WorldWideScience

Sample records for erythraea rifampicin-resistant rif

  1. Phenotypes and gene expression profiles of Saccharopolyspora erythraea rifampicin-resistant (rif mutants affected in erythromycin production

    Directory of Open Access Journals (Sweden)

    Bicciato Silvio

    2009-03-01

    Full Text Available Abstract Background There is evidence from previous works that bacterial secondary metabolism may be stimulated by genetic manipulation of RNA polymerase (RNAP. In this study we have used rifampicin selection as a strategy to genetically improve the erythromycin producer Saccharopolyspora erythraea. Results Spontaneous rifampicin-resistant (rif mutants were isolated from the parental strain NRRL2338 and two rif mutations mapping within rpoB, S444F and Q426R, were characterized. With respect to the parental strain, S444F mutants exhibited higher respiratory performance and up to four-fold higher final erythromycin yields; in contrast, Q426R mutants were slow-growing, developmental-defective and severely impaired in erythromycin production. DNA microarray analysis demonstrated that these rif mutations deeply changed the transcriptional profile of S. erythraea. The expression of genes coding for key enzymes of carbon (and energy and nitrogen central metabolism was dramatically altered in turn affecting the flux of metabolites through erythromycin feeder pathways. In particular, the valine catabolic pathway that supplies propionyl-CoA for biosynthesis of the erythromycin precursor 6-deoxyerythronolide B was strongly up-regulated in the S444F mutants, while the expression of the biosynthetic gene cluster of erythromycin (ery was not significantly affected. In contrast, the ery cluster was down-regulated ( Conclusion Rifampicin selection is a simple and reliable tool to investigate novel links between primary and secondary metabolism and morphological differentiation in S. erythraea and to improve erythromycin production. At the same time genome-wide analysis of expression profiles using DNA microarrays allowed information to be gained about the mechanisms underlying the stimulatory/inhibitory effects of the rif mutations on erythromycin production.

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

    Science.gov (United States)

    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

  3. Evaluation of rifampicin resistance and 81-bp rifampicin resistant determinant region of rpoB gene mutations of Mycobacterium tuberculosis detected with XpertMTB/Rif in Cross River State, Nigeria

    Directory of Open Access Journals (Sweden)

    Ernest A Ochang

    2016-01-01

    Conclusion: In our setting, 6.0% of tuberculosis isolates are rifampicin resistant. Mutations associated with probe E commonly due to codon 531 are the most predominant cause of rifampicin resistance. Mutations at probe C (codons 518–523 were uncommon. A change in mutation may have occurred in one of the patients.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  7. TUBERCULOSIS AND RIFAMPICIN RESISTANCE AMONG MIGRANTS IN KYRGYZSTAN: DETECTION BY A NEW DIAGNOSTIC TEST

    Science.gov (United States)

    BARMANKULOVA, AIGUL; HIGUCHI, MICHIYO; SARKER, MOHAMMAD ABUL BASHAR; ALIM, MD. ABDUL; HAMAJIMA, NOBUYUKI

    2015-01-01

    ABSTRACT This cross-sectional study aimed to describe suspected tuberculosis (TB) cases among migrants in Kyrgyzstan and to estimate the accuracy of Xpert MTB/RIF, which has been operated in Kyrgyzstan since 2012. Characteristics of 3,714 suspected cases among migrants were analysed. In addition, by using data of 300 cases with culture results, sensitivity and specificity of Xpert MTB/RIF, both for detection of TB and rifampicin susceptibility, were assessed. Among 3,714 suspected cases, 56.1% were male, and the median age was 35 years old. Of the suspected cases, 17.2% were previously-treated. In total, 809 (21.8%) were smear-positive; 36.8% among previously-treated cases and 18.7% among new cases. Among 300 selected participants, 235 (78.3%) were culture-positive. Of those who were confirmed as TB positive, recurrent cases showed a higher proportion of rifampicin resistance than new cases (59.3% vs 42.6%). For detection of TB, the sensitivity and specificity of XpertMTB/RIF (81.3% and 98.2%) were higher than those of microscopy (70.2% and 71.4%). Sensitivity and specificity for detection of rifampicin resistance were 96.8% and 91.8%, respectively. The rifampicin resistance rate in the study population was higher than the national average. Xpert MTB/RIF showed higher accuracy in detecting TB cases than microscopic diagnosis. Higher accuracy and earlier detection of drug susceptibility is especially important for those who have difficulty in accessing healthcare and those who are easily lost from tracking, including migrants. PMID:25797969

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Methylbenzene-Containing Polyketides from a Streptomyces that Spontaneously Acquired Rifampicin Resistance: Structural Elucidation and Biosynthesis.

    Science.gov (United States)

    Thong, Wei Li; Shin-ya, Kazuo; Nishiyama, Makoto; Kuzuyama, Tomohisa

    2016-04-22

    Conventional screening for novel bioactive compounds in actinomycetes often results in the rediscovery of known compounds. In contrast, recent genome sequencing revealed that most of the predicted gene clusters for secondary metabolisms are not expressed under standard cultivation conditions. To explore the potential metabolites produced by these gene clusters, we implemented a cryptic gene activation strategy by screening mutants that acquire resistance to rifampicin. The induction of rifampicin resistance in 11 actinomycete strains generated 164 rifampicin-resistant mutants (rif mutants). The comparison of the metabolic profiles between the rif mutants and their wild-type strains indicated that one mutant (TW-R50-13) overproduced an unidentified metabolite (1). During the isolation and structural elucidation of metabolite 1, an additional metabolite was found; both are unprecedented compounds featuring a C5N unit and a methylbenzene moiety. Of these partial structures, the biosynthesis of the latter has not been reported. A feeding experiment using (13)C-labeled precursors demonstrated that the methylbenzene moiety is most likely synthesized by the action of polyketide synthase. The gene deletion experiments revealed that the genes for the methylbenzene moiety are located at a different locus than the genes for the C5N unit.

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

    African Journals Online (AJOL)

    unhcc

    policy changes. Lancet. 2007; 369: 2042–49. 14. Lawn SD, Nicol MP. Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. FutMicrobiol. 2011;. 6(9):1067-1082. 15. Auld S, Moore B, Killam W, Eng B, Nong K,. Pevzner E, et al.

  11. Disseminated tuberculosis in an HIV-infected child: rifampicin resistance detected by GeneXpert in a lymph node aspirate but not in cerebrospinal fluid.

    Science.gov (United States)

    Gamell, Anna; Ntamatungiro, Alex John; Battegay, Manuel; Letang, Emilio

    2015-08-03

    A 9-year-old HIV-infected child previously treated with inadequate doses of antitubercular drugs based on weight was admitted 5 months after initial tuberculosis (TB) diagnosis with acute hemiplegia and inguinal lymphadenopathies in a rural hospital in Tanzania. He was diagnosed with TB meningitis and lymphadenitis using Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay. Rifampicin resistance was detected in the lymph node aspirate but not in the cerebrospinal fluid. His TB therapy was optimised based on available medications and antiretroviral treatment was initiated 6 weeks later. Despite these efforts, the clinical evolution was poor and the child died 12 weeks after admission. 2015 BMJ Publishing Group Ltd.

  12. Impact of replacing smear microscopy with Xpert MTB/RIF for diagnosing tuberculosis in Brazil: a stepped-wedge cluster-randomized trial

    NARCIS (Netherlands)

    Durovni, Betina; Saraceni, Valeria; van den Hof, Susan; Trajman, Anete; Cordeiro-Santos, Marcelo; Cavalcante, Solange; Menezes, Alexandre; Cobelens, Frank

    2014-01-01

    Abundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the

  13. Early Outcomes Of Decentralized Care for Rifampicin-Resistant Tuberculosis in Johannesburg, South Africa: An Observational Cohort Study.

    Directory of Open Access Journals (Sweden)

    Rebecca Berhanu

    Full Text Available We describe baseline characteristics, time to treatment initiation and interim patient outcomes at a decentralized, outpatient treatment site for rifampicin-resistant TB (RR-TB.Prospective observational cohort study of RR-TB patients from March 2013 until December 2014. Study subjects were followed until completion of the intensive phase of treatment (6 months, transfer out, or a final outcome (loss from treatment (LFT or death.214 patients with RR-TB were enrolled in the study. Xpert MTB/RIF was the diagnostic test of rifampicin resistance for 87% (n = 186, followed by direct PCR on AFB positive specimen in 14 (7% and indirect PCR on cultured isolate in 5 (2%. Median time between sputum testing and treatment initiation was 10 days (IQR 6-21. Interim outcomes were available in 148 patients of whom 78% (n = 115 were still on treatment, 9% (n = 13 had died, and 14% (n = 20 were LFT. Amongst 131 patients with culture positive pulmonary TB, 85 (64.9% were culture negative at 6 months, 12 were still sputum culture positive (9.2% and 34 had no culture documented or contaminated culture (26%. Patients who initiated as outpatients within 1 week of sputum collection for diagnosis of RR-TB had a significantly lower incidence of LFT (IRR 0.30, 95% CI: 0.09-0.98. HIV co-infection occurred in 178 patients (83% with a median CD4 count 88 cells/ml3 (IQR 27-218.Access to decentralized treatment coupled with the rapid diagnosis of RR-TB has resulted in short time to treatment initiation. Despite the lack of treatment delays, early treatment outcomes remain poor with high rates of death and loss from care.

  14. Isolation of rifampicin resistant Flavobacterium psychrophilum strains and their potential as live attenuated vaccine candidates

    Science.gov (United States)

    Previous studies have demonstrated that passage of pathogenic bacteria on increasing concentrations of the antibiotic rifampicin leads to the attenuation of virulence and these resistant strains may serve as live attenuated vaccines. Two rifampicin resistant strains of Flavobacterium psychrophilum,...

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

    Science.gov (United States)

    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 .

  16. Rifampicin resistant initiation of chromosome replication from oriC in ihf mutants

    DEFF Research Database (Denmark)

    von Freiesleben, Ulrik; Rasmussen, Knud V.; Atlung, Tove

    2000-01-01

    C in a rifampicin-resistant initiation mode but requires fully functional DnaA protein. The origin per mass ratio, determined by a quantitative Southern blotting technique, showed that the ihf mutants had an origin per mass ratio that was 60% of the wild type although it had a normal DnaA protein concentration...

  17. Performance of Xpert® MTB/RIF among tuberculosis outpatients in Lilongwe, Malawi

    Directory of Open Access Journals (Sweden)

    Tarsizio Chikaonda

    2017-03-01

    Full Text Available Background: Xpert® MTB/RIF is a molecular test for the detection of Mycobacterium tuberculosis and rifampicin resistance. It is considered to be a great advance over smear microscopy and culture. However, there is very little information regarding the performance characteristics of Xpert MTB/RIF in Malawi. Objective: We aimed to evaluate the performance of Xpert MTB/RIF in a Malawian setting. Methods: Stored sputum pellets were processed on Xpert MTB/RIF between June 2012 andMay 2014. Results were compared to mycobacteria growth indicator tube and Löwenstein-Jensen cultures, LED fluorescent microscopy and GenoType® MTBDRplus assay. Rifampicinresistance was confirmed by DNA sequencing. Results: Of the 348 specimens with valid Xpert MTB/RIF results, 129/348 (37% were smearpositive and 198/348 (57% were culture-positive. Xpert MTB/RIF demonstrated a sensitivity of 93.8% (95% CI 89.4% – 96.8% and specificity of 97.4% (95% CI 93.5% – 99.3%, with a positive predictive value of 97.8% (95% CI 94.6% – 99.4% and a negative predictive value of 92.6% (95% CI 87.4% – 96.1%. Xpert MTB/RIF correctly identified 185/186 (99.5% rifampicin sensitive and 2/2 (100% rifampicin-resistant M. tuberculosis strains. Mutations were notdetected by sequencing in one isolate which was rifampicin resistant on Xpert MTB/RIF butsensitive on MTBDRplus. Four non-tuberculous mycobacteria grew from four smear-negativespecimens, namely, M. avium (n = 1 and M. intracellulare (n = 3. No cross-reactivity wasobserved with any of the non-tuberculous mycobacteria when using Xpert MTB/RIF. Conclusion: When fully implemented, Xpert MTB/RIF may have an impact on patient care inMalawi. The increased diagnostic yield of Xpert MTB/RIF over smear microscopy can increaselaboratory-confirmed tuberculosis detection and ensure that treatment is given to appropriateindividuals or groups.

  18. Rifampicin resistant initiation of chromosome replication from oriC in ihf mutants

    DEFF Research Database (Denmark)

    von Freiesleben, Ulrik; Rasmussen, Knud V.; Atlung, Tove

    2000-01-01

    C in a rifampicin-resistant initiation mode but requires fully functional DnaA protein. The origin per mass ratio, determined by a quantitative Southern blotting technique, showed that the ihf mutants had an origin per mass ratio that was 60% of the wild type although it had a normal DnaA protein concentration....... This shows that the initiation mass was substantially higher in the ihf mutants. The oriC per terminus ratio, which was also determined by Southern blotting, was very low in the ihf mutant, although it grew with the same doubling times as the wild-type strain. This indicates that cells lacking IHF replicate...

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

    Science.gov (United States)

    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.

  20. Impact of replacing smear microscopy with Xpert MTB/RIF for diagnosing tuberculosis in Brazil: a stepped-wedge cluster-randomized trial.

    Science.gov (United States)

    Durovni, Betina; Saraceni, Valeria; van den Hof, Susan; Trajman, Anete; Cordeiro-Santos, Marcelo; Cavalcante, Solange; Menezes, Alexandre; Cobelens, Frank

    2014-12-01

    Abundant evidence on Xpert MTB/RIF accuracy for diagnosing tuberculosis (TB) and rifampicin resistance has been produced, yet there are few data on the population benefit of its programmatic use. We assessed whether the implementation of Xpert MTB/RIF in routine conditions would (1) increase the notification rate of laboratory-confirmed pulmonary TB to the national notification system and (2) reduce the time to TB treatment initiation (primary endpoints). We conducted a stepped-wedge cluster-randomized trial from 4 February to 4 October 2012 in 14 primary care laboratories in two Brazilian cities. Diagnostic specimens were included for 11,705 baseline (smear microscopy) and 12,522 intervention (Xpert MTB/RIF) patients presumed to have TB. Single-sputum-sample Xpert MTB/RIF replaced two-sputum-sample smear microscopy for routine diagnosis of pulmonary TB. In total, 1,137 (9.7%) tests in the baseline arm and 1,777 (14.2%) in the intervention arm were positive (pReplacing smear microscopy with Xpert MTB/RIF in Brazil increased confirmation of pulmonary TB. An additional benefit was the accurate detection of rifampicin resistance. However, no increase on overall notification rates was observed, possibly because of high rates of empirical TB treatment. ClinicalTrials.gov NCT01363765. Please see later in the article for the Editors' Summary.

  1. Environmental variation alters the fitness effects of rifampicin resistance mutations in Pseudomonas aeruginosa.

    Science.gov (United States)

    Gifford, Danna R; Moss, Ethan; MacLean, R Craig

    2016-03-01

    The fitness effects of antibiotic resistance mutations in antibiotic-free conditions play a key role in determining the long-term maintenance of resistance. Although resistance is usually associated with a cost, the impact of environmental variation on the cost of resistance is poorly understood. Here, we test the impact of heterogeneity in temperature and resource availability on the fitness effects of antibiotic resistance using strains of the pathogenic bacterium Pseudomonas aeruginosa carrying clinically important rifampicin resistance mutations. Although the rank order of fitness was generally maintained across environments, fitness effects relative to the wild type differed significantly. Changes in temperature had a profound impact on the fitness effects of resistance, whereas changes in carbon substrate had only a weak impact. This suggests that environmental heterogeneity may influence whether the costs of resistance are likely to be ameliorated by second-site compensatory mutations or by reversion to wild-type rpoB. Our results highlight the need to consider environmental heterogeneity and genotype-by-environment interactions for fitness in models of resistance evolution. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  2. Evolution of Escherichia coli rifampicin resistance in an antibiotic-free environment during thermal stress.

    Science.gov (United States)

    Rodríguez-Verdugo, Alejandra; Gaut, Brandon S; Tenaillon, Olivier

    2013-02-22

    Beneficial mutations play an essential role in bacterial adaptation, yet little is known about their fitness effects across genetic backgrounds and environments. One prominent example of bacterial adaptation is antibiotic resistance. Until recently, the paradigm has been that antibiotic resistance is selected by the presence of antibiotics because resistant mutations confer fitness costs in antibiotic free environments. In this study we show that it is not always the case, documenting the selection and fixation of resistant mutations in populations of Escherichia coli B that had never been exposed to antibiotics but instead evolved for 2000 generations at high temperature (42.2°C). We found parallel mutations within the rpoB gene encoding the beta subunit of RNA polymerase. These amino acid substitutions conferred different levels of rifampicin resistance. The resistant mutations typically appeared, and were fixed, early in the evolution experiment. We confirmed the high advantage of these mutations at 42.2°C in glucose-limited medium. However, the rpoB mutations had different fitness effects across three genetic backgrounds and six environments. We describe resistance mutations that are not necessarily costly in the absence of antibiotics or compensatory mutations but are highly beneficial at high temperature and low glucose. Their fitness effects depend on the environment and the genetic background, providing glimpses into the prevalence of epistasis and pleiotropy.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  6. Label-free DNA-based detection of Mycobacterium tuberculosis and rifampicin resistance through hydration induced stress in microcantilevers.

    Science.gov (United States)

    Domínguez, Carmen M; Kosaka, Priscila M; Sotillo, Alma; Mingorance, Jesús; Tamayo, Javier; Calleja, Montserrat

    2015-02-03

    We have developed a label-free assay for the genomic detection of Mycobacterium tuberculosis and rifampicin resistance. The method relies on the quantification of the hydration induced stress on microcantilever biosensors functionalized with oligonucleotide probes, before and after hybridization with specific targets. We have found a limit of detection of 10 fg/mL for PCR amplified products of 122 bp. Furthermore, the technique can successfully target genomic DNA (gDNA) fragments of length >500 bp, and it can successfully discriminate single mismatches. We have used both loci IS6110 and rpoB as targets to detect the mycobacteria and the rifampicin resistance from gDNA directly extracted from bacterial culture and without PCR amplification. We have been able to detect 2 pg/mL target concentration in samples with an excess of interfering DNA and in a total analysis time of 1 h and 30 min. The detection limit found demonstrates the capability to develop direct assays without the need for long culture steps or PCR amplification. The methodology can be easily translated to different microbial targets, and it is suitable for further development of miniaturized devices and multiplexed detection.

  7. Victimas del Rif

    Directory of Open Access Journals (Sweden)

    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.

  8. Evaluation of rapid GeneXpert MTB/RIF method using DNA tissue specimens of vertebral bones in patients with suspected spondylitis TB.

    Science.gov (United States)

    Massi, Muhammad Nasrum; Biatko, Karya Triko; Handayani, Irda; Pratama, Muhammad Yogi; Septriani, Sari; Nurdin, Gaby Maulida; Ali, Marina B

    2017-03-01

    To detect Mycobacterium tuberculosis DNA and rifampicin resistance in vertebral bone tissue specimens from spondylitis TB suspects. The rapid GeneXpert MTB/RIF and MGIT 960 liquid culture methods have been used in the specimens. Results from 70 suspects with spondylitis TB shown that 31.42% identified positive for spondylitis TB using culture method, while 88.57% shown positive results using rapid GeneXpert MTB/RIF method. The validity of GeneXpert MTB/RIF shown sensitivity value of 100%, specificity value of 16.6%, PPV of 35.48%, and NPV of 100%. GeneXpert has a high sensitivity but low specificity value in this study.

  9. A model of tuberculosis screening for pregnant women in resource-limited settings using Xpert MTB/RIF.

    Science.gov (United States)

    Turnbull, Eleanor R; Kancheya, Nzali G; Harris, Jennifer B; Topp, Stephanie M; Henostroza, German; Reid, Stewart E

    2012-01-01

    Timely diagnosis and treatment of maternal tuberculosis (TB) is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO) recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.

  10. A Model of Tuberculosis Screening for Pregnant Women in Resource-Limited Settings Using Xpert MTB/RIF

    Directory of Open Access Journals (Sweden)

    Eleanor R. Turnbull

    2012-01-01

    Full Text Available Timely diagnosis and treatment of maternal tuberculosis (TB is important to reduce morbidity and mortality for both the mother and child, particularly in women who are coinfected with HIV. The World Health Organization (WHO recommends the integration of TB/HIV screening into antenatal services but available diagnostic tools are slow and insensitive, resulting in delays in treatment initiation. Recently the WHO endorsed Xpert MTB/RIF, a highly sensitive, real-time PCR assay for Mycobacterium tuberculosis that simultaneously detects rifampicin resistance directly from sputum and provides results within 100 minutes. We propose a model for same-day TB screening and diagnosis of all pregnant women at antenatal care using Xpert MTB/RIF. Pilot studies are urgently required to evaluate strategies for the integration of TB screening into antenatal clinics using new diagnostic technologies.

  11. 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.

  12. 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

  13. 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).

  14. DOT or SAT for Rifampicin-resistant tuberculosis? A non-randomized comparison in a high HIV-prevalence setting.

    Science.gov (United States)

    Mohr, Erika; Daniels, Johnny; Beko, Busisiwe; Isaakidis, Petros; Cox, Vivian; Steele, Sarah Jane; Muller, Odelia; Snyman, Leigh; De Azevedo, Virginia; Shroufi, Amir; Trivino Duran, Laura; Hughes, Jennifer

    2017-01-01

    Daily directly-observed therapy (DOT) is recommended for rifampicin-resistant tuberculosis (RR-TB) patients throughout treatment. We assessed the impact of self-administered treatment (SAT) in a South African township with high rates of RR-TB and HIV. Community-supported SAT for patients who completed the intensive phase was piloted in five primary care clinics in Khayelitsha. We compared final treatment outcomes among RR-TB patients initiating treatment before (standard-of-care (SOC)-cohort, January 2010-July 2013) and after the implementation of the pilot (SAT-cohort, January 2012-December 2014). All patients with outcomes before January 1, 2017 were considered in the analysis of outcomes. One-hundred-eighteen patients in the SOC-cohort and 174 patients in the SAT-cohort had final RR-TB treatment outcomes; 70% and 73% were HIV-co-infected, respectively. The proportion of patients with a final outcome of loss to follow-up (LTFU) did not differ whether treated in the SOC (25/118, 21.2%) or SAT-cohort (31/174, 17.8%) (P = 0.47). There were no significant differences in the time to 24-month LTFU among HIV-infected and uninfected patients (HR 0.90, 95% CI: 0.51-1.6, P = 0.71), or among patients enrolled in the SOC-cohort versus the SAT-cohort (HR 0.83, 95% CI: 0.49-1.4, P = 0.50) who received at least 6-months of RR-TB treatment. The introduction of SAT during the continuation phase of RR-TB treatment does not adversely affect final RR-TB treatment outcomes in a high TB and HIV-burden setting. This differentiated, patient-centred model of care could be considered in RR-TB programmes to decrease the burden of DOT on patients and health facilities.

  15. A rifampicin-resistant (rpoB) mutation in Pseudomonas protegens Pf-5 strain leads to improved antifungal activity and elevated production of secondary metabolites.

    Science.gov (United States)

    Xie, Yali; Liu, Zhengqiang; Zhang, Guoyong; Mo, Xiangtao; Ding, Xuezhi; Xia, Liqiu; Hu, Shengbiao

    2016-10-01

    Ribosome engineering has proven to be a practical method for increasing antibiotic production, and is extensively applied to strain improvement in antibiotic production and activation of silent genes in several prokaryotes. In this study, ribosome engineering was used to improve production of bioactive secondary metabolites produced by Pseudomonas protegens Pf-5. Rifampicin-resistant mutants that bear the H531N in the β-subunit of RNA polymerase showed improved antifungal activity and morphological changes. The production of several secondary metabolites in R55 mutant was significantly improved using high-performance liquid chromatography (HPLC) analysis. Two antibiotics with antifungal activity, 2, 4-diacetylphloroglucinol (Phl) and pyoluteorin (Plt), which may contribute to the improved antifungal activity of the R55 mutant, were identified by mass spectrometer (MS) analysis. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  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. 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

  19. 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

  20. Direct Detection by the Xpert MTB/RIF Assay and Characterization of Multi and Poly Drug-Resistant Tuberculosis in Guinea-Bissau, West Africa.

    Directory of Open Access Journals (Sweden)

    Paulo Rabna

    Full Text Available This study aimed to evaluate the usefulness of the Xpert MTB/RIF assay for the rapid direct detection of M. tuberculosis complex (MTBC strains and rifampicin resistance associated mutations in a resource-limited setting such as Guinea-Bissau and its implications in the management of tuberculosis (TB and drug resistant tuberculosis, complementing the scarce information on resistance and genotypic diversity of MTBC strains in this West African country.This cross-sectional prospective study included 100 consecutive TB patients with positive acid-fast smears at two months of anti-tuberculosis treatment or in a re-treatment situation, between May and December 2012. Resistance to rifampicin was detected using the GeneXpert system and the Xpert MTB/RIF assay. MTBC isolates obtained with the BACTEC MGIT 960 system were tested for susceptibility to first- and second-line anti-tuberculosis drugs. Overall, the prevalence of multidrug-resistant tuberculosis (MDR-TB was found to be 9 cases. Of these, 67% (6 patients of confirmed MDR-TB cases had no past history of TB treatment and 33% (3 patients were previously treated cases. Extensively drug-resistant TB was not found. Molecular typing of the MDR-TB strains revealed recent transmission patterns of imported MDR strains.The Xpert MTB/RIF assay was reliable for the detection of rifampicin resistant MTBC strains directly from sputum samples of patients undergoing first-line treatment for two months, being more trustworthy than the simple presence of acid-fast bacilli in the smear. Its implementation is technically simple, does not require specialized laboratory infrastructures and is suitable for resource-limited settings when a regular source of electricity and maintenance is available as well as financial and operation sustainability is guaranteed by the health authorities. A high prevalence of MDR-TB among patients at risk of MDR-TB after two months of first-line treatment was found, in support of the WHO

  1. Polybrominated diphenyl ethers (PBDEs) in herbaceous Centaurium erythraea affected by various sources of environmental pollution.

    Science.gov (United States)

    Brudzińska-Kosior, Anna; Kosior, Grzegorz; Klánová, Jana; Vaňková, Lenka; Kukučka, Petr; Chropeňová, Mária; Samecka-Cymerman, Aleksandra; Kolon, Krzysztof; Mróz, Lucyna; Kempers, Alexander J

    2015-01-01

    Polybrominated diphenyl ethers (PBDEs) are persistent xenobiotics with harmful effects on humans and wildlife. Their levels in the environment and accumulation in biota must be carefully controlled especially in species harvested from wild populations and commonly used as medicines. Our objective has been to determine PBDE concentrations (BDEs 28, 47, 66, 85, 99, 100, 153, 154, 183 and 209) in Centaurium erythraea collected at sites with various levels of environmental pollution. PBDE congener profiles in C. erythraea were dominated by BDE209, which accounted for 47-89% of the total PBDE burden in the plants. Principal Component and Classification Analysis, which classifies the concentration of PBDEs in C. erythraea, allowed us to distinguish the pattern of these compounds characteristic for the origin of pollution: BDEs 28, 47, 66, 85, 99, 100 for lignite and general chemical industry and the vicinity of an expressway and BDEs 183 and 209 for a thermal power plant and ferrochrome smelting industry. Careful selection of sites with C. erythraea for medicinal purposes is necessary as this herb can accumulate PBDEs while growing at polluted sites.

  2. Mycobacterial genomic DNA from used Xpert MTB/RIF cartridges can be utilised for accurate second-line genotypic drug susceptibility testing and spoligotyping.

    Science.gov (United States)

    Venter, Rouxjeane; Derendinger, Brigitta; de Vos, Margaretha; Pillay, Samantha; Dolby, Tanya; Simpson, John; Kitchin, Natasha; Ruiters, Ashley; van Helden, Paul D; Warren, Robin M; Theron, Grant

    2017-11-01

    Xpert MTB/RIF (Xpert) is a widely-used test for tuberculosis (TB) and rifampicin-resistance. Second-line drug susceptibility testing (DST), which is recommended by policymakers, typically requires additional specimen collection that delays effective treatment initiation. We examined whether cartridge extract (CE) from used Xpert TB-positive cartridges was, without downstream DNA extraction or purification, suitable for both genotypic DST (MTBDRplus, MTBDRsl), which may permit patients to rapidly receive a XDR-TB diagnosis from a single specimen, and spoligotyping, which could facilitate routine genotyping. To determine the limit-of-detection and diagnostic accuracy, CEs from dilution series of drug-susceptible and -resistant bacilli were tested (MTBDRplus, MTBDRsl). Xpert TB-positive patient sputa CEs (n = 85) were tested (56 Xpert-rifampicin-susceptible, MTBDRplus and MTBDRsl; 29 Xpert-rifampicin-resistant, MTBDRsl). Spoligotyping was done on CEs from dilution series and patient sputa (n = 10). MTBDRplus had high non-valid result rates. MTBDRsl on CEs from dilutions ≥10 3 CFU/ml (C T  ≤ 24, >"low" Xpert semiquantitation category) was accurate, had low indeterminate rates and, on CE from sputa, highly concordant with MTBDRsl isolate results. CE spoligotyping results from dilutions ≥10 3 CFU/ml and sputa were correct. MTBDRsl and spoligotyping on CE are thus highly feasible. These findings reduce the need for additional specimen collection and culture, for which capacity is limited in high-burden countries, and have implications for diagnostic laboratories and TB molecular epidemiology.

  3. 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.

  4. 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.

  5. Identification and characterization of a new erythromycin biosynthetic gene cluster in Actinopolyspora erythraea YIM90600, a novel erythronolide-producing halophilic actinomycete isolated from salt field.

    Directory of Open Access Journals (Sweden)

    Dandan Chen

    Full Text Available Erythromycins (Ers are clinically potent macrolide antibiotics in treating pathogenic bacterial infections. Microorganisms capable of producing Ers, represented by Saccharopolyspora erythraea, are mainly soil-dwelling actinomycetes. So far, Actinopolyspora erythraea YIM90600, a halophilic actinomycete isolated from Baicheng salt field, is the only known Er-producing extremophile. In this study, we have reported the draft genome sequence of Ac. erythraea YIM90600, genome mining of which has revealed a new Er biosynthetic gene cluster encoding several novel Er metabolites. This Er gene cluster shares high identity and similarity with the one of Sa. erythraea NRRL2338, except for two absent genes, eryBI and eryG. By correlating genotype and chemotype, the biosynthetic pathways of 3'-demethyl-erythromycin C, erythronolide H (EH and erythronolide I have been proposed. The formation of EH is supposed to be sequentially biosynthesized via C-6/C-18 epoxidation and C-14 hydroxylation from 6-deoxyerythronolide B. Although an in vitro enzymatic activity assay has provided limited evidence for the involvement of the cytochrome P450 oxidase EryFAc (derived from Ac. erythraea YIM90600 in the catalysis of a two-step oxidation, resulting in an epoxy moiety, the attempt to construct an EH-producing Sa. erythraea mutant via gene complementation was not successful. Characterization of EryKAc (derived from Ac. erythraea YIM90600 in vitro has confirmed its unique role as a C-12 hydroxylase, rather than a C-14 hydroxylase of the erythronolide. Genomic characterization of the halophile Ac. erythraea YIM90600 will assist us to explore the great potential of extremophiles, and promote the understanding of EH formation, which will shed new insights into the biosynthesis of Er metabolites.

  6. 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

    2018-04-17

    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.

  7. Implementation of Xpert MTB/RIF for routine point-of-care diagnosis ...

    African Journals Online (AJOL)

    tuberculosis and rifampicin resistance. However, little is known about routine ... some patients did not receive same-day results. Loss to follow-up was an unforeseen challenge, overcome by clinic flow changes, marking of clinic files, documenting patients' physical description and locating patients in the clinic by cell phone.

  8. Shared Savings Program ACO Provider-level RIF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare (CM) has created a set of standard analytical files that contain Shared Savings Program Accountable Care Organizations. Provider-level RIF...

  9. 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.

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

    African Journals Online (AJOL)

    mobility shift was visible (lane 7, Rg. 2). This resutt indicated that ~ is possible to detect rpoB gene mutations by the. SSCP procedure directly from cultures in BACTEC medium. ~er a relatively short culture period. Direct detection of mutations from sputum samples. Four ZN-positive sputum samples were used. Templates for.

  11. Cultivation of Staphylococcus epidermidis in the Human Spaceflight Environment Leads to Alterations in the Frequency and Spectrum of Spontaneous Rifampicin-Resistance Mutations in the rpoB Gene.

    Science.gov (United States)

    Fajardo-Cavazos, Patricia; Nicholson, Wayne L

    2016-01-01

    Bacteria of the genus Staphylococcus are persistent inhabitants of human spaceflight habitats and represent potential opportunistic pathogens. The effect of the human spaceflight environment on the growth and the frequency of mutations to antibiotic resistance in the model organism Staphylococcus epidermidis strain ATCC12228 was investigated. Six cultures of the test organism were cultivated in biological research in canisters-Petri dish fixation units for 122 h on orbit in the International Space Station (ISS) as part of the SpaceX-3 resupply mission. Asynchronous ground controls (GCs) consisted of identical sets of cultures cultivated for 122 h in the ISS Environmental Simulator at Kennedy Space Center. S. epidermidis exhibited significantly lower viable counts but significantly higher frequencies of mutation to rifampicin (Rif) resistance in space vs. GC cultures. The spectrum of mutations in the rpoB gene leading to Rif(R) was altered in S. epidermidis isolates cultivated in the ISS compared to GCs. The results suggest that the human spaceflight environment induces unique physiologic stresses on growing bacterial cells leading to changes in mutagenic potential.

  12. 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

  13. 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

  14. Schedule Optimization Study, Hanford RI/FS Program

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-01

    A Schedule Optimization Study (SOS) of the US Department of Energy (DOE) Hanford Site Remedial Investigation/Feasibility Study (RI/FS) Program was conducted by an independent team of professionals from other federal agencies and the private sector experienced in environmental restoration. This team spent two weeks at Hanford in September 1992 examining the reasons for the lengthy RI/FS process at Hanford and developing recommendations to expedite the process. The need for the study arose out of a schedule dispute regarding the submission of the 1100-EM-1 Operable Unit RI/FS Work Plan. This report documents the study called for in the August 29, 1991, Dispute Resolution Committee Decision Statement. Battelle's Environmental Management Operations (EMO) coordinated the effort for DOE's Richland Field Office (RL).

  15. 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.

  16. Use of XpertMTB/RIF for Mycobacterium tuberculosis identification

    Directory of Open Access Journals (Sweden)

    Roberto Deg'Innocenti

    2014-12-01

    Full Text Available In this study we describe the use of Xpert MTB/RIF to give a rapid answer in case of strong clinical suspicion of tuberculosis and/or positive microscopy slide, from sample or culture, for auramine-rhodamine stain.

  17. Functional diversification of yeast telomere associated protein, Rif1, in higher eukaryotes

    Directory of Open Access Journals (Sweden)

    Sreesankar Easwaran

    2012-06-01

    Full Text Available Abstract Background Telomeres are nucleoprotein complexes at the end of linear eukaryotic chromosomes which maintain the genome integrity by regulating telomere length, preventing recombination and end to end fusion events. Multiple proteins associate with telomeres and function in concert to carry out these functions. Rap1 interacting factor 1 (Rif1, was identified as a protein involved in telomere length regulation in yeast. Rif1 is conserved upto mammals but its function has diversified from telomere length regulation to maintenance of genome integrity. Results We have carried out detailed bioinformatic analyses and identified Rif1 homologues in 92 organisms from yeast to human. We identified Rif1 homologues in Drosophila melanogaster, even though fly telomeres are maintained by a telomerase independent pathway. Our analysis shows that Drosophila Rif1 (dRif1 sequence is phylogenetically closer to the one of vertebrates than yeast and has identified a few Rif1 specific motifs conserved through evolution. This includes a Rif1 family specific conserved region within the HEAT repeat domain and a motif involved in protein phosphatase1 docking. We show that dRif1 is nuclear localized with a prominent heterochromatin association and unlike human Rif1, it does not respond to DNA damage by localizing to damaged sites. To test the evolutionary conservation of dRif1 function, we expressed the dRif1 protein in yeast and HeLa cells. In yeast, dRif1 did not perturb yeast Rif1 (yRif1 functions; and in HeLa cells it did not colocalize with DNA damage foci. Conclusions Telomeres are maintained by retrotransposons in all Drosophila species and consequently, telomerase and many of the telomere associated protein homologues are absent, including Rap1, which is the binding partner of Rif1. We found that a homologue of yRif1 protein is present in fly and dRif1 has evolutionarily conserved motifs. Functional studies show that dRif1 responds differently to DNA

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Centaurium erythraea methanol extract protects red blood cells from oxidative damage in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Đorđević, Miloš; Mihailović, Mirjana; Arambašić Jovanović, Jelena; Grdović, Nevena; Uskoković, Aleksandra; Tolić, Anja; Sinadinović, Marija; Rajić, Jovana; Mišić, Danijela; Šiler, Branislav; Poznanović, Goran; Vidaković, Melita; Dinić, Svetlana

    2017-04-18

    Centaurium erythraea Rafn (CE) is a traditional medicinal herb in Serbia with antidiabetic, digestive, antipyretic and antiflatulent effects AIM OF THE STUDY: To investigate the potential protective effects of the methanol extract of the aerial parts of CE against glyco-oxidative stress in red blood cells (RBCs) in rats with experimentally induced diabetes. Diabetes was induced in Wistar rats by intraperitoneal (i.p.) injection of multiple low-dose streptozotocin (STZ) (40mg/kg, for five consecutive days), with the 1st day after the last STZ injection taken as the day of diabetes onset. The methanol extract of CE (100mg/kg) was administered orally and daily, two weeks before the first STZ injection, during the 5-day treatment with STZ, and for four weeks after the STZ injections (pre-treated group) or for four weeks after diabetes onset (post-treated group). The effect of CE extract administration on the redox status of RBCs was evaluated by assessing lipid peroxidation, the ratio of reduced/oxidized glutathione (GSH/GSSG), the level of S-glutathionylated proteins (GSSP) and the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in RBCs four weeks after diabetes onset. The major biochemical parameters of diabetes, protein glycation/glycosylation of erythrocytes and parameters which correlate with their aggregation and deformability were also evaluated. Daily application of CE extract to STZ-induced diabetic rats provided important antidiabetic effects, observed in both pre-treated and post-treated groups of diabetic rats as elevated serum insulin concentration, reduction of blood glucose and glycated hemoglobin concentrations and an improved lipid profile. Antioxidant effects of CE extract were detected in RBCs of diabetic rats and observed as decreased lipid peroxidation and ameliorated oxidative damage as a result of increased SOD, CAT and GR activities, an improved GSH/GSSG ratio and

  3. Delays and loss to follow-up before treatment of drug-resistant tuberculosis following implementation of Xpert MTB/RIF in South Africa: A retrospective cohort study.

    Directory of Open Access Journals (Sweden)

    Helen Cox

    2017-02-01

    Full Text Available South Africa has a large burden of rifampicin-resistant tuberculosis (RR-TB, with 18,734 patients diagnosed in 2014. The number of diagnosed patients has increased substantially with the introduction of the Xpert MTB/RIF test, used for tuberculosis (TB diagnosis for all patients with presumptive TB. Routine aggregate data suggest a large treatment gap (pre-treatment loss to follow-up between the numbers of patients with laboratory-confirmed RR-TB and those reported to have started second-line treatment. We aimed to assess the impact of Xpert MTB/RIF implementation on the delay to treatment initiation and loss to follow-up before second-line treatment for RR-TB across South Africa.A nationwide retrospective cohort study was conducted to assess second-line treatment initiation and treatment delay among laboratory-diagnosed RR-TB patients. Cohorts, including approximately 300 sequentially diagnosed RR-TB patients per South African province, were drawn from the years 2011 and 2013, i.e., before and after Xpert implementation. Patients with prior laboratory RR-TB diagnoses within 6 mo and currently treated patients were excluded. Treatment initiation was determined through data linkage with national and local treatment registers, medical record review, interviews with health care staff, and direct contact with patients or household members. Additional laboratory data were used to track cases. National estimates of the percentage of patients who initiated treatment and time to treatment were weighted to account for the sampling design. There were 2,508 and 2,528 eligible patients in the 2011 and 2013 cohorts, respectively; 92% were newly diagnosed with RR-TB (no prior RR-TB diagnoses. Nationally, among the 2,340 and 2,311 new RR-TB patients in the 2011 and 2013 cohorts, 55% (95% CI 53%-57% and 63% (95% CI 61%-65%, respectively, started treatment within 6 mo of laboratory receipt of their diagnostic specimen (p < 0.001. However, in 2013, there was no

  4. Rif1 regulates initiation timing of late replication origins throughout the S. cerevisiae genome.

    Directory of Open Access Journals (Sweden)

    Jared M Peace

    Full Text Available Chromosomal DNA replication involves the coordinated activity of hundreds to thousands of replication origins. Individual replication origins are subject to epigenetic regulation of their activity during S-phase, resulting in differential efficiencies and timings of replication initiation during S-phase. This regulation is thought to involve chromatin structure and organization into timing domains with differential ability to recruit limiting replication factors. Rif1 has recently been identified as a genome-wide regulator of replication timing in fission yeast and in mammalian cells. However, previous studies in budding yeast have suggested that Rif1's role in controlling replication timing may be limited to subtelomeric domains and derives from its established role in telomere length regulation. We have analyzed replication timing by analyzing BrdU incorporation genome-wide, and report that Rif1 regulates the timing of late/dormant replication origins throughout the S. cerevisiae genome. Analysis of pfa4Δ cells, which are defective in palmitoylation and membrane association of Rif1, suggests that replication timing regulation by Rif1 is independent of its role in localizing telomeres to the nuclear periphery. Intra-S checkpoint signaling is intact in rif1Δ cells, and checkpoint-defective mec1Δ cells do not comparably deregulate replication timing, together indicating that Rif1 regulates replication timing through a mechanism independent of this checkpoint. Our results indicate that the Rif1 mechanism regulates origin timing irrespective of proximity to a chromosome end, and suggest instead that telomere sequences merely provide abundant binding sites for proteins that recruit Rif1. Still, the abundance of Rif1 binding in telomeric domains may facilitate Rif1-mediated repression of non-telomeric origins that are more distal from centromeres.

  5. 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

  6. 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.

  7. Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program.

    Science.gov (United States)

    Foti, Rossana; Gnan, Stefano; Cornacchia, Daniela; Dileep, Vishnu; Bulut-Karslioglu, Aydan; Diehl, Sarah; Buness, Andreas; Klein, Felix A; Huber, Wolfgang; Johnstone, Ewan; Loos, Remco; Bertone, Paul; Gilbert, David M; Manke, Thomas; Jenuwein, Thomas; Buonomo, Sara C B

    2016-01-21

    DNA replication is temporally and spatially organized in all eukaryotes, yet the molecular control and biological function of the replication-timing program are unclear. Rif1 is required for normal genome-wide regulation of replication timing, but its molecular function is poorly understood. Here we show that in mouse embryonic stem cells, Rif1 coats late-replicating domains and, with Lamin B1, identifies most of the late-replicating genome. Rif1 is an essential determinant of replication timing of non-Lamin B1-bound late domains. We further demonstrate that Rif1 defines and restricts the interactions between replication-timing domains during the G1 phase, thereby revealing a function of Rif1 as organizer of nuclear architecture. Rif1 loss affects both number and replication-timing specificity of the interactions between replication-timing domains. In addition, during the S phase, Rif1 ensures that replication of interacting domains is temporally coordinated. In summary, our study identifies Rif1 as the molecular link between nuclear architecture and replication-timing establishment in mammals. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. 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

  9. The Pedagogy of Riffing: Cultivating Meta-Awareness and Citizenship through Metacommentary

    Science.gov (United States)

    Miller, Daisy S.

    2016-01-01

    This article proposes a "pedagogy of riffing" and examines how satire and some earlier forms of metacommentary can help first-year composition students appreciate the mediated nature of contemporary current-events discourse. Beginning with comic news and working back to those pioneers of cultural riffing, "Mystery Science Theater…

  10. Da Serra de Tavira ao Rif marroquino: analogias e mitos

    OpenAIRE

    Campaniço, Carlos

    2007-01-01

    Dissertação de mest., Cultura Árabe e Islâmica e o Mediterrâneo, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2007 O presente trabalho teve como objectivo estudar a Organização do Espaço Rural na Serra de Tavira e no Rif Ocidental e confrontar as análises efectuadas, para aquilatar das suas semelhanças. O estudo da Organização do Espaço Rural, de ambos os espaços, foi conduzido por um estudo comparativo de caso entre dois pequenos povoados de montanhas, Alcaria do Cume...

  11. Estudio floristico del Rif occidental calizo (N. de Marruecos)

    OpenAIRE

    Mateos Cordero, Marco Antonio

    2003-01-01

    Se ha realizado un estudio Florístico del Rif Occidental Calizo, situado en la provincia de Chefchaouen, en Marruecos. El área de estudio posee una superficie de 70.000 ha. Y está limitada al N por el mar Mediterráneo, al W por el río Laou, el E por el río Bouhya y al S por los cursos altos de ambos ríos, salvando de valle de Ametras por la curva de nivel de los 900m. El grandiente altitudinal en la zona es grande, 2159 m. Estando presentes en la misma una diversidad de sustratos bastante imp...

  12. 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.

  13. 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 ...

  14. Analisis Tindak Tutur Direktif dalam Novel Amazing Genius Karya Komikus Rif'an

    OpenAIRE

    Butar Butar, God Friend Immanuel

    2017-01-01

    Email: Abstract The purpose of this research are to describe and analysis types and functions of directive utterances in Amazing Genius novel by Komikus Rif'an. This research use descriptive method and the type of this research is qualitative research. The results of description and analysis conversation between speaker and listeners in Amazing Genius novel by Komikus Rif'an are: 1) The requestive functions of directive utterances are to ask, to supplicate, to pray, and...

  15. Rif1: a conserved regulator of DNA replication and repair hijacked by telomeres in yeasts

    Directory of Open Access Journals (Sweden)

    Stefano eMattarocci

    2016-03-01

    Full Text Available Rif1 was originally identified in the budding yeast S. cerevisiae as a telomere-binding protein that negatively regulates telomerase-mediated telomere elongation. Although this function is conserved in the distantly related fission yeast S. pombe, recent studies, both in yeasts and in metazoans, reveal that Rif1 also functions more globally, both in the temporal control of DNA replication and in DNA repair. Rif1 proteins are large and characterized by N-terminal HEAT repeats, predicted to form an elongated alpha-helical structure. In addition, all Rif1 homologues contain two short motifs, abbreviated RVxF/SILK, that are implicated in recruitment of the PP1 (yeast Glc7 phosphatase. In yeasts the RVxF/SILK domains have been shown to play a role in control of DNA replication initiation, at least in part through targeted de-phosphorylation of proteins in the pre-Replication Complex. In human cells Rif1 is recruited to DNA double-strand breaks through an interaction with 53BP1 where it counteracts DNA resection, thus promoting repair by non-homologous end-joining. This function requires the N-terminal HEAT repeat-containing domain. Interestingly, this domain is also implicated in DNA end protection at un-capped telomeres in yeast. We conclude by discussing the deployment of Rif1 at telomeres in yeasts from both an evolutionary perspective and in light of its recently discovered global functions.

  16. Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation.

    Science.gov (United States)

    Menzies, Nicolas A; Cohen, Ted; Lin, Hsien-Ho; Murray, Megan; Salomon, Joshua A

    2012-01-01

    The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. We evaluated potential health and economic consequences of implementing Xpert in five southern African countries--Botswana, Lesotho, Namibia, South Africa, and Swaziland--where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000-284,000) TB cases and 182,000 (97,000-302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%-40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294-699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633-1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482-1,785) in Swaziland to US$1,257 (767-2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert

  17. Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation.

    Directory of Open Access Journals (Sweden)

    Nicolas A Menzies

    Full Text Available The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert.We evaluated potential health and economic consequences of implementing Xpert in five southern African countries--Botswana, Lesotho, Namibia, South Africa, and Swaziland--where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000-284,000 TB cases and 182,000 (97,000-302,000 TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%-40% by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294-699 million over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633-1,485 per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482-1,785 in Swaziland to US$1,257 (767-2,276 in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences

  18. Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial.

    Directory of Open Access Journals (Sweden)

    Helen S Cox

    2014-11-01

    Full Text Available Xpert MTB/RIF is approved for use in tuberculosis (TB and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden.A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982 and routine (n = 1,003 diagnostic algorithms (ITT analysis; 882 received Xpert and 1,063 routine (per protocol analysis. 13% (32/257 of individuals with bacteriologically confirmed TB (smear, culture, or Xpert did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167 in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33-0.77, p = 0.0052. The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003 with routine diagnosis and 26% (257/982 with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32-1.87, p<0.001. This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003 and 28% (277/982 in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06-1.44, p = 0.013. Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63-0.92, p = 0.005 and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53-0.85, p = 0

  19. Results of Xpert®MTB/RIF implementation in Kyrgyzstan.

    Science.gov (United States)

    Kurbaniyazova, G; Joncevska, M; Kalon, S; Kalmambetova, G; Mohr, T; Toktogonova, A; Takieva, K; Islam, K M Monirul; Luelmo, F

    2017-03-01

    In July 2012, the United States Agency for International Development (USAID) Quality Health Care Project introduced the Xpert® MTB/RIF assay at the facility level of the primary health care system in Kyrgyzstan. This study analysed the results of the implementation of Xpert. Test results from 2734 patients from July 2012 to December 2014 were analysed. The sensitivity and specificity of Xpert in routine programme conditions were evaluated using culture and phenotypic drug susceptibility testing (DST) as gold standard. Contribution to early start of treatment for multidrug-resistant tuberculosis (MDR-TB) was expressed as the median time between availability of the test result and start of treatment. Compared to culture, the sensitivity and specificity of Xpert were respectively 92.7% and 90.4%. For the detection of rifampicin (RMP) resistance, Xpert sensitivity and specificity were respectively 90.1% and 90.7%. The median time to initiation of MDR-TB treatment decreased to 10 days (interquartile range [IQR] 6-16) in 2014 from 20 days (IQR 12-40, P < 0.001) in 2013. The Xpert assay demonstrated good agreement in the detection of both Mycobacterium tuberculosis and RMP-resistant pulmonary TB in routine clinical practice. Although Xpert improved the time to treatment initiation from 2013 to 2014, more efforts are needed to further reduce this delay.

  20. Budding Yeast Rif1 Controls Genome Integrity by Inhibiting rDNA Replication.

    Directory of Open Access Journals (Sweden)

    Maksym Shyian

    2016-11-01

    Full Text Available The Rif1 protein is a negative regulator of DNA replication initiation in eukaryotes. Here we show that budding yeast Rif1 inhibits DNA replication initiation at the rDNA locus. Absence of Rif1, or disruption of its interaction with PP1/Glc7 phosphatase, leads to more intensive rDNA replication. The effect of Rif1-Glc7 on rDNA replication is similar to that of the Sir2 deacetylase, and the two would appear to act in the same pathway, since the rif1Δ sir2Δ double mutant shows no further increase in rDNA replication. Loss of Rif1-Glc7 activity is also accompanied by an increase in rDNA repeat instability that again is not additive with the effect of sir2Δ. We find, in addition, that the viability of rif1Δ cells is severely compromised in combination with disruption of the MRX or Ctf4-Mms22 complexes, both of which are implicated in stabilization of stalled replication forks. Significantly, we show that removal of the rDNA replication fork barrier (RFB protein Fob1, alleviation of replisome pausing by deletion of the Tof1/Csm3 complex, or a large deletion of the rDNA repeat array all rescue this synthetic growth defect of rif1Δ cells lacking in addition either MRX or Ctf4-Mms22 activity. These data suggest that the repression of origin activation by Rif1-Glc7 is important to avoid the deleterious accumulation of stalled replication forks at the rDNA RFB, which become lethal when fork stability is compromised. Finally, we show that Rif1-Glc7, unlike Sir2, has an important effect on origin firing outside of the rDNA locus that serves to prevent activation of the DNA replication checkpoint. Our results thus provide insights into a mechanism of replication control within a large repetitive chromosomal domain and its importance for the maintenance of genome stability. These findings may have important implications for metazoans, where large blocks of repetitive sequences are much more common.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Hermsen Cornelus C

    2010-05-01

    Full Text Available 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 to the bloodstream. Sexual stage parasite surface proteins are of interest as candidate target antigens for transmission blocking vaccines. Methods In this study, the transcript profiles of rif and var genes, known to encode surface antigens in asexual blood stage parasites, were investigated at different stages of 3D7/NF54 gametocytogenesis and in sporozoites. Results Gametocytes exhibited a rif transcript profile unlinked to the rif and var transcript profile of the asexual progenitors. At stage V, mature gametocytes produced high levels of a single rif gene, PF13_0006, which also dominated the rif transcript profile of sporozoites. All var genes appeared to be silenced in sporozoites. Conclusions The most prominent variant surface antigen transcribed in both gametocytes and sporozoites of 3D7/NF54 is a single variant of the RIFIN protein family. This discovery may lead to the identification of the parasites binding ligands responsible for the adhesion during sexual stages and potentially to novel vaccine candidates.

  3. 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.

  4. 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.

  5. El Rif y el poder central: Una perspectiva histórica

    OpenAIRE

    Madariaga, María Rosa de

    2010-01-01

    Esta comunicación aborda la definición del término Rif desde el punto de vista histórico, geográfico y lingüistico haciendo un repaso de las diferentes definiciones que los autores han dado al término Rif para posteriormente analizar como es la relación de este territorio con el poder central siempre en tensión justificadas desde el exterior por ser el Rif un territorio marroquí o en continua rebeldía frente al sultán. La visión interna ejemplarizada en la figura de Abd- El Kri...

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

    Directory of Open Access Journals (Sweden)

    Zaiyad G. Habib

    2015-01-01

    Full Text Available 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.

  7. Schedule Optimization Study, Hanford RI/FS Program. Volume 2, Final report

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-01

    A Schedule Optimization Study (SOS) of the US Department of Energy (DOE) Hanford Site Remedial Investigation/Feasibility Study (RI/FS) Program was conducted by an independent team of professionals from other federal agencies and the private sector experienced in environmental restoration. This team spent two weeks at Hanford in September 1992 examining the reasons for the lengthy RI/FS process at Hanford and developing recommendations to expedite the process. The need for the study arose out of a schedule dispute regarding the submission of the 1100-EM-1 Operable Unit RI/FS Work Plan. This report documents the study called for in the August 29, 1991, Dispute Resolution Committee Decision Statement. Battelle`s Environmental Management Operations (EMO) coordinated the effort for DOE`s Richland Field Office (RL).

  8. A Multisite Assessment of the Quantitative Capabilities of the Xpert MTB/RIF Assay

    Science.gov (United States)

    Blakemore, Robert; Nabeta, Pamela; Davidow, Amy L.; Vadwai, Viral; Tahirli, Rasim; Munsamy, Vanisha; Nicol, Mark; Jones, Martin; Persing, David H.; Hillemann, Doris; Ruesch-Gerdes, Sabine; Leisegang, Felicity; Zamudio, Carlos; Rodrigues, Camilla; Boehme, Catharina C.; Perkins, Mark D.

    2011-01-01

    Rationale: The Xpert MTB/RIF is an automated molecular test for Mycobacterium tuberculosis that estimates bacterial burden by measuring the threshold-cycle (Ct) of its M. tuberculosis–specific real-time polymerase chain reaction. Bacterial burden is an important biomarker for disease severity, infection control risk, and response to therapy. Objectives: Evaluate bacterial load quantitation by Xpert MTB/RIF compared with conventional quantitative methods. Methods: Xpert MTB/RIF results were compared with smear-microscopy, semiquantiative solid culture, and time-to-detection in liquid culture for 741 patients and 2,008 samples tested in a multisite clinical trial. An internal control real-time polymerase chain reaction was evaluated for its ability to identify inaccurate quantitative Xpert MTB/RIF results. Measurements and Main Results: Assays with an internal control Ct greater than 34 were likely to be inaccurately quantitated; this represented 15% of M. tuberculosis–positive tests. Excluding these, decreasing M. tuberculosis Ct was associated with increasing smear microscopy grade for smears of concentrated sputum pellets (rs = −0.77) and directly from sputum (rs = −0.71). A Ct cutoff of approximately 27.7 best predicted smear-positive status. The association between M. tuberculosis Ct and time-to-detection in liquid culture (rs = 0.68) and semiquantitative colony counts (rs = −0.56) was weaker than smear. Tests of paired same-patient sputum showed that high-viscosity sputum samples contained ×32 more M. tuberculosis than nonviscous samples. Comparisons between the grade of the acid-fast bacilli smear and Xpert MTB/RIF quantitative data across study sites enabled us to identify a site outlier in microscopy. Conclusions: Xpert MTB/RIF quantitation offers a new, standardized approach to measuring bacterial burden in the sputum of patients with tuberculosis. PMID:21836139

  9. Memory as Protest. Mediating Memories of Violence and Bread Revolts in the Rif

    NARCIS (Netherlands)

    Karrouche, N.F.F.

    2017-01-01

    This chapter discusses the mediated circulation of local memories of war and violence in the Rif region of Morocco. Karrouche focuses on how what she calls ‘mediating memories’ shape the identities and agency of several generations of Berber activists in both Morocco and its diaspora. She focuses on

  10. 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

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

    Science.gov (United States)

    Ghariani, Asma; Jaouadi, Taha; Smaoui, Selma; Mehiri, Emna; Marouane, Chama; Kammoun, Sana; Essalah, Leila; Driss, Maha; Messadi, Feriele; Slim-Saidi, Leila

    2015-12-01

    GeneXpert MTB/RIF is a fully-automated diagnostic molecular test which simultaneously detects tuberculosis (TB) and rifampicin (RIF) drug resistance. The purpose of this study is to evaluate the performance of the GeneXpert MTB/RIF test for the detection of Mycobacterium tuberculosis complex (MTBC) in lymph node specimens and to show the place of Mycobacterium bovis as a major cause of TB lymphadenitis. This study was conducted simultaneously in the National Reference Laboratory for Mycobacteria of Ariana and the Central Laboratory of Sfax, from January to December 2013. In total, 174 lymph node specimens were processed simultaneously for Ziehl-Neelsen, auramine and immuno-histochemical staining. Conventional culture on both Lowenstein-Jensen and liquid medium (Bactec MGIT 960 BD system) and the new molecular-based GeneXpert MTB/RIF assay system were performed. Positive cultures were confirmed using molecular identification (Genotype MTBC Hain Lifescience). Among the 174 samples tested, the GeneXpert detected the DNA of MTBC in 134 samples (77%). Standard bacteriological assays, including AFB microscopy and culture, were positive, respectively, in 41 (23.6%) and 79 (45.4%) specimens. M. bovis was isolated in 76% of positive cultures. GeneXpert sensitivity and specificity results were assessed according to smear and culture results, clinical and histological findings. The sensitivity and specificity of the Xpert assay were 87.5% (126/144) and 73.3%, respectively. The implementation of the GeneXpert MTB/RIF assay may dramatically improve the rapid diagnosis of lymph node TB. Copyright © 2015 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

  12. Limited value of whole blood Xpert(®) MTB/RIF for diagnosing tuberculosis in children.

    Science.gov (United States)

    Pohl, Christian; Rutaihwa, Liliana K; Haraka, Frederick; Nsubuga, Martin; Aloi, Francesco; Ntinginya, Nyanda E; Mapamba, Daniel; Heinrich, Norbert; Hoelscher, Michael; Marais, Ben J; Jugheli, Levan; Reither, Klaus

    2016-10-01

    We evaluated the ability of the Xpert(®) MTB/RIF assay to detect Mycobacterium tuberculosis in whole blood of children with tuberculosis in tuberculosis endemic settings with high rates of HIV infection. From June 2011 to September 2012 we prospectively enrolled children with symptoms or signs suggestive of tuberculosis at three research centres in Tanzania and Uganda. After clinical assessment, respiratory specimens were collected for microscopy and culture, as well as whole blood for Xpert(®) MTB/RIF. Children were classified according to standardised case definitions. A total of 232 children were evaluated; 14 (6.0%) had culture-confirmed tuberculosis. The Xpert(®) MTB/RIF assay detected M. tuberculosis in 5/232 (2.2%) blood samples with 1 (0.4%) error reading and presumably 1 (0.4%) false-positive result. The sensitivity of the assay in children with culture-confirmed (1/14) versus no tuberculosis (1/117) was 7.1% (95% CI, 1.3-31.5). Three of the five Xpert(®) MTB/RIF positive patients had negative cultures, but were classified as probable tuberculosis cases. Assay sensitivity against a composite reference standard (culture-confirmed, highly probable or probable tuberculosis) was 5.4% (95% CI, 2.1-13.1). Whole blood Xpert(®) MTB/RIF demonstrated very poor sensitivity, although it may enhance the diagnostic yield in select cases, with culture-negative tuberculosis. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  13. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa

    OpenAIRE

    Lebina, Limakatso; Fuller, Nigel; Osoba, Tolu; Scott, Lesley; Motlhaoleng, Katlego; Rakgokong, Modiehi; Abraham, Pattamukkil; Variava, Ebrahim; Martinson, Neil Alexander

    2016-01-01

    Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household cont...

  14. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Reinartz, S.D.; Diefenbach, B.S.; Kuhl, C.K.; Mahnken, A.H. [University Hospital, RWTH Aachen University, Department of Diagnostic and Interventional Radiology, Aachen (Germany); Allmendinger, T. [Siemens Healthcare Sector, Department of Computed Tomography, Forchheim (Germany)

    2012-12-15

    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.)

  16. 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.

  17. 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.

  18. Performance of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis and rifampin resistance in a low-incidence, high-resource setting.

    Directory of Open Access Journals (Sweden)

    Jason P Rice

    Full Text Available Performance of the Xpert MTB/RIF assay, designed to simultaneously detect Mycobacterium tuberculosis complex (MTBC and rifampin (RIF resistance, has been well documented in low-resource settings with high TB-incidence. However, few studies have assessed its accuracy in low TB incidence settings. We evaluated the performance of Xpert MTB/RIF using clinical sputum specimens routinely collected from suspect pulmonary TB patients over a 4-year time period in San Diego County, California. Xpert MTB/RIF results were compared to acid-fast bacilli (AFB smear microscopy, mycobacterial culture, and phenotypic drug susceptibility testing (DST. Of 751 sputum specimens, 134 (17.8% were MTBC culture-positive and 2 (1.5% were multidrug-resistant (MDR. For the detection of MTBC, Xpert MTB/RIF sensitivity was 89.6% (97.7% and 74.5% in smear-positive and -negative sputa, respectively and specificity was 97.2%; while AFB smear sensitivity and specificity were 64.9% and 77.8%, respectively. Xpert MTB/RIF detected 35 of 47 smear-negative culture-positive specimens, and excluded 124 of 137 smear-positive culture-negative specimens. Xpert MTB/RIF also correctly excluded 99.2% (121/122 of nontuberculous mycobacteria (NTM specimens, including all 33 NTM false-positives by smear microscopy. For the detection of RIF resistance, Xpert MTB/RIF sensitivity and specificity were 100% and 98.3%, respectively. Our findings demonstrate that Xpert MTB/RIF is able to accurately detect MTBC and RIF resistance in routinely collected respiratory specimens in a low TB-incidence setting, with comparable performance to that achieved in high-incidence settings; and suggest that under these conditions the assay has particular utility in detecting smear-negative TB cases, excluding smear-positive patients without MTBC disease, and differentiating MTBC from NTM.

  19. Subtelomeric repetitive elements determine TERRA regulation by Rap1/Rif and Rap1/Sir complexes in yeast

    Science.gov (United States)

    Iglesias, Nahid; Redon, Sophie; Pfeiffer, Verena; Dees, Martina; Lingner, Joachim; Luke, Brian

    2011-01-01

    Telomeric repeat-containing RNA (TERRA) has been implicated in the control of heterochromatin and telomerase. We demonstrate that yeast TERRA is regulated by telomere-binding proteins in a chromosome-end-specific manner that is dependent on subtelomeric repetitive DNA elements. At telomeres that contain only X-elements, the Rap1 carboxy-terminal domain recruits the Sir2/3/4 and Rif1/2 complexes to repress transcription in addition to promoting Rat1-nuclease-dependent TERRA degradation. At telomeres that contain Y′ elements, however, Rap1 represses TERRA through recruitment of Rif1 and Rif2. Our work emphasizes the importance of subtelomeric DNA in the control of telomeric protein composition and telomere transcription. PMID:21525956

  20. Systematic review: Comparison of Xpert MTB/RIF, LAMP and SAT methods for the diagnosis of pulmonary tuberculosis.

    Science.gov (United States)

    Yan, Liping; Xiao, Heping; Zhang, Qing

    2016-01-01

    Technological advances in nucleic acid amplification have led to breakthroughs in the early detection of PTB compared to traditional sputum smear tests. The sensitivity and specificity of loop-mediated isothermal amplification (LAMP), simultaneous amplification testing (SAT), and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis were evaluated. A critical review of previous studies of LAMP, SAT, and Xpert MTB/RIF for the diagnosis of pulmonary tuberculosis that used laboratory culturing as the reference method was carried out together with a meta-analysis. In 25 previous studies, the pooled sensitivity and specificity of the diagnosis of tuberculosis were 93% and 94% for LAMP, 96% and 88% for SAT, and 89% and 98% for Xpert MTB/RIF. The I(2) values for the pooled data were >80%, indicating significant heterogeneity. In the smear-positive subgroup analysis of LAMP, the sensitivity increased from 93% to 98% (I(2) = 2.6%), and specificity was 68% (I(2) = 38.4%). In the HIV-infected subgroup analysis of Xpert MTB/RIF, the pooled sensitivity and specificity were 79% (I(2) = 72.9%) and 99% (I(2) = 64.4%). In the HIV-negative subgroup analysis for Xpert MTB/RIF, the pooled sensitivity and specificity were 72% (I(2) = 49.6%) and 99% (I(2) = 64.5%). LAMP, SAT and Xpert MTB/RIF had comparably high levels of sensitivity and specificity for the diagnosis of tuberculosis. The diagnostic sensitivity and specificity of three methods were similar, with LAMP being highly sensitive for the diagnosis of smear-positive PTB. The cost effectiveness of LAMP and SAT make them particularly suitable tests for diagnosing PTB in developing countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Estudo fitoquímico de Erythraea centaurium, Jacaranda caroba, Remijia ferruginea e Solanum paniculatum visando identificar marcadores químicos para o fitoterápico Ierobina®

    Directory of Open Access Journals (Sweden)

    F.C. Braga

    Full Text Available O fitoterápico Ierobina®, comercializado no mercado nacional há 67 anos, tem uso indicado para o tratamento de dispepsias. O fitoterápico é constituído pelos extratos fluidos de três espécies nativas (Solanum paniculatum, Remijia ferruginea e Jacaranda caroba e uma exótica (Erythraea centaurium. O presente estudo descreve a identificação de marcadores químicos para os extratos das espécies constituintes da Ierobina® e a obtenção de perfis cromatográficos de referência para os mesmos, os quais contribuirão para o estabelecimento de protocolos para o controle de qualidade do fitoterápico.

  2. IR absorption and reflectometric interference spectroscopy (RIfS) combined to a new sensing approach for gas analytes absorbed into thin polymer films

    Science.gov (United States)

    Leopold, Nicolae; Busche, Stefan; Gauglitz, Günter; Lendl, Bernhard

    2009-06-01

    Hydrophobic polymer layers (3 μm) were spin-coated on Si or Ge plates and placed in a flow through gas chamber. FTIR reflection spectra of the layers were recorded showing the characteristic IR absorption bands of the polymer and the interference pattern generated by layered structure of the polymer film. Upon exposure of the polymer layer to gaseous analytes enrichment in the polymer film occurred. This was evidenced by the appearance of analyte specific absorption particular in the mid-IR part of the spectrum, as well as by a shift in the interference pattern across the whole spectrum. Qualitative information concerning the analyte was accessible in the mid-IR part of the spectrum, whereas quantitative assessment was obtained from the interference pattern. Polyetherurethane, polydimethylsiloxane, Makrolon ® and polyisobutylene polymer layers were tested for such IR-RIfS measurements, whereas toluene, o-dichlorobenzene, m-xylene, ethyl acetate and cyclohexane were employed as analytes. There was no influence of water vapour neither on the IR absorptions nor the interference pattern as hydrophobic polymers were used.

  3. 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)

  4. Pumpellyite and coexisting minerals in metapelites and veins from the Federico Units in the Internal Zone of the Rif, Spain

    Czech Academy of Sciences Publication Activity Database

    Ruiz Cruz, M. D.; Sanz de Galdeano, C.; Alvarez-Valero, A.; Novák, Jiří Karel

    2010-01-01

    Roč. 48, č. 1 (2010), s. 183-203 ISSN 0008-4476 Institutional research plan: CEZ:AV0Z30130516 Keywords : Betic-Rif Cordillera * Alpine metamorphism * Federico units * metamorphism (Marocco/Spain) Subject RIV: DB - Geology ; Mineralogy Impact factor: 1.289, year: 2010

  5. 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.

  6. The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West Province, South Africa

    Directory of Open Access Journals (Sweden)

    Limakatso Lebina

    2016-01-01

    Full Text Available Introduction. Tuberculosis is a major cause of morbidity and mortality especially in high HIV burden settings. Active case finding is one strategy to potentially reduce TB disease burden. Xpert MTB/Rif has recently been recommended for diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy and culture in household contacts of patients recently diagnosed with TB. Results. 2464 household contacts enrolled into the study from 768 active TB index cases. 1068 (44% were unable to give sputum, but 24 of these were already on TB treatment. 863 (53% participants sputum samples were tested with smear and culture and 2.7% (23/863; CI: 1.62–3.78 were diagnosed with active TB. Xpert MTB/Rif was used in 515 (21% participants; active TB was diagnosed in 1.6% (8/515; CI: 0.52–2.68. Discussion and Conclusions. Additional 31 cases were diagnosed with contact tracing of household members. When Xpert MTB/Rif is compared with culture, there is no significant difference in diagnostic yield.

  7. Deformation characterization of a regional thrust zone in the northern Rif (Chefchaouen, Morocco)

    Science.gov (United States)

    Vitale, Stefano; Zaghloul, Mohamed Najib; Tramparulo, Francesco D.'Assisi; El Ouaragli, Bilal

    2014-07-01

    This paper provides the structural analysis of the Chefchaouen area in the northern Rif. Here the Dorsale Calcaire superposes, by means of an excellently exposed thrust fault, onto the Predorsalian succession in turn tectonically covering the Massylian Unit. Hanging wall carbonates of the Dorsale Calcaire Unit form a WSW-verging regional fold with several parasitic structures, deformed by late reverse faults in places indicating an ENE vergence. A 200 m thick shear zone characterizes the upper part of the Predorsalian succession, located at footwall of the Dorsale Calcaire Unit. Here the dominantly pelitic levels are highly deformed by (i) C‧ type shear bands indicating a mean WSW tectonic transport and (ii) conjugate extensional shear planes marking an extension both orthogonal and parallel to the shear direction. The Massylian Unit is characterized by a strain gradient increasing toward the tectonic contact with the overlying Predorsalian succession, where the dominantly pelitic levels are so highly deformed so as appearing as a broken formation. Such as the previous succession, conjugate extensional shear bands and normal faults indicate a horizontal extension parallel to the thrust front synchronous with the mainly WSW-directed overthrusting. The whole thrust sheet pile recorded a further shortening, characterized by a NW-SE direction, expressed by several reverse and thrust faults and related folds. Finally strike-slip and normal faults were the last deformation structures recorded in the analyzed rocks. A possible tectonic evolution for these successions is provided. In the late Burdigalian, the Dorsale Calcaire Unit tectonically covered the Predorsalian succession and together the Massylian Unit. The latter two successions were completely detached from their basement and accreted in the orogenic wedge within a general NE-SW shortening for the analyzed sector of the northern Rif. At lithosphere scale the thrust front migration was driven by roll back and

  8. Comparison of GeneXpert MTB/RIF and conventional methods for the diagnosis of tuberculosis in Kosovo.

    Science.gov (United States)

    Bajrami, Rrezarta; Mulliqi, Gjyle; Kurti, Arsim; Lila, Greta; Raka, Lul

    2016-04-28

    Tuberculosis (TB) is a major public health problem worldwide, with the highest mortality occurring in developing countries. The burden of TB in Kosovo is among the highest in Europe. The aim of this study was to compare Cepheid GeneXpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex (MTBC) and rifampin (RIF) resistance with conventional methods. A cross-sectional design to evaluate diagnostic tests was carried out at the Department of Microbiology, National Institute of Public Health of Kosovo and Lung Clinic, from January to June 2014. The detection of MTBC and RIF resistance using the Xpert MTB/RIF assay was assessed in 116 specimens received from 110 patients suspected of having TB and compared with conventional smear microscopy and culture methods. Fifty-eight patients (52.7%) were male, and the mean age was 48.6±18.1 years. Twenty-nine patients (26.4%) had underlying lung diseases. Of the 116 specimens investigated, 28 (24.1%) were MTBC-positive by culture, while 34 (29.3%) were positive by Xpert assay. Two samples showed false-negative Xpert results. Compared with culture, the Xpert assay achieved 82.3% (95% CI: 65.5%-93.2%) sensitivity, and 97.6% (95% CI: 91.5%-99.7%) specificity. GeneXpert could detect 11.7% and 50% additional positive cases as compared to Lowenstein-Jensen culture and smear microscopy, respectively. Three cases with resistance to rifampin were detected from clinical isolates. The GeneXpert MTB/RIF assay is a helpful tool for rapid diagnosis and prompt treatment of TB.

  9. GeneXpert MTB/RIF assay as initial test for diagnosis of tuberculous meningitis

    Science.gov (United States)

    Shrestha, Poojan; Paudyal, Buddhi; Basnyat, Buddha

    2015-01-01

    Tuberculous meningitis (TBM) remains the most dangerous form of tuberculosis with high mortality and potential complications. The prompt diagnosis and treatment of this condition remains a key for better prognosis. A 39-year-old woman presented with severe headache, fever, nausea and vomiting, with a history of headache for a month. On examination, confusion, neck rigidity, ptosis and upward plantar reflexes were present. After 7 days of empiric treatment without resolution of her symptoms, she had another spinal tap performed. The diagnosis of TBM was performed by the GeneXpert MTB/RIF assay from her cerebrospinal fluid (CSF). Antitubercular chemotherapy was started. The patient subsequently improved. Where available, the GeneXpert assay should be used immediately in CSF samples of patients suspected of TBM as an adjunct to clinical algorithms to increase the chance of a prompt diagnosis and treatment. PMID:26071438

  10. La Cruz Roja en la La Guerra del Rif (1921-1926: ensayo bibliográfico

    Directory of Open Access Journals (Sweden)

    Martínez-Antonio, Francisco Javier

    2009-05-01

    Full Text Available This paper attempts at presenting the existing secondary bibliography on Red Cross initiatives during the Rif War, produced either in Spain or in the international context. This bibliography has provided a basic yet unsystematic account of the activities of the International Committee of the Red Cross, of the Spanish and French Red Cross societies, of several European and non-European Red Cross societies and of other humanitarian associations during the harsh conflict thataffected northern Morocco between 1921 and 1926.

  11. Development and validation of 'AutoRIF': Software for the automated analysis of radiation-induced foci

    OpenAIRE

    McVean, A; Kent, S; Bakanov, A; Hobbs, T; Anderson, RM

    2012-01-01

    Copyright @ 2012 McVean et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been made available through the Brunel Open Access Publishing Fund. Background: The quantification of radiation-induced foci (RIF) to invest...

  12. Rapid diagnosis of pleural tuberculosis by Xpert MTB/RIF assay using pleural biopsy and pleural fluid specimens

    OpenAIRE

    Du, Jinghui; Huang, Zikun; Luo, Qing; Xiong, Guoliang; Xu, Xiaomeng; Li, Weiting; Liu, Xu; Li, Junming

    2015-01-01

    Background: Early pleural tuberculosis (TB) diagnosis is particularly difficult. The aim of this study was to investigate the diagnostic accuracy of the Xpert MTB/RIF (Xpert) (Cepheid, Sunnyvale, CA) assay using pleural biopsy and pleural fluid specimens in patients with suspected pleural TB but who had a negative sputum acid-fast bacilli (AFB) smear. Materials and Methods: In this study, 134 sputum smear-negative suspected pleural TB patients were selected. Paired pleural fluid and pleural b...

  13. Impact of land use on soil organic carbon distribution in toposequences of the Central Rif, Morocco

    Science.gov (United States)

    Mesrar, Haytam; Sadiki, Abdelhamid; Faleh, Ali; Quijano, Laura; Gaspar, Leticia; Navas, Ana

    2017-04-01

    Mediterranean mountain agroecosystems are sensitive areas to soil degradation mainly due to erodible soils, occasional heavy rainfalls and anthropogenic activities that have transformed large surfaces of natural forest into croplands. In the mountains of the central Rif (Morocco) the anthropogenic pressure by intensive agriculture on steep slopes and grazing practices is causing large impacts on soils. In the region soil losses have further indirect impact on water resources due to siltation of water bodies from canals, small check dams to large reservoirs. Besides the loss of the upper rich organic soil horizons containing the largest amounts of organic matter is causing decreases in soil fertility and losses in crop productivity. Soil erosion affects the spatial variability of soil nutrients of which soil organic carbon (SOC) is one of the most important because is directly linked to soil quality and soil functions. The artificially emitted 137Cs has been found to effectively trace soil redistribution because of its associated movement with fine soil particles including the organic matter. To assess the contents of SOC under different land uses a set of transects were set up in the Sahla catchment that holds a reservoir and is representative of the Rif mountain agroecosystems. Along the transects soil sampling was done to collect soil cores extending until a depth of 25 cm that were sectioned at 5cm depth intervals. The SOC content (%) was measured by the oxidation method in the < 2mm fraction of the interval subsamples. The lateral and vertical variations of SOC contents were examined in combination with the 137Cs profiles to gain information on the nutrient content in the soils under the most characteristic land uses existing in the catchment. In general the SOC contents are low but the mean contents in the croplands are much lower than in the uncultivated lands that present the highest variations in the SOC percentages. In croplands the depth distribution of

  14. 40Ar/39Ar constraints on the activity of the Temsamane extensional detachment (eastern Rif, Morocco)

    Science.gov (United States)

    Jabaloy Sánchez, A.; Booth-Rea, G.; Azdimousa, A.; Asebriy, L.; Vázquez-Vílchez, M.; Martínez-Martínez, J. M.; Gabites, J.

    2012-04-01

    The subducted North Maghrebian passive margin was exhumed by an upper crustal brittle-ductile extensional detachment and brittle low-angle normal faults in a continental subduction transform setting. The Temsamane detachment in the eastern Rif is defined by a ductile shear zone approximately 100 m thick with a low-angle ramp geometry that cuts down into the Temsamane fold-nappe stack. The shear zone shows southwestward kinematics and separates epizone metapelites of the Temsamane units below from the epizone to diagenetic rocks of the Tanger-Ketama-Aknoul units above. To the east, the detachment becomes brittle, branching into a listric-fan that cuts through 10-6 Ma sediments and volcanoclastics in the Tres Forcas cape. New 40Ar/39Ar radiometric ages on amphiboles and micas from the footwall of the Temsamane detachment indicate that the metamorphic peak was reached in the footwall (Temsamane units) at ca. 21 Ma, producing the amphibolite epidote facies in the Ras Afrou Unit. The cooling of the footwall rocks below the 325 °C occurred between the 16 and 13 Ma, while apatite fission track ages indicate that the cooling below the 120 °C occurred at ca. 11 Ma. The 40Ar/39Ar radiometric ages on amphiboles and micas of the metamorphic klippes over the Temsamene units (Ait-Amrâne massif) indicates that the Jurassic marbles of the Tanger-Ketama Unit reached their metamorphic peak at ca. 80 Ma, in agreement with previously published K/Ar ages in micas. The rocks of the Tanger-Ketama Unit cooled below the 120 °C between 17.0 ± 2.4 Ma and 13.9 ± 1.8 Ma. We interpret the increase of cooling rates of the footwall rocks between 15-13 Ma and 11 Ma as due to the activity of the Temsamane detachment fault. Thus, both the North Maghrebian and the South Iberian subducted passive margins were exhumed in the Betic and Rif branches of the Gibraltar arc by SW-directed brittle-ductile detachments during the Late Miocene in an oblique collisional setting.

  15. Decreased Time to Treatment Initiation for Multidrug-Resistant Tuberculosis Patients after Use of Xpert MTB/RIF Test, Latvia.

    Science.gov (United States)

    Stagg, Helen R; White, Peter J; Riekstiņa, Vija; Cīrule, Andra; Šķenders, Ģirts; Leimane, Vaira; Kuksa, Liga; Dravniece, Gunta; Brown, James; Jackson, Charlotte

    2016-03-01

    Few studies have examined whether the Xpert MTB/RIF test improves time to treatment initiation for persons with multidrug-resistant tuberculosis (MDR TB). We determined the impact of this test in Latvia, where it was introduced in 2010. After descriptive analyses of pulmonary MDR TB patients in Latvia during 2009-2012, time to treatment initiation was calculated, and univariate and multivariable accelerated failure time models were constructed. Univariate results showed strong evidence of an association between having rifampin-resistant TB detected by Xpert MTB/RIF and reduced time to treatment initiation versus the test not being used. A multivariable model stratifying by previous TB showed similar results. Our finding that in Latvia, time to treatment initiation was decreased for MDR TB cases that were rifampin-resistant TB by XpertMTB/RIF has implications for the use of this test in other settings with a high burden of MDR TB in which rifampin resistance is highly predictive of MDR TB.

  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. An evaporite-bearing accretionary complex in the northern front of the Betic-Rif orogen

    Science.gov (United States)

    Pérez-Valera, Fernando; Sánchez-Gómez, Mario; Pérez-López, Alberto; Pérez-Valera, Luis Alfonso

    2017-06-01

    The Guadalquivir Accretionary Complex forms a largely oblique prism at the northern edge of the Betic-Rif orogen, where Miocene sediments plus allochthonous evaporite-bearing units were accreted during the displacement of the Alborán Domain toward the west. Traditional interpretations end the tectonic structuring of the Betic Cordillera at the present topographic front, beyond which gravitational and/or diapiric processes would predominate. However, this study shows pervasive tectonic deformation in the outer prism with coherent oblique shortening kinematics, which is achieved through an alternation of roughly N-S arcuate thrust systems connected by E-W transfer fault zones. These structures accord well with the geophysical models that propose westward rollback subduction. The main stage of tectonic activity occurred in the early-middle Miocene, but deformation lasted until the Quaternary with the same kinematics. Evaporite rocks played a leading role in the deformation as evidenced by the suite of ductile structures in gypsum distributed throughout the area. S- and L- gypsum tectonites, scaly clay fabrics, and brittle fabrics coexist and consistently indicate westward motion (top to 290°), with subordinate N-S contraction almost perpendicular to the transfer zones. This work reveals ductile tectonic fabrics in gypsum as a valuable tool to elucidate the structure and deformational history of complex tectonic mélanges involving evaporites above the décollement level of accretionary wedges.

  18. 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.

  19. 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.

  20. The impact and cost of scaling up GeneXpert MTB/RIF in South Africa.

    Directory of Open Access Journals (Sweden)

    Gesine Meyer-Rath

    Full Text Available We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa.We parameterised a population-level decision model with data from national-level TB databases (n = 199,511 and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached.At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%-37% and the number of MDR-TB cases diagnosed by 69%-71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60-61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797-873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287-316 million over six years.Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation.

  1. 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.

  2. Low-cost rapid detection of rifampicin resistant tuberculosis using bacteriophage in Kampala, Uganda

    Directory of Open Access Journals (Sweden)

    Smith Peter G

    2007-01-01

    Full Text Available Abstract Background Resistance to anti-tuberculosis drugs is a serious public health problem. Multi-drug resistant tuberculosis (MDR-TB, defined as resistance to at least rifampicin and isoniazid, has been reported in all regions of the world. Current phenotypic methods of assessing drug susceptibility of M. tuberculosis are slow. Rapid molecular methods to detect resistance to rifampicin have been developed but they are not affordable in some high prevalence countries such as those in sub Saharan Africa. A simple multi-well plate assay using mycobacteriophage D29 has been developed to test M. tuberculosis isolates for resistance to rifampicin. The purpose of this study was to investigate the performance of this technology in Kampala, Uganda. Methods In a blinded study 149 M. tuberculosis isolates were tested for resistance to rifampicin by the phage assay and results compared to those from routine phenotypic testing in BACTEC 460. Three concentrations of drug were used 2, 4 and 10 μg/ml. Isolates found resistant by either assay were subjected to sequence analysis of a 81 bp fragment of the rpoB gene to identify mutations predictive of resistance. Four isolates with discrepant phage and BACTEC results were tested in a second phenotypic assay to determine minimal inhibitory concentrations. Results Initial analysis suggested a sensitivity and specificity of 100% and 96.5% respectively for the phage assay used at 4 and 10 μg/ml when compared to the BACTEC 460. However, further analysis revealed 4 false negative results from the BACTEC 460 and the phage assay proved the more sensitive and specific of the two tests. Of the 39 isolates found resistant by the phage assay 38 (97.4% were found to have mutations predictive of resistance in the 81 bp region of the rpoB gene. When used at 2 μg/ml false resistant results were observed from the phage assay. The cost of reagents for testing each isolate was estimated to be 1.3US$ when testing a batch of 20 isolates on a single 96 well plate. Results were obtained in 48 hours. Conclusion The phage assay can be used for screening of isolates for resistance to rifampicin, with high sensitivity and specificity in Uganda. The test may be useful in poorly resourced laboratories as a rapid screen to differentiate between rifampicin susceptible and potential MDR-TB cases.

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

    African Journals Online (AJOL)

    A prospective study was done comparing performance of the rapid phage test with conventional culture and drug susceptibility testing (DST) in AFB-positive TB patients. Setting. Five primary health clinics and one TB referral centre in the Port Elizabeth Metropolitan area, Eastern Cape. Outcome measures. Sensitivity ...

  4. Screening new tuberculosis patients in Mali for rifampicin resistance at 2 months

    Directory of Open Access Journals (Sweden)

    Bassirou Diarra

    2016-01-01

    Conclusion: Although we cannot exclude additional MDR patients having been missed by our screening strategy, our screening algorithm at 2M detected five out of nine MDR patients. Detecting patients at 2M allowed for earlier referral, and potentially less acquired drug resistance and lower mortality. This strategy may be advantageous while awaiting further rollout of Xpert machines that will permit universal DST.

  5. 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

  6. 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

    . Whereas PfEMP1s are known to mediate cytoadhesion, the function of RIFINs is unknown. The sequence diversity and organisation of rif genes of the P. falciparum clones 3D7, HB3, DD2, and IT/FCR3 were investigated using a tree-building method which allowed sub-grouping of RIFINs into distinct groups. Two...

  7. Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis

    NARCIS (Netherlands)

    van't Hoog, Anna H.; Cobelens, Frank; Vassall, Anna; van Kampen, Sanne; Dorman, Susan E.; Alland, David; Ellner, Jerrold

    2013-01-01

    High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable

  8. Rapid and accurate detection of Mycobacterium tuberculosis in sputum samples by Cepheid Xpert MTB/RIF assay--a clinical validation study.

    Directory of Open Access Journals (Sweden)

    Andrea Rachow

    Full Text Available BACKGROUND: A crucial impediment to global tuberculosis control is the lack of an accurate, rapid diagnostic test for detection of patients with active TB. A new, rapid diagnostic method, (Cepheid Xpert MTB/RIF Assay, is an automated sample preparation and real-time PCR instrument, which was shown to have good potential as an alternative to current reference standard sputum microscopy and culture. METHODS: We performed a clinical validation study on diagnostic accuracy of the Xpert MTB/RIF Assay in a TB and HIV endemic setting. Sputum samples from 292 consecutively enrolled adults from Mbeya, Tanzania, with suspected TB were subject to analysis by the Xpert MTB/RIF Assay. The diagnostic performance of Xpert MTB/RIF Assay was compared to standard sputum smear microscopy and culture. Confirmed Mycobacterium tuberculosis in a positive culture was used as a reference standard for TB diagnosis. RESULTS: Xpert MTB/RIF Assay achieved 88.4% (95%CI = 78.4% to 94.9% sensitivity among patients with a positive culture and 99% (95%CI = 94.7% to 100.0% specificity in patients who had no TB. HIV status did not affect test performance in 172 HIV-infected patients (58.9% of all participants. Seven additional cases (9.1% of 77 were detected by Xpert MTB/RIF Assay among the group of patients with clinical TB who were culture negative. Within 45 sputum samples which grew non-tuberculous mycobacteria the assay's specificity was 97.8% (95%CI = 88.2% to 99.9%. CONCLUSIONS: The Xpert MTB/RIF Assay is a highly sensitive, specific and rapid method for diagnosing TB which has potential to complement the current reference standard of TB diagnostics and increase its overall sensitivity. Its usefulness in detecting sputum smear and culture negative patients needs further study. Further evaluation in high burden TB and HIV areas under programmatic health care settings to ascertain applicability, cost-effectiveness, robustness and local acceptance are required.

  9. 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

  10. 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.

  11. Comparison of pH, bloodflow, and antigenicity in a heat-sensitive (EMT6) and a heat-resistant (RIF) tumor

    International Nuclear Information System (INIS)

    Van Kersen, I.; Marmor, J.B.; McDougall, I.R.; Coleman, D.; Hahn, G.M.

    1985-01-01

    The authors studied 2 transplantable murine tumors that have different heat sensitivities. Exposure to 43 0 /1h results in 100% cure of EMT6 tumors as opposed to no cure in RIF tumors. They saw little difference between the heat sensitivities of the 2 tumor lines in vitro at either pH 7.4 or 6.7. Measurement of pH in vivo was performed immediately before and 1 and 6h after heating. There was no significant change at 1h after heating, although at 6h after heating there was a reduction in pH of the EMT6 tumor, which was not mirrored in the RIF tumor. Bloodflow data were inferred from measurements of intravascular volume. Bloodflow was reduced to 10% of control values at 12h after heating, but gradually recovered to approximately 50% of control values by 48h in both tumors. The EMT6 tumor displays a more rapid decrease in bloodflow but also recovers faster than the RIF tumor. The authors also performed experiments to establish the degree of antigenicity of the two cell lines. TD/sub 50/ rose from 5-10 cells in controls to over 2000 cells in pre-immunized animals with the EMT6 tumor. No change in TD/sub 50/ was seen when RIF cells were employed. The results suggest that the combination of the increased acidity of heated EMT6 tumors and its antigenicity are responsible for the difference in cure rates between the two tumor lines

  12. Evaluation of the Xpert MTB/RIF assay for the diagnosis of smear-negative pulmonary and extrapulmonary tuberculosis in Madagascar

    Directory of Open Access Journals (Sweden)

    R. Rakotoarivelo

    2018-04-01

    Full Text Available Objective: To evaluate the feasibility of the implementation of a commercial rapid molecular diagnostic test (Xpert MTB/RIF for the routine diagnosis of smear-negative or extrapulmonary tuberculosis (TB and its diagnostic accuracy, and to assess HIV prevalence in a real-life setting in Madagascar. This study was set in a tertiary care hospital in Madagascar. Methods: A prospective cohort study was conducted of all consecutive cases with suspected smear-negative and/or extrapulmonary TB over a 2-year period. Cases were classified as proven, probable, or possible TB cases, or as having an alternative diagnosis. Results: Of the 363 patients included, 183 (50.4% had suspected smear-negative pulmonary TB and 180 (49.6% had suspected extrapulmonary TB. For proven cases, the sensitivity, specificity, positive and negative predictive values of Xpert MTB/RIF were 82.4%, 98.8%, 98.3%, and 86.6%, respectively; for proven and probable cases grouped together, these values were 65%, 98.8%, 98.5%, and 64%, respectively. The diagnostic accuracy was slightly lower for extrapulmonary TB compared to smear-negative pulmonary TB. The prevalence of HIV infection was 12.1%, but almost half of these cases did not have TB (alternative diagnosis group. Conclusions: The implementation of a rapid diagnosis programme for TB in a resource-poor setting is feasible. The performance of the Xpert-MTB/RIF was remarkable in this difficult-to-diagnose population. HIV prevalence in this study was much higher than the prevalence reported in the general population in Madagascar, in patients with TB and patients with conditions other than TB. Keywords: Extrapulmonary tuberculosis, Smear-negative pulmonary tuberculosis, HIV, Molecular diagnostic test, Low resource countries, Xpert MTB/RIF

  13. 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

  14. Variations of the crustal thickness in the Betic-Rif domain and their foreland regions, by P-Receiver Functions

    Science.gov (United States)

    Stich, D.; Mancilla, F.; Morales, J.; Martin, R.; Diaz, J.; Pazos, A.; Cordoba, D.; Pulgar, J. A.; Ibarra, P.; Harnafi, M.; Gonzalez-Lodeiro, F.

    2012-12-01

    To image the crustal structure of the Betic-Rif Range and the surrounding area we perform a P-receiver function study (PRF). We calculate PRFs at 110 broadband stations located in South Iberia Peninsula and North Morocco to obtain thickness and average Vp/Vs ratio for the Crust. The Crustal thickness values show strong lateral variations throughout the region. Crustal thicknesses vary between ~19 km and ~46 km. The Betic and Rif ranges are underlined by a thickened crust with crustal thicknesses between ~35 km and ~46 km, reaching the highest values in the contact between the Alboran Domain and External Zones. Southeast Iberia and Northeast Morocco are affected by significant crustal thinning, with crustal thicknesses ranging from ~19 km to ~30 km, with the shallowest Moho along the Mediterranean coast. The transition from thick to thin crust is coincident with the faults system of the Trans-Alboran Shear Zone. Toward the North, the Iberian Massif is an homogeneous domain of average 30-31 km crustal thickness and flat Moho discontinuity with low average Vp/Vs ratios ~1.72. Further south an extended domain, which includes the Atlas domain and its foreland regions, presents crustal thickness of 27-34km. Vp/Vs ratios in north Morocco show normal values of ~1.75 for most stations except for the Atlas domain, where several stations present low Vp/Vs ratios around 1.71. The obtained PRFs are migrated to depth building cross-section images to delineate the crustal mantle discontinuity (Moho) along the study area. In the migrated images, we include altogether ~11.200 PFRs to follow the Moho discontinuity from the Iberian Massif, in the North, along the Gribraltar arc towards the Moroccan Massif in the South. These images show how, in the North, the Iberian crust underthrust the Alboran domain along their contact with the observation of a slab, from the western limit until the 3°W longitude, reaching the maximum depth of ~70 km under the coast coincide with the

  15. 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

  16. The effect of cisplatin on the repair of radiation damage in RIF1 mouse tumours in vivo

    International Nuclear Information System (INIS)

    Begg, A.C.; Bohlken, S.; Bartelink, H.

    1989-01-01

    The effect of the antitumour agent cisplatin on repair of X-ray-induced damage was studied in RIF1 mouse tumours treated in situ. The response of tumours, assessed by growth delay, to 4 fractions of X-rays given at 5-h intervals was compared with that after single doses. The displacement between the curves was taken as a measure of repair. A single dose of 6 mg·kg -1 cisplatin given 0.5 h before the first fraction resulted in no detectable inhibition of repair despite a significant growth delay caused by drug alone. A dose of 2 mg/kg cisplatin given 0.5 h before each of the X-ray fractions, did, however, cause some repair inhibition; a result confirmed by tumour control experiments. The schedule dependence for repair inhibition was the same whether the irradiations were carried out on clamped (fully hypoxic) tumours or under ambient conditions. Significant enhancement of radiation damage was seen after correcting for the effects of drug alone, wheter or not repair inhibition occurred. The effects of cisplatin on normal stroma within the tumour (vascular damage) was also investigated by monitoring the regrowth rates of recurrent tumours. In contrast to the effects on tumour cells, no enhancement of damage or inhibition of repair was seen for this assay in the combined treatment schedules. (author). 39 refs.; 7 figs.; 2 tabs

  17. 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

  18. 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.

  19. Cost analysis of different diagnostic algorithms for pulmonary tuberculosis varying in placement of Xpert MTB/RIF.

    Science.gov (United States)

    Chadha, V K; Sebastian, George; Kumar, P

    2016-01-01

    We undertook cost analysis for diagnosis of pulmonary tuberculosis (PTB) using present algorithm under Revised National Tuberculosis Control programme and using Xpert MTB/RIF (Xpert) as frontline test or in conjunction with smear microscopy and/or chest radiography. Costs were estimated for different strategies: (A) present algorithm involving sputum smear examination followed by antibiotic trial in smear negative patients, repeat smear examination (RE) if symptoms continue and chest radiography if RE negative; (B) direct Xpert; (C) smear microscopy followed by Xpert in smear negative patients; (D) radiography followed by Xpert in those having abnormal pulmonary shadows; and (E) smear examination followed by radiography among smear negative patients and Xpert in presence of abnormal pulmonary shadow. Cost to program was estimated lowest with Strategy A and highest with Strategy B. Compared to the latter, program cost reduces by 7%, 4.5%, and 17.4% by strategies C, D, and E, respectively. Cost to the group of individuals with presumptive PTB and their attendants is significantly higher for Strategy A compared to other four strategies. Among the latter, the patients' cost was minimum with Strategy B and maximum with Strategy C. Program cost per case diagnosed was lowest by Strategy A and highest by Strategy B. Patient cost per case diagnosed was highest by Strategy A and lowest by Strategy B. Using Xpert, Strategy E had the lowest program as well as overall cost per case diagnosed. Strategy E may be chosen for diagnosis of PTB. When resources would no longer be a constraint, direct Xpert would reduce costs incurred by the patients. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  20. Modeling the patient and health system impacts of alternative xpert® MTB/RIF algorithms for the diagnosis of pulmonary tuberculosis in Addis Ababa, Ethiopia.

    Science.gov (United States)

    Tesfaye, Abraham; Fiseha, Daniel; Assefa, Dawit; Klinkenberg, Eveline; Balanco, Silvia; Langley, Ivor

    2017-05-02

    To reduce global tuberculosis (TB) burden, the active disease must be diagnosed quickly and accurately and patients should be treated and cured. In Ethiopia, TB diagnosis mainly relies on spot-morning-spot (SMS) sputum sample smear analysis using Ziehl-Neelsen staining techniques (ZN). Since 2014 targeted use of xpert has been implemented. New diagnostic techniques have higher sensitivity and are likely to detect more cases if routinely implemented. The objective of our study was to project the effects of alternative diagnostic algorithms on the patient, health system, and costs, and identify cost-effective algorithms that increase TB case detection in Addis Ababa, Ethiopia. An observational quantitative modeling framework was applied using the Virtual Implementation approach. The model was designed to represent the operational and epidemiological context of Addis Ababa, the capital city of Ethiopia. We compared eight diagnostic algorithm with ZN microscopy, light emitting diode (LED) fluorescence microscopy and Xpert MTB/RIF. Interventions with an annualized cost per averted disability adjusted life year (DALY) of less than the Gross Domestic Product (GDP) per capita are considered cost-effective interventions. With a cost lower than the average per-capita GDP (US$690 for Ethiopia) for each averted disability adjusted life year (DALY), three of the modeled algorithms are cost-effective. Implementing them would have important patient, health system, and population-level effects in the context of Addis Ababa ❖ The full roll-out of Xpert MTB/RIF as the primary test for all presumptive TB cases would avert 91170 DALYs (95% credible interval [CrI] 54888 - 127448) with an additional health system cost of US$ 11.6 million over the next 10 years. The incremental cost-effectiveness ratio (ICER) is $370 per DALY averted. ❖ Same day LED fluorescence microscopy for all presumptive TB cases combined with Xpert MTB/RIF targeted to HIV-positive and High multidrug resistant

  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. 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

    to the bloodstream. Sexual stage parasite surface proteins are of interest as candidate target antigens for transmission blocking vaccines. METHODS: In this study, the transcript profiles of rif and var genes, known to encode surface antigens in asexual blood stage parasites, were investigated at different stages......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...... of the parasites binding ligands responsible for the adhesion during sexual stages and potentially to novel vaccine candidates....

  3. [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.

  4. 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

  5. False-Positive Xpert MTB/RIF Results in Retested Patients with Previous Tuberculosis: Frequency, Profile, and Prospective Clinical Outcomes.

    Science.gov (United States)

    Theron, Grant; Venter, Rouxjeane; Smith, Liezel; Esmail, Aliasgar; Randall, Philippa; Sood, Vishesh; Oelfese, Suzette; Calligaro, Greg; Warren, Robin; Dheda, Keertan

    2018-03-01

    Globally, Xpert MTB/RIF (Xpert) is the most widely used PCR test for the diagnosis of tuberculosis (TB). Positive results in previously treated patients, which are due to old DNA or active disease, are a diagnostic dilemma. We prospectively retested sputum from 238 patients, irrespective of current symptoms, who were previously diagnosed to be Xpert positive and treated successfully. Patients who retested as Xpert positive and culture negative were exhaustively investigated (repeat culture, chest radiography, bronchoscopy with bronchoalveolar lavage, long-term clinical follow-up). We evaluated whether the duration since previous treatment completion, mycobacterial burden (the Xpert cycle threshold [ C T ] value), and reclassification of Xpert-positive results with a very low semiquantitation level to Xpert-negative results reduced the rate of false positivity. A total of 229/238 (96%) of patients were culture negative. Sixteen of 229 (7%) were Xpert positive a median of 11 months (interquartile range, 5 to 19 months) after treatment completion. The specificity was 93% (95% confidence interval [CI], 89 to 96%). Nine of 15 (40%) Xpert-positive, culture-negative patients reverted to Xpert negative after 2 to 3 months (1 patient declined further participation). Patients with false-positive Xpert results had a lower mycobacterial burden than patients with true-positive Xpert results ( C T , 28.7 [95% CI, 27.2 to 30.4] versus 17.6 [95% CI, 16.9 to 18.2]; P < 0.001), an increased likelihood of a chest radiograph not compatible with active TB (5/15 patients versus 0/5 patients; P = 0.026), and less-viscous sputum (15/16 patients versus 2/5 patients whose sputum was graded as mucoid or less; P = 0.038). All patients who initially retested as Xpert positive and culture negative ("Xpert false positive") were clinically well without treatment after follow-up. The duration since the previous treatment poorly predicted false-positive results (a duration of ≤2 years identified

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

    OpenAIRE

    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 community consists of 60 species, among which 4, found in the Rif, are new to science: Protonemura sp. (Plecoptera), Obuchovia sp. (Diptera, Simuliidae), Rhyacophila fonticola n. sp., and Philopot...

  7. Evaluation of Xpert® MTB/RIF Assay in Induced Sputum and Gastric Lavage Samples from Young Children with Suspected Tuberculosis from the MVA85A TB Vaccine Trial.

    Science.gov (United States)

    Bunyasi, Erick Wekesa; Tameris, Michele; Geldenhuys, Hennie; Schmidt, Bey-Marrie; Luabeya, Angelique Kany Kany; Mulenga, Humphrey; Scriba, Thomas J; Hanekom, Willem A; Mahomed, Hassan; McShane, Helen; Hatherill, Mark

    2015-01-01

    Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert® MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting. We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009-2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar's χ2 test; and Wilson's score method to calculate sensitivity and specificity. 1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2-44.4] for two induced sputum samples and 7/31[22.6%; 11.4-39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6-100] and 885/890[99.4%;98.7-99.8] respectively [p = 0.025]. Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum

  8. Impact of introduction of Xpert MTB/RIF test on tuberculosis (TB) diagnosis in a city with high TB incidence in Brazil.

    Science.gov (United States)

    Pereira, Giovana Rodrigues; Barbosa, Márcia Silva; Dias, Natan José Dutra; Almeida, Carlos Podalirio Borges de; Silva, Denise Rossato

    2018-01-01

    Xpert MTB/RIF is increasingly used in many countries as the initial diagnostic test for tuberculosis (TB). Few studies have evaluated the effect of Xpert on TB diagnosis under programmatic conditions in Brazil. The aim of the present study was to evaluate the impact of introduction of Xpert MTB/RIF on TB diagnosis in a city with high TB incidence in Brazil. We included patients evaluated with conventional diagnostic tests during one year before Xpert introduction (pre-Xpert group) and patients evaluated using Xpert during one year after the test introduction (post-Xpert group). 620 patients met the inclusion criteria (208 in the pre-Xpert group and 412 in the post-Xpert group) and were included in the analysis. The time until TB diagnosis was shorter in post-Xpert group (0.7 day, IQR: 0.5-1.0 day) than in pre-Xpert group (2.0 days, IQR: 2.0-2.0 days) (pTB were more common in post-Xpert group than in pre-Xpert group (pTB diagnosis, especially in cases with atypical disease manifestations. These results are likely to be generalizable to settings with a similar high TB incidence.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

    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...... 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Faunistic notes on Cryptophagidae and Latridiidae of Talassemtane National Park, Western Rif, Morocco, with the description of a new species (Coleoptera, Cucujoidea).

    Science.gov (United States)

    Otero, José Carlos; Benyahia, Yousra; Brustel, Hervé

    2017-01-01

    In order to contribute to the knowledge of beetles (Coleoptera) of the mountainous region of Morocco, Talassemtane National Park (Western Rif, Chefchaouen district, Morocco) was surveyed. This is an exceptional protected area of the Mediterranean Intercontinental Biosphere Reserve (RIBM). The checklist was made using different traps combined with active periodical searches during 2013-2015. A total of 153 beetles belonging to 19 species from four subfamilies (Cryptophagidae: Cryptophaginae and Atomariinae; Latridiidae: Latridiinae and Corticariinae) was collected. Dienerella (Cartoderema) talassemata, a new species (Coleoptera: Latridiidae) was compared to other morphologically related species. One species is recorded for the first time for North Africa; three species are new records for Morocco. In addition, amongst the species listed, three are endemic to Morocco: Dienerella talassemtana sp. n ., Caenoscelis humifera and Dienerella besucheti .

  16. Faunistic notes on Cryptophagidae and Latridiidae of Talassemtane National Park, Western Rif, Morocco, with the description of a new species (Coleoptera, Cucujoidea

    Directory of Open Access Journals (Sweden)

    José Carlos Otero

    2017-04-01

    Full Text Available In order to contribute to the knowledge of beetles (Coleoptera of the mountainous region of Morocco, Talassemtane National Park (Western Rif, Chefchaouen district, Morocco was surveyed. This is an exceptional protected area of the Mediterranean Intercontinental Biosphere Reserve (RIBM. The checklist was made using different traps combined with active periodical searches during 2013–2015. A total of 153 beetles belonging to 19 species from four subfamilies (Cryptophagidae: Cryptophaginae and Atomariinae; Latridiidae: Latridiinae and Corticariinae was collected. Dienerella (Cartoderema talassemata, a new species (Coleoptera: Latridiidae was compared to other morphologically related species. One species is recorded for the first time for North Africa; three species are new records for Morocco. In addition, amongst the species listed, three are endemic to Morocco: Dienerella talassemtana sp. n., Caenoscelis humifera and Dienerella besucheti.

  17. 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

    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...... 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...... 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. Conclusion: We have implemented and validated a network-based approach to prioritize genes for human diseases based...

  18. Thermal Structure and Tectono-Metamorphic Evolution of the Alboran Domain. New Insights From the Rif belt (Northern Morocco) and Correlations With the Betics (Southern Spain)

    Science.gov (United States)

    Negro, F.; Beyssac, O.; Goffe, B.; Saddiqi, O.; Bouybaouene, M.

    2005-12-01

    The Betico-Rifan Cordilleras represent the western termination of the Alpine Mediterranean orogen. The internal zone of this orogen is the Alboran Domain which consists in a complex stacking of metamorphic nappes including, locally, mantle-derived bodies: the Ronda and Beni Bousera peridotites. In order to assess the tectono-metamorphic evolution of theses nappes and their relation with the underlying peridotites, we have combined RSCM (Raman spectroscopy of carbonaceous material) thermometry and P-T estimates based on chlorite-phengite local equilibria together with a careful analysis of ductile deformation. In the inner Rif, the lower units (lower Sebtides) of the Alboran Domain are directly on top of the Beni Bousera peridotites. Our study shows that peak T was reached during thinning of these units, and that heating continued after this event. A Miocene thermal imprint is also recorded at the base of the upper units of the Alboran Domain (Ghomarides) and evidenced by an increase of T coeval with resetting of K-Ar ages. Retrograde P-T paths in the HP-LT units of the Sebtide Complex also agree with this thermal structure. The units located near the peridotites experienced heating during final decompression stages whereas the more distant units underwent mostly isothermal decompression. In addition analysis of ductile deformation shows that the whole complex was exhumed in a single tectonic event characterized by N-S to NW-SE stretching and top-to-the-N senses of shear. The same approach in the equivalent units (Alpujarrides) from Western Betics evidences a very similar thermal structure over the Ronda peridotites but tectonic dismembering of the orogenic prism was stronger in the Betics compared to the Rif. Finally, analysis of these observations at orogenic scale shows that the Alboran Domain underwent a strong thermal event during the Early Miocene. This event can be interpreted as the result of ascending hot mantle units coeval with thinning of the whole

  19. 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.

  20. 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

  1. Diagnostic accuracy of xpert test in tuberculosis detection: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Ravdeep Kaur

    2016-01-01

    Full Text Available Background: World Health Organization (WHO recommends the use of Xpert MTB/RIF assay for rapid diagnosis of tuberculosis (TB and detection of rifampicin resistance. This systematic review was done to know about the diagnostic accuracy and cost-effectiveness of the Xpert MTB/RIF assay. Methods: A systematic literature search was conducted in following databases: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PUBMED, Scopus, Science Direct and Google Scholar for relevant studies for studies published between 2010 and December 2014. Studies given in the systematic reviews were accessed separately and used for analysis. Selection of studies, data extraction and assessment of quality of included studies was performed independently by two reviewers. Studies evaluating the diagnostic accuracy of Xpert MTB/RIF assay among adult or predominantly adult patients (≥14 years, presumed to have pulmonary TB with or without HIV infection were included in the review. Also, studies that had assessed the diagnostic accuracy of Xpert MTB/RIF assay using sputum and other respiratory specimens were included. Results: The included studies had a low risk of any form of bias, showing that findings are of high scientific validity and credibility. Quantitative analysis of 37 included studies shows that Xpert MTB/RIF is an accurate diagnostic test for TB and detection of rifampicin resistance. Conclusion: Xpert MTB/RIF assay is a robust, sensitive and specific test for accurate diagnosis of tuberculosis as compared to conventional tests like culture and microscopic examination.

  2. Enhancement of nisin production in milk by conjugal transfer of the protease-lactose plasmid pLP712 to the wild strain Lactococcus lactis UQ2

    OpenAIRE

    García-Parra, María D.; Campelo, Ana B.; García-Almendárez, Blanca E.; Regalado, Carlos; Rodríguez González, Ana; Martínez Fernández, Beatriz

    2010-01-01

    Lactococcus lactis UQ2 is a wild nisin A producer isolated from a Mexican cheese that grows poorly in milk. Conjugal matings with L. lactis NCDO712 to transfer the Lac+ Prt+ plasmid pLP712 and selection with nisin and lactose yielded L. lactis NCDO712 NisA+. Naturally rifampicin resistant L. lactis UQ2Rif was isolated to provide an additional selective marker. The identity of a transconjugant L. lactis UQ2Rif Lac+ was confirmed by RAPD-PCR fingerprinting, nisA PCR amplification, nisin product...

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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 < Mw < 5.5) implies the pore-fluid physical effect in undrained and drained conditions. The 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

  6. The Application of GeneXpert MTB/RIF for Smear-Negative TB Diagnosis as a Fee-Paying Service at a South Asian General Hospital

    Directory of Open Access Journals (Sweden)

    Poojan Shrestha

    2015-01-01

    Full Text Available The GeneXpert MTB/RIF assay (Xpert is a novel automated diagnostic tool for tuberculosis but its optimal placement in the healthcare system has not been determined. The objective of this study was to determine the possibility of additional case detection for pulmonary tuberculosis (PTB by offering Xpert to smear-negative patients in a low-HIV burden setting with no Mycobacterium tuberculosis (M.tb. culture facilities. Patients routinely presenting with symptoms suggestive of PTB with negative smears were offered single Xpert test on a fee-paying basis. Data were retrospectively reviewed to determine case detection in patients tested from February to December 2013. Symptoms associated with a positive test were analysed to determine if refinement of clinical criteria would reduce unnecessary testing. 258 smear-negative patients were included and M.tb. was detected in 55 (21.32%, n=55/258. Using standard clinical assessment for selection, testing 5 patients detected one case of smear-negative PTB. These results demonstrate that fee-paying Xpert service in low-income setting can increase TB case confirmation substantially and further systematic studies of health economic implications should be conducted to determine optimal implementation models to increase access to Xpert in low- and middle-income countries.

  7. The Application of GeneXpert MTB/RIF for Smear-Negative TB Diagnosis as a Fee-Paying Service at a South Asian General Hospital

    Science.gov (United States)

    Arjyal, Amit; Caws, Maxine; Prajapati, Krishna Govinda; Karkey, Abhilasha; Dongol, Sabina; Pathak, Saruna; Prajapati, Shanti; Basnyat, Buddha

    2015-01-01

    The GeneXpert MTB/RIF assay (Xpert) is a novel automated diagnostic tool for tuberculosis but its optimal placement in the healthcare system has not been determined. The objective of this study was to determine the possibility of additional case detection for pulmonary tuberculosis (PTB) by offering Xpert to smear-negative patients in a low-HIV burden setting with no Mycobacterium tuberculosis (M.tb.) culture facilities. Patients routinely presenting with symptoms suggestive of PTB with negative smears were offered single Xpert test on a fee-paying basis. Data were retrospectively reviewed to determine case detection in patients tested from February to December 2013. Symptoms associated with a positive test were analysed to determine if refinement of clinical criteria would reduce unnecessary testing. 258 smear-negative patients were included and M.tb. was detected in 55 (21.32%, n = 55/258). Using standard clinical assessment for selection, testing 5 patients detected one case of smear-negative PTB. These results demonstrate that fee-paying Xpert service in low-income setting can increase TB case confirmation substantially and further systematic studies of health economic implications should be conducted to determine optimal implementation models to increase access to Xpert in low- and middle-income countries. PMID:25949825

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Environnements et sociétés dans les basses montagnes du Rif (Maroc : des potentialités peu exploitéesa

    Directory of Open Access Journals (Sweden)

    Ftaïta T.

    2012-10-01

    Full Text Available L’agriculture marocaine représente seulement 19 % du PIB national alors que 40 % de la population vit de ce secteur, elle connait aujourd’hui de profondes transformations sous l’impulsion d’un Plan national « Maroc Vert » (PMV qui vise à améliorer la productivité agricole, et par là même contribuer à un meilleur revenu pour les agriculteurs (fellahs. Le Rif qui a longtemps été un espace en marge des centres décisionnels n’échappe pas à cette volonté. Malgré des contraintes que nous aborderons, des potentialités agricoles et touristiques existent qui valoriseraient cet espace, et ce, dans un contexte de développement durable. Nous proposons dans cet article de faire un premier point sur les valeurs ajoutées envisageables, ainsi que sur une nouvelle méthodologie employée pour les évaluer à savoir l’outil Bayesia Expert Knowledge Elicitation Environment(BEKEE. Des exemples d’espaces déjà mis en valeur, notamment par des techniques d’irrigation modernes sont également présentés.

  11. Diagnostic accuracy and effectiveness of the Xpert MTB/RIF assay for the diagnosis of HIV-associated lymph node tuberculosis.

    Science.gov (United States)

    Van Rie, A; Page-Shipp, L; Mellet, K; Scott, L; Mkhwnazi, M; Jong, E; Omar, T; Beylis, N; Stevens, W; Sanne, I; Menezes, C N

    2013-11-01

    Xpert MTB/RIF (Xpert) is recommended for human immunodeficiency virus (HIV)-associated pulmonary tuberculosis but not extrapulmonary tuberculosis. We assessed the performance of Xpert for HIV-associated lymph node tuberculosis (LNTB), the most common type of extrapulmonary tuberculosis. Among HIV-infected adults suspected of LNTB presenting for fine needle aspirate (FNA) at a South African hospital, we assessed the diagnostic accuracy of Xpert using either FNA culture or a composite of microscopy, culture, and cytology as the reference standard, and evaluated the impact of different diagnostics on patient management. Among 344 adults with valid FNA culture and Xpert results, 84 (24 %) were positive on microscopy, 149 (43 %) on culture, 152 (53 %) on Xpert, and 181 (57 %) had a cytology result suggestive of tuberculosis. Using liquid culture as the reference standard, the specificity of a single Xpert was suboptimal (88.2 %) but the sensitivity was high [93.3 %, 95 % confidence interval (CI) 87.6-96.6] and increased with decreasing CD4 count (from 87.0 % for CD4 >250 to 98.6 % for CD4 <100 cells/mm(3)). Using a composite reference standard reduced the sensitivity to 79.2 % but increased the specificity to 98.6 %. All Xpert-positive patients initiated treatment within one day, compared to 70 % of culture-positive but Xpert-negative and 13 % of culture- and Xpert-negative but cytology-positive patients. Xpert is accurate and effective and could be endorsed as the initial diagnostic for HIV-associated LNTB.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Optimal Triage Test Characteristics to Improve the Cost-Effectiveness of the Xpert MTB/RIF Assay for TB Diagnosis: A Decision Analysis

    Science.gov (United States)

    van’t Hoog, Anna H.; Cobelens, Frank; Vassall, Anna; van Kampen, Sanne; Dorman, Susan E.; Alland, David; Ellner, Jerrold

    2013-01-01

    Background High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. Methods In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. Findings A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. Conclusions A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such. PMID:24367555

  14. 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

  15. Comparing Tuberculosis Diagnostic Yield in Smear/Culture and Xpert® MTB/RIF-Based Algorithms Using a Non-Randomised Stepped-Wedge Design.

    Science.gov (United States)

    Naidoo, Pren; Dunbar, Rory; Lombard, Carl; du Toit, Elizabeth; Caldwell, Judy; Detjen, Anne; Squire, S Bertel; Enarson, Donald A; Beyers, Nulda

    2016-01-01

    Primary health services in Cape Town, South Africa. To compare tuberculosis (TB) diagnostic yield in an existing smear/culture-based and a newly introduced Xpert® MTB/RIF-based algorithm. TB diagnostic yield (the proportion of presumptive TB cases with a laboratory diagnosis of TB) was assessed using a non-randomised stepped-wedge design as sites transitioned to the Xpert® based algorithm. We identified the full sequence of sputum tests recorded in the electronic laboratory database for presumptive TB cases from 60 primary health sites during seven one-month time-points, six months apart. Differences in TB yield and temporal trends were estimated using a binomial regression model. TB yield was 20.9% (95% CI 19.9% to 22.0%) in the smear/culture-based algorithm compared to 17.9% (95%CI 16.4% to 19.5%) in the Xpert® based algorithm. There was a decline in TB yield over time with a mean risk difference of -0.9% (95% CI -1.2% to -0.6%) (pculture-based algorithm compared to 19.3% (95% CI 17.7% to 20.9%) in the Xpert® based algorithm with a risk difference of 0.3% (95% CI -1.8% to 2.3%) (p = 0.796). Culture tests were undertaken for 35.5% of smear-negative compared to 17.9% of Xpert® negative low MDR-TB risk cases and for 82.6% of smear-negative compared to 40.5% of Xpert® negative high MDR-TB risk cases in respective algorithms. Introduction of an Xpert® based algorithm did not produce the expected increase in TB diagnostic yield. Studies are required to assess whether improving adherence to the Xpert® negative algorithm for HIV-infected individuals will increase yield. In light of the high cost of Xpert®, a review of its role as a screening test for all presumptive TB cases may be warranted.

  16. Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings

    Science.gov (United States)

    Luetkemeyer, Anne F.; Firnhaber, Cynthia; Kendall, Michelle A.; Wu, Xingye; Mazurek, Gerald H.; Benator, Debra A.; Arduino, Roberto; Fernandez, Michel; Guy, Elizabeth; Johnson, Pamela; Metchock, Beverly; Sattler, Fred; Telzak, Edward; Wang, Yun F.; Weiner, Marc; Swindells, Susan; Sanne, Ian M.; Havlir, Diane V.; Grinsztejn, Beatriz; Alland, David

    2016-01-01

    Background. The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well as rpoB mutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Methods. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Results. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB+] sputum, 59.3% with AFB smear-negative [AFB–] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB+, 71.4% if AFB–), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB+/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. Conclusions. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation

  17. Performance of Xpert MTB/RIF and Alternative Specimen Collection Methods for the Diagnosis of Tuberculosis in HIV-Infected Children.

    Science.gov (United States)

    Marcy, Olivier; Ung, Vibol; Goyet, Sophie; Borand, Laurence; Msellati, Philippe; Tejiokem, Mathurin; Nguyen Thi, Ngoc Lan; Nacro, Boubacar; Cheng, Sokleaph; Eyangoh, Sara; Pham, Thu Hang; Ouedraogo, Abdoul-Salam; Tarantola, Arnaud; Godreuil, Sylvain; Blanche, Stéphane; Delacourt, Christophe

    2016-05-01

    The diagnosis of tuberculosis in human immunodeficiency virus (HIV)-infected children is challenging. We assessed the performance of alternative specimen collection methods for tuberculosis diagnosis in HIV-infected children using Xpert MTB/RIF (Xpert). HIV-infected children aged ≤13 years with suspected intrathoracic tuberculosis were enrolled in 8 hospitals in Burkina Faso, Cambodia, Cameroon, and Vietnam. Gastric aspirates were taken for children aged children aged ≥10 years (standard samples); nasopharyngeal aspirate and stool were taken for all children, and a string test was performed if the child was aged ≥4 years (alternative samples). All samples were tested with Xpert. The diagnostic accuracy of Xpert for culture-confirmed tuberculosis was analyzed in intention-to-diagnose and per-protocol approaches. Of 281 children enrolled, 272 (96.8%) had ≥1 specimen tested with Xpert (intention-to-diagnose population), and 179 (63.5%) had all samples tested with Xpert (per-protocol population). Tuberculosis was culture-confirmed in 29/272 (10.7%) children. Intention-to-diagnose sensitivities of Xpert performed on all, standard, and alternative samples were 79.3% (95% confidence interval [CI], 60.3-92.0), 72.4% (95% CI, 52.8-87.3), and 75.9% (95% CI, 56.5-89.7), respectively. Specificities were ≥97.5%. Xpert combined on nasopharyngeal aspirate and stool had intention-to-diagnose and per-protocol sensitivities of 75.9% (95% CI, 56.5-89.7) and 75.0% (95% CI, 47.6-92.7), respectively. The combination of nasopharyngeal aspirate and stool sample is a promising alternative to methods usually recommended by national programs. Xpert performed on respiratory and stools samples enables rapid confirmation of tuberculosis diagnosis in HIV-infected children. The ANRS (Agence Nationale de Recherche sur le Sida) 12229 PAANTHER (Pediatric Asian African Network for Tuberculosis and HIV Research) 01 study is registered at ClinicalTrials.gov (NCT01331811). © The Author 2016

  18. 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.

  19. Savoirs paysans autour des huiles d’olive, (zaytun, Olea europaea var. europaea) et d’oléastre, (əl-bərri, Olea europaea var. sylvestris) Rif, nord du Maroc

    OpenAIRE

    Aumeeruddy-Thomas, Yildiz; Caubet, Dominique

    2017-01-01

    Dans cet article, nous nous intéressons centralement aux produits de l’olivier et de l’oléastre du Nord du Maroc, aux modalités techniques d’obtention de différents types d’huile et ce que ces produits représentent pour les habitants. Il s’agit de comprendre si le Rif détient une particularité sur ce sujet. Nous suggérons que ces techniques et les savoirs et savoir-faire sur les huiles ont pu influencer des processus pré-domesticatoire et de création variétale dans le nord du Maroc. Nous cher...

  20. Resistência a isoniazida e rifampicina e história de tratamento anterior para tuberculose Isoniazid and rifampicin resistance and prior treatment for tuberculosis

    Directory of Open Access Journals (Sweden)

    Sonia Natal

    2003-10-01

    Full Text Available Em um estudo caso-controle, realizado no Rio de Janeiro, em 1994, foram incluídos 552 doentes de tuberculose com cultura positiva para Mycobacterium tuberculosis. A resistência a rifampicina e isoniazida foi de 1,8%. A variável de exposição foi "história de tratamento para tuberculose", associada estatisticamente com a resistência. Testou-se a hipótese de não haver dependência entre as associações observadas de acordo com a exposição anterior às drogas, utilizou-se a proporção binomial verificando-se uma dependência das resistências entre a rifampicina e isoniazida superior à esperada.A case-control study in Rio de Janeiro in 1994 included 552 patients with a positive culture for Mycobacterium tuberculosis and reported a 1.8% resistance rate to rifampicin and isoniazid. Prior treatment for tuberculosis (the exposure factor was associated with resistance. The binomial proportion was used to test the hypothesis of no dependence between the observed associations based on prior exposure to the drugs. This test showed a greater than expected dependence between resistances to rifampicin and isoniazid.

  1. Increasing metronidazole and rifampicin resistance of Helicobacter pylori isolates obtained from children and adolescents between 2002 and 2015 in southwest Germany.

    Science.gov (United States)

    Regnath, Thomas; Raecke, Olaf; Enninger, Axel; Ignatius, Ralf

    2017-02-01

    Increasing antibiotic resistance has been reported for Helicobacter pylori, but data on the prevalence of antibiotic resistance of H. pylori in pediatric patients and the development of resistance over time are sparse. Data for 610 H. pylori isolates obtained between 2002 and 2015 from gastric biopsies of 582 (mainly treatment-naïve) pediatric patients from southwest Germany were analyzed retrospectively regarding the antibiotic susceptibility determined by Etest and patients' characteristics. Overall resistance to metronidazole, clarithromycin, and rifampicin was 28.7%, 23.2%, and 13.3%, respectively, while resistance to amoxicillin was rare (0.8%). Simultaneous resistance to metronidazole and clarithromycin was observed for 7.7% of the isolates, and 2.3% were resistant to metronidazole, clarithromycin, and rifampicin. Differences between primary vs secondary resistance existed for metronidazole (24.7% vs 38.8%, P=.01) and clarithromycin (17.2% vs 54.1%, P=.0001). From 2002-2008 to 2009-2015, resistance to metronidazole increased from 20.8% to 34.4% (P=.003) and to rifampicin from 3.9% to 18.8% (P=.0001); this was not associated with increased numbers of patients previously treated for H. pylori infection in the second study period. In contrast, resistance to clarithromycin did not change significantly over time. Resistance was not associated with age, sex, or family origin in Europe. The considerable antibiotic resistance of H. pylori isolates argues for standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of antibiotic therapy. © 2016 John Wiley & Sons Ltd.

  2. Genotypic detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis strains by DNA sequencing: a randomized trial

    Directory of Open Access Journals (Sweden)

    El mashad Noha

    2009-01-01

    Full Text Available Abstract Background Tuberculosis is a growing international health concern. It is the biggest killer among the infectious diseases in the world today. Early detection of drug resistance allows starting of an appropriate treatment. Resistance to drugs is due to particular genomic mutations in specific genes of Mycobacterium tuberculosis(MTB. The aim of this study was to identify the presence of Isoniazid (INH and Rifampicin(RIF drug resistance in new and previously treated tuberculosis (TB cases using DNA sequencing. Methods This study was carried out on 153 tuberculous patients with positive Bactec 460 culture for acid fast bacilli. Results Of the 153 patients, 105 (68.6% were new cases and 48 (31.4% were previously treated cases. Drug susceptibility testing on Bactec revealed 50 resistant cases for one or more of the first line antituberculous. Genotypic analysis was done only for rifampicin resistant specimens (23 cases and INH resistant specimens (26 cases to detect mutations responsible for drug resistance by PCR amplification of rpoB gene for rifampicin resistant cases and KatG gene for isoniazid resistant cases. Finally, DNA sequencing was done for detection of mutation within rpoB and KatG genes. Genotypic analysis of RIF resistant cases revealed that 20/23 cases (86.9% of RIF resistance were having rpoB gene mutation versus 3 cases (13.1% having no mutation with a high statistical significant difference between them (P Conclusion We can conclude that rifampicin resistance could be used as a useful surrogate marker for estimation of multidrug resistance. In addition, Genotypic method was superior to that of the traditional phenotypic method which is time-consuming taking several weeks or longer.

  3. The cost of multiple drug resistance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Ward, H; Perron, G G; Maclean, R C

    2009-05-01

    The spread of bacterial antibiotic resistance mutations is thought to be constrained by their pleiotropic fitness costs. Here we investigate the fitness costs of resistance in the context of the evolution of multiple drug resistance (MDR), by measuring the cost of acquiring streptomycin resistance mutations (StrepR) in independent strains of the bacterium Pseudomonas aeruginosa carrying different rifampicin resistance (RifR) mutations. In the absence of antibiotics, StrepR mutations are associated with similar fitness costs in different RifR genetic backgrounds. The cost of StrepR mutations is greater in a rifampicin-sensitive (RifS) background, directly demonstrating antagonistic epistasis between resistance mutations. In the presence of rifampicin, StrepR mutations have contrasting effects in different RifR backgrounds: StrepR mutations have no detectable costs in some RifR backgrounds and massive fitness costs in others. Our results clearly demonstrate the importance of epistasis and genotype-by-environment interactions for the evolution of MDR.

  4. Lles enseignements paléogéographiques des épandages alluviaux villafranchiens de la région de Karia-ba-Mohamed (Bassin du Moyen Sebou, Prérif Central

    Directory of Open Access Journals (Sweden)

    A. Faleh

    2004-01-01

    Full Text Available En el Prerif central los materiales aluviales antiguos de la región de Karia-Ba-Mohamed se conservan principalmente en los sectores de Cherraga y de Hajaoua. Estos materiales se emplazan actualmente en la cuenca hidrográfi ca del Sebou prerifeño. Comparativamente con otros depósitos similares existentes en numerosas regiones del Rif datan probablemente del Villafranquiense. En la parte baja de estos depósitos se encuentran restos de un largo glacis moldeado que domina numerosas terrazas aluviales cuaternarias el Sebou. Un corte-tipo, situado en el corredor aluvial de Hajaoua, ha servido de referencia para estudiar el material de estos sedimentos aluviales. Muestra dos series sedimentarias principales: una serie basal esencialmente arenosa, colocada por los regímenes de escorrentía de débil capacidad, sobrepuesta por otra serie más gruesa, con fuerte proporción de guijarros embotados colocados por regatos potentes, refl ejando fuertes crecidas fl uviales. En los dos casos los depósitos aluviales son muy ricos en elementos deríticos silicios de origen rifeño. Los elementos calcáreos están ausentes. En conjunto, las observaciones geomorfológicas, así como las características sdimentológicas y petrográfi cas de estos antiguos materiales, muestran que son testimonios de paleoderrames del Ourga efectuados durante el Villafranquiense, hacia el valle del Sebou, situado entonces más al sur. Después, tras este periodo, parece que los avenamientos tectodinámicos, asociados netamente a la subsidencia de la cuenca del Rharb, han sido responsables del retorno de derrames del Ourgha hacia el oeste.

  5. The sensitivity and specificity of using a computer aided diagnosis program for automatically scoring chest X-rays of presumptive TB patients compared with Xpert MTB/RIF in Lusaka Zambia.

    Directory of Open Access Journals (Sweden)

    Monde Muyoyeta

    Full Text Available OBJECTIVE: To determine the sensitivity and specificity of a Computer Aided Diagnosis (CAD program for scoring chest x-rays (CXRs of presumptive tuberculosis (TB patients compared to Xpert MTB/RIF (Xpert. METHOD: Consecutive presumptive TB patients with a cough of any duration were offered digital CXR, and opt out HIV testing. CXRs were electronically scored as normal (CAD score ≤ 60 or abnormal (CAD score > 60 using a CAD program. All patients regardless of CAD score were requested to submit a spot sputum sample for testing with Xpert and a spot and morning sample for testing with LED Fluorescence Microscopy-(FM. RESULTS: Of 350 patients with evaluable data, 291 (83.1% had an abnormal CXR score by CAD. The sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV of CXR compared to Xpert were 100% (95%CI 96.2-100, 23.2% (95%CI 18.2-28.9, 33.0% (95%CI 27.6-38.7 and 100% (95% 93.9-100, respectively. The area under the receiver operator curve (AUC for CAD was 0.71 (95%CI 0.66-0.77. CXR abnormality correlated with smear grade (r = 0.30, p<0.0001 and with Xpert CT(r = 0.37, p<0.0001. CONCLUSIONS: To our knowledge this is the first time that a CAD program for TB has been successfully tested in a real world setting. The study shows that the CAD program had high sensitivity but low specificity and PPV. The use of CAD with digital CXR has the potential to increase the use and availability of chest radiography in screening for TB where trained human resources are scarce.

  6. 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

  7. A radio frequency interferometer (RIF) system

    International Nuclear Information System (INIS)

    Goldwire, H.C. Jr.

    1993-01-01

    The authors describe a radio frequency interferometer (RFI) system developed and tested by Lawrence Livermore National Laboratory over the last several years. The basic theory of operation, sample data, and analyzed results are presented and compared to results obtained by conventional TDR means (CORRTEX). A typical shock location measurement used for hydro-yield determination or for energy flow diagnostics comprises a coaxial sensing cable extending from the detonation region to a CORRTEX recording instrument. The single digitizer-based RFI system uses an identical sensing cable installation technique. Recording equipment consists of a CAMAC digitizer module, which produces a sinusoidal probing signal (the signal sent downhole) for each sensing channel (cable), while also coherently sampling the phase of the reflected signal. Each channel is recorded using a single digitizer, providing maximal temporal and spatial resolution, but independent of channel gain or quadruture errors inherent to dual digitizer systems. Interpolation software with suitable look-ahead logic permits determination of complete quadruture information using a single digitizer. This RFI system provides several times better spatial resolution and two orders of magnitude better temporal sampling density than does CORRTEX. It also is less susceptible to electromagnetic pulse distortion and provides a direct means for identifying (and rejecting) any data so contaminated

  8. (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.

  9. 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.

  10. Diagnostic yield of Bronchoalveolar Lavage gene Xpert in smear-negative and sputum-scarce pulmonary tuberculosis.

    Science.gov (United States)

    Khalil, Kanwal Fatima; Butt, Tariq

    2015-02-01

    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. An analytical study. Department of Pulmonology, Fauji Foundation Hospital (FFH), Rawalpindi, from December 2012 to August 2013. 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. 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. 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.

  11. Rapid phenotypic assay of antimycobacterial susceptibility pattern by direct mycobacteria growth indicator tube and phage amplified biological assay compared to BACTEC 460 TB.

    Science.gov (United States)

    El-Sayed Zaki, Maysaa; Goda, Tarek

    2007-03-01

    The performance of antimycobacterial susceptibility testing for the first line drugs (isoniazid, streptomycine, rifampicin and ethambutol) with mycobacteria growth indicator tube (MGIT) and by bacteriophage amplified biological assay by FAST-plaque TB-MDR were compared to automated radiometric BACTEC 460 TB system. This study was carried on 84 sputum samples of positive Zhiel-Neelsen (ZN) smears. Sputum samples were subjected to culture and antimycobacterial susceptibility testing by BACTEC 460 TB. Samples were also tested by direct susceptibility tests for isoniazid (INH), ethambutol, rifampicin (RIF) and streptomycine by MGIT. Sensitive and resistant isolates for RIF were further studied by FAST-plaque TB-MDR for RIF resistance. The commonest resistance pattern by BACTEC 460 TB was for INH (32%) followed by RIF (24%) either alone or in combination with other drugs. Multiple drugs resistance was 20%. The agreement between BACTEC 460 TB and direct MGIT for resistant strains was 100% for INH and ethambutol, 91.7% for rifampicin, 80% for streptomycine and was 90% for MDR. FAST-plaque TB-MDR detected correctly all RIF resistant strains and 97.2% of the sensitive strains. For majority of strains direct susceptibility tests were available within 6.34-6.404 days (95% confidence interval) with direct mycobacteria growth tube, while results for FAST-plaque TB-MDR appear within 10.5-11.5 days from the time that the sputum was received in the laboratory (95% confidence interval). From this study, we could conclude that direct MGIT AST is the quickest method for screening antimycobacterial susceptibility pattern for the drugs commonly used (INH, RIF, etambutol, streptomycin) as results were available within 6.34-6.404 days. Also FAST-plaque TB-MDR method is accurate for detection of rifampicin resistance after primary culture which can be used as a surrogate marker for presence of MDR strains and the results were available within 10.5-11.5 days.

  12. 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

  13. 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)

  14. La rebelión del Rif (1958-1959

    Directory of Open Access Journals (Sweden)

    María Concepción Ybarra

    1997-01-01

    Full Text Available La rebelión de las tribus rifeñas contra el gobierno de Marruecos, dos años después de la independencia de este país magrebí, es uno de los acontecimientos más ignorados de la historia del imperio alauita. El famoso Abdelkrím el Jattabi estuvo involucrado en dicho conflicto a la vez que el gobierno de Francia dirigido por De Gaulle. La misma España fue acusada de proteger a los rebeldes rífenos que amenazaban no sólo la estabilidad del nuevo régimen marroquí sino el mantenimiento del predominio francés en Argelia. En este trabajo se analizan las causas y consecuencias del «último levantamiento rifeño».The rebelion of the riffian tribes against Morocco government, two years after the independence of this mogrebi country, is one of the most ignored events of the alaouit Empire. The famous Abdelkrím El Khatabi was involved in said conflict at the same time that the french goverment ruled by De Gaulle. Spain itself was accused of protecting the riffian rebels which threatened not only the stability of the new moroccan government but also the continuation of the french hegemony in Algería. This report analizes the origin and consecuences of the «last riffian revolt».

  15. Evaluation of XpertMTB/RIF performance for diagnosis of ...

    African Journals Online (AJOL)

    Dr Mollel

    ³Kilimanjaro Clinical Research Institute, P.O. Box 2236, Moshi, Tanzania ... Demographic, clinical, laboratory and radiological data were .... All laboratory procedures were performed at Kibong'oto Hospital Laboratory. Regardless of their sputum results, all study participants had chest radiography, provided blood for full ...

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

    African Journals Online (AJOL)

    unhcc

    Xpert) assay for the diagnosis of tuberculosis (TB) and multidrug resistant ... diagnosis of MD/X/R-TB is less practiced due to shortage of laboratory facilities. ... Invalid/error results were repeated and the final results were registered. Laboratory staffs ...

  17. Shared Savings Program ACO Beneficiary-level RIF

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Centers for Medicare (CM) has created a set of standard analytical files that contain Shared Savings Program Accountable Care Organizations. Beneficiary-level...

  18. Spontane bastaarden bij Duizendguldenkruid (Centaurium Hill) in Nederland: Centaurium erythraea x littorale en C. littorale x pulchellum

    NARCIS (Netherlands)

    Bakker, den Henk C.

    1998-01-01

    The identification of Centaurium plants is sometimes difficult, partly because of the occurrence of hybrids, partly because of the insufficient set of diagnostic characters. The new diagnostic characters presented here are: form of the stigma / length of the pedicel / presence of papillae on pedicel

  19. 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.

  20. 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

  1. [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.

  2. 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

  3. 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

  4. 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.

  5. [Identification and antagonistic activities of an endophytic bacterium MGP3 isolated from papaya fruit].

    Science.gov (United States)

    Shi, Jingying; Liu, Aiyuan; Li, Xueping; Chen, Weixin

    2011-09-01

    Postharvest decay resulted from anthracnose caused by pathogens Colletotrichum gloeosporioides and blight diseases caused by Phytophthora nicotianae leads to significant loss of papaya fruits. In order to reduce such loss, we isolated endophytic bacteria that may possess powerful antagonistic activities toward these pathogens for effective biological control of anthracnose and blight diseases. The methods of dilution and inhibition circle were used for isolating and screening endophytic bacteria from papaya fruit. Based on morphological, physiological and biochemical characteristics, and homology analysis of the partial sequence of 16S rDNA, an endophytic bacterium was identified. The colonization of the antagonistic endophyte in papaya was detected by inoculating suspension of strains in caudices of papaya plant after Rifampicin-resistant mutants (rif(r)) induction. The effects on diseases caused by Colletotrichum gloeosporioides and Phytophthora nicotianae were tested by preharvest and postharvest experiments. One of the endophytic bacteria named MGP3 was selected from the papaya pericarp and identified as Pseudomonas aeruginosa (Accession No. JF708186). This bacterium was able to colonize in the laminae, leafstalk or pericarp of papaya, and strongly inhibit 10 phytopathogens. In the postharvest experiment, MGP3 inhibited 50% anthracnose and 71% blight of harvested papaya fruits. The application of MGP3 at five preharvest stages of papaya significantly reduced latent infection rate of Colletotrichum gloeosporioides and disease index of anthracnose. Antagonistic endophytic bacterium MGP3 isolated from papaya fruit had potential application value as a biological control agent.

  6. [Multi-drug resistant tuberculosis and the red queen - diagnosis speed is crucial].

    Science.gov (United States)

    Costeira, João; Pina, Jaime

    2007-01-01

    The multi-drug resistant Tuberculosis (MDRTB) is a huge menace to Tuberculosis control. The early detection of MDRTB is essential to best appropriate measures. The detection methods for drug resistance based in evaluation of the genetic determinants (genotypic methods), instead of phenotypic methods, allows for faster results, the possibility of direct application in clinical samples and simultaneous identification of Mycobacterium tuberculosis complex. The inpatients data analysis in the "Serviço de Pneumologia 2 do Hospital Pulido Valente", showed a high prevalence of MDRTB (10.3%). In 34.1% of the MDRTB patients the multi-drug resistance was not been identified, with a mortality ratio in this cases of 31% versus 18.4% in the subset of patients with resistance previously identified. Moreover the mortality ratio was worst in MDRTB/AIDS patients with 50% versus 15%, respectively. Targeting for rapid drug resistance detection, in hospitalized patients at "Serviço de Pneumologia 2 do Hospital Pulido Valente", the test INNO-LIPA Rif.TB, to identify the rifampicin resistance as a marker of multi-drug resistance, was evaluated. The test was performed in 113 samples and had a high ratio of sensitivity (91.6%), specificity (98%), positive predictive value (84, 6%) and negative predictive value (99%). Time to obtain the results was 7.6 days for the genotypic test versus 23.4 days to the phenotypic test (BACTEC MGIT 960). The INNO-LIPA Rif.TB test is, now, performed in every patient with smear-positive Tuberculosis with no previous knows resistance profile, with good outcome. Rev

  7. 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.

  8. 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.

  9. 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 ...

  10. [Ribosome engineering of streptomyces sp. FJ3 from Three Gorges reservoir area and metabolic product of the selected mutant strain].

    Science.gov (United States)

    Hai, Le; Huang, Yuqi; Liao, Guojian; Hu, Changhua

    2011-07-01

    To explore new resource from inactive actinomycete strains, we screened resistant mutant strains by ribosome engineering, and analyzed the products derived from the selected mutant strains. Three Gorges reservoir area-derived actinomycete strains including BD20, FJ3, WZ20 and FJ5 were used as initial strains, which showed no-antibacterial activities. The streptomycin-resistant (str(R)) mutants and rifampicin-resistant (rif(R)) mutants were screened by single colony isolation on streptomycin-containing plates and rifampicin-containing plates according to the method for obtaining drug-resistant mutants in ribosome engineering. The four initial strains and their str(R)-mutants and rif(R)-mutants were fermented in a liquid medium with the same composition. Mutants with anti-Staphylococcus aureus activity were obtained by paper chromatography. The components of fermentation broth were analyzed by high performance liquid chromatography (HPLC) and high performance liquid chromatography-mass spectrometry (LC-MS). Furthermore, FJ3 strain was identified by 16S rDNA and morphology. The minimal inhibitory concentration (MIC) of streptomycin and rifampicin for FJ3 was: 0.5 microg/mL and 110 microg/mL, respectively. Twenty-four strR-mutant strains and 20 rif(R)-mutant strains of FJ3 mutant strains were selected for bioassay. The result of the antibacterial activity screening demonstrated that six strains inhibited bacteria. Two strains (FJ3-2 and FJ3-6) were screened from the streptomycin-resistance mutants of inactive strain FJ3. The result of bioassay showed that the fermentation broth of FJ3-2 and FJ3-6 exhibited obvious anti-Staphylococcus aureus activity. The assay of paper chromatography showed that the active substance may be nucleic acid class antibiotic via using solvent system Doskochilova. Moreover, the results of HPLC and LC-MS exhibited that this substance may be thiolutin. Ribosome engineering for changing the secondary metabolic function of the inactive wild

  11. The Ghomarides Nappes, Rif Coastal Range, Morocco: A Variscan chip in the Alpine Belt

    Science.gov (United States)

    Chalouan, Ahmed; Michard, André

    1990-12-01

    The Ghomarides nappes are the uppermost basement nappes in the Rifan Alpine belt. Paleozoic rocks constitute the prominent part of these nappes, together with Triassic and younger cover sediments. Four nappes are distinguished, each one with a distinct stratigraphical sequence, especially for the Devonian and Carboniferous periods. Sedimentological and structural arguments plead for an initial location on the northern margin of the African continent. The main folding and metamorphic events are shown to be Eo-Variscan (late Acadian). Tectonic vergence was to the north (present coordinates). Late Variscan (Hercynian) shortening gave upright, NW-SE trending folds. Alpine ductile overprints are scarce except at the base of the lowest nappe where K/Ar phengite ages are about 25 Ma. The Ghomarides nappes correlate with the Malaguides nappes (Betic Cordilleras, southern Spain), the Kabylian (northern Algeria) and Calabrian (southern Italy) Paleozoic nappes, the Tuscan-South-Alpine basement and the Upper Austro-Alpine nappes. The proposed correlations allow us to restaure the southern margin of the Hercynian belt along northwestern Africa.

  12. 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

  13. 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…

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

    Science.gov (United States)

    1994-02-23

    SG17-10 9A 7,92 SW.11 Z TOLUENE i NO ND I, ODIO ugA SG17-10 9A M S=w I :2. TIUCHLADROETHYLENE (TCE) 0.010 ug/1SG17-10 9/17o92 1 10 IVINYLCHLA)RIDE ND...0.010 .&A SG40.1013 SW9021 FD ND NI) 0.010 .&49/2Z92 to !BEN2ENE_ SCAG 10 IFrHYLBENZENE i ND ND ODIO ugA _sG40 to ýM.P-XYLENE (SUM OF ISOMERS) ND ND

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

    NARCIS (Netherlands)

    Wang, C.W.; Mwakalinga, S.B.; Sutherland, C.J.; Schwank, S.; Sharp, S.; Hermsen, C.C.; Sauerwein, R.W.; Theander, T.G.; Lavstsen, T.

    2010-01-01

    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 to the bloodstream. Sexual

  16. 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)

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

    African Journals Online (AJOL)

    a 'South African revolution is inevitable'; and that the battle against the ... The fourth chapter starts with the rhetorical ques- tion, 'South Africa: A ... As for an industrial strike, a formidable political weapon, there would be considerable obstacles in the way of such an action. The main reason is that South Africa's labour force is ...

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

    African Journals Online (AJOL)

    struggle in America.' In their opinion our country is, because of its multi-ethnic population, more similar to Cyprus than to the United States. 'It is like other. African countries split by ... dependence of the United States on oil from the. Middle East. Secondly ... As for an industrial strike, a formidable political weapon, there would.

  19. Effectiveness of a Commercial Lactic Acid Bacteria Intervention Applied to Inhibit Shiga Toxin-Producing Escherichia coli on Refrigerated Vacuum-Aged Beef

    Directory of Open Access Journals (Sweden)

    Katie R. Kirsch

    2017-01-01

    Full Text Available Because of their antagonistic activity towards pathogenic and spoilage bacteria, some members of the lactic acid bacteria (LAB have been evaluated for use as food biopreservatives. The objectives of this study were to assess the antimicrobial utility of a commercial LAB intervention against O157 and non-O157 Shiga-toxigenic E. coli (STEC on intact beef strip loins during refrigerated vacuum aging and determine intervention efficacy as a function of mode of intervention application. Prerigor strip loins were inoculated with a cocktail (8.9±0.1 log10 CFU/ml of rifampicin-resistant (100.0 μg/ml; RifR O157 and non-O157 STEC. Inoculated loins were chilled to ≤4°C and treated with 8.7±0.1 log10 CFU/ml LAB intervention using either a pressurized tank air sprayer (conventional application or air-assisted electrostatic sprayer (ESS. Surviving STEC were enumerated on tryptic soy agar supplemented with 100.0 μg/ml rifampicin (TSAR to determine STEC inhibition as a function of intervention application method (conventional, ESS and refrigerated aging period (14, 28 days. Intervention application reduced STEC by 0.4 log10 CFU/cm2 (p0.05. Data indicate that the LAB biopreservative may assist beef safety protection when utilized within a multi-intervention beef harvest, fabrication, and aging process.

  20. 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.

  1. Pediatric multi-drug resistant-tuberculosis and HIV co-infection in a resource-limited setting: a case report.

    Science.gov (United States)

    Jouego, Christelle Géneviève; Agbor, Valirie Ndip; Noeske, Juergen; Manuel, Ndo Akono; Ayuk, Leo Njock

    2018-01-22

    Tuberculosis remains a major cause of morbidity and mortality worldwide, especially in developing countries. The diagnosis and treatment of multi-drug resistant tuberculosis (MDR-TB) in children remain a major limitation in this setting, largely due to difficulties in isolating Mycobacterium tuberculosis from pediatric specimens, management with toxic second line drugs, and practically the inexistence of contact tracing. In 2016, the World Health Organization (WHO) recommended a standardized 9-month regimen for adults and children in zones which are highly endemic for the human immunodeficiency virus (HIV). Herein, we present a case of pediatric MDR-TB/HIV co-infection highlighting the difficulties in treatment and the importance of contact tracing. A 6-year old male infant from the West Region of Cameroon infected with HIV who presented at a local health center with a 10 days history of productive cough associated with nocturnal fever and abdominal pains non responsive to broad spectrum antibiotics. A sputum sample analysis requested was smear positive for acid-fast bacilli, and he was initiated on quadritherapy for drug sensitive pulmonary tuberculosis. Since he was a household contact of the mother who was being managed in a referral hospital for MDR-TB at 1 month of treatment, and given his critical clinical situation, a gastric aspirate was repeated and sent for Xpert MTB/RIF to the Tuberculosis Reference Laboratory which was positive for a Rifampicin resistant strain of M. tuberculosis. The short 9 months regimen against MDR-TB was then initiated. During the course of his management, he developed minor side effects of the drugs which were managed symptomatically. Even though pediatric MDR-TB is difficult to confirm, it can be treated with favorable clinical outcomes using the short regimen recommended by the WHO. Experts involved in the control of tuberculosis over the national territory should consider adopting routine contact tracing for all cases of

  2. 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

  3. A tuberculose multirresistente e a rainha vermelha - A rapidez do diagnóstico é decisiva Multi-drug resistant tuberculosis and the red queen - Diagnosis speed is crucial

    Directory of Open Access Journals (Sweden)

    João Costeira

    2007-12-01

    in evaluation of the genetic determinants (genotypic methods, instead of phenotypic methods, allows for faster results, the possibility of direct application in clinical samples and simultaneous identification of Mycobacterium tuberculosis complex. The inpatients data analysis in the "Serviço de Pneumologia 2 do Hospital Pulido Valente", showed a high prevalence of MDRTB (10.3%. In 34.1% of the MDRTB patients the multi-drug resistance was not been identified, with a mortality ratio in this cases of 31% versus 18.4% in the subset of patients with resistance previously identified. Moreover the mortality ratio was worst in MDRTB/AIDS patients with 50% versus 15%, respectively. Targeting for rapid drug resistance detection, in hospitalized patients at "Serviço de Pneumologia 2 do Hospital Pulido Valente", the test INNO-LIPA Rif.TB, to identify the rifampicin resistance as a marker of multi-drug resistance, was evaluated. The test was performed in 113 samples and had a high ratio of sensitivity (91.6%, specificity (98%, positive predictive value (84, 6% and negative predictive value (99%. Time to obtain the results was 7.6 days for the genotypic test versus 23.4 days to the phenotypic test (BACTEC MGIT 960. The INNO-LIPA Rif.TB test is, now, performed in every patient with smear-positive Tuberculosis with no previous knows resistance profile, with good outcome.

  4. 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.

  5. Vertical and lateral distribution of fallout 137Cs and soil properties along representative toposequences of central Rif, Morocco.

    Science.gov (United States)

    Mesrar, Haytam; Sadiki, Abdelhamid; Faleh, Ali; Quijano, Laura; Gaspar, Leticia; Navas, Ana

    2017-04-01

    The purpose of this study is to understand and quantify the relationships between current 137 Cs inventories and the soil properties and the physiographic characteristics. A total of 36 cores were taken in seven transects with different slopes, lithology and land use. The analysis focused on the 137 Cs mass activity as well as inventories and its relationship with soil properties as grain size and organic matter. The mass activity of 137 Cs and the inventories varied between 3.6 and 63.7 Bq kg -1 and between 521.7 and 3304.4 Bq m -2 , respectively. At uncultivated soils, high concentrations of 137 Cs are located in the top 10 cm and decreased exponentially in depth. Cultivated soils record disturbed and heterogeneous 137 Cs profiles with values of mass activity and inventories up to 38.7 Bq kg -1 and 2510.8 Bq m -2 , respectively. The 137 Cs inventories were significantly higher in uncultivated soils (mean: 2086.9 Bq m -2 ) compared to cultivated soils (mean: 1397.1 Bq m -2 ). The 137 Cs mass activity showed a significant positive correlation with organic matter, silt and clay, but it was negatively correlated with sand and pH respectively. High levels of 137 Cs were found at altitudes between 500 m and 640 m a.s.l, and at slopes from 8° to 11°, as well as in dense scrub land and Fersialitic soils. A principal component analysis showed that more than 86.7% of the variance in 137 Cs mass activity was explained by the organic matter content and the land use. The results of this study provide insights into the effects of soil properties and physiographic factors on the behaviour of 137 Cs in soils of Mediterranean environments of North Africa and strengthen the reliability of this radioisotope as an erosion tracer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. 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.

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

    Science.gov (United States)

    2010-04-07

    mutual support between the two colonial powers at that time due to their poor diplomatic relationships.11 Marshal Lyau- tey’s personal Spanish- phobia ...and devoted believer in the civilizing virtues of colonialism, who built the French protectorate over Morocco. Despite a childhood spinal injury

  8. Stratigraphy, age and petrography of the Beni Issef successions (External Rif; Morocco): Insights for the evolution of the Maghrebian Chain

    Science.gov (United States)

    Di Staso, Angelida; Perrone, Vincenzo; Perrotta, Sonia; Zaghloul, Mohamed Najib; Durand-Delga, Michel

    2010-09-01

    In the Beni Issef Massif, nearly 30 km west of Chefchaouen (Morocco), the thickest post-nappe succession within the Rifian sector of the Maghrebian Chain seals the tectonic contact between the Intrarifian External Tanger and Loukkos Units, related to the Rifian External Domain. This succession is very important for the reconstruction of the deformation timing of the Rifian Maghrebids. The age of its base, in fact, is an important constraint for defining an upper boundary to the stacking of both the Intrarifian and Maghrebian Flysch Basin Units, because clasts fed by the Melloussa and Numidian Flysch Nappes are abundant in the conglomerate layers. Field and biostratigraphic analyses pointed out the presence of a Lower Beni Issef Fm, unconformable on the Intrarifian External Tanger and Loukkos Units, and an Upper Beni Issef Fm, unconformable on both the Intrarifian Units and the Lower Beni Issef Fm. The Lower Beni Issef Fm, 150 m thick, consists of lenticular conglomerates with huge blocks in a marly-clayey matrix, followed by marls and minor sandstones. It deposited in a siliciclastic platform, shows a fining upward trend and is affected by metre- to hectometre-sized, locally reversed, folds. Samples collected 45-50 m above the base of the formation resulted not older than Late Tortonian in age, but an older age for the base of the formation cannot be excluded. The Upper Beni Issef Fm, up to 550 m thick, starts with coarse conglomerates followed by medium- to coarse-grained well-bedded sandstones and by grey-blue marls and mudrocks. It indicates deposition in a channelized marine delta, with evolution towards pro-delta pelites, and shows sub-horizontal or gently dipping beds towards the east. Biostratigraphic data indicate a probable Messinian age for this formation. The composition of the arenites of both Lower Beni Issef and Upper Beni Issef Fms is quartzolithic and all samples show a notable content of monocrystalline well-rounded quartz and sedimentary lithic fragments. Detrital modes, all falling in the Quartzose Recycled and Transitional Recycled fields, suggest a provenance from recycling of sedimentary successions, easily recognizable in the Flysch Basin and External Units, mainly the Numidian Nappe sandstones. A Tortonian age of the Lower Beni Issef Fm would agree with the Late Serravallian age of the uppermost beds of the External Tanger Unit and indicate that the most probable age for the stacking of the Intrarifian Units falls in the Late Serravallian-Middle Tortonian time span. The Lower Beni Issef Fm was involved in a compressive tectonic phase testified by north-south striking folds. Later, probably during Messinian, the Upper Beni Issef Fm deposited in a younger intramontane basin, resting on both the Intrarifian Units and the Lower Beni Issef Fm. Successively, the Upper Beni Issef Fm was passively transported piggyback on top of the fold and thrust belt during later tectonic evolution of the Rifian Maghrebids. This tectonic evolution results quite similar to that recognized in the Tellian and Sicilian Maghrebids and also in the southern Apennines.

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

    Science.gov (United States)

    1992-08-07

    FINAL.. S AUG 2. 1 1992 L PREPARED FOR: .... ... McCLELLAN AFB IEM McCLELLAN AFB, CALIFORNIA 9652-599 ................... fr pu licrele se...Torts Branch, Civil Division Mr. William E. Michaels, Trial Attorney Washington, DC 20530 Todd & Associates 1 Attn: Mr. Clifford Wallman 2914 Domingo...El 5.9 Sediment Sampling ............................. . l 5.10 Soil Gas Sampling ........................... ... . 6.0 SAMPLE CUSTODY

  10. GeneXpert MTB/RIF on bronchoalveolar lavage samples in children with suspected complicated intrathoracic tuberculosis: a pilot study.

    Science.gov (United States)

    Walters, Elisabetta; Goussard, Pierre; Bosch, Corne; Hesseling, Anneke C; Gie, Robert P

    2014-11-01

    Children with complicated intrathoracic tuberculosis (TB) require rapid confirmation of TB diagnosis and of drug susceptibility to institute appropriate therapy. In a pilot study, we evaluated the feasibility and potential utility of GeneXpert (Xpert) on bronchoalveolar lavage (BAL) samples in children undergoing routine diagnostic bronchoscopy. We included children Children's Hospital, October 1, 2012-May 15, 2013. A minimum of two respiratory specimens in addition to BAL were obtained from each child. In addition to fluorescent smear microscopy and automated liquid culture performed on all samples, BAL samples were analyzed by Xpert. Drug susceptibility was confirmed by GenoType(®) MTBDRplus. Fourteen children (2 HIV positive, median age 16 months) were included. The Mantoux tuberculin skin test was positive in 11. On chest radiograph, six children had expansile pneumonia and nine had airway compression (one had both). The median duration of TB treatment before bronchoscopy was 8 days. TB was confirmed by either culture or Xpert from any sample in 11 (78%) children. Among 9/14 (64%) cases confirmed by culture, BAL Xpert was positive in 7 (78% sensitivity); in addition, Xpert confirmed 2 cases who had negative culture (14% additional diagnostic yield). Two drug resistant cases were identified: one by BAL Xpert and one from genotypic testing of a culture from gastric aspirate. All children were initiated on anti-TB treatment and responded well to therapy. BAL Xpert resulted in additional diagnostic yield and also in the rapid detection of drug resistance in children with complicated intrathoracic TB. The clinical impact of this modality should be further evaluated in children. © 2013 Wiley Periodicals, Inc.

  11. Stool Xpert MTB/RIF and urine lipoarabinomannan for the diagnosis of tuberculosis in hospitalized HIV-infected children.

    Science.gov (United States)

    LaCourse, Sylvia M; Pavlinac, Patricia B; Cranmer, Lisa M; Njuguna, Irene N; Mugo, Cyrus; Gatimu, John; Stern, Joshua; Walson, Judd L; Maleche-Obimbo, Elizabeth; Oyugi, Julius; Wamalwa, Dalton; John-Stewart, Grace

    2018-01-02

    Tuberculosis (TB) causes substantial morbidity and mortality in HIV-infected children. Sample collection and the paucibacillary nature of TB in children makes diagnosis challenging. Rapid diagnostic tools using easily obtained specimens are urgently needed. Hospitalized, HIV-infected children aged 12 years or less enrolled in a randomized controlled trial (NCT02063880) comparing urgent to post-stabilization antiretroviral therapy initiation in Kenya underwent TB evaluation. At enrollment, sputum or gastric aspirates were collected for TB culture and Xpert, stool for Xpert, and urine for lipoarabinomannan (LAM). When possible, a second sputum/gastric aspirate for culture was obtained. Stool Xpert and urine LAM performance were compared to reference sputum/gastric aspirate culture. Among 165 HIV-infected children, median age was 24 months [interquartile range (IQR) 13-58], median CD4% was 14.3 (IQR 8.9-22.0%), and 114 (69.5%) had severe immunosuppression. Thirteen (7.9%) children had confirmed TB (positive culture and/or Xpert). Sputum/gastric aspirate Xpert, stool Xpert, and urine LAM sensitivities were 60% [95% confidence interval (CI) 26-88%], 63% (95% CI 25-92%), and 43% (95% CI 10-82%), respectively. Specificity was 98% (95% CI 94-100%) for sputum/gastric aspirate Xpert, 99% (95% CI 95-100%) for stool Xpert, and 91% (95% CI 84-95%) for urine LAM. Stool Xpert and urine LAM sensitivity increased among children with severe immunosuppression [80% (95% CI 28-100) and 60% (95% Cl 15-95%)]. Stool Xpert had similar performance compared with sputum/gastric aspirate Xpert to detect TB. Urine LAM had lower sensitivity and specificity, but increased among children with severe immunosuppression. Stool Xpert and urine LAM can aid rapid detection of TB in HIV-infected children using easily accessible samples.

  12. The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar: an observational study.

    Science.gov (United States)

    Thit, Swe Swe; Aung, Ne Myo; Htet, Zaw Win; Boyd, Mark A; Saw, Htin Aung; Anstey, Nicholas M; Kyi, Tint Tint; Cooper, David A; Kyi, Mar Mar; Hanson, Josh

    2017-08-04

    The use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test's clinical utility is poorly defined outside sub-Saharan Africa. The study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. On enrolment, patients had a LF-LAM test performed according to the manufacturer's instructions. Clinicians managing the patients were unaware of the LF-LAM result, which was correlated with the patient's clinical course over the ensuing 6 months. The study enrolled 54 inpatients and 463 outpatients between July 1 and December 31, 2015. On enrolment, the patients' median (interquartile range) CD4 T-cell count was 270 (128-443) cells/mm 3 . The baseline LF-LAM test was positive in 201/517 (39%). TB was confirmed microbiologically during follow-up in 54/517 (10%), with rifampicin resistance present in 8/54 (15%). In the study's resource-limited setting, extrapulmonary testing for TB was not possible, but after 6 months, 97/201 (48%) with a positive LF-LAM test on enrolment had neither died, required hospitalisation, received a TB diagnosis or received empirical anti-TB therapy, suggesting a high rate of false-positive results. Of the 97 false-positive tests, 89 (92%) were grade 1 positive, suggesting poor test specificity using this cut-off. Only 21/517 (4%) patients were inpatients with TB symptoms and a CD4 T-cell count of < 100 cells/mm 3 . Five (24%) of these 21 died, three of whom had a positive LF-LAM test on enrolment. However, all three received anti-TB therapy before death - two after diagnosis with Xpert MTB/RIF testing, while the other received empirical treatment. It is unlikely that knowledge of the baseline LF-LAM result would have averted any of the study's other 11 deaths; eight had a negative test, and of the three patients with a positive test, two received anti-TB therapy before death, while one died from laboratory

  13. 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

  14. 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

  15. 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

  16. Introduction of some Odonata species (Insecta from northern Iran

    Directory of Open Access Journals (Sweden)

    Elham Elham Yoosefi Lafooraki

    2014-01-01

    *Anax parthenope, *Calopteryx splendens intermedia, Calopteryx splendens orientalis, *Coenagrion vanbrinckae, Crocothemis erythraea, *Epallage fatime, *Ischnura pumilio, *Lestes virevs, *Libellula depressa, *Orthetrum albistylum, Orthetrum sabina, *Platycnemis dealbata, Sympetrum fonscolombei and Sympetrum striolatum.

  17. Anurans Collected in West Malaysia

    DEFF Research Database (Denmark)

    Cedhagen, Tomas

    1997-01-01

    on the same stones just above the water surface on August 27. Other species observed were Bulo melanostictus, Bulo asper, Leptobrachium hasseltii, Kaloula pulchra, Limnonectes laticeps, Limflonectes macrodon, Rana erythraea, Rana glandulosa, Rana nicobarieflsis, and Rhacophorus prominanus....

  18. Algunos problemas geológicos de la Cordillera Bética y del Rif (Y discusión de varios modelos geotectónicos propuestos)

    OpenAIRE

    Sanz de Galdeano, Carlos

    1992-01-01

    En el presente capítulo se pretende mostrar algunos de los numerosos problemas geológicos pendientes en el ámbito Bético-Rifeño, a Ja vez que se presentan y discuten diversos modelos geotectónicos propuestos. Dado el número de los modelos existentes no podrán ser comentados extensamente y sólo se hará especial hincapié en algunos de ellos. Al mismo tiempo se presentan algunos rasgosgeológícos objetivos(al menos aparentemente), con el fin de sopesar las hipótesis y obtener al...

  19. 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.

  20. Evaluation of GeneXpert MTB/RIF for the detection of Mycobacterium tuberculosis and resistance to rifampin in extra-pulmonary specimens

    Directory of Open Access Journals (Sweden)

    Chema Marouane

    2015-01-01

    Conclusion: The GX is a simple, rapid technique for real-time PCR and has increased the sensitivity of detection of Mycobacterium tuberculosis complex. It must be part of the diagnostic arsenal of tuberculosis without replacing conventional microbiological tools and allow early diagnosis and appropriate treatment.

  1. Conversando con mujeres marroquíes en su espacio público y privado: entrevistas del Rif al Sáhara

    OpenAIRE

    Garro Sánchez, Inmaculada

    2018-01-01

    El siguiente estudio es una muestra de un trabajo de campo que todavía está en proceso basado en entrevistas a 97 mujeres en diferentes zonas tanto urbanas como rurales de Marruecos. De las ocho poblaciones analizadas mostraremos algunos de los datos obtenidos en tres de ellas como muestra representativa de pueblo de montaña (Chefchaouen), gran ciudad del interior (Beni Mellal) y una ciudad de la costa (Agadir). El objetivo principal es acercarnos a los usos que las mujeres de estas ciudades ...

  2. “ Sedimentology and geochemistry of recent alluvium of the wadi Beht mean (Furrow south western Rif, Morocco): dynamics of implementation and hydrological and climatic meanings ”

    OpenAIRE

    Ahmed LAABIDI; Lahcen Gourari; Abdellah EL HMAIDI

    2016-01-01

    The watershed of the river Beht is located northwest of Morocco and occupies the southwestern part of the Sebou basin. This study focuses on the sedimentological and geochemical analysis of current alluvial floodplain and meandering filling abandoned Middle Beht. The results revealed that the sediments exhibit an alkaline pH, low levels of carbonates, low values of the electrical conductivity and relatively high contents of organic matter mostly in the finest sediment. Deposits ar...

  3. 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.

  4. 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.

  5. 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.

  6. Punctuated Neogene tectonics and stratigraphy of the African-Iberian plate-boundary zone: concurrent development of Betic-Rif basins (southern Spain, northern Morocco)

    NARCIS (Netherlands)

    Sissingh, W.

    2008-01-01

    This paper integrates the sequence stratigraphic and tectonic data related to the Neogene geodynamic and palaeogeographic development of the African-Iberian plate boundary zone between Spain and Morocco. Though the dating of individual tectonostratigraphic sequences and their delimiting sequence

  7. 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.

  8. 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.

  9. 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

  10. 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,

  11. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 519 ... ... Ethnographic study of diarrhoeal diseases among under-five children in Mana District, Jimma Zone, Southwest Ethiopia, Abstract PDF. Mirgissa Kaba, Fekadu Ayele. Vol 19, No 1 (2005), Evaluation of a direct colorimetric assay for rapid detection of rifampicin resistant Mycobacterium tuberculosis ...

  12. 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...

  13. 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 ...

  14. Effect of an Alcaligenes faecalis inoculant strain on bacterial communities in flooded soil microcosms planted with rice seedlings

    NARCIS (Netherlands)

    Lin, M.; Smalla, K.; Heuer, H.; Elsas, van J.D.

    2000-01-01

    The fate and impact of Alcaligenes faecalis strain A1501R, a rifampicin-resistant derivative of a rice inoculant strain, were studied in flooded silt loam microcosms planted with rice seedlings. Selective plating revealed that strain A1501R survived at high, initially stable and later slowly

  15. 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...

  16. South African Medical Journal - Vol 86, No 1 (1996)

    African Journals Online (AJOL)

    Rifampicin resistance in Mycobacterium tuberculosis - rapid detection and implications in chemotherapy · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. G.S. Pretorius, F.A. Sirgel, H.S. Schaaf, P.D. van Helden, T.C. Victor ...

  17. 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

  18. 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.

  19. Effect of ofloxacin and norfloxacin on rifampicin pharmacokinetics in man.

    Science.gov (United States)

    Ezejiofor, Ndidi A; Brown, Sinyeofori; Barikpoar, Ebenezer; Orisakwe, Orish E

    2015-01-01

    The in vivo effects of norfloxacin (NXC) and ofloxacin (OXC) on rifampicin (RIF) pharmacokinetics were investigated in 5 apparently healthy volunteers aged 18-39 years after informed consent. The study was carried out in 3 phases with an interval drug washout period of at least 1 week in between the phases. In phase 1 (RIF alone), the subject received 600 mg of RIF. In phase 2 (RIF + OXC), 600 mg of RIF was coadministered with 200 mg of OXC. In phase 3 (RIF + NXC), each subject received 600 mg of RIF together with 400 mg of NXC after 1 week drug washout period. Drugs were taken orally with 350 mL of water after an overnight fast, and the subjects fasted 3 hours after the administration of drug. Plasma, saliva, and urine concentration of RIF were predetermined at 0 hour and then hourly until the 8th, 12th, 24th, and 48th hour. The urine samples were further collected at 72 hours after drug(s) administration using validated methods. Various pharmacokinetics parameters were calculated. NXC reduced the extent and rate of absorption of RIF. Various pharmacokinetic parameters of RIF significantly differ when administered alone or in combination with OXC and NXC. The mean saliva to plasma ratio of RIF concentration was approximately 0.15. The bioavailability indices of RIF in the saliva and plasma were similar in all the groups. Several pharmacokinetic parameters could be calculated using different body fluid concentrations of RIF. The determination of RIF levels in saliva may be useful in therapeutic drug monitoring and pharmacokinetic studies.

  20. 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

  1. 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.

  2. Detection of wide genetic diversity and several novel strains among non-avium nontuberculous mycobacteria isolated from farmed and wild animals in Hungary.

    Science.gov (United States)

    Rónai, Z; Eszterbauer, E; Csivincsik, Á; Guti, C F; Dencső, L; Jánosi, S; Dán, Á

    2016-07-01

    Besides Mycobacterium avium numerous nontuberculous Mycobacterium (NTM) species exist, which pose constant health risk to both humans and animals. The aim of our study was to identify non-avium NTM isolates from veterinary origin in Hungary, and to detect the occurrence of rifampicin resistance among them. Two hundred and twenty-five strains isolated between 2006 and 2013 from domestic and wild animals and veterinary important samples were identified on the basis of partial DNA sequences of different structural or coding genes, besides commercial kits and multiplex PCR. From 14 different sources, 28 NTM strains and 8 hitherto unidentified strain types were detected. Mycobacterium nonchromogenicum was the most frequently occurring strain (25·78%). Besides, new hosts and mycobacteria-related pathological symptoms were detected. Noticeable rifampicin resistance (42·76%) was found among 159 strains from six different host species. Furthermore, we described the problematics of strain-misidentifications using commercial kits. Our study identified the most common non-avium NTM strains in Hungary, and provided account of their occurrence, host range, and pathogenicity. The detected high rifampicin resistance among the strains isolated mainly from fallow and red deer clearly shows that more attention should be paid to the examination of wild animals especially to those ones which may have contact or shared territory with farmed animals. In domestic animal husbandry the maintenance of tuberculosis free status is of primary importance. As immunological cross-reactions due to NTM hamper the diagnosis of bovine tuberculosis, the precise identification of NTM strains would be essential in the veterinary diagnostics, especially for potentially zoonotic strains. This is the first study investigating the strain diversity of non-avium NTM in Hungary. © 2016 The Society for Applied Microbiology.

  3. An assessment of the potential of herbivorous insect gut bacteria to develop competence for natural transformation.

    Science.gov (United States)

    Ray, Jessica L; Andersen, Helga K; Young, Sandra; Nielsen, Kaare M; O'Callaghan, Maureen

    2007-01-01

    Whereas the capability of DNA uptake has been well established for numerous species and strains of bacteria grown in vitro, the broader distribution of natural transformability within bacterial communities remains largely unexplored. Here, we investigate the ability of bacterial isolates from the gut of grass grub larvae (Costelytra zealandica (White); Coleoptera: Scarabaeidae) to develop natural genetic competence in vitro. A total of 37 mostly species-divergent strains isolated from the gut of grass grub larvae were selected for spontaneous rifampicin-resistance. Genomic DNA was subsequently isolated from the resistant strains and exposed to sensitive strains grown individually using established filter transformation protocols. DNA isolated from wild-type strains was used as a control. None of the 37 isolates tested exhibited a frequency of conversion to rifampicin-resistance in the presence of DNA at rates that were significantly higher than the rate of spontaneous mutation to rifampicin-resistance in the presence of wild-type DNA (the limit of detection was approximately gut, we employed the competent bacterium Acinetobacter baylyi strain BD413 as a recipient species for in vivo studies. However, no transformants could be detected above the detection limit of 1 transformant per 10(3) cells, possibly due to low population density and limited growth of A. baylyi cells in grass grub guts. PCR analysis indicated that chromosomal Acinetobacter DNA remains detectable by PCR for up to 3 days after direct inoculation into the alimentary tract of grass grub larvae. Nevertheless, neither transforming activity of the DNA recovered from the alimentary tract of grass grubs larvae nor competence of bacterial cells recovered from inoculated larvae could be shown.

  4. The role of drug susceptibility testing in controlling drug resistant tuberculosis: Challenges and possibilities

    Directory of Open Access Journals (Sweden)

    Sven Hoffner

    2015-01-01

    Conclusions: Reliable and timely detection of drug-resistant TB is needed, which is best achieved with molecular assays. In this author's opinion, rapid detection of resistance to isoniazid should be included with rifampicin resistance examination. In MDR, timely detection of the XDR defining agents and PZA is urgently needed. Development and validation of such tests should be a priority, as well as establishing QMS for the implementation and routine use of molecular rapid diagnostics. Each country should develop national diagnostic algorithms for how, when and where rapid molecular assays should be used for early detection of drug-resistant TB.

  5. The influence of whole wheat feeding on salmonella infection and gut flora composition in broilers

    DEFF Research Database (Denmark)

    Friis-Holm, Lotte Bjerrum; Pedersen, Karl; Engberg, R.M.

    2005-01-01

    experimental groups. Quantitative cultivation of different groups of bacteria belonging to the natural intestinal microflora showed that whole wheat feeding significantly reduced the numbers of Clostridium perfringens in the intestinal tract of the birds. The present results indicate that the gizzard has......In an experiment with broilers infected with a rifampicin-resistant Salmonella Typhimurium strain at 15 days of a e, it was demonstrated that whole wheat feeding influenced the course of infection. The pH in the contents of the gizzard decreased as the amount of whole wheat in the diet increased...

  6. 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...

  7. 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)

  8. Efficacy of Rifampin Plus Clofazimine in a Murine Model of Mycobacterium ulcerans Disease.

    Directory of Open Access Journals (Sweden)

    Paul J Converse

    Full Text Available Treatment of Buruli ulcer, or Mycobacterium ulcerans disease, has shifted from surgical excision and skin grafting to antibiotic therapy usually with 8 weeks of daily rifampin (RIF and streptomycin (STR. Although the results have been highly favorable, administration of STR requires intramuscular injection and carries the risk of side effects, such as hearing loss. Therefore, an all-oral, potentially less toxic, treatment regimen has been sought and encouraged by the World Health Organization. A combination of RIF plus clarithromycin (CLR has been successful in patients first administered RIF+STR for 2 or 4 weeks. Based on evidence of efficacy of clofazimine (CFZ in humans and mice with tuberculosis, we hypothesized that the combination of RIF+CFZ would be effective against M. ulcerans in the mouse footpad model of M. ulcerans disease because CFZ has similar MIC against M. tuberculosis and M. ulcerans. For comparison, mice were also treated with the gold standard of RIF+STR, the proposed RIF+CLR alternative regimen, or CFZ alone. Treatment was initiated after development of footpad swelling, when the bacterial burden was 4.64±0.14log10 CFU. At week 2 of treatment, the CFU counts had increased in untreated mice, remained essentially unchanged in mice treated with CFZ alone, decreased modestly with either RIF+CLR or RIF+CFZ, and decreased substantially with RIF+STR. At week 4, on the basis of footpad CFU counts, the combination regimens were ranked as follows: RIF+STR>RIF+CLR>RIF+CFZ. At weeks 6 and 8, none of the mice treated with these regimens had detectable CFU. Footpad swelling declined comparably with all of the combination regimens, as did the levels of detectable mycolactone A/B. In mice treated for only 6 weeks and followed up for 24 weeks, there were no relapses in RIF+STR treated mice, one (5% relapse in RIF+CFZ-treated mice, but >50% in RIF+CLR treated mice. On the basis of these results, RIF+CFZ has potential as a continuation phase

  9. 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.

  10. Methylation of 23S rRNA caused by tlrA (ermSF), a tylosin resistance determinant from Streptomyces fradiae.

    Science.gov (United States)

    Zalacain, M; Cundliffe, E

    1989-01-01

    Ribosomes from Streptomyces griseofuscus expressing tlrA, a resistance gene isolated from the tylosin producer Streptomyces fradiae, are resistant to macrolide and lincosamide antibiotics in vitro. The tlrA product was found to be a methylase that introduces two methyl groups into a single base within 23S rRNA, generating N6,N6-dimethyladenine at position 2058. This activity is therefore similar to the ermE resistance mechanism in Saccharopolyspora erythraea (formerly Streptomyces erythraeus). Images PMID:2753855

  11. 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 ...

  12. Correlation between genotypic and phenotypic testing for resistance to rifampin in Mycobacterium tuberculosis clinical isolates in Haiti: investigation of cases with discrepant susceptibility results.

    Directory of Open Access Journals (Sweden)

    Oksana Ocheretina

    Full Text Available The World Health Organization has recommended use of molecular-based tests MTBDRplus and GeneXpert MTB/RIF to diagnose multidrug-resistant tuberculosis in developing and high-burden countries. Both tests are based on detection of mutations in the Rifampin (RIF Resistance-Determining Region of DNA-dependent RNA Polymerase gene (rpoB. Such mutations are found in 95-98% of Mycobacterium tuberculosis strains determined to be RIF-resistant by the "gold standard" culture-based drug susceptibility testing (DST. We report the phenotypic and genotypic characterization of 153 consecutive clinical Mycobacterium tuberculosis strains diagnosed as RIF-resistant by molecular tests in our laboratory in Port-au-Prince, Haiti. 133 isolates (86.9% were resistant to both RIF and Isoniazid and 4 isolates (2.6% were RIF mono-resistant in MGIT SIRE liquid culture-based DST. However the remaining 16 isolates (10.5% tested RIF-sensitive by the assay. Five strains with discordant genotypic and phenotypic susceptibility results had RIF minimal inhibitory concentration (MIC close to the cut-off value of 1 µg/ml used in phenotypic susceptibility assays and were confirmed as resistant by DST on solid media. Nine strains had sub-critical RIF MICs ranging from 0.063 to 0.5 µg/ml. Finally two strains were pan-susceptible and harbored a silent rpoB mutation. Our data indicate that not only detection of the presence but also identification of the nature of rpoB mutation is needed to accurately diagnose resistance to RIF in Mycobacterium tuberculosis. Observed clinical significance of low-level resistance to RIF supports the re-evaluation of the present critical concentration of the drug used in culture-based DST assays.

  13. 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.

  14. 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.

  15. [Inactivation and reactivation of antibiotic-resistant bacteria during and after UV disinfection in reclaimed water].

    Science.gov (United States)

    Huang, Jing-Jing; Tang, Fang; Xi, Jin-Ying; Pang, Yu-Chen; Hu, Hong-Ying

    2014-04-01

    Prevalence of antibiotic-resistant bacteria in wastewater effluents is concerned as an emerging contaminant. To estimate inactivation and reactivation potentials of antibiotic-resistant bacteria by UV disinfection, inactivation and reactivation of penicillin-, ampicillin-, cephalexin-, chloramphenicol-and rifampicin-resistant bacteria in the secondary effluent were studied under different UV doses. The results showed that the inactivation ratios of penicillin-, ampicillin-, cephalexin-and chloramphenicol-resistant bacteria were higher than 4-log, which was closed to that of total heterotrophic bacteria; however, the inactivation ratio of rifampicin-resistant bacteria was lower (3.7-log) under 20 mJ x cm(-2) UV exposure. After 22 h standing incubation, antibiotic-resistant bacteria widely reactivated. The colony forming ability of antibiotic-resistant bacteria was as high as 3-log when exposed to 20 mJ x cm(-2) UV light. Hence, conventional UV dose can not effectively control reactivation of antibiotic-resistant bacteria in reclaimed water by UV disinfection.

  16. [Introdoction of bioluminescence genes into silicate-dissolving bacteria strain NBT].

    Science.gov (United States)

    He, Linyan; Huang, Weiyi

    2004-07-01

    In this study, silicate-dissolving bacteria NBT strain was grown with 0.25% maltose as carbon source, and the rifampicin-resistance was generated by ultraviolet mutagenesis and streak naturalized to 200 microg x ml(-1). Through triparental cross, the luxAB genes were introduced into NBT-R200 at the help of pRK2013. The luminescence activity of the hybrid strain was tested, which indicated that all colonies had a high luminescence activity and kanamycin-, tetracyctine-and rifampicin-resistance. The NBT-R200 cells prepared from initial logarithmic growth phage were more likely to be sensitive to foreign DNA, and the maximum translocation frequency was up to 6.70 x 10(-5). In addition, the optimal mating ratio was 1:1:1. The potassium release ability from feldspar and the luminescence of luxAB genes marked silicate-dissolving bacteria RL85 strain were stable, and hence, the RL85 was available to rhizosphere microecology researches.

  17. [New diagnostic tests for tuberculosis in southern countries: from theory to practice in southern countries].

    Science.gov (United States)

    Bonnet, M

    2011-12-01

    Tuberculosis (TB) is responsible of 1.7 millions of deaths per year worldwide. In high burden countries sputum smear-microscopy diagnoses only half of the cases of pulmonary TB. It is unlikely that a new test will replace smear-microscopy in peripheral services in the short term. Between 2007 and 2009 WHO recommended the introduction of seven new tests or diagnostic approaches for high burden countries, for peripheral laboratories : 1) the optimisation of smear-microscopy using the revised smear-positive case definitions; 2) examination of two specimens instead of three; 3) examination of two specimens collected on the same day; 4) the use of light-emitting diode based fluorescence microscopy and for reference laboratories: 5) the use of liquid medium culture; 6) the use of rapid antigenic identification tests; 7) the rapid detection of rifampicin resistance. The recent development of a fully automated nucleic acid amplification test for both TB detection and detection of rifampicin resistance will soon improve the diagnosis of TB in HIV infected patients outside reference laboratories in high burden countries. Despite the recent advances in TB diagnosis, there is need for more research to develop point of care tests that do not depend on sputum specimens, that are practicable at peripheral units and that are highly sensitive in HIV infected patients and children. Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  18. The cost of antibiotic resistance depends on evolutionary history in Escherichia coli

    Science.gov (United States)

    2013-01-01

    Background The persistence of antibiotic resistance depends on the fitness effects of resistance elements in the absence of antibiotics. Recent work shows that the fitness effect of a given resistance mutation is influenced by other resistance mutations on the same genome. However, resistant bacteria acquire additional beneficial mutations during evolution in the absence of antibiotics that do not alter resistance directly but may modify the fitness effects of new resistance mutations. Results We experimentally evolved rifampicin-resistant and sensitive Escherichia coli in a drug-free environment, before measuring the effects of new resistance elements on fitness in antibiotic-free conditions. Streptomycin-resistance mutations had small fitness effects in rifampicin-resistant genotypes that had adapted to antibiotic-free growth medium, compared to the same genotypes without adaptation. We observed a similar effect when resistance was encoded by a different mechanism and carried on a plasmid. Antibiotic-sensitive bacteria that adapted to the same conditions showed the same pattern for some resistance elements but not others. Conclusions Epistatic variation of costs of resistance can result from evolution in the absence of antibiotics, as well as the presence of other resistance mutations. PMID:23914906

  19. 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.

  20. 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.

  1. 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 ...

  2. 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 ...

  3. Thyroid Autoimmunity is Associated with Decreased Cytotoxicity T Cells in Women with Repeated Implantation Failure

    Directory of Open Access Journals (Sweden)

    Chunyu Huang

    2015-08-01

    Full Text Available Thyroid autoimmunity (TAI, which is defined as the presence of autoantibodies against thyroid peroxidase (TPO and/or thyroglobulin (TG, is related to repeated implantation failure (RIF. It is reported that TAI was involved in reproductive failure not only through leading thyroid function abnormality, but it can also be accompanied with immune imbalance. Therefore, this study was designed to investigate the association of thyroid function, immune status and TAI in women with RIF. Blood samples were drawn from 72 women with RIF to evaluate the prevalence of TAI, the thyroid function, the absolute numbers and percentages of lymphocytes. The prevalence of thyroid function abnormality in RIF women with TAI was not significantly different from that in RIF women without TAI (c2 = 0.484, p > 0.05. The absolute number and percentage of T cells, T helper (Th cells, B cells and natural killer (NK cells were not significantly different in RIF women with TAI compared to those without TAI (all p > 0.05. The percentage of T cytotoxicity (Tc cells was significantly decreased in RIF women with TAI compared to those without TAI (p < 0.05. Meanwhile, Th/Tc ratio was significantly increased (p < 0.05. These results indicated that the decreased Tc percentage and increased Th/Tc ratio may be another influential factor of adverse pregnancy outcomes in RIF women with TAI.

  4. 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...

  5. Al-Naz‘ah al-Khārijīyah fī Afkāri wa Ḥarakāti al-Shaykh Ahmad Rifā‘i bi Kālī Sālāk

    OpenAIRE

    Muhlisin Sa'ad

    2014-01-01

    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 ...

  6. Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

    Science.gov (United States)

    Raizada, Neeraj; Khaparde, Sunil D; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M; Singh, Varinder; Umadevi, K R; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C H Surya; Mall, Shalini; Singh, Pooja; Saha, B K; Denkinger, Claudia M; Boehme, Catharina; Sarin, Sanjay

    2018-01-01

    Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising

  7. BRCA1 Directs the Repair Pathway to Homologous Recombination by Promoting 53BP1 Dephosphorylation

    Directory of Open Access Journals (Sweden)

    Mayu Isono

    2017-01-01

    Full Text Available BRCA1 promotes homologous recombination (HR by activating DNA-end resection. By contrast, 53BP1 forms a barrier that inhibits DNA-end resection. Here, we show that BRCA1 promotes DNA-end resection by relieving the 53BP1-dependent barrier. We show that 53BP1 is phosphorylated by ATM in S/G2 phase, promoting RIF1 recruitment, which inhibits resection. 53BP1 is promptly dephosphorylated and RIF1 released, despite remaining unrepaired DNA double-strand breaks (DSBs. When resection is impaired by CtIP/MRE11 endonuclease inhibition, 53BP1 phosphorylation and RIF1 are sustained due to ongoing ATM signaling. BRCA1 depletion also sustains 53BP1 phosphorylation and RIF1 recruitment. We identify the phosphatase PP4C as having a major role in 53BP1 dephosphorylation and RIF1 release. BRCA1 or PP4C depletion impairs 53BP1 repositioning, EXO1 recruitment, and HR progression. 53BP1 or RIF1 depletion restores resection, RAD51 loading, and HR in PP4C-depleted cells. Our findings suggest that BRCA1 promotes PP4C-dependent 53BP1 dephosphorylation and RIF1 release, directing repair toward HR.

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

    Science.gov (United States)

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

    2013-12-01

    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.

  9. 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.

  10. 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.

  11. 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.

  12. Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System.

    Science.gov (United States)

    Poole, Keith; Gilmour, Christie; Farha, Maya A; Mullen, Erin; Lau, Calvin Ho-Fung; Brown, Eric D

    2016-06-01

    A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5-linked aminoglycoside (AG), against wild-type Pseudomonas aeruginosa identified the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5-linked AGs, such as neomycin and ribostamycin, but not the clinically important 4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant lacking the AmgRS envelope stress response two-component system (TCS), which protects the organism from AG-generated membrane-damaging aberrant polypeptides and, thus, promotes AG resistance, an indication that RIF was acting via this TCS in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF-resistant RNA polymerase mutant, consistent with its potentiation of AG activity being dependent on RNA polymerase perturbation. PAR-inducible expression of the AmgRS-dependent genes htpX and yccA was reduced by RIF, suggesting that AG activation of this TCS was compromised by this agent. Still, RIF did not compromise the membrane-protective activity of AmgRS, an indication that it impacted some other function of this TCS. RIF potentiated the activities of 4,5-linked AGs against several AG-resistant clinical isolates, in two cases also potentiating the activity of the 4,6-linked AGs. These cases were, in one instance, explained by an observed AmgRS-dependent expression of the MexXY multidrug efflux system, which accommodates a range of AGs, with RIF targeting of AmgRS undermining mexXY expression and its promotion of resistance to 4,5- and 4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG resistance in P. aeruginosa, RIF might be a useful adjuvant in the AG treatment of P. aeruginosa infections. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. Survival of Dermatophilus congolensis in tropical clay soils submitted to different water potentials.

    Science.gov (United States)

    Martinez, D; Prior, P

    1991-10-01

    The survival of a rifampicin-resistant mutant of Dermatophilus congolensis in vertisol and oxisol soils from Guadeloupe and in their constitutive clays was studied using a pneumatic device for controlling water potentials (pF). Experiments were carried out at two pF values simulating the wet season and the dry season. Survival time depended on the type of soil and its water content. Organic matter had a protective effect on the microorganism in oxisol but not in vertisol. The pathogenicity of D. congolensis was preserved in the soils which could therefore act as temporary reservoirs of this pathogen. Long-term survival of this organism in soils mixed with water suggests that ponds and dipping tanks may constitute sources of infection for cattle.

  14. Mutagenic effects of lead (II) bromide.

    Science.gov (United States)

    Maslat, A O; Haas, H J

    1989-12-01

    The mutagenicity of lead (II) bromide (a combustion product of the gasoline additives lead (IV) tetraethyl and 1,2-dibromoethane) was investigated using various strains of bacteria. Taking prodigiosin (the red pigment) production as a marker, lead (II) bromide was found to be mutagenic in S. marcescens, leading to the appearance of white mutant colonies that are unable to produce such a pigment. This compound was also found to be mutagenic in E. coli KMBL1851, resulting in the appearance of rifampicin-resistant mutants in addition to Met+ and His+ revertants. Some of the S. marcescens mutants were found to be reversible, able to resynthesize prodigiosin. Differences in the sensitivity to antibiotics as well as in the biochemical properties were detected between the mutants and their corresponding wild types. Lead (II) bromide gave positive results in the Ames test performed with strain TA 1535.

  15. Mutagenic and genotoxic potential of direct electric current in Escherichia coli and Salmonella thyphimurium strains.

    Science.gov (United States)

    Gomes, Marina das Neves; Cardoso, Janine Simas; Leitão, Alvaro Costa; Quaresma, Carla Holandino

    2016-05-01

    Direct electric current has several therapeutic uses such as antibacterial and antiprotozoal action, tissues scarring and regeneration, as well as tumor treatment. This method has shown promising results in vivo and in vitro, with significant efficacy and almost no side effects. Considering lack of studies regarding direct electric current mutagenic and/or genotoxic effects, the present work evaluated both aspects by using five different bacterial experimental assays: survival of repair-deficient mutants, Salmonella-histidine reversion mutagenesis (Ames test), forward mutations to rifampicin resistance, phage reactivation, and lysogenic induction. In these experimental conditions, cells were submitted to an approach that allows evaluation of anodic, cathodic, and electro-ionic effects generated by 2 mA of direct electric current, with doses ranging from 0.36 to 3.60 Coulombs. Our results showed these doses did not induce mutagenic or genotoxic effects. © 2016 Wiley Periodicals, Inc.

  16. Update on the diagnosis and treatment of pulmonary tuberculosis.

    Science.gov (United States)

    Caminero Luna, J A

    2016-03-01

    Tuberculosis (TB) remains the most important human infectious disease. Currently, the TB diagnosis is still based on the clinical presentation, radiographic findings and microbiological results; all of which have sensitivity or specificity issues. For that reason, the immediate future involves rapid molecular microbiological techniques, in particular GeneXpert (which is more sensitive than bacilloscopy and is able to detect rifampicin resistance) and GenoType. The current six-month treatment for TB has remained unchanged for decades. Attempts to shorten this treatment have failed. In recent years, new drugs have been reported that could contribute to TB treatment in the near future, and are already being used in multi-drug-resistance TB. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  17. 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

  18. 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...

  19. 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

  20. 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.

  1. Mutations in rpoB and fusA cause resistance to rifampicin and fusidic acid in methicillin-resistant Staphylococcus aureus strains from a tertiary hospital in Malaysia.

    Science.gov (United States)

    Lim, King-Ting; Teh, Cindy Shuan Ju; Yusof, Mohd Yasim Mohd; Thong, Kwai-Lin

    2014-02-01

    The prevalence of resistance to rifampicin and fusidic acid among Malaysian strains of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. This study aimed to determine the mechanisms of rifampicin and fusidic acid resistance and the genetic diversity of MRSA strains from a Malaysian tertiary hospital. Minimum inhibitory concentrations (MIC) for 21 MRSA strains were determined by agar dilution test and Etest. The resistance genes, staphylococcal chromosome cassette mec (SCCmec) types, multilocus-sequence typing (MLST) types and spa types, were determined by PCR and DNA sequencing. MIC for rifampicin and fusidic acid resistance ranged from causes high rifampicin resistance while a mutational change (461Leu/Lys) in fusA was observed in seven strains highly resistant to fusidic acid. Five of the seven were also resistant to rifampicin (MIC 8 µg/ml) and carried a mutated rpoB gene (484Arg/His). No other acquired fusidic acid resistance gene (fusB, fusC or fusD) was detected. Most (14/21) of the strains belonged to clone ST239-III-t037. Three belonged to ST22-IV-t1378 and the remaining four to ST239-III-t2029, ST239-III-t421, ST1178-IV-t1107 and ST241-III-t363, respectively. The study showed that both rifampicin and fusidic acid resistance was associated with mutational change in rpoB and fusA, respectively. All rifampicin-resistant strains were from the same clone ST239-III-t037 whereas strains resistant to fusidic acid were genetically more diverse.

  2. 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 ...

  3. Synthesis, characterization and drug-delivery activity of rifampin ...

    Indian Academy of Sciences (India)

    Rif.) and further characterized by. WAFS, differential scanning calorimetry (DSC), ultraviolet– visible (UV–visible) techniques, and swelling properties [9]. PVA was also structurally modified with isopropylacryl amide [10], hydroxyl acids [11], ...

  4. Use of string test and stool specimens to diagnose pulmonary tuberculosis.

    Science.gov (United States)

    DiNardo, Andrew R; Hahn, Andrew; Leyden, Jacinta; Stager, Charles; Jo Baron, Ellen; Graviss, Edward A; Mandalakas, Anna M; Guy, Elizabeth

    2015-12-01

    The Xpert MTB/RIF (MTB/RIF) test has advanced the field of tuberculosis (TB) diagnostics; however, depending on age and HIV status, 10-85% of individuals with presumed pulmonary TB (PTB) are unable to produce sputum. The feasibility of using MTB/RIF and culture on stool and string test specimens from 13 adult patients with presumed PTB was studied. The string test was well tolerated with a median Wong Baker Faces score of 2. The string test had 100% sensitivity and specificity by MTB/RIF and 87.5% sensitivity and 100% specificity by culture. In stool, Mycobacterium tuberculosis DNA was detected in all cases of culture-confirmed PTB. The string test and stool provide diagnostic specimens that warrant further investigation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. 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...... 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...... found (1) that speakers who were perceived as experts induced greater levels of social contagion and lower levels of SS-RIF than non-expert speakers, and (2) that, likewise, trust in the speaker had similar mnemonic consequences, in that neutral speakers induced more social contagion and less SS...

  6. 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...

  7. A bio-economic farm household model to assess cropping systems in the Rift valley of Ethiopia : towards climate smart agriculture: do food security and mitigration goals match?

    NARCIS (Netherlands)

    Hengsdijk, H.; Verhagen, A.

    2012-01-01

    Modelling approach for rain fed farm household systems in the Central Rif Valley of Ethiopia to assess the possible effects of intensification of cereal-based cropping systems to farm income, mitigation of GHG emissions and other household indicators

  8. 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

    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. PMID:26785963

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Resistance to rifampicin: a review.

    Science.gov (United States)

    Goldstein, Beth P

    2014-09-01

    Resistance to rifampicin (RIF) is a broad subject covering not just the mechanism of clinical resistance, nearly always due to a genetic change in the β subunit of bacterial RNA polymerase (RNAP), but also how studies of resistant polymerases have helped us understand the structure of the enzyme, the intricacies of the transcription process and its role in complex physiological pathways. This review can only scratch the surface of these phenomena. The identification, in strains of Escherichia coli, of the positions within β of the mutations determining resistance is discussed in some detail, as are mutations in organisms that are therapeutic targets of RIF, in particular Mycobacterium tuberculosis. Interestingly, changes in the same three codons of the consensus sequence occur repeatedly in unrelated RIF-resistant (RIF(r)) clinical isolates of several different bacterial species, and a single mutation predominates in mycobacteria. The utilization of our knowledge of these mutations to develop rapid screening tests for detecting resistance is briefly discussed. Cross-resistance among rifamycins has been a topic of controversy; current thinking is that there is no difference in the susceptibility of RNAP mutants to RIF, rifapentine and rifabutin. Also summarized are intrinsic RIF resistance and other resistance mechanisms.

  16. Comparative Modulation of Levels of Oxidative Stress in the Liver of Anti-Tuberculosis Drug Treated Wistar Rats by Vitamin B12, Beta-Carotene, and Spirulina fusiformis: Role of NF-κB, iNOS, IL-6, and IL-10.

    Science.gov (United States)

    Joseph Martin, Sherry; Evan Prince, Sabina

    2017-11-01

    Isoniazid (INH) and Rifampicin (RIF) are known hepatotoxic agents. We compared the efficacy of Spirulina fusiformis and its active components vitamin B12 and beta-carotene in attenuating INH and RIF induced hepatotoxicity. We also tried to elucidate the inflammatory mechanism behind anti-tuberculosis drug induced hepatotoxicity. INH and RIF were administered to Wistar albino rats for 28 days to induce hepatotoxicity. S. fusiformis, vitamin B12, and beta-carotene were co-administered with INH and RIF and their hepatoprotective, antioxidant, and immunomodulatory roles were studied through blood and liver analysis. Changes induced by INH and RIF in antioxidants, cytokines (IL-6 and IL-10) and expression of Nuclear Factor-κB (NF-κB) and Nitric Oxide Synthase (iNOS) were also studied. Supplement treatment caused restoration of liver function parameters to normal levels along with reversal of inflammatory changes in IL-6 and IL-10 levels. Liver PCNA, iNOS, and NF-κB expression were reduced in the supplement treated tissues compared to INH and RIF treated rats as evidenced by immunohistochemistry and quantitative PCR. Correlation of IL-6 levels, PCNA, and iNOS with NF-κB showed its pivotal role in the inflammatory process. Study shows the pivotal role of NF-kB and the equivalence in antioxidant efficacy of vitamin B12 and beta-carotene compared to Spirulina fusiformis. J. Cell. Biochem. 118: 3825-3833, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Functional properties of peripheral CD8+ T cells in patients with repeated implantation failure.

    Science.gov (United States)

    Yin, Biao; Zeng, Yong; Wu, Tonghua; Yu, Shuyi; Xu, Jian; Liu, Su; Diao, Lianghui; Zhao, Zhenfu; Liang, Desheng; Li, Yuye

    2017-08-01

    CD8 + T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the amount of peripheral CD8 + T cells and their functions during the window of implantation in recurrent implantation failure (RIF) patients are limited. Peripheral blood was obtained from 56 women with RIF and 16 fertile women in the mid-luteal phase of the menstrual cycle, and the CD8 + T cells were determined by FACS analysis. No statistical differences in the proportion of peripheral CD8 + T cells were observed among the women with RIF and the control group. However, the levels of IFN-γ + and TNF-α + CD8 + T cells in the RIF group were significantly higher than those in the control group. The cytolytic activity and regulatory proportion of CD8 + T cells in RIF were similar to that in the control group. Our data indicated that the elevated expression levels of IFN-γ and TNF-α in peripheral CD8 + T cells may contribute to an impaired immune tolerance in women with RIF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. 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

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

    Science.gov (United States)

    Al-Musayeib, Nawal M; Mothana, Ramzi A; Matheeussen, An; Cos, Paul; Maes, Louis

    2012-04-20

    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. 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 IC(50) 4. 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 IC(50) < 10 μg/ml) and hence non-specific activities were noted in Cupressus sempervirens, Kanahia laniflora and Kniphofia sumarae. 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.

  20. 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.

  1. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Kim, Hye In; Kim, Tae Hyuk; Kim, Hosu; Kim, Young Nam; Jang, Hye Won; Chung, Jae Hoon; Moon, Seong Mi; Jhun, Byung Woo; Lee, Hyun; Koh, Won-Jung; Kim, Sun Wook

    2017-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:28081173

  4. 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)

  5. 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.

  6. 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.

  7. Sierra Nevada Rock Glaciers: Biodiversity Refugia in a Warming World?

    Science.gov (United States)

    Millar, C. I.; Westfall, R. D.

    2007-12-01

    Rock glaciers and related periglacial rock-ice features (RIFs) are common landforms in high, dry mountain ranges, and widely distributed throughout canyons of the Sierra Nevada, California, USA (Millar & Westfall, in press). Due to insulating rock carapaces, active rock glaciers (ice-cored) have been documented to maintain ice longer, and thus contribute to more enduring hydrologic output, under past warming climates than typical ice glaciers. This function has been suggested for the coming century. We propose a broader hydrologic and ecologic role for RIFs as temperatures rise in the future. For the Sierra Nevada, we suggest that canyons with either active or relict RIFs (Holocene and Pleistocene) maintain water longer and distribute water more broadly than canyons that were scoured by ice glaciers and are defined by primary river and lake systems. RIFs provide persistent, distributed water for extensive wetland habitat, rare in these otherwise barren, high, and dry locations. We mapped and assessed the area of wetlands surrounding active and relict RIFs from the central eastern Sierra Nevada; from these we delineated wetland vegetation community types and recorded plant species found in RIF-supported wetlands. Mid-elevation RIFs, likely inactive or with transient ice, develop soil patches on their rock matrix. At the Barney Rock Glacier (Duck Pass, Mammoth Crest), we inventoried plant species on all soil patches, and measured cover for each species per patch and total plant cover for the rock glacier. RIF landforms also appear to support high-elevation mammals. We show that American beaver (Castor canadensis) is associated with canyons dominated by active or relict RIFs and propose that the articulating, persistent, and distributed nature of streams makes dam-building easier than other canyons. Beavers further contribute to maintaining water and creating wetland habitat in upper watersheds by engineering ponds and marshes, and contributing to riparian extent. We

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Chemotherapy-associated changes of histopathological features of Mycobacterium ulcerans lesions in a Buruli ulcer mouse model.

    Science.gov (United States)

    Ruf, Marie-Thérèse; Schütte, Daniela; Chauffour, Aurélie; Jarlier, Vincent; Ji, Baohong; Pluschke, Gerd

    2012-02-01

    Combination chemotherapy with rifampin and streptomycin (RIF-STR) for 8 weeks is currently recommended by the WHO as the first-line treatment for Mycobacterium ulcerans infection (Buruli ulcer). To gain better insight into the mode of action of these antibiotics against established M. ulcerans infection foci and to characterize recovery of local immune responses during chemotherapy, we conducted a detailed histopathological study of M. ulcerans-infected and RIF-STR-treated mice. Mice were inoculated with M. ulcerans in the footpad and 11 weeks later treated with RIF-STR. Development of lesions during the first 11 weeks after infection and subsequent differences in disease progression between RIF-STR-treated and untreated mice were studied. Changes in histopathological features, footpad swelling, and number of CFU were analyzed. After inoculation with M. ulcerans, massive infiltrates dominated by polymorphonuclear leukocytes developed at the inoculation site but did not prevent bacterial multiplication. Huge clusters of extracellular bacteria located in large necrotic areas and surrounded by dead leukocytes developed in the untreated mice. Chemotherapy with RIF-STR led to a rapid drop in CFU associated with loss of solid Ziehl-Neelsen staining of acid-fast bacilli. Development of B-lymphocyte clusters and of macrophage accumulations surrounding the mycobacteria demonstrated the resolution of local immune suppression. Results demonstrate that the experimental M. ulcerans mouse infection model will be a valuable tool to investigate efficacy of new treatment regimens and of candidate vaccines.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Evaluation of antibiotic resistance to orally administrable antibiotics in staphylococcal bone and joint infections in one of the largest university hospitals in Germany: is there a role for fusidic acid?

    Science.gov (United States)

    Klein, Sabrina; Nurjadi, Dennis; Eigenbrod, Tatjana; Bode, Konrad A

    2016-02-01

    Bone and joint infections (BJIs) are often difficult to treat. Staphylococcus spp. is the major pathogen causing these infections, which is often associated with biofilm formation on prosthetic materials. Therapeutic measures are complex, ranging from surgical intervention to initial intravenous and supportive long-term oral antibiotic therapy. The options for oral antimicrobial therapy are limited, mainly due to the resistance profile of the causative pathogen and the unfavourable pharmacodynamic and pharmacokinetic properties of most antibiotics in biofilm. Data analysis over a 5-year period was performed on staphylococci isolated from BJI patients in the Orthopaedic Department of the University Hospital Heidelberg (Heidelberg, Germany) to assess the plausibility of fusidic acid (FA)-based alternative oral treatment regimens. Six percent of BJIs were caused by meticillin-resistant Staphylococcus aureus (MRSA), and multiresistance was common. Over 75% of MRSA in BJIs were resistant to the commonly used rifampicin (RIF)-based combinations. Resistance to FA-based combinations was high. However, over 80% were susceptible to the combination RIF+FA. In coagulase-negative staphylococci, resistance to RIF-based combinations was similar to FA-based combinations. Almost two-thirds of the isolates tested were susceptible to RIF+FA. These data suggest FA as a possible option as a substitution for RIF or as a combination companion in case of resistance or unavailability. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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

  19. 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.

  20. Attenuation of anti-tuberculosis therapy induced hepatotoxicity by Spirulina fusiformis, a candidate food supplement.

    Science.gov (United States)

    Martin, Sherry Joseph; Baskaran, Udhaya Lavinya; Vedi, Mahima; Sabina, Evan Prince

    2014-12-01

    Therapy using Isoniazid (INH) and Rifampicin (RIF) leads to induction of hepatotoxicity in some individuals undergoing anti-tuberculosis treatment. In this study, we assessed the effect of Spirulina fusiformis on INH and RIF induced hepatotoxicity in rats compared with hepatoprotective drug Silymarin. Induction of hepatotoxicity was measured by changes in the liver marker enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase). The antioxidant status was also analyzed in liver tissue homogenate and plasma by measurement of superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, and lipid peroxidation levels. We also aimed to study the binding and interactions of the transcription factors Pregnane X Receptor (PXR) and Farnesoid X Receptor (FXR) with INH, RIF, and representative active compounds of Spirulina fusiformis by in silico methods. The administration of INH and RIF resulted in significant (p Spirulina fusiformis was seen to protect the parameters from significant changes upon challenge with INH and RIF in a dose-dependent manner. This was corroborated by histological examination of the liver. The results of the in silico analyses further support the wet lab results.

  1. Potential of Zanthoxylum leprieurii as a source of active compounds against drug resistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Bunalema, Lydia; Fotso, Ghislain Wabo; Waako, Paul; Tabuti, John; Yeboah, Samuel O

    2017-02-02

    Tuberculosis (TB) is still a global health problem mainly due to development of resistance and co-infection with the Human immune Virus (HIV). Treatment of multi and extensively drug resistant TB requires use of second line drugs which are less efficacious, expensive and very toxic. This has necessitated a need to search for new treatment regimens especially from medicinal plants. Zanthoxylum leprieurii, a plant species from Rutaceae is used locally in the treatment of tuberculosis in Uganda. The aim of the study was to isolate, identify and characterize bio active compounds from Z. leprieurii stem bark with antimycobacterial activity. Crude extracts, fractions and compounds from air dried stem bark of Z. leprieurii were tested against pan sensitive (H37rv), isoniazid resistant (TMC 301) and rifampicin resistant (TMC 331) strains of M. tuberculosis using micro plate alamar blue assay. Isolation of active compounds was done by using column chromatography and thin layer chromatography. They were analysed using nuclear magnetic resonance spectroscopy and mass spectroscopy. The methanol extract had minimum inhibitory concentrations (MIC) of 47.5, 75.3 and 125.0 μg/ml on the pan sensitive strain, rifampicin resistant and isozianid resistant strains of M. tuberculosis respectively. The chloroform extract had MIC values of 260 μg/ml agnaist the pan sensitive strain and 156 μg/ml on the rifampicin resistant strain. Of the sixteen fractions from the methanol extract, fraction Za 4 (MIC = 6.3 μg/mL, 23.0 μg/mL, 11.7 μg/mL) and Za 6 (MIC = 11.7 μg/mL 31.2 μg/ml, 31.2 μg/ml) were the most active. Three acridone alkaloids; hydroxy-1, 3-dimethoxy-10-methyl-9-acridone (1), 1-hydroxy-3-methoxy-10-methyl-9-acridone (2) and 3-hydroxy-1, 5, 6-trimethoxy-9-acridone (3) were isolated from Za 4 and Za 6 . The MIC of compound 3 was found to be 5.1 μg/ml, 4.5 μg/ml and 3.9 μg/ml on H37rv, TMC 331 and TMC 301 while that of 1 was found to be 1.5 μg/ml, 8.3

  2. Nanoporous Anodic Alumina Platforms: Engineered Surface Chemistry and Structure for Optical Sensing Applications

    Directory of Open Access Journals (Sweden)

    Tushar Kumeria

    2014-07-01

    Full Text Available Electrochemical anodization of pure aluminum enables the growth of highly ordered nanoporous anodic alumina (NAA structures. This has made NAA one of the most popular nanomaterials with applications including molecular separation, catalysis, photonics, optoelectronics, sensing, drug delivery, and template synthesis. Over the past decades, the ability to engineer the structure and surface chemistry of NAA and its optical properties has led to the establishment of distinctive photonic structures that can be explored for developing low-cost, portable, rapid-response and highly sensitive sensing devices in combination with surface plasmon resonance (SPR and reflective interference spectroscopy (RIfS techniques. This review article highlights the recent advances on fabrication, surface modification and structural engineering of NAA and its application and performance as a platform for SPR- and RIfS-based sensing and biosensing devices.

  3. 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.

  4. 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...

  5. 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

  6. Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters.

    Science.gov (United States)

    Medellín-Garibay, S E; Cortez-Espinosa, N; Milán-Segovia, R C; Magaña-Aquino, M; Vargas-Morales, J M; González-Amaro, R; Portales-Pérez, D P; Romano-Moreno, S

    2015-12-01

    Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. 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.

  8. Sterol 27-hydroxylase gene dosage and the antiatherosclerotic effect of Rifampicin in mice.

    Science.gov (United States)

    Zurkinden, Line; Sviridov, Dmitri; Vogt, Bruno; Escher, Geneviève

    2018-02-28

    Sterol 27-hydroxylase (CYP27A1) catalyzes the hydroxylation of cholesterol to 27-hydroxycholesterol (27-OHC) and regulates cholesterol homeostasis. In Cyp27a1/ Apolipoprotein E ( ApoE ) double knockout (KO) mice fed with Western diet (WD), the atherosclerotic phenotype found in ApoE KO mice was reversed. As protective mechanism, up-regulation of Cyp3a11 and Cyp7a1 was proposed. Cyp27a1 heterozygote/ ApoE KO (het) mice, with reduced Cyp27a1 expression and normal levels of Cyp7a1 and Cyp3a11 , developed more severe lesions than ApoE KO mice. To analyze the contribution of Cyp3a11 to the protection of atherosclerosis development, Cyp3a11 was induced by Rifampicin (RIF) in ApoE KO and het mice. Males were fed with WD and treated daily with RIF (10 mg/kg ip) or vehicle for 4 weeks. Atherosclerosis was quantified in the aortic valve. Plasma lipids and 27-hydroxycholesterol (27-OHC), expression of cytochromes P450 and genes involved in cholesterol transport and bile acids (BAs) signaling in liver and intestine, and intestinal cholesterol absorption were analyzed. RIF increased expression of hepatic but not intestinal Cyp3a11 4-fold in both genotypes. In ApoE KO mice treated with RIF, we found a 2-fold decrease in plasma cholesterol, and a 2-fold increase in high-density lipoprotein/low-density lipoprotein ratio and CY27A1 activity. Intestinal cholesterol absorption remained unchanged and atherosclerotic lesions decreased approximately 3-fold. In het mice, RIF had no effect on plasma lipids composition, CYP27A1 activity, and atherosclerotic plaque development, despite a reduction in cholesterol absorption. In conclusion, the antiatherogenic effect of Cyp3a11 induction by RIF was also dependent on Cyp27a1 expression. © 2018 The Author(s).

  9. The HLA-G 14-bp polymorphism and recurrent implantation failure: a meta-analysis.

    Science.gov (United States)

    Fan, Wei; Huang, Zhongying; Li, Shangwei; Xiao, Zhun

    2017-11-01

    The human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion polymorphism was implicated in recurrent implantation failure (RIF), but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of HLA-G 14-bp polymorphism on RIF risk. A comprehensive search for relevant articles was conducted. The odds ratios (ORs) and 95% confidence intervals (CIs) for HLA-G 14-bp polymorphism and RIF were calculated. A total of five studies were included. In studies conducted in RIF patients and controls who had at least one spontaneous pregnancy, meta-analysis revealed no statistically significant association between the HLA-G 14-bp polymorphism and RIF in allele contrast and all genetic models in the overall population, but significant association was found in the population of Caucasian origin under allele contrast (OR = 1.73, 95% CI, 1.20, 2.50) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 3.09, 95% CI, 1.43, 6.65). In studies conducted in RIF patients and controls who had successful pregnancy following IVF-ET, the meta-analysis showed that there was statistically significant association between the HLA-G 14 bp polymorphism and RIF in allele contrast (OR = 1.74, 95% CI, 1.13, 2.67) and genetic models of +14 bp/+14 bp vs. -14 bp/-14 bp (OR = 10.20, 95% CI, 2.47, 42.14) and dominant model (OR = 4.34, 95% CI, 1.72, 10.92). No publication bias was found in the present studies. This meta-analysis suggested that the HLA-G 14-bp insertion allele may increase the risk of RIF in Caucasians. Further studies with large sample size of different ethnic populations are necessary.

  10. 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

  11. 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

  12. HLA-DQA1*0505 sharing and killer immunoglobulin-like receptors in sub fertile couples: report from the 15th International Histocompatibility Workshop.

    Science.gov (United States)

    Varla-Leftherioti, M; Keramitsoglou, T; Parapanissiou, E; Kurpisz, M; Kontopoulou-Antonopoulou, V; Tsekoura, C; Kamieniczna, M; Novokowska, B; Paparistidis, N; Vrani, V; Daniilidis, M; Spyropoulou-Vlachou, M

    2010-06-01

    This aim of the study was to investigate whether human leukocyte antigen (HLA)-DQA1*0505 sharing or the maternal killer immunoglobulin-like receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA) or repeated implantation failure (RIF). The study included 224 couples with RSA, 61 couples with RIF, 182 fertile couples, and 10 couples with successful in vitro fertilization and embryo transfer (IVF)/ET at first cycle. HLA-DQA1*0505 typing using polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) was performed in 185 RSA (117 with alloimmune abnormalities and 68 of autoimmune etiology), 61 RIF and 182 control couples, and KIR genotyping using polymerase chain reaction-sequence-specific primer (PCR-SSP) in 167 RSA and 55 RIF cases as well as 46 RSA and 10 IVF controls. No differences in DQA1*0505 sharing were found between patients and controls. In RSA and RIF women, the ratio of inhibitory to activating KIRs was slightly lower (1.53 and 1.85 vs 2.03 in controls). The analysis of maternal inhKIR and fetal HLA-C molecule pairs showed that the 'less inhibiting' combination KIR2DL3-C1 was found in higher percentage in subfertile (mainly RIF) than in fertile couples. In contrast, the percentage of cases possessing the 'strong inhibiting' combination KIR2DL1-C2 was lower in the RSA and RIF groups in comparison with that in the control groups (17.36% vs 23.91 and 16.36% vs 40%, respectively). In women with >or= 6 implantation failures, the KIR2DL1-C2 combination was not found in any of them (P = 0.0014), and the KIR2DL3-C1 combination was not found in the control IVF group. The results oppose the suggestion that increased HLA-DQA1*0505 sharing predispose to RSA or RIF. The KIR2DL3-C1 combination (or lack of the KIR2DL1-C2 one) is associated with implantation failure.

  13. Link between streptomycin and rifampicin mutation

    International Nuclear Information System (INIS)

    Chakrabarti, S.L.; Gorini, L.

    1975-01-01

    Introduction of strA mutations frequently make ''male'' strains of Escherichia coli permissive to bacteriophage T7; certain rif mutations reverse the permissive effect of strA mutation. Permissiveness of the strA mutation is accompanied by enhanced transcription of bacteriophage T7 genome. Introduction of the nonpermissive rif allele to the permissive strA strain reduces or abolishes the transcription of T7 genome. Thus, a link is implied in the functioning of the ribosome and the RNA polymerase(RNA nucleotidyltransferase, EC 2.7.7.6). (U.S.)

  14. 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

  15. Domain V of 23S rRNA contains all the structural elements necessary for recognition by the ErmE methyltransferase

    DEFF Research Database (Denmark)

    Vester, B; Douthwaite, S

    1994-01-01

    investigated what structural elements in 23S rRNA are required for specific recognition by the ErmE methyltransferase. The ermE gene was cloned into R1 plasmid derivatives, providing a means of inducible expression in Escherichia coli. Expression of the methyltransferase in vivo confers resistance...... to erythromycin and clindamycin. The degree of resistance corresponds to the level of ermE expression. In turn, ermE expression also correlates with the proportion of 23S rRNA molecules that are dimethylated at adenine 2058. The methyltransferase was isolated in an active, concentrated form from E. coli......The ErmE methyltransferase from the erythromycin-producing actinomycete Saccharopolyspora erythraea dimethylates the N-6 position of adenine 2058 in domain V of 23S rRNA. This modification confers resistance to erythromycin and to other macrolide, lincosamide, and streptogramin B antibiotics. We...

  16. Checklist and Simple Identification Key for Frogs and Toads from District IV of The MADA Scheme, Kedah, Malaysia

    Science.gov (United States)

    Jaafar, Ibrahim; Chai, Teoh Chia; Sah, Shahrul Anuar Mohd; Akil, Mohd Abdul Muin Md.

    2009-01-01

    A survey was conducted to catalogue the diversity of anurans in District IV of the Muda Agriculture Development Authority Scheme (MADA) in Kedah Darul Aman, Malaysia, from July 1996 to January 1997. Eight species of anurans from three families were present in the study area. Of these, the Common Grass Frog (Fejevarya limnocharis) was the most abundant, followed by Mangrove Frog (Fejevarya cancrivora), Long-legged Frog (Hylarana macrodactyla), and Common Toad (Duttaphrynus melanostictus). Puddle Frog (Occidozyga lima), Taiwanese Giant Frog (Hoplobatrachus rugulosus), and Banded Bullfrog (Kaluola pulchra) were rare during the sampling period, and only one Paddy Frog (Hylarana erythraea) was captured. A simple identification key for the anurans of this area is included for use by scientists and laymen alike. PMID:24575178

  17. 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

  18. Maize seed endophytic bacteria: dominance of antagonistic, lytic enzyme-producing Bacillus spp.

    Science.gov (United States)

    Bodhankar, Shrey; Grover, Minakshi; Hemanth, Sunaina; Reddy, Gopal; Rasul, Shaik; Yadav, Sushil Kumar; Desai, Suseelendra; Mallappa, Manjunath; Mandapaka, Maheswari; Srinivasarao, Ch

    2017-08-01

    Beneficial aspects of endophytic microorganisms have motivated researchers to explore plant endophytic world. The present study was aimed to isolate and characterize the seed-borne endophytic bacteria from diverse maize genotypes. Eighty maize seed endophytic bacteria (MSEB), isolated from 30 maize genotypes, were characterized using polyphasic approach. The dendrograms and phylogenetic tree generated on the basis of ARDRA analysis and metabolic profiling of endophytic bacteria revealed genotypic and biochemical diversity among MSEB. The 16S rDNA sequence analysis revealed Bacillus as the most dominant encountered genus affiliated with Phylum Firmicutes. Few isolates belonged to genus Staphylococcus, whereas one isolate was identified as Corynebacterium sp. under Phylum Actinobacteria. Majority of the MSEB isolates exhibited antagonism against phytopathogenic fungi, production of ammonia, and secretion of lytic enzymes; some isolates also exhibited indole acetic acid production, the traits of which can be helpful in endophytic establishment and advantageous to the host plant. Besides, many MSEB exhibited tolerance to salinity (10%), osmotic stress (40% PEG6000), and temperature (60 °C), indicating their possible application under stress conditions. Endophytic nature of the selected MSEB isolates was confirmed by tracking their presence in shoots, leaves, and roots of the host seedlings with the help of biochemical marker (rifampicin resistance). Thus, the MSEB identified in the present study can be explored as potential bioinputs for improving plant growth and productivity under stressed conditions, besides helping in understanding the plant-endophyte interactions.

  19. 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.

  20. Purification and Characterization of the Principal Antimutagenic Bioactive as Ethoxy-Substituted Phylloquinone from Spinach (Spinacea oleracea L.) Based on Evaluation in Models Including Human Lymphoblast TK+/-Cells.

    Science.gov (United States)

    Kumar, Sanjeev; Chatterjee, Suchandra; Tripathi, Jyoti; Gautam, Satyendra

    2016-11-23

    During in vitro analysis, spinach (Spinacea oleracea L.) leaf extracts displayed varying antimutagenicity when analyzed in models including human lymphoblast (TK +/- ) cell line (thymidine kinase gene mutation assay) and Escherichia coli MG1655 (rifampicin resistance assay) against chemically (ethyl methanesulfonate and 5-azacytidine) induced mutagenicity. Highest antimutagenicity was displayed by the quinone extract. The principal bioactive compound exhibited fluorescence in TLC at 366 nm (termed C4) resolved at R f 0.32 and t R 15.2 min in TLC and HPLC, respectively. On the TLC plate, three spots (C1-C3), observed at 254 nm, displayed comparatively lesser antimutagenicity. Furthermore, biochemical and spectroscopic analyses using MALDI-TOF MS and NMR indicated the nature of the potent compound (C4) as an ethoxy-substituted phylloquinone derivative [2-ethoxy-3-((E)-3,7,11,15-tetramethylhexadec-2-enyl)naphthalene-1,4-dione]. The C4 compound did not display any cytotoxicity and hence possesses significant nutraceutical-based intervention possibility to combat the onset of mutation-associated disease(s).

  1. A mid-gut microbiota is not required for the pathogenicity of Bacillus thuringiensis to diamondback moth larvae.

    Science.gov (United States)

    Raymond, Ben; Johnston, Paul R; Wright, Denis J; Ellis, Richard J; Crickmore, Neil; Bonsall, Michael B

    2009-10-01

    The mode of action of the entomopathogenic bacterium Bacillus thuringiensis (Bt) remains a matter of debate. Recent reports have claimed that aseptic lepidopteran hosts were not susceptible to Bt and that inoculation with mid-gut bacteria restores pathogenicity. These claims are controversial because larvae were rendered aseptic by consuming antibiotics, although the effect of these antibiotics on Bt was not examined. We tested the generality of the mid-gut bacteria hypothesis in the diamondback moth, Plutella xylostella using properly controlled experiments that investigated the effect of antibiotic consumption and absence of gut microbiota separately. We found that purified Bt toxin and spore/toxin mixtures were fully pathogenic to larvae reared aseptically. Persistence of antibiotics in larval tissues was implicated in reducing host mortality because larval consumption of the antibiotic rifampicin reduced the pathogenicity of rifampicin-sensitive Bt strains but not rifampicin-resistant strains. Inoculating larvae with Enterobacter sp. Mn2 reduced the mortality of larvae feeding on Bt HD-1 and the presence of a culturable gut microbiota also reduced the pathogenicity of the Bt toxin Cry1Ac, in agreement with other studies indicating that an intestinal microbiota can protect taxonomically diverse hosts from pathogen attack. As ingestion of antibiotics suppresses host mortality the vegetative growth of Bt in the host must be important for its pathogenicity. Furthermore, claims that aseptic larvae are not susceptible to Bt must be supported by experiments that control for the effect of administering antibiotics.

  2. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas.

    Science.gov (United States)

    Vogwill, T; Kojadinovic, M; MacLean, R C

    2016-05-11

    Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds. © 2016 The Authors.

  3. [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.

  4. Evaluation of cheddar cheese as a food carrier for delivery of a probiotic strain to the gastrointestinal tract.

    Science.gov (United States)

    Gardiner, G; Stanton, C; Lynch, P B; Collins, J K; Fitzgerald, G; Ross, R P

    1999-07-01

    Cheddar cheese was evaluated as a food carrier for the delivery of viable microorganisms of Enterococcus faecium (Fargo 688; Quest Int., Naarden, The Netherlands) to the gastrointestinal tract. This strain had previously been shown to possess properties required of a probiotic microorganism including the ability to relieve irritable bowel syndrome. The strain was found to survive to high numbers in Cheddar cheese during ripening at 8 degrees C for 15 mo (4 x 10(8) cfu/g) and in yogurt during storage at 4 degrees C for 21 d (4 x 10(7) cfu/g). In an in vitro model system, Cheddar cheese was found to have a greater protective effect than yogurt upon exposure of the probiotic culture to porcine gastric juice at pH 2. Subsequently, a feeding trial involving 8 pigs per group was performed in which a rifampicin-resistant variant of the probiotic strain was fed for 21 d at a mean daily intake of 1.3 x 10(10) cfu/d from Cheddar cheese or 3.7 x 10(9) cfu/d from yogurt. During the feeding period, Cheddar cheese yielded a significantly higher mean fecal probiotic count (2 x 10(6) cfu/g of feces) than did yogurt (5.2 x 10(5) cfu/g of feces). These data indicate that mature Cheddar cheese compares very favorably with fresh yogurt as a delivery system for viable probiotic microorganisms to the gastrointestinal tract.

  5. Use of Genotype MTBDRplus Assay for Diagnosis of Multidrug-Resistant Tuberculosis in Nepal

    Directory of Open Access Journals (Sweden)

    Elina Maharjan

    2017-01-01

    Full Text Available The main aims of this study were to study the patterns of mutations in rpoB, katG, and inhA genes in Mycobacterium tuberculosis strains isolated from patients from Nepal and to evaluate the performance of genotype MTBDRplus assay, taking conventional drug susceptibility testing as gold standard for diagnosis of MDR-TB. A total of 69 Mycobacterium tuberculosis strains isolated from 73 smear positive sputum samples from patients suspected of suffering from multidrug-resistant tuberculosis were used in our study. The drug susceptibility pattern of Mycobacterium tuberculosis isolated from these sputum specimens was determined by using genotype MTBDRplus assay taking conventional drug susceptibility testing as reference. The sensitivity and specificity of the genotype MTBDRplus assay for the detection of MDR-TB were found to be 88.7% and 100%, respectively. 88.7% of the rifampicin resistant isolates had mutations in rpoB gene. Similarly, 79.7% and 9.4% of isoniazid resistant isolates had mutations in katG and inhA genes, respectively. Genotype MTBDRplus assay was found to be very rapid and highly sensitive and specific method for diagnosis of MDR-TB and will be very helpful for early diagnosis of MDR-TB in high tuberculosis burden countries.

  6. The activity of flavones and oleanolic acid from Lippia lacunosa against susceptible and resistant Mycobacterium tuberculosis strains

    Directory of Open Access Journals (Sweden)

    Aline Castellar

    2011-10-01

    Full Text Available Tuberculosis (TB, caused by Mycobacterium tuberculosis, is the world's number one killer among infectious diseases. The search for new naturalproducts that can act as drugs against TB has received increased attention duringthe last years. In this work we describe the isolation and identification of the active antimycobacterial principles of the dichloromethane extract from Lippia lacunosa Mart. & Schauer, Verbenaceae. Compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis (susceptible and rifampicin resistantstrain using a redox bioassay. From the dichloromethane extract of L. lacunosa leaves, seven methoxy-flavones named cirsimaritin (1, eupatilin (2, eupatorin (3, salvigenin (4, 3'-O-methyl-eupatorin (5, 3',7-dimethoxy-5,6,4'- trihydroxyflavone (6, and 7'-O-methylapigenin (7, and one triterpene, named oleanolic acid (8, were isolated. All compounds were found to display antimycobacterial activity against susceptible strain, with MIC ranging from 25 to 200 µg/mL. None of them was active against rifampicin resistant strain. This is the first report in the antimycobacterial activity of 6-substituted flavones, as well as the first report of the occurrence of these substances in L. lacunosa.

  7. The activity of flavones and oleanolic acid from Lippia lacunosa against susceptible and resistant Mycobacterium tuberculosis strains

    Directory of Open Access Journals (Sweden)

    Aline Castellar

    2011-05-01

    Full Text Available Tuberculosis (TB, caused by Mycobacterium tuberculosis, is the world's number one killer among infectious diseases. The search for new naturalproducts that can act as drugs against TB has received increased attention duringthe last years. In this work we describe the isolation and identification of the active antimycobacterial principles of the dichloromethane extract from Lippia lacunosa Mart. & Schauer, Verbenaceae. Compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis (susceptible and rifampicin resistantstrain using a redox bioassay. From the dichloromethane extract of L. lacunosa leaves, seven methoxy-flavones named cirsimaritin (1, eupatilin (2, eupatorin (3, salvigenin (4, 3'-O-methyl-eupatorin (5, 3',7-dimethoxy-5,6,4'- trihydroxyflavone (6, and 7'-O-methylapigenin (7, and one triterpene, named oleanolic acid (8, were isolated. All compounds were found to display antimycobacterial activity against susceptible strain, with MIC ranging from 25 to 200 µg/mL. None of them was active against rifampicin resistant strain. This is the first report in the antimycobacterial activity of 6-substituted flavones, as well as the first report of the occurrence of these substances in L. lacunosa.

  8. Prevalence of drug resistance in clinical isolates of tuberculosis from GCC: a literature review from January 2002 to March 2013.

    Science.gov (United States)

    Areeshi, Mohammed Yahya; Bisht, Shekhar Chandra; Mandal, Raju Kumar; Haque, Shafiul

    2014-09-12

    The prevalence of drug resistance in clinical isolates of Mycobacterium tuberculosis from the Gulf Cooperation Council (GCC; Saudi Arabia, Qatar, Bahrain, Kuwait, Oman, United Arab Emirates [UAE]) countries was appraised using reports published between January 2002 and March 2013. A total of 11,393 tuberculosis (TB) isolates from the GCC were studied through published literature and were analyzed statistically. Most of the isolates were resistant to isoniazid, followed by streptomycin, rifampin, ethambutol, and pyrazinamide. The highest prevalence rate of multidrug-resistant-TB (MDR-TB) was found in UAE (9.2%), followed by Kuwait (5.9%) and Saudi Arabia (4.3%). The overall MDR-TB prevalence rate was recorded as 4.0% in the entire GCC region. Automated linear modeling revealed that isoniazid resistance had a strong relationship with the prevalence of MDR-TB in all the GCC countries and was found to be the strongest predictor for MDR-TB. Interestingly, rifampicin resistance was significantly associated with the prevalence of MDR-TB in Oman, Kuwait, and Saudi Arabia, while isoniazid was identified for UAE. On the basis of a number of reports and isolates, the principal component analysis showed that, among all GCC member countries, the highest burden of TB was in Saudi Arabia and Kuwait, and maximum drug resistance was present in UAE. The study demonstrates that the prevalence of MDR-TB in GCC countries is almost equal to other developing and developed countries, and requires immediate attention for surveillance and control.

  9. Multi drug resistant tuberculosis in Mosango, a rural area in the Democratic Republic of Congo.

    Directory of Open Access Journals (Sweden)

    Michel Kayomo Kaswa

    Full Text Available Multidrug Resistant Tuberculosis (MDR-TB is a serious threat which jeopardizes the worldwide efforts to control TB. The Democratic Republic of Congo (DRC is one of 27 countries with a high burden of MDR-TB. Data on the magnitude, trends, and the distribution of MDR-TB in DRC are scanty. Kinshasa, the capital city of DRC which accounts for 20% of all TB cases nationwide, is notifying more than 80% of all MDR suspects. We report here a cluster of MDR-TB cases that was investigated in the Mosango health district, in the Bandundu south Province, DRC in 2008. Phenotypic Drug Sensitivity Testing and DNA sequencing were performed on 18 sputum specimens collected from 4 MDR-TB suspects and 5 household contacts. Sequencing data confirmed that the 4 suspects were indeed Rifampicin resistant cases. Sequencing of the rpoB gene showed that 3 cases (patients A, B and D had a single mutation encoding a substitution to 526Tyr, 531Trp and 526Leu respectively. Patient C had a double mutation encoding a change to 531Leu and 633Leu. Two of the investigated cases died within 4 months of a second-line treatment course. Results highlight the need to enhance adequate laboratory services within the country for both clinical as well as surveillance purposes.

  10. 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.

  11. 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.

  12. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

    Science.gov (United States)

    Kojadinovic, M.; MacLean, R. C.

    2016-01-01

    Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas. We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas. Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds. PMID:27170722

  13. Small mammals as sentinels of antimicrobial-resistant staphylococci.

    Science.gov (United States)

    Kmeť, Vladimír; Čuvalová, Anna; Stanko, Michal

    2018-03-09

    A total of 39 coagulase-negative staphylococci and seven Staphylococcus aureus strains were isolated from small mammal feces, i.e., the striped field mouse (Apodemus agrarius) and the yellow-necked mouse (A. flavicollis) in two sampling areas, deciduous forest and karst plains. MALDI-TOF analysis revealed five species of coagulase-negative staphylococci: S. sciuri, S. hominis, S. warneri, S. haemolyticus, and S. xylosus. All strains were susceptible to tetracycline, linezolid, vancomycin, and teicoplanin. Three MRSA strains with the mecA gene were detected. The beta-lactamase gene blaZ was detected in ampicillin-resistant staphylococci and in the high-level resistant strains (oxacillin over 2 mg/L) mecA gene. The mecC gene was not detected by PCR. Erythromycin-resistant staphylococci harbored the ermC gene and/or the efflux gene msrA. There were no detectable dfr genes in trimethoprim-resistant staphylococci and the rifampicin-resistant strains were without mutation in the rpoB gene. In summary, wild small mammals may serve as sentinels of mecA-positive S. aureus with erythromycin resistance genes ermC and efflux msrA. Small mammals appear to be useful indicators of antibiotic resistance.

  14. Anti-mycobacterial activities of synthetic cationic α-helical peptides and their synergism with rifampicin.

    Science.gov (United States)

    Khara, Jasmeet S; Wang, Ying; Ke, Xi-Yu; Liu, Shaoqiong; Newton, Sandra M; Langford, Paul R; Yang, Yi Yan; Ee, Pui Lai Rachel

    2014-02-01

    The rapid emergence of multi-drug resistant tuberculosis (TB) and the lack of effective therapies have prompted the development of compounds with novel mechanisms of action to tackle this growing public health concern. In this study, a series of synthetic cationic α-helical antimicrobial peptides (AMPs) modified with different hydrophobic amino acids was investigated for their anti-mycobacterial activity, both alone and in synergistic combinations with the frontline anti-tuberculosis drug rifampicin. The addition of thiol groups by incorporating cysteine residues in the AMPs did not improve anti-mycobacterial activity against drug-susceptible and drug-resistant Mycobacterium tuberculosis, while the enhancement of peptide hydrophobicity by adding methionine residues increased the efficacy of the primary peptide against all strains tested, including clinically isolated multidrug-resistant mycobacteria. The peptide with the optimal composition M(LLKK)2M was bactericidal, and eradicated mycobacteria via a membrane-lytic mechanism as demonstrated by confocal microscopic studies. Mycobacteria did not develop resistance after multiple exposures to sub-lethal doses of the peptide. In addition, the peptide displayed synergism with rifampicin against both Mycobacterium smegmatis and Mycobacterium bovis BCG and additivity against M. tuberculosis. Moreover, such combination therapy is effective in delaying the emergence of rifampicin resistance. The ability to potentiate anti-TB drug activity, kill drug-resistant bacteria and prevent drug resistance highlights the potential utility of the peptide in combating multidrug-resistant TB. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. [Microbiological diagnosis of tuberculosis. 20 years in the province of Soria. Performance and basic opportunities of improvement].

    Science.gov (United States)

    García-De Cruz, S; Aldea-Mansilla, C; Campos-Bueno, A; Del Villar-Sordo, V

    2018-03-19

    The aim of the study was to describe the bacteriological diagnosis of the tuberculosis in the province of Soria (Spain), as well as to analyse the techniques diagnostic performance and the use of the microbiology laboratory regarding tuberculosis. An observational, descriptive and retrospective study was designed, including all patients with tuberculosis of any location that had their residence in the province of Soria. The period of study included patients diagnosed between 1994 and 2013 and a 24 months follow-up after the beginning of treatment was realized. A total of 337 patients were detected during the studied period. No sample was sent to the microbiology laboratory in more than 3% of the patients (23% in skeletal tuberculosis and 33% in lymphatic tuberculosis). Bacteriological confirmation was obtained in 80% and 32% were smear-positive. Specimens were culture on solid and in liquid media; 10% of the strains were only isolated in one type of media. There were 2.9% isoniazid-resistant strains, 0.3% multi-drug resistant strains, and 0.3% rifampicin-resistant strains. A total of 36% of smear-positive pulmonary tuberculosis patients had no specimens sent for a follow-up study. It is essential to combine the use of a liquid and a solid medium. Physicians should be encouraged to submit specimens for mycobacteriological diagnostic and follow-up. © The Author 2018. Published by Sociedad Española de Quimioterapia.

  16. 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.

  17. 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.

  18. 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.

  19. Inactivation and regrowth of antibiotic-resistant bacteria by PAA disinfection in the secondary effluent of a municipal wastewater treatment plant.

    Science.gov (United States)

    Huang, Jing Jing; Xi, Jing Ying; Hu, Hong Ying; Tang, Fang; Pang, Yu Chen

    2013-10-01

    Inactivation and microbial regrowth of penicillin-, ampicillin-, cefalexin-, tetracycline-, chloramphenicol-, and rifampicin-resistant bacteria were studied to explore risks associated with selection and regrowth of antibiotic-resistant bacteria after PAA disinfection. The results showed that after exposure to 20 mg/L PAA for 10 min, inactivation of ampicillin-resistant bacteria reached 2.3-log, which was significantly higher than that of total heterotrophic bacteria with a decrease of 2.0-log. In contrast, inactivation of tetracycline- resistant bacteria was significantly less efficient, reaching only 1.1-log. Chloramphenicol-and tetracycline-resistant bacteria, as well as total heterotrophic bacteria regrew more than 10 fold compared to those in the untreated wastewater sample with 22 h stilling culture after exposure to 2 or 5 mg/L PAA as for 10 min. Selection and potential regrowth of tetracycline-and chloramphenicol-resistant bacteria are potential risks when utilizing PAA disinfection, which may induce the spread of specific antibiotic-resistant bacteria in reclaimed water.

  20. Multiple Resistance at No Cost: Rifampicin and Streptomycin a Dangerous Liaison in the Spread of Antibiotic Resistance.

    Science.gov (United States)

    Durão, Paulo; Trindade, Sandra; Sousa, Ana; Gordo, Isabel

    2015-10-01

    Evidence is mounting that epistasis is widespread among mutations. The cost of carrying two deleterious mutations, or the advantage of acquiring two beneficial alleles, is typically lower that the sum of their individual effects. Much less is known on epistasis between beneficial and deleterious mutations, even though this is key to the amount of genetic hitchhiking that may occur during evolution. This is particularly important in the context of antibiotic resistance: Most resistances are deleterious, but some can be beneficial and remarkably rifampicin resistance can emerge de novo in populations evolving without antibiotics. Here we show pervasive positive pairwise epistasis on Escherichia coli fitness between beneficial mutations, which confer resistance to rifampicin, and deleterious mutations, which confer resistance to streptomycin. We find that 65% of double resistant strains outcompete sensitive bacteria in an environment devoid of antibiotics. Weak beneficial mutations may therefore overcome strong deleterious mutations and can even render double mutants strong competitors. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Strong decrease in streptomycin-resistance and absence of XDR 12 years after the Reorganization of the National Tuberculosis Control Program in the Central Region of Cameroon.

    Science.gov (United States)

    Sidze, Larissa Kamgue; Mouafo Tekwu, Emmanuel; Kuaban, Christopher; Assam Assam, Jean-Paul; Tedom, Jean-Claude; Eyangoh, Sara; Fouda, François-Xavier; Nolna, Désiré; Ntoumi, Francine; Frank, Matthias; Penlap Beng, Véronique N

    2014-01-01

    In the 1990s, resistance rates of 15% for streptomycin-resistance and 0.6% for multidrug-resistance (MDR) were reported from the Central Region of Cameroon. This work assesses drug resistant tuberculosis in this region 12 years after reorganization of the National Tuberculosis Control Program (NTCP). This cross-sectional study was conducted from April 2010 to March 2011 in Jamot Hospital in Yaoundé, Cameroon. Only patients with smear positive pulmonary tuberculosis were included. Sputa were cultured and subsequently underwent drug susceptibility testing (DST). All consenting individuals were tested for their HIV status. A total of 665 smear positive pulmonary tuberculosis patients were enrolled. The HIV prevalence was 28.5% (95%CI [25.2-32.1]). Of the 582 sputa that grew Mycobacterium tuberculosis complex species, DST results were obtained for 576. The overall resistance rate was 10.9% (63/576). The overall resistance rates for single drug resistance were: isoniazid-resistance 4.7% (27/576), streptomycin-resistance 3.3% (19/576), rifampicin-resistance 0.2% (1/576), kanamycin-resistance 0.2% (1/576) and ofloxacin-resistance 0.2% (1/576). The MDR rate was 1.1% (6/576) and no extensively drug resistant tuberculosis (XDR) was detected. The data show that reorganization of the NTCP resulted in a strong decrease in streptomycin-resistance and suggest that it prevented the emergence of XDR in the Central Region of Cameroon.

  2. The Pseudomonas secondary metabolite 2,4-diacetylphloroglucinol is a signal inducing rhizoplane expression of Azospirillum genes involved in plant-growth promotion.

    Science.gov (United States)

    Combes-Meynet, Emeline; Pothier, Joël F; Moënne-Loccoz, Yvan; Prigent-Combaret, Claire

    2011-02-01

    During evolution, plants have become associated with guilds of plant-growth-promoting rhizobacteria (PGPR), which raises the possibility that individual PGPR populations may have developed mechanisms to cointeract with one another on plant roots. We hypothesize that this has resulted in signaling phenomena between different types of PGPR colonizing the same roots. Here, the objective was to determine whether the Pseudomonas secondary metabolite 2,4-diacetylphloroglucinol (DAPG) can act as a signal on Azospirillum PGPR and enhance the phytostimulation effects of the latter. On roots, the DAPG-producing Pseudomonas fluorescens F113 strain but not its phl-negative mutant enhanced the phytostimulatory effect of Azospirillum brasilense Sp245-Rif on wheat. Accordingly, DAPG enhanced Sp245-Rif traits involved in root colonization (cell motility, biofilm formation, and poly-β-hydroxybutyrate production) and phytostimulation (auxin production). A differential fluorescence induction promoter-trapping approach based on flow cytometry was then used to identify Sp245-Rif genes upregulated by DAPG. DAPG enhanced expression of a wide range of Sp245-Rif genes, including genes involved in phytostimulation. Four of them (i.e., ppdC, flgE, nirK, and nifX-nifB) tended to be upregulated on roots in the presence of P. fluorescens F113 compared with its phl-negative mutant. Our results indicate that DAPG can act as a signal by which some beneficial pseudomonads may stimulate plant-beneficial activities of Azospirillum PGPR.

  3. 75 FR 55199 - Science and Technology Reinvention Laboratory Personnel Management Demonstration Project...

    Science.gov (United States)

    2010-09-09

    ... impressive statistics on increased job satisfaction and quality of employees versus that for the Federal... current position/job descriptions. The Factor Descriptors of each pay band will serve as an important... delegated examining; (6) Modified reduction-in-force (RIF) procedures; (7) Simplified job classification; (8...

  4. Evaluation of a PCR-Based Universal Heteroduplex Generator Assay as a Tool for Rapid Detection of Multidrug-Resistant Mycobacterium tuberculosis in Peru

    Science.gov (United States)

    Mayta, Holger; Gilman, Robert H.; Arenas, Fanny; Valencia, Teresa; Caviedes, Luz; Montenegro, Sonia H.; Ticona, Eduardo; Ortiz, Jaime; Chumpitaz, Rosa; Evans, Carlton A.; Williams, Diana L.

    2003-01-01

    Multidrug-resistant tuberculosis is an increasing health problem worldwide, especially in developing countries. The PCR-UHG-Rif assay, which detects mutations within the rpoB gene associated with rifampin resistance, was evaluated for its ability and reliability to detect and identify drug-resistant Mycobacterium tuberculosis in a developing country where tuberculosis is highly endemic. PMID:14662980

  5. REDUCTION OF INTRATUMORAL PH BY THE MITOCHONDRIAL INHIBITOR M-IODOBENZYLGUANIDINE AND MODERATE HYPERGLYCEMIA

    NARCIS (Netherlands)

    KUIN, A; SMETS, L; VOLK, T; PAANS, A; ADAMS, G; ATEMA, A; JAHDE, E; MAAS, A; RAJEWSKY, MF; VISSER, G; WOOD, P

    1994-01-01

    The interstitial pH of RIF-1 tumors was selectively lowered by i.p. administration of the mitochondrial inhibitor meta-iodobenzylguanidine (MIBG; 40-100 mg/kg), supported by sustained moderate hyperglycemia (plasma glucose concentration, 14 mM) in rats or by a single i.p. bolus injection of glucose

  6. 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.

  7. 78 FR 30941 - Frank Russell Company, et al.; Notice of Application

    Science.gov (United States)

    2013-05-23

    ... RIF is comprised of ten separate registered funds, each with its own investment objective, policies... separate funds in registration, each with its own investment objective, policies and restrictions.\\1\\ \\1... development of the investment program for the Fund all in accordance with the investment objectives, policies...

  8. Antibacterial Nucleoside-Analog Inhibitor of Bacterial RNA Polymerase.

    Science.gov (United States)

    Maffioli, Sonia I; Zhang, Yu; Degen, David; Carzaniga, Thomas; Del Gatto, Giancarlo; Serina, Stefania; Monciardini, Paolo; Mazzetti, Carlo; Guglierame, Paola; Candiani, Gianpaolo; Chiriac, Alina Iulia; Facchetti, Giuseppe; Kaltofen, Petra; Sahl, Hans-Georg; Dehò, Gianni; Donadio, Stefano; Ebright, Richard H

    2017-06-15

    Drug-resistant bacterial pathogens pose an urgent public-health crisis. Here, we report the discovery, from microbial-extract screening, of a nucleoside-analog inhibitor that inhibits bacterial RNA polymerase (RNAP) and exhibits antibacterial activity against drug-resistant bacterial pathogens: pseudouridimycin (PUM). PUM is a natural product comprising a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 6'-amino-pseudouridine. PUM potently and selectively inhibits bacterial RNAP in vitro, inhibits bacterial growth in culture, and clears infection in a mouse model of Streptococcus pyogenes peritonitis. PUM inhibits RNAP through a binding site on RNAP (the NTP addition site) and mechanism (competition with UTP for occupancy of the NTP addition site) that differ from those of the RNAP inhibitor and current antibacterial drug rifampin (Rif). PUM exhibits additive antibacterial activity when co-administered with Rif, exhibits no cross-resistance with Rif, and exhibits a spontaneous resistance rate an order-of-magnitude lower than that of Rif. PUM is a highly promising lead for antibacterial therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Clinical utility of a novel molecular assay in various combination strategies with existing methods for diagnosis of HIV-related tuberculosis in Uganda

    NARCIS (Netherlands)

    Ssengooba, Willy; Nakiyingi, Lydia; Armstrong, Derek T.; Cobelens, Frank G.; Alland, David; Manabe, Yukari C.; Dorman, Susan E.; Ellner, Jerrold J.; Joloba, Moses L.

    2014-01-01

    Low income, high-tuberculosis burden, countries are considering selective deployment of Xpert MTB/RIF assay (Xpert) due to high cost per test. We compared the diagnostic gain of the Xpert add-on strategy with Xpert replacement strategy for pulmonary tuberculosis diagnosis among HIV-infected adults

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

    Indian Academy of Sciences (India)

    Unknown

    ceramics viz. a hot pressed silicon nitride (HPSN), sintered alumina of two different grain sizes viz. 1 µm and. 25 µm, and a sintered silicon ... the sintered silicon carbide was found out to be linked to its previous thermal history. Keywords. Indentation fatigue .... This presence of a grain size effect in the RIF behaviour of the ...

  11. 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.

  12. 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)

  13. Rectangular ion funnel: a new ion funnel interface for structures for lossless ion manipulations.

    Science.gov (United States)

    Chen, Tsung-Chi; Webb, Ian K; Prost, Spencer A; Harrer, Marques B; Norheim, Randolph V; Tang, Keqi; Ibrahim, Yehia M; Smith, Richard D

    2015-01-06

    Structures for lossless ion manipulations (SLIM) have recently demonstrated the ability for near lossless ion focusing, transfer, and trapping in subatmospheric pressure regions. While lossless ion manipulations are advantageously applied to the applications of ion mobility separations and gas phase reactions, ion introduction through ring electrode ion funnels or more conventional ion optics to SLIM can involve discontinuities in electric fields or other perturbations that result in ion losses. In this work, we developed and investigated a new funnel design that aims to seamlessly couple to SLIM at the funnel exit. This rectangular ion funnel (RIF) was initially evaluated by ion simulations, fabricated utilizing printed circuit board technology, and tested experimentally. The RIF was integrated to a SLIM-time of flight (TOF) MS system, and the operating parameters, including RF, DC bias of the RIF electrodes, and electric fields for effectively interfacing with a SLIM, were characterized. The RIF provided a 2-fold sensitivity increase without significant discrimination over a wide m/z range and well matched to that of SLIM, along with greatly improved SLIM operational stability.

  14. Tanzania Journal of Health Research - Vol 19, No 1 (2017)

    African Journals Online (AJOL)

    Evaluation of XpertMTB/Rif performance for diagnosis of tuberculosis among HIV positive patients in northern Tanzania · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Edson W. Mollel, Jaffu O. Chilongola, Stellah G. Mpagama, Gibson S. Kibiki.

  15. The fine structure of the sperm and spermatid differentiation in the ...

    African Journals Online (AJOL)

    The fine structure of the sperm and spermatid differentiation in the brown mussel Perna perna. RIF. Bernard and A.N. Hodgson. Department of Zoology and Entomology, Rhodes University, Grahamstown. The mature sperm of Perna perna is 50-55 Ilm long and comprises three regions: a head, a mid-piece and a tail. The.

  16. Outcomes of a clinical diagnostic algorithm for management of ...

    African Journals Online (AJOL)

    Introduction: Diagnostic guidelines for Tuberculosis (TB) in HIV infected patients previously relied on microscopy where the value of initial antibiotic treatment for exclusion of pulmonary TB (PTB) was limited. New guidelines rely on the Xpert MTB Rif test (Xpert). However, the value of the antibiotic treatment remains unclear ...

  17. Resazurin tube method: rapid, simple, and inexpensive method for detection of drug resistance in the clinical isolates of mycobacterium tuberculosis.

    Science.gov (United States)

    Patil, Santosh S; Mohite, Shivajirao T; Kulkarni, Sunanda A; Udgaonkar, Usha S

    2014-10-01

    Tuberculosis (TB) remains a serious public health problem worldwide. The emergence of drug resistance and multidrug resistance (MDR) has become the main threat to TB treatment and control programs. Rapid detection is critical for the effective treatment of patients. In recent times, a new method using the colorimetric indicator resazurin has been proposed for drug susceptibility of Mycobacterium tuberculosis. In this study, the resazurin reduction assay was adapted to screw cap tubes. Using the Resazurin Tube Method (RTM), a total of 100 clinical isolates were tested against Rifampicin (RIF) and Isoniazide (INH). By visual reading, the minimum inhibitory concentrations (MICs) were obtained after eight days. The results obtained were compared with the gold standard proportion method. Excellent results were obtained for RTM with a sensitivity of 100% for both RIF and INH, with a specificity of 98.7 and 95.3%, respectively. Kappa is the measure of agreement between the RTM and proportion method (PM) for RIF and INH, which was found to be 0.972 and 0.935 for RIF and INH, respectively. The RTM appears to be a reliable method for the rapid and simultaneous detection of MDR-TB and drug susceptibility testing (DST) of M. tuberculosis. It is simple, inexpensive, and with no biohazard risk involved.

  18. The double ring sign in ultrasound of appendiceal mucocele. A case. Signo del doble anillo en la ecografia del mucocele apendicular. Presentacion de un caso

    Energy Technology Data Exchange (ETDEWEB)

    Menarques Irles, M.A.; Garcia Aguayo, F.J.; Esquitino Jaime, D.; Morales Sanchez, S.

    1993-10-01

    The combination of the findings of a sac-like anechoic mass in right iliac fossa (RIF) with the double ring sign in ultrasound together with an extrinsic, somooth-edged impression at the cecal pole, with no sign of the appendix in barium enema (BE) indicates a diagnosis of appendiceal mucocele. Author (11 refs.)

  19. 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

  20. 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

  1. 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)

  2. CME 9097 (ONLINE).indd

    African Journals Online (AJOL)

    Xpert also detects rifampicin (RIF) resistance, an indicator of more extensive drug resistance, allowing rapid initiation of effective second- line treatment. Definitive .... lower-level resistance and be overcome by higher doses of INH ..... efforts are being made to increase access to new drugs for DR-TB patients with severely.

  3. 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.

  4. Antioxidant, Hepatoprotective Potential and Chemical Profiling of Propolis Ethanolic Extract from Kashmir Himalaya Region Using UHPLC-DAD-QToF-MS

    Science.gov (United States)

    Wali, Adil F.; Avula, Bharathi; Ali, Zulfiqar; Khan, Ikhlas A.; Mushtaq, Ahlam; Rehman, Muneeb U.; Akbar, Seema; Masoodi, Mubashir Hussain

    2015-01-01

    The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt) from Kashmir Himalaya against isoniazid and rifampicin (INH-RIF) induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg) intraperitoneal (i.p.) injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight) distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS) were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids. PMID:26539487

  5. Antioxidant, Hepatoprotective Potential and Chemical Profiling of Propolis Ethanolic Extract from Kashmir Himalaya Region Using UHPLC-DAD-QToF-MS

    Directory of Open Access Journals (Sweden)

    Adil F. Wali

    2015-01-01

    Full Text Available The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt from Kashmir Himalaya against isoniazid and rifampicin (INH-RIF induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg intraperitoneal (i.p. injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids.

  6. 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.

  7. The Law on Reduction-in-Force: A Summary of Legislation and Litigation. ERS Monograph.

    Science.gov (United States)

    Zirkel, Perry A.; Bargerstock, Charles T.

    Declining enrollment and lower teacher turnover have forced many school districts to reduce the number of professional personnel employed. State legislatures, the courts, and local collective negotiations have been the principal scenes of legal activity concerning reduction in force (RIF). In this monograph, both technical legal information and…

  8. 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.

  9. Une nouvelle espèce de Geotrogus Guérin-Méneville pour la faune du Maroc et catalogue actualisé des espèces du genre (Coleoptera: Scarabaeoidea: Melolonthidae: Rhizotrogini)

    OpenAIRE

    Miessen , Geoffrey; Benyahia, Yousra; Brustel, Hervé

    2017-01-01

    Une nouvelle espèce de Geotrogus Guérin-Méneville, 1842 est décrite du Parc National de Talassemtane (Rif occidental, district de Chefchaouen, Maroc). Le genre regroupe à présent 43 espèces dont nous donnons un catalogue actualisé.

  10. Human chorionic gonadotropin potentially affects pregnancy outcome in women with recurrent implantation failure by regulating the homing preference of regulatory T cells.

    Science.gov (United States)

    Diao, Liang-Hui; Li, Guan-Gui; Zhu, Yuan-Chang; Tu, Wen-Wei; Huang, Chun-Yu; Lian, Ruo-Chun; Chen, Xian; Li, Yu-Ye; Zhang, Tao; Huang, Yong; Zeng, Yong

    2017-03-01

    Human chorionic gonadotropin (hCG) and regulatory T cells (Tregs) have been suggested to play important roles during the initial stage of pregnancy. However, the clinical relevance and mechanism of the effects of hCG on Treg functions in women with recurrent implantation failure (RIF) remain to be elucidated. Thirty-four RIF and twenty-three control women were included in the study. Endometrial and peripheral Tregs were analyzed by immunohistochemistry and flow cytometry, respectively. Tregs were generated from naïve CD4 + T cells by stimulation with anti-CD3/CD28 in the presence or absence of hCG, and the subsets were analyzed by flow cytometry, Western blotting, and qPCR. The percentages of endometrial FOXP3 + Tregs and peripheral CCR4 + FOXP3 + Tregs were significantly lower in the women with RIF than in the healthy controls. In addition, the percentages of CCR4 + FOXP3 + Tregs and TGF-β-expressing FOXP3 + Tregs were increased following the stimulation of naïve CD4 + T cells with anti-CD3/CD28, and these increases were concomitant with AKT and ERK dephosphorylation. The results of this study provide novel evidence supporting a role of hCG in regulating the differentiation of peripheral FOXP3 + Tregs. The alterations of circulating Tregs may positively affect the pregnancy outcomes of patients with a history of RIF. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. [Susceptibility of M. tuberculosis to antituberculosis drugs as determined by two methods, in Sucre state, Venezuela].

    Science.gov (United States)

    Mendoza, Rosmy; De Donato, Marcos; de Waard, Jacobus H; Takiff, Howard; Bello, Teresita; Chirinos, Gladys

    2010-12-01

    The objective of this study was to evaluate the resistance to isoniazid (INH), rifampicin (RIF), streptomycin (STR) and ethambutol (EMB), with the Canetti's proportions method (PM) and the nitrate reductase assay (NRA) of 59 clinical strains of Mycobacterium tuberculosis, isolated in the period of august 2005 to december 2006, in Sucre state, Venezuela. Primary and acquired drug resistance was 6.3% and 14.3%, respectively. Only one strain was found to be multidrug resistant (MDR). The overall agreement between the NRA and PM was 100% for INH, RIF and EMB, and 96% for STR. The time to obtain results was 10 to 14 days for the NRA, compared to 42 days for the PM. The NRA was easy to perform and therefore represents a useful tool for rapid and accurate determination of drug-resistant M. tuberculosis. The sequence of the rpoB gene of the RIF resistant strain demonstrated a never described mutation (change in the codon 456; TCG > CAG) in the hypervariable region of 81 base pairs where most of the mutations of the RIF resistant strains have been reported. Comparison of our results with those of the last resistance prevalence study carried out in the years 1998-1999, shows a decrease in the studied area.

  12. Delay in commencing treatment for MDR TB at a specialised TB ...

    African Journals Online (AJOL)

    Culture and drug sensitivity testing (DST) takes 8 weeks or longer to obtain results while line probe assays (LPAs) can give a result in hours. LPAs and the GeneXpert MTB/Rif (GX) are ground-breaking discoveries for TB diagnosis. However, they are not easily accessible or available to those needing it, so culture and ...

  13. 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

  14. Impact of Ramadan Intermittent Fasting on Oxidative Stress Measured by Urinary 15-F2t-Isoprostane

    Science.gov (United States)

    Faris, Mo'ez Al-Islam Ezzat; Hussein, Rand Nidal; Al-Kurd, Ref'at Ahmad; Al-Fararjeh, Mohammed Ahmed; Bustanji, Yasser Khalil; Mohammad, Mohammad Khalil

    2012-01-01

    Fasting and caloric restriction have been associated with reduced incidence of chronic diseases and cancers. These effects have been attributed to reduced oxidative stress. Since Ramadan intermittent fasting (RIF) has been associated with reduced caloric intake, it was hypothesized that RIF would alleviate oxidative stress in healthy volunteers. The study was designed to elucidate the impact of RIF on oxidative stress measured by 15-F2t-Isoprostane (15FIP). Fifty healthy subjects (23 men and 27 women) who intended to fast Ramadan were recruited. Urine and serum sampling and anthropometric and dietary assessments were conducted one week before Ramadan (T0), at the end of the third week of Ramadan (T1), and one month after Ramadan (T2). Biochemical measurements included urinary 15FIP, creatinine, and hematological indices. Results revealed that the urinary level of 15FIP measured at T0 was normal, while they showed a significantly (P < 0.05) higher level when measured at T1 concomitant with a significant (P < 0.05) increase in the body weight and total body fat percent. In conclusion, results suggest that increased body weight is associated with increased lipid peroxidation and oxidative stress, and the impact of RIF on oxidative stress is mediated by the changes in body weight at the end of the month. PMID:23150812

  15. 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.

  16. Ecological risk assessment guidance for preparation of remedial investigation/feasibility study work plans

    Energy Technology Data Exchange (ETDEWEB)

    Pentecost, E.D.; Vinikour, W.S. [Argonne National Lab., IL (United States)

    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.

  17. ORIGINAL ARTICLE

    African Journals Online (AJOL)

    number of MTB strain is less than 39,062,500 and. 4,444,444,444 with selective effect to INH and RIF ..... random generated cycles was used as the empirical data to further assess the simulated results of the ... Basically, the process is a form of pseudo sampling from the original dataset to determine the variability.

  18. 76 FR 81840 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

    Science.gov (United States)

    2011-12-29

    ... and Hazardous Substances Pollution Contingency Plan; National Priorities List: Deletion of the Hipps... constitutes Appendix B of 40 CFR part 300, which is the National Oil and Hazardous Substances Pollution... compounds detected in Site soil were present at concentrations of toxicological concern. The RI/FS was...

  19. 78 FR 47205 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

    Science.gov (United States)

    2013-08-05

    ... and Hazardous Substances Pollution Contingency Plan; National Priorities List: Direct Deletion of the... concentrations of benzo(a)pyrene and arsenic. The soil concentrations ranged from 1 mg/kg to 90 mg/kg for arsenic... for the ODEQ conducted a RI/FS including field sampling and investigation activities of soil, sediment...

  20. Deformation monitoring in Zafarraya fault and Sierra Tejeda antiform (Betic cordillera, Spain) using satellite radar interferometry

    NARCIS (Netherlands)

    Ruiz-Armenteros, A.M.; Delgado, J.M.; Sousa, J.J.; Hanssen, R.F.; Caro, M.; Gil, A.J.; Galindo-Zaldívar, J.; Galdeano, C.S. de

    2015-01-01

    The Betic-Rif cordilleras are build-up in the western Mediterranean by the deformations related to the Eurasian-African plate boundary. The recent NW-SE convergence produces the simultaneous development of large folds and faults in the central part of the Internal Zones of the Betic Cordilleras,

  1. 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.

  2. 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).

  3. 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).

  4. 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).

  5. Reflectometric measurement of n-hexane adsorption on ZnO2 nanohybrid film modified by hydrophobic gold nanoparticles

    Science.gov (United States)

    Sebők, Dániel; Csapó, Edit; Ábrahám, Nóra; Dékány, Imre

    2015-04-01

    Zinc-peroxide/poly(styrenesulfonate) nanohybrid thin films (containing 20 bilayers: [ZnO2/PSS]20, d ∼ 500 nm) were prepared using layer-by-layer (LbL) method. The thin film surface was functionalized by different surface modifying agents (silanes, alkylthiols and hydrophobized nanoparticles). Based on the experimental results of quartz crystal microbalance (QCM) and contact angle measurements (as prequalifications) the octanethiol covered gold nanoparticles (OT-AuNPs) were selected for further vapour adsorption studies. Reflectometric interference spectroscopy (RIfS) was used to measure n-hexane vapour adsorption on the original and modified nanohybrid films in a gas flow platform. The thin film provides only the principle of the measurement (by interference phenomenon), the selectivity and hydrophobicity is controlled and enhanced by surface functionalization (by dispersion interaction between the alkyl chains). The interference pattern shift (Δλ) caused by the increase of the optical thickness of the thin film due to vapour adsorption was investigated. It was found that due to the surface functionalization by hydrophobic nanoparticles the effect of water vapour adsorption decreased significantly, while for n-hexane opposite tendency was observed (the effective refractive index and thus the interference pattern shift increased drastically). The correlation between QCM technique and optical method (RIfS) was specified: linear specific adsorbed amount vs. wavelength shift calibration curves were determined in the pr = 0-0.4 relative vapour pressure range. The thin film is suitable for sensorial application (e.g. volatile organic compound/VOC sensor).

  6. 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

  7. Rifampicin: Cytotoxic and Genotoxic Action | Olufunsho | Nigerian ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the cytotoxic and genotoxic effects of Rif to better understand its mutagenicity. The study was carried out using three methods: Standard Allium cepa (Linn.) assay, modified Ames test (which is a modification of the standard Ames assay) and micronucleus test (an in vivo method ...

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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)

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Management of Latent Tuberculosis Infection Among Healthcare Workers: 10-Year Experience at a Single Center.

    Science.gov (United States)

    Arguello Perez, Esther; Seo, Susan K; Schneider, William J; Eisenstein, Cynthia; Brown, Arthur E

    2017-11-29

    The risk of infection with Mycobacterium tuberculosis among healthcare workers (HCWs) is estimated to be higher than the general population. However, HCW acceptance and compliance with available latent tuberculosis infection (LTBI) treatment regimens has been problematic. Recently, regimens have become available that might improve HCW acceptance and compliance with LTBI treatment. A retrospective single-center review of Employee Health and Wellness Services records of all HCWs diagnosed with LTBI was conducted. HCWs diagnosed with LTBI were offered 9-month isoniazid (INH), 4-month rifampin (RIF), weekly rifapentine/isoniazid (RPT/INH) for 12 weeks, or no treatment. Acceptance, completion rates, and side effects were reported for each regimen. Comparisons of regimens were assessed using Fisher exact test. Between 2005 and 2014, 363 of 927 (39%) HCWs diagnosed with LTBI accepted treatment. Of 363, 202 chose INH, 106 RIF, and 55 RPT/INH. Completion rates for each regimen were 58%, 80%, and 87%, respectively. HCWs were significantly more likely to have completed treatment with RIF (P < .0001) or RPT/INH (P < .0001) than INH. Rates of discontinuation owing to side effects were 35% for INH, 21% for RIF, and 10% for RPT/INH. Discontinuation of therapy due to side effects was significantly more frequent in the INH than the RPT/INH group (P = .0042). Completion of RIF and RPT/INH for LTBI in an HCW population is more likely than INH. Rates of discontinuation due to side effects were lower among those taking RPT/INH. Shorter LTBI treatment regimens should be more widely considered for HCWs in the United States. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. Tuberculosis in Antiretroviral Treatment Programs in Lower Income Countries: Availability and Use of Diagnostics and Screening

    Science.gov (United States)

    Fenner, Lukas; Ballif, Marie; Graber, Claire; Nhandu, Venerandah; Dusingize, Jean Claude; Cortes, Claudia P.; Carriquiry, Gabriela; Anastos, Kathryn; Garone, Daniela; Jong, Eefje; Gnokoro, Joachim Charles; Sued, Omar; Ajayi, Samuel; Diero, Lameck; Wools-Kaloustian, Kara; Kiertiburanakul, Sasisopin; Castelnuovo, Barbara; Lewden, Charlotte; Durier, Nicolas; Sterling, Timothy R.; Egger, Matthias

    2013-01-01

    Objectives In resource-constrained settings, tuberculosis (TB) is a common opportunistic infection and cause of death in HIV-infected persons. TB may be present at the start of antiretroviral therapy (ART), but it is often under-diagnosed. We describe approaches to TB diagnosis and screening of TB in ART programs in low- and middle-income countries. Methods and findings We surveyed ART programs treating HIV-infected adults in sub-Saharan Africa, Asia and Latin America in 2012 using online questionnaires to collect program-level and patient-level data. Forty-seven sites from 26 countries participated. Patient-level data were collected on 987 adult TB patients from 40 sites (median age 34.7 years; 54% female). Sputum smear microscopy and chest radiograph were available in 47 (100%) sites, TB culture in 44 (94%), and Xpert MTB/RIF in 23 (49%). Xpert MTB/RIF was rarely available in Central Africa and South America. In sites with access to these diagnostics, microscopy was used in 745 (76%) patients diagnosed with TB, culture in 220 (24%), and chest X-ray in 688 (70%) patients. When free of charge culture was done in 27% of patients, compared to 21% when there was a fee (p = 0.033). Corresponding percentages for Xpert MTB/RIF were 26% and 15% of patients (p = 0.001). Screening practices for active disease before starting ART included symptom screening (46 sites, 98%), chest X-ray (38, 81%), sputum microscopy (37, 79%), culture (16, 34%), and Xpert MTB/RIF (5, 11%). Conclusions Mycobacterial culture was infrequently used despite its availability at most sites, while Xpert MTB/RIF was not generally available. Use of available diagnostics was higher when offered free of charge. PMID:24147059

  3. Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic.

    Science.gov (United States)

    Isakova, Jainagul; Sovkhozova, Nurmira; Vinnikov, Denis; Goncharova, Zoy; Talaibekova, Elnura; Aldasheva, Nazira; Aldashev, Almaz

    2018-03-22

    The aim of this study was to identify mutations of rpoB, katG, inhA and ahp-genes associated Mycobacterium tuberculosis resistance to rifampicin (RIF) and isoniazid (INH) in Kyrgyz Republic. We studied 633 smear samples from the primary pulmonary tuberculosis (TB) patients. We verified Mycobacterium tuberculosis susceptibility to RIF and INH using culture method of absolute concentrations, and commercially available test named "TB-BIOCHIP" (Biochip-IMB, Moscow, Russian Federation). For RIF-resistance, TB-BIOCHIP's sensitivity and specificity were 88% and 97%, 84% and 95% for INH-resistance, and 90% and 97% for multi-drug resistance (MDR). In RIF-resistant strains, TB-BIOCHIP showed mutations in codons 531 (64.8%), 526 (17.3%), 516 (8.1%), 511 (5.4%), 533 (3.2%), 522 (0.6%) and 513 (0.6%) of rpoB gene. The most prevalent was Ser531 > Leu mutation (63.7%). 91.2% of mutations entailing resistance to INH were in katG gene, 7% in inhA gene, and 1.8% in ahpC gene. Ser315→Thr (88.6%) was the most prevalent mutation leading to resistance to INH. In Kyrgyz Republic, the most prevalent mutation in RIF-resistant strains was Ser531 → Leu in rpoB gene, as opposed to Ser315 → Thr in katG gene in INH-resistant Mycobacterium tuberculosis. In Kyrgyz Republic, the major reservoir of MDR Mycobacterium tuberculosis were strains with combined mutations Ser531 → Leu in rpoB gene and Ser315 → Thr in katG gene. TB-BIOCHIP has shown moderate sensitivity with the advantage of obtaining results in only two days.

  4. Right Iliac Fossa Pain Treatment (RIFT) Study: protocol for an international, multicentre, prospective observational study.

    Science.gov (United States)

    2018-01-13

    Patients presenting with right iliac fossa (RIF) pain are a common challenge for acute general surgical services. Given the range of potential pathologies, RIF pain creates diagnostic uncertainty and there is subsequent variation in investigation and management. Appendicitis is a diagnosis which must be considered in all patients with RIF pain; however, over a fifth of patients undergoing appendicectomy, in the UK, have been proven to have a histologically normal appendix (negative appendicectomy). The primary aim of this study is to determine the contemporary negative appendicectomy rate. The study's secondary aims are to determine the rate of laparoscopy for appendicitis and to validate the Appendicitis Inflammatory Response (AIR) and Alvarado prediction scores. This multicentre, international prospective observational study will include all patients referred to surgical specialists with either RIF pain or suspected appendicitis. Consecutive patients presenting within 2-week long data collection periods will be included. Centres will be invited to participate in up to four data collection periods between February and August 2017. Data will be captured using a secure online data management system. A centre survey will profile local policy and service delivery for management of RIF pain. Research ethics are not required for this study in the UK, as determined using the National Research Ethics Service decision tool. This study will be registered as a clinical audit in participating UK centres. National leads in countries outside the UK will oversee appropriate registration and study approval, which may include completing full ethical review. The study will be disseminated by trainee-led research collaboratives and through social media. Peer-reviewed publications will be published under corporate authorship including 'RIFT Study Group' and 'West Midlands Research Collaborative'. © Article author(s) (or their employer(s) unless otherwise stated in the text of the

  5. 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

  6. 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

  7. 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.

  8. Prueba molecular Genotype® MTBDRplus, una alternativa para la detección rápida de tuberculosis multidrogorresistente Molecular test Genotype® MTBDRplus, an alternative to rapid detection of multidrug resistance tuberculosis

    Directory of Open Access Journals (Sweden)

    Luis Asencios

    2012-03-01

    Full Text Available La prueba molecular Genotype®MTBDRplus, es un método que permite identificar las mutaciones más frecuentes asociadas con la resistencia a las drogas antituberculosas de primera línea: isoniacida (INH y rifampicina (RIF. El objetivo de este estudio fue evaluar el desempeño de la prueba molecular con cultivos y muestras de esputo con baciloscopía positiva. Se evaluó 95 cultivos y 100 esputos con perfiles de resistencia previamente determinados por el método de referencia "proporciones agar en placa" (APP. La prueba molecular a partir de cultivos mostró una sensibilidad de 100%; 97,5% y 96,9% para RIF, INH y multidrogorresistente (MDR respectivamente; mientras que para esputo la sensibilidad fue de 95,7%; 96,8% y 95,2% para RIF, INH y MDR respectivamente. Se concluye que Genotype®MTBDRplus es una herramienta muy útil para la detección rápida de la resistencia a INH y RIF simultáneamente (MDR en un máximo de 72 h a partir de esputo o de cultivo.The Genotype®MTBDRplus molecular test is a method that allows identification of the most frequent mutations associated with resistance to major first-line antituberculosis drugs, Isoniazid (INH and Rifampicin (RFP. The aim of this study was to evaluate the performance of the molecular test with culture and smear- positive sputum samples. We evaluated 95 cultures and 100 sputum samples with resistance profiles previously determined by the reference method "Agar Plate Proportions" (APP. The molecular test from cultures showed a sensitivity of 100 %, 97,5 % and 96,97 % for RIF, INH and MDR respectively while from sputums the sensitivity was 95,65 %, 96,77 % and 95,24 % for RIF, INH and MDR respectively. We conclude that the molecular test Genotype®MTBDRplus is a very useful tool to detect resistance to isoniazid and rifampicin simultaneously (MDR-TB in up to 72 hours from sputum samples or cultures.

  9. Incorporating geometric ray tracing to generate initial conditions for intensity modulated arc therapy optimization.

    Science.gov (United States)

    Oliver, Mike; Gladwish, Adam; Craig, Jeff; Chen, Jeff; Wong, Eugene

    2008-07-01

    Intensity modulated arc therapy (IMAT) is a rotational variant of Intensity modulated radiation therapy (IMRT) that is achieved by allowing the multileaf collimator (MLC) positions to vary as the gantry rotates around the patient. This work describes a method to generate an IMAT plan through the use of a fast ray tracing technique based on dosimetric and geometric information for setting initial MLC leaf positions prior to final IMAT optimization. Three steps were used to generate an IMAT plan. The first step was to generate arcs based on anatomical contours. The second step was to generate ray importance factor (RIF) maps by ray tracing the dose distribution inside the planning target volume (PTV) to modify the MLC leaf positions of the anatomical arcs to reduce the maximum dose inside the PTV. The RIF maps were also segmented to create a new set of arcs to improve the dose to low dose voxels within the PTV. In the third step, the MLC leaf positions from all arcs were put through a leaf position optimization (LPO) algorithm and brought into a fast Monte Carlo dose calculation engine for a final dose calculation. The method was applied to two phantom cases, a clinical prostate case and the Radiological Physics Center (RPC)'s head and neck phantom. The authors assessed the plan improvements achieved by each step and compared plans with and without using RIF. They also compared the IMAT plan with an IMRT plan for the RPC phantom. All plans that incorporated RIF and LPO had lower objective function values than those that incorporated LPO only. The objective function value was reduced by about 15% after the generation of RIF arcs and 52% after generation of RIF arcs and leaf position optimization. The IMAT plan for the RPC phantom had similar dose coverage for PTV1 and PTV2 (the same dose volume histogram curves), however, slightly lower dose to the normal tissues compared to a six-field IMRT plan. The use of a ray importance factor can generate initial IMAT arcs

  10. 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.

  11. [Application of Gene Xpert Mycobacterium tuberculosis DNA and resistance to rifampicin assay in the rapid detection of tuberculosis in children].

    Science.gov (United States)

    Zhang, A M; Li, F; Liu, X H; Xia, L; Lu, S H

    2016-05-01

    To detect Mycobacterium tuberculosis (MTB) and rifampin resistance of the clinical specimens in children by Xpert MTB DNA and resistance to rifampicin(MTB/RIF) detection system, and evaluate the application value of this method in children with tuberculosis. Data of 109 children cases of clinically suspected tuberculosis were collected (including 46 gastric lavage aspirate, 19 sputum, 10 fine needle aspiration biopsy, 4 pus, 14 cerebrospinal fluid, 11 Serous membrance fluid, 1 marrow, 3 stool, 1 urine specimens)between April 2014 and March 2015. All specimens were detected by smear fluorescence staining microscopy, MGIT 960 BACTEC liquid culture, Xpert MTB/RIF assay and T-SPOT.TB test respectively. The sensitivity and specificity of Xpert MTB/RIF assay were analyzed in those clinical specimens. The sensitivity and specificity of the Xpert MTB/RIF assay for MTB detection in childhood tuberculosis clinical specimen were 28.6% and 87.5%. The sensitivity of 65 pulmonary tuberculosis(46 gastric lavage aspirate, 19 sputum) which included gastric lavage aspirates and sputum was 33.3% and 57.1%, the specificity of the two was 100.0%. In 44 extrapulmonary tuberculosis, the sensitivity of the pus and the puncture fluid was higher and approached 100.0%. The detection rate of the cerebrospinal fluid and serous cavity effusion was very low. The sensitivity was 100.0% in smear-positive and culture-positive samples and only 30.8% to 50.0% in smear-negative and culture-positive samples. The sensitivity and specificity of Xpert MTB/RIF assay to detect rifampin resistance were 100.0%. In clinical samples, the sensitivity of Xpert MTB/RIF assay was higher than that of smear fluorescence staining microscopy, but the difference was not statistically significant (χ(2)=0, P>0.05). The result was equivalent to that of MGIT 960 BACTEC liquid culture (28.6% vs. 27.3%, χ(2)=2.50, P>0.05), and far below that of T-SPOT.TB(28.6% vs 59.7%, χ(2)=13.92, Ptuberculosis, especially in serous

  12. Inactivation and reactivation of antibiotic-resistant bacteria by chlorination in secondary effluents of a municipal wastewater treatment plant.

    Science.gov (United States)

    Huang, Jing-Jing; Hu, Hong-Ying; Tang, Fang; Li, Yi; Lu, Sun-Qin; Lu, Yun

    2011-04-01

    Reports state that chlorination of drinking water and wastewater affects the proportions of antibiotic-resistant bacteria by potentially assisting in microbial selection. Studies on the effect of chlorination on like species of antibiotic-resistant bacteria, however, have shown to be conflicting; furthermore, few studies have inspected the regrowth or reactivation of antibiotic-resistant bacteria after chlorination in wastewater. To understand the risks of chlorination resulting from potentially selecting for antibiotic-resistant bacteria, inactivation and reactivation rates of both total heterotrophic bacteria and antibiotic-resistant bacteria (including penicillin-, ampicillin-, tetracycline-, chloramphenicol-, and rifampicin-resistant bacteria) were examined after chlorinating secondary effluent samples from a municipal wastewater treatment plant in this study. Our experimental results indicated similar inactivation rates of both total heterotrophic bacteria and antibiotic-resistant bacteria. Microbial community composition, however, was affected by chlorination: treating samples with 10 mg Cl(2)/L for 10 min resulted in chloramphenicol-resistant bacteria accounting for nearly 100% of the microbial population in contrast to 78% before chlorination. This trend shows that chlorination contributes to selection of some antibiotic-resistant strains. Reactivation of antibiotic-resistant bacteria occurred at 2.0 mg Cl(2)/L for 10 min; specifically, chloramphenicol-, ampicillin-, and penicillin-resistant bacteria were the three prevalent groups present, and the reactivation of chloramphenicol-resistant bacteria exceeded 50%. Regrowth and reactivation of antibiotic-resistant bacteria in secondary effluents after chlorination with a long retention time could threaten public health security during wastewater reuse. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Characterization of a mutagenic DNA adduct formed from 1,2-dibromoethane by O6-alkylguanine-DNA alkyltransferase.

    Science.gov (United States)

    Liu, Liping; Hachey, David L; Valadez, Gerardo; Williams, Kevin M; Guengerich, F Peter; Loktionova, Natalia A; Kanugula, Sreenivas; Pegg, Anthony E

    2004-02-06

    It has been proposed that the DNA repair protein O6-alkylguanine-DNA alkyltransferase increases the mutagenicity of 1,2-dibromoethane by reacting with it at its cysteine acceptor site to form a highly reactive half-mustard, which can then react with DNA (Liu, L., Pegg, A. E., Williams, K. M., and Guengerich, F. P. (2002) J. Biol. Chem. 277, 37920-37928). Incubation of Escherichia coli-expressed human alkyltransferase with 1,2-dibromoethane and single-stranded oligodeoxyribonucleotides led to the formation of covalent transferaseoligo complexes. The order of reaction determined was Gua>Thy>Cyt>Ade. Mass spectrometry analysis of the tryptic digest of the reaction product indicated that some of the adducts led to depurination with the release of the Gly136-Arg147 peptide cross-linked to a Gua at the N7 position, with the site of reaction being the active site Cys145 as established by chromatographic retention time and the fragmentation pattern determined by tandem mass spectrometry of a synthetic peptide adduct. The alkyltransferase-mediated mutations produced by 1,2-dibromoethane were predominantly Gua to Ade transitions but, in the spectrum of such rifampicin-resistant mutations in the RpoB gene, 20% were Gua to Thy transversions. The latter are likely to have arisen from the apurinic site generated from the Gua-N7 adduct. Support exists for an additional adduct/mutagenic pathway because evidence was obtained for DNA adducts other than at the Gua N7 atom and for mutations other than those attributable to depurination. Thus, chemical and biological evidence supports the existence of at least two alkyltransferase-dependent pathways for 1,2-dibromoethane-induced mutagenicity, one involving Gua N7-alkylation by alkyltransferase-S-CH2CH2Br and depurination, plus another as yet uncharacterized system(s).

  14. Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug resistant setting.

    Science.gov (United States)

    Perdigão, João; Silva, Hugo; Machado, Diana; Macedo, Rita; Maltez, Fernando; Silva, Carla; Jordao, Luisa; Couto, Isabel; Mallard, Kim; Coll, Francesc; Hill-Cawthorne, Grant A; McNerney, Ruth; Pain, Arnab; Clark, Taane G; Viveiros, Miguel; Portugal, Isabel

    2014-11-18

    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. 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. 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.

  15. Strong Decrease in Streptomycin-Resistance and Absence of XDR 12 Years after the Reorganization of the National Tuberculosis Control Program in the Central Region of Cameroon

    Science.gov (United States)

    Kuaban, Christopher; Assam Assam, Jean-Paul; Tedom, Jean-Claude; Eyangoh, Sara; Fouda, François-Xavier; Nolna, Désiré; Ntoumi, Francine; Frank, Matthias; Penlap Beng, Véronique N.

    2014-01-01

    Background In the 1990s, resistance rates of 15% for streptomycin-resistance and 0.6% for multidrug-resistance (MDR) were reported from the Central Region of Cameroon. This work assesses drug resistant tuberculosis in this region 12 years after reorganization of the National Tuberculosis Control Program (NTCP). Methods This cross-sectional study was conducted from April 2010 to March 2011 in Jamot Hospital in Yaoundé, Cameroon. Only patients with smear positive pulmonary tuberculosis were included. Sputa were cultured and subsequently underwent drug susceptibility testing (DST). All consenting individuals were tested for their HIV status. Results A total of 665 smear positive pulmonary tuberculosis patients were enrolled. The HIV prevalence was 28.5% (95%CI [25.2–32.1]). Of the 582 sputa that grew Mycobacterium tuberculosis complex species, DST results were obtained for 576. The overall resistance rate was 10.9% (63/576). The overall resistance rates for single drug resistance were: isoniazid-resistance 4.7% (27/576), streptomycin-resistance 3.3% (19/576), rifampicin-resistance 0.2% (1/576), kanamycin-resistance 0.2% (1/576) and ofloxacin-resistance 0.2% (1/576). The MDR rate was 1.1% (6/576) and no extensively drug resistant tuberculosis (XDR) was detected. Conclusions The data show that reorganization of the NTCP resulted in a strong decrease in streptomycin-resistance and suggest that it prevented the emergence of XDR in the Central Region of Cameroon. PMID:24901982

  16. Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.

    Directory of Open Access Journals (Sweden)

    Yuanli Liu

    Full Text Available Reactive oxygen species (ROS; superoxide, peroxide, and hydroxyl radical are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. The possibility has been raised that consumption of antioxidants in food may interfere with the lethal action of antimicrobials. Whether nutritional supplements containing antioxidant activity are also likely to interfere with antimicrobial lethality is unknown. To examine this possibility, resveratrol, a popular antioxidant dietary supplement, was added to cultures of Escherichia coli and Staphylococcus aureus that were then treated with antimicrobial and assayed for bacterial survival and the recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Resveratrol, at concentrations likely to be present during human consumption, caused a 2- to 3-fold reduction in killing during a 2-hr treatment with moxifloxacin or kanamycin. At higher, but still subinhibitory concentrations, resveratrol reduced antimicrobial lethality by more than 3 orders of magnitude. Resveratrol also reduced the increase in reactive oxygen species (ROS characteristic of treatment with quinolone (oxolinic acid. These data support the general idea that the lethal activity of some antimicrobials involves ROS. Surprisingly, subinhibitory concentrations of resveratrol promoted (2- to 6-fold the recovery of rifampicin-resistant mutants arising from the action of ciprofloxacin, kanamycin, or daptomycin. This result is consistent with resveratrol reducing ROS to sublethal levels that are still mutagenic, while the absence of resveratrol allows ROS levels to high enough to kill mutagenized cells. Suppression of antimicrobial lethality and promotion of mutant recovery by resveratrol suggests that the antioxidant may contribute to the emergence of resistance to several antimicrobials, especially if new derivatives and/or formulations of resveratrol markedly increase bioavailability.

  17. Deciphering Staphylococcus sciuri SAT-17 Mediated Anti-oxidative Defense Mechanisms and Growth Modulations in Salt Stressed Maize (Zea mays L.).

    Science.gov (United States)

    Akram, Muhammad S; Shahid, Muhammad; Tariq, Mohsin; Azeem, Muhammad; Javed, Muhammad T; Saleem, Seemab; Riaz, Saba

    2016-01-01

    Soil salinity severely affects plant nutrient use efficiency and is a worldwide constraint for sustainable crop production. Plant growth-promoting rhizobacteria, with inherent salinity tolerance, are able to enhance plant growth and productivity by inducing modulations in various metabolic pathways. In the present study, we reported the isolation and characterization of a salt-tolerant rhizobacterium from Kallar grass [Leptochloa fusca (L.) Kunth]. Sequencing of the 16S rRNA gene revealed its lineage to Staphylococcus sciuri and it was named as SAT-17. The strain exhibited substantial potential of phosphate solubilization as well as indole-3-acetic acid production (up to 2 M NaCl) and 1-aminocyclopropane-1-carboxylic acid deaminase activity (up to 1.5 M NaCl). Inoculation of a rifampicin-resistant derivative of the SAT-17 with maize, in the absence of salt stress, induced a significant increase in plant biomass together with decreased reactive oxygen species and increased activity of cellular antioxidant enzymes. The derivative strain also significantly accumulated nutrients in roots and shoots, and enhanced chlorophyll and protein contents in comparison with non-inoculated plants. Similar positive effects were observed in the presence of salt stress, although the effect was more prominent at 75 mM in comparison to higher NaCl level (150 mM). The strain survived in the rhizosphere up to 30 days at an optimal population density (ca. 1 × 10(6) CFU mL(-1)). It was concluded that S. sciuri strain SAT-17 alleviated maize plants from salt-induced cellular oxidative damage and enhanced growth. Further field experiments should be conducted, considering SAT-17 as a potential bio-fertilizer, to draw parallels between PGPR inoculation, elemental mobility patterns, crop growth and productivity in salt-stressed semi-arid and arid regions.

  18. Transmission of multidrug-resistant Mycobacterium tuberculosis in Shanghai, China: a retrospective observational study using whole-genome sequencing and epidemiological investigation

    Science.gov (United States)

    Wu, Jie; Gan, Mingyu; Xu, Peng; Wu, Zheyuan; Lin, Senlin; Tian, Jiyun; Liu, Qingyun; Yuan, ZhengAn; Mei, Jian; DeRiemer, Kathryn; Gao, Qian

    2016-01-01

    Summary Background Multidrug-resistant tuberculosis (MDR-TB) is a significant threat to tuberculosis elimination worldwide. Understanding the transmission pattern is crucial for its control. We used a genomic epidemiological approach to assess the recent transmission of MDR-TB and potential risk factors for transmission. Methods In a population-based retrospective study, we performed variable-number-of-tandem-repeat (VNTR) genotyping, followed by whole-genome sequencing (WGS) of isolates from all MDR-TB patients in Shanghai, China, 2009-2012. We measured strain diversity within and between genomically clustered patients. Genomic and epidemiologic data were combined to construct transmission networks. Findings 367 (5%) of 7982 patients with tuberculosis had MDR tuberculosis and 324 (88%) of these had isolates available for genomic analysis. 103 (32%) of the 324 MDR strains were in 38 genomic clusters that differed by 12 or fewer single nucleotide polymorphisms (SNPs), indicating recent transmission of MDR strains. Patients who had delayed diagnosis or were older than 45 years had high risk of recent transmission. 235 (73%) patients with MDR tuberculosis probably had transmission of MDR strains. Transmission network analysis showed that 33 (87%) of the 38 clusters accumulated additional drug-resistance mutations through emergence or fixation of mutations during transmission. 68 (66%) of 103 clustered MDR strains had compensatory mutations of rifampicin resistance. Interpretation Recent transmission of MDR strains, with increasing drug-resistance, helps drive the MDR-TB epidemic in Shanghai, China. WGS provides a measure of the heterogeneity of drug-resistant mutations within and between hosts and enhances our ability to determine the transmission patterns of MDR-TB. Funding National Science and Technology Major Project, National Natural Science Foundation of China, and US National Insitutes of Health. PMID:27919643

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Coselection for resistance to multiple late-generation human therapeutic antibiotics encoded on tetracycline resistance plasmids captured from uncultivated stream and soil bacteria.

    Science.gov (United States)

    Herrick, J B; Haynes, R; Heringa, S; Brooks, J M; Sobota, L T

    2014-08-01

    Transmissible plasmids captured from stream and soil bacteria conferring resistance to tetracycline in Pseudomonas were evaluated for linked resistance to antibiotics used in the treatment of human infections. Cells released from stream sediments and soils were conjugated with a rifampicin-resistant, plasmid-free Pseudomonas putida recipient and selected on tetracycline and rifampicin. Each transconjugant contained a single 50-80 kb plasmid. Resistance to 11 antibiotics, in addition to tetracycline, was determined for the stream transconjugants using a modification of the Stokes disc diffusion antibiotic susceptibility assay. Nearly half of plasmids conferred resistance to six or more antibiotics. Resistance to streptomycin, gentamicin, and/or ticarcillin was conferred by a majority of the plasmids, and resistance to additional human clinical use antibiotics such as piperacillin/tazobactam, ciprofloxacin and aztreonam was observed. MICs of 16 antibiotics for representative sediment and soil transconjugants revealed large increases, relative to the Ps. putida recipient, for 11 of 16 antibiotics tested, including the expanded spectrum antibiotics cefotaxime and ceftazidime, as well as piperacillin/tazobactam, lomefloxacin and levofloxacin. Resistance to multiple antibiotics-including those typically used in clinical Pseudomonas and enterobacterial infections-can be conferred by transmissible plasmids in streams and soils. Selective pressure exerted by the use of one antibiotic, such as the common agricultural antibiotic tetracycline, may result in the persistence of linked genes conferring resistance to important human clinical antibiotics. This may impact the spread of resistance to human use antibiotics even in the absence of direct selection. © 2014 The Society for Applied Microbiology.

  5. 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.

  6. 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.

  7. Molecular detection of fluoroquinolone-resistance in multi-drug resistant tuberculosis in Cambodia suggests low association with XDR phenotypes

    Directory of Open Access Journals (Sweden)

    Murray Alan

    2011-09-01

    Full Text Available Abstract Background Drug susceptibility testing (DST remains an important concern for implementing treatment of MDR tuberculosis patients. Implementation of molecular tests for drug resistance identification would facilitate DST particularly in developing countries where culturing is difficult to perform. We have characterized multidrug resistant strains in Cambodia using MDTDRsl tests, drug target sequencing and phenotypic tests. Methods A total of 65 non-MDR and 101 MDR TB isolates collected between May 2007 and June 2009 were tested for resistance to fluoroquinolones and aminoglycosides/cyclic peptides using the GenoType® MTBDRsl assay and gene sequencing. Rifampicin resistance (RMP-R was tested using gene sequencing and genotyping was assessed by spoligotyping. Results A total of 95 of the 101 MDR strains were confirmed to be RMP-R by rpoB gene sequencing. Fourteen of the 101 MDR isolates (14% carried a gyrA mutation associated with fluoroquinolone-resistance (FQ-R (detected by the MTBDRsl assay and sequencing compared with only 1 (1.5% of the 65 non-MDR strains. Only 1 (1% of the MDR isolates was found to be XDR TB. The MDR group contained a higher proportion of Beijing or Beijing like strains (58% than the non MDR group (28%. This percentage is higher in MDR FQ-R strains (71%. Conclusions The new GenoType® MTBDRsl assay combined with molecular tests to detect RMP-R and isoniazid resistance (INH-R represents a valuable tool for the detection of XDR TB. In Cambodia there is a low rate of XDR amongst MDR TB including MDR FQ-R TB. This suggests a low association between FQ-R and XDR TB. Strain spoligotyping confirms Beijing strains to be more prone to accumulate antibiotic resistance.

  8. Strain-specific quantification of root colonization by plant growth promoting rhizobacteria Bacillus firmus I-1582 and Bacillus amyloliquefaciens QST713 in non-sterile soil and field conditions

    Science.gov (United States)

    Mendis, Hajeewaka C.; Thomas, Varghese P.; Schwientek, Patrick; Salamzade, Rauf; Chien, Jung-Ting; Waidyarathne, Pramuditha; Kloepper, Joseph

    2018-01-01

    Bacillus amyloliquefaciens QST713 and B. firmus I-1582 are bacterial strains which are used as active ingredients of commercially-available soil application and seed treatment products Serenade® and VOTiVO®, respectively. These bacteria colonize plant roots promoting plant growth and offering protection against pathogens/pests. The objective of this study was to develop a qPCR protocol to quantitate the dynamics of root colonization by these two strains under field conditions. Primers and TaqMan® probes were designed based on genome comparisons of the two strains with publicly-available and unpublished bacterial genomes of the same species. An optimized qPCR protocol was developed to quantify bacterial colonization of corn roots after seed treatment. Treated corn seeds were planted in non-sterile soil in the greenhouse and grown for 28 days. Specific detection of bacteria was quantified weekly, and showed stable colonization between ~104–105 CFU/g during the experimental period for both bacteria, and the protocol detected as low as 103 CFU/g bacteria on roots. In a separate experiment, streptomycin-resistant QST713 and rifampicin-resistant I-1582 strains were used to compare dilution-plating on TSA with the newly developed qPCR method. Results also indicated that the presence of natural microflora and another inoculated strain does not affect root colonization of either one of these strains. The same qPCR protocol was used to quantitate root colonization by QST713 and I-1582 in two corn and two soybean varieties grown in the field. Both bacteria were quantitated up to two weeks after seeds were planted in the field and there were no significant differences in root colonization in either bacteria strain among varieties. Results presented here confirm that the developed qPCR protocol can be successfully used to understand dynamics of root colonization by these bacteria in plants growing in growth chamber, greenhouse and the field. PMID:29447287

  9. Strain-specific quantification of root colonization by plant growth promoting rhizobacteria Bacillus firmus I-1582 and Bacillus amyloliquefaciens QST713 in non-sterile soil and field conditions.

    Science.gov (United States)

    Mendis, Hajeewaka C; Thomas, Varghese P; Schwientek, Patrick; Salamzade, Rauf; Chien, Jung-Ting; Waidyarathne, Pramuditha; Kloepper, Joseph; De La Fuente, Leonardo

    2018-01-01

    Bacillus amyloliquefaciens QST713 and B. firmus I-1582 are bacterial strains which are used as active ingredients of commercially-available soil application and seed treatment products Serenade® and VOTiVO®, respectively. These bacteria colonize plant roots promoting plant growth and offering protection against pathogens/pests. The objective of this study was to develop a qPCR protocol to quantitate the dynamics of root colonization by these two strains under field conditions. Primers and TaqMan® probes were designed based on genome comparisons of the two strains with publicly-available and unpublished bacterial genomes of the same species. An optimized qPCR protocol was developed to quantify bacterial colonization of corn roots after seed treatment. Treated corn seeds were planted in non-sterile soil in the greenhouse and grown for 28 days. Specific detection of bacteria was quantified weekly, and showed stable colonization between ~104-105 CFU/g during the experimental period for both bacteria, and the protocol detected as low as 103 CFU/g bacteria on roots. In a separate experiment, streptomycin-resistant QST713 and rifampicin-resistant I-1582 strains were used to compare dilution-plating on TSA with the newly developed qPCR method. Results also indicated that the presence of natural microflora and another inoculated strain does not affect root colonization of either one of these strains. The same qPCR protocol was used to quantitate root colonization by QST713 and I-1582 in two corn and two soybean varieties grown in the field. Both bacteria were quantitated up to two weeks after seeds were planted in the field and there were no significant differences in root colonization in either bacteria strain among varieties. Results presented here confirm that the developed qPCR protocol can be successfully used to understand dynamics of root colonization by these bacteria in plants growing in growth chamber, greenhouse and the field.

  10. 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.

  11. 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

  12. Rapid Molecular Detection of Multidrug-Resistant Tuberculosis by PCR-Nucleic Acid Lateral Flow Immunoassay

    Science.gov (United States)

    Kamphee, Hatairat; Chaiprasert, Angkana; Prammananan, Therdsak; Wiriyachaiporn, Natpapas; Kanchanatavee, Airin; Dharakul, Tararaj

    2015-01-01

    Several existing molecular tests for multidrug-resistant tuberculosis (MDR-TB) are limited by complexity and cost, hindering their widespread application. The objective of this proof of concept study was to develop a simple Nucleic Acid Lateral Flow (NALF) immunoassay as a potential diagnostic alternative, to complement conventional PCR, for the rapid molecular detection of MDR-TB. The NALF device was designed using antibodies for the indirect detection of labeled PCR amplification products. Multiplex PCR was optimized to permit the simultaneous detection of the drug resistant determining mutations in the 81-bp hot spot region of the rpoB gene (rifampicin resistance), while semi-nested PCR was optimized for the S315T mutation detection in the katG gene (isoniazid resistance). The amplification process additionally targeted a conserved region of the genes as Mycobacterium tuberculosis (Mtb) DNA control. The optimized conditions were validated with the H37Rv wild-type (WT) Mtb isolate and Mtb isolates with known mutations (MT) within the rpoB and katG genes. Results indicate the correct identification of WT (drug susceptible) and MT (drug resistant) Mtb isolates, with the least limit of detection (LOD) being 104 genomic copies per PCR reaction. NALF is a simple, rapid and low-cost device suitable for low resource settings where conventional PCR is already employed on a regular basis. Moreover, the use of antibody-based NALF to target primer-labels, without the requirement for DNA hybridization, renders the device generic, which could easily be adapted for the molecular diagnosis of other infectious and non-infectious diseases requiring nucleic acid detection. PMID:26355296

  13. Rapid Molecular Detection of Multidrug-Resistant Tuberculosis by PCR-Nucleic Acid Lateral Flow Immunoassay.

    Directory of Open Access Journals (Sweden)

    Hatairat Kamphee

    Full Text Available Several existing molecular tests for multidrug-resistant tuberculosis (MDR-TB are limited by complexity and cost, hindering their widespread application. The objective of this proof of concept study was to develop a simple Nucleic Acid Lateral Flow (NALF immunoassay as a potential diagnostic alternative, to complement conventional PCR, for the rapid molecular detection of MDR-TB. The NALF device was designed using antibodies for the indirect detection of labeled PCR amplification products. Multiplex PCR was optimized to permit the simultaneous detection of the drug resistant determining mutations in the 81-bp hot spot region of the rpoB gene (rifampicin resistance, while semi-nested PCR was optimized for the S315T mutation detection in the katG gene (isoniazid resistance. The amplification process additionally targeted a conserved region of the genes as Mycobacterium tuberculosis (Mtb DNA control. The optimized conditions were validated with the H37Rv wild-type (WT Mtb isolate and Mtb isolates with known mutations (MT within the rpoB and katG genes. Results indicate the correct identification of WT (drug susceptible and MT (drug resistant Mtb isolates, with the least limit of detection (LOD being 104 genomic copies per PCR reaction. NALF is a simple, rapid and low-cost device suitable for low resource settings where conventional PCR is already employed on a regular basis. Moreover, the use of antibody-based NALF to target primer-labels, without the requirement for DNA hybridization, renders the device generic, which could easily be adapted for the molecular diagnosis of other infectious and non-infectious diseases requiring nucleic acid detection.

  14. 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

  15. Epidemic levels of drug resistant tuberculosis (MDR and XDR-TB in a high HIV prevalence setting in Khayelitsha, South Africa.

    Directory of Open Access Journals (Sweden)

    Helen S Cox

    Full Text Available BACKGROUND: Although multidrug-resistant tuberculosis (MDR-TB is emerging as a significant threat to tuberculosis control in high HIV prevalence countries such as South Africa, limited data is available on the burden of drug resistant tuberculosis and any association with HIV in such settings. We conducted a community-based representative survey to assess the MDR-TB burden in Khayelitsha, an urban township in South Africa with high HIV and TB prevalence. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was conducted among adult clinic attendees suspected for pulmonary tuberculosis in two large primary care clinics, together constituting 50% of the tuberculosis burden in Khayelitsha. Drug susceptibility testing (DST for isoniazid and rifampicin was conducted using a line probe assay on positive sputum cultures, and with culture-based DST for first and second-line drugs. Between May and November 2008, culture positive pulmonary tuberculosis was diagnosed in 271 new and 264 previously treated tuberculosis suspects (sample enriched with previously treated cases. Among those with known HIV status, 55% and 71% were HIV infected respectively. MDR-TB was diagnosed in 3.3% and 7.7% of new and previously treated cases. These figures equate to an estimated case notification rate for MDR-TB of 51/100,000/year, with new cases constituting 55% of the estimated MDR-TB burden. HIV infection was not significantly associated with rifampicin resistance in multivariate analyses. CONCLUSIONS/SIGNIFICANCE: There is an extremely high burden of MDR-TB in this setting, most likely representing ongoing transmission. These data highlight the need to diagnose drug resistance among all TB cases, and for innovative models of case detection and treatment for MDR-TB, in order to interrupt transmission and control this emerging epidemic.

  16. 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.

  17. 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

  18. 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.

  19. On-site laboratory support of the Oak Ridge National Laboratory remedial investigation/feasibility study

    International Nuclear Information System (INIS)

    Burn, J.L.E.; Brooksbank, R.D.; Dillener, J.L.; Jeskie, T.R.

    1992-10-01

    In 1987, a remedial investigation/feasibility study (RI/FS) was begun at Oak Ridge National Laboratory (ORNL). ORNL had established a number of waste area groupings (WAGs), each of which was to be studied and characterized separately. Although the nature and extent of contamination at the WAGs vary widely, samples from each WAG might be radiologically and/or chemically contaminated. To comply with Department of Transportation (DOT) regulations regarding the shipment of hazardous and radioactive materials, all samples are screened for radioactivity before shipment to independent laboratories for further analysis. In 1989 a Close Support Laboratory (CSL) was established at the RI/FS Field Operations Facility at ORNL. The CSL began as a screening facility and has evolved into a laboratory where high-quality analytical results on a number of different parameters are usually available within 24 hours of sampling. CSL capabilities include three basic areas: radiochemistry, volatile organic analysis (VOA), and wet chemistry

  20. Susceptibilidad a la rifaximina y otros antimicrobianos de bacterias aisladas en pacientes con infecciones gastrointestinales agudas en el sureste de México

    Directory of Open Access Journals (Sweden)

    O. Novoa-Farias

    2017-07-01

    Resultados: La mayoría de las bacterias fueron Escherichia coli (55% en todas sus variantes patógenas, Shigella (16.8%, Salmonella (15.3%, Aeromonas (7.8% y menos de 5% Campylobacter, Yersinia, Vibrio y Plesiomonas. La susceptibilidad global acumulada a RIF fue del 69.1, el 90.8, el 98.9 y el 100% a las concentraciones de 100, 200, 400 y 800 μg/ml, respectivamente. La susceptibilidad global a los otros antibióticos fue: FOS 82.8%, CLO 76.8%, CIP 73.9%, FUR 64%, T-S 58.7%, NEO 55.8% y AMP 23.8%. La susceptibilidad a RIF 400 y 800 μg fue significativamente mayor que con los otros antimicrobianos (p  98% de las cepas bacterianas y alta frecuencia de resistencia a varios antimicrobianos comunes.

  1. DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity

    DEFF Research Database (Denmark)

    Gupta, Rajat; Somyajit, Kumar; Narita, Takeo

    2018-01-01

    -switch recombination (CSR), and fusion of unprotected telomeres. Shieldin functions as a downstream effector of 53BP1-RIF1 in restraining DNA end resection and in sensitizing BRCA1-deficient cells to PARP inhibitors. These findings have implications for understanding cancer-associated PARPi resistance...... expressed DNA repair factors 53BP1, BRCA1, and MDC1. Our spatially resolved interaction maps reveal rich network intricacies, identify shared and bait-specific interaction modules, and implicate previously concealed regulators in this process. We identified a novel vertebrate-specific protein complex......, shieldin, comprising REV7 plus three previously uncharacterized proteins, RINN1 (CTC-534A2.2), RINN2 (FAM35A), and RINN3 (C20ORF196). Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168-53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class...

  2. Color image coding based on recurrent iterated function systems

    Science.gov (United States)

    Kim, Kwon; Park, Rae-Hong

    1998-02-01

    This paper proposes a color image coding method based on recurrent iterated function systems (RIFSs). To encode a set of multispectral images, we apply a RIFS to multiset data consisting of three images. In the proposed method, the mappings not only between blocks within an individual spectral image but also between blocks of different spectral images are performed with contraction constraint. Simulation results show that the fractal coding based on the RIFS is useful for encoding concurrently a set of images by describing the similarity existing between a pair of images. In addition, the proposed color coding method can be applied to subband images and moving image sequences consisting of a set of images having similar gray patterns.

  3. Mantle dynamics beneath the Gibraltar Arc (western Mediterranean) from shear-wave splitting measurements on a dense seismic array

    Science.gov (United States)

    Diaz, J.; Gallart, J.; Villaseñor, A.; Mancilla, F.; Pazos, A.; Córdoba, D.; Pulgar, J. A.; Ibarra, P.; Harnafi, M.

    2010-09-01

    Controversial evolutionary models have been proposed for the Gibraltar Arc system, a complex interaction zone between the Eurasia and African plates. Here we derive new mantle anisotropic constraints from SKS splitting measurements on a dense network of about 90 broad-band stations deployed over South Iberia and North Morocco. The inferred fast polarization directions (FPD) clearly show a spectacular rotation along the arc following the curvature of the Rif-Betic chain, while stations located at the South and South-East edges show distinct patterns. These results support geodynamical processes invoking a fast retreating slab rather than convective-removal and delamination models. The FPD variations along the Gibraltar arc can be explained by fossil anisotropy acquired during the Western Mediterranean Eocene subduction, while changes to the South and South-East of the Rif-Betic chain could be the imprint of a flow episode around an Alboran high velocity slab during its Miocene fragmentation from the Algerian slab.

  4. Surface-enhanced infrared absorption studies towards a new optical biosensor

    Directory of Open Access Journals (Sweden)

    Lothar Leidner

    2016-11-01

    Full Text Available Reflectometric interference spectroscopy (RIfS, which is well-established in the visual regime, measures the optical thickness change of a sensitive layer caused, e.g., by binding an analyte. When operated in the mid-infrared range the sensor provides additional information via weak absorption spectra (fingerprints. The originally poor spectra are magnified by surface-enhanced infrared absorption (SEIRA. This is demonstrated using the broad complex fluid water band at 3300 cm−1, which is caused by superposition of symmetric, antisymmetric stretching vibration, and the first overtone of the bending vibration under the influence of H-bonds and Fermi resonance effect. The results are compared with a similar experiment performed with an ATR (attenuated total reflectance set-up.

  5. 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)

  6. Accelerated detection of mycolactone production and response to antibiotic treatment in a mouse model of Mycobacterium ulcerans disease.

    Directory of Open Access Journals (Sweden)

    Paul J Converse

    Full Text Available Diagnosis of the neglected tropical disease, Buruli ulcer, can be made by acid-fast smear microscopy, specimen culture on mycobacterial growth media, polymerase chain reaction (PCR, and/or histopathology. All have drawbacks, including non-specificity and requirements for prolonged culture at 32°C, relatively sophisticated laboratory facilities, and expertise, respectively. The causative organism, Mycobacterium ulcerans, produces a unique toxin, mycolactone A/B (ML that can be detected by thin layer chromatography (TLC or mass spectrometric analysis. Detection by the latter technique requires sophisticated facilities. TLC is relatively simple but can be complicated by the presence of other lipids in the specimen. A method using a boronate-assisted fluorogenic chemosensor in TLC can overcome this challenge by selectively detecting ML when visualized with UV light. This report describes modifications in the fluorescent TLC (F-TLC procedure and its application to the mouse footpad model of M. ulcerans disease to determine the kinetics of mycolactone production and its correlation with footpad swelling and the number of colony forming units in the footpad. The response of all three parameters to treatment with the current standard regimen of rifampin (RIF and streptomycin (STR or a proposed oral regimen of RIF and clarithromycin (CLR was also assessed. ML was detectable before the onset of footpad swelling when there were 10(5 CFU per footpad. Mycolactone concentrations increased as swelling increased whereas CFU levels reached a plateau. Treatment with either RIF+STR or RIF+CLR resulted in comparable reductions of mycolactone, footpad swelling, and CFU burden. Storage in absolute ethanol appears critical to successful detection of ML in footpads and would be practical for storage of clinical samples. F-TLC may offer a new tool for confirmation of suspected clinical lesions and be more specific than smear microscopy, much faster than culture, and

  7. Putative regulatory factors associated with intramuscular fat content.

    Directory of Open Access Journals (Sweden)

    Aline S M Cesar

    Full Text Available Intramuscular fat (IMF content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG, biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA and co-expression network methods, such as partial correlation coefficient with information theory (PCIT, regulatory impact factor (RIF and phenotypic impact factor (PIF were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H and low (L GEBV and 77 DEG (FDR 10% were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1, MPC1 and UBL5 (RIF2 and a host of small RNAs, including miR-1281 (PIF. These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption.

  8. Work plan addendum for the remedial investigation and feasibility study of the Salmon Site

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-11-01

    This document is intended as an addendum to the Remedial Investigation and Feasibility Study (RI/FS) Work Plan for the Salmon Site (SS) (formerly the Tatum Dome Test Site) Lamar County, Mississippi. The original work plan - Remedial Investigation and Feasibility Study of the Tatum Dome Test Site, Lamar County, Mississippi (herein after called the Work Plan) was approved by the state of Mississippi in 1992 and was intended as the operative document for investigative activities at the Tatum Dome Test Site. Subsequent to the approval of the document a series of activities were undertaken under the auspices of the work plan. This document is organized in the same manner as the original work plan: (1) Introduction; (2) Site Background and History; (3) Initial Evaluation; (4) Data Quality Objectives; (5) RI/FS Tasks; (6) Project Schedule; (7) Project Management; and (8) Reference. This addendum will identify changes to the original work plan that are necessary because of additional information acquired at the SS. This document is not intended to replace the work plan, rather, it is intended to focus the remaining work in the context of additional site knowledge gained since the development of the original work plan. The U.S. Department of Energy (DOE) is conducting a focused and phased site characterization as a part, of the RI/FS. The RI/FS is the methodology under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) for evaluating hazardous waste sites on the National Priorities List (NPL). The SS is not listed on the NPL, but DOE has voluntarily elected to conduct the evaluation of the SS in accordance with CERCLA.

  9. Comparative activity of tedizolid and glycopeptide combination therapies for the treatment of Staphylococcus aureus infections: an in vitro and in vivo evaluation against strains with reduced susceptibility to glycopeptides.

    Science.gov (United States)

    Betts, J W; Abdul Momin, H F; Phee, L M; Wareham, D W

    2018-02-01

    Glycopeptides are widely used for the treatment of meticillin-resistant Staphylococcus aureus (MRSA) infections. Although difficult to detect, isolates with reduced (GISA), hetero (hGISA) or complete (GRSA) resistance to glycopeptides are increasingly reported. Optimal therapy for such strains is unknown. We compared the in vitro and in vivo activity of tedizolid (TED), a recently licensed oxazolidonone, with vancomycin (VAN) and teicoplanin (TEIC) combined with fusidic acid (FD) or rifampicin (RIF) against S. aureus (SA) with reduced susceptibility to glycopeptides. Susceptibility was determined for six (GISA, hGISA and GRSA) reference strains and 72 clinical MRSA isolates screened for hGISA/GISA-like phenotypes. Synergy and bactericidal activity were assessed using chequerboard and time-kill assays. The G. mellonella wax moth caterpillar model was used to measure the activity of TED and the combinations in vivo. Glycopeptide MICs (VAN/TEIC) ranged from 0.5-8/4 and 0.125-1 for TED. No significant synergy was noted when VAN/TEIC were combined with either RIF or FD. Time-kill assays confirmed that TED was bacteriostatic but superior to VAN and TEIC against GISA strains. In G. mellonella TED was more effective than TEIC monotherapy versus GISA strains. The combination of TEIC with RIF was the most effective combination overall, both in vitro and in vivo. TED had good in vitro activity versus MRSA including those with reduced susceptibility to glycopeptides. Although bacteriostatic, it was effective in the G. mellonella model and superior to TEIC in the treatment of GISA. Although this supports the use of TED for MRSA and GISA, the TEIC/RIF combination also warrants further study.

  10. Detection of rifampin resistance patterns in Mycobacterium tuberculosis strains isolated in Iran by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing methods

    Directory of Open Access Journals (Sweden)

    Bahram Nasr Isfahani

    2006-09-01

    Full Text Available Mutations in the rpoB locus confer conformational changes leading to defective binding of rifampin (RIF to rpoB and consequently resistance in Mycobacterium tuberculosis. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP was established as a rapid screening test for the detection of mutations in the rpoB gene, and direct sequencing has been unambiguously applied to characterize mutations. A total of 37 of Iranian isolates of M. tuberculosis, 16 sensitive and 21 resistant to RIF, were used in this study. A 193-bp region of the rpoB gene was amplified and PCR-SSCP patterns were determined by electrophoresis in 10% acrylamide gel and silver staining. Also, 21 samples of 193-bp rpoB amplicons with different PCR-SSCP patterns from RIFr and 10 from RIFs were sequenced. Seven distinguishable PCR-SSCP patterns were recognized in the 21 Iranian RIFr strains, while 15 out of 16 RIFs iso