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Sample records for erythraea rifampicin-resistant rif

  1. Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study.

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    Dorman, Susan E; Schumacher, Samuel G; Alland, David; Nabeta, Pamela; Armstrong, Derek T; King, Bonnie; Hall, Sandra L; Chakravorty, Soumitesh; Cirillo, Daniela M; Tukvadze, Nestani; Bablishvili, Nino; Stevens, Wendy; Scott, Lesley; Rodrigues, Camilla; Kazi, Mubin I; Joloba, Moses; Nakiyingi, Lydia; Nicol, Mark P; Ghebrekristos, Yonas; Anyango, Irene; Murithi, Wilfred; Dietze, Reynaldo; Lyrio Peres, Renata; Skrahina, Alena; Auchynka, Vera; Chopra, Kamal Kishore; Hanif, Mahmud; Liu, Xin; Yuan, Xing; Boehme, Catharina C; Ellner, Jerrold J; Denkinger, Claudia M

    2018-01-01

    The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439

  2. Scaling-up the Xpert MTB/RIF assay for the detection of tuberculosis and rifampicin resistance in India: An economic analysis

    NARCIS (Netherlands)

    Khaparde, Sunil; Raizada, Neeraj; Nair, Sreenivas Achuthan; Denkinger, Claudia; Sachdeva, Kuldeep Singh; Paramasivan, Chinnambedu Nainarappan; Salhotra, Virender Singh; Vassall, Anna; van 't Hoog, Anja

    2017-01-01

    India is considering the scale-up of the Xpert MTB/RIF assay for detection of tuberculosis (TB) and rifampicin resistance. We conducted an economic analysis to estimate the costs of different strategies of Xpert implementation in India. Using a decision analytical model, we compared four diagnostic

  3. Implementing the Xpert® MTB/RIF Diagnostic Test for Tuberculosis and Rifampicin Resistance: Outcomes and Lessons Learned in 18 Countries.

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    Elisa Ardizzoni

    Full Text Available The Xpert® MTB/RIF (Xpert is an automated molecular test for simultaneous detection of tuberculosis (TB and rifampicin resistance, recommended by the World Health Organization as the preferred diagnostic method for individuals presumed to have multi-drug resistant TB (MDR-TB or HIV-associated TB. We describe the performance of Xpert and key lessons learned during two years of implementation under routine conditions in 33 projects located in 18 countries supported by Médecins Sans Frontières across varied geographic, epidemiological and clinical settings.Xpert was used following three strategies: the first being as the initial test, with microscopy in parallel, for all presumptive TB cases; the second being only for patients at risk of MDR-TB, or with HIV- associated TB, or presumptive paediatric TB; and the third being as the initial test for these high-risk patients plus as an add-on test to microscopy in others. Routine laboratory data were collected, using laboratory registers. Qualitative data such as logistic aspects, human resources, and tool acceptance were collected using a questionnaire.In total, 52,863 samples underwent Xpert testing from April 2011 to December 2012. The average MTB detection rate was 18.5%, 22.3%, and 11.6% for the three different strategies respectively. Analysis of the results on samples tested in parallel showed that using Xpert as add-on test to microscopy would have increased laboratory TB confirmation by 49.7%, versus 42.3% for Xpert replacing microscopy. The main limitation of the test was the high rate of inconclusive results, which correlated with factors such as defective modules, cartridge version (G3 vs. G4 and staff experience. Operational and logistical hurdles included infrastructure renovation, basic computer training, regular instrument troubleshooting and maintenance, all of which required substantial and continuous support.The implementation of Xpert was feasible and significantly increased TB

  4. Evaluation of the geneXpert MTB/RIF assay for early diagnosis of tuberculosis and detection of rifampicin resistance in pulmonary and extrapulmonary specimens

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    Ali Albay

    2016-09-01

    Conclusion: GeneXpert MTB / RIF test is an effectual automated molecular diagnostic technique with its successful and reliable performance in early diagnosis of tuberculosis and detecting multi-drug resistant strains. [Cukurova Med J 2016; 41(3.000: 548-553

  5. Mutations inside rifampicin-resistance determining region of rpoB gene associated with rifampicin-resistance in Mycobacterium tuberculosis.

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    Zaw, Myo T; Emran, Nor A; Lin, Zaw

    2018-04-26

    Rifampicin (RIF) plays a pivotal role in the treatment of tuberculosis due to its bactericidal effects. Because the action of RIF is on rpoB gene encoding RNA polymerase β subunit, 95% of RIF resistant mutations are present in rpoB gene. The majority of the mutations in rpoB gene are found within an 81bp RIF-resistance determining region (RRDR). Literatures on RIF resistant mutations published between 2010 and 2016 were thoroughly reviewed. The most commonly mutated codons in RRDR of rpoB gene are 531, 526 and 516. The possibilities of absence of mutation in RRDR of rpoB gene in MDR-TB isolates in few studies was due to existence of other rare rpoB mutations outside RRDR or different mechanism of rifampicin resistance. Molecular methods which can identify extensive mutations associated with multiple anti-tuberculous drugs are in urgent need so that the research on drug resistant mutations should be extended. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Survival of a Rifampicin-Resistant Pseudomonas fluorescens Strain in Nine Mollisols

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    Tami L. Stubbs

    2014-01-01

    Full Text Available Pseudomonas fluorescens strain D7 (P.f. D7 is a naturally occurring soil bacterium that shows promise as a biological herbicide to inhibit growth of annual grass weeds, including downy brome (Bromus tectorum L., in crop- and rangelands. Pseudomonas fluorescens strain D7rif (P.f. D7rif is a rifampicin-resistant strain of P.f. D7. One of the greatest obstacles to successful biological weed control is survival of the organism under field conditions. Nine soils in the taxonomic order of Mollisols, collected from downy brome-infested areas of the Western and Central United States, were inoculated with P.f. D7rif and incubated in the laboratory to determine the effects of soil type, soil properties, incubation temperature, and soil water potential on survival of P.f. D7rif over 63 days. Silt loam soils from Lind, Washington, and Moro, Oregon, sustained the highest P.f. D7rif populations, and recovery was the lowest from Pendleton, Oregon soil. Survival and recovery of P.f. D7rif varied with soil type and temperature but not with the two soil water potentials tested. After 63 days, P.f. D7rif was recovered at levels greater than log 5.5 colony forming units (CFU g−1 soil from five of the nine test soils, a level adequate to suppress downy brome under field or range conditions.

  7. Alterations in the Spectrum of Spontaneous Rifampicin-Resistance Mutations in the Bacillus subtilis rpoB Gene after Cultivation in the Human Spaceflight Environment.

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    Fajardo-Cavazos, Patricia; Leehan, Joshua D; Nicholson, Wayne L

    2018-01-01

    The effect of Bacillus subtilis exposure to the human spaceflight environment on growth, mutagenic frequency, and spectrum of mutations to rifampicin resistance (Rif R ) was investigated. B. subtilis cells were cultivated in Biological Research in Canister-Petri Dish Fixation Units (BRIC-PDFUs) on two separate missions to the International Space Station (ISS), dubbed BRIC-18 and BRIC-21, with matching asynchronous ground controls. No statistically significant difference in either growth or in the frequency of mutation to Rif R was found in either experiment. However, nucleotide sequencing of the Rif R regions of the rpoB gene from Rif R mutants revealed dramatic differences in the spectrum of mutations between flight (FL) and ground control (GC) samples, including two newly discovered rpoB alleles in the FL samples (Q137R and L489S). The results strengthen the idea that exposure to the human spaceflight environment causes unique stresses on bacteria, leading to alterations in their mutagenic potential.

  8. Factors Associated with Tuberculosis and Rifampicin-Resistant Tuberculosis amongst Symptomatic Patients in India: A Retrospective Analysis.

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    Sreenivas Achuthan Nair

    Full Text Available Tuberculosis remains a major public health challenge for India. Various studies have documented different levels of TB and multi-drug resistant (MDR TB among diverse groups of the population. In view of renewed targets set under the End TB strategy by 2035, there is an urgent need for TB diagnosis to be strengthened. Drawing on data from a recent, multisite study, we address key questions for TB diagnosis amongst symptomatics presenting for care: are there subgroups of patients that are more likely than others, to be positive for TB? In turn, amongst these positive cases, are there factors-apart from treatment history-that may be predictive for multi-drug resistance?We used data from a multi-centric prospective demonstration study, conducted from March 2012 to December 2013 in 18 sub-district level TB programme units (TUs in India and covering a population of 8.8 million. In place of standard diagnostic tests, upfront Xpert MTB/RIF testing was offered to all presumptive TB symptomatics. Here, using data from this study, we used logistic regression to identify association between risk factors and TB and Rifampicin-Resistant TB among symptomatics enrolled in the study.We find that male gender; history of TB treatment; and adult age compared with either children or the elderly are risk factors associated with high TB detection amongst symptomatics, across the TUs. While treatment history is found be a significant risk factor for rifampicin-resistant TB, elderly (65+ yrs people have significantly lower risk than other age groups. However, pediatric TB cases have no less risk of rifampicin resistance as compared with adults (OR 1.23 (95% C.I. 0.85-1.76. Similarly, risk of rifampicin resistance among both the genders was the same. These patterns applied across the study sites involved. Notably in Mumbai, amongst those patients with microbiological confirmation of TB, female patients showed a higher risk of having MDR-TB than male patients.Our results

  9. Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

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    Schininà Maria

    2010-09-01

    Full Text Available Abstract Background Several mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE combined with mass spectrometry. Results In our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible. Conclusions The analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the

  10. Evaluation of a rapid screening test for rifampicin resistance in re ...

    African Journals Online (AJOL)

    Sensitivity, specificity and overall accuracy of the phage test were determined compared with gold standard culture and DST. Discrepant results were resolved by molecular detection of mutations conferring rifampicin resistance. The proportion of rifampicin-resistant strains that were MDR was also determined. Results.

  11. Understanding Rifampicin Resistance in Tuberculosis through a Computational Approach

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    Satish Kumar

    2014-12-01

    Full Text Available The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB, remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF, the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L and 445 (H445Y is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains.

  12. Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

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    Sachdeva, Kuldeep Singh; Raizada, Neeraj; Sreenivas, Achuthan; van't Hoog, Anna H.; van den Hof, Susan; Dewan, Puneet K.; Thakur, Rahul; Gupta, R. S.; Kulsange, Shubhangi; Vadera, Bhavin; Babre, Ameet; Gray, Christen; Parmar, Malik; Ghedia, Mayank; Ramachandran, Ranjani; Alavadi, Umesh; Arinaminpathy, Nimalan; Denkinger, Claudia; Boehme, Catharina; Paramasivan, C. N.

    2015-01-01

    Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India.

  13. Rifampicin-Resistance Mutations in the rpoB Gene in Bacillus velezensis CC09 have Pleiotropic Effects.

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    Cai, Xun-Chao; Xi, Huan; Liang, Li; Liu, Jia-Dong; Liu, Chang-Hong; Xue, Ya-Rong; Yu, Xiang-Yang

    2017-01-01

    Rifampicin resistance (Rif r ) mutations in the RNA polymerase β subunit ( rpoB ) gene exhibit pleiotropic phenotypes as a result of their effects on the transcription machinery in prokaryotes. However, the differences in the effects of the mutations on the physiology and metabolism of the bacteria remain unknown. In this study, we isolated seven Rif r mutations in rpoB , including six single point mutations (H485Y, H485C, H485D, H485R, Q472R, and S490L) and one double point mutation (S490L/S617F) from vegetative cells of an endophytic strain, Bacillus velezensis CC09. Compared to the wild-type (WT) strain (CC09), the H485R and H485D mutants exhibited a higher degree of inhibition of Aspergillus niger spore germination, while the H485Y, S490L, Q472R, and S490L/S617F mutants exhibited a lower degree of inhibition due to their lower production of the antibiotic iturin A. These mutants all exhibited defective phenotypes in terms of pellicle formation, sporulation, and swarming motility. A hierarchical clustering analysis of the observed phenotypes indicated that the four mutations involving amino acid substitutions at H485 in RpoB belonged to the same cluster. In contrast, the S490L and Q472R mutations, as well as the WT strain, were in another cluster, indicating a functional connection between the mutations in B. velezensis and phenotypic changes. Our data suggest that Rif r mutations cannot only be used to study transcriptional regulation mechanisms, but can also serve as a tool to increase the production of bioactive metabolites in B. velezensis .

  14. Alterations in the Spectrum of Spontaneous Rifampicin-Resistance Mutations in the Bacillus subtilis rpoB Gene after Cultivation in the Human Spaceflight Environment

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    Patricia Fajardo-Cavazos

    2018-02-01

    Full Text Available The effect of Bacillus subtilis exposure to the human spaceflight environment on growth, mutagenic frequency, and spectrum of mutations to rifampicin resistance (RifR was investigated. B. subtilis cells were cultivated in Biological Research in Canister-Petri Dish Fixation Units (BRIC-PDFUs on two separate missions to the International Space Station (ISS, dubbed BRIC-18 and BRIC-21, with matching asynchronous ground controls. No statistically significant difference in either growth or in the frequency of mutation to RifR was found in either experiment. However, nucleotide sequencing of the RifR regions of the rpoB gene from RifR mutants revealed dramatic differences in the spectrum of mutations between flight (FL and ground control (GC samples, including two newly discovered rpoB alleles in the FL samples (Q137R and L489S. The results strengthen the idea that exposure to the human spaceflight environment causes unique stresses on bacteria, leading to alterations in their mutagenic potential.

  15. Enriched whole genome sequencing identified compensatory mutations in the RNA polymerase gene of rifampicin-resistant Mycobacterium leprae strains.

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    Lavania, Mallika; Singh, Itu; Turankar, Ravindra P; Gupta, Anuj Kumar; Ahuja, Madhvi; Pathak, Vinay; Sengupta, Utpal

    2018-01-01

    Despite more than three decades of multidrug therapy (MDT), leprosy remains a major public health issue in several endemic countries, including India. The emergence of drug resistance in Mycobacterium leprae (M. leprae) is a cause of concern and poses a threat to the leprosy-control program, which might ultimately dampen the achievement of the elimination program of the country. Rifampicin resistance in clinical strains of M. leprae are supposed to arise from harboring bacterial strains with mutations in the 81-bp rifampicin resistance determining region (RRDR) of the rpoB gene. However, complete dynamics of rifampicin resistance are not explained only by this mutation in leprosy strains. To understand the role of other compensatory mutations and transmission dynamics of drug-resistant leprosy, a genome-wide sequencing of 11 M. leprae strains - comprising five rifampicin-resistant strains, five sensitive strains, and one reference strain - was done in this study. We observed the presence of compensatory mutations in two rifampicin-resistant strains in rpoC and mmpL7 genes, along with rpoB , that may additionally be responsible for conferring resistance in those strains. Our findings support the role for compensatory mutation(s) in RNA polymerase gene(s), resulting in rifampicin resistance in relapsed leprosy patients.

  16. Enriched whole genome sequencing identified compensatory mutations in the RNA polymerase gene of rifampicin-resistant Mycobacterium leprae strains

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    Lavania M

    2018-01-01

    Full Text Available Mallika Lavania,1 Itu Singh,1 Ravindra P Turankar,1 Anuj Kumar Gupta,2 Madhvi Ahuja,1 Vinay Pathak,1 Utpal Sengupta1 1Stanley Browne Laboratory, The Leprosy Mission Trust India, TLM Community Hospital Nand Nagari, 2Agilent Technologies India Pvt Ltd, Jasola District Centre, New Delhi, India Abstract: Despite more than three decades of multidrug therapy (MDT, leprosy remains a major public health issue in several endemic countries, including India. The emergence of drug resistance in Mycobacterium leprae (M. leprae is a cause of concern and poses a threat to the leprosy-control program, which might ultimately dampen the achievement of the elimination program of the country. Rifampicin resistance in clinical strains of M. leprae are supposed to arise from harboring bacterial strains with mutations in the 81-bp rifampicin resistance determining region (RRDR of the rpoB gene. However, complete dynamics of rifampicin resistance are not explained only by this mutation in leprosy strains. To understand the role of other compensatory mutations and transmission dynamics of drug-resistant leprosy, a genome-wide sequencing of 11 M. leprae strains – comprising five rifampicin-resistant strains, five sensitive strains, and one reference strain – was done in this study. We observed the presence of compensatory mutations in two rifampicin-resistant strains in rpoC and mmpL7 genes, along with rpoB, that may additionally be responsible for conferring resistance in those strains. Our findings support the role for compensatory mutation(s in RNA polymerase gene(s, resulting in rifampicin resistance in relapsed leprosy patients. Keywords: leprosy, rifampicin resistance, compensatory mutations, next generation sequencing, relapsed, MDT, India

  17. A novel marRAB operon contributes to the rifampicin resistance in Mycobacterium smegmatis.

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    Zhang, Haiwei; Gao, Long; Zhang, Jiaoling; Li, Weihui; Yang, Min; Zhang, Hua; Gao, Chunhui; He, Zheng-Guo

    2014-01-01

    The multiple-antibiotic resistance regulator (MarR) plays an important role in modulating bacterial antibiotic resistance. However, the regulatory model of the marRAB operon in mycobacteria remains to be characterized. Here we report that a MarR, encoded by Ms6508, and its marRAB operon specifically contribute to rifampicin (RIF) resistance in Mycobacterium smegmatis. We show that the MarR recognizes a conserved 21-bp palindromic motif and negatively regulates the expression of two ABC transporters in the operon, encoded by Ms6509-6510. Unlike other known drug efflux pumps, overexpression of these two ABC transporters unexpectedly increased RIF sensitivity and deletion of these two genes increased mycobacterial resistance to the antibiotic. No change can be detected for the sensitivity of recombinant mycobacterial strains to three other anti-TB drugs. Furthermore, HPLC experiments suggested that Ms6509-Ms6510 could pump RIF into the mycobacterial cells. These findings indicated that the mycobacterial MarR functions as a repressor and constitutively inhibits the expression of the marRAB operon, which specifically contributes to RIF resistance in M. smegmatis. Therefore, our data suggest a new regulatory mechanism of RIF resistance and also provide the new insight into the regulatory model of a marRAB operon in mycobacteria.

  18. Direct costs of managing adverse drug reactions during rifampicin-resistant tuberculosis treatment in South Africa.

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    Schnippel, K; Firnhaber, C; Berhanu, R; Page-Shipp, L; Sinanovic, E

    2018-04-01

    To estimate the provider costs of managing adverse drug reactions (ADRs) to standard long-course treatment for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) according to South African guidelines. We parameterised a published Markov health state model for MDR/RR-TB with guidelines-based, bottom-up public-sector provider costing of ADR management. Frequency of ADR occurrence was extracted from the literature. Costs were estimated over 10 years, discounted 3% annually and tested using probabilistic sensitivity analysis. On average, guidelines-based costing of moderate ADRs weighted by the frequency of occurrence was US$135.76 (standard deviation [SD] US$17.18) and the cost of serious ADRs was US$521.29 (SD US$55.99). We estimated that the incremental costs of ADR management were US$380.17 annually per patient initiating MDR/RR-TB treatment. The incremental costs of ADR management for the public health sector in South Africa was US$4.76 million, 8.3% of the estimated cohort costs of MDR/RR-TB treatment ($57.55 million) for the 2015 cohort of 12 527 patients. Management of multiple ADRs and serious ADRs, which are common during the first 6 months of standard, long-course MDR/RR-TB treatment, substantially increases provider treatment costs. These results need to be taken into account when comparing regimen costs, and highlight the urgent need to identify drug regimens with improved safety profiles.

  19. Pathogenicity Assay of Vibrio harveyi in Tiger Shrimp Larvae Employing Rifampicin-Resistant as A Molecular Marker

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    . Widanarni

    2007-12-01

    Full Text Available Rifampicin-resistant marker was employed as a reporter to assay pathogenicity of Vibrio harveyi  in shrimp larvae.  V. harveyi M. G3 and G7 that difference not schizotyping as shown by Pulsed-Filed Gel Electrophoresis (PFGE used in this study. Spontaneous mutation was conducted to generate V. harveyi resistant to rifampicin. Two groups of shrimp post-larvae (PL5 were immersed for 30 min in 106 CFU/ml of mutants and wild type of V. harveyi, respectively; and then placed in a 2 liter shrimp rearing tank for five days. A control group was immersed in sterile seawater. Growth curve analysis and pathogenicity assay of V. harveyi  showed that each of the V. harveyi mutant exhibited almost identical profiles to that of the wild type parental strain and did not show alteration in their pathogenicity. Sample from dead shrimp larvae showed that the dead shrimp larvae were infected by V. harveyi RfR, indicated that rifampicin-resistant marker effective as a reporter to assay pathogenicity of Vibrio harveyi in shrimp larvae. Key words: shrimp larvae, Vibrio harveyi, rifampicin-resistant, molecular marker

  20. Performance of PCR-reverse blot hybridization assay for detection of rifampicin-resistant Mycobacterium leprae.

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    Wang, Hye-young; Kim, Hyunjung; Kim, Yeun; Bang, Hyeeun; Kim, Jong-Pill; Hwang, Joo Hwan; Cho, Sang-Nae; Kim, Tae Ue; Lee, Hyeyoung

    2015-10-01

    Drug resistance in Mycobacterium leprae is a significant problem in countries where leprosy is endemic. A sensitive, specific, and high-throughput reverse blot hybridization assay (REBA) for the detection of genotypic resistance to rifampicin (RIF) was designed and evaluated. It has been shown that resistance to RIF in M. leprae involves mutations in the rpoB gene encoding the -subunit of the RNA polymerase. The PCR-REBA simultaneously detects both 6 wild-type regions and 5 different mutations (507 AGC, 513 GTG, 516 TAT, 531 ATG, and 531 TTC) including the most prevalent mutations at positions 507 and 531. Thirty-one clinical isolates provided by Korea Institute of Hansen-s Disease were analyzed by PCR-REBA with RIF resistance of rpoB gene. As a result, missense mutations at codons 507 AGC and 531 ATG with 2-nucleotide substitutions were found in one sample, and a missense mutation at codon 516 TAT and ΔWT6 (deletion of 530-534) was found in another sample. These cases were confirmed by DNA sequence analysis. This rapid, simple, and highly sensitive assay provides a practical alternative to sequencing for genotypic evaluation of RIF resistance in M. leprae.

  1. Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries.

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    Creswell, Jacob; Codlin, Andrew J; Andre, Emmanuel; Micek, Mark A; Bedru, Ahmed; Carter, E Jane; Yadav, Rajendra-Prasad; Mosneaga, Andrei; Rai, Bishwa; Banu, Sayera; Brouwer, Miranda; Blok, Lucie; Sahu, Suvanand; Ditiu, Lucica

    2014-01-02

    The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the

  2. Investigation of Rifampicin Resistance Outcome among Tuberculosis Patients Visiting Two Major Health Facilities in Port Harcourt in Niger Delta

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    Wokem Gloria Ngozika

    2018-03-01

    Full Text Available Background: Tuberculosis is caused by Mycobacterium tuberculosis and is spread mainly through contact with air droplets and respiratory fluid from an infected person. Drug of choice for its treatment are rifampicin and isoniazid respectively. However, in recent times, resistance to these drugs as with other antibiotics has been observed across the globe. This study was thus aimed at determining the prevalence of rifampicin resistance strain among TB patients attending two major hospitals (Braithwaite Memorial Hospital and University of Port Harcourt Teaching Hospital in Port Harcourt. Method: Sputum of patients was collected, tested for the presence of TB and rifampicin resistance of the isolates were determined using GeneXpert assay approach. Result: A total of 158 isolates from patients who were TB positive were tested for rifampicin resistance. 13.3% of these were resistant to rifampicin drug. 8.9% was from UPTH while 4.4% was from BMSH. 9.5% were less than age 45 while 3.8% were greater than or equal to age 45 (≥45. Males made up 8.2% of the total prevalence while females made up 5.1% of the total prevalence. Alternative drugs to rifampicin and isoniazid drug should however, be prescribed in confirmed cases of resistance outcome in our health facilities especially in the rural communities. Conclusion: Nonetheless, the use of antibiotics indiscriminately without the effective laboratory assay and physician’s prescription should be discouraged at all levels and patients receiving treatment should be monitored to adhere strictly to the desired dosage as non-adhering to the gold standard option may lead to drug resistance outcome among vulnerable patients who are literally exposed to lack of health education and functional health facilities in the remote communities which are also hard to reach area due to the environmental terrine

  3. Pathogenicity Assay of Vibrio harveyi in Tiger Shrimp Larvae Employing Rifampicin-Resistant as A Molecular Marker

    OpenAIRE

    . Widanarni; D. Meha; Sri Nuryati; . Sukenda; A. Suwanto

    2007-01-01

    Rifampicin-resistant marker was employed as a reporter to assay pathogenicity of Vibrio harveyi  in shrimp larvae.  V. harveyi M. G3 and G7 that difference not schizotyping as shown by Pulsed-Filed Gel Electrophoresis (PFGE) used in this study. Spontaneous mutation was conducted to generate V. harveyi resistant to rifampicin. Two groups of shrimp post-larvae (PL5) were immersed for 30 min in 106 CFU/ml of mutants and wild type of V. harveyi, respectively; and then placed in a 2 liter shrimp r...

  4. Variations in the occurrence of specific rpoB mutations in rifampicin-resistant Mycobacterium tuberculosis isolates from patients of different ethnic groups in Kuwait.

    Science.gov (United States)

    Ahmad, Suhail; Al-Mutairi, Noura M; Mokaddas, Eiman

    2012-05-01

    Frequency of resistance-conferring mutations vary among isoniazid- and ethambutol-resistant Mycobacterium tuberculosis isolates obtained from patients of various ethnic groups. This study was aimed to determine the occurrence of specific rpoB mutations in rifampicin-resistant M. tuberculosis isolates from tuberculosis patients of various ethnic groups in Kuwait. Rifampicin-resistant M. tuberculosis isolates (n=119) from South Asian (n=55), Southeast Asian (n=23), Middle Eastern (n=39) and other (n=2) patients and 107 rifampicin-susceptible isolates were tested. Mutations in rpoB were detected by DNA sequencing. Polymorphisms at katG463 and gyrA95 were detected by PCR-RFLP for genetic group assignment. None of rifampicin-susceptible but 116 of 119 rifampicin-resistant isolates showed rpoB mutation(s). Mutations among isolates from South Asian patients were distributed at rpoB516 (20%), rpoB526 (24%) and rpoB531 (27%) while 78 and 51 per cent of isolates from Southeast Asian and Middle Eastern patients, respectively, contained a mutated rpoB531. All isolates with rpoB N-terminal and cluster II mutations were obtained from Middle Eastern and South Asian patients. Most isolates from South Asian (84%) and Southeast Asian (70%) patients belonged to genetic group I while nearly all remaining isolates belonged to genetic group II. Isolates from Middle Eastern patients were distributed among genetic group I (46%), genetic group II (33%) and genetic group III (21%). The occurrence of specific rpoB mutations varied considerably in rifampicin-resistant M. tuberculosis isolates obtained from patients of different ethnic groups within the same country. The present data have important implications for designing region-specific rapid methods for detecting majority of rifampicin-resistant strains.

  5. Victimas del Rif

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    Pablo La Porte

    2011-07-01

    Full Text Available This article explores the memory of the Rif War victims (1921-1926 in present-day Morocco and the role of the International Committee of the Red Cross (ICRC in the conflict. It argues that ICRC’s approach to humanitarian action in the Rif was influenced by changes in the perception of victims after the First World War. Humanitarian assistance in the Rif was, however, undermined by diplomatic tensions between the ICRC and the French and Spanish governments. Lessons from the conflict can be drawn to assess the role of humanitarian associations in conflict situations.

  6. Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal, South Africa Using Lot Quality Assurance Sampling.

    Directory of Open Access Journals (Sweden)

    Christine L Heidebrecht

    Full Text Available KwaZulu-Natal (KZN has the highest burden of notified multidrug-resistant tuberculosis (MDR TB and extensively drug-resistant (XDR TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses.Between July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS study to classify the burden of rifampicin (RIF-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases were based on consultation with local policy makers.We classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border.Our study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited.

  7. Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal, South Africa Using Lot Quality Assurance Sampling.

    Science.gov (United States)

    Heidebrecht, Christine L; Podewils, Laura J; Pym, Alexander; Mthiyane, Thuli; Cohen, Ted

    2016-01-01

    KwaZulu-Natal (KZN) has the highest burden of notified multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant (XDR) TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses. Between July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS) study to classify the burden of rifampicin (RIF)-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases) were based on consultation with local policy makers. We classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border. Our study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited.

  8. Rifampicin resistance in mycobacterium tuberculosis patients using GeneXpert at Livingstone Central Hospital for the year 2015: a cross sectional explorative study.

    Science.gov (United States)

    Masenga, Sepiso K; Mubila, Harrison; Hamooya, Benson M

    2017-09-22

    Since the recent introduction of GeneXepert for the detection of Tuberculosis (TB) drug resistance mutations in both primary resistance and acquired resistance in Zambia, little has been documented in literature on the issue of rifampicin resistance especially in the face of a high National TB burden. The study aimed to determine the prevalence of rifampicin resistance in tuberculosis patients at Livingstone Central Hospital for the year 2015. This was a cross sectional study conducted at Livingstone Central Hospital where we reviewed 152 records (from January 1, 2015 to 31st December, 2015) involving patients who presented with clinically suspected TB or documented TB, whose samples were sent to the laboratory for GeneXpert Mycobacterium tuberculosis/rifampicin testing. Statistical evaluations used a one-sample test of proportion and Fisher's exact test. The age of participants ranged from 8 months to 73 years old (median = 34). Of the participants with complete data on gender, 99 (66%) and 52 (34%) were males and females respectively. The TB co-infection with HIV prevalence was 98.3% (p < 0.001). Prevalence of rifampicin resistance was 5.9% and there was no statistical significant difference between being male or female (p = 0.721). We were able to show from our study, evidence of rifampicin resistance at Livingstone Central Hospital. Hence, there was need for further in-depth research and appropriate interventions (i.e close follow-up and patient care for drug resistance positive patients).

  9. Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB.

    Directory of Open Access Journals (Sweden)

    Neeraj Raizada

    Full Text Available Diagnosis of pulmonary tuberculosis (PTB in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India.The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU, with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm.4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8 pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2 of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4 who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV for rifampicin resistance detection was high (98%, CI 90.1-99.9, with no statistically significant variation with respect to past history of treatment.Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising

  10. Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.

    Directory of Open Access Journals (Sweden)

    Philly O'Riordan

    2008-09-01

    Full Text Available Multi-drug resistant tuberculosis (MDR-TB is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43% of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.

  11. Analytical and clinical performance characteristics of the Abbott RealTime MTB RIF/INH Resistance, an assay for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis in pulmonary specimens.

    Science.gov (United States)

    Kostera, Joshua; Leckie, Gregor; Tang, Ning; Lampinen, John; Szostak, Magdalena; Abravaya, Klara; Wang, Hong

    2016-12-01

    Clinical management of drug-resistant tuberculosis patients continues to present significant challenges to global health. To tackle these challenges, the Abbott RealTime MTB RIF/INH Resistance assay was developed to accelerate the diagnosis of rifampicin and/or isoniazid resistant tuberculosis to within a day. This article summarizes the performance of the Abbott RealTime MTB RIF/INH Resistance assay; including reliability, analytical sensitivity, and clinical sensitivity/specificity as compared to Cepheid GeneXpert MTB/RIF version 1.0 and Hain MTBDRplus version 2.0. The limit of detection (LOD) of the Abbott RealTime MTB RIF/INH Resistance assay was determined to be 32 colony forming units/milliliter (cfu/mL) using the Mycobacterium tuberculosis (MTB) strain H37Rv cell line. For rifampicin resistance detection, the Abbott RealTime MTB RIF/INH Resistance assay demonstrated statistically equivalent clinical sensitivity and specificity as compared to Cepheid GeneXpert MTB/RIF. For isoniazid resistance detection, the assay demonstrated statistically equivalent clinical sensitivity and specificity as compared to Hain MTBDRplus. The performance data presented herein demonstrate that the Abbott RealTime MTB RIF/INH Resistance assay is a sensitive, robust, and reliable test for realtime simultaneous detection of first line anti-tuberculosis antibiotics rifampicin and isoniazid in patient specimens. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

  12. SACE_0012, a TetR-Family Transcriptional Regulator, Affects the Morphogenesis of Saccharopolyspora erythraea

    OpenAIRE

    Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

    2013-01-01

    Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR,...

  13. Temporal dynamics of the Saccharopolyspora erythraea phosphoproteome.

    Science.gov (United States)

    Licona-Cassani, Cuauhtemoc; Lim, Sooa; Marcellin, Esteban; Nielsen, Lars K

    2014-05-01

    Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest ("metabolic switch") preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO(2) enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of

  14. Temporal Dynamics of the Saccharopolyspora erythraea Phosphoproteome*

    Science.gov (United States)

    Licona-Cassani, Cuauhtemoc; Lim, SooA; Marcellin, Esteban; Nielsen, Lars K.

    2014-01-01

    Actinomycetes undergo a dramatic reorganization of metabolic and cellular machinery during a brief period of growth arrest (“metabolic switch”) preceding mycelia differentiation and the onset of secondary metabolite biosynthesis. This study explores the role of phosphorylation in coordinating the metabolic switch in the industrial actinomycete Saccharopolyspora erythraea. A total of 109 phosphopeptides from 88 proteins were detected across a 150-h fermentation using open-profile two-dimensional LC-MS proteomics and TiO2 enrichment. Quantitative analysis of the phosphopeptides and their unphosphorylated cognates was possible for 20 pairs that also displayed constant total protein expression. Enzymes from central carbon metabolism such as putative acetyl-coenzyme A carboxylase, isocitrate lyase, and 2-oxoglutarate dehydrogenase changed dramatically in the degree of phosphorylation during the stationary phase, suggesting metabolic rearrangement for the reutilization of substrates and the production of polyketide precursors. In addition, an enzyme involved in cellular response to environmental stress, trypsin-like serine protease (SACE_6340/NC_009142_6216), decreased in phosphorylation during the growth arrest stage. More important, enzymes related to the regulation of protein synthesis underwent rapid phosphorylation changes during this stage. Whereas the degree of phosphorylation of ribonuclease Rne/Rng (SACE_1406/NC_009142_1388) increased during the metabolic switch, that of two ribosomal proteins, S6 (SACE_7351/NC_009142_7233) and S32 (SACE_6101/NC_009142_5981), dramatically decreased during this stage of the fermentation, supporting the hypothesis that ribosome subpopulations differentially regulate translation before and after the metabolic switch. Overall, we show the great potential of phosphoproteomic studies to explain microbial physiology and specifically provide evidence of dynamic protein phosphorylation events across the developmental cycle of

  15. Catching the missing million: experiences in enhancing TB & DR-TB detection by providing upfront Xpert MTB/RIF testing for people living with HIV in India.

    Directory of Open Access Journals (Sweden)

    Neeraj Raizada

    Full Text Available A critical challenge in providing TB care to People Living with HIV (PLHIV is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities.The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU, with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing.2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI 29.4‒32.8 HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3 of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1 who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8 and 16 (11.2%, CI 6.7‒17.1 rifampicin resistance cases, respectively. Positive predictive value (PPV for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8, with no significant difference with or without prior history of TB treatment.The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.

  16. Anaerobic growth of Bacillus subtilis alters the spectrum of spontaneous mutations in the rpoB gene leading to rifampicin resistance.

    Science.gov (United States)

    Nicholson, Wayne L; Park, Roy

    2015-12-01

    Spontaneous rifampicin-resistant (RFM(R)) mutants were isolated from Bacillus subtilis 168 cultivated in the presence or absence of oxygen. By DNA sequencing, the mutations were located within Cluster I of the rpoB gene encoding the β subunit of RNA polymerase. The spectrum of RFM(R) rpoB mutations isolated from B. subtilis cells grown anaerobically differed from aerobically grown cells, not only with respect to the location of mutations within Cluster I but also in the class of mutation observed (transition versus transversion). In the absence of RFM, RFM(R) mutants exhibited poorer growth under anaerobic conditions than did the wild-type strain, indicating their lower fitness in the absence of antibiotic selection. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Detección de cepas de Neisseria meningitidis resistentes a rifampicina en el Uruguay Detection of rifampicin-resistant strains of Neisseria meningitidis in Uruguay

    Directory of Open Access Journals (Sweden)

    Gabriel Pérez Giffoni

    2011-12-01

    Full Text Available El objetivo de este trabajo fue caracterizar fenotípica y genotípicamente dos aislamientos de Neisseria meningitidis resistentes a rifampicina relacionados con dos eventos independientes de transmisión de enfermedad meningocócica grave que se presentaron en septiembre y octubre de 2010 en Montevideo, Uruguay. Se revisó también la base de datos de la vigilancia nacional de resistencia a los antimicrobianos de los últimos 10 años, para estimar la frecuencia de la particularidad de los meningococos caracterizados. La resistencia a rifampicina se estudió por el método epsilométrico. El serotipo y serosubtipo de los aislamientos se determinaron por ELISA y la caracterización genotípica se realizó por digestión del ADN con NheI y electroforesis en gel con campo pulsátil. Ambos aislamientos eran idénticos, B:2a:P1.5, y su fenotipo no figuraba en la colección de 408 cepas de N. meningitidis aisladas en el Uruguay en los últimos 10 años, con la excepción de dos aislamientos sensibles a rifampicina. Los dos aislamientos estudiados también compartían un pulsotipo único, diferente del de otros dos aislamientos resistentes a rifampicina obtenidos en 2003 y 2007. Por lo tanto, ambos eventos de transmisión fueron causados por una única cepa resistente a rifampicina, que podría haberse introducido al país desde otras regiones o haberse originado por un cambio del serogrupo C al B, como producto de la presión selectiva ejercida por vacunas administradas a la población. Es necesario mantener y extremar la vigilancia. No obstante, en vista de que hasta el momento este tipo de hallazgo ha sido esporádico, no se justifica cambiar el fármaco antimicrobiano que se administra a los contactos para la profilaxis, a menos que se identifique un caso secundario.The objective of this study was to characterize the phenotype and genotype of two isolates of rifampicin-resistant Neisseria meningitidis associated with two independent events

  18. Correlation between rpoB gene mutation in Mycobacterium avium subspecies paratuberculosis and clinical rifabutin and rifampicin resistance for treatment of Crohn’s disease

    OpenAIRE

    Beckler, Daniel R; Elwasila, Sammer; Ghobrial, George; Valentine, John F; Naser, Saleh A

    2008-01-01

    AIM: To investigate overlapping regions of the rpoB gene previously involved with rifamycin resistance in M. tuberculosis and seek correlation between rpoB mutations in clinical MAP strains with susceptibility to RIF and RFB.

  19. Evaluation of Xpert MTB/RIF assay in children with presumed pulmonary tuberculosis in Papua New Guinea.

    Science.gov (United States)

    Kasa Tom, Sharon; Welch, Henry; Kilalang, Cornelia; Tefuarani, Nakapi; Vince, John; Lavu, Evelyn; Johnson, Karen; Magaye, Ruth; Duke, Trevor

    2017-05-11

    The Gene Xpert MTB/ RIF assay (Xpert) is used for rapid, simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin resistance. This study examined the accuracy of Xpert in children with suspected pulmonary tuberculosis (PTB). Children admitted to Port Moresby General Hospital with suspected PTB were prospectively enrolled between September 2014 and March 2015. They were classified into probable, possible and TB-unlikely groups. Sputum or gastric aspirates were tested by Xpert and smear microscopy; mycobacterial culture was undertaken on a subset. Children were diagnosed with TB on the basis of standard criteria which were used as the primary reference standard. Xpert, smear for acid-fast bacilli (AFB) and the Edwards TB score were compared with the primary reference standard. A total of 93 children ≤14 years with suspected PTB were enrolled; 67 (72%) were classified as probable, 21 (22%) possible and 5 (5.4%) TB-unlikely. Eighty were treated for TB based on the primary reference standard. Xpert was positive in 26/93 (28%) MTB cases overall, including 22/67 (33%) with probable TB and 4/21 (19%) with possible TB. Three (13%) samples identified rifampicin resistance. Xpert confirmed more cases of TB than AFB smear (26 vs 13, p = 0.019). The sensitivity of Xpert, AFB smear and an Edwards TB score of ≥7 was 31% (25/80), 16% (13/80) and 90% (72/80), respectively, and the specificity was 92% (12/13), 100% (13/13) and 31% (4/13), respectively, when compared with the primary reference standard. Xpert sensitivity is sub-optimal and cannot be relied upon for diagnosing TB, although a positive result is confirmatory. A detailed history and examination, standardised clinical criteria, radiographs and available tests remain the most appropriate way of diagnosing TB in children in resource-limited countries. Xpert helps confirm PTB better than AFB smear, and identifies rifampicin resistance. Practical guidelines should be used to identify children who

  20. Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea

    OpenAIRE

    Wu, Hang; Wang, Yansheng; Yuan, Li; Mao, Yongrong; Wang, Weiwei; Zhu, Lin; Wu, Panpan; Fu, Chengzhang; Müller, Rolf; Weaver, David T.; Zhang, Lixin; Zhang, Buchang

    2016-01-01

    Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea; however, its biosynthetic cluster lacks a regulatory gene, limiting the yield enhancement via regulation engineering of S. erythraea. Herein, six TetR family transcriptional regulators (TFRs) belonging to three genomic context types were individually inactivated in S. erythraea A226, and one of them, SACE_3446, was proved to play a negative role in regulating erythromycin biosynthesis. EMSA and qRT-PCR analysi...

  1. High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana.

    Science.gov (United States)

    Boakye-Appiah, Justice K; Steinmetz, Alexis R; Pupulampu, Peter; Ofori-Yirenkyi, Stephen; Tetteh, Ishmael; Frimpong, Michael; Oppong, Patrick; Opare-Sem, Ohene; Norman, Betty R; Stienstra, Ymkje; van der Werf, Tjip S; Wansbrough-Jones, Mark; Bonsu, Frank; Obeng-Baah, Joseph; Phillips, Richard O

    2016-06-01

    Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays such as the GeneXpert Mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. The objective of this study is to evaluate the use of GeneXpert in the diagnosis of pulmonary TB since it was introduced into two tertiary hospitals in Ghana in 2013. A 2-year retrospective audit of clinical cases involving patients who presented with clinically suspected TB or documented TB not improving on standard therapy and had samples sent for GeneXpert testing. GeneXpert identified 169 cases of TB, including 17 cases of rifampicin-resistant TB. Of the seven cases with final culture and drug susceptibility testing results, six demonstrated further drug resistance and five of these were multidrug-resistant TB. These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting. Copyright © 2016. Published by Elsevier Ltd.

  2. [Role of GeneXpert MTB/RIF test in the screening for pulmonary tuberculosis at the General Referral Provincial Hospital of Bukavu, in the East of the Democratic Republic of the Congo: balance after 10 months of use].

    Science.gov (United States)

    Lupande, David; Kaishusha, David; Mihigo, Carine; Itongwa, Moise; Yenga, Gustave; Katchunga, Philippe

    2017-01-01

    In sub-Saharan Africa, diagnostic methods for tuberculosis are inadequate and are essentially based on microscopy. They constitute a real obstacle to the control of tuberculosis. This study aimed to evaluate the performance of GeneXpert MTB/RIF test compared to classical Ziehl-Neelsen staining at the the general referral provincial hospital of Bukavu, in the east of the Democratic Republic of the Congo after 10 months of use. The results of Ziehl-Neelsen staining and GeneXpert MTB/RIF molecular biology test performed in 452 patients with suspected tuberculosis were collected. This study compares the validity of these different diagnostic tests in the detection of tuberculosis. In the entire group, the frequency of the pulmonary tuberculosis was 16.3%. The positivity rate was significantly higher in GeneXpert MTB/RIF test than in Ziehl-Neelsen staining in the entire group (15.9% vs 9.3%, p = 0.03) and in HIV seropositive patients (52.0% vs 24.0%; p = 0.007). However, the sensitivity of GeneXpert MTB/RIF test compared to that in Ziehl-Neelsen staining wasn't maximum (95.2%). Finally, GeneXpert MTB/RIF test detected rifampicin resistance in 20.8%. This study confirms the superiority of GeneXpert MTB/RIF test compared to Ziehl-Neelsen staining in the detection of tuberculosis and in the prediction of multi-resistance. Its systematic use coupled with Ziehl-Neelsen staining would better control tuberculosis in sub-Saharan Africa.

  3. Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success.

    Science.gov (United States)

    Daniels, Johnny Flippie; Khogali, Mohammed; Mohr, Erika; Cox, Vivian; Moyo, Sizulu; Edginton, Mary; Hinderaker, Sven Gudmund; Meintjes, Graeme; Hughes, Jennifer; De Azevedo, Virginia; van Cutsem, Gilles; Cox, Helen Suzanne

    2015-01-01

    Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection. To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes. A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation. Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2-8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2-8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1-18.1), CD4 count ≤100 (aHR 2.1, CI 1.0-4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1-5.4). Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.

  4. Complete gene expression profiling of Saccharopolyspora erythraea using GeneChip DNA microarrays

    Directory of Open Access Journals (Sweden)

    Bordoni Roberta

    2007-11-01

    Full Text Available Abstract Background The Saccharopolyspora erythraea genome sequence, recently published, presents considerable divergence from those of streptomycetes in gene organization and function, confirming the remarkable potential of S. erythraea for producing many other secondary metabolites in addition to erythromycin. In order to investigate, at whole transcriptome level, how S. erythraea genes are modulated, a DNA microarray was specifically designed and constructed on the S. erythraea strain NRRL 2338 genome sequence, and the expression profiles of 6494 ORFs were monitored during growth in complex liquid medium. Results The transcriptional analysis identified a set of 404 genes, whose transcriptional signals vary during growth and characterize three distinct phases: a rapid growth until 32 h (Phase A; a growth slowdown until 52 h (Phase B; and another rapid growth phase from 56 h to 72 h (Phase C before the cells enter the stationary phase. A non-parametric statistical method, that identifies chromosomal regions with transcriptional imbalances, determined regional organization of transcription along the chromosome, highlighting differences between core and non-core regions, and strand specific patterns of expression. Microarray data were used to characterize the temporal behaviour of major functional classes and of all the gene clusters for secondary metabolism. The results confirmed that the ery cluster is up-regulated during Phase A and identified six additional clusters (for terpenes and non-ribosomal peptides that are clearly regulated in later phases. Conclusion The use of a S. erythraea DNA microarray improved specificity and sensitivity of gene expression analysis, allowing a global and at the same time detailed picture of how S. erythraea genes are modulated. This work underlines the importance of using DNA microarrays, coupled with an exhaustive statistical and bioinformatic analysis of the results, to understand the transcriptional

  5. SACE_0012, a TetR-family transcriptional regulator, affects the morphogenesis of Saccharopolyspora erythraea.

    Science.gov (United States)

    Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

    2013-12-01

    Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR, the relative transcription of SACE_7115, the amfC homolog for an aerial mycelium formation protein, was dramatically increased in SACE_0012 mutant, whereas erythromycin biosynthetic gene eryA, a pleiotropic regulatory gene bldD, and the genes SACE_2141, SACE_6464, SACE_6040, that are the homologs to the sporulation regulators WhiA, WhiB, WhiG, were not differentially expressed. SACE_0012 disruption could not restore its defect of aerial development in bldD mutant, and also did not further accelerate the mycelium formation in the mutant of SACE_7040 gene, that was previously identified to be a morphogenesis repressor. Furthermore, the transcriptional level of SACE_0012 had not markedly changed in bldD and SACE_7040 mutant over A226. Taken together, these results suggest that SACE_0012 is a negative regulator of S. erythraea morphogenesis by mainly increasing the transcription of amfC gene, independently of the BldD regulatory system.

  6. SACE_3986, a TetR family transcriptional regulator, negatively controls erythromycin biosynthesis in Saccharopolyspora erythraea.

    Science.gov (United States)

    Wu, Panpan; Pan, Hui; Zhang, Congming; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhou, Ying; Ye, Bang-ce; Weaver, David T; Zhang, Lixin; Zhang, Buchang

    2014-07-01

    Erythromycin, a medically important antibiotic, is produced by Saccharopolyspora erythraea. Unusually, the erythromycin biosynthetic gene cluster lacks a regulatory gene, and the regulation of its biosynthesis remains largely unknown. In this study, through gene deletion, complementation and overexpression experiments, we identified a novel TetR family transcriptional regulator SACE_3986 negatively regulating erythromycin biosynthesis in S. erythraea A226. When SACE_3986 was further inactivated in an industrial strain WB, erythromycin A yield of the mutant was increased by 54.2 % in average compared with that of its parent strain, displaying the universality of SACE_3986 as a repressor for erythromycin production in S. erythraea. qRT-PCR analysis indicated that SACE_3986 repressed the transcription of its adjacent gene SACE_3985 (which encodes a short-chain dehydrogenase/reductase), erythromycin biosynthetic gene eryAI and the resistance gene ermE. As determined by EMSA analysis, purified SACE_3986 protein specifically bound to the intergenic region between SACE_3985 and SACE_3986, whereas it did not bind to the promoter regions of eryAI and ermE. Furthermore, overexpression of SACE_3985 in A226 led to enhanced erythromycin A yield by at least 32.6 %. These findings indicate that SACE_3986 is a negative regulator of erythromycin biosynthesis, and the adjacent gene SACE_3985 is one of its target genes. The present study provides a basis to increase erythromycin production by engineering of SACE_3986 and SACE_3985 in S. erythraea.

  7. Identification of SACE_7040, a member of TetR family related to the morphological differentiation of Saccharopolyspora erythraea.

    Science.gov (United States)

    Han, Shu; Song, Ping; Ren, Ting; Huang, Xunduan; Cao, Cheng; Zhang, Buchang

    2011-08-01

    SACE_7040 is presumed to be a member of the TetR family of transcriptional regulators in Saccharopolyspora erythraea, but its biological function is unknown. It was shown that the SACE_7040 gene knockout mutant formed aerial mycelium earlier than its original strain, and this phenotype could be restored by complementation of a single copy of SACE_7040 gene, demonstrating that SACE_7040 is an important regulator of the morphological differentiation of Sac. erythraea. When SACE_7040 gene was disrupted in the bldD mutant, we intriguingly found that the defect in aerial development exhibited by the bldD mutant could be overcome, suggesting a crosstalk between SACE_7040 and BldD in Sac. erythraea morphogenesis. These findings provide novel insights toward the Sac. erythraea developmental biology.

  8. Capturing the target genes of BldD in Saccharopolyspora erythraea using improved genomic SELEX method.

    Science.gov (United States)

    Wu, Hang; Mao, Yongrong; Chen, Meng; Pan, Hui; Huang, Xunduan; Ren, Min; Wu, Hao; Li, Jiali; Xu, Zhongdong; Yuan, Hualing; Geng, Ming; Weaver, David T; Zhang, Lixin; Zhang, Buchang

    2015-03-01

    BldD (SACE_2077), a key developmental regulator in actinomycetes, is the first identified transcriptional factor in Saccharopolyspora erythraea positively regulating erythromycin production and morphological differentiation. Although the BldD of S. erythraea binds to the promoters of erythromycin biosynthetic genes, the interaction affinities are relatively low, implying the existence of its other target genes in S. erythraea. Through the genomic systematic evolution of ligands by exponential enrichment (SELEX) method that we herein improved, four DNA sequences of S. erythraea A226, corresponding to the promoter regions of SACE_0306 (beta-galactosidase), SACE_0811 (50S ribosomal protein L25), SACE_3410 (fumarylacetoacetate hydrolase), and SACE_6014 (aldehyde dehydrogenase), were captured with all three BldD concentrations of 0.5, 1, and 2 μM, while the previously identified intergenic regions of eryBIV-eryAI and ermE-eryCI plus the promoter region of SACE_7115, the amfC homolog for aerial mycelium formation, could be captured only when the BldD's concentration reached 2 μM. Electrophoretic mobility shift assay (EMSA) analysis indicated that BldD specifically bound to above seven DNA sequences, and quantitative real-time PCR (qRT-PCR) assay showed that the transcriptional levels of the abovementioned target genes decreased when bldD was disrupted in A226. Furthermore, SACE_7115 and SACE_0306 in A226 were individually inactivated, showing that SACE_7115 was predominantly involved in aerial mycelium formation, while SACE_0306 mainly controlled erythromycin production. This study provides valuable information for better understanding of the pleiotropic regulator BldD in S. erythraea, and the improved method may be useful for uncovering regulatory networks of other transcriptional factors.

  9. GlnR-mediated regulation of nitrogen metabolism in the actinomycete Saccharopolyspora erythraea.

    Science.gov (United States)

    Yao, Li-Li; Liao, Cheng-Heng; Huang, Gang; Zhou, Ying; Rigali, Sebastien; Zhang, Buchang; Ye, Bang-Ce

    2014-09-01

    Nitrogen source sensing, uptake, and assimilation are central for growth and development of microorganisms which requires the participation of a global control of nitrogen metabolism-associated genes at the transcriptional level. In soil-dwelling antibiotic-producing actinomycetes, this role is played by GlnR, an OmpR family regulator. In this work, we demonstrate that SACE_7101 is the ortholog of actinomycetes' GlnR global regulators in the erythromycin producer Saccharopolyspora erythraea. Indeed, the chromosomal deletion of SACE_7101 severely affects the viability of S. erythraea when inoculated in minimal media supplemented with NaNO3, NaNO2, NH4Cl, glutamine, or glutamate as sole nitrogen source. Combination of in silico prediction of cis-acting elements, subsequent in vitro (through gel shift assays) and in vivo (real-time reverse transcription polymerase chain reaction) validations of the predicted target genes revealed a very large GlnR regulon aimed at adapting the nitrogen metabolism of S. erythraea. Indeed, enzymes/proteins involved in (i) uptake and assimilation of ammonium, (ii) transport and utilization of urea, (iii) nitrite/nitrate, (iv) glutamate/glutamine, (v) arginine metabolism, (vi) nitric oxide biosynthesis, and (vii) signal transduction associated with the nitrogen source supplied have at least one paralog gene which expression is controlled by GlnR. Our work highlights a GlnR-binding site consensus sequence (t/gna/cAC-n6-GaAAc) which is similar although not identical to the consensus sequences proposed for other actinomycetes. Finally, we discuss the distinct and common features of the GlnR-mediated transcriptional control of nitrogen metabolism between S. erythraea and the model organism Streptomyces coelicolor.

  10. DasR is a pleiotropic regulator required for antibiotic production, pigment biosynthesis, and morphological development in Saccharopolyspora erythraea.

    Science.gov (United States)

    Liao, Cheng-Heng; Xu, Ya; Rigali, Sébastien; Ye, Bang-Ce

    2015-12-01

    The GntR-family transcription regulator, DasR, was previously identified as pleiotropic, controlling the primary amino sugar N-acetylglucosamine (GlcNAc) and chitin metabolism in Saccharopolyspora erythraea and Streptomyces coelicolor. Due to the remarkable regulatory impact of DasR on antibiotic production and development in the model strain of S. coelicolor, we here identified and characterized the role of DasR to secondary metabolite production and morphological development in industrial erythromycin-producing S. erythraea. The physiological studies have shown that a constructed deletion of dasR in S. erythraea resulted in antibiotic, pigment, and aerial hyphae production deficit in a nutrient-rich condition. DNA microarray assay, combined with quantitative real-time reverse transcription PCR (qRT-PCR), confirmed these results by showing the downregulation of the genes relating to secondary metabolite production in the dasR null mutant. Notably, electrophoretic mobility shift assays (EMSA) showed DasR as being the first identified regulator that directly regulates the pigment biosynthesis rpp gene cluster. In addition, further studies indicated that GlcNAc, the major nutrient signal of DasR-responsed regulation, blocked secondary metabolite production and morphological development. The effects of GlcNAc were shown to be caused by DasR mediation. These findings demonstrated that DasR is an important pleiotropic regulator for both secondary metabolism and morphological development in S. erythraea, providing new insights for the genetic engineering of S. erythraea with increased erythromycin production.

  11. Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

    Science.gov (United States)

    Floridia, Marco; Ciccacci, Fausto; Andreotti, Mauro; Hassane, Archa; Sidumo, Zita; Magid, Nurja A; Sotomane, Horacio; David, Muhlavasse; Mutemba, Elsa; Cebola, Junia; Mugunhe, Remigio Josè; Riccardi, Fabio; Marazzi, Maria Cristina; Giuliano, Marina; Palombi, Leonardo; Mancinelli, Sandro

    2017-11-13

    Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/μL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation

  12. Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Liu, Jing; Chen, Yunfu; Wang, Weiwei; Ren, Min; Wu, Panpan; Wang, Yansheng; Li, Changrun; Zhang, Lixin; Wu, Hang; Weaver, David T; Zhang, Buchang

    2017-01-01

    Leucine-responsive regulatory proteins (Lrps) are a group of transcriptional regulators that regulate diverse cellular processes in bacteria and archaea. However, the regulatory role of Lrps in antibiotic biosynthesis remains poorly understood. In this study, we show that SACE_5388, an Lrp family regulator named as SACE_Lrp, is an efficient regulator for transporting and catabolizing branched-chain amino acids (BCAAs), playing an important role in regulating erythromycin production in Saccharopolyspora erythraea. SACE_Lrp directly controlled the expression of the divergently transcribed SACE_5387-5386 operon putatively encoding a BCAA ABC transporter by interacting with the intergenic region between SACE_Lrp and SACE_5387 (SACE_Lrp-5387-int), and indirectly controlled the expression of ilvE putatively encoding an aminotransferase catabolizing BCAAs. BCAA catabolism is one source of the precursors for erythromycin biosynthesis. Lysine and arginine promoted the dissociation of SACE_Lrp from SACE_Lrp -5387-int, whereas histidine increased their binding. Gene disruption of SACE_Lrp (ΔSACE_Lrp) in S. erythraea A226 resulted in a 25% increase in erythromycin production, while overexpression of SACE_5387-5386 in A226 enhanced erythromycin production by 36%. Deletion of SACE_Lrp (WBΔSACE_Lrp) in the industrial strain S. erythraea WB enhanced erythromycin production by 19%, and overexpression of SACE_5387-5386 in WBΔSACE_Lrp (WBΔSACE_Lrp/5387-5386) increased erythromycin production by 41% compared to WB. Additionally, supplement of 10mM valine to WBΔSACE_Lrp/5387-5386 culture further increased total erythromycin production up to 48%. In a 5-L fermenter, the erythromycin accumulation in the engineered strain WBΔSACE_Lrp/5387-5386 with 10mM extra valine in the industrial culture media reached 5001mg/L, a 41% increase over 3503mg/L of WB. These insights into the molecular regulation of antibiotic biosynthesis by SACE_Lrp in S. erythraea are instrumental in increasing

  13. Dissecting and engineering of the TetR family regulator SACE_7301 for enhanced erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Wu, Hang; Chen, Meng; Mao, Yongrong; Li, Weiwei; Liu, Jingtao; Huang, Xunduan; Zhou, Ying; Ye, Bang-Ce; Zhang, Lixin; Weaver, David T; Zhang, Buchang

    2014-11-13

    Saccharopolyspora erythraea was extensively utilized for the industrial-scale production of erythromycin A (Er-A), a macrolide antibiotic commonly used in human medicine. Yet, S. erythraea lacks regulatory genes in the erythromycin biosynthetic gene (ery) cluster, hampering efforts to enhance Er-A production via the engineering of regulatory genes. By the chromosome gene inactivation technique based on homologous recombination with linearized DNA fragments, we have inactivated a number of candidate TetR family transcriptional regulators (TFRs) and identified one TFR (SACE_7301) positively controlling erythromycin biosynthesis in S. erythraea A226. qRT-PCR and EMSA analyses demonstrated that SACE_7301 activated the transcription of erythromycin biosynthetic gene eryAI and the resistance gene ermE by interacting with their promoter regions with low affinities, similar to BldD (SACE_2077) previously identified to regulate erythromycin biosynthesis and morphological differentiation. Therefore, we designed a strategy for overexpressing SACE_7301 with 1 to 3 extra copies under the control of PermE* in A226. Following up-regulated transcriptional expression of SACE_7301, eryAI and ermE, the SACE_7301-overexpressed strains all increased Er-A production over A226 proportional to the number of copies. Likewise, when SACE_7301 was overexpressed in an industrial S. erythraea WB strain, Er-A yields of the mutants WB/7301, WB/2×7301 and WB/3×7301 were respectively increased by 17%, 29% and 42% relative to that of WB. In a 5 L fermentor, Er-A accumulation increased to 4,230 mg/L with the highest-yield strain WB/3×7301, an approximately 27% production improvement over WB (3,322 mg/L). We have identified and characterized a TFR, SACE_7301, in S. erythraea that positively regulated erythromycin biosynthesis, and overexpression of SACE_7301 in wild-type and industrial S. erythraea strains enhanced Er-A yields. This study markedly improves our understanding of the unusual

  14. Application of In Vitro Transposon Mutagenesis to Erythromycin Strain Improvement in Saccharopolyspora erythraea.

    Science.gov (United States)

    Weber, J Mark; Reeves, Andrew; Cernota, William H; Wesley, Roy K

    2017-01-01

    Transposon mutagenesis is an invaluable technique in molecular biology for the creation of random mutations that can be easily identified and mapped. However, in the field of microbial strain improvement, transposon mutagenesis has scarcely been used; instead, chemical and physical mutagenic methods have been traditionally favored. Transposons have the advantage of creating single mutations in the genome, making phenotype to genotype assignments less challenging than with traditional mutagens which commonly create multiple mutations in the genome. The site of a transposon mutation can also be readily mapped using DNA sequencing primer sites engineered into the transposon termini. In this chapter an in vitro method for transposon mutagenesis of Saccharopolyspora erythraea is presented. Since in vivo transposon tools are not available for most actinomycetes including S. erythraea, an in vitro method was developed. The in vitro method involves a significant investment in time and effort to create the mutants, but once the mutants are made and screened, a large number of highly relevant mutations of direct interest to erythromycin production can be found.

  15. Reoxygenation in the RIF-1 tumor

    International Nuclear Information System (INIS)

    Dorie, M.J.; Kallman, R.F.

    1984-01-01

    The proportion of hypoxic cells in the RIF-1 tumor was examined for 13 days following a 15 Gy conditioning dose. The paired survival curve technique indicated that 100% of the surviving cells were hypoxic immediately following this treatment. However, within 1 hour, only about 50% remained hypoxic; this proportion continued to drop to about 10% but did not reach the pretreatment level of 1.1% for the duration of the study

  16. Muhammad Rif`at dan Turath Bacaannya

    Directory of Open Access Journals (Sweden)

    WAN HILMI WAN ABDULLAH

    2013-12-01

    Full Text Available Shaykh Muhammad Rif`at is one of the famous reciters in Egypt in the era of the 90's. His stature continues evident after officially been invited as a qari to the opening ceremony of Qari al-Misriyyah Idha`at in 1934. During his involvement in the world of Quranic recitation, Shaykh Muhammad Rif`at had recited the Quran in the mosque of Fadil Basha for 25 years. His determinations to deliver and spread Holy Quran with an intermediate reading in mosques, haflah-haflah and ma’tam also have strongly influenced the next generations of qurra’. Many of the reciters like Shaykh Mustafa Isma`il, Shaykh Abu al-`Aynin Sha`isha', Shaykh `Abdul Fattah and others recognize that he has the greatness and uniqueness of its own in the art of reading the Quran. This is evidenced by some of the titles given to him as Amir al-Qurra’, Qitharah al-Sama’ and Sawt al-Malaikah by his contemporary reciters. After Shaykh Muhammad Rif`at died in 1950, then relics of his recited turath were uncovered which compiled by his friend, Zakaria Basha and compatriot Muhammad Khamis, as they managed to gather a total of 278 cds contains 19 chapters with the duration of 21 hours.

  17. Random transposon mutagenesis of the Saccharopolyspora erythraea genome reveals additional genes influencing erythromycin biosynthesis

    Science.gov (United States)

    Fedashchin, Andrij; Cernota, William H.; Gonzalez, Melissa C.; Leach, Benjamin I.; Kwan, Noelle; Wesley, Roy K.; Weber, J. Mark

    2015-01-01

    A single cycle of strain improvement was performed in Saccharopolyspora erythraea mutB and 15 genotypes influencing erythromycin production were found. Genotypes generated by transposon mutagenesis appeared in the screen at a frequency of ∼3%. Mutations affecting central metabolism and regulatory genes were found, as well as hydrolases, peptidases, glycosyl transferases and unknown genes. Only one mutant retained high erythromycin production when scaled-up from micro-agar plug fermentations to shake flasks. This mutant had a knockout of the cwh1 gene (SACE_1598), encoding a cell-wall-associated hydrolase. The cwh1 knockout produced visible growth and morphological defects on solid medium. This study demonstrated that random transposon mutagenesis uncovers strain improvement-related genes potentially useful for strain engineering. PMID:26468041

  18. Rifampicin resistance in Mycobacterium tuberculosis - rapid ...

    African Journals Online (AJOL)

    PH.D. T. C. VJCtor. PH.O. National Tuberculosis Research Programme, Pretoria ... together with. MDR profiles of clinical isolates of M. tuberculosis to assess ..... values in a population." This analysis ..... increased after the mid-1980s but the contribution of social science has ... Schall argues that this is a worst- case scenario ...

  19. High GC Content Cas9-Mediated Genome-Editing and Biosynthetic Gene Cluster Activation in Saccharopolyspora erythraea.

    Science.gov (United States)

    Liu, Yong; Wei, Wen-Ping; Ye, Bang-Ce

    2018-05-18

    The overexpression of bacterial secondary metabolite biosynthetic enzymes is the basis for industrial overproducing strains. Genome editing tools can be used to further improve gene expression and yield. Saccharopolyspora erythraea produces erythromycin, which has extensive clinical applications. In this study, the CRISPR-Cas9 system was used to edit genes in the S. erythraea genome. A temperature-sensitive plasmid containing the PermE promoter, to drive Cas9 expression, and the Pj23119 and PkasO promoters, to drive sgRNAs, was designed. Erythromycin esterase, encoded by S. erythraea SACE_1765, inactivates erythromycin by hydrolyzing the macrolactone ring. Sequencing and qRT-PCR confirmed that reporter genes were successfully inserted into the SACE_1765 gene. Deletion of SACE_1765 in a high-producing strain resulted in a 12.7% increase in erythromycin levels. Subsequent PermE- egfp knock-in at the SACE_0712 locus resulted in an 80.3% increase in erythromycin production compared with that of wild type. Further investigation showed that PermE promoter knock-in activated the erythromycin biosynthetic gene clusters at the SACE_0712 locus. Additionally, deletion of indA (SACE_1229) using dual sgRNA targeting without markers increased the editing efficiency to 65%. In summary, we have successfully applied Cas9-based genome editing to a bacterial strain, S. erythraea, with a high GC content. This system has potential application for both genome-editing and biosynthetic gene cluster activation in Actinobacteria.

  20. Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Wu, Hang; Wang, Yansheng; Yuan, Li; Mao, Yongrong; Wang, Weiwei; Zhu, Lin; Wu, Panpan; Fu, Chengzhang; Müller, Rolf; Weaver, David T; Zhang, Lixin; Zhang, Buchang

    2016-03-01

    Erythromycin A is a widely used antibiotic produced by Saccharopolyspora erythraea ; however, its biosynthetic cluster lacks a regulatory gene, limiting the yield enhancement via regulation engineering of S. erythraea . Herein, six TetR family transcriptional regulators (TFRs) belonging to three genomic context types were individually inactivated in S. erythraea A226, and one of them, SACE_3446, was proved to play a negative role in regulating erythromycin biosynthesis. EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N-terminal DNA binding domain specifically bound to the promoter regions of erythromycin biosynthetic gene eryAI , the resistant gene ermE and the adjacent gene SACE_3447 (encoding a long-chain fatty-acid CoA ligase), and repressed their transcription. Furthermore, we explored the interaction relationships of SACE_3446 and previously identified TFRs (SACE_3986 and SACE_7301) associated with erythromycin production. Given demonstrated relatively independent regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis, we individually and concomitantly inactivated them in an industrial S. erythraea WB. Compared with WB, the WBΔ 3446 and WBΔ 3446 Δ 3986 mutants respectively displayed 36% and 65% yield enhancement of erythromycin A, following significantly elevated transcription of eryAI and ermE . When cultured in a 5 L fermentor, erythromycin A of WBΔ 3446 and WBΔ 3446 Δ 3986 successively reached 4095 mg/L and 4670 mg/L with 23% and 41% production improvement relative to WB. The strategy reported here will be useful to improve antibiotics production in other industrial actinomycete.

  1. SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.

    Science.gov (United States)

    Kirm, Benjamin; Magdevska, Vasilka; Tome, Miha; Horvat, Marinka; Karničar, Katarina; Petek, Marko; Vidmar, Robert; Baebler, Spela; Jamnik, Polona; Fujs, Štefan; Horvat, Jaka; Fonovič, Marko; Turk, Boris; Gruden, Kristina; Petković, Hrvoje; Kosec, Gregor

    2013-12-17

    Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bld

  2. Preferential transcription of conserved rif genes in two phenotypically distinct Plasmodium falciparum parasite lines

    DEFF Research Database (Denmark)

    Wang, Christian W; Magistrado, Pamela A; Nielsen, Morten A

    2009-01-01

    transcribed in the VAR2CSA-expressing parasite line. In addition, two rif genes were found transcribed at early and late intra-erythrocyte stages independently of var gene transcription. Rif genes are organised in groups and inter-genomic conserved gene families, suggesting that RIFIN sub-groups may have......Plasmodium falciparum variant surface antigens (VSA) are targets of protective immunity to malaria. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and repetitive interspersed family (RIFIN) proteins are encoded by the two variable multigene families, var and rif genes, respectively...... novel rif gene groups, rifA1 and rifA2, containing inter-genomic conserved rif genes, were identified. All rifA1 genes were orientated head-to-head with a neighbouring Group A var gene whereas rifA2 was present in all parasite genomes as a single copy gene with a unique 5' untranslated region. Rif...

  3. (Prérif central, Maroc septentrional

    Directory of Open Access Journals (Sweden)

    Abdelghani Gartet

    2005-01-01

    Full Text Available El artículo tiene por objeto evaluar la degradación específi ca, y especialmente cuantifi car la carga de transporte sólido, en la cuenca del oued Lebène (Prérif central, caracterizada por altas tasas de erosión hídrica. La fuerte erosionabilidad de las rocas, la agresividad climática y las frecuentes variaciones de caudal hacen que el volumen de los materiales transportados por el Lebène alcancen una magnitud considerable. La irregularidad espacio-temporal de las precipitaciones y caudales condicionan el volumen de los transportes sólidos, de ahí las estrechas correlaciones existentes entre las tres variables. Los análisis relativos a la turbidez de las aguas y a la naturaleza granulométrica de los sedimentos refuerzan dicha relación.

  4. Gastroprotective effect of small centaury (Centaurium erythraea L) on aspirin-induced gastric damage in rats.

    Science.gov (United States)

    Tuluce, Yasin; Ozkol, Halil; Koyuncu, Ismail; Ine, Hatice

    2011-09-01

    The aim of this study was to determine the antiulcer and antioxidant activities of Centaurium erythraea L (small centaury) in aspirin (ASA) induced acute gastric ulcer model. The gastroprotective effect of the 50% aqueous-ethanolic small centaury (SC) extract was investigated in rats at a dose of ASA 200 mg/kg body weight. Twenty-one Sprague-Dawley albino rats were divided into three groups of seven rats each as follows: (1) control group; (2) acute ASA-treated group and (3) ASA plus SC group. At the end of the 4-h drug administration, ulcer index, oxidant and antioxidant levels were measured and compared between the groups. The percentage of lesion area to total gastric surface area (ulcer index) was significantly reduced (77%) in ASA plus SC group as compared with acute ASA-treated group. The oral administration of ASA decreased catalase (CAT), reduced glutathione (GSH), and increased lipid peroxidation (LPO) levels. Although myeloperoxidase (MPO) activity was increased by ASA, it was found to be lower in the ASA plus SC group. GSH and Vitamin A levels were determined higher in the ASA plus SC group compared with ASA group. These results suggest that SC extract protects against ASA-induced damage due to its antioxidizing activity.

  5. Identifying modules of coexpressed transcript units and their organization of Saccharopolyspora erythraea from time series gene expression profiles.

    Directory of Open Access Journals (Sweden)

    Xiao Chang

    Full Text Available BACKGROUND: The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization. METHODOLOGY/PRINCIPAL FINDINGS: In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A, and secondary metabolism is induced when the growth is slowed down (phase B. Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected. CONCLUSIONS: This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies

  6. Identifying modules of coexpressed transcript units and their organization of Saccharopolyspora erythraea from time series gene expression profiles.

    Science.gov (United States)

    Chang, Xiao; Liu, Shuai; Yu, Yong-Tao; Li, Yi-Xue; Li, Yuan-Yuan

    2010-08-12

    The Saccharopolyspora erythraea genome sequence was released in 2007. In order to look at the gene regulations at whole transcriptome level, an expression microarray was specifically designed on the S. erythraea strain NRRL 2338 genome sequence. Based on these data, we set out to investigate the potential transcriptional regulatory networks and their organization. In view of the hierarchical structure of bacterial transcriptional regulation, we constructed a hierarchical coexpression network at whole transcriptome level. A total of 27 modules were identified from 1255 differentially expressed transcript units (TUs) across time course, which were further classified in to four groups. Functional enrichment analysis indicated the biological significance of our hierarchical network. It was indicated that primary metabolism is activated in the first rapid growth phase (phase A), and secondary metabolism is induced when the growth is slowed down (phase B). Among the 27 modules, two are highly correlated to erythromycin production. One contains all genes in the erythromycin-biosynthetic (ery) gene cluster and the other seems to be associated with erythromycin production by sharing common intermediate metabolites. Non-concomitant correlation between production and expression regulation was observed. Especially, by calculating the partial correlation coefficients and building the network based on Gaussian graphical model, intrinsic associations between modules were found, and the association between those two erythromycin production-correlated modules was included as expected. This work created a hierarchical model clustering transcriptome data into coordinated modules, and modules into groups across the time course, giving insight into the concerted transcriptional regulations especially the regulation corresponding to erythromycin production of S. erythraea. This strategy may be extendable to studies on other prokaryotic microorganisms.

  7. Overexpression of Arabidopsis cytokinin oxidase/dehydrogenase genes AtCKX1 and AtCKX2 in transgenic Centaurium erythraea Rafn

    Czech Academy of Sciences Publication Activity Database

    Trifunovic, M.; Cingel, A.; Simonovic, A.; Jevremovic, S.; Petric, M.; Dragicevic, I.; Motyka, Václav; Dobrev, Petre; Zahajská, Lenka; Subotic, A.

    2013-01-01

    Roč. 115, č. 2 (2013), s. 139-150 ISSN 0167-6857 R&D Projects: GA ČR(CZ) GAP506/11/0774 Institutional research plan: CEZ:AV0Z50380511 Keywords : Centaurium erythraea Rafn. * Agrobacterium tumefaciens * Genetic transformation Subject RIV: EF - Botanics Impact factor: 2.612, year: 2013

  8. Changes in cytokinin content and altered cytokinin homeostasis in AtCKX1 and AtCKX2-overexpressing centaury (Centaurium erythraea Rafn.) plants grown in vitro

    Czech Academy of Sciences Publication Activity Database

    Trifunovic, M.; Motyka, Václav; Cingel, A.; Subotic, A.; Jevremovic, S.; Petric, M.; Holík, Josef; Malbeck, Jiří; Dobrev, Petre; Dragicevic, I.

    2015-01-01

    Roč. 120, č. 2 (2015), s. 767-777 ISSN 0167-6857 R&D Projects: GA ČR(CZ) GAP506/11/0774 Institutional support: RVO:61389030 Keywords : Centaurium erythraea Rafn. * Cytokinin * Cytokinin oxidase/dehydrogenase Subject RIV: EF - Botanics Impact factor: 2.390, year: 2015

  9. A feedback regulatory model for RifQ-mediated repression of rifamycin export in Amycolatopsis mediterranei.

    Science.gov (United States)

    Lei, Chao; Wang, Jingzhi; Liu, Yuanyuan; Liu, Xinqiang; Zhao, Guoping; Wang, Jin

    2018-01-29

    Due to the important role of rifamycin in curing tuberculosis infection, the study on rifamycin has never been stopped. Although RifZ, which locates within the rifamycin biosynthetic cluster, has recently been characterized as a pathway-specific regulator for rifamycin biosynthesis, little is known about the regulation of rifamycin export. In this work, we proved that the expression of the rifamycin efflux pump (RifP) was regulated by RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact on bacterial growth, but resulted in improved rifamycin production, which was consistent with the reverse transcription PCR results that RifQ negatively regulated rifP's transcription. With electrophoretic mobility shift assay and DNase I Footprinting assay, RifQ was found to directly bind to the promoter region of rifP, and a typical inverted repeat was identified within the RifQ-protected sequences. The transcription initiation site of rifP was further characterized and found to be upstream of the RifQ binding sites, well explaining the RifQ-mediated repression of rifP's transcription in vivo. Moreover, rifamycin B (the end product of rifamycin biosynthesis) remarkably decreased the DNA binding affinity of RifQ, which led to derepression of rifamycin export, reducing the intracellular concentration of rifamycin B as well as its toxicity against the host. Here, we proved that the export of rifamycin B was repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression could be specifically relieved by rifamycin B, the end product of rifamycin biosynthesis, based on which a feedback model was proposed for regulation of rifamycin export. With the findings here, one could improve the antibiotic yield by simply inactivating the negative regulator of the antibiotic transporter.

  10. Effect of Introducing Xpert MTB/RIF to Test and Treat Individuals at Risk of Multidrug-Resistant Tuberculosis in Kazakhstan: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Sanne Christine van Kampen

    Full Text Available Xpert MTB/RIF (Xpert was piloted in Kazakhstan to detect tuberculosis (TB and rifampicin resistance (RR-TB among individuals at risk of multidrug-resistant (MDR- TB. This study assessed the performance of Xpert compared to conventional diagnostic methods, RR-TB case detection among various risk groups, treatment initiation and time to diagnosis and treatment.Eligible individuals were tested with Xpert, smear microscopy, culture and drug-susceptibility testing (DST at the national TB reference laboratory and three provincial laboratories. Data was collected prospectively from August 2012 to May 2013 from routine laboratory and treatment registers.A total of 5,611 Xpert tests were performed mostly targeting contacts of MDR-TB patients, 'other' presumptive MDR-TB patients, and retreatment cases (26%, 24% and 22%, respectively. Compared to phenotypic DST, the positive predictive value of Xpert to detect RR-TB was 93.1% and 96.4% and the negative predictive value was 94.6% and 92.7% using solid and liquid culture media, respectively. RR-TB detection was highest among (former prisoners, retreatment cases, people living with HIV/AIDS (PLWHA, and TB patients with positive smears after intensive phase of treatment (59%, 58%, 54% and 53% among TB positives, respectively. 88.9% of RR-TB patients were registered to have started second-line TB treatment. Median time to diagnosis with Xpert was 0.0 days (IQR 0.0-1.0, time from diagnosis to start of first-line treatment 3.0 days (IQR 1.0-7.0, and to start of second-line treatment 7.0 days (IQR 4.0-16.Compared to conventional culture and DST, Xpert had a shorter result turn-around-time and excellent concordance to detect RR-TB. Time from sputum collection to start of second-line treatment was reduced to one week. The yield of Xpert could be maximized by increasing referrals from penitentiary and HIV centers to TB centers.

  11. Effect of Introducing Xpert MTB/RIF to Test and Treat Individuals at Risk of Multidrug-Resistant Tuberculosis in Kazakhstan: A Prospective Cohort Study.

    Science.gov (United States)

    van Kampen, Sanne Christine; Tursynbayeva, Aigul; Koptleuova, Aliya; Murzakhmetova, Zauresh; Murzabekova, Zauresh; Bigalieva, Lyazzat; Aubakirova, Moldir; Pak, Svetlana; van den Hof, Susan

    2015-01-01

    Xpert MTB/RIF (Xpert) was piloted in Kazakhstan to detect tuberculosis (TB) and rifampicin resistance (RR-)TB among individuals at risk of multidrug-resistant (MDR-) TB. This study assessed the performance of Xpert compared to conventional diagnostic methods, RR-TB case detection among various risk groups, treatment initiation and time to diagnosis and treatment. Eligible individuals were tested with Xpert, smear microscopy, culture and drug-susceptibility testing (DST) at the national TB reference laboratory and three provincial laboratories. Data was collected prospectively from August 2012 to May 2013 from routine laboratory and treatment registers. A total of 5,611 Xpert tests were performed mostly targeting contacts of MDR-TB patients, 'other' presumptive MDR-TB patients, and retreatment cases (26%, 24% and 22%, respectively). Compared to phenotypic DST, the positive predictive value of Xpert to detect RR-TB was 93.1% and 96.4% and the negative predictive value was 94.6% and 92.7% using solid and liquid culture media, respectively. RR-TB detection was highest among (former) prisoners, retreatment cases, people living with HIV/AIDS (PLWHA), and TB patients with positive smears after intensive phase of treatment (59%, 58%, 54% and 53% among TB positives, respectively). 88.9% of RR-TB patients were registered to have started second-line TB treatment. Median time to diagnosis with Xpert was 0.0 days (IQR 0.0-1.0), time from diagnosis to start of first-line treatment 3.0 days (IQR 1.0-7.0), and to start of second-line treatment 7.0 days (IQR 4.0-16). Compared to conventional culture and DST, Xpert had a shorter result turn-around-time and excellent concordance to detect RR-TB. Time from sputum collection to start of second-line treatment was reduced to one week. The yield of Xpert could be maximized by increasing referrals from penitentiary and HIV centers to TB centers.

  12. France and the Rif War: Lessons from a Forgotten Counterinsurgency War (Northern Morocco - April 1925 - May 1927)

    Science.gov (United States)

    2010-04-07

    Points Histoire , 2009. - Harris, Walter, France, Spain and the Rif. London: Edward Arnold & CO., 1927. Woolman, David, Rebels in the Rif, Abd el...Marmie, Laguerre du Rif(Paris: Points Histoire , 2009), 17. 6 On the youth and education of Abd El Krim see Cow·celle-Labrousse, Laguerre du Rif, 213

  13. Reciprocal Regulation of GlnR and PhoP in Response to Nitrogen and Phosphate Limitations in Saccharopolyspora erythraea

    Science.gov (United States)

    Yao, Li-li

    2015-01-01

    Nitrogen and phosphate source sensing, uptake, and assimilation are essential for the growth and development of microorganisms. In this study, we demonstrated that SACE_6965 encodes the phosphate regulator PhoP, which controls the transcription of genes involved in phosphate metabolism in the erythromycin-producing Saccharopolyspora erythraea. We found that PhoP and the nitrogen regulator GlnR both regulate the transcription of glnR as well as other nitrogen metabolism-related genes. Interestingly, both GlnR- and PhoP-binding sites were identified in the phoP promoter region. Unlike the nonreciprocal regulation of GlnR and PhoP observed in Streptomyces coelicolor and Streptomyces lividans, GlnR negatively controls the transcription of the phoP gene in S. erythraea. This suggests that GlnR directly affects phosphate metabolism and demonstrates that the cross talk between GlnR and PhoP is reciprocal. Although GlnR and PhoP sites in the glnR and phoP promoter regions are located in close proximity to one another (separated by only 2 to 4 bp), the binding of both regulators to their respective region was independent and noninterfering. These results indicate that two regulators could separately bind to their respective binding sites and control nitrogen and phosphate metabolism in response to environmental changes. The reciprocal cross talk observed between GlnR and PhoP serves as a foundation for understanding the regulation of complex primary and secondary metabolism in antibiotic-producing actinomycetes. PMID:26519391

  14. Analysis of iridoids, secoiridoids and xanthones in Centaurium erythraea, Frasera caroliniensis and Gentiana lutea using LC-MS and RP-HPLC.

    Science.gov (United States)

    Aberham, Anita; Pieri, Valerio; Croom, Edward M; Ellmerer, Ernst; Stuppner, Hermann

    2011-02-20

    This study presents a new and validated HPLC method for the simultaneous determination of bioactive compounds in Centaurium erythraea, Frasera caroliniensis and Gentiana lutea. The iridoid loganic acid, four secoiridoids and 29 xanthones were separated on a RP-18 column, using aqueous o-phosphoric acid (0.085%, v/v) and acetonitrile as mobile phase. Phytochemical investigation of C. erythraea herb and F. caroliniensis roots resulted into isolation of 25 xanthones and three secoiridoids the structure of which was elucidated by spectroscopic means (NMR, MS and UV). 1,3,8-Trihydroxy-5,6-dimethoxyxanthone, isolated from C. erythraea, turned out to be a novel xanthone. The stability of the analytes was tested by subjecting samples to light, moisture and different temperatures. After six months of storage, decomposition of gentiopicroside and sweroside was observed. The swertiamarin content was nearly unchanged when stored at room temperature or in the refrigerator, but high temperature conditions reduced the content to 85%. In contrast, xanthones were stable under long-term, refrigerated and accelerated conditions. The established chromatographic method has been successfully applied for the quantification of the bioactive compounds in the three plants. The presence and distribution of polyoxygenated xanthones within the three members of the Gentianaceae family and their significance as analytical markers are discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Effective management of regulator RI/FS comments

    International Nuclear Information System (INIS)

    Wolinsky, S.M.; Lojek, D.; George, R.D.; Houser, S.M.; Strimbu, M.J.

    1995-01-01

    This paper describes a successful strategy that facilitates regulatory approval of CERCLA documents required by compliance agreement and CERCLA, based on the experience of Operable Unit 1, Waste Storage Area, of the Fernald Environmental Management Project (FEMP). This strategy, which has become the site standard at the FEMP, was instrumental in obtaining regulator approval of the OU1 RI and FS, and early approval of the Record of Decision during a very tight compliance agreement-driven schedule. This strategy can be applied at any DOE Superfund site, especially where there is need to recover lost schedule, an incentive to meet milestones early, a need to improve the relationship between the DOE and the regulators, or where the regulatory agencies have historically provided a large volume of comments on CERCLA documents. The strategy focuses on early identification and resolution of issues relating to draft RI/FS documents, as raised in regulatory agency review comments. This pro-active strategy has the potential for schedule and cost savings, as well as for improved communication between DOE and the regulators. The strategy includes preparation of a separate comment response document, integration of comment responses with RI/FS documents, development of a database of agency comments and their resolution, and sharing lessons learned with preparers of subsequent RI/FS documents. The paper provides background on the FEMP and describes the FEMP comment response strategy; DOE and regulator interface; the Sitewide Comment Database; networked electronic file management; the process for classifying, analyzing, and responding to comments; integration with base RI/FS documents; and a conclusion

  16. Effective management of regulator RI/FS comments

    Energy Technology Data Exchange (ETDEWEB)

    Wolinsky, S.M.; Lojek, D.; George, R.D.; Houser, S.M.; Strimbu, M.J.

    1995-12-31

    This paper describes a successful strategy that facilitates regulatory approval of CERCLA documents required by compliance agreement and CERCLA, based on the experience of Operable Unit 1, Waste Storage Area, of the Fernald Environmental Management Project (FEMP). This strategy, which has become the site standard at the FEMP, was instrumental in obtaining regulator approval of the OU1 RI and FS, and early approval of the Record of Decision during a very tight compliance agreement-driven schedule. This strategy can be applied at any DOE Superfund site, especially where there is need to recover lost schedule, an incentive to meet milestones early, a need to improve the relationship between the DOE and the regulators, or where the regulatory agencies have historically provided a large volume of comments on CERCLA documents. The strategy focuses on early identification and resolution of issues relating to draft RI/FS documents, as raised in regulatory agency review comments. This pro-active strategy has the potential for schedule and cost savings, as well as for improved communication between DOE and the regulators. The strategy includes preparation of a separate comment response document, integration of comment responses with RI/FS documents, development of a database of agency comments and their resolution, and sharing lessons learned with preparers of subsequent RI/FS documents. The paper provides background on the FEMP and describes the FEMP comment response strategy; DOE and regulator interface; the Sitewide Comment Database; networked electronic file management; the process for classifying, analyzing, and responding to comments; integration with base RI/FS documents; and a conclusion.

  17. Classification of plant associated bacteria using RIF, a computationally derived DNA marker.

    Directory of Open Access Journals (Sweden)

    Kevin L Schneider

    Full Text Available A DNA marker that distinguishes plant associated bacteria at the species level and below was derived by comparing six sequenced genomes of Xanthomonas, a genus that contains many important phytopathogens. This DNA marker comprises a portion of the dnaA replication initiation factor (RIF. Unlike the rRNA genes, dnaA is a single copy gene in the vast majority of sequenced bacterial genomes, and amplification of RIF requires genus-specific primers. In silico analysis revealed that RIF has equal or greater ability to differentiate closely related species of Xanthomonas than the widely used ribosomal intergenic spacer region (ITS. Furthermore, in a set of 263 Xanthomonas, Ralstonia and Clavibacter strains, the RIF marker was directly sequenced in both directions with a success rate approximately 16% higher than that for ITS. RIF frameworks for Xanthomonas, Ralstonia and Clavibacter were constructed using 682 reference strains representing different species, subspecies, pathovars, races, hosts and geographic regions, and contain a total of 109 different RIF sequences. RIF sequences showed subspecific groupings but did not place strains of X. campestris or X. axonopodis into currently named pathovars nor R. solanacearum strains into their respective races, confirming previous conclusions that pathovar and race designations do not necessarily reflect genetic relationships. The RIF marker also was sequenced for 24 reference strains from three genera in the Enterobacteriaceae: Pectobacterium, Pantoea and Dickeya. RIF sequences of 70 previously uncharacterized strains of Ralstonia, Clavibacter, Pectobacterium and Dickeya matched, or were similar to, those of known reference strains, illustrating the utility of the frameworks to classify bacteria below the species level and rapidly match unknown isolates to reference strains. The RIF sequence frameworks are available at the online RIF database, RIFdb, and can be queried for diagnostic purposes with RIF

  18. TetR Family Transcriptional Regulator PccD Negatively Controls Propionyl Coenzyme A Assimilation in Saccharopolyspora erythraea.

    Science.gov (United States)

    Xu, Zhen; Wang, Miaomiao; Ye, Bang-Ce

    2017-10-15

    Propanol stimulates erythromycin biosynthesis by increasing the supply of propionyl coenzyme A (propionyl-CoA), a starter unit of erythromycin production in Saccharopolyspora erythraea Propionyl-CoA is assimilated via propionyl-CoA carboxylase to methylmalonyl-CoA, an extender unit of erythromycin. We found that the addition of n -propanol or propionate caused a 4- to 16-fold increase in the transcriptional levels of the SACE_3398-3400 locus encoding propionyl-CoA carboxylase, a key enzyme in propionate metabolism. The regulator PccD was proved to be directly involved in the transcription regulation of the SACE_3398-3400 locus by EMSA and DNase I footprint analysis. The transcriptional levels of SACE_3398-3400 were upregulated 15- to 37-fold in the pccD gene deletion strain (Δ pccD ) and downregulated 3-fold in the pccD overexpression strain (WT/pIB- pccD ), indicating that PccD was a negative transcriptional regulator of SACE_3398-3400. The Δ pccD strain has a higher growth rate than that of the wild-type strain (WT) on Evans medium with propionate as the sole carbon source, whereas the growth of the WT/pIB- pccD strain was repressed. As a possible metabolite of propionate metabolism, methylmalonic acid was identified as an effector molecule of PccD and repressed its regulatory activity. A higher level of erythromycin in the Δ pccD strain was observed compared with that in the wild-type strain. Our study reveals a regulatory mechanism in propionate metabolism and suggests new possibilities for designing metabolic engineering to increase erythromycin yield. IMPORTANCE Our work has identified the novel regulator PccD that controls the expression of the gene for propionyl-CoA carboxylase, a key enzyme in propionyl-CoA assimilation in S. erythraea PccD represses the generation of methylmalonyl-CoA through carboxylation of propionyl-CoA and reveals an effect on biosynthesis of erythromycin. This finding provides novel insight into propionyl-CoA assimilation, and

  19. A feasibility study of the Xpert MTB/RIF test at the peripheral level laboratory in China

    Directory of Open Access Journals (Sweden)

    Xichao Ou

    2015-02-01

    Conclusions: The introduction of MTB/RIF could increase the accuracy of detection of MTB and rifampin resistance in peripheral-level TB laboratories in China. One single specimen is adequate for TB diagnosis by MTB/RIF.

  20. Initiation of continental accretion in the Betic-Rif domain

    Science.gov (United States)

    Maxime, Daudet; Frederic, Mouthereau; Stéphanie, Brichau; Ana, Crespo-Blanc; Arnaud, Vacherat

    2017-04-01

    The Betic - Rif cordillera in southern Spain and northern Morocco, respectively, form one of the tightest orogenic arc on Earth. The formation of this arcuate orogenic belt resulted from the westward migration of the Alboran crustal domain, constituted by the internal zone of the orogeny and the basement of the Alboran back-arc basin, that collided with the rifted margins of Iberia and Africa at least since the early Miocene. This collision is intimately linked to the post-35-30Ma regional slab roll-back and back-arc extension in the western Mediterranean region. The geodynamics of the Betic-Rif domain, which is of great importance for the paleogeographic reconstructions of the Tethys-Altantic and the Mediterranean sea, is still largely debated. Answers will come from a more detailed structural analyses, including refinement of the time-temperature paths and kinematics of the main structural units, which is one of the main objectives of the OROGEN research project, co-financed by BRGM, TOTAL & CNRS. In this study, we focus on the well-developed flysch-type sediments now accreted in the Betics-Rif but initially deposited in a basin, north of the african margin and on the iberian margin from the Early Cretaceous to the Early Miocene. Using low-temperature thermochronology (fission-track and (U-Th)/He analyses) combined with zircon U-Pb geochronology on the flyschs deposited on the most distal part of the margin, we aim to constrain the thermal history of both the source rocks and accreted thrust sheets at the earliest stages of continental accretion. Sample have been collected in flyschs series ranging from Mesozoic, Paleogene to Neogene ages. Additional samples have been collected in the Rif where Cretaceous series are more developed. Combined with a detailed structural analysis, LT thermochronological constraints will refine the kinematics of thrust units when continental accretion started before the final thrust emplacement occurred in the Early Miocene

  1. Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries

    NARCIS (Netherlands)

    Creswell, Jacob; Codlin, Andrew J.; Andre, Emmanuel; Micek, Mark A.; Bedru, Ahmed; Carter, E. Jane; Yadav, Rajendra-Prasad; Mosneaga, Andrei; Rai, Bishwa; Banu, Sayera; Brouwer, Miranda; Blok, Lucie; Sahu, Suvanand; Ditiu, Lucica

    2014-01-01

    The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is

  2. Business rules for creating process flexibility : Mapping RIF rules and BDI rules

    NARCIS (Netherlands)

    Gong, Y.; Overbeek, S.J.; Janssen, M.

    2011-01-01

    Business rules and software agents can be used for creating flexible business processes. The Rule Interchange Format (RIF) is a new W3C recommendation standard for exchanging rules among disparate systems. Yet, the impact that the introduction of RIF has on the design of flexible business processes

  3. Rif1 acts through Protein Phosphatase 1 but independent of replication timing to suppress telomere extension in budding yeast.

    Science.gov (United States)

    Kedziora, Sylwia; Gali, Vamsi K; Wilson, Rosemary H C; Clark, Kate R M; Nieduszynski, Conrad A; Hiraga, Shin-Ichiro; Donaldson, Anne D

    2018-05-04

    The Rif1 protein negatively regulates telomeric TG repeat length in the budding yeast Saccharomyces cerevisiae, but how it prevents telomere over-extension is unknown. Rif1 was recently shown to control DNA replication by acting as a Protein Phosphatase 1 (PP1)-targeting subunit. Therefore, we investigated whether Rif1 controls telomere length by targeting PP1 activity. We find that a Rif1 mutant defective for PP1 interaction causes a long-telomere phenotype, similar to that of rif1Δ cells. Tethering PP1 at a specific telomere partially substitutes for Rif1 in limiting TG repeat length, confirming the importance of PP1 in telomere length control. Ablating Rif1-PP1 interaction is known to cause precocious activation of telomere-proximal replication origins and aberrantly early telomere replication. However, we find that Rif1 still limits telomere length even if late replication is forced through deletion of nearby replication origins, indicating that Rif1 can control telomere length independent of replication timing. Moreover we find that, even at a de novo telomere created after DNA synthesis during a mitotic block, Rif1-PP1 interaction is required to suppress telomere lengthening and prevent inappropriate recruitment of Tel1 kinase. Overall, our results show that Rif1 controls telomere length by recruiting PP1 to directly suppress telomerase-mediated TG repeat lengthening.

  4. Protein Phosphatase 1 Recruitment by Rif1 Regulates DNA Replication Origin Firing by Counteracting DDK Activity

    Directory of Open Access Journals (Sweden)

    Anoushka Davé

    2014-04-01

    Full Text Available The firing of eukaryotic origins of DNA replication requires CDK and DDK kinase activities. DDK, in particular, is involved in setting the temporal program of origin activation, a conserved feature of eukaryotes. Rif1, originally identified as a telomeric protein, was recently implicated in specifying replication timing in yeast and mammals. We show that this function of Rif1 depends on its interaction with PP1 phosphatases. Mutations of two PP1 docking motifs in Rif1 lead to early replication of telomeres in budding yeast and misregulation of origin firing in fission yeast. Several lines of evidence indicate that Rif1/PP1 counteract DDK activity on the replicative MCM helicase. Our data suggest that the PP1/Rif1 interaction is downregulated by the phosphorylation of Rif1, most likely by CDK/DDK. These findings elucidate the mechanism of action of Rif1 in the control of DNA replication and demonstrate a role of PP1 phosphatases in the regulation of origin firing.

  5. Dysphonia – the single symptom of rifampicin resistant laryngeal tuberculosis

    Directory of Open Access Journals (Sweden)

    Paulauskienė Iveta

    2016-01-01

    Full Text Available Tuberculosis is still the most frequent granulomatous laryngeal disease. Absence of pathognomonic symptoms and change in clinical pattern frequently leads to misdiagnosis and delayed treatment. Hoarseness is the commonest symptom of laryngeal tuberculosis and constitutional symptoms are usually rare. However dysphonia can be caused by many other more common conditions. Hoarseness can be a symptom of organic (nodules and polyps of vocal folds, tumors, vocal fold paresis or functional (functional dysphonia, laryngeal conversion disorder, paradoxical vocal folds motion conditions. Rarely systemic diseases as amyloidosis, sarcoidosis, Wegener’s granulomatosis or tuberculosis can cause vocal dysfunction too. That is why laryngeal tuberculosis is often forgotten in case of persistent hoarseness. In this article, we present a case of a young previously healthy woman, complaining of persistent hoarseness with no other leading symptoms. Though endoscopic image suggested a malignancy, histology showed granulomatous lesion. Detailed examination revealed laryngeal and pulmonary tuberculosis resistant to rifampicin. Conclusion: Dysphonia can be the only one symptom of laryngeal tuberculosis. The disease should be taken into consideration when a patient complains of persistent hoarseness in order to avoid delays in treatment and spread of infection.

  6. Diagnosis of lymph node tuberculosis using the GeneXpert MTB/RIF in Tunisia

    Directory of Open Access Journals (Sweden)

    Taha Jaouadi

    2015-01-01

    Conclusion: The implementation of the GeneXpert MTB/RIF assay may dramatically improve the rapid diagnosis of lymph node TB. This rapid TB test may complete usual methods (conventional microscopy, culture and histopathology.

  7. Comparaison du filtre adaptatif RIF et du filtre a base de reseau de ...

    African Journals Online (AJOL)

    Comparaison du filtre adaptatif RIF et du filtre a base de reseau de neurones pour le filtrage du courant de reference pour la commande du filtre actif parallele. C Benachaiba, A Bassou, B Mazari ...

  8. Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex.

    Science.gov (United States)

    Hiraga, Shin-Ichiro; Alvino, Gina M; Chang, Fujung; Lian, Hui-Yong; Sridhar, Akila; Kubota, Takashi; Brewer, Bonita J; Weinreich, Michael; Raghuraman, M K; Donaldson, Anne D

    2014-02-15

    Initiation of eukaryotic DNA replication requires phosphorylation of the MCM complex by Dbf4-dependent kinase (DDK), composed of Cdc7 kinase and its activator, Dbf4. We report here that budding yeast Rif1 (Rap1-interacting factor 1) controls DNA replication genome-wide and describe how Rif1 opposes DDK function by directing Protein Phosphatase 1 (PP1)-mediated dephosphorylation of the MCM complex. Deleting RIF1 partially compensates for the limited DDK activity in a cdc7-1 mutant strain by allowing increased, premature phosphorylation of Mcm4. PP1 interaction motifs within the Rif1 N-terminal domain are critical for its repressive effect on replication. We confirm that Rif1 interacts with PP1 and that PP1 prevents premature Mcm4 phosphorylation. Remarkably, our results suggest that replication repression by Rif1 is itself also DDK-regulated through phosphorylation near the PP1-interacting motifs. Based on our findings, we propose that Rif1 is a novel PP1 substrate targeting subunit that counteracts DDK-mediated phosphorylation during replication. Fission yeast and mammalian Rif1 proteins have also been implicated in regulating DNA replication. Since PP1 interaction sites are evolutionarily conserved within the Rif1 sequence, it is likely that replication control by Rif1 through PP1 is a conserved mechanism.

  9. Rif1 Binding and Control of Chromosome-Internal DNA Replication Origins Is Limited by Telomere Sequestration.

    Science.gov (United States)

    Hafner, Lukas; Lezaja, Aleksandra; Zhang, Xu; Lemmens, Laure; Shyian, Maksym; Albert, Benjamin; Follonier, Cindy; Nunes, Jose Manuel; Lopes, Massimo; Shore, David; Mattarocci, Stefano

    2018-04-24

    The Saccharomyces cerevisiae telomere-binding protein Rif1 plays an evolutionarily conserved role in control of DNA replication timing by promoting PP1-dependent dephosphorylation of replication initiation factors. However, ScRif1 binding outside of telomeres has never been detected, and it has thus been unclear whether Rif1 acts directly on the replication origins that it controls. Here, we show that, in unperturbed yeast cells, Rif1 primarily regulates late-replicating origins within 100 kb of a telomere. Using the chromatin endogenous cleavage ChEC-seq technique, we robustly detect Rif1 at late-replicating origins that we show are targets of its inhibitory action. Interestingly, abrogation of Rif1 telomere association by mutation of its Rap1-binding module increases Rif1 binding and origin inhibition elsewhere in the genome. Our results indicate that Rif1 inhibits replication initiation by interacting directly with origins and suggest that Rap1-dependent sequestration of Rif1 increases its effective concentration near telomeres, while limiting its action at chromosome-internal sites. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. Active tectonics of the Rif Mountains (Morocco) from geomorphic and geochronological data

    Science.gov (United States)

    Ritz, Jean-François; Poujol, Antoine; Tahayt, Abdelilah; Vernant, Philippe; Condomines, Michel; Blard, Pierre-Henri; Braucher, Régis; Benedetti, Lucilla; Bourles, Didier; Leroux-Mallouf, Romain; Ferry, Matthieu; Maate, Soufian

    2014-05-01

    We present results of a geomorphological and morphotectonic analysis of the Rif Mountains (Morocco). We show that the present day kinematics of the Rif is characterized by active deformation along normal and left-lateral strike-slip faults in the North-East (Trougout, Rouadi, Boujibar and Nekor faults), reverse fault in the South (the South Rif Front) and inherited fold structures in the West. Digital Elevation Models of offset drainage features (streams, fluvial terraces) allow determining horizontal cumulative displacements of ~25-35m along the Trougout fault and ~40m along the Nekor fault. 14C dating of tectonic markers yields vertical and horizontal slip rates of ~2.8 mm/yr and ~2.3 mm/yr respectively, along the Trougout fault. For the first time, cosmogenic 3He method is used on volcanic rocks to date the successive exposure of the fault plane. Along the Trougout fault, this yields recurrence time between 3,1 and 4,1 ka. The present-day localized transtension seen in the northeastern Rif morphology (Ras Tarf) is coeval with uplifted marine terraces near the Al Hoceima Bay. U/Th dating of shells yields an average uplift rate of ~0.2 mm/yr during the past 500 Ka. These data show that active transtension in the northeastern Rif is also associated with uplift. Comparison with cosmogenic 10Be/3He dating of perched fluvial surface located above these marine terraces is in progress and may allow us to confirm or not this uplift rate. In the western Rif, geomorphic markers allow us to suggest that active deformation is accommodated along blind thrust and NNW-SSE inherited folds. These new morphotectonic constraints are consistent with the GPS measurements showing southwestward overall motion of most of the Rif belt with respect to stable Africa and suggest a continuum of the deformation from the Pliocene.

  11. Remedial Investigation/Feasibility Study (RI/FS) process, elements and techniques guidance

    Energy Technology Data Exchange (ETDEWEB)

    1993-12-01

    This manual provides detailed guidance on Remedial Investigation/Feasibility Studies (RI/FSs) conducted pursuant to the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) at Department of Energy (DOE) facilities. The purpose of the RI/FS, to assess the risk posed by a hazardous waste site and to determine the best way to reduce that risk, and its structure (site characterization, risk assessment, screening and detailed analysis of alternatives, etc.) is defined in the National Oil and Hazardous Substances Pollution Contingency Plan (NCP) and further explained in the Environmental Protection Agency`s (EPA`s) Guidance for Conducting Remedial Investigations and Feasibility Studies Under CERCLA (Interim Final) 540/G-89/004, OSWER Directive 9355.3-01, October 1988. Though issued in 1988, the EPA guidance remains an excellent source of information on the conduct and structure of an RI/FS. This document makes use of supplemental RI/FS-related guidance that EPA has developed since its initial document was issued in 1988, incorporates practical lessons learned in more than 12 years of experience in CERCLA hazardous site remediation, and drawing on those lessons, introduces the Streamlined Approach For Environmental Restoration (SAFER), developed by DOE as a way to proceed quickly and efficiently through the RI/FS process at DOE facilities. Thus as its title implies, this guidance is intended to describe in detail the process and component elements of an RI/FS, as well as techniques to manage the RI/FS effectively.

  12. Role of GeneXpert MTB/Rif Assay in Diagnosing Tuberculosis in Pregnancy and Puerperium.

    Science.gov (United States)

    Habib, Zaiyad G; Dayyab, Farouq M; Sanda, Abdallah; Tambuwal, Sirajo H; Dalhat, Mahmood M; Muhammad, Hamza; Iliyasu, Garba; Nashabaru, Ibrahim; Habib, Abdulrazaq G

    2015-01-01

    Presentation of tuberculosis (TB) in pregnancy may be atypical with diagnostic challenges. Two patients with complicated pregnancy outcomes, foetal loss and live premature delivery at 5 and 7 months of gestation, respectively, and maternal loss, were diagnosed with pulmonary TB. Chest radiography and computed tomography showed widespread reticuloalveolar infiltrates and consolidation with cavitations, respectively. Both patients were Human Immunodeficiency Virus (HIV) seronegative and sputum smear negative for TB. Sputum GeneXpert MTB/Rif (Xpert MTB/RIF) was positive for Mycobacterium tuberculosis. To strengthen maternal and childhood TB control, screening with same-day point-of-care Xpert MTB/RIF is advocated among both HIV positive pregnant women and symptomatic HIV negative pregnant women during antenatal care in pregnancy and at puerperium.

  13. [Application value of Xpert MTB/RIF in diagnosis of spinal tuberculosis and detection of rifampin resistance].

    Science.gov (United States)

    Jin, Yang-Hui; Shi, Shi-Yuan; Zheng, Qi; Shen, Jian; Ying, Xiao-Zhang; Wang, Yi-Fan

    2017-09-25

    To investigate the application value of Xpert MTB/RIF in diagnosis of spinal tuberculosis and detection of rifampin resistance. The 109 pus specimens were obtained from patients who were primaryly diagnosed as spinal tuberculosis. All of the pus specimens were detected by acid-fast stain, liquid fast culturing by BACTEC MGIT 960 and Xpert MTB/RIF assay to definite the differences in sensitivity and specificity of mycobacterium tuberculosis among detecting methods. Pus specimens obtained by different methods were deteceded by MTB/RIF test to analyze the self-influence on Xpert MTB/RIF test. The result of liquid fast culturing by BACTEC MGIT 960 was used as the gold standard; and the value of Xpert MTB/RIF assay in detecting rifampin resistance was analyzed. The sensitivity of acid-fast stain, liquid fast culturing by BACTEC MGIT 960 and Xpert MTB/RIF assay were 25.92%, 48.15%, 77.78%, respectively. The sensitivity of pus specimens obtained from open surgery, ultrasound positioning puncture and biopsy the sensitivity were 83.78%, 76.47%, 44.68% respectively deteceded by MTB/RIF test. According to the gold standard of the results of liquid fast culturing by BACTEC MGIT 960 assay, the sensitivity and specificity of Xpert MTB/RIF assay in detecting rifampin resistance were 80%(4/5) and 90.70%(39/43), respectively. Xpert MTB/RIF assay has higher value in diagnosis of spinal tuberculosi, and also can detect rifampin resistance. The number of mycobacterium tuberculosis in pus specimens has a great influence in the sensitivity of Xpert MTB/RIF assay.

  14. Diagnostic accuracy of GeneXpert MTB/RIF in musculoskeletal ...

    African Journals Online (AJOL)

    GeneXpert MTB/RIF is an accurate test for the detection of TB in tissue samples of HIV-infected .... continuous data were summarised by means and 95% CIs and non- ... One sample was excluded as the culture sample was sent in formalin.

  15. Integrating semantic web and software agents : Exchanging RIF and BDI rules

    NARCIS (Netherlands)

    Gong, Y.; Overbeek, S.J.

    2011-01-01

    Software agents and rules are both used for creating flexibility. Exchanging rules between Semantic Web and agents can ensure consistency in rules and support easy updating and changing of rules. The Rule Interchange Format (RIF) is a new W3C recommendation Semantic Web standard for exchanging rules

  16. [Contribution of the Xpert MTB/RIF to the etiological diagnosis of tuberculous pleurisy].

    Science.gov (United States)

    Touré, N O; Wayzani, M; Thiam, K; Cissé, M F; Mbaye, F B

    2017-09-01

    Performance of the Xpert MTB/RIF for the detection of Mycobacterium tuberculosis in pleural liquid is poorly described. The aim of this study was to determine its usefulness for the etiological diagnosis of a tuberculous pleurisy. We performed a descriptive cross-sectional study, with analytical design, including all the patients having a unilateral serofibrinous pleurisy, exudative, lymphocytic, and sterile. The diagnosis of pleural tuberculosis was considered based on epidemiological, clinical, paraclinical and therapeutic arguments. The Xpert MTB/RIF of the pleural fluid was carried out among all patients. Pleural tuberculosis was confirmed in 301 patients. The median age was 32years. Our study has included 217 men (72.1%) with a final sex ratio of 2.6. The cost of the pleural biopsy coupled with histology made it practicable in only 90 patients (29.9%) with a yield of 80%. The Xpert MTB/RIF of the pleural liquid was positive in only 10 patients (3.3% of the cases). Gene amplification by Xpert MTB/RIF of the pleural liquid is much less effective in establishing the diagnosis of tuberculous pleurisy than pleural biopsy, which remains the gold standard. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  17. Diagnosing Xpert MTB/RIF-negative TB: Impact and cost of ...

    African Journals Online (AJOL)

    Background. Use of Xpert MTB/RIF is being scaled up throughout South Africa for improved diagnosis of tuberculosis (TB). A large proportion of HIV-infected patients with possible TB are Xpert-negative on their initial test, and the existing diagnostic algorithm calls for these patients to have sputum culture (Xpert followed by ...

  18. Librarian - phase 2. Subproject: the application of reflectometric interference spectroscopy (RIfS) in biological systems. Final report; Librarian - Phase 2. Teilprojekt: Anwendung des Verfahrens der Reflektometrischen Schichtdickenmessung zur Signaldetektion in biologischen Testsystemen und Festphasensynthesen. Schlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Birk, G.; Hadamovsky, S.

    2000-07-01

    Label free methods that do not require fluorescence markers or radioactive isotopes are of interest for high throughput screening applications. Thus, a new assay type for the RIfS technology was developed. These phosphorylation assay experiments were tested for reproducibility and were validated, initially using a single channel machine. The use of surface active materials to reduce or eliminate non specific binding is recommended. The non specific binding of the individual reagents was an important factor for their integration in the RIfS method. The immobilisation of binding reagents was tested using various methods. Since the various combinations are essentially limitless, they could not be explored to their full extent within the confines of this project. The application of the assay into microtitre plate format was not fully completed within the time frame allotted, however, has since been completed by one of the project participants as part of a further cooperation. Theoretically, this method is also suited to the robotics and sample throughput integral to a HTS system A comprehensive evaluation of RIfS technology regarding its entry into high throughput screening, however can only be made with reservation, due to the limited experience with its use in 96 and 384 microtitre plates. (orig.)

  19. Reconstructions with identical filling (RIF) of the heart: a physiological approach to image reconstruction in coronary CT angiography

    International Nuclear Information System (INIS)

    Reinartz, S.D.; Diefenbach, B.S.; Kuhl, C.K.; Mahnken, A.H.; Allmendinger, T.

    2012-01-01

    To compare image quality in coronary artery computed tomography angiography (cCTA) using reconstructions with automated phase detection and Reconstructions computed with Identical Filling of the heart (RIF). Seventy-four patients underwent ECG-gated dual source CT (DSCT) between November 2009 and July 2010 for suspected coronary heart disease (n = 35), planning of transcatheter aortic valve replacement (n = 34) or evaluation of ventricular function (n = 5). Image data sets by the RIF formula and automated phase detection were computed and evaluated with the AHA 15-segment model and a 5-grade Likert scale (1: poor, 5: excellent quality). Subgroups regarding rhythm (sinus rhythm = SR; arrhythmia = ARR) and potential premedication were evaluated by a per-segment, per-vessel and per-patient analysis. RIF significantly improved image quality in 10 of 15 coronary segments (P < 0.05). More diagnostic segments were provided by RIF regarding the entire cohort (n = 693 vs. 590, P < 0.001) and all of the subgroups (e.g. ARR: n = 143 vs. 72, P < 0.001). In arrhythmic patients (n = 19), more diagnostic vessels (e.g. LAD: n = 10 vs. 3; P < 0.014) and complete data sets (n = 7 vs. 1; P < 0.001) were produced. RIF reconstruction is superior to automatic diastolic non-edited reconstructions, especially in arrhythmic patients. RIF theory provides a physiological approach for determining the optimal image reconstruction point in ECG-gated CT angiography. (orig.)

  20. Modification of ChPL (chitosan protein–lipid nanoparticles for in vitro release of rifampicin (RIF

    Directory of Open Access Journals (Sweden)

    Poopak Farnia

    2015-01-01

    Results and conclusions: The average size of RIF ChPL-NPs was about 50–250nm. The release of RIF from the dialysis bag started after 30 min which was 2400ng/ml; after 16 h the release of RIF was 15,000ng/ml; and at 40 h the concentration reached to 19,600ng/ml. Therefore, these results showed a slow release of RIF from ChPL-NPs. Basically, the intensity of the surface charges in nanoparticle is important as it determines their interaction with bioactive compound. In RIF ChPL-NPs, lipid had negative charges, whereas chitosan and gelatin had positive charges. The electrostatic interaction between oppositely charged ions would ultimately cause an effective system drug delivery. RIF ChPL-NPs is not only suitable for intravenous administration, but it can be used as an inhalation aerosol, because this nanoparticle has a capacity to adhere to mucosal surfaces and transiently open the tight junction.

  1. DETERMINATION OF ATTENUATION INDEX CURVE "Ri(f" FOR HOMOGENEOUS DOUBLE LOCKING ELEMENTS

    Directory of Open Access Journals (Sweden)

    BUZATU G. C.

    2016-12-01

    Full Text Available The paper is structured in three parts. In the first part of the paper, are presented some theoretical notions regarding the sound, noise, the sound insulations materials. Also in the first part of the paper are presented some characteristic regarding the insulation materials and there effects. In the second part it is described an calculation example for a homogeneous wall with double structure in order to determine the attenuation index curve "Ri(f". The example calculation contains 10 steps that must be followed and the final results are presented in table 7 and figure 3. The last part of the paper is represented by conclusions, where the authors tried to explain the importance of the curve "Ri(f" for reducing the noise in the buildings.

  2. Xpert® MTB/RIF: Usefulness for the diagnosis of tuberculosis and resistance to rifampicin.

    Science.gov (United States)

    Vergara Gómez, Andrea; González-Martín, Julià; García-Basteiro, Alberto L

    2017-11-09

    The advent of the Xpert® MTB/RIF technique was a revolution in the diagnosis of tuberculosis, especially in areas with high incidence and low resources. It allows the detection of Mycobacterium tuberculosis complex and simultaneously the most common resistance mutations to rifampicin in less than 2h. For respiratory samples the sensitivity is very high, but it decreases for extrapulmonary samples and children. Although it is faster and simpler than conventional methods, it presents some limitations and new and better techniques are needed to reduce the number of cases and deaths caused by tuberculosis. This review aims to assess the scientific evidence around the diagnostic performance of Xpert® MTB/RIF in different types of samples and populations, as well as analyse its strengths and limitations for TB diagnosis. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  3. Microrefugia, Climate Change, and Conservation of Cedrus atlantica in the Rif Mountains, Morocco

    Directory of Open Access Journals (Sweden)

    Rachid Cheddadi

    2017-10-01

    Full Text Available This study reconstructs and interprets the changing range of Atlas cedar in northern Morocco over the last 9,000 years. A synthesis of fossil pollen records indicated that Atlas cedars occupied a wider range at lower elevations during the mid-Holocene than today. The mid-Holocene geographical expansion reflected low winter temperatures and higher water availability over the whole range of the Rif Mountains relative to modern conditions. A trend of increasing aridity observed after 6,000 years BP progressively reduced the range of Atlas cedar and prompted its migration toward elevations above 1,400 masl. To assess the impact of climate change on cedar populations over the last decades, we performed a transient model simulation for the period between 1960 and 2010. Our simulation showed that the range of Atlas cedar decreased by about 75% over the last 50 years and that the eastern populations of the range in the Rif Mountains were even more threatened by the overall lack of water availability than the western ones. Today, Atlas cedar populations in the Rif Mountains are persisting in restricted and isolated areas (Jbel Kelti, Talassemtane, Jbel Tiziren, Oursane, Tidighine that we consider to be modern microrefugia. Conservation of these isolated populations is essential for the future survival of the species, preserving polymorphisms and the potential for population recovery under different climatic conditions.

  4. Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a key organizer of higher-order chromatin architecture.

    Science.gov (United States)

    Moriyama, Kenji; Yoshizawa-Sugata, Naoko; Masai, Hisao

    2018-03-09

    Rap1-interacting protein 1 (Rif1) regulates telomere length in budding yeast. We previously reported that, in metazoans and fission yeast, Rif1 also plays pivotal roles in controlling genome-wide DNA replication timing. We proposed that Rif1 may assemble chromatin compartments that contain specific replication-timing domains by promoting chromatin loop formation. Rif1 also is involved in DNA lesion repair, restart after replication fork collapse, anti-apoptosis activities, replicative senescence, and transcriptional regulation. Although multiple physiological functions of Rif1 have been characterized, biochemical and structural information on mammalian Rif1 is limited, mainly because of difficulties in purifying the full-length protein. Here, we expressed and purified the 2418-amino-acid-long, full-length murine Rif1 as well as its partially truncated variants in human 293T cells. Hydrodynamic analyses indicated that Rif1 forms elongated or extended homo-oligomers in solution, consistent with the presence of a HEAT-type helical repeat segment known to adopt an elongated shape. We also observed that the purified murine Rif1 bound G-quadruplex (G4) DNA with high specificity and affinity, as was previously shown for Rif1 from fission yeast. Both the N-terminal (HEAT-repeat) and C-terminal segments were involved in oligomer formation and specifically bound G4 DNA, and the central intrinsically disordered polypeptide segment increased the affinity for G4. Of note, pulldown assays revealed that Rif1 simultaneously binds multiple G4 molecules. Our findings support a model in which Rif1 modulates chromatin loop structures through binding to multiple G4 assemblies and by holding chromatin fibers together. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Acetyl coenzyme A synthetase is acetylated on multiple lysine residues by a protein acetyltransferase with a single Gcn5-type N-acetyltransferase (GNAT) domain in Saccharopolyspora erythraea.

    Science.gov (United States)

    You, Di; Yao, Li-Li; Huang, Dan; Escalante-Semerena, Jorge C; Ye, Bang-Ce

    2014-09-01

    Reversible lysine acetylation (RLA) is used by cells of all domains of life to modulate protein function. To date, bacterial acetylation/deacetylation systems have been studied in a few bacteria (e.g., Salmonella enterica, Bacillus subtilis, Escherichia coli, Erwinia amylovora, Mycobacterium tuberculosis, and Geobacillus kaustophilus), but little is known about RLA in antibiotic-producing actinomycetes. Here, we identify the Gcn5-like protein acetyltransferase AcuA of Saccharopolyspora erythraea (SacAcuA, SACE_5148) as the enzyme responsible for the acetylation of the AMP-forming acetyl coenzyme A synthetase (SacAcsA, SACE_2375). Acetylated SacAcsA was deacetylated by a sirtuin-type NAD(+)-dependent consuming deacetylase (SacSrtN, SACE_3798). In vitro acetylation/deacetylation of SacAcsA enzyme was studied by Western blotting, and acetylation of lysine residues Lys(237), Lys(380), Lys(611), and Lys(628) was confirmed by mass spectrometry. In a strain devoid of SacAcuA, none of the above-mentioned Lys residues of SacAcsA was acetylated. To our knowledge, the ability of SacAcuA to acetylate multiple Lys residues is unique among AcuA-type acetyltransferases. Results from site-specific mutagenesis experiments showed that the activity of SacAcsA was controlled by lysine acetylation. Lastly, immunoprecipitation data showed that in vivo acetylation of SacAcsA was influenced by glucose and acetate availability. These results suggested that reversible acetylation may also be a conserved regulatory posttranslational modification strategy in antibiotic-producing actinomycetes. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Direct detection of Mycobacterium tuberculosis and drug resistance in respiratory specimen using Abbott Realtime MTB detection and RIF/INH resistance assay.

    Science.gov (United States)

    Tam, Kingsley King-Gee; Leung, Kenneth Siu-Sing; To, Sabrina Wai-Chi; Siu, Gilman Kit-Hang; Lau, Terrence Chi-Kong; Shek, Victor Chi-Man; Tse, Cindy Wing-Sze; Wong, Samson Sai-Yin; Ho, Pak-Leung; Yam, Wing-Cheong

    2017-10-01

    Abbott RealTime MTB (Abbott-RT) in conjunction with Abbott RealTime MTB RIF/INH Resistance (Abbott-RIF/INH) is a new, high-throughput automated nucleic acid amplification platform (Abbott-MDR) for detection of Mycobacterium tuberculosis complex (MTBC) and the genotypic markers for rifampicin (RIF) and isoniazid (INH) resistance directly from respiratory specimens. This prospective study evaluated the diagnostic performance of this new platform for MTBC and multidrug-resistant tuberculosis (MDR-TB) using 610 sputum specimens in a tuberculosis high-burden setting. Using conventional culture results and clinical background as reference standards, Abbott-RT exhibited an overall sensitivity and specificity of 95.2% and 99.8%, respectively. Genotypic RIF/INH resistance of 178 "MTB detected" specimens was subsequently analyzed by Abbott-RIF/INH. Compared to phenotypic drug susceptibility test results, Abbott-RIF/INH detected resistance genotypic markers in 84.6% MDR-TB, 80% mono-RIF-resistant and 66.7% mono-INH-resistant specimens. Two of the RIF-resistant specimens carried a novel single, nonsense mutation at rpoB Q513 and in silico simulation demonstrated that the truncated RpoB protein failed to bind with other subunits for transcription. Overall, Abbott-MDR platform provided high throughput and reliable diagnosis of MDR-TB within a TB high-burden region. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

    International Nuclear Information System (INIS)

    Moulder, J.E.; Hopwood, L.E.; Volk, D.M.; Davies, B.M.

    1991-01-01

    The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiation doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors

  8. Tholeitic basalts and ophiolitic complexes of the Mesorif Zone (External Rif, Morocco) at the Jurassic-Cretaceous boundary and the importance of the Ouerrha Accident in the palaeogeographic and geodynamic evolution of the Rif Mountains

    Energy Technology Data Exchange (ETDEWEB)

    Benzaggagh, M.

    2016-10-01

    The stratigraphical series around the Jurassic-Cretaceous boundary of the External Rif Mountains, in particular those in the Mesorif Zone, exhibits many outcrops with volcanic materials spread westwards over 200 km. These materials show diverse aspects: basalt lithoclasts reworked into calcareous breccia beds or in marly matrix breccia, interstratified lava flows and volcanoclastic complexes incorporated within the Berriasian marls. In the Central Rif, several magmatic blocks outcrop, usually regarded as granite scales from the Paleozoic basement or as intrusive gabbros of Barremian age. Actually these magmatic massifs display typical ophiolitic sequences and they are overlaid by mega-olistoliths of Jurassic materials and locally by radiolarite layers. Geochemical analysis of several basalt and gabbro samples belonging to the Mesorif Zone evidenced that both display a typical E-MORB magma indicating at least partial oceanization of the Mesorif basement. Concerning geodynamics, the Mesorif Zone had undergone, at the Jurassic-Cretaceous boundary interval, two successive palaeogeographic phases: an uplift, close to emersion during the Kimmeridgian-Early Tithonian interval, stressed by important submarine volcanic activities and intense brecciation of the carbonate formations, followed by a general collapse at the Late Tithonian, underlined by lava flows, slumping as mega-olistoliths and the formation of an oceanic crust, at least in the Central Rif. These magmatic materials, distributed on both sides of the Ouerrha Valley, evidence that this westwards extending valley (the Nekor Accident), may correspond in the Central Rif, to two palaeo-subduction planes which become two major overlapping thrusts in the western part of the Rif Mountains. (Author)

  9. Effective testing for pulmonary tuberculosis using Xpert MTB/RIF assay for stool specimens in immunocompetent Pakistani children

    Directory of Open Access Journals (Sweden)

    Zahra Hasan

    2016-01-01

    Conclusion: Use of Xpert MTB/RIF assay for stool-based diagnosis of pulmonary TB in immunocompetent children is useful in a resource poor setting. This is a valuable and noninvasive diagnostic alternative for the diagnosis of childhood TB and can be adapted by pediatric arms of national TB programs.

  10. Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens.

    Science.gov (United States)

    Marlowe, Elizabeth M; Novak-Weekley, Susan M; Cumpio, Joven; Sharp, Susan E; Momeny, Michelle A; Babst, Anna; Carlson, Jonathan S; Kawamura, Masae; Pandori, Mark

    2011-04-01

    A total of 217 specimens submitted for routine smear and culture from three different sites within the western United States were used to evaluate the GeneXpert MTB/RIF assay (for research use only) (Cepheid, Sunnyvale, CA). Overall agreement compared to culture was 89% (98% for smear positives and 72% for smear negatives) for detection of Mycobacterium tuberculosis.

  11. Evaluation of the Cepheid Xpert MTB/RIF Assay for Direct Detection of Mycobacterium tuberculosis Complex in Respiratory Specimens▿

    Science.gov (United States)

    Marlowe, Elizabeth M.; Novak-Weekley, Susan M.; Cumpio, Joven; Sharp, Susan E.; Momeny, Michelle A.; Babst, Anna; Carlson, Jonathan S.; Kawamura, Masae; Pandori, Mark

    2011-01-01

    A total of 217 specimens submitted for routine smear and culture from three different sites within the western United States were used to evaluate the GeneXpert MTB/RIF assay (for research use only) (Cepheid, Sunnyvale, CA). Overall agreement compared to culture was 89% (98% for smear positives and 72% for smear negatives) for detection of Mycobacterium tuberculosis. PMID:21289151

  12. Performance of the Abbott RealTime MTB RIF/INH resistance assay when used to test Mycobacterium tuberculosis specimens from Bangladesh

    Directory of Open Access Journals (Sweden)

    Kostera J

    2018-05-01

    Full Text Available Joshua Kostera, Gregor Leckie, Klara Abravaya, Hong Wang Abbott Molecular, Abbott Laboratories, Des Plaines, IL, USA Introduction: The Abbott RealTime MTB RIF/INH Resistance Assay (RT MTB RIF/INH is an assay for the detection of rifampicin (RIF- and/or isoniazid (INH-resistant Mycobacterium tuberculosis (MTB. The assay can be used to test sputum, bronchial alveolar lavage, and N-Acetyl-L-Cysteine (NALC/NaOH pellets prepared from these samples. The assay can be used in direct testing mode, or in reflex mode following a MTB positive result produced by its companion assay, Abbott RT MTB. Methods: In this study, the direct testing mode was used to test paired sputum and NALC/NaOH pellets prepared from sputum collected from Bangladesh TB patients. One hundred and thirty two paired samples were tested. Results: The RT MTB RIF/INH inhibition rate was 0%. One hundred and twenty-two paired samples had results above the assay limit of detection and were analyzed by comparing with results from phenotypic drug sensitivity testing, GeneXpert MTB/RIF (Xpert, and MTBDR plus (Hain. RT MTB RIF/INH results were in good agreement with those of GeneXpert and Hain. Conclusion: The ability of this assay to detect RIF and INH resistance may contribute to the global control of multidrug resistant tuberculosis. Keywords: tuberculosis, rifampicin, isoniazid, resistance

  13. Patterns of cross-sensitivity in the responses of clonal subpopulations isolated from the RIF-1 mouse sarcoma to selected nitrosoureas and nitrogen mustards.

    OpenAIRE

    Reeve, J. G.; Wright, K. A.; Workman, P.

    1984-01-01

    The response of clonal subpopulations isolated from the RIF-1 mouse sarcoma to melphalan treatment is independent of cell ploidy, whereas a clear relationship exists between ploidy and cell sensitivity to CCNU treatment. In the present study RIF-1 clones have been exposed to nitrogen mustard, aniline mustard and chlorambucil, and to nitrosoureas BCNU, MeCCNU and chlorozotocin, in order to evaluate whether or not the different physiochemical and biological activities of these agents would affe...

  14. Patterns of cross-sensitivity in the responses of clonal subpopulations isolated from the RIF-1 mouse sarcoma to selected nitrosoureas and nitrogen mustards.

    Science.gov (United States)

    Reeve, J. G.; Wright, K. A.; Workman, P.

    1984-01-01

    The response of clonal subpopulations isolated from the RIF-1 mouse sarcoma to melphalan treatment is independent of cell ploidy, whereas a clear relationship exists between ploidy and cell sensitivity to CCNU treatment. In the present study RIF-1 clones have been exposed to nitrogen mustard, aniline mustard and chlorambucil, and to nitrosoureas BCNU, MeCCNU and chlorozotocin, in order to evaluate whether or not the different physiochemical and biological activities of these agents would affect the patterns of drug sensitivity obtained for melphalan and CCNU. Irrespective of the different lipophilicities, transport properties and chemical reactivities of the nitrogen mustards, RIF-1 clones showed the same pattern of sensitivity as previously observed for melphalan. Similarly, RIF-1 clones when exposed to nitrosoureas BCNU, MeCCNU and chlorozotocin, showed the same pattern of sensitivity as that obtained for CCNU exposure. These data suggest (a) that the variation in the sensitivity of RIF-1 clones to treatment by the nitrogen mustards is unlikely to reflect differences in either membrane permeability or in drug transport and (b) that the ploidy dependent nitrosourea responses shown by RIF-1 clones similarly do not reflect differences in drug uptake. PMID:6466534

  15. Neurotrophin Promotes Neurite Outgrowth by Inhibiting Rif GTPase Activation Downstream of MAPKs and PI3K Signaling.

    Science.gov (United States)

    Tian, Xiaoxia; Yan, Huijuan; Li, Jiayi; Wu, Shuang; Wang, Junyu; Fan, Lifei

    2017-01-13

    Members of the well-known semaphorin family of proteins can induce both repulsive and attractive signaling in neural network formation and their cytoskeletal effects are mediated in part by small guanosine 5'-triphosphatase (GTPases). The aim of this study was to investigate the cellular role of Rif GTPase in the neurotrophin-induced neurite outgrowth. By using PC12 cells which are known to cease dividing and begin to show neurite outgrowth responding to nerve growth factor (NGF), we found that semaphorin 6A was as effective as nerve growth factor at stimulating neurite outgrowth in PC12 cells, and that its neurotrophic effect was transmitted through signaling by mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K). We further found that neurotrophin-induced neurite formation in PC12 cells could be partially mediated by inhibition of Rif GTPase activity downstream of MAPKs and PI3K signaling. In conclusion, we newly identified Rif as a regulator of the cytoskeletal rearrangement mediated by semaphorins.

  16. Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor.

    Science.gov (United States)

    Waldow, S M; Russell, G E; Wallner, P E

    1992-01-01

    Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment.

  17. A military officer in Rif: Jesús Jiménez Ortoneda (1911-1936

    Directory of Open Access Journals (Sweden)

    José Luis Villanova

    2009-08-01

    Full Text Available This paper uses original and for the most part unpublished documentation in order to examine the career of Jesús Jiménez Ortoneda, a highly successful career officer who served in the Spanish Protectorate of Morocco between 1907 and 1936. He occupied important positions in the political administration of the Protectorate (as director of the political section of Melilla’s Oficina Central de Intervenciones and a senior official in the Department of Indigenous Affairs; he was fluent in Arab and Tamazight, and gained a sound knowledge of the geography of the Rif mountains. His military career, in which he achieved the rank of lieutenant colonel, was characterized by his strictly professional attitude. He was one of the few career officers in Africa who were faithful to Spain’s republican government and who did not participate in the military uprising of 1936. This discussion of his career brings into question some well-established ideas concerning Spanish colonial policy in Morocco.

  18. Reduced blood flow increases the in vivo ammonium ion concentration in the RIF-1 tumor

    International Nuclear Information System (INIS)

    Constantinidis, Ioannis; Gamcsik, Michael P.

    1995-01-01

    Purpose: Previous studies from our laboratory have suggested that pooling of ammonium in tumor tissues may be caused by its inefficient removal due to the poor vasculature commonly found in tumors. The purpose of these experiments was to validate the relationship between tumor ammonium ion concentration and tumor blood flow, and to determine whether large concentrations of ammonium ion detected by Nuclear Magnetic Resonance (NMR) spectroscopy are either produced within the tumor or simply imported into the tumor through the blood stream. Methods and Materials: To test this hypothesis, we reduced blood flow in subcutaneously grown Radiation Induced Fibrosarcoma-1 (RIF-1) tumors, either by creating partial ischemia with a bolus injection of hydralazine or by occlusion with surgical sutures. 14 N and 31 P NMR spectroscopy were used to detect the presence of ammonium, and to assess the bioenergetic status of the tumors, respectively. Results: A correlation between ammonium ion concentration and (PCr(P i )) ratio was established for untreated tumors. An increase in the in vivo tumor ammonium ion concentration was observed for every tumor that experienced a reduction in blood flow caused by either hydralazine injection or suture ligation. Changes in ammonium ion concentration paralleled changes in the bioenergetics of hydralazine-treated tumors. Conclusion: Our results support the hypothesis that a reduction in tumor blood flow is responsible for the accumulation of ammonium in tumors, and that detected ammonium originated from within the tumor

  19. Radiation induction of drug resistance in RIF-1 tumors and tumor cells

    International Nuclear Information System (INIS)

    Hopwood, L.E.; Moulder, J.E.

    1989-01-01

    The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not for ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance

  20. Microscopic observation drug-susceptibility assay vs. Xpert® MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost-utility analysis.

    Science.gov (United States)

    Wikman-Jorgensen, Philip E; Llenas-García, Jara; Pérez-Porcuna, Tomàs M; Hobbins, Michael; Ehmer, Jochen; Mussa, Manuel A; Ascaso, Carlos

    2017-06-01

    To compare the cost-utility of microscopic observation drug-susceptibility assay (MODS) and Xpert ® MTB/RIF implementation for tuberculosis (TB) diagnosis in rural northern Mozambique. Stochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and Xpert ® MTB/RIF were evaluated as replacement test of smear microscopy (SM) or as an add-on test after a negative SM. Costs were calculated in 2013 USD, effects in disability-adjusted life years (DALY). Willingness to pay threshold (WPT) was established at once the per capita Gross National Income of Mozambique. MODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. Xpert ® MTB/RIF as an add-on test to negative SM yielded ICER of 345.71USD/DALY averted. Xpert ® MTB/RIF as a substitute for SM obtained an ICER of 122.13USD/DALY averted. TB prevalence and risk of infection were the main factors impacting MODS and Xpert ® MTB/RIF ICER in the one-way sensitivity analysis. In the probabilistic sensitivity analysis, Xpert ® MTB/RIF was most likely to have an ICER below the WPT, whereas MODS was not. Our cost-utility analysis favours the implementation of Xpert ® MTB/RIF as a replacement of SM for all TB suspects in this rural high TB/HIV prevalence African setting. © 2017 John Wiley & Sons Ltd.

  1. Off-line coupling of new generation centrifugal partition chromatography device with preparative high pressure liquid chromatography-mass spectrometry triggering fraction collection applied to the recovery of secoiridoid glycosides from Centaurium erythraea Rafn. (Gentianaceae).

    Science.gov (United States)

    Mandova, Tsvetelina; Audo, Grégoire; Michel, Sylvie; Grougnet, Raphaël

    2017-09-01

    A purification sequence including a Gilson CPC 250 PRO device coupled to PrepHPLC hyphenated with a MS triggering fraction collector was applied to isolate secoiridoid glycosides from a complex methanolic extract of Centaurium erythraea. This species is widely used for ethnomedicinal purposes around the Mediterranean Sea. The solvent system ethyle acetate/ethanol/water 7.5/3/5 was determined using shake-flask method targeting swertiamarin, the major secoiridoid of the extract. Optimization of CPC experimental parameters enabled the injection of 4g of extract with a flow rate of 40mL/min at 3000rpm to provide a secoiridoid glycosides enriched fraction. 130mg of this latter was submitted to a second step of purification by preparative HPLC (gradient water/formic acid (19:1) (A) and methanol (B) as follows: 0min, 85% A; 8min, 60% A; 12min, 55% A; 35min, 55% A; 40min, 10% A; 50min, 10% A; 52min, 85% A; 55min, 85% A) to give swertiamarin (36mg, yield 27.7%, purity 98.2%). Other secoiridoid glycosides (sweroside, gentiopicroside, secologanol, secoxyloganin) were also isolated in minor amounts. As these monoterpene derivatives are responsible for several biological activities, their quick recovery with high yield and purity may serve as a model for further scale-up and industrial development. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The genomic basis of adaptation to the fitness cost of rifampicin resistance in Pseudomonas aeruginosa

    OpenAIRE

    Qi, Qin; Toll-Riera, Macarena; Heilbron, Karl; Preston, Gail M.; MacLean, R. Craig

    2016-01-01

    This paper aims to reveal the role played by open innovation schemes in the development of new competitive advantages. Furthermore, it aims to present a normative model for networking knowledge clusters, that is, traditional clusters that are applied to the case of the Cova da Beira region (Portugal) such as Agro-Food, Textile, and Public Sector; and a set of emergent clusters that include Bioscience, Biotechnology, Multimedia, Tourism, Health, and Knowledge. In this paper, the basic framewor...

  3. The New Xpert MTB/RIF Ultra: Improving Detection of Mycobacterium tuberculosis and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing.

    Science.gov (United States)

    Chakravorty, Soumitesh; Simmons, Ann Marie; Rowneki, Mazhgan; Parmar, Heta; Cao, Yuan; Ryan, Jamie; Banada, Padmapriya P; Deshpande, Srinidhi; Shenai, Shubhada; Gall, Alexander; Glass, Jennifer; Krieswirth, Barry; Schumacher, Samuel G; Nabeta, Pamela; Tukvadze, Nestani; Rodrigues, Camilla; Skrahina, Alena; Tagliani, Elisa; Cirillo, Daniela M; Davidow, Amy; Denkinger, Claudia M; Persing, David; Kwiatkowski, Robert; Jones, Martin; Alland, David

    2017-08-29

    The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ultra assay (Ultra) to improve performance. Ultra and Xpert limits of detection (LOD), dynamic ranges, and RIF-R rpoB mutation detection were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M. tuberculosis H37Rv or Mycobacterium bovis BCG CFU. Frozen and prospectively collected clinical samples from patients suspected of having TB, with and without culture-confirmed TB, were also tested. For M. tuberculosis H37Rv, the LOD was 15.6 CFU/ml of sputum for Ultra versus 112.6 CFU/ml of sputum for Xpert, and for M. bovis BCG, it was 143.4 CFU/ml of sputum for Ultra versus 344 CFU/ml of sputum for Xpert. Ultra resulted in no false-positive RIF-R specimens, while Xpert resulted in two false-positive RIF-R specimens. All RIF-R-associated M. tuberculosis rpoB mutations tested were identified by Ultra. Testing on clinical sputum samples, Ultra versus Xpert, resulted in an overall sensitivity of 87.5% (95% confidence interval [CI], 82.1, 91.7) versus 81.0% (95% CI, 74.9, 86.2) and a sensitivity on sputum smear-negative samples of 78.9% (95% CI, 70.0, 86.1) versus 66.1% (95% CI, 56.4, 74.9). Both tests had a specificity of 98.7% (95% CI, 93.0, 100), and both had comparable accuracies for detection of RIF-R in these samples. Ultra should significantly improve TB detection, especially in patients with paucibacillary disease, and may provide more-reliable RIF-R detection. IMPORTANCE The Xpert MTB/RIF assay (Xpert), the first point-of-care assay for tuberculosis (TB), was endorsed by the World Health Organization in December 2010. Since then, 23 million Xpert tests have been procured in 130 countries. Although Xpert showed high overall sensitivity and

  4. Addressing the reproductive health needs of women with drug ...

    African Journals Online (AJOL)

    capreomycin, para-aminosalicylic acid, clofazimine, linezolid and bedaquiline. SA has universal testing for rifampicin resistance with public sector coverage of Xpert MTB/RIF since the end of 2013. Data extraction and analysis. The Electronic DR-TB Register (EDRweb) is the RR-TB national case register and, since 2012, ...

  5. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice.

    Science.gov (United States)

    Escribano-Díaz, Cristina; Orthwein, Alexandre; Fradet-Turcotte, Amélie; Xing, Mengtan; Young, Jordan T F; Tkáč, Ján; Cook, Michael A; Rosebrock, Adam P; Munro, Meagan; Canny, Marella D; Xu, Dongyi; Durocher, Daniel

    2013-03-07

    DNA double-strand break (DSB) repair pathway choice is governed by the opposing activities of 53BP1 and BRCA1. 53BP1 stimulates nonhomologous end joining (NHEJ), whereas BRCA1 promotes end resection and homologous recombination (HR). Here we show that 53BP1 is an inhibitor of BRCA1 accumulation at DSB sites, specifically in the G1 phase of the cell cycle. ATM-dependent phosphorylation of 53BP1 physically recruits RIF1 to DSB sites, and we identify RIF1 as the critical effector of 53BP1 during DSB repair. Remarkably, RIF1 accumulation at DSB sites is strongly antagonized by BRCA1 and its interacting partner CtIP. Lastly, we show that depletion of RIF1 is able to restore end resection and RAD51 loading in BRCA1-depleted cells. This work therefore identifies a cell cycle-regulated circuit, underpinned by RIF1 and BRCA1, that governs DSB repair pathway choice to ensure that NHEJ dominates in G1 and HR is favored from S phase onward. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. The Effects of Ramadan Intermittent Fasting (RIF) on Spirometric Data of Stable COPD Patients: A Pilot Study.

    Science.gov (United States)

    Zouari, Hajer; Latiri, Imed; Mahjoub, Mohamed; Boussarsar, Mohamed; Benzarti, Mohamed; Abdelghani, Ahmed; Ben Saad, Helmi

    2018-03-01

    No previous study has raised the effects of RIF on lung function data of chronic obstructive pulmonary disease (COPD) patients. The objective of the present study was to assess the effects of RIF on spirometric data measured in male patients with a stable COPD. Sixteen patients with stable COPD (mean ± SD of age: 64 ± 7 years) who fasted during Ramadan volunteered to the study. Three sessions (Before-R, End-R, and After-R) were selected for spirometry tests that were consistently performed 2.5-4.5 hr before fasting break. Assessment sessions comprised: forced vital capacity (FVC), 1st s forced expiratory volume (FEV 1 ), FEV 1 /FVC, peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), and forced expiratory flow rate at the x% of FVC to be exhaled (FEFx%). A reversibility test was performed only during the Before-Ramadan session. Spirometric data were expressed in percentages of local reference values. Findings were analyzed by applying repeated measures analysis of variance. The mean ± SD of the postbronchodilator FEV 1 /FVC ratio and the FEV 1 were, respectively, 0.52 ± 0.14 and 48 ± 19%. The mean ± SD of FEV 1 (Before-R: 47 ± 19, End-R: 45 ± 18, After-R: 44 ± 19%), FVC (Before-R: 73 ± 18, End-R: 71 ± 16, After-R: 69 ± 17%), FEV 1 /FVC (Before-R: 67 ± 16, End-R: 66 ± 16, After-R: 65 ± 16%), PEF (Before-R: 46 ± 19, End-R: 47 ± 22, After-R: 45 ± 21%), MMEF (Before-R: 19 ± 10, End-R: 18 ± 8, After-R: 18 ± 9%), FEF 25% (Before-R: 16 ± 6, End-R: 16 ± 5, After-R: 15 ± 5%), FEF 50% (Before-R: 21 ± 14, End-R: 20 ± 12, After-R: 20 ± 12%) and FEF 75% (Before-R: 27 ± 19, End-R: 27 ± 19, After-R: 27 ± 19%) were not significantly influenced by RIF. RIF did not bring about any significant changes in the spirometric data of stable COPD male patients fasting the 2016 holy month of Ramadan.

  7. Study of relief changes related to active doming in the eastern Moroccan Rif (Morocco) using geomorphological indices

    Science.gov (United States)

    Barcos, L.; Jabaloy, A.; Azdimousa, A.; Asebriy, L.; Gómez-Ortiz, D.; Rodríguez-Peces, M. J.; Tejero, R.; Pérez-Peña, J. V.

    2014-12-01

    This work studies the influence of active tectonics in the drainage networks and topography of the eastern Rif belt, eastern Middle Atlas, and Rekkame high plateau. We have performed a trend-topographic surface analysis at small to medium scales, several landscape analyses at medium scale, and the slope analysis of the relief. Furthermore, we have determined several geomorphic indices in the drainage networks of the study area: hypsometric curve analysis and normalised stream-length gradient (SLk) estimations. The trend-topography surface analysis identifies a NE-SW trending undulation that correspond to the positive topography of the Middle and High Atlas mountain ranges and the Rekkame high plateau as well as an E-W elongated dome in the eastern Rif-Beni Snassen massif. The geomorphologic indices indicate that drainage network is strongly deformed in the vicinity of the Trougout-Nekor active fault system. Furthermore, the Oued Molouya catchment is deformed in the northern limit of the Beni Snassen massif by active deformations accommodating a roughly N-S shortening. According to the available geochronological data from volcanic rocks as well as from Neogene to Quaternary sediments, the most likely age for the deformation of the drainage network producing the anomalous high geomorphic indexes was Placenzian to Present.

  8. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study

    NARCIS (Netherlands)

    Boehme, Catharina C.; Nicol, Mark P.; Nabeta, Pamela; Michael, Joy S.; Gotuzzo, Eduardo; Tahirli, Rasim; Gler, Ma Tarcela; Blakemore, Robert; Worodria, William; Gray, Christen; Huang, Laurence; Caceres, Tatiana; Mehdiyev, Rafail; Raymond, Lawrence; Whitelaw, Andrew; Sagadevan, Kalaiselvan; Alexander, Heather; Albert, Heidi; Cobelens, Frank; Cox, Helen; Alland, David; Perkins, Mark D.

    2011-01-01

    The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to

  9. Reversal of DDK-Mediated MCM Phosphorylation by Rif1-PP1 Regulates Replication Initiation and Replisome Stability Independently of ATR/Chk1.

    Science.gov (United States)

    Alver, Robert C; Chadha, Gaganmeet Singh; Gillespie, Peter J; Blow, J Julian

    2017-03-07

    Dbf4-dependent kinases (DDKs) are required for the initiation of DNA replication, their essential targets being the MCM2-7 proteins. We show that, in Xenopus laevis egg extracts and human cells, hyper-phosphorylation of DNA-bound Mcm4, but not phosphorylation of Mcm2, correlates with DNA replication. These phosphorylations are differentially affected by the DDK inhibitors PHA-767491 and XL413. We show that DDK-dependent MCM phosphorylation is reversed by protein phosphatase 1 (PP1) targeted to chromatin by Rif1. Loss of Rif1 increased MCM phosphorylation and the rate of replication initiation and also compromised the ability of cells to block initiation when challenged with replication inhibitors. We also provide evidence that Rif1 can mediate MCM dephosphorylation at replication forks and that the stability of dephosphorylated replisomes strongly depends on Chk1 activity. We propose that both replication initiation and replisome stability depend on MCM phosphorylation, which is maintained by a balance of DDK-dependent phosphorylation and Rif1-mediated dephosphorylation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records

    DEFF Research Database (Denmark)

    Jiang, Li; Edwards, Stefan M.; Thomsen, Bo

    2014-01-01

    from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text...

  11. Feasibility of measuring radiation-induced DNA double strand breaks and their repair by pulsed field gel electrophoresis in freshly isolated cells from the mouse RIF-1 tumor

    International Nuclear Information System (INIS)

    Waarde, Maria A.W.H. van; Assen, Annette J. van; Konings, Antonius W.T.; Kampinga, Harm H.

    1996-01-01

    Purpose: To examine the technical feasibility of pulsed field gel electrophoresis (PFGE) as a predictive assay for the radio responsiveness of tumors. Induction and repair of DNA double strand breaks (DSBs) in a freshly prepared cell suspension from a RIF-1 tumor (irradiated ex vivo) was compared with DSB induction and repair in exponentially growing RIF-1 cells in culture (irradiated in vitro). Methods and Materials: A murine RIF-1 tumor grown in vivo was digested, and cells were exposed to x-rays (ex vivo) at doses of 1 to 75 Gy. DNA damage was measured using CHEF (clamped homogeneous electric fields) electrophoresis. Repair kinetics were studied at 37 deg. C for 4 h after irradiation. Radiosensitivity was determined by clonogenic assay, and cell cycle distributions by flow cytometry. For comparison, a trypsinized suspension of exponentially growing RIF-1 cells in vitro was run parallel with each ex vivo experiment. Results: Induction of DSBs, expressed as % DNA extracted from the plug, was similar in the in vitro and ex vivo irradiated cells. Compared to repair rates in in vitro cultured RIF-1 cells, repair kinetics in a freshly prepared cell suspension from the tumor were decreased, unrelated to differences in radiosensitivity. Differences in repair could not be explained by endogenous DNA degradation, nor by influences of enzymes used for digestion of the tumor. A lower plating efficiency and differences in ploidy (as revealed by flow cytometry) were the only reproducible differences between in vivo and in vitro grown cells that may explain the differences in repair kinetics. Conclusions: The current results do not support the idea that PFGE is a technique robust enough to be a predictive assay for the radiosensitivity of tumor cells

  12. A comparison between the efficiency of the Xpert MTB/RIF assay and nested PCR in identifying Mycobacterium tuberculosis during routine clinical practice.

    Science.gov (United States)

    Kim, Cheol-Hong; Woo, Heungjeong; Hyun, In Gyu; Kim, Changhwan; Choi, Jeong-Hee; Jang, Seung-Hun; Park, Sang Myeon; Kim, Dong-Gyu; Lee, Myung Goo; Jung, Ki-Suck; Hyun, Jeongwon; Kim, Hyun Soo

    2014-06-01

    Polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis (MTB) is more sensitive, specific, and rapid than the conventional methods of acid-fast bacilli (AFB) smear and culture. The aim of this study was to determine if the Xpert MTB/rifampicin (RIF) assay had additional advantages over nested PCR for the detection of MTB in a geographical area with intermediate tuberculosis (TB) incidence. Between February and December 2013, the Xpert MTB/RIF assay and MTB nested PCR, as well as AFB smear and culture, were simultaneously performed on 198 clinical samples (160 pulmonary and 38 non-pulmonary specimens) collected from 171 patients hospitalized at Hallym University Medical Center for possible TB. The accuracy of the diagnosis of MTB culture-positive TB and the turnaround time of reporting laboratory results were calculated and compared. Rifampin resistance by the Xpert MTB/RIF assay was reviewed with that of conventional drug susceptibility testing (DST). The sensitivity, specificity, and positive and negative predictive values of the Xpert MTB/RIF assay and MTB nested PCR for diagnosis of MTB culture-positive pulmonary TB were 86.1% vs. 69.4% (P=0.1563), 97.8% vs. 94.1% (P=0.2173), 91.2% vs. 75.8% (P=0.1695), and 96.4% vs. 92.0% (P=0.2032), respectively. The median turnaround times of the Xpert MTB/RIF assay and MTB nested PCR were 0 [0-4] days and 4 [1-11] days, respectively (Pnested PCR for identifying MTB among clinically suspected TB patients, and the assay can be valuable in giving a timely identification of resistance to rifampin.

  13. La conspiración turco-comunista: espías, contrabandistas e instructores en el Rif

    Directory of Open Access Journals (Sweden)

    Daniel Macías Fernández

    2016-12-01

    Full Text Available The Moroccan Wars (1909-1927, specially one of them, the Rif War (1921-1927, also called the Second Moroccan War, was a tough and hard mission put in charge of the most operational and ambitious section within the early twentieth-century Spanish army. According to the international treaties, the Spanish task in northern Morocco was bringing peace to the area, but the troubles and obstacles to accomplish it were so huge that the intelligence branch of the army ultimately resorted to foreign sources of information. Secret agents, informants and counter-espionage nets attached to the Spanish Protectorate of Morocco administration or to the Spanish foreign legations all over the world produced tons of documents which amount shows how important was that activity. Many soldiers warned about foreign plots in the Spanish Protectorate and deliveries of war supplies to the native rebel militias.

  14. A Prospective Study of the Prevalence of Tuberculosis and Bacteraemia in Bangladeshi Children with Severe Malnutrition and Pneumonia Including an Evaluation of Xpert MTB/RIF Assay

    Science.gov (United States)

    Chisti, Mohammod Jobayer; Graham, Stephen M.; Duke, Trevor; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, Abu Syed Golam; La Vincente, Sophie; Banu, Sayera; Raqib, Rubhana; Salam, Mohammed Abdus

    2014-01-01

    Background Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain. Methods We prospectively investigated severely malnourished young children (<5 years) with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital. Results 405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4%) children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396) of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16%) additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24–94) and 92% (95% CI: 87–95) respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital. Conclusion and Significance TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes. PMID:24695758

  15. A prospective study of the prevalence of tuberculosis and bacteraemia in Bangladeshi children with severe malnutrition and pneumonia including an evaluation of Xpert MTB/RIF assay.

    Directory of Open Access Journals (Sweden)

    Mohammod Jobayer Chisti

    Full Text Available Severe malnutrition is a risk factor for pneumonia due to a wide range of pathogens but aetiological data are limited and the role of Mycobacterium tuberculosis is uncertain.We prospectively investigated severely malnourished young children (<5 years with radiological pneumonia admitted over a 15-month period. Investigations included blood culture, sputa for microscopy and mycobacterial culture. Xpert MTB/RIF assay was introduced during the study. Study children were followed for 12 weeks following their discharge from the hospital.405 eligible children were enrolled, with a median age of 10 months. Bacterial pathogens were isolated from blood culture in 18 (4.4% children, of which 72% were Gram negatives. Tuberculosis was confirmed microbiologically in 7% (27/396 of children that provided sputum - 10 by culture, 21 by Xpert MTB/RIF assay, and 4 by both tests. The diagnostic yield from induced sputum was 6% compared to 3.5% from gastric aspirate. Sixty (16% additional children had tuberculosis diagnosed clinically that was not microbiologically confirmed. Most confirmed tuberculosis cases did not have a positive contact history or positive tuberculin test. The sensitivity and specificity of Xpert MTB/RIF assay compared to culture was 67% (95% CI: 24-94 and 92% (95% CI: 87-95 respectively. Overall case-fatality rate was 17% and half of the deaths occurred in home following discharge from the hospital.TB was common in severely malnourished Bangladeshi children with pneumonia. X-pert MTB/RIF assay provided higher case detection rate compared to sputum microscopy and culture. The high mortality among the study children underscores the need for further research aimed at improved case detection and management for better outcomes.

  16. Higher cost of implementing Xpert(®) MTB/RIF in Ugandan peripheral settings: implications for cost-effectiveness.

    Science.gov (United States)

    Hsiang, E; Little, K M; Haguma, P; Hanrahan, C F; Katamba, A; Cattamanchi, A; Davis, J L; Vassall, A; Dowdy, D

    2016-09-01

    Initial cost-effectiveness evaluations of Xpert(®) MTB/RIF for tuberculosis (TB) diagnosis have not fully accounted for the realities of implementation in peripheral settings. To evaluate costs and diagnostic outcomes of Xpert testing implemented at various health care levels in Uganda. We collected empirical cost data from five health centers utilizing Xpert for TB diagnosis, using an ingredients approach. We reviewed laboratory and patient records to assess outcomes at these sites and10 sites without Xpert. We also estimated incremental cost-effectiveness of Xpert testing; our primary outcome was the incremental cost of Xpert testing per newly detected TB case. The mean unit cost of an Xpert test was US$21 based on a mean monthly volume of 54 tests per site, although unit cost varied widely (US$16-58) and was primarily determined by testing volume. Total diagnostic costs were 2.4-fold higher in Xpert clinics than in non-Xpert clinics; however, Xpert only increased diagnoses by 12%. The diagnostic costs of Xpert averaged US$119 per newly detected TB case, but were as high as US$885 at the center with the lowest volume of tests. Xpert testing can detect TB cases at reasonable cost, but may double diagnostic budgets for relatively small gains, with cost-effectiveness deteriorating with lower testing volumes.

  17. Drug resistance following irradiation of RIF-1 tumors: Influence of the interval between irradiation and drug treatment

    International Nuclear Information System (INIS)

    Hopwood, L.E.; Davies, B.M.; Moulder, J.E.

    1990-01-01

    RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance

  18. Evidence of oceanic units in the core of the External Rif (Morocco): intramargin hiatus or South-Tethyan remnants?

    Science.gov (United States)

    Benzaggagh, Mohamed; Mokhtari, Abdelkhader; El Maz, Abdelkhader; Rossi, Philippe; Michard, André; Saddiqi, Omar; Chalouan, Ahmed; Rjimati, Ech-Cherki

    2013-04-01

    Our work is based on extensive field campaigns in the central area of the External Rif Belt and on petrological-geochemical study of the magmatic samples. The aim is to disclose the westward extension of the Mesorif suture zone evidenced in the Temsamane zone of eastern Rif (Michard et al., 2007). We first describe Jurassic-Early Cretaceous sections involving basaltic rocks, spread along the 200 km-long, arcuate Prerif-Mesorif boundary zone west of the Temsamane massif. These sections are thoroughly dated by ammonites and calpionelles from the late Oxfordian to late Berriasian (Benzaggagh, 2011). They display varied traces of submarine, basic volcanism such as volcanoclastic complexes within Upper Berriasian marls, and basalt flows, olistoliths and clasts in the upper Oxfordian-lower Berriasian clayey breccias or in the lower Tithonian brecciated calcareous beds. Volcanic activity took place at the margin of a carbonate platform during the Kimmeridgian-early Tithonian interval, then in a pelagic basin from late Tithonian onward. Petrographic and geochemical studies point to E-MORB basaltic magmas (Rossi, in Benzaggah, 2011), thus testifying for strong crustal thinning in this part of the African paleomargin. Strong support to this inference is found in the occurrence of two small tectonic units of gabbros associated with basalt flows, fault-scarp breccias and radiolarites. A preliminary study of the gabbros reveals that, in thin section, many petrographic types display ortho- to heteradcumulate texture. The typical sequence of cristallization is plag-ol-cpx-ilm and the composition ranges from troctolitic olivine gabbro [An 66-60; Fo 73-71 & 68; cpx Wo 46, En 44, Fs 10 with content in Cr2O3 up to 1%]) to ferrogabbro [(An 50-45); Fo 53; cpx Wo 44, En 40, Fs 16]). Plot of these rocks onto an AFM projection fall on the cumulative composition field along the FM joint and TR patterns display systematic Eu positive anomaly characterizing cumulative plagioclase. Some more

  19. Xpert MTB/RIF testing in a low tuberculosis incidence, high-resource setting: limitations in accuracy and clinical impact.

    Science.gov (United States)

    Sohn, Hojoon; Aero, Abebech D; Menzies, Dick; Behr, Marcel; Schwartzman, Kevin; Alvarez, Gonzalo G; Dan, Andrei; McIntosh, Fiona; Pai, Madhukar; Denkinger, Claudia M

    2014-04-01

    Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in low-income countries. However, little information is available on its performance in low-incidence, high-resource countries. We evaluated the accuracy of Xpert in a university hospital tuberculosis clinic in Montreal, Canada, for the detection of pulmonary tuberculosis on induced sputum samples, using mycobacterial cultures as the reference standard. We also assessed the potential reduction in time to diagnosis and treatment initiation. We enrolled 502 consecutive patients who presented for evaluation of possible active tuberculosis (most with abnormal chest radiographs, only 18% symptomatic). Twenty-five subjects were identified to have active tuberculosis by culture. Xpert had a sensitivity of 46% (95% confidence interval [CI], 26%-67%) and specificity of 100% (95% CI, 99%-100%) for detection of Mycobacterium tuberculosis. Sensitivity was 86% (95% CI, 42%-100%) in the 7 subjects with smear-positive results, and 28% (95% CI, 10%-56%) in the remaining subjects with smear-negative, culture-positive results; in this latter group, positive Xpert results were obtained a median 12 days before culture results. Subjects with positive cultures but negative Xpert results had minimal disease: 11 of 13 had no symptoms on presentation, and mean time to positive liquid culture results was 28 days (95% CI, 25-47 days) compared with 14 days (95% CI, 8-21 days) in Xpert/culture-positive cases. Our findings suggest limited potential impact of Xpert testing in high-resource, low-incidence ambulatory settings due to lower sensitivity in the context of less extensive disease, and limited potential to expedite diagnosis beyond what is achieved with the existing, well-performing diagnostic algorithm.

  20. Evaluation of molecular detection of extrapulmonary tuberculosis and resistance to rifampicin with GeneXpert® MTB/RIF.

    Science.gov (United States)

    Marouane, C; Smaoui, S; Kammoun, S; Slim, L; Messadi-Akrout, F

    2016-02-01

    We aimed to evaluate the GeneXpert® MTB/RIF test for the diagnosis of extrapulmonary tuberculosis. The test simultaneously detects Mycobacterium tuberculosis complex and resistance to rifampicin. We analyzed 153 clinical samples collected in a tertiary hospital in Sfax, Tunisia, between 2013 and 2014. We performed the GeneXpert® test, a Ziehl-Neelsen and auramine-rhodamine staining, conventional culture on MGIT 960 and LJ media, and we tested the resistance to anti-tuberculosis drugs on MGIT 960 and LJ media for each sample. Diagnosis was based on clinical, radiological, microbiological, pathological, and therapeutic data. We considered that 59 patients out of 153 presented with tuberculosis. PCR was positive in 50 samples and all of these samples were susceptible to rifampicin. Sensitivity, specificity, positive predictive value, and negative predictive value of the GeneXpert® test were 84.7%, 96.8%, 94.3%, and 91%, respectively, compared with diagnosis. We observed a statistically significant difference between the direct test and the GeneXpert® test, and between culture and the GeneXpert® test. No statistically significant difference was observed between pathological results and the GeneXpert® test. Sensitivity of the GeneXpert® test was 87.5% in biopsies, 80% in pus and abscesses, and 66.7% in biological fluids. All strains were susceptible to rifampicin with culture and GeneXpert® test. The GeneXpert® test helped detect a higher proportion of M. tuberculosis complex. It does not replace conventional diagnostic methods but it is a useful addition to achieve better sensitivity and obtain rapid results. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Mutations in circularly permuted GTPase family genes AtNOA1/RIF1/SVR10 and BPG2 suppress var2-mediated leaf variegation in Arabidopsis thaliana.

    Science.gov (United States)

    Qi, Yafei; Zhao, Jun; An, Rui; Zhang, Juan; Liang, Shuang; Shao, Jingxia; Liu, Xiayan; An, Lijun; Yu, Fei

    2016-03-01

    Leaf variegation mutants constitute a unique group of chloroplast development mutants and are ideal genetic materials to dissect the regulation of chloroplast development. We have utilized the Arabidopsis yellow variegated (var2) mutant and genetic suppressor analysis to probe the mechanisms of chloroplast development. Here we report the isolation of a new var2 suppressor locus SUPPRESSOR OF VARIEGATION (SVR10). Genetic mapping and molecular complementation indicated that SVR10 encodes a circularly permuted GTPase that has been reported as Arabidopsis thaliana NITRIC OXIDE ASSOCIATED 1 (AtNOA1) and RESISTANT TO INHIBITION BY FOSMIDOMYCIN 1 (RIF1). Biochemical evidence showed that SVR10/AtNOA1/RIF1 likely localizes to the chloroplast stroma. We further demonstrate that the mutant of a close homologue of SVR10/AtNOA1/RIF1, BRASSINAZOLE INSENSITIVE PALE GREEN 2 (BPG2), can also suppress var2 leaf variegation. Mutants of SVR10 and BPG2 are impaired in photosynthesis and the accumulation of chloroplast proteins. Interestingly, two-dimensional blue native gel analysis showed that mutants of SVR10 and BPG2 display defects in the assembly of thylakoid membrane complexes including reduced levels of major photosynthetic complexes and the abnormal accumulation of a chlorophyll-protein supercomplex containing photosystem I. Taken together, our findings suggest that SVR10 and BPG2 are functionally related with VAR2, likely through their potential roles in regulating chloroplast protein homeostasis, and both SVR10 and BPG2 are required for efficient thylakoid protein complex assembly and photosynthesis.

  2. Computational Simulation Techniques to Understand Rifampicin Resistance Mutation (S425L) of rpoB in M. leprae.

    Science.gov (United States)

    Nisha, J; Shanthi, V

    2015-07-01

    Mycobacterium leprae, the etiologic agent of leprosy, is non-cultivable in vitro. Consequently, the assessment of antibiotic activity against M. leprae hinge mainly upon the time consuming mouse footpad system. As M. leprae develops resistance against most of the drugs, the evolution of new long acting antimycobacterial compounds stand in need for leprosy control. The rpoB of M. leprae is the target of antimycobacterial drug, rifampicin. Recently, cases were reported that rpoB mutation (S425L) became resistant to rifampicin and the mechanism of resistance is still not well understood. The present study is aimed at studying the molecular and structural mechanism of the rifampicin binding to both native and mutant rpoB through computational approaches. From molecular docking, we demonstrated the stable binding of rifampicin through two hydrogen bonding with His420 residue of native than with mutant rpoB where one hydrogen bonding was found with Ser406. The difference in binding energies observed in the docking study evidently signifies that rifampicin is less effective in the treatment of patients with S425L variant. Moreover, the molecular dynamics studies also highlight the stable binding of rifampicin with native than mutant (S425L) rpoB. © 2015 Wiley Periodicals, Inc.

  3. Evaluation of genotype MTBDRplus assay for rapid detection of isoniazid and rifampicin resistance in Mycobacterium tuberculosis clinical isolates from Pakistan

    Directory of Open Access Journals (Sweden)

    Hasnain Javed

    2016-01-01

    Conclusions: As evidenced in this study, the major concern with the GenoType MTBDRplus assay were false negative results. In comparison to conventional drug susceptibility testing, the assay was unable to detect 30 (30/100; 30% strains resistant to INH and 23 (23/100; 23% strains resistant to RMP. The GenoType MTBDRplus failed to identify 38 MDR (38/100; 38% strains. Resistance in those strains probably originate from mutations in other codons and/or genes than those covered by the test. For detecting INH and RMP resistance in TB cases, especially in high TB incidence countries, such as Pakistan, molecular approaches should still be a complement rather than areplacement to conventional drug susceptibility testing.

  4. CCR2 V64I polymorphism in rifampicin resistant tuberculosis patients in Moewardi General Hospital Surakarta, Indonesia

    Science.gov (United States)

    Marwoto; Agung Prasetyo, Afiono; Reviono; Suradi

    2018-05-01

    CC chemokine receptor-2 (CCR2) play important roles in inflammation. The CCR2 V64I polymorphism already reported associated with many diseases; however, the association of CCR2 V64I polymorphism with tuberculosis is still unknown. Also, there is no report about the presentation of CCR2 V64I polymorphisms in Indonesian tuberculosis patients with rifampicin-mono resistant status has ever been published, to the best of our knowledge. This study evaluated the presence of CCR2 V64I polymorphisms in Javanese rifampicin-mono resistant tuberculosis patients. In an ongoing molecular epidemiology study of human genomic polymorphisms and infection, 51 Javanese rifampicin-mono resistant tuberculosis patients in Dr. Moewardi General Hospital in Surakarta were enrolled in the study. The blood samples were aliquoted and fractionated. The nucleic acids were extracted from all blood samples and subjected to the CCR2 V64I polymorphisms detection by a polymerase chain reaction-sequence-specific primer (PCR-SSP) technique. PCR products were analyzed in 3% agarose. CCR2 64V and 64I homozygote were found in 23.5% (12/51) and 23.5% (12/51) blood samples, respectively. The CCR2 VI genotype was found in 52.9% (27/51) blood samples. The CCR2 VI genotype was found predominant in Javanese rifampicin-mono resistant tuberculosis patients and may have anassociation with the clinical progression.

  5. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records

    DEFF Research Database (Denmark)

    Jiang, Li; Edwards, Stefan M.; Thomsen, Bo

    2014-01-01

    from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining......Background: Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic...

  6. [Budget impact of the incorporation of GeneXpert MTB/RIF for diagnosis of pulmonary tuberculosis from the perspective of the Brazilian Unified National Health System, Brazil, 2013-2017].

    Science.gov (United States)

    Pinto, Márcia Ferreira Teixeira; Steffen, Ricardo; Entringer, Aline; Costa, Ana Carolina Carioca da; Trajman, Anete

    2017-10-09

    The study aimed to estimate the budget impact of GeneXpert MTB/RIF for diagnosis of tuberculosis from the perspective of the Brazilian National Program for Tuberculosis Control, drawing on a static model using the epidemiological method, from 2013 to 2017. GeneXpert MTB/RIF was compared with two diagnostic sputum smear tests. The study used epidemiological, population, and cost data, exchange rates, and databases from the Brazilian Unified National Health System. Sensitivity analysis of scenarios was performed. Incorporation of GeneXpert MTB/RIF would cost BRL 147 million (roughly USD 45 million) in five years and would have an impact of 23 to 26% in the first two years and some 11% between 2015 and 2017. The results can support Brazilian and other Latin American health administrators in planning and managing the decision on incorporating the technology.

  7. Oceanic units in the core of the External Rif (Morocco): Intramargin hiatus or South-Tethyan remnants?

    Science.gov (United States)

    Benzaggagh, Mohamed; Mokhtari, Abdelkader; Rossi, Philippe; Michard, André; El Maz, Abdelkhader; Chalouan, Ahmed; Saddiqi, Omar; Rjimati, Ech-Cherki

    2014-07-01

    The aim of this paper is to describe the mafic rocks that crop out in the central-western Mesorif Zone (External Rif Belt), and discuss their geodynamic signification. Basalt flows, olistoliths and breccias occur in Oxfordian-Berriasian deposits of Mesorif units ascribed to the distal part of the African paleomargin. The climax of volcanic activity is observed at the northern border of a Kimmeridgian carbonate platform progressively dismembered during the Tithonian-Berriasian. In spite of the alteration of the basalts, their petrological and geochemical characters point to E-MORB affinities. The studied gabbro massifs (Bou Adel, Kef el Rhar west and north) occur as restricted slivers or klippes within the Senhadja nappe or mélange of the internal Mesorif, which overlies the basalt-bearing units and other, more external Mesorif units. The compositions range from troctolitic olivine gabbro to ferrogabbro with frequent ortho- to heteradcumulate textures; they display typical tholeiitic affinity. The gabbro massifs are crosscut by trondjhemite dykes and overlain by metabasalts, fault-scarp breccias, ophicalcites, marbles and radiolarites. Composition featuring initial near liquid composition, display multi elements patterns close to those of E-MORB, with a weak Eu negative anomaly and evidence of slight crustal contamination. These gabbro massifs were regarded as Jurassic-Cretaceous intrusions, locally dated (K-Ar) at 166 ± 3 Ma. Conversely, we assume they represent discrete samples of a Jurassic-Cretaceous oceanic basement (ophiolites), emplaced tectonically in the Senhadja nappe (mélange) of the central Mesorif. The correlation of both these types of mafic rock associations (paleomargin basalts and ophiolite klippes) with the serpentinites of the eastern Mesorif (Beni Malek) and Oran mountains (Algeria) is then briefly discussed. We conclude that the previous hypothesis of an intramargin “Mesorif suture zone” must be reconsidered, being challenged by that of a

  8. The Response of RIF-1 Fibrosarcomas to the Vascular-Disrupting Agent ZD6126 Assessed by In Vivo and Ex Vivo1H Magnetic Resonance Spectroscopy

    Directory of Open Access Journals (Sweden)

    Basetti Madhu

    2006-07-01

    Full Text Available The response of radiation-induced fibrosarcoma1 (RIF-1 tumors treated with the vascular-disrupting agent (VDA ZD6126 was assessed by in vivo and ex vivo1H magnetic resonance spectroscopy (MRS methods. Tumors treated with 200 mg/kg ZD6126 showed a significant reduction in total choline (tCho in vivo 24 hours after treatment, whereas control tumors showed a significant increase in tCho. This response was investigated further within both ex vivo unprocessed tumor tissues and tumor tissue metabolite extracts. Ex vivo high-resolution magic angle spinning (HRMAS and 1H MRS of metabolite extracts revealed a significant reduction in phosphocholine and glycerophosphocholine in biopsies of ZD6126-treated tumors, confirming in vivo tCho response. ZD6126-induced reduction in choline compounds is consistent with a reduction in cell membrane turnover associated with necrosis and cell death following disruption of the tumor vasculature. In vivo tumor tissue water diffusion and lactate measurements showed no significant changes in response to ZD6126. Spin-spin relaxation times (T2 of water and metabolites also remained unchanged. Noninvasive 1H MRS measurement of tCho in vivo provides a potential biomarker of tumor response to VDAs in RIF-1 tumors.

  9. The potentiation of radiation effects on the Meth-a and RIF tumors and hela s-3 cells by the glycolytic inhibitor, Lonidamine

    International Nuclear Information System (INIS)

    Kim, J.H.; Alfieri, A.A.; Kim, S.H.; He, S.Q.; Young, C.W.

    1984-01-01

    The indazole carboxylic acid Lonidamine (L) a glycolytic inhibitor and antispermatogenic agent previously found to have hyperthermia sensitization properties was evaluated as a radiopotentiating agent in vitro and in vivo. Tumoricidal effects of (L) i.p. and single dose x-irradiation (3.0 or 3.2 Gy) was evaluated on 300-1000 mm/sup 3/ i.m. Meth-A in BALB/c and the RIF fibrosarcoma in C/sub 3/H/He mice L preceded or proceeded the radiation event to 1 hr intervals with maximum separation between treatments of 4 hrs. L conc in sera was biphasic (t1/2 -- 1 hr.). Optimal treatment efficacy was found at minimal time intervals between L and radiation interaction. TCD /sub 50/ for RIF and Meth-A resulted in DMF's of 1.15 - 1.35 (L dose dependent). Chronic L (50mg/kg/dy x 30) + fractionated radiation was found to be well tolerated as concomitant L potentiated combination therapy. Cell culture studies on monolayer and spheroids demonstrate L as an effective inhibitor of potential lethal radiation damage with L potential to be dependent upon both dose/fraction, number of fractions and total radiation dose accumulated

  10. Late Miocene to present-day exhumation and uplift of the Internal Zone of the Rif chain: Insights from low temperature thermochronometry and basin analysis

    Science.gov (United States)

    Romagny, A.; Ph. Münch; Cornée, J.-J.; Corsini, M.; Azdimousa, A.; Melinte-Dobrinescu, M. C.; Drinia, H.; Bonno, M.; Arnaud, N.; Monié, P.; Quillévéré, F.; Ben Moussa, A.

    2014-07-01

    Located on the margin of the west Alboran basin, the Gibraltar Arc (Betic-Rif mountain belt) displays post-Pliocene vertical movements evidenced by uplifted marine sedimentary basins and marine terraces. Quantification of vertical movements is an important clue to understand the origin of present-day relief generation in the Betic-Rif mountain chain together with the causes of the Messinian Salinity Crisis. In this paper, we present the results of a pluridisciplinary study combining an analysis of low temperature thermochronology and Pliocene basins evolution to constrain the exhumation history and surface uplift of internals units of the Rif belt (Northern Morocco). The mean (U-Th)/He apatite ages obtained from 11 samples are comprised between 14.1 and 17.8 Ma and display a wide dispersion, which could be explained by a great variability of apatite chemistries in the analyzed samples. No correlations between altitude and age have been found along altitudinal profile suggesting a rapid exhumation during this period. Thermal modeling using our (U-Th)/He apatite ages and geochronological data previously obtained in the same area (40Ar/39Ar and K/Ar data on biotite, zircon and apatite fission track) allow us to propose a cooling history. The rocks suffered a rapid cooling at 60-100 °C/Ma between 22.5 and 19 Ma, then cooled to temperatures around 40 °C between 19 and 18 Ma. They were re-heated at around 110 °C between 18 and 15 Ma then rapidly cooled and exhumed to reach the surface temperature at around 13 Ma. The re-heating could be related to a renewal in thrusting and burying of the inner zones. Between 15 and 13 Ma the cooling resumed at a rate of 50 °C/Ma indicating an exhumation rate of 0.8 mm/y considering an average 40 °C/km geothermal gradient. This exhumation may be linked to the extension in the Alboran Sea. Otherwise biostratigraphic and sedimentological analysis of Pliocene basins of the internal Rif provided informations on the more recent events

  11. Riffing on the universe

    Science.gov (United States)

    Cox, Trevor

    2016-05-01

    Music and physics might seem like polar opposites, one having great emotional potency and the other being a cerebral subject of equations, theories and deductions. Both, however, benefit from improvisers - people who stand on the shoulders of giants, taking earlier triumphs and building on them to create something new. For me, analogies like these, which draw parallels between physicists and jazz musicians, are the most fascinating revelations in Stephon Alexander's book The Jazz of Physics.

  12. Les sources du Moyen Atlas et de Rif (Maroc): Faunistique (description de deux espèces nouvelles de Trichoptères), écologie, intérêt biogéographique

    NARCIS (Netherlands)

    Giudicelli, Jean; Dakki, Mohamed

    1984-01-01

    Seven springs in the Middle Atlas and five in the Rif have been studied. These show a great diversity of crenal habitats: water temperature ranges from 8.7° to 21°C, and the flow from 1 l/s to 1,800 l/s. Based on hydrologic and thermic characteristics, a spring typology is provided. The invertebrate

  13. Rendimiento de la prueba Xpert MTB/RIF en muestras respiratorias en el escenario real de trabajo en un país en desarrollo

    Directory of Open Access Journals (Sweden)

    Santiago Atehortúa

    2015-03-01

    Full Text Available Introducción. La prueba Xpert MTB/RIF detecta el ADN del complejo Mycobacterium tuberculosis y la sensibilidad a rifampicina. La prueba ha sido evaluada en condiciones “ideales” que incluyen la centrifugación de esputo y el lavado broncoalveolar, la tinción de Ziehl Neelsen (ZN y de auramina-rodamina y los métodos de cultivo sólido y de cultivo líquido automatizado. Los resultados de tales evaluaciones no pueden extrapolarse a países de bajos ingresos que no utilizan habitualmente todos estos procesos. Objetivo. Evaluar el rendimiento de la prueba Xpert MTB/RIF en muestras respiratorias bajo condiciones “reales” de trabajo y su correlación con las pruebas fenotípicas de sensibilidad. Materiales y métodos. Se llevó a cabo un estudio transversal para evaluar el rendimiento de la prueba Xpert MTB/RIF en pacientes ≥12 años con sospecha de tuberculosis pulmonar. En el procesamiento rutinario de muestras en el Hospital del estudio no se usa la centrifugación del esputo, la tinción con auramina-rodamina ni el cultivo líquido automatizado. Resultados.Se incluyeron 152 pacientes, de los cuales 108 eran elegibles y 103 se incluyeron en el análisis. El 34 % de las muestras fueron positivas; la sensibilidad de la prueba fue de 91 %, la especificidad de 92 %, el valor diagnóstico positivo de 83 % y el valor diagnóstico negativo global de 96 %. En las muestras negativas con Ziehl Neelsen, la sensibilidad fue de 87 %, la especificidad de 91 % y los valores diagnósticos positivo y negativo alcanzaron 68 y 97 %, respectivamente. Los resultados de sensibilidad o resistencia a la rifampicina concordaron con los de la prueba fenotípica de sensibilidad (valor de kappa=1, p<0,0001. Conclusiones. El rendimiento global de la prueba fue similar al obtenido bajo condiciones “ideales”. En las muestras negativas con Ziehl Neelsen se obtuvo un mejor rendimiento en las condiciones “reales” de trabajo de un país de bajos ingresos

  14. Direct Application of the INNO-LiPA Rif.TB Line-Probe Assay for Rapid Identification of Mycobacterium tuberculosis Complex Strains and Detection of Rifampin Resistance in 360 Smear-Positive Respiratory Specimens from an Area of High Incidence of Multidrug-Resistant Tuberculosis

    Science.gov (United States)

    Viveiros, Miguel; Leandro, Clara; Rodrigues, Liliana; Almeida, Josefina; Bettencourt, Rosário; Couto, Isabel; Carrilho, Lurdes; Diogo, José; Fonseca, Ana; Lito, Luís; Lopes, João; Pacheco, Teresa; Pessanha, Mariana; Quirim, Judite; Sancho, Luísa; Salfinger, Max; Amaral, Leonard

    2005-01-01

    The INNO-LiPA Rif.TB assay for the identification of Mycobacterium tuberculosis complex strains and the detection of rifampin (RIF) resistance has been evaluated with 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis (MDR-TB). The sensitivity when compared to conventional identification/culture methods was 82.2%, and the specificity was 66.7%; the sensitivity and specificity were 100.0% and 96.9%, respectively, for the detection of RIF resistance. This assay has the potential to provide rapid information that is essential for the effective management of MDR-TB. PMID:16145166

  15. La práctica internacional de las disculpas de estado: España, Marruecos y el Rif en el centenario del protectorado (1912-2012

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    Pablo La Porte

    2012-01-01

    Full Text Available The last two decades have seen a proliferation of state apologies whereby a number of states have acknowledged previous wrongs against other states and apologized for historical injustices committed against domestic minorities. This article examines demands for apologies related to the use of chemical warfare by the Spanish army during the Rif War (Morocco, 1921-1926. The article explores the limits and constraints of the so-called "apologetic diplomacy" and its influence in bilateral relations between Spain and Morocco. It argues that demands for apologies present Spain a problem and also an opportunity to improve relations with Morocco in the centenary of the Treaty of Protectorate (1912-2012.

  16. Detecting early response to cyclophosphamide treatment of RIF-1 tumors using selective multiple quantum spectroscopy (SelMQC) and dynamic contrast enhanced imaging.

    Science.gov (United States)

    Poptani, Harish; Bansal, Navin; Graham, Robert A; Mancuso, Anthony; Nelson, David S; Glickson, Jerry D

    2003-04-01

    The purpose of this study was to develop a reliable, noninvasive method for early detection of tumor response to therapy that would facilitate optimization of treatment regimens to the needs of the individual patient. In the present study, the effects of cyclophosphamide (Cp, a widely used alkylating agent) were monitored in a murine radiation induced fibrosarcoma (RIF-1) using in vivo (1)H NMR spectroscopy and imaging to evaluate the potential of these techniques towards early detection of treatment response. Steady-state lactate levels and Gd-DTPA uptake kinetics were measured using selective multiple quantum coherence (Sel-MQC) transfer spectroscopy and dynamic contrast enhanced imaging, respectively in RIF-1 tumors before, 24 and 72 h after 300 mg/kg of Cp administration. High-resolution (1)H NMR spectra of perchloric acid extracts of the tumor were correlated with lactate and glucose concentrations determined enzymatically. In vivo NMR experiments showed a decrease in steady-state lactate to water ratios (5.4 +/- 1.6 to 0.6 +/- 0.5, p < 0.05) and an increase in Gd-DTPA uptake kinetics following treatment response. The data indicate that decreases in lactate result from decreased glycolytic metabolism and an increase in tumor perfusion/permeability. Perchloric acid extracts confirmed the lower lactate levels seen in vivo in treated tumors and also indicated a higher glycerophosphocholine/phosphocholine (GPC/PC) integrated intensity ratio (1.39 +/- 0.09 vs 0.97 +/- 0.04, p < 0.01), indicative of increased membrane degradation following Cp treatment. Steady-state lactate levels provide metabolic information that correlates with changes in tumor physiology measured by Gd-DTPA uptake kinetics with high spatial and temporal resolution. Both of these parameters may be useful for monitoring early tumor response to therapy. Copyright 2003 John Wiley & Sons, Ltd.

  17. From the Atlas to the Rif a Crustal seismic image across Morocco: The SIMA & RIFSEIS control source wide-angle seismic reflection data

    Science.gov (United States)

    Carbonell, Ramon; Ayarza, Puy; Gallart, Josep; Diaz, Jordi; Harnafi, Mimoun; Levander, Alan; Teixell, Antonio

    2014-05-01

    The velocity structure of the crust and the geometry of the Moho across Morocco has been the main target of two recently acquired wide-angle seismic reflection transects. One is the SIMA experiment which provided seismic constraints beneath the Atlas Mountains and the second has been the RIFSEIS experiment which sampled the RIF orogen. Jointly these controlled source wide-angle seismic reflection data results in an almost 700 km, seismic profile going from the the Sahara craton across the High and Middle Atlas and Rif Mountain till the Gibraltar-Arc (Alboran). Current work on the interpretation of the seismic data-set is based on forward modeling, ray-tracing, as well as low fold wide-angle stacking. The data has resulted in a detailed crustal structure and velocity model for the Atlas Mountains and a 700 km transect revealing the irregular topography of the Moho beneath these two mountain orogens. Results indicate that the High Atlas features a moderate crustal thickness and that shortening is resolved at depth through a crustal root where the Saharan crust under-thrusts below the Moroccan crust, defining a lower crust imbrication which locally places the Moho boundary at, approximately, 40 km depth. The P-wave velocity model is characterized, in averaged, by relatively low velocities. These low deep crustal velocities together with other geophysical observables such as: conductivity estimates derived from Mt measurements; moderate Bouguer gravity anomaly; surface exposures of recent alkaline volcanics; lead the interpretation to propose that partial melts are currently emplaced in the deep crustal levels and in the upper mantle. The Moho discontinuity defines a crust which is in average relatively thin beneath the Atlas which is almost a 4000 m high orogenic belt. The resulting model supports existence of mantle upwelling as a possible mechanism that contributes, significantly, to maintain the High Atlas topography.

  18. Leishmaniose canine dans le Rif (côte méditerranéenne marocaine : enquête séro-épidémiologique

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    Rami M.

    2003-03-01

    Full Text Available Dans le but d'évaluer la situation de la leishmaniose canine dans le foyer situé dans le versant Nord-Est de la chaîne montagneuse du Rif, une enquête séro-épidémiologique a été menée dans différentes localités de la province de Nador (côte méditerranéenne marocaine. Des échantillons de sérum collectés sur 257 chiens ont été analysés par les techniques d'immunofluorescence indirecte (IFI et d'enzyme-linked immunosorbent assay (ELISA pour détecter les anticorps anti-Leishmania infantum. Les résultats montrent que 48 (18,7 % des chiens examinés sont positifs en IFI et 54 (21,0 % le sont en ELISA ; la concordance des deux méthodes étant de 96,1 %. D'autre part, le taux d'infection est significativemenl plus élevé chez les chiens âgés de plus de quatre ans et ne dépend pas du sexe de l'animal. Les symptômes les plus fréquemment relevés sur les chiens séropositifs sont la polyadénite (57,4 %, l'amyotrophie (51,9 % et les lésions cutanéo-muqueuses ( 25,9 %. Cependant, 38,9 % de ces mêmes chiens ne présentent pas de symptômes pouvant évoquer la leishmaniose. Des Leishmania isolées sur trois des chiens examinés ont toutes été identifiées comme étant L. infantum MON-1. Ces résultats montrent que le versant Nord-Est des montagnes du Rif est l'un des foyers les plus actifs de leishmaniose viscérale dans le pourtour méditerranéen et confirment le rôle que joue le chien comme principal réservoir de L. infantum.

  19. New constraints on the evolution of the Gibraltar Arc from palaeomagnetic data of the Ceuta and Beni Bousera peridotites (Rif, northern Africa)

    Science.gov (United States)

    Berndt, Thomas; Ruiz-Martínez, Vicente Carlos; Chalouan, Ahmed

    2015-03-01

    The Betic Cordillera and the Moroccan Rif together form one of the smallest and tightest orogenic arcs on Earth and almost completely close the Mediterranean to the west. For the explanation of the geodynamic evolution of the mountain belt, palaeomagnetic data that generally found clockwise block rotations in the Iberian and anticlockwise rotations in the Moroccan part of the mountain belt, have played a key role in recent works. This palaeomagnetic study has found new constraints on the rotations and timing of the peridotitic bodies outcropping in the key position at the westernmost margin of the mountain belt, in Ceuta and Beni Bousera (Rif, northern Africa). Detailed thermal demagnetization of 115 individually oriented samples from 14 sites was combined with rock magnetic and scanning electron microscopic experiments to analyze the magnetic mineralogy responsible for the remanences and the mechanisms and relative times of their acquisition. In Ceuta, up to three magnetic components, and in Beni Bousera, up to two magnetic components have been found, that are all to be interpreted as chemical remanent magnetizations (CRM). The data suggests the following succession of geodynamic events affecting the peridotites until recent times: (1) after their exhumation and subsequent cooling about 20 Ma ago, they recorded a characteristic remanent magnetization of both normal and reversed polarities, carried by (pseudo-)single-domain magnetite grains; (2) after their dismembering, the Ceuta peridotites were tilted southward by 22-34° about a horizontal or tilted axis (up to plunge 50°) with an azimuth of 72-145° and the Beni Bousera peridotites were rotated anticlockwise by 72.3 ± 12.1° about a vertical axis and (3) both recorded another magnetic signal of normal polarity only, carried by multi-domain magnetite grains; and finally (4) the Ceuta peridotites rotated anticlockwise by 19.7 ± 5.9° about a vertical axis. This study provides the first palaeomagnetic data for

  20. The Al Hoceima earthquake sequence of 1994, 2004 and 2016: Stress transfer and poroelasticity in the Rif and Alboran Sea region

    Science.gov (United States)

    Kariche, J.; Meghraoui, M.; Timoulali, Y.; Cetin, E.; Toussaint, R.

    2018-01-01

    The 2016 January 25 earthquake (Mw 6.3) follows in sequence from the1994 May 26 earthquake (Mw 6.0) and the 2004 February 24 earthquake (Mw 6.4) in the Rif Mountains and Alboran Sea. The earlier two seismic events which were destructive took place on inland conjugate faults, and the third event occurred on an offshore fault. These earthquake sequences occurred within a period of 22 yr at ˜25 km distance and 11-16-km depth. The three events have similar strike-slip focal mechanism solutions with NNE-SSW trending left-lateral faulting for the 1994 and 2016 events and NW-SE trending right-lateral faulting for the 2004 event. This shallow seismic sequence offers the possibility (i) to model the change in Coulomb Failure Function (ΔCFF with low μ΄ including the pore pressure change) and understand fault-rupture interaction, and (ii) to analyse the effect of pore fluid on the rupture mechanism, and infer the clock-time advance. The variation of static stress change has a direct impact on the main shock, aftershocks and related positive lobes of the 2004 earthquake rupture with a stress change increase of 0.7-1.1 bar. Similarly, the 2004 main shock and aftershocks indicate loading zones with a stress change (>0.25 bar) that includes the 2016 earthquake rupture. The tectonic loading of 19-24 nanostrain yr-1 obtained from the seismicity catalogue of Morocco is comparable to the 5.0 × 1017 N.m yr-1 seismic strain release in the Rif Mountains. The seismic sequence is apparently controlled by the poroelastic properties of the seismogenic layer that depend on the undrained and drained fluid conditions. The short interseismic period between main shocks and higher rate of aftershocks with relatively large magnitudes (4 stress-rate ranges between 461 and 582 Pa yr-1 with a ΔCFF of 0.2-1.1 bar. The computed clock-time advance reaches 239 ± 22 yr in agreement with the ˜10 yr delay between main shocks. The calculated static stress change of 0.9-1.3 bar, under pore

  1. Effect of treatment in fractionated schedules with the combination of x-irradiation and six cytotoxic drugs on the RIF-1 tumor and normal mouse skin

    International Nuclear Information System (INIS)

    Lelieveld, P.; Scoles, M.A.; Brown, J.M.; Phil, D.; Kallman, R.F.

    1985-01-01

    RIF-1 tumors, implanted syngeneically in the gastrocnemius muscles of the right hind legs of C3H/Km mice, were treated either with X ray alone, drug alone, or drug and X ray combined. The drugs tested were bleomycin, BCNU, cis-diamminedichloro platinum, adriamycin, cyclophosphamide, and actinomycin-D. All drugs were administered either in the maximum tolerated dose or a dose that causes minimal tumor growth delay. Both drugs and X rays were administered either as a single dose or in five daily fractions. In addition to the single modality controls, seven different schedules of combined modalities were tested. Tumors were measured periodically after treatment in order that the day at which each tumor reached 4 times its initial cross-sectional area, i.e., its size at the time of treatment, could be determined. The effect of treatment on tumors was based upon excess growth delay (GD), i.e., T400% (treated)-T400% (untreated control). Treatment effects for the same combined modality schedules were also determined for normal skin, using the early skin reaction as an endpoint. Dose effect factors (DEF) were computed for all combined modality schedules and were based upon calculated radiation dose equivalents. We also calculated supra-additivity ratios, SR/sub I/ and SR/sub II/, therapeutic gain factors and adjusted therapeutic gain factors. The only drugs to produce significant supra-additivity with X rays were cis-Pt and cyclo

  2. Xpert(®) MTB/RIF for improved case detection of extra-pulmonary TB in a tertiary care setting in urban India.

    Science.gov (United States)

    Nataraj, G; Kanade, S; Mehta, P

    2016-07-01

    Department of microbiology at a tertiary care hospital, Mumbai, India. To determine 1) the sensitivity and specificity of the Xpert(®) MTB/RIF assay in comparison with microscopy and culture in extra-pulmonary tuberculosis (EPTB), and 2) the number of additional cases of EPTB and rifampicin (RMP) resistance detected using this assay. The study was conducted from July 2013 to April 2015. All consecutive patients with clinically suspected EPTB referred for microscopic examination to the Department of Microbiology that were sufficient in specimen volume were included in the study. Of the 728 specimens included in the study, respectively 5.5%, 23.5% and 20.9% were positive on smear, culture and Xpert. Compared to culture, Xpert had a sensitivity of 84.2% (95%CI 81.4-86.6) and specificity of 98.2% (95%CI 90-104). All specimens with high and medium load on assay were positive on culture; 28 (18.4%) specimens were RMP-resistant and 124 (81.6%) were Xpert-susceptible. No additional RMP-resistant cases were detected using Xpert as compared to phenotypic drug susceptibility testing. The ability of the Xpert assay to rapidly detect a significantly greater number of bacteriologically confirmed EPTB cases, including RMP-resistant cases, makes it an important diagnostic tool in a TB-endemic country.

  3. Spatial correlation between the predictor variables and the weighting values calculated during the mapping of the environmental factors of mass movements in the Beni Idder region (northern Rif

    Directory of Open Access Journals (Sweden)

    Ait Brahim L.

    2018-01-01

    Full Text Available The Tleta of Beni Ider region located in the SW of Tetouan (Rif Septentrional knows many mass instabilities. The diagnostic via the inventory, the mapping and the characterization of mass movements was made by using satellite imagery, aerial photography and field data coupled with existing documents (geological, geomorphological,…. The understanding of both their spatial distribution and the mechanism generating them, is very complex because of the existence of an important number of natural factors (geological, geomorphological, hydrological in a relative mountainous landscape with deep valleys, steep slopes and significant elevation changes. Thus, a multidisciplinary approach was adopted to elaborate the landslide susceptibility map of the region taking into account interactions and causal relationships between the various natural parameters that tend to accentuate and aggravate the setting of landslides. The multidisciplinary database allowed us to evaluate the susceptibility thanks to a bivariate probabiliste model (Weight of Evidence. The obtained landslide susceptibility map is a major contribution to the development of urban development plans in the region.

  4. Investigation of OMNIgene·SPUTUM performance in delayed tuberculosis testing by smear, culture, and Xpert MTB/RIF assays in Uganda

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    C.D. Kelly-Cirino

    2017-06-01

    Full Text Available OMNIgene·SPUTUM (OM-S is a sample transport reagent designed to work with all tuberculosis diagnostics while eliminating the need for cold chain. OM-S-treated sputum samples were assayed in several tests after multiday holds. Raw sputa from 100 patients underwent direct smear microscopy, were manually split and assigned to the OM-S group [OM-S added at collection (no other processing required and tested after 0- to 5-day holds at room temperature] or standard-of-care (SOC group (NaOH/N-acetyl l-cysteine decontamination, all tested on day of collection. Concentrated smear microscopy, Lowenstein Jensen (LJ culture, and mycobacteria growth indicator tube (MGIT culture were performed. For patients with negative direct smear, a second sample was split, with SOC (raw sputum and OM-S portions (sediment tested in the Xpert MTB/RIF (Xpert assay. OM-S group and SOC group results were strongly concordant on all four tests [range, 89% (MGIT–97% (Xpert]. OM-S MGIT, LJ, and Xpert tests were in statistical agreement with SOC MGIT as reference. OM-S specimens had lower culture contamination rates (3% vs. 10% LJ; 2% vs. 5% MGIT but required, on average, 5.6 additional days to become MGIT-positive. The findings suggest that samples held/transported in OM-S are compatible with smear microscopy, LJ or MGIT culture, and Xpert, and perform comparably to fresh sputum samples. Larger feasibility studies are warranted.

  5. Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture Conversion and Bacteriological Cure in Pulmonary TB.

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    Shubhada Shenai

    Full Text Available Biomarkers are needed to monitor tuberculosis (TB treatment and predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert assay as a biomarker for TB treatment during and at the end of the 24 weeks therapy.Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was analyzed using Xpert at time points before and during anti-TB therapy. Results were compared against culture. Direct Xpert cycle-threshold (Ct, a change in the Ct (delta Ct, or a novel "percent closing of baseline Ct deficit" (percent closing were evaluated as classifiers of same-day and end-of-treatment culture and therapeutic outcomes.Xpert was positive in 29/95 (30.5% of subjects at week 24; and positive one year after treatment in 8/64 (12.5% successfully-treated patients who remained free of tuberculosis. We identified a relationship between initial bacterial load measured by baseline Xpert Ct and time to culture conversion (hazard ratio 1.06, p = 0.0023, and to the likelihood of being among the 8 treatment failures at week 24 (AUC = 72.8%. Xpert Ct was even more strongly associated with culture conversion on the day the test was performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24, respectively. Compared to baseline Ct measures alone, a combined measure of baseline Ct plus either Delta Ct or percent closing improved the classification of treatment failure status to a 75% sensitivity and 88.9% specificity.Genome loads measured by Xpert provide a potentially-useful biomarker for classifying same day culture status and predicting response to therapy.

  6. Impact of GeneXpert MTB/RIF assay on triage of respiratory isolation rooms for inpatients with presumed tuberculosis: a hypothetical trial.

    Science.gov (United States)

    Chaisson, Lelia H; Roemer, Marguerite; Cantu, David; Haller, Barbara; Millman, Alexander J; Cattamanchi, Adithya; Davis, J Lucian

    2014-11-15

    Placing inpatients with presumed active pulmonary tuberculosis in respiratory isolation pending results of serial sputum acid-fast bacilli (AFB) smear microscopy is standard practice in high-income countries. However, this diagnostic strategy is slow and yields few tuberculosis diagnoses. We sought to determine if replacing microscopy with the GeneXpert MTB/RIF (Xpert) nucleic acid amplification assay could reduce testing time and usage of isolation rooms. We prospectively followed inpatients at San Francisco General Hospital undergoing tuberculosis evaluation. We performed smear microscopy and Xpert testing on concentrated sputum, and calculated diagnostic accuracy for both strategies in reference to serial sputum mycobacterial culture. We measured turnaround time for microscopy and estimated hypothetical turnaround times for Xpert on concentrated and unconcentrated sputum. We compared median and total isolation times for microscopy to those estimated for the 2 Xpert strategies. Among 139 patients with 142 admissions, median age was 54 years (interquartile range [IQR], 43-60 years); 32 (23%) patients were female, and 42 (30%) were HIV seropositive. Serial sputum smear microscopy and a single concentrated sputum Xpert had identical sensitivity (89%; 95% confidence interval [CI], 52%-100%) and similar specificity (99% [95% CI, 96%-100%] vs 100% [95% CI, 97%-100%]). A single concentrated sputum Xpert could have saved a median of 35 hours (IQR, 24-36 hours) in unnecessary isolation compared with microscopy, and a single unconcentrated sputum Xpert, 45 hours (IQR, 35-46 hours). Replacing serial sputum smear microscopy with a single sputum Xpert could eliminate most unnecessary isolation for inpatients with presumed tuberculosis, greatly benefiting patients and hospitals. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. A random set scoring model for prioritization of disease candidate genes using protein complexes and data-mining of GeneRIF, OMIM and PubMed records.

    Science.gov (United States)

    Jiang, Li; Edwards, Stefan M; Thomsen, Bo; Workman, Christopher T; Guldbrandtsen, Bernt; Sørensen, Peter

    2014-09-24

    Prioritizing genetic variants is a challenge because disease susceptibility loci are often located in genes of unknown function or the relationship with the corresponding phenotype is unclear. A global data-mining exercise on the biomedical literature can establish the phenotypic profile of genes with respect to their connection to disease phenotypes. The importance of protein-protein interaction networks in the genetic heterogeneity of common diseases or complex traits is becoming increasingly recognized. Thus, the development of a network-based approach combined with phenotypic profiling would be useful for disease gene prioritization. We developed a random-set scoring model and implemented it to quantify phenotype relevance in a network-based disease gene-prioritization approach. We validated our approach based on different gene phenotypic profiles, which were generated from PubMed abstracts, OMIM, and GeneRIF records. We also investigated the validity of several vocabulary filters and different likelihood thresholds for predicted protein-protein interactions in terms of their effect on the network-based gene-prioritization approach, which relies on text-mining of the phenotype data. Our method demonstrated good precision and sensitivity compared with those of two alternative complex-based prioritization approaches. We then conducted a global ranking of all human genes according to their relevance to a range of human diseases. The resulting accurate ranking of known causal genes supported the reliability of our approach. Moreover, these data suggest many promising novel candidate genes for human disorders that have a complex mode of inheritance. We have implemented and validated a network-based approach to prioritize genes for human diseases based on their phenotypic profile. We have devised a powerful and transparent tool to identify and rank candidate genes. Our global gene prioritization provides a unique resource for the biological interpretation of data

  8. Survival response of RIF tumor cells to heat-x-radiation combinations: Parallel measurements in culture and by the excision assay

    International Nuclear Information System (INIS)

    Henle, K.J.; Nagle, W.A.; Moss, A.J.

    1984-01-01

    The cytotoxicity of heat-radiation (hX) combinations in vivo may differ from that measured in vitro. The authors have used the RIF tumor, grown in mouse feet, to compare the survival response after in situ hX-treatments with identical hX in vitro. The radiation survival curve, determined by the excision assay showed a slightly larger D/sub o/ than that measured in vitro (250, 200 rad, respective) and survival measurements appeared independent of excision time after irradiation. The 45 0 -heat survival curve was similar in both assays, but only when the excision followed immediately after h. A 24-hr delayed excision removed the shoulder and lowered survival 30-fold after either 20 or 30 min, 45 0 . Similar survival values were measured after 10 min, 45 0 +X (hX) in vitro and with immediate excision, although the excision survival curve had no shoulder and a D/sub o/ of 180 rad vs. 120 rad in vitro. The survival curve with delayed excision (24 hr) also appeared as a simple exponential curve with an apparent D/sub o/ of 310 rad (n=0.02). Two fractions of combined hX, separated by 24 hr (hx+24+hX), yielded D/sub o/=90 rad, D/sub q/=230 rad in vitro but 370 and 400 rad, respectively, when measured by delayed excision. The apparent radioresistance in vivo is consistent with data by Song of increased hypoxic fractions after heating in vivo and argues against combining hx in every fraction for optimal tumor control

  9. Extending 'Contact Tracing' into the Community within a 50-Metre Radius of an Index Tuberculosis Patient Using Xpert MTB/RIF in Urban, Pakistan: Did It Increase Case Detection?

    Directory of Open Access Journals (Sweden)

    Razia Fatima

    Full Text Available Currently, only 62% of incident tuberculosis (TB cases are reported to the national programme in Pakistan. Several innovative interventions are being recommended to detect the remaining 'missed' TB cases. One such intervention involved expanding contact investigation to the community using the Xpert MTB/RIF test.This was a before and after intervention study involving retrospective record review. Passive case finding and household contact investigation was routinely done in the pre-intervention period July 2011-June 2013. Four districts with a high concentration of slums were selected as intervention areas; Lahore, Rawalpindi, Faisalabad and Islamabad. Here, in the intervention period, July 2013-June 2015, contact investigation beyond household was conducted: all people staying within a radius of 50 metres (using Geographical Information System from the household of smear positive TB patients were screened for tuberculosis. Those with presumptive TB were investigated using smear microscopy and the Xpert MTB/RIF test was performed on smear negative patients. All the diagnosed TB patients were linked to TB treatment and care.A total of 783043 contacts were screened for tuberculosis: 23741(3.0% presumptive TB patients were identified of whom, 4710 (19.8% all forms and 4084(17.2% bacteriologically confirmed TB patients were detected. The contribution of Xpert MTB/RIF to bacteriologically confirmed TB patients was 7.6%. The yield among investigated presumptive child TB patients was 5.1%. The overall yield of all forms TB patients among investigated was 22.3% among household and 19.1% in close community. The intervention contributed an increase of case detection of bacteriologically confirmed tuberculosis by 6.8% and all forms TB patients by 7.9%.Community contact investigation beyond household not only detected additional TB patients but also increased TB case detection. However, further long term assessments and cost-effectiveness studies are

  10. The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C polymorphisms in reproductive failures: Experience from an RSA and RIF study on a Polish population.

    Science.gov (United States)

    Nowak, Izabela; Bylińska, Aleksandra; Wilczyńska, Karolina; Wiśniewski, Andrzej; Malinowski, Andrzej; Wilczyński, Jacek R; Radwan, Paweł; Radwan, Michał; Barcz, Ewa; Płoski, Rafał; Motak-Pochrzęst, Hanna; Banasik, Małgorzata; Sobczyński, Maciej; Kuśnierczyk, Piotr

    2017-01-01

    Almost 1600 individuals from the Polish population were recruited to this study. Among them 319 were fertile couples, 289 were recurrent spontaneous abortion (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF) following in vitro fertilization. The aim of this study was to evaluate the MTHFR c.c.677 C>T and c.c.1298 A>C polymorphisms' association with RSA and RIF. We used PCR-RFLP with HinfI (677 C>T) and MboII (1298 A>C) digestion. We observed a protective effect of the female AC genotype (OR = 0.64, p = 0.01) and the C allele (AC+CC genotypes; OR = 0.65, p = 0.009) against RSA. Moreover, 1298 AA/677 CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison to fertile women (22.88%), although this difference was significant only in the case of RSA (p = 0.022, OR = 1.52). Male combined genotype analysis revealed no association with reproductive failure of their partners. Nevertheless, the female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA couples (p = 0.049, OR = 1.49). However, the significant results became insignificant after Bonferroni correction. In addition, analysis of haplotypes showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the female control group than in the female RSA group (p = 0.03, OR = 0.77). Moreover, the association between elevated homocysteine (Hcy) level in plasma of RSA and RIF women and MTHFR polymorphisms was investigated but did not reveal significant differences. In conclusion, for clinical practice, it is better to check the homocysteine level in plasma and, if the Hcy level is increased, to recommend patients to take folic acid supplements rather than undergo screening of MTHFR for 1298 A>C and 677 C>T polymorphisms.

  11. The diagnostic performance of a single GeneXpert MTB/RIF assay in an intensified tuberculosis case finding survey among HIV-infected prisoners in Malaysia.

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    Haider Abdulrazzaq Abed Al-Darraji

    Full Text Available Delays in tuberculosis (TB diagnosis, particularly in prisons, is associated with detrimental outcomes. The new GeneXpert MTB/RIF assay (Xpert offers accurate and rapid diagnosis of active TB, but its performance in improving case detection in high-transmission congregate settings has yet to be evaluated. We assessed the diagnostic accuracy of a single Xpert assay in an intensified case finding survey among HIV-infected prisoners in Malaysia.HIV-infected prisoners at a single site provided two early-morning sputum specimens to be examined using fluorescence smear microscopy, BACTEC MGIT 960 liquid culture and a single Xpert. The sensitivity, specificity, negative and positive predictive values of Xpert were calculated relative to gold-standard results using MGIT 960 liquid culture. Relevant clinical and demographic data were used to examine correlates of active TB disease.The majority of enrolled subjects with complete data (N=125 were men (90.4%, age <40 years (61.6% and had injected drugs (75.2%. Median CD4 lymphocyte count was 337 cells/µL (IQR 149-492; only 19 (15.2% were receiving antiretroviral therapy. Of 15 culture-positive TB cases, single Xpert assay accurately detected only eight previously undiagnosed TB cases, resulting in a sensitivity, specificity, positive predictive value and negative predictive value of 53.3% (95% CI 30.12-75.2%, 100% (95% CI 96.6-100%, 100% (95% CI 67.56-100% and 94.0% (95% CI 88.2-97.1%, respectively. Only 1 of 15 (6.7% active TB cases was smear-positive. The prevalence (12% of undiagnosed active pulmonary TB (15 of 125 prisoners was high and associated with longer duration of drug use (AOR 1.14, 95% CI 1.03-1.26, for each year of drug use.Single Xpert assay improved TB case detection and outperformed AFB smear microscopy, but yielded low screening sensitivity. Further examination of the impact of HIV infection on the diagnostic performance of the new assay alongside other screening methods in correctional

  12. The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model

    Science.gov (United States)

    Salje, Henrik; Andrews, Jason R.; Deo, Sarang; Satyanarayana, Srinath; Sun, Amanda Y.; Pai, Madhukar; Dowdy, David W.

    2014-01-01

    Background India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. Methods and Findings We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: −1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: −5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior

  13. Cost-effectiveness analysis of microscopic observation drug susceptibility test versus Xpert MTB/Rif test for diagnosis of pulmonary tuberculosis in HIV patients in Uganda.

    Science.gov (United States)

    Walusimbi, Simon; Kwesiga, Brendan; Rodrigues, Rashmi; Haile, Melles; de Costa, Ayesha; Bogg, Lennart; Katamba, Achilles

    2016-10-10

    Microscopic Observation Drug Susceptibility (MODS) and Xpert MTB/Rif (Xpert) are highly sensitive tests for diagnosis of pulmonary tuberculosis (PTB). This study evaluated the cost effectiveness of utilizing MODS versus Xpert for diagnosis of active pulmonary TB in HIV infected patients in Uganda. A decision analysis model comparing MODS versus Xpert for TB diagnosis was used. Costs were estimated by measuring and valuing relevant resources required to perform the MODS and Xpert tests. Diagnostic accuracy data of the tests were obtained from systematic reviews involving HIV infected patients. We calculated base values for unit costs and varied several assumptions to obtain the range estimates. Cost effectiveness was expressed as costs per TB patient diagnosed for each of the two diagnostic strategies. Base case analysis was performed using the base estimates for unit cost and diagnostic accuracy of the tests. Sensitivity analysis was performed using a range of value estimates for resources, prevalence, number of tests and diagnostic accuracy. The unit cost of MODS was US$ 6.53 versus US$ 12.41 of Xpert. Consumables accounted for 59 % (US$ 3.84 of 6.53) of the unit cost for MODS and 84 % (US$10.37 of 12.41) of the unit cost for Xpert. The cost effectiveness ratio of the algorithm using MODS was US$ 34 per TB patient diagnosed compared to US$ 71 of the algorithm using Xpert. The algorithm using MODS was more cost-effective compared to the algorithm using Xpert for a wide range of different values of accuracy, cost and TB prevalence. The cost (threshold value), where the algorithm using Xpert was optimal over the algorithm using MODS was US$ 5.92. MODS versus Xpert was more cost-effective for the diagnosis of PTB among HIV patients in our setting. Efforts to scale-up MODS therefore need to be explored. However, since other non-economic factors may still favour the use of Xpert, the current cost of the Xpert cartridge still needs to be reduced further by more than

  14. Analyse de l’interaction entre l’éclosion des feux de forêts et les types de bioclimat au Nord du Maroc – cas de la région du Rif occidental -

    Directory of Open Access Journals (Sweden)

    Hicham MHARZI ALAOUI

    2015-12-01

    Full Text Available Morocco, as a country with arid and semi-arid climate is vulnerable to climate change and presents many challenges for the future of the forest resources, mainly their vulnerability to forest fires. In addition, Moroccan forests are extremely flammable, especially in summer when the water content of plants, soil and the air become very low. This is especially noticeable in the Rif region (North of Morocco where almost 65% of the phenomenon of wildfires across the country are concentrated. To deal with this new situation, the development of a prevention plan against forest fires requires an appropriate analysis of forest fire phenomenon and its response to the climate and vegetation changes. The present study has the goal to establish a spatio-temporal analysis of fires based on bioclimatic types because of the inclusive relationship between vegetation and climate. The fires that occurred in the rif region between 1997-2011 were analyzed and classified according to the affected area during the fire episode. The analysis has shown that almost 80% of the burnt area during the year were recorded only during August and September. Thereafter, using a two-factor ANOVA showed a significant difference of the fires spatial distribution according to the bioclimatic types, mainly for the warm variant of bioclimatic type where the development of the biomass is very important.

  15. High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana

    NARCIS (Netherlands)

    Boakye-Appiah, Justice K; Steinmetz, Alexis R; Pupulampu, Peter; Ofori-Yirenkyi, Stephen; Tetteh, Ishmael; Frimpong, Michael; Oppong, Patrick; Opare-Sem, Ohene; Norman, Betty R; Stienstra, Ymkje; van der Werf, Tjip S; Wansbrough-Jones, Mark; Bonsu, Frank; Obeng-Baah, Joseph; Phillips, Richard O

    2016-01-01

    OBJECTIVE/BACKGROUND: Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays

  16. High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana

    Directory of Open Access Journals (Sweden)

    Justice K Boakye-Appiah

    2016-01-01

    Conclusion: These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting.

  17. Response of the RIF-1 tumor in vitro and in C3H/Km mice to x-radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages

    International Nuclear Information System (INIS)

    Brown, J.M.; Twentyman, P.R.; Zamvil, S.S.

    1980-01-01

    The radiation response of logarithmic growth phase and fed plateau phase RIF-1 cells in vitro was found to be characterized by D 0 values of 110 and 133 rads and extrapolation numbs of 36 and 28, respectively. The response of the tumor in vivo to X-irradiation in nonanesthetized mice showed a dependence on the tumor implantation site. In the leg muscle, the response indicated that most cells were at an intermediate level of oxygenation, whereas in the subcutaneous tissue of the flank, the response of the tumor indicated that it had a small fraction of hypoxic cells of maximum radioresistance. Misonidazole radiosensitized the leg-implanted tumor as measured both by cell survival and regrowth delay. The tumor was relatively insensitive to a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea, sensitive to a single dose of cis-platinum, and highly sensitive to a single dose of cyclophosphamide

  18. GeneXpert MTB/RIF dans le dépistage de la tuberculose pulmonaire à l’Hôpital Provincial Général de Référence de Bukavu, à l’Est de la République Démocratique du Congo: quelles leçons tirées après 10 mois d’utilisation?

    Science.gov (United States)

    Lupande, David; Kaishusha, David; Mihigo, Carine; Itongwa, Moise; Yenga, Gustave; Katchunga, Philippe

    2017-01-01

    Introduction En Afrique subsaharienne, les méthodes de diagnostic de la tuberculose sont insuffisantes et reposent essentiellement sur la microscopie. Elles constituent un réel frein pour le contrôle de la tuberculose. La présente étude voudrait évaluer les performances du GeneXpert MTB/RIF vis à vis de la microscopie classique de Ziehl-Neelsen à l’Hôpital Provincial Général de Référence de Bukavu, à l’Est de la République Démocratique du Congo après 10 mois d’utilisation. Méthodes Les résultats de la coloration au Ziehl-Neelsen et de la biologie moléculaire sur GeneXpert MTB/RIF de 452 patients suspects de tuberculose ont été colligés. La validité d’un test par rapport à l’autre dans la détection de la tuberculose a été étudiée. Résultats Dans le groupe entier, la fréquence de la tuberculose pulmonaire était de 16.3%. La positivité était significativement plus élevée pour le GeneXpert MTB/RIF que pour le Ziehl-Neelsen dans le groupe entier (15.9% vs 9.3%, p= 0.03) et chez les séropositifs pour le VIH (52.0% vs 24.0%; p = 0.007). Cependant, la sensibilité de GeneXpert MTB/RIF comparé au Ziehl-Neelsen n’était pas maximale (95.2%). Enfin, GeneXpert MTB/RIF a détecté 20.8% de résistance à la rifampicine. Conclusion La présente étude confirme la supériorité de GeneXpert MTB/RIF sur la coloration de Ziehl-Neelsen dans la détection de la tuberculose et dans la prédiction de la multi résistance. Son utilisation systématique couplée au Ziehl-Neelsen permettrait de mieux contrôler la tuberculose en Afrique subSaharienne. PMID:29187929

  19. Characterization of mutations causing rifampicin and isoniazid resistance of Mycobacterium tuberculosis in Syria.

    Science.gov (United States)

    Madania, Ammar; Habous, Maya; Zarzour, Hana; Ghoury, Ifad; Hebbo, Barea

    2012-01-01

    In order to characterize mutations causing rifampicin and isoniazid resistance of M. tuberculosis in Syria, 69 rifampicin resistant (Rif(r)) and 72 isoniazid resistant (Inh(r)) isolates were screened for point mutations in hot spots of the rpoB, katG and inhA genes by DNA sequencing and real time PCR. Of 69 Rif(r) isolates, 62 (90%) had mutations in the rifampin resistance determining region (RRDR) of the rpoB gene, with codons 531 (61%), 526 (13%), and 516 (8.7%) being the most commonly mutated. We found two new mutations (Asp516Thr and Ser531Gly) described for the first time in the rpoB-RRDR in association with rifampicin resistance. Only one mutation (Ile572Phe) was found outside the rpoB-RRDR. Of 72 Inh(r) strains, 30 (41.6%) had a mutation in katGcodon315 (with Ser315Thr being the predominant alteration), and 23 (32%) harbored the inhA(-15C-->T) mutation. While the general pattern of rpoB-RRDR and katG mutations reflected those found worldwide, the prevalence of the inhA(-15C-->T mutation was above the value found in most other countries, emphasizing the great importance of testing the inhA(-15C-->T) mutation for prediction of isoniazid resistance in Syria. Sensitivity of a rapid test using real time PCR and 3'-Minor groove binder (MGB) probes in detecting Rif(r) and Inh(r) isolates was 90% and 69.4%, respectively. This demonstrates that a small set of MGB-probes can be used in real time PCR in order to detect most mutations causing resistance to rifampicin and isoniazid.

  20. Diagnostic Yield of Bronchoalveolar Lavage Gene Xpert in Smear-Negative and Sputum-Scarce Pulmonary Tuberculosis

    International Nuclear Information System (INIS)

    Khalil, K. F.; Butt, T.

    2015-01-01

    Objective: To measure the diagnostic yield of Bronchoalveolar Lavage (BAL) gene Xpert (Xpert MTB/RIF assay), to detect Mycobacterium tuberculosis (MTB) and rifampicin resistance and compare it with that of mycobacterial cultures in a suspected case of pulmonary tuberculosis. Study Design: An analytical study. Place and Duration of Study: Department of Pulmonology, Fauji Foundation Hospital (FFH), Rawalpindi, from December 2012 to August 2013. Methodology: BAL specimens of 93 patients with suspected pulmonary tuberculosis with smear-negative or sputumscarce disease, who presented to the Department of Pulmonology, FFH, Rawalpindi were inducted. A smear-negative case was one in whom three consecutive early morning sputum samples did not reveal acid fast bacilli when examined by microscopy with Zeihl Nelson (ZN) stain. Patients who had sputum amount less than 1 ml were defined to have sputumscarce disease. The same was evaluated with ZN stain, gene Xpert and mycobacterial cultures. Sensitivity analysis was carried out using culture as the gold standard. Results: The frequency of positive mycobacterial cultures was 85 (91.4%). The sensitivity, specificity, positive predictive value and negative predictive values of BAL gene Xpert to detect Mycobacterium tuberculosis were 91.86%, 71.42%, 97.53% and 41.66% respectively. Xpert MTB/RIF assay had a sensitivity and specificity of 83.33% and 100% to detect rifampicin resistance. Conclusion: Bronchoalveolar lavage gene Xpert had a superior diagnostic yield in patients with either smear-negative or sputum-scarce pulmonary tuberculosis. Hence a positive Xpert MTB/RIF assay may be a useful adjunct to diagnosis and detection of MDR-TB in bronchoalveolar lavage specimens. (author)

  1. (Prérif Central, Maroc septentrional

    Directory of Open Access Journals (Sweden)

    Abdelghani Gartet

    2006-01-01

    Full Text Available El diapiro de sal de Tissa, situado en el Prerif central marroquí, afl ora en una zona de contacto estructural anormal donde la morfogénesis kárstica es muy activa. La solubilidad de las formaciones del complejo triásico es excesivamente fuerte. El macizo yesífero-salino representa un yacimiento de sal gema casi inagotable. Sin embargo, las aguas de Oued Lebène, en época de crecidas, socavan intensamente la base del macizo y terminan siendo afectadas por la contaminación química. La explotación de la cantera de sal, siendo tradicional, plantea numerosos problemas de planifi cación, a la vez que atenta severamente contra el medio ambiente (natural y urbano y contra la sociedad humana. Las medidas de defensa del medio ambiente adoptadas al respecto resultan por el momento insufi cientes dada la falta de una legislación práctica y rigurosa.

  2. Comparison between Radioisotopic and Non-radioisotopic Polymerase Chain Reaction-Single Strand Conformation Polymorphism (PCR-SSCP) Procedures in the Detection of Mutations at the rpoB Gene Associated with Rifampicin Resistance in Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Lee, H.; Bang, H.E.; Johnson, R.; Jordaan, A.M.; Victor, T.C. . E-mail : tv@sun.ac.za; Dar, L.; Khan, B.K.; Cho, S.N. . E-mail : raycho@yonsei.ac.kr

    2006-01-01

    Rapid and sensitive detection of mutations at the rpoB gene of Mycobacterium tuberculosis would be of great importance for proper management of tuberculosis (TB) patients and control of multi-drug resistant TB. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) using both radioisotopic and non-radioisotopic methods have been widely used for detecting such mutations. However, the silver staining method, which is the most frequently employed in PCR-SSCP, has been reported to be producing results of varying sensitivity. Radioisotope-based methods have shown greater sensitivity in detecting the rpoB mutations than the silver staining method. The primary objective of this study was therefore to compare the radioisotopic method with the silver staining method detection of mutations of rpoB gene by PCR-SSCP in the same laboratory. Purified DNAs from M. tuberculosis H37Rv were serially diluted and used for PCR amplification with and without radionuclides. The PCR products were then detected by silver staining and autoradiography methods. In addition, clinical isolates were analyzed by PCR-SSCP. The radioisotopic method showed about four-fold increase in the detection of PCR products over ethidium bromide staining in agarose gel. When compared with silver staining, the radioisotopic method gave a sensitivity of more than 10-fold in detecting PCR products and about 8-fold in PCR-SSCP. Radioisotope-based detection methods provided a clearer resolution in PCR-SSCP than the silver staining method when applied to clinical isolates of M. tuberculosis. Radioisotope-based detection method was shown to be more sensitive than non-isotope-based method in detecting PCR products and mutations at the rpoB gene of M. tuberculosis by PCR-SSCP. It may be noted that mutations in the rpoB gene as a marker have significant clinical importance because of the increasing number of MDR-TB cases in the world. It is especially relevant to MDR and Extreme Drug Resistance TB (XDR-TB) which are difficult to treat. A molecular method can supplement the control program for the rapid and sensitive detection of MDR and XDR-TB and thereby helping to stop further transmission events. (author)

  3. Activités volcaniques sous-marines à la limite Jurassique-Crétacé dans le Rif externe (Maroc). Âge et relation avec la sédimentation et la paléogéographie du sillon rifain externe

    Science.gov (United States)

    Benzaggagh, Mohamed

    2011-04-01

    Following the recent stratigraphic works carried out on the Jurassic-Cretaceous boundary in the external Rif chain (Mesorif area and Bou Haddoud nappe), numerous submarine volcanism traces have been discovered in Upper Oxfordian to Upper Berriasian deposits. These traces display various aspects: volcaniclastic complexes incorporated within Upper Berriasian marls; volcanic lavas and basalt clasts included in the breccias with clay matrix of Upper Oxfordian to Lower Berriasian age, or in brecciated Lower Tothonian calcareous beds of the Early Tithonian. These submarine volcanic activities took place in a carbonate platform environment during the Kimmeridgian to Early Tithonian interval or in a pelagic basin from Late Tithonian onwards. They caused an intense brecciation of Upper Jurassic carbonate formations and a general dismantling of marly calcareous alternations of Upper Tithonian-Lower Berriasian. Therefore, the Upper Tithonian-Lower Berriasian deposits are marked by frequent stratigraphic gaps in many outcrops of Mesorif, Prerif areas and in the Bou Haddoud nappe.

  4. Study of anti mutagenic and mutagenic effect of different chemicals on clinically isolated strains of pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Qureshi, A.M.; Durrani, F.; Janjua, M.

    1994-01-01

    This project was undertaken to study the effect of twelve different compounds to test their anti mutagenic and mutagenic activity against clinically isolated strains of Pseudomonas aeruginosa. The effect of these compounds was estimated by counting the number of rifampicin resistant colonies growing in a particular time in a compound. The results were interpreted by plotting graphs between 10g N/NO (Rif R Colonies/ ml) and time to estimate the forward mutation rat. The results revealed that acridine, Basic fuchsin, Caffeine, cycloheximide, Ethidium bromide and Histidine probably have an anti mutagenic effect, while Cysteine, folic acid, Ethyl methane, suplphonate, Manganous Chloride and N-nitrosodietylamine acted as mutagen. Ecoli was used as control through out the study. (author)

  5. Endogenous Phytohormones in Spontaneously Regenerated Centaurium erythraea Rafn. Plants Grown In Vitro

    Czech Academy of Sciences Publication Activity Database

    Trifunovic-Momcilov, M.; Motyka, Václav; Dragicevic, I.C.; Petric, M.; Jevremovic, S.; Malbeck, Jiří; Holík, Josef; Dobrev, Petre; Subotic, A.

    2016-01-01

    Roč. 35, č. 2 (2016), s. 543-552 ISSN 0721-7595 R&D Projects: GA ČR(CZ) GAP506/11/0774 Institutional support: RVO:61389030 Keywords : Common centaury * Root explants * Hormone metabolism Subject RIV: EF - Botanics Impact factor: 2.073, year: 2016

  6. Identification of Two Novel Anti-Fibrotic Benzopyran Compounds Produced by Engineered Strains Derived from Streptomyces xiamenensis M1-94P that Originated from Deep-Sea Sediments

    Directory of Open Access Journals (Sweden)

    Lei Feng

    2013-10-01

    Full Text Available The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif, and a mutated rpsL gene to confer streptomycin resistance (Str, was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1 and D (2, were isolated from the crude extracts of a selected Str-Rif double mutant (M6 of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26, and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds.

  7. [Comparison of two different real-time PCR systems in postmortem diagnosis of tuberculosis in paraffin-embedded tissues].

    Science.gov (United States)

    Yağmur, Gülhan; Albayrak, Nurhan; Daş, Taner; Yıldırım, Muzaffer; Ozgün, Ayşe; Büyük, Yalçın

    2014-10-01

    Xpert MTB/RIF system, 15 were found rifampicin-susceptible, and three were rifampicin-resistant. In two samples in which M. tuberculosis DNA was low positive, rifampicin resistance could not be detected. The identification of M.tuberculosis infections in postmortem cases will contribute epidemiological data in Turkey. In these cases, effective sampling and diagnosing of M.tuberculosis infections by acid-fast stain and culture methods are crucial. However, in cases without microbiological sampling the detection of M.tuberculosis DNA in paraffin-embedded tissues with PCR, although there are differences between PCR systems has diagnostic value. In conclusion, our data indicated that Xpert MTB/RIF system is more favourable to detect M.tuberculosis DNA in paraffin-embedded tissues, with the advantages of determination of rifampicin resistance, and detection of more positive results within a shorter time.

  8. Bacillus subtilis and Enterobacter cloacae endophytes from healthy Theobroma cacao L. trees can systemically colonize seedlings and promote growth.

    Science.gov (United States)

    Leite, Hianna Almeida Câmara; Silva, Anderson Barbosa; Gomes, Fábio Pinto; Gramacho, Karina Peres; Faria, José Cláudio; de Souza, Jorge Teodoro; Loguercio, Leandro Lopes

    2013-03-01

    Clonal genotypes resistant to fungal diseases are an important component of the cocoa production system in southeastern Bahia state (Brazil), so that technologies for faster production of stronger and healthier plantlets are highly desirable. In this study, the effects of inoculated bacterial endophytes isolated from healthy adult cacao plants on seedlings, and aspects related to inoculation methods, colonization patterns, and photosynthesis were investigated. Sequencing of 16S rRNA, hsp-60, and rpo-B genes placed the wild-type isolates within the species Enterobacter cloacae (isolates 341 and 344) and Bacillus subtilis (isolate 629). Spontaneous rifampicin-resistant (rif(R)) variants for 344 were also produced and tested. Endophytic application was either by immersion of surface sterilized seeds in bacterial suspensions or direct inoculation into soil, 20 days after planting non-inoculated seeds into pots. Results from in vitro recovery of inoculated isolates showed that the wild-type endophytes and rif(R) variants systemically colonized the entire cacao seedlings in 15-20 days, regardless of the inoculation method. Some endophytic treatments showed significant increases in seedlings' height, number of leaves, and dry matter. Inoculation methods affected the combined application of endophytes, which maintained the growth-promotion effects, but not in the same manner as in single applications. Interestingly, the 344-3.2 rif(R) variant showed improved performance in relation to both the wild type and another related variant. Photosynthetic rates and stomatal conductance increased significantly for some endophytic treatments, being partially associated with effects on growth and affected by the inoculation method. The results suggest that E. cloacae and B. subtilis endophytes from healthy adult plants (not transmitted by seeds) were able to promote vegetative growth on cacao seedlings. The development of products for large-scale use in seedlings

  9. RESEARCH Diagnosing Xpert MTB/RIF-negative TB: Impact and ...

    African Journals Online (AJOL)

    Health Economics and Epidemiology Research O ce, Department of Internal ... have a positive culture result, accounting for only 10% of all TB ... information and patient follow-up systems, results may only reach ..... Raviglione M, Zumla A, Marais B, Horton R, Motsoaledi A. A sustainable agenda for tuberculosis control.

  10. Xpert MTB/RIF assay for the diagnosis of Mycobacterium ...

    African Journals Online (AJOL)

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    attention and most likely they have accustomed to visit nearby and relatively ... be reasons for the discrepancies in Xpert test results. In this study ... This might be the possible reason that .... Drug-Resistant Tuberculosis Patients in Indonesia:.

  11. Nonprenylated Xanthones from Gentiana lutea, Frasera caroliniensis, and Centaurium erythraea as Novel Inhibitors of Vascular Smooth Muscle Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Birgit Waltenberger

    2015-11-01

    Full Text Available Aberrant proliferation of vascular smooth muscle cells (VSMC plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of novel VSMC proliferation inhibitors. A natural product screening approach using a resazurin conversion assay enabled the identification of gentisin (1 from Gentiana lutea as a novel inhibitor of VSMC proliferation with an IC50 value of 7.84 µM. Aiming to identify further anti-proliferative compounds, 13 additional nonprenylated xanthones, isolated from different plant species, were also tested. While some compounds showed no or moderate activity at 30 µM, 1-hydroxy-2,3,4,5-tetramethoxyxanthone (4, swerchirin (6, and methylswertianin (7 showed IC50 values between 10.2 and 12.5 µM. The anti-proliferative effect of 1, 4, 6, and 7 was confirmed by the quantification of DNA synthesis (BrdU incorporation in VSMC. Cell death quantification (determined by LDH release in the culture medium revealed that the compounds are not cytotoxic in the investigated concentration range. In conclusion, nonprenylated xanthones are identified as novel, non-toxic VSMC proliferation inhibitors, which might contribute to the development of new therapeutic applications to combat restenosis.

  12. Nonprenylated Xanthones from Gentiana lutea, Frasera caroliniensis, and Centaurium erythraea as Novel Inhibitors of Vascular Smooth Muscle Cell Proliferation.

    Science.gov (United States)

    Waltenberger, Birgit; Liu, Rongxia; Atanasov, Atanas G; Schwaiger, Stefan; Heiss, Elke H; Dirsch, Verena M; Stuppner, Hermann

    2015-11-13

    Aberrant proliferation of vascular smooth muscle cells (VSMC) plays a major role in restenosis, the pathological renarrowing of the blood vessel lumen after surgical treatment of stenosis. Since available anti-proliferative pharmaceuticals produce unfavorable side effects, there is high demand for the identification of novel VSMC proliferation inhibitors. A natural product screening approach using a resazurin conversion assay enabled the identification of gentisin (1) from Gentiana lutea as a novel inhibitor of VSMC proliferation with an IC50 value of 7.84 µM. Aiming to identify further anti-proliferative compounds, 13 additional nonprenylated xanthones, isolated from different plant species, were also tested. While some compounds showed no or moderate activity at 30 µM, 1-hydroxy-2,3,4,5-tetramethoxyxanthone (4), swerchirin (6), and methylswertianin (7) showed IC50 values between 10.2 and 12.5 µM. The anti-proliferative effect of 1, 4, 6, and 7 was confirmed by the quantification of DNA synthesis (BrdU incorporation) in VSMC. Cell death quantification (determined by LDH release in the culture medium) revealed that the compounds are not cytotoxic in the investigated concentration range. In conclusion, nonprenylated xanthones are identified as novel, non-toxic VSMC proliferation inhibitors, which might contribute to the development of new therapeutic applications to combat restenosis.

  13. The occurrence and frequency of genomic mutations that mediate ...

    African Journals Online (AJOL)

    The occurrence and frequency of genomic mutations that mediate Isoniazid and Rifampicin resistance in Mycobacterium tuberculosis isolates from untreated pulmonary Tuberculosis cases in urban Blantyre, Malawi.

  14. Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis.

    Science.gov (United States)

    Drobniewski, Francis; Cooke, Mary; Jordan, Jake; Casali, Nicola; Mugwagwa, Tendai; Broda, Agnieszka; Townsend, Catherine; Sivaramakrishnan, Anand; Green, Nathan; Jit, Mark; Lipman, Marc; Lord, Joanne; White, Peter J; Abubakar, Ibrahim

    2015-05-01

    introducing rapid molecular testing (in addition to culture and drug sensitivity testing). Probabilistic sensitivity analysis was performed to evaluate the impact on cost-effectiveness of diagnostic and treatment time delays, diagnosis and treatment costs, and associated QALYs. A total of 8922 titles and abstracts were identified, with 557 papers being potentially eligible. Of these, 56 studies contained sufficient test information for analysis. All three commercial tests performed well when detecting drug resistance in clinical samples, although with evidence of heterogeneity between studies. Pooled sensitivity for GenoType® MTBDRplus (Hain Lifescience, Nehren, Germany) (isoniazid and rifampicin resistance), INNO-LiPA Rif.TB® (Fujirebio Europe, Ghent, Belgium) (rifampicin resistance) and Xpert® MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) (rifampicin resistance) was 83.4%, 94.6%, 95.4% and 96.8%, respectively; equivalent pooled specificity was 99.6%, 98.2%, 99.7% and 98.4%, respectively. Results of the transmission model suggest that all of the rapid assays considered here, if added to the current diagnostic pathway, would be cost-saving and achieve a reduction in expected QALY loss compared with current practice. GenoType MTBDRplus appeared to be the most cost-effective of the rapid tests in the South Asian population, although results were similar for GeneXpert. In all other scenarios GeneXpert appeared to be the most cost-effective strategy. Rapid molecular tests for rifampicin and isoniazid resistance were sensitive and specific. They may also be cost-effective when added to culture drug susceptibility testing in the UK. There is global interest in point-of-care testing and further work is needed to review the performance of emerging tests and the wider health-economic impact of decentralised testing in clinics and primary care, as well as non-health-care settings, such as shelters and prisons. This study is registered as PROSPERO CRD42011001537. The National Institute

  15. Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis.

    Science.gov (United States)

    Drobniewski, Francis; Cooke, Mary; Jordan, Jake; Casali, Nicola; Mugwagwa, Tendai; Broda, Agnieszka; Townsend, Catherine; Sivaramakrishnan, Anand; Green, Nathan; Jit, Mark; Lipman, Marc; Lord, Joanne; White, Peter J; Abubakar, Ibrahim

    2015-01-01

    economic model was used to evaluate the cost-effectiveness of introducing rapid molecular testing (in addition to culture and drug sensitivity testing). Probabilistic sensitivity analysis was performed to evaluate the impact on cost-effectiveness of diagnostic and treatment time delays, diagnosis and treatment costs, and associated QALYs. RESULTS A total of 8922 titles and abstracts were identified, with 557 papers being potentially eligible. Of these, 56 studies contained sufficient test information for analysis. All three commercial tests performed well when detecting drug resistance in clinical samples, although with evidence of heterogeneity between studies. Pooled sensitivity for GenoType® MTBDRplus (Hain Lifescience, Nehren, Germany) (isoniazid and rifampicin resistance), INNO-LiPA Rif.TB® (Fujirebio Europe, Ghent, Belgium) (rifampicin resistance) and Xpert® MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) (rifampicin resistance) was 83.4%, 94.6%, 95.4% and 96.8%, respectively; equivalent pooled specificity was 99.6%, 98.2%, 99.7% and 98.4%, respectively. Results of the transmission model suggest that all of the rapid assays considered here, if added to the current diagnostic pathway, would be cost-saving and achieve a reduction in expected QALY loss compared with current practice. GenoType MTBDRplus appeared to be the most cost-effective of the rapid tests in the South Asian population, although results were similar for GeneXpert. In all other scenarios GeneXpert appeared to be the most cost-effective strategy. CONCLUSIONS Rapid molecular tests for rifampicin and isoniazid resistance were sensitive and specific. They may also be cost-effective when added to culture drug susceptibility testing in the UK. There is global interest in point-of-care testing and further work is needed to review the performance of emerging tests and the wider health-economic impact of decentralised testing in clinics and primary care, as well as non-health-care settings, such as shelters and

  16. The Burden of Drug-Resistant Tuberculosis in Papua New Guinea: Results of a Large Population-Based Survey.

    Directory of Open Access Journals (Sweden)

    Paul Aia

    Full Text Available Reliable estimates of the burden of multidrug-resistant tuberculosis (MDR-TB are crucial for effective control and prevention of tuberculosis (TB. Papua New Guinea (PNG is a high TB burden country with limited information on the magnitude of the MDR-TB problem.A cross-sectional study was conducted in four PNG provinces: Madang, Morobe, National Capital District and Western Province. Patient sputum samples were tested for rifampicin resistance by the Xpert MTB/RIF assay and those showing the presence of resistance underwent phenotypic susceptibility testing to first- and second-line anti-TB drugs including streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, ofloxacin, amikacin, kanamycin and capreomycin.Among 1,182 TB patients enrolled in the study, MDR-TB was detected in 20 new (2.7%; 95% confidence intervals [CI] 1.1-4.3% and 24 previously treated (19.1%; 95%CI: 8.5-29.8% TB cases. No case of extensively drug-resistant TB (XDR-TB was detected. Thirty percent (6/20 of new and 33.3% (8/24 of previously treated cases with MDR-TB were detected in a single cluster in Western Province.In PNG the proportion of MDR-TB in new cases is slightly lower than the regional average of 4.4% (95%CI: 2.6-6.3%. A large proportion of MDR-TB cases were identified from a single hospital in Western Province, suggesting that the prevalence of MDR-TB across the country is heterogeneous. Future surveys should further explore this finding. The survey also helped strengthening the use of smear microscopy and Xpert MTB/RIF testing as diagnostic tools for TB in the country.

  17. Molecular approaches for detection of the multi-drug resistant tuberculosis (MDR-TB in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Tafsina Haque Aurin

    Full Text Available The principal obstacles in the treatment of tuberculosis (TB are delayed and inaccurate diagnosis which often leads to the onset of the drug resistant TB cases. To avail the appropriate treatment of the patients and to hinder the transmission of drug-resistant TB, accurate and rapid detection of resistant isolates is critical. Present study was designed to demonstrate the efficacy of molecular techniques inclusive of line probe assay (LPA and GeneXpert MTB/RIF methods for the detection of multi-drug resistant (MDR TB. Sputum samples from 300 different categories of treated and new TB cases were tested for the detection of possible mutation in the resistance specific genes (rpoB, inhA and katG through Genotype MTBDRplus assay or LPA and GeneXpert MTB/RIF tests. Culture based conventional drug susceptibility test (DST was also carried out to measure the efficacy of the molecular methods employed. Among 300 samples, 191 (63.7% and 193 (64.3% cases were found to be resistant against rifampicin in LPA and GeneXpert methods, respectively; while 189 (63% cases of rifampicin resistance were detected by conventional DST methods. On the other hand, 196 (65.3% and 191 (63.7% isolates showed isoniazid resistance as detected by LPA and conventional drug susceptibility test (DST, respectively. Among the drug resistant isolates (collectively 198 in LPA and 193 in conventional DST, 189 (95.6% and 187 (96.9% were considered to be MDR as examined by LPA and conventional DST, respectively. Category-II and -IV patients encountered higher frequency of drug resistance compared to those from category-I and new cases. Considering the higher sensitivity, specificity and accuracy along with the required time to results significantly shorter, our study supports the adoption of LPA and GeneXpert assay as efficient tools in detecting drug resistant TB in Bangladesh.

  18. Molecular characterization of resistance to Rifampicin in an emerging hospital-associated Methicillin-resistant Staphylococcus aureus clone ST228, Spain

    Directory of Open Access Journals (Sweden)

    Liñares Josefina

    2010-03-01

    Full Text Available Abstract Background Methicillin-resistant S. aureus (MRSA has been endemic in Hospital Universitari de Bellvitge, Barcelona, since 1990. During the 1990-95 period the Iberian clone (ST-247; SCCmec-I was dominant. Isolates of clonal complex 5 (ST-125; SCCmec-IV gradually replaced the Iberian clone from 1996 to 2003. A new multiresistant MRSA phenotype showing rifampicin resistance emerged in 2004 and rapidly increased from 25% in 2004 to 45% in 2006. The aims of this study were i the molecular characterisation of rifampicin resistant MRSA isolates, ii the study of the rifampicin resistance expression by disk diffusion, microdilution and E-test, and iii the analysis of the rpoB gene mutations involved in rifampicin resistance. Results A sample of representative 108 rifampicin-resistant MRSA isolates belonged to a single PFGE genotype, ST-228, SCCmec type I and spa type t041. Of 108 isolates, 104 (96% had a low-level rifampicin resistance (MICs, 2 to 4 mg/L and 4 a high-level rifampicin resistance (MICs, 128 - ≥ 256 mg/L. Disk diffusion and E-test methods failed to identify a low-level rifampicin resistance in 20 and 12 isolates, respectively. A low-level rifampicin resistance was associated with amino acid substitution 481His/Asn in the beta-subunit of RNA polymerase. Isolates with a high-level rifampicin resistance carried additional mutations in the rpoB gene. Conclusions The emergence of MRSA clone ST228-SCCmecI, related to the Southern Germany clone, involved a therapeutical challenge for treating serious MRSA infections. Decreased susceptibility to rifampicin in MRSA strains of ST228-SCCmecI was associated with one or two specific mutations in the rpoB gene. One fifth of isolates with low-level rifampicin-resistance were missed by the diffusion methods.

  19. Molecular characterization of rpoB gene encoding the RNA ...

    African Journals Online (AJOL)

    Polymerase chain reaction (PCR) mediated direct DNA sequencing was evaluated for rapid detection of Rifampicin resistance (RMPr) of Mycobacterium tuberculosis. After amplification of the rpoB gene, the product was sequenced using ABI 310 Genetic Analyzer and the rifampicin resistance in M. tuberculosis were ...

  20. On the phosphorylase activity of GH3 enzymes: A β-N-acetylglucosaminidase from Herbaspirillum seropedicae SmR1 and a glucosidase from Saccharopolyspora erythraea.

    Science.gov (United States)

    Ducatti, Diogo R B; Carroll, Madison A; Jakeman, David L

    2016-11-29

    A phosphorolytic activity has been reported for beta-N-acetylglucosaminidases from glycoside hydrolase family 3 (GH3) giving an interesting explanation for an unusual histidine as catalytic acid/base residue and suggesting that members from this family may be phosphorylases [J. Biol. Chem. 2015, 290, 4887]. Here, we describe the characterization of Hsero1941, a GH3 beta-N-acetylglucosaminidase from the endophytic nitrogen-fixing bacterium Herbaspirillum seropedicae SmR1. The enzyme has significantly higher activity against pNP-beta-D-GlcNAcp (K m  = 0.24 mM, k cat  = 1.2 s -1 , k cat /K m  = 5.0 mM -1 s -1 ) than pNP-beta-D-Glcp (K m  = 33 mM, k cat  = 3.3 × 10 -3 s -1 , k cat /K m  = 9 × 10 -4  mM -1 s -1 ). The presence of phosphate failed to significantly modify the kinetic parameters of the reaction. The enzyme showed a broad aglycone site specificity, being able to hydrolyze sugar phosphates beta-D-GlcNAc 1P and beta-D-Glc 1P, albeit at a fraction of the rate of hydrolysis of aryl glycosides. GH3 beta-glucosidase EryBI, that does not have a histidine as the general acid/base residue, also hydrolyzed beta-D-Glc 1P, at comparable rates to Hsero1941. These data indicate that Hsero1941 functions primarily as a hydrolase and that phosphorolytic activity is likely adventitious. The prevalence of histidine as a general acid/base residue is not predictive, nor correlative, with GH3 beta-N-acetylglucosaminidases having phosphorolytic activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Tuberculous lymphadenitis in Northern Ethiopia: in a public health and microbiological perspectives.

    Directory of Open Access Journals (Sweden)

    Fantahun Biadglegne

    Full Text Available BACKGROUND: The actual burden and causative agent of tuberculous lymphadenitis (TBLN cases is not well known due to lack of strong surveillance system and diagnostic facilities in Ethiopia. This study was conducted to determine the prevalence of TBLN, its causative agent and risk factors for acquiring this infection. METHODS: A cross-sectional study was conducted from April to May 2012 at four main hospitals and one diagnostic clinic located in northern Ethiopia. Fine needle aspirates (FNAs from TBLN suspects were taken for acid fast bacilli (AFB microscopy, culture and molecular typing. RESULTS: Among 437 aspirates, culture yielded AFB in 226 (51.7% of cases. Sixty one culture negative cases (30.5% of 200 cases were positive by Xpert MTB/RIF test. Moreover, a rifampicin resistant AFB was detected from culture negative cases. The overall prevalence of FNAs positive TBLN cases was 65.8 %. The BacT/AlerT 3D system proved to be a more rapid method with higher recovery rate than Lowenstein-Jensen (L-J and/or Gottsacker media (P<0.0001. Molecular typing identified all culture positive isolates as M.tuberculosis. The main risk factors for TBLN were pediatric age (OR 2.8, 95% CI, 1.09- 7.05 and cough (OR 2, 95%CI, 1.09-3.7. CONCLUSIONS: The results of this study revealed a high prevalence of TBLN in the study sites and that pediatric age and cough are key predictors of the disease. TBLN is an important public health problem that needs to be addressed in the area. It is important to note that MDR strains of TB could be involved and aetiological confirmation and drug sensitivity testing of TBLN isolates should be expanded. Further studies on the M.tuberculosis lineages, circulating strains and transmission dynamics, are recommended.

  2. Antimutagenic and antibacterial properties of honey and effect of radiation hygienization

    International Nuclear Information System (INIS)

    Saxena, Sudhanshu; Gautam, Satyendra

    2015-01-01

    As mutation is the well known mechanism of neoplastic induction, therefore foods having bioactive compounds with potential to combat mutagenesis are of immense significance. Although honey is a well known natural functional food with associated health supporting quality attributes, there are limited reports with respect to its antimutagenic potential and the effect of floral type on the same. Antimutagenicity or the ability to prevent neoplastic inductions is being considered as an effective strategy to combat mutagen associated diseases. Therefore different regional Indian honeys varying in natural floral types procured were evaluated for their comparative antimutagenicity using a novel E. coli based forward mutation detection assay where mutation(s) in rpoB gene abolishes its interaction with rifampicin and thus confers rifampicin resistant mutator phenotype (RifR) to E. coli cells. Honey displayed wide variation in their ability to prevent induced mutagenesis and among 24 honey samples collected, 'Karanj' honey (Pongammia pinnata) displayed prominent (∼ 80%) antimutagenicity. Besides, honeys were also evaluated for their comparative antibacterial activity against various bacteria such as S. typhimurium, S. aureus, P. syringae etc. Surprisingly, honey of same floral type differed in their antibacterial potentials. Although honey is acidic in nature, the acidity of honey was not found to be the contributing factor of antibacterial activity. Instead, in almost all the cases the antibacterial activity was attributed to the peroxide component of honey. Besides, gamma radiation treatment was also standardized to ensure microbial safety of honey as it may contain burden of pathogenic microbial spores. Radiation (15 kGy) treatment of honey did not affect its antimutagenicity and antibacterial activity. Thus, the current findings provide credible evidence supporting health protective effects of honey and its retention in radiation hygienized honey. (author)

  3. LA SUSCEPTIBILITE AUX MOUVEMENTS DE TERRAIN DANS LA PROVINCE DECHEFCHAOUEN (Rif Central, Maroc)

    OpenAIRE

    Mastere , Mohamed

    2011-01-01

    Geological hazards represent a research topic that is in constant development. Populated areas are ever expanding and the requirements for the control of the hazards they represent are becoming increasingly significant. Orogenic zones are among the areas affected by different types of hazards. This study focuses on the evaluation of mass movement (MM) hazard which is the most common hazard in the Northwest part of the Rifain belt in Morocco. It introduces a three-step procedure to assess mass...

  4. Remedial Investigation/Feasibility Study (RI/FS) Report, David Global Communications Site. Volume 2

    Science.gov (United States)

    1994-02-23

    locations were measured with a rag tape and a compass . Subsurface Conditions Subsurface conditions were generally quite uniform in the test pit...prepared for each specific sample delivery group ( SDG ) and each specific parameter. The laboratory groups samples into SDGs ; the samples in an SDG have...34advisory" flag) These SDG specific detailed reports are kept in project files. All the samples have been reviewed for QC data in accordance with EPA

  5. Lessons Learned from the Great Recession: Layoffs and the RIF-Induced Teacher Shuffle

    Science.gov (United States)

    Goldhaber, Dan; Strunk, Katharine O.; Brown, Nate; Knight, David S.

    2016-01-01

    One consequence of the Great Recession is that teacher layoffs occurred at a scale previously unseen. In this article, we assess the effects of receiving a layoff notice on teacher mobility using data from Los Angeles and Washington State. Our analyses are based on 6-year panels of data in each site, including 4 years of layoffs. We find that the…

  6. The magnetic fabric in undeformed clays: AMS and neutron texture analyses from the Rif Chain (Morocco)

    Czech Academy of Sciences Publication Activity Database

    Cifelli, F.; Mattei, M.; Chadima, Martin; Lenser, S.; Hirt, A. M.

    2009-01-01

    Roč. 466, 1-2 (2009), s. 79-88 ISSN 0040-1951 Institutional research plan: CEZ:AV0Z30130516 Keywords : anisotropy of magnetic susceptibility * neutron texture analysis * magnetic lineation * mineral fabric Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 1.935, year: 2009

  7. Prelude to a RIF: older workers, part-time hours, and unemployment.

    Science.gov (United States)

    Reynolds, Jeremy; Wenger, Jeffrey B

    2010-04-01

    Since the beginning of the most recent recession in December 2007, involuntary part-time employment (part-time for economic reasons) in the United States has increased from 4.2 million workers to 9.1 million, more than doubling. In this paper, we examine whether such increases in involuntary part-time employment have helped combat unemployment in the past or placed a disproportionate burden on older workers. Using Current Population Survey (outgoing rotation group) data from 1983 to 2002, we find that increases in involuntary part-time work in an industry raise the industry unemployment rate. Furthermore, the connection between rising rates of involuntary part-time work and unemployment is stronger among older workers than among younger workers. We conclude that reducing work hours through the use of part-time work does not ameliorate the effects of recessions on workers. Rather, it is a harbinger of unemployment, especially among those older than 55.

  8. l3(M;kbf?sp"f?kings /13. .k Rf?rif?wS

    African Journals Online (AJOL)

    South Africans today have practically resigned themselves to expect nothing more than emotional- ly subjective works when foreign academics dis- cuss the Afrikaner people and their republic at the southern tip of Africa. It was, therefore, a pleasant surpris,e to read Drs Gann and. Duignan's calm analysis of certain key ...

  9. Remedial Investigation/Feasibility Study (RI/FS) Report, Davis Global Communications Site. Volume 3

    Science.gov (United States)

    1994-02-23

    HLOROETHY LENE -- D 0.00) M1 ., qwE -F- 5/16/9 SW8010 N 󈧜,.00 v.r- 1. 2- DICH LOR OETHE NE ND --)-oe-- 1., ,1 -- F M -3 5/AN91 S•� N 22•4.00 1,2,3...8217le A-9.5 -I, 2/1/ SW/l9fl0 N 1.2-DICHLOROBENZENE ND_ 4 ~ ’ 1M.c- I 2/393 W/l0 FE) TOTAL XYLENES ND 33 %EWE 12 2/3/93 SW8020 FE) TOLLENE NED S qWE

  10. Streamlined RI/FS planning for the groundwater operable unit at the Weldon Spring Site

    International Nuclear Information System (INIS)

    Picel, M.H.; Durham, L.A.; Blunt, D.L.; Hartmann, H.M.

    1995-01-01

    The U.S. Department of Energy (DOE) is conducting cleanup activities at the chemical plant area of the Weldon Spring Site located in St. Charles County, Missouri, about 48 km (30 mi) west of St. Louis and 22 km (14 mi) southwest of the City of St. Charles. The 88-ha (217-acre) chemical plant area is chemically and radioactively contaminated as a result of uranium processing activities conducted by the U.S. Atomic Energy Commission during the 1950s and 1960s. The Army also used the chemical plant area for the production of explosives in the 1940s. The Weldon Spring Site chemical plant area was listed on the National Priorities List (NPL) in 1989. Adjacent to the chemical plant area is another NPL site known as the Weldon Spring Ordnance Works. The ordnance works area is a former explosive production facility that manufactured trinitrotoluene (TNT) and dinitrotoluene (DNT) during World War II. The ordnance works area covers 7,000 ha (17,232 acres); cleanup of this site is managed by the U.S. Army Corps of Engineers (CE)

  11. Detailed RIF decomposition with selection : the gender pay gap in Italy

    OpenAIRE

    Töpfer, Marina

    2017-01-01

    In this paper, we estimate the gender pay gap along the wage distribution using a detailed decomposition approach based on unconditional quantile regressions. Non-randomness of the sample leads to biased and inconsistent estimates of the wage equation as well as of the components of the wage gap. Therefore, the method is extended to account for sample selection problems. The decomposition is conducted by using Italian microdata. Accounting for labor market selection may be particularly rele...

  12. Desarrollo humano sostenible: el ejemplo de la "cultura del cannabis" en el Rif (Norte de Marruecos)

    OpenAIRE

    J. Sánchez Alhama; A. V. González Martos; J. Molero Mesa; A. Merzouki

    2005-01-01

    En un mundo cada vez más cambiante las interacciones a nivel local y global son más evidentes. El Desarrollo Humano, es la base de una mayor seguridad humana que actúa sobre la vulnerabilidad social, económica, política y medio ambiental de las naciones del mundo. Estos elementos constituyen los medios para evitar las desigualdades y favorecer un Desarrollo Humano Sostenible. En este trabajo se analizan los factores sociales, culturales y medio ambientales del cultivo del cannabis en...

  13. Rapid Screening of MDR-TB in Cases of Extra Pulmonary Tuberculosis Using Geno Type MTBDRplus.

    Directory of Open Access Journals (Sweden)

    Richa Kumari

    Full Text Available Drug resistance in tuberculosis is a major public health challenge in developing countries. The limited data available on drug resistance in extra pulmonary tuberculosis stimulated us to design our study on anti-tuberculosis drug resistance pattern in cases of extra pulmonary tuberculosis in a tertiary referral hospital of North India. We performed Geno Type MTBDRplus assay in comparison with conventional drug susceptibility testing by proportion method to study the mutation patterns in rpoB, katG and inhA genes.A total of 510 extra pulmonary samples were included in this study. After the smear microscopy, all the specimens were subjected for culture on Lowenstein Jensen (LJ media. Phenotypic drug susceptibility testing (DST was performed on LJ media for all the MTB isolates and compared with the results of Geno Type MTBDRplus assay which was performed with the DNA isolated from the culture by conventional method.Of 510 specimens cultured, the total culture positivity obtained was 11.8% (60 encompassing 54 (10.6% Mycobacterium tuberculosis and 6 (1.2% non-tubercular mycobacteria (NTM. DST results by Geno Type MTBDRplus assay and solid culture methods were compared in 51 MTB isolates excluding the two Rif indeterminate and one invalid test. Geno Type MTBDRplus accurately identified 13 of 14 rifampicin-resistant strains, 14 of 15 isoniazid-resistant strains and 13 of 14 as multi drug resistant tuberculosis (MDR-TB in comparison with conventional method. Sensitivity and specificity were 92.86% and 97.30% respectively for detection of RIF resistance, 93.33% and 94.44% respectively for detection of INH resistance, 92.86% and 97.30% respectively for detection of MDR-TB, while the overall concordance of Geno Type MTBDRplus assay with conventional DST was 94.11%. The turn-around time for performing Geno Type MTBDRplus assay test was 48 hours.The problem of MDR in extra pulmonary tuberculosis (EPTB cannot be overlooked and due attention on patients

  14. McClellan AFB, California, RI/FS Quality Assurance Project Plan. Installation Restoration Program (IRP) Stage 3.

    Science.gov (United States)

    1992-08-07

    for homes near the base. A monitoring well network has been installed and includes on- and off-base wells that are located upgradient and downgradient...sites, expand the monitoring well network to allow more complete charac- terization of the extent of groundwater contamination, and to sample surface...To Neron Responibis tar Action: ___________________________ Psud MOM bq~ft Ad~m son I LAW: ljps: Mcurni 0 Dloaunmmalon 03 Spam 0 Otiur oats 1 Tm

  15. Reducing Production Basis Risk through Rainfall Intensity Frequency (RIF) Indexes: Global Sensitivity Analysis' Implication on Policy Design

    Science.gov (United States)

    Muneepeerakul, Chitsomanus; Huffaker, Ray; Munoz-Carpena, Rafael

    2016-04-01

    The weather index insurance promises financial resilience to farmers struck by harsh weather conditions with swift compensation at affordable premium thanks to its minimal adverse selection and moral hazard. Despite these advantages, the very nature of indexing causes the presence of "production basis risk" that the selected weather indexes and their thresholds do not correspond to actual damages. To reduce basis risk without additional data collection cost, we propose the use of rain intensity and frequency as indexes as it could offer better protection at the lower premium by avoiding basis risk-strike trade-off inherent in the total rainfall index. We present empirical evidences and modeling results that even under the similar cumulative rainfall and temperature environment, yield can significantly differ especially for drought sensitive crops. We further show that deriving the trigger level and payoff function from regression between historical yield and total rainfall data may pose significant basis risk owing to their non-unique relationship in the insured range of rainfall. Lastly, we discuss the design of index insurance in terms of contract specifications based on the results from global sensitivity analysis.

  16. Landslide susceptibility mapping using AHP method and GIS in the peninsula of Tangier (Rif-northern morocco

    Directory of Open Access Journals (Sweden)

    Ait Brahim L

    2018-01-01

    Full Text Available The peninsula of Tangier (Northern Morocco is submitted to a significant number of landslides each year due to its lithological, structural and morphological complexity; which cause a lot of damage to the road network and other related infrastructure. The main objective of this study is to create a landslide indexed susceptibility map of Tangier peninsula, by using AHP (Analytical Hierarchical Processes model to calculate each factor’s weight. The work is made via GIS by using an ArcGIS AHP extension. In the current research, First of all, the four main types of landslides were identified and mapped from existing documents, works and new data which came from either remote sensing or fieldwork. Lithology, land use, slope, hypsometry, exposure, fault density and drainage network density were used as main parameters controlling the occurrence of the selected landslides. Then, afterward, each parameter is classified into a number of significant classes based on their relative influence on gravitational movement genesis. The validity of the susceptibility zoning map which is obtained through linear summation of indexed maps was tested and cross-checked by inventoried and studied landslides. The obtained landslide susceptibility map constitutes a powerful decision-making tool in land-use planning, i.e. New highways, secondary highways, railways, etc. within the national development program in the Northern provinces. It is a necessary step for the landslides hazard assessment in the Tangier peninsula in northern Morocco.

  17. Benefits and challenges of molecular diagnostics for childhood tuberculosis

    Directory of Open Access Journals (Sweden)

    Cristina Gutierrez

    2016-01-01

    Full Text Available Expanding tuberculosis (TB-diagnostic services, including access to rapid tests, is a World Health Organization (WHO strategy to accelerate progress toward ending TB. Faster and more sensitive molecular tests capable of diagnosing TB and drug-resistant TB have the technical capacity to address limitations associated with smears and cultures by increasing accuracy and shortening turnaround times as compared with those of these conventional laboratory methods. Nucleic acid amplification assays used to detect and analyze Mycobacterium tuberculosis (MTB-complex nucleic acids can be used directly on specimens from patients suspected of having TB. Recently, several commercial molecular tests were developed to detect MTB and determine the drug resistance (DR based on detection of specific genetic mutations conferring resistance. The first to be endorsed by the WHO was molecular line-probe assay technology. This test uses polymerase chain reaction (PCR and reverse-hybridization methods to rapidly identify MTB and DR-related mutations simultaneously. More recently, the WHO endorsed Xpert MTB/RIF, Cepheid Inc, CA, USA, a fully automated assay used for TB diagnosis that relies upon PCR techniques for detection of TB and rifampicin resistance-related mutations. Other promising molecular TB assays for simplifying PCR-based testing protocols and increasing their accuracy are under development and evaluation. Although we lack a practical gold standard for the diagnosis of childhood TB, its bacteriological confirmation is always recommended to be sought whenever possible prior to a diagnostic decision being made. Conventional diagnostic laboratory TB tests are less efficient for children as compared with adults, because sufficient sputum samples are more difficult to collect from infants and young children, and their disease is often paucibacillary, resulting in smear-negative disease. These inherent challenges associated with childhood TB are due to

  18. Benefits and challenges of molecular diagnostics for childhood tuberculosis.

    Science.gov (United States)

    Gutierrez, Cristina

    2016-12-01

    Expanding tuberculosis (TB)-diagnostic services, including access to rapid tests, is a World Health Organization (WHO) strategy to accelerate progress toward ending TB. Faster and more sensitive molecular tests capable of diagnosing TB and drug-resistant TB have the technical capacity to address limitations associated with smears and cultures by increasing accuracy and shortening turnaround times as compared with those of these conventional laboratory methods. Nucleic acid amplification assays used to detect and analyze Mycobacterium tuberculosis (MTB)-complex nucleic acids can be used directly on specimens from patients suspected of having TB. Recently, several commercial molecular tests were developed to detect MTB and determine the drug resistance (DR) based on detection of specific genetic mutations conferring resistance. The first to be endorsed by the WHO was molecular line-probe assay technology. This test uses polymerase chain reaction (PCR) and reverse-hybridization methods to rapidly identify MTB and DR-related mutations simultaneously. More recently, the WHO endorsed Xpert MTB/RIF, Cepheid Inc, CA, USA, a fully automated assay used for TB diagnosis that relies upon PCR techniques for detection of TB and rifampicin resistance-related mutations. Other promising molecular TB assays for simplifying PCR-based testing protocols and increasing their accuracy are under development and evaluation. Although we lack a practical gold standard for the diagnosis of childhood TB, its bacteriological confirmation is always recommended to be sought whenever possible prior to a diagnostic decision being made. Conventional diagnostic laboratory TB tests are less efficient for children as compared with adults, because sufficient sputum samples are more difficult to collect from infants and young children, and their disease is often paucibacillary, resulting in smear-negative disease. These inherent challenges associated with childhood TB are due to immunological- and

  19. NCBI nr-aa BLAST: CBRC-TNIG-22-0115 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TNIG-22-0115 ref|YP_001104909.1| putative exporter of polyketide antibiotics-l...ike protein [Saccharopolyspora erythraea NRRL 2338] emb|CAM01984.1| putative exporter of polyketide antibiotics

  20. Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

    NARCIS (Netherlands)

    Fregonese, Federica; Ahuja, Shama D; Akkerman, Onno W; Arakaki-Sanchez, Denise; Ayakaka, Irene; Baghaei, Parvaneh; Bang, Didi; Bastos, Mayara; Benedetti, Andrea; Bonnet, Maryline; Cattamanchi, Adithya; Cegielski, Peter; Chien, Jung-Yien; Cox, Helen; Dedicoat, Martin; Erkens, Connie; Escalante, Patricio; Falzon, Dennis; Garcia-Prats, Anthony J; Gegia, Medea; Gillespie, Stephen H; Glynn, Judith R; Goldberg, Stefan; Griffith, David; Jacobson, Karen R; Johnston, James C; Jones-López, Edward C; Khan, Awal; Koh, Won-Jung; Kritski, Afranio; Lan, Zhi Yi; Lee, Jae Ho; Li, Pei Zhi; Maciel, Ethel L; Galliez, Rafael Mello; Merle, Corinne S C; Munang, Melinda; Narendran, Gopalan; Nguyen, Viet Nhung; Nunn, Andrew; Ohkado, Akihiro; Park, Jong Sun; Phillips, Patrick P J; Ponnuraja, Chinnaiyan; Reves, Randall; Romanowski, Kamila; Seung, Kwonjune; Schaaf, H Simon; Skrahina, Alena; Soolingen, Dick van; Tabarsi, Payam; Trajman, Anete; Trieu, Lisa; Banurekha, Velayutham V; Viiklepp, Piret; Wang, Jann-Yuan; Yoshiyama, Takashi; Menzies, Dick

    Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and

  1. Comparison of different treatments for isoniazid-resistant tuberculosis : an individual patient data meta-analysis

    NARCIS (Netherlands)

    Fregonese, Federica; Ahuja, Shama D; Akkerman, Onno W; Arakaki-Sanchez, Denise; Ayakaka, Irene; Baghaei, Parvaneh; Bang, Didi; Bastos, Mayara; Benedetti, Andrea; Bonnet, Maryline; Cattamanchi, Adithya; Cegielski, Peter; Chien, Jung-Yien; Cox, Helen; Dedicoat, Martin; Erkens, Connie; Escalante, Patricio; Falzon, Dennis; Garcia-Prats, Anthony J; Gegia, Medea; Gillespie, Stephen H; Glynn, Judith R; Goldberg, Stefan; Griffith, David; Jacobson, Karen R; Johnston, James C; Jones-López, Edward C; Khan, Awal; Koh, Won-Jung; Kritski, Afranio; Lan, Zhi Yi; Lee, Jae Ho; Li, Pei Zhi; Maciel, Ethel L; Galliez, Rafael Mello; Merle, Corinne S C; Munang, Melinda; Narendran, Gopalan; Nguyen, Viet Nhung; Nunn, Andrew; Ohkado, Akihiro; Park, Jong Sun; Phillips, Patrick P J; Ponnuraja, Chinnaiyan; Reves, Randall; Romanowski, Kamila; Seung, Kwonjune; Schaaf, H Simon; Skrahina, Alena; Soolingen, Dick van; Tabarsi, Payam; Trajman, Anete; Trieu, Lisa; Banurekha, Velayutham V; Viiklepp, Piret; Wang, Jann-Yuan; Yoshiyama, Takashi; Menzies, Dick

    BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success,

  2. 8__Aisha_Detection ofMDR-TB

    African Journals Online (AJOL)

    User

    Among the MDR-TB cases rifampicin resistance was associated with rpoB WT gene and rpoB MUT gene in 100% and 62% of the ... diagnosis of TB patients, and proper treatment and management of the infected cases to minimize the spread and ..... in an amino acid change and concluded that this is one of the reasons ...

  3. Persistence and transmission of Escherichia coli and Salmonella in a watermelon field ammended with poultry itter: year two

    Science.gov (United States)

    Introduction:Poultry litter (PL) is a nutrient-rich soil amendmentfor crop production; however, use of PL in soils may introduce enteric pathogens tofruits and vegetables. Purpose:This study was to evaluated the persistence of a non-pathogenic rifampicin-resistant E. coli strain (TVS 355) and the p...

  4. Effect of high pressure processing on reduction of Listeria monocytogenes in packaged Queso Fresco

    Science.gov (United States)

    The effect of high hydrostatic pressure processing (HPP) on the survival of a five-strain rifampicin-resistant cocktail of Listeria monocytogenes in Queso Fresco (QF) was evaluated as a post-packaging intervention. QF was made using pasteurized, homogenized milk, was starter-free and was not pressed...

  5. Handbook to Support the Installation Restoration Program (IRP) statements of Work. Volume 1. Remedial Investigation/Feasibility Studies (RI/FS)

    Science.gov (United States)

    1991-05-01

    resources 1.1.6 Surface and subsurface features (e.g., number and volume of tanks, lagoons , structures, drums). 2.0 SITE HISTORY 2.1 Describe Site...and are considered representative soil macroinvertebrates . An example of an earthworm test is the Eiseuia foetida earthworm 14-day soil acute

  6. DÉGRADATION DE LA QUALITÉ DES EAUX DU BARRAGE SAHLA: TRAITEMENT ET GESTION DES RISQUES DE POLLUTION. (Province de Taounate, Rif - Maroc septentrional

    Directory of Open Access Journals (Sweden)

    Abdelghani Gartet

    2009-01-01

    a nivel ecológico y medioambiental, así como en el grado de explotación de los recursos hídricos de la presa. Para solucionar este problema, se han realizado propuestas relativas al saneamiento de aguas y a la utilización de métodos ecológicos de extracción de aceite de oliva sin producción de desechos. Finalmente, se describe la necesidad de popularizar dichas medidas y sensibilizar a los gerentes de las aceiterías y responsables administrativos, así como aplicar con mayor rigor las leyes de protección medioambiental y la ley del agua.

  7. Analysis of the recent Plio-Quaternary deformation and the correlation with the focal mechanisms of the significant earthquakes in the Bokoya, Ras Tarf (Eastern Rif

    Directory of Open Access Journals (Sweden)

    El Mahsani A.

    2018-01-01

    surface. A reduced number of faults shows a generall direction NNE-SSO to N-S through the Quaternary formations in the NO of Al Hoceima city, the direction NO does not show a good correlation with the directions of surface rupture, as well as with the deducted directions from focals mechanisms. This study drives us to propose that faults of direction NNE-SSO to NE-SO, represent the major directions of the faults in the Al Hoceima region, which represents the main cause of the seismic activity in the region.

  8. Mass movement susceptibility mapping - A comparison of logistic regression and Weight of evidence methods in Taounate-Ain Aicha region (Central Rif, Morocco

    Directory of Open Access Journals (Sweden)

    JEMMAH A I

    2018-01-01

    Full Text Available Taounate region is known by a high density of mass movements which cause several human and economic losses. The goal of this paper is to assess the landslide susceptibility of Taounate using the Weight of Evidence method (WofE and the Logistic Regression method (LR. Seven conditioning factors were used in this study: lithology, fault, drainage, slope, elevation, exposure and land use. Over the years, this site and its surroundings have experienced repeated landslides. For this reason, landslide susceptibility mapping is mandatory for risk prevention and land-use management. In this study, we have focused on recent large-scale mass movements. Finally, the ROC curves were established to evaluate the degree of fit of the model and to choose the best landslide susceptibility zonation. A total mass movements location were detected; 50% were randomly selected as input data for the entire process using the Spatial Data Model (SDM and the remaining locations were used for validation purposes. The obtained WofE’s landslide susceptibility map shows that high to very high susceptibility zones contain 62% of the total of inventoried landslides, while the same zones contain only 47% of landslides in the map obtained by the LR method. This landslide susceptibility map obtained is a major contribution to various urban and regional development plans under the Taounate Region National Development Program.

  9. Extraction of the predisposition parameters for mapping the susceptibility of slides lands, in the region of EL Quola, province of Larache (Nothern Rif

    Directory of Open Access Journals (Sweden)

    El hamdouni Ikram

    2018-01-01

    Full Text Available Slide lands (Lands mass movements are among the natural risks that Morocco faces in the Rifaines regions in particular. They generally constitute small-scale, punctual phenomena. But their diversity and frequency are nevertheless responsible for significant and costly damages and injuries. To deal with this problem, the study of field instabilities must take into account that: ithe ground movements must be taken in a context of the overall dynamics of the watershed, ii-the choice of more objective methods, which is not based on the very subjective opinion of the expert; iii-the choice of an adapted approach to the scale of work. In this article, we used the evidence theory "WofE" to evaluate the sensibility of landslide in the El Quola area. This method is based on the analysis of the relationships between landslides that occurred in the past (the so-called modelable variable Vm and the spatial distribution of some predictive parameters of instability (Vp. The result obtained is a landslide susceptibility map that is the result of multi-disciplinary and multi-temporal data. This method has been described as one of the most performing by several authors; however, it requires a conditional independence between the different predictive factors. The quality of the performances was evaluated with success curves.

  10. Susceptibility assessment of landslides: A comparison of two GIS-based methods in the region of Al Hoceima (Eastern Rif, Morocco.

    Directory of Open Access Journals (Sweden)

    El Fahchouch A. N.

    2018-01-01

    Full Text Available The evaluation of the degree of susceptibility to landslides has become a major concern in mountainous areas, it is a key component of manager policies efforts in disaster prevention, mitigate risk and manage the consequences. The region of Al Hoceima is one of most mountain regions in Morocco, and is highly exposed landslides events. For this reason, the area was selected in order to determine its susceptibility to landslides using two methods. The purpose of this study is to evaluate and to compare the results of multivariate (logical regression and bivariate (landslide susceptibility methods in Geographical Information System (GIS based landslide susceptibility assessment procedures. In order to achieve this goal, the selected methods were compared by the Seed Cell Area Indexes (SCAI and by the spatial locations of the resultant susceptibility pixels. We found that both of the methods converge in 80% of the area; however, the weighting algorithm in the bivariate technique (landslide susceptibility method had some severe deficiencies, as the resultant hazard classes in overweighed areas did not converge with the factual landslide inventory map. The result of the multivariate technique (logical regression was more sensitive to the different local features of the test zone and it resulted in more accurate and homogeneous susceptibility maps. This information may have direct applications in landslides susceptibility research programs and can assist decision-makers in the implementation of preventive management strategies in the most sensitive areas.

  11. Identification of a major rif transcript common to gametocytes and sporozoites of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Wang, Christian W; Mwakalinga, Steven B; Sutherland, Colin J

    2010-01-01

    ABSTRACT: BACKGROUND: The Plasmodium falciparum parasite is transmitted in its sexual gametocyte stage from man to mosquito and as asexual sporozoites from mosquito to man. Developing gametocytes sequester preferentially in the bone marrow, but mature stage gametocytes are released...

  12. Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study

    Directory of Open Access Journals (Sweden)

    Prof Heather J Zar, PhD

    2013-08-01

    Funding: National Institutes of Health, National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, the National Research Foundation South Africa, the European and Developing Countries Clinical Trials Partnership.

  13. Pharmacokinetics of Rifampin and Clarithromycin in Patients Treated for Mycobacterium ulcerans Infection

    NARCIS (Netherlands)

    Alffenaar, J. W. C.; Nienhuis, W. A.; de Velde, F.; Zuur, A. T.; Wessels, A. M. A.; Almeida, D.; Grosset, J.; Adjei, O.; Uges, D. R. A.; van der Werf, T. S.

    In a randomized controlled trial in Ghana, treatment of Mycobacterium ulcerans infection with streptomycin (SM)-rifampin (RIF) for 8 weeks was compared with treatment with SM-RIF for 4 weeks followed by treatment with RIF-clarithromycin (CLA) for 4 weeks. The extent of the interaction of RIF and CLA

  14. La coupe d'Ouled Haddou (Rif externe oriental) : un affleurement continu de la transition Crétacé Paléogène au Maroc, révélé par les Foraminifères planctoniquesThe Ouled Haddou section (oriental external Rif): a continuous outcrop of the Cretaceous Palaeogene transition in Morocco, revealed by planktonic Foraminifera

    Science.gov (United States)

    Toufiq, Abdelkabir; Bellier, Jean-Pierre; Boutakiout, Mohamed; Feinberg, Hugues

    2002-10-01

    In the Ouled Haddou section, deposits of the Uppermost Maastrichtian correspond to the Abathomphalus mayaroensis Biozone. The index species is regularly present until the Cretaceous-Palaeogene boundary, which is marked by a mass extinction affecting 41 species (large and complex). Some Cretaceous small species persist in the Lowermost Danian. The first levels of the Danian are assigned to the Guembelitria cretacea Biozone, in which the species index persist without being affected, and the first species of the Tertiary appear. The upper part of the Lower Danian corresponds to the succession of Parvularugoglobigerina eugubina, Parasubbotina pseudobulloides, and Subbotina triloculinoides Biozones. From the P. eugubina Biozone, associations of Danian vary to undergo a complete renewal in the upper zones. The Ouled Haddou section, described for the first time, presents, according to planktonic Foraminifera, a complete record of the Cretaceous-Palaeogene transition. To cite this article: A. Toufiq et al., C. R. Geoscience 334 (2002) 995-1001.

  15. Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into emergence and spread of multidrug resistance

    Science.gov (United States)

    Manson, Abigail L.; Cohen, Keira A.; Abeel, Thomas; Desjardins, Christopher A.; Armstrong, Derek T.; Barry, Clifton E.; Brand, Jeannette; Chapman, Sinéad B.; Cho, Sang-Nae; Gabrielian, Andrei; Gomez, James; Jodals, Andreea M.; Joloba, Moses; Jureen, Pontus; Lee, Jong Seok; Malinga, Lesibana; Maiga, Mamoudou; Nordenberg, Dale; Noroc, Ecaterina; Romancenco, Elena; Salazar, Alex; Ssengooba, Willy; Velayati, A. A.; Winglee, Kathryn; Zalutskaya, Aksana; Via, Laura E.; Cassell, Gail H.; Dorman, Susan E.; Ellner, Jerrold; Farnia, Parissa; Galagan, James E.; Rosenthal, Alex; Crudu, Valeriu; Homorodean, Daniela; Hsueh, Po-Ren; Narayanan, Sujatha; Pym, Alexander S.; Skrahina, Alena; Swaminathan, Soumya; Van der Walt, Martie; Alland, David; Bishai, William R.; Cohen, Ted; Hoffner, Sven; Birren, Bruce W.; Earl, Ashlee M.

    2017-01-01

    Multidrug-resistant tuberculosis (MDR-TB), caused by drug resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. In this study, we examined a dataset of 5,310 M. tuberculosis whole genome sequences from five continents. Despite great diversity with respect to geographic point of isolation, genetic background and drug resistance, patterns of drug resistance emergence were conserved globally. We have identified harbinger mutations that often precede MDR. In particular, the katG S315T mutation, conferring resistance to isoniazid, overwhelmingly arose before rifampicin resistance across all lineages, geographic regions, and time periods. Molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of pre-MDR polymorphisms, particularly katG S315, into molecular diagnostics will enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB. PMID:28092681

  16. Phylogeny of rock-inhabiting fungi related to Dothideomycetes

    NARCIS (Netherlands)

    Ruibal, C.; Gueidan, C.; Selbmann, L.; Gorbushina, A.A.; Crous, P.W.; Groenewald, J.Z.; Muggia, L.; Grube, M.; Isola, D.; Schoch, C.L.; Staley, J.T.; Lutzoni, F.; Hoog, de G.S.

    2009-01-01

    The class Dothideomycetes (along with Eurotiomycetes) includes numerous rock-inhabiting fungi (RIF), a group of ascomycetes that tolerates surprisingly well harsh conditions prevailing on rock surfaces. Despite their convergent morphology and physiology, RIF are phylogenetically highly diverse in

  17. Semantic Integration as a Boundary Condition on Inhibitory Processes in Episodic Retrieval

    Science.gov (United States)

    Goodmon, Leilani B.; Anderson, Michael C.

    2011-01-01

    Recalling an experience often impairs the later retention of related traces, a phenomenon known as retrieval-induced forgetting (RIF). Research has shown that episodic associations protect competing memories from RIF (Anderson & McCulloch, 1999). We report 4 experiments that examined whether semantic associations also protect against RIF. In…

  18. Courtship in Frogs

    Indian Academy of Sciences (India)

    well-defined physical characteristics and a clear biological meaning. ... men t most successfully were the frogs and toads (hereafter referred ... Sound Pressure Level (SPL) in decibels = 20 loglOPt/Pr where,. Pt is the .... R.erythraea (left) and mean spectrum and sonagram of the female ... and egg laying activities initiated. 5.

  19. Data in support of substrate flexibility of a mutated acyltransferase domain and implications for polyketide biosynthesis

    Directory of Open Access Journals (Sweden)

    Stephan Klopries

    2015-12-01

    Full Text Available Enzyme-directed mutasynthesis is an emerging strategy for the targeted derivatization of natural products. Here, data on the synthesis of malonic acid derivatives for feeding studies in Saccharopolyspora erythraea , the mutagenesis of DEBS and bioanalytical data on the experimental investigation of studies on the biosynthetic pathway towards erythromycin are presented.

  20. Effect of Ramadan intermittent fasting on selective fitness profile parameters in young untrained Muslim men.

    Science.gov (United States)

    Roy, Anindita Singha; Bandyopadhyay, Amit

    2015-01-01

    The present study was aimed at investigating the effects of sleep deprivation and dietary irregularities during Ramadan intermittent fasting (RIF) on selective fitness profile parameters in young untrained male Muslim individuals. 77 untrained Muslim men were recruited in the study. They were divided into the experimental group (EG; n=37, age: 22.62±1.77 years) and the control group (CG; n=40, age: 23.00±1.48 years). EG was undergoing RIF while CG abstained. Aerobic fitness, anaerobic capacity or high-intensity efforts (HIEs), agility, flexibility, vertical jump height and handgrip strength were measured on 8 separate occasions-15 days before RIF, 7 days before RIF, 1st day of RIF, 7th day of RIF, 15th day of RIF, 21st day of RIF, last day of RIF and 15 days after RIF. Aerobic fitness and HIE showed a significant difference (p<0.05) during RIF in EG. Agility and flexibility score showed a significant decrease in EG during RIF, whereas changes in the vertical jump score (VJT) and handgrip strength were statistically insignificant. Studied parameters showed an insignificant variation in CG during RIF. Aerobic fitness, HIEs, agility and flexibility showed a significant intergroup variation during different experimental trials. The present investigation revealed that RIF had adverse effects on aerobic fitness, HIEs, agility and flexibility of young untrained Muslims of Kolkata, India. VJT, waist-hip ratio and handgrip strength were not affected by RIF in the studied population. Mild but statistically insignificant reduction in body mass was also reflected after the mid-Ramadan week.

  1. Application des analyses minéralogiques et géotechniques des Argiles dans l’étude des glissements de terrains: exemples du Prérif central (Maroc septentrional

    Directory of Open Access Journals (Sweden)

    Faleh Ali

    2002-01-01

    Full Text Available En el Prerif central resulta muy común el paisaje de vertientes afectadas por deslizamientos de terrenos, recientes o reactivados. Los factores responsables de esta morfodinámica acelerada están ligados al predominio de rocas blandas, a las precipitaciones intensas e irregulares y a las fuertes pendientes. El objetivo principal de este trabajo es determinar la susceptibilidad de las diferentes facies a los movimientos en masa, en relación con las características mineralógicas y geotécnicas de las arcillas.

  2. Hydrochimie des eaux, dissolution spécifique et salinité des cours d’eau dans le bassin de l’Oued Lebène (Prérif Central, Maroc septentrional

    Directory of Open Access Journals (Sweden)

    Abdelghani Gartet

    2001-01-01

    Full Text Available El estudio de los parámetros físico-químicos del oued Lebéne —en el Prerif central marroquí— se centra principalmente en la evaluación de la disolución específica y en la caracterización de las facies químicas de sus aguas. Aun siendo excesivo, el grado de disolución específica hace que las aguas del Lebéne, bicarbonatadas magnésicas aguas arriba, se coviertan en cloruro-sódicas en los tramos medio e inferior de su curso. Las variaciones espaciotemporales de los elementos rocosos disueltos en el agua permiten calcular el volumen medio de las rocas disueltas y, por lo tanto, el tonelaje exportado. Paralelamente a estos aspectos cuantitativos, la salinidad de las cuencas media e inferior subraya la implicación de los afloramientos triásicos. El lavado de los terrenos atravesados por las aguas de escorrentía y la contaminación de las aguas en los macizos triásicos a través de los oueds hacen que la polución sea muy fuerte. Las intervenciones, en el marco de la ordenación territorial, resultan insuficientes ya que persiste un alto grado de polución hídrica.

  3. Design and evaluation of enteric-coated tablets for rifampicin and isoniazid combinations.

    Science.gov (United States)

    Wang, Yongjun; Liu, Hongzhuo; Liu, Kai; Sun, Jin; He, Zhonggui

    2013-01-01

    In order to improve the bioavailability of rifampicin (RIF) from rifampicin and isoniazid (INH) combination formulations, the physicochemical characteristics of RIF, stability of RIF in different pH buffers in the presence of INH, as well as the effect of particle size of RIF materials on the dissolution rate were investigated. On the basis of the above examinations, enteric-coated tablets for RIF and INH combinations were designed and prepared. RIF showed low solubility and high apparent distribution coefficient in the intestinal pH (pH 4.0-7.4). With the decrease in pH, the degradation of RIF increase and the presence of INH deepen the degradation. Enteric-coated tablets were prepared after grinding the RIF materials by dry granulation technique. The pharmacokinetics of RIF and INH of self-made enteric-coated tablets in dogs were studied by comparing with the reference tablets. The AUC(0-48) of RIF in both reference and test tablets were 304.77 ± 42.27 and 353.79 ± 31.63 µg·h·mL(-1), respectively. The AUC(0-48) of INH in both reference and test tablets were 17.14 ± 8.59 and 19.62 ± 10.57 µg·h·mL(-1), respectively. Enteric-coated tablets may minimize the decomposition of RIF in gastrointestinal tract and improve the bioavailability.

  4. Restriction des communications entre l'Atlantique et la Méditerranée au Messinien : apport de la téphrochronologie dans la plate-forme carbonatée et le bassin de Melilla Nador (Rif nord-oriental, Maroc)Restriction of the seawater exchanges between the Atlantic and the Mediterranean during the Messinian: contribution of the tephrochronology of the Melilla Nador area (north-eastern Rif, Morocco)

    Science.gov (United States)

    Münch, Philippe; Roger, Stephan; Cornée, Jean-Jacques; Saint Martin, Jean-Paul; Féraud, Gilbert; Moussa, Abdelkhalak Ben

    2001-05-01

    Thirty-eight volcanic layers have been found, from the littoral carbonate platform to the basin, interbedded within the Neogene deposits of the Melilla-Nador area. Ten of them, whose stratigraphic location and geographic extension have been established, were petrographically and mineralogically studied. They have been used as markers to establish an overall platform/basin correlation sketch. Together with these correlations and a synthesis of available ages, we show that the sedimentation areas, and thus the oceanic circulations, progressively restricted in this region between 6.5 and 5.77 Ma as a consequence of tectono-magmatic activity of the Gourougou magmatic field.

  5. Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15.

    Science.gov (United States)

    Cambau, E; Saunderson, P; Matsuoka, M; Cole, S T; Kai, M; Suffys, P; Rosa, P S; Williams, D; Gupta, U D; Lavania, M; Cardona-Castro, N; Miyamoto, Y; Hagge, D; Srikantam, A; Hongseng, W; Indropo, A; Vissa, V; Johnson, R C; Cauchoix, B; Pannikar, V K; Cooreman, E A W D; Pemmaraju, V R R; Gillini, L

    2018-03-01

    Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Transmission of Drug-Resistant Leprosy in Guinea-Conakry Detected Using Molecular Epidemiological Approaches.

    Science.gov (United States)

    Avanzi, Charlotte; Busso, Philippe; Benjak, Andrej; Loiseau, Chloé; Fomba, Abdoulaye; Doumbia, Glodia; Camara, Idrissa; Lamou, André; Sock, Gouressy; Drame, Tiguidanké; Kodio, Mamadou; Sakho, Fatoumata; Sow, Samba O; Cole, Stewart T; Johnson, Roch Christian

    2016-12-01

    Molecular drug susceptibility testing was performed on skin biopsies from 24 leprosy patients from Guinea-Conakry for the first time. We identified primary drug resistance in 4 cases and a dapsone-resistant cluster caused by the same strain. Primary transmission of drug-resistant Mycobacterium leprae, including a rifampicin-resistant strain, is reported. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. Phaeobacter inhibens as biocontrol agent against Vibrio vulnificus in oyster models

    DEFF Research Database (Denmark)

    Porsby, Cisse Hedegaard; Gram, Lone

    2016-01-01

    acid (TDA), inhibited V. vulnificus as did pure TDA (MIC of 1-3.9 μM). P. inhibens DSM 17395 (at 106 cfu/ml) eradicated 105 cfu/ml V. vulnificus CMCP6 (a rifampicin resistant variant) from a co-culture oyster model system (oyster juice) whereas the pathogen grew to 107 cfu/ml when co......, the presence of P. inhibens could not prevent subsequently added V. vulnificus from entering the live animals, likely because of too low levels of the biocontrol strain. Whilst the oyster model studies provided indication that P. inhibens DSM 17395 could be a good candidate as biocontrol agent against V...

  8. Adherence And Pathogenicity Assay Of Vibrio Harveyi In Tiger Shrimp (Penaeus Monodon) Larvae For Screening Biocontrol Agent

    OpenAIRE

    SUWANTO, ANTONIUS; HALA, YUSMINAH; AFFANDI, RIDWAN; Jr., MUHAMMAD ZAIRIN

    2002-01-01

    Rifampicin-resistant marker was employed as a reporter to detect the adherence and colonization of V. harveyi in shrimp larvae. Vibrio harveyi P1B and YA32.2 were isolated from dead shrimp larvae in Besuki, Northern Coast of East Java, while V. harveyi HB3, was isolated from pristine sea water in Pacitan, Southern Coast of East Java. Vibrio metschnikovii used as biocontrol agent was isolated from healthy shrimp larvae in Serang, West Java. Spontaneous mutation was conducted to generate V. h...

  9. Synthesis and antituberculosis activity of new fatty acid amides.

    Science.gov (United States)

    D'Oca, Caroline Da Ros Montes; Coelho, Tatiane; Marinho, Tamara Germani; Hack, Carolina Rosa Lopes; Duarte, Rodrigo da Costa; da Silva, Pedro Almeida; D'Oca, Marcelo Gonçalves Montes

    2010-09-01

    This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H(37)Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 microg/mL for resistance strains. Copyright 2010 Elsevier Ltd. All rights reserved.

  10. Synthesis and antimycobacterial activity of isoniazid derivatives from renewable fatty acids.

    Science.gov (United States)

    Rodrigues, Marieli O; Cantos, Jéssica B; D'Oca, Caroline R Montes; Soares, Karina L; Coelho, Tatiane S; Piovesan, Luciana A; Russowsky, Dennis; da Silva, Pedro A; D'Oca, Marcelo G Montes

    2013-11-15

    This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Occurrence of weak mutators among avian pathogenic Escherichia coli (APEC) isolates causing salpingitis and peritonitis in broiler breeders

    DEFF Research Database (Denmark)

    Pires dos Santos, Teresa M S; Bisgaard, Magne; Kyvsgaard, Niels Christian

    2014-01-01

    A collection of 46 avian pathogenic Escherichia coli (APEC) isolates was examined for the presence of mutators by determining the rate of mutation to rifampicin resistance. The collection included 34 E. coli isolates obtained in pure culture from chronic lesions of salpingitis and peritonitis in 34...... broiler breeders, of which 12 were associated with the development of secondary septicemia. Twelve additional isolates were obtained from a clonal outbreak (ST95) of E. coli peritonitis syndrome (EPS), the lesions of which changed gradually over time into a subacute/chronic form. The hypothesis...

  12. Characterization of drug susceptibility of Mycobacterium tuberculosis isolated from new cases of tuberculosis concurrent with HIV infection

    Directory of Open Access Journals (Sweden)

    G. V. Panov

    2015-01-01

    Full Text Available The paper characterizes drug susceptibility in Mycobacterium tuberculosis isolated from new cases of tuberculosis concurrent with HIV infection. The investigators have studied the spectrum of drug resistance in Mycobacterium tuberculosis isolated from new cases of tuberculosis concurrent with and without HIV infection (172 and 309 clinical isolates, respectively. There are differences in the rate of primary drug resistance to antituberculosis drugs in patients with and without HIV infection (59 and 43.5% of the cases, respectively. The HIV-infected have also shown high rifampicin resistance rates in Mycobacterium tuberculosis (41.7%. The reasons for these differences are as yet unknown and call for further investigation.

  13. The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity

    Directory of Open Access Journals (Sweden)

    Mohyeldin SM

    2016-05-01

    Full Text Available Salma M Mohyeldin, Mohammed M Mehanna, Nazik A Elgindy Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Purpose: This article investigated the influence of novel rifampicin nanosuspension (RIF NS for enhancing drug delivery properties. Methods: RIF NS was fabricated using the antisolvent precipitation technique. The impact of solvent type and flow rate, stabilizer type and concentration, and stirring time and apparatus together with the solvent–antisolvent volume ratio on its controlled nanocrystallization has been evaluated. NSs were characterized by transmission electron microscopy, particle size and zeta potential analysis, solubility, and dissolution profiles. The compatibility between RIF and the stabilizer was investigated via Fourier transform infrared spectroscopy and the differential scanning calorimetry techniques. The shelf-life stability of the RIF NS was assessed within a period of 3 months at different storage temperatures. Cell cytotoxicity was evaluated using 3(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay on lung epithelial cells. Results: Polyvinyl alcohol at 0.4% w/v, 1:15 methanol to deionized water volume ratio and 30-minutes sonication were the optimal parameters for RIF NS preparation. Nanocrystals were obtained with a nanometeric particle size (101 nm and a negative zeta potential (-26 mV. NS exhibited a 50-fold enhancement in RIF solubility and 97% of RIF was dissolved after 10 minutes. The RIF NS was stable at 4±0.5°C with no significant change in particle size or zeta potential. The MTT cytotoxicity assay of RIF NS demonstrated a good safety profile and reduction in cell cytotoxicity with half maximal inhibitory concentration values of 0.5 and 0.8 mg/mL for free RIF and RIF NS, respectively. Conclusion: A novel RIF NS could be followed as an approach for enhancing RIF physicochemical characteristics with a prominence of a safer and better drug

  14. In vitro testing of daptomycin plus rifampin againstmethicillin-resistant Staphylococcus aureus resistant to rifampin

    International Nuclear Information System (INIS)

    Khaswneh, Faisal A.; Ashcraft, Deborah S.; Pankey, George A.

    2008-01-01

    Objective was to test for synergy between daptomycin (DAP) and rifampin(RIF) against RIF-resistant methicillin-resistant Staphylococcus aureus(MRSA) isolates. Synergy testing using time-kill assay (TKA) was performed on6 clinically and genetically unique RIF-resistant MRSA isolates. The isolateswere identified out of 489 (1.2%) samples collected during April 2003 toAugust 2006, from patients at the Ochsner Medical Center in New Orleans,Louisiana, United States of America. Synergy testing of DAP plus RIF by TKAshowed that 5 isolates were different, but one isolate was antagonistic. Ourin-vitro study failed to demonstrate synergy between DAP plus RIF, againstour RIF-resistant MRSA isolates. Clinical failure of this combination shouldprompt the clinician to consider antagonism as one of the potential causes.(author)

  15. Protozoan parasites of four species of wild anurans from a local zoo in Malaysia.

    Science.gov (United States)

    Mohammad, K N; Badrul, M M; Mohamad, N; Zainal-Abidin, A H

    2013-12-01

    The parasitic protozoan fauna in sixty-six anurans comprising of Duttaphrynus melanostictus, Phrynoidis juxtaspera, Hylarana erythraea and Polypedates leucomystax collected from Zoo Negara Malaysia was investigated. The distribution and prevalence rate of parasitic species in the digestive tract and blood were examined. Seven species of intestinal protozoa (Opalina ranarum, Cepedea dimidiata, Nycthetorus cordiformis, Entamoeba ranarum, Iodamoeba butschlii, Endamoeba blattae, and Tritrichomonas sp.) and two species of blood protozoa (Lankesterella sp. and Trypanosoma sp.) were recorded. Opalina ranarum was the most common protozoan found in the rectum and intestine (prevalence rate: 34.8%) infecting all host species, with P. juxtaspera heavily infected with the parasite, whereas Tritrichomonas sp. was the least prevalent intestinal species infecting only D. melanostictus. Both Lankesterella sp. and Trypanosoma sp. were found in the blood of H. erythraea.

  16. Sucralose Increases Antimicrobial Resistance and Stimulates Recovery of Escherichia coli Mutants.

    Science.gov (United States)

    Qu, Yilin; Li, Rongyan; Jiang, Mingshan; Wang, Xiuhong

    2017-07-01

    Because of heavy use of antimicrobials, antimicrobial resistance in bacteria has become of great concern. The effect of some widely used food additives such as sucralose on bacteria in the gut and the environment has also drawn increasing attention. In this study, we investigated the interaction between antimicrobials and sucralose impacting antimicrobial resistance and mutation of Escherichia coli (E. coli). To examine antimicrobial resistance and mutation frequency, different subinhibitory concentrations of sucralose were added to cultures of E.coli BW25113 that were then treated with antimicrobials, oxolinic acid, or moxifloxacin. Then the E.coli were assayed for bacterial survival and recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Pre-treatment of E.coli BW25113 with 1/2 minimal inhibitory concentration (MIC) of sucralose increased the survival rate in oxolinic acid or moxifloxacin. A 1/3 MIC of sucralose increased rifampicin-resistant mutation rate of E.coli BW25113 after 72 h, while rifampicin-resistant mutation rate was increased when co-treated with 1/8 MIC, 1/4 MIC, 1/3 MIC sucralose, and oxolinic acid after 24 h. Sucralose can increase the antimicrobial resistance and mutation frequency of E.coli to some antimicrobials.

  17. Diagnostic performance of automated liquid culture and molecular line probe assay in smear-negative pulmonary tuberculosis.

    Science.gov (United States)

    Kotwal, Aarti; Biswas, Debasis; Raghuvanshi, Shailendra; Sindhwani, Girish; Kakati, Barnali; Sharma, Shweta

    2017-04-01

    The diagnosis of smear-negative pulmonary tuberculosis (PTB) is particularly challenging, and automated liquid culture and molecular line probe assays (LPA) may prove particularly useful. The objective of our study was to evaluate the diagnostic potential of automated liquid culture (ALC) technology and commercial LPA in sputum smear-negative PTB suspects. Spot sputum samples were collected from 145 chest-symptomatic smear-negative patients and subjected to ALC, direct drug susceptibility test (DST) testing and LPA, as per manufacturers' instructions. A diagnostic yield of 26.2% was observed among sputum smear-negative TB suspects with 47.4% of the culture isolates being either INH- and/or rifampicin-resistant. Complete agreement was observed between the results of ALC assay and LPA except for two isolates which demonstrated sensitivity to INH and rifampicin at direct DST but were rifampicin-resistant in LPA. Two novel mutations were also detected among the multidrug isolates by LPA. In view of the diagnostic challenges associated with the diagnosis of TB in sputum smear-negative patients, our study demonstrates the applicability of ALC and LPA in establishing diagnostic evidence of TB.

  18. Mutation at codon 442 in the rpoB gene of Mycobacterium leprae does not confer resistance to rifampicin.

    Science.gov (United States)

    Lavania, Mallika; Hena, Abu; Reja, Hasanoor; Nigam, Astha; Biswas, Nibir Kumar; Singh, Itu; Turankar, Ravindra P; Gupta, Ud; Kumar, Senthil; Rewaria, Latika; Patra, Pradip K R; Sengupta, Utpal; Bhattacharya, Basudeb

    2016-03-01

    Rifampicin is the major drug in the treatment of leprosy. The rifampicin resistance of Mycobacterium leprae results from a mutation in the rpoB gene, encoding the β subunit of RNA polymerase. As M. leprae is a non-cultivable organism observation of its growth using mouse food-pad (MFP) is the only Gold Standard assay used for confirmation of "in-vivo" drug resistance. Any mutation at molecular level has to be verified by MFP assay for final confirmation of drug resistance in leprosy. In the present study, M. leprae strains showing a mutation only at codon 442 Gln-His and along with mutation either at codon 424 Val-Gly or at 438 Gln-Val within the Rifampicin Resistance Determining Region (RRDR) confirmed by DNA sequencing and by high resolution melting (HRM) analysis were subjected for its growth in MFP. The M. leprae strain having the new mutation at codon 442 Gln-His was found to be sensitive to all the three drugs and strains having additional mutations at 424 Val-Gly and 438 Gln-Val were conferring resistance with Multi drug therapy (MDT) in MFP. These results indicate that MFP is the gold standard method for confirming the mutations detected by molecular techniques.

  19. The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges.

    Science.gov (United States)

    Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

    2017-11-06

    While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)-coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. The overall tuberculosis burden was estimated to be 532005 cases (range, 333760-764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  20. Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.

    Science.gov (United States)

    Mieras, Liesbeth; Anthony, Richard; van Brakel, Wim; Bratschi, Martin W; van den Broek, Jacques; Cambau, Emmanuelle; Cavaliero, Arielle; Kasang, Christa; Perera, Geethal; Reichman, Lee; Richardus, Jan Hendrik; Saunderson, Paul; Steinmann, Peter; Yew, Wing Wai

    2016-06-08

    Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

  1. Dicty_cDB: Contig-U03221-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available e) Botryotinia fuckeliana polyketide ... 53 2e-05 AF079138_6( AF079138 |pid:none) Streptomyces venezuelae me...id:none) Saccharopolyspora erythraea NRR... 52 5e-05 AF079138_3( AF079138 |pid:none) Streptomyces venezuelae...Gibberella moniliformis polyketide... 51 8e-05 AF015823_1( AF015823 |pid:none) Streptomyces venezuelae venA

  2. Étude ethnobotanique des plantes médicinales utilisées dans le ...

    African Journals Online (AJOL)

    La surexploitation menace certaines espèces peu abondantes, comme Origanum compactum, Centaurium Erythraea et Salvia verbenaca (Sauge à feuilles de verveine) de disparition de la forêt d'Izarène. D'où l'intérêt d'adopter une approche de gestion durable pour assurer la conservation et la préservation de ces ...

  3. The effect of listening to others remember on subsequent memory: The roles of expertise and trust in socially shared retrieval-induced forgetting and social contagion

    DEFF Research Database (Denmark)

    Koppel, Jonathan Mark; Wohl, Dana; Meksin, Robert

    2014-01-01

    Speakers reshape listeners’ memories through at least two discrete means: (1) social contagion and (2) socially shared retrieval-induced forgetting (SS-RIF). Three experiments explored how social relationships between speaker and listener moderate these conversational effects, focusing specifically......-RIF than untrustworthy speakers. These findings suggest that how speakers shape listeners’ memories depends on the social dynamic that exists between speaker and listener....... on two speaker characteristics, expertise and trustworthiness. We examined their effect on SS-RIF and contrasted, within-subjects, their effects on both SS-RIF and the previously studied social contagion. Experiments 1 and 2 explored the effects of perceived expertise; Experiment 3 explored trust. We...

  4. CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

    Science.gov (United States)

    Meziani, Lydia; Mondini, Michele; Petit, Benoît; Boissonnas, Alexandre; Thomas de Montpreville, Vincent; Mercier, Olaf; Vozenin, Marie-Catherine; Deutsch, Eric

    2018-03-01

    Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic.These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF. Copyright ©ERS 2018.

  5. Insecticidal effects of Moroccan plant extracts on development, energy reserves and enzymatic activities of Plodia interpunctella

    Energy Technology Data Exchange (ETDEWEB)

    Bouayard, N.; Rharrabe, K.; Ghailani, N. N.; Jbilou, R.; Castanera, P.; Ortego, F.

    2013-05-01

    The aim of this work was to study the effects of methanol extracts of ten plant species used in traditional medicine in Morocco (Peganum harmala, Ajuga iva, Rosmarinus officinalis, Lavandula stoechas, Lavandula dentata, Cistus ladanifer, Cistus salviaefolius, Cistus monspeliensis, Centaurium erythraea and Launaea arborescens) on Plodia interpunctella Hubner (Lepidoptera: Pyralidae) larvae. Firstly, we studied the effects of the ingestion of these extracts at 500 ppm on post-embryonic development parameters. Most plant extracts provoked a notable decrease of larval weight 8 days after treatment (up to 33% weight loss with C. erythraea) and caused significant alterations on pupation (ranging from 5% to 85%) and adult emergence (below 2.5% with R. officinalis, C. erythraea and A. iva). The plant extracts that showed strongest effects on post-embryonic development were selected to test their effects on the following physiological parameters: larval reserve substances (at 500 ppm); and midgut activities of hydrolytic and detoxification enzymes (at 500, 750 and 1000 ppm). All treatments provoked a significant reduction of protein and carbon hydrate larval contents, the inhibition of proteases and {alpha}-amylase activities in a dose depended manner, and the induction of glutathione S-transferase and esterase (using MtB as substrate) activities, whereas the activity of cytochrome P450 monooxygenases and esterases (using 1-NA as substrate) increase or decrease depending on the extract concentration and the plant analyzed. (Author) 65 refs.

  6. Insecticidal effects of Moroccan plant extracts on development, energy reserves and enzymatic activities of Plodia interpunctella

    Directory of Open Access Journals (Sweden)

    N. Bouayad

    2012-10-01

    Full Text Available The aim of this work was to study the effects of methanol extracts of ten plant species used in traditional medicine in Morocco (Peganum harmala, Ajuga iva, Rosmarinus officinalis, Lavandula stoechas, Lavandula dentata, Cistus ladanifer, Cistus salviaefolius, Cistus monspeliensis, Centaurium erythraea and Launaea arborescens on Plodia interpunctella Hübner (Lepidoptera: Pyralidae larvae. Firstly, we studied the effects of the ingestion of these extracts at 500 ppm on post-embryonic development parameters. Most plant extracts provoked a notable decrease of larval weight 8 days after treatment (up to 33% weight loss with C. erythraea and caused significant alterations on pupation (ranging from 5% to 85% and adult emergence (below 2.5% with R. officinalis, C. erythraea and A. iva. The plant extracts that showed strongest effects on post-embryonic development were selected to test their effects on the following physiological parameters: larval reserve substances (at 500 ppm; and midgut activities of hydrolytic and detoxification enzymes (at 500, 750 and 1000 ppm. All treatments provoked a significant reduction of protein and carbon hydrate larval contents, the inhibition of proteases and α-amylase activities in a dose depended manner, and the induction of glutathione S-transferase and esterase (using MtB as substrate activities, whereas the activity of cytochrome P450 monooxygenases and esterases (using 1-NA as substrate increase or decrease depending on the extract concentration and the plant analyzed.

  7. Preparation of rifampicin/poly(d,l-lactice) nanoparticles for sustained release by supercritical assisted atomization technique

    CSIR Research Space (South Africa)

    Labuschagne, Philip W

    2014-11-01

    Full Text Available In this work supercritical assisted atomization (SAA) process was used for the co-precipitation of poly(d,l-lactide) (PDLLA) and rifampicin (RIF) as nanoparticles for sustained release applications. The effect of the variation of PDLLA/RIF ratio...

  8. Recurrent implantation failure is a pathology with a specific transcriptomic signature

    DEFF Research Database (Denmark)

    Macklon, Nick

    2017-01-01

    Recurrent implantation failure (RIF) is a source of distress and frustration to both patients and their clinicians. In the absence of clinically useful tests, the therapeutic approach has been largely empirical, with limited efficacy. In recent years, new insights into the role of the endometrium...... be identified. Evidence is presented of a specific transcriptomic signature that is highly predictive of RIF....

  9. Current scenario

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Current scenario. India , like other parts of the world, is also facing the problem of increase in the incidence of drug resistance in tuberculosis. Multi-drug resistance (MDR, resistance to RIF & INH) and extensively drug resistant strains (X-DR, resistance to RIF, INH, FQs ...

  10. Indentation fatigue in silicon nitride, alumina and silicon carbide ...

    Indian Academy of Sciences (India)

    Repeated indentation fatigue (RIF) experiments conducted on the same spot of different structural ceramics viz. a hot pressed silicon nitride (HPSN), sintered alumina of two different grain sizes viz. 1 m and 25 m, and a sintered silicon carbide (SSiC) are reported. The RIF experiments were conducted using a Vicker's ...

  11. A fast resonance interference treatment scheme with subgroup method

    International Nuclear Information System (INIS)

    Cao, L.; He, Q.; Wu, H.; Zu, T.; Shen, W.

    2015-01-01

    A fast Resonance Interference Factor (RIF) scheme is proposed to treat the resonance interference effects between different resonance nuclides. This scheme utilizes the conventional subgroup method to evaluate the self-shielded cross sections of the dominant resonance nuclide in the heterogeneous system and the hyper-fine energy group method to represent the resonance interference effects in a simplified homogeneous model. In this paper, the newly implemented scheme is compared to the background iteration scheme, the Resonance Nuclide Group (RNG) scheme and the conventional RIF scheme. The numerical results show that the errors of the effective self-shielded cross sections are significantly reduced by the fast RIF scheme compared with the background iteration scheme and the RNG scheme. Besides, the fast RIF scheme consumes less computation time than the conventional RIF schemes. The speed-up ratio is ~4.5 for MOX pin cell problems. (author)

  12. Al-Naz‘ah Al-Khārijīyah Fī Afkāri Wa ḤArakāti Al-Shaykh Ahmad Rifā‘i BI Kālī Sālāk

    OpenAIRE

    Sa'ad, Muhlisin

    1995-01-01

    Rifa'i is a 'scholar who spent over 20 years old to study in the Middle East, particularly in Mecca and Cairo. Upon returning from the Middle East, Rifa'i settled in Kaliwungi, Kendal, Central Java. There he devote attention to teaching religious sciences as well write the book. He also actively engage students and the general public to raise awareness of the socio-religious people in order to erode the moral crisis is the result of the work of the Dutch colonial behavior. To that end, Ahmad ...

  13. Activation of the SOS response increases the frequency of small colony variants

    DEFF Research Database (Denmark)

    Vestergaard, Martin; Paulander, Wilhelm Erik Axel; Ingmer, Hanne

    2015-01-01

    BACKGROUND: In Staphylococcus aureus sub-populations of slow-growing cells forming small colony variants (SCVs) are associated with persistent and recurrent infections that are difficult to eradicate with antibiotic therapies. In SCVs that are resistant towards aminoglycosides, mutations have been...... with different mechanism of action influence the formation of SCVs that are resistant to otherwise lethal concentrations of the aminoglycoside, gentamicin. We found that exposure of S. aureus to fluoroquinolones and mitomycin C increased the frequency of gentamicin resistant SCVs, while other antibiotic classes...... failed to do so. The higher proportion of SCVs in cultures exposed to fluoroquinolones and mitomycin C compared to un-exposed cultures correlate with an increased mutation rate monitored by rifampicin resistance and followed induction of the SOS DNA damage response. CONCLUSION: Our observations suggest...

  14. Experimental analysis of a TEM plane transmission line for DNA studies at 900 MHz EM fields

    International Nuclear Information System (INIS)

    Belloni, F; Doria, D; Lorusso, A; Nassisi, V; Velardi, L; Alifano, P; Monaco, C; Tala, A; Tredici, M; Raino, A

    2006-01-01

    A suitable plane transmission line was developed and its behaviour analysed at 900 MHz radiofrequency fields to study DNA mutability and the repair of micro-organisms. In this work, utilizing such a device, we investigated the behaviour of DNA mutability and repair of Escherichia coli strains. The transmission line was very simple and versatile in changing its characteristic resistance and field intensity by varying its sizes. In the absence of cell samples inside the transmission line, the relative modulation of the electric and/or magnetic field was ±31% with respect to the mean values, allowing the processing of more samples at different exposure fields in a single run. A slight decrease in spontaneous mutability to rifampicin-resistance of the E. coli JC411 strain was demonstrated in mismatch-repair proficient samples exposed to the radio-frequency fields during their growth on solid medium

  15. U.v.-induced and N-methyl-N'-nitrosoguanidine-induced mutagenesis in Bacillus thuringiensis

    International Nuclear Information System (INIS)

    Auffray, Y.; Boutibonnes, P.

    1987-01-01

    The lethal and mutagenic effects of u.v. light and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on Bacillus thuringiensis were investigated. Lethality studies demonstrated that B. thuringiensis was relatively sensitive to these agents. This bacterium was mutated at the rifampicin resistance marker by u.v. light and to a lesser extent by the direct acting alkylating agent MNNG. One mutant selected for its greater sensitivity to u.v. light expressed a higher frequency of mutagenesis after u.v. light treatment and appeared to be defective in an excision repair pathway. However, this mutant was only slightly mutable by MNNG in comparison with the wild-type strain. This unusual phenotype does not yet have a parallel among the radiation sensitive mutants described in other bacterial species. (author)

  16. Apramycin treatment affects selection and spread of a multidrug-resistant Escherichia coli strain able to colonize the human gut in the intestinal microbiota of pigs

    DEFF Research Database (Denmark)

    Herrero-Fresno, Ana; Zachariasen, Camilla; Hansen, Monica Hegstad

    2016-01-01

    of treatment, and apramycin treatment resulted in significantly higher counts compared to the non-treated group. This represents the first demonstration of how antimicrobial treatment affects spread of resistant bacteria in pig production. The use of apramycin may lead to enhanced spread of gentamicin-resistant......The effect of apramycin treatment on transfer and selection of an Escherichia coli strain (E. coli 912) in the intestine of pigs was analyzed through an in vivo experiment. The strain was sequenced and assigned to the sequence type ST101 and serotype O11. It carried resistance genes to apramycin......-treated (pen 3), along with a non-inoculated control group (pen 1). Two pigs of pen 2 and 3 were inoculated intragastrically with a rifampicin resistant variant of the strain. Apramycin treatment in pen 2 was initiated immediately after inoculation. Strain colonization was assessed in the feces from all pigs...

  17. A novel approach to eliminate Wolbachia infections in Nasonia vitripennis revealed different antibiotic resistance between two bacterial strains.

    Science.gov (United States)

    Liu, Hai-Yang; Wang, Yan-Kun; Zhi, Cong-Cong; Xiao, Jin-Hua; Huang, Da-Wei

    2014-06-01

    Wolbachia are widespread in insects and can manipulate host reproduction. Nasonia vitripennis is a widely studied organism with a very high prevalence of Wolbachia infection. To study the effect of Wolbachia infection in Nasonia spp., it is important to obtain noninfected individuals by artificial methods. Current methods that employ sugar water-containing antibiotics can successfully eliminate Wolbachia from the parasitic wasps; however, treatment of at least three generations is required. Here, we describe a novel, feasible, and effective approach to eliminate Wolbachia from N. vitripennis by feeding fly pupae continuously offering antibiotics to Nasonia populations, which shortened the time to eliminate the pathogens to two generations. Additionally, the Wolbachia Uni and CauB strains have obviously different rifampicin-resistance abilities, which is a previously unknown phenomenon. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  18. Prevalence of drug-resistant tuberculosis and imputed burden in South Africa: a national and sub-national cross-sectional survey.

    Science.gov (United States)

    Ismail, Nazir Ahmed; Mvusi, Lindiwe; Nanoo, Ananta; Dreyer, Andries; Omar, Shaheed V; Babatunde, Sanni; Molebatsi, Thabo; van der Walt, Martie; Adelekan, Adeboye; Deyde, Varough; Ihekweazu, Chikwe; Madhi, Shabir A

    2018-04-20

    Globally, per-capita, South Africa reports a disproportionately high number of cases of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We sought to estimate the prevalence of resistance to tuberculosis drugs in newly diagnosed and retreated patients with tuberculosis provincially and nationally, and compared these with the 2001-02 estimates. A cross-sectional survey was done between June 15, 2012-June 14, 2014, using population proportionate randomised cluster sampling in the nine provinces in South Africa. 343 clusters were included, ranging between 31 and 48 per province. A patient was eligible for inclusion in the survey if he or she presented as a presumptive case during the intake period at a drug resistance survey enrolling facility. Consenting participants (≥18 years old) completed a questionnaire and had a sputum sample tested for resistance to first-line and second-line drugs. Analysis was by logistic regression with robust SEs, inverse probability weighted against routine data, and estimates were derived using a random effects model. 101 422 participants were tested in 2012-14. Nationally, the prevalence of MDR tuberculosis was 2·1% (95% CI 1·5-2·7) among new tuberculosis cases and 4·6% (3·2-6·0) among retreatment cases. The provincial point prevalence of MDR tuberculosis ranged between 1·6% (95% CI 0·9-2·9) and 5·1% (3·7-7·0). Overall, the prevalence of rifampicin-resistant tuberculosis (4·6%, 95% CI 3·5-5·7) was higher than the prevalence of MDR tuberculosis (2·8%, 2·0-3·6; p=0·01). Comparing the current survey with the previous (2001-02) survey, the overall MDR tuberculosis prevalence was 2·8% versus 2·9% and prevalance of rifampicin-resistant tuberculosis was 3·4% versus 1·8%, respectively. The prevalence of isoniazid mono-resistant tuberculosis was above 5% in all provinces. The prevalence of ethionamide and pyrazinamide resistance among MDR tuberculosis cases was 44·7% (95% CI 25

  19. Delivery of rifampicin-chitin nanoparticles into the intracellular compartment of polymorphonuclear leukocytes.

    Science.gov (United States)

    Smitha, K T; Nisha, N; Maya, S; Biswas, Raja; Jayakumar, R

    2015-03-01

    Polymorphonuclear leukocytes (PMNs) provide the primary host defence against invading pathogens by producing reactive oxygen species (ROS) and microbicidal products. However, few pathogens can survive for a prolonged period of time within the PMNs. Additionally their intracellular lifestyle within the PMNs protect themselves from the additional lethal action of host immune systems such as antibodies and complements. Antibiotic delivery into the intracellular compartments of PMNs is a major challenge in the field of infectious diseases. In order to deliver antibiotics within the PMNs and for the better treatment of intracellular bacterial infections we synthesized rifampicin (RIF) loaded amorphous chitin nanoparticles (RIF-ACNPs) of 350±50 nm in diameter. RIF-ACNPs nanoparticles are found to be non-hemolytic and non-toxic against a variety of host cells. The release of rifampicin from the prepared nanoparticles was ∼60% in 24 h, followed by a sustained pattern till 72 h. The RIF-ACNPs nanoparticles showed 5-6 fold enhanced delivery of RIF into the intracellular compartments of PMNs. The RIF-ACNPs showed anti-microbial activity against Escherichia coli, Staphylococcus aureus and a variety of other bacteria. In summary, our results suggest that RIF-ACNPs could be used to treat a variety of intracellular bacterial infections. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Reaction-in-flight neutrons as a signature for shell mixing in National Ignition Facility capsules

    International Nuclear Information System (INIS)

    Hayes, A. C.; Bradley, P. A.; Grim, G. P.; Jungman, Gerard; Wilhelmy, J. B.

    2010-01-01

    Analytic calculations and results from computational simulations are presented that suggest that reaction-in-flight (RIF) neutrons can be used to diagnose mixing of the ablator shell material into the fuel in deuterium-tritium (DT) capsules designed for the National Ignition Facility (NIF) [J. A. Paisner, J. D. Boyes, S. A. Kumpan, W. H. Lowdermilk, and M. S. Sorem, Laser Focus World 30, 75 (1994)]. Such mixing processes in NIF capsules are of fundamental physical interest and can have important effects on capsule performance, quenching the total thermonuclear yield. The sensitivity of RIF neutrons to hydrodynamical mixing arises through the dependence of RIF production on charged-particle stopping lengths in the mixture of DT fuel and ablator material. Since the stopping power in the plasma is a sensitive function of the electron temperature and density, it is also sensitive to mix. RIF production scales approximately inversely with the degree of mixing taking place, and the ratio of RIF to down-scattered neutrons provides a measure of the mix fraction and/or the mixing length. For sufficiently high-yield capsules, where spatially resolved RIF images may be possible, neutron imaging could be used to map RIF images into detailed mix images.

  1. In vitro activity of rifampicin alone and in combination with imipenem against multidrug-resistant Acinetobacter baumannii harboring the blaOXA-72 resistance gene.

    Science.gov (United States)

    Majewski, Piotr; Wieczorek, Piotr; Ojdana, Dominika; Sacha, Paweł Tomasz; Wieczorek, Anna; Tryniszewska, Elżbieta Anna

    2014-04-01

    The growing incidence of multidrug resistance (MDR) in bacteria is an emerging challenge in the treatment of infections. Acinetobacter baumannii is an opportunistic pathogen prone to exhibit MDR that contributes significantly to nosocomial infections, particularly in severely ill patients. Thus, we performed research on rifampicin activity against selected MDR OXA-72 carbapenemase-producing A. baumannii strains. Since it is widely accepted that rifampicin should not be used as monotherapy in order to avoid the rapid development of rifampicin resistance, we evaluated the efficacy of combination therapy with imipenem. Minimal inhibitory concentrations (MICs) of both rifampicin and imipenem were determined by use of the broth microdilution method. Evaluations of the interactions between rifampicin and imipenem were performed by analysis of the fractional inhibitory concentration index (∑FIC), determined using the checkerboard titration method. All tested isolates showed full susceptibility to rifampicin. The checkerboard method revealed synergism in 5 isolates (29%) and an additive effect in another 5 isolates (29%); no difference was reported in the remaining 7 isolates (41%). Strains moderately resistant to imipenem (MIC ≤ 64 mg/l) tended to show synergy or additive interaction. We conclude that in vitro synergism or an additive interaction between rifampicin and imipenem most likely occurs in A. baumannii strains showing moderate resistance to imipenem (MIC ≤ 64 mg/l). Moreover, utilizing this combination in the therapy of infections caused by strains exhibiting higher levels of resistance (MIC > 64 mg/l) is not recommended since in this setting imipenem could not prevent the development of rifampicin resistance.

  2. THE DIFFERENCE OF MAP1LC3 LEVEL AS MACROPHAGE AUTOPHAGY MARKER BETWEEN RESISTANT AND SENSITIVE TUBERCULOSIS PATIENTS ON RIFAMPICIN

    Directory of Open Access Journals (Sweden)

    Dian novita W

    2018-04-01

    Full Text Available Mycobacterium tuberculosis (MTB is an intracelular bacteria that live in the host macrophage cells. Several organs can be affected by tuberculosis but most major illnesses are lung diseases. Immediately after infection, MTB will be phagocytosed by the alveolar macrophage cells and can survive in the phagosome. The macrophage plays a role in innate immunity towards an infection using autophagy by removing the microbe directly via phagocytosis. When bacteria phagocytosized, vacuole membrane formed double membranes called autophagosome, and followed by degradation by lysosome, which known as autolysosome. Induction of autophagy can be observed on the formation of microtubule-associated proteins 1B lightchain 3B (MAP1LC3B/LC3. MAP1LC3B is protein that have role at autophagic way for selection autophagy substrate and biogenesis. In this study we are used serum from patients TB with rifampicin resistant and rifampicin sensitive as control. Samples were divided using gene expert to differentiate between resistant and sensitive rifampicin.This research aims to compare MAP1LC3B levels in resistant and sensitive rifampicin to study macrophages respond in autophagic way in tuberculosis patients, and give information for define therapy plan to improve therapy for MDR-TB patients. Type of this research is a case control study design with cross sectional research with each groups sample is 19 from age 18-65 years old. Result, MAP1LC3B serum levels on the rifampicin resistant group are lower compared to rifampicin sensitive group. This occur because MTB is able to hide and evade innate immune defense mechanisms. MTB can maintain intracellular growth inside the phagosome by inhibiting phagolysosome formation in autophagy process especially inhibit MAP1LC3B formation by PDIM.

  3. Has introduction of rapid drug susceptibility testing at diagnosis impacted treatment outcomes among previously treated tuberculosis patients in Gujarat, India?

    Directory of Open Access Journals (Sweden)

    Paresh Dave

    Full Text Available Revised National TB Control Programme (RNTCP in India recommends that all previously-treated TB (PT patients are offered drug susceptibility testing (DST at diagnosis, using rapid diagnostics and screened out for rifampicin resistance before being treated with standardized, eight-month, retreatment regimen. This is intended to improve the early diagnosis of rifampicin resistance and its appropriate management and improve the treatment outcomes among the rest of the patients. In this state-wide study from Gujarat, India, we assess proportion of PT patients underwent rapid DST at diagnosis and the impact of this intervention on their treatment outcomes.This is a retrospective cohort study involving review of electronic patient-records maintained routinely under RNTCP. All PT patients registered for treatment in Gujarat during January-June 2013 were included. Information on DST and treatment outcomes were extracted from 'presumptive DR-TB patient register' and TB treatment register respectively. We performed a multivariate analysis to assess if getting tested is independently associated with unfavourable outcomes (death, loss-to-follow-up, failure, transfer out.Of 5,829 PT patients, 5306(91% were tested for drug susceptibility with rapid diagnostics. Overall, 71% (4,113 TB patients were successfully treated - 72% among tested versus 60% among non-tested. Patients who did not get tested at diagnosis had a 34% higher risk of unsuccessful outcomes as compared to those who got tested (aRR - 1.34; 95% CI 1.20-1.50 after adjusting for age, sex, HIV status and type of TB. Unfavourable outcomes (particularly failure and switched to category IV were higher among INH-resistant patients (39% as compared to INH-sensitive (29%.Offering DST at diagnosis improved the treatment outcomes among PT patients. However, even among tested, treatment outcomes remained suboptimal and were related to INH resistance and high loss-to-follow-up. These need to be addressed

  4. Contributions of culture and antimicrobial susceptibility tests to the retreatment of patients with pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Bruno Horta Andrade

    2013-08-01

    Full Text Available Introduction This study evaluated the efficacy of retreatment of pulmonary tuberculosis (TB with regard to treatment outcomes and antimicrobial susceptibility testing (ST profiles. Methods This retrospective cohort study analyzed 144 patients treated at a referral hospital in Brazil. All of them had undergone prior treatment, were smear-positive for TB and received a standardized retreatment regimen. Fisher's 2-tailed exact test and the χ2 test were used; RRs and 95% CIs were calculated using univariate and multivariate binary logistic regression. Results The patients were cured in 84 (58.3% cases. Failure was associated with relapsed treatment and abandonment (n=34. Culture tests were obtained for 103 (71.5% cases; 70 (48.6% had positive results. ST results were available for 67 (46.5% cases; the prevalence of acquired resistance was 53.7%. There were no significant differences between those who achieved or not therapeutic success (p=0.988, despite being sensitive or resistant to 1 or more drugs. Rifampicin resistance was independently associated with therapeutic failure (OR: 4.4, 95% CI:1.12-17.37, p=0.034. For those cases in which cultures were unavailable, a 2nd model without this information was built. In this, return after abandonment was significantly associated with retreatment failure (OR: 3.59, 95% CI:1.17-11.06, p=0.026. Conclusions In this cohort, the general resistance profile appeared to have no influence on treatment outcome, except in cases of rifampicin resistance. The form of reentry was another independent predictor of failure. The use of bacterial culture identification and ST in TB management must be re-evaluated. The recommendations for different susceptibility profiles must also be improved.

  5. Drug resistant tuberculosis in Saudi Arabia: an analysis of surveillance data 2014-2015.

    Science.gov (United States)

    Al Ammari, Maha; Al Turaiki, Abdulrahman; Al Essa, Mohammed; Kashkary, Abdulhameed M; Eltigani, Sara A; Ahmed, Anwar E

    2018-01-01

    There is limited data that investigates the national rates of drug-resistant tuberculosis (TB) in Saudi Arabia.This study aimed to estimate the rates of multi-drug-resistant tuberculosis (MDR-TB), rifampicin-resistant tuberculosis (RR-TB), and monoresistance (MR) in Saudi Arabia. A retrospective cohort study was conducted on all TB cases reported to the National TB Control and Prevention Program (NTCPP) registry at the Saudi Ministry of Health between January 1, 2014 and December 31, 2015. A total of 2098 TB patients with positive TB cultures were included in the study. Subgroup analyses and multivariate binary logistic regression models were performed with IBM SPSS 23.0. Of the total TB cases, 4.4% (95% CI: 3.59%-5.40%) were found to have MDR-TB. The rates of MR were 3.8% (95% CI: 2.99%-4.67%) for ethambutol, 5.4% (95% CI: 4.50%-6.49%) for pyrazinamide, 10.2% (95% CI: 5.89%-11.52%) for isoniazid, 11% (95% CI: 9.70%-12.43%) for streptomycin, and 5.9% (95% CI: 4.90%-6.96%) for rifampicin. The high rates of MDR and RR-TB were found among the younger age group, female gender, and those who had a previous history of TB. We also discovered that renal failure tends to increase the risk of rifampicin resistance. National TB data in Saudi Arabia shows that the rate of MDR-TB was similar to the global rate reported by the World Health Organization (WHO). It is a relatively high rate as compared to Western countries. The proportion of MDR/RR-TB patients tends to be higher in the younger age group, female gender, and in patients with a previous history of TB treatment. Effective strategies for prevention of all multi-drug-resistant TB cases are warranted.

  6. Use of Mycobacterium smegmatis deficient in ADP-ribosyltransferase as surrogate for Mycobacterium tuberculosis in drug testing and mutation analysis.

    Science.gov (United States)

    Agrawal, Priyanka; Miryala, Sandeep; Varshney, Umesh

    2015-01-01

    Rifampicin (Rif) is a first line drug used for tuberculosis treatment. However, the emergence of drug resistant strains has necessitated synthesis and testing of newer analogs of Rif. Mycobacterium smegmatis is often used as a surrogate for M. tuberculosis. However, the presence of an ADP ribosyltransferase (Arr) in M. smegmatis inactivates Rif, rendering it impractical for screening of Rif analogs or other compounds when used in conjunction with them (Rif/Rif analogs). Rifampicin is also used in studying the role of various DNA repair enzymes by analyzing mutations in RpoB (a subunit of RNA polymerase) causing Rif resistance. These analyses use high concentrations of Rif when M. smegmatis is used as model. Here, we have generated M. smegmatis strains by deleting arr (Δarr). The M. smegmatis Δarr strains show minimum inhibitory concentration (MIC) for Rif which is similar to that for M. tuberculosis. The MICs for isoniazid, pyrazinamide, ethambutol, ciprofloxacin and streptomycin were essentially unaltered for M. smegmatis Δarr. The growth profiles and mutation spectrum of Δarr and, Δarr combined with ΔudgB (udgB encodes a DNA repair enzyme that excises uracil) strains were similar to their counterparts wild-type for arr. However, the mutation spectrum of ΔfpgΔarr strain differed somewhat from that of the Δfpg strain (fpg encodes a DNA repair enzyme that excises 8-oxo-G). Our studies suggest M. smegmatis Δarr strain as an ideal model system in drug testing and mutation spectrum determination in DNA repair studies.

  7. Use of Mycobacterium smegmatis deficient in ADP-ribosyltransferase as surrogate for Mycobacterium tuberculosis in drug testing and mutation analysis.

    Directory of Open Access Journals (Sweden)

    Priyanka Agrawal

    Full Text Available Rifampicin (Rif is a first line drug used for tuberculosis treatment. However, the emergence of drug resistant strains has necessitated synthesis and testing of newer analogs of Rif. Mycobacterium smegmatis is often used as a surrogate for M. tuberculosis. However, the presence of an ADP ribosyltransferase (Arr in M. smegmatis inactivates Rif, rendering it impractical for screening of Rif analogs or other compounds when used in conjunction with them (Rif/Rif analogs. Rifampicin is also used in studying the role of various DNA repair enzymes by analyzing mutations in RpoB (a subunit of RNA polymerase causing Rif resistance. These analyses use high concentrations of Rif when M. smegmatis is used as model. Here, we have generated M. smegmatis strains by deleting arr (Δarr. The M. smegmatis Δarr strains show minimum inhibitory concentration (MIC for Rif which is similar to that for M. tuberculosis. The MICs for isoniazid, pyrazinamide, ethambutol, ciprofloxacin and streptomycin were essentially unaltered for M. smegmatis Δarr. The growth profiles and mutation spectrum of Δarr and, Δarr combined with ΔudgB (udgB encodes a DNA repair enzyme that excises uracil strains were similar to their counterparts wild-type for arr. However, the mutation spectrum of ΔfpgΔarr strain differed somewhat from that of the Δfpg strain (fpg encodes a DNA repair enzyme that excises 8-oxo-G. Our studies suggest M. smegmatis Δarr strain as an ideal model system in drug testing and mutation spectrum determination in DNA repair studies.

  8. Noncompetitive retrieval practice causes retrieval-induced forgetting in cued recall but not in recognition.

    Science.gov (United States)

    Grundgeiger, Tobias

    2014-04-01

    Retrieving a subset of learned items can lead to the forgetting of related items. Such retrieval-induced forgetting (RIF) can be explained by the inhibition of irrelevant items in order to overcome retrieval competition when the target item is retrieved. According to the retrieval inhibition account, such retrieval competition is a necessary condition for RIF. However, research has indicated that noncompetitive retrieval practice can also cause RIF by strengthening cue-item associations. According to the strength-dependent competition account, the strengthened items interfere with the retrieval of weaker items, resulting in impaired recall of weaker items in the final memory test. The aim of this study was to replicate RIF caused by noncompetitive retrieval practice and to determine whether this forgetting is also observed in recognition tests. In the context of RIF, it has been assumed that recognition tests circumvent interference and, therefore, should not be sensitive to forgetting due to strength-dependent competition. However, this has not been empirically tested, and it has been suggested that participants may reinstate learned cues as retrieval aids during the final test. In the present experiments, competitive practice or noncompetitive practice was followed by either final cued-recall tests or recognition tests. In cued-recall tests, RIF was observed in both competitive and noncompetitive conditions. However, in recognition tests, RIF was observed only in the competitive condition and was absent in the noncompetitive condition. The result underscores the contribution of strength-dependent competition to RIF. However, recognition tests seem to be a reliable way of distinguishing between RIF due to retrieval inhibition or strength-dependent competition.

  9. The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

    Science.gov (United States)

    Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

    2014-09-01

    Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley

  10. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  11. [Genetic improvement of technological characteristics of starters for fermented milk products].

    Science.gov (United States)

    Oganesian, G G; Barsegian, A A; Grigorian, N G; Toptsian, A V

    2010-01-01

    Possibility for improvement of technological characteristics of lactobacilli using mutations of resistance to rifampicin (rif(r)) and streptomycin (str(r)) was studied. Using starter model of Narine Lactobacillus acidophilus INMIA-9602 Armenian diet milk product, it was showed that a possibility for selecting strains with increased rate of milk fermentation and acid production is higher in Rif(r) and Str(r) mutants induced by nitrosoguanidine than in cultures sensitive to antibiotics. The milk products obtained using Rif(r) and Str(r) strains had high viscosity, improved texture, increased amount of alive cells and good organoleptic features.

  12. An investigation of response competition in retrieval-induced forgetting

    Directory of Open Access Journals (Sweden)

    Gina A. Glanc

    2015-12-01

    Full Text Available It has been demonstrated that retrieval practice on a subset of studied items can cause forgetting of different related studied items. This retrieval-induced forgetting (the RIF effect has been demonstrated in a variety of recall studies and has been attributed to an inhibitory mechanism activated during retrieval practice by competition for a shared retrieval cue. The current study generalizes the RIF effect to recognition memory and investigates this competition assumption. Experiment 1 demonstrated an effect of RIF effect in item recognition with incidental encoding of category-exemplar association during the study phase. Experiment 2 demonstrated evidence of RIF with use of an independent retrieval cue during retrieval practice. Results from this study indicate that response competition may occur outside of the retrieval-practice phase, or may not be limited to situations where there is an overt link to a shared category cue.

  13. Boceprevir

    Science.gov (United States)

    ... Rifadin, Rimactane, in IsonaRif, in Rifamate, in Rifater); sildenafil (only Revatio brand used for lung disease); simvastatin ( ... dexamethasone; certain medications for erectile dysfunction such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra, Staxyn); certain ...

  14. 77 FR 58912 - Additional Designations, Foreign Narcotics Kingpin Designation Act

    Science.gov (United States)

    2012-09-24

    ...(b) of the Kingpin Act. Individual: 1. LOPEZ PERDIGON, Roberto Manuel; DOB 09 Sep 1971; POB Caracas... Cruz, Venezuela; RIF J-31327555-7 (Venezuela) [SDNTK]. Dated: September 13, 2012. Adam J. Szubin...

  15. Retrieval-practice task affects relationship between working memory capacity and retrieval-induced forgetting.

    Science.gov (United States)

    Storm, Benjamin C; Bui, Dung C

    2016-11-01

    Retrieving a subset of items from memory can cause forgetting of other items in memory, a phenomenon referred to as retrieval-induced forgetting (RIF). Individuals who exhibit greater amounts of RIF have been shown to also exhibit superior working memory capacity (WMC) and faster stop-signal reaction times (SSRTs), results which have been interpreted as suggesting that RIF reflects an inhibitory process that is mediated by the processes of executive control. Across four experiments, we sought to further elucidate this issue by manipulating the way in which participants retrieved items during retrieval practice and examining how the resulting effects of forgetting correlated with WMC (Experiments 1-3) and SSRT (Experiment 4). Significant correlations were observed when participants retrieved items from an earlier study phase (within-list retrieval practice), but not when participants generated items from semantic memory (extra-list retrieval practice). These results provide important new insight into the role of executive-control processes in RIF.

  16. Binding of Multiple Rap1 Proteins Stimulates Chromosome Breakage Induction during DNA Replication.

    Directory of Open Access Journals (Sweden)

    Greicy H Goto

    2015-08-01

    Full Text Available Telomeres, the ends of linear eukaryotic chromosomes, have a specialized chromatin structure that provides a stable chromosomal terminus. In budding yeast Rap1 protein binds to telomeric TG repeat and negatively regulates telomere length. Here we show that binding of multiple Rap1 proteins stimulates DNA double-stranded break (DSB induction at both telomeric and non-telomeric regions. Consistent with the role of DSB induction, Rap1 stimulates nearby recombination events in a dosage-dependent manner. Rap1 recruits Rif1 and Rif2 to telomeres, but neither Rif1 nor Rif2 is required for DSB induction. Rap1-mediated DSB induction involves replication fork progression but inactivation of checkpoint kinase Mec1 does not affect DSB induction. Rap1 tethering shortens artificially elongated telomeres in parallel with telomerase inhibition, and this telomere shortening does not require homologous recombination. These results suggest that Rap1 contributes to telomere homeostasis by promoting chromosome breakage.

  17. Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis

    DEFF Research Database (Denmark)

    Rødningen, Olaug Kristin; Børresen-Dale, Anne-Lise; Alsner, Jan

    2008-01-01

    BACKGROUND AND PURPOSE: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last...... years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients. MATERIALS AND METHODS: Fibroblast cell lines from 31 individuals......-treated fibroblasts. Transcriptional differences in basal and radiation-induced gene expression profiles were investigated using 15K cDNA microarrays, and results analyzed by both SAM and PAM. RESULTS: Sixty differentially expressed genes were identified by applying SAM on 10 patients with the highest risk of RIF...

  18. Cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the Brazilian Unified Health Care System

    Directory of Open Access Journals (Sweden)

    Márcia Pinto

    2015-12-01

    Full Text Available ABSTRACT We estimated the costs of a molecular test for Mycobacterium tuberculosis and resistance to rifampin (Xpert MTB/RIF and of smear microscopy, within the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System. In SUS laboratories in the cities of Rio de Janeiro and Manaus, we performed activity-based costing and micro-costing. The mean unit costs for Xpert MTB/RIF and smear microscopy were R$35.57 and R$14.16, respectively. The major cost drivers for Xpert MTB/RIF and smear microscopy were consumables/reagents and staff, respectively. These results might facilitate future cost-effectiveness studies and inform the decision-making process regarding the expansion of Xpert MTB/RIF use in Brazil.

  19. Cost analysis of nucleic acid amplification for diagnosing pulmonary tuberculosis, within the context of the Brazilian Unified Health Care System.

    Science.gov (United States)

    Pinto, Márcia; Entringer, Aline Piovezan; Steffen, Ricardo; Trajman, Anete

    2015-01-01

    We estimated the costs of a molecular test for Mycobacterium tuberculosis and resistance to rifampin (Xpert MTB/RIF) and of smear microscopy, within the Brazilian Sistema Único de Saúde (SUS, Unified Health Care System). In SUS laboratories in the cities of Rio de Janeiro and Manaus, we performed activity-based costing and micro-costing. The mean unit costs for Xpert MTB/RIF and smear microscopy were R$35.57 and R$14.16, respectively. The major cost drivers for Xpert MTB/RIF and smear microscopy were consumables/reagents and staff, respectively. These results might facilitate future cost-effectiveness studies and inform the decision-making process regarding the expansion of Xpert MTB/RIF use in Brazil.

  20. Transforming Growth Factor β-1 (TGF-β1) Is a Serum Biomarker of Radiation Induced Fibrosis in Patients Treated With Intracavitary Accelerated Partial Breast Irradiation: Preliminary Results of a Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Boothe, Dustin L. [Weill Cornell Medical College of Cornell University, New York, New York (United States); Coplowitz, Shana [Department of Radiation Oncology, Stich Radiation Center, Weill Cornell Medical College of Cornell University, New York, New York (United States); Greenwood, Eleni [Weill Cornell Medical College of Cornell University, New York, New York (United States); Barney, Christian L. [Department of Radiation Oncology, Ohio State University, Columbus, Ohio (United States); Christos, Paul J. [Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College of Cornell University, New York, New York (United States); Parashar, Bhupesh; Nori, Dattatreyudu; Chao, K. S. Clifford [Department of Radiation Oncology, Stich Radiation Center, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9008@med.cornell.edu [Department of Radiation Oncology, Stich Radiation Center, Weill Cornell Medical College of Cornell University, New York, New York (United States)

    2013-12-01

    Purpose: To examine a relationship between serum transforming growth factor β -1 (TGF-β1) values and radiation-induced fibrosis (RIF). Methods and Materials: We conducted a prospective analysis of the development of RIF in 39 women with American Joint Committee on Cancer stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via intracavitary brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, R and D, Minneapolis, MN) was used to measure serum TGF-β1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, nontreated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess RIF. Results: The median time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20 patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively. The mean serum TGF-β1 values were significantly higher in patients before surgery than in disease-free controls, as follows: all cancer patients (30,201 ± 5889 pg/mL, P=.02); patients with any type of RIF (32,273 ± 5016 pg/mL, P<.0001); and women with moderate to severe RIF (34,462 ± 4713 pg/mL, P<0.0001). Patients with moderate to severe RIF had significantly elevated TGF-β1 levels when compared with those with none to mild RIF before surgery (P=.0014) during IBAPBI (P≤0001), and the elevation persisted at 6 months (P≤.001), 12 months (P≤.001), 18 months (P≤.001), and 24 months (P=.12). A receiver operating characteristic (ROC) curve of TGF-β1 values predicting moderate to severe RIF was generated with an area under the curve (AUC){sub ROC} of 0.867 (95% confidence interval 0.700-1.000). The TGF-β1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively. Conclusions: TGF-β1 levels correlate with

  1. Whole Genome Sequencing Investigation of a Tuberculosis Outbreak in Port-au-Prince, Haiti Caused by a Strain with a "Low-Level" rpoB Mutation L511P - Insights into a Mechanism of Resistance Escalation.

    Directory of Open Access Journals (Sweden)

    Oksana Ocheretina

    Full Text Available The World Health Organization recommends diagnosing Multidrug-Resistant Tuberculosis (MDR-TB in high burden countries by detection of mutations in Rifampin (RIF Resistance Determining Region of Mycobacterium tuberculosis rpoB gene with rapid molecular tests GeneXpert MTB/RIF and Hain MTBDRplus. Such mutations are found in >95% of Mycobacterium tuberculosis strains resistant to RIF by conventional culture-based drug susceptibility testing (DST. However routine diagnostic screening with molecular tests uncovered specific "low level" rpoB mutations conferring resistance to RIF below the critical concentration of 1 μg/ml in some phenotypically susceptible strains. Cases with discrepant phenotypic (susceptible and genotypic (resistant results for resistance to RIF account for at least 10% of resistant diagnoses by molecular tests and urgently require new guidelines to inform therapeutic decision making. Eight strains with a "low level" rpoB mutation L511P were isolated by GHESKIO laboratory between 2008 and 2012 from 6 HIV-negative and 2 HIV-positive patients during routine molecular testing. Five isolates with a single L511P mutation and two isolates with double mutation L511P&M515T had MICs for RIF between 0.125 and 0.5 μg/ml and tested susceptible in culture-based DST. The eighth isolate carried a double mutation L511P&D516C and was phenotypically resistant to RIF. All eight strains shared the same spoligotype SIT 53 commonly found in Haiti but classic epidemiological investigation failed to uncover direct contacts between the patients. Whole Genome Sequencing (WGS revealed that L511P cluster isolates resulted from a clonal expansion of an ancestral strain resistant to Isoniazid and to a very low level of RIF. Under the selective pressure of RIF-based therapy the strain acquired mutation in the M306 codon of embB followed by secondary mutations in rpoB and escalation of resistance level. This scenario highlights the importance of subcritical

  2. Abnormal phenotype of cultured fibroblasts in human skin with chronic radiotherapy damage

    International Nuclear Information System (INIS)

    Delanian, S.; Martin, M.; Lefaix, J.-L.; Bravard, A.; Luccioni, C.

    1998-01-01

    Purpose: The pathophysiological aspects of radiation-induced fibrosis (RIF) have not been well characterized. We therefore cultured human fibroblasts from samples of skin with RIF to investigate the long-term effects of therapeutic irradiation. Materials and methods: Biopsies of normal and RIF skin were obtained from patients previously irradiated for cancer, without recurrence. Cells were extracted from dermis samples by the outgrowth technique, seeded as monolayers and cultured at confluence. Enzyme activities and proteins were assayed, RNA was isolated and Northern blot analysis was performed on surviving cells between passages 2 and 5. Results: RIF cell cultures displayed heterogeneous fibroblasts populations. The initial outgrowth consisted of one-third small cells that floated rapidly, one-third spindle-shaped cells migrating far from the explant to form islets and one-third large pleiomorphic cells. In subsequent subcultures, surviving cells exhibited either myofibroblastic characteristics with a normal proliferative capacity or senescent morphology with a reduced proliferative capacity. These RIF cells had a brief finite lifespan, with dramatically reduced growth rate during their initial outgrowth and the following passages. Study of the antioxidant metabolism showed that Mn superoxide dismutase and catalase activities were significantly weaker in surviving RIF cells than healthy fibroblasts. These exhausted RIF cells exhibited no overexpression of transforming growth factor β or tissue inhibitor of metalloproteinase. Conclusion: Irradiation may lead to apparently contradictory effects such as fibrosis and necrosis in clinical practice. In cell culture, we observed two main cellular phenotypes which may be related to both processes, i.e. myofibroblast-like cells and fibrocyte-like cells. These two phenotypes may represent two steps in the differentiation induced as a long-term effect of therapeutic irradiation of the skin. Cell culture probably

  3. Temporary storage area characterization report

    International Nuclear Information System (INIS)

    1990-01-01

    The preferred alternative identified in the Remedial Investigation/Feasibility Study (RI/FS) for the Weldon Spring Quarry Bulk Wastes is to remove the wastes from the quarry and transport them by truck to temporary storage facility at the chemical plant site. To support the RI/FS, this report provides data to characterize the temporary storage area (TSA) site and to ensure the suitability of the proposed location. 31 refs., 14 figs., 7 tabs

  4. The Rise of Syria’s Urban Poor: Why the War for Syria’s Future Will Be Fought Over the Country’s New Urban Villages

    Science.gov (United States)

    2014-01-01

    the words rif and medina have developed not just geographic connotations, but social ones as well. The rif not only describes village farmers but...growing in. The poor farmers were bringing their customs… to cosmopolitan Aleppo. …They were turning their apartments into compact versions of their...opposition activity. Baba Amr, a slum of Homs adjacent to the orchards that once fed the city, is synonymous with the THE RISE OF SYRIA’S POOR

  5. It's in the details: The role of selective discussion in forgetting of children's autobiographical memories.

    Science.gov (United States)

    Glynn, Ruth; Salmon, Karen; Low, Jason

    2018-03-01

    This experiment investigated whether retrieval-induced forgetting (RIF) would be found in children's self-generated autobiographical memory recall. An adapted version of the RIF paradigm for adults' autobiographical memories was administered to 8- and 9-year-old children (N = 65). We hypothesized that RIF would be found in terms of both number of memories recalled and amount of memory detail reported. The relationship between memory detail at the retrieval practice phase and RIF magnitude was also investigated. Consistent with hypotheses, RIF was found for both the number of memories recalled and the amount of memory detail reported. In addition, memory detail at retrieval practice was associated with increased RIF magnitude. Findings extend the current literature in three ways. First, they indicate that selective discussion of autobiographical events with children can cause forgetting of similar non-discussed events. Second, even when these non-discussed events are recalled, they contain sparser memory detail. Finally, when events are selectively discussed in greater detail, forgetting of similar non-discussed events occurs to a greater extent. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Reaction-in-flight neutrons as a test of stopping power in degenerate plasmas

    Science.gov (United States)

    Hayes, A. C.; Jungman, Gerard; Schulz, A. E.; Boswell, M.; Fowler, M. M.; Grim, G.; Klein, A.; Rundberg, R. S.; Wilhelmy, J. B.; Wilson, D.; Cerjan, C.; Schneider, D.; Sepke, S. M.; Tonchev, A.; Yeamans, C.

    2015-08-01

    We present the first measurements of reaction-in-flight (RIF) neutrons in an inertial confinement fusion system. The experiments were carried out at the National Ignition Facility, using both Low Foot and High Foot drives and cryogenic plastic capsules. In both cases, the high-energy RIF ( En> 15 MeV) component of the neutron spectrum was found to be about 10-4 of the total. The majority of the RIF neutrons were produced in the dense cold fuel surrounding the burning hotspot of the capsule, and the data are consistent with a compressed cold fuel that is moderately to strongly coupled (Γ˜ 0.6) and electron degenerate (θFermi/θe˜ 4). The production of RIF neutrons is controlled by the stopping power in the plasma. Thus, the current RIF measurements provide a unique test of stopping power models in an experimentally unexplored plasma regime. We find that the measured RIF data strongly constrain stopping models in warm dense plasma conditions, and some models are ruled out by our analysis of these experiments.

  7. Putting retrieval-induced forgetting in context: an inhibition-free, context-based account.

    Science.gov (United States)

    Jonker, Tanya R; Seli, Paul; MacLeod, Colin M

    2013-10-01

    We present a new theoretical account of retrieval-induced forgetting (RIF) together with new experimental evidence that fits this account and challenges the dominant inhibition account. RIF occurs when the retrieval of some material from memory produces later forgetting of related material. The inhibition account asserts that RIF is the result of an inhibition mechanism that acts during retrieval to suppress the representations of interfering competitors. This inhibition is enduring, such that the suppressed material is difficult to access on a later test and is, therefore, recalled more poorly than baseline material. Although the inhibition account is widely accepted, a growing body of research challenges its fundamental assumptions. Our alternative account of RIF instead emphasizes the role of context in remembering. According to this context account, both of 2 tenets must be met for RIF to occur: (a) A context change must occur between study and subsequent retrieval practice, and (b) the retrieval practice context must be the active context during the final test when testing practiced categories. The results of 3 experiments, which directly test the divergent predictions of the 2 accounts, support the context account but cannot be explained by the inhibition account. In an extensive discussion, we survey the literature on RIF and apply our context account to the key findings, demonstrating the explanatory power of context. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  8. Increased circulating cell-derived microparticle count is associated with recurrent implantation failure after IVF and embryo transfer.

    Science.gov (United States)

    Martínez-Zamora, M Angeles; Tàssies, Dolors; Reverter, Juan Carlos; Creus, Montserrat; Casals, Gemma; Cívico, Salvadora; Carmona, Francisco; Balasch, Juan

    2016-08-01

    Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) (n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups (P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosphatidylserine equivalent [PS eq]; IVF group: 10.9 ± 5.3 nM PS eq; FER group: 9.6 ± 4.0 nM PS eq). No statistical difference was found in cMP count between the IVF and FER groups. Increased cMP count is, therefore, associated with RIF after IVF and embryo transfer. Copyright © 2016. Published by Elsevier Ltd.

  9. Biotransformation and recovery of the isoflavones genistein and daidzein from industrial antibiotic fermentations

    Science.gov (United States)

    Weber, J. Mark; Reeves, Andrew R.; Seshadri, Ramya; Cernota, William H.; Gonzalez, Melissa C.; Gray, Danielle L.; Wesley, Roy K.

    2013-01-01

    The objective of this study was to follow the metabolic fate of isoflavone glucosides from the soybean meal in a model industrial fermentation to determine if commercially useful isoflavones could be harvested as coproducts from the spent broth at the end of the fermentation. The isoflavone aglycones, genistein and daidzein, together make up 0.1 - 0.2% of the soybean meal by weight but serve no known function in the manufacturing process. After feeding genistein to washed cells of the erythromycin-producing organism, Saccharopolyspora erythraea, the first biotransformation product (Gbp1) was determined by x-ray crystallography to be genistein-7-O-α-rhamnoside (rhamnosylgenistein). Subsequent feeding of rhamnosylgenistein to growing cells of S. erythraea led to the production of a second biotransformation product, Gbp2. Chromatographic evidence suggested that Gbp2 accumulated in the spent broth of the erythromycin fermentation. When the spent broth was hydrolyzed with acid or industrial enzyme preparations the isoflavone biotransformation products were returned back to their parental forms, genistein and daidzein, which were then recovered as coproducts. Desirable features of this method are that it does not require modification of the erythromycin manufacturing process or genetic engineering of the producing organism to be put into practice. A preliminary investigation of five additional antibiotic fermentations of industrial importance were also found to have isoflavone coproduct potential. PMID:23604533

  10. In vitro antiplasmodial, antileishmanial and antitrypanosomal activities of selected medicinal plants used in the traditional Arabian Peninsular region

    Directory of Open Access Journals (Sweden)

    Al-Musayeib Nawal M

    2012-04-01

    Full Text Available Abstract Background Worldwide particularly in developing countries, a large proportion of the population is at risk for tropical parasitic diseases. Several medicinal plants are still used traditionally against protozoal infections in Yemen and Saudi Arabia. Thus the present study investigated the in vitro antiprotozoal activity of twenty-five plants collected from the Arabian Peninsula. Methods Plant materials were extracted with methanol and screened in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxic activity was determined against MRC-5 cells to assess selectivity. The criterion for activity was an IC50 T. brucei and selectivity index of >4. Results Antiplasmodial activity was found in the extracts of Chrozophora oblongifolia, Ficus ingens, Lavandula dentata and Plectranthus barbatus. Amastigotes of T. cruzi were affected by Grewia erythraea, L. dentata, Tagetes minuta and Vernonia leopoldii. Activity against T. brucei was obtained in G. erythraea, L. dentata, P. barbatus and T. minuta. No relevant activity was found against L. infantum. High levels of cytotoxicity (MRC-5 IC50 Cupressus sempervirens, Kanahia laniflora and Kniphofia sumarae. Conclusion The results endorse that medicinal plants can be promising sources of natural products with antiprotozoal activity potential. The results support to some extent the traditional uses of some plants for the treatment of parasitic protozoal diseases.

  11. Characterizing the DNA Damage Response by Cell Tracking Algorithms and Cell Features Classification Using High-Content Time-Lapse Analysis.

    Directory of Open Access Journals (Sweden)

    Walter Georgescu

    Full Text Available Traditionally, the kinetics of DNA repair have been estimated using immunocytochemistry by labeling proteins involved in the DNA damage response (DDR with fluorescent markers in a fixed cell assay. However, detailed knowledge of DDR dynamics across multiple cell generations cannot be obtained using a limited number of fixed cell time-points. Here we report on the dynamics of 53BP1 radiation induced foci (RIF across multiple cell generations using live cell imaging of non-malignant human mammary epithelial cells (MCF10A expressing histone H2B-GFP and the DNA repair protein 53BP1-mCherry. Using automatic extraction of RIF imaging features and linear programming techniques, we were able to characterize detailed RIF kinetics for 24 hours before and 24 hours after exposure to low and high doses of ionizing radiation. High-content-analysis at the single cell level over hundreds of cells allows us to quantify precisely the dose dependence of 53BP1 protein production, RIF nuclear localization and RIF movement after exposure to X-ray. Using elastic registration techniques based on the nuclear pattern of individual cells, we could describe the motion of individual RIF precisely within the nucleus. We show that DNA repair occurs in a limited number of large domains, within which multiple small RIFs form, merge and/or resolve with random motion following normal diffusion law. Large foci formation is shown to be mainly happening through the merging of smaller RIF rather than through growth of an individual focus. We estimate repair domain sizes of 7.5 to 11 µm2 with a maximum number of ~15 domains per MCF10A cell. This work also highlights DDR which are specific to doses larger than 1 Gy such as rapid 53BP1 protein increase in the nucleus and foci diffusion rates that are significantly faster than for spontaneous foci movement. We hypothesize that RIF merging reflects a "stressed" DNA repair process that has been taken outside physiological conditions when

  12. Effect of Rifampin on Thyroid Function Test in Patients on Levothyroxine Medication.

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    Hye In Kim

    Full Text Available Levothyroxine (LT4 and rifampin (RIF are sometimes used together; however, no clinical studies have assessed the effects of these drugs on thyroid function or the need to adjust LT4 dose.We retrospectively reviewed the records of 71 Korean patients who started RIF during LT4 treatment. Clinically relevant cases that required dose adjustment according to the American Thyroid Association (ATA/American Association of Clinical Endocrinologists (AACE guidelines were identified, and risk factors of increased LT4 dose were analyzed.After administering RIF, median serum thyroid-stimulating hormone (TSH level (2.58 mIU/L, interquartile range [IQR] 0.21-7.44 was significantly higher than that before RIF (0.25 mIU/L, IQR, 0.03-2.62; P < 0.001. An increased LT4 dose was required for 50% of patients in the TSH suppression group for thyroid cancer and 26% of patients in the replacement group for hypothyroidism. Risk factor analysis showed that remaining thyroid gland (odds ratio [OR] 9.207, P = 0.002, the time interval between starting RIF and TSH measurement (OR 1.043, P = 0.019, and baseline LT4 dose per kg body weight (OR 0.364, P = 0.011 were clinically relevant variables.In patients receiving LT4, serum thyroid function test should be performed after starting RIF treatment. For patients with no remnant thyroid gland and those receiving a lower LT4 dose, close observation is needed when starting RIF and TB medication.

  13. Rapid screening of rpoB and katG mutations in Mycobacterium tuberculosis isolates by high-resolution melting curve analysis

    Directory of Open Access Journals (Sweden)

    M Haeili

    2014-01-01

    Full Text Available Background: Early detection of multidrug-resistant tuberculosis (MDR-TB is essential to prevent its transmission in the community and initiate effective anti-TB treatment regimen. Materials and Methods: High-resolution melting curve (HRM analysis was evaluated for rapid detection of resistance conferring mutations in rpoB and katG genes. We screened 95 Mycobacterium tuberculosis clinical isolates including 20 rifampin resistant (RIF-R, 21 isoniazid resistant (INH-R and 54 fully susceptible (S isolates determined by proportion method of drug susceptibility testing. Nineteen M. tuberculosis isolates with known drug susceptibility genotypes were used as references for the assay validation. The nucleotide sequences of the target regions rpoB and katG genes were determined to investigate the frequency and type of mutations and to confirm HRM results. Results: HRM analysis of a 129-bp fragment of rpoB allowed correct identification of 19 of the 20 phenotypically RIF-R and all RIF-S isolates. All INH-S isolates generated wild-type HRM curves and 18 out of 21 INH-R isolates harboured any mutation in 109-bp fragment of katG exhibited mutant type HRM curves. However, 1 RIF-R and 3 INH-R isolates were falsely identified as susceptible which were confirmed for having no mutation in their target regions by sequencing. The main mutations involved in RIF and INH resistance were found at codons rpoB531 (60% of RIF-R isolates and katG315 (85.7% of INH-R isolates, respectively. Conclusion: HRM was found to be a reliable, rapid and low cost method to characterise drug susceptibility of clinical TB isolates in resource-limited settings.

  14. Why did the FDA approve efavirenz 800 mg when co-administered with rifampin?

    Science.gov (United States)

    Liu, Jiang; Chan-Tack, Kirk M; Jadhav, Pravin; Seo, Shirley; Robertson, Sarah M; Kraft, Jeffrey; Singer, Mary E; Struble, Kimberly A; Arya, Vikram

    2014-06-01

    Literature reports regarding the efficacy of efavirenz (EFV) 600 mg with rifampin (RIF) are not consistent. Evaluation of a drug-drug interaction (DDI) study and supportive semi-mechanistic population pharmacokinetic (PK) analyses were undertaken to help delineate this issue. DDI study and supportive semi-mechanistic population PK analyses were provided by BMS. Population PK analysis was based on six studies with intensive EFV PK sampling. An ACTG study with sparse PK sampling was used for model evaluation. Simulations compared EFV exposure at various doses in combination with RIF to EFV exposures at 600 mg once daily (QD). Effects of CYP2B6 genotypes on the magnitude of EFV-RIF interaction were also explored. In DDI study, co-administering EFV 600 mg QD and RIF reduced mean EFV exposure by ~ 30%. Population PK model provided acceptable predictive performance of central tendency and variability for EFV C0, Cmax, and AUC. Simulations predicted that increasing EFV to 800 mg QD with RIF would result in EFV AUC and Cmax similar to EFV 600 mg QD alone. EFV AUC and Cmax were ~ 2 times higher in subjects with reduced function CYP2B6 genotypes. However, the RIF effect was consistent across all genotypes. EFV dose adjustment to 800 mg QD did not increase the risk of overexposure compared to 600 mg EFV QD within each genotype. Dose adjustment based on matching systemic exposure was recommended to mitigate the potential for sub-therapeutic EFV exposures. Our review did not reveal any safety concerns in subjects receiving EFV 800 mg QD with RIF.

  15. Exploring Genetic Attributions Underlying Radiotherapy-Induced Fatigue in Prostate Cancer Patients.

    Science.gov (United States)

    Hashemi, Sepehr; Fernandez Martinez, Juan Luis; Saligan, Leorey; Sonis, Stephen

    2017-09-01

    Despite numerous proposed mechanisms, no definitive pathophysiology underlying radiotherapy-induced fatigue (RIF) has been established. However, the dysregulation of a set of 35 genes was recently validated to predict development of fatigue in prostate cancer patients receiving radiotherapy. To hypothesize novel pathways, and provide genetic targets for currently proposed pathways implicated in RIF development through analysis of the previously validated gene set. The gene set was analyzed for all phenotypic attributions implicated in the phenotype of fatigue. Initially, a "directed" approach was used by querying specific fatigue-related sub-phenotypes against all known phenotypic attributions of the gene set. Then, an "undirected" approach, reviewing the entirety of the literature referencing the 35 genes, was used to increase analysis sensitivity. The dysregulated genes attribute to neural, immunological, mitochondrial, muscular, and metabolic pathways. In addition, certain genes suggest phenotypes not previously emphasized in the context of RIF, such as ionizing radiation sensitivity, DNA damage, and altered DNA repair frequency. Several genes also associated with prostate cancer depression, possibly emphasizing variable radiosensitivity by RIF-prone patients, which may have palliative care implications. Despite the relevant findings, many of the 35 RIF-predictive genes are poorly characterized, warranting their investigation. The implications of herein presented RIF pathways are purely theoretical until specific end-point driven experiments are conducted in more congruent contexts. Nevertheless, the presented attributions are informative, directing future investigation to definitively elucidate RIF's pathoetiology. This study demonstrates an arguably comprehensive method of approaching known differential expression underlying a complex phenotype, to correlate feasible pathophysiology. Copyright © 2017 American Academy of Hospice and Palliative Medicine. All

  16. Synthesis of biocompatible nanoparticle drug complexes for inhibition of mycobacteria

    International Nuclear Information System (INIS)

    Bhave, Tejashree; Ghoderao, Prachi; Sanghavi, Sonali; Babrekar, Harshada; Bhoraskar, S V; Ganesan, V; Kulkarni, Anjali

    2013-01-01

    Tuberculosis (TB) is one of the most critical infectious diseases affecting the world today. Current TB treatment involves six months long daily administration of four oral doses of antibiotics. Due to severe side effects and the long treatment, a patient's adherence is low and this results in relapse of symptoms causing an alarming increase in the prevalence of multi-drug resistant (MDR) TB. Hence, it is imperative to develop a new drug delivery technology wherein these effects can be reduced. Rifampicin (RIF) is one of the widely used anti-tubercular drugs (ATD). The present study discusses the development of biocompatible nanoparticle–RIF complexes with superior inhibitory activity against both Mycobacterium smegmatis (M. smegmatis) and Mycobacterium tuberculosis (M. tuberculosis). Iron oxide nanoparticles (NPs) synthesized by gas phase condensation and NP-RIF complexes were tested against M. smegmatis SN2 strain as well as M. tuberculosis H37Rv laboratory strain. These complexes showed significantly better inhibition of M. smegmatis SN2 strain at a much lower effective concentration (27.5 μg ml −1 ) as compared to neat RIF (125 μg ml −1 ). Similarly M. tuberculosis H37Rv laboratory strain was susceptible to both nanoparticle–RIF complex and neat RIF at a minimum inhibitory concentration of 0.22 and 1 μg ml −1 , respectively. Further studies are underway to determine the efficacy of NPs–RIF complexes in clinical isolates of M. tuberculosis as well as MDR isolates. (paper)

  17. Image-Based Modeling Reveals Dynamic Redistribution of DNA Damageinto Nuclear Sub-Domains

    Energy Technology Data Exchange (ETDEWEB)

    Costes Sylvain V., Ponomarev Artem, Chen James L.; Nguyen, David; Cucinotta, Francis A.; Barcellos-Hoff, Mary Helen

    2007-08-03

    Several proteins involved in the response to DNA doublestrand breaks (DSB) f orm microscopically visible nuclear domains, orfoci, after exposure to ionizing radiation. Radiation-induced foci (RIF)are believed to be located where DNA damage occurs. To test thisassumption, we analyzed the spatial distribution of 53BP1, phosphorylatedATM, and gammaH2AX RIF in cells irradiated with high linear energytransfer (LET) radiation and low LET. Since energy is randomly depositedalong high-LET particle paths, RIF along these paths should also berandomly distributed. The probability to induce DSB can be derived fromDNA fragment data measured experimentally by pulsed-field gelelectrophoresis. We used this probability in Monte Carlo simulations topredict DSB locations in synthetic nuclei geometrically described by acomplete set of human chromosomes, taking into account microscope opticsfrom real experiments. As expected, simulations produced DNA-weightedrandom (Poisson) distributions. In contrast, the distributions of RIFobtained as early as 5 min after exposure to high LET (1 GeV/amu Fe) werenon-random. This deviation from the expected DNA-weighted random patterncan be further characterized by "relative DNA image measurements." Thisnovel imaging approach shows that RIF were located preferentially at theinterface between high and low DNA density regions, and were morefrequent than predicted in regions with lower DNA density. The samepreferential nuclear location was also measured for RIF induced by 1 Gyof low-LET radiation. This deviation from random behavior was evidentonly 5 min after irradiation for phosphorylated ATM RIF, while gammaH2AXand 53BP1 RIF showed pronounced deviations up to 30 min after exposure.These data suggest that DNA damage induced foci are restricted to certainregions of the nucleus of human epithelial cells. It is possible that DNAlesions are collected in these nuclear sub-domains for more efficientrepair.

  18. Study on enhancement protease-producing of Bacillus subtilis by combining ribosome engineering and gamma irradiation

    International Nuclear Information System (INIS)

    Tran Bang Diep; Nguyen Thi Thom; Hoang Dang Sang; Nguyen Van Binh; Tran Xuan An; Hoang Phuong Thao; Pham Duy Duong; Tran Minh Quynh; Ta Bich Thuan; Vo Thi Thuong Lan

    2017-01-01

    Bacillus subtilis B5, Bacillus subtilis H12 and Bacillus subtilis VI are high protease-producing bacteria selected from various domestic laboratories. The suspensions in logarithmic growth phase and nutrient agar plates inoculated these bacteria were irradiated at dose ranging 0-3000 Gy under gamma Cobalt-60 source at Hanoi Irradiation Center. In both cases of irradiation treatment, the viability of Bacillus subtilis strains was much affected by gamma radiation and the survival rate of bacteria decreases with the increasing dose. The rate of high protease-producing mutation in three kinds of Bacillus strains seems to be greater at the dose range of 700-1500 Gy, at which the survival cells of bacteria was reduced by 3-4 log unit. In this study, the effect of gamma irradiation at different doses to mutation frequency of antibiotic resistance (rifampicin 0.2 µg/ml and streptomycin 20 µg/ml) of Bacillus subtilis strains is also investigated. The results show that the mutation frequency of antibiotic resistance was improved significantly by radiation treatment. The frequency of rifampicin-resistance reached the highest value at dose of 2000 Gy, 0.93-5.46x10 3 times higher than the frequency of spontaneous mutation. On the other hand, the highest streptomycin mutation frequency was obtained by irradiation at 1000 Gy. After the first screening, 82 potential 0.2 µg/ml rifampicin-resistant and 25 potential 20 µg/ml streptomycin-resistant colonies with higher production of protease than original strain were selected from the irradiated Bacillus subtilis B5 and H12. In the subsequent screening, some mutants having 2-2.5 times higher of protease activity than that of parent strain were obtained by using the culture medium containing incrementally higher antibiotic concentrations. The results of PCR, cloning and sequencing techniques proved that the antibiotic-resistance of Bacillus subtilis due to mutate in rpoB gene involved in these bacteria’s protease synthesis

  19. Primary drug-resistant tuberculosis in Hanoi, Viet Nam: present status and risk factors.

    Directory of Open Access Journals (Sweden)

    Nguyen Thi Le Hang

    Full Text Available INTRODUCTION: Resistance of Mycobacterium tuberculosis (MTB to anti-tuberculosis (TB drugs presents a serious challenge to TB control worldwide. We investigated the status of drug resistance, including multidrug-resistant (MDR TB, and possible risk factors among newly diagnosed TB patients in Hanoi, the capital of Viet Nam. METHODS: Clinical and epidemiological information was collected from 506 newly diagnosed patients with sputum smear- and culture-positive TB, and 489 (96.6% MTB isolates were subjected to conventional drug susceptibility testing, spoligotyping, and 15-locus variable numbers of tandem repeats typing. Adjusted odds ratios (aORs were calculated to analyze the risk factors for primary drug resistance. RESULTS: Of 489 isolates, 298 (60.9% were sensitive to all drugs tested. Resistance to isoniazid, rifampicin, streptomycin, ethambutol, and MDR accounted for 28.2%, 4.9%, 28.2%, 2.9%, and 4.5%, respectively. Of 24 isolates with rifampicin resistance, 22 (91.7% were MDR and also resistant to streptomycin, except one case. Factors associated with isoniazid resistance included living in old urban areas, presence of the Beijing genotype, and clustered strains [aOR = 2.23, 95% confidence interval (CI 1.15-4.35; 1.91, 1.18-3.10; and 1.69, 1.06-2.69, respectively. The Beijing genotype was also associated with streptomycin resistance (aOR = 2.10, 95% CI 1.29-3.40. Human immunodeficiency virus (HIV coinfection was associated with rifampicin resistance and MDR (aOR = 5.42, 95% CI 2.07-14.14; 6.23, 2.34-16.58, respectively. CONCLUSION: Isoniazid and streptomycin resistance was observed in more than a quarter of TB patients without treatment history in Hanoi. Transmission of isoniazid-resistant TB among younger people should be carefully monitored in urban areas, where Beijing strains and HIV coinfection are prevalent. Choosing an optimal treatment regimen on the basis of the results of drug susceptibility tests and monitoring of treatment

  20. Bactericidal activity does not predict sterilizing activity: the case of rifapentine in the murine model of Mycobacterium ulcerans disease.

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    Deepak V Almeida

    Full Text Available Since 2004, treatment of Mycobacterium ulcerans disease, or Buruli ulcer, has shifted from surgery to daily treatment with streptomycin (STR + rifampin (RIF for 8 weeks. For shortening treatment duration, we tested the potential of daily rifapentine (RPT, a long-acting rifamycin derivative, as a substitute for RIF.BALB/c mice were infected with M. ulcerans in the right hind footpad and treated either daily (7/7 with STR+RIF or five days/week (5/7 with STR+RIF or STR+RPT for 4 weeks, beginning 28 days after infection when CFU counts were 4.88±0.51. The relative efficacy of the drug treatments was compared by footpad CFU counts during treatment and median time to footpad swelling after treatment cessation as measure of sterilizing activity. All drug treatments were bactericidal. After 1 week of treatment, the decline in CFU counts was significantly greater in treated mice but not different between the three treated groups. After 2 weeks of treatment, the decline in CFU was greater in mice treated with STR+RPT 5/7 than in mice treated with STR+RIF 7/7 and STR+RIF 5/7. After 3 and 4 weeks of treatment, CFU counts were nil in mice treated with STR+RPT and reduced by more than 3 and 4 logs in mice treated with STR+RIF 5/7 and STR+RIF 7/7, respectively. In sharp contrast to the bactericidal activity, the sterilizing activity was not different between all drug regimens although it was in proportion to the treatment duration.The better bactericidal activity of daily STR+RIF and especially of STR+RPT did not translate into better prevention of relapse, possibly because relapse-freecure after treatment of Buruli ulcer is more related to the reversal of mycolactone-induced local immunodeficiency by drug treatment rather than to the bactericidal potency of drugs.

  1. Influences of Realgar-Indigo naturalis, A Traditional Chinese Medicine Formula, on the Main CYP450 Activities in Rats Using a Cocktail Method

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    Huan-Hua Xu

    2017-01-01

    Full Text Available The purpose of this work was to study the influences of Realgar-Indigo naturalis (RIF and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities. The results showed that RIF could inhibit CYP1A2 enzyme activity and induce CYP2C11 enzyme activity significantly. Interestingly, in realgar high dosage group, CYP3A1/2 enzyme activity was inhibited significantly, and different dosage of realgar manifested a good dose-dependent manner. The RIF results indicated that drug coadministrated with RIF may need to be paid attention in relation to drug-drug interactions (DDIs. Realgar, a toxic traditional Chinese medicine (TCM, does have curative effect on acute promyelocytic leukemia (APL. Its toxicity studies should be focused on. We found that, in realgar high dosage group, CYP3A1/2 enzymes activity was inhibited. This phenomenon may explain its potential toxicity mechanism.

  2. Proceedings of the remedial investigation/feasibility study workshop

    International Nuclear Information System (INIS)

    1988-12-01

    The objective of this workshop was to familiarize Department of Energy (DOE) personnel and contractors with all aspects of developing, managing, and conducting an RI/FS, based on HAZWRAP SCO experience in similar activities as part of the Installation Restoration program (IRP). The HAZWRAP SCO participation in Department of Defense (DOD) restoration activities provides an opportunity to develop capability and experience which are transferable to DOE activities. Paul Franco, Program Manager for the IRP, provided an overview of the IRP experience in conducting an RI/FS for a National Priorities List (NPL) site and a non-NPL site. A non-NPL site does not require an RI/FS by regulation; however, the RI/FS process can be used to determine whether to proceed with a feasibility study or terminate the action with a decision document. Al Porell, Program Manager for ICP, discussed the use of decision documents to remove non-NPL sites from regulatory consideration. DOE-Idaho has used similar documentation to remove numerous sites from their list of potential remedial action sites. Mr. Porell also discussed the use of the Technical Review Committee (TRC), which is established to coordinate activities during the RI/FS process. The TRC includes state, local, and federal authorities, and Air Force installation personnel

  3. Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection

    Energy Technology Data Exchange (ETDEWEB)

    Vani, R; Sridevi, T S; Kalkura, S Narayana [Crystal Growth Centre, Anna University, Chennai 600 025 (India); Raja, Subramaniya Bharathi; Savithri, K; Devaraj, S Niranjali [Department of Biochemistry, University of Madras, Chennai 600 025 (India); Girija, E K [Department of Physics, Periyar University, Salem 636 011 (India); Thamizhavel, A, E-mail: kalkurasn@annauniv.edu, E-mail: kalkura@yahoo.com [Tata Institute of Fundamental Research, Mumbai 400005 (India)

    2011-07-15

    Mesoporous nanocrystalline hydroxyapatite (nHAp) rods of size 40-75 nm long and 25 nm wide (resembling bone mineral) were synthesized under microwave irradiation without using any surfactants or modifiers. The surface area and average pore size of the nHAp were found to be 32 m{sup 2} g{sup -1} and 4 nm, respectively. Rifampicin (RIF) and ciprofloxacin (CPF) loaded nHAp displayed an initial burst followed by controlled release (zero order kinetics). Combination of CPF and RIF loaded nHAp showed enhanced bacterial growth inhibition against Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli) compared to individual agent loaded nHAp and pure nHAp. In addition, decreased bacterial adhesion (90%) was observed on the surface of CPF plus RIF loaded nHAp. The biocompatibility test toward MG63 cells infected with micro-organisms showed better cell viability and alkaline phosphatase activity (ALP) for the combination of CPF and RIF loaded nHAp. The influence on cell viability of infected MG63 cells was attributed to the simultaneous and controlled release of CPF and RIF from nHAp, which prevented the emergence of subpopulations that were resistant to each other. Hence, apart from the issue of the rapid synthesis of nHAp without surfactants or modifiers, the simultaneous and controlled release of dual drugs from nHAp would be a simple, non-toxic and cost-effective method to treat bone infections.

  4. The Relationship between Vascular Endothelial Growth Factor 1154G/A Polymorphism and Recurrent Implantation Failure

    Science.gov (United States)

    Vagnini, Laura D.; Nascimento, Adriana M.; Canas, Maria do Carmo T.; Renzi, Adriana; Oliveira-Pelegrin, Gabriela R.; Petersen, Claudia G.; Mauri, Ana L.; Oliveira, João Batista A.; Baruffi, Ricardo L.R.; Cavagna, Mario; Franco, José G.

    2015-01-01

    Objective The aim of this study was to investigate the relationship between herpesvirus-associated ubiquitin-specific protease (HAUSP A/G, rs1529916), tumor protein p53 (TP53 Arg/Pro, rs1042522), leukemia inhibitory factor (LIF G/T, rs929271), glycoprotein 130 (gp130 A/T, rs1900173) and vascular endothelial growth factor (VEGF G/A, rs1570360) polymorphisms and recurrent implantation failure (RIF) in Brazilian women. Subjects and Methods A total of 120 women with RIF (i.e. those with ≥5 cleaved embryos transferred and a minimum of 2 failed in vitro fertilization/intracytoplasmic sperm injection attempts) were included. The control group involved 89 women who had experienced at least 1 live birth (without any infertility treatment). DNA was extracted from the peripheral blood of all participants, and the abovementioned single-nucleotide polymorphisms (SNPs) were genotyped by real-time polymerase chain reaction. The data were evaluated using Fisher's test. Results A significant difference between the RIF and control groups was found in the VEGF gene where the GG genotype showed a 2.1-fold increased chance of not being included in the RIF group, while the presence of an A allele increased this risk 1.6-fold. No significant differences were found for the other polymorphisms. Conclusion This study showed an association between the VEGF -1154G/A polymorphism and RIF in Brazilian women. PMID:26305668

  5. Evaluation of four colourimetric susceptibility tests for the rapid detection of multidrug-resistant Mycobacterium tuberculosisisolates

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz Coban

    2015-08-01

    Full Text Available The purpose of this study is to evaluate four rapid colourimetric methods, including the resazurin microtitre assay (REMA, malachite green decolourisation assay (MGDA, microplate nitrate reductase assay (MNRA and crystal violet decolourisation assay (CVDA, for the rapid detection of multidrug-resistant (MDR tuberculosis. Fifty Mycobacterium tuberculosisisolates were used in this study. Eighteen isolates were MDR, two isolates were only resistant to isoniazid (INH and the remaining isolates were susceptible to both INH and rifampicin (RIF. INH and RIF were tested in 0.25 µg/mL and 0.5 µg/mL, respectively. The agar proportion method was used as a reference method. MNRA and REMA were performed with some modifications. MGDA and CVDA were performed as defined in the literature. The agreements of the MNRA for INH and RIF were 96% and 94%, respectively, while the agreement of the other assays for INH and RIF were 98%. In this study, while the specificities of the REMA, MGDA and CVDA were 100%, the specificity of the MNRA was lower than the others (93.3% for INH and 90.9% for RIF. In addition, while the sensitivity of the MNRA was 100%, the sensitivities of the others were lower than that of the MNRA (from 94.1-95%. The results were reported on the seventh-10th day of the incubation. All methods are reliable, easy to perform, inexpensive and easy to evaluate and do not require special equipment.

  6. Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection

    International Nuclear Information System (INIS)

    Vani, R; Sridevi, T S; Kalkura, S Narayana; Raja, Subramaniya Bharathi; Savithri, K; Devaraj, S Niranjali; Girija, E K; Thamizhavel, A

    2011-01-01

    Mesoporous nanocrystalline hydroxyapatite (nHAp) rods of size 40-75 nm long and 25 nm wide (resembling bone mineral) were synthesized under microwave irradiation without using any surfactants or modifiers. The surface area and average pore size of the nHAp were found to be 32 m 2 g -1 and 4 nm, respectively. Rifampicin (RIF) and ciprofloxacin (CPF) loaded nHAp displayed an initial burst followed by controlled release (zero order kinetics). Combination of CPF and RIF loaded nHAp showed enhanced bacterial growth inhibition against Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli) compared to individual agent loaded nHAp and pure nHAp. In addition, decreased bacterial adhesion (90%) was observed on the surface of CPF plus RIF loaded nHAp. The biocompatibility test toward MG63 cells infected with micro-organisms showed better cell viability and alkaline phosphatase activity (ALP) for the combination of CPF and RIF loaded nHAp. The influence on cell viability of infected MG63 cells was attributed to the simultaneous and controlled release of CPF and RIF from nHAp, which prevented the emergence of subpopulations that were resistant to each other. Hence, apart from the issue of the rapid synthesis of nHAp without surfactants or modifiers, the simultaneous and controlled release of dual drugs from nHAp would be a simple, non-toxic and cost-effective method to treat bone infections.

  7. Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Li Xiang-Xin

    2014-01-01

    Full Text Available Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA, Realgar-Indigo naturalis formula (RIF and chemotherapy (CT were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL. Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen, while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX plus 6-mercaptopurine (6-MP alternately (ATRA/CTlow regimen. The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

  8. The management of right iliac fossa pain - is timing everything?

    LENUS (Irish Health Repository)

    McCartan, D P

    2012-01-31

    BACKGROUND: Right iliac fossa (RIF) pain remains the commonest clinical dilemma encountered by general surgeons. We prospectively audited the management of acute RIF pain, examining the relationship between symptom duration, use of pre-operative radiological imaging and patient outcome. METHODS: Over a six-month period, 302 patients, median age 18 years, 59% female, were admitted with RIF pain. Symptoms, clinical findings and laboratory results were documented. Patient management, timing of radiological investigations and operations, and outcome were recorded prospectively. RESULTS: Non-specific abdominal pain (26%), gynaecological (22%) and miscellaneous causes (14%) accounted for most admissions. Ultimately, 119 patients (39%) had appendicitis. Anorexia, tachycardia or rebound tenderness in the RIF significantly predicted a final diagnosis of appendicitis. Patients with perforated appendicitis (n = 29) had a longer duration of pre-hospital symptoms (median 50h) compared to those with simple appendicitis (median 17 h) (p<0.001). The use of pre-operative imaging resulted in an increased time to surgery but was not associated with increased post-operative morbidity or perforated appendicitis. CONCLUSION: The majority of patients presenting to hospital with RIF pain did not have appendicitis. Increased duration of pre-hospital symptoms was the main factor associated with perforated appendicitis. However, increased in-hospital time to theatre was not associated with perforated appendicitis or post-operative morbidity.

  9. Memorable objects are more susceptible to forgetting: Evidence for the inhibitory account of retrieval-induced forgetting.

    Science.gov (United States)

    Reppa, I; Williams, K E; Worth, E R; Greville, W J; Saunders, J

    2017-11-01

    Retrieval of target information can cause forgetting for related, but non-retrieved, information - retrieval-induced forgetting (RIF). The aim of the current studies was to examine a key prediction of the inhibitory account of RIF - interference dependence - whereby 'strong' non-retrieved items are more likely to interfere during retrieval and therefore, are more susceptible to RIF. Using visual objects allowed us to examine and contrast one index of item strength -object typicality, that is, how typical of its category an object is. Experiment 1 provided proof of concept for our variant of the recognition practice paradigm. Experiment 2 tested the prediction of the inhibitory account that the magnitude of RIF for natural visual objects would be dependent on item strength. Non-typical objects were more memorable overall than typical objects. We found that object memorability (as determined by typicality) influenced RIF with significant forgetting occurring for the memorable (non-typical), but not non-memorable (typical), objects. The current findings strongly support an inhibitory account of retrieval-induced forgetting. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection

    Science.gov (United States)

    Vani, R.; Bharathi Raja, Subramaniya; Sridevi, T. S.; Savithri, K.; Niranjali Devaraj, S.; Girija, E. K.; Thamizhavel, A.; Narayana Kalkura, S.

    2011-07-01

    Mesoporous nanocrystalline hydroxyapatite (nHAp) rods of size 40-75 nm long and 25 nm wide (resembling bone mineral) were synthesized under microwave irradiation without using any surfactants or modifiers. The surface area and average pore size of the nHAp were found to be 32 m2 g - 1 and 4 nm, respectively. Rifampicin (RIF) and ciprofloxacin (CPF) loaded nHAp displayed an initial burst followed by controlled release (zero order kinetics). Combination of CPF and RIF loaded nHAp showed enhanced bacterial growth inhibition against Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli) compared to individual agent loaded nHAp and pure nHAp. In addition, decreased bacterial adhesion (90%) was observed on the surface of CPF plus RIF loaded nHAp. The biocompatibility test toward MG63 cells infected with micro-organisms showed better cell viability and alkaline phosphatase activity (ALP) for the combination of CPF and RIF loaded nHAp. The influence on cell viability of infected MG63 cells was attributed to the simultaneous and controlled release of CPF and RIF from nHAp, which prevented the emergence of subpopulations that were resistant to each other. Hence, apart from the issue of the rapid synthesis of nHAp without surfactants or modifiers, the simultaneous and controlled release of dual drugs from nHAp would be a simple, non-toxic and cost-effective method to treat bone infections.

  11. Incorporating ecological risk assessment into remedial investigation/feasibility study work plans

    International Nuclear Information System (INIS)

    1994-06-01

    This guidance document (1) provides instructions on preparing the components of an ecological work plan to complement the overall site remedial investigation/feasibility study (RI/FS) work plan and (2) directs the user on how to implement ecological tasks identified in the plan. Under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), as amended by the Superfund Amendments and Reauthorization Act of 1986 (SARA), and RI/FS work plan will have to be developed as part of the site-remediation scoping process. Specific guidance on the RI/FS process and the preparation of work plans has been developed by the US Environmental Protection Agency (EPA 1988a). This document provides guidance to US Department of Energy (DOE) staff and contractor personnel for incorporation of ecological information into environmental remediation planning and decision making at CERCLA sites

  12. Peritoneal macrophages mediated delivery of chitosan/siRNA nanoparticle to the lesion site in a murine radiation-induced fibrosis model

    DEFF Research Database (Denmark)

    Nawroth, Isabel; Alsner, Jan; Deleuran, B.W.

    2013-01-01

    of chitosan/siRNA nanoparticles directed towards silencing TNF alpha in local macrophage populations, but the mechanism for the therapeutic effect at the lesion site remains unclear. Methods. Using the same murine RIF model we utilized an optical imaging technique and fluorescence microscopy to investigate...... the uptake of chitosan/fluorescently labeled siRNA nanoparticles by peritoneal macrophages and their subsequent migration to the inflamed tissue in the RIF model. Results. We observed strong accumulation of the fluorescent signal in the lesion site of the irradiated leg up to 24 hours using the optical...... imaging system. We further confirm by immunohistochemical staining that Cy3 labeled siRNA resides in macrophages of the irradiated leg. Conclusion. We provide a proof-of-concept for host macrophage trafficking towards the inflamed region in a murine RIF model, which thereby suggests that the chitosan...

  13. Incorporating ecological risk assessment into remedial investigation/feasibility study work plans

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    This guidance document (1) provides instructions on preparing the components of an ecological work plan to complement the overall site remedial investigation/feasibility study (RI/FS) work plan and (2) directs the user on how to implement ecological tasks identified in the plan. Under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), as amended by the Superfund Amendments and Reauthorization Act of 1986 (SARA), and RI/FS work plan will have to be developed as part of the site-remediation scoping process. Specific guidance on the RI/FS process and the preparation of work plans has been developed by the US Environmental Protection Agency (EPA 1988a). This document provides guidance to US Department of Energy (DOE) staff and contractor personnel for incorporation of ecological information into environmental remediation planning and decision making at CERCLA sites.

  14. Rhabdomyosarcoma Arising in a Previously Irradiated Field: An Analysis of 43 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Dang, Nguyen D. [Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas (United States); Teh, Bin S. [Department of Radiation Oncology, The Methodist Hospital and Methodist Hospital Research Institute, Houston, Texas (United States); Paulino, Arnold C., E-mail: apaulino@tmhs.org [Department of Radiation Oncology, The Methodist Hospital and Methodist Hospital Research Institute, Houston, Texas (United States)

    2013-03-01

    Patients with soft tissue sarcomas that arise from previously irradiated fields have traditionally been reported to have a poor prognosis. In this report, we examined the characteristics and outcomes of patients who developed a rhabdomyosarcoma in a previously irradiated field (RMS-RIF); we hypothesize that these patients should have a better outcome compared to other postradiation soft tissue sarcomas as these tumors are chemosensitive and radiosensitive. A PubMed search of the literature from 1961-2010 yielded 33 studies with data for patients with RMS-RIF. The study included 43 patients with a median age of 6.5 years at the time of radiation therapy (RT) for the initial tumor. The median RT dose was 48 Gy. The median latency period, the time from RT to development of RMS-RIF, was 8 years. The 3-year overall survival for RMS-RIF was 42%. The 3-year overall survival was 66% for patients receiving chemotherapy and local treatment (surgery and/or RT) compared to 29% for those who had systemic treatment only or local treatment only (P=.049). Other factors associated with increased 3-year overall survival included retinoblastoma initial diagnosis (P<.001), age ≤18 years at diagnosis of RMS-RIF (P=.003), favorable site (P=.008), and stage 1 disease (P=.002). Age at time of RMS-RIF, retinoblastoma initial tumor, favorable site, stage 1 disease, and use of both systemic and local treatment were found to be favorable prognostic factors for 3-year overall survival.

  15. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway

    International Nuclear Information System (INIS)

    Delanian, Sylvie; Lefaix, Jean-Louis

    2004-01-01

    The radiation-induced fibroatrophic process (RIF) constitutes a late, local and unavoidable sequela to high-dose radiotherapy, traditionally considered irreversible. Today, this process is partly reversible, thanks to recent progress in understanding the physiopathology of the lesions it causes and the results of recent clinical trials using antioxidant therapy. This review includes a synthetic description of the static and dynamic features of the RIF process, as reflected by its clinical, instrumental and histopathological characteristics, and by its cellular and molecular regulation. Schematically, three successive clinical and histopathological phases can be distinguished: a pre-fibrotic aspecific inflammatory phase, a constitutive fibrotic cellular phase, and a matrix densification and remodelling phase, possibly ending in terminal tissular necrosis. The respective roles of the chief actors in the RIF process are defined, as well as their development with time. A fibroblastic stromal hypothesis is suggested revolving around a 'gravitational effect' exerted by the couple ROS (reactive oxygen species)--fibroblasts, and partly mediated by TGF-β1. A variety of strategies have been tested for the management of RIF. In the light of the mechanisms described, a curative procedure has been proposed via the antioxidant pathway. In particular, it was showed that superoxide dismutase and combined pentoxifylline-tocopherol treatment enables the process of established radiation-induced fibroatrophy to be greatly reduced or even reversed, both in clinical practice and animal experiments. The efficacy of combined pentoxifylline-tocopherol treatment in superficial RIF was confirmed in a randomised clinical trial, and then in successful phase II trials especially in uterine fibroatrophy and osteoradionecrosis. It is of critical importance to evaluate these new management approaches in larger clinical trials and to improve the recording of results for better outcome analysis

  16. Measurement of the dynamic behavior of thin poly(N-isopropylacrylamide) hydrogels and their phase transition temperatures measured using reflectometric interference spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Fuminori [Konica Minolta, INC. (Japan); Akiyama, Yoshikatsu, E-mail: akiyama.yoshikatsu@twmu.ac.jp, E-mail: akiyama.yoshikatsu@abmes.twmu.ac.jp; Kobayashi, Jun [Tokyo Women’s Medical University (TWIns), Institute of Advanced Biomedical Engineering and Science (Japan); Ninomiya, Hidetaka [Konica Minolta, INC. (Japan); Kanazawa, Hideko [Keio University, Faculty of Pharmacy (Japan); Yamato, Masayuki; Okano, Teruo [Tokyo Women’s Medical University (TWIns), Institute of Advanced Biomedical Engineering and Science (Japan)

    2015-03-15

    Temperature-responsive cell culture surfaces prepared by modifying tissue-culture polystyrene with nanoscale poly(N-isopropylacrylamide) (PIPAAm) hydrogels are widely used as intelligent surfaces for the fabrication of various cell sheets that change with temperature. In this work, the characteristics of nanoscale PIPAAm hydrogels were phenomenologically elucidated on the basis of time-dependent surface evaluations under conditions of changing temperature. Because the dynamic characteristics of the nanoscale hydrogel did not exhibit good performance, the nanoscale PIPAAm hydrogel was analyzed by monitoring its temperature-dependent dynamic swelling/deswelling changes using reflectometric interference spectroscopy (RIfS) on an instrument equipped with a microfluidic system. RIfS measurements under ambient atmosphere provided the precise physical thickness of the dry PIPAAm hydrogel (6.7 nm), which agreed with the atomic force microscopy results (6.6 nm). Simulations of the reflectance spectra revealed that changes in the wavelength of the minimum reflectance (Δλ) were attributable to the changes in the refractive index of the thin PIPAAm hydrogel induced by a temperature-dependent volume phase transition. The temperature-dependent Δλ change was used to monitor the swelling/deswelling behavior of the nanoscale PIPAAm hydrogel. In addition, the phase transition temperature of the thin PIPAAm hydrogel under aqueous conditions was also determined to be the inflection point of the plot of the change in Δλ as a function of temperature. The dynamic behavior of a thin PIPAAm hydrogel chemically deposited on a surface was readily analyzed using a new analytical system with RIfS and microfluidic devices.

  17. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway.

    Science.gov (United States)

    Delanian, Sylvie; Lefaix, Jean-Louis

    2004-11-01

    The radiation-induced fibroatrophic process (RIF) constitutes a late, local and unavoidable sequela to high-dose radiotherapy, traditionally considered irreversible. Today, this process is partly reversible, thanks to recent progress in understanding the physiopathology of the lesions it causes and the results of recent clinical trials using antioxidant therapy. This review includes a synthetic description of the static and dynamic features of the RIF process, as reflected by its clinical, instrumental and histopathological characteristics, and by its cellular and molecular regulation. Schematically, three successive clinical and histopathological phases can be distinguished: a pre-fibrotic aspecific inflammatory phase, a constitutive fibrotic cellular phase, and a matrix densification and remodelling phase, possibly ending in terminal tissular necrosis. The respective roles of the chief actors in the RIF process are defined, as well as their development with time. A fibroblastic stromal hypothesis is suggested revolving around a 'gravitational effect' exerted by the couple ROS (reactive oxygen species)--fibroblasts, and partly mediated by TGF-beta1. A variety of strategies have been tested for the management of RIF. In the light of the mechanisms described, a curative procedure has been proposed via the antioxidant pathway. In particular, it was showed that superoxide dismutase and combined pentoxifylline-tocopherol treatment enables the process of established radiation-induced fibroatrophy to be greatly reduced or even reversed, both in clinical practice and animal experiments. The efficacy of combined pentoxifylline-tocopherol treatment in superficial RIF was confirmed in a randomised clinical trial, and then in successful phase II trials especially in uterine fibroatrophy and osteoradionecrosis. It is of critical importance to evaluate these new management approaches in larger clinical trials and to improve the recording of results for better outcome analysis

  18. Impact of biocontrol Pseudomonas fluorescens CHA0 and a genetically modified derivative on the diversity of culturable fungi in the cucumber rhizosphere.

    Science.gov (United States)

    Girlanda, M; Perotto, S; Moenne-Loccoz, Y; Bergero, R; Lazzari, A; Defago, G; Bonfante, P; Luppi, A M

    2001-04-01

    Little is known about the effects of Pseudomonas biocontrol inoculants on nontarget rhizosphere fungi. This issue was addressed using the biocontrol agent Pseudomonas fluorescens CHA0-Rif, which produces the antimicrobial polyketides 2,4-diacetylphloroglucinol (Phl) and pyoluteorin (Plt) and protects cucumber from several fungal pathogens, including Pythium spp., as well as the genetically modified derivative CHA0-Rif(pME3424). Strain CHA0-Rif(pME3424) overproduces Phl and Plt and displays improved biocontrol efficacy compared with CHA0-Rif. Cucumber was grown repeatedly in the same soil, which was left uninoculated, was inoculated with CHA0-Rif or CHA0-Rif(pME3424), or was treated with the fungicide metalaxyl (Ridomil). Treatments were applied to soil at the start of each 32-day-long cucumber growth cycle, and their effects on the diversity of the rhizosphere populations of culturable fungi were assessed at the end of the first and fifth cycles. Over 11,000 colonies were studied and assigned to 105 fungal species (plus several sterile morphotypes). The most frequently isolated fungal species (mainly belonging to the genera Paecilomyces, Phialocephala, Fusarium, Gliocladium, Penicillium, Mortierella, Verticillium, Trichoderma, Staphylotrichum, Coniothyrium, Cylindrocarpon, Myrothecium, and Monocillium) were common in the four treatments, and no fungal species was totally suppressed or found exclusively following one particular treatment. However, in each of the two growth cycles studied, significant differences were found between treatments (e.g., between the control and the other treatments and/or between the two inoculation treatments) using discriminant analysis. Despite these differences in the composition and/or relative abundance of species in the fungal community, treatments had no effect on species diversity indices, and species abundance distributions fit the truncated lognormal function in most cases. In addition, the impact of treatments at the 32-day

  19. Transfer, attachment, and formation of biofilms by Escherichia coli O157:H7 on meat-contact surface materials.

    Science.gov (United States)

    Simpson Beauchamp, Catherine; Dourou, Dimitra; Geornaras, Ifigenia; Yoon, Yohan; Scanga, John A; Belk, Keith E; Smith, Gary C; Nychas, George-John E; Sofos, John N

    2012-06-01

    Studies examined the effects of meat-contact material types, inoculation substrate, presence of air at the liquid-solid surface interface during incubation, and incubation substrate on the attachment/transfer and subsequent biofilm formation by Escherichia coli O157:H7 on beef carcass fabrication surface materials. Materials studied as 2 × 5 cm coupons included stainless steel, acetal, polypropylene, and high-density polyethylene. A 6-strain rifampicin-resistant E. coli O157:H7 composite was used to inoculate (6 log CFU/mL, g, or cm²) tryptic soy broth (TSB), beef fat/lean tissue homogenate (FLH), conveyor belt-runoff fluids, ground beef, or beef fat. Coupons of each material were submerged (4 °C, 30 min) in the inoculated fluids or ground beef, or placed between 2 pieces of inoculated beef fat with pressure (20 kg) applied. Attachment/transfer of the pathogen was surface material and substrate dependent, although beef fat appeared to negate differences among surface materials. Beef fat was the most effective (P transfer and subsequent biofilm formation by E. coli O157:H7. The results highlight the importance of thoroughly cleaning soiled surfaces to remove all remnants of beef fat or other organic material that may harbor or protect microbial contaminants during otherwise lethal antimicrobial interventions. © 2012 Institute of Food Technologists®

  20. [Tuberculosis and drug-resistance tuberculosis in prisoners. Colombia, 2010-2012].

    Science.gov (United States)

    Gómez, Ingrid T; Llerena, Claudia R; Zabaleta, Angie P

    2015-01-01

    To characterize tuberculosis drug-resistance using anti-tuberculosis drug-sensitivity tests in Colombian prisoners. Descriptive-retrospective analyses were performed on cases of tuberculosis in prisoners. Samples were evaluated by the National Reference Laboratory. Conditions like gender, TB/VIH co-infection and drug-resistance were evaluated. Anti-tuberculosis drug-sensitivity tests were carried out on 72 prisoners. Results showed a distribution of 90.7 % of cases in males and 9.3 % of cases in females. 12 % of cases were TB/VIH co-infections, 94 % of the cases had not received any anti-tuberculosis treatment before, six isolates were drug-resistant corresponding to 8.8 % of total cases, and two cases were multi drug-resistant representing 1.3 % of the cases. Of the drug-resistant cases, 83.3 % were TB/VIH co-infected. Previously treated cases corresponded to 5.6 % of the total cases analyzed. One case with TB/VIH co-infection and rifampicin resistance was observed, representing 1.3 % of the total cases. The government must create a clear policy for prisoners in Colombia, because a high rate of disease in prisoners was observed. In addition, the results showed an association between drug-resistance and TB/VIH co-infection. Overcrowding and low quality of life in penitentiaries could become an important public health problem.

  1. A novel immunotherapy of Brucellosis in cows monitored non invasively through a specific biomarker.

    Directory of Open Access Journals (Sweden)

    Hari Mohan Saxena

    2018-04-01

    Full Text Available Brucellosis is an important zoonotic disease causing huge economic losses worldwide. Currently no effective immunotherapy for Brucellosis or any biomarker to monitor the efficacy of therapy is available. Treatment is ineffective and animals remain carrier lifelong. S19 and RB51 are live attenuated vaccine strains of Brucella abortus. However, S19 induces only antibody, ineffective for intracellular pathogen. RB51 induces cell mediated immunity (CMI but it is Rifampicin resistant. Both organisms are secreted in milk and can infect humans and cause abortions in animals. Phage lysed bacteria (lysates retain maximum immunogenicity as opposed to killing by heat or chemicals. We report here the successful immunotherapy of bovine Brucellosis by phage lysates of RB51 (RL and S19 (SL. The SL induced strong antibody response and RL stimulated CMI. In vitro restimulation of leukocytes from RL immunized cattle induced interferon gamma production. A single subcutaneous dose of 2 ml of cocktail lysate (both RL and SL, eliminated live virulent Brucella from Brucellosis affected cattle with plasma level of Brucella specific 223 bp amplicon undetectable by RT-PCR and blood negative for live Brucella by culture in 3 months post-immunization. This is the first report on minimally invasive monitoring of the efficacy of antibacterial therapy employing plasma RNA specific for live bacteria as a biomarker as well as on the use of RB51 phage lysate for successful immunotherapy of Brucellosis in cattle.

  2. Au-nanoprobes for detection of SNPs associated with antibiotic resistance in Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Veigas, Bruno; Baptista, Pedro V; Machado, Diana; Couto, Isabel; Viveiros, Miguel; Perdigao, Joao; Portugal, Isabel

    2010-01-01

    Tuberculosis (TB) is one of the leading causes of infection in humans, causing high morbility and mortality all over the world. The rate of new cases of multidrug resistant tuberculosis (MDRTB) continues to increase, and since these infections are very difficult to manage, they constitute a serious health problem. In most cases, drug resistance in Mycobacterium tuberculosis has been related to mutations in several loci within the pathogen's genome. The development of fast, cheap and simple screening methodologies would be of paramount relevance for the early detection of these mutations, essential for the timely and effective diagnosis and management of MDRTB patients. The use of gold nanoparticles derivatized with thiol-modified oligonucleotides (Au-nanoprobes) has led to new approaches in molecular diagnostics. Based on the differential non-cross-linking aggregation of Au-nanoprobes, we were able to develop a colorimetric method for the detection of specific sequences and to apply this approach to pathogen identification and single base mutations/single nucleotide polymorphisms (SNP) discrimination. Here we report on the development of Au-nanoprobes for the specific identification of SNPs within the beta subunit of the RNA polymerase (rpoB locus), responsible for resistance to rifampicin in over 95% of rifampicin resistant M. tuberculosis strains.

  3. Rapid molecular diagnostics for multi-drug resistant tuberculosis in India.

    Science.gov (United States)

    Ramachandran, Rajeswari; Muniyandi, M

    2018-03-01

    Rapid molecular diagnostic methods help in the detection of TB and Rifampicin resistance. These methods detect TB early, are accurate and play a crucial role in reducing the burden of drug resistant tuberculosis. Areas covered: This review analyses rapid molecular diagnostic tools used in the diagnosis of MDR-TB in India, such as the Line Probe Assay and GeneXpert. We have discussed the burden of MDR-TB and the impact of recent diagnostic tools on case detection and treatment outcomes. This review also discusses the costs involved in establishing these new techniques in India. Expert commentary: Molecular methods have considerable advantages for the programmatic management of drug resistant TB. These include speed, standardization of testing, potentially high throughput and reduced laboratory biosafety requirements. There is a desperate need for India to adopt modern, rapid, molecular tools with point-of-care tests being currently evaluated. New molecular diagnostic tests appear to be cost effective and also help in detecting missing cases. There is enough evidence to support the scaling up of these new tools in India.

  4. [Description of Mycobacterium tuberculosis mutations conferring resistance to rifampicin and isoniazid detected by GenoType® MTBDRplus V.2 in Colombia].

    Science.gov (United States)

    Llerena, Claudia; Medina, Raquel

    2017-01-24

    The GenoType®MTBDRplusV.2 assay is a molecular technique endorsed by the World Health Organization and the Pan American Health Organization that allows for the identification of the Mycobacterium tuberculosis complex and the detection of mutations in the rpoβ gene for rifampicin resistance, and katG and inhA genes for isoniazid resistance. Due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these new diagnostic technologies and their use under program conditions as rapid tests. To describe the mutations identified by the GenoType®MTBDRplusV.2 assay in pulmonary samples and Mycobacterium tuberculosis isolates in the Laboratorio Nacional de Referencia of the Instituto Nacional de Salud in 2014. We conducted a retrospective, descriptive study to detect the expression of inhA, KatG and rpoβ genes, responsible for resistence against isoniazid and rifampicin using the GenoType® MTBDRplus V.2 assay in 837 samples and isolates from tuberculosis cases. Several mutations in the rpoβ gene were identified. Ser531Leu was the most frequent (36.6%) followed by Asp516Val (21.6%), while Ser315Thr1 was the most frequent mutation in the katG gene (91.9%). We were able to identify different mutations present in MDR-TB strains in the country, with frequencies similar to those reported in other countries in the South American region.

  5. Differences in mutagenic and recombinational DNA repair in enterobacteria

    International Nuclear Information System (INIS)

    Sedgwick, S.G.; Goodwin, P.A.

    1985-01-01

    The incidence of recombinational DNA repair and inducible mutagenic DNA repair has been examined in Escherichia coli and 11 related species of enterobacteria. Recombinational repair was found to be a common feature of the DNA repair repertoire of at least 6 genera of enterobacteria. This conclusion is based on observations of (i) damage-induced synthesis of RecA-like proteins, (ii) nucleotide hybridization between E. coli recA sequences and some chromosomal DNAs, and (iii) recA-negative complementation by plasmids showing SOS-inducible expression of truncated E. coli recA genes. The mechanism of DNA damage-induced gene expression is therefore sufficiently conserved to allow non-E. coli regulatory elements to govern expression of these cloned truncated E. coli recA genes. In contrast, the process of mutagenic repair, which uses umuC+ umuD+ gene products in E. coli, appeared less widespread. Little ultraviolet light-induced mutagenesis to rifampicin resistance was detected outside the genus Escherichia, and even within the genus induced mutagenesis was detected in only 3 out of 6 species. Nucleotide hybridization showed that sequences like the E. coli umuCD+ gene are not found in these poorly mutable organisms. Evolutionary questions raised by the sporadic incidence of inducible mutagenic repair are discussed

  6. A user-friendly mathematical modelling web interface to assist local decision making in the fight against drug-resistant tuberculosis.

    Science.gov (United States)

    Ragonnet, Romain; Trauer, James M; Denholm, Justin T; Marais, Ben J; McBryde, Emma S

    2017-05-30

    Multidrug-resistant and rifampicin-resistant tuberculosis (MDR/RR-TB) represent an important challenge for global tuberculosis (TB) control. The high rates of MDR/RR-TB observed among re-treatment cases can arise from diverse pathways: de novo amplification during initial treatment, inappropriate treatment of undiagnosed MDR/RR-TB, relapse despite appropriate treatment, or reinfection with MDR/RR-TB. Mathematical modelling allows quantification of the contribution made by these pathways in different settings. This information provides valuable insights for TB policy-makers, allowing better contextualised solutions. However, mathematical modelling outputs need to consider local data and be easily accessible to decision makers in order to improve their usefulness. We present a user-friendly web-based modelling interface, which can be used by people without technical knowledge. Users can input their own parameter values and produce estimates for their specific setting. This innovative tool provides easy access to mathematical modelling outputs that are highly relevant to national TB control programs. In future, the same approach could be applied to a variety of modelling applications, enhancing local decision making.

  7. DNA polymerase III of Escherichia coli is required for UV and ethyl methanesulfonate mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Hagensee, M.E.; Timme, T.L.; Bryan, S.K.; Moses, R.E.

    1987-06-01

    Strains of Escherichia coli possessing the pcbA1 mutation, a functional DNA polymerase I, and a temperature-sensitive mutation in DNA polymerase III can survive at the restrictive temperature (43 degrees C) for DNA polymerase III. The mutation rate of the bacterial genome of such strains after exposure to either UV light or ethyl methanesulfonate was measured by its rifampicin resistance or amino acid requirements. In addition, Weigle mutagenesis of preirradiated lambda phage was also measured. In all cases, no increase in mutagenesis was noted at the restrictive temperature for DNA polymerase III. Introduction of a cloned DNA polymerase III gene returned the mutation rate of the bacterial genome as well as the Weigle mutagenesis to normal at 43 degrees C. Using a recA-lacZ fusion, the SOS response after UV irradiation was measured and found to be normal at the restrictive and permissive temperature for DNA polymerase III, as was induction of lambda prophage. Recombination was also normal at either temperature. Our studies demonstrate that a functional DNA polymerase III is strictly required for mutagenesis at a step other than SOS induction.

  8. Long-term effects of inducible mutagenic DNA repair on relative fitness and phenotypic diversification in Pseudomonas cichorii 302959.

    Science.gov (United States)

    Weigand, Michael R; Sundin, George W

    2009-01-01

    Mutagenic DNA repair (MDR) employs low-fidelity DNA polymerases capable of replicating past DNA lesions resulting from exposure to high-energy ultraviolet radiation (UVR). MDR confers UVR tolerance and activation initiates a transient mutator phenotype that may provide opportunities for adaptation. To investigate the potential role of MDR in adaptation, we have propagated parallel lineages of the highly mutable epiphytic plant pathogen Pseudomonas cichorii 302959 with daily UVR activation (UVR lineages) for approximately 500 generations. Here we examine those lineages through the measurement of relative fitness and observation of distinct colony morphotypes that emerged. Isolates and population samples from UVR lineages displayed gains in fitness relative to the ancestor despite increased rates of inducible mutation to rifampicin resistance. Regular activation of MDR resulted in the maintenance of genetic diversity within UVR lineages, including the reproducible diversification and coexistence of "round" and "fuzzy" colony morphotypes. These results suggest that inducible mutability may present a reasonable strategy for adaptive evolution in stressful environments by contributing to gains in relative fitness and diversification.

  9. Titanium-tethered vancomycin prevents resistance to rifampicin in Staphylococcus aureus in vitro.

    Directory of Open Access Journals (Sweden)

    Martin Rottman

    Full Text Available Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone. Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.

  10. Where antibiotic resistance mutations meet quorum-sensing

    Directory of Open Access Journals (Sweden)

    Rok Krašovec

    2014-06-01

    Full Text Available We do not need to rehearse the grim story of the global rise of antibiotic resistant microbes. But what if it were possible to control the rate with which antibiotic resistance evolves by de novo mutation? It seems that some bacteria may already do exactly that: they modify the rate at which they mutate to antibiotic resistance dependent on their biological environment. In our recent study [Krašovec, et al. Nat. Commun. (2014, 5, 3742] we find that this modification depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress. Specifically, the wild-type strains of Escherichia coli we used will, in minimal glucose media, modify their rate of mutation to rifampicin resistance according to the density of wild-type cells. Intriguingly, the higher the density, the lower the mutation rate (Figure 1. Why this novel density-dependent ‘mutation rate plasticity’ (DD-MRP occurs is a question at several levels. Answers are currently fragmentary, but involve the quorum-sensing gene luxS and its role in the activated methyl cycle.

  11. Improvement of phytoremediation of an aged petroleum hydrocarbon-contaminated soil by Rhodococcus erythropolis CD 106 strain.

    Science.gov (United States)

    Płociniczak, Tomasz; Fic, Ewa; Pacwa-Płociniczak, Magdalena; Pawlik, Małgorzata; Piotrowska-Seget, Zofia

    2017-07-03

    The aim of this study was to assess the impact of soil inoculation with the Rhodococcus erythropolis CD 106 strain on the effectiveness of the phytoremediation of an aged hydrocarbon-contaminated [approx. 1% total petroleum hydrocarbon (TPH)] soil using ryegrass (Lolium perenne). The introduction of CD 106 into the soil significantly increased the biomass of ryegrass and the removal of hydrocarbons in planted soil. The fresh weight of the shoots and roots of plants inoculated with CD 106 increased by 49% and 30%, respectively. After 210 days of the experiment, the concentration of TPH was reduced by 31.2%, whereas in the planted, non-inoculated soil, it was reduced by 16.8%. By contrast, the concentration of petroleum hydrocarbon decreased by 18.7% in non-planted soil bioaugmented with the CD 106 strain. The rifampicin-resistant CD 106 strain survived after inoculation into soil and was detected in the soil during the entire experimental period, but the number of CD 106 cells decreased constantly during the enhanced phytoremediation and bioaugmentation experiments. The plant growth-promoting and hydrocarbon-degrading properties of CD 106, which are connected with its long-term survival and limited impact on autochthonous microflora, make this strain a good candidate for improving the phytoremediation efficiency of soil contaminated with hydrocarbons.

  12. Apramycin treatment affects selection and spread of a multidrug-resistant Escherichia coli strain able to colonize the human gut in the intestinal microbiota of pigs

    DEFF Research Database (Denmark)

    Herrero-Fresno, Ana; Zachariasen, Camilla; Hansen, Monica Hegstad

    2016-01-01

    . E. coli 912 was shown to spread to non-inoculated pigs in both groups. The selective effect did not persist beyond 3 days post-treatment, and the strain was not detected from this time point in pen 2. We demonstrated that E. coli 912 was able to spread between pigs in the same pen irrespective....../gentamicin, sulphonamide, tetracycline, hygromycin B, β-lactams and streptomycin [aac(3)-IV, sul2, tet(X), aph(4), bla TEM-1 and strA/B], with all but tet(X) located on the same conjugative plasmid. Nineteen pigs were randomly allocated into two inoculation groups, one treated with apramycin (pen 2) and one non......-treated (pen 3), along with a non-inoculated control group (pen 1). Two pigs of pen 2 and 3 were inoculated intragastrically with a rifampicin resistant variant of the strain. Apramycin treatment in pen 2 was initiated immediately after inoculation. Strain colonization was assessed in the feces from all pigs...

  13. POTENCY OF VIBRIO ISOLATES FOR BIOCONTROL OF VIBRIOSIS IN TIGER SHRIMP (PENAEUS MONODON LARVAE

    Directory of Open Access Journals (Sweden)

    B. W. LAY

    2003-01-01

    Full Text Available This study was carried out to obtain Vibrio isolates able to function as biocontr ol of vibriosis in shrimp hatchery. Thirty one Vibrio isolates were isolated from tiger shrimp larvae and hatchery environments, i.e. Labuan, Pangandaran, and Lampung, Indonesia. Pathogenic V. harveyi MR5339 was obtained from Maros, South-Sulawesi and was made as a rifampicin resistant mutant (RFR to screen for those 31 Vibrio isolates in in vitro assays and to allow us to monitor their presence in shrimp larvae and larval rearing water. Almost all Vibrio isolates could inhibit the growth of pathogenic V. harveyi MR5339 RFR. SKT-b isolate from Skeletonema was the most effective to inhibit the growth of V. harveyi MR5339 Rf* and significantly reduced larval mortality in pathogen challenge assays. These prospective biocontrol bacteria, at concentration of 10" CFU/ml, did not show pathogenicity to shrimp larvae. SKT-b was Gram negative, short rod-shape, exhibited yellow colonies on TCBS and swarming on SWC-agar media, motile, u tilized glucose and sucrose but not lactose: produced extra-cellular protease and amylase, but did not produce chitmase. Partial sequencing of 16S-rRNA gene SKT-b showed SKT-b similarity to Vibrio alginofyticus.

  14. Virulence of luminescent and non-luminescent isogenic vibrios towards gnotobiotic Artemia franciscana larvae and specific pathogen-free Litopenaeus vannamei shrimp.

    Science.gov (United States)

    Phuoc, L H; Defoirdt, T; Sorgeloos, P; Bossier, P

    2009-04-01

    This study was conducted to test the virulence of luminescent (L) and non-luminescent (NL) isogenic strains of Vibrio campbellii LMG21363, Vibrio harveyi BB120 (wild type) and quorum-sensing mutant strains derived from the wild type such as Vibrio harveyi BB152, BB170, MM30 and BB886. The NL strains could be obtained by culturing rifampicin-resistant luminescent strains in the dark under static condition. The virulence of the L and NL strains was tested in gnotobiotic Artemia franciscana larvae challenged with 10(4) CFU ml(-1) of bacteria. All luminescent isogenic tested strains showed higher virulence compared to the NL strains. The virulence of L and NL V. campbellii and V. harveyi BB120 was also tested in specific pathogen-free juvenile shrimp upon intramuscular injection with 10(6) CFU of bacteria. In contrast with Artemia, there was no significant difference in mortality between the groups challenged with L and NL strains (P > 0.05). The non-luminescent strains were not able to revert back to the luminescent state and quorum sensing did not influence this phenotypic shift. Luminescent Vibrio strains can switch to a non-luminescent state by culturing them in static conditions. The NL strains become less virulent as verified in Artemia. The luminescent state of Vibrio cells in a culture needs to be verified in order to assure maintenance of virulence.

  15. Molecular Genetic Analysis of Multi-drug Resistance in Indian Isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Noman Siddiqi

    1998-09-01

    Full Text Available A total of 116 isolates from patients attending the out-patient department at the All India Institute of Medical Sciences, New Delhi and the New Delhi Tuberculosis Centre, New Delhi, India were collected. They were analyzed for resistance to drugs prescribed in the treatment for tuberculosis. The drug resistance was initially determined by microbiological techniques. The Bactec 460TB system was employed to determine the type and level of resistance in each isolate. The isolates were further characterized at molecular level. The multi-drug loci corresponding to rpo b, gyr A, kat G were studied for mutation(s by the polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP technique. The SSCP positive samples were sequenced to characterize the mutations in rpo b, and gyr A loci. While previously reported mutations in the gyr A and rpo b loci were found to be present, several novel mutations were also scored in the rpo b locus. Interestingly, analysis of the gyr A locus showed the presence of point mutation(s that could not be detected by PCR-SSCP. Furthermore, rifampicin resistance was found to be an important marker for checking multi-drug resistance (MDR in clinical isolates of Mycobacterium tuberculosis. This is the first report on molecular genetic analysis of MDR tuberculosis one from India, highlights the increasing incidence of MDR in the Indian isolates of M. tuberculosis.

  16. Synergism between Medihoney and rifampicin against methicillin-resistant Staphylococcus aureus (MRSA.

    Directory of Open Access Journals (Sweden)

    Patrick Müller

    Full Text Available Skin and chronic wound infections caused by highly antibiotic resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA are an increasing and urgent health problem worldwide, particularly with sharp increases in obesity and diabetes. New Zealand manuka honey has potent broad-spectrum antimicrobial activity, has been shown to inhibit the growth of MRSA strains, and bacteria resistant to this honey have not been obtainable in the laboratory. Combinational treatment of chronic wounds with manuka honey and common antibiotics may offer a wide range of advantages including synergistic enhancement of the antibacterial activity, reduction of the effective dose of the antibiotic, and reduction of the risk of antibiotic resistance. The aim of this study was to investigate the effect of Medihoney in combination with the widely used antibiotic rifampicin on S. aureus. Using checkerboard microdilution assays, time-kill curve experiments and agar diffusion assays, we show a synergism between Medihoney and rifampicin against MRSA and clinical isolates of S. aureus. Furthermore, the Medihoney/rifampicin combination stopped the appearance of rifampicin-resistant S. aureus in vitro. Methylglyoxal (MGO, believed to be the major antibacterial compound in manuka honey, did not act synergistically with rifampicin and is therefore not the sole factor responsible for the synergistic effect of manuka honey with rifampicin. Our findings support the idea that a combination of honey and antibiotics may be an effective new antimicrobial therapy for chronic wound infections.

  17. Industrial application of an antilisterial strain of Lactobacillus sakei as a protective culture and its effect on the sensory acceptability of cooked, sliced, vacuum-packaged meats.

    Science.gov (United States)

    Bredholt, S; Nesbakken, T; Holck, A

    2001-06-15

    The application of a protective lactic acid bacterium (LAB) during the commercial production of cooked meat products is described. The LAB, a strain of Lactobacillus sakei, was previously isolated from cooked ham and inhibited growth of Listeria monocytogenes and Escherichia coli O157:H7 in this product. L. sakei was applied to the cooked products at a concentration of 10(5)-10(6) cfu/g immediately before slicing and vacuum-packaging using a hand-operated spraying bottle. The LAB strain inhibited growth of 10(3) cfu/g of a cocktail of three rifampicin resistant mutant L. monocytogenes strains both at 8 degrees C and 4 degrees C. Consumer acceptance tests of cooked ham and of servelat sausage, a Norwegian non-fermented cooked meat sausage, showed that control and inoculated products were equally acceptable. The products were still acceptable after storage for 28 days at 4 degrees C and, after opening the packages, for a further 5 days at 4 degrees C. The findings presented here confirm that the L. sakei strain is suitable for use as a protective culture and may technically easily be implemented in the commercial production of cooked meat products.

  18. [Thin layer agar represents a cost-effective alternative for the rapid diagnosis of multi-drug resistant tuberculosis].

    Science.gov (United States)

    Hernández-Sarmiento, José M; Martínez-Negrete, Milton A; Castrillón-Velilla, Diana M; Mejía-Espinosa, Sergio A; Mejía-Mesa, Gloria I; Zapata-Fernández, Elsa M; Rojas-Jiménez, Sara; Marín-Castro, Andrés E; Robledo-Restrepo, Jaime A

    2014-01-01

    Using cost-benefit analysis for comparing the thin-layer agar culture method to the standard multiple proportion method used in diagnosing multidrug-resistant tuberculosis (MDR TB). A cost-benefit evaluation of two diagnostic tests was made at the Corporación para Investigaciones Biológicas (CIB) in Medellín, Colombia. 100 patients were evaluated; 10.8% rifampicin resistance and 14.3% isoniazid resistance were found. A computer-based decision tree model was used for cost-effectiveness analysis (Treeage Pro); the thin-layer agar culture method was most cost-effective, having 100% sensitivity, specificity and predictive values for detecting rifampicin and isoniazid resistance. The multiple proportion method value was calculated as being US$ 71 having an average 49 day report time compared to US$ 18 and 14 days for the thin-layer agar culture method. New technologies have been developed for diagnosing tuberculosis which are apparently faster and more effective; their operating characteristics must be evaluated as must their effectiveness in terms of cost-benefit. The present study established that using thin-layer agar culture was cheaper, equally effective and could provide results more quickly than the traditional method. This implies that a patient could receive MDR TB treatment more quickly.

  19. Au-nanoprobes for detection of SNPs associated with antibiotic resistance in Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Veigas, Bruno; Baptista, Pedro V [CIGMH, Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, Caparica (Portugal); Machado, Diana; Couto, Isabel; Viveiros, Miguel [Unidade de Micobacterias, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL) (Portugal); Perdigao, Joao; Portugal, Isabel, E-mail: pmvb@fct.unl.pt [Centro de Patogenese Molecular/URIA, Faculdade de Farmacia, Universidade de Lisboa, Lisboa (Portugal)

    2010-10-15

    Tuberculosis (TB) is one of the leading causes of infection in humans, causing high morbility and mortality all over the world. The rate of new cases of multidrug resistant tuberculosis (MDRTB) continues to increase, and since these infections are very difficult to manage, they constitute a serious health problem. In most cases, drug resistance in Mycobacterium tuberculosis has been related to mutations in several loci within the pathogen's genome. The development of fast, cheap and simple screening methodologies would be of paramount relevance for the early detection of these mutations, essential for the timely and effective diagnosis and management of MDRTB patients. The use of gold nanoparticles derivatized with thiol-modified oligonucleotides (Au-nanoprobes) has led to new approaches in molecular diagnostics. Based on the differential non-cross-linking aggregation of Au-nanoprobes, we were able to develop a colorimetric method for the detection of specific sequences and to apply this approach to pathogen identification and single base mutations/single nucleotide polymorphisms (SNP) discrimination. Here we report on the development of Au-nanoprobes for the specific identification of SNPs within the beta subunit of the RNA polymerase (rpoB locus), responsible for resistance to rifampicin in over 95% of rifampicin resistant M. tuberculosis strains.

  20. Management of multidrug-resistant tuberculosis in human immunodeficiency virus patients

    Science.gov (United States)

    Jamil, K. F.

    2018-03-01

    Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis(MTB). 10.4 million new TB cases will appear in 2015 worldwide. There were an estimated 1.4 million TB deaths in 2015, and an additional 0.4 million deaths resulting from TB disease among people living with human immunodeficiency virus (HIV). Multidrug- resistant and extensively drug-resistant tuberculosis (MDR and XDR-TB) are major public health concerns worldwide. 480.000 new cases of MDR-TB will appear in 2015 and an additional 100,000 people with rifampicin-resistant TB (RR-TB) who were also newly eligible for MDR-TB treatment. Their association with HIV infection has contributed to the slowing down of TB incidence decline over the last two decades, therefore representing one important barrier to reach TB elimination. Patients infected with MDR-TB require more expensive treatment regimens than drug-susceptible TB, with poor treatment.Patients with multidrug- resistant tuberculosis do not receive rifampin; drug interactions risk is markedly reduced. However, overlapping toxicities may limit options for co-treatment of HIV and multidrug- resistant tuberculosis.

  1. Effect of NaCl on seed germination in some Centaurium Hill. Species (Gentianaceae

    Directory of Open Access Journals (Sweden)

    Živković S.

    2007-01-01

    Full Text Available The influence of high NaCl concentrations on seed germination in both light and darkness was examined in the species Centaurium pulchellum, C. erythraea, C. littorale, C. spicatum, and C. tenuiflorum. Salt tolerance was found to depend on the life history of the seeds. To be specific, seeds of all five species failed to complete germination when exposed to continuous white light if kept all the time in the presence of 100-200 mM and greater NaCl concentrations. However, when after two weeks NaCl was rinsed from the seeds and the seeds were left in distilled water under white light for an additional two weeks, all species completed germination to a certain extent. The percent of germination not only depended on NaCl concentration in the prior medium, but was also species specific. Thus, seeds of C. pulchellum, C. erythraea, and C. littorale completed germination well almost irrespective of the salt concentration previously experienced. On the other hand, seeds of C. tenuiflorum completed germination poorly if NaCl concentrations in the prior media were greater than 200 mM. When seeds after washing were transferred to darkness for an additional 14 days, they failed to complete germination if previously imbibed on media containing NaCl concentrations greater than 400 mM. However, the seeds of all species, even if previously imbibed at 800 mM NaCl, could be induced to complete germination in darkness by 1 mM gibberellic acid. .

  2. Fatty acids in six small pelagic fish species and their crustacean prey from the mindanao sea, southern Philippines.

    Science.gov (United States)

    Metillo, Ephrime Bicoy; Aspiras-Eya, Anna Arlene

    2014-08-01

    Fatty acids are important in human health and useful in the analysis of the marine food web, however information on tropical pelagic organisms is scarce. Six zooplanktivorous small pelagic fish species (Decapterus kurroides, Decapterus macarellus, Selar crumenophthalmus, Sardinella lemuru, Spratilloides gracilis and Stolephorus insularis) and four of their zooplanktonic crustacean prey [three sergestoid species (Acetes erythraeus, Acetes intermedius and Lucifer penicillifer) and one calanoid copepod (Acartia erythraea)] were collected from the Mindanao Sea, and their fatty acids were profiled. The resulting profiles revealed 17 fatty acids that were specific to certain species and 9 {myristic acid [C14:0], palmitic acid [C16:0], stearic acid [C18:0]; palmitoleic acid [C16:1], oleic acid [C18:1n9c], linoleic acid [C18:2n6c], linolenic acid [C18:3n3], eicosapentaenoic acid (EPA) [C20:5n3] and docosahexaenoic acid (DHA) [C22:6n3]} that were common to all species. Cluster analysis and non-metric multidimensional scaling (NMDS) of fatty acids indicate a high similarity in profiles in all species, but separate fish and zooplankton clusters were obtained. Mackerel species (D. macarellus, D. kurroides and S. crumenophthalmus) had concentrations of total n-3 fatty acids that match those of their Acetes prey. The copepod A. erythraea and the sergestoid L. penicillifer exhibited the lowest values of the EPA:DHA ratio, which was most likely due to their phytoplanktivorous feeding habits, but the occurrence of the highest values of the ratio in Acetes suggests the inclusion of plant detritus in their diet. DHA values appear to affirm the trophic link among copepod, Lucifer, Acetes and mackerel species.

  3. Regional changes in renal cortical glucose, lactate and urea during acute unilateral ureteral obstruction

    DEFF Research Database (Denmark)

    Krarup, Peter-Martin; Stolle, Lars B; Rawashdeh, Yazan F

    2007-01-01

    . Furthermore, we investigated regional variations in renal interstitial fluid (RIF) glucose, lactate and urea during acute UUO. MATERIAL AND METHODS: Eight anesthetized pigs were used. Microdialysis probes were inserted in the upper, middle and lower thirds of the left renal cortex and perfused with Ringer...... third. RIF lactate did not change. Interstitial urea increased in all regions of the kidney, but most markedly in the upper and lower poles. CONCLUSIONS: Microdialysis is of potential value for assessing the renal interstitial milieu under different pathophysiological conditions. Ureteral obstruction...

  4. Fabrication and Optimization of Bilayered Nanoporous Anodic Alumina Structures as Multi-Point Interferometric Sensing Platform

    Science.gov (United States)

    Nemati, Mahdieh; Santos, Abel

    2018-01-01

    Herein, we present an innovative strategy for optimizing hierarchical structures of nanoporous anodic alumina (NAA) to advance their optical sensing performance toward multi-analyte biosensing. This approach is based on the fabrication of multilayered NAA and the formation of differential effective medium of their structure by controlling three fabrication parameters (i.e., anodization steps, anodization time, and pore widening time). The rationale of the proposed concept is that interferometric bilayered NAA (BL-NAA), which features two layers of different pore diameters, can provide distinct reflectometric interference spectroscopy (RIfS) signatures for each layer within the NAA structure and can therefore potentially be used for multi-point biosensing. This paper presents the structural fabrication of layered NAA structures, and the optimization and evaluation of their RIfS optical sensing performance through changes in the effective optical thickness (EOT) using quercetin as a model molecule. The bilayered or funnel-like NAA structures were designed with the aim of characterizing the sensitivity of both layers of quercetin molecules using RIfS and exploring the potential of these photonic structures, featuring different pore diameters, for simultaneous size-exclusion and multi-analyte optical biosensing. The sensing performance of the prepared NAA platforms was examined by real-time screening of binding reactions between human serum albumin (HSA)-modified NAA (i.e., sensing element) and quercetin (i.e., analyte). BL-NAAs display a complex optical interference spectrum, which can be resolved by fast Fourier transform (FFT) to monitor the EOT changes, where three distinctive peaks were revealed corresponding to the top, bottom, and total layer within the BL-NAA structures. The spectral shifts of these three characteristic peaks were used as sensing signals to monitor the binding events in each NAA pore in real-time upon exposure to different concentrations of

  5. Fabrication and Optimization of Bilayered Nanoporous Anodic Alumina Structures as Multi-Point Interferometric Sensing Platform

    Directory of Open Access Journals (Sweden)

    Mahdieh Nemati

    2018-02-01

    Full Text Available Herein, we present an innovative strategy for optimizing hierarchical structures of nanoporous anodic alumina (NAA to advance their optical sensing performance toward multi-analyte biosensing. This approach is based on the fabrication of multilayered NAA and the formation of differential effective medium of their structure by controlling three fabrication parameters (i.e., anodization steps, anodization time, and pore widening time. The rationale of the proposed concept is that interferometric bilayered NAA (BL-NAA, which features two layers of different pore diameters, can provide distinct reflectometric interference spectroscopy (RIfS signatures for each layer within the NAA structure and can therefore potentially be used for multi-point biosensing. This paper presents the structural fabrication of layered NAA structures, and the optimization and evaluation of their RIfS optical sensing performance through changes in the effective optical thickness (EOT using quercetin as a model molecule. The bilayered or funnel-like NAA structures were designed with the aim of characterizing the sensitivity of both layers of quercetin molecules using RIfS and exploring the potential of these photonic structures, featuring different pore diameters, for simultaneous size-exclusion and multi-analyte optical biosensing. The sensing performance of the prepared NAA platforms was examined by real-time screening of binding reactions between human serum albumin (HSA-modified NAA (i.e., sensing element and quercetin (i.e., analyte. BL-NAAs display a complex optical interference spectrum, which can be resolved by fast Fourier transform (FFT to monitor the EOT changes, where three distinctive peaks were revealed corresponding to the top, bottom, and total layer within the BL-NAA structures. The spectral shifts of these three characteristic peaks were used as sensing signals to monitor the binding events in each NAA pore in real-time upon exposure to different

  6. Natural Object Categorization.

    Science.gov (United States)

    1987-11-01

    gram (MEG)) Igr-pen IR)) (gr-rif CS))£ (gr-kan (R)) (dole ( porn )) - (esculin (po*n)) (bile (a)) (gic (18)) :(Saaicln (nag poxn)) :( arab (Poo...glc (Is)) (fsailn (nlaq pas)) ;( arab (pas)) (rham ( porn )) (nfl (1 2 3 4)) (nf2 C1 2 3 4))))) 206% % %V *A A 0 (dofvar 3ACTZ3Z&-YX-S13C (make-instance...qr-rif MS) (qr-kan (R)) (dole (nag)) (exculin (pasn)) (bile (a)) (gIG (12)) ;(sailcin rnag)) ŕ ( arab Ineg)) (rham (nag)) (nfl (1 23 4)))) (defvar M

  7. A Hybrid MCMC Sampler for Unconditional Quantile Based on Influence Function

    Directory of Open Access Journals (Sweden)

    El Moctar Laghlal

    2018-05-01

    Full Text Available In this study, we provide a Bayesian estimation method for the unconditional quantile regression model based on the Re-centered Influence Function (RIF. The method makes use of the dichotomous structure of the RIF and estimates a non-linear probability model by a logistic regression using a Gibbs within a Metropolis-Hastings sampler. This approach performs better in the presence of heavy-tailed distributions. Applied to a nationally-representative household survey, the Senegal Poverty Monitoring Report (2005, the results show that the change in the rate of returns to education across quantiles is substantially lower at the primary level.

  8. Label-free detection of C-reactive protein using reflectometric interference spectroscopy-based sensing system

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyung Woo; Sakata, Yasuhiko [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan); Kurihara, Yoshikazu [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan); KONICA MINOLTA OPTO, Inc., 1 Sakura-machi, Hino-shi, Tokyo 191-8511 (Japan); Ooya, Tooru [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan); Takeuchi, Toshifumi, E-mail: takeuchi@gold.kobe-u.ac.jp [Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501 (Japan)

    2012-05-30

    Highlights: Black-Right-Pointing-Pointer A new RIfS-based label-free biosensing system for C-reactive protein was developed. Black-Right-Pointing-Pointer Silicon-based inexpensive chips and the simple optical setup were employed. Black-Right-Pointing-Pointer Owing to the TMS treatment and the use of protein A, the sensitivity was enhanced. Black-Right-Pointing-Pointer It can be applied to other target as a substitute of SPR-based expensive sensors. - Abstract: Reflectometric interference spectroscopy (RIfS) is a label-free, time-resolved technique, and suitable for detecting antibody-antigen interaction. This work describes a continuous flow biosensor for C-reactive protein (CRP), involving an effective immobilization method of a monoclonal antibody against CRP (anti-CRP) to achieve highly sensitive RIfS-based detection of CRP. The silicon nitride-coated silicon chip (SiN chip) for the RIfS sensing was first treated with trimethylsilylchloride (TMS), followed by UV-light irradiation to in situ generation of homogeneous silanols on the surface. Following amination by 3-aminopropyltriethoxysilane, carboxymethyldextran (CMD) was grafted, and subsequently, protein A was immobilized to create the oriented anti-CRP surface. The immobilization process of protein A and anti-CRP was monitored with the RIfS system by consecutive injections of an amine coupling reagent, protein A and anti-CRP, respectively, to confirm the progress of each step in real time. The sensitivity was enhanced when all of the processes were adopted, suggesting that the oriented immobilization of anti-CRP via protein A that was coupled with the grafted CMD on the aminated surface of TMS-treated SiN chip. The feasibility of the present sensing system was demonstrated on the detection of CRP, where the silicon-based inexpensive chips and the simple optical setup were employed. It can be applied to other target molecules in various fields of life science as a substitute of surface plasmon resonance

  9. Genetic and proteomic characterization of rpoB mutations and their effect on nematicidal activity in Photorhabdus luminescens LN2.

    Directory of Open Access Journals (Sweden)

    Xuehong Qiu

    Full Text Available Rifampin resistant (Rif(R mutants of the insect pathogenic bacterium Photorhabdus luminescens LN2 from entomopathogenic nematode Heterorhabditis indica LN2 were genetically and proteomically characterized. The Rif(R mutants showed typical phase one characters of Photorhabdus bacteria, and insecticidal activity against Galleria mellonella larvae, but surprisingly influenced their nematicidal activity against axenic infective juveniles (IJs of H. bacteriophora H06, an incompatible nematode host. 13 out of 34 Rif(R mutants lost their nematicidal activity against H06 IJs but supported the reproduction of H06 nematodes. 7 nematicidal-producing and 7 non-nematicidal-producing Rif(R mutants were respectively selected for rpoB sequence analysis. rpoB mutations were found in all 14 Rif(R mutants. The rpoB (P564L mutation was found in all 7 mutants which produced nematicidal activity against H06 nematodes, but not in the mutants which supported H06 nematode production. Allelic exchange assays confirmed that the Rif-resistance and the impact on nematicidal activity of LN2 bacteria were conferred by rpoB mutation(s. The non-nematicidal-producing Rif(R mutant was unable to colonize in the intestines of H06 IJs, but able to colonize in the intestines of its indigenous LN2 IJs. Proteomic analysis revealed different protein expression between wild-type strain and Rif(R mutants, or between nematicidal-producing and non nematicidal-producing mutants. At least 7 putative proteins including DsbA, HlpA, RhlE, RplC, NamB (a protein from T3SS, and 2 hypothetical proteins (similar to unknown protein YgdH and YggE of Escherichia coli respectively were probably involved in the nematicidal activity of LN2 bacteria against H06 nematodes. This hypothesis was further confirmed by creating insertion-deletion mutants of three selected corresponding genes (the downregulated rhlE and namB, and upregulated dsbA. These results indicate that the rpoB mutations greatly influence the

  10. Comparison of indirect immunofluorescence test for measles antibodies with haemagglutination inhibition and plaque neutralization tests Comparação da reação de imunofluorescência indireta para o vírus do sarampo com as reações de inibição da hemaglutinação e neutralização por redução de placas

    Directory of Open Access Journals (Sweden)

    Vanda Akico Ueda Fick de Souza

    1990-10-01

    Full Text Available Indirect Immunofluorescence (IFA, Plaque Reduction Neutralization (PRN and Haemagglutination Inhibition (HI tests for measles antibodies were carried out in 197 sera obtained from umbilical cord and vaccinated children. The IFA was also applied to blood samples collected with filter paper. IFA results demonstrated that the test is relatively simple to perform, with good reproducibility for different antigen lots. Good correlation was obtained between IFA, PRN and HI antibody titers. Better correlation was demonstrated with IFA and PRN than with HI and PRN tests. Sensitivity of IFA in detecting antibody was less effective than PRN, however more effective than HI using rhesus monkey red blood cells. PRN antibody titers over 100 were detected by IFA but not by HI (9.7% with negative results. IFA may be of considerable practical use and able to substitute HI in Seroepidemiological surveys and to evaluate vaccine efficacy. It also can be simplified by employing filter paper collected samples.As reações de imunofluorescência indireta (RIF, neutralização por redução de placas (RNP e inibição da hemaglutinação (RIH para detecção de anticorpos para o vírus do sarampo foram aplicadas a 197 soros provenientes de cordão umbilical e de crianças vacinadas contra o sarampo. Avaliou-se ainda a aplicação da RIF em amostras colhidas em papel de filtro. A RIF apresentou-se como uma prova de execução relativamente simples, de boa reprodutibilidade com diferentes partidas de antígeno. Observou-se boa correlação entre os títulos de anticorpos obtidos por RIF, RNP e RIH. Com a RNP, a RIF apresentou maior correlação que a RIH. A sensibilidade da RIF na detecção de anticorpos contra o sarampo foi menor que RNP, porém superior à da RIH com hemácias de macaco rhesus. Anticorpos com títulos superiores a 100 pela RNP foram sistematicamente detectados pela RIF, mas não por RIH (9,7% de resultados negativos. A RIF pode ser de grande utilidade

  11. Potential of improving the treatment of tuberculosis through nanomedicine

    CSIR Research Space (South Africa)

    Semete, B

    2012-03-01

    Full Text Available allowing its attachment onto the cell (Trewyn et al., 2008). It is equally admitted that spherical particles offer maximum volume for drug incorporation. We also observed that the use of lactose in the spray dried formulation helped to decrease...: in vivo release of free drugs vs spray dried nanoparticles encapsulating RIF, INH and PZA. A. Samples with high concentration of lactose (5%w/v) and B. samples with low concentration of lactose (4%w/v). C. The multidose indicates a formulation where RIF...

  12. In vivo/in vitro pharmacokinetic and pharmacodynamic study of spray-dried poly-(dl-lactic-co-glycolic) acid nanoparticles encapsulating rifampicin and isoniazid

    CSIR Research Space (South Africa)

    Booysen, LLIJ

    2013-02-01

    Full Text Available . tb.) (strain H(sub37)Rv). Sustained drug release over seven days were observed for these drugs following once-off oral administration in mice with subsequent drug distribution of up to 10 days in the liver and lungs for RIF and INH, respectively...

  13. The adaptive response of mouse tumours to anaemia and retransfusion

    International Nuclear Information System (INIS)

    Hirst, D.G.; Wood, P.J.

    1987-01-01

    Exchange transfusion methods have been developed to alter the haematocrit of tumour-bearing mice. The effects of anaemia and its correction by blood transfusion on the radiosensitivity of two mouse tumours (SCCVII/St and RIF-1) were studied using excision, in vivo/in vitro assay. Acute reduction in haematocrit caused a high degree of radioresistance equivalent to an increase in the hypoxic fractions by factors of 10 (SCCVII/St) and 30 (RIF-1). As the duration of anaemia was prolonged, radioresistance was lost until within about 6 h normal radiosensitivity was observed even though the anaemia persisted. The restoration of the normal haematocrit by red blood cell transfusion after 24 h of anaemia caused increased radiosensitivity equivalent to a reduction in the hypoxic fraction by factors of 5 (SCCVII/St) and 10 (RIF-1), but again the effect was transient and normal radiosensitivity re-established within 24-48 h of retransfusion. Measurements of 14 C misonidazole (MISO) binding to RIF-1 tumours after these procedures indicated changes in the number of hypoxic cells which were qualitatively almost identical to those using the cell survival endpoint, leading to the belief that changes in oxygenation were reponsible for the altered radiosensitivity. (author)

  14. Waste Management Plan for the Oak Ridge National Remedial Investigation/Feasibility Study

    International Nuclear Information System (INIS)

    1988-04-01

    In accordance with the requirements of the Remedial Investigation/Feasibility Study (RI/FS) Project Quality Assurance Plan, this Waste Management Plan establishes clear lines of responsibility and authority, documentation requirements, and operational guidance for the collection, identification, segregation, classification, packaging, certification, and storage/disposal of wastes. These subjects are discussed in the subsequent sections of this document

  15. Effects of Phonological and Musical Training on the Reading Readiness of Native- and Foreign-Spanish-Speaking Children

    Science.gov (United States)

    Herrera, Lucia; Lorenzo, Oswaldo; Defior, Sylvia; Fernandez-Smith, Gerard; Costa-Giomi, Eugenia

    2011-01-01

    The purpose of this study was to evaluate the effectiveness of a music training program on children's phonological awareness and naming speed in Spanish. Participants were preschool children whose first language was either Spanish (n = 45) or Tamazight ( n = 52), a Berber dialect spoken in Morocco's Rif area. The two-year pretest/posttest study…

  16. Feasibility study report for Operable Unit 4: Volume 1

    International Nuclear Information System (INIS)

    1994-02-01

    This report documents the Feasibility Study (FS) phase of the Fernald Environmental Management Project (FEMP) Operable Unit 4 Remedial Investigation/Feasibility Study (RI/FS) Program. The FEMP, formerly known as the Feed Materials Production Center (FMPC), is a US Department of Energy (DOE) facility that operated from 1952 to 1989. The facility's primarily function was to provide high purity uranium metal products to support United States defense programs. Production operations were suspended in 1989 to focus on environmental restoration and waste management activities at the facility. The RI/FS is being conducted pursuant to the terms of a Consent Agreement between DOE and the US Environmental Protection Agency (EPA) under Sections 120 and 106(a) of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended. The Ohio Environmental Protection Agency (OEPA) is also participating in the RI/FS process at the FEMP through direct involvement in program review meetings and technical review of project documentation. The objective of the RI/FS process is to gather information to support an informed risk management decision regarding which remedy appears to be the most appropriate action for addressing the environmental concerns identified at the FEMP

  17. Feasibility study report for Operable Unit 4: Volume 2

    International Nuclear Information System (INIS)

    1994-02-01

    This report documents the Feasibility Study (FS) phase of the Fernald Environmental Management Project (FEMP) Operable Unit 4 Remedial Investigation/Feasibility Study (RI/FS) Program. The FEMP, formerly known as the Feed Materials Production Center (FMPC), is a US Department of Energy (DOE) facility that operated from 1952 to 1989. The facility's primarily function was to provide high purity uranium metal products to support United States defense programs. Production operations were suspended in 1989 to focus on environmental restoration and waste management activities at the facility. The RI/FS is being conducted pursuant to the terms of a Consent Agreement between DOE and the US Environmental Protection Agency (EPA) under Sections 120 and 106(a) of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended. The Ohio Environmental Protection Agency (OEPA) is also participating in the RI/FS process at the FEMP through direct involvement in program review meetings and technical review of project documentation. The objective of the RI/FS process is to gather information to support an informed risk management decision regarding which remedy appears to be the most appropriate action for addressing the environmental concerns identified at the FEMP. This volume contains appendices A--E

  18. Feasibility study report for Operable Unit 4: Fernald Environmental Management Project, Fernald, Ohio: Remedial investigation and feasibility study: Volume 3: Final report

    International Nuclear Information System (INIS)

    1994-02-01

    This report documents the Feasibility Study (FS) phase of the Fernald Environmental Management Project (FEMP) Operable Unit 4 Remedial Investigation/Feasibility Study (RI/FS) Program. The FEMP, formerly known as the Feed Materials Production Center (FMPC), is a US Department of Energy (DOE) facility that operated from 1952 to 1989. The facility's primarily function was to provide high purity uranium metal products to support United States defense programs. Production operations were suspended in 1989 to focus on environmental restoration and waste management activities at the facility. The RI/FS is being conducted pursuant to the terms of a Consent Agreement between DOE and the US Environmental Protection Agency (EPA) under Sections 120 and 106(a) of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), as amended. The Ohio Environmental Protection Agency (OEPA) is also participating in the RI/FS process at the FEMP through direct involvement in program review meetings and technical review of project documentation. The objective of the RI/FS process is to gather information to support an informed risk management decision regarding which remedy appears to be the most appropriate action for addressing the environmental concerns identified at the FEMP. This volume contains appendices F--J

  19. Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and non-coding regions

    DEFF Research Database (Denmark)

    Lavstsen, Thomas; Salanti, Ali; Jensen, Anja T R

    2003-01-01

    and organization of the 3D7 PfEMP1 repertoire was investigated on the basis of the complete genome sequence. METHODS: Using two tree-building methods we analysed the coding and non-coding sequences of 3D7 var and rif genes as well as var genes of other parasite strains. RESULTS: var genes can be sub...

  20. 75 FR 15465 - RMR Real Estate Income Fund, et al.; Notice of Application

    Science.gov (United States)

    2010-03-29

    ... Real Estate Income Fund, et al.; Notice of Application March 23, 2010. AGENCY: Securities and Exchange.... APPLICANTS: RMR Real Estate Income Fund and RMR Advisors, Inc. FILING DATES: December 31, 2003, September 23.... Applicants' Representations 1. RMR Real Estate Income Fund (``RIF'') is a closed-end management investment...

  1. 100-N Area Decision Unit Target Analyte List Development for Soil

    Energy Technology Data Exchange (ETDEWEB)

    Ovink, R.

    2012-09-18

    This report documents the process used to identify source area target analytes in support of the 100-N Area remedial investigation/feasibility study (RI/FS) addendum to the Integrated 100 Area Remedial Investigation/Feasibility Study Work Plan (DOE/RL-2008-46, Rev. 0).

  2. Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

    Science.gov (United States)

    Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

    2002-02-21

    Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

  3. Data base management plan for the remedial investigation/feasibility study at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    International Nuclear Information System (INIS)

    1993-11-01

    This Data Base Management (DBM) Plan has been prepared for use by Bechtel National, Inc. (Bechtel) and its subcontractors in the performance of the Oak Ridge National Laboratory (ORNL) Remedial Investigation/Feasibility Study (RI/FS) program activities. The RI/FS program is being performed under subcontract to Martin Marietta Energy Systems, Inc. (Energy Systems), the contractor operating ORNL for the Department of Energy. This DBM Plan defines the procedures and protocol to be followed in developing and maintaining the data base used by Bechtel and its subcontractors for RI/FS activities at ORNL; describes the management controls, policies, and guidelines to be followed; and identifies responsible positions and their Energy Systems functions. The Bechtel RI/FS data base will be compatible with the Oak Ridge Environmental Information System and will include data obtained from field measurements and laboratory and engineering analyses. Personnel health and safety information, document control, and project management data will also be maintained as part of the data base. The computerized data management system is being used to organize the data according to application and is capable of treating data from any given site as a variable entity. The procedures required to implement the DBM Plan are cross-referenced to specific sections of the plan

  4. Restoring mussel bed : A guide on how to survive on an intertidal mudflat

    NARCIS (Netherlands)

    de Paoli, Hélène Claudine

    2017-01-01

    Rif-vormende schelpdieren zoals mosselen en oesters zijn bijzonder belangrijk op bij eb droogvallende platen, doordat de complexe en solide banken die ze vormen een leefgebied bieden voor tal van soorten. In de Waddenzee is aan het eind van de jaren '80 het areaal aan droogvallende mosselbanken

  5. Basic radio interferometry for future lunar missions

    NARCIS (Netherlands)

    Aminaei, Amin; Klein Wolt, Marc; Chen, Linjie; Bronzwaer, Thomas; Pourshaghaghi, Hamid Reza; Bentum, Marinus Jan; Falcke, Heino

    2014-01-01

    In light of presently considered lunar missions, we investigate the feasibility of the basic radio interferometry (RIF) for lunar missions. We discuss the deployment of two-element radio interferometer on the Moon surface. With the first antenna element is envisaged to be placed on the lunar lander,

  6. Ramadan model of intermittent fasting for 28 d had no major effect on body composition, glucose metabolism, or cognitive functions in healthy lean men

    DEFF Research Database (Denmark)

    Harder-Lauridsen, Nina M.; Rosenberg, Astrid; Benatti, Fabiana B.

    2017-01-01

    Objectives: There has been a parallel increase in the incidence of obesity and diabetes as well as the number of daily meals. However, evidence is lacking regarding the role of intermittent fasting. The aim of this study was to determine the effects of a Ramadan model of intermittent fasting (RIF...

  7. Transforming growth factor-β1/Smad/connective tissue growth factor axis: The main pathway in radiation-induced fibrosis of osteoradionecrosis?

    Directory of Open Access Journals (Sweden)

    Qian Wei Zhuang

    2013-01-01

    Full Text Available Introduction: Osteoradionecrosis (ORN of the mandible is a serious complication following radiation therapy for malignancies of the head and neck. Radiation-induced fibrosis (RIF is a new theory that accounts for the damage to normal tissues after radiotherapy, and the radiation-induced fibroatrophic mechanism includes the free-radical formation, endothelial dysfunction, inflammation, microvascular thrombosis, fibrosis and remodeling, and finally bone and tissue necrosis. The Hypothesis: Previous studies revealed that transforming growth factor-β1 (TGF-β1 is the master switch cytokine responsible for the regulation of fibroblast proliferation and differentiation that result in RIF. Among the targets of TGF-β1, connective tissue growth factor (CTGF is a downstream mediator through the Smad3/4 pathway and plays an important role in connective tissue homeostasis and fibroblast proliferation. Studies have proved that the TGF-β1/Smad/CTGF signaling pathway is involved in the RIF of soft tissues, so the authors put forward a hypothesis that the TGF-β1/Smad/CTGF axis is also the main pathway in RIF of ORN. Evaluation of the Hypothesis: The validation of our hypothesis may provide new insights for better understanding the pathogenesis of ORN and open new perspectives for anti-fibrotic therapies, and pioneer novel approaches to treat ORN.

  8. Measurement of the 209Bi(n ,4 n )206Bi and 169Tm(n ,3 n )167Tm cross sections between 23.5 and 30.5 MeV relevant to reaction-in-flight neutron studies at the National Ignition Facility

    Science.gov (United States)

    Gooden, M. E.; Bredeweg, T. A.; Champine, B.; Combs, D. C.; Finch, S.; Hayes-Sterbenz, A.; Henry, E.; Krishichayan, Rundberg, R.; Tornow, W.; Wilhelmy, J.; Yeamans, C.

    2017-08-01

    At the National Ignition Facility, experiments are being performed to measure charged-particle stopping powers in the previously unexplored warm dense plasma regime. These measurements are done using reaction-in-flight (RIF) neutrons from an inertial confinement fusion system. RIF neutrons are produced with a continuum of energies up to 30 MeV. By making activation measurements utilizing threshold reactions for neutrons in the energy range of 15 RIF neutrons can be determined and from this the stopping power of the deuterium and tritium ions that produced the RIF neutrons can be inferred. Currently, the 169Tm(n ,3 n )167Tm reaction has been used. However, in an effort to provide a secondary complimentary measurement, efforts are underway to make use of the 209Bi(n ,4 n )206Bi reaction, with a threshold of 22.5 MeV. The cross sections were measured at the 10 MV tandem Van De Graaff accelerator at the Triangle Universities Nuclear Laboratory with quasimonoenergetic neutrons between 23.5 and 30.5 MeV, where few previous measurements have been made. Cross-section data are compared to calculations and other available measurements.

  9. Is Retrieval-Induced Forgetting behind the Bilingual Disadvantage in Word Production?

    Science.gov (United States)

    Runnqvist, Elin; Costa, Albert

    2012-01-01

    Levy, Mc Veigh, Marful and Andreson (2007) found that naming pictures in L2 impaired subsequent recall of the L1 translation words. This was interpreted as evidence for a domain-general inhibitory mechanism (RIF) underlying first language attrition. Because this result is at odds with some previous findings and theoretical assumptions, we wanted…

  10. [Competition-dependence on retrieval-induced forgetting: the influence of the amount of retrieval cues].

    Science.gov (United States)

    Yamada, Yohei; Tsukimoto, Takashi; Hirano, Tetsuji

    2010-02-01

    Remembering some of the studied (target) items impairs subsequent remembrance of relevant (non-target) items. This phenomenon, retrieval-induced forgetting (RIF), occurs when non-targets actively compete with the retrieval of a target. Researchers suggest that suppression mechanisms reduce interference from relevant items to facilitate the retrieval of target items (Anderson, 2003). Competition-dependence is one of the properties that support the suppression hypothesis (Anderson, Bjork, & Bjork, 1994). In the present study, we manipulated the type of retrieval practice (normal, last-letter, or category-name) in order to vary the degree of competition between the target and the non-targets. For the high-scoring retrieval practice group, RIF occurred in the normal retrieval condition, but not in the last-letter or in the category-name conditions. For the low-scoring retrieval practice group, RIF did not occur in any of the conditions. These findings provide new evidence that the occurrence of RIF depends on the degree of competition between a target item and related non-target items during retrieval practice.

  11. Contextual Match and Cue-Independence of Retrieval-Induced Forgetting: Testing the Prediction of the Model by Norman, Newman, and Detre (2007)

    Science.gov (United States)

    Hanczakowski, Maciej; Mazzoni, Giuliana

    2013-01-01

    Retrieval-induced forgetting (RIF) is the finding of impaired memory performance for information stored in long-term memory due to retrieval of a related set of information. This phenomenon is often assigned to operations of a specialized mechanism recruited to resolve interference during retrieval by deactivating competing memory representations.…

  12. On the Status of Cue Independence as a Criterion for Memory Inhibition: Evidence against the Covert Blocking Hypothesis

    Science.gov (United States)

    Weller, Peter D.; Anderson, Michael C.; Gómez-Ariza, Carlos J.; Bajo, M. Teresa

    2013-01-01

    Retrieving memories can impair recall of other related traces. Items affected by this retrieval-induced forgetting (RIF) are often less accessible when tested with independent probes, a characteristic known as cue independence. Cue independence has been interpreted as evidence for inhibitory mechanisms that suppress competing items during…

  13. Less we forget: retrieval cues and release from retrieval-induced forgetting.

    Science.gov (United States)

    Jonker, Tanya R; Seli, Paul; Macleod, Colin M

    2012-11-01

    Retrieving some items from memory can impair the subsequent recall of other related but not retrieved items, a phenomenon called retrieval-induced forgetting (RIF). The dominant explanation of RIF-the inhibition account-asserts that forgetting occurs because related items are suppressed during retrieval practice to reduce retrieval competition. This item inhibition persists, making it more difficult to recall the related items on a later test. In our set of experiments, each category was designed such that each exemplar belonged to one of two subcategories (e.g., each BIRD exemplar was either a bird of prey or a pet bird), but this subcategory information was not made explicit during study or retrieval practice. Practicing retrieval of items from only one subcategory led to RIF for items from the other subcategory when cued only with the overall category label (BIRD) at test. However, adapting the technique of Gardiner, Craik, and Birtwistle (Journal of Learning and Verbal Behavior 11:778-783, 1972), providing subcategory cues during the final test eliminated RIF. The results challenge the inhibition account's fundamental assumption of cue independence but are consistent with a cue-based interference account.

  14. Ecological risk assessment guidance for preparation of remedial investigation/feasibility study work plans

    International Nuclear Information System (INIS)

    Pentecost, E.D.; Vinikour, W.S.

    1993-08-01

    This guidance document (1) provides instructions on preparing the components of an ecological work plan to complement the overall site remedial assessment investigation/feasibility study (RI/FS) work plan and (2) directs the user on how to implement ecological tasks identified in the plan. Under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), as amended by the Superfired Amendments and Reauthorization Act of 1986 (SARA), an RI/FS work plan win have to be developed as part of the site-remediation scoping the process. Specific guidance on the RI/FS process and the preparation of work plans has been developed by the US Environmental Protection Agency (EPA 1988a). This document provides guidance to US Department of Energy (DOE) staff and contractor personnel for incorporation of ecological information into environmental remediation planning and decision making at CERCLA sites. An overview analysis of early ecological risk assessment methods (i.e., in the 1980s) at Superfund sites was conducted by the EPA (1989a). That review provided a perspective of attention given to ecological issues in some of the first RI/FS studies. By itself, that reference is of somewhat limited value; it does, however, establish a basis for comparison of past practices in ecological risk with current, more refined methods

  15. THE STRUCTURE OF RIFF.

    Science.gov (United States)

    APPLEGATE, JOSEPH R.

    THE PURPOSE OF THIS DESCRIPTIVE STUDY IS TO DEFINE THE MAJOR STRUCTURAL FEATURES OF RIFF, A BERBER LANGUAGE SPOKEN BY THE BERBER TRIBESMEN OF THE RIF IN NORTHERN MOROCCO. THE DESCRIPTION IS PRESENTED IN THREE PARTS--PHONOLOGY, MORPHOLOGY, AND SYNTAX. THE PHONEMES ARE DESCRIBED IN TERMS OF DISTINCTIVE FEATURES. PHARYNGEALIZATION AND TENSION ARE…

  16. Rapid detection of multidrug-resistant Mycobacterium tuberculosis using the malachite green decolourisation assay

    Science.gov (United States)

    Coban, Ahmet Yilmaz; Uzun, Meltem

    2013-01-01

    Early detection of drug resistance in Mycobacterium tuberculosis isolates allows for earlier and more effective treatment of patients. The aim of this study was to investigate the performance of the malachite green decolourisation assay (MGDA) in detecting isoniazid (INH) and rifampicin (RIF) resistance in M. tuberculosis clinical isolates. Fifty M. tuberculosis isolates, including 19 multidrug-resistant, eight INH-resistant and 23 INH and RIF-susceptible samples, were tested. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and agreement of the assay for INH were 92.5%, 91.3%, 92.5%, 91.3% and 92%, respectively. Similarly, the sensitivity, specificity, PPV, NPV and agreement of the assay for RIF were 94.7%, 100%, 100%, 96.8% and 98%, respectively. There was a major discrepancy in the tests of two isolates, as they were sensitive to INH by the MGDA test, but resistant by the reference method. There was a minor discrepancy in the tests of two additional isolates, as they were sensitive to INH by the reference method, but resistant by the MGDA test. The drug susceptibility test results were obtained within eight-nine days. In conclusion, the MGDA test is a reliable and accurate method for the rapid detection of INH and RIF resistance compared with the reference method and the MGDA test additionally requires less time to obtain results. PMID:24402143

  17. Rapid detection of multidrug-resistant Mycobacterium tuberculosis using the malachite green decolourisation assay

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz Coban

    2013-12-01

    Full Text Available Early detection of drug resistance in Mycobacterium tuberculosis isolates allows for earlier and more effective treatment of patients. The aim of this study was to investigate the performance of the malachite green decolourisation assay (MGDA in detecting isoniazid (INH and rifampicin (RIF resistance in M. tuberculosis clinical isolates. Fifty M. tuberculosis isolates, including 19 multidrug-resistant, eight INH-resistant and 23 INH and RIF-susceptible samples, were tested. The sensitivity, specificity, positive predictive value (PPV, negative predictive value (NPV and agreement of the assay for INH were 92.5%, 91.3%, 92.5%, 91.3% and 92%, respectively. Similarly, the sensitivity, specificity, PPV, NPV and agreement of the assay for RIF were 94.7%, 100%, 100%, 96.8% and 98%, respectively. There was a major discrepancy in the tests of two isolates, as they were sensitive to INH by the MGDA test, but resistant by the reference method. There was a minor discrepancy in the tests of two additional isolates, as they were sensitive to INH by the reference method, but resistant by the MGDA test. The drug susceptibility test results were obtained within eight-nine days. In conclusion, the MGDA test is a reliable and accurate method for the rapid detection of INH and RIF resistance compared with the reference method and the MGDA test additionally requires less time to obtain results.

  18. Indentation fatigue in silicon nitride, alumina and silicon carbide ...

    Indian Academy of Sciences (India)

    Unknown

    carbide ceramics. A K MUKHOPADHYAY. Central Glass and Ceramic Research Institute, Kolkata 700 032, India. Abstract. Repeated indentation fatigue (RIF) experiments conducted on the same spot of different structural ceramics viz. a hot pressed silicon nitride (HPSN), sintered alumina of two different grain sizes viz.

  19. Remedial investigation/feasibility study Work Plan and addenda for Operable Unit 4-12: Central Facilities Area Landfills II and III at the Idaho National Engineering Laboratory

    International Nuclear Information System (INIS)

    Keck, K.N.; Stormberg, G.J.; Porro, I.; Sondrup, A.J.; McCormick, S.H.

    1993-07-01

    This document is divided into two main sections -- the Work Plan and the addenda. The Work Plan describes the regulatory history and physical setting of Operable Unit 4-12, previous sampling activities, and data. It also identifies a preliminary conceptual model, preliminary remedial action alternatives, and preliminary applicable or relevant and appropriate requirements. In addition, the Work Plan discusses data gaps and data quality objectives for proposed remedial investigation activities. Also included are tasks identified for the remedial investigation/feasibility study (RI/FS) and a schedule of RI/FS activities. The addenda include details of the proposed field activities (Field Sampling Plan), anticipated quality assurance activities (Quality Assurance Project Plan), policies and procedures to protect RI/FS workers and the environment during field investigations (Health and Safety Plan), and policies, procedures, and activities that the Department of Energy will use to involve the public in the decision-making process concerning CFA Landfills II and III RI/FS activities (Community Relations Plan)

  20. "Keeping in mind the gender stereotype": the role of need for closure in the retrieval-induced forgetting of female managers' qualities.

    Science.gov (United States)

    Pica, Gennaro; Pierro, Antonio; Pellegrini, Valerio; De Cristofaro, Valeria; Giannini, Annamaria; Kruglanski, Arie W

    2018-05-19

    The present research addressed the question of whether need for closure (NFC; Kruglanski in The psychology of closed mindedness, Psychology Press, New York, 2004) biases individuals' memory of female leaders. Merging research on role congruity theory of leadership (Koenig et al. in Psychol Bull 4:616-642, 2011. https://doi.org/10.1037/a0023557 ) and research on retrieval-induced forgetting (RIF, Anderson et al. in J Exp Psychol Learn Mem Cognit 20:1063-1087, 1994. https://doi.org/10.1037/0022-3514.65.5.861 ), we hypothesized and found that high-NFC participants show (1) a higher RIF of dimensions commonly associated with the leadership prototype (agentic/masculine) ascribed to female manager targets, when selectively retrieved dimensions commonly associated with the female prototype (communal/feminine) were ascribed to the same target; and (2) a lessened RIF of female stereotypical dimensions ascribed to female manager targets, when selectively retrieved prototypical leadership dimensions were ascribed to the same target. Overall, the present findings suggest that when faced with women leaders, high NfC enhances the accessibility of gender stereotype-congruent memories and reduces the accessibility of prototypical leadership ones, thus reducing the RIF of communal/feminine memories.

  1. Resonance interference method in lattice physics code stream

    International Nuclear Information System (INIS)

    Choi, Sooyoung; Khassenov, Azamat; Lee, Deokjung

    2015-01-01

    Newly developed resonance interference model is implemented in the lattice physics code STREAM, and the model shows a significant improvement in computing accurate eigenvalues. Equivalence theory is widely used in production calculations to generate the effective multigroup (MG) cross-sections (XS) for commercial reactors. Although a lot of methods have been developed to enhance the accuracy in computing effective XSs, the current resonance treatment methods still do not have a clear resonance interference model. The conventional resonance interference model simply adds the absorption XSs of resonance isotopes to the background XS. However, the conventional models show non-negligible errors in computing effective XSs and eigenvalues. In this paper, a resonance interference factor (RIF) library method is proposed. This method interpolates the RIFs in a pre-generated RIF library and corrects the effective XS, rather than solving the time consuming slowing down calculation. The RIF library method is verified for homogeneous and heterogeneous problems. The verification results using the proposed method show significant improvements of accuracy in treating the interference effect. (author)

  2. 100-K Target Analyte List Development for Soil

    Energy Technology Data Exchange (ETDEWEB)

    Ovink, R.

    2012-09-18

    This report documents the process used to identify source area target analytes in support of the 100-K Area remedial investigation/feasibility study (RI/FS) addendum to the Integrated 100 Area Remedial Investigation/Feasibility Study Work Plan (DOE/RL-2008-46, Rev. 0).

  3. 100-F Target Analyte List Development for Soil

    Energy Technology Data Exchange (ETDEWEB)

    Ovink, R.

    2012-09-18

    This report documents the process used to identify source area target analytes in support of the 100-F Area remedial investigation/feasibility study (RI/FS) addendum to the Integrated 100 Area Remedial Investigation/Feasibility Study Work Plan (DOE/RL-2008-46, Rev. 0).

  4. Unexpected Jurasic to Neogene vertical movements in "stable" parts of NW Africa revealed by low temperature geochronology

    NARCIS (Netherlands)

    Ghorbal, B.; Bertotti, G.V.; Foeken, J.P.T.; Andriessen, P.A.M.

    2008-01-01

    In Morocco, it is generally considered that post-Hercynian vertical movements were limited to the Atlas system, the passive continental margin and the Rif. Apatite FT and He ages from the Moroccan Meseta (Rehamna and Zaer Massif) document instead two episodes of subsidence and exhumation in

  5. Retrieval-induced forgetting in schizophrenia.

    Science.gov (United States)

    Nestor, Paul G; Piech, Richard; Allen, Christopher; Niznikiewicz, Margaret; Shenton, Martha; McCarley, Robert W

    2005-06-15

    Retrieving category associates (e.g., FRUIT-ORANGE) may induce forgetting other category members (e.g., FRUIT-BANANA), a phenomenon known as retrieval-induced forgetting (RIF). We designed 2 experiments to examine the role of RIF in the associative memory impairment of schizophrenia (SZ). Subjects studied 36 category-exemplar pairs, generated from 6 categories composed of 6 members each. For half of the studied category-exemplar pairs, subjects practiced retrieval by completing word stems, followed by a delayed category-cued recall on all of the practiced and unpracticed items. Experiment 1 used unrelated category exemplars-pairs (e.g., FRUIT-ORANGE, METALS-IRON), whereas experiment 2 included related category exemplar pairs (e.g., COTTON-SHIRT, LEATHER-SKIRT). SZ showed reduced associative memory but normal RIF for unrelated categories used in experiment 1. For experiment 2, SZ showed a significant decline in associative memory for related but not unrelated category-exemplars in comparison to controls. Results suggested faulty specificity/distinctiveness for encoding and retrieval, but not abnormal RIF in the associative memory disturbance of SZ.

  6. Individual Differences in Working Memory Capacity Predict Retrieval-Induced Forgetting

    Science.gov (United States)

    Aslan, Alp; Bauml, Karl-Heinz T.

    2011-01-01

    Selectively retrieving a subset of previously studied information enhances memory for the retrieved information but causes forgetting of related, nonretrieved information. Such retrieval-induced forgetting (RIF) has often been attributed to inhibitory executive-control processes that supposedly suppress the nonretrieved items' memory…

  7. Nanolabel for TNF-α determination

    Energy Technology Data Exchange (ETDEWEB)

    Say, Rıdvan, E-mail: rsay@anadolu.edu.tr [Anadolu University, Faculty of Sciences, Department of Chemistry 26470 Eskişehir (Turkey); Diltemiz, Sibel Emir, E-mail: semir@anadolu.edu.tr [Anadolu University, Faculty of Sciences, Department of Chemistry 26470 Eskişehir (Turkey); Çelik, Suzan, E-mail: syazar@gmail.com [Sanovel İlaç San. ve Tic. A.Ş. 34460 İstinye, Sarıyer/Istanbul (Turkey); Ersöz, Arzu, E-mail: arzuersoz@anadolu.edu.tr [Anadolu University, Faculty of Sciences, Department of Chemistry 26470 Eskişehir (Turkey)

    2013-06-15

    Tumor necrosis factor-α (TNF-α), also known as cachectin, is one of the most important regulatory cytokines and mediates a variety of cell functions, including the stimulation of nitric oxide (NO) production which has been related to oxidative stress and diseases such as arthritis, diabetes, stroke, and chronic inflammation. Determination of TNF-α concentration in human serum might be helpful in the staging and prognosis of diseases. And it is also very important for the understanding of tumor biological processes, inherent mechanisms, and discovering drugs as well as having a therapeutic potential for the treatment of diseases. So, in this study, sensor systems based on Reflectometric Interference Spectroscopy (RIfS) have been prepared for selectively recognition and binding of TNF-α biomolecules. For this purpose, photosensitive nano structured TNF-α has been synthesized applying AmiNoAcid (monomer) Decorated and Light Underpining Conjugation Approach (ANADOLUCA) method using bis (2-2′-bipyridyl) MATyr-MATyr-ruthenium(II) (MATyr-Ru-MATyr) as a photosensitive monomer. Then, these photosensitive nano structured TNF-α have been used for TNF-α recognition as an alternative and unique sensor method. Also, the affinity constant of RIfS sensor has been calculated. The method has been showed high sensitivity, good precision and accuracy, and suited for the detection of TNF-α from aqueous solution.

  8. Correspondence

    African Journals Online (AJOL)

    A new algorithm for the diagnosis of all forms of tuberculosis is required for. South Africa. To the Editor: I write in response to 'Diagnosing Xpert MTB/RIF- negative TB: Impact and cost of alternative algorithms for South. Africa' published in the SAMJ in February 2013.[1]. Modelling the impact and cost of alternative algorithms ...

  9. Prospective Study Validating Inter- and Intraobserver Variability of Tissue Compliance Meter in Breast Tissue of Healthy Volunteers: Potential Implications for Patients With Radiation-Induced Fibrosis of the Breast

    International Nuclear Information System (INIS)

    Wernicke, A. Gabriella; Parashar, Bhupesh; Kulidzhanov, Fridon; Riley, Lillian; Christos, Paul J.; Fischer, Andrew; Nori, Dattatreyudu; Chao, K.S. Clifford

    2011-01-01

    Purpose: Accurate detection of radiation-induced fibrosis (RIF) is crucial in management of breast cancer survivors. Tissue compliance meter (TCM) has been validated in musculature. We validate TCM in healthy breast tissue with respect to interobserver and intraobserver variability before applying it in RIF. Methods and Materials: Three medical professionals obtained three consecutive TCM measurements in each of the four quadrants of the right and left breasts of 40 women with no breast disease or surgical intervention. The intraclass correlation coefficient (ICC) assessed interobserver variability. The paired t test and Pearson correlation coefficient (r) were used to assess intraobserver variability within each rater. Results: The median age was 45 years (range, 24-68 years). The median bra size was 35C (range, 32A-40DD). Of the participants, 27 were white (67%), 4 black (10%), 5 Asian (13%), and 4 Hispanic (10%). ICCs indicated excellent interrater reliability (low interobserver variability) among the three raters, by breast and quadrant (all ICC ≥0.99). The paired t test and Pearson correlation coefficient both indicated low intraobserver variability within each rater (right vs. left breast), stratified by quadrant (all r≥ 0.94, p < 0.0001). Conclusions: The interobserver and intraobserver variability is small using TCM in healthy mammary tissue. We are now embarking on a prospective study using TCM in women with breast cancer at risk of developing RIF that may guide early detection, timely therapeutic intervention, and assessment of success of therapy for RIF.

  10. Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huaijun; Keyzer, Frederik de; Jin, Lixin; Yu, Jie; Marchal, Guy; Ni, Yicheng [Catholic University of Leuven, Department of Radiology, University Hospitals, Leuven (Belgium); Putte, Marie van de; Witte, Peter de [K.U. Leuven, Laboratory for Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, Leuven (Belgium); Chen, Feng [Catholic University of Leuven, Department of Radiology, University Hospitals, Leuven (Belgium); Southeast University, Department of Radiology, Zhong Da Hospital, Nanjing, Jiangsu Province (China)

    2008-07-15

    We sought to establish and characterize a mouse liver tumor model as a platform for preclinical assessment of new diagnostics and therapeutics. Radiation-induced fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with postmortem microangiography and histopathology. Implantation procedure succeeded in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in 21 mice with volume doubling time of 2.55{+-}0.88 days and final size of 216.2{+-}150.4 mm{sup 3} at day 14. Three mice were found without tumor growth and one only with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI, maximal initial slope of contrast-time curve and volume transfer constant per unit volume of tissue, K, differed between the tumor and liver with only the former significantly lower in the tumor than in the liver (P<0.05). Liver implantation of RIF-1 in mice proves a feasible and reproducible model and appears promising for use to screen new diagnostics and therapeutics under noninvasive monitoring even with a clinical MRI system. (orig.)

  11. Tuberculosis diagnosis in resource-limited settings: Clinical use of ...

    African Journals Online (AJOL)

    EB

    GeneXpert in the diagnosis of smear-negative PTB: a case report ... Background: The Xpert MTB/RIF test (GeneXpert) has recently been endorsed for use in resource-limited settings for the ... normochromic anemia (9.2g/dl), hypoalbuminemia.

  12. Intraperitoneal administration of chitosan/DsiRNA nanoparticles targeting TNFα prevents radiation-induced fibrosis

    International Nuclear Information System (INIS)

    Nawroth, Isabel; Alsner, Jan; Behlke, Mark A.; Besenbacher, Flemming; Overgaard, Jens; Howard, Kenneth A.; Kjems, Jorgen

    2010-01-01

    Background and purpose: One of the most common and dose-limiting long-term adverse effects of radiation therapy is radiation-induced fibrosis (RIF), which is characterized by restricted tissue flexibility, reduced compliance or strictures, pain and in severe cases, ulceration and necrosis. Several strategies have been proposed to ameliorate RIF but presently no effective one is available. Recent studies have reported that tumor necrosis factor-α (TNFα) plays a role in fibrogenesis. Material and methods: Male CDF1 mice were radiated with a single dose of 45 Gy. Chitosan/DsiRNA nanoparticles targeting TNFα were intraperitoneal injected and late radiation-induced fibrosis (RIF) was assessed using a modification of the leg contracture model. Additionally, the effect of these nanoparticles on tumor growth and tumor control probability in the absence of radiation was examined in a C3H mammary carcinoma model. Results: We show in this work, that targeting TNFα in macrophages by intraperitoneal administration of chitosan/DsiRNA nanoparticles completely prevented radiation-induced fibrosis in CDF1 mice without revealing any cytotoxic side-effects after a long-term administration. Furthermore, such TNFα targeting was selective without any significant influence on tumor growth or irradiation-related tumor control probability. Conclusion: This nanoparticle-based RNAi approach represents a novel approach to prevent RIF with potential application to improve clinical radiation therapeutic strategies.

  13. 76 FR 20546 - National Oil and Hazardous Substance Pollution Contingency Plan; National Priorities List...

    Science.gov (United States)

    2011-04-13

    ...'s Dump Superfund Site. Remedial Investigation and Feasibility Study (RI/FS) The Remedial... Investigation Report and Risk Assessment for both the Spiegelberg and Rasmussen's Dump Superfund sites due to... and operating an on-site pump and treat treatment pilot plant. Construction activities included: site...

  14. Remedial investigation/feasibility study Work Plan and addenda for Operable Unit 4-12: Central Facilities Area Landfills II and III at the Idaho National Engineering Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Keck, K.N.; Stormberg, G.J.; Porro, I.; Sondrup, A.J.; McCormick, S.H.

    1993-07-01

    This document is divided into two main sections -- the Work Plan and the addenda. The Work Plan describes the regulatory history and physical setting of Operable Unit 4-12, previous sampling activities, and data. It also identifies a preliminary conceptual model, preliminary remedial action alternatives, and preliminary applicable or relevant and appropriate requirements. In addition, the Work Plan discusses data gaps and data quality objectives for proposed remedial investigation activities. Also included are tasks identified for the remedial investigation/feasibility study (RI/FS) and a schedule of RI/FS activities. The addenda include details of the proposed field activities (Field Sampling Plan), anticipated quality assurance activities (Quality Assurance Project Plan), policies and procedures to protect RI/FS workers and the environment during field investigations (Health and Safety Plan), and policies, procedures, and activities that the Department of Energy will use to involve the public in the decision-making process concerning CFA Landfills II and III RI/FS activities (Community Relations Plan).

  15. Optical sensors for therapeutic drug monitoring of antidepressants for a better medication adjustment

    Science.gov (United States)

    Krieg, Anne K.; Hess, Stefan; Gauglitz, Günter

    2013-05-01

    Therapeutic drug monitoring provides the attending physicians with detailed information on a patient's individual serum level especially during long-term medication. Due to the fact that each patient tolerates drugs or their metabolites differently a medication adjustment can reduce the number and intensity of noticeable side-effects. In particular, psychotropic drugs can cause unpleasant side-effects that affect a patient's life almost as much as the mental disease itself. The tricyclic antidepressants amitriptyline is commonly used for treatment of depressions and was selected for the development of an immunoassay using the direct optical sensor technique Reflectometric Interference Spectroscopy (RIfS). RIfS is a simple, robust and label-free method for direct monitoring of binding events on glass surfaces. Binding to the surface causes a shift of the interference spectrum by a change of the refractive index or physical thickness. This technique can be used for time-resolved observation of association and dissociation of amitriptyline (antigen) and a specific antibody using the binding inhibition test format. An amitriptyline derivative is immobilized on the sensor surface and a specific amount of antibodies can bind to the surface unless the binding is inhibited by free amitriptyline in a sample. No fluorescent label is needed making the whole assay less expensive than label-based methods. With this recently developed immunoassay amitriptyline concentrations in buffer (PBS) can easily be detected down to 500 ng/L.

  16. 76 FR 32081 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

    Science.gov (United States)

    2011-06-03

    ... of August 1974. During landfill operation, latex waste sludge was discharged into unlined trenches... investigation during the RI/FS included waste, leachate, groundwater, surface water and sediment, soil, and air... County. Groundwater near the Site is used for domestic purposes, including drinking water. Landfill No. 1...

  17. A novel automatic molecular test for detection of multidrug resistance tuberculosis in sputum specimen: A case control study.

    Science.gov (United States)

    Li, Qiang; Ou, Xi C; Pang, Yu; Xia, Hui; Huang, Hai R; Zhao, Bing; Wang, Sheng F; Zhao, Yan L

    2017-07-01

    MiniLab tuberculosis (ML TB) assay is a new automatic diagnostic tool for diagnosis of multidrug resistance tuberculosis (MDR-TB). This study was conducted with aims to know the performance of this assay. Sputum sample from 224 TB suspects was collected from tuberculosis suspects seeking medical care at Beijing Chest hospital. The sputum samples were directly used for smear and ML TB test. The left sputum sample was used to conduct Xpert MTB/RIF, Bactec MGIT culture and drug susceptibility test (DST). All discrepancies between the results from DST, molecular and phenotypic methods were confirmed by DNA Sequencing. The sensitivity and specificity of ML TB test for detecting MTBC from TB suspects were 95.1% and 88.9%, respectively. The sensitivity for smear negative TB suspects was 64.3%. For detection of RIF resistance, the sensitivity and specificity of ML TB test were 89.2% and 95.7%, respectively. For detection of INH resistance, the sensitivity and specificity of ML TB test were 78.3% and 98.1%, respectively. ML TB test showed similar performance to Xpert MTB/RIF for detection of MTBC and RIF resistance. In addition, ML TB also had good performance for INH resistance detection. Copyright © 2017. Published by Elsevier Ltd.

  18. Toward Direct Reaction-in-Flight Measurements

    Science.gov (United States)

    Wilhelmy, Jerry; Bredeweg, Todd; Fowler, Malcolm; Gooden, Matthew; Hayes, Anna; Rusev, Gencho; Caggiano, Joseph; Hatarik, Robert; Henry, Eugene; Tonchev, Anton; Yeaman, Charles; Bhike, Megha; Krishichayan, Krishi; Tornow, Werner

    2016-03-01

    At the National Ignition Facility (NIF) neutrons having energies greater than the equilibrium 14.1 MeV value can be produced via Reaction-in-Flight (RIF) interactions between plasma atoms and upscattered D or T ions. The yield and spectrum of these RIF produced neutrons carry information on the plasma properties as well as information on the stopping power of ions under plasma conditions. At NIF the yield of these RIF neutrons is predicted to be 4-7 orders of magnitude below the peak 14 MeV neutron yield. The current generation of neutron time of flight (nTOF) instrumentation has so far been incapable of detecting these low-yield neutrons primarily due to high photon backgrounds. To date, information on RIF neutrons has been obtained in integral activation experiments using reactions with high energy thresholds such as 169Tm(n,3n)167Tm and 209Bi(n,4n) 206Bi. Initial experiments to selectively suppress photon backgrounds have been performed at TUNL using pulsed monoenergetic neutron beams of 14.9, 18.5, 24.2, and 28.5 MeV impinging on a Bibenzyl scintillator. By placing 5 cm of Pb before the scintillator we were able to selectively suppress the photons from the flash occurring at the production target and enhance the n/_signal by ~6 times.

  19. Annotating the Function of the Human Genome with Gene Ontology and Disease Ontology.

    Science.gov (United States)

    Hu, Yang; Zhou, Wenyang; Ren, Jun; Dong, Lixiang; Wang, Yadong; Jin, Shuilin; Cheng, Liang

    2016-01-01

    Increasing evidences indicated that function annotation of human genome in molecular level and phenotype level is very important for systematic analysis of genes. In this study, we presented a framework named Gene2Function to annotate Gene Reference into Functions (GeneRIFs), in which each functional description of GeneRIFs could be annotated by a text mining tool Open Biomedical Annotator (OBA), and each Entrez gene could be mapped to Human Genome Organisation Gene Nomenclature Committee (HGNC) gene symbol. After annotating all the records about human genes of GeneRIFs, 288,869 associations between 13,148 mRNAs and 7,182 terms, 9,496 associations between 948 microRNAs and 533 terms, and 901 associations between 139 long noncoding RNAs (lncRNAs) and 297 terms were obtained as a comprehensive annotation resource of human genome. High consistency of term frequency of individual gene (Pearson correlation = 0.6401, p = 2.2e - 16) and gene frequency of individual term (Pearson correlation = 0.1298, p = 3.686e - 14) in GeneRIFs and GOA shows our annotation resource is very reliable.

  20. Diagnóstico molecular de tuberculosis extrapulmonar y sensibilidad a rifampicina con un método automatizado en tiempo real

    Directory of Open Access Journals (Sweden)

    Adrián Peñata

    2016-04-01

    Conclusión. La prueba Xpert® MTB/RIF tuvo un buen desempeño en muestras de diferentes tejidos y líquidos, y constituye un avance significativo como apoyo para el diagnóstico de la tuberculosis extrapulmonar en términos de tiempo y porcentaje de positividad.

  1. Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology

    International Nuclear Information System (INIS)

    Wang, Huaijun; Keyzer, Frederik de; Jin, Lixin; Yu, Jie; Marchal, Guy; Ni, Yicheng; Putte, Marie van de; Witte, Peter de; Chen, Feng

    2008-01-01

    We sought to establish and characterize a mouse liver tumor model as a platform for preclinical assessment of new diagnostics and therapeutics. Radiation-induced fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with postmortem microangiography and histopathology. Implantation procedure succeeded in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in 21 mice with volume doubling time of 2.55±0.88 days and final size of 216.2±150.4 mm 3 at day 14. Three mice were found without tumor growth and one only with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI, maximal initial slope of contrast-time curve and volume transfer constant per unit volume of tissue, K, differed between the tumor and liver with only the former significantly lower in the tumor than in the liver (P<0.05). Liver implantation of RIF-1 in mice proves a feasible and reproducible model and appears promising for use to screen new diagnostics and therapeutics under noninvasive monitoring even with a clinical MRI system. (orig.)

  2. Engineering of Surface Chemistry for Enhanced Sensitivity in Nanoporous Interferometric Sensing Platforms.

    Science.gov (United States)

    Law, Cheryl Suwen; Sylvia, Georgina M; Nemati, Madieh; Yu, Jingxian; Losic, Dusan; Abell, Andrew D; Santos, Abel

    2017-03-15

    We explore new approaches to engineering the surface chemistry of interferometric sensing platforms based on nanoporous anodic alumina (NAA) and reflectometric interference spectroscopy (RIfS). Two surface engineering strategies are presented, namely (i) selective chemical functionalization of the inner surface of NAA pores with amine-terminated thiol molecules and (ii) selective chemical functionalization of the top surface of NAA with dithiol molecules. The strong molecular interaction of Au 3+ ions with thiol-containing functional molecules of alkane chain or peptide character provides a model sensing system with which to assess the sensitivity of these NAA platforms by both molecular feature and surface engineering. Changes in the effective optical thickness of the functionalized NAA photonic films (i.e., sensing principle), in response to gold ions, are monitored in real-time by RIfS. 6-Amino-1-hexanethiol (inner surface) and 1,6-hexanedithiol (top surface), the most sensitive functional molecules from approaches i and ii, respectively, were combined into a third sensing strategy whereby the NAA platforms are functionalized on both the top and inner surfaces concurrently. Engineering of the surface according to this approach resulted in an additive enhancement in sensitivity of up to 5-fold compared to previously reported systems. This study advances the rational engineering of surface chemistry for interferometric sensing on nanoporous platforms with potential applications for real-time monitoring of multiple analytes in dynamic environments.

  3. Waste Management Plan for the Oak Ridge National Remedial Investigation/Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    1988-04-01

    In accordance with the requirements of the Remedial Investigation/Feasibility Study (RI/FS) Project Quality Assurance Plan, this Waste Management Plan establishes clear lines of responsibility and authority, documentation requirements, and operational guidance for the collection, identification, segregation, classification, packaging, certification, and storage/disposal of wastes. These subjects are discussed in the subsequent sections of this document.

  4. Evaluation of the efficacy of valproic acid and suberoylanilide hydroxamic acid (vorinostat in enhancing the effects of first-line tuberculosis drugs against intracellular Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Martin Rao

    2018-04-01

    Full Text Available Background: New tuberculosis (TB drug treatment regimens are urgently needed. This study evaluated the potential of the histone deacetylase inhibitors (HDIs valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA to enhance the effects of first-line anti-TB drugs against intracellular Mycobacterium tuberculosis. Methods: M. tuberculosis H37Rv cultures were exposed to VPA or SAHA over 6 days, in the presence or absence of isoniazid (INH and rifampicin (RIF. The efficacy of VPA and SAHA against intracellular M. tuberculosis with and without INH or RIF was tested by treating infected macrophages. Bactericidal activity was assessed by counting mycobacterial colony-forming units (CFU. Results: VPA treatment exhibited superior bactericidal activity to SAHA (2-log CFU reduction, while both HDIs moderately improved the activity of RIF against extracellular M. tuberculosis. The bactericidal effect of VPA against intracellular M. tuberculosis was greater than that of SAHA (1-log CFU reduction and equalled that of INH (1.5-log CFU reduction. INH/RIF and VPA/SAHA combination treatment inhibited intracellular M. tuberculosis survival in a shorter time span than monotherapy (3 days vs. 6 days. Conclusions: VPA and SAHA have adjunctive potential to World Health Organization-recommended TB treatment regimens. Clinical evaluation of the two drugs with regard to reducing the treatment duration and improving treatment outcomes in TB is warranted. Keywords: Mycobacterium tuberculosis, Adjunct host-directed therapy, Tuberculosis, Histone deacetylase inhibitors, Repurposed drugs

  5. 77 FR 44718 - Unblocking of Specially Designated Nationals and Blocked Persons Pursuant to Executive Order 12978

    Science.gov (United States)

    2012-07-30

    ..., Jorge Enrique (a.k.a. ``EL ONLI''), c/o ERA DE LUZ LTDA. LIBRERIA CAFE, Cali, Colombia; DOB 09 Aug 1968..., Venezuela; RIF J-30460672-9 (Venezuela) [SDNT] 3. ERA DE LUZ LTDA. LIBRERIA CAFE, Calle 16 No. 100-98, Cali...

  6. [A study of the value of three molecular diagnostic techniques in the diagnosis of tuberculosis].

    Science.gov (United States)

    Huang, Fang; Dang, Liyun; Sun, Huiping; Yang, Han; Wu, Xia

    2015-09-01

    To evaluate the diagnostic value of real-time fluorescent RNA isothermal amplification detection technology (simultaneous amplification and testing, SAT), Mycobacterium nucleic acid detection (PCR-fluorescence probe)method (TB-NTM-PCR) and Xpert MTB/RIF detection in the diagnosis of tuberculosis. A total of 378 sputum specimens from pulmonary tuberculosis patients were collected between April to July 2014 in Xi'an Thoracic Tumor and Tuberculosis Hospital. The specimens were detected by 5 methods at the same time including acid-fast stain, SAT method, TB-NTM-PCR method, TB 960 rapid liquid culture and Xpert MTB/RIF. The sensitivity and specificity of SAT method, TB-NTM-PCR method and Xpert MTB/RIF were calculated according to the results of TB 960 rapid liquid culture and staining. The difference among all the 3 methods was analyzed by Chi-squared test. The positive rate of SAT-TB,TB-NTM-PCR and Xpert MTB/RIF were 37.6% (142/378), 37.8% (143/378) and 53.4% (202/378), respectively. In specimens both positive for acid-fast stain and culture, the positive rate of SAT method was 84.6% (77/91), that of TB-NTM-PCR was 91.2% (83/91), and that of Xpert MTB/RIF was 96.7% (88/91), the difference being significant (P=0.018 2). In specimens negative for acid-fast stain but positive for culture, the positive rate of SAT method was 61.9% (60 /97), that of TB-NTM-PCR was 44.3% (43/97), and that of Xpert MTB/RIF was 80.4% (78/97), the difference being significant (Pmolecular detection methods showed good results for the auxiliary diagnosis of tuberculosis. Xpert MTB/RIF had the best performance both in smear positive and negative specimens and it can detect rifampicin related rpoB gene mutations at the same time.

  7. Repeated implantation failure versus repeated implantation success: discrimination at a metabolomic level.

    Science.gov (United States)

    RoyChoudhury, Sourav; Singh, Apoorva; Gupta, Nalini J; Srivastava, Sudha; Joshi, Mamata V; Chakravarty, Baidyanath; Chaudhury, Koel

    2016-06-01

    Is there any difference at the serum metabolic level between women with recurrent implantation failure (RIF) and women with recurrent implantation success (RIS) when undergoing in vitro fertilization (IVF)? Eight metabolites, including valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea, were found to be significantly up-regulated in women with RIF when compared with women with RIS. Despite transfer of three high-grade embryos per cycle, RIF following three or more consecutive IVF attempts occurs in a group of infertile women. Conversely, there is a group of women who undergo successful implantation each cycle, yet have a poor obstetric history. This study was conducted over a period of 10 years (January 2004-October 2014). Groups of 28 women with RIF (age ≤40 years and BMI ≤28) and 24 women with RIS (age and BMI matched) were selected from couples with primary infertility reporting at the Institute of Reproductive Medicine, Kolkata, India. Women recruited in the RIF group had history of implantation failure in at least three consecutive IVF attempts, in which three embryos of high-grade quality were transferred in each cycle. Blood samples were collected from both the groups during the implantation window following overnight fasting for at least 10 h (7-10 days post ovulation). Samples were analyzed using a 700 MHz NMR spectrometer and acquired spectra were subjected to chemometric and statistical analysis. Serum levels of endothelial nitric oxide synthase (eNOS) were measured using an enzyme immunoassay technique. Valine, adipic acid, l-lysine, creatine, ornithine, glycerol, d-glucose and urea were found to be significantly down-regulated in women with RIS when compared with those with RIF, with fold change values of 0.81, 0.82, 0.79, 0.80, 0.78, 0.68, 0.76 and 0.74, respectively. Further, serum eNOS was found to be significantly lower in women with RIF when compared with RIS (P failure. One of the authors, S.R.C. acknowledges the

  8. Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

    Energy Technology Data Exchange (ETDEWEB)

    Vadhavkar, Nikhil [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Pham, Christopher [University of Texas, Houston, TX (United States). MD Anderson Cancer Center; Georgescu, Walter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Deschamps, Thomas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Heuskin, Anne-Catherine [Univ. of Namur (Belgium). Namur Research inst. for Life Sciences (NARILIS), Research Center for the Physics of Matter and Radiation (PMR); Tang, Jonathan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Costes, Sylvain V. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2014-09-01

    In contrast to the classic view of static DNA double-strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (m). As X-ray dose increases, the probability of having DSB clusters increases as does the probability of misrepair and cell death. Experimental work characterizing the X-ray dose dependence of radiation-induced foci (RIF) in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSBs at the submicron level. Two mechanisms for DSB clustering, namely random coalescence of DSBs versus active movement of DSBs into repair domains are compared and tested. Simulations that best predicted both RIF dose dependence and cell survival after X-ray irradiation favored the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~;;1.55 m sides. Applying the same approach to high-linear energy transfer (LET) ion tracks, we are able to predict experimental RIF/m along tracks with an overall relative error of 12percent, for LET ranging between 30 350 keV/m and for three different ions. Finally, cell death was predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. Relative biological effectiveness (RBE) predictions for cell survival of MCF10A exposed to high-LET showed an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the submicron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. Conversely, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model

  9. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Science.gov (United States)

    Gruel, Gaëtan; Villagrasa, Carmen; Voisin, Pascale; Clairand, Isabelle; Benderitter, Marc; Bottollier-Depois, Jean-François; Barquinero, Joan Francesc

    2016-01-01

    Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF) per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This comparison allowed us to

  10. Cell to Cell Variability of Radiation-Induced Foci: Relation between Observed Damage and Energy Deposition.

    Directory of Open Access Journals (Sweden)

    Gaëtan Gruel

    Full Text Available Most studies that aim to understand the interactions between different types of photon radiation and cellular DNA assume homogeneous cell irradiation, with all cells receiving the same amount of energy. The level of DNA damage is therefore generally determined by averaging it over the entire population of exposed cells. However, evaluating the molecular consequences of a stochastic phenomenon such as energy deposition of ionizing radiation by measuring only an average effect may not be sufficient for understanding some aspects of the cellular response to this radiation. The variance among the cells associated with this average effect may also be important for the behaviour of irradiated tissue. In this study, we accurately estimated the distribution of the number of radiation-induced γH2AX foci (RIF per cell nucleus in a large population of endothelial cells exposed to 3 macroscopic doses of gamma rays from 60Co. The number of RIF varied significantly and reproducibly from cell to cell, with its relative standard deviation ranging from 36% to 18% depending on the macroscopic dose delivered. Interestingly, this relative cell-to-cell variability increased as the dose decreased, contrary to the mean RIF count per cell. This result shows that the dose effect, in terms of the number of DNA lesions indicated by RIF is not as simple as a purely proportional relation in which relative SD is constant with dose. To analyse the origins of this observed variability, we calculated the spread of the specific energy distribution for the different target volumes and subvolumes in which RIF can be generated. Variances, standard deviations and relative standard deviations all changed similarly from dose to dose for biological and calculated microdosimetric values. This similarity is an important argument that supports the hypothesis of the conservation of the association between the number of RIF per nucleus and the specific energy per DNA molecule. This

  11. Coalescence of DNA Double Strand Breaks Induced by Galactic Cosmic Radiation is Modulated by Genetics in 15 Inbred Strains of Mice

    Science.gov (United States)

    Penninckx, Sebastien; Ray, Shayoni; Staatz, Kevin; Degorre, Charlotte; Guiet, Elodie; Viger, Louise; Snijders, Antoine M.; Mao, Jian-Hua; Karpen, Gary; Costes, Sylvain V.

    2018-01-01

    In this manuscript we address the challenges associated with the ability to predict radiation sensitivity associated with exposure to either cosmic radiation or X-rays in a population study, by monitoring DNA damage sensing protein 53BP1 forming small nuclear radiation-induced foci (RIF) as a surrogate biomarker of DNA double strand breaks (DSB). 76 primary skin fibroblasts were isolated from 10 collaborative cross strains and five reference inbred mice (C57Bl/6, BALB/CByJ, B6C3, C3H and CBA/CaJ) and exposed to three different charged nuclei of increasing LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and X-ray. Our data brings strong evidence against the classic "contact-first" model where DSBs are assumed to be immobile and repaired at the lesion site. In contrast, our model suggests nearby DSBs move into single repair unit characterized by large RIF before the repair machinery kicks in. Such model has the advantage of being much more efficient molecularly but is poorly suited to deal with cosmic radiation, where energy is concentrated along the particle trajectory, inducing a large density of DSBs along each particle track. In accordance with this model, RIF quantification after X-ray exposition showed a saturated dose response for early time points post-irradiation for all strains. Similarly, the high-LET response showed that RIF number matched the number of track per cell, not the number of expected DSB per cell (1). At the temporal level, we noted that the percentage of unrepaired high-LET tracks over a 48 hour time-course increased with LET, confirming that the DNA repair process becomes more difficult as more DSB coalesce into single RIF. There was also good agreement between persistent RIF levels measured in-vitro in the primary skin cultures and survival levels of T-cells and B-cells collected in blood samples from 10 CC strains 24 hours after 0.1 Gy whole-body dose of X-ray. This suggests that persistent RIF 24 hour post-IR is a good surrogate in

  12. New records of Trichoptera in reference Mediterranean-climate rivers of the Iberian Peninsula and north of Africa: taxonomical, faunistical and ecological aspects

    Directory of Open Access Journals (Sweden)

    Bonada, N.

    2008-12-01

    Full Text Available Trichoptera is a very rich order in the Western Mediterranean, but knowledge of caddisflies in the Iberian Peninsula and northern Africa is still not complete. We present records of caddisflies collected in 114 sites of the Mediterranean climate region of the Iberian Peninsula and the western Rif. We also provide notes on ecological aspects and taxonomical remarks on some species. Atotal of 86 species were identified and 8 species extended their distribution range. Considering the four differentiated geological regions in the western Mediterranean Basin during the Tertiary, 60 species were collected in the Iberian plate region, 29 in the Transition, 30 in the Betic and 18 in the Rif. Local richness was not significantly different between the four regions but significant differences were found among several river ecotypes within regions. Temporary sites had lower local richness than other ecotypes in all regions except in the Rif, whereas headwaters had similar richness in any region regardless of their geology. The Rif region had the lowest Trichoptera richness, which is not only the result of the scarcity of faunistic studies in the area but also of the high frequency of temporary rivers and the isolation of the area. Our results suggest that conservation measures addressed to preserve the biodiversity of the Western Mediterranean should be enforced, especially in the Rif region.

    El orden Trichoptera es rico en especies en la zona del Mediterráneo Occidental, pero el conocimiento de este grupo en la Península Ibérica y el norte de África resta aún de ser completo. Presentamos datos de tricópteros recolectados en 114 localidades de la región Mediterránea de la Península Ibérica y del Rif occidental. Además, proporcionamos datos sobre la ecología de algunas especies así como notas taxonómicas. Se identificaron un total de 86 especies y el rango de distribución aumentó para 8 de ellas. Sesenta especies se recolectaron en la

  13. Persistent DNA damage after high dose in vivo gamma exposure of minipig skin.

    Directory of Open Access Journals (Sweden)

    Emad A Ahmed

    Full Text Available Exposure to high doses of ionizing radiation (IR can lead to localized radiation injury of the skin and exposed cells suffer dsDNA breaks that may elicit cell death or stochastic changes. Little is known about the DNA damage response after high-dose exposure of the skin. Here, we investigate the cellular and DNA damage response in acutely irradiated minipig skin.IR-induced DNA damage, repair and cellular survival were studied in 15 cm(2 of minipig skin exposed in vivo to ~50 Co-60 γ rays. Skin biopsies of control and 4 h up to 96 days post exposure were investigated for radiation-induced foci (RIF formation using γ-H2AX, 53BP1, and active ATM-p immunofluorescence. High-dose IR induced massive γ-H2AX phosphorylation and high 53BP1 RIF numbers 4 h, 20 h after IR. As time progressed RIF numbers dropped to a low of 3-fold elevated at all subsequent time points. Replicating basal cells (Ki67+ were reduced 3 days post IR followed by increased proliferation and recovery of epidermal cellularity after 28 days.Acute high dose irradiation of minipig epidermis impaired stem cell replication and induced elevated apoptosis from 3 days onward. DNA repair cleared the high numbers of DBSs in skin cells, while RIFs that persisted in <1% cells marked complex and potentially lethal DNA damage up to several weeks after exposure. An elevated frequency of keratinocytes with persistent RIFs may thus serve as indicator of previous acute radiation exposure, which may be useful in the follow up of nuclear or radiological accident scenarios.

  14. Susceptibility to rifaximin and other antimicrobials of bacteria isolated in patients with acute gastrointestinal infections in Southeast Mexico.

    Science.gov (United States)

    Novoa-Farias, O; Frati-Munari, A C; Peredo, M A; Flores-Juárez, S; Novoa-García, O; Galicia-Tapia, J; Romero-Carpio, C E

    Enteropathogenic bacteria isolated in Mexico City have shown a high rate of resistance to different antibiotics, with the exception of rifaximin (RIF). RIF is a nonabsorbable antibiotic that reaches high fecal concentrations (≈ 8,000μg/g). Susceptibility to antimicrobials can vary in different geographic regions. To study the susceptibility to rifaximin and other antimicrobials of enteropathogenic bacteria isolated in patients with acute diarrhea in the southeastern region of Mexico. A total of 614 strains of bacteria isolated from patients with acute diarrhea from 4 cities in Southeast Mexico were analyzed. An antibiogram with the following antibiotics was created: ampicillin (AMP), trimethoprim/sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), ciprofloxacin (CIP), chloramphenicol (CHL), and fosfomycin (FOS), assessed through the agar diffusion method at the standard concentrations recommended by the Clinical and Laboratory Standards Institute (CLSI) and the American Society for Microbiology (ASM), and RIF, assessed through microdilution at 4 concentrations. The bacteria were Escherichia coli (55%), as the majority, in all its pathogenic variants, Shigella (16.8%), Salmonella (15.3%), Aeromonas (7.8%), and less than 5% Campylobacter, Yersinia, Vibrio, and Plesiomonas. The accumulated overall susceptibility to RIF was 69.1, 90.8, 98.9, and 100% at concentrations of 100, 200, 400, and 800μg/ml, respectively. Overall susceptibility to other antibiotics was FOS 82.8%, CHL 76.8%, CIP 73.9%, FUR 64%, T-S 58.7%, NEO 55.8%, and AMP 23.8%. Susceptibility to RIF at 400 and 800μg was significantly greater than with the other antimicrobials (P 98% of the bacterial strains and a high frequency of resistance to several common antimicrobials. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  15. Effect of Ramadan intermittent fasting on aerobic and anaerobic performance and perception of fatigue in male elite judo athletes.

    Science.gov (United States)

    Chaouachi, Anis; Coutts, Aaron J; Chamari, Karim; Wong, Del P; Chaouachi, Mustapha; Chtara, Moktar; Roky, Rachida; Amri, Mohamed

    2009-12-01

    The aim of the present study was to evaluate the influence of the Ramadan intermittent fast (RIF) on aerobic and anaerobic exercise performance in elite judo athletes (Judokas) maintaining their usual training loads. Physical performance tests (squat jump [SJ]), countermovement jump [CMJ], 30-second repeated jump, 30-m sprint, and the multistage fitness test) and fatigue scores were measured in 15 elite Judokas on 4 occasions: before Ramadan (T1), at the beginning of Ramadan (T2), at the end of Ramadan (T3) and 3 weeks after Ramadan. Results showed that 30-m sprint performance, multistage shuttle run test, SJ, and CMJ did not change during Ramadan. However, average power during the 30-second repeated jump test was slightly lower at the end of Ramadan (22.4 +/- 2.3 W/kg; P Ramadan (23.4 +/- 2.3 W/kg). There was a minor reduction of 1.3 kg in body mass and an increase in total fatigue scores (T2, 19 +/- 5; T3, 16 +/- 4; both P Ramadan in comparison with the control period (T1, 12 +/- 3). These results show that the RIF has little effect on aerobic performance and on very short duration sprinting and jumping test performance in elite Judokas. Additionally, experienced athletes can maintain both sufficient energy intake and normal training loads during the RIF. The slight reduction in the 30-second jump test may be associated with reduced central drive and body mass. Collectively, these results suggest that the RIF has little effect on the performance of experienced Judokas, but Muslim athletes who train during the RIF should carefully periodize their training load and monitor their food intake and fatigue levels to avoid performance decrements.

  16. Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials.

    Directory of Open Access Journals (Sweden)

    Robin Hellerstedt

    Full Text Available Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit-Apple. Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit-Ma__?. We investigated the event-related potential (ERP correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks-Wy__ and compared it with a non-retrieval presentation baseline condition (Occupation-Dentist. The participants' memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval

  17. Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials

    Science.gov (United States)

    Hellerstedt, Robin; Johansson, Mikael

    2016-01-01

    Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit—Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit—Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks—Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation—Dentist). The participants’ memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval

  18. Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models.

    Science.gov (United States)

    Rao, Ch V; Rawat, A K S; Singh, Anil P; Singh, Arpita; Verma, Neeraj

    2012-04-01

    To evaluate the hepatoprotective potential of ethanolic (50%) extract of Ziziphus oenoplia (L.) Mill (Z. oenoplia) root against isoniazid (INH) and rifampicin (RIF) induced liver damage in animal models. Five groups of six rats each were selected for the study. Ethanolic extract at a dose of 150 and 300 mg/kg as well as silymarin (100 mg/kg) were administered orally once daily for 21 d in INH + RIF treated groups. The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), and bilirubin were estimated along with activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione peroxidase, and hepatic melondialdehyde formation. Histopathological analysis was carried out to assess injury to the liver. The considerably elevated serum enzymatic activities of glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin due to INH + RIF treatment were restored towards normal in a dose dependent manner after the treatment with ethanolic extract of Z. oenoplia roots. Meanwhile, the decreased activities of superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were also restored towards normal dose dependently. In addition, ethanolic extract also significantly prevented the elevation of hepatic melondialdehyde formation in the liver of INH + RIF intoxicated rats in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethanolic extract of Z. oenoplia has a potent hepatoprotective action against INH + RIF induced hepatic damage in rats. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  19. Chaos game representation of functional protein sequences, and simulation and multifractal analysis of induced measures

    International Nuclear Information System (INIS)

    Zu-Guo, Yu; Qian-Jun, Xiao; Long, Shi; Jun-Wu, Yu; Anh, Vo

    2010-01-01

    Investigating the biological function of proteins is a key aspect of protein studies. Bioinformatic methods become important for studying the biological function of proteins. In this paper, we first give the chaos game representation (CGR) of randomly-linked functional protein sequences, then propose the use of the recurrent iterated function systems (RIFS) in fractal theory to simulate the measure based on their chaos game representations. This method helps to extract some features of functional protein sequences, and furthermore the biological functions of these proteins. Then multifractal analysis of the measures based on the CGRs of randomly-linked functional protein sequences are performed. We find that the CGRs have clear fractal patterns. The numerical results show that the RIFS can simulate the measure based on the CGR very well. The relative standard error and the estimated probability matrix in the RIFS do not depend on the order to link the functional protein sequences. The estimated probability matrices in the RIFS with different biological functions are evidently different. Hence the estimated probability matrices in the RIFS can be used to characterise the difference among linked functional protein sequences with different biological functions. From the values of the D q curves, one sees that these functional protein sequences are not completely random. The D q of all linked functional proteins studied are multifractal-like and sufficiently smooth for the C q (analogous to specific heat) curves to be meaningful. Furthermore, the D q curves of the measure μ based on their CGRs for different orders to link the functional protein sequences are almost identical if q ≥ 0. Finally, the C q curves of all linked functional proteins resemble a classical phase transition at a critical point. (cross-disciplinary physics and related areas of science and technology)

  20. Using Top-down and Bottom-up Costing Approaches in LMICs: The Case for Using Both to Assess the Incremental Costs of New Technologies at Scale.

    Science.gov (United States)

    Cunnama, Lucy; Sinanovic, Edina; Ramma, Lebogang; Foster, Nicola; Berrie, Leigh; Stevens, Wendy; Molapo, Sebaka; Marokane, Puleng; McCarthy, Kerrigan; Churchyard, Gavin; Vassall, Anna

    2016-02-01

    Estimating the incremental costs of scaling-up novel technologies in low-income and middle-income countries is a methodologically challenging and substantial empirical undertaking, in the absence of routine cost data collection. We demonstrate a best practice pragmatic approach to estimate the incremental costs of new technologies in low-income and middle-income countries, using the example of costing the scale-up of Xpert Mycobacterium tuberculosis (MTB)/resistance to riframpicin (RIF) in South Africa. We estimate costs, by applying two distinct approaches of bottom-up and top-down costing, together with an assessment of processes and capacity. The unit costs measured using the different methods of bottom-up and top-down costing, respectively, are $US16.9 and $US33.5 for Xpert MTB/RIF, and $US6.3 and $US8.5 for microscopy. The incremental cost of Xpert MTB/RIF is estimated to be between $US14.7 and $US17.7. While the average cost of Xpert MTB/RIF was higher than previous studies using standard methods, the incremental cost of Xpert MTB/RIF was found to be lower. Costs estimates are highly dependent on the method used, so an approach, which clearly identifies resource-use data collected from a bottom-up or top-down perspective, together with capacity measurement, is recommended as a pragmatic approach to capture true incremental cost where routine cost data are scarce. © 2016 The Authors. Health Economics published by John Wiley & Sons Ltd.

  1. The effects of Ramadan intermittent fasting on athletic performance: recommendations for the maintenance of physical fitness.

    Science.gov (United States)

    Chaouachi, Anis; Leiper, John B; Chtourou, Hamdi; Aziz, Abdul Rashid; Chamari, Karim

    2012-01-01

    The behavioural modifications that accompany Ramadan intermittent fasting (RIF) are usually associated with some alterations in the metabolic, physiological, and psychological responses of athletes that may affect sport performance. Muslim athletes who are required to train and/or compete during the month-long, diurnal fast must adopt coping strategies that allow them to maintain physical fitness and motivation if they are to perform at the highest level. This updated review aims to present the current state of knowledge of the effects of RIF on training and performance, focusing on key-factors that contribute to the effects of Ramadan on exercise performance: energy restriction, sleep deprivation, circadian rhythm perturbation, dehydration, and alterations in the training load. The available literature contain few studies that have examined the effects of RIF on physical performance in athletes and, to date, the results are inconclusive, so the effects of RIF on competition outcomes are not at present wholly understood. The diverse findings probably indicate individual differences in the adaptability and self-generated coping strategies of athletes during fasting and training. However, the results of the small number of well-controlled studies that have examined the effects of Ramadan on athletic performance suggest that few aspects of physical fitness are negatively affected, and where decrements are observed these are usually modest. Subjective feelings of fatigue and other mood indicators are often cited as implying additional stress on the athlete throughout Ramadan, but most studies show that these factors may not result in decreases in performance and that perceived exercise intensity is unlikely to increase to any significant degree. Current evidence from good, well-controlled research supports the conclusion that athletes who maintain their total energy and macronutrient intake, training load, body composition, and sleep length and quality are unlikely to

  2. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. Competitive Semantic Memory Retrieval: Temporal Dynamics Revealed by Event-Related Potentials.

    Science.gov (United States)

    Hellerstedt, Robin; Johansson, Mikael

    2016-01-01

    Memories compete for retrieval when they are related to a common retrieval cue. Previous research has shown that retrieval of a target memory may lead to subsequent retrieval-induced forgetting (RIF) of currently irrelevant competing memories. In the present study, we investigated the time course of competitive semantic retrieval and examined the neurocognitive mechanisms underlying RIF. We contrasted two theoretical accounts of RIF by examining a critical aspect of this memory phenomenon, namely the extent to which it depends on successful retrieval of the target memory. Participants first studied category-exemplar word-pairs (e.g. Fruit-Apple). Next, we recorded electrophysiological measures of brain activity while the participants performed a competitive semantic cued-recall task. In this task, the participants were provided with the studied categories but they were instructed to retrieve other unstudied exemplars (e.g. Fruit-Ma__?). We investigated the event-related potential (ERP) correlates of retrieval success by comparing ERPs from successful and failed retrieval trials. To isolate the ERP correlates of continuous retrieval attempts from the ERP correlates of retrieval success, we included an impossible retrieval condition, with incompletable word-stem cues (Drinks-Wy__) and compared it with a non-retrieval presentation baseline condition (Occupation-Dentist). The participants' memory for all the studied exemplars was tested in the final phase of the experiment. Taken together, the behavioural results suggest that RIF is independent of target retrieval. Beyond investigating the mechanisms underlying RIF, the present study also elucidates the temporal dynamics of semantic cued-recall by isolating the ERP correlates of retrieval attempt and retrieval success. The ERP results revealed that retrieval attempt is reflected in a late posterior negativity, possibly indicating construction of candidates for completing the word-stem cue and retrieval monitoring

  4. Investigation of early DNA damage after radioiodine therapy in patients with thyroid cancer using the gamma-H2AX focus assay

    International Nuclear Information System (INIS)

    Eberlein, U.; Lassmann, M.; Bluemel, C.; Buck, A.K.; Nowak, C.; Meineke, V.; Scherthan, H.

    2015-01-01

    Full text of publication follows. Objectives: the Aim of the study is to investigate the DNA damage formation in blood lymphocytes and the correlation to the absorbed dose to the blood in patients with differentiated thyroid carcinoma (DTC) after their first radionuclide therapy with I-131 as measured by the induction, persistence and decay behaviour of γ-H2AX and 53BP1 DNA damage-induced foci. Radiation-induced DNA double strand breaks (DSBs) cause in their vicinity the formation of microscopically visible foci of the phospho-histone H2AX (γ-H2AX) and the 53BP1 protein that binds to and signals damaged chromatin at the DSB site. Nuclear foci containing both markers thus represent radiation-induced DSBs. Methods: we investigated 19 patients with DTC during the first treatment with 3.5±0.3 GBq I-131. Between 7 and 10 sequential peripheral blood samples (at least four within the first 5 hours) were taken before and between 0.5 h and 144 h post administration. The physical dosimetry procedures were performed according to the EANM DTC SOP. White blood cells were recovered by density centrifugation in CPT tubes (BD Biosciences) and subjected to two-colour immunofluorescence staining. The average frequencies of the radiation-induced γ-H2AX foci/nucleus that co localized with 53BP1 foci were derived from immuno-stained mononuclear peripheral blood lymphocyte samples. The number of foci was counted manually using a red/green double band pass filter (Chroma) in a Zeiss microscope by an experienced observer. Results: The mean I-131 absorbed dose to the blood was (0.04±0.01) Gy at t=2 h, (0.07±0.02) Gy at t=4 h, and (0.21±0.05) Gy at t=24 h, respectively. The mean value of the total absorbed dose to the blood was (0.36±0.08) Gy. The highest number of radiation-induced foci per nucleus (RIF) and per absorbed dose (median: 8.8 RIF/Gy, range 3.1-10.9 RIF/Gy) was observed in the first three hours post administration. Four hours after radioiodine administration the number

  5. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update.

    Science.gov (United States)

    Falzon, Dennis; Schünemann, Holger J; Harausz, Elizabeth; González-Angulo, Licé; Lienhardt, Christian; Jaramillo, Ernesto; Weyer, Karin

    2017-03-01

    Antimicrobial resistance is a major global concern. Tuberculosis (TB) strains resistant to rifampicin and other TB medicines challenge patient survival and public health. The World Health Organization (WHO) has published treatment guidelines for drug-resistant TB since 1997 and last updated them in 2016 based on reviews of aggregated and individual patient data from published and unpublished studies. An international expert panel formulated recommendations following the GRADE approach. The new WHO guidelines recommend a standardised 9-12 months shorter treatment regimen as first choice in patients with multidrug- or rifampicin-resistant TB (MDR/RR-TB) strains not resistant to fluoroquinolones or second-line injectable agents; resistance to these two classes of core second-line medicines is rapidly detectable with molecular diagnostics also approved by WHO in 2016. The composition of longer regimens for patients ineligible for the shorter regimen was modified. A first-ever meta-analysis of individual paediatric patient data allowed treatment recommendations for childhood MDR/RR-TB to be made. Delamanid is now also recommended in patients aged 6-17 years. Partial lung resection is a recommended option in MDR/RR-TB care. The 2016 revision highlighted the continued shortage of high-quality evidence and implementation research, and reiterated the need for clinical trials and best-practice studies to improve MDR/RR-TB patient treatment outcomes and strengthen policy. The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2017.

  6. The contribution of Nth and Nei DNA glycosylases to mutagenesis in Mycobacterium smegmatis.

    Science.gov (United States)

    Moolla, Nabiela; Goosens, Vivianne J; Kana, Bavesh D; Gordhan, Bhavna G

    2014-01-01

    The increased prevalence of drug resistant strains of Mycobacterium tuberculosis (Mtb) indicates that significant mutagenesis occurs during tuberculosis disease in humans. DNA damage by host-derived reactive oxygen/nitrogen species is hypothesized to be critical for the mutagenic process in Mtb thus, highlighting an important role for DNA repair enzymes in maintenance of genome fidelity. Formamidopyrimidine (Fpg/MutM/Fapy) and EndonucleaseVIII (Nei) constitute the Fpg/Nei family of DNA glycosylases and together with EndonucleaseIII (Nth) are central to the base excision repair pathway in bacteria. In this study we assess the contribution of Nei and Nth DNA repair enzymes in Mycobacterium smegmatis (Msm), which retains a single nth homologue and duplications of the Fpg (fpg1 and fpg2) and Nei (nei1 and nei2) homologues. Using an Escherichia coli nth deletion mutant, we confirm the functionality of the mycobacterial nth gene in the base excision repair pathway. Msm mutants lacking nei1, nei2 and nth individually or in combination did not display aberrant growth in broth culture. Deletion of nth individually results in increased UV-induced mutagenesis and combinatorial deletion with the nei homologues results in reduced survival under oxidative stress conditions and an increase in spontaneous mutagenesis to rifampicin. Deletion of nth together with the fpg homolgues did not result in any growth/survival defects or changes in mutation rate. Furthermore, no differential emergence of the common rifampicin resistance conferring genotypes were noted. Collectively, these data confirm a role for Nth in base excision repair in mycobacteria and further highlight a novel interplay between the Nth and Nei homologues in spontaneous mutagenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Increasing Prevalence of Pediatric Drug-Resistant Tuberculosis in Mumbai, India and its Outcome.

    Science.gov (United States)

    Shah, Miti A; Shah, Ira

    2018-03-24

    B.J.Wadia Hospital,Mumbai OBJECTIVE:: The prevalence and type of DR-TB was evaluated pre and post-2013 and outcome was studied. Descriptive retrospective study. Children were defined as having DR-TB on the basis of GeneXpert or LPA and/or drug susceptibility testing(DST) of MTB grown on culture or from contact's DST. The prevalence of DR-TB was 110 out of 1145 cases (9.6%) which showed an increase, compared to 5.6% pre-2010 and 7% in 2010-2013(p=0.014408). Twenty-two (20%) children had pulmonary-TB(PTB) and 88(80%) had extra-pulmonary-TB(EPTB) with disseminated-TB being the most common presentation in 31 children (28.18%). Ninety-six (87.3%) children were bacteriologically confirmed TB cases and 14 (12.7%) were clinically diagnosed-TB and treated as per contact DST. Eight (7.2%) cases were monoresistant, 7 (6.3%) polyresistant, MDR-TB seen in 28 (25.45%) patients, 32 (29.09%) had pre-XDR-TB, 9 (8.18%) had XDR-TB and 12 (10.9%) were rifampicin resistant. Ethionamide resistance increased from 26.1% pre-2013 to 60.8% post-2013(p=0.014408) and ofloxacin resistance rose from 30.4% pre-2010, to 47.6% in 2010-2013 and 56.9% post-2013(p=0.080863). Moxifloxacin resistance showed an acute rise from 8.7% pre-2010, to 46% in 2010-2013 and 57% post-2013(p=0.000275). Thirty-three (30%) patients had completed their treatment, 21(19.09%) were lost to follow up and 56(50.09%) patients are still on treatment.

  8. Soil Type Dependent Rhizosphere Competence and Biocontrol of Two Bacterial Inoculant Strains and Their Effects on the Rhizosphere Microbial Community of Field-Grown Lettuce

    Science.gov (United States)

    Schreiter, Susanne; Sandmann, Martin; Smalla, Kornelia; Grosch, Rita

    2014-01-01

    Rhizosphere competence of bacterial inoculants is assumed to be important for successful biocontrol. Knowledge of factors influencing rhizosphere competence under field conditions is largely lacking. The present study is aimed to unravel the effects of soil types on the rhizosphere competence and biocontrol activity of the two inoculant strains Pseudomonas jessenii RU47 and Serratia plymuthica 3Re4-18 in field-grown lettuce in soils inoculated with Rhizoctonia solani AG1-IB or not. Two independent experiments were carried out in 2011 on an experimental plot system with three soil types sharing the same cropping history and weather conditions for more than 10 years. Rifampicin resistant mutants of the inoculants were used to evaluate their colonization in the rhizosphere of lettuce. The rhizosphere bacterial community structure was analyzed by denaturing gradient gel electrophoresis of 16S rRNA gene fragments amplified from total community DNA to get insights into the effects of the inoculants and R. solani on the indigenous rhizosphere bacterial communities. Both inoculants showed a good colonization ability of the rhizosphere of lettuce with more than 106 colony forming units per g root dry mass two weeks after planting. An effect of the soil type on rhizosphere competence was observed for 3Re4-18 but not for RU47. In both experiments a comparable rhizosphere competence was observed and in the presence of the inoculants disease symptoms were either significantly reduced, or at least a non-significant trend was shown. Disease severity was highest in diluvial sand followed by alluvial loam and loess loam suggesting that the soil types differed in their conduciveness for bottom rot disease. Compared to effect of the soil type of the rhizosphere bacterial communities, the effects of the pathogen and the inoculants were less pronounced. The soil types had a surprisingly low influence on rhizosphere competence and biocontrol activity while they significantly affected

  9. Current trends and intricacies in the management of HIV-associated pulmonary tuberculosis.

    Science.gov (United States)

    Gopalan, Narendran; Chandrasekaran, Padmapriyadarsini; Swaminathan, Soumya; Tripathy, Srikanth

    2016-01-01

    Human immunodeficiency virus (HIV) epidemic has undoubtedly increased the incidence of tuberculosis (TB) globally, posing a formidable global health challenge affecting 1.2 million cases. Pulmonary TB assumes utmost significance in the programmatic perspective as it is readily transmissible as well as easily diagnosable. HIV complicates every aspect of pulmonary tuberculosis from diagnosis to treatment, demanding a different approach to effectively tackle both the diseases. In order to control these converging epidemics, it is important to diagnose early, initiate appropriate therapy for both infections, prevent transmission and administer preventive therapy. Liquid culture methods and nucleic acid amplification tests for TB confirmation have replaced conventional solid media, enabling quicker and simultaneous detection of mycobacterium and its drug sensitivity profile Unique problems posed by the syndemic include Acquired rifampicin resistance, drug-drug interactions, malabsorption of drugs and immune reconstitution inflammatory syndrome or paradoxical reaction that complicate dual and concomitant therapy. While the antiretroviral therapy armamentarium is constantly reinforced by discovery of newer and safer drugs every year, only a few drugs for anti tuberculosis treatment have successfully emerged. These include bedaquiline, delamanid and pretomanid which have entered phase III B trials and are also available through conditional access national programmes. The current guidelines by WHO to start Antiretroviral therapy irrespective of CD4+ cell count based on benefits cited by recent trials could go a long way in preventing various complications caused by the deadly duo. This review provides a consolidated gist of the advancements, concepts and updates that have emerged in the management of HIV-associated pulmonary TB for maximizing efficacy, offering latest solutions for tackling drug-drug interactions and remedial measures for immune reconstitution inflammatory

  10. Effects of diabetes mellitus on the clinical presentation and treatment response in tuberculosis.

    Science.gov (United States)

    Leung, Chi C; Yew, Wing W; Mok, Thomas Y W; Lau, Kam S; Wong, Chi F; Chau, Chi H; Chan, Chi K; Chang, Kwok C; Tam, Greta; Tam, Cheuk M

    2017-08-01

    With the colliding global epidemics of diabetes mellitus (DM) and tuberculosis (TB), we studied the effects of DM on the presentation of TB and its response to treatment. Consecutive TB patients from 2006 to 2010 in a territory-wide treatment programme offering 9-month extended treatment for TB patients with DM were examined and followed up prospectively to assess their treatment response. Successful treatment completers were tracked through the TB registry and death registry for relapse, death or till 31 December 2014, whichever was the earliest. DM was independently associated with more chest symptoms (adjusted OR (AOR): 1.13) and systemic symptoms (AOR: 1.30) but less with other site-specific symptoms (AOR: 0.58) at TB presentation. There was more frequent pulmonary involvement (AOR: 1.69), with more extensive lung lesion (AOR: 1.25), lung cavity (AOR: 2.00) and positive sputum smear (AOR: 1.83) and culture (AOR: 1.38), but no difference in the proportion of retreatment cases or isoniazid and/or rifampicin resistance. After treatment initiation, there was higher overall incidence (AOR: 1.38) of adverse effects (mainly gastrointestinal symptoms, renal impairment and peripheral neuropathy but less fever and skin hypersensitivity reactions), more smear non-conversion (AOR: 1.59) and culture non-conversion (AOR: 1.40) at 2 months, and lower combined cure/treatment completion rate at 12 months (AOR: 0.79), but no difference in the relapse rate after having successfully completed treatment. DM adversely affected the clinical presentation and treatment response of TB, but there was no difference in the drug resistance and relapse rates. © 2017 Asian Pacific Society of Respirology.

  11. Rapid diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis using a molecular-based diagnostic algorithm.

    Science.gov (United States)

    Simons, S O; van der Laan, T; Mulder, A; van Ingen, J; Rigouts, L; Dekhuijzen, P N R; Boeree, M J; van Soolingen, D

    2014-10-01

    There is an urgent need for rapid and accurate diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis (MDR-TB). No diagnostic algorithm has been validated in this population. We hypothesized that pncA sequencing added to rpoB mutation analysis can accurately identify patients with pyrazinamide-resistant MDR-TB. We identified from the Dutch national database (2007-11) patients with a positive Mycobacterium tuberculosis culture containing a mutation in the rpoB gene. In these cases, we prospectively sequenced the pncA gene. Results from the rpoB and pncA mutation analysis (pncA added to rpoB) were compared with phenotypic susceptibility testing results to rifampicin, isoniazid and pyrazinamide (reference standard) using the Mycobacterial Growth Indicator Tube 960 system. We included 83 clinical M. tuberculosis isolates containing rpoB mutations in the primary analysis. Rifampicin resistance was seen in 72 isolates (87%), isoniazid resistance in 73 isolates (88%) and MDR-TB in 65 isolates (78%). Phenotypic reference testing identified pyrazinamide-resistant MDR-TB in 31 isolates (48%). Sensitivity of pncA sequencing added to rpoB mutation analysis for detecting pyrazinamide-resistant MDR-TB was 96.8%, the specificity was 94.2%, the positive predictive value was 90.9%, the negative predictive value was 98.0%, the positive likelihood was 16.8 and the negative likelihood was 0.03. In conclusion, pyrazinamide-resistant MDR-TB can be accurately detected using pncA sequencing added to rpoB mutation analysis. We propose to include pncA sequencing in every isolate with an rpoB mutation, allowing for stratification of MDR-TB treatment according to pyrazinamide susceptibility. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  12. Rhizospheric bacterial strain Brevibacterium casei MH8a colonizes plant tissues and enhances Cd, Zn, Cu phytoextraction by white mustard

    Directory of Open Access Journals (Sweden)

    Tomasz ePłociniczak

    2016-02-01

    Full Text Available Environmental pollution by heavy metals has become a serious problem in the world. Phytoextraction, which is one of the plant-based technologies, has attracted the most attention for the bioremediation of soils polluted with these contaminants.The aim of this study was to determine whether the multiple-tolerant bacterium, Brevibacterium casei MH8a isolated from the heavy metal-contaminated rhizosphere soil of Sinapis alba L., is able to promote plant growth and enhance Cd, Zn and Cu uptake by white mustard under laboratory conditions. Additionally, the ability of the rifampicin-resistant spontaneous mutant of MH8a to colonize plant tissues and its mechanisms of plant growth promotion were also examined. In order to assess the ecological consequences of bioaugmentation on autochthonous bacteria, the phospholipid fatty acid (PLFA analysis was used. The MH8a strain exhibited the ability to produce ammonia, 1-amino-cyclopropane-1-carboxylic acid deaminase, indole 3-acetic acid and HCN but was not able to solubilize inorganic phosphate and produce siderophores. Introduction of MH8a into soil significantly increased S. alba biomass and the accumulation of Cd (208%, Zn (86% and Cu (39% in plant shoots in comparison with those grown in non-inoculated soil. Introduced into the soil, MH8a was able to enter the plant and was found in the roots and leaves of inoculated plants thus indicating its endophytic features. PLFA analysis revealed that the MH8a that was introduced into soil had a temporary influence on the structure of the autochthonous bacterial communities. The plant growth-promoting features of the MH8a strain and its ability to enhance the metal uptake by white mustard and its long-term survival in soil as well as its temporary impact on autochthonous microorganisms make the strain a suitable candidate for the promotion of plant growth and the efficiency of phytoextraction.

  13. ADHERENCE AND PA THOGENICITY ASSA Y OF VIBRIO HARVE YI IN TIGER SHRIMP (PENAEUS MONODON LARVAE FOR SC REENING BIOCONTROL AGE NT

    Directory of Open Access Journals (Sweden)

    YUSMINAH H ALA

    2002-01-01

    Full Text Available Rifampicin-resistant marker w as empl oyed as a repor ter t o detect the ad here nce and colonization of V. harve yi in s hrimp larvae. Vibri o h arve yi P1B and YA3 2. 2 were isolated f rom dead s hrimp la rv ae i n Besuki, Norther n C oast of East Jav a, while V. harveyi HB3, was isolated from pris tine sea water in Pacita n, S outhe rn Coast of E ast Ja va . Vi brio metsc hnikovii used a s bioc ontr ol a gent was i solated fr om healthy shrimp larvae in Serang, We st Java. Spontane ous mutation was c onducted to generate V. harveyi P1B, YA32.2 and HB3 resistant to rifampi cin. These mutants exhibit ed similar survival ability to t heir parent al (wild type strai ns. Signifi cant larval mortalit y was o bserv ed i n s hrimp l arv ae i noculated with YA32.2 than that of larvae ino culated with P1B. Larvae inoculated with H B 3 showed the lo w est mortality. Bacterial cell c ount of Vi brio Rf* in dead larvae w ere 103-104 cells/larvae. Isolates of Vi brio metschnikovii Z an d M as biocontrol candid ates effectively r educed the growth a nd a dherence ability of YA32.2 t o shrimp larvae. Larval mort ality in rearing water inoculat ed simultaneousl y w ith YA32.2 and V. metschnikovii was lower than the one inoculated with YA32.2 alone. Therefore, Vibrio metschnikovii Z or M could be develope d as an effective pro biotic or biocontrol agent for V. harvey i in shrimp hatcheri es.

  14. Ribonucleotide reductase as a drug target against drug resistance Mycobacterium leprae: A molecular docking study.

    Science.gov (United States)

    Mohanty, Partha Sarathi; Bansal, Avi Kumar; Naaz, Farah; Gupta, Umesh Datta; Dwivedi, Vivek Dhar; Yadava, Umesh

    2018-06-01

    Leprosy is a chronic infection of skin and nerve caused by Mycobacterium leprae. The treatment is based on standard multi drug therapy consisting of dapsone, rifampicin and clofazamine. The use of rifampicin alone or with dapsone led to the emergence of rifampicin-resistant Mycobacterium leprae strains. The emergence of drug-resistant leprosy put a hurdle in the leprosy eradication programme. The present study aimed to predict the molecular model of ribonucleotide reductase (RNR), the enzyme responsible for biosynthesis of nucleotides, to screen new drugs for treatment of drug-resistant leprosy. The study was conducted by retrieving RNR of M. leprae from GenBank. A molecular 3D model of M. leprae was predicted using homology modelling and validated. A total of 325 characters were included in the analysis. The predicted 3D model of RNR showed that the ϕ and φ angles of 251 (96.9%) residues were positioned in the most favoured regions. It was also conferred that 18 α-helices, 6 β turns, 2 γ turns and 48 helix-helix interactions contributed to the predicted 3D structure. Virtual screening of Food and Drug Administration approved drug molecules recovered 1829 drugs of which three molecules, viz., lincomycin, novobiocin and telithromycin, were taken for the docking study. It was observed that the selected drug molecules had a strong affinity towards the modelled protein RNR. This was evident from the binding energy of the drug molecules towards the modelled protein RNR (-6.10, -6.25 and -7.10). Three FDA-approved drugs, viz., lincomycin, novobiocin and telithromycin, could be taken for further clinical studies to find their efficacy against drug resistant leprosy. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Rhizospheric Bacterial Strain Brevibacterium casei MH8a Colonizes Plant Tissues and Enhances Cd, Zn, Cu Phytoextraction by White Mustard.

    Science.gov (United States)

    Płociniczak, Tomasz; Sinkkonen, Aki; Romantschuk, Martin; Sułowicz, Sławomir; Piotrowska-Seget, Zofia

    2016-01-01

    Environmental pollution by heavy metals has become a serious problem in the world. Phytoextraction, which is one of the plant-based technologies, has attracted the most attention for the bioremediation of soils polluted with these contaminants. The aim of this study was to determine whether the multiple-tolerant bacterium, Brevibacterium casei MH8a isolated from the heavy metal-contaminated rhizosphere soil of Sinapis alba L., is able to promote plant growth and enhance Cd, Zn, and Cu uptake by white mustard under laboratory conditions. Additionally, the ability of the rifampicin-resistant spontaneous mutant of MH8a to colonize plant tissues and its mechanisms of plant growth promotion were also examined. In order to assess the ecological consequences of bioaugmentation on autochthonous bacteria, the phospholipid fatty acid (PLFA) analysis was used. The MH8a strain exhibited the ability to produce ammonia, 1-amino-cyclopropane-1-carboxylic acid deaminase, indole 3-acetic acid and HCN but was not able to solubilize inorganic phosphate and produce siderophores. Introduction of MH8a into soil significantly increased S. alba biomass and the accumulation of Cd (208%), Zn (86%), and Cu (39%) in plant shoots in comparison with those grown in non-inoculated soil. Introduced into the soil, MH8a was able to enter the plant and was found in the roots and leaves of inoculated plants thus indicating its endophytic features. PLFA analysis revealed that the MH8a that was introduced into soil had a temporary influence on the structure of the autochthonous bacterial communities. The plant growth-promoting features of the MH8a strain and its ability to enhance the metal uptake by white mustard and its long-term survival in soil as well as its temporary impact on autochthonous microorganisms make the strain a suitable candidate for the promotion of plant growth and the efficiency of phytoextraction.

  16. Soil type dependent rhizosphere competence and biocontrol of two bacterial inoculant strains and their effects on the rhizosphere microbial community of field-grown lettuce.

    Directory of Open Access Journals (Sweden)

    Susanne Schreiter

    Full Text Available Rhizosphere competence of bacterial inoculants is assumed to be important for successful biocontrol. Knowledge of factors influencing rhizosphere competence under field conditions is largely lacking. The present study is aimed to unravel the effects of soil types on the rhizosphere competence and biocontrol activity of the two inoculant strains Pseudomonas jessenii RU47 and Serratia plymuthica 3Re4-18 in field-grown lettuce in soils inoculated with Rhizoctonia solani AG1-IB or not. Two independent experiments were carried out in 2011 on an experimental plot system with three soil types sharing the same cropping history and weather conditions for more than 10 years. Rifampicin resistant mutants of the inoculants were used to evaluate their colonization in the rhizosphere of lettuce. The rhizosphere bacterial community structure was analyzed by denaturing gradient gel electrophoresis of 16S rRNA gene fragments amplified from total community DNA to get insights into the effects of the inoculants and R. solani on the indigenous rhizosphere bacterial communities. Both inoculants showed a good colonization ability of the rhizosphere of lettuce with more than 10(6 colony forming units per g root dry mass two weeks after planting. An effect of the soil type on rhizosphere competence was observed for 3Re4-18 but not for RU47. In both experiments a comparable rhizosphere competence was observed and in the presence of the inoculants disease symptoms were either significantly reduced, or at least a non-significant trend was shown. Disease severity was highest in diluvial sand followed by alluvial loam and loess loam suggesting that the soil types differed in their conduciveness for bottom rot disease. Compared to effect of the soil type of the rhizosphere bacterial communities, the effects of the pathogen and the inoculants were less pronounced. The soil types had a surprisingly low influence on rhizosphere competence and biocontrol activity while they

  17. Soil type dependent rhizosphere competence and biocontrol of two bacterial inoculant strains and their effects on the rhizosphere microbial community of field-grown lettuce.

    Science.gov (United States)

    Schreiter, Susanne; Sandmann, Martin; Smalla, Kornelia; Grosch, Rita

    2014-01-01

    Rhizosphere competence of bacterial inoculants is assumed to be important for successful biocontrol. Knowledge of factors influencing rhizosphere competence under field conditions is largely lacking. The present study is aimed to unravel the effects of soil types on the rhizosphere competence and biocontrol activity of the two inoculant strains Pseudomonas jessenii RU47 and Serratia plymuthica 3Re4-18 in field-grown lettuce in soils inoculated with Rhizoctonia solani AG1-IB or not. Two independent experiments were carried out in 2011 on an experimental plot system with three soil types sharing the same cropping history and weather conditions for more than 10 years. Rifampicin resistant mutants of the inoculants were used to evaluate their colonization in the rhizosphere of lettuce. The rhizosphere bacterial community structure was analyzed by denaturing gradient gel electrophoresis of 16S rRNA gene fragments amplified from total community DNA to get insights into the effects of the inoculants and R. solani on the indigenous rhizosphere bacterial communities. Both inoculants showed a good colonization ability of the rhizosphere of lettuce with more than 10(6) colony forming units per g root dry mass two weeks after planting. An effect of the soil type on rhizosphere competence was observed for 3Re4-18 but not for RU47. In both experiments a comparable rhizosphere competence was observed and in the presence of the inoculants disease symptoms were either significantly reduced, or at least a non-significant trend was shown. Disease severity was highest in diluvial sand followed by alluvial loam and loess loam suggesting that the soil types differed in their conduciveness for bottom rot disease. Compared to effect of the soil type of the rhizosphere bacterial communities, the effects of the pathogen and the inoculants were less pronounced. The soil types had a surprisingly low influence on rhizosphere competence and biocontrol activity while they significantly affected

  18. Cytotoxic and antibacterial substances against multi-drug resistant pathogens from marine sponge symbiont: Citrinin, a secondary metabolite of Penicillium sp.

    Science.gov (United States)

    Subramani, Ramesh; Kumar, Rohitesh; Prasad, Pritesh; Aalbersberg, William; Retheesh, S T

    2013-04-01

    To Isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus Penicillium sp. FF001 and to elucidate its structure. The fungal strain FF001 with an interesting bioactivity profile was isolated from a marine Fijian sponge Melophlus sp. Based on conidiophores aggregation, conidia development and mycelia morphological characteristics, the isolate FF001 was classically identified as a Penicillium sp. The bioactive compound was identified using various spectral analysis of UV, high resolution electrospray ionization mass spectra, 1H and 13C NMR spectral data. Further minimum inhibitory concentrations (MICs) assay and brine shrimp cytotoxicity assay were also carried out to evaluate the biological properties of the purified compound. Bioassay guided fractionation of the EtOAc extract of a static culture of this Penicillium sp. by different chromatographic methods led the isolation of an antibacterial, anticryptococcal and cytotoxic active compound, which was identified as citrinin (1). Further, citrinin (1) is reported for its potent antibacterial activity against methicillin-resistant Staphylococcus aureus (S. aureus), rifampicin-resistant S. aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium showed MICs of 3.90, 0.97, 1.95 and 7.81 µg/mL, respectively. Further citrinin (1) displayed significant activity against the pathogenic yeast Cryptococcus neoformans (MIC 3.90 µg/mL), and exhibited cytotoxicity against brine shrimp larvae LD50 of 96 µg/mL. Citrinin (1) is reported from sponge associated Penicillium sp. from this study and for its strong antibacterial activity against multi-drug resistant human pathogens including cytotoxicity against brine shrimp larvae, which indicated that sponge associated Penicillium spp. are promising sources of natural bioactive metabolites.

  19. Root colonization and growth promotion of sunflower (Helianthus annuus L.) by phosphate solubilizing Enterobacter sp. Fs-11.

    Science.gov (United States)

    Shahid, Muhammad; Hameed, Sohail; Imran, Asma; Ali, Saira; van Elsas, Jan Dirk

    2012-08-01

    An Enterobacter sp. Fs-11 was isolated from sunflower rhizosphere, identified on the basis of 16S rRNA gene sequence analysis (GeneBank accession no. GQ179978) and studied for its root colonization and growth promotion ability in sunflower. Morphologically, it was rod shaped Gram-negative, motile bacterium, producing 4.5 μg mL(-1) indole acetic acid in tryptophan-supplemented medium. It utilized 27 out of 95 substrates in BIOLOG GN2 micro plate system. It was able to convert insoluble tri-calcium phosphate to soluble phosphorus up to 43.5 μg mL(-1) with decrease in pH of the medium up to 4.5 after 10 days incubation at 28 ± 2 °C in the Pikovskaya's broth. High performance liquid chromatography of cell free supernatant showed that Fs-11 produced malic acid and gluconic acid (2.43 and 16.64 μg mL(-1), respectively) in Pikovskaya's broth. Analysis of 900 bp fragment of pyrroloquinoline quinine pqqE gene sequence showed 98 % homology with that of E. cloacae pqqE gene. Confocal laser scanning microscope revealed strong colonization of fluorescently labeled Fs-11 with sunflower roots. Sunflower inoculation with Fs-11 and its rifampicin resistant derivative in sterile sand and natural soil showed that Fs-11 colonized sunflower roots up to 30 days after transplanting in both sterile sand as well as natural soil. Moreover, Fs-11 inoculation resulted in increased plant height, fresh weight, dry weight and total phosphorus contents as compared to un-inoculated plants. The data showed that Enterobacter sp. Fs-11 is an efficient phosphate solubilizing and plant growth promoting rhizobacterium and has great potential to be used as bio-inoculant for sunflower under phosphorus deficient conditions.

  20. BAKTERI PROBIOTIK DALAM BUDIDAYA UDANG: SELEKSI, MEKANISME AKSI, KARAKTERISASI, DAN APLIKASINYA SEBAGAI AGEN BIOKONTROL

    Directory of Open Access Journals (Sweden)

    Widanarni

    2008-08-01

    Full Text Available Bacterial disease attack occurs at the hatchery stage, which is considered to be the most serious threat, and often results in mass mortality of shrimp larvae by vibrosis which is that caused by a luminous bacterium identified as Vibrio harveyi. This research was carried out to obtain local isolates of probiotic bacteria that were able to inhibit the growth of V. harveyi and effectively apply it as a biocontrol of vibriosis in shrimp cultures. The research was carried out as follows: (1 In vitro and in vivo selection of probiotic bacteria candidates, (2 Study of the action mechanism and characterization of the selected pro biotic bacteria, (3 Study on application of the selected probiotic bacteria as a biocontrol agent in shrimp cultures. Results of in vitro and in vivo selection provided the best three isolates, which were 1Ub, SKT-b and Ua. The survival rate of shrimp larvae which were not only inoculated by V. harveyi but also with 1Ub, SKT-b and Ua probiotic bacteria were 88.33, 83.33, and 81.67% respectively; where as the positive control treatment (merely inoculated with V. harveyi gave a 41.67% survival rate and the negative control (without bacterial addition was 68.33%. Studies using a rifampicin resistant marker (RfR demonstrated that the number of V. harveyi MR5339 RfR cells in treatments without probiotic addition were higher than the treatment with the probiotic bacteria, in dead larvae, living larvae, as well as in the culture media. Partial sequencing of the I6S-rRNA gene showed that the I Ub isolate was similar to Pseudoalteromonas piscicida, whereas the SKT -b and Ua isolates were similar to Vibrio alginolyticus. Selected probiotic bacteria could be applied directly to shrimp larva culture media, or orally through enrichment of both natural and artificial food

  1. Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting

    KAUST Repository

    Perdigão, João

    2014-11-18

    Background Multidrug- (MDR) and extensively drug resistant (XDR) tuberculosis (TB) presents a challenge to disease control and elimination goals. In Lisbon, Portugal, specific and successful XDR-TB strains have been found in circulation for almost two decades. Results In the present study we have genotyped and sequenced the genomes of 56 Mycobacterium tuberculosis isolates recovered mostly from Lisbon. The genotyping data revealed three major clusters associated with MDR-TB, two of which are associated with XDR-TB. Whilst the genomic data contributed to elucidate the phylogenetic positioning of circulating MDR-TB strains, showing a high predominance of a single SNP cluster group 5. Furthermore, a genome-wide phylogeny analysis from these strains, together with 19 publicly available genomes of Mycobacterium tuberculosis clinical isolates, revealed two major clades responsible for M/XDR-TB in the region: Lisboa3 and Q1 (LAM). The data presented by this study yielded insights on microevolution and identification of novel compensatory mutations associated with rifampicin resistance in rpoB and rpoC. The screening for other structural variations revealed putative clade-defining variants. One deletion in PPE41, found among Lisboa3 isolates, is proposed to contribute to immune evasion and as a selective advantage. Insertion sequence (IS) mapping has also demonstrated the role of IS6110 as a major driver in mycobacterial evolution by affecting gene integrity and regulation. Conclusions Globally, this study contributes with novel genome-wide phylogenetic data and has led to the identification of new genomic variants that support the notion of a growing genomic diversity facing both setting and host adaptation.

  2. Development and efficacy of an attenuated Vibrio harveyi vaccine candidate with cross protectivity against Vibrio alginolyticus.

    Science.gov (United States)

    Hu, Yong-hua; Deng, Tian; Sun, Bo-guang; Sun, Li

    2012-06-01

    Vibrio harveyi is a Gram-negative bacterial pathogen that can infect a wide range of marine animals. In previous studies, we have reported a virulent V. harveyi strain, T4D. In the present study, an attenuated mutant of T4D, T4DM, was obtained by selection of rifampicin resistance. Compared to the wild type, T4DM was different in whole-cell protein profile and much slower in growth rate when cultured in stress conditions caused by iron depletion. Virulence analysis showed that compared to T4D, T4DM exhibited a dramatically increased median lethal dose, impaired tissue dissemination capacity, defective hemolytic activity, and significantly reduced resistance against the killing effect of host serum. To examine the potential of T4DM as a live attenuated vaccine, Japanese flounder (Paralichthys olivaceus) were vaccinated with T4DM via intraperitoneal injection or immersion. The results showed that at one and two months post-vaccination, fish administered with T4DM via both approaches, in particular that of immersion, were effectively protected against not only V. harveyi but also Vibrio alginolyticus, another important fish pathogen. Microbiological analysis showed that following immersion vaccination, T4DM was recovered from the internal organs of the vaccinated fish in a time-dependent manner within the first 6 days post-vaccination. Serum antibodies against V. harveyi and V. alginolyticus were detected in T4DM-vaccinated fish, and, compared to serum from control fish, serum from T4DM-vaccinated fish was significantly enhanced in bactericidal activity. These results indicate that T4DM is an attenuated strain with residual infectivity and that T4DM can induce effective cross-species protection against both V. harveyi and V. alginolyticus when used as a live immersion vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial.

    Science.gov (United States)

    Lee, Ji Yeon; Kim, Deog Kyeom; Lee, Jung-Kyu; Yoon, Ho Il; Jeong, Ina; Heo, Eunyoung; Park, Young Sik; Lee, Jae Ho; Park, Sung Soo; Lee, Sang-Min; Lee, Chang-Hoon; Lee, Jinwoo; Choi, Sun Mi; Park, Jong Sun; Joh, Joon-Sung; Cho, Young-Jae; Lee, Yeon Joo; Kim, Se Joong; Hwang, Young Ran; Kim, Hyeonjeong; Ki, Jongeun; Choi, Hyungsook; Han, Jiyeon; Ahn, Heejung; Hahn, Seokyung; Yim, Jae-Joon

    2017-02-13

    Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis. This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total). This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future. ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

  4. Evolution of extensively drug-resistant tuberculosis over four decades revealed by whole genome sequencing of Mycobacterium tuberculosis from KwaZulu-Natal, South Africa

    Directory of Open Access Journals (Sweden)

    Keira A Cohen

    2015-01-01

    Full Text Available The largest global outbreak of extensively drug-resistant (XDR tuberculosis (TB was identified in Tugela Ferry, KwaZulu-Natal (KZN, South Africa in 2005. The antecedents and timing of the emergence of drug resistance in this fatal epidemic XDR outbreak are unknown, and it is unclear whether drug resistance in this region continues to be driven by clonal spread or by the development of de novo resistance. A whole genome sequencing and drug susceptibility testing (DST was performed on 337 clinical isolates of Mycobacterium tuberculosis (M.tb collected in KZN from 2008 to 2013, in addition to three historical isolates, one of which was isolated during the Tugela Ferry outbreak. Using a variety of whole genome comparative approaches, 11 drug-resistant clones of M.tb circulating from 2008 to 2013 were identified, including a 50-member clone of XDR M.tb that was highly related to the Tugela Ferry XDR outbreak strain. It was calculated that the evolutionary trajectory from first-line drug resistance to XDR in this clone spanned more than four decades and began at the start of the antibiotic era. It was also observed that frequent de novo evolution of MDR and XDR was present, with 56 and 9 independent evolutions, respectively. Thus, ongoing amplification of drug-resistance in KwaZulu-Natal is driven by both clonal spread and de novo acquisition of resistance. In drug-resistant TB, isoniazid resistance was overwhelmingly the initial resistance mutation to be acquired, which would not be detected by current rapid molecular diagnostics that assess only rifampicin resistance.

  5. Complete Genome Sequence of Vibrio campbellii LMB 29 Isolated from Red Drum with Four Native Megaplasmids

    Directory of Open Access Journals (Sweden)

    Jinxin Liu

    2017-10-01

    Full Text Available Vibrio spp. are the most common pathogens for animals reared in aquaculture. Vibrio campbellii, which is often involved in shrimp, fish and mollusks diseases, is widely distributed in the marine environment worldwide, but our knowledge about its pathogenesis and antimicrobial resistance is very limited. The existence of this knowledge gap is at least partially because that V. campbellii was originally classified as Vibrio harveyi, and the detailed information of its comparative genome analysis to other Vibrio spp. is currently lacking. In this study, the complete genome of a V. campbellii predominant strain, LMB29, was determined by MiSeq in conjunction with PacBio SMRT sequencing. This genome consists of two circular DNA chromosomes and four megaplasmids. Comparative genome analysis indicates that LMB29 shares a 96.66% similarity (average nucleotide identity with the V. campbellii ATCC strain BAA-1116 based on a 75% AF (average fraction calculations, and its functional profile is very similar to V. campbellii E1 and V. campbellii CAIM115. Both type III secretion system (T3SS and type VI secretion system (T6SS, along with the tlh gene which encodes a thermolabile hemolysin, are present in LMB29 which may contribute to the bacterial pathogenesis. The virulence of this strain was experimental confirmed by performing a LDH assay on a fish cell infection model, and cell death was observed as early as within 3 h post infection. Thirty-seven antimicrobial resistance genes (>45% identity were predicted in LMB29 which includes a novel rifampicin ADP ribosyltransferase, arr-9, in plasmid pLMB157. The gene arr-9 was predicted on a genomic island with horizontal transferable potentials which may facilitate the rifampicin resistance dissemination. Future researches are needed to explore the pathogenesis of V. campbellii LMB29, but the availability of this genome sequence will certainly aid as a basis for further analysis.

  6. Increased levels of CCR7(lo)PD-1(hi) CXCR5+ CD4+ T cells, and associated factors Bcl-6, CXCR5, IL-21 and IL-6 contribute to repeated implantation failure.

    Science.gov (United States)

    Gong, Qiaoqiao; Zhu, Yuejie; Pang, Nannan; Ai, Haiquan; Gong, Xiaoyun; La, Xiaolin; Ding, Jianbing

    2017-12-01

    In vitro fertilization-embryo transfer (IVF-ET) can be used by infertile couples to assist with reproduction; however, failure of the embryo to implant into the endometrial lining results in failure of the IVF treatment. The present study investigated the expression of chemokine receptor 7 (CCR7)(lo) programmed death-1(PD-1)(hi) chemokine receptor type 5 (CXCR5) + cluster of differentiation 4 (CD4) + T cells and associated factors in patients with repeated implantation failure (RIF). A total of 30 females with RIF and 30 healthy females were enrolled in the current study. Flow cytometry was used to detect the proportion of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells in the peripheral blood. Cytokine bead arrays were performed to detect the levels of interleukin (IL)-6, -4 and -2 in the serum. ELISAs were used to detect the level of IL-21 in the serum. Quantitative real time polymerase chain reaction analysis and immunohistochemistry were used to investigate the expression of B-cell lymphoma 6 (Bcl-6), chemokine receptor type 5 (CXCR5) and IL-21 in the endometrium. The results revealed that the percentage of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells was increased in the RIF group compared with the control group during the mid luteal phase. The mRNA and protein levels of Bcl-6, IL-21 and CXCR5 in the endometrium and the concentrations of IL-21 and IL-6 in the serum were significantly increased in the RIF group; however, no significant difference was observed between the two groups in regards to the expression of IL-4 and IL-2. Furthermore, a significant positive correlation was identified between the percentage of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells and IL-21 and IL-6 levels. The expression of IL-21 also had a positive correlation with Bcl-6 and CXCR5 expression in the RIF group. These results suggest that increased levels of CCR7(lo)PD-1(hi) CXCR5 + CD4 + T cells and associated factors contribute to RIF and could therefore be a potential therapeutic target.

  7. Temporal kinetics and concentration-response relationships for induction of CYP1A, CYP2B, and CYP3A in primary cultures of beagle dog hepatocytes.

    Science.gov (United States)

    Graham, Richard A; Tyler, Lindsey O; Krol, Wojciech L; Silver, Ivin S; Webster, Lindsey O; Clark, Philip; Chen, Liangfu; Banks, Troy; LeCluyse, Edward L

    2006-01-01

    Compared to other species, little information is available on the xenobiotic-induced regulation of cytochrome P450 enzymes in the beagle dog. Dogs are widely used in the pharmaceutical industry for many study types, including those that will impact decisions on compound progression. The purpose of this study was (1) to determine the temporal kinetics of drug-induced changes in canine CYP1A, CYP2B, and CYP3A mRNA and enzymatic activity, and (2) to characterize concentration-response relationships for CYP1A2, CYP2B11, and CYP3A12 using primary cultures of canine hepatocytes treated with beta-naphthoflavone (BNF), phenobarbital (PB), and rifampin (RIF), respectively. CYP1A1 and CYP1A2 mRNA exhibited maximal expression (12,700-fold and 206-fold, respectively) after 36 h of treatment with BNF. PB treatment, but not RIF treatment, caused maximal induction of CYP2B11 mRNA (149-fold) after 48 h of treatment. CYP3A12 and CYP3A26 mRNA levels were increased maximally after 72 h of treatment with PB and RIF (CYP3A12, 35-fold and 18-fold, and CYP3A26, 72-fold and 22-fold with PB and RIF treatment, respectively). Concentration-response relationships for BNF induced 7-ethoxyresorufin O-dealkylation (EROD) (EC(50) = 7.8 +/- 4.2 microM), PB induced 7-benzyloxyresorufin O-dealkylation (BROD) (EC(50) = 123 +/- 30 microM), and PB and RIF induced testosterone 6beta-hydroxylation (EC(50) = 132 +/- 28 microM and 0.98 +/- 0.16 microM) resembled the relationship for human CYP induction compared to that of rodent. Interestingly, RIF had no effect on CYP2B11 expression, which represents a species difference overlooked in previous investigations. Overall, the induction of dog CYP1A, CYP2B, and CYP3A exhibits characteristics that are intermediate to those of rodent and human. (c) 2006 Wiley Periodicals, Inc.

  8. Organizational downsizing and age discrimination litigation: the influence of personnel practices and statistical evidence on litigation outcomes.

    Science.gov (United States)

    Wingate, Peter H; Thornton, George C; McIntyre, Kelly S; Frame, Jennifer H

    2003-02-01

    The present study examined relationships between reduction-in-force (RIF) personnel practices, presentation of statistical evidence, and litigation outcomes. Policy capturing methods were utilized to analyze the components of 115 federal district court opinions involving age discrimination disparate treatment allegations and organizational downsizing. Univariate analyses revealed meaningful links between RIF personnel practices, use of statistical evidence, and judicial verdict. The defendant organization was awarded summary judgment in 73% of the claims included in the study. Judicial decisions in favor of the defendant organization were found to be significantly related to such variables as formal performance appraisal systems, termination decision review within the organization, methods of employee assessment and selection for termination, and the presence of a concrete layoff policy. The use of statistical evidence in ADEA disparate treatment litigation was investigated and found to be a potentially persuasive type of indirect evidence. Legal, personnel, and evidentiary ramifications are reviewed, and a framework of downsizing mechanics emphasizing legal defensibility is presented.

  9. The 300 area waste acid treatment system closure plan

    International Nuclear Information System (INIS)

    Luke, S.N.

    1996-01-01

    The 300 Area Waste Acid Treatment System (WATS) is located within operable units 300-FF-2 (source) and 300-FF-5 (groundwater), as designated in the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) . Operable units 300-FF-2 and 300-FF-5 are scheduled to be remediated using the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) Remedial Investigation/Feasibility Study (RI/FS) process. Thus, any remediation of the 300 Area WATS with respect to contaminants not produced by those facilities and soils and groundwater will be deferred to the CERCLA RI/FS process. Final closure activities will be completed in 3 phases and certified in accordance with the 300 Area WATS closure plan by the Washington State Department of Ecology (Ecology) and the U.S. Environmental Protection Agency (EPA). It is anticipated that the 300 Area WATS closure would take 2 years to complete

  10. Variation in tumor response to fluosol-DA (20%)

    International Nuclear Information System (INIS)

    Sasai, K.; Ono, K.; Nishidai, T.; Tsutsui, K.; Shibamoto, Y.; Takahashi, M.; Abe, M.

    1989-01-01

    The effects of Fluosol-DA 20% (FDA) and carbogen (95% O2/5% CO 2 ) on radiosensitivity of the three experimental tumors, SCC VII tumor, RIF-I tumor, and transplanted mammary tumor of C 3 H/He mouse, subcutaneously inoculated in the leg were examined. The effect of FDA plus carbogen, and carbogen alone on radiosensitivity of SCC VII and RIF-I tumors was tested using the in vivo-in vitro assay. The growth curves were obtained for both SCC VII tumor and transplanted mammary tumor. The effect of the combination of FDA and carbogen was only observed in the transplanted mammary tumor. In the other two tumors, only the effect of inspiring carbogen was observed. We concluded that the effect of FDA on the radiosensitivity of experimental tumors varies with the kind of tumor systems

  11. Exploring the role of internal friction in the dynamics of unfolded proteins using simple polymer models

    Science.gov (United States)

    Cheng, Ryan R.; Hawk, Alexander T.; Makarov, Dmitrii E.

    2013-02-01

    Recent experiments showed that the reconfiguration dynamics of unfolded proteins are often adequately described by simple polymer models. In particular, the Rouse model with internal friction (RIF) captures internal friction effects as observed in single-molecule fluorescence correlation spectroscopy (FCS) studies of a number of proteins. Here we use RIF, and its non-free draining analog, Zimm model with internal friction, to explore the effect of internal friction on the rate with which intramolecular contacts can be formed within the unfolded chain. Unlike the reconfiguration times inferred from FCS experiments, which depend linearly on the solvent viscosity, the first passage times to form intramolecular contacts are shown to display a more complex viscosity dependence. We further describe scaling relationships obeyed by contact formation times in the limits of high and low internal friction. Our findings provide experimentally testable predictions that can serve as a framework for the analysis of future studies of contact formation in proteins.

  12. The Department of Energy's Remedial Action Assessment System (RAAS): Decision support tools for performing streamlined feasibility studies

    International Nuclear Information System (INIS)

    White, M.K.

    1994-06-01

    The United States Department of Energy (DOE) faces the major task of cleaning up hundreds of waste sites across the nation, which will require completion of a large number of remedial investigation/feasibility studies (RI/FSs). The intent of each RI/FS is to characterize the waste problems and environmental conditions at the operable unit level, segment the remediation problem into manageable medium-specific and contaminant-specific pieces, define corresponding remediation objectives, and identify remedial response actions to satisfy those objectives. The RI/FS team can then identify combinations of remediation technologies that will meet the remediation objectives. Finally, the team must evaluate these remedial alternatives in terms of effectiveness, implementability, cost, and acceptability. The Remedial Action Assessment System (RAAS) is being developed by Pacific Northwest Laboratory (PNL) to support DOE in this effort

  13. Molecular mechanisms underlying radio-induced fibro-genic differentiation and fibrosis targeted therapies

    International Nuclear Information System (INIS)

    Bourgier, C.

    2008-01-01

    Intestinal complications after radiotherapy are caused by transmural fibrosis (RIF) that impaired the quality of life of cancer patient survivors and considered permanent and irreversible until recently but recent molecular characterization of RIF offered new targeted opportunities for the development of anti-fibrotic therapies. In this thesis work, we identified activation of the Rho/ROCK pathway which is involved in the persistence of fibro-genic signals. In addition, among the new anti-fibrotic targeted therapies, we asked whether specific inhibition of Rho pathway, by Pravastatin could elicit anti-fibrotic action. Therefore, the therapeutic relevance of pravastatin as anti-fibrotic strategy was validated using two different models of intestinal and lung fibrosis. As statins are safe and well tolerated compounds, phase II clinical trial is envisioned within the next months to reverse established fibrosis after radiotherapy. (author)

  14. The actin homologue MreB organizes the bacterial cell membrane.

    Science.gov (United States)

    Strahl, Henrik; Bürmann, Frank; Hamoen, Leendert W

    2014-03-07

    The eukaryotic cortical actin cytoskeleton creates specific lipid domains, including lipid rafts, which determine the distribution of many membrane proteins. Here we show that the bacterial actin homologue MreB displays a comparable activity. MreB forms membrane-associated filaments that coordinate bacterial cell wall synthesis. We noticed that the MreB cytoskeleton influences fluorescent staining of the cytoplasmic membrane. Detailed analyses combining an array of mutants, using specific lipid staining techniques and spectroscopic methods, revealed that MreB filaments create specific membrane regions with increased fluidity (RIFs). Interference with these fluid lipid domains (RIFs) perturbs overall lipid homeostasis and affects membrane protein localization. The influence of MreB on membrane organization and fluidity may explain why the active movement of MreB stimulates membrane protein diffusion. These novel MreB activities add additional complexity to bacterial cell membrane organization and have implications for many membrane-associated processes.

  15. Qualitative risk assessment as a remediation management tool

    International Nuclear Information System (INIS)

    Knutson, D.E.

    1991-01-01

    The technique used to complete this thesis utilizes existing NRC and EPA guidance on health-based risk to qualitatively prioritize preliminary assessments and provide a tool for the direction and management of remediation activities. This method is intended as a decision making tool to aid in prioritizing the remediation effort and manage the remedial investigation and feasibility study (RI/FS) process. It is not a replacement for the RI/FS. The methodology for qualitative risk assessment utilizes data gathered in preliminary assessments and calculates the health-based hazards and consequences from contaminants found at each individual location. The health-based qualitative risk indicated that number-sign 6 fuel oil, carbon tetrachloride, depleted uranium, and enriched uranium were the contaminants of major concern, in that order. Plutonium ranked approximately sixth in the contaminant of concern priority. 38 refs., 1 fig., 9 tabs

  16. Combining reflectometry and fluorescence microscopy: an assay for the investigation of leakage processes across lipid membranes.

    Science.gov (United States)

    Stephan, Milena; Mey, Ingo; Steinem, Claudia; Janshoff, Andreas

    2014-02-04

    The passage of solutes across a lipid membrane plays a central role in many cellular processes. However, the investigation of transport processes remains a serious challenge in pharmaceutical research, particularly the transport of uncharged cargo. While translocation reactions of ions across cell membranes is commonly measured with the patch-clamp, an equally powerful screening method for the transport of uncharged compounds is still lacking. A combined setup for reflectometric interference spectroscopy (RIfS) and fluorescence microscopy measurements is presented that allows one to investigate the passive exchange of uncharged compounds across a free-standing membrane. Pore-spanning lipid membranes were prepared by spreading giant 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) vesicles on porous anodic aluminum oxide (AAO) membranes, creating sealed attoliter-sized compartments. The time-resolved leakage of different dye molecules (pyranine and crystal violet) as well as avidin through melittin induced membrane pores and defects was investigated.

  17. Does autoimmunity play a role in the risk of implantation failures?

    Science.gov (United States)

    Motak-Pochrzest, Hanna; Malinowski, Andrzej

    2018-02-01

    158 non-pregnant women with recurrent implantation failures after IVF/ET procedures were tested for peripheral blood autoimmune profile. The control group consisted of 76 patients after first successful IVF procedure and pregnancy outcome. The objective of this study was to investigate different autoantibodies peripheral blood profile after excluding anatomical, endocrinological, endometrial and genetic disorders and to estimate the risk of implantation failures. The study's including criteria were 1.indications for IVF/ET determined by male factor and unexplained infertility 2. absence of implantation after two consecutive cycles of IVF, ICSI or frozen embryo replacement cycles. The presence of ANA in the sera increased the risk of RIF after ET/IVF procedures, especially in older patients. Patients with RIF have a higher frequency of the presence of autoantibodies ACA IgG, IgM and anti-β2GP I IgG in the sera than in patients with successful pregnancies after IVF/ET procedures.

  18. Inhibition of adenocarcinoma TA3 ascites tumor growth by rifamycin derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, A M; Tenforde, T S; Calvin, M; Bissell, M J; Tischler, A N; Bennett, E L

    1978-01-01

    A growth inhibitory effect on adenocarcinoma TA3 ascites tumors in LAF/sub 1//J mice resulted from the repeated IP administration of subtoxic doses of 3 rifamycin derivatives: rifampicin (Rif)/sup 1/, dimethylbenzyldesmethylrifampicin (DMB), and rifazone-8/sub 2/ (R-8/sub 2/). A high-viscosity methylcellulose vehicle was found to be essential for obtaining a uniform drug suspension and a significant antitumor effect by the least water soluble derivatives, DMB and and R-8/sub 2/. The more hydrophilic derivative, Rif, was found to have a comparable growth inhibitory effect on TA3 cells when prepared in 0.9% NaCl solution with or without added methylcellulose. Oral or SC drug injections did not have an antitumor effect. The results of this study point to the importance of vehicle and route of administration in chemotherapy trials with these compounds.

  19. Quantification of rifampicin in human plasma and cerebrospinal fluid by a highly sensitive and rapid liquid chromatographic-tandem mass spectrometric method.

    Science.gov (United States)

    Srivastava, Abhishek; Waterhouse, David; Ardrey, Alison; Ward, Stephen A

    2012-11-01

    A highly sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed to measure the levels of the antitubercular drug rifampicin (RIF) in human plasma and cerebrospinal fluid (CSF). The analyte and internal standard (IS) were isolated from plasma and CSF by a simple organic solvent based precipitation of proteins followed by centrifugation. Detection was carried out by electrospray positive ionization mass spectrometry in the multiple-reaction monitoring (MRM) mode. The assay was linear in the concentration range 25-6400 ng/mL with intra- and inter-day precision of <7% and <8%, respectively. The validated method was applied to the study of RIF pharmacokinetics in human CSF and plasma over 25 h period after a 10 mg/kg oral dose. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. 31P NMR spectroscopy and HbO2 cryospectrophotometry in prediction of tumor radioresistance caused by hypoxia.

    Science.gov (United States)

    Rofstad, E K; DeMuth, P; Fenton, B M; Ceckler, T L; Sutherland, R M

    1989-04-01

    The aim of this study was to search for possible relationships between the fraction of radiobiologically hypoxic cells in tumors and their 31P NMR spectral parameters and intracapillary HbO2 saturations. Four different tumor lines, two murine sarcomas (KHT, RIF-1) and two human ovarian carcinoma xenografts (MLS, OWI), were used. When tumor volume increased from about 200 mm3 to about 2000 mm3, hypoxic fraction increased from 12 to 23% for the KHT line, from 0.9 to 1.7% for the RIF-1 line, and from 9 to 28% for the MLS line. The OWI line showed similar hypoxic fractions at 200 (17%) and 2000 mm3 (15%). Tumor bioenergetic status decreased, that is, the inorganic phosphate (Pi) resonance increased and the phosphocreatine (PCr) and nucleoside triphosphate beta (NTP beta) resonances decreased, with increasing tumor volume for the KHT, RIF-1, and MLS lines, whereas the OWI line did not show any changes in the 31P NMR spectral parameters during tumor growth. Similarly, tumor HbO2 saturation status, that is, the fraction of vessels with HbO2 saturation above 30%, decreased with increasing tumor volume for the KHT, RIF-1, and MLS lines, but remained unchanged during tumor growth for the OWI line. Although the data indicated a relationship between hypoxic fraction and tumor bioenergetic status as well as tumor HbO2 saturation status within a specific line during tumor growth, there was no correlation between hypoxic fraction and tumor bioenergetic status or tumor HbO2 saturation status across the four tumor lines. This may have occurred because cell survival time under hypoxic stress as well as fraction of non-clonogenic, but metabolically active hypoxic cells differed among the tumor lines. This indicates that 31P NMR spectroscopy and HbO2 cryospectrophotometry data have to be supplemented with other data to be useful in prediction of tumor radioresistance caused by hypoxia.

  1. Evaluation of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis for the detection of the rpoB mutations associated with resistance to rifampicin in Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Lee, H.; Cho, S.-N.; Bang, H.-E.; Kim, S.-C.; Victor, T.C.; Jordaan, A.; Suffys, P.N.; Gomes, H.M.; Singh, U.; Suresh, V.N.; Khan, B.K.

    2003-01-01

    Resistance of Mycobacterium tuberculosis to rifampicin (RIF) has been associated with mutations of the rpoB gene, which encodes for the RNA polymerase B subunit. Based on this information, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) has been suggested as a sensitive and rapid screening test for the detection of RIF-resistant M. tuberculosis from clinical isolates. PCR-SSCP analyses with radioisotopes and without radioisotopes were employed to detect mutations of the rpoB gene associated with resistance to RIF in four laboratories, and results were compared with those of sequence analysis and the conventional proportion method of drug susceptibility test between laboratories. Radioisotopic PCR-SSCP showed an excellent correlation with sequence analysis of the 157 bp region of the rpoB gene by identifying correctly all 32 isolates analyzed in this study, with a high resolution of the banding patterns obtained. In a separate study, non-radioisotopic PCR-SSCP also gave a good correlation with sequence analysis in 22 isolates, but two (9.1%) isolates were classified as resistant by PCR-SSCP despite wild type sequences. When PCR-SSCP was compared with the results obtained using the proportion method, sensitivity of 44% to 85% were obtained in the 4 laboratories that participated in this study. Possible reasons for discordant results are discussed. It has been concluded that despite discordant results, which were sometimes observed, depending on the experimental conditions, PCR-SSCP appears to be an effective and promising method for the rapid detection of RIF-resistant M. tuberculosis, a marker of multidrug resistant tuberculosis. (author)

  2. Detection of multidrug-resistant tuberculosis from stored DNA Samples: A multicenter study

    OpenAIRE

    Marie Sylvianne Rabodoarivelo; A Brandao; M C Cergole Novella; A G C. Bombonatte; B Imperiale; N Rakotosamimanana; N Morcillo; V Rasolofo; J C Palomino; A Martin

    2018-01-01

    Background: In low-income countries, rapid detection of tuberculosis (TB) drug resistance is often restricted by the difficulties of transporting and storing sputum samples from remote health centers to the reference laboratories where molecular tests are available. The aim of this study was to evaluate the performance of four transport and storage systems for molecular detection of rifampicin (RIF) and isoniazid (INH) resistance. Methods: This was a multicenter study. Molecular detection of ...

  3. Susceptibility of bacteria isolated from acute gastrointestinal infections to rifaximin and other antimicrobial agents in Mexico.

    Science.gov (United States)

    Novoa-Farías, O; Frati-Munari, A C; Peredo, M A; Flores-Juárez, S; Novoa-García, O; Galicia-Tapia, J; Romero-Carpio, C E

    2016-01-01

    Bacterial resistance may hamper the antimicrobial management of acute gastroenteritis. Bacterial susceptibility to rifaximin, an antibiotic that achieves high fecal concentrations (up to 8,000μg/g), has not been evaluated in Mexico. To determine the susceptibility to rifaximin and other antimicrobial agents of enteropathogenic bacteria isolated from patients with acute gastroenteritis in Mexico. Bacterial strains were analyzed in stool samples from 1,000 patients with diagnosis of acute gastroenteritis. The susceptibility to rifaximin (RIF) was tested by microdilution (<100, <200, <400 and <800μg/ml) and susceptibility to chloramphenicol (CHL), trimethoprim-sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), fosfomycin (FOS), ampicillin (AMP) and ciprofloxacin (CIP) was tested by agar diffusion at the concentrations recommended by the Clinical & Laboratory Standards Institute and the American Society for Microbiology. Isolated bacteria were: enteropathogenic Escherichia coli (E. coli) (EPEC) 531, Shigella 120, non-Typhi Salmonella 117, Aeromonas spp. 80, enterotoxigenic E. coli (ETEC) 54, Yersinia enterocolitica 20, Campylobacter jejuni 20, Vibrio spp. 20, Plesiomonas shigelloides 20, and enterohemorrhagic E. coli (EHEC 0:157) 18. The overall cumulative susceptibility to RIF at <100, <200, <400, and <800μg/ml was 70.6, 90.8, 99.3, and 100%, respectively. The overall susceptibility to each antibiotic was: AMP 32.2%, T-S 53.6%, NEO 54.1%, FUR 64.7%, CIP 67.3%, CLO 73%, and FOS 81.3%. The susceptibility to RIF <400 and RIF <800μg/ml was significantly greater than with the other antibiotics (p<0.001). Resistance of enteropathogenic bacteria to various antibiotics used in gastrointestinal infections is high. Rifaximin was active against 99-100% of these enteropathogens at reachable concentrations in the intestine with the recommended dose. Copyright © 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  4. Description of codes and models to be used in risk assessment

    International Nuclear Information System (INIS)

    1991-09-01

    Human health and environmental risk assessments will be performed as part of the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) remedial investigation/feasibility study (RI/FS) activities at the Hanford Site. Analytical and computer encoded numerical models are commonly used during both the remedial investigation (RI) and feasibility study (FS) to predict or estimate the concentration of contaminants at the point of exposure to humans and/or the environment. This document has been prepared to identify the computer codes that will be used in support of RI/FS human health and environmental risk assessments at the Hanford Site. In addition to the CERCLA RI/FS process, it is recommended that these computer codes be used when fate and transport analyses is required for other activities. Additional computer codes may be used for other purposes (e.g., design of tracer tests, location of observation wells, etc.). This document provides guidance for unit managers in charge of RI/FS activities. Use of the same computer codes for all analytical activities at the Hanford Site will promote consistency, reduce the effort required to develop, validate, and implement models to simulate Hanford Site conditions, and expedite regulatory review. The discussion provides a description of how models will likely be developed and utilized at the Hanford Site. It is intended to summarize previous environmental-related modeling at the Hanford Site and provide background for future model development. The modeling capabilities that are desirable for the Hanford Site and the codes that were evaluated. The recommendations include the codes proposed to support future risk assessment modeling at the Hanford Site, and provides the rational for the codes selected. 27 refs., 3 figs., 1 tab

  5. 44 Apport du SIG et de la télédétection dans la modélisation spatiale ...

    African Journals Online (AJOL)

    Unicornis

    44. ISSN 1813-548X, http://www.afriquescience.info. Ahmed Nasreddine El FAHCHOUCH et al. Apport du SIG et de la télédétection dans la modélisation spatiale de la susceptibilité aux mouvements de terrain dans la région d'Al Hoceima,. Rif Oriental, Maroc. Ahmed NasreddineEl FAHCHOUCH*, Lahsen AIT BRAHIM, ...

  6. Differential gene expression before and after ionizing radiation of subcutaneous fibroblasts identifies breast cancer patients resistant to radiation-induced fibrosis

    International Nuclear Information System (INIS)

    Alsner, Jan; Rodningen, Olaug K.; Overgaard, Jens

    2007-01-01

    Background and purpose: Differentially gene expression between patients with either very low or very high risk of radiation-induced fibrosis (RIF) in patient-derived fibroblasts after irradiation has previously been reported. In the present study, we are investigating the robustness of radiation-induced changes in gene expression in fibroblasts, whether differential expression is more pronounced when looking at the fold induction levels, taking into account the differences in background expression levels between patients, and whether there is a linear correlation between individual risk of RIF and changes in radiation-induced gene expression in fibroblasts. Material and methods: Gene expression was analysed by quantitative real-time PCR before and after a fractionated scheme with 3 x 3.5 Gy/3 days in fibroblasts derived from 26 patients with breast cancer treated with post-mastectomy radiotherapy. Results: Robust radiation-induced changes in gene expression were observed, with differential gene expression between low and high risk patients being most pronounced for the fold induction level ('after' value divided by 'before' value for each patient). When including patients with intermediate risk, there was no linear correlation between individual risk of RIF and differential expression of the genes investigated. Rather, differential gene expression could divide patients into two clearly separated groups, a larger, sensitive group and a smaller resistant group. Conclusions: Differential gene expression in irradiated fibroblasts might be an important tool in the identification of differences in the genetic background between patients with variable risk of RIF, and in the identification of new targets for prevention and intervention of the fibrotic process

  7. Studies of murine tumor control using x-ray fractionation schedules alone or in combination with hyperthermia

    International Nuclear Information System (INIS)

    Imbra, R.J.

    1981-01-01

    The effectiveness of an experimental radiation fractionation schedule of decreasing-sized dose fractions administered at optimal time intervals was compared with a conventional fractionation schedule of constant-sized dose fractions administered five times per week. Also, the effect of the addition of hyperthermia (42.5 0 C) to radiation therapy was investigated. For some experiments, Ehrlich mammary tumors were growth in the right thighs of Swiss mice. The tumor response was determined by measuring the tumor-bearing leg diameter and converting this value to volume. The time for the treated tumor to regrow to its pre-tratment volume was used as an endpoint in Swiss mice. The maximum total treatment dose is limited by the amount of normal tissue damage. A total treatment dose of six thousand rads was most suitable for the further investigations. Definitive investigations were performed using the RIF-1 tumor grown in the right thigh of C3H mice. The length of mitotic delay of RIF-1 cells, in vivo, was determined after various single doses of x radiation. A direct (exponential) relationship betwen x-ray dose and mitotic delay time was observed. Times of release of the RIF-1 cells from radiation-induced mitotic delay were used to determine the optimum time intervals to deliver the decreasing-sized dose fractions. Six thousand rads administered as decreasing-sized dose fractions resulted in significantly greater RIF-1 tumor control, as compared to conventional radiation therapy. The best treatment schedule, overall, was decreasing-sized dose fractions plus hyperthermia

  8. Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.

    Science.gov (United States)

    Gayathri, N K; Aparna, V; Maya, S; Biswas, Raja; Jayakumar, R; Mohan, C Gopi

    2017-12-01

    We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Using social media data to understand mobile customer experience and behavior

    OpenAIRE

    Hsu, Wenling; Jacobsen, Guy; Jin, Yu; Skudlark, Ann

    2011-01-01

    Understanding mobile customer experience and behavior is an important task for cellular service providers to improve the satisfaction of their customers. To that end, cellular service providers regularly measure the properties of their mobile network, such as signal strength, dropped calls, call blockage, and radio interface failures (RIFs). In addition to these passive measurements collected within the network, understanding customer sentiment from direct customer feedback is also an importa...

  10. Nitazoxanide is active against Mycobacterium leprae

    Science.gov (United States)

    Bailey, Mai Ann; Na, Hana; Duthie, Malcolm S.; Gillis, Thomas P.; Lahiri, Ramanuj

    2017-01-01

    Nitazoxanide (NTZ) is an anti-parasitic drug that also has activity against bacteria, including Mycobacterium tuberculosis. Our data using both radiorespirometry and live-dead staining in vitro demonstrate that NTZ similarly has bactericidal against M. leprae. Further, gavage of M. leprae-infected mice with NTZ at 25mg/kg provided anti-mycobacterial activity equivalent to rifampicin (RIF) at 10 mg/kg. This suggests that NTZ could be considered for leprosy treatment. PMID:28850614