SCCmecIVc-spat019-PVL positive in an immunocompetent adult patient. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Trend and seasonality of community-acquired Escherichia coli antimicrobial resistance and its dynamic relationship with antimicrobial use assessed by ARIMA models.

    Science.gov (United States)

    Asencio Egea, María Ángeles; Huertas Vaquero, María; Carranza González, Rafael; Herráez Carrera, Óscar; Redondo González, Olga; Arias Arias, Ángel

    2017-12-04

    We studied the trend and seasonality of community-acquired Escherichia coli resistance and quantified its correlation with the previous use of certain antibiotics. A time series study of resistant community-acquired E. coli isolates and their association with antibiotic use was conducted in a Primary Health Care Area from 2008 to 2012. A Poisson regression model was constructed to estimate the trend and seasonality of E. coli resistance. A significant increasing trend in mean E. coli resistance to cephalosporins, aminoglycosides and nitrofurantoin was observed. Seasonal resistance to ciprofloxacin and amoxicillin-clavulanic acid was significantly higher in autumn-winter. There was a delay of 7, 10 and 12 months between the use of cotrimoxazole (P<0.038), fosfomycin (P<0.024) and amoxicillin-clavulanic acid (P<0.015), respectively, and the occurrence of E. coli resistance. An average delay of 10 months between the previous use of amoxicillin-clavulanic acid, cotrimoxazole and fosfomycin and the appearance of resistant community-acquired E. coli strains was detected. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  1. Comparative genomics of community-acquired ST59 methicillin-resistant Staphylococcus aureus in Taiwan: novel mobile resistance structures with IS1216V.

    Directory of Open Access Journals (Sweden)

    Wei-Chun Hung

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA with ST59/SCCmecV and Panton-Valentine leukocidin gene is a major community-acquired MRSA (CA-MRSA lineage in Taiwan and has been multidrug-resistant since its initial isolation. In this study, we studied the acquisition mechanism of multidrug resistance in an ST59 CA-MRSA strain (PM1 by comparative genomics. PM1's non-β-lactam resistance was encoded by two unique genetic traits. One was a 21,832-bp composite mobile element structure (MES(PM1, which was flanked by direct repeats of enterococcal IS1216V and was inserted into the chromosomal sasK gene; the target sequence (att was 8 bp long and was duplicated at both ends of MES(PM1. MES(PM1 consisted of two regions: the 5'-end side 12.4-kb region carrying Tn551 (with ermB and Tn5405-like (with aph[3']-IIIa and aadE, similar to an Enterococcus faecalis plasmid, and the 3'-end side 6,587-bp region (MES(cat that carries cat and is flanked by inverted repeats of IS1216V. MES(cat possessed att duplication at both ends and additional two copies of IS1216V inside. MES(PM1 represents the first enterococcal IS1216V-mediated composite transposon emerged in MRSA. IS1216V-mediated deletion likely occurred in IS1216V-rich MES(PM1, resulting in distinct resistance patterns in PM1-derivative strains. Another structure was a 6,025-bp tet-carrying element (MES(tet on a 25,961-bp novel mosaic penicillinase plasmid (pPM1; MES(tet was flanked by direct repeats of IS431, but with no target sequence repeats. Moreover, the PM1 genome was deficient in a copy of the restriction and modification genes (hsdM and hsdS, which might have contributed to the acquisition of enterococcal multidrug resistance.

  2. 12 CFR 617.7610 - What should the System institution do when it decides to sell acquired agricultural real estate?

    Science.gov (United States)

    2010-01-01

    ... decides to sell acquired agricultural real estate? 617.7610 Section 617.7610 Banks and Banking FARM CREDIT... institution do when it decides to sell acquired agricultural real estate? (a) Notify the previous owner, (1) Within 15 days of the System institution's decision to sell acquired agricultural real estate, it must...

  3. Bacteriology of hospital-acquired infection and antibiotic resistance in a hospital university of Bushehr Port Fatemeh Zahra (s in 2002-2003

    Directory of Open Access Journals (Sweden)

    Katayoon Vahdat

    2005-02-01

    Full Text Available Nosocomial infection is an increasing problem. The global problem of antimicrobial resistance is particularly pressing in developing countries, where the infectious disease burden is high and cost constraints prevent the widespread application of newer, more expensive agents. In a prospective study, 203 consecutive cases with hospital-acquired infection in a university hospital in Bushehr port were evaluated. The most common hospital-acquired infection was urinary (76 cases, conjunctivitis (16 cases, bacteremia (8 cases, meningitis (5 cases, wound (3 cases, empyema (2 cases and peritonitis (1 case. The patients with hospital-acquired infection were from surgical and internal medicine I.C.Us (53.2% & 15.6%, respectively. The most frequent isolated organisms were Pseudomonas aeruginosa (25.6%, Acinetobacter baumannii (19.7%, E. coli (13.3%, Klebsiella pneumoniae (11.3%, Staphylococcus aureus (8.4%, Staphylococcus epidermidis (7.9%, Enterobacter species (7%, Streptococcus species (6.4%, and Proteus mirabilis (0.5%. The most resistant organisms to antimicrobial agents were Acinetobacter baumannii and Pseudomonas aeruginosa 97 & 93.3% of these bacteria were resistant to third generation cephalosporins. The isolated Staphylococcal species were resistant to amikacin (94%. In conclusion, gram negative bacteria were the most common etiologic agent of hospital-acquired infection and had a high level of resistance to amikacin and third generation cephalosporins. Therefore, new therapeutic strategies should be designed to combat these microorganisms.

  4. Efficacy of a hospital-wide environmental cleaning protocol on hospital-acquired methicillin-resistant Staphylococcus aureus rates.

    Science.gov (United States)

    Watson, Paul Andrew; Watson, Luke Robert; Torress-Cook, Alfonso

    2016-07-01

    Environmental contamination has been associated with over half of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in hospitals. We explored if a hospital-wide environmental and patient cleaning protocol would lower hospital acquired MRSA rates and associated costs. This study evaluates the impact of implementing a hospital-wide environmental and patient cleaning protocol on the rate of MRSA infection and the potential cost benefit of the intervention. A retrospective, pre-post interventional study design was used. The intervention comprised a combination of enhanced environmental cleaning of high touch surfaces, daily washing of patients with benzalkonium chloride, and targeted isolation of patients with active infection. The rate of MRSA infection per 1000 patient days (PD) was compared with the rate after the intervention (Steiros Algorithm ® ) was implemented. A cost-benefit analysis based on the number of MRSA infections avoided was conducted. The MRSA rates decreased by 96% from 3.04 per 1000 PD to 0.11 per 1000 PD ( P reduction in MRSA infections, avoided an estimated $1,655,143 in healthcare costs. Implementation of this hospital-wide protocol appears to be associated with a reduction in the rate of MRSA infection and therefore a reduction in associated healthcare costs.

  5. GLP-1 responses are heritable and blunted in acquired obesity with high liver fat and insulin resistance

    DEFF Research Database (Denmark)

    Matikainen, Niina; Bogl, Leonie H; Hakkarainen, Antti

    2014-01-01

    OBJECTIVE Impaired incretin response represents an early and uniform defect in type 2 diabetes, but the contributions of genes and the environment are poorly characterized. RESEARCH DESIGN AND METHODS We studied 35 monozygotic (MZ) and 75 dizygotic (DZ) twin pairs (discordant and concordant for o...... Whereas the GLP-1 response to the OGTT is heritable, an acquired unhealthy pattern of obesity characterized by liver fat accumulation and insulin resistance is closely related to impaired GLP-1 response in young adults....... under the curve was 67% (95% CI 45-80). Cotwins from weight-concordant MZ and DZ pairs and weight-discordant MZ pairs but concordant for liver fat content demonstrated similar glucose, insulin, and incretin profiles after the OGTT and meal tests. In contrast, higher insulin responses and blunted 60-min...... GLP-1 responses during the OGTT were observed in the heavier as compared with leaner MZ cotwins discordant for BMI, liver fat, and insulin sensitivity. Blunted GLP-1 response to OGTT was observed in heavier as compared with leaner DZ cotwins discordant for obesity and insulin sensitivity. CONCLUSIONS...

  6. Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in critically-ill patients: systematic review

    Directory of Open Access Journals (Sweden)

    Nuria Carballo

    2017-03-01

    Full Text Available Introduction: Community-acquired pneumonia (CAP is associated with high morbidity and mortality rates. Despite methicillin-resistant Staphylococcus aureus (MRSA having often been associated with nosocomial pneumonia, the condition of some MRSA CAP patients is severe enough to warrant their being admitted to ICU. Objective: The purpose of this study is to conduct a systematic review of the literature on antibiotic treatment of MRSA CAP in critically-ill patients. Material and methods: An online search was conducted for locating articles on MRSA CAP in critically ill patients. Relevant publications were identified in PUBMED, the BestPractice database, UpToDate database and the Cochrane Library for articles published in English within the December 2001 - April 2016 time frame. Results: A total of 70 articles were found to have been published, 13 (18.8% having been included and 57 (81.4% excluded. Cohort studies were predominant, having totaled 16 in number (20.7% as compared to one sole cross-sectional study (3.5%. Conclusions: The experience in the treatment of MRSA CAP in patients requiring admission to ICU is quite limited. Vancomycin or linezolid seem to be the treatments of choice for MRSA CAP, although there not be any specific recommendation in this regard. It may be useful to use alternative routes, such as administration via aerosolized antibiotics, continuous infusion or in association with other antibiotics.

  7. Radiological findings of community-acquired methicillin-resistant and methicillin-susceptible staphylococcus aureus pediatric pneumonia in Hawaii

    International Nuclear Information System (INIS)

    Erdem, Guliz; Bergert, Lora; Len, Kyra; Melish, Marian; Kon, Kevin; DiMauro, Robert

    2010-01-01

    Community-acquired Staphylococcus aureus (CA-SA) infections are common among pediatric patients in Hawaii. We wanted to characterize the radiological features of methicillin-susceptible (CA-MSSA) and methicillin-resistant (CA-MRSA) staphylococcal pneumonia in Hawaiian children. We retrospectively reviewed medical records and imaging studies of children with SA pneumonia identified from 1996 through 2007. Of 40 children, 26 (65%) had CA-MRSA pneumonia and 14 patients (35%) had CA-MSSA pneumonia. CA-MRSA patients were significantly younger than CA-MSSA patients (65% younger than 1 year vs. 36% older). In a majority (62%) of CA-MRSA patients, the consolidation was unilateral; in most of the CA-MSSA cases (79%), the consolidation was bilateral. Fifty percent of the patients with CA-MRSA and 21% of those with CA-MSSA had pneumatoceles (P = 0.1). CA-MRSA patients more commonly had pleural effusions (85% vs. 64% for CA-MSSA) and pleural thickening (50% vs. 36% for CA-MSSA). This case series describes the radiologic characteristics of CA-MRSA and CA-MSSA pneumonia in children in a highly endemic area. We found that CA-MRSA pneumonias are unilateral in a majority of pediatric pneumonia cases, are more common in children 1 year or younger, and have higher rates of complications in comparison to CA-MSSA patients. (orig.)

  8. The Impact of a Universal Decolonization Protocol on Hospital-Acquired Methicillin-Resistant Staphylococcus aureus in a Burn Population.

    Science.gov (United States)

    Johnson, Arthur T; Nygaard, Rachel M; Cohen, Ellie M; Fey, Ryan M; Wagner, Anne Lambert

    Hospital-acquired (HA) methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of HA infections and a significant concern for burn centers. The use of 2% chlorhexidine-impregnated wipes and nasal mupirocin significantly decreases the rate of HA-MRSA in adult intensive care units. The aim of this study was to examine the impact of universal decolonization on the rate of MRSA conversion in an American Burn Association verified adult and pediatric burn center. Universal decolonization protocol consisting of daily chlorhexidine baths and a 5-day course of nasal mupirocin was implemented in the burn unit. MRSA screening both on admission and weekly and contact isolation practices were in place in pre-decolonization and post-decolonization periods. Patient data were analyzed 2 years before and 1 year after implementation of the protocol. The incidence rate of MRSA was significantly decreased after the implementation of the decolonization protocol (11.8 vs 1.0 per 1000 patient days, P burn patients are at greater risk for invasive infection leading to severe complications and death. The prevalence of HA-MRSA at our institution's burn center was significantly decreased after the implementation of a universal decolonization protocol.

  9. Radiological findings of community-acquired methicillin-resistant and methicillin-susceptible staphylococcus aureus pediatric pneumonia in Hawaii

    Energy Technology Data Exchange (ETDEWEB)

    Erdem, Guliz; Bergert, Lora; Len, Kyra; Melish, Marian [University of Hawaii, John A. Burns School of Medicine, Department of Pediatrics, Honolulu, HI (United States); Kon, Kevin; DiMauro, Robert [Kapiolani Medical Center for Women and Children, Department of Radiology, Honolulu, HI (United States)

    2010-11-15

    Community-acquired Staphylococcus aureus (CA-SA) infections are common among pediatric patients in Hawaii. We wanted to characterize the radiological features of methicillin-susceptible (CA-MSSA) and methicillin-resistant (CA-MRSA) staphylococcal pneumonia in Hawaiian children. We retrospectively reviewed medical records and imaging studies of children with SA pneumonia identified from 1996 through 2007. Of 40 children, 26 (65%) had CA-MRSA pneumonia and 14 patients (35%) had CA-MSSA pneumonia. CA-MRSA patients were significantly younger than CA-MSSA patients (65% younger than 1 year vs. 36% older). In a majority (62%) of CA-MRSA patients, the consolidation was unilateral; in most of the CA-MSSA cases (79%), the consolidation was bilateral. Fifty percent of the patients with CA-MRSA and 21% of those with CA-MSSA had pneumatoceles (P = 0.1). CA-MRSA patients more commonly had pleural effusions (85% vs. 64% for CA-MSSA) and pleural thickening (50% vs. 36% for CA-MSSA). This case series describes the radiologic characteristics of CA-MRSA and CA-MSSA pneumonia in children in a highly endemic area. We found that CA-MRSA pneumonias are unilateral in a majority of pediatric pneumonia cases, are more common in children 1 year or younger, and have higher rates of complications in comparison to CA-MSSA patients. (orig.)

  10. Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells.

    Science.gov (United States)

    Liu, Xin; Ban, Li-Li; Luo, Gang; Li, Zhi-Yao; Li, Yun-Feng; Zhou, Yong-Chun; Wang, Xi-Cai; Jin, Cong-Guo; Ye, Jia-Gui; Ma, Ding-Ding; Xie, Qing; Huang, You-Guang

    2016-06-01

    Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial-mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and β-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG-resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and β-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in

  11. [Systemic lupus erythematosus masking the acquired immunodeficiency syndrome. A report on four cases].

    Science.gov (United States)

    Kotyla, Przemysław; Kucharz, Eugeniusz J

    2012-01-01

    Systemic lupus erythematosus (SLE) is a systemic inflammatory disease of connective tissue with an unknown etiology and a rich clinical picture with involvement of multiple organs. Given the rich symptomatology, application of the current classification criteria is associated with a significant risk of attributing symptoms of other pathologies to lupus and/or other connective tissue disease. Inherited and acquired immune deficiencies may sometimes demonstrate a lupus-like clinical symptomatology. In this work we reviewed 4 of cases referred to the Department of Internal Diseases and Rheumatology of the Silesian Medical University in Katowice with suspected or confirmed systemic lupus erythematosus. A positive anti-HIV antibody test led to the diagnosis of the acquired immunodeficiency syndrome (AIDS). Due to the close similarity of the clinical picture and the presence of antinuclear antibodies in both diseases, the authors postulate that the anti-HIV antibody test should be done routinely in patients with connective tissue diseases.

  12. Understanding The Resistance to Health Information Systems

    Directory of Open Access Journals (Sweden)

    David Ackah

    2017-07-01

    Full Text Available User resistance is users’ opposition to system implementation. Resistance often occurs as a result of a mismatch between management goals and employee preferences. There are two types of resistance to health iformation system namely active resistance and passive resistance. The manifestation of active resistance are being critical,  blaming/accusing, blocking, fault finding, sabotaging, undermining, ridiculing, intimidating/threatening, starting rumors, appealing to fear, manipulating arguing, using facts selectively, distorting facts and  raising objections. The manifestation of passive resistance are agreeing verbally but not following through, failing to implement change, procrastinating/dragging feet, feigning ignorance, withholding information, suggestions, help or support, and standing by and allowing the change to fail.

  13. Local cytokine profile and cytological status in children with community-acquired pneumonia arising on the background of the reduced resistance of the organism

    Directory of Open Access Journals (Sweden)

    T. G. Malanicheva

    2017-01-01

    Full Text Available Research objective: to study the features of the cytokine profile and cytological status in children with community-acquired pneumonia, proceeding against a background of reduced resistance of the organism for improving treatment methods. 53 children aged 3 to 7 years were examined. The main group consisted of 30 children with community-acquired pneumonia, which ran against a background of reduced resistance of the body. The comparison group consisted of 23 children with community-acquired pneumonia who had good resistance. Local immunity was studied on the basis of  valuation of cytokine status parameters (tumor necrotic factor-α, interleukin-8, and interferon-γ and cellular composition with an estimate of destructive changes in neutrophils in induced sputum. It was revealed that in the main group of children there is a depression of the neutrophils’ release into the bronchial secretion and a marked increase in the number of neutrophils with maximum signs of destruction of the nucleus and cytoplasm against the background of cytokine status imbalance, manifested in an increase in the content of the tumor necrotic factor-α and a decrease in interleukin-8 and interferon- γ. Inclusion in the traditional therapy of community-acquired pneumonia in children who have a reduced resistance, anti-inflammatory drug fenspiride, eliminates the imbalance of proinflammatory cytokines and increases the release of functionally complete neutrophils in the bronchial secret.

  14. Changing prevalence and antibiotic drug resistance pattern of pathogens seen in community-acquired pediatric urinary tract infections at a tertiary care hospital of North India

    Directory of Open Access Journals (Sweden)

    Vrushali Patwardhan

    2017-01-01

    Conclusion: Although E. coli remains the prime pathogen in pediatric UTI, the prevalence of resistance has dramatically increased over the 5-year study period. Our study highlights the emergence of community-acquired ESBL-producing uropathogens in children proclaiming treatment challenges.

  15. A Case of Acquired Rifampin Resistance in Mycobacterium bovis Bacillus Calmette-Guérin-Induced Cystitis: Necessity for Treatment Guidelines

    Directory of Open Access Journals (Sweden)

    Joyce N Wolfe

    2006-01-01

    Full Text Available A case of presumed bacillus Calmette-Guérin (BCG cystitis in an elderly female patient following direct intravesical BCG instillation treatment for papillary transitional cell carcinoma is reported. The organism cultured from urine samples was eventually identified as a rifampin-resistant Mycobacterium bovis BCG isolate. Because the patient had received rifampin monotherapy during the course of treatment for presumed BCG disease, the clinical picture favoured acquired rifampin resistance. Sequencing of the target gene for rifampin (rpoB confirmed a known mutation responsible for conferring high levels of resistance to both rifampin and rifabutin (Ser531Tyr. To the authors' knowledge, this is the first reported case of M bovis BCG disease in a non-HIV patient where the organism had acquired drug resistance to rifampin, and the second reported case of M bovis BCG that had acquired drug resistance. The present case demonstrates the necessity to re-evaluate appropriate guidelines for the effective treatment of BCG disease.

  16. Speech and language therapists' views about AAC system acceptance by people with acquired communication disorders.

    Science.gov (United States)

    Pampoulou, Eliada

    2018-04-18

    Some adults with acquired communication disorders are faced with an inability to communicate coherently through verbal speech with their communication partners. Despite the fact that a variety of augmentative and alternative communication (AAC) aided systems is available to assist them in communicating, not all adults accept them. In Cyprus, there is scant research focusing on the factors that are linked to AAC system acceptance and abandonment. To address this gap, this research involves exploring the experiences of six speech and language therapists supporting adults with acquired communication disorders, who could benefit from the use of AAC systems. The main research question is: What are the factors that influence AAC system acceptance or abandonment? The method used for data collection, was semi-structured interviews and the transcripts were analyzed thematically. The findings show that a number of factors influence the acceptance of AAC systems. These include the time since onset and acceptance of disability, the person's attitude towards communication facilitators, and the perceptions about AAC systems. These findings indicate that the process of accepting an AAC system is multi-layered and these layers are interrelated. More research is warranted focusing directly on the experiences of people with acquired communication disorders and their communication partners. Implications for Rehabilitation The different myths about AAC systems need to be challenged such that awareness about their usefulness is raised. AAC specialists need to find ways to spread the message that AAC systems can actually support language, speech and communication through different dissemination avenues, such as articles in newspapers and talks through the media.

  17. A Low Cost 3D Acquiring System for Mushroom Robot Based on Webcam and Line Laser

    Directory of Open Access Journals (Sweden)

    Gang Sun

    2014-03-01

    Full Text Available This paper presents a low cost 3D acquiring system for mushroom robot based on webcam and line laser. The system comprises Webcam, semiconductor line laser, motion platform and data process unit. The system can get the 3D information of the Pleurotus eryngii in bottle based on structured light scanning theory. Field test shows the accuracy of the height is less than 2mm and it can be use to locate the buds in the bottle correctly. It has the potention to fulfill the requirement of the location of the mushroom for thinning bud robot.

  18. Identification of Conflicts between Transmission and Distribution System Operators when Acquiring Ancillary Services from Electric Vehicles

    DEFF Research Database (Denmark)

    Zecchino, Antonio; Knezovic, Katarina; Marinelli, Mattia

    2017-01-01

    ancillary services from flexible units. The investigation is carried out considering a 3-area power system which allows to take into account local constraints as well as system-wide needs. As outcome, this paper identifies the conflicts from both a theoretical and a practical point of view, by means...... products according to requests coming from both distribution and transmission system operators. The goal of this paper is to provide an identification procedure that is able to detect, identify and catalogue possible conflicts among the involved stakeholders that take place when requesting and/or acquiring...

  19. Transformation of sweet orange [Citrus sinensis (L.) Osbeck] with pthA-nls for acquiring resistance to citrus canker disease.

    Science.gov (United States)

    Yang, Li; Hu, Chunhua; Li, Na; Zhang, Jiayin; Yan, Jiawen; Deng, Ziniu

    2011-01-01

    The COOH terminal of pthA encoding three nuclear localizing signals (NLS) was amplified by polymerase chain reaction (PCR) from the plasmid of Xanthomonas axonopodis pv. citri, the pathogen of citrus canker disease. Then the sense and antisense strands of the nls were cloned into pBI121 vector. pthA-nls driven by the CaMV35 s promoter was transferred into sweet orange via Agrobacterium -mediated transformation. Successful integration was confirmed by PCR and Southern blotting, and 12 sense-nls (nls (+)) and 9 antisense-nls (nls (-)) transgenic clones were obtained. The expression of nls fragment was analyzed by RT-PCR, Real time q-PCR and Western blotting, in which the specific NLS protein was detected only in nls (+) transgenic clones. In an in vitro assay, when pin-puncture inoculation was performed with 2.5 × 10(7) cfu/ml of bacterial solution, the nls (+) transgenic clones showed no typical lesion development, while typical symptoms were observed in the wild types and the nls (-) transgenic clones. In vivo assay results indicated that the nls (+) transgenic clones showed less disease incidence, in comparison with the wild types and the nls (-) transgenic clones, when pin-puncture inoculation was performed with 10(4)-10(5) cfu/ml. The minimum disease incidence was 23.3% for 'Sucarri' sweet orange and 33.3% for 'Bingtang' sweet orange. When 10(4)-10(7) cfu/ml of pathogen was spray inoculated, the nls (+) transgenic clones did not show any symptom, and even the concentration raised to 10(9) cfu/ml, the disease incidence was 20-80%, while the wild types and the nls (-) transgenic clones had 100% disease development with whatever concentration of inoculum. Two transgenic clones were confirmed to be resistant to citrus canker disease in the repeated inoculation. The results suggested that the transformation of nls sense strands may offer an effective way to acquire resistance to citrus canker disease.

  20. Frequency of escherichia coli in patients with community acquired urinary tract infection and their resistance pattern against some commonly used anti bacterials

    International Nuclear Information System (INIS)

    Ahmad, W.; Jamshed, F.; Ahmad, W.

    2015-01-01

    Urinary tract infection (UTI) is a very common health problem and Escherichia coli (E coli) are the most common organisms associated with community acquired UTI. Unfortunately these bacteria have developed extensive resistance against most of the commonly used anti-bacterials. The objective of this study was to determine the frequency and resistance pattern of E coli in patients of community acquired UTI in an area in northern part of Pakistan. Methods: Urine specimens were collected from patients who were clinically diagnosed as community acquired UTI. Urine routine examination (Urine RE) was done and samples positive for UTI (Pus cells >10/High Power Field) were included in the study. These samples were inoculated on Eosin Methylene Blue (EMB) agar plates and incubated at 37 degree C for 36 hours. Suspected colonies were then inoculated further on EMB plates for pure cultures of E coli characterized by certain morphological characteristics. IMViC was applied for the confirmation of E coli. In vitro antibiotic susceptibility tests of E coli were performed with standardized commercial susceptibility discs (OXOID). Results: Out of 50 specimens, positive for UTI by urine RE, 20 showed pure growth of E coli on culture (40%). The majority of the isolates (28%; n=14) were from women while only 12% (n=6) were from men. Escherichia coli showed a high rate of resistance towards Ampicillin (90%), Tetracycline (70%), Erythromycin (70%) and Trimethoprim-Sulfamethoxazole (55%). Sparfloxacin showed better results (45%) than ciprofloxacin (50%). Out of 20 E coli isolates, two (10%) were resistant to all the antibacterials except chloramphenicol, eight isolates (40%) showed resistance to six or more than six while 14 (70%) were resistant to four or more than four drugs. Conclusion: Rate of resistance of E coli against commonly used antibacterials was quite high and majority of the strains showed multidrug resistance. (author)

  1. Overcoming acquired drug resistance in colorectal cancer cells by targeted delivery of 5-FU with EGF grafted hollow mesoporous silica nanoparticles

    Science.gov (United States)

    Chen, Lijue; She, Xiaodong; Wang, Tao; He, Li; Shigdar, Sarah; Duan, Wei; Kong, Lingxue

    2015-08-01

    Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The effect and mechanism of 5-FU loaded EGF grafted HMSNs (EGF-HMSNs-5-FU) in overcoming acquired drug resistance in SW480/ADR cells were studied. The EGF-HMSNs were demonstrated to be specifically internalized in EGFR overexpressed SW480/ADR cells via a receptor-mediated endocytosis and can escape from endo-lysosomes. The EGF-HMSNs-5-FU exhibited much higher cytotoxicity on SW480/ADR cells than HMSNs-5-FU and free 5-FU while the plain HMSNs did not show significant cytotoxicity. The mechanism of EGF-HMSNs-5-FU in overcoming drug resistance in SW480/ADR cells could be attributed to the specific internalization of EGF-HMSNs-5-FU in EGFR overexpressed cells which can lead to high intracellular drug accumulation and cause cell death through S phase arrest.Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The

  2. Acquired EGFR L718V mutation mediates resistance to osimertinib in non-small cell lung cancer but retains sensitivity to afatinib.

    Science.gov (United States)

    Liu, Yutao; Li, Yan; Ou, Qiuxiang; Wu, Xue; Wang, Xiaonan; Shao, Yang W; Ying, Jianming

    2018-04-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are promising targeted therapies for EGFR-mutated non-small-cell lung cancer (NSCLC) patients. However, acquired resistance inevitably develops. Comprehensive and dynamic companion genomic diagnosis can gain insights into underlying resistance mechanisms, thereby help oncologists and patients to make informed decision on the potential benefit of the treatment. A 67-year-old male who was initially diagnosed of EGFR L858R-mediated NSCLC received multiple lines of chemotherapy and EGFR TKI therapies after surgery. The EGFR mutational status of individual metastatic lesion was determined by genetic testing of the tumor tissue biopsies using next generation sequencing (NGS) throughout the patient's clinical course. An acquired potentially drug-resistant EGFR mutation was functionally validated in vitro and its sensitivity to different EGFR TKIs was assessed simultaneously. We have identified distinct resistance mechanisms to EGFR blockade in different metastatic lung lesions. Acquired EGFR T790M was first detected that leads to the resistance to the gefitinib treatment. Consequently, osimertinib was administrated and the response lasted until disease progressed. We identified a newly acquired EGFR L718V mutation in one lesion in conjunction with L858R, but not T790M, which showed stable disease on the following erlotinib treatment, while EGFR C797S together with L858R/T790M was detected in the other lesion that continuously progressed. In vitro functional studies demonstrated that EGFR-L858R/L718V confers resistance to osimertinib, but retains sensitivity to the second generation TKI afatinib. We reported that distinct resistance mechanisms could arise in different metastases within the same patient in response to EGFR blockade. We also demonstrated in vitro that EGFR L718V mutation mediates resistance to osimertinib, but retains sensitivity to afatinib. We evidenced that dynamic companion genomic

  3. "Population structure of drug-susceptible, -resistant and ESBL-producing Escherichia coli from community-acquired urinary tract infections"

    DEFF Research Database (Denmark)

    Hertz, Frederik Boetius; Nielsen, Jesper Boye; Schønning, Kristian

    2016-01-01

    BACKGROUND: Escherichia coli is the most common cause of urinary tract infection (UTI). The pathogenic isolates are becoming increasingly resistant to antibiotics; with a worldwide dissemination of resistant sequence types (ST). We characterized three different uropathogenic E. coli populations...

  4. Development of a system for acquiring, reconstructing, and visualizing three-dimensional ultrasonic angiograms

    Science.gov (United States)

    Edwards, Warren S.; Ritchie, Cameron J.; Kim, Yongmin; Mack, Laurence A.

    1995-04-01

    We have developed a three-dimensional (3D) imaging system using power Doppler (PD) ultrasound (US). This system can be used for visualizing and analyzing the vascular anatomy of parenchymal organs. To create the 3D PD images, we acquired a series of two-dimensional PD images from a commercial US scanner and recorded the position and orientation of each image using a 3D magnetic position sensor. Three-dimensional volumes were reconstructed using specially designed software and then volume rendered for display. We assessed the feasibility and geometric accuracy of our system with various flow phantoms. The system was then tested on a volunteer by scanning a transplanted kidney. The reconstructed volumes of the flow phantom contained less than 1 mm of geometric distortion and the 3D images of the transplanted kidney depicted the segmental, arcuate, and interlobar vessels.

  5. Type tests to the automatic thermoluminescent dosimetry system acquired by the CPHR for personal dosimetry

    International Nuclear Information System (INIS)

    Molina P, D.; Pernas S, R.; Martinez G, A.

    2006-01-01

    The CPHR individual monitoring service acquired an automatic RADOS TLD system to improve its capacities to satisfy the increasing needs of their national customers. The TLD system consists of: two automatic TLD reader, model DOSACUS, a TLD irradiator and personal dosimeters card including slide and holders. The dosimeters were composed by this personal dosimeters card and LiF:Mg,Cu,P (model GR-200) detectors. These readers provide to detectors a constant temperature readout cycle using hot nitrogen gas. In order to evaluate the performance characteristics of the system, different performance tests recommended by the IEC 1066 standard were carried out. Important dosimetric characteristics evaluated were batch homogeneity, reproducibility, detection threshold, energy dependence, residual signal and fading. The results of the tests showed good performance characteristics of the system. (Author)

  6. Type tests to the automatic system of thermoluminescent dosimetry acquired by the CPHR for personnel dosimetry

    International Nuclear Information System (INIS)

    Molina P, D.; Pernas S, R.

    2005-01-01

    The CPHR individual monitoring service acquired an automatic RADOS TLD system to improve its capacities to satisfy the increasing needs of their national customers. The TLD system consists of: two automatic TLD reader, model DOSACUS, a TLD irradiator and personal dosimeters card including slide and holders. The dosimeters were composed by this personal dosimeters card and LiF: Mg,Cu,P (model GR-200) detectors. These readers provide to detectors a constant temperature readout cycle using hot nitrogen gas. In order to evaluate the performance characteristics of the system, different performance tests recommended by the IEC 1066 standard were carried out. Important dosimetric characteristics evaluated were batch homogeneity, reproducibility, detection threshold, energy dependence, residual signal and fading. The results of the tests showed good performance characteristics of the system. (Author)

  7. Changing prevalence and antibiotic drug resistance pattern of pathogens seen in community-acquired pediatric urinary tract infections at a tertiary care hospital of North India

    OpenAIRE

    Patwardhan, Vrushali; Kumar, Dinesh; Goel, Varun; Singh, Sarman

    2017-01-01

    b>Introduction: Timely treatment of urinary tract infection (UTI) with appropriate antibiotic administration is of immense importance in children to reduce the consequences. Aims and Objectives: The aim and objective of this study was to assess the temporal changes in the microbiological profiles and antimicrobial resistance patterns of uropathogens in pediatric community-acquired UTI. Materials and Methods: This is a retrospective analysis of data collected over a Scattered period of 5...

  8. 12 CFR 617.7615 - What should the System institution do when it decides to lease acquired agricultural real estate?

    Science.gov (United States)

    2010-01-01

    ... decides to lease acquired agricultural real estate? 617.7615 Section 617.7615 Banks and Banking FARM... the System institution do when it decides to lease acquired agricultural real estate? (a) Notify the... real estate at a rate equivalent to the appraised rental value of the property. (1) Within 15 days...

  9. Identification and functional characterisation of Complement Regulator Acquiring Surface Protein-1 of serum resistant Borrelia garinii OspA serotype 4

    Directory of Open Access Journals (Sweden)

    Zipfel Peter F

    2010-02-01

    Full Text Available Abstract Background B. burgdorferi sensu lato (sl is the etiological agent of Lyme borreliosis in humans. Spirochetes have adapted themselves to the human immune system in many distinct ways. One important immune escape mechanism for evading complement activation is the binding of complement regulators Factor H (CFH or Factor H-like protein1 (FHL-1 to Complement Regulator-Acquiring Surface Proteins (CRASPs. Results We demonstrate that B. garinii OspA serotype 4 (ST4 PBi resist complement-mediated killing by binding of FHL-1. To identify the primary ligands of FHL-1 four CspA orthologs from B. garinii ST4 PBi were cloned and tested for binding to human CFH and FHL-1. Orthologs BGA66 and BGA71 were found to be able to bind both complement regulators but with different intensities. In addition, all CspA orthologs were tested for binding to mammalian and avian CFH. Distinct orthologs were able to bind to CFH of different animal origins. Conclusions B. garinii ST4 PBi is able to evade complement killing and it can bind FHL-1 to membrane expressed proteins. Recombinant proteins BGA66 can bind FHL-1 and human CFH, while BGA71 can bind only FHL-1. All recombinant CspA orthologs from B. garinii ST4 PBi can bind CFH from different animal origins. This partly explains the wide variety of animals that can be infected by B. garinii.

  10. Drug-resistance in Streptococcus pneumoniae isolates among Spanish middle aged and older adults with community-acquired pneumonia

    Directory of Open Access Journals (Sweden)

    Raga-Luria Xavier

    2009-03-01

    Full Text Available Abstract Background Pneumococcal diseases remain a major cause of morbidity and mortality worldwide. Updated data on drug-resistance from different populations may be important to recognize changes in disease patterns. This study assessed current levels of penicilin resistance among Streptococcus Pneumoniae causing pneumonia in Spanish middle age and older adults. Methods Antimicrobial susceptibility was tested for 104 consecutive isolates of Streptococcus pneumoniae recovered from patients 50 years or older with radiographically confirmed pneumonia in the region of Tarragona (Spain between 2002 and 2007. According to the minimum inhibitory concentration of tested antimicrobials (penicillin, erythromycin, cefotaxime and levofloxacin strains were classified as susceptible or resistant. Antimicrobial resistance was determined for early cases (2002–2004 and contemporary cases (2005–2007. Results Twenty-seven (25.9% were penicillin-resistant strains (19 strains with intermediate resistance and 8 strains with high resistance. Penicillin-resistance was higher in 2002–2004 than in 2005–2007 (39.5% vs 18.2%, p = 0.017. Of 27 penicillin-resistant strains, 10 (37% were resistant to erythromycin, 8 (29.6% to cefotaxime, 2 (7.4% to levofloxacin, and 4 (14.8% were identified as multidrug resistant. Case-fatality rate was higher among those patients who had an infection caused by any penicillin susceptible strain (16.9% than in those with infections due to penicillin-resistant strains. Conclusion Resistance to penicillin among Streptococcus pneumoniae remains high, but such resistance does not result in increased mortality in patients with pneumococcal pneumonia.

  11. Sepse por Staphylococus aureus resistente à meticilina adquirida na comunidade no sul do Brasil Sepsis due to community-acquired methicillin-resistant Staphylococcus aureus in southern Brazil

    Directory of Open Access Journals (Sweden)

    Luciane Cristina Gelatti

    2009-08-01

    Full Text Available Staphylococcus aureus resistente à meticilina foi inicialmente descrito como um típico microrganismo adquirido em infecções nosocomiais. No entanto, nos últimos anos Staphylococcus aureus resistente à meticilina adquirido na comunidade é causa de infecções de pele e tecidos moles, mas infecções graves como pneumonia e sepse podem ocorrer. Este relato descreve um caso de sepse em criança, complicado com pneumonia secundária a lesão em partes moles por Staphylococcus aureus resistente à meticilina adquirido na comunidade no Sul do Brasil. O paciente foi atendido em Unidade de Emergência com história de ferimento provocado por trauma em membro inferior que evoluiu para celulite, pneumonia e sepse.Methicillin-resistant Staphylococcus aureus was initially described as a typical microorganism acquired in nosocomial infections. However, over recent years, community-acquired methicillin-resistant Staphylococcus aureus has been a cause of skin and soft-tissue infections. Serious infections such as pneumonia and sepsis can also occur. This report describes a case of sepsis in a child that was complicated by pneumonia secondary to soft tissue lesions that were due to community-acquired methicillin-resistant Staphylococcus aureus in southern Brazil. The patient was attended at the Emergency Unit with a history of injury caused by lower-limb trauma that evolved to cellulitis, pneumonia and sepsis.

  12. SYSTEM OF EXERCISES FOR ACQUIRING FOREIGN LANGUAGE MEDIA COMPETENCE BY FUTURE JOURNALISTS

    Directory of Open Access Journals (Sweden)

    Анна Палієнко

    2015-05-01

    Full Text Available The article propounds a communicative and cognitive methodological framework of developing an foreign language media competence of the students majoring in journalism. The media competence as an integrative quality is defined and its main constituents are characterized. The definition of a media text as a specialized speech meadi product is specificated. The role of practical operations in acquiring media competence are inicated. They are revealed while accomplishing cognitive and communicative tasks posed in relevant exercises. The appropriate requirements to these exercises are examined and its correlates are exposed.  Exercises included in the system are explored, justified and illustrated with examples. It is established that the designed system of exercises comprises cognitive and communicative exercises of receptive, reproductive and productive character. Congruous mental operations implemented in such exercises and relevant principles of processing media information are specified.

  13. Effects of hereditary and acquired risk factors of venous thrombosis on a thrombin generation-based APC resistance test

    NARCIS (Netherlands)

    Curvers, J; Thomassen, MCLGD; Rimmer, J; Hamulyak, K; van der Meer, J; Tans, G; Preston, FE; Rosing, J

    Background. Several hereditary and acquired risk factors for venous thromboembolism (VTE) are associated with impaired down-regulation of thrombin formation via the protein C pathway. To identify individuals at risk, functional tests are needed that estimate the risk to develop venous thrombosis.

  14. Acquired resistance L747S mutation in an epidermal growth factor receptor-tyrosine kinase inhibitor-naïve patient: A report of three cases.

    Science.gov (United States)

    Yamaguchi, Fumihiro; Fukuchi, Kunihiko; Yamazaki, Yohei; Takayasu, Hiromi; Tazawa, Sakiko; Tateno, Hidetsugu; Kato, Eisuke; Wakabayashi, Aya; Fujimori, Mami; Iwasaki, Takuya; Hayashi, Makoto; Tsuchiya, Yutaka; Yamashita, Jun; Takeda, Norikazu; Kokubu, Fumio

    2014-02-01

    The purpose of the present study was to report cases of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-naïve patients carrying a mutation associated with acquired resistance to the drug. Gene alterations in 77 lung carcinoma patients were analyzed by collecting and studying curette lavage fluid at the time of diagnosis. PCRs were performed to amplify mutation hotspot regions in EGFR genes. The PCR products were direct-sequenced and the mutations confirmed by resequencing using different primers. Case 1 was a 78-year-old Japanese male diagnosed with stage IB lung adenocarcinoma who was found to have two EGFR mutations, G719S and L747S. Case 2 was a 73-year-old Japanese male diagnosed with stage IV squamous cell lung carcinoma and bone metastasis who had the EGFR mutation, L747S. Case 3 was an 82-year-old Japanese male diagnosed with hyponatremia due to inappropriate secretion of antidiuretic hormone and stage IIIB small cell lung carcinoma (SCLC) who had the EGFR mutation, L747S. Thus, the EGFR mutation L747S associated with acquired EGFR-TKI resistance was detected in two non-small cell lung carcinoma (NSCLC) patients and one SCLC patient, none of whom had ever received EGFR-TKI. The patients were current smokers with stages at diagnosis ranging from IB to IV, and their initial tumors contained resistant clones carrying L747S. L747S may be associated with primary resistance. To the best of our knowledge, this study is the first report of an EGFR mutation associated with resistance to EGFR-TKI in SCLC patients. The early detection of EGFR-TKI resistance mutations may be beneficial in making treatment decisions for lung carcinoma patients, including those with SCLC.

  15. An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer.

    Science.gov (United States)

    Hanker, Ariella B; Brewer, Monica Red; Sheehan, Jonathan H; Koch, James P; Sliwoski, Gregory R; Nagy, Rebecca; Lanman, Richard; Berger, Michael F; Hyman, David M; Solit, David B; He, Jie; Miller, Vincent; Cutler, Richard E; Lalani, Alshad S; Cross, Darren; Lovly, Christine M; Meiler, Jens; Arteaga, Carlos L

    2017-06-01

    We report a HER2 T798I gatekeeper mutation in a patient with HER2 L869R -mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2 L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3 E928G , also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2 T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2 T798I reduces neratinib binding. Neratinib blocked HER2-mediated signaling and growth in cells expressing HER2 L869R but not HER2 L869R/T798I In contrast, afatinib and the osimertinib metabolite AZ5104 strongly suppressed HER2 L869R/T798I -induced signaling and cell growth. Acquisition of HER2 T798I upon development of resistance to neratinib in a breast cancer with an initial activating HER2 mutation suggests HER2 L869R is a driver mutation. HER2 T798I -mediated neratinib resistance may be overcome by other irreversible HER2 inhibitors like afatinib. Significance: We found an acquired HER2 gatekeeper mutation in a patient with HER2 -mutant breast cancer upon clinical progression on neratinib. We speculate that HER2 T798I may arise as a secondary mutation following response to effective HER2 tyrosine kinase inhibitors (TKI) in other cancers with HER2 -activating mutations. This resistance may be overcome by other irreversible HER2 TKIs, such as afatinib. Cancer Discov; 7(6); 575-85. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 539 . ©2017 American Association for Cancer Research.

  16. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

    2015-01-01

    of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further...... and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels...

  17. Prevalence of quinolone resistance mechanisms in Enterobacteriaceae producing acquired AmpC β-lactamases and/or carbapenemases in Spain.

    Science.gov (United States)

    Machuca, Jesús; Agüero, Jesús; Miró, Elisenda; Conejo, María Del Carmen; Oteo, Jesús; Bou, Germán; González-López, Juan José; Oliver, Antonio; Navarro, Ferran; Pascual, Álvaro; Martínez-Martínez, Luis

    2017-10-01

    Quinolone resistance in Enterobacteriaceae species has increased over the past few years, and is significantly associated to beta-lactam resistance. The aim of this study was to evaluate the prevalence of chromosomal- and plasmid-mediated quinolone resistance in acquired AmpC β-lactamase and/or carbapenemase-producing Enterobacteriaceae isolates. The presence of chromosomal- and plasmid-mediated quinolone resistance mechanisms [mutations in the quinolone resistance determining region (QRDR) of gyrA and parC and qnr, aac(6')-Ib-cr and qepA genes] was evaluated in 289 isolates of acquired AmpC β-lactamase- and/or carbapenemase-producing Enterobacteriaceae collected between February and July 2009 in 35 Spanish hospitals. Plasmid mediated quinolone resistance (PMQR) genes were detected in 92 isolates (31.8%), qnr genes were detected in 83 isolates (28.7%), and the aac(6')-Ib-cr gene was detected in 20 isolates (7%). qnrB4 gene was the most prevalent qnr gene detected (20%), associated, in most cases, with DHA-1. Only 14.6% of isolates showed no mutations in gyrA or parC with a ciprofloxacin MIC of 0.5mg/L or higher, whereas PMQR genes were detected in 90% of such isolates. qnrB4 gene was the most prevalent PMQR gene detected, and was significantly associated with acquired AmpC β-lactamase DHA-1. PMQR determinants in association with other chromosomal-mediated quinolone resistance mechanisms, different to mutations in gyrA and parC (increased energy-dependent efflux, altered lipopolysaccharide or porin loss), could lead to ciprofloxacin MIC values that exceed breakpoints established by the main international committees to define clinical antimicrobial susceptibility breakpoints. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Fire Resistant Aircraft Hydraulic System.

    Science.gov (United States)

    1982-07-01

    Chemical Division "Fluorinert" FC-48 - Fluorinated Hydrocarbon "Fluorinert" FC-70 - Fluorinated Hydrocarbon Montedison S. p. A. "Fomblin" Z-04...forming substances such as varnish which could seize a spool valve or other small-clearance sliding surfaces. The test setup is pictorially described in...breakdown products such as solid particles, gels, and sludge’can plug system filters and even small fluid passages, nozzles, and orifices. Varnish -like

  19. Acquired partial lipodystrophy and C3 glomerulopathy: Dysregulation of the complement system as a common mechanism

    Directory of Open Access Journals (Sweden)

    Fernando Corvillo

    2018-05-01

    Full Text Available The activation of the alternative pathway of the complement is involved in the development of several renal diseases, such as atypical haemolytic uraemic syndrome and C3 glomerulopathy. In C3 glomerulopathy, a high percentage of patients have circulating levels of the autoantibody called C3NeF, which causes systemic dysregulation of the complement system. In some cases, the presence of this antibody has been related with abnormalities of adipose tissue, causing acquired partial lipodystrophy (Barraquer–Simons syndrome. Acquired partial lipodystrophy is an extremely rare disorder affecting the distribution of subcutaneous adipose tissue and that mainly onsets during childhood. These patients, in addition to possibly presenting with all the metabolic disorders associated with the adipose tissue defect, present with C3 hypocomplementemia and C3NeF and 25% have developed C3 glomerulopathy. Although it has been known for some time how the dysregulation of the complement system affects the kidneys, it remains unknown how it exactly affects adipose tissue; nevertheless, the relationship is quite clear. In this paper, we describe the connection between the complement system with the biology of the adipose tissue and its pathogenesis reflected from acquired partial lipodystrophy. Resumen: La activación de la vía alternativa del complemento interviene en el desarrollo de varias enfermedades renales, como el síndrome hemolítico urémico atípico o la glomerulopatía C3. En esta última enfermedad un elevado porcentaje de los pacientes presentan niveles circulantes de un autoanticuerpo denominado C3NeF, causante de la desregulación del complemento a nivel sistémico. En ciertos casos, la presencia de este anticuerpo se asocia con alteraciones en el tejido adiposo, causando lipodistrofia parcial adquirida (síndrome de Barraquer-Simons, una enfermedad ultra-rara que afecta a la distribución del tejido adiposo subcutáneo y que comienza principalmente

  20. Trends towards Lower Antimicrobial Susceptibility and Characterization of Acquired Resistance among Clinical Isolates of Brachyspira hyodysenteriae in Spain

    DEFF Research Database (Denmark)

    Hidalgo, Alvaro; Carvajal, Ana; Vester, Birte

    2011-01-01

    The antimicrobial susceptibility of clinical isolates of Brachyspira hyodysenteriae in Spain was monitored, and the underlying molecular mechanisms of resistance were investigated. MICs of tylosin, tiamulin, valnemulin, lincomycin, and tylvalosin were determined for 87 B. hyodysenteriae isolates...

  1. User resistance to information system implementations

    DEFF Research Database (Denmark)

    Campbell, Robert H.; Grimshaw, Mark

    2016-01-01

    Users often resist information system implementations and it has been established that this can cause an implementation to fail. In this paper, the user attitudes that can cause resistance are examined using an established attitude change theory from social and cognitive psychology: the Elaboration......-ranging study are presented that, in addition to supporting this argument, identifies and classifies 19 new heuristics and peripheral influences (in addition to the nine already known) that commonly, and adversely, affect user attitudes and responses to new information system implementations....

  2. Proliferation resistance assessment of nuclear systems

    International Nuclear Information System (INIS)

    1978-09-01

    The first part of the present paper describes the basic assessment procedure that is adopted in the analysis of the three generic nuclear systems. Once-through, fast breeder, and thermal recycle systems are then treated in Sections II, III, and IV, respectively. In each of these sections, a reference system is examined, possible technical and institutional improvements are considered, and alternative system types are indicated. Section V then discusses the relative proliferation resistance of the three generic systems. Although this paper emphasizes the analysis and comparison of individual fuel cycle alternatives, Section V indicates briefly how these analyses then have to be considered in a broader context where systems coexist

  3. Knowledge acquired during the implementation of the BWR emergency procedures tracking system

    International Nuclear Information System (INIS)

    Petrick, W.; Sun, B.K.H.; Naser, J.

    1992-01-01

    An Emergency Operating Procedures Tracking System (EOPTS) has been developed, installed and tested at Taiwan Power Company's Kuo Sheng BWR plant. The EOPTS is based on artificial intelligence methodologies to meet project objectives that could not be met using conventional techniques. The plant EOP's were encoded into a rule-based expert system developed specifically for this application. The EOPTS executes within the GE/ERFIS system to provide close integration with the plant SPDS. The initial EOPTS was implemented in the Kuo Sheng simulator to allow quantitative crew evaluations of the system. Statistical analysis techniques were used to demonstrate that the crews using the EOPTS showed faster responses, fewer errors, and more consistent actions than the crews using the EOP flowcharts. The knowledge acquired during the EOPTS project resulted in improved understanding of related areas such as the EPG'S, plant EOPS, man-machine interfaces, and simulator models for severe transients. These experiences will be used in the future to transfer the technology to US utilities with the objective to improve operator training of the plant EOPs during severe multiple failure transients. To this end, EPRI has developed a technology assessment package that is available to interested utilities. 9 refs., 1 fig

  4. Acquired resistance to cetuximab is associated with the overexpression of Ras family members and the loss of radiosensitization in head and neck cancer cells

    International Nuclear Information System (INIS)

    Saki, Mohammad; Toulany, Mahmoud; Rodemann, H. Peter

    2013-01-01

    Purpose: Cetuximab in combination with radiation therapy is used to treat patients with head and neck squamous cell carcinoma (HNSCC). In the present study, the mechanism of acquired resistance to cetuximab in HNSCC cells was investigated in vitro. Material and methods: The HNSCC cell lines UT5 and SAS and UT5 cells with acquired resistance to cetuximab (UT5R9) were used. The radiotoxicity potentials of cetuximab and inhibitors of PI3K, MAPK and farnesylation were tested using a clonogenic survival assay. Western blotting was used to evaluate protein expression. The levels of EGFR ligands were detected by ELISA. Results: Cetuximab inhibited proliferation and induced radiosensitization in UT5 cells but not in SAS cells. In comparison with UT5 cells, cetuximab-resistant SAS cells markedly overexpressed the K-Ras, H-Ras and N-Ras proteins, as detected by Western blotting. Resistance in UT5R9 cells was associated with the overexpression of the K-Ras, H-Ras and N-Ras proteins as well as an increase in the autocrine production of the EGFR ligands amphiregulin and transforming growth factor α (TGFα). UT5R9 cells were significantly more radioresistant than UT5 cells. Radioresistant UT5R9 cells were not radiosensitized by cetuximab, but knocking down H-RAS and N-RAS with siRNA and targeting Ras farnesylation using the farnesyltransferase inhibitor lonafarnib induced radiosensitization in these cells. Targeting PI3K and MEK revealed that the activation of the PI3K/Akt pathway but not the MAPK/ERK pathway is associated with radioresistance in UT5R9 cells. Conclusion: Targeting Ras and PI3K activity improves the outcome of irradiation in cetuximab-resistant HNSCC cell lines in vitro

  5. Impact of carbapenem resistance on the outcome of patients' hospital-acquired bacteraemia caused by Klebsiella pneumoniae.

    Science.gov (United States)

    Hussein, K; Raz-Pasteur, A; Finkelstein, R; Neuberger, A; Shachor-Meyouhas, Y; Oren, I; Kassis, I

    2013-04-01

    Carbapenem-resistant Enterobacteriaceae, especially Klebsiella spp., have become a major health problem recently worldwide. Since 2006 the incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections has increased substantially in Israel. Bloodstream infections (BSIs) caused by these strains have been associated with high rates of treatment failure and mortality. This study was designed to identify risk factors for carbapenem resistance among patients with healthcare-related (HCR) K. pneumoniae bacteraemia and predictors of mortality associated with HCR-CRKP bacteraemia compared with carbapenem-susceptible K. pneumoniae (CSKP). In this retrospective case-control study, all cases of K. pneumoniae bacteraemia during 2006-2008 were identified. Resistance patterns, underlying morbidities, risk factors for drug resistance and mortality rates were compared for patients with CRKP and CSKP bacteraemia. Two hundred and fourteen patients with CSKP bacteraemia were compared with 103 patients with CRKP bacteraemia. Severe, chronic comorbidities and prior antibiotic use were more frequent among patients with CRKP bacteraemia. On multivariate analysis prior use of macrolides and antibiotic exposure for ≥14 days remained the only independent factors associated with CRKP bacteraemia. Mortality rates of CRKP patients were significantly higher than those of CSKP patients. On multivariate analyses: bedridden status, chronic liver disease, Charlson comorbidity index ≥5, mechanical ventilation, and haemodialysis remained independently associated with mortality among patients with K. pneumoniae bacteraemia. Carbapenem resistance was not a risk factor for mortality. Previous antibiotic exposure is a risk factor for CRKP-BSI. Mortality among patients with K. pneumoniae bacteraemia is associated with serious comorbidities, but not with carbapenem resistance. Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  6. Bacterial Aetiology and Antibiotic Resistance Pattern of Community-Acquired Urinary Tract Infections in Children in a Tertiary Care Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    Lazina Sharmin

    2017-09-01

    Full Text Available Background: Urinary tract infections (UTIs in children are among the most common bacterial infections. Community-acquired urinary tract infections (CAUTI are often treated empirically with broad-spectrum antibiotics. Pattern of aetiologic agents and their antibiotic sensitivity may vary according to geographical and regional location. So, knowledge of antibiotic resistance trends is important for improving evidence-based recommendations for empirical treatment of UTIs. Objectives: To determine the common bacterial aetiologies of CAUTIs and their antibiotic resistance patterns in a tertiary care hospital, Savar. Materials and Methods: This cross-sectional descriptive study was conducted at Enam Medical College Hospital, Savar from May 2016 to April 2017. We collected clean-catch mid-stream urine samples from 257 patients having clinical diagnosis of UTI and submitted to the clinical microbiology laboratory for culture and sensitivity. Results: A total of 120 (46.7% samples were positive for bacterial growth. Escherichia coli (79% was the most common pathogen, followed by Klebsiella spp. (14%. Bacterial isolates showed high prevalence of resistance to multiple antibiotics. Resistance against amoxicillin/clavulanic acid, co-trimoxazole and ciprofloxacin was higher compared to newer quinolones and aminoglycosides. Conclusion: Esch. coli and Klebsiella spp. were the predominant bacterial pathogens. The resistance pattern to commonly prescribed antibiotics was quite high and alarming.

  7. The Antibiotic Resistance Profiles of Bacterial Strains Isolated from Patients with Hospital-Acquired Bloodstream and Urinary Tract Infections

    Directory of Open Access Journals (Sweden)

    Hamed Ghadiri

    2012-01-01

    Full Text Available Treatment of nosocomial infections is becoming difficult due to the increasing trend of antibiotics resistance. Current knowledge on antibiotic resistance pattern is essential for appropriate therapy. We aimed to evaluate antibiotic resistance profiles in nosocomial bloodstream and urinary tract pathogens. A total of 129 blood stream and 300 urinary tract positive samples were obtained from patients referring to Besat hospital over a two-year period (2009 and 2010. Antibiotic sensitivity was ascertained using the Kirby-Bauer disk diffusion technique according to CLSI guidelines. Patient's data such as gender and age were recorded. The ratio of gram-negative to gram-positive bacteria in BSIs was 1.6 : 1. The most prevalent BSI pathogen was Coagulase-Negative Staphylococci (CoNS. The highest resistance rate of CoNS was against penicillin (91.1% followed by ampicillin (75.6%, and the lowest rate was against vancomycin (4.4%. Escherichia coli was the most prevalent pathogen isolated from urinary tract infections (UTIs. Ratio of gram-negative to gram-positive bacteria was 3.2 : 1. The highest resistance rate of E. coli isolates was against nalidixic acid (57.7%. The present study showed that CoNS and E. coli are the most common causative agents of nosocomial BSIs and UTIs, and control of infection needs to be addressed in both antibiotic prescription and general hygiene.

  8. Functional cooperation between HIF-1α and c-Jun in mediating primary and acquired resistance to gefitinib in NSCLC cells with activating mutation of EGFR.

    Science.gov (United States)

    Meng, Shuyan; Wang, Guorui; Lu, Yang; Fan, Zhen

    2018-07-01

    Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) are important transcription factors regulating expression of genes involved in cell survival. HIF-1α and c-Jun are key components of HIF-1 and AP-1, respectively, and are regulated by epidermal growth factor receptor (EGFR)-mediated cell signaling and tumor microenvironmental cues. The roles of HIF-1α and c-Jun in development of resistance to EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) with activating mutation of EGFR have not been explored. In this study, we investigated the roles of HIF-1α and c-Jun in mediating primary and acquired resistance to gefitinib in NSCLC cells with activating mutation of EGFR. Changes in HIF-1α protein and in total and phosphorylated c-Jun levels in relation to changes in total and phosphorylated EGFR levels before and after gefitinib treatment were measured using Western blot analysis in NSCLC cells sensitive or resistant to gefitinib. The impact of overexpression of a constitutively expressed HIF-1α (HIF-1α/ΔODD) or a constitutively active c-Jun upstream regulator (SEK1 S220E/T224D mutant) on cell response to gefitinib was also examined. The effect of pharmacological inhibition of SEK1-JNK-c-Jun pathway on cell response to gefitinib was evaluated. Downregulation of HIF-1α and total and phosphorylated c-Jun levels correlated with cell inhibitory response to gefitinib better than decrease in phosphorylated EGFR did in NSCLC cells with intrinsic or acquired resistance to gefitinib. Overexpression of HIF-1α/ΔODD or SEK1 S220E/T224D mutant conferred resistance to gefitinib. There exists a positive feed-forward regulation loop between HIF-1 and c-Jun. The JNK inhibitor SP600125 sensitized gefitinib-resistant NSCLC cells to gefitinib. HIF-1α and c-Jun functionally cooperate in development of resistance to gefitinib in NSCLC cells. The translational value of inhibiting HIF-1α/c-Jun cooperation in overcoming resistance to EGFR TKI

  9. Spread of community-acquired meticillin-resistant Staphylococcus aureus skin and soft-tissue infection within a family: implications for antibiotic therapy and prevention.

    LENUS (Irish Health Repository)

    Amir, N H

    2010-04-01

    Outbreaks or clusters of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) within families have been reported. We describe a family cluster of CA-MRSA skin and soft-tissue infection where CA-MRSA was suspected because of recurrent infections which failed to respond to flucloxacillin. While the prevalence of CA-MRSA is low worldwide, CA-MRSA should be considered in certain circumstances depending on clinical presentation and risk assessment. Surveillance cultures of family contacts of patients with MRSA should be considered to help establish the prevalence of CA-MRSA and to inform the optimal choice of empiric antibiotic treatment.

  10. An automatic system to search, acquire, and analyse chromosomal aberrations obtained using FISH technique

    International Nuclear Information System (INIS)

    Esposito, R.D.

    2003-01-01

    Full text: Chromosomal aberrations (CA) analysis in peripheral blood lymphocytes is useful both in prenatal diagnoses and cancer cytogenetics, as well as in toxicology to determine the biologically significant dose of specific, both physical and chemical, genotoxic agents to which an individual is exposed. A useful cytogenetic technique for CAs analysis is Fluorescence-in-situ-Hybridization (FISH) which simplifies the automatic Identification and characterisation of aberrations, allowing the visualisation of chromosomes as bright signals on a dark background, and a fast analysis of stable aberrations, which are particularly interesting for late effects. The main limitation of CA analysis is the rarity with which these events occur, and therefore the time necessary to single out a statistically significant number of aberrant cells. In order to address this problem, a prototype system, capable of automatically searching, acquiring, and recognising chromosomal images of samples prepared using FISH, has been developed. The system is able to score large number of samples in a reasonable time using predefined search criteria. The system is based on the appropriately implemented and characterised automatic metaphase finder Metafer4 (MetaSystems), coupled with a specific module for the acquisition of high magnification metaphase images with any combination of fluorescence filters. These images are then analysed and classified using our software. The prototype is currently capable of separating normal metaphase images from presumed aberrant ones. This system is currently in use in our laboratories both by ourselves and by other researchers not involved in its development, in order to carry out analyses of CAs induced by ionising radiation. The prototype allows simple acquisition and management of large quantities of images and makes it possible to carry out methodological studies -such as the comparison of results obtained by different operators- as well as increasing the

  11. Predicting hospital-acquired infections by scoring system with simple parameters.

    Directory of Open Access Journals (Sweden)

    Ying-Jui Chang

    Full Text Available BACKGROUND: Hospital-acquired infections (HAI are associated with increased attributable morbidity, mortality, prolonged hospitalization, and economic costs. A simple, reliable prediction model for HAI has great clinical relevance. The objective of this study is to develop a scoring system to predict HAI that was derived from Logistic Regression (LR and validated by Artificial Neural Networks (ANN simultaneously. METHODOLOGY/PRINCIPAL FINDINGS: A total of 476 patients from all the 806 HAI inpatients were included for the study between 2004 and 2005. A sample of 1,376 non-HAI inpatients was randomly drawn from all the admitted patients in the same period of time as the control group. External validation of 2,500 patients was abstracted from another academic teaching center. Sixteen variables were extracted from the Electronic Health Records (EHR and fed into ANN and LR models. With stepwise selection, the following seven variables were identified by LR models as statistically significant: Foley catheterization, central venous catheterization, arterial line, nasogastric tube, hemodialysis, stress ulcer prophylaxes and systemic glucocorticosteroids. Both ANN and LR models displayed excellent discrimination (area under the receiver operating characteristic curve [AUC]: 0.964 versus 0.969, p = 0.507 to identify infection in internal validation. During external validation, high AUC was obtained from both models (AUC: 0.850 versus 0.870, p = 0.447. The scoring system also performed extremely well in the internal (AUC: 0.965 and external (AUC: 0.871 validations. CONCLUSIONS: We developed a scoring system to predict HAI with simple parameters validated with ANN and LR models. Armed with this scoring system, infectious disease specialists can more efficiently identify patients at high risk for HAI during hospitalization. Further, using parameters either by observation of medical devices used or data obtained from EHR also provided good prediction

  12. Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study

    NARCIS (Netherlands)

    Rosing, J.; Middeldorp, S.; Curvers, J.; Christella, M.; Thomassen, L. G.; Nicolaes, G. A.; Meijers, J. C.; Bouma, B. N.; Büller, H. R.; Prins, M. H.; Tans, G.

    1999-01-01

    BACKGROUND: We have reported previously that, compared with use of second-generation oral contraceptives, the use of third-generation oral contraceptives is associated with increased resistance to the anticoagulant action of activated protein C (APC). Owing to the cross-sectional design of that

  13. Changing prevalence and antibiotic drug resistance pattern of pathogens seen in community-acquired pediatric urinary tract infections at a tertiary care hospital of North India.

    Science.gov (United States)

    Patwardhan, Vrushali; Kumar, Dinesh; Goel, Varun; Singh, Sarman

    2017-01-01

    The aim and objective of this study was to assess the temporal changes in the microbiological profiles and antimicrobial resistance patterns of uropathogens in pediatric community-acquired UTI. This is a retrospective analysis of data collected over a Scattered period of 5 years. The baseline data collected were from January to December 2009, and the second period considered for comparison was from January to December 2014. Urine specimens from children (Antibiotic sensitivity was put up by Kirby-Bauer disc diffusion method as per the Clinical and Laboratory Standard Institute guidelines. In the year 2009, 340 of 2104 (16.15%) urine specimens yielded significant colony count, whereas in 2014, it was 407 of 2212 (18.39%) ( P = 0.051). Escherichia coli was the predominant pathogen and was significantly more prevalent in girls than in boys ( P resistance to ampicillin (from 40.29% to 58.72%), amoxyclav (from 26.17% to 40.54%), nitrofurantoin (from 28.82% to 39.06%), and norfloxacin (from 30% to 41.42%). However, the maximum increase in the resistance was noted for co-trimoxazole from 35.58% in 2009 to 63.39% in 2014 ( P = 0.0000058). The prevalence of extended-spectrum beta-lactamases (ESBLs) has also significantly increased from 21.7% to 33.16% ( P = 0.0045). Although E. coli remains the prime pathogen in pediatric UTI, the prevalence of resistance has dramatically increased over the 5-year study period. Our study highlights the emergence of community-acquired ESBL-producing uropathogens in children proclaiming treatment challenges.

  14. Infectious caused by community-acquired Methicillin-Resistant Staphylococcus aureus (CA-MRSA: three-years experience of an universitary hospital in Rome

    Directory of Open Access Journals (Sweden)

    Anna Altieri

    2010-06-01

    Full Text Available To date methicillin-resistant Staphylococcus aureus (MRSA is one of the most common pathogens causing nosocomial infections(1. In Europe the proportion of MRSA is increasing sharply and the distribution varies from country to country. In recent years there has, in various parts of the world, the emergence of infection with strains of S. aureus methicillin-resistant community-acquired (CA-MRSA than those circulating in hospitals(2. These strains contain a gene that confers resistance to methicillin (mec A SSC mec IV which is usually associated with the gene for Leukocidin Panton Valentine (PVL toxin responsible for necrosis of skin and soft tissue (3. In 2006-2008, at the Laboratory of Bacteriology PolyclinicTor Vergata,were isolated a total of 738 strains of S. aureus from biological samples of different nature (oral, vaginal secretions, wound swab, secreted headset, etc ... of patients related to our surgeries.The identification and study of drug sensitivity of strains were performed with the automatic VITEK2 (bioMérieux. Of the 738 strains of S. aureus identified 212 (28.7% were resistant to methicillin (MRSA, with an increasing trend over the years: 46 isolates, respectively, in 2006, 76 in 2007 and 90 in 2008. The highest frequency of MRSA (varying between 85% and 95% was detected in wound swabs from the dispensary and diabetes (diabetic foot.

  15. Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib.

    Science.gov (United States)

    Amengual, Jennifer E; Prabhu, Sathyen A; Lombardo, Maximilian; Zullo, Kelly; Johannet, Paul M; Gonzalez, Yulissa; Scotto, Luigi; Serrano, Xavier Jirau; Wei, Ying; Duong, Jimmy; Nandakumar, Renu; Cremers, Serge; Verma, Akanksha; Elemento, Olivier; O'Connor, Owen A

    2017-06-15

    Purpose: Pan-class I/II histone deacetylase (HDAC) inhibitors are effective treatments for select lymphomas. Isoform-selective HDAC inhibitors are emerging as potentially more targeted agents. ACY-1215 (ricolinostat) is a first-in-class selective HDAC6 inhibitor. To better understand the discrete function of HDAC6 and its role in lymphoma, we developed a lymphoma cell line resistant to ACY-1215. Experimental Design: The diffuse large B-cell lymphoma cell line OCI-Ly10 was exposed to increasing concentrations of ACY-1215 over an extended period of time, leading to the development of a resistant cell line. Gene expression profiling (GEP) was performed to investigate differentially expressed genes. Combination studies of ACY-1215 and ibrutinib were performed in cell lines, primary human lymphoma tissue, and a xenograft mouse model. Results: Systematic incremental increases in drug exposure led to the development of distinct resistant cell lines with IC 50 values 10- to 20-fold greater than that for parental lines. GEP revealed upregulation of MAPK10, HELIOS, HDAC9, and FYN, as well as downregulation of SH3BP5 and LCK. Gene-set enrichment analysis (GSEA) revealed modulation of the BTK pathway. Ibrutinib was found to be synergistic with ACY-1215 in cell lines as well as in 3 primary patient samples of lymphoma. In vivo confirmation of antitumor synergy was demonstrated with a xenograft of DLBCL. Conclusions: The development of this ACY-1215-resistant cell line has provided valuable insights into the mechanistic role of HDAC6 in lymphoma and offered a novel method to identify rational synergistic drug combinations. Translation of these findings to the clinic is underway. Clin Cancer Res; 23(12); 3084-96. ©2016 AACR . ©2016 American Association for Cancer Research.

  16. Current-limiting and ultrafast system for the characterization of resistive random access memories.

    Science.gov (United States)

    Diaz-Fortuny, J; Maestro, M; Martin-Martinez, J; Crespo-Yepes, A; Rodriguez, R; Nafria, M; Aymerich, X

    2016-06-01

    A new system for the ultrafast characterization of resistive switching phenomenon is developed to acquire the current during the Set and Reset process in a microsecond time scale. A new electronic circuit has been developed as a part of the main setup system, which is capable of (i) applying a hardware current limit ranging from nanoampers up to miliampers and (ii) converting the Set and Reset exponential gate current range into an equivalent linear voltage. The complete system setup allows measuring with a microsecond resolution. Some examples demonstrate that, with the developed setup, an in-depth analysis of resistive switching phenomenon and random telegraph noise can be made.

  17. Towards a Continuous Biometric System Based on ECG Signals Acquired on the Steering Wheel

    Directory of Open Access Journals (Sweden)

    João Ribeiro Pinto

    2017-09-01

    Full Text Available Electrocardiogram signals acquired through a steering wheel could be the key to seamless, highly comfortable, and continuous human recognition in driving settings. This paper focuses on the enhancement of the unprecedented lesser quality of such signals, through the combination of Savitzky-Golay and moving average filters, followed by outlier detection and removal based on normalised cross-correlation and clustering, which was able to render ensemble heartbeats of significantly higher quality. Discrete Cosine Transform (DCT and Haar transform features were extracted and fed to decision methods based on Support Vector Machines (SVM, k-Nearest Neighbours (kNN, Multilayer Perceptrons (MLP, and Gaussian Mixture Models - Universal Background Models (GMM-UBM classifiers, for both identification and authentication tasks. Additional techniques of user-tuned authentication and past score weighting were also studied. The method’s performance was comparable to some of the best recent state-of-the-art methods (94.9% identification rate (IDR and 2.66% authentication equal error rate (EER, despite lesser results with scarce train data (70.9% IDR and 11.8% EER. It was concluded that the method was suitable for biometric recognition with driving electrocardiogram signals, and could, with future developments, be used on a continuous system in seamless and highly noisy settings.

  18. Towards a Continuous Biometric System Based on ECG Signals Acquired on the Steering Wheel.

    Science.gov (United States)

    Pinto, João Ribeiro; Cardoso, Jaime S; Lourenço, André; Carreiras, Carlos

    2017-09-28

    Electrocardiogram signals acquired through a steering wheel could be the key to seamless, highly comfortable, and continuous human recognition in driving settings. This paper focuses on the enhancement of the unprecedented lesser quality of such signals, through the combination of Savitzky-Golay and moving average filters, followed by outlier detection and removal based on normalised cross-correlation and clustering, which was able to render ensemble heartbeats of significantly higher quality. Discrete Cosine Transform (DCT) and Haar transform features were extracted and fed to decision methods based on Support Vector Machines (SVM), k-Nearest Neighbours (kNN), Multilayer Perceptrons (MLP), and Gaussian Mixture Models - Universal Background Models (GMM-UBM) classifiers, for both identification and authentication tasks. Additional techniques of user-tuned authentication and past score weighting were also studied. The method's performance was comparable to some of the best recent state-of-the-art methods (94.9% identification rate (IDR) and 2.66% authentication equal error rate (EER)), despite lesser results with scarce train data (70.9% IDR and 11.8% EER). It was concluded that the method was suitable for biometric recognition with driving electrocardiogram signals, and could, with future developments, be used on a continuous system in seamless and highly noisy settings.

  19. The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

    Science.gov (United States)

    Erdem, H; Inan, A; Guven, E; Hargreaves, S; Larsen, L; Shehata, G; Pernicova, E; Khan, E; Bastakova, L; Namani, S; Harxhi, A; Roganovic, T; Lakatos, B; Uysal, S; Sipahi, O R; Crisan, A; Miftode, E; Stebel, R; Jegorovic, B; Fehér, Z; Jekkel, C; Pandak, N; Moravveji, A; Yilmaz, H; Khalifa, A; Musabak, U; Yilmaz, S; Jouhar, A; Oztoprak, N; Argemi, X; Baldeyrou, M; Bellaud, G; Moroti, R V; Hasbun, R; Salazar, L; Tekin, R; Canestri, A; Čalkić, L; Praticò, L; Yilmaz-Karadag, F; Santos, L; Pinto, A; Kaptan, F; Bossi, P; Aron, J; Duissenova, A; Shopayeva, G; Utaganov, B; Grgic, S; Ersoz, G; Wu, A K L; Lung, K C; Bruzsa, A; Radic, L B; Kahraman, H; Momen-Heravi, M; Kulzhanova, S; Rigo, F; Konkayeva, M; Smagulova, Z; Tang, T; Chan, P; Ahmetagic, S; Porobic-Jahic, H; Moradi, F; Kaya, S; Cag, Y; Bohr, A; Artuk, C; Celik, I; Amsilli, M; Gul, H C; Cascio, A; Lanzafame, M; Nassar, M

    2017-09-01

    Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

  20. Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

    Directory of Open Access Journals (Sweden)

    Hiscox Stephen

    2012-10-01

    Full Text Available Abstract Background Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. Methods CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression or MCF7 cells (± transfection with the CD44 gene were treated with the CD44 ligand, hyaluronon (HA, or heregulin and their in vitro growth (MTT, migration (Boyden chamber and wound healing and invasion (Matrigel transwell migration determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. Results TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2

  1. NVP-BEZ235 overcomes gefitinib-acquired resistance by down-regulating PI3K/AKT/ mTOR phosphorylation

    Directory of Open Access Journals (Sweden)

    Sun ZH

    2015-01-01

    Full Text Available Zhihua Sun,2,* Qiuhui li,1,* Sheng Zhang,1 Jing Chen,1 Lili Huang,3 Jinghua Ren,1 Yu Chang,1 Yichen Liang,1 Gang Wu1 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Oncology department, Xiangyang central Hospital, Xiangyang, Hubei, People’s Republic of China; 3Radiation Oncology Department, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China *These authors contributed equally to this work Background: Patients harboring activating mutations in epidermal growth factor receptors (EGFR are particularly sensitive to EGFR tyrosine kinase inhibitors (TKIs. However, most patients develop an acquired resistance after a period of about 10 months. This study focuses on the therapeutic effect of NVP-BEZ235, a dual inhibitor of phosphatidylinositol- 3-kinase/mammalian target of rapamycin (PI3K/mTOR, in gefitinib-resistant non-small cell lung cancer. Methods: H1975 cell line was validated as a gefitinib-resistant cell model by the nucleotide-sequence analysis. We used the 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay to detect the growth of H1975 cell line in vitro. H1975 cells' migration was detected by the migration assay. Xenograft models were used to investigate the growth of gefitinib-resistant non-small cell lung cancer in vivo. Western blot and immunohistochemical analysis were used to investigate the level of PI3K/protein kinase B(AKT/mTOR signaling pathway proteins. Results: We show that NVP-BEZ235 effectively inhibited the growth of H1975 cells in vivo as well as in vitro. Similarly, H1975 cell migration was reduced by NVP-BEZ235. Further experiments revealed that NVP-BEZ235 attenuated the phosphorylation of PI3K/AKT/mTOR signaling pathway proteins. Conclusion: Taken together, we suggest that NVP-BEZ235 inhibits gefitinib-resistant tumor growth by downregulating PI3K

  2. Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

    International Nuclear Information System (INIS)

    Hiscox, Stephen; Gee, Julia; Baruha, Bedanta; Smith, Chris; Bellerby, Rebecca; Goddard, Lindy; Jordan, Nicola; Poghosyan, Zaruhi; Nicholson, Robert I; Barrett-Lee, Peter

    2012-01-01

    Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR) MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression) or MCF7 cells (± transfection with the CD44 gene) were treated with the CD44 ligand, hyaluronon (HA), or heregulin and their in vitro growth (MTT), migration (Boyden chamber and wound healing) and invasion (Matrigel transwell migration) determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2 and EGFR and induction of cell migration

  3. Epidemic of medical errors and hospital-acquired infections: systemic and social causes

    National Research Council Canada - National Science Library

    Charney, William

    2012-01-01

    ...) and pharmaceutical errors combined are the second or third leading killer of Americans annually: approximately 300,000 die from a combination of medical errors, hospital acquired infections (HAIs...

  4. Trends towards lower antimicrobial susceptibility and characterization of acquired resistance among clinical isolates of Brachyspira hyodysenteriae in Spain.

    Science.gov (United States)

    Hidalgo, Álvaro; Carvajal, Ana; Vester, Birte; Pringle, Märit; Naharro, Germán; Rubio, Pedro

    2011-07-01

    The antimicrobial susceptibility of clinical isolates of Brachyspira hyodysenteriae in Spain was monitored, and the underlying molecular mechanisms of resistance were investigated. MICs of tylosin, tiamulin, valnemulin, lincomycin, and tylvalosin were determined for 87 B. hyodysenteriae isolates recovered from 2008 to 2009 by broth dilution. Domain V of the 23S rRNA gene and the ribosomal protein L3 gene were sequenced in 20 isolates for which the tiamulin MIC was ≥ 4 μg/ml, presenting decreased susceptibility, and in 18 tiamulin-susceptible isolates (MIC ≤ 0.125 μg/ml), and all isolates were typed by multiple-locus variable-number tandem repeats analysis. A comparison with antimicrobial susceptibility data from 2000 to 2007 showed an increase in pleuromutilin resistance over time, doubling the number of isolates with decreased susceptibility to tiamulin. No alteration in susceptibility was detected for lincomycin, and the MIC of tylosin remained high (MIC(50) > 128 μg/ml). The decreased susceptibility to tylosin and lincomycin can be explained by mutations at position A2058 of the 23S rRNA gene (Escherichia coli numbering). A2058T was the predominant mutation, but A2058G also was found together with a change of the neighboring base pair at positions 2057 to 2611. The role of additional point mutations in the vicinity of the peptidyl transferase center and mutations in the L3 at amino acids 148 and 149 and their possible involvement in antimicrobial susceptibility are considered. An association between G2032A and high levels of tiamulin and lincomycin MICs was found, suggesting an increasing importance of this mutation in antimicrobial resistance of clinical isolates of B. hyodysenteriae.

  5. Trends towards Lower Antimicrobial Susceptibility and Characterization of Acquired Resistance among Clinical Isolates of Brachyspira hyodysenteriae in Spain ▿

    Science.gov (United States)

    Hidalgo, Álvaro; Carvajal, Ana; Vester, Birte; Pringle, Märit; Naharro, Germán; Rubio, Pedro

    2011-01-01

    The antimicrobial susceptibility of clinical isolates of Brachyspira hyodysenteriae in Spain was monitored, and the underlying molecular mechanisms of resistance were investigated. MICs of tylosin, tiamulin, valnemulin, lincomycin, and tylvalosin were determined for 87 B. hyodysenteriae isolates recovered from 2008 to 2009 by broth dilution. Domain V of the 23S rRNA gene and the ribosomal protein L3 gene were sequenced in 20 isolates for which the tiamulin MIC was ≥4 μg/ml, presenting decreased susceptibility, and in 18 tiamulin-susceptible isolates (MIC ≤ 0.125 μg/ml), and all isolates were typed by multiple-locus variable-number tandem repeats analysis. A comparison with antimicrobial susceptibility data from 2000 to 2007 showed an increase in pleuromutilin resistance over time, doubling the number of isolates with decreased susceptibility to tiamulin. No alteration in susceptibility was detected for lincomycin, and the MIC of tylosin remained high (MIC50 > 128 μg/ml). The decreased susceptibility to tylosin and lincomycin can be explained by mutations at position A2058 of the 23S rRNA gene (Escherichia coli numbering). A2058T was the predominant mutation, but A2058G also was found together with a change of the neighboring base pair at positions 2057 to 2611. The role of additional point mutations in the vicinity of the peptidyl transferase center and mutations in the L3 at amino acids 148 and 149 and their possible involvement in antimicrobial susceptibility are considered. An association between G2032A and high levels of tiamulin and lincomycin MICs was found, suggesting an increasing importance of this mutation in antimicrobial resistance of clinical isolates of B. hyodysenteriae. PMID:21555771

  6. Prion Fragment Peptides Are Digested with Membrane Type Matrix Metalloproteinases and Acquire Enzyme Resistance through Cu2+-Binding

    Directory of Open Access Journals (Sweden)

    Aya Kojima

    2014-05-01

    Full Text Available Prions are the cause of neurodegenerative disease in humans and other mammals. The structural conversion of the prion protein (PrP from a normal cellular protein (PrPC to a protease-resistant isoform (PrPSc is thought to relate to Cu2+ binding to histidine residues. In this study, we focused on the membrane-type matrix metalloproteinases (MT-MMPs such as MT1-MMP and MT3-MMP, which are expressed in the brain as PrPC-degrading proteases. We synthesized 21 prion fragment peptides. Each purified peptide was individually incubated with recombinant MT1-MMP or MT3-MMP in the presence or absence of Cu2+ and the cleavage sites determined by LC-ESI-MS analysis. Recombinant MMP-7 and human serum (HS were also tested as control. hPrP61-90, from the octapeptide-repeat region, was cleaved by HS but not by the MMPs tested here. On the other hand, hPrP92-168 from the central region was cleaved by MT1-MMP and MT3-MMP at various sites. These cleavages were inhibited by treatment with Cu2+. The C-terminal peptides had higher resistance than the central region. The data obtained from this study suggest that MT-MMPs expressed in the brain might possess PrPC-degrading activity.

  7. Adenocarcinoma of the Lung Acquiring Resistance to Afatinib by Transformation to Small Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Jun Nishimura

    2017-07-01

    Full Text Available A 65-year-old woman visited our hospital due to right chest pain and dyspnea on exertion. Chest radiography revealed decreased permeability of the right lung. Computed tomography demonstrated a huge mass in the right upper lobe and right pleural effusion. Right pleural effusion cytology yielded a diagnosis of adenocarcinoma and was positive for mutation of epidermal growth factor receptor (EGFR; exon 21 L858R. Afatinib was selected for the initial treatment. Multiple tumors regressed remarkably, but then rapidly progressed 3 months later. We performed re-biopsy to detect the mechanism of resistance to afatinib. Histopathology revealed a mixture of small cell carcinoma (SCC and adenocarcinoma harboring same EGFR mutation. To the best of our knowledge, this is the first report of transformation to SCC after treatment with afatinib.

  8. Antibiotic resistance patterns of community-acquired urinary tract infections in children with vesicoureteral reflux receiving prophylactic antibiotic therapy.

    Science.gov (United States)

    Cheng, Chi-Hui; Tsai, Ming-Horng; Huang, Yhu-Chering; Su, Lin-Hui; Tsau, Yong-Kwei; Lin, Chi-Jen; Chiu, Cheng-Hsun; Lin, Tzou-Yien

    2008-12-01

    The goal was to examine bacterial antimicrobial resistance of recurrent urinary tract infections in children receiving antibiotic prophylaxis because of primary vesicoureteral reflux. We reviewed data retrospectively for children with documented vesicoureteral reflux in 2 hospitals during a 5-year follow-up period. The patients were receiving co-trimoxazole, cephalexin, or cefaclor prophylaxis or prophylaxis with a sequence of different antibiotics (alternative monotherapy). Demographic data, degree of vesicoureteral reflux, prophylactic antibiotics prescribed, and antibiotic sensitivity results of first urinary tract infections and breakthrough urinary tract infections were recorded. Three hundred twenty-four patients underwent antibiotic prophylaxis (109 with co-trimoxazole, 100 with cephalexin, 44 with cefaclor, and 71 with alternative monotherapy) in one hospital and 96 children underwent co-trimoxazole prophylaxis in the other hospital. Breakthrough urinary tract infections occurred in patients from both hospitals (20.4% and 25%, respectively). Escherichia coli infection was significantly less common in children receiving antibiotic prophylaxis, compared with their initial episodes of urinary tract infection, at both hospitals. Children receiving cephalosporin prophylaxis were more likely to have an extended-spectrum beta-lactamase-producing organism for breakthrough urinary tract infections, compared with children with co-trimoxazole prophylaxis. Antimicrobial susceptibilities to almost all antibiotics decreased with cephalosporin prophylaxis when recurrent urinary tract infections developed. The extent of decreased susceptibilities was also severe for prophylaxis with a sequence of different antibiotics. However, antimicrobial susceptibilities decreased minimally in co-trimoxazole prophylaxis groups. Children receiving cephalosporin prophylaxis are more likely to have extended-spectrum beta-lactamase-producing bacteria or multidrug-resistant uropathogens

  9. [Investigation of bacterial and viral etiology in community acquired central nervous system infections with molecular methods].

    Science.gov (United States)

    Kahraman, Hasip; Tünger, Alper; Şenol, Şebnem; Gazi, Hörü; Avcı, Meltem; Örmen, Bahar; Türker, Nesrin; Atalay, Sabri; Köse, Şükran; Ulusoy, Sercan; Işıkgöz Taşbakan, Meltem; Sipahi, Oğuz Reşat; Yamazhan, Tansu; Gülay, Zeynep; Alp Çavuş, Sema; Pullukçu, Hüsnü

    2017-07-01

    In this multicenter prospective cohort study, it was aimed to evaluate the bacterial and viral etiology in community-acquired central nervous system infections by standart bacteriological culture and multiplex polymerase chain reaction (PCR) methods. Patients hospitalized with central nervous system infections between April 2012 and February 2014 were enrolled in the study. Demographic and clinical information of the patients were collected prospectively. Cerebrospinal fluid (CSF) samples of the patients were examined by standart bacteriological culture methods, bacterial multiplex PCR (Seeplex meningitis-B ACE Detection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B streptococci) and viral multiplex PCR (Seeplex meningitis-V1 ACE Detection kits herpes simplex virus-1 (HSV1), herpes simplex virus-2 (HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV6)) (Seeplex meningitis-V2 ACE Detection kit (enteroviruses)). Patients were classified as purulent meningitis, aseptic meningitis and encephalitis according to their clinical, CSF (leukocyte level, predominant cell type, protein and glucose (blood/CSF) levels) and cranial imaging results. Patients who were infected with a pathogen other than the detection of the kit or diagnosed as chronic meningitis and other diseases during the follow up, were excluded from the study. A total of 79 patients (28 female, 51 male, aged 42.1 ± 18.5) fulfilled the study inclusion criteria. A total of 46 patients were classified in purulent meningitis group whereas 33 were in aseptic meningitis/encephalitis group. Pathogens were detected by multiplex PCR in 41 patients. CSF cultures were positive in 10 (21.7%) patients (nine S.pneumoniae, one H.influenzae) and PCR were positive for 27 (58.6%) patients in purulent meningitis group. In this group one type of bacteria were detected in 18 patients (14 S.pneumoniae, two N

  10. Genomic and transcriptomic differences in community acquired methicillin resistant Staphylococcus aureus USA300 and USA400 strains.

    Science.gov (United States)

    Jones, Marcus B; Montgomery, Christopher P; Boyle-Vavra, Susan; Shatzkes, Kenneth; Maybank, Rosslyn; Frank, Bryan C; Peterson, Scott N; Daum, Robert S

    2014-12-19

    Staphylococcus aureus is a human pathogen responsible for substantial morbidity and mortality through its ability to cause a number of human infections including bacteremia, pneumonia and soft tissue infections. Of great concern is the emergence and dissemination of methicillin-resistant Staphylococcus aureus strains (MRSA) that are resistant to nearly all β-lactams. The emergence of the USA300 MRSA genetic background among community associated S. aureus infections (CA-MRSA) in the USA was followed by the disappearance of USA400 CA-MRSA isolates. To gain a greater understanding of the potential fitness advantages and virulence capacity of S. aureus USA300 clones, we performed whole genome sequencing of 15 USA300 and 4 USA400 clinical isolates. A comparison of representative genomes of the USA300 and USA400 pulsotypes indicates a number of differences in mobile genome elements. We examined the in vitro gene expression profiles by microarray hybridization and the in vivo transcriptomes during lung infection in mice of a USA300 and a USA400 MRSA strain by performing complete genome qRT-PCR analysis. The unique presence and increased expression of 6 exotoxins in USA300 (12- to 600-fold) compared to USA400 may contribute to the increased virulence of USA300 clones. Importantly, we also observed the up-regulation of prophage genes in USA300 (compared with USA400) during mouse lung infection (including genes encoded by both prophages ΦSa2usa and ΦSa3usa), suggesting that these prophages may play an important role in vivo by contributing to the elevated virulence characteristic of the USA300 clone. We observed differences in the genetic content of USA300 and USA400 strains, as well as significant differences of in vitro and in vivo gene expression of mobile elements in a lung pneumonia model. This is the first study to document the global transcription differences between USA300 and USA400 strains during both in vitro and in vivo growth.

  11. A reliable user authentication and key agreement scheme for Web-based Hospital-acquired Infection Surveillance Information System.

    Science.gov (United States)

    Wu, Zhen-Yu; Tseng, Yi-Ju; Chung, Yufang; Chen, Yee-Chun; Lai, Feipei

    2012-08-01

    With the rapid development of the Internet, both digitization and electronic orientation are required on various applications in the daily life. For hospital-acquired infection control, a Web-based Hospital-acquired Infection Surveillance System was implemented. Clinical data from different hospitals and systems were collected and analyzed. The hospital-acquired infection screening rules in this system utilized this information to detect different patterns of defined hospital-acquired infection. Moreover, these data were integrated into the user interface of a signal entry point to assist physicians and healthcare providers in making decisions. Based on Service-Oriented Architecture, web-service techniques which were suitable for integrating heterogeneous platforms, protocols, and applications, were used. In summary, this system simplifies the workflow of hospital infection control and improves the healthcare quality. However, it is probable for attackers to intercept the process of data transmission or access to the user interface. To tackle the illegal access and to prevent the information from being stolen during transmission over the insecure Internet, a password-based user authentication scheme is proposed for information integrity.

  12. Bacterial Gibberellins Induce Systemic Resistance of Plants

    Directory of Open Access Journals (Sweden)

    I. N. FEKLISTOVA

    2014-06-01

    Full Text Available It is generally agreed today that some rhizosphere bacteria can ensure induced systemic resistance to pathogens. In this paper we tested the ability of gibberellins produced by rhizosphere non-pathogenic bacteria Pseudomonas aurantiaca to induce systemic resistance to alternariosis agent – Alternaria brassicicola – in oilseed rape plants.Oilseed rape (Brássica nápus is one of the most promising oil-bearing croppers. It allows improving the supply of population with vegetable oil, animal and poultry industries with high quality vegetable protein. It is used for biofuel production as well.Gibberellin preparation was isolated from liquid culture of strain Pseudomonas aurantiaca grown in 250 mL of M9 medium (48 h, 28 °C under darkroom conditions. Gibberellins were extracted according procedure described by Tien et al. (1979. Gibberellins concentration in the medium was determined by fluorometric method.Elicitor activity of bacterial metabolites – gibberellins – was analyzed in model system of artificial inoculation of oilseed rape germs with phytopathogenic fungi Alternaria brassicicola. The elicitor action efficiency was evaluated on the 15th day of oilseed rape cultivation based on the percentage of leaf surface covered by necrotic lesions.Gibberellins were shown to induce systemic resistance resulted in decreasing of oil seed plants   vulnerability by 52.7%.It is known that under the unfavorable conditions plants synthesis the reactive oxygen intermediates   which activate destructive processes. One of the first organism reactions to stress action is the change of the lipid peroxidation level. It was shown that treatment of the soil with gibberellins resulted in decreasing of the lipid peroxidation level twofold.Gibberellins were shown to have a similar effect on permeability of cell membranes for free nucleotides. The permeability of cell membranes in leaves decreased 2.8-fold at room temperature. We suggest that gibberellins

  13. Invasive Community-Acquired Methicillin-Resistant Staphylococcus aureus in a Japanese Girl with Disseminating Multiple Organ Infection: A Case Report and Review of Japanese Pediatric Cases

    Directory of Open Access Journals (Sweden)

    Ryuta Yonezawa

    2015-01-01

    Full Text Available Pediatric invasive community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA infection is very serious and occasionally fatal. This infectious disease is still a relatively rare and unfamiliar infectious disease in Japan. We report a positive outcome in a 23-month-old Japanese girl with meningitis, osteomyelitis, fasciitis, necrotizing pneumonia, urinary tract infection, and bacteremia due to CA-MRSA treated with linezolid. PCR testing of the CA-MRSA strain was positive for PVL and staphylococcal enterotoxin b and negative for ACME. SCC mec was type IVa. This case underscores the selection of effective combinations of antimicrobial agents for its treatment. We need to be aware of invasive CA-MRSA infection, which rapidly progresses with a serious clinical course, because the incidence of the disease may be increasing in Japan.

  14. Acquired neuropathies.

    Science.gov (United States)

    Lozeron, Pierre; Trocello, Jean-Marc; Kubis, Nathalie

    2013-09-01

    Acquired neuropathies represent most of the neuropathies encountered in clinical practice. Hundreds of causes have been identified even though up to 41% of patients are still classified as idiopathic (Rajabally and Shah in J Neurol 258:1431-1436, 1). Routine evaluation relies on comprehensive medical history taking, clinical examination, nerve conduction studies and laboratory tests. Other investigations such as nerve biopsy or nerve or muscle imaging are performed in specific settings. This review focuses on recent advances in acquired neuropathies.

  15. Positron emission tomography of tumour [{sup 18}F]fluoroestradiol uptake in patients with acquired hormone-resistant metastatic breast cancer prior to oestradiol therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kruchten, Michel van; Schroeder, Carolien P.; Vries, Elisabeth G.E. de; Hospers, Geke A.P. [University of Groningen, Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Glaudemans, Andor W.J.M.; Vries, Erik F.J. de [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen (Netherlands)

    2015-10-15

    Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[{sup 18}F]fluoro-17β-oestradiol ({sup 18}F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent {sup 18}F-FES-PET/CT imaging at baseline. Tumour {sup 18}F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUV{sub max}). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. {sup 18}F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37 %) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of {sup 18}F-FES-PET for response to treatment were 60 % (95 % CI: 31-83 %) and 80 % (95 % CI: 38-96 %), respectively, using SUV{sub max} >1.5. {sup 18}F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy. (orig.)

  16. Non-Escherichia coli versus Escherichia coli community-acquired urinary tract infections in children hospitalized in a tertiary center: relative frequency, risk factors, antimicrobial resistance and outcome.

    Science.gov (United States)

    Marcus, Nir; Ashkenazi, Shai; Yaari, Arnon; Samra, Zmira; Livni, Gilat

    2005-07-01

    Currently hospitalization for children with urinary tract infections (UTIs) is reserved for severe or complicated cases. Changes may have taken place in the characteristics and causative uropathogens of hospital-treated community-acquired UTI. To study children hospitalized in a tertiary center with community-acquired UTI, compare Escherichia coli and non-E. coli UTI, define predictors for non-E. coli UTI and elucidate the appropriate therapeutic approach. A prospective clinical and laboratory study from 2001 through 2002 in a tertiary pediatric medical center. Patients were divided by results of the urine culture into E. coli and non-E. coli UTI groups, which were compared. Of 175 episodes of culture-proved UTI, 70 (40%) were caused by non-E. coli pathogens. Non-E. coli UTI was more commonly found in children who were male (P = 0.005), who had underlying renal abnormalities (P = 0.0085) and who had received antibiotic therapy in the prior month (P = 0.0009). Non-E. coli uropathogens were often resistant to antibiotics usually recommended for initial therapy for UTI, including cephalosporins and aminoglycosides; 19% were initially treated with inappropriate empiric intravenous antibiotics (compared with 2% for E. coli UTI, P = 0.0001), with a longer hospitalization. Current treatment routines are often inappropriate for hospitalized children with non-E. coli UTI, which is relatively common in this population. The defined risk factors associated with non-E. coli UTIs and its antimicrobial resistance patterns should be considered to improve empiric antibiotic therapy for these infections.

  17. Acquired Tumor Cell Radiation Resistance at the Treatment Site Is Mediated Through Radiation-Orchestrated Intercellular Communication

    Energy Technology Data Exchange (ETDEWEB)

    Aravindan, Natarajan, E-mail: naravind@ouhsc.edu [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Aravindan, Sheeja; Pandian, Vijayabaskar; Khan, Faizan H.; Ramraj, Satish Kumar; Natt, Praveen [Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Natarajan, Mohan [Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States)

    2014-03-01

    Purpose: Radiation resistance induced in cancer cells that survive after radiation therapy (RT) could be associated with increased radiation protection, limiting the therapeutic benefit of radiation. Herein we investigated the sequential mechanistic molecular orchestration involved in radiation-induced radiation protection in tumor cells. Results: Radiation, both in the low-dose irradiation (LDIR) range (10, 50, or 100 cGy) or at a higher, challenge dose IR (CDIR), 4 Gy, induced dose-dependent and sustained NFκB-DNA binding activity. However, a robust and consistent increase was seen in CDIR-induced NFκB activity, decreased DNA fragmentation, apoptosis, and cytotoxicity and attenuation of CDIR-inhibited clonal expansion when the cells were primed with LDIR prior to challenge dose. Furthermore, NFκB manipulation studies with small interfering RNA (siRNA) silencing or p50/p65 overexpression unveiled the influence of LDIR-activated NFκB in regulating CDIR-induced DNA fragmentation and apoptosis. LDIR significantly increased the transactivation/translation of the radiation-responsive factors tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), cMYC, and SOD2. Coculture experiments exhibit LDIR-influenced radiation protection and increases in cellular expression, secretion, and activation of radiation-responsive molecules in bystander cells. Individual gene-silencing approach with siRNAs coupled with coculture studies showed the influence of LDIR-modulated TNF-α, IL-1α, cMYC, and SOD2 in induced radiation protection in bystander cells. NFκB inhibition/overexpression studies coupled with coculture experiments demonstrated that TNF-α, IL-1α, cMYC, and SOD2 are selectively regulated by LDIR-induced NFκB. Conclusions: Together, these data strongly suggest that scattered LDIR-induced NFκB-dependent TNF-α, IL-1α, cMYC, and SOD2 mediate radiation protection to the subsequent challenge dose in tumor cells.

  18. A Comprehensive Program to Reduce Rates of Hospital-Acquired Pressure Ulcers in a System of Community Hospitals.

    Science.gov (United States)

    Englebright, Jane; Westcott, Ruth; McManus, Kathryn; Kleja, Kacie; Helm, Colleen; Korwek, Kimberly M; Perlin, Jonathan B

    2018-03-01

    The prevention of hospital-acquired pressure ulcers (PrUs) has significant consequences for patient outcomes and the cost of care. Providers are challenged with evaluating available evidence and best practices, then implementing programs and motivating change in various facility environments. In a large system of community hospitals, the Reducing Hospital Acquired-PrUs Program was developed to provide a toolkit of best practices, timely and appropriate data for focusing efforts, and continuous implementation support. Baseline data on PrU rates helped focus efforts on the most vulnerable patients and care situations. Facilities were empowered to use and adapt available resources to meet local needs and to share best practices for implementation across the system. Outcomes were measured by the rate of hospital-acquired PrUs, as gathered from patient discharge records. The rate of hospital-acquired stage III and IV PrUs decreased 66.3% between 2011 and 2013. Of the 149 participating facilities, 40 (27%) had zero hospital-acquired stage III and IV PrUs and 77 (52%) had a reduction in their PrU rate. Rates of all PrUs documented as present on admission did not change during this period. A comparison of different strategies used by the most successful facilities illustrated the necessity of facility-level flexibility and recognition of local workflows and patient demographics. Driven by the combination of a repository of evidence-based tools and best practices, readily available data on PrU rates, and local flexibility with processes, the Reducing Hospital Acquired-PrUs Program represents the successful operationalization of improvement in a wide variety of facilities.

  19. Quality study of portal images acquired by computed radiography and screen-film system under megavoltage ray

    International Nuclear Information System (INIS)

    Cao Guoquan; Jin Xiance; Wu Shixiu; Xie Congying; Zhang Li; Yu Jianyi; Li Yueqing

    2007-01-01

    Objective: To evaluate the quality of the portal images acquired by computed radiography (CR) system and conventional screen-film system, respectively. Methods: Imaging plates (IP) and X-ray films ora home-devised lead phantom with a leakage of 6.45% were acquired, and modulation transfer function (MTF) curves of the both images were measured using edge method. Portal images of 40 nasopharyngeal cancer patients were acquired by IP and screen-film system respectively. Two doctors with similar experience evaluated the damage degree of petrosal bone, the receiver operating characteristic (ROC) curve of CR images and general images were drawn according to two doctors evaluation results. Results: The identification frequency of CR system and screen-film system were 1.159 and 0.806 Lp/mm respectively. For doctor one, the area under ROC curve of CR images and general images were 0.802 and 0.742 respectively. For doctor two, the area under ROC curve of CR images and general images were 0.751 and 0.600 respectively. The MTF curve and ROC curve of CR are both better than those of screen-film system. Conclusion: The image quality of CR portal imaging is much better than that of screen-film system. The utility of CR in linear accelerator for portal imaging is promising in clinic. (authors)

  20. Design of online testing system of material radiation resistance

    International Nuclear Information System (INIS)

    Wan Junsheng; He Shengping; Gao Xinjun

    2014-01-01

    The capability of radiation resistance is important for some material used in some specifically engineering fields. It is the same principal applied in all existing test system that compares the performance parameter after radiation to evaluate material radiation resistance. A kind of new technique on test system of material radiation resistance is put forward in this paper. Experimentation shows that the online test system for material radiation resistance works well and has an extending application outlook. (authors)

  1. Novel pharmacotherapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by resistant gram-negative bacteria.

    Science.gov (United States)

    Kidd, James M; Kuti, Joseph L; Nicolau, David P

    2018-03-01

    Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are among the most prevalent infections in hospitalized patients, particularly those in the intensive care unit. Importantly, the frequency of multidrug resistant (MDR) Gram-negative (GN) bacteria as the bacteriologic cause of HABP/VABP is increasing. These include MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem resistant Enterobacteriaceae (CRE). Few antibiotics are currently available when such MDR Gram-negatives are encountered and older agents such as polymyxin B, colistin (polymyxin E), and tigecycline have typically performed poorly in HABP/VABP. Areas covered: In this review, the authors summarize novel antibiotics which have reached phase 3 clinical trials including patients with HABP/VABP. For each agent, the spectrum of activity, pertinent pharmacological characteristics, clinical trial data, and potential utility in the treatment of MDR-GN HABP/VABP is discussed. Expert opinion: Novel antibiotics currently available, and those soon to be, will expand opportunities to treat HABP/VABP caused by MDR-GN organisms and minimize the use of more toxic, less effective drugs. However, with sparse clinical data available, defining the appropriate role for each of the new agents is challenging. In order to maximize the utility of these antibiotics, combination therapy and the role of therapeutic drug monitoring should be investigated.

  2. Tumors initiated by constitutive Cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression

    DEFF Research Database (Denmark)

    Corsino, P.; Davis, B.; Law, M.

    2007-01-01

    ) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. Cell lines isolated from MMTV-cyclin D1-Cdk2 (MMTV-D1K2) tumors exhibit Rb and p130 hyperphosphorylation and up-regulation of the protein products of E2F-dependent genes. These results suggest that cyclin D1/Cdk2 complexes may...... sites. Together, these results suggest that deregulation of the Cdk/Rb/E2F axis reprograms mammary epithelial cells to initiate a paracrine loop with tumor-associated fibroblasts involving TGF beta and HGF, resulting in desmoplasia. The MMTV-DIK2 mice should provide a useful model system...

  3. [Cetuximab in combination with icotinib overcomes the acquired resistance caused by EGFR T790M mutation in non-small cell lung cancer].

    Science.gov (United States)

    Wang, Meng; Zhang, Lianmin; Zhao, Xiaoliang; Liu, Jun; Chen, Yulong; Wang, Changli

    2014-09-01

    The aim of this study was to investigate the effects of combination of icotinib and cetuximab on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC, and provide experimental evidence for rational treatment of NSCLC. The effects of these two agents on cell proliferation, apoptosis, and EGFR-dependent signaling were evaluated using 3-(4, 5-dimethylthiazol-2-yl)- 5-diphenyltetrazolium bromide (MTT) assay, annexin V staining, and Western blotting. The expression of molecular markers of tumor proliferation PCNA and Ki-67 protein was further examined by immunohistochemistry, and the expression of EGFR-signaling-related proteins in tissue sections taken from H1975 tumor xenografts was assessed by Western blot assay. Sensitivity to EGFR inhibitors was detected in human H1975 tumor xenograft in nude mice. The in vitro experiment showed that the proliferative ability of H1975 cells was inhibited in a dose-dependent manner, along with the increasing doses of cetuximab and icotinib, and the combination of cetuximab with icotinib resulted in a more pronounced growth inhibition of the H1975 cells. The apoptosis rate of H1975 cells after treatment with 0.5 µmol/L icotinib and 1 µg/ml cetuximab was (22.03 ± 2.41)% and that after treatment with 5 µmol/L icotinib and 10 µg/ml cetuximab was (42.75 ± 2.49)%, both were significantly higher than that after treatment with the same dose of icotinib or cetuximab alone (P icotinib treatment, but (30.8 ± 2.0) mm(3) in the cetuximab treatment group and 0 mm(3) in the cetuximab combined with icotinib group. There was a significantly decreased expression of Ki-67 and PCNA proteins and down-regulation of phosphorylation of EGFR signaling-related proteins in the cetuximab combined with icotinib group. The combination of icotinib with cetuximab can exert synergistic inhibitory effect on the acquired drug resistance caused by T790M mutation of EGFR in NSCLC H1975 cells, interrupts the EGFR-downstream signaling pathway

  4. Evidence for different mechanisms of ‘unhooking’ for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

    Directory of Open Access Journals (Sweden)

    Spanswick Victoria J

    2012-09-01

    Full Text Available Abstract Background DNA interstrand cross-links (ICLs are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma and solid tumours (ovarian cancer that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Methods Using a modification of the single cell gel electrophoresis (Comet assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Results Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The

  5. Evidence for different mechanisms of ‘unhooking’ for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

    International Nuclear Information System (INIS)

    Spanswick, Victoria J; Hartley, John A; Lowe, Helen L; Newton, Claire; Bingham, John P; Bagnobianchi, Alessia; Kiakos, Konstantinos; Craddock, Charles; Ledermann, Jonathan A; Hochhauser, Daniel

    2012-01-01

    DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Using a modification of the single cell gel electrophoresis (Comet) assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The RAD51 foci response was both drug and cell line

  6. High-levels of acquired drug resistance in adult patients failing first-line antiretroviral therapy in a rural HIV treatment programme in KwaZulu-Natal, South Africa.

    Directory of Open Access Journals (Sweden)

    Justen Manasa

    Full Text Available To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa.Cross-sectional study nested within HIV treatment programme.Adult (≥ 18 years HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART regimen and with evidence of virological failure (one viral load >1000 copies/ml were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms.A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%; and stavudine, lamivudine and nevirapine (24%. Median duration of ART was 42 months (interquartile range (IQR 32-53 and median duration of antiretroviral failure was 27 months (IQR 17-40. One hundred and ninety one (86% had at least one drug resistance mutation. For 34 individuals (15%, the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR 5.70, 95% confidence interval (CI 2.60-12.49.There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved.

  7. Nasal carriage of a single clone of community-acquired methicillin-resistant Staphylococcus aureus among kindergarten attendees in northern Taiwan

    Directory of Open Access Journals (Sweden)

    Lee Shih-Yi

    2007-06-01

    Full Text Available Abstract Background: To evaluate the prevalence and microbiological characterization of community-acquired (CA methicillin-resistant Staphylococcus aureus (MRSA nasal carriage in a kindergarten. Methods: Point prevalence study. Nasal swabs were collected from healthy children younger than 7 years of age who were attending a kindergarten in Taipei, Taiwan. A parent questionnaire regarding MRSA risk factors was administered simultaneously. All CA-MRSA colonization isolates were archived for subsequent antimicrobial susceptibility and molecular typing. Results: Of the 68 children who participated in the study, 17 (25% had S. aureus isolated from nasal swabs. Nine (13.2% of the 68 children had CA-MRSA carriage, and none of them had any identified risk factors. Antimicrobial susceptibility testing revealed all of the 9 CA-MRSA colonization isolates had uniformly high resistance (100% to both clindamycin and erythromycin, the macrolide-lincosamide-streptogramin-constitutive phenotype and the ermB gene. Pulsed-field gel electrophoresis revealed 8 (88.9% of 9 CA-MRSA colonization isolates were genetically related and multilocus sequence typing revealed all isolates had sequence type 59. All of the colonization isolates carried the staphylococcal cassette chromosome mec type IV, but none were positive for the Panton-Valentine leukocidin genes. Conclusion: The results of this study suggest that a single predominant CA-MRSA colonization strain featuring high clindamycin resistance circulated in this kindergarten. Additionally, due to the established transmissibility of colonization isolates, the high prevalence of nasal carriage of CA-MRSA among healthy attendees in kindergartens may indicate the accelerated spread of CA-MRSA in the community.

  8. Testing of SNS-032 in a Panel of Human Neuroblastoma Cell Lines with Acquired Resistance to a Broad Range of Drugs12

    Science.gov (United States)

    Löschmann, Nadine; Michaelis, Martin; Rothweiler, Florian; Zehner, Richard; Cinatl, Jaroslav; Voges, Yvonne; Sharifi, Mohsen; Riecken, Kristoffer; Meyer, Jochen; von Deimling, Andreas; Fichtner, Iduna; Ghafourian, Taravat; Westermann, Frank; Cinatl, Jindrich

    2013-01-01

    Novel treatment options are needed for the successful therapy of patients with high-risk neuroblastoma. Here, we investigated the cyclin-dependent kinase (CDK) inhibitor SNS-032 in a panel of 109 neuroblastoma cell lines consisting of 19 parental cell lines and 90 sublines with acquired resistance to 14 different anticancer drugs. Seventy-three percent of the investigated neuroblastoma cell lines and all four investigated primary tumor samples displayed concentrations that reduce cell viability by 50% in the range of the therapeutic plasma levels reported for SNS-032 (<754 nM). Sixty-two percent of the cell lines and two of the primary samples displayed concentrations that reduce cell viability by 90% in this concentration range. SNS-032 also impaired the growth of the multidrug-resistant cisplatin-adapted UKF-NB-3 subline UKF-NB-3rCDDP1000 in mice. ABCB1 expression (but not ABCG2 expression) conferred resistance to SNS-032. The antineuroblastoma effects of SNS-032 did not depend on functional p53. The antineuroblastoma mechanism of SNS-032 included CDK7 and CDK9 inhibition-mediated suppression of RNA synthesis and subsequent depletion of antiapoptotic proteins with a fast turnover rate including X-linked inhibitor of apoptosis (XIAP), myeloid cell leukemia sequence 1 (Mcl-1), baculoviral IAP repeat containing 2 (BIRC2; cIAP-1), and survivin. In conclusion, CDK7 and CDK9 represent promising drug targets and SNS-032 represents a potential treatment option for neuroblastoma including therapy-refractory cases. PMID:24466371

  9. Identification of novel risk factors for community-acquired Clostridium difficile infection using spatial statistics and geographic information system analyses.

    Directory of Open Access Journals (Sweden)

    Deverick J Anderson

    Full Text Available The rate of community-acquired Clostridium difficile infection (CA-CDI is increasing. While receipt of antibiotics remains an important risk factor for CDI, studies related to acquisition of C. difficile outside of hospitals are lacking. As a result, risk factors for exposure to C. difficile in community settings have been inadequately studied.To identify novel environmental risk factors for CA-CDI.We performed a population-based retrospective cohort study of patients with CA-CDI from 1/1/2007 through 12/31/2014 in a 10-county area in central North Carolina. 360 Census Tracts in these 10 counties were used as the demographic Geographic Information System (GIS base-map. Longitude and latitude (X, Y coordinates were generated from patient home addresses and overlaid to Census Tracts polygons using ArcGIS; ArcView was used to assess "hot-spots" or clusters of CA-CDI. We then constructed a mixed hierarchical model to identify environmental variables independently associated with increased rates of CA-CDI.A total of 1,895 unique patients met our criteria for CA-CDI. The mean patient age was 54.5 years; 62% were female and 70% were Caucasian. 402 (21% patient addresses were located in "hot spots" or clusters of CA-CDI (p<0.001. "Hot spot" census tracts were scattered throughout the 10 counties. After adjusting for clustering and population density, age ≥ 60 years (p = 0.03, race (<0.001, proximity to a livestock farm (0.01, proximity to farming raw materials services (0.02, and proximity to a nursing home (0.04 were independently associated with increased rates of CA-CDI.Our study is the first to use spatial statistics and mixed models to identify important environmental risk factors for acquisition of C. difficile and adds to the growing evidence that farm practices may put patients at risk for important drug-resistant infections.

  10. Acquired Methemoglobinaemia

    Directory of Open Access Journals (Sweden)

    Adil Al-Lawati

    2012-05-01

    Full Text Available Acquired methemoglobinaemia is a relatively rare condition and, therefore infrequently encountered in acute medical practice. Suspicion of the condition may be triggered when the measured PaO2 is ‘out of keeping’ with the oxygen saturations that are discovered with pulse oximetry. We describe two separate cases of acquired methemoglobinaemia secondary to the recreational use of alkyl nitrites (’poppers’. The patients presented at separate times to two different teaching hospitals in London, UK. The similarity of these cases has led the authors to conclude that a raised awareness of this potentially fatal condition, and its association with a widely-available recreational drug, is necessary to ensure a correct and timely diagnosis.

  11. Infecciones adquiridas en la comunidad por Staphylococcus aureus resistente a meticilina en un hospital de agudos Community-acquired methicillin-resistant Staphylococcus aureus infections in a hospital for acute diseases

    Directory of Open Access Journals (Sweden)

    S. Palombarani

    2007-09-01

    factors (Panton-Valentine Leucocidin -PVL- and g-haemolysin as well as the cassette mec type were screened by PCR. All the patients were previously healthy. Four patients under 12, presented bacteremia, one had serious pneumonia, and the three remaining patients had osteoarticular infections; all the patients over 12, had skin and soft tissue infections without systemic damage. The C-MRSA strains harboured cassette mec type IV, and the PVL and g-haemolysin genes. They were methicillin-resistant, with no other associated resistances. It is important to consider the presence of these community- acquired strains in order to develop strategies for their correct treatment.

  12. Combined Targeting of JAK2 and Bcl-2/Bcl-xL to Cure Mutant JAK2-Driven Malignancies and Overcome Acquired Resistance to JAK2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Michaela Waibel

    2013-11-01

    Full Text Available To design rational therapies for JAK2-driven hematological malignancies, we functionally dissected the key survival pathways downstream of hyperactive JAK2. In tumors driven by mutant JAK2, Stat1, Stat3, Stat5, and the Pi3k and Mek/Erk pathways were constitutively active, and gene expression profiling of TEL-JAK2 T-ALL cells revealed the upregulation of prosurvival Bcl-2 family genes. Combining the Bcl-2/Bcl-xL inhibitor ABT-737 with JAK2 inhibitors mediated prolonged disease regressions and cures in mice bearing primary human and mouse JAK2 mutant tumors. Moreover, combined targeting of JAK2 and Bcl-2/Bcl-xL was able to circumvent and overcome acquired resistance to single-agent JAK2 inhibitor treatment. Thus, inhibiting the oncogenic JAK2 signaling network at two nodal points, at the initiating stage (JAK2 and the effector stage (Bcl-2/Bcl-xL, is highly effective and provides a clearly superior therapeutic benefit than targeting just one node. Therefore, we have defined a potentially curative treatment for hematological malignancies expressing constitutively active JAK2.

  13. Enhanced B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation contributes to ABCC1-mediated chemoresistance and glutathione-mediated survival in acquired topoisomerase II poison-resistant cancer cells.

    Science.gov (United States)

    Chen, Huang-Hui; Chang, Hsin-Huei; Chang, Jang-Yang; Tang, Ya-Chu; Cheng, Yung-Chi; Lin, Li-Mei; Cheng, Shu-Ying; Huang, Chih-Hsiang; Sun, Man-Wu; Chen, Chiung-Tong; Kuo, Ching-Chuan

    2017-12-01

    Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation. To investigate whether NRF2 directly contributed to acquired resistance against Top II poisons, we manipulated NRF2 by genetic and pharmacological approaches. The result demonstrated that silencing of NRF2 by RNA interference increased the sensitivity and treatment with NRF2 activator decreased the sensitivity of KB and KB-7D cells toward Top II poisons. Further, increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation activated NRF2 signaling in KB-7D cells. Moreover, increased binding of NRF2 to an ARE in the promoter of ATP-binding cassette subfamily C member 1 (ABCC1) directly contributed to Top II poison resistance. In addition, activation of NRF2 increased glutathione level and antioxidant capacity in KB-7D cells compared with that in KB cells; moreover, high glutathione level provided survival advantage to KB-7D cells. Our study is the first to show that aberrant NRF2 activation is via increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation, which increases the acquired resistance and promote the survival of Top II poison-resistant cancer cells. Importantly, NRF2 downstream effectors ABCC1 and glutathione directly contribute to acquired resistance and survival, respectively. These results suggest that blockade of NRF2 signaling may enhance therapeutic efficacy and reduce the survival of Top II poison-refractory tumors in clinical. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Incoherent digital holograms acquired by interferenceless coded aperture correlation holography system without refractive lenses.

    Science.gov (United States)

    Kumar, Manoj; Vijayakumar, A; Rosen, Joseph

    2017-09-14

    We present a lensless, interferenceless incoherent digital holography technique based on the principle of coded aperture correlation holography. The acquired digital hologram by this technique contains a three-dimensional image of some observed scene. Light diffracted by a point object (pinhole) is modulated using a random-like coded phase mask (CPM) and the intensity pattern is recorded and composed as a point spread hologram (PSH). A library of PSHs is created using the same CPM by moving the pinhole to all possible axial locations. Intensity diffracted through the same CPM from an object placed within the axial limits of the PSH library is recorded by a digital camera. The recorded intensity this time is composed as the object hologram. The image of the object at any axial plane is reconstructed by cross-correlating the object hologram with the corresponding component of the PSH library. The reconstruction noise attached to the image is suppressed by various methods. The reconstruction results of multiplane and thick objects by this technique are compared with regular lens-based imaging.

  15. Pediatric patient with systemic lupus erythematosus & congenital acquired immunodeficiency syndrome: An unusual case and a review of the literature

    Directory of Open Access Journals (Sweden)

    Rezaee Fariba

    2008-05-01

    Full Text Available Abstract The coexistence of systemic lupus erythematosus (SLE in patients with congenital human immunodeficiency virus (HIV infection is rare. This is a case report of a child diagnosed with SLE at nine years of age. She initially did well on non-steroidal anti-inflammatory agents, hydroxychloroquine, and steroids. She then discontinued her anti-lupus medications and was lost to follow-up. At 13 years of age, her lupus symptoms had resolved and she presented with intermittent fevers, cachexia, myalgias, arthralgias, and respiratory symptoms. Through subsequent investigations, the patient was ultimately diagnosed with congenitally acquired immunodeficiency syndrome (AIDS.

  16. Community-acquired pneumonia due to pandemic A(H1N12009 influenzavirus and methicillin resistant Staphylococcus aureus co-infection.

    Directory of Open Access Journals (Sweden)

    Ronan J Murray

    Full Text Available BACKGROUND: Bacterial pneumonia is a well described complication of influenza. In recent years, community-onset methicillin-resistant Staphylococcus aureus (cMRSA infection has emerged as a contributor to morbidity and mortality in patients with influenza. Since the emergence and rapid dissemination of pandemic A(H1N12009 influenzavirus in April 2009, initial descriptions of the clinical features of patients hospitalized with pneumonia have contained few details of patients with bacterial co-infection. METHODOLOGY/PRINCIPAL FINDINGS: Patients with community-acquired pneumonia (CAP caused by co-infection with pandemic A(H1N12009 influenzavirus and cMRSA were prospectively identified at two tertiary hospitals in one Australian city during July to September 2009, the period of intense influenza activity in our region. Detailed characterization of the cMRSA isolates was performed. 252 patients with pandemic A(H1N12009 influenzavirus infection were admitted at the two sites during the period of study. Three cases of CAP due to pandemic A(H1N12009/cMRSA co-infection were identified. The clinical features of these patients were typical of those with S. aureus co-infection or sequential infection following influenza. The 3 patients received appropriate empiric therapy for influenza, but inappropriate empiric therapy for cMRSA infection; all 3 survived. In addition, 2 fatal cases of CAP caused by pandemic A(H1N12009/cMRSA co-infection were identified on post-mortem examination. The cMRSA infections were caused by three different cMRSA clones, only one of which contained genes for Panton-Valentine Leukocidin (PVL. CONCLUSIONS/SIGNIFICANCE: Clinicians managing patients with pandemic A(H1N12009 influenzavirus infection should be alert to the possibility of co-infection or sequential infection with virulent, antimicrobial-resistant bacterial pathogens such as cMRSA. PVL toxin is not necessary for the development of cMRSA pneumonia in the setting of pandemic

  17. ConoSurf: Open-source 3D scanning system based on a conoscopic holography device for acquiring surgical surfaces.

    Science.gov (United States)

    Brudfors, Mikael; García-Vázquez, Verónica; Sesé-Lucio, Begoña; Marinetto, Eugenio; Desco, Manuel; Pascau, Javier

    2017-09-01

    A difficulty in computer-assisted interventions is acquiring the patient's anatomy intraoperatively. Standard modalities have several limitations: low image quality (ultrasound), radiation exposure (computed tomography) or high costs (magnetic resonance imaging). An alternative approach uses a tracked pointer; however, the pointer causes tissue deformation and requires sterilizing. Recent proposals, utilizing a tracked conoscopic holography device, have shown promising results without the previously mentioned drawbacks. We have developed an open-source software system that enables real-time surface scanning using a conoscopic holography device and a wide variety of tracking systems, integrated into pre-existing and well-supported software solutions. The mean target registration error of point measurements was 1.46 mm. For a quick guidance scan, surface reconstruction improved the surface registration error compared with point-set registration. We have presented a system enabling real-time surface scanning using a tracked conoscopic holography device. Results show that it can be useful for acquiring the patient's anatomy during surgery. © 2016 The Authors. The International Journal of Medical Robotics and Computer Assisted Surgery Published by John Wiley & Sons Ltd.

  18. Response to HER2 Inhibition in a Patient With Brain Metastasis With EGFR TKI Acquired Resistance and an HER2 Amplification

    Directory of Open Access Journals (Sweden)

    Arenda D. Meedendorp

    2018-05-01

    Full Text Available A 62-year-old man was referred to our university hospital for treatment of advanced adenocarcinoma of the lung after disease progression on two lines of EGFR TKI and one line of chemotherapy. Fluorescent in situ hybridization analysis upon progression showed an HER2 amplification. At our weekly Molecular Tumor Board (MTB, a decision was made to treat this patient with afatinib, which resulted in a partial response. However, progression was observed with a facial nerve paresis due to a metastasis in the skull. A biopsy of a location in the thorax revealed the presence of an EGFR-T790M mutation associated with acquired resistance, after which treatment with osimertinib was started. After 6 months, disease progression was observed, and a new biopsy was taken from the pelvic bone, which revealed the original amplification of HER2 together with the EGFR-L858R mutation, the EGFR-T790M mutation was not detected. The MTB decided to treat the patient with trastuzumab/paclitaxel. A partial response was observed in different bone lesions, while the skull metastasis with ingrowth in the brain remained stable for 6 months. Because of progression of the bone metastases after 6 months, a biopsy of a lesion in the thorax wall was taken. In this lesion, the EGFR-T790M mutation could be detected again. The MTB advised to start treatment with a combination of osimertinib and afatinib. This resulted in an impressive clinical improvement and a partial response of the bone metastases on the most recent 18-fluorodeoxyglucose positron emission tomography and computer tomography-scan. In conclusion, adjusting treatment to the mutational make-up of the tumor is a great challenge. For optimal treatment response multiple biopsies and re-biopsy upon progression are imperative. As more genes are investigated, treatment decision becomes increasingly difficult, therefore, expert opinions from an MTB is essential.

  19. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

    Directory of Open Access Journals (Sweden)

    Abhay Sharma

    Full Text Available Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1 adults after treating F(0 adult males with PTZ and of F(2 adults resulting from a cross between F(1 males and normal females. Surprisingly, microarray clustering showed F(1 male profile as closest to F(1 female and F(0 male profile closest to F(2 male. Differentially expressed genes in F(1 males, F(1 females and F(2 males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2 males. Next, we generated microarray expression profiles of adult testis from F(0 and F(1 males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying

  20. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

    Science.gov (United States)

    Sharma, Abhay; Singh, Priyanka

    2009-06-02

    Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ) induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1) adults after treating F(0) adult males with PTZ and of F(2) adults resulting from a cross between F(1) males and normal females. Surprisingly, microarray clustering showed F(1) male profile as closest to F(1) female and F(0) male profile closest to F(2) male. Differentially expressed genes in F(1) males, F(1) females and F(2) males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2) males. Next, we generated microarray expression profiles of adult testis from F(0) and F(1) males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying the

  1. Resistive-wall Wake Effect in the Beam Delivery System

    International Nuclear Information System (INIS)

    Delayen, J.R.; Jefferson Lab; Wu, Juhao; Raubenheimer, T.O.; SLAC; Wang, Jiunn-Ming; BNL, NSLS

    2005-01-01

    General formulae for resistive-wall induced beam dilution are presented and then applied to the final beam delivery system of linear colliders. Criteria for the design of final beam delivery systems are discussed

  2. A Master-Slave Surveillance System to Acquire Panoramic and Multiscale Videos

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-01-01

    Full Text Available This paper describes a master-slave visual surveillance system that uses stationary-dynamic camera assemblies to achieve wide field of view and selective focus of interest. In this system, the fish-eye panoramic camera is capable of monitoring a large area, and the PTZ dome camera has high mobility and zoom ability. In order to achieve the precise interaction, preprocessing spatial calibration between these two cameras is required. This paper introduces a novel calibration approach to automatically calculate a transformation matrix model between two coordinate systems by matching feature points. In addition, a distortion correction method based on Midpoint Circle Algorithm is proposed to handle obvious horizontal distortion in the captured panoramic image. Experimental results using realistic scenes have demonstrated the efficiency and applicability of the system with real-time surveillance.

  3. A portable system for acquiring and removing motion artefact from ECG signals

    Science.gov (United States)

    Griffiths, A.; Das, A.; Fernandes, B.; Gaydecki, P.

    2007-07-01

    A novel electrocardiograph (ECG) signal acquisition and display system is under development. It is designed for patients ranging from the elderly to athletes. The signals are obtained from electrodes integrated into a vest, amplified, digitally processed and transmitted via Bluetooth to a PC with a Labview ® interface. Digital signal processing is performed to remove movement artefact and electromyographic (EMG) noise, which severely distorts signal morphology and complicates clinical diagnosis. Independent component analysis (ICA) is also used to improve the signal quality. The complete system will integrate the electronics into a single module which will be embedded in the vest.

  4. A portable system for acquiring and removing motion artefact from ECG signals

    Energy Technology Data Exchange (ETDEWEB)

    Griffiths, A; Das, A; Fernandes, B; Gaydecki, P [School of Electrical and Electronic Engineering, University of Manchester, PO Box 88, Manchester M60 1QD (United Kingdom)

    2007-07-15

    A novel electrocardiograph (ECG) signal acquisition and display system is under development. It is designed for patients ranging from the elderly to athletes. The signals are obtained from electrodes integrated into a vest, amplified, digitally processed and transmitted via Bluetooth to a PC with a Labview (registered) interface. Digital signal processing is performed to remove movement artefact and electromyographic (EMG) noise, which severely distorts signal morphology and complicates clinical diagnosis. Independent component analysis (ICA) is also used to improve the signal quality. The complete system will integrate the electronics into a single module which will be embedded in the ves000.

  5. Puncture resistance of Type B transport systems

    International Nuclear Information System (INIS)

    Rack, H.J.; Cheresh, M.C.

    1980-01-01

    This report describes a recent attempt to develop a test method for use in screening materials and for evaluating the effects of certain parameters, for example section stiffness, on container penetration resistance. In addition, it illustrates the application of this procedure to the selection of a sheet steel for a transuranic waste (TRUPACT) container. The test consists of penetrating a specimen, normally 0.6 m square, with a punch (tup) attached to a falling weight and recording and analyzing the force-time history to determine the energy absorption during the impact event. The test as developed simulates certain aspects of the 10CFR71 drop test in order to provide a means of comparing, for example, the penetrating resistance of various steels, this resistance being defined as the energy required to initiate fracture in the specimen. In summary, this examination suggests that it should be possible to develop a laboratory test to rank and select materials for maximum puncture resistance. Although the initial results appear promising, more effort will be required before this procedure can be routinely applied to examining the various factors which control the puncture resistance of these materials. These results do, nonetheless, show that high-strength, low-alloy steels do offer significant advantages over mild steel for container penetration protection. Indeed, one of these steels, NAX-80, is presently considered as a prime candidate for the TRUPACT container being developed at Sandia National Laboratories

  6. Nervous system manifestations and neuroradiologic findings in acquired immunodeficiency syndrome (AIDS)

    International Nuclear Information System (INIS)

    Rodesch, G.; Parizel, P.M.; Lalmand, B.; Vanderhofstadt, A.; Baleriaux, D.; Farber, C.M.; Calck, M. van; Przedborski, S.; Haens, J. d'; Taelman, H.

    1989-01-01

    We report a series of thirteen patients with nervous system complications out of a total of thirty AIDS patients admitted to our hospital over the last two years for which CT and/or MRI have been performed. Five were homosexual men and eight patients (5 men, 3 women) were of African origin (Zaire and Rwanda) (n=5) or had had sexual intercourse with the local African population (n=3). The nervous system complications encountered included: Toxoplasma gondii brain abscess (2 patients); cryptococcus neoformans meningitis+toxoplasmosis (1 patient); toxoplasmosis+lymphoma (2 patients); progressive multifocal leucoencephalopathy (1 patient); lymphocytic meningitis or encephalitis (3 patients); lymphoma (1 patient); polyradiculoneuritis (3 patients). Three of thirteen patients had multiple intracranial abnormalities: One had concomitant intraparenchymal toxoplasma abscess and cryptococcal meningitis; in one patient a lymphoma developed after the successful medical treatment of a toxoplasma abscess; conversely, one patient developed a toxoplasma abscess two years after mediastinal radiotherapy for a systemic non-Hodgkin lymphoma. In conclusion, in our experience, nervous system toxoplasmosis is the most frequent AIDS related CNS complication. Our series demonstrates the high frequency of a second neurological disease occurring either concomitantly or separately. In these cases, while CT may readily identify the intracranial abnormalities, it contributes little towards an etiological diagnosis. Finally, our series illustrates the importance of a central African endemic focus for AIDS. (orig.)

  7. Nervous system manifestations and neuroradiologic findings in acquired immunodeficiency syndrome (AIDS)

    Energy Technology Data Exchange (ETDEWEB)

    Rodesch, G.; Parizel, P.M.; Lalmand, B.; Vanderhofstadt, A.; Baleriaux, D.; Farber, C.M.; Calck, M. van; Przedborski, S.; Haens, J. d' ; Taelman, H.

    1989-03-01

    We report a series of thirteen patients with nervous system complications out of a total of thirty AIDS patients admitted to our hospital over the last two years for which CT and/or MRI have been performed. Five were homosexual men and eight patients (5 men, 3 women) were of African origin (Zaire and Rwanda) (n=5) or had had sexual intercourse with the local African population (n=3). The nervous system complications encountered included: Toxoplasma gondii brain abscess (2 patients); cryptococcus neoformans meningitis+toxoplasmosis (1 patient); toxoplasmosis+lymphoma (2 patients); progressive multifocal leucoencephalopathy (1 patient); lymphocytic meningitis or encephalitis (3 patients); lymphoma (1 patient); polyradiculoneuritis (3 patients). Three of thirteen patients had multiple intracranial abnormalities: One had concomitant intraparenchymal toxoplasma abscess and cryptococcal meningitis; in one patient a lymphoma developed after the successful medical treatment of a toxoplasma abscess; conversely, one patient developed a toxoplasma abscess two years after mediastinal radiotherapy for a systemic non-Hodgkin lymphoma. In conclusion, in our experience, nervous system toxoplasmosis is the most frequent AIDS related CNS complication. Our series demonstrates the high frequency of a second neurological disease occurring either concomitantly or separately. In these cases, while CT may readily identify the intracranial abnormalities, it contributes little towards an etiological diagnosis. Finally, our series illustrates the importance of a central African endemic focus for AIDS.

  8. 76 FR 16795 - The National Antimicrobial Resistance Monitoring System Strategic Plan 2011-2015; Request for...

    Science.gov (United States)

    2011-03-25

    ...] The National Antimicrobial Resistance Monitoring System Strategic Plan 2011-2015; Request for Comments..., FDA requested comments on a document for the National Antimicrobial Resistance Monitoring System....fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/NationalAntimicrobialResistance...

  9. First report in South America of companion animal colonization by the USA1100 clone of community-acquired meticillin-resistant Staphylococcus aureus (ST30) and by the European clone of methicillin-resistant Staphylococcus pseudintermedius (ST71).

    Science.gov (United States)

    Quitoco, Isidório Mebinda Zuco; Ramundo, Mariana Severo; Silva-Carvalho, Maria Cícera; Souza, Raquel Rodrigues; Beltrame, Cristiana Ossaille; de Oliveira, Táya Figueiredo; Araújo, Rodrigo; Del Peloso, Pedro Fernandez; Coelho, Leonardo Rocchetto; Figueiredo, Agnes Marie Sá

    2013-08-27

    Methicillin-resistant staphylococci can colonize and cause diseases in companion animals. Unfortunately, few molecular studies have been carried out in Brazil and other countries with the aim of characterizing these isolates. Consequently, little is known about the potential role of companion animals in transmitting these resistant bacteria to humans. In this work we searched for mecA gene among Staphylococcus isolates obtained from nasal microbiota of 130 healthy dogs and cats attended in a veterinary clinic located in the west region of Rio de Janeiro. The isolates recovered were identified to the species level and characterized using molecular tools. A community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate related to USA1100 (Southwest Pacific clone) and susceptible to all non-β-lactams was detected in a cat (1.7%, 1/60). Another coagulase-positive isolate harboring mecA was recovered from a dog (1.4%, 1/70) and identified as Staphylococcus pseudintermedius (MRSP) related to the European clone (ST71). The two isolates of Staphylococcus conhii subsp. urealyticus (1.4%, 1/70 dogs and 1.7%, 1/60 cats), similarly to the MRSP isolate, also presented high-level multiresistance. The majority of the methicillin-resistant coagulase-negative staphylococci recovered were Staphylococcus saprophyticus (5.7%, 4/70 dogs and 6.7%, 4/60 cats) and all clustered into the same PFGE type. This work demonstrates that mecA-harboring Staphylococcus isolates are common members of the nasal microbiota of the healthy companion animals studied (9.2%, 12/130 animals), including some high-level multiresistant isolates of S. pseudintermedius and S. conhii subsp. urealyticus. The detection, for the first time in South America, of USA1100-related CA-MRSA and of ST71 MRSP (European clone), colonizing companion animals, is of concern. Both S. pseudintermedius and S. aureus are important agents of infections for animals. The USA1100 CA-MRSA is a causative of severe and

  10. Digital system for acquiring signals from photodiode arrays. No. Program Element 2317-08-03

    International Nuclear Information System (INIS)

    Le Guen, M.; Meric, B.

    1981-01-01

    A model of circuit allowing the digitization and the memorization of signals coming from linear arrays of photodiodes have been realized. The authors first recall the organization and present in the second part some test results on experimental sites. The model consists of 1 - an acquisition, memorization and visualization card (AMV card) for the data from RETICON 121 photodiode strips, 2 - a series transfer card for the memorized data, and 3 - an interface and multiplexing card associated with a system using a 6800 microprocessor allowing the management of eight acquisition cards [fr

  11. Study on excitation and fluorescence spectrums of Japanese citruses to construct machine vision systems for acquiring fluorescent images

    Science.gov (United States)

    Momin, Md. Abdul; Kondo, Naoshi; Kuramoto, Makoto; Ogawa, Yuichi; Shigi, Tomoo

    2011-06-01

    Research was conducted to acquire knowledge of the ultraviolet and visible spectrums from 300 -800 nm of some common varieties of Japanese citrus, to investigate the best wave-lengths for fluorescence excitation and the resulting fluorescence wave-lengths and to provide a scientific background for the best quality fluorescent imaging technique for detecting surface defects of citrus. A Hitachi U-4000 PC-based microprocessor controlled spectrophotometer was used to measure the absorption spectrum and a Hitachi F-4500 spectrophotometer was used for the fluorescence and excitation spectrums. We analyzed the spectrums and the selected varieties of citrus were categorized into four groups of known fluorescence level, namely strong, medium, weak and no fluorescence.The level of fluorescence of each variety was also examined by using machine vision system. We found that around 340-380 nm LEDs or UV lamps are appropriate as lighting devices for acquiring the best quality fluorescent image of the citrus varieties to examine their fluorescence intensity. Therefore an image acquisition device was constructed with three different lighting panels with UV LED at peak 365 nm, Blacklight blue lamps (BLB) peak at 350 nm and UV-B lamps at peak 306 nm. The results from fluorescent images also revealed that the findings of the measured spectrums worked properly and can be used for practical applications such as for detecting rotten, injured or damaged parts of a wide variety of citrus.

  12. Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.

    Science.gov (United States)

    Zecena, Helma; Tveit, Daniel; Wang, Zi; Farhat, Ahmed; Panchal, Parvita; Liu, Jing; Singh, Simar J; Sanghera, Amandeep; Bainiwal, Ajay; Teo, Shuan Y; Meyskens, Frank L; Liu-Smith, Feng; Filipp, Fabian V

    2018-04-04

    Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma. The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032. We conducted transcriptomic expression profiling using RNA-Seq and RT-qPCR arrays. Pathways of melanogenesis, MAPK signaling, cell cycle, and metabolism were significantly enriched among the set of differentially expressed genes of vemurafenib-resistant cells vs control. The underlying mechanism of treatment resistance and pathway rewiring was uncovered to be based on non-genomic adaptation and validated in two distinct melanoma models, SK-MEL-28 and A375. Both cell lines have activating BRAF mutations and display metastatic potential. Downregulation of dual specific phosphatases, tumor suppressors, and negative MAPK regulators reengages mitogenic signaling. Upregulation of growth factors, cytokines, and cognate receptors triggers signaling pathways circumventing BRAF blockage. Further, changes in amino acid and one-carbon metabolism support cellular proliferation despite MAPK inhibitor treatment. In addition, treatment-resistant cells upregulate pigmentation and melanogenesis, pathways which partially overlap with MAPK signaling. Upstream regulator analysis discovered significant perturbation in oncogenic forkhead box and hypoxia inducible factor family transcription factors. The established cellular models offer mechanistic insight into cellular changes and therapeutic targets under inhibitor resistance in malignant melanoma. At a systems biology level, the MAPK pathway undergoes major rewiring while acquiring inhibitor resistance

  13. Optimizing preoperative blood ordering with data acquired from an anesthesia information management system.

    Science.gov (United States)

    Frank, Steven M; Rothschild, James A; Masear, Courtney G; Rivers, Richard J; Merritt, William T; Savage, Will J; Ness, Paul M

    2013-06-01

    The maximum surgical blood order schedule (MSBOS) is used to determine preoperative blood orders for specific surgical procedures. Because the list was developed in the late 1970s, many new surgical procedures have been introduced and others improved upon, making the original MSBOS obsolete. The authors describe methods to create an updated, institution-specific MSBOS to guide preoperative blood ordering. Blood utilization data for 53,526 patients undergoing 1,632 different surgical procedures were gathered from an anesthesia information management system. A novel algorithm based on previously defined criteria was used to create an MSBOS for each surgical specialty. The economic implications were calculated based on the number of blood orders placed, but not indicated, according to the MSBOS. Among 27,825 surgical cases that did not require preoperative blood orders as determined by the MSBOS, 9,099 (32.7%) had a type and screen, and 2,643 (9.5%) had a crossmatch ordered. Of 4,644 cases determined to require only a type and screen, 1,509 (32.5%) had a type and crossmatch ordered. By using the MSBOS to eliminate unnecessary blood orders, the authors calculated a potential reduction in hospital charges and actual costs of $211,448 and $43,135 per year, respectively, or $8.89 and $1.81 per surgical patient, respectively. An institution-specific MSBOS can be created, using blood utilization data extracted from an anesthesia information management system along with our proposed algorithm. Using these methods to optimize the process of preoperative blood ordering can potentially improve operating room efficiency, increase patient safety, and decrease costs.

  14. Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1

    Science.gov (United States)

    Pirazzoli, Valentina; Nebhan, Caroline; Song, Xiaoling; Wurtz, Anna; Walther, Zenta; Cai, Guoping; Zhao, Zhongming; Jia, Peilin; de Stanchina, Elisa; Shapiro, Erik M.; Gale, Molly; Yin, Ruonan; Horn, Leora; Carbone, David P.; Stephens, Philip J; Miller, Vincent; Gettinger, Scott; Pao, William; Politi, Katerina

    2014-01-01

    SUMMARY Patients with EGFR-mutant lung adenocarcinomas (LUADs) who initially respond to first-generation TKIs develop resistance to these drugs. A combination of the irreversible TKI afatinib and the EGFR antibody cetuximab can be used to overcome resistance to first-generation TKIs; however, resistance to this drug combination eventually emerges. We identified activation of the mTORC1 signaling pathway as a mechanism of resistance to dual inhibition of EGFR in mouse models. Addition of rapamycin reversed resistance in vivo. Analysis of afatinib+cetuximab-resistant biopsy specimens revealed the presence of genomic alterations in genes that modulate mTORC1 signaling including NF2 and TSC1. These findings pinpoint enhanced mTORC1 activation as a mechanism of resistance to afatinib+cetuximab and identify genomic mechanisms that lead to activation of this pathway, revealing a potential therapeutic strategy for treating patients with resistance to these drugs. PMID:24813888

  15. "Population structure of drug-susceptible, -resistant and ESBL-producing Escherichia coli from community-acquired urinary tract infections"

    DEFF Research Database (Denmark)

    Hertz, Frederik Boetius; Nielsen, Jesper Boye; Schønning, Kristian

    2016-01-01

    BACKGROUND: Escherichia coli is the most common cause of urinary tract infection (UTI). The pathogenic isolates are becoming increasingly resistant to antibiotics; with a worldwide dissemination of resistant sequence types (ST). We characterized three different uropathogenic E. coli populations...

  16. Resistance patterns and outcomes in intensive care unit (ICU)-acquired pneumonia. Validation of European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification of multidrug resistant organisms.

    Science.gov (United States)

    Martin-Loeches, Ignacio; Torres, Antonio; Rinaudo, Mariano; Terraneo, Silvia; de Rosa, Francesca; Ramirez, Paula; Diaz, Emili; Fernández-Barat, Laia; Li Bassi, Gian Luigi; Ferrer, Miquel

    2015-03-01

    Bacterial resistance has become a major public health problem. To validate the definition of multidrug-resistant organisms (MDRO) based on the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification. Prospective, observational study in six medical and surgical Intensive-Care-Units (ICU) of a University hospital. Three-hundred-and-forty-three patients with ICU-acquired pneumonia (ICUAP) were prospectively enrolled, 140 patients had no microbiological confirmation (41%), 82 patients (24%) developed ICUAP for non-MDRO, whereas 121 (35%) were MDROs. Non-MDRO, MDRO and no microbiological confirmation patients did not present either a significant different previous antibiotic use (p 0.18) or previous hospital admission (p 0.17). Appropriate antibiotic therapy was associated with better ICU survival (105 [92.9%] vs. 74 [82.2%]; p = 0.03). An adjusted multivariate regression logistic analysis identified that only MDRO had a higher ICU-mortality than non-MDRO and no microbiological confirmation patients (OR 2.89; p < 0.05; 95% CI for Exp [β]. 1.02-8.21); Patients with MDRO ICUAP remained in ICU for a longer period than MDRO and no microbiological confirmation respectively (p < 0.01) however no microbiological confirmation patients had more often antibiotic consumption than culture positive ones. Patients who developed ICUAP due to MDRO showed a higher ICU-mortality than non-MDRO ones and use of ICU resources. No microbiological confirmation patients had more often antibiotic consumption than culture positive patients. Risk factors for MDRO may be important for the selection of initial antimicrobial therapy, in addition to local epidemiology. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  17. Magnetic resonance imaging: early detection of central nervous system involvement in acquired immunodeficiency syndrome (AIDS)

    International Nuclear Information System (INIS)

    Trotot, P.M.; Sansonetti, P.J.; Levillain, R.; Cabanis, E.A.; Lavayssiere, R.; Sandoz-Tronca, C.

    1988-01-01

    Central Nervous System (CNS) involvement, whether primary by the Human Immunodeficiency Virus - HIV - itself, or secondary (toxoplasmosis or lymphoma) is remarkably frequent in AIDS, in 40 to 70% of cases, depending upon the author. In order to study the natural history of this illness, a cohort of 25 asymptomatic seropositive patients have been established. Every 6 months these patients undergo biological and clinical examinations, as well as Magnetic Resonance brain scans. After two examinations at a 6 month's interval, the first results are reported. Out of these 25 cases, 9 present anomalies: One patient with diffuse cerebral atrophy and 8 others with high signal intensity areas on T2 weighted sequences, like those of the Multiple Sclerosis. No relationship could be demonstrated between the existence of these lesions and various criteria such as age, sex, risk factors and T4 cells count. The nature of these lesions is not lear. They certainly indicate early involvement of the CNS after primary infection by the HIV virus. They may either represent scars of the primary infection or early alterations announcing developing encephalopathy [fr

  18. Description of new systems for acquiring in situ data from deep wells

    International Nuclear Information System (INIS)

    Peyrus, J.C.; Vinson, J.M.

    1984-02-01

    The studies being made by CEA/IPSN in respect of storage sites in a granite medium require a knowledge of the physico-chemical parameters of the water in the geological formation, since these waters are the principal vectors of hydrogeological transfers. In order to attain this objective, the design, construction and operation of two new experimental systems for sampling water in a deep well without modifying the pressure of the fluid as well was undertaken, at the same time as the measurement of pH, oxidation-reduction potential and water temperature of the aqueous medium. A pressure-compensated combined pH-Eh electrode for completely representative measurements down to 2000 metres was studied. The first results obtained at the Auriat site in France show confrontation with water belonging to the sodium bicarbonate facies, which is rich in CO 2 , CH 4 and H 2 , and that pH and Eh vary as a function of the mineralogical nature of the granite and tectonic fractures

  19. 14 CFR 29.952 - Fuel system crash resistance.

    Science.gov (United States)

    2010-01-01

    ... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Powerplant Fuel System § 29.952 Fuel system... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fuel system crash resistance. 29.952... of fuel fires to occupants following an otherwise survivable impact (crash landing), the fuel systems...

  20. 14 CFR 27.952 - Fuel system crash resistance.

    Science.gov (United States)

    2010-01-01

    ... AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Powerplant Fuel System § 27.952 Fuel system... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fuel system crash resistance. 27.952... of fuel fires to occupants following an otherwise survivable impact (crash landing), the fuel systems...

  1. Development of a CB Resistant Durable, Flexible Hydration System

    National Research Council Canada - National Science Library

    Hall, Peyton W; Zeller, Frank T; Bulluck, John W; Dingus, Michael L

    2002-01-01

    A durable, flexible hydration system resistant to contamination by contact with VX, GD, and HD chemical agents, as well as damage by the decontaminants sodium hypochlorite and DS-2 is being developed for aviator use...

  2. A Study of Transport Airplane Crash-Resistant Fuel Systems

    National Research Council Canada - National Science Library

    Robertson, S

    2002-01-01

    ...), of transport airplane crash-resistant fuel system (CRFS). The report covers the historical studies related to aircraft crash fires and fuel containment concepts undertaken by the FAA, NASA, and the U.S...

  3. Application of Various Lasers to Laser Trimming Resistance System

    Institute of Scientific and Technical Information of China (English)

    SUN Ji-feng

    2007-01-01

    Though the laser trimming resistance has been an old laser machining industry for over 30 years, the development of technology brings new alternative lasers which can be used for the traditional machining. The paper describes application of various lasers to laser trimming resistance system including early traditional krypton arc lamp pumped Nd:YAG to laser, modern popular diode pumped solid state laser and the present advanced harmonic diode pumped solid state laser. Using the new alternative lasers in the laser trimming resistance system can dramatically improve the yields and equipment performance.

  4. Antibacterial resistance of community-acquired respiratory tract pathogens recovered from patients in Latin America: results from the PROTEKT surveillance study (1999-2000

    Directory of Open Access Journals (Sweden)

    Mendes C.

    2003-01-01

    Full Text Available PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms. Thirteen centers from Argentina, Brazil and Mexico participat ed during 1999-2000; they collected 1,806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277. Overall, 218 (42.1% of the S. pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3% were penicillin-resistant and 79 (15.3% were erythromycin-resistant. Mexico had the highest prevalence of penicillin (76.5% and erythromycin (31.2% resistance. Of 77 erythromycin-resistant S. pneumoniae tested for resistance genotype, 43 possessed mef(A, 33 possessed erm(B and 1 possessed both erm(B and mef(A mechanism. All S. pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H. influenzae isolates, 88 (16.9% produced b-lactamase, ranging from 11% (Brazil to 24.5% (Mexico. Among M. catarrhalis isolates, 138 (98.6% produced b-lactamase. Twenty-four (8.7% of the S. pyogenes isolates were erythromycin-resistant; resistance being attributable to mefA (n=18, ermTR (n=5 and ermB (n=1. All H. influenzae, M. catarrhalis and S. pyogenes were fully susceptible to telithromycin. Methicillin resistance was found in 26.5% of the S. aureus isolates (Argentina 15%; Mexico 20%; Brazil 31.3%. Telithromycin was effective against 97.7% of methicillin-susceptible isolates. PROTEKT confirms that antibacterial resistance is an emerging problem in Latin America. The previously reported high levels of pneumococcal resistance to the b-lactam and macrolides were exceeded. New agents that do not induce resistance or that exert low selective pressure, e.g. telithromycin, are essential to safeguard future antibacterial efficacy.

  5. SoK: Making Sense of Censorship Resistance Systems

    Directory of Open Access Journals (Sweden)

    Khattak Sheharbano

    2016-10-01

    Full Text Available An increasing number of countries implement Internet censorship at different scales and for a variety of reasons. Several censorship resistance systems (CRSs have emerged to help bypass such blocks. The diversity of the censor’s attack landscape has led to an arms race, leading to a dramatic speed of evolution of CRSs. The inherent complexity of CRSs and the breadth of work in this area makes it hard to contextualize the censor’s capabilities and censorship resistance strategies. To address these challenges, we conducted a comprehensive survey of CRSs-deployed tools as well as those discussed in academic literature-to systematize censorship resistance systems by their threat model and corresponding defenses. To this end, we first sketch a comprehensive attack model to set out the censor’s capabilities, coupled with discussion on the scope of censorship, and the dynamics that influence the censor’s decision. Next, we present an evaluation framework to systematize censorship resistance systems by their security, privacy, performance and deployability properties, and show how these systems map to the attack model. We do this for each of the functional phases that we identify for censorship resistance systems: communication establishment, which involves distribution and retrieval of information necessary for a client to join the censorship resistance system; and conversation, where actual exchange of information takes place. Our evaluation leads us to identify gaps in the literature, question the assumptions at play, and explore possible mitigations.

  6. Ensemble Classifiers for Predicting HIV-1 Resistance from Three Rule-Based Genotypic Resistance Interpretation Systems.

    Science.gov (United States)

    Raposo, Letícia M; Nobre, Flavio F

    2017-08-30

    Resistance to antiretrovirals (ARVs) is a major problem faced by HIV-infected individuals. Different rule-based algorithms were developed to infer HIV-1 susceptibility to antiretrovirals from genotypic data. However, there is discordance between them, resulting in difficulties for clinical decisions about which treatment to use. Here, we developed ensemble classifiers integrating three interpretation algorithms: Agence Nationale de Recherche sur le SIDA (ANRS), Rega, and the genotypic resistance interpretation system from Stanford HIV Drug Resistance Database (HIVdb). Three approaches were applied to develop a classifier with a single resistance profile: stacked generalization, a simple plurality vote scheme and the selection of the interpretation system with the best performance. The strategies were compared with the Friedman's test and the performance of the classifiers was evaluated using the F-measure, sensitivity and specificity values. We found that the three strategies had similar performances for the selected antiretrovirals. For some cases, the stacking technique with naïve Bayes as the learning algorithm showed a statistically superior F-measure. This study demonstrates that ensemble classifiers can be an alternative tool for clinical decision-making since they provide a single resistance profile from the most commonly used resistance interpretation systems.

  7. Isolation and identification of antibiotic resistance genes in Staphylococcus aureus isolates from respiratory system infections in shahrekord, Iran

    Directory of Open Access Journals (Sweden)

    Maryam Reisi

    2014-07-01

    Full Text Available   Introduction : Staphylococcus aureus is considered as one of pathogenic agents in humans, that engages different body parts including respiratory system and causes to spend lots of costs and extending patient’s treatment period. This study which is performed to separate and investigate the pattern of antibiotic resistance in Staphylococcus aureus isolates from upper respiratory system infections in Shahrekord.   Materials and methods: This study was done by sectional-descriptive method On 200 suspicious persons to the upper respiratory system infections who were referred to the Imam Ali clinic in Shahrekord in 2012. After isolation of Staphylococcus aureus from cultured nose discharges, antibiotic resistance genes were identified by polymerase chain reaction (PCR by using defined primer pairs .   Results : Among 200 investigated samples in 60 cases (30% Staphylococcus aureus infection (by culturing and PCR method was determined. Isolates showed the lowest amount of antibiotic resistance to vancomycin (0.5% and the highest amount of resistance to the penicillin G and cefotaxime (100%. mecA gene (encoding methicillin resistance with frequency of 85.18% and aacA-D gene (encoding resistance to aminoglycosides with frequency of 28.33% showed the highest and lowest frequency of antibiotic resistance genes coding in Staphylococcus aureus isolates respectively .   Discussion and conclusion : Notable prevalence of resistant Staphylococcus aureus isolates in community acquired respiratory infections, recommend continuous control necessity to impede the spreading of these bacteria and their infections.  

  8. Activation of ErbB3, EGFR and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant

    DEFF Research Database (Denmark)

    Frogne, Thomas; Benjaminsen, Rikke; Sonne-Hansen, Katrine

    2008-01-01

    cell lines concomitant with inhibition of Erk and unaltered Akt activation. In concert, inhibition of Erk with U0126 preferentially reduced growth of resistant cell lines. Treatment with ErbB3 neutralizing antibodies inhibited ErbB3 activation and resulted in a modest but statistically significant...... activation was observed only in the parental MCF-7 cells. The downstream kinases pAkt and pErk were increased in five of seven and in all seven resistant cell lines, respectively. Treatment with the EGFR inhibitor gefitinib preferentially inhibited growth and reduced the S phase fraction in the resistant...... growth inhibition of two resistant cell lines. These data indicate that ligand activated ErbB3 and EGFR, and Erk signaling play important roles in fulvestrant resistant cell growth. Furthermore, the decreased level of ErbB4 in resistant cells may facilitate heterodimerization of ErbB3 with EGFR and ErbB2...

  9. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1

    Directory of Open Access Journals (Sweden)

    Valentina Pirazzoli

    2014-05-01

    Full Text Available Patients with EGFR-mutant lung adenocarcinomas (LUADs who initially respond to first-generation tyrosine kinase inhibitors (TKIs develop resistance to these drugs. A combination of the irreversible TKI afatinib and the EGFR antibody cetuximab can be used to overcome resistance to first-generation TKIs; however, resistance to this drug combination eventually emerges. We identified activation of the mTORC1 signaling pathway as a mechanism of resistance to dual inhibition of EGFR in mouse models. The addition of rapamycin reversed resistance in vivo. Analysis of afatinib-plus-cetuximab-resistant biopsy specimens revealed the presence of genomic alterations in genes that modulate mTORC1 signaling, including NF2 and TSC1. These findings pinpoint enhanced mTORC1 activation as a mechanism of resistance to afatinib plus cetuximab and identify genomic mechanisms that lead to activation of this pathway, revealing a potential therapeutic strategy for treating patients with resistance to these drugs.

  10. High prevalence of hospital-acquired infections caused by gram-negative carbapenem resistant strains in Vietnamese pediatric ICUs: A multi-centre point prevalence survey

    NARCIS (Netherlands)

    Le, N.K.; Wertheim, H.F.L.; Vu, P.D.; Khu, D.T.; Le, H.T.; Hoang, B.T.; Vo, V.T.; Lam, Y.M.; Vu, D.T.; Nguyen, Thanh Son; Thai, T.Q.; Nilsson, L.E.; Rydell, U.; Nguyen, K.V.; Nadjm, B.; Clarkson, L.; Hanberger, H.; Larsson, M.

    2016-01-01

    There is scarce information regarding hospital-acquired infections (HAIs) among children in resource-constrained settings. This study aims to measure prevalence of HAIs in Vietnamese pediatric hospitals.Monthly point prevalence surveys (PPSs) in 6 pediatric intensive care units (ICUs) in 3 referral

  11. c-Met Overexpression Contributes to the Acquired Apoptotic Resistance of Nonadherent Ovarian Cancer Cells through a Cross Talk Mediated by Phosphatidylinositol 3-Kinase and Extracellular Signal-Regulated Kinase 1/2

    Directory of Open Access Journals (Sweden)

    Maggie K.S. Tang

    2010-02-01

    Full Text Available Ovarian cancer is the most lethal gynecologic cancer mainly because of widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis, which also underlies their resistance to chemotherapy. Here, we used a nonadherent cell culture model to investigate the molecular mechanisms of apoptotic resistance of ovarian cancer cells that may mimic the chemoresistance found in solid tumors. We found that ovarian cancer cells acquired a remarkable resistance to anoikis and apoptosis induced by exposure to clinically relevant doses of two front-line chemotherapeutic drugs cisplatin and paclitaxel when grown in three-dimensional than monolayer cultures. Inhibition of the hepatocyte growth factor (HGF receptor c-Met, which is frequently overexpressed in ovarian cancer, by a specific inhibitor or small interfering RNA blocked the acquired anoikis resistance and restored chemosensitivity in three-dimensional not in two-dimensional cultures. These effects were found to be dependent on both phosphatidylinositol 3-kinase (PI3K/Akt and extracellular signal-regulated kinase (ERK 1/2 signaling pathways. Inhibitors of PI3K/Akt abrogated ERK1/2 activation and its associated anoikis resistance in response to HGF, suggesting a signaling relay between these two pathways. Furthermore, we identified a central role of Ras as a mechanism of this cross talk. Interestingly, Ras did not lie upstream of PI3K/Akt, whereas PI3K/Akt signaling to ERK1/2 involved Ras. These findings shed new light on the apoptotic resistance mechanism of nonadherent ovarian cancer ascites cells and may have important clinical implications.

  12. Assessing the User Resistance to Recommender Systems in Exhibition

    OpenAIRE

    Chulmo Koo; Namho Chung; Juyeon Ham

    2017-01-01

    Under the paradigm shift toward smart tourism, the exhibition industry is making efforts to introduce innovative technologies that can provide more diverse and valuable experiences to attendees. However, various new information technologies have failed in a market in practice due to the user’s resistance against it. Since innovative technology, such as booth recommender systems (BRS), is changing, creating uncertainty among consumers, consumer’s resistance to innovative technology can be cons...

  13. MR findings of central nervous system involvement in acquired immunodeficiency syndrome patient : a report of two cases

    International Nuclear Information System (INIS)

    Hong, Hye Suk; Kim, Dong Ik; Lee, Byeong Hee; Jeong, Sun Yang

    1996-01-01

    Central nervous system (CNS) manifestations in acquired immunodeficiency syndrome (AIDS) patients are an early and common feature. The spectrum of AIDS-related CNS diseases are encephalitis caused by the human immunodeficiency virus(HIV) itself, opportunistic infection, infarct and malignancy. We experienced two cases of CNS involvement in AIDS and they were serologically diagnosed as HIV encephalitis and CNS toxoplasmosis, respectively. In the case of the HIV encephalitis patient, brain MRI showed a non-enhancing lesion with high signal intensity on T2WI and low signal on T1WI and there was no mass effect on the right frontal lobe, periventricular white matter, splenium of the corpus callosum or bilateral basal ganglia. In the other case of CNS toxoplasmosis, MR showed multiple nodular and rim enhanced mass lesions in the right basal ganglia, thalamus and periventricular white matter, which were of low signal intensity on T1WI and of high intensity on T2WI. We thus report the related MRI findings

  14. SU-C-BRD-06: Sensitivity Study of An Automated System to Acquire and Analyze EPID Exit Dose Images

    Energy Technology Data Exchange (ETDEWEB)

    Olch, A; Zhuang, A [University of Southern California, Los Angeles, CA (United States)

    2015-06-15

    Purpose: The dosimetric consequences of errors in patient setup or beam delivery and anatomical changes are not readily known. A new product, PerFRACTION (Sun Nuclear Corporation), is designed to detect these errors by comparing the EPID exit dose image from each field of each fraction to those from baseline fraction images. This work investigates the sensitivity of PerFRACTION to detect the deviation of induced errors in a variety of realistic scenarios. Methods: Eight plans were created mimicking potential delivery or setup errors. The plans consisted of a nominal field and the field with an induced error. These were used to irradiate the EPID simulating multiple fractions with and without the error. Integrated EPID images were acquired in clinical mode and saved in ARIA. PerFRACTION automatically pulls the images into its database and performs the user defined comparison. In some cases, images were manually pushed to PerFRACTION. We varied the distance-to-agreement or dose tolerance until PerFRACTION showed failing pixels in the affected region and recorded the values. We induced errors of 1mm and greater in jaw, MLC, and couch position, 2 degree collimation rotation (patient yaw), and 0.5% to 1.5% in machine output. Both static and arc fields with the rails in or out were also acquired and compared. Results: PerFRACTION detected position errors of the jaws, MLC, and couch with an accuracy of better than 0.5 mm, and 0.2 degrees for collimator and gantry error. PerFRACTION detected a machine output error within 0.2% and detected the change in rail position. Conclusion: A new automated system for monitoring daily treatments for machine or patient variations from the first fraction using integrated EPID images was found to be sensitive enough to detect small positional, angular, and dosimetric errors within 0.5mm, 0.2 degrees, and 0.2%, respectively. Sun Nuclear Corporation has provided a software license for the product described.

  15. 76 FR 37356 - 2011 Scientific Meeting of the National Antimicrobial Resistance Monitoring System; Public...

    Science.gov (United States)

    2011-06-27

    ... animal and retail sampling methods for the National Antimicrobial Resistance Monitoring System (NARMS... Web site at http://www.fda.gov/AnimalVeterinary/SafetyHealth/AntimicrobialResistance/National...] 2011 Scientific Meeting of the National Antimicrobial Resistance Monitoring System; Public Meeting...

  16. miR Profiling Identifies Cyclin-Dependent Kinase 6 Downregulation as a Potential Mechanism of Acquired Cisplatin Resistance in Non-Small-Cell Lung Carcinoma.

    Science.gov (United States)

    Bar, Jair; Gorn-Hondermann, Ivan; Moretto, Patricia; Perkins, Theodore J; Niknejad, Nima; Stewart, David J; Goss, Glenwood D; Dimitroulakos, Jim

    2015-11-01

    To identify the mechanisms of cisplatin resistance, global microRNA (miR) expression was tested. The expression of miR-145 was consistently higher in resistant cells. The expression of cyclin-dependent kinase 6 (CDK6), a potential target of miR-145, was lower in resistant cells, and inhibition of CDK4/6 protected cells from cisplatin. Cell cycle inhibition, currently being tested in clinical trials, might be antagonistic to cisplatin and other cytotoxic drugs. Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Platinum-based chemotherapeutic drugs are the most active agents in treating advanced disease. Resistance to these drugs is common and multifactorial; insight into the molecular mechanisms involved will likely enhance efficacy. A set of NSCLC platinum-resistant sublines was created from the Calu6 cell line. Cell viability was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Differentially expressed microRNAs (miRs) in these lines were identified using Affymetrix miR arrays. The potential genes targeted by these miRs were searched using the TargetScan algorithm. The expression levels of miRs and mRNA were tested using real-time polymerase chain reaction. miR-145 was reproducibly elevated in all the resistant sublines tested; however, modulation of miR-145 levels alone in these cells did not affect their response to cisplatin. A potential target of miR-145 is cyclin-dependent kinase 6 (CDK6), an important regulator of cell proliferation. The mRNA and protein levels of CDK6 were both downregulated in the resistant sublines. An inhibitor of CDK4/6 (PD0332991) protected parental NSCLC cells from cisplatin cytotoxicity. In the present study, we identified miRs differentially expressed in cisplatin-resistant cell lines, including miR-145. A predicted target of miR-145 is CDK6, and its expression was found to be downregulated in the resistant sublines, although not directly by miR-145. Inhibition

  17. Modeling of the bacterial mechanism of methicillin-resistance by a systems biology approach.

    Directory of Open Access Journals (Sweden)

    Ida Autiero

    Full Text Available BACKGROUND: A microorganism is a complex biological system able to preserve its functional features against external perturbations and the ability of the living systems to oppose to these external perturbations is defined "robustness". The antibiotic resistance, developed by different bacteria strains, is a clear example of robustness and of ability of the bacterial system to acquire a particular functional behaviour in response to environmental changes. In this work we have modeled the whole mechanism essential to the methicillin-resistance through a systems biology approach. The methicillin is a beta-lactamic antibiotic that act by inhibiting the penicillin-binding proteins (PBPs. These PBPs are involved in the synthesis of peptidoglycans, essential mesh-like polymers that surround cellular enzymes and are crucial for the bacterium survival. METHODOLOGY: The network of genes, mRNA, proteins and metabolites was created using CellDesigner program and the data of molecular interactions are stored in Systems Biology Markup Language (SBML. To simulate the dynamic behaviour of this biochemical network, the kinetic equations were associated with each reaction. CONCLUSIONS: Our model simulates the mechanism of the inactivation of the PBP by methicillin, as well as the expression of PBP2a isoform, the regulation of the SCCmec elements (SCC: staphylococcal cassette chromosome and the synthesis of peptidoglycan by PBP2a. The obtained results by our integrated approach show that the model describes correctly the whole phenomenon of the methicillin resistance and is able to respond to the external perturbations in the same way of the real cell. Therefore, this model can be useful to develop new therapeutic approaches for the methicillin control and to understand the general mechanism regarding the cellular resistance to some antibiotics.

  18. Control system of power supply for resistance welding machine

    Directory of Open Access Journals (Sweden)

    Світлана Костянтинівна Поднебенна

    2017-06-01

    Full Text Available This article describes the existing methods of heat energy stabilizing, which are realized in thyristor power supplies for resistance welding machines. The advantages and features of thyristor power supplies have been described. A control system of power supply for resistance welding machine with stabilization of heat energy in a welding spot has been developed. Measurements are performed in primary winding of a welding transformer. Weld spot heating energy is calculated as the difference between the energy, consumed from the mains, and the energy losses in the primary and secondary circuits of the welding transformer as well as the energy losses in the transformer core. Algorithms of digital signal processing of the developed control system are described in the article. All measurements and calculations are preformed automatically in real-time. Input signals to the control system are: transformer primary voltage and current, temperature of the welding circuit. The designed control system ensures control of the welding heat energy and is not influenced by the supply voltage and impedance changes caused by insertion of the ferromagnetic mass in the welding circuit, the temperature change during the welding process. The developed control system for resistance welding machine makes it possible to improve the quality of welded joints, increase the efficiency of the resistance welding machine

  19. Double control systems for human T-cell leukemia virus type 1 by innate and acquired immunity.

    Science.gov (United States)

    Kannagi, Mari; Hasegawa, Atsuhiko; Kinpara, Shuichi; Shimizu, Yukiko; Takamori, Ayako; Utsunomiya, Atae

    2011-04-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the causative retrovirus of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-specific T-cell responses elicit antitumor and antiviral effects in experimental models, and are considered to be one of the most important determinants of the disease manifestation, since they are activated in HAM/TSP but not in ATL patients. The combination of low T-cell responses and elevated HTLV-1 proviral loads are features of ATL, and are also observed in a subpopulation of HTLV-1 carriers at the asymptomatic stage, suggesting that these features may be underlying risk factors. These risks may potentially be reduced by vaccination to activate HTLV-1-specific T-cell responses. HAM/TSP and ATL patients also differ in their levels of HTLV-1 mRNA expression, which are generally low in vivo but slightly higher in HAM/TSP patients. Our recent study indicated that viral expression in HTLV-1-infected T-cells is suppressed by stromal cells in culture through type-I IFNs. The suppression was reversible after isolation from the stromal cells, mimicking a long-standing puzzling phenomenon in HTLV-1 infection where the viral expression is very low in vivo and rapidly induced in vitro. Collectively, HTLV-1 is controlled by both acquired and innate immunity in vivo: HTLV-1-specific T-cells survey infected cells, and IFNs suppress viral expression. Both effects would contribute to a reduction in viral pathogenesis, although they may potentially influence or conflict with one another. The presence of double control systems for HTLV-1 infection provides a new concept for understanding the pathogenesis of HTLV-1-mediated malignant and inflammatory diseases. © 2011 Japanese Cancer Association.

  20. Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Costas Tsioufis

    2011-01-01

    Full Text Available Resistant hypertension (RH is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH.

  1. Trends in occcurrence of antimicrobial resistance in Campylobacter jejuni isolates from broiler chickens, broiler chicken meat, and human domestically acquired cases and travel associated cases ind Denmark

    DEFF Research Database (Denmark)

    Skjøt-Rasmussen, Line; Ethelberg, Steen; Emborg, Hanne-Dorthe

    2009-01-01

    Campylobacter jejuni is a frequent cause of bacterial gastroenteritis. Often it causes self-limiting disease but severe or prolonged cases may require antimicrobial treatment. The agricultural use of antimicrobial agents selects for resistance among C. jejuni which is transmitted to humans via food...

  2. Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents

    NARCIS (Netherlands)

    Michaelis, M.; Rothweiler, F.; Agha, B.; Barth, S.; Voges, Y.; Loeschmann, N.; von Deimling, A.; Breitling, R.; Doerr, H. Wilhelm; Roedel, F.; Speidel, D.; Cinatl, J.; Cinatl Jr., J.; Stephanou, A.

    Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3,

  3. Technical features to enhance proliferation resistance of nuclear energy systems

    International Nuclear Information System (INIS)

    2010-01-01

    It is generally accepted that proliferation resistance is an essential issue for the continued development and sustainability of nuclear energy. Several comprehensive assessment activities on the proliferation resistance of the nuclear fuel cycle have previously been completed, notably the International Nuclear Fuel Cycle Evaluation (INFCE) carried out under the auspices of the IAEA, and the Non-proliferation Alternative Systems Assessment Program (NASAP) review carried out by the USA. There have been, however, relatively few comprehensive treatments of the issue following these efforts in the 1970s. However, interest in and concern about this issue have increased recently, particularly because of greater interest in innovative nuclear fuel cycles and systems. In 2000, the IAEA initiated the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) and the US Department of Energy initiated the Generation IV International Forum (GIF). These projects are aimed at the selection and development of concepts of innovative nuclear energy systems and fuel cycles. Proliferation resistance is one of the fundamental considerations for both projects. In this context, the IAEA in 2001 initiated a study entitled 'Technical Aspects of Increasing Proliferation Resistance of the Nuclear Fuel Cycle'. This task is not intended as an effort to assess the merits of a particular fuel cycle system for the future, but to describe a qualitative framework for an examination of the proliferation resistance provided by the intrinsic features of an innovative nuclear energy system and fuel cycle. This task also seeks to provide a high level survey of a variety of innovative nuclear energy systems and fuel cycles with respect to that framework. The concept of proliferation resistance is considered in terms of intrinsic features and extrinsic measures. The intrinsic features, sometimes referred to as the physical/technical aspects, are those features that result from the

  4. PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors.

    Directory of Open Access Journals (Sweden)

    Anella Yahiaoui

    Full Text Available Activated B-cell-like diffuse large B-cell lymphoma relies on B-cell receptor signaling to drive proliferation and survival. Downstream of the B-cell receptor, the key signaling kinases Bruton's tyrosine kinase and phosphoinositide 3-kinase δ offer opportunities for therapeutic intervention by agents such as ibrutinib, ONO/GS-4059, and idelalisib. Combination therapy with such targeted agents could provide enhanced efficacy due to complimentary mechanisms of action. In this study, we describe both the additive interaction of and resistance mechanisms to idelalisib and ONO/GS-4059 in a model of activated B-cell-like diffuse large B-cell lymphoma. Significant tumor regression was observed with a combination of PI3Kδ and Bruton's tyrosine kinase inhibitors in the mouse TMD8 xenograft. Acquired resistance to idelalisib in the TMD8 cell line occurred by loss of phosphatase and tensin homolog and phosphoinositide 3-kinase pathway upregulation, but not by mutation of PIK3CD. Sensitivity to idelalisib could be restored by combining idelalisib and ONO/GS-4059. Further evaluation of targeted inhibitors revealed that the combination of idelalisib and the phosphoinositide-dependent kinase-1 inhibitor GSK2334470 or the AKT inhibitor MK-2206 could partially overcome resistance. Characterization of acquired Bruton's tyrosine kinase inhibitor resistance revealed a novel tumor necrosis factor alpha induced protein 3 mutation (TNFAIP3 Q143*, which led to a loss of A20 protein, and increased p-IκBα. The combination of idelalisib and ONO/GS-4059 partially restored sensitivity in this resistant line. Additionally, a mutation in Bruton's tyrosine kinase at C481F was identified as a mechanism of resistance. The combination activity observed with idelalisib and ONO/GS-4059, taken together with the ability to overcome resistance, could lead to a new therapeutic option in activated B-cell-like diffuse large B-cell lymphoma. A clinical trial is currently underway to

  5. Outcomes in elderly Danish citizens admitted with community-acquired pneumonia. Regional differences, in a public healthcare system

    DEFF Research Database (Denmark)

    Hedegaard Klausen, Henrik; Petersen, J; Lindhardt, T

    2012-01-01

    OBJECTIVES: To evaluate regional differences in and risk factors for admission, length of stay, mortality, and readmission for community-acquired pneumonia in elderly Danish patients. METHODS: National registry study on elderly Danish citizens with an acute admission in 2009 owing to community....... RESULTS: A total of 11,332 elderly citizens were admitted with community-acquired pneumonia. Mortality during admission and 30-days from discharge were 11.6% and 16.2%, respectively. Readmission rates within 30 days of discharge were 12.3%. There were significantly differences between hospitals in length...

  6. A Comparative Study of Coping Strategies and the Features of Interpersonal Relations and Life Orientations of People with Congenital and Acquired Diseases of the Musculoskeletal System

    Science.gov (United States)

    Romanova, E. V.; Tolkacheva, O. N.

    2016-01-01

    The article presents the results of a comparative study of the features of the coping strategies, life orientations, and interpersonal relations of disabled people with acquired and congenital diseases of the musculoskeletal system. The authors discovered differences in interpersonal behavior in the area of control, and they revealed factors that…

  7. Arrester Resistive Current Measuring System Based on Heterogeneous Network

    Science.gov (United States)

    Zhang, Yun Hua; Li, Zai Lin; Yuan, Feng; Hou Pan, Feng; Guo, Zhan Nan; Han, Yue

    2018-03-01

    Metal Oxide Arrester (MOA) suffers from aging and poor insulation due to long-term impulse voltage and environmental impact, and the value and variation tendency of resistive current can reflect the health conditions of MOA. The common wired MOA detection need to use long cables, which is complicated to operate, and that wireless measurement methods are facing the problems of poor data synchronization and instability. Therefore a novel synchronous measurement system of arrester current resistive based on heterogeneous network is proposed, which simplifies the calculation process and improves synchronization, accuracy and stability and of the measuring system. This system combines LoRa wireless network, high speed wireless personal area network and the process layer communication, and realizes the detection of arrester working condition. Field test data shows that the system has the characteristics of high accuracy, strong anti-interference ability and good synchronization, which plays an important role in ensuring the stable operation of the power grid.

  8. Rapid containment of nosocomial transmission of a rare community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone, responsible for the Staphylococcal Scalded Skin Syndrome (SSSS)

    OpenAIRE

    Lamanna, Onofrio; Bongiorno, Dafne; Bertoncello, Lisa; Grandesso, Stefano; Mazzucato, Sandra; Pozzan, Giovanni Battista; Cutrone, Mario; Chirico, Michela; Baesso, Flavia; Brugnaro, Pierluigi; Cafiso, Viviana; Stefani, Stefania; Campanile, Floriana

    2017-01-01

    Background The aims of this study were to identify the source and the transmission pathway for a Staphylococcal Scalded Skin Syndrome (SSSS) outbreak in a maternity setting in Italy over 2?months, during 2014; to implement appropriate control measures in order to prevent the epidemic spread within the maternity ward; and to identify the Methicillin-Resistant Staphylococcus aureus (MRSA) epidemic clone. Methods Epidemiological and microbiological investigations, based on phenotyping and genoty...

  9. Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in EGFR Mutant and ALK Positive Lung Cancers

    Science.gov (United States)

    2016-10-01

    University Philips Institute for Oral Health Research, Virginia Commonwealth University School of Dentistry, Richmond, Virginia, USA. 12Virginia...resistance. We have gained tremendous new knowledge about this arena thanks to the funding we received from DOD. Specifically, we have studied in detail...we compared the transcriptional profiles parental PC9 cells with those of PC9-GR2 and PC9-GR3. Gene-set enrichment analysis revealed the upregulation

  10. The predictive validity of naturally acquired delayed-type hypersensitivity to leishmanin in resistance to Leishmania major-associated cutaneous leishmaniasis.

    Science.gov (United States)

    Ben Salah, Afif; Louzir, Hechmi; Chlif, Sadok; Mokni, Mourad; Zaatour, Amor; Raouene, Mohamed; Ismail, Riadh Ben; Dellagi, Koussay

    2005-12-01

    To accurately quantify the different outcomes of Leishmania major infection and to evaluate the fraction of zoonotic cutaneous leishmaniasis (ZCL) cases prevented by naturally acquired leishmanin skin test (LST) reactivity, a cohort of 470 children was followed up in 2 endemic foci, Remada and Dhiba, in southern Tunisia. During May 1997, before the ZCL emergence season, LST was performed, and results were reassessed 12 months later. Active case detection during the ZCL emergence season showed a high incidence of ZCL: 57.0% in Remada and 13.7% in Dhiba. The preventive fraction of ZCL conferred by LST reactivity increased proportionally with the reaction size before the emergence season, revealing a dose-response effect of approximately 70%. In addition, asymptomatic L. major infection appeared to be a significant form of natural immunization, particularly in the context of relatively low transmission. These findings may help in the design and evaluation of vaccines.

  11. Translocation of integron-associated resistance in a natural system: Acquisition of resistance determinants by Inc P and Inc W Plasmids from Salmonella enterica Typhimurium DT104

    DEFF Research Database (Denmark)

    Sandvang, Dorthe; Diggle, M.; Platt, D.J.

    2002-01-01

    to determinate the genetic content. Translocation to R751 and R388 was associated with the loss of the indigenous trimethoprim cassette to both plasmids and also acquisition of sulfonamide resistance by R751 and RP4::Tn7, which indicated movement of the 3' terminus of one or both of the DT104 integrons......Salmonella enterica Typhimurium DT104, 961368, a veterinary field isolate that encodes a chromosomal cluster of resistance genes as well as two integrons, was used to study the mobility of resistance cassettes (aadA2 and pse-1) and nonintegron-associated resistance determinants (chloramphenicol...... and tetracycline). A range of natural plasmids was used as targets for the translocation of resistance. Plasmids that acquired resistance from the DT104 chromosome were segregated by conjugation into Escherichia coli K12. Plasmids R751, R388, and RP4::Tn7 acquired several combinations of resistance determinant...

  12. Estimating spatially distributed turbulent heat fluxes from high-resolution thermal imagery acquired with a UAV system.

    Science.gov (United States)

    Brenner, Claire; Thiem, Christina Elisabeth; Wizemann, Hans-Dieter; Bernhardt, Matthias; Schulz, Karsten

    2017-05-19

    In this study, high-resolution thermal imagery acquired with a small unmanned aerial vehicle (UAV) is used to map evapotranspiration (ET) at a grassland site in Luxembourg. The land surface temperature (LST) information from the thermal imagery is the key input to a one-source and two-source energy balance model. While the one-source model treats the surface as a single uniform layer, the two-source model partitions the surface temperature and fluxes into soil and vegetation components. It thus explicitly accounts for the different contributions of both components to surface temperature as well as turbulent flux exchange with the atmosphere. Contrary to the two-source model, the one-source model requires an empirical adjustment parameter in order to account for the effect of the two components. Turbulent heat flux estimates of both modelling approaches are compared to eddy covariance (EC) measurements using the high-resolution input imagery UAVs provide. In this comparison, the effect of different methods for energy balance closure of the EC data on the agreement between modelled and measured fluxes is also analysed. Additionally, the sensitivity of the one-source model to the derivation of the empirical adjustment parameter is tested. Due to the very dry and hot conditions during the experiment, pronounced thermal patterns developed over the grassland site. These patterns result in spatially variable turbulent heat fluxes. The model comparison indicates that both models are able to derive ET estimates that compare well with EC measurements under these conditions. However, the two-source model, with a more complex treatment of the energy and surface temperature partitioning between the soil and vegetation, outperformed the simpler one-source model in estimating sensible and latent heat fluxes. This is consistent with findings from prior studies. For the one-source model, a time-variant expression of the adjustment parameter (to account for the difference between

  13. Human neuroblastoma cells with acquired resistance to the p53 activator RITA retain functional p53 and sensitivity to other p53 activating agents.

    Science.gov (United States)

    Michaelis, M; Rothweiler, F; Agha, B; Barth, S; Voges, Y; Löschmann, N; von Deimling, A; Breitling, R; Doerr, H Wilhelm; Rödel, F; Speidel, D; Cinatl, J

    2012-04-05

    Adaptation of wild-type p53 expressing UKF-NB-3 cancer cells to the murine double minute 2 inhibitor nutlin-3 causes de novo p53 mutations at high frequency (13/20) and multi-drug resistance. Here, we show that the same cells respond very differently when adapted to RITA, a drug that, like nutlin-3, also disrupts the p53/Mdm2 interaction. All of the 11 UKF-NB-3 sub-lines adapted to RITA that we established retained functional wild-type p53 although RITA induced a substantial p53 response. Moreover, all RITA-adapted cell lines remained sensitive to nutlin-3, whereas only five out of 10 nutlin-3-adapted cell lines retained their sensitivity to RITA. In addition, repeated adaptation of the RITA-adapted sub-line UKF-NB-3(r)RITA(10 μM) to nutlin-3 resulted in p53 mutations. The RITA-adapted UKF-NB-3 sub-lines displayed no or less pronounced resistance to vincristine, cisplatin, and irradiation than nutlin-3-adapted UKF-NB-3 sub-lines. Furthermore, adaptation to RITA was associated with fewer changes at the expression level of antiapoptotic factors than observed with adaptation to nutlin-3. Transcriptomic analyses indicated the RITA-adapted sub-lines to be more similar at the gene expression level to the parental UKF-NB-3 cells than nutlin-3-adapted UKF-NB-3 sub-lines, which correlates with the observed chemotherapy and irradiation sensitivity phenotypes. In conclusion, RITA-adapted cells retain functional p53, remain sensitive to nutlin-3, and display a less pronounced resistance phenotype than nutlin-3-adapted cells.

  14. Antimicrobial resistance: A global emerging threat to public health systems.

    Science.gov (United States)

    Ferri, Maurizio; Ranucci, Elena; Romagnoli, Paola; Giaccone, Valerio

    2017-09-02

    Antimicrobial resistance (AMR) became in the last two decades a global threat to public health systems in the world. Since the antibiotic era, with the discovery of the first antibiotics that provided consistent health benefits to human medicine, the misuse and abuse of antimicrobials in veterinary and human medicine have accelerated the growing worldwide phenomenon of AMR. This article presents an extensive overview of the epidemiology of AMR, with a focus on the link between food producing-animals and humans and on the legal framework and policies currently implemented at the EU level and globally. The ways of responding to the AMR challenges foresee an array of measures that include: designing more effective preventive measures at farm level to reduce the use of antimicrobials; development of novel antimicrobials; strengthening of AMR surveillance system in animal and human populations; better knowledge of the ecology of resistant bacteria and resistant genes; increased awareness of stakeholders on the prudent use of antibiotics in animal productions and clinical arena; and the public health and environmental consequences of AMR. Based on the global nature of AMR and considering that bacterial resistance does not recognize barriers and can spread to people and the environment, the article ends with specific recommendations structured around a holistic approach and targeted to different stakeholders.

  15. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet

    Science.gov (United States)

    Mabuchi, Yuko; Frankel, Theresa L.

    2016-01-01

    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons. PMID:27069640

  16. Assessing the User Resistance to Recommender Systems in Exhibition

    Directory of Open Access Journals (Sweden)

    Chulmo Koo

    2017-11-01

    Full Text Available Under the paradigm shift toward smart tourism, the exhibition industry is making efforts to introduce innovative technologies that can provide more diverse and valuable experiences to attendees. However, various new information technologies have failed in a market in practice due to the user’s resistance against it. Since innovative technology, such as booth recommender systems (BRS, is changing, creating uncertainty among consumers, consumer’s resistance to innovative technology can be considered a normal reaction. Therefore, it is important for a company to understand the psychological aspect of the consumer’s resistance and make measures to overcome the resistance. Accordingly, based on the model of Kim and Kankanhalli (2009, by applying the perceived value, the technology acceptance model, and the status quo bias theory, this study focused on the importance of self-efficacy and technical support in the context of using BRS. To do this purpose, a total of 455 survey data that was collected from “Korea franchise exhibition” attendees were used to analyze the proposed model. Structural equation modeling was applied for data analysis. The result shows that perceived value was affected by relative advantage and switching cost, also switching cost reduced the perceived value. However, self-efficacy reduced the switching cost, thereby decreasing the resistance of exhibition attendees. In addition, technical support increased the relative advantage switching cost and the perceived value. Exhibition attendee’s resistance was significantly negatively affected by perceived value, and positively affected by switching cost. The results will provide balanced viewpoints between the relative advantage and switching cost for exhibition marketers, helping to strengthen the competitiveness in terms of sustainable tourism of exhibition.

  17. Detecting the Hormonal Pathways in Oilseed Rape behind Induced Systemic Resistance by Trichoderma harzianum TH12 to Sclerotinia sclerotiorum.

    Science.gov (United States)

    Alkooranee, Jawadayn Talib; Aledan, Tamarah Raad; Ali, Ali Kadhim; Lu, Guangyuan; Zhang, Xuekun; Wu, Jiangsheng; Fu, Chunhua; Li, Maoteng

    2017-01-01

    Plants have the ability to resist pathogen attack after infection or treatment with biotic and abiotic elicitors. In oilseed rape plant Brassica napus AACC and in the artificially synthesized Raphanus alboglabra RRCC, the root-colonizing Trichoderma harzianum TH12 fungus triggers induced systemic resistance (ISR), and its culture filtrate (CF) triggers a systemic acquired resistance (SAR) response against infection by the Sclerotinia sclerotiorum. Salicylic acid (SA) and jasmonic acid/ethylene (JA/ET) are plant hormone signals that play important roles in the regulation of ISR and SAR. In this study, at six different time points (1, 2, 4, 6, 8 and 10 days post-infection [dpi]), six resistance genes were used as markers of signaling pathways: JA/ET signaling used AOC3, PDF1.2 and ERF2 genes, while PR-1, TGA5 and TGA6 genes were used as markers of SA signaling. The results of quantitative real-time polymerase chain reaction (qRT-PCR) showed that AOC3, PDF1.2 and ERF2 expression levels in infected leaves of AACC and RRCC increase at 1 and 2 dpi with S. sclerotiorum or inoculation with TH12. PR-1, TGA5 and TGA6 expression levels increased at 8 and 10 dpi in infected leaves. PR-1, TGA5 and TGA6 expression levels increased early in plants treated with CF in both of the healthy genotypes. Furthermore, induction of SA- and JA/ET-dependent defense decreased disease symptoms in infected leaves at different times. The results suggest that the RRCC genotype exhibits resistance to disease and that the ability of TH12 and its CF to induce systemic resistance in susceptible and resistant oilseed rape genotypes exists. In addition, the results indicate for the first time that in RRCC the SA signaling pathway is involved in resistance to necrotrophic pathogens.

  18. Acquiring research-grade ERPs on a shoestring budget: A comparison of a modified Emotiv and commercial SynAmps EEG system.

    Science.gov (United States)

    Barham, Michael P; Clark, Gillian M; Hayden, Melissa J; Enticott, Peter G; Conduit, Russell; Lum, Jarrad A G

    2017-09-01

    This study compared the performance of a low-cost wireless EEG system to a research-grade EEG system on an auditory oddball task designed to elicit N200 and P300 ERP components. Participants were 15 healthy adults (6 female) aged between 19 and 40 (M = 28.56; SD = 6.38). An auditory oddball task was presented comprising 1,200 presentations of a standard tone interspersed by 300 trials comprising a deviant tone. EEG was simultaneously recorded from a modified Emotiv EPOC and a NeuroScan SynAmps RT EEG system. The modifications made to the Emotiv system included attaching research grade electrodes to the Bluetooth transmitter. Additional modifications enabled the Emotiv system to connect to a portable impedance meter. The cost of these modifications and portable impedance meter approached the purchase value of the Emotiv system. Preliminary analyses revealed significantly more trials were rejected from data acquired by the modified Emotiv compared to the SynAmps system. However, the ERP waveforms captured by the Emotiv system were found to be highly similar to the corresponding waveform from the SynAmps system. The latency and peak amplitude of N200 and P300 components were also found to be similar between systems. Overall, the results indicate that, in the context of an oddball task, the ERP acquired by a low-cost wireless EEG system can be of comparable quality to research-grade EEG acquisition equipment. © 2017 Society for Psychophysiological Research.

  19. Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate

    DEFF Research Database (Denmark)

    Sørensen, Belinda Halling; Thorsteinsdottir, Unnur Arna; Lambert, Ian Henry

    2014-01-01

    Cisplatin resistance is a major challenge in the treatment of cancer and develops through reduced drug accumulation and an increased ability to avoid drug-induced cell damage, cell shrinkage, and hence initiation of apoptosis. Uptake and release of the semiessential amino acid taurine contribute...... to cell volume homeostasis, and taurine has been reported to have antiapoptotic effects. Here we find that volume-sensitive taurine release in cisplatin-sensitive [wild-type (WT)] human ovarian cancer A2780 cells is reduced in the presence of the phospholipase A2 inhibitor bromenol lactone, the 5......-induced cell death in RES A2780 cells correlates with an increased accumulation of taurine, due to an increased taurine uptake and a concomitant impairment of the volume-sensitive taurine release pathway, as well an inability to reduce cell volume after osmotic cell swelling. Downregulation of volume...

  20. Dual HER2\\PIK3CA targeting overcomes single-agent acquired resistance in HER2 amplified uterine serous carcinoma cell lines in vitro and in vivo

    Science.gov (United States)

    Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L.; English, Diana P.; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E.; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D.

    2015-01-01

    HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC), and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA mutated and PIK3CA-wild type HER2/neu amplified USC cell lines. Cell viability and cell cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC-xenografts. We found both single agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long lasting growth inhibition in both USC xenografts when compared to single agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0/G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA or pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild type PIK3CA resistant to chemotherapy. PMID:26333383

  1. Dual HER2/PIK3CA Targeting Overcomes Single-Agent Acquired Resistance in HER2-Amplified Uterine Serous Carcinoma Cell Lines In Vitro and In Vivo.

    Science.gov (United States)

    Lopez, Salvatore; Cocco, Emiliano; Black, Jonathan; Bellone, Stefania; Bonazzoli, Elena; Predolini, Federica; Ferrari, Francesca; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Terranova, Corrado; Angioli, Roberto; Santin, Alessandro D

    2015-11-01

    HER2/neu gene amplification and PIK3CA driver mutations are common in uterine serous carcinoma (USC) and may represent ideal therapeutic targets against this aggressive variant of endometrial cancer. We examined the sensitivity to neratinib, taselisib, and the combination of the two compounds in in vitro and in vivo experiments using PIK3CA-mutated and PIK3CA wild-type HER2/neu-amplified USC cell lines. Cell viability and cell-cycle distribution were assessed using flow-cytometry assays. Downstream signaling was assessed by immunoblotting. Preclinical efficacy of single versus dual inhibition was evaluated in vivo using two USC xenografts. We found both single-agent neratinib and taselisib to be active but only transiently effective in controlling the in vivo growth of USC xenografts harboring HER2/neu gene amplification with or without oncogenic PIK3CA mutations. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in both USC xenografts when compared with single-agent therapy. Combined targeting of HER2 and PIK3CA was associated with a significant and dose-dependent increase in the percentage of cells in the G0-G1 phase of the cell cycle and a dose-dependent decline in the phosphorylation of S6. Importantly, dual inhibition therapy initiated after tumor progression in single-agent-treated mice was still remarkably effective at inducing tumor regression in both large PIK3CA and pan-ErbB inhibitor-resistant USC xenografts. Dual HER2/PIK3CA blockade may represent a novel therapeutic option for USC patients harboring tumors with HER2/neu gene amplification and mutated or wild-type PIK3CA resistant to chemotherapy. ©2015 American Association for Cancer Research.

  2. Antimicrobial resistance, heavy metal resistance and integron content in bacteria isolated from a South African tilapia aquaculture system.

    Science.gov (United States)

    Chenia, Hafizah Y; Jacobs, Anelet

    2017-11-21

    Antibacterial compounds and metals co-select for antimicrobial resistance when bacteria harbour resistance genes towards both types of compounds, facilitating the proliferation and evolution of antimicrobial and heavy metal resistance. Antimicrobial and heavy metal resistance indices of 42 Gram-negative bacteria from a tilapia aquaculture system were determined to identify possible correlations between these phenotypes. Agar dilution assays were carried out to determine susceptibility to cadmium, copper, lead, mercury, chromate and zinc, while susceptibility to 21 antimicrobial agents was investigated by disk diffusion assays. Presence of merA, the mercury resistance gene, was determined by dot-blot hybridizations and PCR. Association of mercury resistance with integrons and transposon Tn21 was also investigated by PCR. Isolates displayed a high frequency of antimicrobial (erythromycin: 100%; ampicillin: 85%; trimethoprim: 78%) and heavy metal (Zn2+: 95%; Cd2+: 91%) resistance. No correlation was established between heavy metal and multiple antibiotic resistance indices. Significant positive correlations were observed between heavy metal resistance profiles, indices, Cu2+ and Cr3+ resistance with erythromycin resistance. Significant positive correlations were observed between merA (24%)/Tn21 (24%) presence and heavy metal resistance profiles and indices; however, significant negative correlations were obtained between integron-associated qacE∆1 (43%) and sulI (26%) gene presence and heavy metal resistance indices. Heavy metal and antimicrobial agents co-select for resistance, with fish-associated, resistant bacteria demonstrating simultaneous heavy metal resistance. Thus, care should be taken when using anti-fouling heavy metals as feed additives in aquaculture facilities.

  3. Enfermedad invasora por Staphylococcus aureus meticilino resistente adquirida en la comunidad Community-acquired methicillin-resistant Staphylococcus aureus disseminated disease

    Directory of Open Access Journals (Sweden)

    Clarisa Brezzo

    2006-10-01

    Full Text Available Se presenta un caso de enfermedad invasora por Staphylococcus aureus meticilino resistente (SAMR adquirido en la comunidad (SAMR-c. Paciente varón de 21 años, previamente sano, que consultó por nódulos subcutáneos compatibles con gomas. La ultrasonografía reveló múltiples abscesos subcutáneos e imágenes consistentes con piomiositis, además de derrame pleural y pericárdico. En el cultivo del material purulento obtenido por punción-aspiración con aguja fina de las lesiones se aisló S. aureus. El antibiograma por difusión mostró resistencia a cefalotina, eritromicina y clindamicina, y sensibilidad a trimetroprima-sulfametoxazol, ciprofloxacina y rifampicina. La meticilino resistencia se confirmó por aglutinación con partículas de látex sensibilizadas con anticuerpos monoclonales dirigidos contra la proteína ligadora de penicilina 2A. El paciente fue tratado con ciprofloxacina y rifampicina durante cuatro semanas, con evolución favorable. La frecuencia de infecciones por SAMR-c está en aumento, observándose en personas sin factores de riesgo aparentes. Esto llevaría a fracaso en el tratamiento empírico para infecciones de la comunidad en los que se presume etiología estafilocócica.A 21 year old man, previously healthy, presented with subcutaneous nodes consistent with gummas. Ultrasonography disclosed multiple subcutaneous abscesses and images suitable with piomiositis, pleural and pericardium effusion. A puncture-aspirate with fine-needle was performed and produced purulent material, with isolate of Staphylococcus aureus. Antimicrobial susceptibility testing by disk diffusion showed resistant to cefalotin, erythromycin and clindamycin, and susceptibility to trimethoprim-sulfamethoxazole, ciprofloxacin and rifampicin. Methicilin-resistance was confirmed by Staphyslide agglutination testing (Biomérieux. The patient was treated with ciprofloxacin and rifampicin during four weeks, with a good clinical response. The

  4. The Hospital Water Environment as a Reservoir for Carbapenem-Resistant Organisms Causing Hospital-Acquired Infections-A Systematic Review of the Literature.

    Science.gov (United States)

    Kizny Gordon, Alice E; Mathers, Amy J; Cheong, Elaine Y L; Gottlieb, Thomas; Kotay, Shireen; Walker, A Sarah; Peto, Timothy E A; Crook, Derrick W; Stoesser, Nicole

    2017-05-15

    Over the last 20 years there have been 32 reports of carbapenem-resistant organisms in the hospital water environment, with half of these occurring since 2010. The majority of these reports have described associated clinical outbreaks in the intensive care setting, affecting the critically ill and the immunocompromised. Drains, sinks, and faucets were most frequently colonized, and Pseudomonas aeruginosa the predominant organism. Imipenemase (IMP), Klebsiella pneumoniae carbapenemase (KPC), and Verona integron-encoded metallo-β-lactamase (VIM) were the most common carbapenemases found. Molecular typing was performed in almost all studies, with pulse field gel electrophoresis being most commonly used. Seventy-two percent of studies reported controlling outbreaks, of which just more than one-third eliminated the organism from the water environment. A combination of interventions seems to be most successful, including reinforcement of general infection control measures, alongside chemical disinfection. The most appropriate disinfection method remains unclear, however, and it is likely that replacement of colonized water reservoirs may be required for long-term clearance. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  5. Rapid containment of nosocomial transmission of a rare community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone, responsible for the Staphylococcal Scalded Skin Syndrome (SSSS).

    Science.gov (United States)

    Lamanna, Onofrio; Bongiorno, Dafne; Bertoncello, Lisa; Grandesso, Stefano; Mazzucato, Sandra; Pozzan, Giovanni Battista; Cutrone, Mario; Chirico, Michela; Baesso, Flavia; Brugnaro, Pierluigi; Cafiso, Viviana; Stefani, Stefania; Campanile, Floriana

    2017-01-06

    The aims of this study were to identify the source and the transmission pathway for a Staphylococcal Scalded Skin Syndrome (SSSS) outbreak in a maternity setting in Italy over 2 months, during 2014; to implement appropriate control measures in order to prevent the epidemic spread within the maternity ward; and to identify the Methicillin-Resistant Staphylococcus aureus (MRSA) epidemic clone. Epidemiological and microbiological investigations, based on phenotyping and genotyping methods, were performed. All neonates involved in the outbreak underwent clinical and microbiological investigations to detect the cause of illness. Parents and healthcare workers were screened for Staphylococcus aureus to identify asymptomatic carriers. The SSSS outbreak was due to the cross-transmission of a rare clone of ST5-CA-MRSA-SCCmecV-spa type t311, exfoliative toxin A-producer, isolated from three neonates, one mother (from her nose and from dermatological lesions due to pre-existing hand eczema) and from a nurse (colonized in her nose by this microorganism). The epidemiological and microbiological investigation confirmed these as two potential carriers. A rapid containment of these infections was obtained only after implementation of robust swabbing of mothers and healthcare workers. The use of molecular methodologies for typing was able to identify all carriers and to trace the transmission.

  6. Design of a CRISPR-Cas system to increase resistance of Bacillus subtilis to bacteriophage SPP1.

    Science.gov (United States)

    Jakutyte-Giraitiene, Lina; Gasiunas, Giedrius

    2016-08-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) together with CRISPR-associated (cas) genes form an adaptive prokaryotic immune system which provides acquired resistance against viruses and plasmids. Bacillus subtilis presently is the best-characterized laboratory model for Gram-positive bacteria and also widely used for industrial production of enzymes, vitamins and antibiotics. In this study, we show that type II-A CRISPR-Cas system from Streptococcus thermophilus can be transferred into B. subtilis and provides heterologous protection against phage infection. We engineered a heterologous host by cloning S. thermophilus Cas9 and a spacer targeting bacteriophage SPP1 into the chromosome of B. subtilis, which does not harbor its own CRISPR-Cas systems. We found that the heterologous CRISPR-Cas system is functionally active in B. subtilis and provides resistance against bacteriophage SPP1 infection. The high efficiency of the acquired immunity against phage could be useful in generation of biotechnologically important B. subtilis strains with engineered chromosomes.

  7. The dominant Australian community-acquired methicillin-resistant Staphylococcus aureus clone ST93-IV [2B] is highly virulent and genetically distinct.

    Directory of Open Access Journals (Sweden)

    Kyra Y L Chua

    Full Text Available Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159 to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding α-hemolysin, Panton-Valentine leukocidin (PVL and α-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total. These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300 share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2. This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid

  8. Identification and functional characterisation of Complement Regulator Acquiring Surface Protein-1 of serum resistant Borrelia garinii OspA serotype 4

    NARCIS (Netherlands)

    van Burgel, Nathalie D.; Kraiczy, Peter; Schuijt, Tim J.; Zipfel, Peter F.; van Dam, Alje P.

    2010-01-01

    B. burgdorferi sensu lato (sl) is the etiological agent of Lyme borreliosis in humans. Spirochetes have adapted themselves to the human immune system in many distinct ways. One important immune escape mechanism for evading complement activation is the binding of complement regulators Factor H (CFH)

  9. MEHODOLOGY FOR PROLIFERATION RESISTANCE FOR ADVANCE NUCLEAR ENERGY SYSTEMS

    International Nuclear Information System (INIS)

    YUE, M.; CHANG, L.Y.; BARI, R.

    2006-01-01

    The Technology Goals for Generation IV nuclear energy systems highlight Proliferation Resistance and Physical Protection (PRandPP) as one of the four goal areas for Generation 1V nuclear technology. Accordingly, an evaluation methodology is being developed by a PRandPP Experts Group. This paper presents a possible approach, which is based on Markov modeling, to the evaluation methodology for Generation IV nuclear energy systems being developed for PRandPP. Using the Markov model, a variety of proliferation scenarios can be constructed and the proliferation resistance measures can be quantified, particularly the probability of detection. To model the system with increased fidelity, the Markov model is further developed to incorporate multiple safeguards approaches in this paper. The approach to the determination of the associated parameters is presented. Evaluations of diversion scenarios for an example sodium fast reactor (ESFR) energy system are used to illustrate the methodology. The Markov model is particularly useful because it can provide the probability density function of the time it takes for the effort to be detected at a specific stage of the proliferation effort

  10. Newer systems for bacterial resistances to toxic heavy metals.

    Science.gov (United States)

    Silver, S; Ji, G

    1994-01-01

    Bacterial plasmids contain specific genes for resistances to toxic heavy metal ions including Ag+, AsO2-, AsO4(3-), Cd2+, Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, Sb3+, and Zn2+. Recent progress with plasmid copper-resistance systems in Escherichia coli and Pseudomonas syringae show a system of four gene products, an inner membrane protein (PcoD), an outer membrane protein (PcoB), and two periplasmic Cu(2+)-binding proteins (PcoA and PcoC). Synthesis of this system is governed by two regulatory proteins (the membrane sensor PcoS and the soluble responder PcoR, probably a DNA-binding protein), homologous to other bacterial two-component regulatory systems. Chromosomally encoded Cu2+ P-type ATPases have recently been recognized in Enterococcus hirae and these are closely homologous to the bacterial cadmium efflux ATPase and the human copper-deficiency disease Menkes gene product. The Cd(2+)-efflux ATPase of gram-positive bacteria is a large P-type ATPase, homologous to the muscle Ca2+ ATPase and the Na+/K+ ATPases of animals. The arsenic-resistance system of gram-negative bacteria functions as an oxyanion efflux ATPase for arsenite and presumably antimonite. However, the structure of the arsenic ATPase is fundamentally different from that of P-type ATPases. The absence of the arsA gene (for the ATPase subunit) in gram-positive bacteria raises questions of energy-coupling for arsenite efflux. The ArsC protein product of the arsenic-resistance operons of both gram-positive and gram-negative bacteria is an intracellular enzyme that reduces arsenate [As(V)] to arsenite [As(III)], the substrate for the transport pump. Newly studied cation efflux systems for Cd2+, Zn2+, and Co2+ (Czc) or Co2+ and Ni2+ resistance (Cnr) lack ATPase motifs in their predicted polypeptide sequences. Therefore, not all plasmid-resistance systems that function through toxic ion efflux are ATPases. The first well-defined bacterial metallothionein was found in the cyanobacterium Synechococcus

  11. Peripheral nervous system insulin resistance in ob/ob mice

    Science.gov (United States)

    2013-01-01

    Background A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. Results The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. Conclusions These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy. PMID:24252636

  12. Microvillar cell surface as a natural defense system against xenobiotics: a new interpretation of multidrug resistance.

    Science.gov (United States)

    Lange, K; Gartzke, J

    2001-08-01

    The phenomenon of multidrug resistance (MDR) is reinterpreted on the basis of the recently proposed concept of microvillar signaling. According to this notion, substrate and ion fluxes across the surface of differentiated cells occur via transporters and ion channels that reside in membrane domains at the tips of microvilli (MV). The flux rates are regulated by the actin-based cytoskeletal core structure of MV, acting as a diffusion barrier between the microvillar tip compartment and the cytoplasm. The expression of this diffusion barrier system is a novel aspect of cell differentiation and represents a functional component of the natural defense system of epithelial cells against environmental hazardous ions and lipophilic compounds. Because of the specific organization of epithelial Ca(2+) signaling and the secretion, lipophilic compounds associated with the plasma membrane are transferred from the basal to the apical cell surface by a lipid flow mechanism. Drug release from the apical pole occurs by either direct secretion from the cell surface or metabolization by the microvillar cytochrome P-450 system and efflux of the metabolites and conjugation products through the large multifunctional anion channels localized in apical MV. The natural microvillar defense system also provides a mechanistic basis of acquired MDR in tumor cells. The microvillar surface organization is lost in rapidly growing cells such as tumor or embryonic cells but is restored during exposure of tumor cells to cytotoxins by induction of a prolonged G(0)/G(1) resting phase.

  13. Large resistivity modulation in mixed-phase metallic systems.

    Science.gov (United States)

    Lee, Yeonbae; Liu, Z Q; Heron, J T; Clarkson, J D; Hong, J; Ko, C; Biegalski, M D; Aschauer, U; Hsu, S L; Nowakowski, M E; Wu, J; Christen, H M; Salahuddin, S; Bokor, J B; Spaldin, N A; Schlom, D G; Ramesh, R

    2015-01-07

    In numerous systems, giant physical responses have been discovered when two phases coexist; for example, near a phase transition. An intermetallic FeRh system undergoes a first-order antiferromagnetic to ferromagnetic transition above room temperature and shows two-phase coexistence near the transition. Here we have investigated the effect of an electric field to FeRh/PMN-PT heterostructures and report 8% change in the electrical resistivity of FeRh films. Such a 'giant' electroresistance (GER) response is striking in metallic systems, in which external electric fields are screened, and thus only weakly influence the carrier concentrations and mobilities. We show that our FeRh films comprise coexisting ferromagnetic and antiferromagnetic phases with different resistivities and the origin of the GER effect is the strain-mediated change in their relative proportions. The observed behaviour is reminiscent of colossal magnetoresistance in perovskite manganites and illustrates the role of mixed-phase coexistence in achieving large changes in physical properties with low-energy external perturbation.

  14. Integrated Thermal Protection Systems and Heat Resistant Structures

    Science.gov (United States)

    Pichon, Thierry; Lacoste, Marc; Glass, David E.

    2006-01-01

    In the early stages of NASA's Exploration Initiative, Snecma Propulsion Solide was funded under the Exploration Systems Research & Technology program to develop integrated thermal protection systems and heat resistant structures for reentry vehicles. Due to changes within NASA's Exploration Initiative, this task was cancelled early. This presentation provides an overview of the work that was accomplished prior to cancellation. The Snecma team chose an Apollo-type capsule as the reference vehicle for the work. They began with the design of a ceramic aft heatshield (CAS) utilizing C/SiC panels as the capsule heatshield, a C/SiC deployable decelerator and several ablators. They additionally developed a health monitoring system, high temperature structures testing, and the insulation characterization. Though the task was pre-maturely cancelled, a significant quantity of work was accomplished.

  15. A Prototype System for Time-Lapse Electrical Resistivity Tomographies

    Directory of Open Access Journals (Sweden)

    Raffaele Luongo

    2012-01-01

    Full Text Available A prototype system for time-lapse acquisition of 2D electrical resistivity tomography (ERT and time domain reflectometry (TDR measurements was installed in a test site affected by a landslide in Basilicata region (southern Italy. The aim of the system is to monitor in real-time the rainwater infiltration into the soil and obtain information about the variation of the water content in the first layers of the subsoil and the possible influence of this variation on landslide activity. A rain gauge placed in the test site gives information on the rainfall intensity and frequency and suggests the acquisition time interval. The installed system and the preliminary results are presented in this paper.

  16. Assessment of proliferation resistance of thermal recycle systems

    International Nuclear Information System (INIS)

    1979-02-01

    An assessment is made of the proliferation resistance of thermal recycle systems. The safeguards aspects are not addressed. Three routes to the acquisition of materials for nuclear weapons are addressed namely; a deliberate political decision by a government involving the use of dedicated facilities, a deliberate political decision by government involving abuse of nuclear fuel cycle facilities and theft by a subnational group. The most sensitive parts of the reference fuel cycle and the alternative technical measures are examined to judge their relative sensitivity. This is done by examining the difference forms in which plutonium can exist in the fuel cycle. The role which different institutional arrangements can play is also evaluated. From this comparative assessment it is concluded that, taking into account the qualitative nature of the assessment, the different stages of development of the various fuel cycles, the various realizations possible in respect of the deployment of facilities within individual countries and the evolutionary nature of the technical and institutional improvements foreseeable no fuel cycle can be made completely free from abuse. Furthermore it appears that following progressive introduction of features that will improve proliferation resistance there will not be significant differences between the various fuel cycles when compared at the point in time when they are introduced into widespread use. Provided such features are developed and implemented there is no reason on proliferation grounds to prefer one cycle to another

  17. Radiation resistance characteristics of optical communication system for single mode

    International Nuclear Information System (INIS)

    Ohe, Masamoto; Chigusa, Yoshiki; Kyodo, Tomohisa; Tanaka, Gohtaro; Watanabe, Hajime; Okamoto, Shin-ichi; Yamamoto, Takao.

    1988-01-01

    Optical communication has been utilized also for nuclear power stations and fuel reporocessing plants. As the sufficient safety countermeasures are required there, the amount of information becomes enormous, therefore, optical communication, by which the required space is expected to be reduced, becomes more important. Also in the application to submarine cables, attention must be paid to the radiation resistance as there are the effects of potassium contained in large amount in seawater and uranium deposits in sea bottom. Therefore, the reliability of the components of optical communication systems against radiation becomes a problem. In this study, single mode optical fibers and transmission and receipt modules were selected, and high dose rate irradiation supposing the case of using in a cell and low dose rate, long time irradiation supposing the case of submarine cables were carried out to evaluate the radiation resistance characteristics. The fibers tested were SiO 2 core/F-SiO 2 clad type and GeO 2 -SiO 2 core/SiO 2 clad type. The characteristics of increasing loss in irradiation and restoration after irradiation of the former type were superior to those of the latter type. The output of a receipt module was normal during irradiation, and the output power of a transmission module decreases, but other problems did not arise. (K.I.)

  18. Development of a plan for a national LLW information management system based on data acquired from a uniform manifest

    International Nuclear Information System (INIS)

    Gingerich, R.; Shimer, R.P.

    1986-01-01

    The Western Governors' Association (WGA), with funding from the Department of Energy's (DOE) National Low-Level Radioactive Waste Management Program, has completed an 18-month national project to develop a plan for a national low-level waste (LLW) information management system based on data from a uniform manifest for shipments of LLW. Under the plan, waste generators would fill out a manifest for a shipment just as they do currently, but they would use a nationally standard form. Shortly after a shipment arrives at a disposal facility or a processor, data from the manifest would be entered into the Program's Low-Level Waste Information Management System (LLWIMS). The data would be available via computer to state, compact and federal officials. This paper provides an overview of the plan for implementing and operating a national information management system linked to manifest data. It reports on the progress that has been made toward implementing the system and outlines the work that remains to be done. Finally, the paper examines the crucial role the system will play in the development of an acceptable system for managing the nation's LLW, particularly in the post-1986 transition period

  19. Epstein-Barr virus-associated primary central nervous system lymphoma in a child with the acquired immunodeficiency syndrome. A case report and review of the literature.

    Science.gov (United States)

    Rodriguez, M M; Delgado, P I; Petito, C K

    1997-12-01

    A 34-month-old black boy who had contracted acquired immunodeficiency syndrome from his mother presented with fever, vomiting, and cough. He was cachectic, hypertonic, and developmentally delayed. A brain computed tomography scan revealed masses in the left frontal horn, subependymal, and periventricular regions; secondary edema; and hydrocephalus. The differential diagnosis was cerebral lymphoma versus toxoplasmosis. The patient had disseminated Mycobacterium avium-intracellulare infection, lymphoid interstitial pneumonitis, as well as Pseudomonas and Klebsiella pneumonia. He died of respiratory insufficiency 53 days after admission. The autopsy confirmed a primary cerebral B-cell lymphoma, large cell type, which was positive for Epstein-Barr virus, latent phase, by in situ hybridization. Primary central nervous system lymphomas are rare in children, in contrast to adults. To our knowledge, only five well-documented cases of primary cerebral lymphomas in infants and children with acquired immunodeficiency syndrome have been reported previously. The current study shows that these childhood lymphomas are associated with and presumably caused by Epstein-Barr virus and thus have a pathogenesis similar to that of primary central nervous system lymphomas in adults.

  20. Results of a multicentre randomised controlled trial of statistical process control charts and structured diagnostic tools to reduce ward-acquired meticillin-resistant Staphylococcus aureus: the CHART Project.

    Science.gov (United States)

    Curran, E; Harper, P; Loveday, H; Gilmour, H; Jones, S; Benneyan, J; Hood, J; Pratt, R

    2008-10-01

    Statistical process control (SPC) charts have previously been advocated for infection control quality improvement. To determine their effectiveness, a multicentre randomised controlled trial was undertaken to explore whether monthly SPC feedback from infection control nurses (ICNs) to healthcare workers of ward-acquired meticillin-resistant Staphylococcus aureus (WA-MRSA) colonisation or infection rates would produce any reductions in incidence. Seventy-five wards in 24 hospitals in the UK were randomised into three arms: (1) wards receiving SPC chart feedback; (2) wards receiving SPC chart feedback in conjunction with structured diagnostic tools; and (3) control wards receiving neither type of feedback. Twenty-five months of pre-intervention WA-MRSA data were compared with 24 months of post-intervention data. Statistically significant and sustained decreases in WA-MRSA rates were identified in all three arms (Pcontrol wards, but with no significant difference between the control and intervention arms (P=0.23). There were significantly more post-intervention 'out-of-control' episodes (P=0.021) in the control arm (averages of 0.60, 0.28, and 0.28 for Control, SPC and SPC+Tools wards, respectively). Participants identified SPC charts as an effective communication tool and valuable for disseminating WA-MRSA data.

  1. 3D spectrum imaging of multi-wall carbon nanotube coupled π-surface modes utilising electron energy-loss spectra acquired using a STEM/Enfina system

    International Nuclear Information System (INIS)

    Seepujak, A.; Bangert, U.; Gutierrez-Sosa, A.; Harvey, A.J.; Blank, V.D.; Kulnitskiy, B.A.; Batov, D.V.

    2005-01-01

    Numerous studies have utilised electron energy-loss (EEL) spectra acquired in the plasmon (2-10 eV) regime in order to probe delocalised π-electronic states of multi-wall carbon nanotubes (MWCNTs). Interpretation of electron energy loss (EEL) spectra of MWCNTs in the 2-10 eV regime. Carbon (accepted for publication); Blank et al. J. Appl. Phys. 91 (2002) 1657). In the present contribution, EEL spectra were acquired from a 2D raster defined on a bottle-shaped MWCNT, using a Gatan UHV Enfina system attached to a dedicated scanning transmission electron microscope (STEM). The technique utilised to isolate and sequentially filter each of the volume and surface resonances is described in detail. Utilising a scale for the intensity of a filtered mode enables one to 'see' the distribution of each resonance in the raster. This enables striking 3D resonance-filtered spectrum images (SIs) of π-collective modes to be observed. Red-shift of the lower energy split π-surface resonance provides explicit evidence of π-surface mode coupling predicted for thin graphitic films (Lucas et al. Phys. Rev. B 49 (1994) 2888). Resonance-filtered SIs are also compared to non-filtered SIs with suppressed surface contributions, acquired utilising a displaced collector aperture. The present filtering technique is seen to isolate surface contributions more effectively, and without the significant loss of statistics, associated with the displaced collector aperture mode. Isolation of collective modes utilising 3D resonance-filtered spectrum imaging, demonstrates a valuable method for 'pinpointing' the location of discrete modes in irregularly shaped nanostructures

  2. The role of the Staphylococcal VraTSR regulatory system on vancomycin resistance and vanA operon expression in vancomycin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Qureshi, Nadia K; Yin, Shaohui; Boyle-Vavra, Susan

    2014-01-01

    Vancomycin is often the preferred treatment for invasive methicillin-resistant Staphylococcus aureus (MRSA) infection. With the increase in incidence of MRSA infections, the use of vancomycin has increased and, as feared, isolates of vancomycin-resistant Staphylococcus aureus (VRSA) have emerged. VRSA isolates have acquired the entercoccal vanA operon contained on transposon (Tn) 1546 residing on a conjugal plasmid. VraTSR is a vancomycin and β-lactam-inducible three-component regulatory system encoded on the S. aureus chromosome that modulates the cell-wall stress response to cell-wall acting antibiotics. Mutation in vraTSR has shown to increase susceptibility to β-lactams and vancomycin in clinical VISA strains and in recombinant strain COLVA-200 which expresses a plasmid borne vanA operon. To date, the role of VraTSR in vanA operon expression in VRSA has not been demonstrated. In this study, the vraTSR operon was deleted from the first clinical VRSA strain (VRS1) by transduction with phage harvested from a USA300 vraTSR operon deletion strain. The absence of the vraTSR operon and presence of the vanA operon were confirmed in the transductant (VRS1Δvra) by PCR. Broth MIC determinations, demonstrated that the vancomycin MIC of VRS1Δvra (64 µg/ml) decreased by 16-fold compared with VRS1 (1024 µg/ml). The effect of the vraTSR operon deletion on expression of the van gene cluster (vanA, vanX and vanR) was examined by quantitative RT-PCR using relative quantification. A 2-5-fold decreased expression of the vanA operon genes occured in strain VRS1Δvra at stationary growth phase compared with the parent strain, VRS1. Both vancomycin resistance and vancomycin-induced expression of vanA and vanR were restored by complementation with a plasmid harboring the vraTSR operon. These findings demonstrate that expression in S. aureus of the horizontally acquired enterococcal vanA gene cluster is enhanced by the staphylococcal three-component cell wall stress regulatory

  3. Surface resistance of superconductors - examples from Nb - O systems

    International Nuclear Information System (INIS)

    Palmer, F.

    1988-01-01

    The observed surface resistance of most superconductors can be written as the sum of two terms. R/sub obs/ = R/sub BCS/ + R/sub res/. This paper is divided into three sections. The first section describes the BCS theory of surface resistance in terms of a simplified two-fluid model. The second section describes several possible causes of residual resistance including normal conducting materials, tunneling across cracks in the surface, and direct generation of phonons by the RF electric field. The last section describes recent experiments having to do with the effects of oxide layers on surface resistance. Layers grown in pure oxygen at room temperature were found to have little or no effect, but if these layers are heated to temperatures near 300 0 C, they can alter both the BCS resistance and the residual resistance. Heated oxide layers also increased the dependence of the residual resistance on ambient magnetic field. 31 references, 13 figures, 3 tables

  4. Ability of Bacillus subtilis protoplasts to repair irradiated bacteriophage deoxyribonucleic acid via acquired and natural enzymatic systems

    International Nuclear Information System (INIS)

    Yasbin, R.E.; Andersen, B.J.; Sutherland, B.M.

    1981-01-01

    A novel form of enzyme therapy was achieved by utilizing protoplasts of Bacillus subtilis. Photoreactivating enzyme of Escherichia coli was successfully inserted into the protoplasts of B. subtilis treated with polyethylene glycol. This enzyme was used to photoreactivate ultraviolet-damaged bacteriophage deoxyribonucleic acid (DNA). Furthermore, in polyethylene glycol-treated protoplasts, ultraviolet-irradiated transfecting bacteriophage DNA was shown to be a functional substrate for the host DNA excision repair system. Previous results (R.E. Yasbin, J.D. Fernwalt, and P.I. Fields, J. Bacteriol.; 137: 391-396) showed that ultraviolet-irradiated bacteriophage DNA could not be repaired via the excision repair system of competent cells. Therefore, the processing of bacteriophage DNA by protoplasts and by competent cells must be different. This sensitive protoplast assay can be used to identify and to isolate various types of DNA repair enzymes

  5. Toward acquiring comprehensive radiosurgery field commissioning data using the PRESAGE/optical-CT 3D dosimetry system

    Energy Technology Data Exchange (ETDEWEB)

    Clift, Corey; Thomas, Andrew; Chang Zheng; Oldham, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710 (United States); Adamovics, John [Department of Chemistry, Rider University, Lawrenceville, NJ 08648 (United States); Das, Indra [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)], E-mail: cclift@montefiore.org

    2010-03-07

    Achieving accurate small field dosimetry is challenging. This study investigates the utility of a radiochromic plastic PRESAGE read with optical-CT for the acquisition of radiosurgery field commissioning data from a Novalis Tx system with a high-definition multileaf collimator (HDMLC). Total scatter factors (S{sub c,p}), beam profiles, and penumbrae were measured for five different radiosurgery fields (5, 10, 20, 30 and 40 mm) using a commercially available optical-CT scanner (OCTOPUS, MGS Research). The percent depth dose (PDD), beam profile and penumbra of the 10 mm field were also measured using a higher resolution in-house prototype CCD-based scanner. Gafchromic EBT film was used for independent verification. Measurements of S{sub c,p} made with PRESAGE and film agreed with mini-ion chamber commissioning data to within 4% for every field (range 0.2-3.6% for PRESAGE, and 1.6-3.6% for EBT). PDD, beam profile and penumbra measurements made with the two PRESAGE/optical-CT systems and film showed good agreement with the high-resolution diode commissioning measurements with a competitive resolution (0.5 mm pixels). The in-house prototype optical-CT scanner allowed much finer resolution compared with previous applications of PRESAGE. The advantages of the PRESAGE (registered) system for small field dosimetry include 3D measurements, negligible volume averaging, directional insensitivity, an absence of beam perturbations, energy and dose rate independence.

  6. Toward acquiring comprehensive radiosurgery field commissioning data using the PRESAGE/optical-CT 3D dosimetry system

    International Nuclear Information System (INIS)

    Clift, Corey; Thomas, Andrew; Chang Zheng; Oldham, Mark; Adamovics, John; Das, Indra

    2010-01-01

    Achieving accurate small field dosimetry is challenging. This study investigates the utility of a radiochromic plastic PRESAGE read with optical-CT for the acquisition of radiosurgery field commissioning data from a Novalis Tx system with a high-definition multileaf collimator (HDMLC). Total scatter factors (S c,p ), beam profiles, and penumbrae were measured for five different radiosurgery fields (5, 10, 20, 30 and 40 mm) using a commercially available optical-CT scanner (OCTOPUS, MGS Research). The percent depth dose (PDD), beam profile and penumbra of the 10 mm field were also measured using a higher resolution in-house prototype CCD-based scanner. Gafchromic EBT film was used for independent verification. Measurements of S c,p made with PRESAGE and film agreed with mini-ion chamber commissioning data to within 4% for every field (range 0.2-3.6% for PRESAGE, and 1.6-3.6% for EBT). PDD, beam profile and penumbra measurements made with the two PRESAGE/optical-CT systems and film showed good agreement with the high-resolution diode commissioning measurements with a competitive resolution (0.5 mm pixels). The in-house prototype optical-CT scanner allowed much finer resolution compared with previous applications of PRESAGE. The advantages of the PRESAGE (registered) system for small field dosimetry include 3D measurements, negligible volume averaging, directional insensitivity, an absence of beam perturbations, energy and dose rate independence.

  7. Toward acquiring comprehensive radiosurgery field commissioning data using the PRESAGE®/ optical-CT 3D dosimetry system

    Science.gov (United States)

    Clift, Corey; Thomas, Andrew; Adamovics, John; Chang, Zheng; Das, Indra; Oldham, Mark

    2010-03-01

    Achieving accurate small field dosimetry is challenging. This study investigates the utility of a radiochromic plastic PRESAGE® read with optical-CT for the acquisition of radiosurgery field commissioning data from a Novalis Tx system with a high-definition multileaf collimator (HDMLC). Total scatter factors (Sc, p), beam profiles, and penumbrae were measured for five different radiosurgery fields (5, 10, 20, 30 and 40 mm) using a commercially available optical-CT scanner (OCTOPUS, MGS Research). The percent depth dose (PDD), beam profile and penumbra of the 10 mm field were also measured using a higher resolution in-house prototype CCD-based scanner. Gafchromic EBT® film was used for independent verification. Measurements of Sc, p made with PRESAGE® and film agreed with mini-ion chamber commissioning data to within 4% for every field (range 0.2-3.6% for PRESAGE®, and 1.6-3.6% for EBT). PDD, beam profile and penumbra measurements made with the two PRESAGE®/optical-CT systems and film showed good agreement with the high-resolution diode commissioning measurements with a competitive resolution (0.5 mm pixels). The in-house prototype optical-CT scanner allowed much finer resolution compared with previous applications of PRESAGE®. The advantages of the PRESAGE® system for small field dosimetry include 3D measurements, negligible volume averaging, directional insensitivity, an absence of beam perturbations, energy and dose rate independence.

  8. Application of photogrammetry to transforming PIV-acquired velocity fields to a moving-body coordinate system

    Science.gov (United States)

    Nikoueeyan, Pourya; Naughton, Jonathan

    2016-11-01

    Particle Image Velocimetry is a common choice for qualitative and quantitative characterization of unsteady flows associated with moving bodies (e.g. pitching and plunging airfoils). Characterizing the separated flow behavior is of great importance in understanding the flow physics and developing predictive reduced-order models. In most studies, the model under investigation moves within a fixed camera field-of-view, and vector fields are calculated based on this fixed coordinate system. To better characterize the genesis and evolution of vortical structures in these unsteady flows, the velocity fields need to be transformed into the moving-body frame of reference. Data converted to this coordinate system allow for a more detailed analysis of the flow field using advanced statistical tools. In this work, a pitching NACA0015 airfoil has been used to demonstrate the capability of photogrammetry for such an analysis. Photogrammetry has been used first to locate the airfoil within the image and then to determine an appropriate mask for processing the PIV data. The photogrammetry results are then further used to determine the rotation matrix that transforms the velocity fields to airfoil coordinates. Examples of the important capabilities such a process enables are discussed. P. Nikoueeyan is supported by a fellowship from the University of Wyoming's Engineering Initiative.

  9. Acquisition War-Gaming Technique for Acquiring Future Complex Systems: Modeling and Simulation Results for Cost Plus Incentive Fee Contract

    Directory of Open Access Journals (Sweden)

    Tien M. Nguyen

    2018-03-01

    Full Text Available This paper provides a high-level discussion and propositions of frameworks and models for acquisition strategy of complex systems. In particular, it presents an innovative system engineering approach to model the Department of Defense (DoD acquisition process and offers several optimization modules including simulation models using game theory and war-gaming concepts. Our frameworks employ Advanced Game-based Mathematical Framework (AGMF and Unified Game-based Acquisition Framework (UGAF, and related advanced simulation and mathematical models that include a set of War-Gaming Engines (WGEs implemented in MATLAB statistical optimization models. WGEs are defined as a set of algorithms, characterizing the Program and Technical Baseline (PTB, technology enablers, architectural solutions, contract type, contract parameters and associated incentives, and industry bidding position. As a proof of concept, Aerospace, in collaboration with the North Carolina State University (NCSU and University of Hawaii (UH, successfully applied and extended the proposed frameworks and decision models to determine the optimum contract parameters and incentives for a Cost Plus Incentive Fee (CPIF contract. As a result, we can suggest a set of acquisition strategies that ensure the optimization of the PTB.

  10. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through

  11. Acquired bleeding disorders

    African Journals Online (AJOL)

    B one marrow aplasia ... Laboratory approach to a suspected acquired bleeding disorder. (LER = leuko- .... lymphocytic leukaemia, and lymphoma). ... cells), a bone marrow aspirate and trephine biopsy (BMAT) is not ..... transplantation.

  12. Pneumonia - children - community acquired

    Science.gov (United States)

    Bronchopneumonia - children; Community-acquired pneumonia - children; CAP - children ... Viruses are the most common cause of pneumonia in infants and children. Ways your child can get CAP include: Bacteria and viruses living in the nose, sinuses, or mouth may spread ...

  13. Markov Networks of Collateral Resistance: National Antimicrobial Resistance Monitoring System Surveillance Results from Escherichia coli Isolates, 2004-2012.

    Directory of Open Access Journals (Sweden)

    William J Love

    2016-11-01

    Full Text Available Surveillance of antimicrobial resistance (AMR is an important component of public health. Antimicrobial drug use generates selective pressure that may lead to resistance against to the administered drug, and may also select for collateral resistances to other drugs. Analysis of AMR surveillance data has focused on resistance to individual drugs but joint distributions of resistance in bacterial populations are infrequently analyzed and reported. New methods are needed to characterize and communicate joint resistance distributions. Markov networks are a class of graphical models that define connections, or edges, between pairs of variables with non-zero partial correlations and are used here to describe AMR resistance relationships. The graphical least absolute shrinkage and selection operator is used to estimate sparse Markov networks from AMR surveillance data. The method is demonstrated using a subset of Escherichia coli isolates collected by the National Antimicrobial Resistance Monitoring System between 2004 and 2012 which included AMR results for 16 drugs from 14418 isolates. Of the 119 possible unique edges, 33 unique edges were identified at least once during the study period and graphical density ranged from 16.2% to 24.8%. Two frequent dense subgraphs were noted, one containing the five β-lactam drugs and the other containing both sulfonamides, three aminoglycosides, and tetracycline. Density did not appear to change over time (p = 0.71. Unweighted modularity did not appear to change over time (p = 0.18, but a significant decreasing trend was noted in the modularity of the weighted networks (p < 0.005 indicating relationships between drugs of different classes tended to increase in strength and frequency over time compared to relationships between drugs of the same class. The current method provides a novel method to study the joint resistance distribution, but additional work is required to unite the underlying biological and genetic

  14. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.

    2008-01-01

    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  15. Nuclear proliferation and civilian nuclear power. Report of the Nonproliferation Alternative Systems Assessment Program. Volume II. Proliferation resistance

    International Nuclear Information System (INIS)

    1980-06-01

    The purpose of this volume is limited to an assessment of the relative effects that particular choices of nuclear-power systems, for whatever reasons, may have on the possible spread of nuclear-weapons capabilities. This volume addresses the concern that non-nuclear-weapons states may be able to initiate efforts to acquire or to improve nuclear-weapons capabilities through civilian nuclear-power programs; it also addresses the concern that subnational groups may obtain and abuse the nuclear materials or facilities of such programs, whether in nuclear-weapons states (NWS's) or nonnuclear-weapons states (NNW's). Accordingly, this volume emphasizes one important factor in such decisions, the resistance of nuclear-power systems to the proliferation of nuclear-weapons capabilities

  16. Acquired type III secretion system determines environmental fitness of epidemic Vibrio parahaemolyticus in the interaction with bacterivorous protists.

    Directory of Open Access Journals (Sweden)

    Carsten Matz

    Full Text Available Genome analyses of marine microbial communities have revealed the widespread occurrence of genomic islands (GIs, many of which encode for protein secretion machineries described in the context of bacteria-eukaryote interactions. Yet experimental support for the specific roles of such GIs in aquatic community interactions remains scarce. Here, we test for the contribution of type III secretion systems (T3SS to the environmental fitness of epidemic Vibrio parahaemolyticus. Comparisons of V. parahaemolyticus wild types and T3SS-defective mutants demonstrate that the T3SS encoded on genome island VPaI-7 (T3SS-2 promotes survival of V. parahaemolyticus in the interaction with diverse protist taxa. Enhanced persistence was found to be due to T3SS-2 mediated cytotoxicity and facultative parasitism of V. parahaemolyticus on coexisting protists. Growth in the presence of bacterivorous protists and the T3SS-2 genotype showed a strong correlation across environmental and clinical isolates of V. parahaemolyticus. Short-term microcosm experiments provide evidence that protistan hosts facilitate the invasion of T3SS-2 positive V. parahaemolyticus into a coastal plankton community, and that water temperature and productivity further promote enhanced survival of T3SS-2 positive V. parahaemolyticus. This study is the first to describe the fitness advantage of GI-encoded functions in a microbial food web, which may provide a mechanistic explanation for the global spread and the seasonal dynamics of V. parahaemolyticus pathotypes, including the pandemic serotype cluster O3:K6, in aquatic environments.

  17. Differences in microbiological profile between community-acquired, healthcare-associated and hospital-acquired infections.

    Science.gov (United States)

    Cardoso, Teresa; Ribeiro, Orquídea; Aragão, Irene; Costa-Pereira, Altamiro; Sarmento, António

    2013-01-01

    Microbiological profiles were analysed and compared for intra-abdominal, urinary, respiratory and bloodstream infections according to place of acquisition: community-acquired, with a separate analysis of healthcare-associated, and hospital-acquired. Prospective cohort study performed at a university tertiary care hospital over 1 year. Inclusion criteria were meeting the Centers for Disease Control definition of intra-abdominal, urinary, respiratory and bloodstream infections. A total of 1035 patients were included in the study. More than 25% of intra-abdominal infections were polymicrobial; multi-drug resistant gram-negatives were 38% in community-acquired, 50% in healthcare-associated and 57% in hospital-acquired. E. coli was the most prevalent among urinary infections: 69% in community-acquired, 56% in healthcare-associated and 26% in hospital-acquired; ESBL producers' pathogens were 10% in healthcare-associated and 3% in community-acquired and hospital-acquired. In respiratory infections Streptococcus pneumoniae was the most prevalent in community-acquired (54%) and MRSA in healthcare-associated (24%) and hospital-acquired (24%). A significant association was found between MRSA respiratory infection and hospitalization in the previous year (adjusted OR = 6.3), previous instrumentation (adjusted OR = 4.3) and previous antibiotic therapy (adjusted OR = 5.7); no cases were documented among patients without risk factors. Hospital mortality rate was 10% in community-acquired, 14% in healthcare-associated and 19% in hospital-acquired infection. This study shows that healthcare-associated has a different microbiologic profile than those from community or hospital acquired for the four main focus of infection. Knowledge of this fact is important because the existing guidelines for community-acquired are not entirely applicable for this group of patients.

  18. Comparative study of isolates from community-acquired and catheter-associated urinary tract infections with reference to biofilm-producing property, antibiotic sensitivity and multi-drug resistance.

    Science.gov (United States)

    Bardoloi, Vishwajeet; Yogeesha Babu, K V

    2017-07-01

    Urinary tract infection (UTI) can be community-acquired (Com-UTI) or catheter-associated (CAUTI) and may be associated with biofilm-producing organisms. A comparative analysis of biofilm-producing property (BPP), antibiotic-sensitivity and multi-drug resistance (MDR) and their relation with the BPP of isolates from Com-UTI and CAUTI has not yet been performed and necessitated this study. (1) isolation of bacteria from CAUTI and Com-UTI and identification of their BPP, antibiotic-sensitivity and MDR status; (2) comparison of the isolates from CAUTI and Com-UTI as regards BPP, MDR status and their relation with BPP. isolates from 100 cases each of Com-UTI and CAUTI were subjected to Congo redagar (CRA) and Safranin tube tests. Antibiotic susceptibility was investigated using the disc diffusion method. Both groups were compared regarding BPP, drug sensitivity and MDR status. Statistical analyses were performed using χ2 and Fisher's exact tests. 76.19 % of isolates from Com-UTI and 60.72 % from CAUTI had BPP (P=0.0252; significant). The Safranin tube test detected more isolates with BPP than the CRA test. MDR is greater in CAUTI than Com-UTI (83.33 % versus 64.76 %; P=0.0039; significant). MDR is greater in isolates with BPP in both Com-UTI and CAUTI (76.47 and 62.35 %; non-significant). BPP was found in both Com-UTI and CAUTI. When used together, the Safranin tube test and the CRA test increased the sensitivity of detecting BPP. MDR was higher in CAUTI than Com-UTI. MDR and BPP are not interrelated or associated, especially in settings where it is not certain that isolates were obtained from a well-formed biofilm. However, this does not rule out a higher incidence or prevalence of MDR in isolates with BPP taken directly from the biofilms.

  19. Differential effectiveness of Serratia plymuthica IC1270-induced systemic resistance against hemibiotrophic and necrotrophic leaf pathogens in rice

    Directory of Open Access Journals (Sweden)

    Höfte Monica M

    2009-01-01

    Full Text Available Abstract Background Induced resistance is a state of enhanced defensive capacity developed by a plant reacting to specific biotic or chemical stimuli. Over the years, several forms of induced resistance have been characterized, including systemic acquired resistance, which is induced upon localized infection by an avirulent necrotizing pathogen, and induced systemic resistance (ISR, which is elicited by selected strains of nonpathogenic rhizobacteria. However, contrary to the relative wealth of information on inducible defense responses in dicotyledoneous plants, our understanding of the molecular mechanisms underlying induced resistance phenomena in cereal crops is still in its infancy. Using a combined cytomolecular and pharmacological approach, we analyzed the host defense mechanisms associated with the establishment of ISR in rice by the rhizobacterium Serratia plymuthica IC1270. Results In a standardized soil-based assay, root treatment with IC1270 rendered foliar tissues more resistant to the hemibiotrophic pathogen Magnaporthe oryzae, causal agent of the devastating rice blast disease. Analysis of the cytological and biochemical alterations associated with restriction of fungal growth in IC1270-induced plants revealed that IC1270 primes rice for enhanced attacker-induced accumulation of reactive oxygen species (ROS and autofluorescent phenolic compounds in and near epidermal cells displaying dense cytoplasmic granulation. Similar, yet more abundant, phenotypes of hypersensitively dying cells in the vicinity of fungal hyphae were evident in a gene-for-gene interaction with an avirulent M. oryzae strain, suggesting that IC1270-inducible ISR and R protein conditioned effector-triggered immunity (ETI target similar defense mechanisms. Yet, this IC1270-inducible ISR response seems to act as a double-edged sword within the rice defense network as induced plants displayed an increased vulnerability to the necrotrophic pathogens Rhizoctonia

  20. National Antimicrobial Resistance Monitoring System: Two Decades of Advancing Public Health Through Integrated Surveillance of Antimicrobial Resistance.

    Science.gov (United States)

    Karp, Beth E; Tate, Heather; Plumblee, Jodie R; Dessai, Uday; Whichard, Jean M; Thacker, Eileen L; Hale, Kis Robertson; Wilson, Wanda; Friedman, Cindy R; Griffin, Patricia M; McDermott, Patrick F

    2017-10-01

    Drug-resistant bacterial infections pose a serious and growing public health threat globally. In this review, we describe the role of the National Antimicrobial Resistance Monitoring System (NARMS) in providing data that help address the resistance problem and show how such a program can have broad positive impacts on public health. NARMS was formed two decades ago to help assess the consequences to human health arising from the use of antimicrobial drugs in food animal production in the United States. A collaboration among the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the United States Department of Agriculture, and state and local health departments, NARMS uses an integrated "One Health" approach to monitor antimicrobial resistance in enteric bacteria from humans, retail meat, and food animals. NARMS has adapted to changing needs and threats by expanding surveillance catchment areas, examining new isolate sources, adding bacteria, adjusting sampling schemes, and modifying antimicrobial agents tested. NARMS data are not only essential for ensuring that antimicrobial drugs approved for food animals are used in ways that are safe for human health but they also help address broader food safety priorities. NARMS surveillance, applied research studies, and outbreak isolate testing provide data on the emergence of drug-resistant enteric bacteria; genetic mechanisms underlying resistance; movement of bacterial populations among humans, food, and food animals; and sources and outcomes of resistant and susceptible infections. These data can be used to guide and evaluate the impact of science-based policies, regulatory actions, antimicrobial stewardship initiatives, and other public health efforts aimed at preserving drug effectiveness, improving patient outcomes, and preventing infections. Many improvements have been made to NARMS over time and the program will continue to adapt to address emerging resistance threats, changes in

  1. Increased systemic vascular resistance in neonates with pulmonary hypertension.

    Science.gov (United States)

    Milstein, J M; Goetzman, B W; Riemenschneider, T A; Wennberg, R P

    1979-11-01

    The time necessary for aortic diastolic pressure to decrease to 50 percent of an initially selected value after dissipation of the dicrotic notch (T 1/2) was determined in newborn infants with and without pulmonary hypertension. The mean T 1/2 was 671 +/- 167 msec in seven infants with clinical evidence of pulmonary hypertension and documented right to left ductus arteriosus shunting; 849 +/- 243 msec in nine infants with clinical evidence of pulmonary hypertension but no documented right to left ductus arteriosus shunting; and 457 +/- 66 msec in eight infants with hyaline membrane disease and no clinical evidence of pulmonary hypertension or a patent ductus arteriosus. The mean T 1/2 values in the former two groups were significantly different from that in the group with no pulmonary hypertension (P less than 0.01). An evaluation of factors affecting T 1/2 leads to the conclusion that the patients with pulmonary hypertension had increased systemic vascular resistance as well. This finding has important diagnostic, etiologic and therapeutic implications.

  2. Using tensorial electrical resistivity survey to locate fault systems

    International Nuclear Information System (INIS)

    Monteiro Santos, Fernando A; Plancha, João P; Marques, Jorge; Perea, Hector; Cabral, João; Massoud, Usama

    2009-01-01

    This paper deals with the use of the tensorial resistivity method for fault orientation and macroanisotropy characterization. The rotational properties of the apparent resistivity tensor are presented using 3D synthetic models representing structures with a dominant direction of low resistivity and vertical discontinuities. It is demonstrated that polar diagrams of the elements of the tensor are effective in delineating those structures. As the apparent resistivity tensor shows great inefficacy in investigating the depth of the structures, it is advised to accomplish tensorial surveys with the application of other geophysical methods. An experimental example, including tensorial, dipole–dipole and time domain surveys, is presented to illustrate the potentiality of the method. The dipole–dipole model shows high-resistivity contrasts which were interpreted as corresponding to faults crossing the area. The results from the time domain electromagnetic (TEM) sounding show high-resistivity values till depths of 40–60 m at the north part of the area. In the southern part of the survey area the soundings show an upper layer with low-resistivity values (around 30 Ω m) followed by a more resistive bedrock (resistivity >100 Ω m) at a depth ranging from 15 to 30 m. The soundings in the central part of the survey area show more variability. A thin conductive overburden is followed by a more resistive layer with resistivity in the range of 80–1800 Ω m. The north and south limits of the central part of the area as revealed by TEM survey are roughly E–W oriented and coincident with the north fault scarp and the southernmost fault detected by the dipole–dipole survey. The pattern of the polar diagrams calculated from tensorial resistivity data clearly indicates the presence of a contact between two blocks at south of the survey area with the low-resistivity block located southwards. The presence of other two faults is not so clear from the polar diagram patterns, but

  3. Using and development of multi adversity resistance system in cotton

    Directory of Open Access Journals (Sweden)

    Metin Durmuş ÇETİN

    2014-12-01

    Full Text Available The basic approach in plant breeding, make it possible to show the full genetic potential of plant. This methods also protect the health of plant growth over the period, by increasing resistance to diseases and pests is expected to provide. For this purpose, by Bird in 1963, with the name of multi adversity resistance has been initiated in cotton breeding and for many years as a result of the work carried out important varieties and germplasm have been developed. Nowadays, those using for varieties resistant to stress factors such as heat and drought are evaluated. And successful results are obtained.

  4. 48 CFR 1845.502-70 - Contractor-acquired property.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contractor-acquired... Possession of Contractors 1845.502-70 Contractor-acquired property. All contractor-acquired property must be... contractor-acquired. (2) Submission of DD Form 1419, DOD Industrial Plant Requisition, or equivalent format...

  5. Bridging the gap between theory and practice: dynamic systems theory as a framework for understanding and promoting recovery of function in children and youth with acquired brain injuries.

    Science.gov (United States)

    Levac, Danielle; DeMatteo, Carol

    2009-11-01

    A theoretical framework can help physiotherapists understand and promote recovery of function in children and youth with acquired brain injuries (ABI). Physiotherapy interventions for this population have traditionally been based in hierarchical-maturational theories of motor development emphasizing the role of the central nervous system (CNS) in controlling motor behaviour. In contrast, Dynamic Systems Theory (DST) views movement as resulting from the interaction of many subsystems within the individual, features of the functional task to be accomplished, and the environmental context in which the movement takes place. DST is now a predominant theoretical framework in pediatric physiotherapy. The purpose of this article is to describe how DST can be used to understand and promote recovery of function after pediatric ABI. A DST-based approach for children and youth with ABI does not treat the impaired CNS in isolation but rather emphasizes the role of all subsystems, including the family and the environment, in influencing recovery. The emphasis is on exploration, problem solving, and practice of functional tasks. A case scenario provides practical recommendations for the use of DST to inform physiotherapy interventions and clinical decision making in the acute phase of recovery from ABI. Future research is required to evaluate the effectiveness of interventions based in this theoretical framework.

  6. Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone? – a time series analysis

    Directory of Open Access Journals (Sweden)

    Black James F

    2008-07-01

    Full Text Available Abstract Background The ideal method to encourage uptake of clinical guidelines in hospitals is not known. Several strategies have been suggested. This study evaluates the impact of academic detailing and a computerised decision support system (CDSS on clinicians' prescribing behaviour for patients with community acquired pneumonia (CAP. Methods The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis. Results The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p Conclusion Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.

  7. Castration-resistant prostate cancer: systemic therapy in 2012

    Directory of Open Access Journals (Sweden)

    Fernando C. Maluf

    2012-01-01

    Full Text Available Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer.

  8. Community-acquired pneumonia.

    Science.gov (United States)

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  9. Acquired hypofibrinogenemia: current perspectives

    Directory of Open Access Journals (Sweden)

    Besser MW

    2016-09-01

    Full Text Available Martin W Besser,1 Stephen G MacDonald2 1Department of Haematology, 2Department of Specialist Haemostasis, The Pathology Partnership, Addenbrooke’s Hospital, Cambridge, UK Abstract: Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient’s fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia. Keywords: Clauss fibrinogen assay, fibrinogen antigen, viscoelastic testing, ­gravimetric fibrinogen assay, PT-derived fibrinogen, functional fibrinogen, direct oral anticoagulant, dysfibrinogenemia, afibrinogenemia

  10. Acquired hypertrichosis lanuginosa

    Directory of Open Access Journals (Sweden)

    Kumar Pramod

    1993-01-01

    Full Text Available Acquired hypertirichosis lanuginose developed rapidly in a patient with no detectable malignancy. Soft, fine, downy hair growth was noticed on the face, ears, limbs and trunk. Bilaterally symmetrical vitiliginous macules were present on the ear and preauricular region. This case is reported because of its rarity, absence of any detectable malignancy and development of vitiligo, which to our knowledge has not been reported earlier.

  11. Impact of doctors' resistance on success of drug utilization review system.

    Science.gov (United States)

    Choi, Jong Soo; Yun, Seong Hyeon; Kim, Dongsoo; Park, Seung Woo

    2014-04-01

    The drug utilization review (DUR) system, which checks any conflict event of medications, contributes to improve patient safety. One of the important barriers in its adoption is doctors' resistance. This study aimed to analyze the impacts of doctors' resistance on the success of the DUR system. This study adopted an augmented the DeLone and McLean Information System (D&M IS) Success Model (2003), which used doctors' resistance as a socio-technological measure. This study framework is the same as that of the D&M IS Success Model in that it is based on qualities, such as system, information, and services. The major difference is that this study excluded the variable 'use' because it was not statistically significant for mandatory systems. A survey of doctors who used computers to enter prescriptions was conducted at a Korean tertiary hospital in February 2012. This study is very meaningful in that it is the first study to explore the success factors of the DUR system associated with doctors' resistance. Doctors' resistance to the DUR system was not statistically associated with user usefulness, whereas it affected user satisfaction. The results indicate that doctors still complain of discomfort in using the DUR system in the outpatient clinical setting, even though they admit that it contributes to patient safety. To mitigate doctors' resistance and raise user satisfaction, more opinions from doctors regarding the DUR system have to be considered and have to be reflected in the system.

  12. Regeneration systems for pyramiding disease resistance into walnut rootstocks

    Science.gov (United States)

    This study was conducted to regenerate selected walnut rootstocks adventitiously. This is an essential step to be able to produce transgenic walnut rootstocks with superior traits, such as disease resistance. A series of plant tissue culture experiments were conducted on RX1 and VX211 rootstocks wit...

  13. A controlled study of funding for human immunodeficiency virus/acquired immunodeficiency syndrome as resource capacity building in the health system in Rwanda.

    Science.gov (United States)

    Shepard, Donald S; Zeng, Wu; Amico, Peter; Rwiyereka, Angelique K; Avila-Figueroa, Carlos

    2012-05-01

    Because human inmmunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) receives more donor funding globally than that for all other diseases combined, some critics allege this support undermines general health care. This empirical study evaluates the impact of HIV/AIDS funding on the primary health care system in Rwanda. Using a quasi-experimental design, we randomly selected 25 rural health centers (HCs) that started comprehensive HIV/AIDS services from 2002 through 2006 as the intervention group. Matched HCs with no HIV/AIDS services formed the control group. The analysis compared growth in inputs and services between intervention and control HCs with a difference-in-difference analysis in a random-effects model. Intervention HCs performed better than control HCs in most services (seven of nine), although only one of these improvements (Bacille Calmette-Guérin vaccination) reached or approached statistical significance. In conclusion, this six-year controlled study found no adverse effects of the expansion of HIV/AIDS services on non-HIV services among rural health centers in Rwanda.

  14. Effector peptides of the renin-angiotensin system in the central mechanisms of acquired and innate behavior in thirst in rats.

    Science.gov (United States)

    Vlasenko, R Ya; Kotov, A V

    2007-03-01

    We report here a comparative analysis of the involvement of a number of components of the renin-angiotensin system in the performance of simple and complex forms of drinking behavior and thirst-associated non-drinking types of behavior. On central (intracerebroventricular) microinjection, [des-Asp1]-angiotensin I at doses equieffective to those of angiotensins II and III was found to be involved only in the performance of simple (taking water from the bowl) and linked forms of activity (comfort behavior, stress grooming, orientational-investigative, and feeding behavior). Angiotensin II was involved in the central mechanisms of complex acquired drinking behavior, selectively modulating its key stages (initial, final), while angiotensin III was involved only in the mechanisms of reproduction of the complex skill. All three substances induced "innate patterns of behavior" specific for each compound, these occurring at fixed periods of time after intracerebral microinjection. The effects of these substances were selectively suppressed by the AT1 receptor blocker losartan potassium.

  15. Mapping of invasive Acacia species in Brazilian Mussununga ecosystems using high- resolution IR remote sensing data acquired with an autonomous Unmanned Aerial System (UAS)

    Science.gov (United States)

    Lehmann, Jan Rudolf Karl; Zvara, Ondrej; Prinz, Torsten

    2015-04-01

    The biological invasion of Australian Acacia species in natural ecosystems outside Australia has often a negative impact on native and endemic plant species and the related biodiversity. In Brazil, the Atlantic rainforest of Bahia and Espirito Santo forms an associated type of ecosystem, the Mussununga. In our days this biologically diverse ecosystem is negatively affected by the invasion of Acacia mangium and Acacia auriculiformis, both introduced to Brazil by the agroforestry to increase the production of pulp and high grade woods. In order to detect the distribution of Acacia species and to monitor the expansion of this invasion the use of high-resolution imagery data acquired with an autonomous Unmanned Aerial System (UAS) proved to be a very promising approach. In this study, two types of datasets - CIR and RGB - were collected since both types provide different information. In case of CIR imagery attention was paid on spectral signatures related to plants, whereas in case of RGB imagery the focus was on surface characteristics. Orthophoto-mosaics and DSM/DTM for both dataset were extracted. RGB/IHS transformations of the imagery's colour space were utilized, as well as NDVIblue index in case of CIR imagery to discriminate plant associations. Next, two test areas were defined in order validate OBIA rule sets using eCognition software. In case of RGB dataset, a rule set based on elevation distinction between high vegetation (including Acacia) and low vegetation (including soils) was developed. High vegetation was classified using Nearest Neighbour algorithm while working with the CIR dataset. The IHS information was used to mask shadows, soils and low vegetation. Further Nearest Neighbour classification was used for distinction between Acacia and other high vegetation types. Finally an accuracy assessment was performed using a confusion matrix. One can state that the IHS information appeared to be helpful in Acacia detection while the surface elevation

  16. Common acquired kidney diseases in children

    African Journals Online (AJOL)

    5. Common acquired kidney diseases in children. Examination of the urine is probably the most important investigation ... result from the same streptococcal infection. .... musculoskeletal system. ... Prediction of histopathology from clinical.

  17. Engineering Plants for Geminivirus Resistance with CRISPR/Cas9 System

    KAUST Repository

    Zaidi, Syed Shan-e-Ali; Mansoor, Shahid; Ali, Zahir; Tashkandi, Manal; Mahfouz, Magdy M.

    2016-01-01

    The CRISPR/Cas9 system is an efficient genome-editing platform for diverse eukaryotic species, including plants. Recent work harnessed CRISPR/Cas9 technology to engineer resistance to geminiviruses. Here, we discuss opportunities, emerging developments, and potential pitfalls for using this technology to engineer resistance against single and multiple geminivirus infections in plants.

  18. Engineering Plants for Geminivirus Resistance with CRISPR/Cas9 System

    KAUST Repository

    Zaidi, Syed Shan-e-Ali

    2016-02-14

    The CRISPR/Cas9 system is an efficient genome-editing platform for diverse eukaryotic species, including plants. Recent work harnessed CRISPR/Cas9 technology to engineer resistance to geminiviruses. Here, we discuss opportunities, emerging developments, and potential pitfalls for using this technology to engineer resistance against single and multiple geminivirus infections in plants.

  19. Scaling theory of quantum resistance distributions in disordered systems

    International Nuclear Information System (INIS)

    Jayannavar, A.M.

    1991-01-01

    The large scale distribution of quantum Ohmic resistance of a disorderd one-dimensional conductor is derived explicitly. It is shown that in the thermodynamic limit this distribution is characterized by two independent parameters for strong disorder, leading to a two-parameter scaling theory of localization. Only in the limit of weak disorder single parameter scaling consistent with existing theoretical treatments is recovered. (author). 33 refs., 4 figs

  20. Scaling theory of quantum resistance distributions in disordered systems

    International Nuclear Information System (INIS)

    Jayannavar, A.M.

    1990-05-01

    We have derived explicitly, the large scale distribution of quantum Ohmic resistance of a disordered one-dimensional conductor. We show that in the thermodynamic limit this distribution is characterized by two independent parameters for strong disorder, leading to a two-parameter scaling theory of localization. Only in the limit of weak disorder we recover single parameter scaling, consistent with existing theoretical treatments. (author). 32 refs, 4 figs

  1. Metagenomic analysis of antibiotic resistance genes in coastal industrial mariculture systems.

    Science.gov (United States)

    Wang, Jian-Hua; Lu, Jian; Zhang, Yu-Xuan; Wu, Jun; Luo, Yongming; Liu, Hao

    2018-04-01

    The overuse of antibiotics has posed a propagation of antibiotic resistance genes (ARGs) in aquaculture systems. This study firstly explored the ARGs profiles of the typical mariculture farms including conventional and recirculating systems using metagenomics approach. Fifty ARGs subtypes belonging to 21 ARGs types were identified, showing the wide-spectrum profiles of ARGs in the coastal industrial mariculture systems. ARGs with multiple antibiotics resistance have emerged in the mariculure systems. The co-occurrence pattern between ARGs and microbial taxa showed that Proteobacteria and Bacteroidetes were potential dominant hosts of ARGs in the industrial mariculture systems. Typical nitrifying bacteria such as Nitrospinae in mariculture systems also carried with some resistance genes. Relative abundance of ARGs in fish ponds and wastewater treatment units was relatively high. The investigation showed that industrial mariculture systems were important ARGs reservoirs in coastal area, indicating the critical role of recirculating systems in the terms of ARGs pollution control. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. The acquired hyperostosis syndrome

    International Nuclear Information System (INIS)

    Dihlmann, W.; Hering, L.; Bargon, G.W.

    1988-01-01

    Sterno-costo-clavicular hyperostosis (SCCH) is the most common manifestation of a syndrome, consisting of increased bone metabolism, mostly new bone formation and heterotopic ossification of fibrous tissue, which we have characterised as the acquired hyperostosis syndrome. In part I we discuss the terminology, radiological appearances, scintigraphy, clinical and laboratory findings, bacteriology, histology, nosology, complications, treatment and differential diagnosis of SCCH. Chronic recurrent multifocal osteomyelitis (CRMO) is regarded as a phaenotype of SCCH, depending on the age. CRMO occurs in children, adolescents and young adults, SCCH predominantly in middleaged and elderly adults. (orig.) [de

  3. Acquired epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Maricel Sucar Batista

    2015-12-01

    Full Text Available Epidermolysis bullosa is a group of diseases or skin disorders genetically transmitted and it is characterized by the appearance of bullae, ulcers and skin wounds. It usually appears at birth or in the first months of life. This is a case of a 72-year-old female patient who comes to the dermatology department with skin lesions of 6 months of evolution. A skin biopsy was performed, taking a sample for direct and indirect immunofluorescence. Acquired epidermolysis bullosa of unknown etiology was diagnosed. Treatment was started with low-dose colchicine to increase it later, according to the patient’s tolerance and disease progression.

  4. Effectiveness of a Wii balance board-based system (eBaViR for balance rehabilitation: a pilot randomized clinical trial in patients with acquired brain injury

    Directory of Open Access Journals (Sweden)

    Alcañiz Mariano

    2011-05-01

    Full Text Available Abstract Background Acquired brain injury (ABI is the main cause of death and disability among young adults. In most cases, survivors can experience balance instability, resulting in functional impairments that are associated with diminished health-related quality of life. Traditional rehabilitation therapy may be tedious. This can reduce motivation and adherence to the treatment and thus provide a limited benefit to patients with balance disorders. We present eBaViR (easy Balance Virtual Rehabilitation, a system based on the Nintendo® Wii Balance Board® (WBB, which has been designed by clinical therapists to improve standing balance in patients with ABI through motivational and adaptative exercises. We hypothesize that eBaViR, is feasible, safe and potentially effective in enhancing standing balance. Methods In this contribution, we present a randomized and controlled single blinded study to assess the influence of a WBB-based virtual rehabilitation system on balance rehabilitation with ABI hemiparetic patients. This study describes the eBaViR system and evaluates its effectiveness considering 20 one-hour-sessions of virtual reality rehabilitation (n = 9 versus standard rehabilitation (n = 8. Effectiveness was evaluated by means of traditional static and dynamic balance scales. Results The final sample consisted of 11 men and 6 women. Mean ± SD age was 47.3 ± 17.8 and mean ± SD chronicity was 570.9 ± 313.2 days. Patients using eBaViR had a significant improvement in static balance (p = 0.011 in Berg Balance Scale and p = 0.011 in Anterior Reaches Test compared to patients who underwent traditional therapy. Regarding dynamic balance, the results showed significant improvement over time in all these measures, but no significant group effect or group-by-time interaction was detected for any of them, which suggests that both groups improved in the same way. There were no serious adverse events during treatment in either group. Conclusions The

  5. Effectiveness of a Wii balance board-based system (eBaViR) for balance rehabilitation: a pilot randomized clinical trial in patients with acquired brain injury.

    Science.gov (United States)

    Gil-Gómez, José-Antonio; Lloréns, Roberto; Alcañiz, Mariano; Colomer, Carolina

    2011-05-23

    Acquired brain injury (ABI) is the main cause of death and disability among young adults. In most cases, survivors can experience balance instability, resulting in functional impairments that are associated with diminished health-related quality of life. Traditional rehabilitation therapy may be tedious. This can reduce motivation and adherence to the treatment and thus provide a limited benefit to patients with balance disorders. We present eBaViR (easy Balance Virtual Rehabilitation), a system based on the Nintendo® Wii Balance Board® (WBB), which has been designed by clinical therapists to improve standing balance in patients with ABI through motivational and adaptative exercises. We hypothesize that eBaViR, is feasible, safe and potentially effective in enhancing standing balance. In this contribution, we present a randomized and controlled single blinded study to assess the influence of a WBB-based virtual rehabilitation system on balance rehabilitation with ABI hemiparetic patients. This study describes the eBaViR system and evaluates its effectiveness considering 20 one-hour-sessions of virtual reality rehabilitation (n = 9) versus standard rehabilitation (n = 8). Effectiveness was evaluated by means of traditional static and dynamic balance scales. The final sample consisted of 11 men and 6 women. Mean ± SD age was 47.3 ± 17.8 and mean ± SD chronicity was 570.9 ± 313.2 days. Patients using eBaViR had a significant improvement in static balance (p = 0.011 in Berg Balance Scale and p = 0.011 in Anterior Reaches Test) compared to patients who underwent traditional therapy. Regarding dynamic balance, the results showed significant improvement over time in all these measures, but no significant group effect or group-by-time interaction was detected for any of them, which suggests that both groups improved in the same way. There were no serious adverse events during treatment in either group. The results suggest that eBaViR represents a safe and effective

  6. Waldenstrom macroglobulinemia cells devoid of BTKC481S or CXCR4WHIM-like mutations acquire resistance to ibrutinib through upregulation of Bcl-2 and AKT resulting in vulnerability towards venetoclax or MK2206 treatment

    OpenAIRE

    Paulus, A; Akhtar, S; Yousaf, H; Manna, A; Paulus, S M; Bashir, Y; Caulfield, T R; Kuranz-Blake, M; Chitta, K; Wang, X; Asmann, Y; Hudec, R; Springer, W; Ailawadhi, S; Chanan-Khan, A

    2017-01-01

    Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9?3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed ...

  7. Differential effectiveness of salicylate-dependent and jasmonate/ethylene-dependent induced resistance in Arabidopsis

    NARCIS (Netherlands)

    Ton, J.; Pelt, J.A. van; Loon, L.C. van; Pieterse, C.M.J.

    2002-01-01

    Salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) are each involved in the regulation of basal resistance against different pathogens. These three signals play important roles in induced resistance as well. SA is a key regulator of pathogen-induced systemic acquired resistance (SAR),

  8. The acid-base resistant zone in three dentin bonding systems.

    Science.gov (United States)

    Inoue, Go; Nikaido, Toru; Foxton, Richard M; Tagami, Junji

    2009-11-01

    An acid-base resistant zone has been found to exist after acid-base challenge adjacent to the hybrid layer using SEM. The aim of this study was to examine the acid-base resistant zone using three different bonding systems. Dentin disks were applied with three different bonding systems, and then a resin composite was light-cured to make dentin disk sandwiches. After acid-base challenge, the polished surfaces were observed using SEM. For both one- and two-step self-etching primer systems, an acid-base resistant zone was clearly observed adjacent to the hybrid layer - but with differing appearances. For the wet bonding system, the presence of an acid-base resistant zone was unclear. This was because the self-etching primer systems etched the dentin surface mildly, such that the remaining mineral phase of dentin and the bonding agent yielded clear acid-base resistant zones. In conclusion, the acid-base resistant zone was clearly observed when self-etching primer systems were used, but not so for the wet bonding system.

  9. Effects of Floor Covering Resistance of a Radiant Floor on System Energy and Exergy Performances

    DEFF Research Database (Denmark)

    Kazanci, Ongun Berk; Shukuya, Masanori; Olesen, Bjarne W.

    2016-01-01

    Floor covering resistance (material and thickness) can be influenced by subjective choices (architectural design, interior design, texture, etc.) with significant effects on the performance of a radiant heating and cooling system. To study the effects of floor covering resistance on system...... performance, a water-based radiant floor heating and cooling system (dry, wooden construction) was considered to be coupled to an air-to-water heat pump, and the effects of varying floor covering resistances (0.05 m2K/W, 0.09 m2K/W and 0.15 m2K/W) on system performance were analyzed in terms of energy...... and exergy. In order to achieve the same heating and cooling outputs, higher average water temperatures are required in the heating mode (and lower temperatures in the cooling mode) with increasing floor covering resistance. These temperature requirements decrease the heat pump’s performance (lower...

  10. The Dutch pork chain: a commodity system resisting threats from the market and society

    NARCIS (Netherlands)

    Greef, de K.H.; Casabianca, F.

    2009-01-01

    The Dutch pork sector can be characterized as one massive, homogeneous commodity system, resisting diversification. A closer look at innovation strategies and initiatives leads to the conclusion that efforts are being made to enhance sustainability (including economic viability) through

  11. Validation of the digital PCR system in tyrosine kinase inhibitor-resistant EGFR mutant non-small-cell lung cancer.

    Science.gov (United States)

    Masago, Katsuhiro; Fujita, Shiro; Hata, Akito; Okuda, Chiyuki; Yoshizumi, Yuko; Kaji, Reiko; Katakami, Nobuyuki; Hirata, Yukio; Yatabe, Yasushi

    2018-03-01

    The aim of this study was to compare the accuracy of the QuantStudio 3D Digital polymerase chain reaction (dPCR) system and a PCR-based next generation sequencing (NGS) system for detecting a secondary mutation in the epidermal growth factor receptor (EGFR) gene T790M in non-small cell lung cancer (NSCLC) patients previously diagnosed with EGFR-activating mutations. Twenty-five patients with NSCLC previously treated with EGFR-TKIs were examined. The patients were treated daily with either erlotinib or gefitinib. New biopsies, followed by DNA sequencing on an Ion Torrent systems using the Ion Torrent AmpliSeq Cancer Hotspot Panel and dPCR were performed. A comparison of NGS, sensitive PCR, and dPCR revealed that the sensitivities of NGS and dPCR were similar in this study. As well, T790M was detected in as low as about 5% of mutant allelic frequencies, which represented 5% of the total reads on site mapped reads in NGS and greater than 5% of the dPCR reads, which represented mutant and wild type copies. The strategy in which NGS sequencing is followed by revealed acquired mutation with dPCR may be a reasonable one. We demonstrated the utility of combining NGS and dPCR as a tool for monitoring T790M. NGS and dPCR with formalin-fixed paraffin-embedded (FFPE) specimens might become a standard genomic test for exploring acquired resistance to targeted molecular medicines. © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  12. Coaxial Tubing Systems Increase Artificial Airway Resistance and Work of Breathing.

    Science.gov (United States)

    Wenzel, Christin; Schumann, Stefan; Spaeth, Johannes

    2017-09-01

    Tubing systems are an essential component of the ventilation circuit, connecting the ventilator to the patient's airways. Coaxial tubing systems incorporate the inspiratory tube within the lumen of the expiratory one. We hypothesized that by design, these tubing systems increase resistance to air flow compared with conventional ones. We investigated the flow-dependent pressure gradient across coaxial, conventional disposable, and conventional reusable tubing systems from 3 different manufacturers. Additionally, the additional work of breathing and perception of resistance during breathing through the different devices were determined in 18 healthy volunteers. The pressure gradient across coaxial tubing systems was up to 6 times higher compared with conventional ones (1.90 ± 0.03 cm H 2 O vs 0.34 ± 0.01 cm H 2 O, P tubing systems, accordingly. Our findings suggest that the use of coaxial tubing systems should be carefully considered with respect to their increased resistance. Copyright © 2017 by Daedalus Enterprises.

  13. Features of the mental status of patients with community-acquired pneumonia, combined with a chronic pathology of the hepatobiliary system of non-viral genesis

    Directory of Open Access Journals (Sweden)

    Razumnyi R.V.

    2017-04-01

    Full Text Available The aim was to study the characteristics of mental status of patients with community-acquired pneumonia (CAP, combined with a chronic pathology of the hepatobiliary system of non-viral genesis. We observed 165 patients with CAP in the age of 25-57 years. All patients were divided into two representative groups: I group (68 patients – CAP was comorbid with hepatic steatosis (HS, II group (96 patients with absence of chronic liver disease. To evaluate the psychological profile of patients’ personality we used a standardized multivariate method of personality research and to evaluate the level of anxiety and depression the scale of Spielberger-Hanin test and Beck’s questionnaire were used. Results of the study revealed that 66.2% of patients with CAP, comorbid with HS, declared the formation of psycho-emotional disorders in the form of neurotic reactions to the disease with prevalence of hypochondria, depression, hysterical manifestations with high psychasthenia, trait anxiety and somatic reactions with prevalence of anxiety and emotional instability, lots of somatic complaints, fixation on their own condition with formation of distinctive thinking mode and behavior by the type of "flight into disease". After completion of the standard treatment of patients with CAP, combined with HS, 42,7% of patients had psycho-emotional disorders, which were moderately expressed. Thus, in the complex of treatment and rehabilitative measures in patients with CAP, combined with HS some characteristics of the psychological profile, in the form of psycho-neurotic reaction to the disease should be considered to take optimal corrective actions.

  14. The Application of a Piezo-Resistive Cardiorespiratory Sensor System in an Automobile Safety Belt

    Science.gov (United States)

    Hamdani, Syed Talha Ali; Fernando, Anura

    2015-01-01

    Respiratory and heart failure are conditions that can occur with little warning and may also be difficult to predict. Therefore continuous monitoring of these bio-signals is advantageous for ensuring human health. The car safety belt is mainly designed to secure the occupants of the vehicle in the event of an accident. In the current research a prototype safety belt is developed, which is used to acquire respiratory and heart signals, under laboratory conditions. The current safety belt is constructed using a copper ink based nonwoven material, which works based on the piezo-resistive effect due to the pressure exerted on the sensor as a result of expansion of the thorax/abdomen area of the body for respiration and due to the principle of ballistocardiography (BCG) in heart signal sensing. In this research, the development of a theoretical model to qualitatively describe the piezo-resistive material is also presented in order to predict the relative change in the resistance of the piezo-resistive material due to the pressure applied. PMID:25831088

  15. The application of a piezo-resistive cardiorespiratory sensor system in an automobile safety belt.

    Science.gov (United States)

    Hamdani, Syed Talha Ali; Fernando, Anura

    2015-03-30

    Respiratory and heart failure are conditions that can occur with little warning and may also be difficult to predict. Therefore continuous monitoring of these bio-signals is advantageous for ensuring human health. The car safety belt is mainly designed to secure the occupants of the vehicle in the event of an accident. In the current research a prototype safety belt is developed, which is used to acquire respiratory and heart signals, under laboratory conditions. The current safety belt is constructed using a copper ink based nonwoven material, which works based on the piezo-resistive effect due to the pressure exerted on the sensor as a result of expansion of the thorax/abdomen area of the body for respiration and due to the principle of ballistocardiography (BCG) in heart signal sensing. In this research, the development of a theoretical model to qualitatively describe the piezo-resistive material is also presented in order to predict the relative change in the resistance of the piezo-resistive material due to the pressure applied.

  16. The Application of a Piezo-Resistive Cardiorespiratory Sensor System in an Automobile Safety Belt

    Directory of Open Access Journals (Sweden)

    Syed Talha Ali Hamdani

    2015-03-01

    Full Text Available Respiratory and heart failure are conditions that can occur with little warning and may also be difficult to predict. Therefore continuous monitoring of these bio-signals is advantageous for ensuring human health. The car safety belt is mainly designed to secure the occupants of the vehicle in the event of an accident. In the current research a prototype safety belt is developed, which is used to acquire respiratory and heart signals, under laboratory conditions. The current safety belt is constructed using a copper ink based nonwoven material, which works based on the piezo-resistive effect due to the pressure exerted on the sensor as a result of expansion of the thorax/abdomen area of the body for respiration and due to the principle of ballistocardiography (BCG in heart signal sensing. In this research, the development of a theoretical model to qualitatively describe the piezo-resistive material is also presented in order to predict the relative change in the resistance of the piezo-resistive material due to the pressure applied.

  17. Robust stator resistance identification of an IM drive using model reference adaptive system

    International Nuclear Information System (INIS)

    Madadi Kojabadi, Hossein; Abarzadeh, Mostafa; Aghaei Farouji, Said

    2013-01-01

    Highlights: ► We estimate the stator resistance and rotor speed of the IM. ► We proposed a new quantity to estimate the speed and stator resistance of IM. ► The proposed algorithm is robust to rotor resistance variations. ► We estimate the IM speed and stator resistance simultaneously to avoid speed error. - Abstract: Model reference adaptive system (MRAS) based robust stator resistance estimator for sensorless induction motor (IM) drive is proposed. The MRAS is formed with a semi-active power quantity. The proposed identification method can be achieved with on-line tuning of the stator resistance with robustness against rotor resistance variations. Stable and efficient estimation of IM speed at low region will be guaranteed by simultaneous identification of IM speed and stator resistance. The stability of proposed stator resistance estimator is checked through Popov’s hyperstability theorem. Simulation and experimental results are given to highlight the feasibility, the simplicity, and the robustness of the proposed method.

  18. Use of high-resolution imagery acquired from an unmanned aircraft system for fluvial mapping and estimating water-surface velocity in rivers

    Science.gov (United States)

    Kinzel, P. J.; Bauer, M.; Feller, M.; Holmquist-Johnson, C.; Preston, T.

    2013-12-01

    The use of unmanned aircraft systems (UAS) for environmental monitoring in the United States is anticipated to increase in the coming years as the Federal Aviation Administration (FAA) further develops guidelines to permit their integration into the National Airspace System. The U.S. Geological Survey's (USGS) National Unmanned Aircraft Systems Project Office routinely obtains Certificates of Authorization from the FAA for utilizing UAS technology for a variety of natural resource applications for the U.S. Department of the Interior (DOI). We evaluated the use of a small UAS along two reaches of the Platte River near Overton Nebraska, USA, to determine the accuracy of the system for mapping the extent and elevation of emergent sandbars and to test the ability of a hovering UAS to identify and track tracers to estimate water-surface velocity. The UAS used in our study is the Honeywell Tarantula Hawk RQ16 (T-Hawk), developed for the U.S. Army as a reconnaissance and surveillance platform. The T-Hawk has been recently modified by USGS, and certified for airworthiness by the DOI - Office of Aviation Services, to accommodate a higher-resolution imaging payload than was originally deployed with the system. The T-Hawk is currently outfitted with a Canon PowerShot SX230 HS with a 12.1 megapixel resolution and intervalometer to record images at a user defined time step. To increase the accuracy of photogrammetric products, orthoimagery and DEMs using structure-from-motion (SFM) software, we utilized ground control points in the study reaches and acquired imagery using flight lines at various altitudes (200-400 feet above ground level) and oriented both parallel and perpendicular to the river. Our results show that the mean error in the elevations derived from SFM in the upstream reach was 17 centimeters and horizontal accuracy was 6 centimeters when compared to 4 randomly distributed targets surveyed on emergent sandbars. In addition to the targets, multiple transects were

  19. Antibiotic stewardship in community-acquired pneumonia.

    Science.gov (United States)

    Viasus, Diego; Vecino-Moreno, Milly; De La Hoz, Juan M; Carratalà, Jordi

    2017-04-01

    Community-acquired pneumonia (CAP) continues to be associated with significant mortality and morbidity. As with other infectious diseases, in recent years there has been a marked increase in resistance to the antibiotics commonly used against the pathogens that cause CAP. Antimicrobial stewardship denotes coordinated interventions to improve and measure the appropriate use of antibiotics by encouraging the selection of optimal drug regimens. Areas covered: Several elements can be applied to antibiotic stewardship strategies for CAP in order to maintain or improve patient outcomes. In this regard, antibiotic de-escalation, duration of antibiotic treatment, adherence to CAP guidelines recommendations about empirical treatment, and switching from intravenous to oral antibiotic therapy may each be relevant in this context. Antimicrobial stewardship strategies, such as prospective audit with intervention and feedback, clinical pathways, and dedicated multidisciplinary teams, that have included some of these elements have demonstrated improvements in antimicrobial use for CAP without negatively affecting clinical outcomes. Expert commentary: Although there are a limited number of randomized clinical studies addressing antimicrobial stewardship strategies in CAP, there is evidence that antibiotic stewardship initiatives can be securely applied, providing benefits to both healthcare systems and patients.

  20. A study on the proliferation resistance evaluation methodology for nuclear energy system

    International Nuclear Information System (INIS)

    Kim, Min Su

    2007-02-01

    The framework of proliferation resistance evaluation methodology, based on attribute analysis and scenario analysis, for nuclear energy system is suggested in order to allow for the comprehensive assessment of proliferation resistance by addressing the intrinsic and extrinsic features of nuclear energy system. Proliferation resistance is viewed within the context of the success tree model of proliferator's diversion attempt and expressed by the value of top event probability of the success tree model. This study focused on the method that the value of top event is estimated. The methodology uses two different methods to quantify the likelihood of basic events constituting the top event. The likelihood of basic event success affected by intrinsic feature of nuclear energy system was assessed by using multi-attribute utility theory and likelihood of basic event related to the diversion detection measures was assessed by direct expert elicitation. The value of top event was calculated based on the intersection of probabilities of basic event success. Feasibility of the methodology was explored by applying it to selected reference nuclear energy systems. System-Integrated Modular Advanced Reactor (SMART) system and Light Water Reactor (LWR) were chosen as reference systems and the value proliferation resistance of SMART and LWR were evaluated. Characteristics of inherent features and hypothesized safeguards measures of both systems were identified and used as input data to evaluate proliferation resistance. The results and conclusions are applicable only within the context of subjectivity of this methodology

  1. A review of methods to evaluate borehole thermal resistances in geothermal heat-pump systems

    Energy Technology Data Exchange (ETDEWEB)

    Lamarche, Louis; Kajl, Stanislaw; Beauchamp, Benoit [Ecole de Technologie Superieure, 1100 Notre-Dame Ouest, Montreal (Canada)

    2010-06-15

    In the design of a ground-source heat pump (GSHP) system, the heat transfer from the fluid to the ground is influenced by the thermal borehole resistance between the fluid and the borehole surface and also by the interference resistance between the two (or four) pipes inside the borehole. Several authors have proposed empirical and theoretical relations to evaluate these resistances as well as methods to evaluate them experimentally. The paper compares the different approaches and proposes good practice to evaluate the resistances. The impact of the different approaches on the design of heat exchanger is also examined. Two-dimensional and fully three-dimensional numerical simulations are used to evaluate the different methods. A new method is also proposed to evaluate the borehole resistances from in situ tests. (author)

  2. VirTUal remoTe labORatories managEment System (TUTORES): Using Cloud Computing to Acquire University Practical Skills

    Science.gov (United States)

    Caminero, Agustín C.; Ros, Salvador; Hernández, Roberto; Robles-Gómez, Antonio; Tobarra, Llanos; Tolbaños Granjo, Pedro J.

    2016-01-01

    The use of practical laboratories is a key in engineering education in order to provide our students with the resources needed to acquire practical skills. This is specially true in the case of distance education, where no physical interactions between lecturers and students take place, so virtual or remote laboratories must be used. UNED has…

  3. Investigating the Acquisition, Generalization, and Emergence of Untrained Verbal Operants for Mands Acquired Using the Picture Exchange Communication System in Adults with Severe Developmental Disabilities

    Science.gov (United States)

    Ziomek, M. M.; Rehfeldt, R. A.

    2008-01-01

    This study compared the total amount of training time and total number of trial blocks for individuals with severe developmental disabilities to acquire mands under control of unconditioned establishing operations and mands under control of transitive conditioned establishing operations for manual sign and for the Picture Exchange Communication…

  4. Analysis of the Factors Affecting Resistance to Changes in Management Accounting Systems

    Directory of Open Access Journals (Sweden)

    Rodrigo Angonese

    2014-12-01

    Full Text Available Despite changes in the environment and management accounting practices, studies indicate that management accounting systems do not change or change at a much slower rate than expected. The stability of the management accounting systems used by companies may relate to resistance to changing these systems. This study analyzes the factors that contribute to resistance to implementing an integrated management system from the perspective of institutional theory, grounded in the old institutional economics. Methodologically, this study provides a qualitative assessment of the problem and a descriptive analysis of the resistance factors through a case-study approach. The data were collected using semi-structured interviews and analyzed through content analysis. Two companies were selected for this study due to their differing characteristics. The following seven factors were analyzed for resistance to implementing integrated management systems: institutional power, ontological insecurity, trust, inertia, lack of knowledge, acceptance of routines and decoupling. However, there was no evidence to characterize hierarchical power. The research findings indicate that changing management accounting systems, through the implementation of an integrated management system, faces internal resistance in these organizations. Each factor varies in intensity but is permanently present in these companies, such as ontological insecurity, trust, inertia, lack of knowledge, acceptance of routines and decoupling. These factors are awakened when the change process begins and, if they gather enough force, can stop the change.

  5. The Epl1 and Sm1 proteins from Trichoderma atroviride and Trichoderma virens differentially modulate systemic disease resistance against different life style pathogens in Solanum lycopersicum

    Directory of Open Access Journals (Sweden)

    Miguel Angel eSalas-Marina

    2015-02-01

    Full Text Available Fungi belonging to the genus Trichoderma, commonly found in soil or colonizing plant roots, exert beneficial effects on plants, including the promotion of growth and the induction of resistance to disease. T. virens and T. atroviride secrete the proteins Sm1 and Epl1, respectively, which elicit local and systemic disease resistance in plants. In this work, we show that these fungi promote growth in tomato (Solanum lycopersicum plants. T. virens was more effective than T. atroviride in promoting biomass gain, and both fungi were capable of inducing systemic protection in tomato against Alternaria solani, Botrytis cinerea, and Pseudomonas syringae pv. tomato (Pst DC3000. Deletion (KO of epl1 in T. atroviride resulted in diminished systemic protection against A. solani and B. cinerea, whereas the T. virens sm1 KO strain was less effective in protecting tomato against Pst DC3000 and B. cinerea. Importantly, over-expression (OE of epl1 and sm1 led to an increase in disease resistance against all tested pathogens. Although the Trichoderma WT strains induced both systemic acquired resistance (SAR- and induced systemic resistance (ISR-related genes in tomato, inoculation of plants with OE and KO strains revealed that Epl1 and Sm1 play a minor role in the induction of these genes. However, we found that Epl1 and Sm1 induce the expression of a peroxidase and an α-dioxygenase encoding genes, respectively, which could be important for tomato protection by Trichoderma spp. Altogether, these observations indicate that colonization by beneficial and/or infection by pathogenic microorganisms dictates many of the outcomes in plants, which are more complex than previously thought.

  6. Hardware Design of Tuber Electrical Resistance Tomography System Based on the Soil Impedance Test and Analysis

    OpenAIRE

    Liu Shuyi; Deng Xiang; Jiang Zili; Tang Yu

    2016-01-01

    The hardware design of tuber electrical resistance tomography (TERT) system is one of the key research problems of TERT data acquisition system. The TERT system can be applied to the tuber growth process monitoring in agriculture, i.e., the TERT data acquisition system can realize the real imaging of tuber plants in soil. In TERT system, the imaging tuber and soil multiphase medium is quite complexity. So, the impedance test and analysis of soil multiphase medium is very important to the desi...

  7. Investigation on the effect of thermal resistances on a highly concentrated photovoltaic-thermoelectric hybrid system

    International Nuclear Information System (INIS)

    Zhang, Jin; Xuan, Yimin

    2016-01-01

    Highlights: • The highly concentrated PV-TE hybrid system is studied. • The performances of different cooling systems are analyzed and compared. • Sandwiching a copper plate between the PV and TE can improve the efficiency. • Four thermal design principles of the system are proposed. - Abstract: A thermal analysis of a highly concentrated photovoltaic-thermoelectric (PV-TE) hybrid system is carried out in this paper. Both the output power and the temperature distribution in the hybrid system are calculated by means of a three-dimensional numerical model. Three possible approaches for designing the highly concentrated PV-TE hybrid system are presented by analyzing the thermal resistance of the whole system. First, the sensitivity analysis shows that the thermal resistance between the TE module and the environment has a more great effect on the output power than the thermal resistance between the PV and the TE. The influence of the natural convection and the radiation can be ignored for the highly concentrated PV-TE hybrid system. Second, it is necessary to sandwich a copper plate between the PV and the TE for decreasing the thermal resistance between the PV and the TE. The role of the copper plate is to improve the temperature uniformity. Third, decreasing the area of PV cells can improve the efficiency of the highly concentrated PV-TE hybrid system. It should be pointed out that decreasing the area of PV cells also increases the total thermal resistance, but the raise of the efficiency is caused by the reduction of the heat transfer rate of the system. Therefore, the principle of minimizing the total thermal resistance may not be suitable for optimizing the area of PV cells.

  8. Thermal resistance analysis and optimization of photovoltaic-thermoelectric hybrid system

    International Nuclear Information System (INIS)

    Yin, Ershuai; Li, Qiang; Xuan, Yimin

    2017-01-01

    Highlights: • A detailed thermal resistance analysis of the PV-TE hybrid system is proposed. • c-Si PV and p-Si PV cells are proved to be inapplicable for the PV-TE hybrid system. • Some criteria for selecting coupling devices and optimal design are obtained. • A detailed process of designing the practical PV-TE hybrid system is provided. - Abstract: The thermal resistance theory is introduced into the theoretical model of the photovoltaic-thermoelectric (PV-TE) hybrid system. A detailed thermal resistance analysis is proposed to optimize the design of the coupled system in terms of optimal total conversion efficiency. Systems using four types of photovoltaic cells are investigated, including monocrystalline silicon photovoltaic cell, polycrystalline silicon photovoltaic cell, amorphous silicon photovoltaic cell and polymer photovoltaic cell. Three cooling methods, including natural cooling, forced air cooling and water cooling, are compared, which demonstrates a significant superiority of water cooling for the concentrating photovoltaic-thermoelectric hybrid system. Influences of the optical concentrating ratio and velocity of water are studied together and the optimal values are revealed. The impacts of the thermal resistances of the contact surface, TE generator and the upper heat loss thermal resistance on the property of the coupled system are investigated, respectively. The results indicate that amorphous silicon PV cell and polymer PV cell are more appropriate for the concentrating hybrid system. Enlarging the thermal resistance of the thermoelectric generator can significantly increase the performance of the coupled system using amorphous silicon PV cell or polymer PV cell.

  9. A WWW-based information system on resistance of bacteria to antibiotics.

    Science.gov (United States)

    Schindler, J; Schindler, Z; Schindler, J

    1998-01-01

    The information system on resistance of bacteria to antibiotics (WARN--World Antibiotic Resistance Network) is implemented as a WWW server at Charles University in Prague (http:/(/)www.warn.cas.cz). Its main goal is to give information about problems of antibiotic resistance of bacteria and to process data on isolated strains. The WARN web-site contains six main topics. Four of them form the core of the system: Topics of Interest bring information on selected timely topics in antibiotic resistance--pneumococci, staphylococci, beta-lactamases, glycopeptide--and aminoglycoside resistance. Global Monitor brings references and reports on resistance in the world as well as recommended method of surveillance. The topic Data contains raw data on strains in particular countries and hospitals. Data can be viewed in their original form as a list of records (strains) or processed to provide statistics about the resistance rates in the selected country or hospital respectively. The topic Search allows one to search for one or several terms in the whole document. Counts of accessed pages show, that there is a standing demand for information about the serious problems of antibiotic therapy of infectious diseases.

  10. Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives.

    Science.gov (United States)

    Yasinzai, Masoom; Khan, Momin; Nadhman, Akhtar; Shahnaz, Gul

    2013-10-01

    Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The arvailable therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.

  11. Static frictional resistance with the slide low-friction elastomeric ligature system.

    Science.gov (United States)

    Jones, Steven P; Ben Bihi, Saida

    2009-11-01

    This ex-vivo study compared the static frictional resistance of a low-friction ligation system against a conventional elastomeric module, and studied the effect of storage in a simulated oral environment on the static frictional resistance of both ligation systems. Eighty stainless steel brackets were tested by sliding along straight lengths of 0.018 inch round and 0.019 x 0.025 inch rectangular stainless steel wires ligated with either conventional elastomerics or the Slide system (Leone, Florence, Italy). During the tests the brackets and wires were lubricated with artificial saliva. A specially constructed jig assembly was used to hold the bracket and archwire securely. The jig was clamped in an Instron universal load testing machine. Crosshead speed was controlled via a microcomputer connected to the Instron machine. The static frictional forces at 0 degree bracket/wire angulation were measured for both systems, fresh from the pack and after storage in artificial saliva at 37 degrees C for 24 hours. The results of this investigation demonstrated that the Slide ligatures produced significantly lower static frictional resistance than conventional elastomeric modules in the fresh condition and after 24 hours of storage in a simulated oral environment (p static frictional resistance of conventional elastomeric modules and the Slide system (p = 0.525). The claim by the manufacturer that the Slide system produces lower frictional resistance than conventional elastomeric modules is upheld.

  12. The University Immune System: Overcoming Resistance to Change

    Science.gov (United States)

    Gilley, Ann; Godek, Marisha; Gilley, Jerry W.

    2009-01-01

    A university, similar to any other organization, has an immune system that erects a powerful barrier against change. This article discusses the university immune system and what can be done to counteract its negative effects and thereby allow change to occur.

  13. Gene expression analysis of two extensively drug-resistant tuberculosis isolates show that two-component response systems enhance drug resistance.

    Science.gov (United States)

    Yu, Guohua; Cui, Zhenling; Sun, Xian; Peng, Jinfu; Jiang, Jun; Wu, Wei; Huang, Wenhua; Chu, Kaili; Zhang, Lu; Ge, Baoxue; Li, Yao

    2015-05-01

    Global analysis of expression profiles using DNA microarrays was performed between a reference strain H37Rv and two clinical extensively drug-resistant isolates in response to three anti-tuberculosis drug exposures (isoniazid, capreomycin, and rifampicin). A deep analysis was then conducted using a combination of genome sequences of the resistant isolates, resistance information, and related public microarray data. Certain known resistance-associated gene sets were significantly overrepresented in upregulated genes in the resistant isolates relative to that observed in H37Rv, which suggested a link between resistance and expression levels of particular genes. In addition, isoniazid and capreomycin response genes, but not rifampicin, either obtained from published works or our data, were highly consistent with the differentially expressed genes of resistant isolates compared to those of H37Rv, indicating a strong association between drug resistance of the isolates and genes differentially regulated by isoniazid and capreomycin exposures. Based on these results, 92 genes of the studied isolates were identified as candidate resistance genes, 10 of which are known resistance-related genes. Regulatory network analysis of candidate resistance genes using published networks and literature mining showed that three two-component regulatory systems and regulator CRP play significant roles in the resistance of the isolates by mediating the production of essential envelope components. Finally, drug sensitivity testing indicated strong correlations between expression levels of these regulatory genes and sensitivity to multiple anti-tuberculosis drugs in Mycobacterium tuberculosis. These findings may provide novel insights into the mechanism underlying the emergence and development of drug resistance in resistant tuberculosis isolates and useful clues for further studies on this issue. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Assessment on the influence of resistive superconducting fault current limiter in VSC-HVDC system

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong-Geon; Khan, Umer Amir; Hwang, Jae-Sang; Seong, Jae-Kyu; Shin, Woo-Ju; Park, Byung-Bae; Lee, Bang-Wook, E-mail: bangwook@hanyang.ac.kr

    2014-09-15

    Highlights: • The role of SFCLs in VSC-HVDC systems was evaluated. • Simulation model based on Korea Jeju-Haenam HVDC power system was designed. • An effect and the feasible locations of resistive SFCLs were evaluated. • DC line-to-line, DC line-to-ground and 3 phase AC faults were imposed and analyzed. - Abstract: Due to fewer risk of commutation failures, harmonic occurrences and reactive power consumptions, Voltage Source Converter (VSC) based HVDC system is known as the optimum solution of HVDC power system for the future power grid. However, the absence of suitable fault protection devices for HVDC system hinders the efficient VSC-HVDC power grid design. In order to enhance the reliability of the VSC-HVDC power grid against the fault current problems, the application of resistive Superconducting Fault Current Limiters (SFCLs) could be considered. Also, SFCLs could be applied to the VSC-HVDC system with integrated AC Power Systems in order to enhance the transient response and the robustness of the system. In this paper, in order to evaluate the role of SFCLs in VSC-HVDC systems and to determine the suitable position of SFCLs in VSC-HVDC power systems integrated with AC power System, a simulation model based on Korea Jeju-Haenam HVDC power system was designed in Matlab Simulink/SimPowerSystems. This designed model was composed of VSC-HVDC system connected with an AC microgrid. Utilizing the designed VSC-HVDC systems, the feasible locations of resistive SFCLs were evaluated when DC line-to-line, DC line-to-ground and three phase AC faults were occurred. Consequently, it was found that the simulation model was effective to evaluate the positive effects of resistive SFCLs for the effective suppression of fault currents in VSC-HVDC systems as well as in integrated AC Systems. Finally, the optimum locations of SFCLs in VSC-HVDC transmission systems were suggested based on the simulation results.

  15. Assessment on the influence of resistive superconducting fault current limiter in VSC-HVDC system

    International Nuclear Information System (INIS)

    Lee, Jong-Geon; Khan, Umer Amir; Hwang, Jae-Sang; Seong, Jae-Kyu; Shin, Woo-Ju; Park, Byung-Bae; Lee, Bang-Wook

    2014-01-01

    Highlights: • The role of SFCLs in VSC-HVDC systems was evaluated. • Simulation model based on Korea Jeju-Haenam HVDC power system was designed. • An effect and the feasible locations of resistive SFCLs were evaluated. • DC line-to-line, DC line-to-ground and 3 phase AC faults were imposed and analyzed. - Abstract: Due to fewer risk of commutation failures, harmonic occurrences and reactive power consumptions, Voltage Source Converter (VSC) based HVDC system is known as the optimum solution of HVDC power system for the future power grid. However, the absence of suitable fault protection devices for HVDC system hinders the efficient VSC-HVDC power grid design. In order to enhance the reliability of the VSC-HVDC power grid against the fault current problems, the application of resistive Superconducting Fault Current Limiters (SFCLs) could be considered. Also, SFCLs could be applied to the VSC-HVDC system with integrated AC Power Systems in order to enhance the transient response and the robustness of the system. In this paper, in order to evaluate the role of SFCLs in VSC-HVDC systems and to determine the suitable position of SFCLs in VSC-HVDC power systems integrated with AC power System, a simulation model based on Korea Jeju-Haenam HVDC power system was designed in Matlab Simulink/SimPowerSystems. This designed model was composed of VSC-HVDC system connected with an AC microgrid. Utilizing the designed VSC-HVDC systems, the feasible locations of resistive SFCLs were evaluated when DC line-to-line, DC line-to-ground and three phase AC faults were occurred. Consequently, it was found that the simulation model was effective to evaluate the positive effects of resistive SFCLs for the effective suppression of fault currents in VSC-HVDC systems as well as in integrated AC Systems. Finally, the optimum locations of SFCLs in VSC-HVDC transmission systems were suggested based on the simulation results

  16. Muscular and Systemic Correlates of Resistance Training-Induced Muscle Hypertrophy

    OpenAIRE

    Mitchell, Cameron J.; Churchward-Venne, Tyler A.; Bellamy, Leeann; Parise, Gianni; Baker, Steven K.; Phillips, Stuart M.

    2013-01-01

    PURPOSE: To determine relationships between post-exercise changes in systemic [testosterone, growth hormone (GH), insulin like grow factor 1 (IGF-1) and interleukin 6 (IL-6)], or intramuscular [skeletal muscle androgen receptor (AR) protein content and p70S6K phosphorylation status] factors in a moderately-sized cohort of young men exhibiting divergent resistance training-mediated muscle hypertrophy. METHODS: Twenty three adult males completed 4 sessions•wk⁻¹ of resistance training for 16 wk....

  17. Radiation-hard ceramic Resistive Plate Chambers for forward TOF and T0 systems

    Energy Technology Data Exchange (ETDEWEB)

    Akindinov, A., E-mail: Alexander.Akindinov@cern.ch [Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Dreyer, J.; Fan, X.; Kämpfer, B. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Kiselev, S. [Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Kotte, R.; Garcia, A. Laso [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Malkevich, D. [Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Naumann, L. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Nedosekin, A.; Plotnikov, V. [Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Stach, D. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Sultanov, R.; Voloshin, K. [Institute for Theoretical and Experimental Physics, Moscow (Russian Federation)

    2017-02-11

    Resistive Plate Chambers with ceramic electrodes are the main candidates for a use in precise multi-channel timing systems operating in high-radiation conditions. We report the latest R&D results on these detectors aimed to meet the requirements of the forward T0 counter at the CBM experiment. RPC design, gas mixture, limits on the bulk resistivity of ceramic electrodes, efficiency, time resolution, counting rate capabilities and ageing test results are presented.

  18. Intercontrole acquiring by Framatome

    International Nuclear Information System (INIS)

    1997-01-01

    The Framatome group, as the worldwide leader in nuclear power plant construction, has reinforced his competences in nuclear services thanks to the acquiring of the Intercontrole company, specialized in non-destructive testing in nuclear and industrial environments. After a presentation of the functioning principle and of the safety aspects of a PWR reactor, this press dossier presents in a first part the role of nuclear services and in particular of non-destructive testing in nuclear power plants (in-service inspection, regulatory aspects, testing processes). This part is illustrated with some examples of inspection performed on some components of the primary coolant loop (steam generators, reactor vessel, pressurizer, pipes, primary pumps). A second part presents the technical centres and units of Framatome in charge of performing non-destructive inspections, while a third part describes the industrial policy and strategy of the group in this domain (market of nuclear park maintenance in France, in the USA and worldwide, creation of the 'inspection and control' centre of Framatome). A last part presents the activities of the Intercontrole company and of its daughter companies with some examples of actions realized in the nuclear and natural gas domains. (J.S.)

  19. Pediatric acquired brain injury.

    Science.gov (United States)

    Bodack, Marie I

    2010-10-01

    Although pediatric patients are sometimes included in studies about visual problems in patients with acquired brain injury (ABI), few studies deal solely with children. Unlike studies dealing with adult patients, in which mechanisms of brain injury are divided into cerebral vascular accident (CVA) and traumatic brain injury (TBI), studies on pediatric patients deal almost exclusively with traumatic brain injury, specifically caused by accidents. Here we report on the vision problems of 4 pediatric patients, ages 3 to 18 years, who were examined in the ophthalmology/optometry clinic at a children's hospital. All patients had an internally caused brain injury and after the initial insult manifested problems in at least one of the following areas: acuity, binocularity, motility (tracking or saccades), accommodation, visual fields, and visual perceptual skills. Pediatric patients can suffer from a variety of oculo-visual problems after the onset of head injury. These patients may or may not be symptomatic and can benefit from optometric intervention. Copyright © 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

  20. Community-acquired pneumonia

    International Nuclear Information System (INIS)

    Poetter-Lang, S.; Herold, C.J.

    2017-01-01

    The diagnosis of community-acquired pneumonia (CAP) is often not possible based only on the clinical symptoms and biochemical parameters. For every patient with the suspicion of CAP, a chest radiograph in two planes should be carried out. Additionally, a risk stratification for the decision between outpatient therapy or hospitalization is recommended. Based on the evaluation of the different radiological patterns as well as their extent and distribution, a rough allocation to so-called pathogen groups as well as a differentiation between viral and bacterial infections are possible; however, because different pathogens cause different patterns an accurate correlation is not feasible by relying purely on imaging. The radiological findings serve as proof or exclusion of pneumonia and can also be used to evaluate the extent of the disease (e.g. monolobular, multilobular, unilateral or bilateral). In cases of prolonged disease, suspicion of complications (e.g. pleural effusion or empyema, necrotizing pneumonia or abscess) or comorbid conditions (e.g. underlying pulmonary or mediastinal diseases) computed tomography is an important diagnostic tool in addition to chest radiography. Ultrasound is often used to diagnose pleural processes (e.g. parapneumonic effusion or pleural empyema). (orig.) [de

  1. Effectiveness of a Wii balance board-based system (eBaViR) for balance rehabilitation: a pilot randomized clinical trial in patients with acquired brain injury

    OpenAIRE

    Gil-Gómez, José-Antonio; Lloréns, Roberto; Alcañiz, Mariano; Colomer, Carolina

    2011-01-01

    Background: Acquired brain injury (ABI) is the main cause of death and disability among young adults. In most cases, survivors can experience balance instability, resulting in functional impairments that are associated with diminished health-related quality of life. Traditional rehabilitation therapy may be tedious. This can reduce motivation and adherence to the treatment and thus provide a limited benefit to patients with balance disorders. We present eBaViR (easy Balance Virtual Rehabilita...

  2. Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time

    NARCIS (Netherlands)

    D. Frentz (Dineke); C.A.B. Boucher (Charles); M. Assel (Matthias); A. de Luca (Andrea); M. Fabbiani (Massimiliano); F. Incardona (Francesca); P. Libin (Pieter); N. Manca (Nino); V. Müller (Viktor); B.O. Nualláin (Breanndán); R. Paredes (Roger); M. Prosperi (Mattia); E. Quiros-Roldan (Eugenia); L. Ruiz (Lidia); P.M.A. Sloot (Peter); C. Torti (Carlo); A.M. Vandamme (Anne Mieke); K. Laethem (Kristel); M. Zazzi (Maurizio); D.A.M.C. van de Vijver (David)

    2010-01-01

    textabstractBackground: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks.

  3. User Resistance and Trust in a Clinical RFID Employee Location Tracking Information System

    Science.gov (United States)

    Wong, Wilson

    2013-01-01

    User resistance has been identified as a factor in information systems implementation failures in the health care industry. RFID, radio frequency identification, is being incorporated into new health care information systems in order to effect cost reductions by tracking, identifying and monitoring individuals and medical items. This is the first…

  4. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

    Directory of Open Access Journals (Sweden)

    Geisla Mary Silva Soares

    2012-06-01

    Full Text Available Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections.

  5. Narcissistic Force Meets Systemic Resistance: The Energy Clash Model.

    Science.gov (United States)

    Sedikides, Constantine; Campbell, W Keith

    2017-05-01

    This article focuses on the interplay between narcissistic leaders and organizations. It attempts to capture the gist of this interplay with a model outlining the narcissistic organizational trajectory. The Energy Clash Model borrows and adapts a phase/state physics metaphor to conceptualize narcissism as a force that enters or emerges in a stable system (i.e., organization) as a leader, destabilizes it, and stabilizes it at a different state or is expelled. The model consists of three time-contingent phases: perturbation, conflict, and resolution. Narcissists create instability through waves of excitement, proposed reforms, and an inspiring vision for organization's future ( perturbation). With the passage of time, though, systemic awareness and alertness intensify, as organizational costs-in terms of human resources and monetary losses-accrue. Narcissistic energy clashes directly with the organization ( conflict), a clash likely to restabilize the system eventually. The conflict may provoke the exit of the narcissistic leader or his or her accommodation, that is, steps or controls negotiated between the system and the leader ( resolution). Although narcissism is subject to organizational liability, narcissistic energy, when managed and directed properly, may contribute to organizational innovation and evolution. Thus, several interventions for working with narcissistic leaders are discussed.

  6. Collusion-resistant audio fingerprinting system in the modulated complex lapped transform domain.

    Directory of Open Access Journals (Sweden)

    Jose Juan Garcia-Hernandez

    Full Text Available Collusion-resistant fingerprinting paradigm seems to be a practical solution to the piracy problem as it allows media owners to detect any unauthorized copy and trace it back to the dishonest users. Despite the billionaire losses in the music industry, most of the collusion-resistant fingerprinting systems are devoted to digital images and very few to audio signals. In this paper, state-of-the-art collusion-resistant fingerprinting ideas are extended to audio signals and the corresponding parameters and operation conditions are proposed. Moreover, in order to carry out fingerprint detection using just a fraction of the pirate audio clip, block-based embedding and its corresponding detector is proposed. Extensive simulations show the robustness of the proposed system against average collusion attack. Moreover, by using an efficient Fast Fourier Transform core and standard computer machines it is shown that the proposed system is suitable for real-world scenarios.

  7. Improved Bilayer Resist System Using Contrast-Enhanced Lithography With Water-Soluble Photopolymer

    Science.gov (United States)

    Sasago, Masaru; Endo, Masayuki; Hirai, Yoshihiko; Ogawa, Kazufurni; Ishihara, Takeshi

    1986-07-01

    A new water-soluble contract enhanced material, WSP (Water-soluble Photopolymer), has been developed. The WSP is composed of a mainpolymer and a photobleachable reagents. The mainpolymer is a water-soluble polymer mixed with pullulan (refined through biotechnological process) and polyvinyl-pyrolidone (PVP). The photo-bleachable reagent is of a diazonium compound gorup. The introduction of the mainpolymer and photobleach-able reagent mixture has improved filmity, gas transparency, photobleaching characteristics and solubility in alkaline which are essential to the device fabrication. Submicron photoresist patterns are successfully fabricated by a simple sequence of photolithography process. The WSP layer has been applied to the bilayer resist system--deep-UV portable conformable masking (PCM)--that is not affected by VLSI's topography, and is able to fabricate highly accurate pattern. The aqueous developable layer, PMGI, with high organic solvent resistance is used in the bottom layer. Therefore, no interfacial mixing with conventional positive resist top layer is observed. Furthermore, deep-UV exposure method has been used for the KrF excimer laser optical system in order to increase high throughput. From the experiments, it has been confirmed that good resist transfer profile can be realized by the use of WSP, and that the submicron resist patterns with high aspect-ratio can be developed on the nonplaner wafer with steps of up to 41m by the combination of the WSP with the PCM system. By this technology, has been improved the weak point: variation in the line width due to the thickness of contrast-enhanced layer when the CEL technology is applied, and dependency of both the finished resist profile and the line-width accuracy on the thickness of the top layer resist when the PCM system is adopted.

  8. Self-Centering Seismic Lateral Force Resisting Systems: High Performance Structures for the City of Tomorrow

    Directory of Open Access Journals (Sweden)

    Nathan Brent Chancellor

    2014-09-01

    Full Text Available Structures designed in accordance with even the most modern buildings codes are expected to sustain damage during a severe earthquake; however; these structures are expected to protect the lives of the occupants. Damage to the structure can require expensive repairs; significant business downtime; and in some cases building demolition. If damage occurs to many structures within a city or region; the regional and national economy may be severely disrupted. To address these shortcomings with current seismic lateral force resisting systems and to work towards more resilient; sustainable cities; a new class of seismic lateral force resisting systems that sustains little or no damage under severe earthquakes has been developed. These new seismic lateral force resisting systems reduce or prevent structural damage to nonreplaceable structural elements by softening the structural response elastically through gap opening mechanisms. To dissipate seismic energy; friction elements or replaceable yielding energy dissipation elements are also included. Post-tensioning is often used as a part of these systems to return the structure to a plumb; upright position (self-center after the earthquake has passed. This paper summarizes the state-of-the art for self-centering seismic lateral force resisting systems and outlines current research challenges for these systems.

  9. Fermi system with planes and charge reservoir: Anisotropic in-plane resistivity

    International Nuclear Information System (INIS)

    Levin, G.A.; Quader, K.F.

    1992-01-01

    The authors explore the normal state in-plane resistivity of a model Fermi system with two planes and a charge reservoir. When the Fermi energy lies near the top of one of the resulting sub-bands, the system can be described by two types of quasiparticle excitations with different energy spectra and relaxation times. They show that for certain stoichiometry, ρ ab is linear in temperature with positive or negative intercepts. A relation between the slopes and intercepts of resistivities in the a and b directions in untwinned crystals is derived. The results are in good agreement with experimental data on YBCO. 7 refs., 1 tab

  10. Advantages and disadvantages of contemporary magnetic resonance systems (resistive, permanent and superconductive)

    International Nuclear Information System (INIS)

    Krawczyk, R.; Matuszek, J.

    1994-01-01

    The purpose of the article is to assess the advantages and disadvantages of the operating MRI systems. There are 3 basic types of magnets useful for producing the B field: permanent magnet, resistive magnet and superconductive magnet. The authors compare basic features of those magnets including field strength, homogeneity, temporal stability and direction. The time of examination and the cost of exploitation was also discussed. In conclusions there are no significant differences between superconductive and resistive mid-field MRI systems. However the MRI spectroscopy and functional imaging requires high magnetic field which can be obtain only with superconductive magnet. (author)

  11. Performance of resistance grading system at 14 UD Pelletron Accelerator Facility, BARC-TIFR, Mumbai

    International Nuclear Information System (INIS)

    Lal, Ram; Matkar, U.V.; Ekambaram, M.; Lokare, R.N.; Yadav, M.L.; Gore, J.A.; Kulkarni, S.G.; Gupta, A.K.; Bhagwat, P.V.; Kale, R.M.; Karande, J.N.; Kurup, M.B.

    2005-01-01

    The 14UD Pelletron Accelerator has been in operation for last sixteen years, progressively with increased efficiency. Since inception the accelerator was operating in slit control mode, however, with the installation of a TPS system, it is now possible to operate the accelerator in GVM mode even with ion beam of low intensities. Recently all the column and tube corona points were replaced by resistances. This has helped in low voltage operation of accelerator. In this paper we will discuss in detail the performance of new Terminal Potential Stabiliser system, particularly, our experience resistance grading, at the Pelletron Accelerator. (author)

  12. Pneumonia - adults (community acquired)

    Science.gov (United States)

    ... Pneumocystis jiroveci can cause pneumonia in people whose immune system is not working well, especially people with advanced HIV infection. Viruses , such as the flu virus, are also a common cause of pneumonia. ...

  13. Demonstration of Three Corrosion-Resistant Sustainable Roofing Systems

    Science.gov (United States)

    2013-06-01

    had no interior ceilings or climate control. A white translucent color was selected for its high light transmission properties— up to 50% of outdoor...Figure 18. Rafter frame system for slope conversion retrofit. ERDC/CERL TR-13-7 15 A concrete pad was poured in-place at the frame-attachment points...one at each corner of the building. Each pad included vertical steel rods (3/8 in. diameter) embedded in the concrete and tied to the pad’s

  14. Learning-by-Being-Acquired

    DEFF Research Database (Denmark)

    Colombo, Massimo Gaetano; Moreira, Solon; Rabbiosi, Larissa

    2016-01-01

    In horizontal acquisitions, the post-acquisition integration of the R&D function often damages the inventive labor force and results in lower innovative productivity of acquired inventors. In this paper we study post-acquisition integration in terms of R&D team reorganization-i.e., the creation...... of new teams with both inventors of the acquiring and acquired firms-and assess the impact of this integration action in the period that immediately follows the acquisition. Drawing on social identity and self-categorization theories, we argue that R&D team reorganization increases the acquired inventors...

  15. VACOSS 3, a versatile and tamper-resistant electronic sealing system

    International Nuclear Information System (INIS)

    Arning, F.; Reuters, H.; Bueker, H.

    1981-01-01

    Seal systems for c/s instrumentation used at present need considerable technical and personal expenditure for installation and verification. This paper describes new electronic seal system VACOSS 3, developed by ProCom GmbH, Aachen, and the Nuclear Research Center Juelich within the frame work of an IAEA research contract. This system allows simple installation, verification, the possibility of remote verification and has high tamper resistance

  16. Research of the Fire Resistance оf Translucent and Composite Facade System

    Directory of Open Access Journals (Sweden)

    Nedryshkin Oleg

    2016-01-01

    Full Text Available The paper aims at researching fire resistance of a prototype facade system “Technocom” (type Alucobond A2. Experimental and theoretical research of fire hazard facade system is carried out. The objectives of the study are to determine compliance with the applicable front of special technical requirements. The status of problem reducing fire hazard facade system is reviewed. The method developed by compensatory measures is applied.

  17. Vision systems for the inspection of resistance welding joints

    Science.gov (United States)

    Hildebrand, Lars; Fathi, Madjid

    2000-06-01

    Many automated quality inspection systems make use of brightness and contrast features of the objects being inspected. This reduces the complexity of the problem solving methods, as well as the demand for computational capacity. Nevertheless a lot of significant information is located in color features of the objects. This paper describes a method, that allows the evaluation of color information in a very compact and efficient way. The described method uses a combination of multi-valued logic and a special color model. We use fuzzy logic as multi-valued logic, and the HSI color model, but any multi-valued logic, that allows rule-based reasoning can be used. The HSI color model can also be exchanged with other color models, if special demands require this.

  18. Development of high electrical resistance persistent current switch for high speed energization system

    International Nuclear Information System (INIS)

    Jizo, Y.; Furuta, Y.; Nakashima, H.

    1986-01-01

    Japanese National Railways is now developing a superconducting magnetically-levitated train system. A persistent current switch is incorporated in the super-conducting magnet used in the magnetically-levitated train. In recent years, the switch has been required to have higher electrical resistance during its off-state in order to realize the high speed energization/de-energization system of the superconducting magnets. The system aims to decrease evaporation volume of liquid helium during the energization/de-energization of the magnet, by means of energizing the superconducting magnet with high current increasing/decreasing rate. Consequently, it would be possible to decrease the dependence of the on-board magnet system upon the ground cooling system. Through the development of a stable superconductive wire material and a coil structure for the persistent current switch using many small model switches which were produced in order to improve their current carrying capacities, the authors have succeeded in manufacturing the high electrical resistance persistent current switch whose electrical resistance was 5 ohms. The switch, of cylindrical shape, has a diameter of about 100mm, a length of about 100mm. These 5 ohm PCSs are now functioning in stable conditions being incorporated in the superconducting magnets of No.2 vehicle of MLU001 at the JNR's Miyazaki test track. Further, the authors are now developing the PCS of still higher resistance values, such as 50 ohms, through studies for stabilization in structural aspects of the winding and obtaining results therefrom

  19. Energy principles for linear dissipative systems with application to resistive MHD stability

    International Nuclear Information System (INIS)

    Pletzer, A.

    1997-04-01

    A formalism for the construction of energy principles for dissipative systems is presented. It is shown that dissipative systems satisfy a conservation law for the bilinear Hamiltonian provided the Lagrangian is time invariant. The energy on the other hand, differs from the Hamiltonian by being quadratic and by having a negative definite time derivative (positive power dissipation). The energy is a Lyapunov functional whose definiteness yields necessary and sufficient stability criteria. The stability problem of resistive magnetohydrodynamic (MHD) is addressed: the energy principle for ideal MHD is generalized and the stability criterion by Tasso is shown to be necessary in addition to sufficient for real growth rates. An energy principle is found for the inner layer equations that yields the resistive stability criterion D R <0 in the incompressible limit, whereas the tearing mode criterion Δ'<0 is shown to result from the conservation law of the bilinear concomitant in the resistive layer. (author) 1 fig., 25 refs

  20. Hemodynamic comparison of mild and severe preeclampsia: concept of stroke systemic vascular resistance index.

    Science.gov (United States)

    Scardo, J; Kiser, R; Dillon, A; Brost, B; Newman, R

    1996-01-01

    Our purpose was to compare baseline hemodynamic parameters of mild and severe preeclampsia. Patients admitted to the Medical University Labor and Delivery Unit with the diagnosis of preeclampsia who had not received prior antihypertensive or magnesium sulfate therapy were recruited for noninvasive hemodynamic monitoring with thoracic electrical bioimpedance. After stabilization in the lateral recumbent position, hemodynamic monitoring was begun. Baseline hemodynamic parameters, mean arterial pressure (MAP), heart rate (HR), systemic vascular resistance index (SVRI), cardiac index (CI), and stroke index (SI) were recorded. Stroke systemic vascular resistance index (SSVRI), the resistance imposed by vasculature on each beat of the heart, was calculated for each patient by multiplying SVRI by HR. For statistical analysis, unpaired Student's t-tests (two-tailed) were utilized (P preclampsia appears to be a more intensely vasoconstricted state than mild preeclampsia. Although CI is inversely proportional to SVRI, increased HR in severe preeclampsia prevents this expected decrease in cardiac output.

  1. DETERMINING THE THERMAL RESISTANCE OF A VENTILATED HINGED FACADE SYSTEM LAYER

    Directory of Open Access Journals (Sweden)

    Gagarin Vladimir Gennad'evich

    2015-03-01

    Full Text Available Enveloping structures with hinged façade systems are nowadays widely used for moisture control of enveloping structures, prevention of overheating of the structures by insolation, saving the constructions from atmospheric moisture and also for correspondence with the raised requirements to thermal protection of the enveloping structures, aimed also at reducing energy consumption. In the winter conditions the influence of air layer on the thermal insulation parameters is usually neglected. In the article the thermal resistance of an air gap and is considered and its effect in the calculation of the heat resistance of a building envelope with hinged facade system is analyzed in the conditions of cold weather. The thermal resistance of the air layer determines how the heat losses decrease.

  2. Assessment on the influence of resistive superconducting fault current limiter in VSC-HVDC system

    Science.gov (United States)

    Lee, Jong-Geon; Khan, Umer Amir; Hwang, Jae-Sang; Seong, Jae-Kyu; Shin, Woo-Ju; Park, Byung-Bae; Lee, Bang-Wook

    2014-09-01

    Due to fewer risk of commutation failures, harmonic occurrences and reactive power consumptions, Voltage Source Converter (VSC) based HVDC system is known as the optimum solution of HVDC power system for the future power grid. However, the absence of suitable fault protection devices for HVDC system hinders the efficient VSC-HVDC power grid design. In order to enhance the reliability of the VSC-HVDC power grid against the fault current problems, the application of resistive Superconducting Fault Current Limiters (SFCLs) could be considered. Also, SFCLs could be applied to the VSC-HVDC system with integrated AC Power Systems in order to enhance the transient response and the robustness of the system. In this paper, in order to evaluate the role of SFCLs in VSC-HVDC systems and to determine the suitable position of SFCLs in VSC-HVDC power systems integrated with AC power System, a simulation model based on Korea Jeju-Haenam HVDC power system was designed in Matlab Simulink/SimPowerSystems. This designed model was composed of VSC-HVDC system connected with an AC microgrid. Utilizing the designed VSC-HVDC systems, the feasible locations of resistive SFCLs were evaluated when DC line-to-line, DC line-to-ground and three phase AC faults were occurred. Consequently, it was found that the simulation model was effective to evaluate the positive effects of resistive SFCLs for the effective suppression of fault currents in VSC-HVDC systems as well as in integrated AC Systems. Finally, the optimum locations of SFCLs in VSC-HVDC transmission systems were suggested based on the simulation results.

  3. A dual resistance gene system prevents infection by three distinct pathogens.

    Science.gov (United States)

    Narusaka, Mari; Kubo, Yasuyuki; Shiraishi, Tomonori; Iwabuchi, Masaki; Narusaka, Yoshihiro

    2009-10-01

    Colletotrichum higginsianum causes typical anthracnose lesions on the leaves, petioles, and stems of cruciferous plants. Inoculation of Arabidopsis thaliana ecotype Columbia leaves with C. higginsianum results in fungal growth and disease symptoms reminiscent of those induced in other cruciferous plants. We performed map-based cloning and natural variation analysis of 19 A. thaliana ecotypes to identify a dominant resistance locus against C. higginsianum. We found that the A. thaliana RCH2 (for recognition of C. higginsianum) locus encodes two NB-LRR proteins, both of which are required for resistance to C. higginsianum in the A. thaliana ecotype Ws-0. Both proteins are well-characterized R proteins involved in resistance against bacterial pathogens; RRS1 (resistance to Ralstonia solanacearum 1) confers resistance to strain Rs1000 of R. solanacearum and RPS4 to Pseudomonas syringae pv. tomato strain DC3000 expressing avrRps4 (Pst-avrRps4). Furthermore, we found that both RRS1-Ws and RPS4-Ws genes are required for resistance to Pst-avrRps4 and to Rs1002 R. solanacearum. We therefore demonstrate that a pair of neighboring genes, RRS1-Ws and RPS4-Ws, function cooperatively as a dual R-gene system against at least three distinct pathogens.

  4. Research on Image Reconstruction Algorithms for Tuber Electrical Resistance Tomography System

    Directory of Open Access Journals (Sweden)

    Jiang Zili

    2016-01-01

    Full Text Available The application of electrical resistance tomography (ERT technology has been expanded to the field of agriculture, and the concept of TERT (Tuber Electrical Resistance Tomography is proposed. On the basis of the research on the forward and the inverse problems of the TERT system, a hybrid algorithm based on genetic algorithm is proposed, which can be used in TERT system to monitor the growth status of the plant tubers. The image reconstruction of TERT system is different from the conventional ERT system for two phase-flow measurement. Imaging of TERT needs more precision measurement and the conventional ERT cares more about the image reconstruction speed. A variety of algorithms are analyzed and optimized for the purpose of making them suitable for TERT system. For example: linear back projection, modified Newton-Raphson and genetic algorithm. Experimental results showed that the novel hybrid algorithm is superior to other algorithm and it can effectively improve the image reconstruction quality.

  5. A collaboration on development of requirements and guidelines for proliferation resistance of future nuclear system in the IAEA INPRO

    International Nuclear Information System (INIS)

    Oh, Keun Bae; Lee, Kwang Seok; Kim, Hyun Jun; Jeong, Ik; Yang, Myung Seung; Ko, Won Il

    2003-10-01

    This study surveyed and analyzed the existing activities and international status concerning proliferation resistance of nuclear energy systems, reviewed the features of proliferation resistance, and derived the requirements of future innovative nuclear energy systems. In IAEA INPRO, guidance for the evaluation of innovative nuclear reactors and fuel cycles on proliferation resistance was finalized through collaboration of member countries including Korea in reviewing technological status and developing the methodology for evaluation of proliferation resistance. This report, first, describes the progress of INPRO and the participation status of Korea in the project, and briefly summarizes the report of phase IA of INPRO. Next, features of proliferation resistance of nuclear systems, collaboration in the GIF and the INPRO for development of requirements and guidelines for proliferation resistance, and the final result of guidance for the evaluation of proliferation resistance were described. Finally, this study proposed measures for participation of further progress of the INPRO

  6. System for rapid detection of antibiotic resistance of airborne pathogens

    Science.gov (United States)

    Fortin, M.; Noiseux, I.; Mouslinkina, L.; Vernon, M. L.; Laflamme, C.; Filion, G.; Duchaine, C.; Ho, J.

    2009-05-01

    This project uses function-based detection via a fundamental understanding of the genetic markers of AR to distinguish harmful organisms from innocuous ones. This approach circumvents complex analyses to unravel the taxonomic details of 1399 pathogen species, enormously simplifying detection requirements. Laval Hospital's fast permeabilization strategy enables AR revelation in <1hr. Packaging the AR protocols in liquid-processing cartridges and coupling these to our in-house miniature fiber optic flow cell (FOFC) provides first responders with timely information on-site. INO's FOFC platform consists of a specialty optical fiber through which a hole is transversally bored by laser micromachining. The analyte solution is injected into the hole of the fiber and the particles are detected and counted. The advantage with respect to classic free space FC is that alignment occurs in the fabrication process only and complex excitation and collection optics are replaced by optical fibers. Moreover, we use a sheathless configuration which has the advantage of increase the portability of the system, to reduce excess biohazard material and the need for weekly maintenance. In this paper we present the principle of our FOFC along with a, demonstration of the basic capability of the platform for detection of bacillus cereus spores using permeabilized staining.

  7. Local decoherence-resistant quantum states of large systems

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Utkarsh; Sen, Aditi; Sen, Ujjwal, E-mail: ujjwal@hri.res.in

    2015-02-06

    We identify an effectively decoherence-free class of quantum states, each of which consists of a “minuscule” and a “large” sector, against local noise. In particular, the content of entanglement and other quantum correlations in the minuscule to large partition is independent of the number of particles in their large sectors, when all the particles suffer passage through local ampl