A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis

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

Bhagavat, Raghu; Kim, Heung -Bok; Kim, Chang -Yub

Nucleoside tri-phosphates (NTP) form an important class of small molecule ligands that participate in, and are essential to a large number of biological processes. Here, we seek to identify the NTP binding proteome (NTPome) in M. tuberculosis (M.tb), a deadly pathogen. Identifying the NTPome is useful not only for gaining functional insights of the individual proteins but also for identifying useful drug targets. From an earlier study, we had structural models of M.tb at a proteome scale from which a set of 13,858 small molecule binding pockets were identified. We use a set of NTP binding sub-structural motifs derived frommore » a previous study and scan the M.tb pocketome, and find that 1,768 proteins or 43% of the proteome can theoretically bind NTP ligands. Using an experimental proteomics approach involving dye-ligand affinity chromatography, we confirm NTP binding to 47 different proteins, of which 4 are hypothetical proteins. Our analysis also provides the precise list of binding site residues in each case, and the probable ligand binding pose. In conclusion, as the list includes a number of known and potential drug targets, the identification of NTP binding can directly facilitate structure-based drug design of these targets.« less

A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis

DOE PAGES

Bhagavat, Raghu; Kim, Heung -Bok; Kim, Chang -Yub; ...

2017-10-02

Nucleoside tri-phosphates (NTP) form an important class of small molecule ligands that participate in, and are essential to a large number of biological processes. Here, we seek to identify the NTP binding proteome (NTPome) in M. tuberculosis (M.tb), a deadly pathogen. Identifying the NTPome is useful not only for gaining functional insights of the individual proteins but also for identifying useful drug targets. From an earlier study, we had structural models of M.tb at a proteome scale from which a set of 13,858 small molecule binding pockets were identified. We use a set of NTP binding sub-structural motifs derived frommore » a previous study and scan the M.tb pocketome, and find that 1,768 proteins or 43% of the proteome can theoretically bind NTP ligands. Using an experimental proteomics approach involving dye-ligand affinity chromatography, we confirm NTP binding to 47 different proteins, of which 4 are hypothetical proteins. Our analysis also provides the precise list of binding site residues in each case, and the probable ligand binding pose. In conclusion, as the list includes a number of known and potential drug targets, the identification of NTP binding can directly facilitate structure-based drug design of these targets.« less

The arms race between man and Mycobacterium tuberculosis: Time to regroup.

PubMed

Hoal, Eileen G; Dippenaar, Anzaan; Kinnear, Craig; van Helden, Paul D; Möller, Marlo

2017-08-23

An arms race is an appropriate metaphor to use for the interaction of man and Mycobacterium tuberculosis (M.tb) through the millennia. Estimates of the time of infection of modern humans with M.tb often pre-date the Out-of-Africa migration. Humans have adapted to the changing environment during the migration with respect to climate, food sources and encounters with local pathogens. More recently, there has been adaptation to the demographic changes brought about in the majority of the human population by the Neolithic revolution. By chance and/or selection, specific variants in immune defence have arisen in different population groups. These select for M.tb strains more fit to cause disease and be transmitted, sometimes by exploiting defence systems effective on other bacteria. The different selection pressures on the M.tb lineages carried by specific human groups have resulted in a worldwide M.tb population that is geographically structured according to the humans historically found there. A similar structure is seen with pathogens such as M. leprae and Helicobacter pylori. Modern M.tb strains have emerged which may be more fit, such as the Beijing lineage, leading to their rapid spread both in the areas where they arose, and into new areas after recent introduction. The speed at which this is occurring is outpacing coevolution for the time being. By using the results of genome wide and other association studies, as well as admixture mapping and 'natural experiments' in areas where both a number of populations, admixed populations, and a variety of M.tb strains occur, we can investigate the forces that have driven the coevolution of man and M.tb. The diversity of human and bacterial genetic background may be used in the future to discover and target the specific host-pathogen interactions leading to tuberculosis diseases, which suggests the potential for rational design of vaccines and host-directed therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Human genetic factors in tuberculosis: an update.

PubMed

van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

2017-09-01

Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

NABIC: A New Access Portal to Search, Visualize, and Share Agricultural Genomics Data.

PubMed

Seol, Young-Joo; Lee, Tae-Ho; Park, Dong-Suk; Kim, Chang-Kug

2016-01-01

The National Agricultural Biotechnology Information Center developed an access portal to search, visualize, and share agricultural genomics data with a focus on South Korean information and resources. The portal features an agricultural biotechnology database containing a wide range of omics data from public and proprietary sources. We collected 28.4 TB of data from 162 agricultural organisms, with 10 types of omics data comprising next-generation sequencing sequence read archive, genome, gene, nucleotide, DNA chip, expressed sequence tag, interactome, protein structure, molecular marker, and single-nucleotide polymorphism datasets. Our genomic resources contain information on five animals, seven plants, and one fungus, which is accessed through a genome browser. We also developed a data submission and analysis system as a web service, with easy-to-use functions and cutting-edge algorithms, including those for handling next-generation sequencing data.

Patients at high risk of tuberculosis recurrence.

PubMed

Mirsaeidi, Mehdi; Sadikot, Ruxana T

2018-01-01

Recurrent tuberculosis (TB) continues to be a significant problem and is an important indicator of the effectiveness of TB control. Recurrence can occur by relapse or exogenous reinfection. Recurrence of TB is still a major problem in high-burden countries, where there is lack of resources and no special attention is being given to this issue. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 47%. This variability is related to differences in regional epidemiology of recurrence and differences in the definitions used by the TB control programs. In addition to treatment failure from noncompliance, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include gender differences, malnutrition; comorbidities such as diabetes, renal failure, and systemic diseases, especially immunosuppressive states such as human immunodeficiency virus; substance abuse; and environmental exposures such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being identified. Information on temporal and geographical trends of TB cases as well as studies with whole-genome sequencing might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and an understanding of host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence.

The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis.

PubMed

Rosenthal, Alex; Gabrielian, Andrei; Engle, Eric; Hurt, Darrell E; Alexandru, Sofia; Crudu, Valeriu; Sergueev, Eugene; Kirichenko, Valery; Lapitskii, Vladzimir; Snezhko, Eduard; Kovalev, Vassili; Astrovko, Andrei; Skrahina, Alena; Taaffe, Jessica; Harris, Michael; Long, Alyssa; Wollenberg, Kurt; Akhundova, Irada; Ismayilova, Sharafat; Skrahin, Aliaksandr; Mammadbayov, Elcan; Gadirova, Hagigat; Abuzarov, Rafik; Seyfaddinova, Mehriban; Avaliani, Zaza; Strambu, Irina; Zaharia, Dragos; Muntean, Alexandru; Ghita, Eugenia; Bogdan, Miron; Mindru, Roxana; Spinu, Victor; Sora, Alexandra; Ene, Catalina; Vashakidze, Sergo; Shubladze, Natalia; Nanava, Ucha; Tuzikov, Alexander; Tartakovsky, Michael

2017-11-01

The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/.

The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis

PubMed Central

Gabrielian, Andrei; Engle, Eric; Hurt, Darrell E.; Alexandru, Sofia; Crudu, Valeriu; Sergueev, Eugene; Kirichenko, Valery; Lapitskii, Vladzimir; Snezhko, Eduard; Kovalev, Vassili; Astrovko, Andrei; Skrahina, Alena; Harris, Michael; Long, Alyssa; Wollenberg, Kurt; Akhundova, Irada; Ismayilova, Sharafat; Skrahin, Aliaksandr; Mammadbayov, Elcan; Gadirova, Hagigat; Abuzarov, Rafik; Seyfaddinova, Mehriban; Avaliani, Zaza; Strambu, Irina; Zaharia, Dragos; Muntean, Alexandru; Ghita, Eugenia; Bogdan, Miron; Mindru, Roxana; Spinu, Victor; Sora, Alexandra; Ene, Catalina; Vashakidze, Sergo; Shubladze, Natalia; Nanava, Ucha; Tuzikov, Alexander; Tartakovsky, Michael

2017-01-01

ABSTRACT The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/. PMID:28904183

Modern contact investigation methods for enhancing tuberculosis control in aboriginal communities.

PubMed

Cook, Victoria J; Shah, Lena; Gardy, Jennifer

2012-05-25

The Aboriginal communities in Canada are challenged by a disproportionate burden of TB infection and disease. Contact investigation (CI) guidelines exist but these strategies do not take into account the unique social structure of different populations. Because of the limitations of traditional CI, new approaches are under investigation and include the use of social network analysis, geographic information systems and genomics, in addition to the widespread use of genotyping to better understand TB transmission. Guidelines for the routine use of network methods and other novel methodologies for TB CI and outbreak investigation do not exist despite the gathering evidence that these approaches can positively impact TB control efforts, even in Aboriginal communities. The feasibility and efficacy of these novel approaches to CI in Aboriginal communities requires further investigation. The successful integration of these novel methodologies will require community involvement, capacity building and ongoing support at every level. The outcome will not only be the systematic collection, analysis, and interpretation of CI data in high-burden communities to assess transmission but the prioritization of contacts who are candidates for treatment of LTBI which will break the cycle of transmission. Ultimately, the measure of success will be a clear and sustained decline in TB incidence in Aboriginal communities.

NABIC: A New Access Portal to Search, Visualize, and Share Agricultural Genomics Data

PubMed Central

Seol, Young-Joo; Lee, Tae-Ho; Park, Dong-Suk; Kim, Chang-Kug

2016-01-01

The National Agricultural Biotechnology Information Center developed an access portal to search, visualize, and share agricultural genomics data with a focus on South Korean information and resources. The portal features an agricultural biotechnology database containing a wide range of omics data from public and proprietary sources. We collected 28.4 TB of data from 162 agricultural organisms, with 10 types of omics data comprising next-generation sequencing sequence read archive, genome, gene, nucleotide, DNA chip, expressed sequence tag, interactome, protein structure, molecular marker, and single-nucleotide polymorphism datasets. Our genomic resources contain information on five animals, seven plants, and one fungus, which is accessed through a genome browser. We also developed a data submission and analysis system as a web service, with easy-to-use functions and cutting-edge algorithms, including those for handling next-generation sequencing data. PMID:26848255

[Genome instability in pulmonary tuberculosis before and after treatment].

PubMed

Dzhokhadze, T A; Buadze, T Zh; Rubanov, K Dzh; Kiriia, N A; Lezhava, T A

2013-11-01

Pulmonary tuberculosis is classified as a disease with a genetic predisposition, and therefore, as with other pathologies related to this group of diseases, by pulmonary tuberculosis, special importance is given to finding those markers that enable early identification of risk groups, such as skrinnig in general population and relatives of patients with tuberculosis, which in turn can provide the basis for preventive measures. One of this markers is the level of genome stability. The aim of this study was a comparative evaluation of the functional parameters of the genome variability in patients with sensitive form of pulmonary tuberculosis before and after treatment, and the possibility of its correction with anti-stress peptide bioregulator - epitalon. The studies were conducted using short-term mitoge -stimulated cell cultures of TB patients, before and after treatment. As an indicator of genome stability has been studied the frequency of structural and numerical chromosome aberrations and fragile sites. It is shown, that in intact cultures from patients with pulmonary tuberculosis, before treatment was significantly higher level of frequency of cells with structural chromosome aberrations, that still retained after the treatment. As for epithalon, it appears that was shown a pronounced protective effect after treatment, on the test of chromosome aberrations, by reducing both overall mean frequency aberrant cells and indicators for all individuals. In the study of fragility of chromosomes in patients with primary tuberculosis was found, that in intact cultures, the proportion of cells with chromosomal fragile sites was higher than in control group of healthy individuals, befor and after treatment. High frequency of chromosome fragility persisted by treatment with peptide bioregulator in both cases - before and after treatment. It is suggested that the identified patterns can be correlated with a high incidence of re- TB.

Chloroplast genome resources and molecular markers differentiate rubber dandelion species from weedy relatives.

PubMed

Zhang, Yingxiao; Iaffaldano, Brian J; Zhuang, Xiaofeng; Cardina, John; Cornish, Katrina

2017-02-02

Rubber dandelion (Taraxacum kok-saghyz, TK) is being developed as a domestic source of natural rubber to meet increasing global demand. However, the domestication of TK is complicated by its colocation with two weedy dandelion species, Taraxacum brevicorniculatum (TB) and the common dandelion (Taraxacum officinale, TO). TB is often present as a seed contaminant within TK accessions, while TO is a pandemic weed, which may have the potential to hybridize with TK. To discriminate these species at the molecular level, and facilitate gene flow studies between the potential rubber crop, TK, and its weedy relatives, we generated genomic and marker resources for these three dandelion species. Complete chloroplast genome sequences of TK (151,338 bp), TO (151,299 bp), and TB (151,282 bp) were obtained using the Illumina GAII and MiSeq platforms. Chloroplast sequences were analyzed and annotated for all the three species. Phylogenetic analysis within Asteraceae showed that TK has a closer genetic distance to TB than to TO and Taraxacum species were most closely related to lettuce (Lactuca sativa). By sequencing multiple genotypes for each species and testing variants using gel-based methods, four chloroplast Single Nucleotide Polymorphism (SNP) variants were found to be fixed between TK and TO in large populations, and between TB and TO. Additionally, Expressed Sequence Tag (EST) resources developed for TO and TK permitted the identification of five nuclear species-specific SNP markers. The availability of chloroplast genomes of these three dandelion species, as well as chloroplast and nuclear molecular markers, will provide a powerful genetic resource for germplasm differentiation and purification, and the study of potential gene flow among Taraxacum species.

The role of ancestry in TB susceptibility of an admixed South African population.

PubMed

Daya, Michelle; van der Merwe, Lize; van Helden, Paul D; Möller, Marlo; Hoal, Eileen G

2014-07-01

Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular Diagnosis of Tuberculosis.

PubMed

Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal

2018-01-01

Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.

Characterization of the M32 metallocarboxypeptidase of Trypanosoma brucei: differences and similarities with its orthologue in Trypanosoma cruzi

PubMed Central

Frasch, Alejandra P.; Carmona, Adriana K.; Juliano, Luiz; Cazzulo, Juan J.; Niemirowicz, Gabriela T.

2012-01-01

Metallocarboxypeptidases (MCP) of the M32 family of peptidases have been identified in a number of prokaryotic organisms but they are absent from eukaryotic genomes with the remarkable exception of those of trypanosomatids. The genome of Trypanosoma brucei, the causative agent of Sleeping Sickness, encodes one such MCP which displays 72% identity to the characterized TcMCP-1 from Trypanosoma cruzi. As its orthologue, TcMCP-1, Trypanosoma brucei MCP is a cytosolic enzyme expressed in both major stages of the parasite. Purified recombinant TbMCP-1 exhibits a significant hydrolytic activity against the carboxypeptidase B substrate FA (furylacryloil)-Ala-Lys at pH 7.0–7.8 resembling the T. cruzi enzyme. S everal divalent cations had little effect on TbMCP-1 activity but increasing amounts of Co2+ inhibited the enzyme. Despite having similar tertiary structure, both protozoan MCPs display different substrate specificity with respect to P1 position. Thus, TcMCP-1 enzyme cleaved Abz-FVK-(Dnp)-OH substrate (where Abz: o-aminobenzoic acid and Dnp: 2,4-dinitrophenyl) whereas TbMCP-1 had no activity on this substrate. Comparative homology models and sequence alignments using TcMCP-1 as a template led us to map several residues that could explain this difference. To verify this hypothesis, site-directed mutagenesis was undertaken replacing the TbMCP-1 residues by those present in TcMCP-1. We found that the substitution A414M led TbMCP-1 to gain activity on Abz-FVK-(Dnp)-OH, thus showing that this residue is involved in specificity determination, probably being part of the S1 sub-site. Moreover, the activity of both protozoan MCPs was explored on two vasoactive compounds such as bradykinin and angiotensin I resulting in two different hydrolysis patterns. PMID:22575602

Identification of Escherichia coli and Shigella Species from Whole-Genome Sequences.

PubMed

Chattaway, Marie A; Schaefer, Ulf; Tewolde, Rediat; Dallman, Timothy J; Jenkins, Claire

2017-02-01

Escherichia coli and Shigella species are closely related and genetically constitute the same species. Differentiating between these two pathogens and accurately identifying the four species of Shigella are therefore challenging. The organism-specific bioinformatics whole-genome sequencing (WGS) typing pipelines at Public Health England are dependent on the initial identification of the bacterial species by use of a kmer-based approach. Of the 1,982 Escherichia coli and Shigella sp. isolates analyzed in this study, 1,957 (98.4%) had concordant results by both traditional biochemistry and serology (TB&S) and the kmer identification (ID) derived from the WGS data. Of the 25 mismatches identified, 10 were enteroinvasive E. coli isolates that were misidentified as Shigella flexneri or S. boydii by the kmer ID, and 8 were S. flexneri isolates misidentified by TB&S as S. boydii due to nonfunctional S. flexneri O antigen biosynthesis genes. Analysis of the population structure based on multilocus sequence typing (MLST) data derived from the WGS data showed that the remaining discrepant results belonged to clonal complex 288 (CC288), comprising both S. boydii and S. dysenteriae strains. Mismatches between the TB&S and kmer ID results were explained by the close phylogenetic relationship between the two species and were resolved with reference to the MLST data. Shigella can be differentiated from E. coli and accurately identified to the species level by use of kmer comparisons and MLST. Analysis of the WGS data provided explanations for the discordant results between TB&S and WGS data, revealed the true phylogenetic relationships between different species of Shigella, and identified emerging pathoadapted lineages. © Crown copyright 2017.

Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa.

PubMed

Comas, Iñaki; Hailu, Elena; Kiros, Teklu; Bekele, Shiferaw; Mekonnen, Wondale; Gumi, Balako; Tschopp, Rea; Ameni, Gobena; Hewinson, R Glyn; Robertson, Brian D; Goig, Galo A; Stucki, David; Gagneux, Sebastien; Aseffa, Abraham; Young, Douglas; Berg, Stefan

2015-12-21

Colonial medical reports claimed that tuberculosis (TB) was largely unknown in Africa prior to European contact, providing a "virgin soil" for spread of TB in highly susceptible populations previously unexposed to the disease [1, 2]. This is in direct contrast to recent phylogenetic models which support an African origin for TB [3-6]. To address this apparent contradiction, we performed a broad genomic sampling of Mycobacterium tuberculosis in Ethiopia. All members of the M. tuberculosis complex (MTBC) arose from clonal expansion of a single common ancestor [7] with a proposed origin in East Africa [3, 4, 8]. Consistent with this proposal, MTBC lineage 7 is almost exclusively found in that region [9-11]. Although a detailed medical history of Ethiopia supports the view that TB was rare until the 20(th) century [12], over the last century Ethiopia has become a high-burden TB country [13]. Our results provide further support for an African origin for TB, with some genotypes already present on the continent well before European contact. Phylogenetic analyses reveal a pattern of serial introductions of multiple genotypes into Ethiopia in association with human migration and trade. In place of a "virgin soil" fostering the spread of TB in a previously naive population, we propose that increased TB mortality in Africa was driven by the introduction of European strains of M. tuberculosis alongside expansion of selected indigenous strains having biological characteristics that carry a fitness benefit in the urbanized settings of post-colonial Africa. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Use of Functional Genomics in Conjunction with Metabolomics for Mycobacterium tuberculosis Research

PubMed Central

Swanepoel, Conrad C.

2014-01-01

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a fatal infectious disease, resulting in 1.4 million deaths globally per annum. Over the past three decades, genomic studies have been conducted in an attempt to elucidate the functionality of the genome of the pathogen. However, many aspects of this complex genome remain largely unexplored, as approaches like genomics, proteomics, and transcriptomics have failed to characterize them successfully. In turn, metabolomics, which is relatively new to the “omics” revolution, has shown great potential for investigating biological systems or their modifications. Furthermore, when these data are interpreted in combination with previously acquired genomics, proteomics and transcriptomics data, using what is termed a systems biology approach, a more holistic understanding of these systems can be achieved. In this review we discuss how metabolomics has contributed so far to characterizing TB, with emphasis on the resulting improved elucidation of M. tuberculosis in terms of (1) metabolism, (2) growth and replication, (3) pathogenicity, and (4) drug resistance, from the perspective of systems biology. PMID:24771957

Genome-wide association study of ancestry-specific TB risk in the South African Coloured population

PubMed Central

Chimusa, Emile R.; Zaitlen, Noah; Daya, Michelle; Möller, Marlo; van Helden, Paul D.; Mulder, Nicola J.; Price, Alkes L.; Hoal, Eileen G.

2014-01-01

The worldwide burden of tuberculosis (TB) remains an enormous problem, and is particularly severe in the admixed South African Coloured (SAC) population residing in the Western Cape. Despite evidence from twin studies suggesting a strong genetic component to TB resistance, only a few loci have been identified to date. In this work, we conduct a genome-wide association study (GWAS), meta-analysis and trans-ethnic fine mapping to attempt the replication of previously identified TB susceptibility loci. Our GWAS results confirm the WT1 chr11 susceptibility locus (rs2057178: odds ratio = 0.62, P = 2.71e−06) previously identified by Thye et al., but fail to replicate previously identified polymorphisms in the TLR8 gene and locus 18q11.2. Our study demonstrates that the genetic contribution to TB risk varies between continental populations, and illustrates the value of including admixed populations in studies of TB risk and other complex phenotypes. Our evaluation of local ancestry based on the real and simulated data demonstrates that case-only admixture mapping is currently impractical in multi-way admixed populations, such as the SAC, due to spurious deviations in average local ancestry generated by current local ancestry inference methods. This study provides insights into identifying disease genes and ancestry-specific disease risk in multi-way admixed populations. PMID:24057671

A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt

PubMed Central

Fiebig, Lena; Kohl, Thomas A; Popovici, Odette; Mühlenfeld, Margarita; Indra, Alexander; Homorodean, Daniela; Chiotan, Domnica; Richter, Elvira; Rüsch-Gerdes, Sabine; Schmidgruber, Beatrix; Beckert, Patrick; Hauer, Barbara; Niemann, Stefan; Allerberger, Franz; Haas, Walter

2017-01-01

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders. PMID:28106529

Pentamidine Is Not a Permeant but a Nanomolar Inhibitor of the Trypanosoma brucei Aquaglyceroporin-2.

PubMed

Song, Jie; Baker, Nicola; Rothert, Monja; Henke, Björn; Jeacock, Laura; Horn, David; Beitz, Eric

2016-02-01

The chemotherapeutic arsenal against human African trypanosomiasis, sleeping sickness, is limited and can cause severe, often fatal, side effects. One of the classic and most widely used drugs is pentamidine, an aromatic diamidine compound introduced in the 1940s. Recently, a genome-wide loss-of-function screen and a subsequently generated trypanosome knockout strain revealed a specific aquaglyceroporin, TbAQP2, to be required for high-affinity uptake of pentamidine. Yet, the underlying mechanism remained unclear. Here, we show that TbAQP2 is not a direct transporter for the di-basic, positively charged pentamidine. Even though one of the two common cation filters of aquaglyceroporins, i.e. the aromatic/arginine selectivity filter, is unconventional in TbAQP2, positively charged compounds are still excluded from passing the channel. We found, instead, that the unique selectivity filter layout renders pentamidine a nanomolar inhibitor of TbAQP2 glycerol permeability. Full, non-covalent inhibition of an aqua(glycero)porin in the nanomolar range has not been achieved before. The remarkable affinity derives from an electrostatic interaction with Asp265 and shielding from water as shown by structure-function evaluation and point mutation of Asp265. Exchange of the preceding Leu264 to arginine abolished pentamidine-binding and parasites expressing this mutant were pentamidine-resistant. Our results indicate that TbAQP2 is a high-affinity receptor for pentamidine. Taken together with localization of TbAQP2 in the flagellar pocket of bloodstream trypanosomes, we propose that pentamidine uptake is by endocytosis.

Recurrence of tuberculosis in a low-incidence setting: a retrospective cross-sectional study augmented by whole genome sequencing.

PubMed

Parvaresh, Laila; Crighton, Taryn; Martinez, Elena; Bustamante, Andrea; Chen, Sharon; Sintchenko, Vitali

2018-06-07

The recurrence of tuberculosis (TB) disease in treated patients can serve as a marker of the efficacy of TB control programs. Recurrent disease represents either endogenous reactivation with the same strain of Mycobacterium tuberculosis due to non-compliance or inadequate therapy or exogenous reinfection with a new strain. Genotyping or whole genome sequencing (WGS) of M. tuberculosis isolates from initial and recurrent cases can differentiate between reinfection and reactivation. This study examined cases of recurrent TB in New South Wales, Australia, using genotyping and WGS. Culture-confirmed TB cases diagnosed at least 12 months apart between January 2011 and December 2016 were included. Isolates of M. tuberculosis from patients were compared using 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-24) typing and WGS. Eighteen cases of recurrent disease were identified but isolates from only 15 (83%) were available for study. MIRU-24 findings classified 13 (13/15; 87%) as reactivation and two (13%), as reinfection. Sequencing 13 cultivable paired isolates demonstrated 11 reactivations and two reinfections. There was genomic similarity in 10 out of 13 pairs while one case (1/13; 8%) had 12 SNPS differences. Two other cases (2/13;15%) had > 200 SNPs differences and were classified as reinfection. No phenotypic or genomic evidence of drug resistance was observed. TB control programs can achieve consistently low rates of recurrent disease in low incidence settings. WGS of implicated isolates augments the differentiation between reactivation and reinfection and indicates that the majority of recurrences are due to reactivation rather than reinfection. Predominance of reactivation over reinfection indicates high-quality public health practices and a low risk of local transmission. This study was approved by the Western Sydney Local Health District (WSLHD) Human Research Ethics Committee (HREC Ref: AU RED LNR/17/WMEAD/190; SSA Ref: LNR SSA/17/WMEAD/191).

The genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute exposure to the androgen, 17β-trenbolone

USGS Publications Warehouse

Dorts, Jennifer; Richter, Catherine A.; Wright-Osment, Maureen K.; Ellersieck, Mark R.; Carter, Barbara J.; Tillitt, Donald E.

2009-01-01

We investigated the genomic transcriptional response of female fathead minnows (Pimephales promelas) to an acute (4 days) exposure to 0.1 or 1.0 ??g/L of 17??-trenbolone (TB), the active metabolite of an anabolic androgenic steroid used as a growth promoter in cattle and a contaminant of concern in aquatic systems. Our objectives were to investigate the gene expression profile induced by TB, define biomarkers of exposure to TB, and increase our understanding of the mechanisms of adverse effects of TB on fish reproduction. In female gonad tissue, microarray analysis using a 22 K oligonucleotide microarray (EcoArray Inc., Gainesville, FL) showed 99 significantly upregulated genes and 741 significantly downregulated genes in response to 1 ??g TB/L. In particular, hydroxysteroid (17??) dehydrogenase 12a (hsd17b12a), zona pellucida glycoprotein 2.2 (zp2.2), and protein inhibitor of activated STAT, 2 (pias2) were all downregulated in gonad. Q-PCR measurements in a larger sample set were consistent with the microarray results in the direction and magnitude of these changes in gene expression. However, several novel potential biomarkers were verified by Q-PCR in the same samples, but could not be validated in independent samples. In liver, Q-PCR measurements showed a significant decrease in vitellogenin 1 (vtg1) mRNA expression. In brain, cytochrome P450, family 19, subfamily A, polypeptide 1b (cyp19a1b, previously known as aromatase B) transcript levels were significantly reduced following TB exposure. Our study provides a candidate gene involved in mediating the action of TB, hsd17b12a, and two potential biomarkers sensitive to acute TB exposure, hepatic vtg1 and brain cyp19a1b.

The Mycobacterium tuberculosis desaturase DesA1 (Rv0824c) is a Ca{sup 2+} binding protein

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

Yeruva, Veena C., E-mail: veenachaitanya@ccmb.res.in; Savanagouder, Mamata; Khandelwal, Radhika

The hallmark feature of Mycobacterium tuberculosis (M.tb) the causative agent of human tuberculosis, is its complex lipid rich cell wall comprised primarily of mycolic acids, long chain fatty acids that play a key role in structural stability and permeability of the cell wall. In addition, they are involved in inhibiting phagosome-lysosome fusion and aid in granuloma formation during the pathogenic process. M.tb DesA1 is an essential acyl-acyl carrier protein desaturase predicted to catalyze the introduction of position specific double bonds during the biosynthesis of mycolic acids. This protein is one among three annotated desaturases (DesA1-3) in the M.tb genome butmore » is unique in containing a βγ-crystallin Greek key signature motif, a well-characterized fold known to mediate Ca{sup 2+} binding in both prokaryotic and eukaryotic organisms. Using Isothermal Titration Calorimetry and {sup 45}CaCl{sub 2} overlay, we demonstrate that Ca{sup 2+} binds to DesA1. Spectroscopic measurements suggested that this binding induces changes in protein conformation but does not lead to significant alterations in the secondary structure of the protein, a feature common to several βγ-crystallins. An M. smegmatis strain over-expressing M.tb desA1 showed a Ca{sup 2+} dependent variation in surface phenotype, revealing a functional role for Ca{sup 2+}in DesA1 activity. This study represents the first identification of a Ca{sup 2+} binding βγ-crystallin in M.tb, emphasizing the implicit role of Ca{sup 2+} in the pathogenesis of M.tb. - Highlights: • Mycobacterium tuberculosis DesA1 is an essential acyl-ACP desaturase. • DesA1 was identified to contain a βγ-crystallin Greek key signature motif. • Ca{sup 2+} binds to DesA1 with an affinity of 53 μM and induces changes in its conformation. • M. smegmatis overexpressing M.tb DesA1 shows a Ca{sup 2+} dependent phenotype. • Targetting the Ca{sup 2+} dependent function of DesA1 could be of therapeutic value.« less

The use of whole-genome sequencing in cluster investigation of a multidrug-resistant tuberculosis outbreak.

PubMed

Lalor, Maeve K; Casali, Nicola; Walker, Timothy M; Anderson, Laura F; Davidson, Jennifer A; Ratna, Natasha; Mullarkey, Cathy; Gent, Mike; Foster, Kirsty; Brown, Tim; Magee, John; Barrett, Anne; Crook, Derrick W; Drobniewski, Francis; Thomas, H Lucy; Abubakar, Ibrahim

2018-06-01

We used whole-genome sequencing (WGS) to delineate transmission networks and investigate the benefits of WGS during cluster investigation.We included clustered cases of multidrug-resistant (MDR) tuberculosis (TB)/extensively drug-resistant (XDR) TB linked by mycobacterial interspersed repetitive unit variable tandem repeat (MIRU-VNTR) strain typing or epidemiological information in the national cluster B1006, notified between 2007 and 2013 in the UK. We excluded from further investigation cases whose isolates differed by greater than 12 single nucleotide polymorphisms (SNPs). Data relating to patients' social networks were collected.27 cases were investigated and 22 had WGS, eight of which (36%) were excluded as their isolates differed by more than 12 SNPs to other cases. 18 cases were ruled into the transmission network based on genomic and epidemiological information. Evidence of transmission was inconclusive in seven out of 18 cases (39%) in the transmission network following WGS and epidemiological investigation.This investigation of a drug-resistant TB cluster illustrates the opportunities and limitations of WGS in understanding transmission in a setting with a high proportion of migrant cases. The use of WGS should be combined with classical epidemiological methods. However, not every cluster will be solvable, regardless of the quality of genomic data. Copyright ©ERS 2018.

Comparative Genomics of Field Isolates of Mycobacterium bovis and M. caprae Provides Evidence for Possible Correlates with Bacterial Viability and Virulence.

PubMed

de la Fuente, José; Díez-Delgado, Iratxe; Contreras, Marinela; Vicente, Joaquín; Cabezas-Cruz, Alejandro; Tobes, Raquel; Manrique, Marina; López, Vladimir; Romero, Beatriz; Bezos, Javier; Dominguez, Lucas; Sevilla, Iker A; Garrido, Joseba M; Juste, Ramón; Madico, Guillermo; Jones-López, Edward; Gortazar, Christian

2015-11-01

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly affect humans and animals worldwide. The life cycle of mycobacteria is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Recently, comparative genomics analyses have provided new insights into the evolution and adaptation of the MTBC to survive inside the host. However, most of this information has been obtained using M. tuberculosis but not other members of the MTBC such as M. bovis and M. caprae. In this study, the genome of three M. bovis (MB1, MB3, MB4) and one M. caprae (MB2) field isolates with different lesion score, prevalence and host distribution phenotypes were sequenced. Genome sequence information was used for whole-genome and protein-targeted comparative genomics analysis with the aim of finding correlates with phenotypic variation with potential implications for tuberculosis (TB) disease risk assessment and control. At the whole-genome level the results of the first comparative genomics study of field isolates of M. bovis including M. caprae showed that as previously reported for M. tuberculosis, sequential chromosomal nucleotide substitutions were the main driver of the M. bovis genome evolution. The phylogenetic analysis provided a strong support for the M. bovis/M. caprae clade, but supported M. caprae as a separate species. The comparison of the MB1 and MB4 isolates revealed differences in genome sequence, including gene families that are important for bacterial infection and transmission, thus highlighting differences with functional implications between isolates otherwise classified with the same spoligotype. Strategic protein-targeted analysis using the ESX or type VII secretion system, proteins linking stress response with lipid metabolism, host T cell epitopes of mycobacteria, antigens and peptidoglycan assembly protein identified new genetic markers and candidate vaccine antigens that warrant further study to develop tools to evaluate risks for TB disease caused by M. bovis/M.caprae and for TB control in humans and animals.

Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa

PubMed Central

Comas, Iñaki; Hailu, Elena; Kiros, Teklu; Bekele, Shiferaw; Mekonnen, Wondale; Gumi, Balako; Tschopp, Rea; Ameni, Gobena; Hewinson, R. Glyn; Robertson, Brian D.; Goig, Galo A.; Stucki, David; Gagneux, Sebastien; Aseffa, Abraham; Young, Douglas; Berg, Stefan

2015-01-01

Summary Colonial medical reports claimed that tuberculosis (TB) was largely unknown in Africa prior to European contact, providing a “virgin soil” for spread of TB in highly susceptible populations previously unexposed to the disease [1, 2]. This is in direct contrast to recent phylogenetic models which support an African origin for TB [3, 4, 5, 6]. To address this apparent contradiction, we performed a broad genomic sampling of Mycobacterium tuberculosis in Ethiopia. All members of the M. tuberculosis complex (MTBC) arose from clonal expansion of a single common ancestor [7] with a proposed origin in East Africa [3, 4, 8]. Consistent with this proposal, MTBC lineage 7 is almost exclusively found in that region [9, 10, 11]. Although a detailed medical history of Ethiopia supports the view that TB was rare until the 20th century [12], over the last century Ethiopia has become a high-burden TB country [13]. Our results provide further support for an African origin for TB, with some genotypes already present on the continent well before European contact. Phylogenetic analyses reveal a pattern of serial introductions of multiple genotypes into Ethiopia in association with human migration and trade. In place of a “virgin soil” fostering the spread of TB in a previously naive population, we propose that increased TB mortality in Africa was driven by the introduction of European strains of M. tuberculosis alongside expansion of selected indigenous strains having biological characteristics that carry a fitness benefit in the urbanized settings of post-colonial Africa. PMID:26687624

Genome expansion and gene loss in powdery mildew fungi reveal functional tradeoffs in extreme parasitism

USDA-ARS?s Scientific Manuscript database

Eukaryotic genomes vary in size over five orders of magnitude ranging from microsporidia (~2.9Mb) to the lung-fish (~1.2Tb). This extraordinary variation is largely a result of the proliferation of mobile DNA elements also referred to as “genomic parasites.” The constraints on genome size may be imp...

Tuberculosis: Is the landscape changing?

PubMed

Khatua, Sutapa; Geltemeyer, Abby M; Gourishankar, Anand

2017-01-01

Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of tuberculosis (TB). During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing mycobacterium tuberculosis. TB is the second most common cause of death from infectious diseases after HIV/AIDS. Drug-resistant TB poses serious challenge to effective management of TB worldwide. Multidrug-resistant TB accounted for about half a million new cases and over 200,000 deaths in 2013. Whole-genome sequencing (first done in 1998) technologies have provided new insight into the mechanism of drug resistance. For the first time in 50 y, new anti TB drugs have been developed. The World Health Organization (WHO) has recently revised their treatment guidelines based on 32 studies. In United States, latent TB affects between 10 and 15 million people, 10% of whom may develop active TB disease. QuantiFERON TB Gold and T-SPOT.TB test are used for diagnosis. Further research will look into the importance of newly discovered gene mutations in causing drug resistance.

Unmasking leading to a health care worker Mycobacterium tuberculosis transmission.

PubMed

Holden, Kerry L; Bradley, Craig W; Curran, Evonne T; Pollard, Christopher; Smith, Grace; Holden, Elisabeth; Glynn, Patricia; Garvey, Mark

2018-05-09

Mycobacterium tuberculosis is a major health burden worldwide. The disease can present as an individual case, community outbreak or more rarely a nosocomial outbreak. Even in countries with a low prevalence such as the UK, tuberculosis (TB) presents a risk to healthcare workers (HCWs). To report an outbreak which manifested 12 months after a patient with pulmonary tuberculosis was admitted to Queen Elizabeth Hospital Birmingham (QEHB). We present the epidemiological and outbreak investigations; the role of whole genome sequencing (WGS) in identifying the outbreak and control measures to prevent further outbreaks. Subsequent to a case of open tuberculosis in a patient transmission was confirmed in one healthcare worker (HCW) who had active TB; HCW cases of latent TB infection (LTBI) were also identified amongst 7 HCW contacts of the index case. Of note, all the LBTI cases had other risk factors for TB. Routine use of Whole Genome Sequencing (WGS) identified the outbreak link between the index case to the HCW with active TB disease, and also informed our investigations. Exposure most likely occurred during an aerosol generating procedure (AGP) which was done in accordance with national guidance at that time without using respiratory protection. Enhanced control measures were implemented following the outbreak. Copyright © 2018. Published by Elsevier Ltd.

Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation

PubMed Central

Marques, Catarina A.; Tiengwe, Calvin; Lemgruber, Leandro; Damasceno, Jeziel D.; Scott, Alan; Paape, Daniel; Marcello, Lucio; McCulloch, Richard

2016-01-01

Abstract Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified by sequence homology. Here we show that three TbORC1/CDC6-interacting factors also act in T. brucei nuclear DNA replication and demonstrate that TbORC1/CDC6 interacts in a high molecular complex in which a diverged Orc4 homologue and one replicative helicase subunit can also be found. Analysing the subcellular localization of four TbORC1/CDC6-interacting factors during the cell cycle reveals that one factor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization and expression, suggesting it positively regulates replication. This work shows that ORC architecture and regulation are diverged features of DNA replication initiation in T. brucei, providing new insight into this key stage of eukaryotic genome copying. PMID:26951375

Discovery of susceptibility loci associated with tuberculosis in Han Chinese.

PubMed

Qi, Hui; Zhang, Yong-Biao; Sun, Lin; Chen, Cheng; Xu, Biao; Xu, Fang; Liu, Jia-Wen; Liu, Jin-Cheng; Chen, Chen; Jiao, Wei-Wei; Shen, Chen; Xiao, Jing; Li, Jie-Qiong; Guo, Ya-Jie; Wang, Yong-Hong; Li, Qin-Jing; Yin, Qing-Qin; Li, Ying-Jia; Wang, Ting; Wang, Xing-Yun; Gu, Ming-Liang; Yu, Jun; Shen, A-Dong

2017-12-01

Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972 TB patients and 1537 controls were retained. After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79). The aforementioned three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta chain paralogue encoding genes, all of which are candidate immune genes associated with TB. Our findings provide new insight into the genetic background of TB in the Han Chinese population. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed Central

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

2017-01-01

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

A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt.

PubMed

Fiebig, Lena; Kohl, Thomas A; Popovici, Odette; Mühlenfeld, Margarita; Indra, Alexander; Homorodean, Daniela; Chiotan, Domnica; Richter, Elvira; Rüsch-Gerdes, Sabine; Schmidgruber, Beatrix; Beckert, Patrick; Hauer, Barbara; Niemann, Stefan; Allerberger, Franz; Haas, Walter

2017-01-12

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders. This article is copyright of The Authors, 2017.

Evidence-based design and evaluation of a whole genome sequencing clinical report for the reference microbiology laboratory.

PubMed

Crisan, Anamaria; McKee, Geoffrey; Munzner, Tamara; Gardy, Jennifer L

2018-01-01

Microbial genome sequencing is now being routinely used in many clinical and public health laboratories. Understanding how to report complex genomic test results to stakeholders who may have varying familiarity with genomics-including clinicians, laboratorians, epidemiologists, and researchers-is critical to the successful and sustainable implementation of this new technology; however, there are no evidence-based guidelines for designing such a report in the pathogen genomics domain. Here, we describe an iterative, human-centered approach to creating a report template for communicating tuberculosis (TB) genomic test results. We used Design Study Methodology-a human centered approach drawn from the information visualization domain-to redesign an existing clinical report. We used expert consults and an online questionnaire to discover various stakeholders' needs around the types of data and tasks related to TB that they encounter in their daily workflow. We also evaluated their perceptions of and familiarity with genomic data, as well as its utility at various clinical decision points. These data shaped the design of multiple prototype reports that were compared against the existing report through a second online survey, with the resulting qualitative and quantitative data informing the final, redesigned, report. We recruited 78 participants, 65 of whom were clinicians, nurses, laboratorians, researchers, and epidemiologists involved in TB diagnosis, treatment, and/or surveillance. Our first survey indicated that participants were largely enthusiastic about genomic data, with the majority agreeing on its utility for certain TB diagnosis and treatment tasks and many reporting some confidence in their ability to interpret this type of data (between 58.8% and 94.1%, depending on the specific data type). When we compared our four prototype reports against the existing design, we found that for the majority (86.7%) of design comparisons, participants preferred the alternative prototype designs over the existing version, and that both clinicians and non-clinicians expressed similar design preferences. Participants showed clearer design preferences when asked to compare individual design elements versus entire reports. Both the quantitative and qualitative data informed the design of a revised report, available online as a LaTeX template. We show how a human-centered design approach integrating quantitative and qualitative feedback can be used to design an alternative report for representing complex microbial genomic data. We suggest experimental and design guidelines to inform future design studies in the bioinformatics and microbial genomics domains, and suggest that this type of mixed-methods study is important to facilitate the successful translation of pathogen genomics in the clinic, not only for clinical reports but also more complex bioinformatics data visualization software.

Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

PubMed

Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

2017-01-20

Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Culture and Next-generation sequencing-based drug susceptibility testing unveil high levels of drug-resistant-TB in Djibouti: results from the first national survey.

PubMed

Tagliani, Elisa; Hassan, Mohamed Osman; Waberi, Yacine; De Filippo, Maria Rosaria; Falzon, Dennis; Dean, Anna; Zignol, Matteo; Supply, Philip; Abdoulkader, Mohamed Ali; Hassangue, Hawa; Cirillo, Daniela Maria

2017-12-15

Djibouti is a small country in the Horn of Africa with a high TB incidence (378/100,000 in 2015). Multidrug-resistant TB (MDR-TB) and resistance to second-line agents have been previously identified in the country but the extent of the problem has yet to be quantified. A national survey was conducted to estimate the proportion of MDR-TB among a representative sample of TB patients. Sputum was tested using XpertMTB/RIF and samples positive for MTB and resistant to rifampicin underwent first line phenotypic susceptibility testing. The TB supranational reference laboratory in Milan, Italy, undertook external quality assurance, genotypic testing based on whole genome and targeted-deep sequencing and phylogenetic studies. 301 new and 66 previously treated TB cases were enrolled. MDR-TB was detected in 34 patients: 4.7% of new and 31% of previously treated cases. Resistance to pyrazinamide, aminoglycosides and capreomycin was detected in 68%, 18% and 29% of MDR-TB strains respectively, while resistance to fluoroquinolones was not detected. Cluster analysis identified transmission of MDR-TB as a critical factor fostering drug resistance in the country. Levels of MDR-TB in Djibouti are among the highest on the African continent. High prevalence of resistance to pyrazinamide and second-line injectable agents have important implications for treatment regimens.

Hit Generation in TB Drug Discovery: From Genome to Granuloma

PubMed Central

2018-01-01

Current tuberculosis (TB) drug development efforts are not sufficient to end the global TB epidemic. Recent efforts have focused on the development of whole-cell screening assays because biochemical, target-based inhibitor screens during the last two decades have not delivered new TB drugs. Mycobacterium tuberculosis (Mtb), the causative agent of TB, encounters diverse microenvironments and can be found in a variety of metabolic states in the human host. Due to the complexity and heterogeneity of Mtb infection, no single model can fully recapitulate the in vivo conditions in which Mtb is found in TB patients, and there is no single “standard” screening condition to generate hit compounds for TB drug development. However, current screening assays have become more sophisticated as researchers attempt to mirror the complexity of TB disease in the laboratory. In this review, we describe efforts using surrogates and engineered strains of Mtb to focus screens on specific targets. We explain model culture systems ranging from carbon starvation to hypoxia, and combinations thereof, designed to represent the microenvironment which Mtb encounters in the human body. We outline ongoing efforts to model Mtb infection in the lung granuloma. We assess these different models, their ability to generate hit compounds, and needs for further TB drug development, to provide direction for future TB drug discovery. PMID:29384369

Comparative Genomics of Field Isolates of Mycobacterium bovis and M. caprae Provides Evidence for Possible Correlates with Bacterial Viability and Virulence

PubMed Central

de la Fuente, José; Díez-Delgado, Iratxe; Contreras, Marinela; Vicente, Joaquín; Cabezas-Cruz, Alejandro; Tobes, Raquel; Manrique, Marina; López, Vladimir; Romero, Beatriz; Bezos, Javier; Dominguez, Lucas; Sevilla, Iker A.; Garrido, Joseba M.; Juste, Ramón; Madico, Guillermo; Jones-López, Edward; Gortazar, Christian

2015-01-01

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly affect humans and animals worldwide. The life cycle of mycobacteria is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Recently, comparative genomics analyses have provided new insights into the evolution and adaptation of the MTBC to survive inside the host. However, most of this information has been obtained using M. tuberculosis but not other members of the MTBC such as M. bovis and M. caprae. In this study, the genome of three M. bovis (MB1, MB3, MB4) and one M. caprae (MB2) field isolates with different lesion score, prevalence and host distribution phenotypes were sequenced. Genome sequence information was used for whole-genome and protein-targeted comparative genomics analysis with the aim of finding correlates with phenotypic variation with potential implications for tuberculosis (TB) disease risk assessment and control. At the whole-genome level the results of the first comparative genomics study of field isolates of M. bovis including M. caprae showed that as previously reported for M. tuberculosis, sequential chromosomal nucleotide substitutions were the main driver of the M. bovis genome evolution. The phylogenetic analysis provided a strong support for the M. bovis/M. caprae clade, but supported M. caprae as a separate species. The comparison of the MB1 and MB4 isolates revealed differences in genome sequence, including gene families that are important for bacterial infection and transmission, thus highlighting differences with functional implications between isolates otherwise classified with the same spoligotype. Strategic protein-targeted analysis using the ESX or type VII secretion system, proteins linking stress response with lipid metabolism, host T cell epitopes of mycobacteria, antigens and peptidoglycan assembly protein identified new genetic markers and candidate vaccine antigens that warrant further study to develop tools to evaluate risks for TB disease caused by M. bovis/M.caprae and for TB control in humans and animals. PMID:26583774

Evidence-based design and evaluation of a whole genome sequencing clinical report for the reference microbiology laboratory

PubMed Central

Crisan, Anamaria; McKee, Geoffrey; Munzner, Tamara

2018-01-01

Background Microbial genome sequencing is now being routinely used in many clinical and public health laboratories. Understanding how to report complex genomic test results to stakeholders who may have varying familiarity with genomics—including clinicians, laboratorians, epidemiologists, and researchers—is critical to the successful and sustainable implementation of this new technology; however, there are no evidence-based guidelines for designing such a report in the pathogen genomics domain. Here, we describe an iterative, human-centered approach to creating a report template for communicating tuberculosis (TB) genomic test results. Methods We used Design Study Methodology—a human centered approach drawn from the information visualization domain—to redesign an existing clinical report. We used expert consults and an online questionnaire to discover various stakeholders’ needs around the types of data and tasks related to TB that they encounter in their daily workflow. We also evaluated their perceptions of and familiarity with genomic data, as well as its utility at various clinical decision points. These data shaped the design of multiple prototype reports that were compared against the existing report through a second online survey, with the resulting qualitative and quantitative data informing the final, redesigned, report. Results We recruited 78 participants, 65 of whom were clinicians, nurses, laboratorians, researchers, and epidemiologists involved in TB diagnosis, treatment, and/or surveillance. Our first survey indicated that participants were largely enthusiastic about genomic data, with the majority agreeing on its utility for certain TB diagnosis and treatment tasks and many reporting some confidence in their ability to interpret this type of data (between 58.8% and 94.1%, depending on the specific data type). When we compared our four prototype reports against the existing design, we found that for the majority (86.7%) of design comparisons, participants preferred the alternative prototype designs over the existing version, and that both clinicians and non-clinicians expressed similar design preferences. Participants showed clearer design preferences when asked to compare individual design elements versus entire reports. Both the quantitative and qualitative data informed the design of a revised report, available online as a LaTeX template. Conclusions We show how a human-centered design approach integrating quantitative and qualitative feedback can be used to design an alternative report for representing complex microbial genomic data. We suggest experimental and design guidelines to inform future design studies in the bioinformatics and microbial genomics domains, and suggest that this type of mixed-methods study is important to facilitate the successful translation of pathogen genomics in the clinic, not only for clinical reports but also more complex bioinformatics data visualization software. PMID:29340235

Use of whole-genome sequencing and evaluation of the apparent sensitivity and specificity of antemortem tuberculosis tests in the investigation of an unusual outbreak of Mycobacterium bovis infection in a Michigan dairy herd.

PubMed

Bruning-Fann, Colleen S; Robbe-Austerman, Suelee; Kaneene, John B; Thomsen, Bruce V; Tilden, John D; Ray, Jean S; Smith, Richard W; Fitzgerald, Scott D; Bolin, Steven R; O'Brien, Daniel J; Mullaney, Thomas P; Stuber, Tod P; Averill, James J; Marks, David

2017-07-15

OBJECTIVE To describe use of whole-genome sequencing (WGS) and evaluate the apparent sensitivity and specificity of antemortem tuberculosis tests during investigation of an unusual outbreak of Mycobacterium bovis infection in a Michigan dairy herd. DESIGN Bovine tuberculosis (bTB) outbreak investigation. ANIMALS Cattle, cats, dog, and wildlife. PROCEDURES All cattle in the index dairy herd were screened for bTB with the caudal fold test (CFT), and cattle ≥ 6 months old were also screened with a γ-interferon (γIFN) assay. The index herd was depopulated along with all barn cats and a dog that were fed unpasteurized milk from the herd. Select isolates from M bovis-infected animals from the index herd and other bTB-affected herds underwent WGS. Wildlife around all affected premises was examined for bTB. RESULTS No evidence of bTB was found in any wildlife examined. Within the index herd, 53 of 451 (11.8%) cattle and 12 of 21 (57%) cats were confirmed to be infected with M bovis. Prevalence of M bovis-infected cattle was greatest among 4- to 7-month-old calves (16/49 [33%]) followed by adult cows (36/203 [18%]). The apparent sensitivity and specificity were 86.8% and 92.7% for the CFT and 80.4% and 96.5% for the γIFN assay when results for those tests were interpreted separately and 96.1% and 91.7% when results were interpreted in parallel. Results of WGS revealed that M bovis-infected barn cats and cattle from the index herd and 6 beef operations were infected with the same strain of M bovis. Of the 6 bTB-affected beef operations identified during the investigation, 3 were linked to the index herd only by WGS results; there was no record of movement of livestock or waste milk from the index herd to those operations. CONCLUSIONS AND CLINICAL RELEVANCE Whole-genome sequencing enhanced the epidemiological investigation and should be used in all disease investigations. Performing the CFT and γIFN assay in parallel improved the antemortem ability to detect M bovis-infected animals. Contact with M bovis-infected cattle and contaminated milk were major risk factors for transmission of bTB within and between herds of this outbreak.

Modelling the social and structural determinants of tuberculosis: opportunities and challenges

PubMed Central

Boccia, D.; Dodd, P. J.; Lönnroth, K.; Dowdy, D. W.; Siroka, A.; Kimerling, M. E.; White, R. G.; Houben, R. M. G. J.

2017-01-01

INTRODUCTION: Despite the close link between tuberculosis (TB) and poverty, most mathematical models of TB have not addressed underlying social and structural determinants. OBJECTIVE: To review studies employing mathematical modelling to evaluate the epidemiological impact of the structural determinants of TB. METHODS: We systematically searched PubMed and personal libraries to identify eligible articles. We extracted data on the modelling techniques employed, research question, types of structural determinants modelled and setting. RESULTS: From 232 records identified, we included eight articles published between 2008 and 2015; six employed population-based dynamic TB transmission models and two non-dynamic analytic models. Seven studies focused on proximal TB determinants (four on nutritional status, one on wealth, one on indoor air pollution, and one examined overcrowding, socioeconomic and nutritional status), and one focused on macro-economic influences. CONCLUSIONS: Few modelling studies have attempted to evaluate structural determinants of TB, resulting in key knowledge gaps. Despite the challenges of modelling such a complex system, models must broaden their scope to remain useful for policy making. Given the intersectoral nature of the interrelations between structural determinants and TB outcomes, this work will require multidisciplinary collaborations. A useful starting point would be to focus on developing relatively simple models that can strengthen our knowledge regarding the potential effect of the structural determinants on TB outcomes. PMID:28826444

Genome organization of Tobacco leaf curl Zimbabwe virus, a new, distinct monopartite begomovirus associated with subgenomic defective DNA molecules.

PubMed

Paximadis, M; Rey, M E

2001-12-01

The complete DNA A of the begomovirus Tobacco leaf curl Zimbabwe virus (TbLCZWV) was sequenced: it comprises 2767 nucleotides with six major open reading frames encoding proteins with molecular masses greater than 9 kDa. Full-length TbLCZWV DNA A tandem dimers, cloned in binary vectors (pBin19 and pBI121) and transformed into Agrobacterium tumefaciens, were systemically infectious upon agroinoculation of tobacco and tomato. Efforts to identify a DNA B component were unsuccessful. These findings suggest that TbLCZWV is a new member of the monopartite group of begomoviruses. Phylogenetic analysis identified TbLCZWV as a distinct begomovirus with its closest relative being Chayote mosaic virus. Abutting primer PCR amplified ca. 1300 bp molecules, and cloning and sequencing of two of these molecules revealed them to be subgenomic defective DNA molecules originating from TbLCZWV DNA A. Variable symptom severity associated with tobacco leaf curl disease and TbLCZWV is discussed.

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement.

PubMed

Domínguez, J; Boettger, E C; Cirillo, D; Cobelens, F; Eisenach, K D; Gagneux, S; Hillemann, D; Horsburgh, R; Molina-Moya, B; Niemann, S; Tortoli, E; Whitelaw, A; Lange, C

2016-01-01

The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.

Structural and spectroscopic investigation of new luminescent hybrid materials based on calix[4]arene-tetracarboxylate and Ln3+ ions (Ln = Gd, Tb or Eu)

NASA Astrophysics Data System (ADS)

Viana, R. S.; Oliveira, C. A. F.; Chojnacki, J.; Barros, B. S.; Alves-Jr, S.; Kulesza, J.

2017-07-01

Lanthanide-calixarene hybrid materials are of particular interest due to the combination of the interesting properties of the ligand cavity-like structure and the luminescent features of lanthanides. The aim of this study was to synthesize and investigate the photophysical properties of Eu3+, Tb3+ and Gd3+ hybrids based on calix[4]arene-tetracarboxylate. The preparation of two structurally different Tb3+ compounds (calix-TA-SC-Tb and calix-TA-Tb) was dictated by the ligand to metal molar ratio and the synthesis time. Analysis of calix-TA-SC-Tb monocrystals revealed the formation of a mononuclear complex of C2 symmetry containing Tb3+ coordinated by four calixarene ionized groups and formate anion encapsulated within the upper cavity. Syntheses of other hybrids failed in producing high-quality crystals and the structures could not be solved. The solid-state luminescent properties of hybrids were evaluated, and the structure/property relationship was investigated. Based on the emission and excitation spectra, the energy diagrams for calix-TA-Eu, calix-TA-Tb and calix-TA-Gd were proposed.

Confirming the Revised C-Terminal Domain of the MscL Crystal Structure

PubMed Central

Maurer, Joshua A.; Elmore, Donald E.; Clayton, Daniel; Xiong, Li; Lester, Henry A.; Dougherty, Dennis A.

2008-01-01

The structure of the C-terminal domain of the mechanosensitive channel of large conductance (MscL) has generated significant controversy. As a result, several structures have been proposed for this region: the original crystal structure (1MSL) of the Mycobacterium tuberculosis homolog (Tb), a model of the Escherichia coli homolog, and, most recently, a revised crystal structure of Tb-MscL (2OAR). To understand which of these structures represents a physiological conformation, we measured the impact of mutations to the C-terminal domain on the thermal stability of Tb-MscL using circular dichroism and performed molecular dynamics simulations of the original and the revised crystal structures of Tb-MscL. Our results imply that this region is helical and adopts an α-helical bundle conformation similar to that observed in the E. coli MscL model and the revised Tb-MscL crystal structure. PMID:18326638

Whole genome sequencing of the monomorphic pathogen Mycobacterium bovis reveals local differentiation of cattle clinical isolates.

PubMed

Lasserre, Moira; Fresia, Pablo; Greif, Gonzalo; Iraola, Gregorio; Castro-Ramos, Miguel; Juambeltz, Arturo; Nuñez, Álvaro; Naya, Hugo; Robello, Carlos; Berná, Luisa

2018-01-02

Bovine tuberculosis (bTB) poses serious risks to animal welfare and economy, as well as to public health as a zoonosis. Its etiological agent, Mycobacterium bovis, belongs to the Mycobacterium tuberculosis complex (MTBC), a group of genetically monomorphic organisms featured by a remarkably high overall nucleotide identity (99.9%). Indeed, this characteristic is of major concern for correct typing and determination of strain-specific traits based on sequence diversity. Due to its historical economic dependence on cattle production, Uruguay is deeply affected by the prevailing incidence of Mycobacterium bovis. With the world's highest number of cattle per human, and its intensive cattle production, Uruguay represents a particularly suited setting to evaluate genomic variability among isolates, and the diversity traits associated to this pathogen. We compared 186 genomes from MTBC strains isolated worldwide, and found a highly structured population in M. bovis. The analysis of 23 new M. bovis genomes, belonging to strains isolated in Uruguay evidenced three groups present in the country. Despite presenting an expected highly conserved genomic structure and sequence, these strains segregate into a clustered manner within the worldwide phylogeny. Analysis of the non-pe/ppe differential areas against a reference genome defined four main sources of variability, namely: regions of difference (RD), variable genes, duplications and novel genes. RDs and variant analysis segregated the strains into clusters that are concordant with their spoligotype identities. Due to its high homoplasy rate, spoligotyping failed to reflect the true genomic diversity among worldwide representative strains, however, it remains a good indicator for closely related populations. This study introduces a comprehensive population structure analysis of worldwide M. bovis isolates. The incorporation and analysis of 23 novel Uruguayan M. bovis genomes, sheds light onto the genomic diversity of this pathogen, evidencing the existence of greater genetic variability among strains than previously contemplated.

Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis.

PubMed

Souza de Lima, D; Ogusku, M M; Sadahiro, A; Pontillo, A

2016-07-01

Tuberculosis (TB) continues to be a major public health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb) but remains asymptomatic (latent TB) and only 5% to 10% of these latent individuals will develop active pulmonary TB. Factors affecting the balance between latent and active TB are mostly unknown, even if host genome has been shown to contribute to the outcome of Mtb response. Acute inflammation and Th1 response are important in the early clearance of the bacteria as it was emphasized by the association between immune genes (i.e.: HLA, IFNG, TNF, NRPAM1, IL10) variants and the development of active pulmonary TB. Recently, the role of the inflammasome in experimental TB has been demonstrated, however, to our knowledge, no data still exist about the contribution of inflammasome genetics to Mtb susceptibility and/or to the development of active TB. For this reason, selected polymorphisms in inflammasome genes were analysed in a case/control cohort of individuals with active pulmonary TB from an endemic area of Brazil Amazon. Our data evidence the novel association between polymorphisms in NLRP3-inflammasome encoding genes and active pulmonary TB, and replicated the association between P2X7 and TB observed in other populations. These results emphasize the role of NLRP3-inflammasome also in human TB, and contribute to our knowledge about pathways involved in the development of active TB, even if deeper investigation are needed to fully elucidate the role of the complex in Mtb infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Multi- and Extensively Drug Resistant Mycobacterium tuberculosis in South Africa: a Molecular Analysis of Historical Isolates.

PubMed

Maningi, Nontuthuko E; Daum, Luke T; Rodriguez, John D; Said, Halima M; Peters, Remco P H; Sekyere, John Osei; Fischer, Gerald W; Chambers, James P; Fourie, P Bernard

2018-05-01

Modern advances in genomics provide an opportunity to reinterpret historical bacterial culture collections. In this study, genotypic antibiotic resistance profiles of Mycobacterium tuberculosis isolates from a historical 20-year-old multidrug-resistant tuberculosis (MDR-TB) culture collection in South Africa are described. DNA samples extracted from the phenotypically MDR-TB isolates ( n = 240) were assayed by Hain line probe assay (LPA) for the confirmation of MDR-TB and by Illumina Miseq whole-genome sequencing (WGS) for the characterization of mutations in eight genes ( rpoB , katG , inhA , rpsL , pncA , embB , gyrA , and rrs ) that are known to code for resistance to commonly used anti-TB agents. LPA identified 71.3% of the TB isolates as MDR-TB, 18.3% as rifampin (RIF) monoresistant, 2% as isoniazid (INH) monoresistant, and 8.3% as susceptible to both RIF and INH (RIF+INH). In a subset of 42 randomly selected isolates designated as RIF+INH resistant by Löwenstein-Jensen (LJ) culture in 1993, LPA and WGS results confirmed MDR-TB. In all five INH-monoresistant isolates by LPA and in all but one (the wild type) of the 34 successfully sequenced RIF-monoresistant isolates, WGS revealed matching mutations. Only 26% of isolates designated as susceptible by LPA, however, were found to be wild type by WGS. Novel mutations were found in the rpoB (Thr480Ala, Gln253Arg, Val249Met, Val251Tyr, Val251Phe), katG (Trp477STOP, Gln88STOP, Trp198STOP, Trp412STOP), embB (Thr11Xaa, Gln59Pro), and pncA (Thr100Ile, Thr159Ala, Ala134Arg, Val163Ala, Thr153Ile, DelGpos7, Phe106Ser) genes. Three MDR-TB isolates showed mutations in both the gyrA and rrs genes, suggesting that extensively drug-resistant tuberculosis existed in South Africa well before its formal recognition in 2006. Copyright © 2018 American Society for Microbiology.

A Global Comparison of the Human and T. brucei Degradomes Gives Insights about Possible Parasite Drug Targets

PubMed Central

Mashiyama, Susan T.; Koupparis, Kyriacos; Caffrey, Conor R.; McKerrow, James H.; Babbitt, Patricia C.

2012-01-01

We performed a genome-level computational study of sequence and structure similarity, the latter using crystal structures and models, of the proteases of Homo sapiens and the human parasite Trypanosoma brucei. Using sequence and structure similarity networks to summarize the results, we constructed global views that show visually the relative abundance and variety of proteases in the degradome landscapes of these two species, and provide insights into evolutionary relationships between proteases. The results also indicate how broadly these sequence sets are covered by three-dimensional structures. These views facilitate cross-species comparisons and offer clues for drug design from knowledge about the sequences and structures of potential drug targets and their homologs. Two protease groups (“M32” and “C51”) that are very different in sequence from human proteases are examined in structural detail, illustrating the application of this global approach in mining new pathogen genomes for potential drug targets. Based on our analyses, a human ACE2 inhibitor was selected for experimental testing on one of these parasite proteases, TbM32, and was shown to inhibit it. These sequence and structure data, along with interactive versions of the protein similarity networks generated in this study, are available at http://babbittlab.ucsf.edu/resources.html. PMID:23236535

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

PubMed

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

2017-03-01

Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

A whole genome bioinformatic approach to determine potential latent phase specific targets in Mycobacterium tuberculosis.

PubMed

Defelipe, Lucas A; Do Porto, Dario Fernández; Pereira Ramos, Pablo Ivan; Nicolás, Marisa Fabiana; Sosa, Ezequiel; Radusky, Leandro; Lanzarotti, Esteban; Turjanski, Adrián G; Marti, Marcelo A

2016-03-01

Current Tuberculosis treatment is long and expensive, faces the increasing burden of MDR/XDR strains and lack of effective treatment against latent form, resulting in an urgent need of new anti-TB drugs. Key to TB biology is its capacity to fight the host's RNOS mediated attack. RNOS are known to display a concentration dependent mycobactericidal activity, which leads to the following hypothesis "if we know which proteins are targeted by RNOS and kill TB, we we might be able to inhibit them with drugs resulting in a synergistic bactericidal effect". Based on this idea, we performed an Mtb metabolic network whole proteome analysis of potential RNOS sensitive and relevant targets which includes target druggability and essentiality criteria. Our results, available at http://tuberq.proteinq.com.ar yield new potential TB targets, like I3PS, while also providing and updated view of previous proposals becoming an important tool for researchers looking for new ways of killing TB. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increasing the structural coverage of tuberculosis drug targets.

PubMed

Baugh, Loren; Phan, Isabelle; Begley, Darren W; Clifton, Matthew C; Armour, Brianna; Dranow, David M; Taylor, Brandy M; Muruthi, Marvin M; Abendroth, Jan; Fairman, James W; Fox, David; Dieterich, Shellie H; Staker, Bart L; Gardberg, Anna S; Choi, Ryan; Hewitt, Stephen N; Napuli, Alberto J; Myers, Janette; Barrett, Lynn K; Zhang, Yang; Ferrell, Micah; Mundt, Elizabeth; Thompkins, Katie; Tran, Ngoc; Lyons-Abbott, Sally; Abramov, Ariel; Sekar, Aarthi; Serbzhinskiy, Dmitri; Lorimer, Don; Buchko, Garry W; Stacy, Robin; Stewart, Lance J; Edwards, Thomas E; Van Voorhis, Wesley C; Myler, Peter J

2015-03-01

High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1 Å, >85% side chain identity, and ≥80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Increasing the Structural Coverage of Tuberculosis Drug Targets

PubMed Central

Baugh, Loren; Phan, Isabelle; Begley, Darren W.; Clifton, Matthew C.; Armour, Brianna; Dranow, David M.; Taylor, Brandy M.; Muruthi, Marvin M.; Abendroth, Jan; Fairman, James W.; Fox, David; Dieterich, Shellie H.; Staker, Bart L.; Gardberg, Anna S.; Choi, Ryan; Hewitt, Stephen N.; Napuli, Alberto J.; Myers, Janette; Barrett, Lynn K.; Zhang, Yang; Ferrell, Micah; Mundt, Elizabeth; Thompkins, Katie; Tran, Ngoc; Lyons-Abbott, Sally; Abramov, Ariel; Sekar, Aarthi; Serbzhinskiy, Dmitri; Lorimer, Don; Buchko, Garry W.; Stacy, Robin; Stewart, Lance J.; Edwards, Thomas E.; Van Voorhis, Wesley C.; Myler, Peter J.

2015-01-01

High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus “homolog-rescue” strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1Å, >85% side chain identity, and ≥80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases. PMID:25613812

Increasing the structural coverage of tuberculosis drug targets

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

Baugh, Loren; Phan, Isabelle; Begley, Darren W.

High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus “homolog-rescue” strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. We found that of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structuresmore » would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1 Å, >85% side chain identity, and ≥80% PS APF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.« less

Increasing the structural coverage of tuberculosis drug targets

DOE PAGES

Baugh, Loren; Phan, Isabelle; Begley, Darren W.; ...

2014-12-19

High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus “homolog-rescue” strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. We found that of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structuresmore » would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with >55% overall sequence identity had active site Cα RMSD <1 Å, >85% side chain identity, and ≥80% PS APF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared >55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.« less

Giant magnetoelectric effect in negative magnetostrictive/piezoelectric/positive magnetostrictive semiring structure

NASA Astrophysics Data System (ADS)

Zeng, Lingyu; Zhou, Minhong; Bi, Ke; Lei, Ming

2016-01-01

Magnetoelectric (ME) Ni/PZT/TbFe2 and TbFe2/PZT composites with two semiring structures are prepared. The dependence between ME coupling and magnetostrictive property of the composite is discussed. Because Ni possesses negative magnetostrictive property and TbFe2 shows positive magnetostrictive property, the ME voltage coefficient of Ni/PZT/TbFe2 semiring structure is much larger than that of TbFe2/PZT. In these composites, the ME voltage coefficient increases and the resonance frequency gradually decreases with the increase of the semiring radius, showing that structural parameters are key factors to the composite properties. Due to the strong ME coupling effect, a giant ME voltage coefficient αE = 44.8 V cm-1 Oe-1 is obtained. This approach opens a way for the design of ME composites with giant ME voltage coefficient.

Hydrothermal synthesis of 4ZnO·B2O3·H2O:Ln3 + (Ln = Eu, Tb) phosphors: Morphology-tunable and luminescence properties

NASA Astrophysics Data System (ADS)

Cao, Shiwei; Jiao, Yang; Han, Weifang; Ge, Chunhua; Song, Bo; Wang, Jie; Zhang, Xiangdong

2018-02-01

4ZnO·B2O3·H2O:Ln3 + (Ln = Eu, Tb) phosphors with different morphologies have been successfully synthesized via one-step hydrothermal method through regulating the molar amount of Eu3 + and Tb3 +. Comprehensive scanning electron microscopy (SEM), X-ray diffraction (XRD) Fourier transform infrared spectrum (FT-IR) and inductively coupled plasma atomic emission spectrometer (ICP-AES) characterizations all confirm that obtained products are 4ZnO·B2O3·H2O:Ln3 + (Ln = Eu, Tb). The experimental results displayed that the morphology and photoluminescence of compounds is regularly changed with increased the molar amount of rare earth ions. For the Eu3 +-doped, Tb3 +-doped and Eu3 +/Tb3 + co-doped 4ZnO·B2O3·H2O phosphors of morphologies, the rod-like structures gradually changed to flower-like structures, fine wire-like structure and hybrid structure, respectively. To their photoluminescence, the Eu3 + shows a red emission (615 nm); the Tb3 + shows a green emission (545 nm); for the Eu3 +/Tb3 + co-doped 4ZnO·B2O3·H2O phosphors, a combination of blue (5d-4f of Eu2 +), green (5D4-7F5 of Tb3 +) and red (5D0-7F2 of Eu3 +) emissions emerges to achieve white emission. In addition, the energy transfer among Eu3 +, Eu2 + and Tb3 + ions was also discussed.

Na3Tb(PO4)2: Synthesis, crystal structure and greenish emitting properties

NASA Astrophysics Data System (ADS)

Zhao, Dan; Ma, Zhao; Liu, Bao-Zhong; Zhang, Rui-Juan; Wu, Zhi-Qiang; Wang, Jian; Duan, Pei-Gao

2018-03-01

A anhydrous orthoborate Na3Tb(PO4)2 has been prepared and its crystal structure was determined by X-Ray diffraction of a non-merohedral twinned single crystal. The results show that the compound crystallizes in monoclinic space group C2/c and the structure features a 3D framework containing PO4, NaO6, NaO7, NaO8 and TbO8 polyhedra. Under near-UV excitation (370 nm), Na3Tb(PO4)2 shows intense characteristic emission bands of Tb3+ (490 nm, 543 nm, 585 nm and 620 nm) with the CIE coordinate of (0.3062, 0.5901), corresponding to greenish color. The excitation spectrum covers a wide range from 340 nm to 390 nm, which indicates that phosphor Na3Tb(PO4)2 can be efficiently activated by near-UV LED ship.

The Cancer Genomics Hub (CGHub): overcoming cancer through the power of torrential data

PubMed Central

Wilks, Christopher; Cline, Melissa S.; Weiler, Erich; Diehkans, Mark; Craft, Brian; Martin, Christy; Murphy, Daniel; Pierce, Howdy; Black, John; Nelson, Donavan; Litzinger, Brian; Hatton, Thomas; Maltbie, Lori; Ainsworth, Michael; Allen, Patrick; Rosewood, Linda; Mitchell, Elizabeth; Smith, Bradley; Warner, Jim; Groboske, John; Telc, Haifang; Wilson, Daniel; Sanford, Brian; Schmidt, Hannes; Haussler, David; Maltbie, Daniel

2014-01-01

The Cancer Genomics Hub (CGHub) is the online repository of the sequencing programs of the National Cancer Institute (NCI), including The Cancer Genomics Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects, with data from 25 different types of cancer. The CGHub currently contains >1.4 PB of data, has grown at an average rate of 50 TB a month and serves >100 TB per week. The architecture of CGHub is designed to support bulk searching and downloading through a Web-accessible application programming interface, enforce patient genome confidentiality in data storage and transmission and optimize for efficiency in access and transfer. In this article, we describe the design of these three components, present performance results for our transfer protocol, GeneTorrent, and finally report on the growth of the system in terms of data stored and transferred, including estimated limits on the current architecture. Our experienced-based estimates suggest that centralizing storage and computational resources is more efficient than wide distribution across many satellite labs. Database URL: https://cghub.ucsc.edu PMID:25267794

Effect of Tb{sup 3+} concentration on the optical and vibrational properties of YBO{sub 3} tri-doped with Eu{sup 3+}, Ce{sup 3+}, and Tb{sup 3+}

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

Sohal, S.; Hassanzadeh, E.; Huang, J. Y.

2014-05-14

Structural and optical studies are reported of yttrium orthoborate YBO{sub 3} when tri-doped with Eu{sup 3+}, Ce{sup 3+}, and Tb{sup 3+}, focusing on the role of terbium concentration. Incorporation of Tb{sup 3+} affects emission properties for photoluminescence (PL) excited by near ultraviolet light. For constant cerium and europium concentrations, increasing the Tb{sup 3+} results in diminished PL from the Ce{sup 3+} and Tb{sup 3+} color centers. Simultaneously, the PL excitation bands related to both Ce{sup 3+} and Tb{sup 3+} increase in intensity for red emission from the Eu{sup 3+}. Results are consistent with a Ce{sup 3+} → (Tb{sup 3+}){sub n} → Eu{sup 3+} energymore » transfer scheme, where (Tb{sup 3+}){sub n} denotes a chain incorporating n terbium ions. A high red to orange PL intensity ratio is obtained, ranging from 1.34 to 2.09. Raman vibrational bands show a systematic change, with Tb{sup 3+} concentration, in the B{sub 3}O{sub 9} ring terminal oxygen bending mode coordinated with the yttrium site where dopant ions substitute. The structural changes are interpreted as variations in the local neighborhood of these sites in the YBO{sub 3}:Ce{sup 3+},Tb{sup 3+},Eu{sup 3+} crystal structure.« less

Molecular Epidemiology of Mycobacterium tuberculosis Isolates in 100 Patients With Tuberculosis Using Pulsed Field Gel Electrophoresis

PubMed Central

Pooideh, Mohammad; Jabbarzadeh, Ismail; Ranjbar, Reza; Saifi, Mahnaz

2015-01-01

Background: Tuberculosis (TB) is a widespread infectious disease. Today, TB has created a public health crisis in the world. Genotyping of Mycobacterium tuberculosis isolates is useful for surveying the dynamics of TB infection, identifying new outbreaks, and preventing the disease. Different molecular methods for clustering of M. tuberculosis isolates have been used. Objectives: During a one year study of genotyping, 100 M. tuberculosis isolates from patients referred to Pasteur Institute of Iran were collected and their genotyping was accomplished using pulsed field gel electrophoresis (PFGE) method. Materials and Methods: Identification of all M. tuberculosis isolates was accomplished using standard biochemical and species-specific polymerase chain reaction (PCR) methods. Antibiotic susceptibility tests were performed using proportional method. After preparing PFGE plaques for each isolate of M. tuberculosis, XbaI restriction enzyme was applied for genome digestion. Finally, the digested DNA fragments were separated on 1% agarose gel and analyzed with GelCompar II software. Results: Genotyping of the studied isolates in comparison with the molecular weight marker revealed two common types; pulsotype A with 71 isolates and one multidrug resistant mycobacterium (MDR) case, and pulsotype B including 29 isolates and three MDR cases. No correlation between the antibiotypes and pulsotypes was observed. Conclusions: Molecular epidemiology studies of infectious diseases have been useful when bacterial isolates have been clustered in a period of time and in different geographical regions with variable antibiotic resistance patterns. In spite of high geographical differences and different antibiotic resistant patterns, low genetic diversity among the studied TB isolates may refer to the low rate of mutations in XbaI restriction sites in the mycobacterial genome. We also identified three MDR isolates in low-incidence pulsotype B, which could be disseminated and is highly important to consider in TB surveillance programs to prevent the spread of MDR-TB isolates in the population. PMID:26396714

Populations of latent Mycobacterium tuberculosis lack a cell wall: Isolation, visualization, and whole-genome characterization.

PubMed

Velayati, Ali Akbar; Abeel, Thomas; Shea, Terrance; Konstantinovich Zhavnerko, Gennady; Birren, Bruce; Cassell, Gail H; Earl, Ashlee M; Hoffner, Sven; Farnia, Parissa

2016-03-01

Mycobacterium tuberculosis (MTB) causes active tuberculosis (TB) in only a small percentage of infected people. In most cases, the infection is clinically latent, where bacilli can persist in human hosts for years without causing disease. Surprisingly, the biology of such persister cells is largely unknown. This study describes the isolation, identification, and whole-genome sequencing (WGS) of latent TB bacilli after 782days (26months) of latency (the ability of MTB bacilli to lie persistent). The in vitro double-stress model of latency (oxygen and nutrition) was designed for MTB culture. After 26months of latency, MTB cells that persisted were isolated and investigated under light and atomic force microscopy. Spoligotyping and WGS were performed to verify the identity of the strain. We established a culture medium in which MTB bacilli arrest their growth, reduce their size (0.3-0.1μm), lose their acid fastness (85-90%) and change their shape. Spoligopatterns of latent cells were identical to original H37Rv, with differences observed at spacers two and 14. WGS revealed only a few genetic changes relative to the already published H37Rv reference genome. Among these was a large 2064-bp insertion (RvD6), which was originally detected in both H37Ra and CDC1551, but not H37Rv. Here, we show cell-wall free cells of MTB bacilli in their latent state, and the biological adaptation of these cells was more phenotypic in nature than genomic. These cell-wall free cells represent a good model for understanding the nature of TB latency. Copyright © 2015 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Structure and Luminescence Properties of New Green-Emitting Phosphor BaAl12O19:Tb

NASA Astrophysics Data System (ADS)

Xiao, Linjiu; He, Mingrui; Tian, Yanwen; Chen, Yongjie; Karaki, Tomoaki; Zhang, Liqing; Wang, Ning

2007-09-01

New green-emitting BaAl12O19:Tb phosphors were prepared by using the sol-gel method, and their structure and luminescence property were characterized by X-ray diffraction (XRD) analysis and fluorescence spectrometry. The results of XRD analysis revealed that a Ba1-xAl12O19:Tbx crystal structure was obtained at 1300 °C and Tb3+ ions substituted Ba2+ ions into the BaAl12O19 phase in the ion range x=0.005--0.05. The excitation peak of BaAl12O19:Tb was a wide band at approximately 240 nm, originating from the 4 f8-4 f75d1 transition of Tb3+. The emission spectrum consisted of eight emission peaks, originating from the 5D3-7Fi (i=6,5,4,3) and 5D4-7Fj ( j=6,5,4,3) transitions of Tb3+. The emission intensity of BaAl12O19:Tb phosphors at 543 nm was strongest when the phosphors were crystallized at 1300 °C for 2 h, and the content of Tb3+ was 2 mol %.

Phenotypic and genomic comparison of Mycobacterium aurum and surrogate model species to Mycobacterium tuberculosis: implications for drug discovery.

PubMed

Namouchi, Amine; Cimino, Mena; Favre-Rochex, Sandrine; Charles, Patricia; Gicquel, Brigitte

2017-07-13

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and represents one of the major challenges facing drug discovery initiatives worldwide. The considerable rise in bacterial drug resistance in recent years has led to the need of new drugs and drug regimens. Model systems are regularly used to speed-up the drug discovery process and circumvent biosafety issues associated with manipulating M. tuberculosis. These include the use of strains such as Mycobacterium smegmatis and Mycobacterium marinum that can be handled in biosafety level 2 facilities, making high-throughput screening feasible. However, each of these model species have their own limitations. We report and describe the first complete genome sequence of Mycobacterium aurum ATCC23366, an environmental mycobacterium that can also grow in the gut of humans and animals as part of the microbiota. This species shows a comparable resistance profile to that of M. tuberculosis for several anti-TB drugs. The aims of this study were to (i) determine the drug resistance profile of a recently proposed model species, Mycobacterium aurum, strain ATCC23366, for anti-TB drug discovery as well as Mycobacterium smegmatis and Mycobacterium marinum (ii) sequence and annotate the complete genome sequence of this species obtained using Pacific Bioscience technology (iii) perform comparative genomics analyses of the various surrogate strains with M. tuberculosis (iv) discuss how the choice of the surrogate model used for drug screening can affect the drug discovery process. We describe the complete genome sequence of M. aurum, a surrogate model for anti-tuberculosis drug discovery. Most of the genes already reported to be associated with drug resistance are shared between all the surrogate strains and M. tuberculosis. We consider that M. aurum might be used in high-throughput screening for tuberculosis drug discovery. We also highly recommend the use of different model species during the drug discovery screening process.

Editorial: Current status and perspective on drug targets in tubercle bacilli and drug design of antituberculous agents based on structure-activity relationship.

PubMed

Tomioka, Haruaki

2014-01-01

Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. However, the development of new drugs for the treatment and prophylaxis of TB, particularly those truly active against dormant and persistent types of tubercle bacilli, has been slow, although some promising drugs, such as diarylquinoline TMC207, nitroimidazopyran PA-824, nitroimidazo-oxazole Delamanid (OPC-67683), oxazolidinone PNU-100480, ethylene diamine SQ-109, and pyrrole derivative LL3858, are currently under phase 1 to 3 clinical trials. Therefore, novel types of antituberculous drug, which act on unique drug targets in Mycobacterium tuberculosis (MTB) pathogens, particularly drug targets related to the establishment of mycobacterial dormancy in the host's macrophages, are urgently needed. In this context, it should be noted that current anti-TB drugs mostly target the metabolic reactions and proteins which are essential for the growth of MTB in extracellular milieus. It may also be promising to develop another type of drug that exerts an inhibitory action against bacterial virulence factors which cross-talk and interfere with signaling pathways of MTB-infected immunocompetent host cells, such as lymphocytes, macrophages, and NK cells, thereby changing the intracellular milieus that are favorable to intramacrophage survival and the growth of infected bacilli. This special issue contains ten review articles, dealing with recent approaches to identify and establish novel drug targets in MTB for the development of new and unique antitubercular drugs, including those related to mycobacterial dormancy and crosstalk with cellular signaling pathways. In addition, this special issue contains some review papers with special reference to the drug design based on quantitative structure-activity relationship (QSAR) analysis, especially three-dimensional (3D)-QSAR. New, critical information on the entire genome of MTB and mycobacterial virulence genes is promoting the elucidation of the molecular structures of drug targets in MTB, and are consequently markedly useful for the design of new, promising antituberculous drugs using QSAR techniques. In this issue, we review the following areas. Firstly, Dr. Li M. Fu reviews the perspective that combines machine learning and genomics for drug discovery in tuberculosis, in relation to the problem that the exhaustive search for useful drug targets over the entire MTB genome would not be as productive as expected in practice [1]. Secondly, the review article by Drs. R. S. Chauhan. S. K. Chanumolu, C. Rout, and R. Shrivastava focuses on analysis of the current state of MTB genomic resources, host-pathogen interaction studies in the context of mycobacterial persistence, and drug target discovery based on the utilization of computational tools and metabolic network analyses [2]. Thirdly, Drs. Daria Bottai, Agnese Serafini, Alessandro Cascioferro, Roland Brosch, and Riccardo Manganelli review the current knowledge on MTB T7SS/ESX secretion systems and their impact on MTB physiology and virulence, and the possible approaches to develop T7SS/ESX inhibitors [3]. Fourthly, Drs. E. Jeffrey North, Mary Jackson, and Richard E. Lee review and analyze new and emerging inhibitors of the mycolic acid biosynthetic pathway, including mycobacterial enzymes for fatty acid synthesis, mycolic acid-modifying enzymes, fatty acid-activating and -condensing enzymes, transporters, and transferases, that have been discovered in the post-genomic era of tuberculosis drug discovery [4]. Fifthly, Drs. Katarina Mikusova, Vadim Makarov, and Joao Neres review the mycobacterial enzyme DprE1, which catalyzes a unique epimerization reaction in the biosynthesis of decaprenylphosphoryl arabinose, a single donor of the arabinosyl residue for the build-up of arabinans, one of the mycobacterial cell wall components, as an important drug target especially for the development of benzothiazinones [5]. Sixthly, I review the present status of global research on novel drug targets related to the Toll-like receptor in the MTB pathogen, with special reference to mycobacterial virulence factors that cross-talk and interfere with signaling pathways of host macrophages [6]. The following four review articles deal with drug design of novel anti-TB agents employing QSAR techniques. Firstly, Drs. Nidhi and Mohammad Imran Siddiqi review 2D and 3D QSAR approaches and the recent trends of these methods integrated with virtual screening using the 3D pharmacophore and molecular docking approaches for the identification and design of novel antituberculous agents, by presenting a comprehensive overview of QSAR studies reported for newer antituberculous agents [7]. Secondly, Drs. Filomena Martins, Cristina Ventura, Susana Santos, and Miguel Viveiros review the current status of different QSAR-based strategies for the design of novel anti-TB drugs based upon the most active anti-TB agent, isoniazid, from the viewpoint of the development of promising derivatives that are active against isoniazid- resistant strains with katG mutations [8]. Thirdly, Drs. Sanchaita Rajkhowa and Ramesh C. Deka review current studies concerning 2D and 3D QSAR models that contain density-functional theory (DFT)-based descriptors as their parameters [9]. Notably, DFT-based descriptors such as atomic charges, molecular orbital energies, frontier orbital densities, and atom-atom polarizabilities are very useful in predicting the reactivity of atoms in molecules. Fourthly, Drs. Renata V. Bueno, Rodolpho C. Braga, Natanael D. Segretti, Elizabeth I. Ferreira, Gustavo H. G. Trossini, and Carolina H. Andrade review the current progress and applications of QSAR analysis for the discovery of innovative tuberculostatic agents as inhibitors of ribonucleotide reductase, DNA gyrase, ATP synthase, and thymidylate kinase enzymes, highlighting present challenges and new opportunities in TB drug design [10]. The aim of this issue is to address the future prospects for the development of new antituberculous drugs. There are a number of difficulties in computational drug-design for the development of new drug formulations with potential antimycobacterial effects, especially therapeutic and prophylactic efficacy against infection due to dormant-type MTB pathogens. In addition, it should be emphasized that the most urgent goal of TB chemotherapy is develop highly active, low-cost drugs which can be used not only in industrialized but also in developing countries, because most global TB incidence occurs in the latter. I am sincerely grateful to the individuals who contributed to this work. All authors are experts in their fields and they made earnest efforts to perform these in-depth reviews. I thank them all.

Hydrothermal synthesis of 4ZnO·B2O3·H2O:Ln3+ (Ln=Eu, Tb) phosphors: Morphology-tunable and luminescence properties.

PubMed

Cao, Shiwei; Jiao, Yang; Han, Weifang; Ge, Chunhua; Song, Bo; Wang, Jie; Zhang, Xiangdong

2018-02-05

4ZnO·B 2 O 3 ·H 2 O:Ln 3+ (Ln=Eu, Tb) phosphors with different morphologies have been successfully synthesized via one-step hydrothermal method through regulating the molar amount of Eu 3+ and Tb 3+ . Comprehensive scanning electron microscopy (SEM), X-ray diffraction (XRD) Fourier transform infrared spectrum (FT-IR) and inductively coupled plasma atomic emission spectrometer (ICP-AES) characterizations all confirm that obtained products are 4ZnO·B 2 O 3 ·H 2 O:Ln 3+ (Ln=Eu, Tb). The experimental results displayed that the morphology and photoluminescence of compounds is regularly changed with increased the molar amount of rare earth ions. For the Eu 3+ -doped, Tb 3+ -doped and Eu 3+ /Tb 3+ co-doped 4ZnO·B 2 O 3 ·H 2 O phosphors of morphologies, the rod-like structures gradually changed to flower-like structures, fine wire-like structure and hybrid structure, respectively. To their photoluminescence, the Eu 3+ shows a red emission (615nm); the Tb 3+ shows a green emission (545nm); for the Eu 3+ /Tb 3+ co-doped 4ZnO·B 2 O 3 ·H 2 O phosphors, a combination of blue (5d-4f of Eu 2+ ), green ( 5 D 4 - 7 F 5 of Tb 3+ ) and red ( 5 D 0 - 7 F 2 of Eu 3+ ) emissions emerges to achieve white emission. In addition, the energy transfer among Eu 3+ , Eu 2+ and Tb 3+ ions was also discussed. Copyright © 2017. Published by Elsevier B.V.

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

Tian, Yue; College of Life Science, Dalian Nationalities University, Dalian, Liaoning 116600; Chen, Baojiu, E-mail: chenmbj@sohu.com

Tb{sup 3+}, Eu{sup 3+} codoped YF{sub 3} nano- and micro-crystals with the morphologies of ellipsoid-like nanoplate, spindle, sandwich-structural rhombus and nanoaggregate were synthesized through a solvothermal method. The morphologies of the prepared products can be tailored by controlling the volume ratio of ethylene glycol (EG) to H{sub 2}O, solvent type or the reaction time. A possible formation mechanism of the sandwich-structural rhombus like YF{sub 3} phosphor was proposed. The emitting colors of YF{sub 3}:Tb{sup 3+},Eu{sup 3+} phosphors can be easily tuned from yellowish green, yellow to orange by increasing Eu{sup 3+} concentration. The energy transfer from Tb{sup 3+} to Eu{supmore » 3+} in YF{sub 3} phosphors was studied. It was found that the interaction type between Tb{sup 3+} and Eu{sup 3+} is electric dipole-dipole interaction. - Graphical abstract: Sandwich-structural rhombus like YF{sub 3}:Tb{sup 3+}, Eu{sup 3+} phosphors were synthesized through a solvothermal process. The formation mechanism of the sandwich-structural rhombus like YF{sub 3}:Tb{sup 3+}, Eu{sup 3+} phosphors was studied. Highlights: Black-Right-Pointing-Pointer YF{sub 3} nano- and micro-crystals were synthesized through solvothermal route. Black-Right-Pointing-Pointer A formation mechanism of the sandwich-structural rhombus like YF{sub 3} was proposed. Black-Right-Pointing-Pointer The emitting colors of YF{sub 3}:Tb{sup 3+},Eu{sup 3+} phosphors can be tuned. Black-Right-Pointing-Pointer Energy transfer from Tb{sup 3+} to Eu{sup 3+} is confirmed as electric dipole-dipole interaction.« less

Identifying patients at high risk of tuberculosis recurrence.

PubMed

Sadikot, Ruxana T

2016-12-01

Several studies have been done in relation to recurrence of tuberculosis (TB) following completion of treatment. However, recurrence of TB is still a major problem from a public health perspective in high-burden countries, where no special attention is being given to this issue. Disease recurrence is an important indicator of the efficacy of antituberculosis treatment. The rate of recurrence is highly variable and has been estimated to range from 4.9% to 25%. This variability is not only a reflection of regional epidemiology of recurrence but differences in the definitions used by the TB control programs. In addition to treatment failure related to medication adherence, there are several key host factors that are associated with high rates of recurrence. The widely recognized host factors independent of treatment program that predispose to TB recurrence include: malnutrition; human immunodeficiency virus; substance abuse including tobacco use; comorbidity such as diabetes, renal failure and systemic diseases, especially immunosuppressive states; and environmental exposure such as silicosis. With improved understanding of the human genome, proteome, and metabolome, additional host-specific factors that predispose to recurrence are being discovered. Information on temporal and geographical trends of TB cases as well as genotyping might provide further information to enable us to fully understand TB recurrence and discriminate between reactivation and new infection. The recently launched World Health Organization End TB Strategy emphasizes the importance of integrated, patient-centered TB care. Continued improvement in diagnosis, treatment approaches, and defining host-specific factors are needed to fully understand the clinical epidemiological and social determinants of TB recurrence. Copyright © 2016.

The CYP7A1 gene rs3808607 variant is associated with susceptibility of tuberculosis in Moroccan population

PubMed Central

Qrafli, Mounia; Amar, Youssef; Bourkadi, Jamaleddine; Ben Amor, Jouda; Iraki, Ghali; Bakri, Youssef; Amzazi, Saaîd; Lahlou, Ouafae; Seghrouchni, Fouad; El Aouad, Rajae; Sadki, Khalid

2014-01-01

Introduction Despite the medical progress in treatment. Tuberculosis (TB) continues to be a serious global health problem. A genome-wide linkage study identified a major susceptibility locus on chromosomal region 8q12-q13 in Moroccan TB patients. The CYP7A1 gene is located in this region and codes for cholesterol 7a-hydroxylase, an enzyme involved in cholesterol catabolism. Methods We selected three SNPs (rs3808607, rs8192875 and rs8192879) and studied their genotype and allele frequencies distribution in patients with pulmonary (PTB) or pleural TB (pTB), and compared them to Healthy Controls (HC). Genotyping of rs8192875 and rs8192879 SNPs was carried out using the Taq Man SNP genotyping Assay while rs3808607 was investigated by PCR-RFLP. Results We reported here for the first time a statistically significant increase in the AA homozygote genotype frequency of rs3808607 in PTB patients compared to HC (p = 0.02, OR = 1.93, 95% CI: 1.93 (1.07;3.49). The increased risk of developing TB was maintained when we combined the groups of patients (PTB-pTB) (p = 0.01, OR= 1.91, 95% CI = (1.07 - 3.42). In contrast, no genetic association was observed between the rs8192875 or rs8192879 polymorphisms and TB. Conclusion Our investigations suggest that rs3808607 may play a role in susceptibility to TB in a Moroccan population. PMID:25360185

Structural, magnetic, magneto-caloric and Mössbauer spectral study of Tb{sub 2}Fe{sub 17} compound synthesized by arc melting

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

Charfeddine, S.; LVMU, Centre National de Recherches en Sciences des Matériaux, Technopole de Borj-Cédria, BP 73 Soliman 8027; Zehani, K.

We have synthesized the intermetallic Tb{sub 2}Fe{sub 17} compound in hexagonal crystal structure by arc-melting without annealing. X-ray diffraction pattern has been refined by Rietveld method. The crystal structure is hexagonal with P6{sub 3}/mmc space group (Th{sub 2}Ni{sub 17}-type). The Mössbauer spectrum of Tb{sub 2}Fe{sub 17} compound has been analyzed with seven magnetic sextets assigned to the inequivalent crystallographic sites. The temperature dependence of magnetization data revealed that Tb{sub 2}Fe{sub 17} exhibits a second-order ferromagnetic to paramagnetic phase transition in the vicinity of Curie temperature (T{sub C}=412 K). The relative cooling power around the magnetic transition and the Arrott plotsmore » are also reported. - Graphical abstract: A 3D surface showing the temperature and applied magnetic field dependencies of the magnetization for Tb{sub 2}Fe{sub 17} compound (left). Rietveld analysis of the XRD pattern (right). Crystal structure for the hexagonal P6{sub 3}/mmc Tb{sub 2}Fe{sub 17} (bottom). Display Omitted - Highlights: • Tb{sub 2}Fe{sub 17} single-phase synthesized by simple arc-melting without any heat treatment. • The crystal structure is hexagonal with P6{sub 3}/mmc space group. • The magnetic entropy change of the sample was determined by Maxwell relation. • Hyperfine parameters, magnetic and magnetocaloric properties were studied.« less

Drug-resistant tuberculosis: An update on disease burden, diagnosis and treatment.

PubMed

Lange, Christoph; Chesov, Dumitru; Heyckendorf, Jan; Leung, Chi C; Udwadia, Zarir; Dheda, Keertan

2018-04-11

The emergence of antimicrobial resistance against Mycobacterium tuberculosis, the leading cause of mortality due to a single microbial pathogen worldwide, represents a growing threat to public health and economic growth. The global burden of multidrug-resistant tuberculosis (MDR-TB) has recently increased by an annual rate of more than 20%. According to the World Health Organization approximately only half of all patients treated for MDR-TB achieved a successful outcome. For many years, patients with drug-resistant tuberculosis (TB) have received standardized treatment regimens, thereby accelerating the development of MDR-TB through drug-specific resistance amplification. Comprehensive drug susceptibility testing (phenotypic and/or genotypic) is necessary to inform physicians about the best drugs to treat individual patients with tailor-made treatment regimens. Phenotypic drug resistance can now often, but with variable sensitivity, be predicted by molecular drug susceptibility testing based on whole genome sequencing, which in the future could become an affordable method for the guidance of treatment decisions, especially in high-burden/resource-limited settings. More recently, MDR-TB treatment outcomes have dramatically improved with the use of bedaquiline-based regimens. Ongoing clinical trials with novel and repurposed drugs will potentially further improve cure-rates, and may substantially decrease the duration of MDR-TB treatment necessary to achieve relapse-free cure. © 2018 Asian Pacific Society of Respirology.

An integrated computational approach of molecular dynamics simulations, receptor binding studies and pharmacophore mapping analysis in search of potent inhibitors against tuberculosis.

PubMed

Agarwal, Shivangi; Verma, Ekta; Kumar, Vivek; Lall, Namrita; Sau, Samaresh; Iyer, Arun K; Kashaw, Sushil K

2018-05-03

Tuberculosis is an infectious chronic disease caused by obligate pathogen Mycobacterium tuberculosis that affects millions of people worldwide. Although many first and second line drugs are available for its treatment, but their irrational use has adversely lead to the emerging cases of multiple drug resistant and extensively drug-resistant tuberculosis. Therefore, there is an intense need to develop novel potent analogues for its treatment. This has prompted us to develop potent analogues against TB. The Mycobacterium tuberculosis genome provides us with number of validated targets to combat against TB. Study of Mtb genome disclosed six epoxide hydrolases (A to F) which convert harmful epoxide into diols and act as a potential drug target for rational drug design. Our current strategy is to develop such analogues which inhibits epoxide hydrolase enzyme present in Mtb genome. To achieve this, we adopted an integrated computational approach involving QSAR, pharmacophore mapping, molecular docking and molecular dynamics simulation studies. The approach envisaged vital information about the role of molecular descriptors, essential pharmacophoric features and binding energy for compounds to bind into the active site of epoxide hydrolase. Molecular docking analysis revealed that analogues exhibited significant binding to Mtb epoxide hydrolase. Further, three docked complexes 2s, 37s and 15s with high, moderate and low docking scores respectively were selected for molecular dynamics simulation studies. RMSD analysis revealed that all complexes are stable with average RMSD below 2 Å throughout the 10 ns simulations. The B-factor analysis showed that the active site residues of epoxide hydrolase are flexible enough to interact with inhibitor. Moreover, to confirm the binding of these urea derivatives, MM-GBSA binding energy analysis were performed. The calculations showed that 37s has more binding affinity (ΔGtotal = -52.24 kcal/mol) towards epoxide hydrolase compared to 2s (ΔGtotal = -51.70 kcal/mol) and 15s (ΔGtotal = -49.97 kcal/mol). The structural features inferred in our study may provide the future directions to the scientists towards the discovery of new chemical entity exhibiting anti-TB property. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessment of Primary Health Care in the Treatment of Tuberculosis in a Brazilian Locality of the International Triple Frontier.

PubMed

Silva-Sobrinho, Reinaldo Antonio; Wysocki, Anneliese Domingues; Scatena, Lúcia Marina; Pinto, Erika Simone Galvão; Beraldo, Aline Ale; Andrade, Rubia Laine Paula; Zilly, Adriana; Munhak da Silva, Rosane Meire; Gomes, Michela Prestes; Mayer, Paulo César Morales; Ruffino-Netto, Antonio; Villa, Tereza Cristina Scatena

2017-01-01

To evaluate the performance of Primary Health Care (PHC) in treatment of TB patients in a triple international border municipality. The present study was an evaluative survey of cross-sectional and quantitative approach conducted with 225 PHC healthcare professionals. Data was collected through a structured and validated instrument, which provided five indicators of "structure" and four indicators of "process" classified as unsatisfactory, regular or satisfactory. The "structure" component was unsatisfactory for the indicator of professionals involved in TB care and training, and regular for the indicator of connection between the units and other levels of care. The "process" component was regular for the indicators of TB information, directly observed treatment and reference and counter reference on TB, and unsatisfactory for external actions on TB control. The "structure" and "process" components points out some weaknesses in terms of management and organization of human resources. Low frequency of training and the turnover influenced the involvement of professionals. Elements of "structure" and "process" show the need for investing in the PHC team and improving the clinical management of cases.

The Cancer Genomics Hub (CGHub): overcoming cancer through the power of torrential data.

PubMed

Wilks, Christopher; Cline, Melissa S; Weiler, Erich; Diehkans, Mark; Craft, Brian; Martin, Christy; Murphy, Daniel; Pierce, Howdy; Black, John; Nelson, Donavan; Litzinger, Brian; Hatton, Thomas; Maltbie, Lori; Ainsworth, Michael; Allen, Patrick; Rosewood, Linda; Mitchell, Elizabeth; Smith, Bradley; Warner, Jim; Groboske, John; Telc, Haifang; Wilson, Daniel; Sanford, Brian; Schmidt, Hannes; Haussler, David; Maltbie, Daniel

2014-01-01

The Cancer Genomics Hub (CGHub) is the online repository of the sequencing programs of the National Cancer Institute (NCI), including The Cancer Genomics Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects, with data from 25 different types of cancer. The CGHub currently contains >1.4 PB of data, has grown at an average rate of 50 TB a month and serves >100 TB per week. The architecture of CGHub is designed to support bulk searching and downloading through a Web-accessible application programming interface, enforce patient genome confidentiality in data storage and transmission and optimize for efficiency in access and transfer. In this article, we describe the design of these three components, present performance results for our transfer protocol, GeneTorrent, and finally report on the growth of the system in terms of data stored and transferred, including estimated limits on the current architecture. Our experienced-based estimates suggest that centralizing storage and computational resources is more efficient than wide distribution across many satellite labs. Database URL: https://cghub.ucsc.edu. Published by Oxford University Press 2014. This work is written by US Government employees and is in the public domain in the US.

Mycobacterium tuberculosis two-component systems and implications in novel vaccines and drugs.

PubMed

Zhou, PeiFu; Long, QuanXin; Zhou, YeXin; Wang, HongHai; Xie, JianPing

2012-01-01

Communication is vital for nearly all organisms to survive and thrive. For some particularly successful intracellular pathogens, a robust and precise signal transduction system is imperative for handling the complex, volatile, and harsh niche. The communication network of the etiology of tuberculosis, Mycobacterium tuberculosis (M.tb), namely two-component system (TCS), the eukaryotic-like Ser/Thr protein kinases(STPKs) system, the protein tyrosine kinase(PTK) system and the extracytoplasmic function σ(ECF-σ) system, determine how the pathogen responds to environmental fluctuations. At least 12 pair TCSs and four orphan proteins (three response regulators, Rv2884, Rv0260c, Rv0818, and one putative sensory transduction protein, Rv3143) can be found in the M.tb H37Rv genome. They regulate various aspects of M.tb, including virulence, dormancy, persistence, and drug resistance. This review focuses on the physiological roles of TCSs and the network of M.tb TCSs from a systems biology perspective. The implications of TCSs for better vaccine and new drug targets against tuberculosis are also examined.

Synthesis and characterization of bright green terbium coordination complex derived from 1,4-bis(carbonylmethyl)terephthalate: Structure and luminescence properties

NASA Astrophysics Data System (ADS)

Ma, Mengjiao; Li, Congcong; Shu, Dengkun; Wang, Chaohua; Xi, Peng

2018-02-01

A photoluminescent terbium (Tb) complex involving a novel benzoic-acid compound with a unique coordinated structure, namely 1,4-bis(carbonylmethyl)terephthalate (BCMT), has been designed and synthesized. The new coordinate structure and energy-transfer mechanism between the ligand and Tb(III) ions were investigated in detail. The results demonstrated that the BCMT-Tb(III) complex shows strong fluorescence intensity (4 × 106 a.u.) and long fluorescence lifetime (1.302 ms), owing to the favorable degree of energy matching between the triplet excited level of the ligand and the resonant level of Tb(III) ions. Based on the analysis of three-dimensional luminescence spectra, the as-prepared Tb(III) complex can be effectively excited in the range of 250-310 nm, and it shows high color purity, with a bright green appearance.

Synthesis, crystal structure, optical and thermal properties of lanthanide hydrogen-polyphosphates Ln[H(PO3)4] (Ln = Tb, Dy, Ho).

PubMed

Förg, Katharina; Höppe, Henning A

2015-11-28

Lanthanide hydrogen-polyphosphates Ln[H(PO3)4] (Ln = Tb, Dy, Ho) were synthesised as colourless (Ln = Tb, Dy) and light pink (Ln = Ho) crystalline powders by reaction of Tb4O7/Dy2O3/Ho2O3 with H3PO3 at 380 °C. All compounds crystallise isotypically (P2(1)/c (no. 14), Z = 4, a(Tb) = 1368.24(4) pm, b(Tb) = 710.42(2) pm, c(Tb) = 965.79(3) pm, β(Tb) = 101.200(1)°, 3112 data, 160 parameters, wR2 = 0.062, a(Ho) = 1363.34(5) pm, b(Ho) = 709.24(3) pm, c(Ho) = 959.07(4) pm, β(Ho) = 101.055(1)°, 1607 data, 158 parameters, wR2 = 0.058). The crystal structure comprises two different infinite helical chains of corner-sharing phosphate tetrahedra. In-between these chains the lanthanide ions are located, coordinated by seven oxygen atoms belonging to four different polyphosphate chains. Vibrational, UV/Vis and fluorescence spectra of Ln[H(PO3)4] (Ln = Tb, Dy, Ho) as well as Dy[H(PO3)4]:Ln (Ln = Ce, Eu) and the magnetic and thermal behaviour of Tb[H(PO3)4] are reported.

Molecularly imprinted sensor based on Russian Matryoshka structured molecules for enhanced specific identification and double amplification in ultra-trace Tb3+ determination.

PubMed

Li, Jianping; Yang, Bin; Pan, Hongcheng; Xu, Guobao

2018-06-30

The selective and sensitive detection of rare earth elements is thought to be difficult because the concentration of those elements in the sample is commonly at a low level and they normally have severe mutual interference which is caused by homologous chemical properties. In this study, a novel molecularly imprinted polymer (MIP) sensor was fabricated for highly sensitive and selective determination of ultra-trace Tb 3+ . The Tb 3+ -ethylenediaminetetraacetic acid complex (Tb-EDTA) as the template molecule was incorporated into mono-6-mercapto-β-cyclodextrin (mono-6-SH-β-CD) to form a Russian Matryoshka (RM)-structured molecule (CD/Tb-EDTA). Titanium isopropoxide was utilized in vapor sol-gel polymerization to construct MIP membrane. Moreover, the selectivity of the RM MIP sensor was remarkably enhanced by the "triple-selectivity" recognition of EDTA-to-Tb 3+ , β-CD-to-(Tb-EDTA), and 3D cavity-to-(CD/Tb-EDTA), while the sensitivity of the MIP sensor was significantly improved by ECL signal enhancement based on double amplification, in other words, the electrochemiluminescence resonance energy transfer (ECL-RET) between the ECL donor of CD/Tb-EDTA and the ECL acceptor of Ru(bpy) 3 2+ , and the ECL enhancement by the co-reactant of CD/Tb-EDTA on Ru(bpy) 3 Cl 2 . When the imprinted cavities were occupied by Tb-EDTA during rebinding, the host-guest inclusion structured complex was formed and the ECL intensities produced by the Ru(bpy) 3 Cl 2 ECL system increased with increasing concentration of Tb-EDTA. The proposed sensor was used for quantitative analysis of Tb 3+ with concentrations ranging from 8.00 × 10 -13 mol/L to 4.00 × 10 -9 mol/L and successfully applied to detect Tb 3+ in seawater samples. The detection limit of the sensor was found to be 3.90 × 10 -13 mol/L (DL = 3δ b /K), which is lower than previously reported values. Thus, the fabricated sensor is feasible for practical applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Concerns about the knowledge and attitude of multidrug-resistant tuberculosis among health care workers and patients in Delta State, Nigeria.

PubMed

Isara, A R; Akpodiete, A

2015-01-01

Inadequate knowledge and wrong perception of multidrug-resistant tuberculosis (MDR-TB) by Health Care Workers (HCWs) and patients are detrimental to tuberculosis control programs. The aim was to assess the knowledge and attitudes of HCWs and TB patients about MDR-TB in Delta State, Nigeria. A cross-sectional study was carried out among HCWs and TB patients in Delta State, Nigeria. Data were collected using a structured interviewer-administered questionnaire and analyzed using IBM SPSS Statistics version 20. Ninety-six HCWs and 114 TB patients were studied. The HCWs (mean age 43.0 ± 10.1 years) were older than the patients (mean age 41.7 ± 16.9 years). A higher proportion (54.2%) of HCWs had tertiary education, but only 15% of the patients had above secondary education. Eight (8.3%) HCWs and majority (60.5%) of the patients had no knowledge about of MDR-TB. Only 18.4% of patients compared to 61.5% of HCWs had good knowledge of MDR-TB. Both groups demonstrated a positive attitude toward MDR-TB. The knowledge of MDR-TB was poor among the TB patients studied as well as among HCWs with low educational status. MDR-TB training program for both HCWs and patients need to be re-structured to allow for greater gain in MDR-TB knowledge among both groups, which in turn may help improve compliance and treatment outcomes among patients.

Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia.

PubMed

Dejene, Sintayehu W; Heitkönig, Ignas M A; Prins, Herbert H T; Lemma, Fitsum A; Mekonnen, Daniel A; Alemu, Zelalem E; Kelkay, Tessema Z; de Boer, Willem F

2016-01-01

Bovine tuberculosis (bTB) infection is generally correlated with individual cattle's age, sex, body condition, and with husbandry practices such as herd composition, cattle movement, herd size, production system and proximity to wildlife-including bTB maintenance hosts. We tested the correlation between those factors and the prevalence of bTB, which is endemic in Ethiopia's highland cattle, in the Afar Region and Awash National Park between November 2013 and April 2015. A total of 2550 cattle from 102 herds were tested for bTB presence using the comparative intradermal tuberculin test (CITT). Data on herd structure, herd movement, management and production system, livestock transfer, and contact with wildlife were collected using semi-structured interviews with cattle herders and herd owners. The individual overall prevalence of cattle bTB was 5.5%, with a herd prevalence of 46%. Generalized Linear Mixed Models with a random herd-effect were used to analyse risk factors of cattle reactors within each herd. The older the age of the cattle and the lower the body condition the higher the chance of a positive bTB test result, but sex, lactation status and reproductive status were not correlated with bTB status. At herd level, General Linear Models showed that pastoral production systems with transhumant herds had a higher bTB prevalence than sedentary herds. A model averaging analysis identified herd size, contact with wildlife, and the interaction of herd size and contact with wildlife as significant risk factors for bTB prevalence in cattle. A subsequent Structural Equation Model showed that the probability of contact with wildlife was influenced by herd size, through herd movement. Larger herds moved more and grazed in larger areas, hence the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased, enhancing the chances for bTB infection. Therefore, future bTB control strategies in cattle in pastoral areas should consider herd size and movement as important risk factors.

The Argonaute protein TbAGO1 contributes to large and mini-chromosome segregation and is required for control of RIME retroposons and RHS pseudogene-associated transcripts.

PubMed

Durand-Dubief, Mickaël; Absalon, Sabrina; Menzer, Linda; Ngwabyt, Sandra; Ersfeld, Klaus; Bastin, Philippe

2007-12-01

The protist Trypanosoma brucei possesses a single Argonaute gene called TbAGO1 that is necessary for RNAi silencing. We previously showed that in strain 427, TbAGO1 knock-out leads to a slow growth phenotype and to chromosome segregation defects. Here we report that the slow growth phenotype is linked to defects in segregation of both large and mini-chromosome populations, with large chromosomes being the most affected. These phenotypes are completely reversed upon inducible re-expression of TbAGO1 fused to GFP, demonstrating their link with TbAGO1. Trypanosomes that do not express TbAGO1 show a general increase in the abundance of transcripts derived from the short retroposon RIME (Ribosomal Interspersed Mobile Element). Supplementary large RIME transcripts emerge in the absence of RNAi, a phenomenon coupled to the disappearance of short transcripts. These fluctuations are reversed by inducible expression of GFP::TbAGO1. Furthermore, we use a combination of Northern blots, RT-PCR and sequencing to reveal that RNAi controls expression of transcripts derived from RHS (Retrotransposon Hot Spot) pseudogenes (RHS genes with retro-element(s) integrated within their coding sequence). Absence of RNAi also leads to an increase of steady-state transcripts from regular RHS genes (those without retro-element), indicating a role for pseudogene in control of gene expression. However, analysis of retroposon abundance and arrangement in the genome of multiple clonal cell lines of TbAGO1-/- failed to reveal movement of mobile elements despite the increased amounts of retroposon transcripts.

Screening and identification of four serum miRNAs as novel potential biomarkers for cured pulmonary tuberculosis.

PubMed

Wang, Chong; Yang, Su; Liu, Chang-Ming; Jiang, Ting-Ting; Chen, Zhong-Liang; Tu, Hui-Hui; Mao, Lian-Gen; Li, Zhong-Jie; Li, Ji-Cheng

2018-01-01

Rapid and efficient methods for the determination of cured pulmonary tuberculosis (TB) are lacking. We screened serum miRNAs using the Solexa sequencing method among untreated TB patients, two-month treated TB patients, cured TB patients, and healthy controls. A total of 100 differentially expressed miRNAs were identified in cured TB patients, including 37 up-regulated (fold change >1.50, P < 0.05) and 63 down-regulated (fold change <0.60, P < 0.05) miRNAs. Gene ontology (GO) enrichment analysis revealed that most of the predicted genes were present in the nucleus with a strong protein binding function. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis strongly suggested alterations in the metabolic pathways. Following quantitative real time chain reaction (qRT-PCR), significantly reduced expression levels of miR-21-5p (0.30, P < 0.001), miR-92a-3p (0.63, P < 0.001), and miR-148b-3p (0.17, P < 0.001) were found in the cured TB patients compared with the untreated TB patients, while significantly increased expression levels of miR-21-5p (2.09, P = 0.001), miR-92a-3p (1.40, P = 0.005), and miR-148b-3p (4.80, P = 0.003) were found in the untreated TB patients compared with the healthy controls. And significantly increased level of miR-125a-5p was found between two-month treated TB patients and untreated TB patients (1.81, P = 0.004). We established a cured TB model with 83.96% accuracy by four miRNAs (miR-21-5p, miR-92a-3p, miR-148b-3p, and miR-125a-5p), and also established a diagnostic model with 70.09% accuracy. Our study provides experimental data for establishing objective indicators of cured TB, and also provides a new experimental basis to understand the pathogenesis and prognosis of TB. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effective electron-density map improvement and structure validation on a Linux multi-CPU web cluster: The TB Structural Genomics Consortium Bias Removal Web Service.

PubMed

Reddy, Vinod; Swanson, Stanley M; Segelke, Brent; Kantardjieff, Katherine A; Sacchettini, James C; Rupp, Bernhard

2003-12-01

Anticipating a continuing increase in the number of structures solved by molecular replacement in high-throughput crystallography and drug-discovery programs, a user-friendly web service for automated molecular replacement, map improvement, bias removal and real-space correlation structure validation has been implemented. The service is based on an efficient bias-removal protocol, Shake&wARP, and implemented using EPMR and the CCP4 suite of programs, combined with various shell scripts and Fortran90 routines. The service returns improved maps, converted data files and real-space correlation and B-factor plots. User data are uploaded through a web interface and the CPU-intensive iteration cycles are executed on a low-cost Linux multi-CPU cluster using the Condor job-queuing package. Examples of map improvement at various resolutions are provided and include model completion and reconstruction of absent parts, sequence correction, and ligand validation in drug-target structures.

Highly Sensitive Detection of Isoniazid Heteroresistance in Mycobacterium tuberculosis by DeepMelt Assay.

PubMed

Liang, Bin; Tan, Yaoju; Li, Zi; Tian, Xueshan; Du, Chen; Li, Hui; Li, Guoli; Yao, Xiangyang; Wang, Zhongan; Xu, Ye; Li, Qingge

2018-02-01

Detection of heteroresistance of Mycobacterium tuberculosis remains challenging using current genotypic drug susceptibility testing methods. Here, we described a melting curve analysis-based approach, termed DeepMelt, that can detect less-abundant mutants through selective clamping of the wild type in mixed populations. The singleplex DeepMelt assay detected 0.01% katG S315T in 10 5 M. tuberculosis genomes/μl. The multiplex DeepMelt TB/INH detected 1% of mutant species in the four loci associated with isoniazid resistance in 10 4 M. tuberculosis genomes/μl. The DeepMelt TB/INH assay was tested on a panel of DNA extracted from 602 precharacterized clinical isolates. Using the 1% proportion method as the gold standard, the sensitivity was found to be increased from 93.6% (176/188, 95% confidence interval [CI] = 89.2 to 96.3%) to 95.7% (180/188, 95% CI = 91.8 to 97.8%) compared to the MeltPro TB/INH assay. Further evaluation of 109 smear-positive sputum specimens increased the sensitivity from 83.3% (20/24, 95% CI = 64.2 to 93.3%) to 91.7% (22/24, 95% CI = 74.2 to 97.7%). In both cases, the specificity remained nearly unchanged. All heteroresistant samples newly identified by the DeepMelt TB/INH assay were confirmed by DNA sequencing and even partially by digital PCR. The DeepMelt assay may fill the gap between current genotypic and phenotypic drug susceptibility testing for detecting drug-resistant tuberculosis patients. Copyright © 2018 American Society for Microbiology.

The Role of Folate Transport in Antifolate Drug Action in Trypanosoma brucei*

PubMed Central

Dewar, Simon; Sienkiewicz, Natasha; Ong, Han B.; Wall, Richard J.; Horn, David

2016-01-01

The aim of this study was to identify and characterize mechanisms of resistance to antifolate drugs in African trypanosomes. Genome-wide RNAi library screens were undertaken in bloodstream form Trypanosoma brucei exposed to the antifolates methotrexate and raltitrexed. In conjunction with drug susceptibility and folate transport studies, RNAi knockdown was used to validate the functions of the putative folate transporters. The transport kinetics of folate and methotrexate were further characterized in whole cells. RNA interference target sequencing experiments identified a tandem array of genes encoding a folate transporter family, TbFT1–3, as major contributors to antifolate drug uptake. RNAi knockdown of TbFT1–3 substantially reduced folate transport into trypanosomes and reduced the parasite's susceptibly to the classical antifolates methotrexate and raltitrexed. In contrast, knockdown of TbFT1–3 increased susceptibly to the non-classical antifolates pyrimethamine and nolatrexed. Both folate and methotrexate transport were inhibited by classical antifolates but not by non-classical antifolates or biopterin. Thus, TbFT1–3 mediates the uptake of folate and classical antifolates in trypanosomes, and TbFT1–3 loss-of-function is a mechanism of antifolate drug resistance. PMID:27703008

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms

PubMed Central

Zhang, Lu; Ru, Huan-wei; Chen, Fu-zeng; Jin, Chun-yan; Sun, Rui-feng; Fan, Xiao-yong; Guo, Ming; Mai, Jun-tao; Xu, Wen-xi; Lin, Qing-xia; Liu, Jun

2016-01-01

Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development. PMID:26643797

Variable Virulence and Efficacy of BCG Vaccine Strains in Mice and Correlation With Genome Polymorphisms.

PubMed

Zhang, Lu; Ru, Huan-Wei; Chen, Fu-Zeng; Jin, Chun-Yan; Sun, Rui-Feng; Fan, Xiao-Yong; Guo, Ming; Mai, Jun-Tao; Xu, Wen-Xi; Lin, Qing-Xia; Liu, Jun

2016-02-01

Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the only vaccine available for tuberculosis (TB) control. However, BCG is not an ideal vaccine and has two major limitations: BCG exhibits highly variable effectiveness against the development of TB both in pediatric and adult populations and can cause disseminated BCG disease in immunocompromised individuals. BCG comprises a number of substrains that are genetically distinct. Whether and how these genetic differences affect BCG efficacy remains largely unknown. In this study, we performed comparative analyses of the virulence and efficacy of 13 BCG strains, representing different genetic lineages, in SCID and BALB/c mice. Our results show that BCG strains of the DU2 group IV (BCG-Phipps, BCG-Frappier, BCG-Pasteur, and BCG-Tice) exhibit the highest levels of virulence, and BCG strains of the DU2 group II (BCG-Sweden, BCG-Birkhaug) are among the least virulent group. These distinct levels of virulence may be explained by strain-specific duplications and deletions of genomic DNA. There appears to be a general trend that more virulent BCG strains are also more effective in protection against Mycobacterium tuberculosis challenge. Our findings have important implications for current BCG vaccine programs and for future TB vaccine development.

Magnetostructural phase transformations in Tb 1-x Mn 2

DOE PAGES

Zou, Junding; Paudyal, Durga; Liu, Jing; ...

2015-01-16

Magnetism and phase transformations in non-stoichiometric Tb 1-xMn 2 (x = 0.056, 0.039) have been studied as functions of temperature and magnetic field using magnetization, heat capacity, and X-ray powder diffraction measurements. Lowering the temperature, the compounds sequentially order ferrimagnetically and antiferromagnetically, and finally, exhibit spin reorientation transitions. Moreover, these structural distortions from room temperature cubic to low temperature rhombohedral structures occur at T N, and are accompanied by large volume changes reaching ~-1.27% and -1.42%, respectively. First principles electronic structure calculations confirm the phase transformation from the ferrimagnetic cubic structure to the antiferromagnetic rhombohedral structure in TbMn 2.

Tight-Binding study of Boron structures

NASA Astrophysics Data System (ADS)

McGrady, Joseph W.; Papaconstantopoulos, Dimitrios A.; Mehl, Michael J.

2014-10-01

We have performed Linearized Augmented Plane Wave (LAPW) calculations for five crystal structures (alpha, dhcp, sc, fcc, bcc) of Boron which we then fitted to a non-orthogonal tight-binding model following the Naval Research Laboratory Tight-Binding (NRL-TB) method. The predictions of the NRL-TB approach for complicated Boron structures such as R105 (or β-rhombohedral) and T190 are in agreement with recent first-principles calculations. Fully utilizing the computational speed of the NRL-TB method we calculated the energy differences of various structures, including those containing vacancies using supercells with up to 5000 atoms.

Status of nosocomial tuberculosis transmission prevention in hospitals in Thailand.

PubMed

Unahalekhaka, Akeau; Lueang-a-papong, Suchada; Chitreecheur, Jittaporn

2014-03-01

A national survey was conducted during July to September 2009 to determine tuberculosis (TB) prevention activities, problems, and support needed of Thai hospitals. Ninety-seven percent of hospitals established TB isolation policy, 96.3% provided guidelines for caring of TB patients, 95% and 91.8% provided prevention of TB transmission and environmental management guideline, and 92.6% established screening system for TB in the outpatient department (OPD). A half of hospitals had problems with isolation rooms and difficulties in screening TB cases in the OPD. Support needed included consultation on structure and ventilation systems, personnel training, national TB prevention, and TB screening guideline. Strengthening TB prevention activities, providing expert consultation, and national guidelines may help hospitals improve their TB prevention activities. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Modeling socio-demography to capture tuberculosis transmission dynamics in a low burden setting

PubMed Central

Ajelli, Marco; Yang, Zhenhua; Merler, Stefano; Furlanello, Cesare; Kirschner, Denise

2011-01-01

Evidence of preferential mixing through selected social routes has been suggested for the transmission of tuberculosis (TB) infection in low burden settings. A realistic modelization of these contact routes is needed to appropriately assess the impact of individually targeted control strategies, such as contact network investigation of index cases and treatment of latent TB infection (LTBI). We propose an age-structured, socio-demographic individual based model (IBM) with a realistic, time-evolving structure of preferential contacts in a population. In particular, transmission within households, schools and work-places, together with a component of casual, distance-dependent contacts are considered. We also compared the model against two other formulations having no social structure of contacts (homogeneous mixing transmission): a baseline deterministic model without age structure and an age-structured IBM. The socio-demographic IBM better fitted recent longitudinal data on TB epidemiology in Arkansas, USA, which serves as an example of a low burden setting. Inclusion of age structure in the model proved fundamental to capturing actual proportions of reactivated TB cases (as opposed to recently transmitted) as well as profiling age-group specific incidence. The socio-demographic structure additionally provides a prediction of TB transmission rates (the rate of infection in household contacts and the rate of secondary cases in household and workplace contacts). These results suggest that the socio-demographic IBM is an optimal choice for evaluating current control strategies, including contact network investigation of index cases, and the simulation of alternative scenarios, particularly for TB eradication targets. PMID:21906603

Pan-London tuberculosis services: a service evaluation

PubMed Central

2012-01-01

Background London has the largest proportion of tuberculosis (TB) cases of any western European capital, with almost half of new cases drug-resistant. Prevalence varies considerably between and within boroughs with research suggesting inadequate control of TB transmission in London. Economic pressures may exacerbate the already considerable challenges for service organisation and delivery within this context. This paper presents selected findings from an evaluation of London’s TB services’ organisation, delivery, professional workforce and skill mix, intended to support development of a strategic framework for a pan-London TB service. These may also interest health service professionals and managers in TB services in the UK, other European cities and countries and in services currently delivered by multiple providers operating independently. Methods Objectives were: 1) To establish how London’s TB services are structured and delivered in relation to leadership, management, organisation and delivery, coordination, staffing and support; 2) To identify tools/models for calculating skill mix as a basis for identifying skill mix requirements in delivering TB services across London; 3) To inform a strategic framework for the delivery of a pan-London TB service, which may be applicable to other European cities. The multi-method service audit evaluation comprised documentary analysis, semi-structured interviews with TB service users (n = 10), lead TB health professionals and managers (n = 13) representing London’s five sectors and focus groups with TB nurses (n = 8) and non-London network professionals (n = 2). Results Findings showed TB services to be mainly hospital-based, with fewer community-based services. Documentary analysis and professionals’ interviews suggested difficulties with early access to services, low suspicion index amongst some GPs and restricted referral routes. Interviews indicated lack of managed accommodation for difficult to treat patients, professional workforce shortages, a need for strategic leadership, nurse-led clinics and structured career paths for TB nurses and few social care/outreach workers to support patients with complex needs. Conclusions This paper has identified key issues relating to London’s TB services’ organisation, delivery, professional workforce and skill mix. The majority of these present challenges which need to be addressed as part of the future development of a strategic framework for a pan-London TB service. More consistent strategic planning/co-ordination and sharing of best practice is needed, together with a review of pan-London TB workforce development strategy, encompassing changing professional roles, skills development needs and patient pathways. These findings may be relevant with the development of TB services in other European cities. PMID:22805234

Effects of proline cis-trans isomerization on TB domain secondary structure.

PubMed Central

Yuan, X.; Werner, J. M.; Knott, V.; Handford, P. A.; Campbell, I. D.; Downing, K.

1998-01-01

The transforming growth factor beta (TGF-beta) binding protein-like (TB) domain is found principally in proteins localized to extracellular matrix fibrils, including human fibrillin-1, the defective protein in the Marfan syndrome. Analysis of the nuclear magnetic resonance (NMR) data for the sixth TB module from human fibrillin-1 has revealed the existence of two stable conformers that differ in the isomerization states of two proline residues. Unusually, the two isoforms do not readily interconvert and are stable on the time scale of milliseconds. We have computed independent structures of the major and minor conformers of TB6 to assess how the domain fold adjusts to incorporate alternatively cis- or trans-prolines. Based on previous observations, it has been suggested that multiple conformers can only be accommodated in flexible regions of protein structure. In contrast, P22, which exists in trans in the major form and cis in the minor form of TB6, is in a rigid region of the domain, which is confirmed by backbone dynamics measurements. Overall, the structures of the major and minor conformers are similar. However, the secondary structure topologies of the two forms differ as a direct consequence of the changes in proline conformation. PMID:9792099

Assessment of Primary Health Care in the Treatment of Tuberculosis in a Brazilian Locality of the International Triple Frontier

PubMed Central

Silva-Sobrinho, Reinaldo Antonio; Wysocki, Anneliese Domingues; Scatena, Lúcia Marina; Pinto, Erika Simone Galvão; Beraldo, Aline Ale; Andrade, Rubia Laine Paula; Zilly, Adriana; Munhak da Silva, Rosane Meire; Gomes, Michela Prestes; Mayer, Paulo César Morales; Ruffino-Netto, Antonio; Villa, Tereza Cristina Scatena

2017-01-01

Objective: To evaluate the performance of Primary Health Care (PHC) in treatment of TB patients in a triple international border municipality. Methods: The present study was an evaluative survey of cross-sectional and quantitative approach conducted with 225 PHC healthcare professionals. Data was collected through a structured and validated instrument, which provided five indicators of "structure" and four indicators of "process" classified as unsatisfactory, regular or satisfactory. Results: The "structure" component was unsatisfactory for the indicator of professionals involved in TB care and training, and regular for the indicator of connection between the units and other levels of care. The "process" component was regular for the indicators of TB information, directly observed treatment and reference and counter reference on TB, and unsatisfactory for external actions on TB control. Conclusion: The "structure" and "process" components points out some weaknesses in terms of management and organization of human resources. Low frequency of training and the turnover influenced the involvement of professionals. Elements of "structure" and "process" show the need for investing in the PHC team and improving the clinical management of cases. PMID:29204229

Crystal structure, electronic structure, and photoluminescent properties of SrMoO{sub 4}:Tb{sup 3+} phosphors

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

Park, Sung Wook; Moon, Byung Kee; Jeong, Jung Hyun, E-mail: jhjeong@pknu.ac.kr

2015-10-15

Highlights: • SrMoO{sub 4}:Tb{sup 3+} phosphor samples were synthesized at different temperatures. • The crystal and electronic structures, and luminescence properties were studied. • The excitation peak shifts to red with increasing the sintering temperature. • The luminescence mechanism of SrMoO{sub 4}:Tb{sup 3+} was suggested. - Abstract: The experimental and theoretical studies of the optical properties of SrMoO{sub 4}:Tb{sup 3+} phosphors were carried out. The structural, optical, and electronical properties of the phosphors were systematically studied. The phosphor samples were crystallized at different temperatures via a sol–gel method. Excitation spectra of SrMoO{sub 4}:Tb{sup 3+} powder samples exhibited gradual red shiftmore » and luminescent intensity changed with increasing the sintering temperature. Such spectral changes depend strongly on the crystallographic properties such as lattice parameters and crystallinity. The shift of the excitation spectra is mainly ascribed to the covalent bond interaction between Mo−O bonds. An energy band model was demonstrated to describe the luminescence mechanism in the material.« less

Recent developments of coumarin-containing derivatives and their anti-tubercular activity.

PubMed

Hu, Yuan-Qiang; Xu, Zhi; Zhang, Shu; Wu, Xiang; Ding, Jun-Wei; Lv, Zao-Sheng; Feng, Lian-Shun

2017-08-18

Tuberculosis (TB) is a lift-threatening chronic deadliest infectious disease caused predominantly by Mycobacterium tuberculosis (MTB) which affects primarily the lungs (pulmonary TB) apart from other vital organs. The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and the recently cases of totally drug resistant (TDR) towards currently accessible standard drugs was increased up to alarming level in the recent decades. In pursuit of searching new anti-TB agents, numerous of derivatives have been synthesized and screened for their anti-TB activity. Coumarins are one of the most important classes of natural products that exhibited various biological activities, and their derivatives regarded as a new class of effective anti-TB candidates owing to their potential anti-TB activity. Thus, coumarin skeleton has attracted great interest in the development of new anti-TB agents. This review outlines the advances in the application of coumarin-containing derivatives as anti-TB agents and the critical aspects of design and structure-activity relationship of these derivatives. Published by Elsevier Masson SAS.

Value of the polymerase chain reaction method for detecting tuberculosis in the bronchial tissue involved by anthracosis.

PubMed

Mirsadraee, Majid; Shafahie, Ahmad; Reza Khakzad, Mohammad; Sankian, Mojtaba

2014-04-01

Anthracofibrosis is the black discoloration of the bronchial mucosa with deformity and obstruction. Association of this disease with tuberculosis (TB) was approved. The objective of this study was to find the additional benefit of assessment of TB by the polymerase chain reaction (PCR) method. Bronchoscopy was performed on 103 subjects (54 anthracofibrosis and 49 control subjects) who required bronchoscopy for their pulmonary problems. According to bronchoscopic findings, participants were classified to anthracofibrosis and nonanthracotic groups. They were examined for TB with traditional methods such as direct smear (Ziehl-Neelsen staining), Löwenstein-Jensen culture, and histopathology and the new method "PCR" for Mycobacterium tuberculosis genome (IS6110). Age, sex, smoking, and clinical findings were not significantly different in the TB and the non-TB groups. Acid-fast bacilli could be detected by a direct smear in 12 (25%) of the anthracofibrosis subjects, and adding the results of culture and histopathology traditional tests indicated TB in 27 (31%) of the cases. Mycobacterium tuberculosis was diagnosed by PCR in 18 (33%) patients, but the difference was not significant. Detection of acid-fast bacilli in control nonanthracosis subjects was significantly lower (3, 6%), but PCR (20, 40%) and accumulation of results from all traditional methods (22, 44%) showed a nonsignificant difference. The PCR method showed a result equal to traditional methods including accumulation of smear, culture, and histopathology.

Report on cascade energy relaxation from PVP to Tb3+:Bi2SiO5 nanophosphor through salicylic acid in composite polymeric film

NASA Astrophysics Data System (ADS)

Kumari, Pushpa; Dwivedi, Y.

2018-05-01

The present article reports structural and spectroscopic properties of Tb:Bi2SiO5 nanophosphors dispersed in Polyvinylpyrrolidone polymer film, in presence of Salicylic acid (SA) molecule, which acts as a sensitizer. Detailed structural and spectroscopic characterizations were carried out using X-ray diffraction patterns, Scanning Electron Microscope, Fourier Transform Infrared and Excitation and photoluminescence techniques. The mean crystallite size of Tb3+:Bi2SiO5 nanophosphor and Tb3+:Bi2SiO5 in Polyvinylpyrrolidone polymer composite was estimated ∼22 nm and ∼28 nm, respectively. We have report atleast two times enhancement in Tb3+ ions emission intensity due to the efficient energy transfer from salicylic acid molecule to Tb ions. In addition to energy transfer from salicylic acid, the Polyvinylpyrrolidone polymeric host was also reported to serve as a sensitizer for SA molecule and Tb3+ ions through a cascade energy relaxation process while exciting with 248 nm photons. On 248 nm photon excitation, atleast five improvements in Tb3+ ion emission intensity are reported. Presence of SA molecule facilitates precise colour tuning as obvious from the CIE coordinates.

Fine mapping of powdery mildew resistance genes PmTb7A.1 and PmTb7A.2 in Triticum boeoticum (Boiss.) using the shotgun sequence assembly of chromosome 7AL.

PubMed

Chhuneja, Parveen; Yadav, Bharat; Stirnweis, Daniel; Hurni, Severine; Kaur, Satinder; Elkot, Ahmed Fawzy; Keller, Beat; Wicker, Thomas; Sehgal, Sunish; Gill, Bikram S; Singh, Kuldeep

2015-10-01

A novel powdery mildew resistance gene and a new allele of Pm1 were identified and fine mapped. DNA markers suitable for marker-assisted selection have been identified. Powdery mildew caused by Blumeria graminis is one of the most important foliar diseases of wheat and causes significant yield losses worldwide. Diploid A genome species are an important genetic resource for disease resistance genes. Two powdery mildew resistance genes, identified in Triticum boeoticum (A(b)A(b)) accession pau5088, PmTb7A.1 and PmTb7A.2 were mapped on chromosome 7AL. In the present study, shotgun sequence assembly data for chromosome 7AL were utilised for fine mapping of these Pm resistance genes. Forty SSR, 73 resistance gene analogue-based sequence-tagged sites (RGA-STS) and 36 single nucleotide polymorphism markers were designed for fine mapping of PmTb7A.1 and PmTb7A.2. Twenty-one RGA-STS, 8 SSR and 13 SNP markers were mapped to 7AL. RGA-STS markers Ta7AL-4556232 and 7AL-4426363 were linked to the PmTb7A.1 and PmTb7A.2, at a genetic distance of 0.6 and 6.0 cM, respectively. The present investigation established that PmTb7A.1 is a new powdery mildew resistance gene that confers resistance to a broad range of Bgt isolates, whereas PmTb7A.2 most probably is a new allele of Pm1 based on chromosomal location and screening with Bgt isolates showing differential reaction on lines with different Pm1 alleles. The markers identified to be linked to the two Pm resistance genes are robust and can be used for marker-assisted introgression of these genes to hexaploid wheat.

Functional expression of TcoAT1 reveals it to be a P1-type nucleoside transporter with no capacity for diminazene uptake☆

PubMed Central

Munday, Jane C.; Rojas López, Karla E.; Eze, Anthonius A.; Delespaux, Vincent; Van Den Abbeele, Jan; Rowan, Tim; Barrett, Michael P.; Morrison, Liam J.; de Koning, Harry P.

2013-01-01

It has long been established that the Trypanosoma brucei TbAT1/P2 aminopurine transporter is involved in the uptake of diamidine and arsenical drugs including pentamidine, diminazene aceturate and melarsoprol. Accordingly, it was proposed that the closest Trypanosoma congolense paralogue, TcoAT1, might perform the same function in this parasite, and an apparent correlation between a Single Nucleotide Polymorphism (SNP) in that gene and diminazene tolerance was reported for the strains examined. Here, we report the functional cloning and expression of TcoAT1 and show that in fact it is the syntenic homologue of another T. brucei gene of the same Equilibrative Nucleoside Transporter (ENT) family: TbNT10. The T. congolense genome does not seem to contain a syntenic equivalent to TbAT1. Two TcoAT1 alleles, differentiated by three independent SNPs, were expressed in the T. brucei clone B48, a TbAT1-null strain that further lacks the High Affinity Pentamidine Transporter (HAPT1); TbAT1 was also expressed as a control. The TbAT1 and TcoAT1 transporters were functional and increased sensitivity to cytotoxic nucleoside analogues. However, only TbAT1 increased sensitivity to diamidines and to cymelarsan. Uptake of [3H]-diminazene was detectable only in the B48 cells expressing TbAT1 but not TcoAT1, whereas uptake of [3H]-inosine was increased by both TcoAT1 alleles but not by TbAT1. Uptake of [3H]-adenosine was increased by all three ENT genes. We conclude that TcoAT1 is a P1-type purine nucleoside transporter and the syntenic equivalent to the previously characterised TbNT10; it does not mediate diminazene uptake and is therefore unlikely to play a role in diminazene resistance in T. congolense. PMID:24533295

Synthesis and characterization of Mg2SiO4:Tb3+, Eu3+ phosphors for white light generation

NASA Astrophysics Data System (ADS)

Cho, Shinho

2016-09-01

The effect of Eu3+ codoping on the structural, morphological, and optical properties of Mg2SiO4:Tb3+ was investigated. The phosphor powders were synthesized by changing the molar concentration of Eu3+ at a fixed Tb3+ content of 5 mol% by using a conventional solid-state reaction. The X-ray diffraction patterns revealed that the crystal structure of all the phosphors, irrespective of the Eu3+ and the Tb3+ contents, showed an orthorhombic structure, and the surface morphology exhibited pebble-like crystalline grains. The emission spectra of Eu3+ and Tb3+-codoped Mg2SiO4 phosphors under an ultraviolet excitation of 252 nm consisted of one intense red band at 619 nm and five weak bands at 448, 488, 598, 658, and 707 nm originating from the transitions of Eu3+, in addition to the several emission bands located at 492, 552, 592, and 628 nm arising from the transitions of Tb3+. As the Eu3+ content was increased, the intensity of the main green emission band at 552 nm decreased markedly and disappeared at 10 mol% Eu3+, when complete energy transfer from Tb3+ to Eu3+ was observed. The results suggest that the emission wavelength and the luminescent intensity of the phosphors can be tuned by modulating the Eu3+ and the Tb3+ contents incorporated into the host matrix.

Natively Inhibited Trypanosoma brucei Cathepsin B Structure Determined by Using an X-ray Laser

PubMed Central

DePonte, Daniel P.; White, Thomas A.; Rehders, Dirk; Barty, Anton; Stellato, Francesco; Liang, Mengning; Barends, Thomas R.M.; Boutet, Sébastien; Williams, Garth J.; Messerschmidt, Marc; Seibert, M. Marvin; Aquila, Andrew; Arnlund, David; Bajt, Sasa; Barth, Torsten; Bogan, Michael J.; Caleman, Carl; Chao, Tzu-Chiao; Doak, R. Bruce; Fleckenstein, Holger; Frank, Matthias; Fromme, Raimund; Galli, Lorenzo; Grotjohann, Ingo; Hunter, Mark S.; Johansson, Linda C.; Kassemeyer, Stephan; Katona, Gergely; Kirian, Richard A.; Koopmann, Rudolf; Kupitz, Chris; Lomb, Lukas; Martin, Andrew V.; Mogk, Stefan; Neutze, Richard; Shoeman, Robert L.; Steinbrener, Jan; Timneanu, Nicusor; Wang, Dingjie; Weierstall, Uwe; Zatsepin, Nadia A.; Spence, John C. H.; Fromme, Petra; Schlichting, Ilme; Duszenko, Michael; Betzel, Christian; Chapman, Henry N.

2013-01-01

The Trypanosoma brucei cysteine protease cathepsin B (TbCatB), which is involved in host protein degradation, is a promising target to develop new treatments against sleeping sickness, a fatal disease caused by this protozoan parasite. The structure of the mature, active form of TbCatB has so far not provided sufficient information for the design of a safe and specific drug against T. brucei. By combining two recent innovations, in vivo crystallization and serial femtosecond crystallography, we obtained the room-temperature 2.1 angstrom resolution structure of the fully glycosylated precursor complex of TbCatB. The structure reveals the mechanism of native TbCatB inhibition and demonstrates that new biomolecular information can be obtained by the “diffraction-before-destruction” approach of x-ray free-electron lasers from hundreds of thousands of individual microcrystals. PMID:23196907

Role of Ga particulates on the structure and optical properties of Y3(Al,Ga)5O12:Tb thin films prepared by PLD

NASA Astrophysics Data System (ADS)

Yousif, A.; Duvenhage, M. M.; Ntwaeaborwa, O. M.; Swart, H. C.

2018-04-01

Y3(Al,Ga)5O12:Tb thin films (70 nm) have been prepared by pulsed laser deposition on a Si (100) substrate at the substrate temperature of 300 °C. The effect of annealing time on the structural, morphological and luminescence properties of Y3(Al,Ga)5O12:Tb thin films at 800 °C were studied. The crystal structure of the samples was studied by X- ray diffraction (XRD) and showed shifts in the peak positions to lower diffraction angles for the annealed film compared to the XRD peak positions of the commercial Y3(Al,Ga)5O12:Tb powder. A new excitation band different from the original Y3(Al,Ga)5O12:Tb powder was also observed for the annealed films. The shift in the XRD pattern and the new excitation band for the annealed film suggested that the films were enriched with Ga after annealing.

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai

PubMed Central

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-01-01

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies. PMID:29863175

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai.

PubMed

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-05-10

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies.

Phase equilibria in the Tb-Mg-Co system at 500 °C, crystal structure and hydrogenation properties of selected compounds

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

Shtender, V.V.; Denys, R.V.; Zavaliy, I.Yu., E-mail: zavaliy@ipm.lviv.ua

2015-12-15

The isothermal section of the Tb–Mg–Co phase diagram at 500 °C has been built on the basis of XRD analysis of forty samples prepared by powder metallurgy. The existence of two ternary compounds Tb{sub 4}Mg{sub 3}Co{sub 2} and Tb{sub 4}MgCo was confirmed. The formation of two solid solutions, Tb{sub 1−x}Mg{sub x}Co{sub 3} (0≤x≤0.4) and Tb{sub 1-−x}Mg{sub x}Co{sub 2} (0≤x≤0.6), was found for the first time. It is shown that Tb{sub 5}Mg{sub 24} also dissolves a small amount of Co. Other binary compounds do not dissolve the third component. The Tb{sub 4}MgCo and TbMgCo{sub 4} compounds form hydrides (12.7 and 5.3more » at.H/f.u. capacity, respectively) that retain the original structure of metallic matrices. Upon thermal desorption the Tb{sub 4}MgCoH{sub 12.7} hydride was stable up to 300 °C and disproportionated at higher temperature. Two other hydrides, Tb{sub 4}Mg{sub 3}Co{sub 2}H{sub ∼4} and Tb{sub 2}MgCo{sub 9}H{sub 12}, are unstable in air and decompose into the initial compounds. - Highlights: • The phase equilibria at 500 °°C in the Tb–Mg–Co system has been studied. • The existence of two ternary compounds, Tb{sub 4}Mg{sub 3}Co{sub 2} and Tb{sub 4}MgCo, was confirmed. • The formation of two solid solutions, Tb{sub 1−x}Mg{sub x}Co{sub 3} and Tb{sub 1−x}Mg{sub x}Co{sub 2}, was found. • Hydrogen sorption–desorption properties have been studied for the selected alloys.« less

In-silico Investigation of Antitrypanosomal Phytochemicals from Nigerian Medicinal Plants

PubMed Central

Setzer, William N.; Ogungbe, Ifedayo V.

2012-01-01

Background Human African trypanosomiasis (HAT), a parasitic protozoal disease, is caused primarily by two subspecies of Trypanosoma brucei. HAT is a re-emerging disease and currently threatens millions of people in sub-Saharan Africa. Many affected people live in remote areas with limited access to health services and, therefore, rely on traditional herbal medicines for treatment. Methods A molecular docking study has been carried out on phytochemical agents that have been previously isolated and characterized from Nigerian medicinal plants, either known to be used ethnopharmacologically to treat parasitic infections or known to have in-vitro antitrypanosomal activity. A total of 386 compounds from 19 species of medicinal plants were investigated using in-silico molecular docking with validated Trypanosoma brucei protein targets that were available from the Protein Data Bank (PDB): Adenosine kinase (TbAK), pteridine reductase 1 (TbPTR1), dihydrofolate reductase (TbDHFR), trypanothione reductase (TbTR), cathepsin B (TbCatB), heat shock protein 90 (TbHSP90), sterol 14α-demethylase (TbCYP51), nucleoside hydrolase (TbNH), triose phosphate isomerase (TbTIM), nucleoside 2-deoxyribosyltransferase (TbNDRT), UDP-galactose 4′ epimerase (TbUDPGE), and ornithine decarboxylase (TbODC). Results This study revealed that triterpenoid and steroid ligands were largely selective for sterol 14α-demethylase; anthraquinones, xanthones, and berberine alkaloids docked strongly to pteridine reductase 1 (TbPTR1); chromenes, pyrazole and pyridine alkaloids preferred docking to triose phosphate isomerase (TbTIM); and numerous indole alkaloids showed notable docking energies with UDP-galactose 4′ epimerase (TbUDPGE). Polyphenolic compounds such as flavonoid gallates or flavonoid glycosides tended to be promiscuous docking agents, giving strong docking energies with most proteins. Conclusions This in-silico molecular docking study has identified potential biomolecular targets of phytochemical components of antitrypanosomal plants and has determined which phytochemical classes and structural manifolds likely target trypanosomal enzymes. The results could provide the framework for synthetic modification of bioactive phytochemicals, de novo synthesis of structural motifs, and lead to further phytochemical investigations. PMID:22848767

Advances in Mycobacterium tuberculosis therapeutics discovery utlizing structural biology

PubMed Central

Chim, Nicholas; Owens, Cedric P.; Contreras, Heidi; Goulding, Celia W.

2013-01-01

In 2012, tuberculosis (TB) remains a global health threat and is exacerbated both by the emergence of drug resistant Mycobacterium tuberculosis strains and its synergy with HIV infection. The waning effectiveness of current treatment regimens necessitates the development of new or repurposed anti-TB therapeutics for improved combination therapies against the disease. Exploiting atomic resolution structural information of proteins in complex with their substrates and/or inhibitors can facilitate structure-based rational drug design. Since our last review in 2009, there has been a wealth of new M. tuberculosis protein structural information. Once again, we have compiled the most promising structures with regards to potential anti-TB drug development and present them in this updated review. PMID:23167715

Self-Propagating Combustion Synthesis, Luminescent Properties and Photocatalytic Activities of Pure Ca12Al14O33: Tb3+(Sm3+)

NASA Astrophysics Data System (ADS)

Liu, Rong; Yan, Yongsheng; Ma, Changchang

2018-03-01

The dual-functional Ca12Al14O33: Tb3+ and Ca12Al14O33: Sm3+ materials were prepared by the Self-Propagating Combustion Synthesis (SPCS) technology. The structure, morphology and light absorption property were investigated by XRD、FT-IR、UV-Vis DRS and SEM etc.. The doping of Tb3+ and Sm3+ ions had not changed cubic structure of Ca12Al14O33 but leaded to the slight lattice dilatation and the red-shifts of absorption peaks/edges. The excitation and emission spectra indicated that Ca12Al14O33: Tb3+ and Ca12Al14O33: Sm3+ are superior green and red luminescent materials, respectively, and displayed the distinctly refined structure characteristics which had importantly reference value for the energy level investigation of Tb3+ and Sm3+ ions. Meanwhile, Ca12Al14O33: Tb3+ and Ca12Al14O33: Sm3+ also exhibited the improved photocatalytic degradation for removing dye MB compared with bare Ca12Al14O33.

Status of tuberculosis-related stigma and associated factors: a cross-sectional study in central China.

PubMed

Yin, Xiaoxv; Yan, Shijiao; Tong, Yeqing; Peng, Xin; Yang, Tingting; Lu, Zuxun; Gong, Yanhong

2018-02-01

Tuberculosis (TB) poses a significant challenge to public health worldwide. Stigma is a major obstacle to TB control by leading to delay in diagnosis and treatment non-adherence. This study aimed to evaluate the status of TB-related stigma and its associated factors among TB patients in China. Cross-sectional survey. Thus, 1342 TB patients were recruited from TB dispensaries in three counties in Hubei Province using a multistage sampling method and surveyed using a structured anonymous questionnaire including validated scales to measure TB-related stigma. A generalised linear regression model was used to identify the factors associated with TB-related stigma. The average score on the TB-related Stigma Scale was 9.33 (SD = 4.25). Generalised linear regression analysis revealed that knowledge about TB (ß = -0.18, P = 0.0025), family function (ß = -0.29, P < 0.0001) and doctor-patient communication (ß = -0.32, P = 0.0005) were negatively associated with TB-related stigma. TB-related stigma was high among TB patients in China. Interventions concentrating on reducing TB patients' stigma in China should focus on improving patients' family function and patients' knowledge about TB. © 2017 John Wiley & Sons Ltd.

Synthesis, structure, and photoluminescence properties of novel KBaSc2 (PO4 )3 :Ce(3+) /Eu(2+) /Tb(3+) phosphors for white-light-emitting diodes.

PubMed

Jiao, Mengmeng; Lü, Wei; Shao, Baiqi; Zhao, Lingfei; You, Hongpeng

2015-08-24

A series of novel KBaSc2 (PO4 )3 :Ce(3+) /Eu(2+) /Tb(3+) phosphors are prepared using a solid-state reaction. X-ray diffraction analysis and Rietveld structure refinement are used to check the phase purity and crystal structure of the prepared samples. Ce(3+) - and Eu(2+) -doped phosphors both have broad excitation and emission bands, owing to the spin- and orbital-allowed electron transition between the 4f and 5d energy levels. By co-doping the KBaSc2 (PO4 )3 :Eu(2+) and KBaSc2 (PO4 )3 :Ce(3+) phosphors with Tb(3+) ions, tunable colors from blue to green can be obtained. The critical distance between the Eu(2+) and Tb(3+) ions is calculated by a concentration quenching method and the energy-transfer mechanism for Eu(2+) →Tb(3+) is studied by utilizing the Inokuti-Hirayama model. In addition, the quantum efficiencies of the prepared samples are measured. The results indicate that KBaSc2 (PO4 )3 :Eu(2+) ,Tb(3+) and KBaSc2 (PO4 )3 :Ce(3+) ,Tb(3+) phosphors might have potential applications in UV-excited white-light-emitting diodes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural and magnetic properties of morphotropic phase boundary involved Tb 1-xGd xFe 2 compounds

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

Murtaza, Adil; Yang, Sen; Zhou, Chao

2016-09-01

In the present paper, structural, magnetic and magnetostrictive properties of Tb 1-xGd xFe 2 (0 <= x <= 1.0) were studied. Synchrotron x-ray diffraction (XRD) results show the non-cubic symmetry of Tb 1-xGd xFe 2 at room temperature and composition-induced crystallographic phase transition from rhombohedral phase to tetragonal phase. The Gd concentration dependent lattice parameters, lattice distortion and change of easy magnetic direction were detected by synchrotron XRD. With the Gd concentration increases, Curie temperature Tc increases while room temperature magnetization and magnetostriction coefficient lambda(111) and the anisotropy of TbFe 2 decrease. The decrease in spontaneous magnetostriction coefficient lambda(111) withmore » increasing Gd substitution can be understood on the basis of the single-ion model; the corresponding decrease of magnetostriction for Tb 1-xGd xFe 2, and the large magnetostriction value occurs on the Tb-rich side, are ascribed to decrease of lambda(111)« less

Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations

PubMed Central

Wright, David; Mallon, Tom; McCormick, Carl; Orton, Richard J.; McDowell, Stanley; Trewby, Hannah; Skuce, Robin A.; Kao, Rowland R.

2012-01-01

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled ‘reservoir’ host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers. PMID:23209404

Single nucleotide polymorphisms may explain the contrasting phenotypes of two variants of a multidrug-resistant Mycobacterium tuberculosis strain.

PubMed

Bigi, María Mercedes; Lopez, Beatriz; Blanco, Federico Carlos; Sasiain, María Del Carmen; De la Barrera, Silvia; Marti, Marcelo A; Sosa, Ezequiel Jorge; Fernández Do Porto, Darío Augusto; Ritacco, Viviana; Bigi, Fabiana; Soria, Marcelo Abel

2017-03-01

Globally, about 4.5% of new tuberculosis (TB) cases are multi-drug-resistant (MDR), i.e. resistant to the two most powerful first-line anti-TB drugs. Indeed, 480,000 people developed MDR-TB in 2015 and 190,000 people died because of MDR-TB. The MDR Mycobacterium tuberculosis M family, which belongs to the Haarlem lineage, is highly prosperous in Argentina and capable of building up further drug resistance without impairing its ability to spread. In this study, we sequenced the whole genomes of a highly prosperous M-family strain (Mp) and its contemporary variant, strain 410, which produced only one recorded tuberculosis case in the last two decades. Previous reports have demonstrated that Mp induced dysfunctional CD8 + cytotoxic T cell activity, suggesting that this strain has the ability to evade the immune response against M. tuberculosis. Comparative analysis of Mp and 410 genomes revealed non-synonymous polymorphisms in eleven genes and five intergenic regions with polymorphisms between both strains. Some of these genes and promoter regions are involved in the metabolism of cell wall components, others in drug resistance and a SNP in Rv1861, a gene encoding a putative transglycosylase that produces a truncated protein in Mp. The mutation in Rv3787c, a putative S-adenosyl-l-methionine-dependent methyltransferase, is conserved in all of the other prosperous M strains here analysed and absent in non-prosperous M strains. Remarkably, three polymorphic promoter regions displayed differential transcriptional activity between Mp and 410. We speculate that the observed mutations/polymorphisms are associated with the reported higher capacity of Mp for modulating the host's immune response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Descriptive Epidemiology and Whole Genome Sequencing Analysis for an Outbreak of Bovine Tuberculosis in Beef Cattle and White-Tailed Deer in Northwestern Minnesota.

PubMed

Glaser, Linda; Carstensen, Michelle; Shaw, Sheryl; Robbe-Austerman, Suelee; Wunschmann, Arno; Grear, Dan; Stuber, Tod; Thomsen, Bruce

2016-01-01

Bovine tuberculosis (bTB) was discovered in a Minnesota cow through routine slaughter surveillance in 2005 and the resulting epidemiological investigation led to the discovery of infection in both cattle and white-tailed deer in the state. From 2005 through 2009, a total of 12 beef cattle herds and 27 free-ranging white-tailed deer (Odocoileus virginianus) were found infected in a small geographic region of northwestern Minnesota. Genotyping of isolates determined both cattle and deer shared the same strain of bTB, and it was similar to types found in cattle in the southwestern United States and Mexico. Whole genomic sequencing confirmed the introduction of this infection into Minnesota was recent, with little genetic divergence. Aggressive surveillance and management efforts in both cattle and deer continued from 2010-2012; no additional infections were discovered. Over 10,000 deer were tested and 705 whole herd cattle tests performed in the investigation of this outbreak.

Descriptive Epidemiology and Whole Genome Sequencing Analysis for an Outbreak of Bovine Tuberculosis in Beef Cattle and White-Tailed Deer in Northwestern Minnesota

PubMed Central

Glaser, Linda; Carstensen, Michelle; Shaw, Sheryl; Robbe-Austerman, Suelee; Wunschmann, Arno; Grear, Dan; Stuber, Tod; Thomsen, Bruce

2016-01-01

Bovine tuberculosis (bTB) was discovered in a Minnesota cow through routine slaughter surveillance in 2005 and the resulting epidemiological investigation led to the discovery of infection in both cattle and white-tailed deer in the state. From 2005 through 2009, a total of 12 beef cattle herds and 27 free-ranging white-tailed deer (Odocoileus virginianus) were found infected in a small geographic region of northwestern Minnesota. Genotyping of isolates determined both cattle and deer shared the same strain of bTB, and it was similar to types found in cattle in the southwestern United States and Mexico. Whole genomic sequencing confirmed the introduction of this infection into Minnesota was recent, with little genetic divergence. Aggressive surveillance and management efforts in both cattle and deer continued from 2010–2012; no additional infections were discovered. Over 10,000 deer were tested and 705 whole herd cattle tests performed in the investigation of this outbreak. PMID:26785113

INHIBITION OF MYCOLIC ACID TRANSPORT ACROSS THE MYCOBACTERIUM TUBERCULOSIS PLASMA MEMBRANE

PubMed Central

Grzegorzewicz, Anna E.; Pham, Ha; Gundi, Vijay A. K. B.; Scherman, Michael S.; North, Elton J.; Hess, Tamara; Jones, Victoria; Gruppo, Veronica; Born, Sarah E. M.; Korduláková, Jana; Chavadi, Sivagami Sundaram; Morisseau, Christophe; Lenaerts, Anne J.; Lee, Richard E.; McNeil, Michael R.; Jackson, Mary

2011-01-01

New chemotherapeutics active against multidrug-resistant Mycobacterium tuberculosis (M. tb) are urgently needed. We report on the identification of an adamantyl urea compound displaying potent bactericidal activity against M. tb and a unique mode of action, namely the abolition of the translocation of mycolic acids from the cytoplasm where they are synthesized to the periplasmic side of the plasma membrane where they are transferred onto cell wall arabinogalactan or used in the formation of virulence-associated outer membrane trehalose-containing glycolipids. Whole genome sequencing of spontaneous resistant mutants of M. tb selected in vitro followed by genetic validation experiments revealed that our prototype inhibitor targets the inner membrane transporter, MmpL3. Conditional gene expression of mmpL3 in mycobacteria and analysis of inhibitor-treated cells validate MmpL3 as essential for mycobacterial growth and support the involvement of this transporter in the translocation of trehalose monomycolate across the plasma membrane. PMID:22344175

Investigation on optical band gap, photoluminescence properties and concentration quenching mechanism of Pb1 - x Tb3 +xWO4 green-emitting phosphors

NASA Astrophysics Data System (ADS)

Chanu, Thokchom Taru Taru; Rajmuhon Singh, N.

2018-02-01

A series of monophasic Tb3 + (2, 5, 7, 10 and 15 at%) doped PbWO4 phosphors were successfully prepared via hydrothermal method. X-ray diffraction patterns revealed that the prepared samples possess a high crystallinity with tetragonal scheelite-type structure. FT-IR and Raman analysis exhibited a Wsbnd O stretching peak of WO42 - group, which is also related to the scheelite structure. UV-visible diffuse reflectance spectra indicated a reduction in the optical band gap with the replacement of Pb2 + by Tb3 + ions. The presence of strong and intense emission peaks characteristic of Tb3 + with the dominant peak at 545 nm (green, 5D4 → 7F5 transition) under UV irradiation at 320 nm demonstrated an efficient energy transfer from the host to Tb3 + ions. Using Van Uitert's model, the concentration quenching mechanism between Tb3 + ions in PbWO4:Tb3 + phosphor was attributed to a dipole-dipole interaction and the critical distance was determined to be 12 Å. The decay lifetimes and CIE chromaticity co-ordinates of PbWO4:Tb3 + phosphors were also investigated in detail. These prepared materials might serve as a potential phosphor for LED applications.

Structure and luminescence properties of Tb3+-doped Lu3Al5O12 films prepared by Pechini sol-gel method

NASA Astrophysics Data System (ADS)

Wang, Jian; Shen, Siqing; Xie, Jianjun; Shi, Ying; Ai, Fei

2011-02-01

Tb3+-doped Lu3Al5O12(hereinafter referred to as LuAG:Tb) films were successfully prepared by Pechini sol-gel process and spin-coating technique on carefully cleaned (111) silicon wafer. The microstructure and optical properties of the LuAG:Tb films were studied by X-ray diffraction (XRD), atomic force microscopy(AFM), as well as photoluminescence (PL) spectra. The XRD results showed that the precursor films started to crystallize at about 900°C. All as-calcined LuAG:Tb films showed the Tb3+ characteristic emission bands.

Structure and luminescence properties of Tb3+-doped Lu3Al5O12 films prepared by Pechini sol-gel method

NASA Astrophysics Data System (ADS)

Wang, Jian; Shen, Siqing; Xie, Jianjun; Shi, Ying; Ai, Fei

2010-10-01

Tb3+-doped Lu3Al5O12(hereinafter referred to as LuAG:Tb) films were successfully prepared by Pechini sol-gel process and spin-coating technique on carefully cleaned (111) silicon wafer. The microstructure and optical properties of the LuAG:Tb films were studied by X-ray diffraction (XRD), atomic force microscopy(AFM), as well as photoluminescence (PL) spectra. The XRD results showed that the precursor films started to crystallize at about 900°C. All as-calcined LuAG:Tb films showed the Tb3+ characteristic emission bands.

A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians.

PubMed

Png, Eileen; Alisjahbana, Bachti; Sahiratmadja, Edhyana; Marzuki, Sangkot; Nelwan, Ron; Balabanova, Yanina; Nikolayevskyy, Vladyslav; Drobniewski, Francis; Nejentsev, Sergey; Adnan, Iskandar; van de Vosse, Esther; Hibberd, Martin L; van Crevel, Reinout; Ottenhoff, Tom H M; Seielstad, Mark

2012-01-13

There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia. In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia. Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.

Impact of Genetic Diversity on the Biology of Mycobacterium tuberculosis Complex Strains.

PubMed

Niemann, Stefan; Merker, Matthias; Kohl, Thomas; Supply, Philip

2016-11-01

Tuberculosis (TB) remains the most deadly bacterial infectious disease worldwide. Its treatment and control are threatened by increasing numbers of multidrug-resistant (MDR) or nearly untreatable extensively drug-resistant (XDR) strains. New concepts are therefore urgently needed to understand the factors driving the TB epidemics and the spread of different strain populations, especially in association with drug resistance. Classical genotyping and, more recently, whole-genome sequencing (WGS) revealed that the world population of tubercle bacilli is more diverse than previously thought. Several major phylogenetic lineages can be distinguished, which are associated with their sympatric host population. Distinct clonal (sub)populations can even coexist within infected patients. WGS is now used as the ultimate approach for differentiating clinical isolates and for linking phenotypic to genomic variation from lineage to strain levels. Multiple lines of evidence indicate that the genetic diversity of TB strains translates into pathobiological consequences, and key molecular mechanisms probably involved in differential pathoadaptation of some main lineages have recently been identified. Evidence also accumulates on molecular mechanisms putatively fostering the emergence and rapid expansion of particular MDR and XDR strain groups in some world regions. However, further integrative studies will be needed for complete elucidation of the mechanisms that allow the pathogen to infect its host, acquire multidrug resistance, and transmit so efficiently. Such knowledge will be key for the development of the most effective new diagnostics, drugs, and vaccination strategies.

The history of tuberculosis management in Sweden.

PubMed

Wallstedt, Helen; Maeurer, Markus

2015-03-01

We review the history of TB in Sweden beginning in 1800, when 25% of mortality in Sweden was associated with TB. The Royal Family was involved in establishing dedicated sanatoria in Sweden to offer better diagnostics and clinical care. TB has declined in Sweden steadily, with some recent increases due to local spread of TB and challenging international and national socio-economical structures. Improved research and clinical knowledge is needed to diagnose and manage drug-susceptible as well as drug-resistant TB. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multi-quasiparticle excitations in145Tb

NASA Astrophysics Data System (ADS)

Zheng, Yong; Zhou, Xiaohong; Zhang, Yuhu; Liu, Minliang; Guo, Yingxiang; Lei, Xiangguo; Hayakawa, T.; Oshima, M.; Toh, T.; Shizuma, T.; Katakura, J.; Hatsukawa, Y.; Matsuda, M.; Kusakari, H.; Sugawara, M.

2004-09-01

High-spin states in145Tb have been populated using the118Sn (32S, 1p4n) reaction at beam energy of 165 MeV. The level scheme of145Tb has been established up to Ex≈7.4 MeV. The level scheme shows characteristics of a spherical or slightly oblate nucleus. Based on the systematic trends of the level structure in the neighboring N=80 isotones, the level structure in145Tb below 2 MeV excitation is well eplained by coupling an h 11/2 valence proton to the even-even144Gd core. Above 2 MeV excitation, most of the yrast levels are interpreted with multi-quasiparticle shell-model configurations.

Factors influencing non-adherence to tuberculosis treatment in Jepara, central Java, Indonesia.

PubMed

Rondags, Angelique; Himawan, Ari Budi; Metsemakers, Job Fm; Kristina, Tri Nur

2014-07-01

One of the most serious problems for tuberculosis (TB) control is non-adherence to TB treatment. We studied the factors influencing non-adherence to TB treatment in Indonesia to inform TB treatment adherence strategies. We con- ducted semi-structured interviews with non-adherent patients and key informants in Jepara, Central Java, Indonesia. Three major themes were found in reasons for non-adherence to TB treatment: 1) knowledge about TB, 2) knowledge about TB treatment and 3) choosing and changing a health care treatment facility. Respondents had an inadequate knowledge about TB and its treatment. Feeling healthy and having financial problems were the most common reasons for TB treatment non-adherence. Respondents sought treatment from many different health care providers, and often changed the treatment facility location. TB treatment adherence might improve by providing better education about the disease and its treatment to those undergoing treatment. Providing information about where to receive treatment and that treatment is free could also improve compliance.

Molecular findings and approaches spotlighting Mycobacterium bovis persistence in cattle.

PubMed

Alvarez, Angel H; Estrada-Chávez, Ciro; Flores-Valdez, Mario Alberto

2009-01-01

Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis (M. bovis) are the etiological agents of human and bovine tuberculosis (TB, bTB) respectively, and share genetic identity over 99% at the whole genome level. Progress has been made towards explaining how mycobacteria and their infected hosts remain in balance without producing clinical symptoms of disease, a phenomenon referred to as latency or persistence, which can be mimicked by certain in vitro conditions. Latency/persistence has mainly been studied using Mtb, where the two-component signalling system, dosRS, has been assigned an instrumental role, and even constitutes the current basis for development of new diagnostic methods and treatment addressing this particular stage of TB. M. bovis conserves homolog genes that in Mtb play a role in human latent TB infection and that, by analogy, would allow it to enter a persistent state in infected cattle; nevertheless, little attention has been paid to this stage in bovine hosts. We suggest that many of the advances acquired through the study of Mtb can and should be taken into consideration by research groups and veterinary professionals dealing with bTB. The study of the infection in bovines, paying particular attention to defining the molecular and cellular markers of a M. bovis persistent infection in cattle, presents great opportunities for the development and trial of new diagnostic tests and vaccines, tools that will surely help in promoting eradication of bTB in high-burden settings.

Tuberculosis stigma as a social determinant of health: a systematic mapping review of research in low incidence countries.

PubMed

Craig, G M; Daftary, A; Engel, N; O'Driscoll, S; Ioannaki, A

2017-03-01

Tuberculosis (TB)-related stigma is an important social determinant of health. Research generally highlights how stigma can have a considerable impact on individuals and communities, including delays in seeking health care and adherence to treatment. There is scant research into the assessment of TB-related stigma in low incidence countries. This study aimed to systematically map out the research into stigma. A particular emphasis was placed on the methods employed to measure stigma, the conceptual frameworks used to understand stigma, and whether structural factors were theorized. Twenty-two studies were identified; the majority adopted a qualitative approach and aimed to assess knowledge, attitudes, and beliefs about TB. Few studies included stigma as a substantive topic. Only one study aimed to reduce stigma. A number of studies suggested that TB control measures and representations of migrants in the media reporting of TB were implicated in the production of stigma. The paucity of conceptual models and theories about how the social and structural determinants intersect with stigma was apparent. Future interventions to reduce stigma, and measurements of effectiveness, would benefit from a stronger theoretical underpinning in relation to TB stigma and the intersection between the social and structural determinants of health. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Data-driven model for the assessment of Mycobacterium tuberculosis transmission in evolving demographic structures

PubMed Central

Arregui, Sergio; Marinova, Dessislava; Sanz, Joaquín

2018-01-01

In the case of tuberculosis (TB), the capabilities of epidemic models to produce quantitatively robust forecasts are limited by multiple hindrances. Among these, understanding the complex relationship between disease epidemiology and populations’ age structure has been highlighted as one of the most relevant. TB dynamics depends on age in multiple ways, some of which are traditionally simplified in the literature. That is the case of the heterogeneities in contact intensity among different age strata that are common to all airborne diseases, but still typically neglected in the TB case. Furthermore, while demographic structures of many countries are rapidly aging, demographic dynamics are pervasively ignored when modeling TB spreading. In this work, we present a TB transmission model that incorporates country-specific demographic prospects and empirical contact data around a data-driven description of TB dynamics. Using our model, we find that the inclusion of demographic dynamics is followed by an increase in the burden levels predicted for the next decades in the areas of the world that are most hit by the disease today. Similarly, we show that considering realistic patterns of contacts among individuals in different age strata reshapes the transmission patterns reproduced by the models, a result with potential implications for the design of age-focused epidemiological interventions. PMID:29563223

Structural, spectroscopic and cytotoxicity studies of TbF3@CeF3 and TbF3@CeF3@SiO2 nanocrystals.

PubMed

Grzyb, Tomasz; Runowski, Marcin; Dąbrowska, Krystyna; Giersig, Michael; Lis, Stefan

2013-01-01

Terbium fluoride nanocrystals, covered by a shell, composed of cerium fluoride were synthesized by a co-precipitation method. Their complex structure was formed spontaneously during the synthesis. The surface of these core/shell nanocrystals was additionally modified by silica. The properties of TbF 3 @CeF 3 and TbF 3 @CeF 3 @SiO 2 nanocrystals, formed in this way, were investigated. Spectroscopic studies showed that the differences between these two groups of products resulted from the presence of the SiO 2 shell. X-ray diffraction patterns confirmed the trigonal crystal structure of TbF 3 @CeF 3 nanocrystals. High resolution transmission electron microscopy in connection with energy-dispersive X-ray spectroscopy showed a complex structure of the formed nanocrystals. Crystallized as small discs, 'the products', with an average diameter around 10 nm, showed an increase in the concentration of Tb 3+ ions from surface to the core of nanocrystals. In addition to photo-physical analyses, cytotoxicity studies were performed on HSkMEC (Human Skin Microvascular Endothelial Cells) and B16F0 mouse melanoma cancer cells. The cytotoxicity of the nanomaterials was neutral for the investigated cells with no toxic or antiproliferative effect in the cell cultures, either for normal or for cancer cells. This fact makes the obtained nanocrystals good candidates for biological applications and further modifications of the SiO 2 shell. .

Structural, spectroscopic and cytotoxicity studies of TbF3@CeF3 and TbF3@CeF3@SiO2 nanocrystals

NASA Astrophysics Data System (ADS)

Grzyb, Tomasz; Runowski, Marcin; Dąbrowska, Krystyna; Giersig, Michael; Lis, Stefan

2013-10-01

Terbium fluoride nanocrystals, covered by a shell, composed of cerium fluoride were synthesized by a co-precipitation method. Their complex structure was formed spontaneously during the synthesis. The surface of these core/shell nanocrystals was additionally modified by silica. The properties of TbF3@CeF3 and TbF3@CeF3@SiO2 nanocrystals, formed in this way, were investigated. Spectroscopic studies showed that the differences between these two groups of products resulted from the presence of the SiO2 shell. X-ray diffraction patterns confirmed the trigonal crystal structure of TbF3@CeF3 nanocrystals. High resolution transmission electron microscopy in connection with energy-dispersive X-ray spectroscopy showed a complex structure of the formed nanocrystals. Crystallized as small discs, `the products', with an average diameter around 10 nm, showed an increase in the concentration of Tb3+ ions from surface to the core of nanocrystals. In addition to photo-physical analyses, cytotoxicity studies were performed on HSkMEC (Human Skin Microvascular Endothelial Cells) and B16F0 mouse melanoma cancer cells. The cytotoxicity of the nanomaterials was neutral for the investigated cells with no toxic or antiproliferative effect in the cell cultures, either for normal or for cancer cells. This fact makes the obtained nanocrystals good candidates for biological applications and further modifications of the SiO2 shell.

Translating childhood tuberculosis case management research into operational policies.

PubMed

Safdar, N; Hinderaker, S G; Baloch, N A; Enarson, D A; Khan, M A; Morkve, O

2011-08-01

The control of childhood tuberculosis (TB) has been of low priority in TB programmes in high-burden settings. The objective of this paper was to describe the development and testing of tools for the management of childhood TB. The Pakistan National TB Control Programme embarked on a number of activities, including the establishment of policy guidelines for the management of childhood TB and later a guidance document, 'Case Management Desk Guide and Structured Monitoring', to demonstrate the implementation of childhood TB interventions in a programme context. Initial results showed improved case finding and treatment outcome in implementation sites compared with control districts. However, further programme attention is required to improve quality.

Tuning of magnetic ordering by Y substitution onto Tb site in the nanocrystalline TbMnO{sub 3}

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

Chakraborty, Keka R., E-mail: kekarc@barc.gov.in, E-mail: smyusuf@barc.gov.in; Mukadam, M. D.; Yusuf, S. M., E-mail: kekarc@barc.gov.in, E-mail: smyusuf@barc.gov.in

2015-10-28

We report the magnetic properties, of nano-crystalline powders Tb{sub 1−x}Y{sub x}MnO{sub 3} (x = 0, 0.1, 0.2, 0.3 and 0.4), as perceived by neutron diffraction, and elucidate the effect of Tb site substitution on the magnetic structure of TbMnO{sub 3}. All samples crystallized in the orthorhombic structure conforming to space group Pnma, and exhibited an incommensurate collinear antiferromagnetic ordering of the Mn ions below ∼40 K. Furthermore, at T ≤ 20 K, all these samples showed a change in magnetic structure (of Mn moments) to a spiral ordering down to 2 K, the lowest measured temperature. For the samples with x = 0, 0.1, and 0.2, a short-ranged twomore » dimensional (2D) ordering of Tb moments was also observed at 2 K. However, for the other samples (x = 0.3 and 0.4), no magnetic ordering of Tb moments was found down to 2 K. So with Y substitution, a crossover from 2D ordering to a disordering of Tb moments was observed. The moments at the Mn site were found to be lower than the full Mn{sup 3+} (4μ{sub B}) moment for all the samples below 40 K. The magnetic properties of all the samples studied by us in nano form are more pronounced than those of the reported single crystals of same compositions [V. Yu. Ivanov et al., JETP Lett. 91, 392–397 (2010)].« less

Clonality and Micro-Diversity of a Nationwide Spreading Genotype of Mycobacterium tuberculosis in Japan

PubMed Central

Wada, Takayuki; Iwamoto, Tomotada; Tamaru, Aki; Seto, Junji; Ahiko, Tadayuki; Yamamoto, Kaori; Hase, Atushi; Maeda, Shinji; Yamamoto, Taro

2015-01-01

Mycobacterium tuberculosis transmission routes can be estimated from genotypic analysis of clinical isolates from patients. In Japan, still a middle-incidence country of TB, a unique genotype strain designated as ‘M-strain’ has been isolated nationwide recently. To ascertain the history of the wide spread of the strain, 10 clinical isolates from different areas were subjected to genome-wide analysis based on deep sequencers. Results show that all isolates possessed common mutations to those of referential strains. The greatest number of accumulated single nucleotide variants (SNVs) from the oldest coalescence was 13 nucleotides, indicating high clonality of these isolates. When an SNV common to the isolates was used as a surrogate marker of the clone, authentic clonal isolates with variation in a reliable subset of variable number of tandem repeat (VNTR) genotyping method can be selected successfully from clinical isolates populations of M. tuberculosis. When the authentic clones can also be assigned to sub-clonal groups by SNVs derived from the genomic comparison, they are classifiable into three sub-clonal groups with a bias of geographical origins. Feedback from genomic analysis of clinical isolates of M. tuberculosis to genotypic markers will be an efficient strategy for the big data in various settings for public health actions against TB. PMID:25734518

Community knowledge, attitudes and practices in relation to tuberculosis in Cameroon.

PubMed

Kwedi Nolna, S; Kammogne, I D; Ndzinga, R; Afanda, B; Ntonè, R; Boum, Y; Nolna, D

2016-09-01

With 15 080 new cases in 2013, Cameroon is a country with high tuberculosis (TB) incidence and prevalence. Understanding the community's knowledge, attitude and practice (KAP) about TB is key to TB control in such endemic settings. To assess TB-related KAP in Cameroon by describing the sociodemographics of respondents, to identify barriers to seeking care and to explore attitudes and experiences of stigma and discrimination related to TB in communities. We conducted a cross-sectional descriptive study using structured questionnaires to assess and compare TB KAP in the entire territory. The results showed that Cameroonians have insufficient understanding of TB, numerous erroneous health assumptions and beliefs concerning TB, and erroneous information about the symptoms and mode of transmission of the disease. Negative attitudes and poor practices are obstacles to elimination and control efforts. The National Tuberculosis Control Programme should generate more effective strategies to reach the populations, paying particular attention to rural populations.

46 CFR 36.05-10 - Protection of personnel-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Protection of personnel-TB/ALL. 36.05-10 Section 36.05-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS ELEVATED TEMPERATURE CARGOES Cargo Tanks § 36.05-10 Protection of personnel—TB/ALL. (a) Decks, bulkheads, or other structures shall...

46 CFR 36.05-10 - Protection of personnel-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Protection of personnel-TB/ALL. 36.05-10 Section 36.05-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS ELEVATED TEMPERATURE CARGOES Cargo Tanks § 36.05-10 Protection of personnel—TB/ALL. (a) Decks, bulkheads, or other structures shall...

Magnetic properties and structural transitions of fluorite-related rare earth osmates Ln3OsO7 (Ln=Pr, Tb)

NASA Astrophysics Data System (ADS)

Hinatsu, Yukio; Doi, Yoshihiro

2013-02-01

Ternary rare-earth osmates Ln3OsO7 (Ln=Pr, Tb) have been prepared. They crystallize in an ortho-rhombic superstructure of cubic fluorite with space group Cmcm. Both of these compounds undergo a structural phase transition at 130 K (Ln=Pr) and 580 K (Ln=Tb). These compounds show complex magnetic behavior at low temperatures. Pr3OsO7 exhibits magnetic transitions at 8 and 73 K, and Tb3OsO7 magnetically orders at 8 and 60 K. The Os moments become one-dimensionally ordered, and when the temperature is furthermore decreased, it provokes the ordering in the Ln3+ sublattice that simultaneously becomes three-dimensionally ordered with the Os sublattice.

Prevalence of hepatitis C virus and human immunodeficiency virus in a group of patients newly diagnosed with active tuberculosis in Porto Alegre, Southern Brazil.

PubMed

Costi, Cintia; Grandi, Tarciana; Halon, Maria Laura; Silva, Márcia Susana Nunes; Silva, Cláudia Maria Dornelles da; Gregianini, Tatiana Schäffer; Possuelo, Lia Gonçalves; Jarczewski, Carla Adriane; Niel, Christian; Rossetti, Maria Lucia Rosa

2017-04-01

Porto Alegre is the Brazilian state capital with second highest incidence of tuberculosis (TB) and the highest proportion of people infected with human immunodeficiency virus (HIV) among patients with TB. Hepatitis C virus (HCV) infection increases the risk of anti-TB drug-induced hepatotoxicity, which may result in discontinuation of the therapy. The aim of this study was (i) to estimate prevalence of HCV and HIV in a group of patients newly diagnosed with active TB in a public reference hospital in Porto Alegre and (ii) to compare demographic, behavioural, and clinical characteristics of patients in relation to their HCV infection status. One hundred and thirty-eight patients with TB were tested for anti-HCV antibody, HCV RNA, and anti-HIV1/2 antibody markers. HCV RNA from real-time polymerase chain reaction (PCR)-positive samples was submitted to reverse transcription and PCR amplification. The 5' non-coding region of the HCV genome was sequenced, and genotypes of HCV isolates were determined. Anti-HCV antibody, HCV RNA, and anti-HIV antibodies were detected in 27 [20%; 95% confidence interval (CI), 13-26%], 17 (12%; 95% CI, 7-18%), and 34 (25%; 95% CI, 17-32%) patients, respectively. HCV isolates belonged to genotypes 1 (n = 12) and 3 (n = 4). Some characteristics were significantly more frequent in patients infected with HCV. Among them, non-white individuals, alcoholics, users of illicit drugs, imprisoned individuals, and those with history of previous TB episode were more commonly infected with HCV (p < 0.05). HCV screening, including detection of anti-HCV antibody and HCV RNA, will be important to improving the management of co-infected patients, given their increased risk of developing TB treatment-related hepatotoxicity.

Structural and optical properties of Tb and Na-Tb co-doped Ca3V2O8 phosphors prepared by sol-gel process

NASA Astrophysics Data System (ADS)

Parab, Shambhu S.; Salker, A. V.

2018-01-01

A malic acid assisted sol-gel route was successfully employed to prepare two distinct series of green emitting Ca3V2O8 phosphors. In the first series, Tb was solely doped whereas in the second series Na and Tb were doped simultaneously in the Ca3V2O8 crystal lattice. X-ray diffraction studies proved the utility of adopted preparative method by confirming the monophasic formation of all compounds from both the series. Spectral analysis like Raman spectroscopy, UV-DRS were undertaken to analyse the local structure, crystallinity and absorptive characteristics. XPS validated the presence of desired oxidation states of all the elements present. Finally, photoluminescence studies were done to elucidate the scope of prepared compounds as green emitting phosphors and also to understand the effect of both doping schemes on the luminescence. Intense green emission was observed in both the cases. Tb concentration of 0.08 was found to be optimum in case of Tb singly doped compounds whereas Tb = 0.12 showed highest intensity among the Na-Tb co-doped samples. Moreover, a red shift in the excitation wavelength was observed after Na doping signifying a change in the local electronic environment which in turn has affected the luminescence pattern. Local crystallinity and vacancy concentrations were found to have a major say on the emission intensities.

Investigation on optical band gap, photoluminescence properties and concentration quenching mechanism of Pb1-x Tb3+xWO4 green-emitting phosphors.

PubMed

Chanu, Thokchom Taru Taru; Rajmuhon Singh, N

2018-02-15

A series of monophasic Tb 3+ (2, 5, 7, 10 and 15at%) doped PbWO 4 phosphors were successfully prepared via hydrothermal method. X-ray diffraction patterns revealed that the prepared samples possess a high crystallinity with tetragonal scheelite-type structure. FT-IR and Raman analysis exhibited a WO stretching peak of WO 4 2- group, which is also related to the scheelite structure. UV-visible diffuse reflectance spectra indicated a reduction in the optical band gap with the replacement of Pb 2+ by Tb 3+ ions. The presence of strong and intense emission peaks characteristic of Tb 3+ with the dominant peak at 545nm (green, 5 D 4 → 7 F 5 transition) under UV irradiation at 320nm demonstrated an efficient energy transfer from the host to Tb 3+ ions. Using Van Uitert's model, the concentration quenching mechanism between Tb 3+ ions in PbWO 4 :Tb 3+ phosphor was attributed to a dipole-dipole interaction and the critical distance was determined to be ~12Å. The decay lifetimes and CIE chromaticity co-ordinates of PbWO 4 :Tb 3+ phosphors were also investigated in detail. These prepared materials might serve as a potential phosphor for LED applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Bayesian methods for estimating GEBVs of threshold traits

PubMed Central

Wang, C-L; Ding, X-D; Wang, J-Y; Liu, J-F; Fu, W-X; Zhang, Z; Yin, Z-J; Zhang, Q

2013-01-01

Estimation of genomic breeding values is the key step in genomic selection (GS). Many methods have been proposed for continuous traits, but methods for threshold traits are still scarce. Here we introduced threshold model to the framework of GS, and specifically, we extended the three Bayesian methods BayesA, BayesB and BayesCπ on the basis of threshold model for estimating genomic breeding values of threshold traits, and the extended methods are correspondingly termed BayesTA, BayesTB and BayesTCπ. Computing procedures of the three BayesT methods using Markov Chain Monte Carlo algorithm were derived. A simulation study was performed to investigate the benefit of the presented methods in accuracy with the genomic estimated breeding values (GEBVs) for threshold traits. Factors affecting the performance of the three BayesT methods were addressed. As expected, the three BayesT methods generally performed better than the corresponding normal Bayesian methods, in particular when the number of phenotypic categories was small. In the standard scenario (number of categories=2, incidence=30%, number of quantitative trait loci=50, h2=0.3), the accuracies were improved by 30.4%, 2.4%, and 5.7% points, respectively. In most scenarios, BayesTB and BayesTCπ generated similar accuracies and both performed better than BayesTA. In conclusion, our work proved that threshold model fits well for predicting GEBVs of threshold traits, and BayesTCπ is supposed to be the method of choice for GS of threshold traits. PMID:23149458

The effect of row structure on soil moisture retrieval accuracy from passive microwave data.

PubMed

Xingming, Zheng; Kai, Zhao; Yangyang, Li; Jianhua, Ren; Yanling, Ding

2014-01-01

Row structure causes the anisotropy of microwave brightness temperature (TB) of soil surface, and it also can affect soil moisture retrieval accuracy when its influence is ignored in the inversion model. To study the effect of typical row structure on the retrieved soil moisture and evaluate if there is a need to introduce this effect into the inversion model, two ground-based experiments were carried out in 2011. Based on the observed C-band TB, field soil and vegetation parameters, row structure rough surface assumption (Q p model and discrete model), including the effect of row structure, and flat rough surface assumption (Q p model), ignoring the effect of row structure, are used to model microwave TB of soil surface. Then, soil moisture can be retrieved, respectively, by minimizing the difference of the measured and modeled TB. The results show that soil moisture retrieval accuracy based on the row structure rough surface assumption is approximately 0.02 cm(3)/cm(3) better than the flat rough surface assumption for vegetated soil, as well as 0.015 cm(3)/cm(3) better for bare and wet soil. This result indicates that the effect of row structure cannot be ignored for accurately retrieving soil moisture of farmland surface when C-band is used.

Rare earth niobate coordination polymers

NASA Astrophysics Data System (ADS)

Muniz, Collin N.; Patel, Hiral; Fast, Dylan B.; Rohwer, Lauren E. S.; Reinheimer, Eric W.; Dolgos, Michelle; Graham, Matt W.; Nyman, May

2018-03-01

Rare-earth (RE) coordination polymers are infinitely tailorable to yield luminescent materials for various applications. Here we described the synthesis of a heterometallic rare-earth coordination compound ((CH3)2SO)3(RE)NbO(C2O4)3((CH3)2SO) = dimethylsulfoxide, DMSO, (C2O2= oxalate), (RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb). The structure was obtained from single crystal X-ray diffraction of the La analogue. The Nb˭O and DMSO terminal-bonding character guides assembly of an open framework structure with noncentrosymmetric RE-coordination geometry, and large spacing between the RE centers. A second structure was observed by PXRD for the smaller rare earths (Dy, Ho, Er, Yb); this structure has not yet been determined. The materials were further characterized using FTIR, and photoluminescence measurements. Characteristic excitation and emission transitions were observed for RE = Nd, Sm, Eu, and Tb. Quantum yield (QY) measurements were performed by exciting Eu and Tb analoges at 394 nm (QY 66%) and 464 nm (QY 71%) for Eu; and 370 nm (QY=40%) for Tb. We attribute the high QY and bright luminescence to two main structure-function properties of the system; namely the absence of water in the structure, and absence of concentration quenching.

An exploration of NHS staff views on tuberculosis service delivery in Scottish NHS boards

PubMed Central

Spence, William

2013-01-01

Tuberculosis (TB) is a bacterial disease and major worldwide killer with an increased UK incidence rate. This study aimed to explore the views of National Health Service (NHS) staff on TB service delivery models of care in NHS boards across Scotland. Eighteen semi-structured interviews were conducted with 13 nurse specialists and five consultants in public health medicine (CPHM) across five Scottish NHS boards. Five main themes emerged and findings showed that: directly observed treatment (DOT) was provided only to patients assessed to be at high risk of poor treatment adherence; contact tracing was conducted by participating NHS boards but screening at ports was thought to be weak; all NHS boards implemented TB awareness campaigns for TB health professionals; three NHS boards conducted team meetings that monitored TB patient progress; participants believed that TB funding should be increased; contact tracing was routinely conducted by TB nurses. Improved TB screening at airports was recommended and a need for TB health education for high risk groups was identified. PMID:28989349

Luminescence and energy transfer in Lu3Al5O12 scintillators co-doped with Ce3+ and Tb3+.

PubMed

Ogiegło, Joanna M; Zych, Aleksander; Ivanovskikh, Konstantin V; Jüstel, Thomas; Ronda, Cees R; Meijerink, Andries

2012-08-23

Lu(3)Al(5)O(12) (LuAG) doped with Ce(3+) is a promising scintillator material with a high density and a fast response time. The light output under X-ray or γ-ray excitation is, however, well below the theoretical limit. In this paper the influence of codoping with Tb(3+) is investigated with the aim to increase the light output. High resolution spectra of singly doped LuAG (with Ce(3+) or Tb(3+)) are reported and provide insight into the energy level structure of the two ions in LuAG. For Ce(3+) zero-phonon lines and vibronic structure are observed for the two lowest energy 5d bands and the Stokes' shift (2 350 cm(-1)) and Huang-Rhys coupling parameter (S = 9) have been determined. Tb(3+) 4f-5d transitions to the high spin (HS) and low spin (LS) states are observed (including a zero-phonon line and vibrational structure for the high spin state). The HS-LS splitting of 5400 cm(-1) is smaller than usually observed and is explained by a reduction of the 5d-4f exchange coupling parameter J by covalency. Upon replacing the smaller Lu(3+) ion with the larger Tb(3+) ion, the crystal field splitting for the lowest 5d states increases, causing the lowest 5d state to shift below the (5)D(4) state of Tb(3+) and allowing for efficient energy transfer from Tb(3+) to Ce(3+) down to the lowest temperatures. Luminescence decay measurements confirm efficient energy transfer from Tb(3+) to Ce(3+) and provide a qualitative understanding of the energy transfer process. Co-doping with Tb(3+) does not result in the desired increase in light output, and an explanation based on electron trapping in defects is discussed.

Structure and luminescent property of complexes of aryl carboxylic acid-functionalized polystyrene with Eu(III) and Tb(III) ions.

PubMed

Gao, Baojiao; Shi, Nan; Qiao, Zongwen

2015-11-05

Via polymer reactions, naphthoic acid (NA) and benzoic acid (BA) were bonded onto the side chains of polystyrene (PS), respectively, and two aryl carboxylic acid-functionalized polystyrenes, PSNA and PSBA, were obtained. Using PSNA and PSBA as macromolecule ligands and Eu(3+) and Tb(3+) ions as central ions, various luminescent binary polymer-rare earth complexes were prepared. At the same time, with 1,10-phenanthroline (Phen) and 4,4'-bipyridine (Bipy) as small-molecule co-ligands, various ternary polymer-rare earth complexes were also prepared. On the basis of characterizing PSNA, PSBA and complexes, the relationship between structure and luminescent property for these prepared complexes were mainly investigated. The study results show that the macromolecule ligands PSNA and PSBA, or the bonded NA and BA ligands, can strongly sensitize the fluorescence emissions of Eu(3+) ion or Tb(3+) ion, but the sensitization effect is strongly dependent on the structure of the ligands and the property of the central ions, namely it is strongly dependent on the matching degree of energy levels. The fluorescence emission of the binary complex PS-(NA)3-Eu(III) is stronger than that PS-(BA)3-Eu(III), indicating ligand NA has stronger sensitization action for Eu(3+) ion than ligand BA; the binary complex PS-(BA)3-Tb(III) emit strong characteristic fluorescence of Tb(3+) ion, displaying that ligand BA can strongly sensitize Tb(3+) ion, whereas the binary complex PS-(NA)3-Tb(III) nearly does not emit the characteristic fluorescence of Tb(3+) ion, showing that ligand NA does not sensitize Tb(3+) ion. The fluorescence intensity of the ternary complexes is much stronger than that of the binary complexes in the same series. Copyright © 2015 Elsevier B.V. All rights reserved.

Color-tunable photoluminescence phosphors of Ce{sup 3+} and Tb{sup 3+} co-doped Sr{sub 2}La{sub 8}(SiO{sub 4}){sub 6}O{sub 2} for UV w-LEDs

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

Guo, Qingfeng; Liao, Libing, E-mail: clayl@cugb.edu.cn; Mei, Lefu

2015-05-15

A series of new luminescent emission-tunable phosphors Sr{sub 2}La{sub 8}(SiO{sub 4}){sub 6}O{sub 2}:Ce{sup 3+}, Tb{sup 3+} with apatite structure have been synthesized by a high temperature solid-state reaction. The phase structure, photoluminescence emission and excitation spectra, lifetime, as well as the effect of Tb{sup 3+} concentration are investigated to characterize the resulting samples. The critical distance was calculated to be 8.26 Å by using the concentration quenching method. The intense green emission was observed in the Sr{sub 2}La{sub 8}(SiO{sub 4}){sub 6}O{sub 2}:Ce{sup 3+}, Tb{sup 3+} phosphors on the basis of the efficient energy transfer from Ce{sup 3+} to Tb{sup 3+}more » with an efficiency of 68.55%. And a possible mechanism of the energy-transfer from Ce{sup 3+} to Tb{sup 3+} ion is also proposed. The results indicate that Sr{sub 2}La{sub 8}(SiO{sub 4}){sub 6}O{sub 2}:Ce{sup 3+}, Tb{sup 3+} phosphors have potential applications to be used as near UV-convertible phosphors for white light-emitting diodes because of the broad excitation in the near-ultraviolet range and the efficient green emission light. - Graphical abstract: Crystal structure and luminescence properties of Sr{sub 2}La{sub 8}(SiO{sub 4}){sub 6}O{sub 2}:Ce{sup 3+},Tb{sup 3+} phosphors have been discussed. - Highlights: • Ce{sup 3+} and Tb{sup 3+} ions entered both La sites in SLSO. • The energy transfer efficiency can reach at 68.55%. • The emitting color of SLSO phosphors shifted from the blue to green region.« less

Tuberculosis and diabetes in Guyana.

PubMed

Alladin, Bibi; Mack, Steve; Singh, Aruna; Singh, Chaitra; Smith, Belinda; Cummings, Emmanuel; Hershfield, Earl; Mohanlall, Jeetendra; Ramotar, Karam; La Fleur, Curtis

2011-12-01

This study was conducted to determine the prevalence of diabetes mellitus among tuberculosis (TB) patients attending three TB clinics in Guyana. A cross-sectional study was conducted among TB patients attending TB clinics in three regions in Guyana. A structured questionnaire was used to collect demographic, clinical, and risk factor data. Random blood sugar testing was done using the OneTouch UltraSmart glucometer (LifeScan, Inc., 2002). One hundred TB patients were recruited; 90 had pulmonary TB and 10 had extrapulmonary disease. Fourteen patients were classified as diabetic: 12 had been previously diagnosed as diabetic by a physician and two had abnormally high random blood sugar at the time of enrolment. Of the 12 known diabetics, seven had been diagnosed before TB was discovered, three were identified at the time TB was diagnosed, and two after TB was diagnosed. All 14 diabetic patients presented with pulmonary TB. Thirty-one patients were HIV-positive and 28 of these had pulmonary TB, whereas three had extrapulmonary TB. None of the diabetics were infected with HIV. TB-diabetic patients tended to be older than non-diabetics (median age 44 vs. 36.5 years), were more likely to have been incarcerated at the time of TB diagnosis than non-diabetics (p=0.06), and were more likely to have an elevated (random) blood sugar level (p=0.02). Clinically, diabetes did not influence the presentation of TB. This study clearly highlights that diabetes and HIV are frequent in Guyanese TB patients. Routine screening of TB patients for diabetes and diabetic patients for TB should be speedily implemented. The National TB Programme should work closely with the diabetes clinics so that TB patients who are diabetics are optimally managed. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Effects of sociodemographic characteristics and patients' health beliefs on tuberculosis treatment adherence in Ethiopia: a structural equation modelling approach.

PubMed

Tola, Habteyes Hailu; Karimi, Mehrdad; Yekaninejad, Mir Saeed

2017-12-15

Patients' beliefs are a major factor affecting tuberculosis (TB) treatment adherence. However, there has been little use of Health Belief Model (HBM) in determining the pathway effect of patients' sociodemographic characteristics and beliefs on TB treatment adherence. Therefore, this study was aimed at determining the effect of sociodemographic characteristics and patients' health beliefs on TB treatment adherence based on the HBM concept in Ethiopia. A cross-sectional study was conducted in Addis Ababa, Ethiopia among TB patients undertaking treatment. Thirty health centres were randomly selected and one hospital was purposely chosen. Six hundred and ninety-eight TB patients who had been on treatment for 1-2 month, were aged 18 years or above, and had the mental capability to provide consent were enrolled consecutively with non-probability sampling technique from the TB registration book until required sample size achieved. Structured questionnaires were used to collect data. Structural equation modelling was employed to assess the pathway relationship between sociodemographic characteristics, patients' beliefs, and treatment adherence. Of the 698 enrolled participants, 401 (57.4%) were male and 490 (70.2%) were aged 35 years and below. The mean age of participants was 32 (± 11.7) and the age range was 18-90 years. Perceived barrier/benefit was shown to be a significant direct negative effect on TB treatment adherence (ß = -0.124, P = 0.032). In addition, cue to action (ß = -0.68, P ≤ 0.001) and psychological distress (ß = 0.08, P < 0.001) were shown significant indirect effects on TB treatment adherence through perceived barrier/benefit. Interventions intended to decrease perceived barriers and maximize perceived benefits should be implemented to enhance TB treatment adherence. In addition, it is crucial that counselling is incorporated with the regular directly observed therapy program. Motivators (cue to actions) such as friends, family, healthcare workers, and the media could be used to promote TB treatment adherence.

The Activity of a Hexameric M17 Metallo-Aminopeptidase Is Associated With Survival of Mycobacterium tuberculosis

PubMed Central

Correa, Andre F.; Bastos, Izabela M. D.; Neves, David; Kipnis, Andre; Junqueira-Kipnis, Ana P.; de Santana, Jaime M.

2017-01-01

Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied. Aminopeptidases constitute a set of proteases that selectively remove amino acids from the N-terminus of proteins and peptides and may act as virulence factors, essential for survival and maintenance of many microbial pathogens. Here, we characterized a leucine aminopeptidase of M. tuberculosis (MtLAP) as a cytosolic oligomeric metallo-aminopeptidase. Molecular and enzymatic properties lead us to classify MtLAP as a typical member of the peptidase family M17. Furthermore, the aminopeptidase inhibitor bestatin strongly inhibited MtLAP activity, in vitro M. tuberculosis growth and macrophage infection. In murine model of TB, bestatin treatment reduced bacterial burden and lesion in the lungs of infected mice. Thus, our data suggest that MtLAP participates in important metabolic pathways of M. tuberculosis necessary for its survival and virulence and consequently may be a promising target for new anti-TB drugs. PMID:28396657

Cloning and functional expression of a gene encoding a P1 type nucleoside transporter from Trypanosoma brucei.

PubMed

Sanchez, M A; Ullman, B; Landfear, S M; Carter, N S

1999-10-15

Nucleoside transporters are likely to play a central role in the biochemistry of the parasite Trypanosoma brucei, since these protozoa are unable to synthesize purines de novo and must salvage them from their hosts. Furthermore, nucleoside transporters have been implicated in the uptake of antiparasitic and experimental drugs in these and other parasites. We have cloned the gene for a T. brucei nucleoside transporter, TbNT2, and shown that this permease is related in sequence to mammalian equilibrative nucleoside transporters. Expression of the TbNT2 gene in Xenopus oocytes reveals that the permease transports adenosine, inosine, and guanosine and hence has the substrate specificity of the P1 type nucleoside transporters that have been previously characterized by uptake assays in intact parasites. TbNT2 mRNA is expressed in bloodstream form (mammalian host stage) parasites but not in procyclic form (insect stage) parasites, indicating that the gene is developmentally regulated during the parasite life cycle. Genomic Southern blots suggest that there are multiple genes related in sequence to TbNT2, implying the existence of a family of nucleoside transporter genes in these parasites.

Tuberculosis Knowledge, Awareness, and Stigma Among African-Americans in Three Southeastern Counties in the USA: a Qualitative Study of Community Perspectives.

PubMed

Royce, Rachel A; Colson, Paul W; Woodsong, Cynthia; Swinson-Evans, Tammeka; Walton, Wanda; Maiuri, Allison; DeLuca, Nickolas

2017-02-01

To inform strategies to address the tuberculosis (TB) excess among US-born African-Americans, we sought to understand the TB experience in the most highly affected southeastern communities. We conducted semi-structured interviews and focus groups in three communities with a TB excess-urban (Georgia and Tennessee) and rural (North Carolina). Participants from five groups provided diverse perspectives-African-Americans: patients with TB disease or latent TB infection (LTBI), or at high risk of contracting TB; and local community leaders and TB program staff. Few differences emerged between sites. Many participants demonstrated low levels of knowledge and awareness and held many misconceptions about TB. Patients expressed a preference for verbal communication of medical information. Patients reported fear of stigmatization and shunning, but few experienced discrimination. Patient trust for TB program staff was high, though community leaders often assumed the opposite. The findings will help guide interventions to improve knowledge and awareness regarding TB, including specific attention to the role of public and private health care providers in dispelling persistent misinformation about TB. The insight from these communities will help build the scientific foundation required to effectively eliminate health inequities.

Socio-demographic factors affecting knowledge level of Tuberculosis patients in Rajshahi City, Bangladesh.

PubMed

Mondal, M N I; Nazrul, Hoque M; Chowdhury, M R K; Howard, J

2014-12-01

The Tuberculosis (TB) control program in Bangladesh is still unsatisfactory due to insufficient knowledge and stigma about TB. Patients with low knowledge may be at higher risk of experiencing delays in diagnosis and appropriate treatment. The aims of this study were to identify the knowledge levels of TB and investigate the factors associated with knowledge level among the TB patients in Bangladesh. A cross-sectional study was conducted at Rajshahi City, Bangladesh. A total of 384 TB patients were interviewed through a pretested, structured questionnaire using purposive sampling techniques. Logistic regression analysis was used to evaluate the effects of selected socio-demographic factors on TB knowledge level. The results revealed that pulmonary TB patients had greater knowledge than that of extra-pulmonary patients, and that sex, age, educational status and TB type were significantly associated with knowledge level. In general, males and young adults, ages 21-35, had greater awareness about transmission and prevention of TB than females and adults over 35. Individuals with higher education and urban area patients were comparatively better informed about TB infection. Patients with greater knowledge about TB were also less likely to experience delays in seeking treatment.

Analysis of mutational characteristics of the drug-resistant gene katG in multi-drug resistant Mycobacterium tuberculosis L-form among patients with pneumoconiosis complicated with tuberculosis.

PubMed

Lu, Jun; Jiang, Shan; Liu, Qian-Ying; Ma, Shuai; Li, Ying; Li, Chao-Pin

2014-05-01

The aim of the present study was to investigate the mutational characteristics of drug‑resistant genetic mutations in the katG gene to isoniazid (INH) in multi‑drug resistant Mycobacterium tuberculosis (MTB) L‑form among patients with pneumoconiosis complicated with tuberculosis (TB), in order to reduce the occurrence of drug resistance in patients, and gain further insight into the mechanisms underlying drug resistance in MDR‑TB L‑form. A total of 114 clinically isolated strains of MTB L‑forms were collected. The MDR‑TB L‑forms were identified using a conventional antimicrobial susceptibility test (AST). The DNA genomes were extracted, the target genes were amplified by polymerase chain reaction technology and the hotspot mutational regions in the katG gene were analyzed by direct sequencing. The results of AST analysis demonstrated that there were 31 strains of MDR‑TB L‑forms in 114 clinical isolates. The mutation rate of katG was 61.29% (19/31) in INH‑resistant isolates, mainly concentrated in codon 315 (Ser315Thr, 48.39% and Ser315Asn, 9.68%) and 431 (Ala431Val, 3.23%). Base substitutions were identified, however, no multisite mutations were found. No mutations in katG were identified in 10 INH‑sensitive strains that were randomly selected. INH‑resistance was more severe in MDR‑TB L‑form isolates among patients with pneumoconiosis complicated with TB. The substitution of highly conserved amino acids encoded by the katG gene resulted in the molecular mechanisms responsible for INH resistance in MDR‑TB L‑form isolates. It was also verified that the katG gene was in diversiform. The katG Ser315Thr mutation is one of the main causes of resistance to INH in MDR‑TB L-form isolates.

Phase transformations and indications for acoustic mode softening in Tb-Gd orthophosphate

DOE PAGES

Tschauner, Oliver; Ushakov, Sergey V.; Navrotsky, Alexandra; ...

2016-01-06

At ambient conditions the anhydrous rare-earth orthophosphates assume either the xenotime (zircon) or the monazite structure, with the latter favored for the heavier rare earths. Tb 0.5Gd 0.5PO 4 assumes the xenotime structure at ambient conditions but is at the border between the xenotime and monazite structures. Here we show that, at high pressure, Tb 0.5Gd 0.5PO 4 does not transform directly to monazite but through an intermediate anhydrite-type structure. We show softening of (c 1133 + c 1313) combined elastic moduli close to the transition from the anhydrite to the monazite structure. Stress response of rare-earth orthophosphate ceramics canmore » be affected by both formation of the anhydrite-type phase and the elastic softening in the vicinity of the monazite-phase. In conclusion, we report the first structural data for an anhydrite-type rare earth orthophosphate.« less

[Preparation and luminescent properties of CaMoO4:Tb3+].

PubMed

Wang, Xi-gui; Bo, Su-ling; Na, Mi-la; Qi, Xia

2010-01-01

The precursor of the sample CaMoO4:Tb3+ was prepared by the coprecipitation method. TG-DTA spectra show that there is, at 850 degrees C, an energy absorption peak, suggesting that the sample reaches the activation spot of its response. The XRD pattern of the roasted sample shows that CaMoO4:Tb3+, in the single phase, is a representative scheelite structure of CaMoO4, but the peaks shift toward right, implying that tiny crystal defect in the crystal is produced. The defect is likely to be formed by the formation of the holes as two Tb3+ replace three Ca2+ in a cell. The excitation and emission spectra of the sample were investigated and revealed that the defect structure of the sample is in favor of the energy transfer of the characteristic peak (488 nm) of the MoO4(2-) effectively to Tb3+, and makes the 4f electrons of the Tb3+ transit, especially the (7)F6-->(5)D4 electronic transition (488 nm) of the Tb3+, to be greatly strengthened. As a result, the emission spectra with lamdaex=488 nm show that the emission intensity of the spontaneously activated fluorescence MoO4(2-) is greatly weakened, while the green light luminescence intensity of the (5)D4-->(7)F5 transition (544 nm) of the Tb3+ is greatly enhanced. This suggests that the sample CaMoO4:Tb3+ will become the luminescence material with potentially great application value.

Impact of a Structured Tuberculosis Awareness Strategy on the Knowledge and Behaviour of the Families in a Slum Area in Chhattisgarh, India.

PubMed

Samal, Janmejaya; Dehury, Ranjit Kumar

2017-03-01

Of different methods of disease prevention, health education and awareness programmes can empower people regarding several aspects of disease management and thereby enabling them in accessing the right treatment, in right time, at right place. The aim of this study was to assess the impact of a structured Tuberculosis (TB) awareness strategy on the knowledge and behaviour of slum dwellers of Durg, Chhattisgarh, India. A TB awareness intervention was implemented in terms of informing the houses of marginalized and vulnerable communities about TB, its symptoms, diagnosis, treatment and Revised National TB Control Program (RNTCP) services and the impact of the same was assessed through a survey questionnaire before and after the implementation of the intervention. Of the knowledge components the improvement was incurred above 90% among the study participants in all components except in two components such as; modes of TB transmission and availability of free treatment facilities. In the behavioural segment, after the implementation of the awareness strategy, 53% and 92% of the respondents reported to visit government health facility for seeking help for their general and TB related problems respectively. Similarly the responses regarding not approaching the government health facility for TB care were changed after the implementation of the awareness strategy and 36% of the respondents said they would prefer to visit government health facility for TB care. Health education activities should be directed to improve the knowledge of slum dwellers regarding the modes of TB transmission and availability of free treatment at public health facilities.

IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population.

PubMed

Shen, Chen; Jiao, Wei-Wei; Feng, Wei-Xing; Wu, Xi-Rong; Xiao, Jing; Miao, Qing; Sun, Lin; Wang, Bin-Bin; Wang, Jing; Liu, Fang; Shen, Dan; Shen, A-Dong

2013-09-01

Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-γ), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case-control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including -1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P = 0.108 and P = 0.088), especially in females (both P = 0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P = 0.026 (borderline non-significance) and P = 0.020, respectively], and in the female subgroup (P = 0.020 and P = 0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P = 0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P = 0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P = 0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN-γ expression) in the extrapulmonary TB subgroup suggests a sufficient IFN-γ expression to be not only an important factor for the onset of TB disease but also for limiting its dissemination to lungs.

Health care workers' knowledge, attitudes and practices on tuberculosis infection control, Nepal.

PubMed

Shrestha, Anita; Bhattarai, Dipesh; Thapa, Barsha; Basel, Prem; Wagle, Rajendra Raj

2017-11-17

Infection control remains a key challenge for Tuberculosis (TB) control program with an increased risk of TB transmission among health care workers (HCWs), especially in settings with inadequate TB infection control measures. Poor knowledge among HCWs and inadequate infection control practices may lead to the increased risk of nosocomial TB transmission. An institution-based cross-sectional survey was conducted in 28 health facilities providing TB services in the Kathmandu Valley, Nepal. A total of 190 HCWs were assessed for the knowledge, attitudes and practices on TB infection control using a structured questionnaire. The level of knowledge on TB infection control among almost half (45.8%) of the HCWs was poor, and was much poorer among administration and lower level staff. The knowledge level was significantly associated with educational status, and TB training and/or orientation received. The majority (73.2%) of HCWs had positive attitude towards TB infection control. Sixty-five percent of HCWs were found to be concerned about being infected with TB. Use of respirators among the HCWs was limited and triage of TB suspects was also lacking. Overall knowledge and practices of HCWs on TB infection control were not satisfactory. Effective infection control measures including regular skill-based training and/or orientation for all categories of HCWs can improve infection control practices in health facilities.

A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

PubMed Central

2012-01-01

Background There is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia. Methods In stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia. Results Our study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4. Conclusions Mechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB. PMID:22239941

Ab - initio study of rare earth magnesium alloy: TbMg

NASA Astrophysics Data System (ADS)

Kumari, Meena; Yadav, Priya; Nautiyal, Shashank; Verma, U. P.

2018-05-01

The structural, electronic and magnetic properties of TbMg were analyzed by using full-potential linearized augmented plane wave method. This intermetallic is stable in structure CsCl (B2 phase) with space group Pm-3m. In electronic properties, we show the electronic band structure and density of states plots. These plots show that this alloy have metallic character because there is no band gap between the valance band and conduction band at Fermi level. The structural properties, i.e. equilibrium lattice constant, bulk modulus and its pressure derivative, energy and volume show good agreement with available data. In this paper, we also present the total magnetic moment along with the magnetic moment on the atomic and interstitial sites of TbMg intermetallic in B2 phase.

Anisotropy induced anomalies in Dy 1$-$xTb xAl 2

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

Khan, M.; Miami Univ., Oxford, OH; Pathak, A. K.

2017-01-02

The Dy 1$-$xTb xAl 2 alloys have been investigated by X-ray powder diffraction, heat capacity, and magnetic measurements. All samples exhibit cubic Laves phase crystal structure at room temperature but at T C, DyAl2 and TbAl 2 show tetragonal and rhombohedral distortions, respectively. First order phase transitions are observed below T C (at the spin-reorientation transition, T SR) in the alloys with 0.15 ≤ x ≤ 0.35. These transitions are signified by sharp heat capacity peaks and corresponding anomalies in the magnetization and ac magnetic susceptibility data. The observations are interpreted by taking into consideration the differences in easy magnetizationmore » directions of DyAl 2 and TbAl 2. Due to the competing magnetic structures, the anisotropy-related instability and magnetic frustrations are prominent in the Dy 1$-$xTb xAl 2 alloys at certain concentrations resulting in the first order transitions.« less

Body Temperature-Related Structural Transitions of Monotremal and Human Hemoglobin

PubMed Central

Digel, I.; Maggakis-Kelemen, Ch.; Zerlin, K. F.; Linder, Pt.; Kasischke, N.; Kayser, P.; Porst, D.; Temiz Artmann, A.; Artmann, G. M.

2006-01-01

In this study, temperature-related structural changes were investigated in human, duck-billed platypus (Ornithorhynchus anatinus, body temperature Tb = 31–33°C), and echidna (Tachyglossus aculeatus, body temperature Tb = 32–33°C) hemoglobin using circular dichroism spectroscopy and dynamic light scattering. The average hydrodynamic radius (Rh) and fractional (normalized) change in the ellipticity (Fobs) at 222 ± 2 nm of hemoglobin were measured. The temperature was varied stepwise from 25°C to 45°C. The existence of a structural transition of human hemoglobin at the critical temperature Tc between 36–37°C was previously shown by micropipette aspiration experiments, viscosimetry, and circular dichroism spectroscopy. Based on light-scattering measurements, this study proves the onset of molecular aggregation at Tc. In two different monotremal hemoglobins (echidna and platypus), the critical transition temperatures were found between 32–33°C, which are close to the species' body temperature Tb. The data suggest that the correlation of the structural transition's critical temperature Tc and the species' body temperature Tb is not mere coincidence but, instead, is a more widespread structural phenomenon possibly including many other proteins. PMID:16844747

Body temperature-related structural transitions of monotremal and human hemoglobin.

PubMed

Digel, I; Maggakis-Kelemen, Ch; Zerlin, K F; Linder, Pt; Kasischke, N; Kayser, P; Porst, D; Temiz Artmann, A; Artmann, G M

2006-10-15

In this study, temperature-related structural changes were investigated in human, duck-billed platypus (Ornithorhynchus anatinus, body temperature T(b) = 31-33 degrees C), and echidna (Tachyglossus aculeatus, body temperature T(b) = 32-33 degrees C) hemoglobin using circular dichroism spectroscopy and dynamic light scattering. The average hydrodynamic radius (R(h)) and fractional (normalized) change in the ellipticity (F(obs)) at 222 +/- 2 nm of hemoglobin were measured. The temperature was varied stepwise from 25 degrees C to 45 degrees C. The existence of a structural transition of human hemoglobin at the critical temperature T(c) between 36-37 degrees C was previously shown by micropipette aspiration experiments, viscosimetry, and circular dichroism spectroscopy. Based on light-scattering measurements, this study proves the onset of molecular aggregation at T(c). In two different monotremal hemoglobins (echidna and platypus), the critical transition temperatures were found between 32-33 degrees C, which are close to the species' body temperature T(b). The data suggest that the correlation of the structural transition's critical temperature T(c) and the species' body temperature T(b) is not mere coincidence but, instead, is a more widespread structural phenomenon possibly including many other proteins.

Genome-wide identification and expression analysis of the ClTCP transcription factors in Citrullus lanatus.

PubMed

Shi, Pibiao; Guy, Kateta Malangisha; Wu, Weifang; Fang, Bingsheng; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

2016-04-12

The plant-specific TCP transcription factor family, which is involved in the regulation of cell growth and proliferation, performs diverse functions in multiple aspects of plant growth and development. However, no comprehensive analysis of the TCP family in watermelon (Citrullus lanatus) has been undertaken previously. A total of 27 watermelon TCP encoding genes distributed on nine chromosomes were identified. Phylogenetic analysis clustered the genes into 11 distinct subgroups. Furthermore, phylogenetic and structural analyses distinguished two homology classes within the ClTCP family, designated Class I and Class II. The Class II genes were differentiated into two subclasses, the CIN subclass and the CYC/TB1 subclass. The expression patterns of all members were determined by semi-quantitative PCR. The functions of two ClTCP genes, ClTCP14a and ClTCP15, in regulating plant height were confirmed by ectopic expression in Arabidopsis wild-type and ortholog mutants. This study represents the first genome-wide analysis of the watermelon TCP gene family, which provides valuable information for understanding the classification and functions of the TCP genes in watermelon.

Cyclic cooperative intramolecular hydrogen bond in p-tert-butylcalix[6]arene according to FTIR spectroscopy and DFT studies

NASA Astrophysics Data System (ADS)

Furer, V. L.; Potapova, L. I.; Kovalenko, V. I.

2017-06-01

This article describes a comparative research of IR spectra and H-bonds in the p-tert-butylcalix[6]arene (TB6) and calix[6]arene (C6). IR spectra were computed for compressed cone conformation by DFT method. The assignment of the bands in the IR spectra of the TB6 and C6 was made. The effect of the bulky tert-butyl substituents on the structure and H-bonding in TB6 was established. Our research has shown that in TB6 and C6 the cyclic H-bond is realized, which ensures the existence of a compressed cone conformation. Introduction of tert-butyl substituents in TB6 leads to hardening of H-bonds. Examination of IR spectra showed that when heated TB6 remains in a compressed cone conformation. In a molecule of TB6 and C6 oxygen atoms are in a ;boat; conformation.

Differentiation of Mycobacterium tuberculosis complex from non-tubercular mycobacteria by nested multiplex PCR targeting IS6110, MTP40 and 32kD alpha antigen encoding gene fragments.

PubMed

Sinha, Pallavi; Gupta, Anamika; Prakash, Pradyot; Anupurba, Shampa; Tripathi, Rajneesh; Srivastava, G N

2016-03-12

Control of the global burden of tuberculosis is obstructed due to lack of simple, rapid and cost effective diagnostic techniques that can be used in resource poor-settings. To facilitate the early diagnosis of TB directly from clinical specimens, we have standardized and validated the use of nested multiplex PCR, targeting gene fragments IS6110, MTP40 and 32kD α-antigen encoding genes specific for Mycobacterium tuberculosis complex and non-tubercular mycobacteria (NTM), in comparison to smear microscopy, solid culture and single step multiplex PCR. The results were evaluated in comparison to a composite reference standard (CRS) comprising of microbiological results (smear and culture), clinical, radiological and cytopathological findings, clinical treatment and response to anti-tubercular therapy. The nested multiplex PCR (nMPCR) assay was evaluated to test its utility in 600 (535 pulmonary and 65 extra-pulmonary specimens) clinically suspected TB cases. All specimens were processed for smear, culture, single step multiplex PCR and nested multiplex PCR testing. Out of 535 screened pulmonary and 65 extra-pulmonary specimens, 329 (61.5%) and 19 (29.2%) cases were culture positive for M. tuberculosis. Based on CRS, 450 patients had "clinical TB" (definitive-TB, probable-TB and possible-TB). Remaining 150 were confirmed "non-TB" cases. For culture, the sensitivity was low, 79.3% for pulmonary and 54.3% for extra-pulmonary cases. The sensitivity and specificity results for nMPCR test were evaluated taken composite reference standard as a gold standard. The sensitivity of the nMPCR assay was 97.1% for pulmonary and 91.4% for extra-pulmonary TB cases with specificity of 100% and 93.3% respectively. Nested multiplex PCR using three gene primers is a rapid, reliable and highly sensitive and specific diagnostic technique for the detection and differentiation of M. tuberculosis complex from NTM genome and will be useful in diagnosing paucibacillary samples. Nested multiplex PCR assay was found to be better than single step multiplex PCR for assessing the diagnosis of TB.

Rare earth niobate coordination polymers

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

Muniz, Collin N.; Patel, Hiral; Fast, Dylan B.

Rare-earth (RE) coordination polymers are infinitely tailorable to yield luminescent materials for various applications. In this paper we described the synthesis of a heterometallic rare-earth coordination compound ((CH 3) 2SO) 3(RE)NbO(C 2O 4) 3 ((CH 3) 2SO) = dimethylsulfoxide, DMSO, (C 2O 2 = oxalate), (RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb). The structure was obtained from single crystal X-ray diffraction of the La analogue. The Nb =O and DMSO terminal-bonding character guides assembly of an open framework structure with noncentrosymmetric RE-coordination geometry, and large spacing between the RE centers. A second structure was observed by PXRD for themore » smaller rare earths (Dy, Ho, Er, Yb); this structure has not yet been determined. The materials were further characterized using FTIR, and photoluminescence measurements. Characteristic excitation and emission transitions were observed for RE = Nd, Sm, Eu, and Tb. Quantum yield (QY) measurements were performed by exciting Eu and Tb analoges at 394 nm (QY 66%) and 464 nm (QY 71%) for Eu; and 370 nm (QY=40%) for Tb. Finally, we attribute the high QY and bright luminescence to two main structure-function properties of the system; namely the absence of water in the structure, and absence of concentration quenching.« less

Rare earth niobate coordination polymers

DOE PAGES

Muniz, Collin N.; Patel, Hiral; Fast, Dylan B.; ...

2018-01-03

Rare-earth (RE) coordination polymers are infinitely tailorable to yield luminescent materials for various applications. In this paper we described the synthesis of a heterometallic rare-earth coordination compound ((CH 3) 2SO) 3(RE)NbO(C 2O 4) 3 ((CH 3) 2SO) = dimethylsulfoxide, DMSO, (C 2O 2 = oxalate), (RE=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb). The structure was obtained from single crystal X-ray diffraction of the La analogue. The Nb =O and DMSO terminal-bonding character guides assembly of an open framework structure with noncentrosymmetric RE-coordination geometry, and large spacing between the RE centers. A second structure was observed by PXRD for themore » smaller rare earths (Dy, Ho, Er, Yb); this structure has not yet been determined. The materials were further characterized using FTIR, and photoluminescence measurements. Characteristic excitation and emission transitions were observed for RE = Nd, Sm, Eu, and Tb. Quantum yield (QY) measurements were performed by exciting Eu and Tb analoges at 394 nm (QY 66%) and 464 nm (QY 71%) for Eu; and 370 nm (QY=40%) for Tb. Finally, we attribute the high QY and bright luminescence to two main structure-function properties of the system; namely the absence of water in the structure, and absence of concentration quenching.« less

A cross-sectional study about knowledge and attitudes toward multidrug-resistant and extensively drug-resistant tuberculosis in a high-burden drug-resistant country.

PubMed

Javed, Hasnain; Tahir, Zarfishan; Hashmi, Hafiza Jawairia; Jamil, Nazia

2016-06-01

Tuberculosis (TB) is a leading cause of death worldwide, with new threats of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. Pakistan is the fifth highest among high-burden TB countries and the fourth highest among high-burden drug-resistant-TB countries. Pakistan is the sixth most populous country in the world, and Pakistani youth is the highest population group in Pakistan and second in the world. This study was aimed at assessing the understanding, awareness, and mindset of university students toward TB, MDR TB, and XDR TB in Lahore. A cross-sectional questionnaire-based study was performed on 1137 individuals from three major public-sector universities in Lahore, Pakistan. Information regarding their knowledge and attitude toward MDR and XDR TB was gathered using a structured questionnaire. Data collected was analyzed using SPSS version 20. Male (531) and female (606) students were asked about different aspects of MDR and XDR TB. Although 80.47% students had good knowledge about simple TB, a very small fraction had awareness and appropriate knowledge about MDR/XDR-TB. Considering TB as a stigma, only 9.3% students disclosed that they had household TB contact. Only 25% students knew about XDR TB. Our results indicated that a small fraction of people knew the exact definition and treatment duration of MDR TB and XDR TB in our society. There is a need to increase the awareness and knowledge status of university students about MDR and XDR TB. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

The socioeconomic impact of multidrug resistant tuberculosis on patients: results from Ethiopia, Indonesia and Kazakhstan.

PubMed

van den Hof, Susan; Collins, David; Hafidz, Firdaus; Beyene, Demissew; Tursynbayeva, Aigul; Tiemersma, Edine

2016-09-05

One of the main goals of the post-2015 global tuberculosis (TB) strategy is that no families affected by TB face catastrophic costs. We revised an existing TB patient cost measurement tool to specifically also measure multi-drug resistant (MDR) TB patients' costs and applied it in Ethiopia, Indonesia and Kazakhstan. Through structured interviews with TB and MDR-TB patients in different stages of treatment, we collected data on the direct (out of pocket) and indirect (loss of income) costs of patients and their families related to the diagnosis and treatment of TB and MDR-TB. Direct costs included costs for hospitalization, follow-up tests, transport costs for health care visits, and food supplements. Calculation of indirect costs was based on time needed for diagnosis and treatment. Costs were extrapolated over the patient's total treatment phase. In total 406 MDR-TB patients and 197 other TB patients were included in the survey: 169 MDR-TB patients and 25 other TB patients in Ethiopia; 143 MDR-TB patients and 118 TB patients in Indonesia; and 94 MDR-TB patients and 54 other TB patients in Kazakhstan. Total costs for diagnosis and current treatment episode for TB patients were estimated to be USD 260 in Ethiopia, USD 169 in Indonesia, and USD 929 in Kazakhstan, compared to USD 1838, USD 2342, and USD 3125 for MDR-TB patients, respectively. These costs represented 0.82-4.6 months of pre-treatment household income for TB patients and 9.3-24.9 months for MDR-TB patients. Importantly, 38-92 % reported income loss and 26-76 % of TB patients lost their jobs due to (MDR) TB illness, further aggravating the financial burden. The financial burden of MDR-TB is alarming, although all TB patients experienced substantial socioeconomic impact of the disease. If the patient is the breadwinner of the family, the combination of lost income and extra costs is generally catastrophic. Therefore, it should be a priority of the government to relieve the financial burden based on the cost mitigation options identified.

Genome Analysis of the First Extensively Drug-Resistant (XDR) Mycobacterium tuberculosis in Malaysia Provides Insights into the Genetic Basis of Its Biology and Drug Resistance

PubMed Central

Kuan, Chee Sian; Chan, Chai Ling; Yew, Su Mei; Toh, Yue Fen; Khoo, Jia-Shiun; Chong, Jennifer; Lee, Kok Wei; Tan, Yung-Chie; Yee, Wai-Yan; Ngeow, Yun Fong; Ng, Kee Peng

2015-01-01

The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia. PMID:26110649

Active Tuberculosis Case Finding Interventions Among Immigrants, Refugees and Asylum Seekers in Italy

PubMed Central

Schepisi, Monica Sañé; Gualano, Gina; Piselli, Pierluca; Mazza, Marta; D’Angelo, Donatella; Fasciani, Francesca; Barbieri, Alberto; Rocca, Giorgia; Gnolfo, Filippo; Olivani, Piefranco; Ferrarese, Maurizio; Codecasa, Luigi Ruffo; Palmieri, Fabrizio; Girardi, Enrico

2016-01-01

In Italy tuberculosis (TB) is largely concentrated in vulnerable groups such as migrants and in urban settings. We analyzed three TB case finding interventions conducted at primary centers and mobile clinics for regular/irregular immigrants and refugees/asylum seekers performed over a four-year period (November 2009-March 2014) at five different sites in Rome and one site in Milan, Italy. TB history and presence of symptoms suggestive of active TB were investigated by verbal screening through a structured questionnaire in migrants presenting for any medical condition to out-patient and mobile clinics. Individuals reporting TB history or symptoms were referred to a TB clinic for diagnostic workup. Among 6347 migrants enrolled, 891 (14.0%) reported TB history or symptoms suggestive of active TB and 546 (61.3%) were referred to the TB clinic. Of them, 254 (46.5%) did not present for diagnostic evaluation. TB was diagnosed in 11 individuals representing 0.17% of those screened and 3.76% of those evaluated. The overall yield of this intervention was in the range reported for other TB screening programs for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. PMID:27403270

Multi-quasiparticle excitations in 145Tb

NASA Astrophysics Data System (ADS)

Zheng, Y.; Zhou, X. H.; Zhang, Y. H.; Hayakawa, T.; Oshima, M.; Toh, Y.; Shizuma, T.; Katakura, J.; Hatsukawa, Y.; Matsuda, M.; Kusakari, H.; Sugawara, M.; Furuno, K.; Komatsubara, T.

2004-04-01

High-spin states in 145Tb have been investigated by means of in-beam ggr-ray spectroscopy techniques with the 118Sn(32S, 1p4n) reaction. Excitation functions, X-ggr-t and ggr-ggr-t coincidences and ggr-ray anisotropies were measured. A level scheme of 145Tb was established up to Exap 7 MeV. The level structure shows characteristics of a spherical nucleus. Based on the systematics of level structure in the odd-A N = 80 isotones, the level structure below 2 MeV excitation is interpreted by coupling an h11/2 proton to the excitations in the even-even 144Gd core. Above 2 MeV excitation, most of the yrast levels are interpreted with multi-quasiparticle shell-model configurations.

Synthesis and anisotropic properties of single crystalline Ln{sub 2}Ru{sub 3}Al{sub 15+x} (Ln=Gd, Tb)

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

Morrison, Gregory; Prestigiacomo, Joseph; Haldolaarachchige, Neel

2016-04-15

Single crystals of Ln{sub 2}Ru{sub 3}Al{sub 15+x} (Ln=Gd, Tb) have been grown using the self-flux method under Ru-poor conditions. The structure of the Gd analog is found to be highly dependent on the synthesis method. Gd{sub 2}Ru{sub 3}Al{sub 15.08} orders antiferromagnetically at 17.5 K. Tb{sub 2}Ru{sub 3}Al{sub 15.05} enters an antiferromagnetic state at 16.6 K followed by a likely incommensurate-to-commensurate transition at 14.9 K for crystals oriented with H//ab. For crystals oriented with H//c, a broad maximum is observed in the temperature dependent M/H, indicative of a highly anisotropic magnetic system with the hard axis in the c-direction. The magnetizationmore » as a function of field and magnetoresistance along the ab-direction of Tb{sub 2}Ru{sub 3}Al{sub 15.05} display a stepwise behavior and indicate strong crystalline electric field effects. - Graphical abstract: Single crystal, structure, and highly anisotropic magnetoresistance due to strong crystalline electric field effects of Tb{sub 2}Ru{sub 3}Al{sub 15.05}. - Highlights: • Single crystals of Ln{sub 2}Ru{sub 3}Al{sub 15+x} were grown for the first time via flux growth. • The structure of Gd{sub 2}Ru{sub 3}Al{sub 15.09} differs from that of arc melted Gd{sub 2}Ru{sub 3.08}Al{sub 15}. • Tb{sub 2}Ru{sub 3}Al{sub 15.05} exhibits highly anisotropic magnetic and transport properties. • The properties of Tb{sub 2}Ru{sub 3}Al{sub 15.05} arise due to crystalline electric field effects.« less

Mucoperiosteal exostoses in the tympanic bulla of African lions (Panthera leo).

PubMed

Novales, M; Ginel, P J; Diz, A; Blanco, B; Zafra, R; Guerra, R; Mozos, E

2015-03-01

Mucoperiosteal exostoses (MpEs) of the tympanic bulla (TB), also referred as middle-ear otoliths, have been occasionally described in dogs and cats in association with clinical signs of otitis media or as an incidental finding, but they have not been recorded in other species. In this report, we describe the radiographic, gross, and histopathologic features of MpEs in 8 African lions (Panthera leo). All animals (5 males and 3 females) were adults that had been kept in captivity and had their skeletons conserved as part of an anatomic academic collection. A radiographic study revealed mineralized structures in the TB consistent with MpEs in 7 of the 16 examined TB; a computed tomography study identified MpEs in 12 of the 16 TB. Six TB from 4 lions were sectioned, and several MpEs were demineralized for histopathologic analysis. Grossly, MpEs appeared variable in number and shape. Some were globular structures that were loosely attached to the mucosal surface of the TB; others were isolated to coalescent bone spicules extending from the mucoperiosteum. Position was also variable, but MpEs frequently developed in the hypotympanum, especially on the ventromedial aspect of the TB wall. Microscopically, MpEs were composed of osteonal bone growing from the periosteum and not by dystrophic calcification of necrotic tissue debris, as is hypothesized in dogs. © The Author(s) 2014.

Impact of a Structured Tuberculosis Awareness Strategy on the Knowledge and Behaviour of the Families in a Slum Area in Chhattisgarh, India

PubMed Central

Dehury, Ranjit Kumar

2017-01-01

Introduction Of different methods of disease prevention, health education and awareness programmes can empower people regarding several aspects of disease management and thereby enabling them in accessing the right treatment, in right time, at right place. Aim The aim of this study was to assess the impact of a structured Tuberculosis (TB) awareness strategy on the knowledge and behaviour of slum dwellers of Durg, Chhattisgarh, India. Materials and Methods A TB awareness intervention was implemented in terms of informing the houses of marginalized and vulnerable communities about TB, its symptoms, diagnosis, treatment and Revised National TB Control Program (RNTCP) services and the impact of the same was assessed through a survey questionnaire before and after the implementation of the intervention. Results Of the knowledge components the improvement was incurred above 90% among the study participants in all components except in two components such as; modes of TB transmission and availability of free treatment facilities. In the behavioural segment, after the implementation of the awareness strategy, 53% and 92% of the respondents reported to visit government health facility for seeking help for their general and TB related problems respectively. Similarly the responses regarding not approaching the government health facility for TB care were changed after the implementation of the awareness strategy and 36% of the respondents said they would prefer to visit government health facility for TB care. Conclusion Health education activities should be directed to improve the knowledge of slum dwellers regarding the modes of TB transmission and availability of free treatment at public health facilities. PMID:28511415

Characterization of 2,4-Diamino-6-oxo-1,6-dihydropyrimidin-5-yl Ureido Based Inhibitors of Trypanosoma brucei FolD and Testing for Antiparasitic Activity

PubMed Central

2015-01-01

The bifunctional enzyme N5,N10-methylenetetrahydrofolate dehydrogenase/cyclo hydrolase (FolD) is essential for growth in Trypanosomatidae. We sought to develop inhibitors of Trypanosoma brucei FolD (TbFolD) as potential antiparasitic agents. Compound 2 was synthesized, and the molecular structure was unequivocally assigned through X-ray crystallography of the intermediate compound 3. Compound 2 showed an IC50 of 2.2 μM, against TbFolD and displayed antiparasitic activity against T. brucei (IC50 49 μM). Using compound 2, we were able to obtain the first X-ray structure of TbFolD in the presence of NADP+ and the inhibitor, which then guided the rational design of a new series of potent TbFolD inhibitors. PMID:26322631

Investigation of mitochondrial sequence variants associated with aminoglycoside-induced ototoxicity in South African TB patients on aminoglycosides.

PubMed

Human, Hanniqué; Hagen, Christian M; de Jong, Greetje; Harris, Tashneem; Lombard, Debbie; Christiansen, Michael; Bardien, Soraya

2010-03-19

A known side effect of aminoglycoside antibiotics is the development of permanent hearing loss. As South Africa is currently facing a tuberculosis (TB) epidemic, with an increasing number of multi-drug resistant tuberculosis (MDR-TB) infections, the use of aminoglycosides is on the increase. It is therefore important to determine whether the mitochondrial mutations associated with aminoglycoside-induced hearing loss occur at high frequencies in particular ethnic groups in our population. A total of 115 mainly MDR-TB patients all on aminoglycosides and 439 controls representative of the main ethnic groups in South Africa were screened for six mutations using the SNaPshot technique. Furthermore, the mitochondrial genomes of eight patients with ototoxicity were sequenced. Homoplasmic mutations were found in controls (A1555G in 0.9% of Black controls and A827G in 1.1% of Afrikaner controls) which reveal that a significant proportion of the South African population is genetically predisposed to developing aminoglycoside-induced hearing loss. The 961 delT+insC((n)) and T961G variants were found at frequencies of >1% indicating that both are probably non-pathogenic polymorphisms. Sequencing of the entire mitochondrial genome in eight patients did not reveal any mutations in the MT-RNR1 gene. However, two potentially pathogenic variants, T10114C (I19T in MT-ND3) and T15312C (I189T in MT-CYB) were found that may impact on the oxidative phosphorylation capacity and warrant further investigation for their possible role in this disorder. It is imperative that the genetic basis of this potentially preventable condition be investigated, particularly in countries where aminoglycosides are still commonly used, in order to identify individuals and/or ethnic groups who are at risk for this type of hearing loss. Copyright 2010 Elsevier Inc. All rights reserved.

Tuberculosis knowledge among injecting drug users visiting syringe exchange programme in Tallinn, Estonia.

PubMed

Rüütel, Kristi; Parker, R David; Sobolev, Igor; Loit, Helle-Mai

2012-12-01

The purpose of the current study was to describe tuberculosis (TB) knowledge, beliefs, and experience with TB services among injecting drug users. Participants for this anonymous, cross-sectional study were recruited from a community based syringe exchange programme in Tallinn, Estonia. A structured questionnaire was completed and included information on socio-demographics, health history, drug use, and knowledge about TB and HIV. The study included 407 people (79% male, mean age 27.9 years, mean injection drug use 9.4 years). 32.9% of participants reported HIV infection and 1.7% lifetime history of TB. 26.4% participants (n=106) reported symptoms suggestive of TB. 93% of participants recognized correctly that TB is air-borne infection and 91% that HIV is a risk factor for TB. Only 40% of the participants knew that TB diagnostics and treatment in Estonia are free of charge for everybody and 58% reported they knew where to get health care services in case they suspected that they had TB. TB transmission and treatment adherence knowledge was better among those in contact with either health care or harm reduction services, e.g the community based syringe exchange programme. Similar to HIV services, TB prevention and education should be integrated into harm reduction and drug treatment programmes to facilitate early diagnosis and treatment of TB among injecting drug users.

When students become patients: TB disease among medical undergraduates in Cape Town, South Africa.

PubMed

Van der Westhuizen, Helene-Mari; Dramowski, Angela

2017-05-24

Medical students acquire latent tuberculosis (TB) infection at a rate of 23 cases/100 person-years. The frequency and impact of occupational TB disease in this population are unknown. A self-administered questionnaire was distributed via email and social media to current medical students and recently graduated doctors (2010 - 2015) at two medical schools in Cape Town. Individuals who had developed TB disease as undergraduate students were eligible to participate. Quantitative and qualitative data collected from the questionnaire and semi-structured interviews were analysed with descriptive statistics and a framework approach to identify emerging themes. Twelve individuals (10 female) reported a diagnosis of TB: pulmonary TB (n=6), pleural TB (n=3), TB lymphadenitis (n=2) and TB spine (n=1); 2/12 (17%) had drug-resistant disease (DR-TB). Mean diagnostic delay post consultation was 8.1 weeks, with only 42% of initial diagnoses being correct. Most consulted private healthcare providers (general practitioners (n=7); pulmonologists (n=4)), and nine underwent invasive procedures (bronchoscopy, pleural fluid aspiration and tissue biopsy). Substantial healthcare costs were incurred (mean ZAR25 000 for drug-sensitive TB, up to  ZAR104 000 for DR-TB). Students struggled to obtain treatment, incurred high transport costs and missed academic time. Students with DR-TB interrupted their studies and experienced severe side-effects (hepatotoxicity, depression and permanent ototoxicity). Most participants cited poor TB infection-control practices at their training hospitals as a major risk factor for occupational TB. Undergraduate medical students in Cape Town are at high risk of occupationally acquired TB, with an unmet need for comprehensive occupational health services and support.

Factors associated with tuberculosis treatment outcomes among tuberculosis patients attending tuberculosis treatment centres in 2016-2017 in Mogadishu, Somalia.

PubMed

Ali, Marian Khalif; Karanja, Simon; Karama, Mohammed

2017-01-01

World Health Organization (WHO) reported that tuberculosis (TB) was a major health problem and the second leading cause of mortality globally. An estimated 1.8 million TB deaths were reported in 2015. In Somalia, the average TB incidence was 274 cases per 100,000 people in 2014; prevalence was 513 per 100,000 population; and mortality rate excluding human immune deficiency virus (HIV)/TB co-infection was 64/100,000. In addition, the prevalence rates of multi-drug resistant (MDR)-TB are still high, 5.2% among new cases and 40.7% for retreatment cases. The objective of this study was to determine individual and institutional level factors associated with TB treatment outcomes (TB-TOs) among patients attending TBTCs in Mogadishu. The study design was cross-sectional, using quantitative and qualitative methods. Data was collected using interviewer administered semi-structured questionnaires and key in-depth interviews in 2016/2017. Qualitative data was coded using NVIVO8 and quantitative data analyzed using descriptive and inferential statistics at 95% confidence interval using SPSS20 software. The study used a sample of 385 TB patients. There were 315(81.8%) successful TB-TOs. Individual level factors-marital status, education level, HIV status, treatment category and knowledge on TB influenced TB-TOs (p-value < 0.05). Being married, educated, HIV-negative, new treatment case and knowledgeable on TB increased odds of successful TB-TOs (OR > 0, p value < 0.05) compared to other patients. TBTCs factors did not influence TB-TOs (p-value > 0.05). TB-TOs were mainly affected by patient individual factors. There was need for patient education on TB management and treatment; and improved patient-health provider relationship.

Factors associated with tuberculosis treatment outcomes among tuberculosis patients attending tuberculosis treatment centres in 2016-2017 in Mogadishu, Somalia

PubMed Central

Ali, Marian Khalif; Karanja, Simon; Karama, Mohammed

2017-01-01

Introduction World Health Organization (WHO) reported that tuberculosis (TB) was a major health problem and the second leading cause of mortality globally. An estimated 1.8 million TB deaths were reported in 2015. In Somalia, the average TB incidence was 274 cases per 100,000 people in 2014; prevalence was 513 per 100,000 population; and mortality rate excluding human immune deficiency virus (HIV)/TB co-infection was 64/100,000. In addition, the prevalence rates of multi-drug resistant (MDR)-TB are still high, 5.2% among new cases and 40.7% for retreatment cases. The objective of this study was to determine individual and institutional level factors associated with TB treatment outcomes (TB-TOs) among patients attending TBTCs in Mogadishu. Methods The study design was cross-sectional, using quantitative and qualitative methods. Data was collected using interviewer administered semi-structured questionnaires and key in-depth interviews in 2016/2017. Qualitative data was coded using NVIVO8 and quantitative data analyzed using descriptive and inferential statistics at 95% confidence interval using SPSS20 software. Results The study used a sample of 385 TB patients. There were 315(81.8%) successful TB-TOs. Individual level factors-marital status, education level, HIV status, treatment category and knowledge on TB influenced TB-TOs (p-value < 0.05). Being married, educated, HIV-negative, new treatment case and knowledgeable on TB increased odds of successful TB-TOs (OR > 0, p value < 0.05) compared to other patients. TBTCs factors did not influence TB-TOs (p-value > 0.05). Conclusion TB-TOs were mainly affected by patient individual factors. There was need for patient education on TB management and treatment; and improved patient-health provider relationship. PMID:29610635

Assessment of knowledge regarding tuberculosis among non-medical university students in Bangladesh: a cross-sectional study.

PubMed

Rana, Masud; Sayem, Abu; Karim, Reazul; Islam, Nurul; Islam, Rafiqul; Zaman, Tunku Kamarul; Hossain, Golam

2015-07-28

Tuberculosis (TB) is the second leading cause of human death and TB is one of the major public health problems in Bangladesh. The aim of the present study was to assess the Knowledge about TB among non-medical university students in Bangladesh. A cross-sectional survey was performed on 839 non-medical university students. Data were collected from University of Rajshahi from March to August 2013 using a standard semi-structured questionnaire. Chi-square test was utilized to find the factors which are associated with students' knowledge about TB. Among 839 students, male and female were 68.2 % and 31.8 % respectively. Most of the students (94.4 %) were informed about the term TB, among them 50 % got information from electronic media. More than 50 % students believed that TB is a communicable disease, 42.8 % students agreed that bacteria is an agent for TB, most of the subjects (93 %) had the knowledge about the vaccination against TB and 97.6 % students believed that TB is curable. However, students had poor knowledge about latent TB (13.7 %) and DOTs program (28.5 %). χ (2)-test demonstrated that gender, residence, type of family and parents education were associated with students' knowledge of TB. In the present study demonstrated that the level of general knowledge about TB was insufficient among non-medical university students. Consequently, health education program is needed to improve the knowledge among university students regarding TB.

Spin reorientation and magnetoelastic coupling in Tb 6Fe 1-xCo xBi 2 (x = 0, 0.125, 0.25, 0.375) alloy system

DOE PAGES

Koehler, Michael R.; Garlea, Vasile O.; McGuire, Michael A.; ...

2014-07-05

Tb 6FeBi 2 adopts a noncentrosymmetric crystal structure and orders ferromagnetically at T C1 = 250 K with an additional magnetic transition at T C2 = 60 K. The low temperature magnetoelastic response in this material is strong, and is enhanced by cobalt substitution. In this paper, the temperature dependence of the atomic and magnetic structure of Tb 6Fe 1-xCo xBi 2 (x = 0, 0.125, 0.25, and 0.375) is reported from powder X-ray diffraction (XRD) and powder neutron diffraction (PND) measurements. Below the Néel temperature a ferrimagnetic ordering between the terbium and iron moments exists in all compounds studied.more » Related to the enhanced magnetostructural response, the Co-doped compounds undergo a crystallographic phase transition below about 60 K. This transition also involves a canting of the magnetic moments away from the c-axis. The structural transition is sluggish and not fully completed in the parent Tb 6FeBi 2 compound, where a mixture of monoclinic and hexagonal phases is identified below 60 K. Lastly, the spin reorientation transition is discussed in terms of competing exchange interactions and magnetocrystalline anisotropies of the two Tb sites and Fe/Co sublattices.« less

Occurrence and Nature of Double Alleles in Variable-Number Tandem-Repeat Patterns of More than 8,000 Mycobacterium tuberculosis Complex Isolates in The Netherlands

PubMed Central

Kamst, Miranda; van Hunen, Rianne; de Zwaan, Carolina Catherina; Mulder, Arnout; Supply, Philip; Anthony, Richard; van der Hoek, Wim; van Soolingen, Dick

2017-01-01

ABSTRACT Since 2004, variable-number tandem-repeat (VNTR) typing of Mycobacterium tuberculosis complex isolates has been applied on a structural basis in The Netherlands to study the epidemiology of tuberculosis (TB). Although this technique is faster and technically less demanding than the previously used restriction fragment length polymorphism (RFLP) typing, reproducibility remains a concern. In the period from 2004 to 2015, 8,532 isolates were subjected to VNTR typing in The Netherlands, with 186 (2.2%) of these exhibiting double alleles at one locus. Double alleles were most common in loci 4052 and 2163b. The variables significantly associated with double alleles were urban living (odds ratio [OR], 1.503; 95% confidence interval [CI], 1.084 to 2.084; P = 0.014) and pulmonary TB (OR, 1.703; 95% CI, 1.216 to 2.386; P = 0.002). Single-colony cultures of double-allele strains were produced and revealed single-allele profiles; a maximum of five single nucleotide polymorphisms (SNPs) was observed between the single- and double-allele isolates from the same patient when whole-genome sequencing (WGS) was applied. This indicates the presence of two bacterial populations with slightly different VNTR profiles in the parental population, related to genetic drift. This observation is confirmed by the fact that secondary cases from TB source cases with double-allele isolates sometimes display only one of the two alleles present in the source case. Double alleles occur at a frequency of 2.2% in VNTR patterns in The Netherlands. They are caused by biological variation rather than by technical aberrations and can be transmitted either as single- or double-allele variants. PMID:29142049

Pathways to multidrug-resistant tuberculosis diagnosis and treatment initiation: a qualitative comparison of patients' experiences in the era of rapid molecular diagnostic tests.

PubMed

Naidoo, Pren; van Niekerk, Margaret; du Toit, Elizabeth; Beyers, Nulda; Leon, Natalie

2015-10-28

Although new molecular diagnostic tests such as GenoType MTBDRplus and Xpert® MTB/RIF have reduced multidrug-resistant tuberculosis (MDR-TB) treatment initiation times, patients' experiences of diagnosis and treatment initiation are not known. This study aimed to explore and compare MDR-TB patients' experiences of their diagnostic and treatment initiation pathway in GenoType MTBDRplus and Xpert® MTB/RIF-based diagnostic algorithms. The study was undertaken in Cape Town, South Africa where primary health-care services provided free TB diagnosis and treatment. A smear, culture and GenoType MTBDRplus diagnostic algorithm was used in 2010, with Xpert® MTB/RIF phased in from 2011-2013. Participants diagnosed in each algorithm at four facilities were purposively sampled, stratifying by age, gender and MDR-TB risk profiles. We conducted in-depth qualitative interviews using a semi-structured interview guide. Through constant comparative analysis we induced common and divergent themes related to symptom recognition, health-care access, testing for MDR-TB and treatment initiation within and between groups. Data were triangulated with clinical information and health visit data from a structured questionnaire. We identified both enablers and barriers to early MDR-TB diagnosis and treatment. Half the patients had previously been treated for TB; most recognised recurring symptoms and reported early health-seeking. Those who attributed symptoms to other causes delayed health-seeking. Perceptions of poor public sector services were prevalent and may have contributed both to deferred health-seeking and to patient's use of the private sector, contributing to delays. However, once on treatment, most patients expressed satisfaction with public sector care. Two patients in the Xpert® MTB/RIF-based algorithm exemplified its potential to reduce delays, commencing MDR-TB treatment within a week of their first health contact. However, most patients in both algorithms experienced substantial delays. Avoidable health system delays resulted from providers not testing for TB at initial health contact, non-adherence to testing algorithms, results not being available and failure to promptly recall patients with positive results. Whilst the introduction of rapid tests such as Xpert® MTB/RIF can expedite MDR-TB diagnosis and treatment initiation, the full benefits are unlikely to be realised without reducing delays in health-seeking and addressing the structural barriers present in the health-care system.

Robust segmentation of trabecular bone for in vivo CT imaging using anisotropic diffusion and multi-scale morphological reconstruction

NASA Astrophysics Data System (ADS)

Chen, Cheng; Jin, Dakai; Zhang, Xiaoliu; Levy, Steven M.; Saha, Punam K.

2017-03-01

Osteoporosis is associated with an increased risk of low-trauma fractures. Segmentation of trabecular bone (TB) is essential to assess TB microstructure, which is a key determinant of bone strength and fracture risk. Here, we present a new method for TB segmentation for in vivo CT imaging. The method uses Hessian matrix-guided anisotropic diffusion to improve local separability of trabecular structures, followed by a new multi-scale morphological reconstruction algorithm for TB segmentation. High sensitivity (0.93), specificity (0.93), and accuracy (0.92) were observed for the new method based on regional manual thresholding on in vivo CT images. Mechanical tests have shown that TB segmentation using the new method improved the ability of derived TB spacing measure for predicting actual bone strength (R2=0.83).

Factors associated with poor knowledge among adults on tuberculosis in Bangladesh: results from a nationwide survey.

PubMed

Hossain, Shahed; Zaman, Khalequ; Quaiyum, Abdul; Banu, Sayera; Husain, Ashaque; Islam, Akramul; Borgdorff, Martien; van Leth, Frank

2015-05-01

In 2012, Bangladesh continues to be one of the 22 high tuberculosis (TB) burden countries in the world. Although free diagnosis and management for TB is available throughout the country, case notification rate/100,000 population for new smear positive (NSP) cases under the national TB control programme (NTP) remained at around 70/100,000 population and have not changed much since 2006. Knowledge on TB disease, treatment and its management could be an important predictor for utilization of TB services and influence case detection under the NTP. Our objective is to describe knowledge of TB among newly diagnosed TB cases and community controls to assess factors associated with poor knowledge in order to identify programmatic implications for control measures. Embedded in TB prevalence survey 2007-2009, we included 240 TB cases from the TB registers and 240 persons ≥ 15 years of age randomly selected from the households where the survey was implemented. All participants were interviewed using a structured, pre-tested questionnaire to evaluate their TB knowledge. Regression analyses were done to assess associations with poor knowledge of TB. Our survey documented that overall there was fair knowledge in all domains investigated. However, based on the number of correct answers to the questionnaires, community controls showed significantly poorer knowledge than the TB cases in the domains of TB transmission (80% vs. 88%), mode of transmission (67% vs. 82%), knowing ≥ 1 suggestive symptoms including cough (78% vs. 89%), curability of TB (90% vs. 98%) and availability of free treatment (75% vs. 95%). Community controls were more likely to have poor knowledge of TB issues compared to the TB cases even after controlling for other factors such as education and occupation in a multivariate model (OR 3.46, 95% CI: 2.00-6.09). Knowledge on various aspects of TB and TB services varies significantly between TB cases and community controls in Bangladesh. The overall higher levels of knowledge in TB cases could identify them as peer educators in ongoing communication approaches to improve care seeking behavior of the TB suspects in the community and hence case detection.

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis.

PubMed

Carpenter, Danielle; Taype, Carmen; Goulding, Jon; Levin, Mike; Eley, Brian; Anderson, Suzanne; Shaw, Marie-Anne; Armour, John A L

2014-01-09

Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0-6 copies per diploid genome (pdg) in Peru, between 0-12 pdg in !Xhosa samples and between 0-10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). The case-control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations.

Layered rare-earth hydroxide and oxide nanoplates of the Y/Tb/Eu system: phase-controlled processing, structure characterization and color-tunable photoluminescence via selective excitation and efficient energy transfer.

PubMed

Wu, Xiaoli; Li, Ji-Guang; Li, Jinkai; Zhu, Qi; Li, Xiaodong; Sun, Xudong; Sakka, Yoshio

2013-02-01

Well-crystallized (Y 0.97- x Tb 0.03 Eu x ) 2 (OH) 5 NO 3 · n H 2 O ( x = 0-0.03) layered rare-earth hydroxide (LRH) nanoflakes of a pure high-hydration phase have been produced by autoclaving from the nitrate/NH 4 OH reaction system under the optimized conditions of 100 °C and pH ∼7.0. The flakes were then converted into (Y 0.97- x Tb 0.03 Eu x ) 2 O 3 phosphor nanoplates with color-tunable photoluminescence. Detailed structural characterizations confirmed that LRH solid solutions contained NO 3 - anions intercalated between the layers. Characteristic Tb 3+ and Eu 3+ emissions were detected in the ternary LRHs by selectively exciting the two types of activators, and the energy transfer from Tb 3+ to Eu 3+ was observed. Annealing the LRHs at 1100 °C produced cubic-lattice (Y 0.97- x Tb 0.03 Eu x ) 2 O 3 solid-solution nanoplates with exposed 222 facets. Multicolor, intensity-adjustable luminescence was attained by varying the excitation wavelength from ∼249 nm (the charge transfer excitation band of Eu 3+ ) to 278 nm (the 4f 8 -4f 7 5d 1 transition of Tb 3+ ). Unitizing the efficient Tb 3+ to Eu 3+ energy transfer, the emission color of (Y 0.97- x Tb 0.03 Eu x ) 2 O 3 was tuned from approximately green to yellowish-orange by varying the Eu 3+ /Tb 3+ ratio. At the optimal Eu 3+ content of x = 0.01, the efficiency of energy transfer was ∼91% and the transfer mechanism was suggested to be electric multipole interactions. The phosphor nanoplates developed in this work may be incorporated in luminescent films and find various lighting and display applications.

An agent-based computational model for tuberculosis spreading on age-structured populations

NASA Astrophysics Data System (ADS)

Graciani Rodrigues, C. C.; Espíndola, Aquino L.; Penna, T. J. P.

2015-06-01

In this work we present an agent-based computational model to study the spreading of the tuberculosis (TB) disease on age-structured populations. The model proposed is a merge of two previous models: an agent-based computational model for the spreading of tuberculosis and a bit-string model for biological aging. The combination of TB with the population aging, reproduces the coexistence of health states, as seen in real populations. In addition, the universal exponential behavior of mortalities curves is still preserved. Finally, the population distribution as function of age shows the prevalence of TB mostly in elders, for high efficacy treatments.

GDC 2: Compression of large collections of genomes

PubMed Central

Deorowicz, Sebastian; Danek, Agnieszka; Niemiec, Marcin

2015-01-01

The fall of prices of the high-throughput genome sequencing changes the landscape of modern genomics. A number of large scale projects aimed at sequencing many human genomes are in progress. Genome sequencing also becomes an important aid in the personalized medicine. One of the significant side effects of this change is a necessity of storage and transfer of huge amounts of genomic data. In this paper we deal with the problem of compression of large collections of complete genomic sequences. We propose an algorithm that is able to compress the collection of 1092 human diploid genomes about 9,500 times. This result is about 4 times better than what is offered by the other existing compressors. Moreover, our algorithm is very fast as it processes the data with speed 200 MB/s on a modern workstation. In a consequence the proposed algorithm allows storing the complete genomic collections at low cost, e.g., the examined collection of 1092 human genomes needs only about 700 MB when compressed, what can be compared to about 6.7 TB of uncompressed FASTA files. The source code is available at http://sun.aei.polsl.pl/REFRESH/index.php?page=projects&project=gdc&subpage=about. PMID:26108279

GDC 2: Compression of large collections of genomes.

PubMed

Deorowicz, Sebastian; Danek, Agnieszka; Niemiec, Marcin

2015-06-25

The fall of prices of the high-throughput genome sequencing changes the landscape of modern genomics. A number of large scale projects aimed at sequencing many human genomes are in progress. Genome sequencing also becomes an important aid in the personalized medicine. One of the significant side effects of this change is a necessity of storage and transfer of huge amounts of genomic data. In this paper we deal with the problem of compression of large collections of complete genomic sequences. We propose an algorithm that is able to compress the collection of 1092 human diploid genomes about 9,500 times. This result is about 4 times better than what is offered by the other existing compressors. Moreover, our algorithm is very fast as it processes the data with speed 200 MB/s on a modern workstation. In a consequence the proposed algorithm allows storing the complete genomic collections at low cost, e.g., the examined collection of 1092 human genomes needs only about 700 MB when compressed, what can be compared to about 6.7 TB of uncompressed FASTA files. The source code is available at http://sun.aei.polsl.pl/REFRESH/index.php?page=projects&project=gdc&subpage=about.

A template-free solvothermal synthesis and photoluminescence properties of multicolor Gd2O2S:xTb3+, yEu3+ hollow spheres

NASA Astrophysics Data System (ADS)

Sang, Xiaotong; Xu, Guangxi; Lian, Jingbao; Wu, Nianchu; Zhang, Xue; He, Jiao

2018-06-01

The multicolor Gd2O2S:xTb3+, yEu3+ hollow spheres were successfully synthesized via a template-free solvothermal route without the use of surfactant from commercially available Ln (NO3)3·6H2O (Ln = Gd, Tb and Eu), absolute ethanol, ethanediamine and sublimed sulfur as the starting materials. The phase, structure, particle morphology and photoluminescence (PL) properties of the as-obtained products were investigated by X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM) and photoluminescence spectra. The influence of synthetic time on phase, structure and morphology was systematically investigated and discussed. The possible formation mechanism depending on synthetic time t for the Gd2O2S phase has been presented. These results demonstrate that the Gd2O2S hollow spheres could be obtained under optimal condition, namely solvothermal temperature T = 220 °C and synthetic time t = 16 h. The as-obtained Gd2O2S sample possesses hollow sphere structure, which has a typical size of about 2.5 μm in diameter and about 0.5 μm in shell thickness. PL spectroscopy reveals that the strongest emission peak for the Gd2O2S:xTb3+ and the Gd2O2S:yEu3+ samples is located at 545 nm and 628 nm, corresponding to 5D4→7F5 transitions of Tb3+ ions and 5D0→7F2 transitions of Eu3+ ions, respectively. The quenching concentration of Tb3+ ions and Eu3+ ions is 7%. In the case of Tb3+ and Eu3+ co-doped samples, when the concentration of Tb3+ or Eu3+ ions is 7%, the optimum concentration of Eu3+ or Tb3+ ions is determined to be 1%. Under 254 nm ultraviolet (UV) light excitation, the Gd2O2S:7%Tb3+, the Gd2O2S:7%Tb3+,1%Eu3+ and the Gd2O2S:7%Eu3+ samples give green, yellow and red light emissions, respectively. And the corresponding CIE coordinates vary from (0.3513, 0.5615), (0.4120, 0.4588) to (0.5868, 0.3023), which is also well consistent with their luminous photographs.

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

Morozkin, A.V., E-mail: morozkin@general.chem.msu.r; Mozharivskyj, Yu.; SvitlyK, V.

The magnetic ordering of the Fe{sub 2}P-type Tb{sub 6}FeTe{sub 2}, Tb{sub 6}CoTe{sub 2} Tb{sub 6}NiTe{sub 2} and Er{sub 6}FeTe{sub 2} phases (space group P6-bar 2m) has been investigated through magnetization measurement and neutron powder diffraction. Tb{sub 6}FeTe{sub 2}, Tb{sub 6}CoTe{sub 2} and Tb{sub 6}NiTe{sub 2} demonstrate high-temperature ferromagnetic and low-temperature spin reorientation transitions, whereas Er{sub 6}FeTe{sub 2} shows antiferromagnetic transition, only. The Tb{sub 6}FeTe{sub 2} and Tb{sub 6}NiTe{sub 2} phases show same high-temperature collinear ferromagnetic structure, whereas Tb{sub 6}FeTe{sub 2} is the commensurate non-collinear ferromagnet and Tb{sub 6}NiTe{sub 2} is the canted ferromagnetic cone with K{sub 1}=[0, 0, {+-}3/10] andmore » K{sub 2}=[{+-}2/9, {+-}2/9, 0] wave vectors at 2 K. The magnetic structure of Er{sub 6}FeTe{sub 2} is a flat spiral with K{sub 1}=[0, 0, {+-}1/10] at 2 K. The magnetic entropy change for Tb{sub 6}NiTe{sub 2} is {Delta}S{sub m}=-4.86 J/kg K at 229 K for the field change {Delta}{mu}{sub 0}H=0-5 T. In addition, novel Fe{sub 2}P-type Gd{sub 6}FeTe{sub 2}, Zr{sub 6}FeTe{sub 2}, Hf{sub 6}FeTe{sub 2}, Dy{sub 6}NiTe{sub 2}, Zr{sub 6}NiTe{sub 2} and Hf{sub 6}NiTe{sub 2} phases have been obtained. -- Graphical abstract: The novel Fe{sub 2}P-type Tb{sub 6{l_brace}}Fe, Co, Te{r_brace}Te{sub 2} and Er{sub 6}FeTe{sub 2} phases (space group P6-bar 2m) show the complex magnetic ordering below 18-228 K. The magnetocaloric effect for Tb{sub 6}NiTe{sub 2} in terms of the isothermal entropy change, -{Delta}S{sub m}, has the maximum value of 4.86 J/kg K at 229 K for the 0-5 T field change.« less

Magnetic and thermal properties of amorphous TbFeCo alloy films

NASA Astrophysics Data System (ADS)

Wang, Ke; Dong, Shuo; Huang, Ya; Qiu, Yuzhen

2017-07-01

Amorphous TbFeCo material with perpendicular magnetic anisotropy is currently attracting more attention for potential applications in spintronic devices and logic memories. We systematically investigate magnetic, structural, thermal, optical and electrical properties of TbFeCo alloy films. It shows out-of-plane easy axis of the films turns into in-plane orientation after annealing. Significant increase in saturation magnetization in the temperature range between 400 and 450 °C is revealed by thermomagnetic measurements. The occurrence of crystallization and oxidation at high temperatures is confirmed by X-ray diffraction measurements. Pronounced changes in optical reflectance and sheet resistance are observed with temperature, in line with structural relaxation and change. The activation barriers for crystallization and oxidation are determined to be 1.01 eV and 0.83 eV, respectively, for FeCo-rich and Tb-rich samples. Better thermal stability against crystallization and oxidation is demonstrated in the FeCo-rich sample than the Tb-rich type. Our results provide some useful information for the alloy used in device fabrication.

Point defect disorder in high-temperature solution grown Sr6Tb0.94Fe1.06(BO3)6 single crystals

NASA Astrophysics Data System (ADS)

Velázquez, M.; Péchev, S.; Duttine, M.; Wattiaux, A.; Labrugère, C.; Veber, Ph.; Buffière, S.; Denux, D.

2018-08-01

New Sr6Tb0.94Fe1.06(BO3)6 single crystals were obtained from lithium borate high-temperature solution growth under controlled atmosphere. Their average crystal structure was found to adopt the trigonal R-3 space group with lattice parameters a = 12.2164 Å and c = 9.1934 Å. A combined multiscale characterization approach, involving diffuse reflectance, X-ray photoelectron (XPS) and Mössbauer spectroscopies, was undertaken to establish the exact nature of the point defect disorder in this crystal structure. The FeTb× antisite disorder in the Sr6Tb0.94Fe1.06(BO3)6 single crystals is different from the kind of point defect disorder known to exist in the powder phase material counterpart. The absence of Tb4+ cations in the crystal lattice was established by XPS, and that of any phase transition down to 4 K was checked by specific heat measurements. The magnetic susceptibility curve was found to follow a Curie-Weiss behaviour in the 4-354 K temperature range.

A comparative study on the luminescence properties of Ce3+/Tb3+ doped Gd-based host nanomaterials

NASA Astrophysics Data System (ADS)

Jadhao, Charushila Vasant; Rani, Barkha; Sahu, Niroj Kumar

2018-04-01

A comparative study on the crystal phases and their respective luminescence behaviour of Gd3+ based host materials such as GdPO4, GdF3, GdVO4 and Gd2O3 sensitized with 7at.% Ce3+ and activated with 5 at.% Tb3+ have been reported. The nanomaterials were prepared by polyol method using ethylene glycol as solvent and found to have different crystal structures such as monoclinic, orthorhombic, tetragonal and cubic phase. Clear characteristics emission from Tb3+ has been observed in all the samples when excited in the absorption wavelength of Ce3+ and Gd3+ (˜280 nm). Among all the above materials, intense emission of Tb3+ is found in GdPO4 followed by GdF3, Gd2O3 and GdVO4 respectively. The Tb3+ emission is strongly influenced by the energy transfer process and crystal structure of the host materials and hence this study will be important for choosing suitable materials for display devices and biomedical applications.

Magnetic Correlations in the Triangular Antiferromagnet TbInO3

NASA Astrophysics Data System (ADS)

Sala, Gabriele; Clark, Lucy; Maharaj, Dalini; Stone, Matthew B.; Knight, Kevin S.; Cheong, Sang-Wook; Gaulin, Bruce D.

TbInO3 crystallizes with a hexagonal P63 cm structure in which layers of edge-sharing triangles of magnetic Tb3+ ions are separated by non-magnetic [InO5]7- units. TbInO3, therefore, realizes an excellent opportunity to explore the behavior of a two-dimensional magnetic triangular lattice, a canonical model of geometric frustration. Here we present our study of a polycrystalline sample of TbInO3. Our high resolution powder neutron diffraction data (HRPD, ISIS) of TbInO3 confirm that the triangular layers of Tb3+ remain undistorted to at least 0 . 46 K. Magnetic susceptibility data follow Curie-Weiss behavior over a wide range of T with θ = - 17 . 19 (3) K indicating the dominance of antiferromagnetic correlations. The susceptibility data also show an absence of conventional long-range spin order down to at least 0 . 55 K, reflecting the frustrated nature of TbInO3. Elastic magnetic diffuse neutron scattering (SEQUOIA, SNS) is observed below ~ 15 K, due to the presence of static two-dimensional spin correlations. The spectrum of crystal field excitations in TbInO3 appears to have an exotic form due to the existence of two crystallographically distinct Tb3+ sites and leads to a strong Ising anisotropy of the spin symmetry.

Energy transfer and color tunable emission in Tb3 +,Eu3 + co-doped Sr3LaNa(PO4)3F phosphors

NASA Astrophysics Data System (ADS)

Li, Shuo; Guo, Ning; Liang, Qimeng; Ding, Yu; Zhou, Huitao; Ouyang, Ruizhuo; Lü, Wei

2018-02-01

A group of color tunable Sr3LaNa(PO4)3F:Tb3 +,Eu3 + phosphors were prepared by conventional high temperature solid state method. The phase structures, luminescence properties, fluorescence lifetimes and energy transfer were investigated in detail. Under 369 nm excitation, owing to efficient energy transfer of Tb3 + → Eu3 +, the emission spectra both have green emission of Tb3 + and red emission of Eu3 +. An efficient energy transfer occur in Tb3 +, Eu3 + co-doped Sr3LaNa(PO4)3F phosphors. The most possible mechanism of energy transfer is dipole-dipole interaction by Dexter's theoretical model. The energy transfer of Tb3 + and Eu3 + was confirmed by the variations of emission and excitation spectra and Tb3 +/Eu3 + decay lifetimes in Sr3LaNa(PO4)3F:Tb3 +,Eu3 +. The color tone can tuned from yellowish-green through yellow and eventually to reddish-orange with fixed Tb3 + content by changing Eu3 + concentrations. The results show that the prepared Tb3 +, Eu3 + co-doped color tunable Sr3LaNa(PO4)3F phosphor can be used for white LED.

HIV-TB Coinfection among 57 Million Pregnant Women, Obstetric Complications, Alcohol Use, Drug Abuse, and Depression.

PubMed

Fernandez, Dorian; Salami, Imoleayo; Davis, Janelle; Mbah, Florence; Kazeem, Aisha; Ash, Abreah; Babino, Justin; Carter, Laquiesha; Salemi, Jason L; Spooner, Kiara K; Olaleye, Omonike A; Salihu, Hamisu M

2018-01-01

HIV and tuberculosis represent diseases of major public health importance worldwide. Very little is known about HIV-TB coinfection among pregnant women, especially from industrialized settings. In this study, we examined the association between TB, HIV, and HIV-TB coinfection among pregnant mothers and obstetric complications, alcohol use, drug abuse, and depression. We examined inpatient hospital discharges in the United States from January 1, 2002, through December 31, 2014. We employed multivariable survey logistic regression to generate adjusted estimates for the association between infection status and study outcomes. We analyzed approximately 57 million records of pregnant women and their delivery information. HIV-TB coinfection was associated with the highest risks for several obstetric complications, alcohol use, and drug abuse. The risk for alcohol abuse was more than twice as high among HIV-monoinfected as compared to TB-monoinfected mothers. That risk gap more than doubled with HIV-TB coinfection. Both HIV-monoinfected and HIV-TB coinfected mothers experienced similarly increased risks for depression. Mothers with HIV-TB coinfection experienced relatively heightened risks for obstetric complications, alcohol use, and drug abuse. The findings of this study underscore the importance of augmenting and enhancing social and structural support systems for HIV-TB coinfected pregnant women.

International non-governmental organizations' provision of community-based tuberculosis care for hard-to-reach populations in Myanmar, 2013-2014.

PubMed

Soe, Kyaw Thu; Saw, Saw; van Griensven, Johan; Zhou, Shuisen; Win, Le; Chinnakali, Palanivel; Shah, Safieh; Mon, Myo Myo; Aung, Si Thu

2017-03-24

National tuberculosis (TB) programs increasingly engage with international non-governmental organizations (INGOs), especially to provide TB care in complex settings where community involvement might be required. In Myanmar, however, there is limited data on how such INGO community-based programs are organized and how effective they are. In this study, we describe four INGO strategies for providing community-based TB care to hard-to-reach populations in Myanmar, and assess their contribution to TB case detection. We conducted a descriptive study using program data from four INGOs and the National TB Program (NTP) in 2013-2014. For each INGO, we extracted information on its approach and key activities, the number of presumptive TB cases referred and undergoing TB testing, and the number of patients diagnosed with TB and their treatment outcomes. The contribution of INGOs to TB diagnosis in their selected townships was calculated as the proportion of INGO-diagnosed new TB cases out of the total NTP-diagnosed new TB cases in the same townships. All four INGOs implemented community-based TB care in challenging contexts, targeting migrants, post-conflict areas, the urban poor, and other vulnerable populations. Two recruited community volunteers via existing community health volunteers or health structures, one via existing community leaderships, and one directly involved TB infected/affected individuals. Two INGOs compensated volunteers via performance-based financing, and two provided financial and in-kind initiatives. All relied on NTP laboratories for diagnosis and TB drugs, but provided direct observation treatment support and treatment follow-up. A total of 21 995 presumptive TB cases were referred for TB diagnosis, with 7 383 (34%) new TB cases diagnosed and almost all (98%) successfully treated. The four INGOs contributed to the detection of, on average, 36% (7 383/20 663) of the total new TB cases in their respective townships (range: 15-52%). Community-based TB care supported by INGOs successfully achieved TB case detection in hard-to-reach and vulnerable populations. This is vital to achieving the World Health Organization End TB Strategy targets. Strategies to ensure sustainability of the programs should be explored, including the need for longer-term commitment of INGOs.

Insights in the electronic structure and redox reaction energy in LiFePO{sub 4} battery material from an accurate Tran-Blaha modified Becke Johnson potential

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

Araujo, Rafael B., E-mail: rafael.barros@physics.uu.se; Almeida, J. de S; Instituto de Física, Universidade Federal da Bahia, Salvador, Bahia

The main goals of this paper are to investigate the accuracy of the Tran-Blaha modified Becke Johnson (TB-mBJ) potential to predict the electronic structure of lithium iron phosphate and the related redox reaction energy with the lithium deintercalation process. The computed electronic structures show that the TB-mBJ method is able to partially localize Fe-3d electrons in LiFePO{sub 4} and FePO{sub 4} which usually is a problem for the generalized gradient approximation (GGA) due to the self interaction error. The energy band gap is also improved by the TB-mBJ calculations in comparison with the GGA results. It turned out, however, thatmore » the redox reaction energy evaluated by the TB-mBJ technique is not in good agreement with the measured one. It is speculated that this disagreement in the computed redox energy and the experimental value is due to the lack of a formal expression to evaluate the exchange and correlation energy. Therefore, the TB-mBJ is an efficient method to improve the prediction of the electronic structures coming form the standard GGA functional in LiFePO{sub 4} and FePO{sub 4}. However, it does not appear to have the same efficiency for evaluating the redox reaction energies for the investigated system.« less

Protective effects of Tualang honey on bone structure in experimental postmenopausal rats

PubMed Central

Zaid, Siti Sarah Mohamad; Sulaiman, Siti Amrah; Othman, Nor Hayati; Soelaiman, Ima-Nirwana; Shuid, Ahmad Nazrun; Mohamad, Norazlina; Muhamad, Norliza

2012-01-01

OBJECTIVE: The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats. METHODS: Forty female, Sprague-Dawley rats were randomly divided into five groups (n = 8): four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum). The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey). Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water), and the baseline control group was sacrificed without treatment. RESULTS: All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and a significant decrease in inter-trabecular space (Tb.Sp) compared with the ovariectomized control group. The trabecular thickness (Tb.Th) in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp) in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group. CONCLUSION: In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium. PMID:22892923

Protective effects of Tualang honey on bone structure in experimental postmenopausal rats.

PubMed

Zaid, Siti Sarah Mohamad; Sulaiman, Siti Amrah; Othman, Nor Hayati; Soelaiman, Ima-Nirwana; Shuid, Ahmad Nazrun; Mohamad, Norazlina; Muhamad, Norliza

2012-07-01

The objective of this study was to evaluate the effects of Tualang honey on trabecular structure and compare these effects with those of calcium supplementation in ovariectomized rats. Forty female, Sprague-Dawley rats were randomly divided into five groups (n =8): four controls and one test arm. The control arm comprised a baseline control, sham-operated control, ovariectomized control, and ovariectomized calcium-treated rats (receiving 1% calcium in drinking water ad libitum). The test arm was composed of ovariectomized, Tualang honey-treated rats (received 0.2 g/kg body weight of Tualang honey). Both the sham-operated control and ovariectomized control groups received vehicle treatment (deionized water), and the baseline control group was sacrificed without treatment. All rats were orally gavaged daily for six weeks after day one post-surgery. The bone structural analysis of rats in the test arm group showed a significant increase in the bone volume per tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) and a significant decrease in inter-trabecular space (Tb.Sp) compared with the ovariectomized control group. The trabecular thickness (Tb.Th) in the test arm group was significantly higher compared with the ovariectomized-calcium treated group, and the inter-trabecular space (Tb.Sp) in the test arm group was significantly narrower compared with the ovariectomized-calcium treated group. In conclusion, ovariectomized rats that received Tualang honey showed more improvements in trabecular bone structure than the rats that received calcium.

Structure and management of tuberculosis control programs in fragile states--Afghanistan, DR Congo, Haiti, Somalia.

PubMed

Mauch, Verena; Weil, Diana; Munim, Aayid; Boillot, Francois; Coninx, Rudi; Huseynova, Sevil; Powell, Clydette; Seita, Akihiro; Wembanyama, Henriette; van den Hof, Susan

2010-07-01

Health care delivery is particularly problematic in fragile states often connected with increased incidence of communicable diseases, among them tuberculosis. This article draws upon experiences in tuberculosis control in four fragile states from which four lessons learned were derived. A structured inventory to extract common themes specific for TB control in fragile states was conducted among twelve providers of technical assistance who have worked in fragile states. The themes were applied to the TB control programs of Afghanistan, DR Congo, Haiti and Somalia during the years 2000-2006. Case notifications and treatment outcomes have increased in all four countries since 2003 (treatment success rates 81-90%). Access to care and case detection however have remained insufficient (case detection rates 39-62%); There are four lessons learned: 1. TB control programs can function in fragile states. 2. National program leadership and stewardship are essential for quality and sustained TB control. 3. Partnerships with non-governmental providers are vital for continuous service delivery; 4. TB control programs in fragile states require consistent donor support. Despite challenges in management, coordination, security, logistics and funding, TB control programs can function in fragile states, but face considerable problems in access to diagnosis and treatment and therefore case detection. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Anomalous magnetoelastic behaviour near morphotropic phase boundary in ferromagnetic Tb 1-xNd xCo 2 system

DOE PAGES

Murtaza, Adil; Yang, Sen; Zhou, Chao; ...

2016-08-04

In this study, we report a morphotropic phase boundary (MPB) involved ferromagnetic system Tb 1-xNd xCo 2 and reveal the corresponding structural and magnetoelastic properties of this system. With high resolution synchrotron X-ray diffractometry, the crystal structure of the TbCo 2-rich side is detected to be rhombohedral and that of NdCo 2-rich side is tetragonal below their respective Curie temperatures TC. The MPB composition Tb 0.35Nd 0.65Co 2 corresponds to the coexistence of the rhombohedral phase (R-phase) and tetragonal phase ( T-phase). Contrary to previously reported MPB involved ferromagnetic systems, the MPB composition of Tb 0.35Nd 0.65Co 2 shows minimummore » magnetization which can be understood as compensation of sublattice moments between the R-phase and the T-phase. Furthermore, magnetostriction of Tb 1-xNd xCo 2 decreases with increasing Nd concentration until x = 0.8 and then increases in the negative direction with further increasing Nd concentration; the optimum point for magnetoelastic properties lies towards the rhombohedral phase. Finally, our work not only shows an anomalous type of ferromagnetic MPB but also provides an effective way to design functional materials.« less

Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB

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

Chen, Wenjing; Biswas, Tapan; Porter, Vanessa R.

2011-09-06

The emergence of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis (TB) is a serious global threat. Aminoglycoside antibiotics are used as a last resort to treat XDR-TB. Resistance to the aminoglycoside kanamycin is a hallmark of XDR-TB. Here, we reveal the function and structure of the mycobacterial protein Eis responsible for resistance to kanamycin in a significant fraction of kanamycin-resistant Mycobacterium tuberculosis clinical isolates. We demonstrate that Eis has an unprecedented ability to acetylate multiple amines of many aminoglycosides. Structural and mutagenesis studies of Eis indicate that its acetylation mechanism is enabled by a complex tripartite fold that includes two generalmore » control non-derepressible 5 (GCN5)-related N-acetyltransferase regions. An intricate negatively charged substrate-binding pocket of Eis is a potential target of new antitubercular drugs expected to overcome aminoglycoside resistance.« less

Assessment of band gaps for alkaline-earth chalcogenides using improved Tran Blaha-modified Becke Johnson potential

NASA Astrophysics Data System (ADS)

Yedukondalu, N.; Kunduru, Lavanya; Roshan, S. C. Rakesh; Sainath, M.

2018-04-01

Assessment of band gaps for nine alkaline-earth chalcogenides namely MX (M = Ca, Sr, Ba and X = S, Se Te) compounds are reported using Tran Blaha-modified Becke Johnson (TB-mBJ) potential and its new parameterization. From the computed electronic band structures at the equilibrium lattice constants, these materials are found to be indirect band gap semiconductors at ambient conditions. The calculated band gaps are improved using TB-mBJ and its new parameterization when compared to local density approximation (LDA) and Becke Johnson potentials. We also observe that TB-mBJ new parameterization for semiconductors below 7 eV reproduces the experimental trends very well for the small band gap semiconducting alkaline-earth chalcogenides. The calculated band profiles look similar for MX compounds (electronic band structures are provided for BaS for representation purpose) using LDA and new parameterization of TB-mBJ potentials.

Does the integration of TB medical services in the general hospital improve the quality of TB care? Evidence from a case study in China.

PubMed

Sun, Qiang; Yin, Jia; Yin, Xiao; Zou, Guanyang; Liang, Mingli; Zhong, Jieming; Walley, John; Wei, Xiaolin

2013-06-01

Moving the clinical services from tuberculosis (TB) dispensary to the integrated county hospital (called integrated approach) has been practiced in China; however, it is unknown the quality of TB care in the integrated approach and in the dispensary approach. A total of 202 new TB patients were investigated using structured questionnaires in three counties implementing the integrated approach and one county implementing the dispensary approach. The quality of TB care is measured based on success rate of treatment, medical expenditure, health system delay and second-line drug use. The integrated approach showed a high success treatment rate. The medical expenditure in the integrated approach was USD 432, significantly lower than that in the dispensary approach (Z = -5.771, P < 0.001). The integrated approach had a shorter health system delay (5 days) than the dispensary approach (32 days). Twenty-six percent of patients in integrated hospitals were prescribed with second-line TB drugs, significantly lower than that in the TB dispensary (47%, χ(2) = 7.452, P = 0.006). However, the medical expenditure, use of second-line anti-TB drug and liver-protection drugs indeed varied greatly across the three integrated hospitals. The integrated approach showed better quality of TB care, but the performance of the integrated hospitals varied greatly. A method to standardize TB treatment and management of this approach is urgent.

Evaluation of the Tuberculosis Infection Control Training Center, Tajikistan, 2014–2015

PubMed Central

Scott, C.; Mangan, J.; Tillova, Z.; Jensen, P. A.; Ahmedov, S.; Ismoilova, J.; Trusov, A.

2017-01-01

SUMMARY SETTING Training center on tuberculosis (TB) infection control (IC) for health care workers in the Central Asian Republics region. OBJECTIVE To assess the effects of TB IC training courses conducted at the Tuberculosis Infection Control Training Center in Machiton, Tajikistan. DESIGN Participants who participated in training (n = 89) during the first year of operation (April 2014–February 2015) were invited to participate in a post-training interview. RESULTS Of the 89 participants, 84 (94%) completed the interview and expressed satisfaction with the training. Eighty (95%) participants reported meeting with workplace leadership to discuss the training. Of these, 69 (85%) reported discussing changes required to meet TB IC standards. Self-reported changes in TB IC practices at work facilities post training included the creation of TB IC committees, designation of a TB IC focal person, TB IC planning, policies to separate infectious patients in waiting rooms, provision of masks for infectious patients, development of cough etiquette policies, improved glove availability, hand hygiene programs, and TB IC posters in waiting rooms. CONCLUSIONS Participant satisfaction and reported changes in TB IC activities illustrate the potential of these training courses to improve TB IC in the region. Future training courses may be tailored to specific audiences using a structured conceptual framework to impact administration, budgeting, and facilities management of TB IC practices. PMID:28399974

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function.

PubMed

Hemingway, Cheryl; Berk, Maurice; Anderson, Suzanne T; Wright, Victoria J; Hamilton, Shea; Eleftherohorinou, Hariklia; Kaforou, Myrsini; Goldgof, Greg M; Hickman, Katy; Kampmann, Beate; Schoeman, Johan; Eley, Brian; Beatty, David; Pienaar, Sandra; Nicol, Mark P; Griffiths, Michael J; Waddell, Simon J; Newton, Sandra M; Coin, Lachlan J; Relman, David A; Montana, Giovanni; Levin, Michael

2017-01-01

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies.

High proportion of modern genotypes of M. tuberculosis and their affinity with drug resistance in northern region of India.

PubMed

Dhatwalia, Sunil Kumar; Yadav, Rakesh; Behera, Digambar; Kaur, Harsimran; Kumar, Manoj; Sethi, Sunil

2017-09-01

Comparative genomics on the basis of TbD1 deletion has differentiated the members of Mycobacterium tuberculosis complex (MTC) in two major genogroups. They exhibit differential distribution and virulence potential. The present study was carried out to see the proportion of these genogroups and their association with drug resistance. The drug resistance pattern of 205 culture positive cases of M. tuberculosis and their relation with TbD1 deletion was analysed from the tertiary care centre. Overall proportion of genotypes (TbD1- and Tbd1+) and their association with drug resistance was also observed from the various studies from India. Our study reports that 85.4% of the isolates of M. tuberculosis were modern genotypes (TbD1-) and rest of 14.6% were ancient genotypes (TbD1+). 37 cases were of multiple drug resistant-TB (MDR-TB), 35 of them belongs to modern genogrop and rest of (2) were in ancient genogroup (p=0.12). Overall pooled estimate of proportion of modern genotype is 75.5% (CI 95%, 73.03-77.87) and 24.55% (CI 95%, 22.13-26.97) for ancient genotypes from the studies carried out in India. Modern genotypes were more rarely drug sensitive phenotypes with a relative risk (RR) of 0.89 (CI 95%, 0.74-1.07) while MDR cases were more in this group with an odds ratio (OR) of 2.27 (CI 95%, 0-1.07). This study demonstrates a higher proportion of modern genotypes in our region/India; which are more likely to be associated with drug resistance. Future, epidemiological/in vitro studies are required to ascertain the relationship between genotypes and their virulence potential. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Insights on the origin of the Tb5Ge4 magnetocaloric effect

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

Belo, J. H.; Barbosa, M. B.; Pires, A. L.

2017-05-01

In this report the magnetic, atomic structures and spin-lattice coupling have been thoroughly studied through high magnetic field magnetometry, Synchrotron X-ray diffraction under applied magnetic field and magnetostriction measurements in the Tb5Ge4 compounds. A field induced phase transition from an antiferromagnetic towards a ferromagnetic ordering was confirmed but with absence of structural transformation. This absence has been confirmed experimentally through synchrotron x-ray diffraction under applied field (up to 30 T). Moreover, this absence was explained via a thermodynamic free energy model: first principles calculations determined a large energy gap (ΔE=0.65 eV) between the two possible structures, O(I) and O(II). Frommore » magnetic and structural properties, a H-T phase diagram has been proposed for Tb5Ge4. Finally it was observed a large magnetostriction (up to 600 ppm) induced by ΔH=7 T.« less

Tracking and responding to an outbreak of tuberculosis using MIRU-VNTR genotyping and whole genome sequencing as epidemiological tools.

PubMed

Black, Anne T; Hamblion, Esther L; Buttivant, Helen; Anderson, Sarah R; Stone, Madeline; Casali, Nicola; Drobniewski, Francis; Nwoguh, Francisca; Marshall, Ben G; Booth, Linda

2017-07-05

We describe an outbreak that contributed to a near doubling of the incidence of tuberculosis in Southampton, UK. We examine the importance of 24 locus mycobacterial interspersed repetitive unit variable number tandem repeat (MIRU-VNTR) genotyping in its identification and management and the role of whole genome sequencing (WGS) in tracing the spread of the strain. Outbreak cases were defined as those diagnosed between January and December 2011 with indistinguishable 24 locus-MIRU-VNTR genotypes or, cases linked epidemiologically. A cluster questionnaire was administered by TB nurses to identify contacts and social settings. Overall, 25 patients fulfilled the case definition. No cases with this MIRU-VNTR genotype had been detected in the UK previously. Connections were found between all cases through household contacts or social venues including a football club, Internet cafe and barber's shop. Public health actions included extended contact tracing, venue screening and TB awareness-raising. The outbreak resulted in a high rate of transmission and high incidence of clinical disease among contacts. This outbreak illustrates the value of combining active case-finding with prospective MIRU-VNTR genotyping to identify settings to undertake public health action. In addition WGS revealed that the VNTR-defined cluster was a single outbreak and that active TB transmission not reactivation was responsible for this outbreak in non-UK born individuals. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Characterization, Localization, Essentiality, and High-Resolution Crystal Structure of Glucosamine 6-Phosphate N-Acetyltransferase from Trypanosoma brucei ▿ ‡ §

PubMed Central

Mariño, Karina; Güther, M. Lucia Sampaio; Wernimont, Amy K.; Qiu, Wei; Hui, Raymond; Ferguson, Michael A. J.

2011-01-01

A gene predicted to encode Trypanosoma brucei glucosamine 6-phosphate N-acetyltransferase (TbGNA1; EC 2.3.1.4) was cloned and expressed in Escherichia coli. The recombinant protein was enzymatically active, and its high-resolution crystal structure was obtained at 1.86 Å. Endogenous TbGNA1 protein was localized to the peroxisome-like microbody, the glycosome. A bloodstream-form T. brucei GNA1 conditional null mutant was constructed and shown to be unable to sustain growth in vitro under nonpermissive conditions, demonstrating that there are no metabolic or nutritional routes to UDP-GlcNAc other than via GlcNAc-6-phosphate. Analysis of the protein glycosylation phenotype of the TbGNA1 mutant under nonpermissive conditions revealed that poly-N-acetyllactosamine structures were greatly reduced in the parasite and that the glycosylation profile of the principal parasite surface coat component, the variant surface glycoprotein (VSG), was modified. The significance of results and the potential of TbGNA1 as a novel drug target for African sleeping sickness are discussed. PMID:21531872

Highly active antiretroviral therapy and tuberculosis control in Africa: synergies and potential.

PubMed Central

Harries, Anthony D.; Hargreaves, Nicola J.; Chimzizi, Rehab; Salaniponi, Felix M.

2002-01-01

HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and TB (tuberculosis) are two of the world's major pandemics, the brunt of which falls on sub-Saharan Africa. Efforts aimed at controlling HIV/AIDS have largely focused on prevention, little attention having been paid to care. Work on TB control has concentrated on case detection and treatment. HIV infection has complicated the control of tuberculosis. There is unlikely to be a decline in the number of cases of TB unless additional strategies are developed to control both this disease and HIV simultaneously. Such strategies would include active case-finding in situations where TB transmission is high, the provision of a package of care for HIV-related illness, and the application of highly active antiretroviral therapy. The latter is likely to have the greatest impact, but for this therapy to become more accessible in Africa the drugs would have to be made available through international support and a programme structure would have to be developed for its administration. It could be delivered by means of a structure based on the five-point strategy called DOTS, which has been adopted for TB control. However, it may be unrealistic to give TB control programmes the responsibility for running such a programme. A better approach might be to deliver highly active antiretroviral therapy within a comprehensive HIV/AIDS management strategy complementing the preventive work already being undertaken by AIDS control programmes. TB programmes could contribute towards the development and implementation of this strategy. PMID:12132003

Exploring workplace TB interventions with foreign-born Latino workers.

PubMed

Eggerth, Donald E; Keller, Brenna M; Flynn, Michael A

2018-05-15

Persons born outside the United States are more likely to be diagnosed with tuberculosis disease (TB) than native-born individuals. Foreign-born Latinos at risk of TB may be difficult to reach with public health interventions due to cultural and institutional barriers. Workplaces employing large concentrations of foreign-born Latinos may be useful locations for TB interventions targeting this high-risk population. This study used a two-phase approach to investigate the feasibility of workplace TB interventions. The first phase investigated employer knowledge of TB and receptiveness to allowing TB interventions in their businesses through 5 structured interviews. The second phase investigated foreign-born workers' knowledge of TB and their receptiveness to receiving TB interventions in their places of employment through 12 focus groups stratified by gender and education. Phase 1: Only 1 of the 5 employers interviewed had a high level of knowledge about TB, and three had no knowledge other than that TB was a disease that involved coughing. They were receptive to workplace TB interventions, but were concerned about lost productivity and customers finding out if an employee had TB. Phase 2: There was no observed differences in responses between gender and between the bottom two education groups, so the final analysis took place between a gender-combined lower education group and higher education group. The higher education group tended to have knowledge that was more accurate and to view TB as a disease associated with poverty. The lower education group tended to have more misconceptions about TB and more often expressed concern that their employers would not support worksite interventions. The results from both phases indicate that more TB education is needed among both foreign-born Latino workers and their employers. Obstacles to implementing workplace TB interventions include knowledge, potential productivity loss, employer liability, and perceived customer response. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Molecular epidemiology of Mycobacterium tuberculosis in Baja California, Mexico: A result of human migration?

PubMed

Flores-López, Carlos A; Zenteno-Cuevas, Roberto; Laniado-Laborín, Rafael; Reynaud, Yann; García-Ortiz, Rosa Alejandra; González-Y-Merchand, Jorge A; Rivera, Sandra; Vázquez-Chacón, Carlos A; Vaughan, Gilberto; Martínez-Guarneros, José Armando; Victoria-Cota, Nelva Lorena; Cruz-Rivera, Mayra; Rastogi, Nalin; Muñiz-Salazar, Raquel

2017-11-01

The State of Baja California (BC) exhibits the highest incidence and prevalence rates of tuberculosis (TB), and multidrug-resistant TB (MDR-TB) in Mexico. However information about the circulation of M. tuberculosis lineages in BC and Mexico as a whole is limited. Here, we describe the genetic relationship and genetic diversity among M. tuberculosis clinical isolates (n=140) collected in BC between October 2009 and April 2011 with other regions of Mexico, the United States, and Latin America. All specimens were genotyped based on 24 mycobacterial interspersed repetitive units (MIRU)-variable number of tandem repeats (VNTR) loci. Population structure and minimum spanning tree (MST) analyses were used to assess the genetic diversity and distribution of BC isolates in comparison to USA and South America strains. Among the nine lineages observed, LAM, Haarlem and S were the most frequent identified in BC. Population structure analysis clustered most BC isolates (41%) into three distinctive groups that included strains from San Diego and South America, whereas other BC strains (22%) clustered with other Mexican strains. A subset of isolates (12%) seemed to be autochthonous of BC, while 25% were cosmopolitan and grouped into multiple clusters. It is highly likely that the TB genetic structure observed in BC is due to human migration. Additional studies are required to determine the mechanism involved in the phylogeographic distribution of M. tuberculosis in Mexico. Implementation of domestic molecular TB surveillance programs is required to better understand the molecular epidemiology of TB not only in the region but at the national level. Copyright © 2016 Elsevier B.V. All rights reserved.

Benzimidazole-core as an antimycobacterial agent.

PubMed

Keri, Rangappa S; Rajappa, Chethana Kolambae; Patil, Siddappa A; Nagaraja, Bhari Mallanna

2016-12-01

Mycobacterium tuberculosis (Mtb) is considered as one of the precarious bacterial infections around the world. Through a projected 8.7 million new tuberculosis (TB) cases and 1.4 million mortalities per annum, this deadly infection resulted insubstantial amount of human deaths than any other single organism bacterial infections. TB is one of India's most threatening human health problems and it accounts for approximately 33% of the global health issues. Subsequently, for TB there is an imperative need for the improvement of existing drug candidates with newer targets and specified mechanism of action. Within the wide spectra of heterocycles, benzimidazole and its substituted analogues were evidenced promising biological efficacies enabling them to perform as new drug or prodrug candidates. Exceptional structural features of this class of heterocycle and versatile biological applications made it a privileged structural backbone in new drug design and discovery. Majorly, 2,5- and 2,6-disubstituted benzimidazole derivatives shown to induce significant antiTB potential. To seek more insights on this unique feature of benzimidazole candidates, there is an urgency to assemble the recent advances in this promising area. This review presents an overview of the recent advancements and focuses on the structural features responsible for unique antiTB applications and compiled published reports on benzimidazole derivatives emphasizing on different approaches employed for their syntheses in order to help medicinal and clinical chemists in designing next generation, yet effective and safer antiTB candidates. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Determining the band alignment of TbAs:GaAs and TbAs:In 0.53Ga 0.47As

DOE PAGES

Bomberger, Cory C.; Vanderhoef, Laura R.; Rahman, Abdur; ...

2015-09-10

Here, we propose and systematically justify a band structure for TbAs nanoparticles in GaAs and In 0.53Ga 0.47As host matrices. Moreover, fluence-dependent optical-pump terahertz-probe measurements suggest the TbAs nanoparticles have a band gap and provide information on the carrier dynamics, which are determined by the band alignment. Spectrophotometry measurements provide the energy of optical transitions in the nanocomposite systems and reveal a large blue shift in the absorption energy when the host matrix is changed from In 0.53Ga 0.47As to GaAs. Finally, Hall data provides the approximate Fermi level in each system. From this data, we deduce that the TbAs:GaAsmore » system forms a type I (straddling) heterojunction and the TbAs:In 0.53Ga 0.47As system forms a type II (staggered) heterojunction.« less

Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog

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

Volkov, Oleg A.; Kinch, Lisa; Ariagno, Carson

Catalytically inactive enzyme paralogs occur in many genomes. Some regulate their active counterparts but the structural principles of this regulation remain largely unknown. We report X-ray structures ofTrypanosoma brucei S-adenosylmethionine decarboxylase alone and in functional complex with its catalytically dead paralogous partner, prozyme. We show monomericTbAdoMetDC is inactive because of autoinhibition by its N-terminal sequence. Heterodimerization with prozyme displaces this sequence from the active site through a complex mechanism involving acis-to-transproline isomerization, reorganization of a β-sheet, and insertion of the N-terminal α-helix into the heterodimer interface, leading to enzyme activation. We propose that the evolution of this intricate regulatory mechanismmore » was facilitated by the acquisition of the dimerization domain, a single step that can in principle account for the divergence of regulatory schemes in the AdoMetDC enzyme family. These studies elucidate an allosteric mechanism in an enzyme and a plausible scheme by which such complex cooperativity evolved.« less

Stochastic agent-based modeling of tuberculosis in Canadian Indigenous communities.

PubMed

Tuite, Ashleigh R; Gallant, Victor; Randell, Elaine; Bourgeois, Annie-Claude; Greer, Amy L

2017-01-13

In Canada, active tuberculosis (TB) disease rates remain disproportionately higher among the Indigenous population, especially among the Inuit in the north. We used mathematical modeling to evaluate how interventions might enhance existing TB control efforts in a region of Nunavut. We developed a stochastic, agent-based model of TB transmission that captured the unique household and community structure. Evaluated interventions included: (i) rapid treatment of active cases; (ii) rapid contact tracing; (iii) expanded screening programs for latent TB infection (LTBI); and (iv) reduced household density. The outcomes of interest were incident TB infections and total diagnosed active TB disease over a 10- year time period. Model-projected incidence in the absence of additional interventions was highly variable (range: 33-369 cases) over 10 years. Compared to the 'no additional intervention' scenario, reducing the time between onset of active TB disease and initiation of treatment reduced both the number of new TB infections (47% reduction, relative risk of TB = 0.53) and diagnoses of active TB disease (19% reduction, relative risk of TB = 0.81). Expanding general population screening was also projected to reduce the burden of TB, although these findings were sensitive to assumptions around the relative amount of transmission occurring outside of households. Other potential interventions examined in the model (school-based screening, rapid contact tracing, and reduced household density) were found to have limited effectiveness. In a region of northern Canada experiencing a significant TB burden, more rapid treatment initiation in active TB cases was the most impactful intervention evaluated. Mathematical modeling can provide guidance for allocation of limited resources in a way that minimizes disease transmission and protects population health.

Electroluminescence color tuning between green and red from metal-oxide-semiconductor devices fabricated by spin-coating of rare-earth (terbium + europium) organic compounds on silicon

NASA Astrophysics Data System (ADS)

Matsuda, Toshihiro; Hattori, Fumihiro; Iwata, Hideyuki; Ohzone, Takashi

2018-04-01

Color tunable electroluminescence (EL) from metal-oxide-semiconductor devices with the rare-earth elements Tb and Eu is reported. Organic compound liquid sources of (Tb + Ba) and Eu with various Eu/Tb ratios from 0.001 to 0.4 were spin-coated on an n+-Si substrate and annealed to form an oxide insulator layer. The EL spectra had only peaks corresponding to the intrashell Tb3+/Eu3+ transitions in the spectral range from green to red, and the intensity ratio of the peaks was appropriately tuned using the appropriate Eu/Tb ratios in liquid sources. Consequently, the EL emission colors linearly changed from yellowish green to yellowish orange and eventually to reddish orange on the CIE chromaticity diagram. The gate current +I G current also affected the EL colors for the medium-Eu/Tb-ratio device. The structure of the surface insulator films analyzed by cross-sectional transmission electron microscopy (TEM), X-ray diffraction (XRD) analysis, and X-ray photoelectron spectroscopy (XPS) has four layers, namely, (Tb4O7 + Eu2O3), [Tb4O7 + Eu2O3 + (Tb/Eu/Ba)SiO x ], (Tb/Eu/Ba)SiO x , and SiO x -rich oxide. The EL mechanism proposed is that electrons injected from the Si substrate into the SiO x -rich oxide and Tb/Eu/Ba-silicate layers become hot electrons accelerated in a high electric field, and then these hot electrons excite Tb3+ and Eu3+ ions in the Tb4O7/Eu2O3 layers resulting in EL emission from Tb3+ and Eu3+ intrashell transitions.

Treatment compliance and challenges among tuberculosis patients across selected health facilities in Osun State Nigeria.

PubMed

Ajao, K O; Ogundun, O A; Afolabi, O T; Ojo, T O; Atiba, B P; Oguntunase, D O

2014-12-01

Tuberculosis (TB) is a major public health problem in the world and Africa has approximately one quarter of the world's cases. One of the greatest challenges facing most TB programmes is the non-compliance to TB treatment among TB patients. This study aimed at determining the challenges of management of tuberculosis (TB) across selected Osun State health facilities. The study employed a descriptive cross-sectional design. A semi-structured questionnaire was used to collect data from 102 TB patients in the health facilities. The instrument measured socio-demographic variables, patient related factors, socio-economic variables, health care system related factors to TB disease and treatment. Data were analysed and summarized using descriptive and inferential statistics. Statistical significance was placed at p < 0.05. TB patients who had no formal education (χ2 = 12.941, p < 0.05), who were smoking during treatment (χ2 = 13.194, p < 0.001), who consumed alcohol during TB treatment (χ2 = 6.371, p < 0.05) and those who were HIV positive (χ2 = 23.039, p < 0.001) significantly failed to comply with TB treatment. TB patients who waited for one hour or more at heath facilities (χ2 = 21.761, p < 0.001), who reported that TB treatment should be stopped before six month (χ2 = 9.804, p < 0.05) or when patient felt better (χ2 = 35.185, p < 0.001) and travelled for 10 km or more (χ2 = 13.610, p < 0.001) significantly failed to comply with TB treatment. This study concluded that non-compliance rate to tuberculosis treatment among TB patients in this study is high. Both health facility and patient-related factors were largely responsible.

Assessing the consequences of stigma for tuberculosis patients in urban Zambia.

PubMed

Cremers, Anne Lia; de Laat, Myrthe Manon; Kapata, Nathan; Gerrets, Rene; Klipstein-Grobusch, Kerstin; Grobusch, Martin Peter

2015-01-01

Stigma is one of the many factors hindering tuberculosis (TB) control by negatively affecting hospital delay and treatment compliance. In Zambia, the morbidity and mortality due to TB remains high, despite extended public health attempts to control the epidemic and to diminish stigma. To enhance understanding of TB-related stigmatizing perceptions and to describe TB patients' experiences of stigma in order to point out recommendations to improve TB policy. We conducted a mixed method study at Kanyama clinic and surrounding areas, in Lusaka, Zambia; structured interviews with 300 TB patients, multiple in-depth interviews with 30 TB patients and 10 biomedical health workers, 3 focus group discussions with TB patients and treatment supporters, complemented by participant observation and policy analysis of the TB control program. Predictors of stigma were identified by use of multivariate regression analyses; qualitative analysis of the in-depth interviews, focus group discussions and participant observation was used for triangulation of the study findings. We focused on the 138/300 patients that described TB-related perceptions and attitudes, of whom 113 (82%) reported stigma. Stigma provoking TB conceptions were associated with human immunodeficiency virus (HIV)-infection, alleged immoral behaviour, (perceived) incurability, and (traditional) myths about TB aetiology. Consequences of stigma prevailed both among children and adults and included low self-esteem, insults, ridicule, discrimination, social exclusion, and isolation leading to a decreased quality of life and social status, non-disclosure, and/or difficulties with treatment compliance and adherence. Women had significantly more stigma-related problems than men. The findings illustrate that many TB patients faced stigma-related issues, often hindering effective TB control and suggesting that current efforts to reduce stigma are not yet optimal. The content and implementation of sensitization programs should be improved and more emphasis needs to be placed on women and children.

Profiling persistent tubercule bacilli from patient sputa during therapy predicts early drug efficacy.

PubMed

Honeyborne, Isobella; McHugh, Timothy D; Kuittinen, Iitu; Cichonska, Anna; Evangelopoulos, Dimitrios; Ronacher, Katharina; van Helden, Paul D; Gillespie, Stephen H; Fernandez-Reyes, Delmiro; Walzl, Gerhard; Rousu, Juho; Butcher, Philip D; Waddell, Simon J

2016-04-07

New treatment options are needed to maintain and improve therapy for tuberculosis, which caused the death of 1.5 million people in 2013 despite potential for an 86 % treatment success rate. A greater understanding of Mycobacterium tuberculosis (M.tb) bacilli that persist through drug therapy will aid drug development programs. Predictive biomarkers for treatment efficacy are also a research priority. Genome-wide transcriptional profiling was used to map the mRNA signatures of M.tb from the sputa of 15 patients before and 3, 7 and 14 days after the start of standard regimen drug treatment. The mRNA profiles of bacilli through the first 2 weeks of therapy reflected drug activity at 3 days with transcriptional signatures at days 7 and 14 consistent with reduced M.tb metabolic activity similar to the profile of pre-chemotherapy bacilli. These results suggest that a pre-existing drug-tolerant M.tb population dominates sputum before and after early drug treatment, and that the mRNA signature at day 3 marks the killing of a drug-sensitive sub-population of bacilli. Modelling patient indices of disease severity with bacterial gene expression patterns demonstrated that both microbiological and clinical parameters were reflected in the divergent M.tb responses and provided evidence that factors such as bacterial load and disease pathology influence the host-pathogen interplay and the phenotypic state of bacilli. Transcriptional signatures were also defined that predicted measures of early treatment success (rate of decline in bacterial load over 3 days, TB test positivity at 2 months, and bacterial load at 2 months). This study defines the transcriptional signature of M.tb bacilli that have been expectorated in sputum after two weeks of drug therapy, characterizing the phenotypic state of bacilli that persist through treatment. We demonstrate that variability in clinical manifestations of disease are detectable in bacterial sputa signatures, and that the changing M.tb mRNA profiles 0-2 weeks into chemotherapy predict the efficacy of treatment 6 weeks later. These observations advocate assaying dynamic bacterial phenotypes through drug therapy as biomarkers for treatment success.

Substrate temperature effect on the structural anisotropy in amorphous Tb-Fe films

NASA Astrophysics Data System (ADS)

Harris, V. G.; Hellman, F.; Elam, W. T.; Koon, N. C.

1993-05-01

Using extended x-ray absorption fine structures (EXAFS) measurements we have investigated the atomic environment around the Fe atom in a series of amorphous Tb0.26Fe0.74 films having different magnetic anisotropy energies owing to different deposition temperatures. The polarization properties of synchrotron radiation allowed the separate study of structure parallel and perpendicular to the sample plane. An anisotropy between these two structures was observed. Modeling results indicate this anisotropy is due to anisotropic pair correlations where the Fe-Fe pairs are statistically preferred in-plane and the Fe-Tb pairs out-of-plane. The amplitude of this anisotropy scales with both the substrate temperature and the magnetic anisotropy energy. A ≊1% in-plane compression of the Fe-Fe distance was measured between the in-plane and out-of-plane structure of the sample grown at 77 K. This sample had no detectable local chemical anisotropy suggesting that intrinsic stress plays an important role in determining its magnetic anisotropy.

Measurement and analysis of electronic energy transfer between Tb 3+ and Eu 3+ ions in Cs 2NaY 1-x-y Tb xEu yCl 6

NASA Astrophysics Data System (ADS)

Moran, Diane M.; May, P. Stanley; Richardson, F. S.

1994-08-01

Electronic energy-transfer processes between Tb 3+5D 4) and Eu 3+ ( 7F 0, 7F 1) ions in crystalline Cs 2NaY 1-x-yTb xEu yCl 6 compounds are examined over a wide range of relative Tb 3+ and Eu 3+ concentrations (at sample temperature of 77 and 295 K). In these systems, the Tb 3+ and Eu 3+ ions are located at centrosymmetric (O h) sites surrounded by six Cl - ions, and the minimum distance between these sites is ≈ 7.6 Å. The host lattice has a cubic structure (space group O h5-Fm3m), and the phonon spectrum of this lattice has a cut-off frequency of ≈ 300 cm -1. The optical spectra of Tb 3+ and Eu 3+ in Cs 2NaYCl 6 exhibit relatively sparse line structures, consisting almost entirely of magnetic-dipole origin lines and one-phonon-assisted electric-dipole vibronic lines that reflect O h selection rules and have relatively low oscillator strenghts. Overlap between Tb 3+ ( 5D 4) emission and Eu 3+ ( 7F 0, 7F 1) absorption spectra occurs only within the Tb 3+ ( 5D 4 → 7 F 4 and Eu 3+ ( 7F 0, 7F 1 → 5D 0 transition regions, and resonances between individual lines in these regions are used to identify possible pathways for Tb 3+ ( 5D 4)-to-Eu 3+ ( 7F 0, 7F 1) energy transfer. Rates of energy transfer are determined from time-resolved Tb 3+ ( 5D 4) luminescence intersity measurements, analyzed in terms of two different models for representing donor (Tb 3+)-acceptor (Eu 3+) site distributions in Cs 2NaY 1-x-yTb xEu yCl 6 systems. In one model, donor-accepator site distances are represented by a continuous radial distribution function, whereas in the second model, these distances are represented by a discrete distribution function. Both models are used to analyze donor luminescence decay data in terms of rate parameters that reflect specific mechanistic contributions to electronic energy transfer. Both electron-exchange and multipole-multipole mechanisms are considered in the analyses. Results from these analyses, combined with spectral overlap considerations and comparisons of 77 versus 295 K rate data, suggest an electric-quadrupole/electric-dipole mechanism in which a 5D 4(T 1g → 7F 4(T 1g) electric-quadrupole transition on Tb 3+ excites a 7F 0(A 1g) + v4(t 1u → 5D 0(A 1g) electric-dipole (vibronic) transition on Eu 3+. Rate data obtained on systems of stoichiometric formulae Cs 2NaY 0.95-xTb xEu 0.05Cl 6 show that Tb 3+( 5D 4)- to-Eu 3+ ( 7F 0, 7F 1) energy-transfer rates a Tb 3+-Tb 3+ energy-migration processes when tx > 0.05. Direct calculations of Tb 3+ ( 5D 4)-Eu 3+ ( 7F 0, 7F 1) and Tb 3+ ( 5D 4-Tb 3+ ( 7F 6) multipole-multipole interaction parameters are performed, and the parameters obtained from these calculations are compared to those derived from parametric fits of experimentally observed rate data. Discrepancies between calculated and ovserved rate parameters are large, and possible explanations for these discrepancies are discussed.

Nitroimidazoles, Quinolones and Oxazolidinones as Fluorine Bearing Antitubercular Clinical Candidates.

PubMed

Patel, Rahul V; Keum, Young-Soo; Park, Se Won

2015-01-01

Tuberculosis is a leading killer of lives worldwide and the global curse of multi-drug resistant tuberculosis is attaining really dangerous levels. Synergistic interaction of HIV and TB is the twin epidemics in resource-limited countries as each potentiate progression of the other. The increasing emergence of MDR-TB and XDR-TB place an immense burden for the treatment of TB with currently available drugs. The situation urgently demands for the discovery of new drugs with novel mode of action and differs in structural features in order to overcome resistance appears in conventional TB therapeutics. The present report covers the discovery of three classes of antituberculosis drugs, Nitroimidazoles, Quinolones and Oxazolidinones, undergoing clinical development with fluorine atom in their structures. Highly electronegative fluorine atom plays a signature role in advancing medicinal innovations as it existence in the drug compounds critically influences metabolic stability and lipophilicity thereby delaying its elimination by the body which results into a long term in vivo efficiency of the drug. Presence of fluorine atom(s) in the drug structures described in this report, has been associated with the several fold increase in the overall potency of the compound as demonstrated since the early discoveries. 6 Fluorinated derivatives from these three classes as pretomanid, delamanid, moxifloxacin, gatifloxacin, linezolid and sutezolid have been discussed with their antituberculosis effects, mode of action, chemical synthetic routes and results of clinical studies.

Energy transfer and color tunable emission in Tb3+,Eu3+ co-doped Sr3LaNa(PO4)3F phosphors.

PubMed

Li, Shuo; Guo, Ning; Liang, Qimeng; Ding, Yu; Zhou, Huitao; Ouyang, Ruizhuo; Lü, Wei

2018-02-05

A group of color tunable Sr 3 LaNa(PO 4 ) 3 F:Tb 3+ ,Eu 3+ phosphors were prepared by conventional high temperature solid state method. The phase structures, luminescence properties, fluorescence lifetimes and energy transfer were investigated in detail. Under 369nm excitation, owing to efficient energy transfer of Tb 3+ →Eu 3+ , the emission spectra both have green emission of Tb 3+ and red emission of Eu 3+ . An efficient energy transfer occur in Tb 3+ , Eu 3+ co-doped Sr 3 LaNa(PO 4 ) 3 F phosphors. The most possible mechanism of energy transfer is dipole-dipole interaction by Dexter's theoretical model. The energy transfer of Tb 3+ and Eu 3+ was confirmed by the variations of emission and excitation spectra and Tb 3+ /Eu 3+ decay lifetimes in Sr 3 LaNa(PO 4 ) 3 F:Tb 3+ ,Eu 3+ . The color tone can tuned from yellowish-green through yellow and eventually to reddish-orange with fixed Tb 3+ content by changing Eu 3+ concentrations. The results show that the prepared Tb 3+ , Eu 3+ co-doped color tunable Sr 3 LaNa(PO 4 ) 3 F phosphor can be used for white LED. Copyright © 2017 Elsevier B.V. All rights reserved.

First report of a complete genome sequence for a begomovirus infecting Jatropha gossypifolia in the Americas.

PubMed

Simmonds-Gordon, R N; Collins-Fairclough, A M; Stewart, C S; Roye, M E

2014-10-01

Jatropha gossypifolia is a weed that is commonly found with yellow mosaic symptoms growing along the roadside and in close proximity to cultivated crops in many farming communities in Jamaica. For the first time, the complete genome sequence of a new begomovirus, designated jatropha mosaic virus-[Jamaica:Spanish Town:2004] (JMV-[JM:ST:04]), was determined from field-infected J. gossypifolia in the western hemisphere. DNA-A nucleotide sequence comparisons showed closest identity (84 %) to two tobacco-infecting viruses from Cuba, tobacco mottle leaf curl virus-[Cuba:Sancti Spiritus:03] (TbMoLCV-[CU:SS:03]) and tobacco leaf curl Cuba virus-[Cuba:Taguasco:2005] (TbLCuCUV-[CU:Tag:05]), and two weed-infecting viruses from Cuba and Jamaica, Rhynchosia rugose golden mosaic virus-[Cuba:Camaguey:171:2009] (RhRGMV- [CU:Cam:171:09]) and Wissadula golden mosaic St. Thomas virus-[Jamaica:Albion:2005] (WGMSTV-[JM:Alb:05]). Phylogenetic analysis revealed that JMV-[JM:ST:04] is most closely related to tobacco and tomato viruses from Cuba and WGMSTV-[JM:Alb:05], a common malvaceous-weed-infecting virus from eastern Jamaica, and that it is distinct from begomoviruses infecting Jatropha species in India and Nigeria.

The Deep-Sea Polyextremophile Halobacteroides lacunaris TB21 Rough-Type LPS: Structure and Inhibitory Activity towards Toxic LPS

PubMed Central

Di Lorenzo, Flaviana; Palmigiano, Angelo; Paciello, Ida; Pallach, Mateusz; Garozzo, Domenico; Bernardini, Maria-Lina; La Cono, Violetta; Yakimov, Michail M.; Molinaro, Antonio; Silipo, Alba

2017-01-01

The structural characterization of the lipopolysaccharide (LPS) from extremophiles has important implications in several biomedical and therapeutic applications. The polyextremophile Gram-negative bacterium Halobacteroides lacunaris TB21, isolated from one of the most extreme habitats on our planet, the deep-sea hypersaline anoxic basin Thetis, represents a fascinating microorganism to investigate in terms of its LPS component. Here we report the elucidation of the full structure of the R-type LPS isolated from H. lacunaris TB21 that was attained through a multi-technique approach comprising chemical analyses, NMR spectroscopy, and Matrix-Assisted Laser Desorption Ionization (MALDI) mass spectrometry. Furthermore, cellular immunology studies were executed on the pure R-LPS revealing a very interesting effect on human innate immunity as an inhibitor of the toxic Escherichia coli LPS. PMID:28653982

Risk Factors Associated with MDR-TB at the Onset of Therapy among New Cases Registered with the RNTCP in Mumbai, India

PubMed Central

Atre, Sachin R.; D’Souza, Desiree T. B.; Vira, Tina S.; Chatterjee, Anirvan; Mistry, Nerges F.

2014-01-01

Background Multidrug-resistant TB (MDR-TB) has emerged as a major threat to global TB control efforts in recent years. Facilities for its diagnosis and treatment are limited in many high-burden countries, including India. In hyper-endemic areas like Mumbai, screening for newly diagnosed cases at a higher risk of acquiring MDR-TB is necessary, for initiating appropriate and timely treatment, to prevent its further spread. Objective To assess risk factors associated with MDR-TB among Category I, new sputum smear-positive cases, at the onset of therapy. Materials and Methods The study applied an unmatched case-control design for 514 patients (106 cases with MDR-TB strains and 408 controls with non-MDR-TB strains). The patients were registered with the Revised National Tuberculosis Control Program (RNTCP) in four selected wards of Mumbai during April 2004-January 2007. Data were collected through semi-structured interviews and drug susceptibility test results. Results Multivariate analysis indicated that infection with the Beijing strain (OR = 3.06; 95% C.I. = 1.12-8.38; P = 0.029) and female gender (OR = 1.68; 95% C.I. = 1.02-2.87; P = 0.042) were significant predictors of MDR-TB at the onset of therapy. Conclusion The study provides a starting point to further examine the usefulness of these risk factors as screening tools in identifying individuals with MDR-TB, in settings where diagnostic and treatment facilities for MDR-TB are limited. PMID:21727675

Detention of People Lost to Follow-Up on TB Treatment in Kenya

PubMed Central

Restoy, Enrique; Kibuchi, Evaline; Holland, Paula; Harries, Anthony D.

2016-01-01

Abstract Adherence to treatment is a key element for global TB control. Public health laws can be used to enforce isolation, adherence, and completion of TB treatment. However, the practical application of public health laws can potentially range from voluntary measures to involuntary detention approaches. This paper explores the potential risks and impacts of using detention approaches to enforce TB treatment adherence. In August 2015, we conducted a literature search regarding the application of public health laws to enforce adherence to TB treatment globally, and specifically in Kenya. Texts were analyzed using narrative synthesis. Results indicated that in Kenya, people lost to follow-up on TB treatment were frequently detained in prisons. However, incarceration and detention approaches curtail the rights to health, informed consent, privacy, freedom from non-consensual treatment, freedom from inhumane and degrading treatment, and freedom of movement of people lost to follow-up. Detention could also worsen social inequalities and lead to a paradoxical increase in TB incidence. We suggest the incorporation of less intrusive solutions in legislation and policies. These include strengthening health systems to reduce dependency on prisons as isolation spaces, decentralizing TB treatment to communities, enhancing treatment education, revising the public health laws, and addressing socioeconomic and structural determinants associated with TB incidence and loss to follow-up. PMID:27780998

[Tuberculosis patient disease knowledge, attitudes and behavioral intentions: the impact of individualized counseling].

PubMed

Wu, Shiau-Jiun; Lu, Po-Liang; Chen, Yen-Hsu; Pan, Hui-Juan; Feng, Ming-Chu

2011-12-01

The Taiwan government currently promotes a case management approach to tuberculosis (TB) treatment to address the growing number of TB and multiple drug-resistant TB cases in Taiwan. The approach aims to improve medical follow-up and monitor quality of care. The efficacy of this case management approach has yet to be evaluated. The current study was designed to evaluate the effect of individualized case manager counseling on TB patient disease knowledge, attitudes, and behavioral intention. This study employed a one-group pretest-posttest quasi-experimental design. Participants first answered an initial questionnaire survey including three structured scales that addressed, respectively, the facets of disease knowledge, attitudes, and behavioral intention. TB case managers then delivered two- stage counseling to participants based on assessed individual needs and outstanding issues identified in questionnaire answers. A second questionnaire survey was administered 30~42 days after the intervention. Data on a total of 96 TB patients were collected. Key study findings were (1) individualized counseling significantly improved TB patient disease knowledge (p < .001) and (2) TB patient attitudes correlated significantly and positively with behavior intention (p < .001). Individualized counseling provided during the early stages of TB helps elevate patient awareness of the importance of treatment, enhances compliance and increases the cure rate.

Electrocatalysis of carbon black- or poly(diallyldimethylammonium chloride)-functionalized activated carbon nanotubes-supported Pd-Tb towards methanol oxidation in alkaline media

NASA Astrophysics Data System (ADS)

Wang, Li; Wang, Yi; Li, An; Yang, Yunshang; Tang, Qinghu; Cao, Hongbin; Qi, Tao; Li, Changming

2014-07-01

The Pd-Tb/C catalysts with different Pd/Tb ratios were synthesized by a simple simultaneous reduction reaction with sodium borohydride in aqueous solution. The structure and morphology of those catalysts had been characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The electrocatalytic performance of those catalysts for methanol oxidation in alkaline media was investigated using cyclic voltammetry (CV), linear sweep voltammetry (LSV) and CO stripping experiments. It is found that the 20%Pd-1%Tb/C catalyst has a higher catalytic activity than the 20%Pd/C catalyst, but the effect of Tb cannot be explained by a bi-functional mechanism. According to the X-Ray photoelectron spectroscopy (XPS) analyses, it is suggested that the higher content of metallic Pd caused by the addition of Tb contributes to the better catalytic activity of 20%Pd-1%Tb/C. Based on the good electrocatalytic performance of 20%Pd-1%Tb/C, the 20%Pd-1%Tb catalyst supported on poly(diallyldimethylammonium chloride) (PDDA)-functionalized activated carbon nanotubes was prepared, and it exhibits a better catalytic activity. The improvement mainly results from the further increase of metallic Pd due to the presence of PDDA.

Cyberinfrastructure for the NSF Ocean Observatories Initiative

NASA Astrophysics Data System (ADS)

Orcutt, J. A.; Vernon, F. L.; Arrott, M.; Chave, A.; Krueger, I.; Schofield, O.; Glenn, S.; Peach, C.; Nayak, A.

2007-12-01

The Internet today is vastly different than the Internet that we knew even five years ago and the changes that will be evident five years from now, when the NSF Ocean Observatories Initiative (OOI) prototype has been installed, are nearly unpredictable. Much of this progress is based on the exponential growth in capabilities of consumer electronics and information technology; the reality of this exponential behavior is rarely appreciated. For example, the number of transistors on a square cm of silicon will continue to double every 18 months, the density of disk storage will double every year, and network bandwidth will double every eight months. Today's desktop 2TB RAID will be 64TB and the 10Gbps Regional Scale Network fiber optical connection will be running at 1.8Tbps. The same exponential behavior characterizes the future of genome sequencing. The first two sequences of composites of individuals' genes cost tens of millions of dollars in 2001. Dr. Craig Venter just published a more accurate complete human genome (his own) at a cost on the order of 100,000. The J. Craig Venter Institute has provided support for the X Prize for Genomics offering 10M to the first successful sequencing of a human genome for $1,000. It's anticipated that the prize will be won within five years. Major advances in technology that are broadly viewed as disruptive or revolutionary rather than evolutionary will often depend upon the exploitation of exponential expansions in capability. Applications of these ideas to the OOI will be discussed. Specifically, the agile ability to scale cyberinfrastructure commensurate with the exponential growth of sensors, networks and computational capability and demand will be described.

[Historical development of tuberculosis since Robert Koch's discovery of the tubercle bacillus in 1882].

PubMed

Murray, J F

2007-12-01

Robert Koch's single-handed discovery of M. tuberculosis, one of the most gigantic scientific accomplishments of all times, provided the necessary foundation for subsequent investigative breakthroughs that have made it possible for experts to begin to contemplate the ultimate eradication of TB: the dreaded pestilence that for centuries was the greatest cause of death in the world. Further important milestones in the fight against TB were the discovery of X-rays, the development of BCG vaccination, the introduction of chemotherapy and chemoprophylaxis, and deciphering the genome of Mycobacterium tuberculosis. First of all, though, we must find a way to deal with the recent resurgence of the disease in the poor countries of sub-Saharan Africa, which is being fueled by another scourge, HIV/AIDS. And there is also the global problem of worsening anti-TB drug resistance. Eradication is conceivable and a worthy goal, but, I suspect, we will need to wait for another one or two additional "milestones" to help us along before the long-awaited nirvana can finally occur.

The intermembrane space protein Erv1 of Trypanosoma brucei is essential for mitochondrial Fe-S cluster assembly and operates alone.

PubMed

Haindrich, Alexander C; Boudová, Michala; Vancová, Marie; Diaz, Priscila Peña; Horáková, Eva; Lukeš, Julius

2017-06-01

Sulfhydryl oxidase Erv1 is a ubiquitous and conserved protein of the mitochondrial intermembrane space that plays a role in the transport of small sulfur-containing proteins. In higher eukaryotes, Erv1 interacts with the mitochondrial import protein Mia40. However, Trypanosoma brucei lacks an obvious Mia40 homologue in its genome. Here we show by tandem affinity purification and mass spectrometry that in this excavate protist, Erv1 functions without a Mia40 homologue and most likely any other interaction partner. Down-regulation of TbErv1 caused a reduction of the mitochondrial membrane potential already within 24h to less than 50% when compared with control cells. The depletion of TbErv1 was accompanied by accumulation of trCOIV precursor, with a concomitant reduction of aconitase activity both in the cytosol and mitochondrion. Overall, TbErv1 seems to have a role in the mitochondrial translocation and Fe-S cluster assembly in the organelle. Copyright © 2017 Elsevier B.V. All rights reserved.

A first insight into high prevalence of undiagnosed smear-negative pulmonary tuberculosis in Northern Ethiopian prisons: implications for greater investment and quality control.

PubMed

Biadglegne, Fantahun; Rodloff, Arne C; Sack, Ulrich

2014-01-01

Tuberculosis (TB) transmission in prisons poses significant risks to inmates as well as the general population. Currently, there are no data on smear-negative pulmonary TB cases in prisons and by extension no data on the impact such cases have on TB incidence. This study was designed to obtain initial data on the prevalence of smear-negative cases of TB in prisons as well as preliminary risk factor analysis for such TB cases. This cross-sectional survey was conducted in November 2013 at eight main prisons located in the state of Amhara, Ethiopia. Interviews using a structured and pretested questionnaire were done first to identify symptomatic prisoners. Three consecutive sputum samples were collected and examined using acid fast bacilli (AFB) microscopy at the point of care. All smear-negative sputum samples were taken for culture and Xpert testing. Descriptive and multivariate analysis was done using SPSS version 16. Overall the prevalence of smear-negative pulmonary TB cases in the study prisons was 8% (16/200). Using multivariate analysis, a contact history to TB patients in prison, educational level, cough and night sweating were found to be predictors of TB positivity among smear-negative pulmonary TB cases (p ≤ 0.05). In the studied prisons, high prevalence of undiagnosed TB cases using AFB microscopy was documented, which is an important public health concern that urgently needs to be addressed. Furthermore, patients with night sweating, non-productive cough, a contact history with TB patients and who are illiterate merit special attention, larger studies are warranted in the future to assess the associations more precisely. Further studies are also needed to examine TB transmission dynamics by patients with smear-negative pulmonary TB in a prison setting.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement.

PubMed

van Hest, N A; Aldridge, R W; de Vries, G; Sandgren, A; Hauer, B; Hayward, A; Arrazola de Oñate, W; Haas, W; Codecasa, L R; Caylà, J A; Story, A; Antoine, D; Gori, A; Quabeck, L; Jonsson, J; Wanlin, M; Orcau, Å; Rodes, A; Dedicoat, M; Antoun, F; van Deutekom, H; Keizer, St; Abubakar, I

2014-03-06

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Community engagement for paediatric MDR-TB clinical trials: principles to support ethical trial implementation.

PubMed

Hoddinott, G; Staples, S; Brown, R; Simwinga, M; Mubekapi-Musadaidzwa, C; Hesseling, A C; Hendricks, G; De Koker, P; McKenna, L

2018-05-01

The paediatric tuberculosis (TB) prevention and treatment landscape is moving into a new and exciting era, with knowledge from clinical trials offering real benefit to children. Community engagement is key to optimising the success of these trials. However, the clinical profile, epidemiology and social perceptions for paediatric multidrug-resistant TB (MDR-TB) complicate the operationalisation of this community engagement. We reflect on a diversity of recent experiences attempting to implement this type of research and the community engagement around it. We describe four recommendations and argue that these should guide the implementation of the community engagement agenda in the new landscape of paediatric MDR-TB clinical trials. Specifically, we argue for 1) dynamic, long-term continuity in community engagement platforms; 2) tiers of TB and research literacy; 3) multiple separate and joint platforms for holding 'stakes'; and 4) addressing the social/structural implications of family participation. We conclude that community-level stakeholders, such as health workers, parents and children, are willing to collaborate in paediatric MDR-TB clinical trials. Using these recommendations, there is considerable opportunity for effective community engagement in this new era of paediatric MDR-TB research.

Volumetric topological analysis: a novel approach for trabecular bone classification on the continuum between plates and rods.

PubMed

Saha, Punam K; Xu, Yan; Duan, Hong; Heiner, Anneliese; Liang, Guoyuan

2010-11-01

Trabecular bone (TB) is a complex quasi-random network of interconnected plates and rods. TB constantly remodels to adapt to the stresses to which it is subjected (Wolff's Law). In osteoporosis, this dynamic equilibrium between bone formation and resorption is perturbed, leading to bone loss and structural deterioration. Both bone loss and structural deterioration increase fracture risk. Bone's mechanical behavior can only be partially explained by variations in bone mineral density, which led to the notion of bone structural quality. Previously, we developed digital topological analysis (DTA) which classifies plates, rods, profiles, edges, and junctions in a TB skeletal representation. Although the method has become quite popular, a major limitation of DTA is that it provides only hard classifications of different topological entities, failing to distinguish between narrow and wide plates. Here, we present a new method called volumetric topological analysis (VTA) for regional quantification of TB topology. At each TB location, the method uniquely classifies its topology on the continuum between perfect plates and perfect rods, facilitating early detections of TB alterations from plates to rods according to the known etiology of osteoporotic bone loss. Several new ideas, including manifold distance transform, manifold scale, and feature propagation have been introduced here and combined with existing DTA and distance transform methods, leading to the new VTA technology. This method has been applied to multidetector computed tomography (CT) and micro-computed tomography ( μCT) images of four cadaveric distal tibia and five distal radius specimens. Both intra- and inter-modality reproducibility of the method has been examined using repeat CT and μCT scans of distal tibia specimens. Also, the method's ability to predict experimental biomechanical properties of TB via CT imaging under in vivo conditions has been quantitatively examined and the results found are very encouraging.

Structural Forces and the Production of TB-related Stigma among Haitians in Two Contexts

PubMed Central

Coreil, Jeannine; Mayard, Gladys; Simpson, Kelly M; Lauzardo, Michael; Zhu, Yiliang; Weiss, Mitchell

2012-01-01

In recent years renewed interest in health-related stigma has underscored the importance of better understanding the structural underpinnings of stigma processes. This study investigated the influence of sociocultural context on perceived components of tuberculosis-related stigma in non-affected persons by comparing Haitians living in South Florida, USA, with Haitians residing in Léogane Commune, Haiti. Using the methods of cultural epidemiology, a two-phase study based on fieldwork between 2004–07 collected ethnographic data on the cultural context and components of tuberculosis (TB) stigma, and administered a stigma scale developed specifically for these populations. Thematic analysis of stigma components expressed in interviews, focus groups and observation revealed commonalities as well as distinctive emphases of TB stigma in the two comparison groups. Factor analyses of stigma scale scores confirmed the thematic differences revealed in ethnographic findings and highlight the influence of political and economic factors in shaping the meaning and experience of illness. Perceived components of TB stigma among Haitians in South Florida incorporated aspects of Haitian identity as a negatively stereotyped minority community within the larger society, while in Haiti, stigma was associated primarily with poverty, malnutrition, and HIV co-infection. Discussion of findings focuses on the social production of perceived and anticipated stigma as it is influenced by structural forces including the influences of politics, economics, institutional policies, and health service delivery structures. The findings also demonstrate the value of a transnational framework encompassing both sending and receiving countries for understanding TB related stigma in immigrant communities. PMID:20724052

Flux Crystal Growth of the RE 2Ru 3Ge 5 ( RE = La, Ce, Nd, Gd, Tb) Series and Their Magnetic and Metamagnetic Transitions

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

Bugaris, Daniel E.; Malliakas, Christos D.; Bud?ko, Sergey L.

Previously synthesized only as powders, single crystals of the RE 2Ru 3Ge 5 (RE = La, Ce, Nd, Gd, Tb) series of compounds have been now been obtained from molten In. We report that these materials crystallize with the U 2Co 3Si 5-type structure in orthorhombic space group Ibam with lattice parameters a ~ 10.00-9.77 Å (La-Tb), b ~ 12.51-12.35 Å, and c ~ 5.92-5.72 Å. The structure is a three-dimensional framework consisting of RuGe 5 and RuGe 6 units, as well as Ge-Ge zigzag chains. This structure type, along with the other five (Sc 2Fe 3Si 5, Lu 2Comore » 3Si 5, Y 2Rh 3Sn 5, Yb 2Ir 3Ge 5, and Yb 2Pt 3Sn 5) to compose the RE 2T 3X 5 phase space, are discussed in depth. For the three compounds with RE = Nd, Gd, and Tb, multiple magnetic transitions and metamagnetic behavior are observed. Lastly, electronic band structure calculations performed on La 2Ru 3Ge 5 indicate that these materials have a negative band gap and are semimetallic in nature.« less

Structural and functional features of enzymes of Mycobacterium tuberculosis peptidoglycan biosynthesis as targets for drug development

PubMed Central

Moraes, Gleiciane Leal; Gomes, Guelber Cardoso; de Sousa, Paulo Robson Monteiro; Alves, Cláudio Nahum; Govender, Thavendran; Kruger, Hendrik G.; Maguire, Glenn E.M.; Lamichhane, Gyanu; Lameira, Jerônimo

2015-01-01

SUMMARY Tuberculosis (TB) is the second leading cause of human mortality from infectious diseases worldwide. The WHO reported 1.3 million deaths and 8.6 million new cases of TB in 2012. Mycobacterium tuberculosis (M. tuberculosis), the infectious bacteria that causes TB, is encapsulated by a thick and robust cell wall. The innermost segment of the cell wall is comprised of peptidoglycan, a layer that is required for survival and growth of the pathogen. Enzymes that catalyse biosynthesis of the peptidoglycan are essential and are therefore attractive targets for discovery of novel antibiotics as humans lack similar enzymes making it possible to selectively target bacteria only. In this paper, we have reviewed the structures and functions of enzymes GlmS, GlmM, GlmU, MurA, MurB, MurC, MurD, MurE and MurF from M. tuberculosis that are involved in peptidoglycan biosynthesis. In addition, we report homology modelled 3D structures of those key enzymes from M. tuberculosis of which the structures are still unknown. We demonstrated that natural substrates can be successfully docked into the active sites of the GlmS and GlmU respectively. It is therefore expected that the models and the data provided herein will facilitate translational research to develop new drugs to treat TB. PMID:25701501

Flux Crystal Growth of the RE 2Ru 3Ge 5 ( RE = La, Ce, Nd, Gd, Tb) Series and Their Magnetic and Metamagnetic Transitions

DOE PAGES

Bugaris, Daniel E.; Malliakas, Christos D.; Bud?ko, Sergey L.; ...

2017-11-21

Previously synthesized only as powders, single crystals of the RE 2Ru 3Ge 5 (RE = La, Ce, Nd, Gd, Tb) series of compounds have been now been obtained from molten In. We report that these materials crystallize with the U 2Co 3Si 5-type structure in orthorhombic space group Ibam with lattice parameters a ~ 10.00-9.77 Å (La-Tb), b ~ 12.51-12.35 Å, and c ~ 5.92-5.72 Å. The structure is a three-dimensional framework consisting of RuGe 5 and RuGe 6 units, as well as Ge-Ge zigzag chains. This structure type, along with the other five (Sc 2Fe 3Si 5, Lu 2Comore » 3Si 5, Y 2Rh 3Sn 5, Yb 2Ir 3Ge 5, and Yb 2Pt 3Sn 5) to compose the RE 2T 3X 5 phase space, are discussed in depth. For the three compounds with RE = Nd, Gd, and Tb, multiple magnetic transitions and metamagnetic behavior are observed. Lastly, electronic band structure calculations performed on La 2Ru 3Ge 5 indicate that these materials have a negative band gap and are semimetallic in nature.« less

Anomalous magnetoelastic behaviour near morphotropic phase boundary in ferromagnetic Tb{sub 1-x}Nd{sub x}Co{sub 2} system

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

Murtaza, Adil; Yang, Sen, E-mail: yang.sen@mail.xjtu.edu.cn; Zhou, Chao

2016-08-01

In this work, we report a morphotropic phase boundary (MPB) involved ferromagnetic system Tb{sub 1-x}Nd{sub x}Co{sub 2} and reveal the corresponding structural and magnetoelastic properties of this system. With high resolution synchrotron X-ray diffractometry, the crystal structure of the TbCo{sub 2}-rich side is detected to be rhombohedral and that of NdCo{sub 2}-rich side is tetragonal below their respective Curie temperatures T{sub C}. The MPB composition Tb{sub 0.35}Nd{sub 0.65}Co{sub 2} corresponds to the coexistence of the rhombohedral phase (R-phase) and tetragonal phase (T-phase). Contrary to previously reported MPB involved ferromagnetic systems, the MPB composition of Tb{sub 0.35}Nd{sub 0.65}Co{sub 2} shows minimummore » magnetization which can be understood as compensation of sublattice moments between the R-phase and the T-phase. Furthermore, magnetostriction of Tb{sub 1-x}Nd{sub x}Co{sub 2} decreases with increasing Nd concentration until x = 0.8 and then increases in the negative direction with further increasing Nd concentration; the optimum point for magnetoelastic properties lies towards the rhombohedral phase. Our work not only shows an anomalous type of ferromagnetic MPB but also provides an effective way to design functional materials.« less

MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei.

PubMed

Kim, Hee-Sook; Park, Sung Hee; Günzl, Arthur; Cross, George A M

2013-01-01

Trypanosoma brucei variant surface glycoprotein (VSG) expression is a classic example of allelic exclusion. While the genome of T. brucei contains >2,000 VSG genes and VSG pseudogenes, only one allele is expressed at the surface of each infectious trypanosome and the others are repressed. Along with recombinatorial VSG switching, allelic exclusion provides a major host evasion mechanism for trypanosomes, a phenomenon known as antigenic variation. To extend our understanding of how trypanosomes escape host immunity by differential expression of VSGs, we attempted to identify genes that contribute to VSG silencing, by performing a loss-of-silencing screen in T. brucei using a transposon-mediated random insertional mutagenesis. One identified gene, which we initially named LOS1, encodes a T. brucei MCM-Binding Protein (TbMCM-BP). Here we show that TbMCM-BP is essential for viability of infectious bloodstream-form (BF) trypanosome and is required for proper cell-cycle progression. Tandem affinity purification of TbMCM-BP followed by mass spectrometry identified four subunits (MCM4-MCM7) of the T. brucei MCM complex, a replicative helicase, and MCM8, a subunit that is uniquely co-purified with TbMCM-BP. TbMCM-BP is required not only for repression of subtelomeric VSGs but also for silencing of life-cycle specific, insect-stage genes, procyclin and procyclin-associated genes (PAGs), that are normally repressed in BF trypanosomes and are transcribed by RNA polymerase I. Our study uncovers a functional link between chromosome maintenance and RNA pol I-mediated gene silencing in T. brucei.

Screening and identification of lncRNAs as potential biomarkers for pulmonary tuberculosis.

PubMed

Chen, Zhong-Liang; Wei, Li-Liang; Shi, Li-Ying; Li, Meng; Jiang, Ting-Ting; Chen, Jing; Liu, Chang-Ming; Yang, Su; Tu, Hui-Hui; Hu, Yu-Ting; Gan, Lin; Mao, Lian-Gen; Wang, Chong; Li, Ji-Cheng

2017-12-01

Pulmonary tuberculosis (TB) is among the diseases with the highest morbidity and mortality worldwide. Effective diagnostic methods for TB are lacking. In this study, we investigated long non-coding RNAs (lncRNAs) in plasma using microarray and the potential diagnostic value of lncRNAs for TB. We found a total of 163 up-regulated lncRNAs and 348 down-regulated lncRNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and coding-noncoding co-expression (CNC) analyses showed that functions of differentially expressed lncRNAs were mainly enriched in the regulation of alpha-beta T cell activation and the T cell receptor signalling pathway. Four differentially expressed lncRNAs, NR_038221 (fold change = 3.79, P < 0.01), NR_003142 (fold change = 1.69, P < 0.05), ENST00000570366 (fold change = 3.04, P < 0.05), and ENST00000422183 (fold change = 2.11, P < 0.001), were verified using RT-qPCR. Among those, NR_038221, NR_003142, and ENST00000570366 were found to be up-regulated, while ENST00000422183 was down-regulated. The value of the area under the curve (AUC) for the diagnostic model consisting of the four lncRNAs was 0.845 (sensitivity = 79.2%, specificity = 75%). We further predicted 85 mRNAs and 404 miRNAs that potentially interact with these lncRNAs. Our study revealed the potential value of lncRNAs as biomarkers for early diagnosis of TB and the underlying mechanisms of these abnormally expressed lncRNAs in the pathogenesis of TB.

CCL3L1 copy number, CCR5 genotype and susceptibility to tuberculosis

PubMed Central

2014-01-01

Background Tuberculosis is a major infectious disease and functional studies have provided evidence that both the chemokine MIP-1α and its receptor CCR5 play a role in susceptibility to TB. Thus by measuring copy number variation of CCL3L1, one of the genes that encode MIP-1α, and genotyping a functional promoter polymorphism -2459A > G in CCR5 (rs1799987) we investigate the influence of MIP-1α and CCR5, independently and combined, in susceptibility to clinically active TB in three populations, a Peruvian population (n = 1132), a !Xhosa population (n = 605) and a South African Coloured population (n = 221). The three populations include patients with clinically diagnosed pulmonary TB, as well as other, less prevalent forms of extrapulmonary TB. Methods and results Copy number of CCL3L1 was measured using the paralogue ratio test and exhibited ranges between 0–6 copies per diploid genome (pdg) in Peru, between 0–12 pdg in !Xhosa samples and between 0–10 pdg in South African Coloured samples. The CCR5 promoter polymorphism was observed to differ significantly in allele frequency between populations (*A; Peru f = 0.67, !Xhosa f = 0.38, Coloured f = 0.48). Conclusions The case–control association studies performed however find, surprisingly, no evidence for an influence of variation in genes coding for MIP-1α or CCR5 individually or together in susceptibility to clinically active TB in these populations. PMID:24405814

Spectroscopic studies on the lanthanide sensitized luminescence and chemiluminescence properties of fluoroquinolone with different structure.

PubMed

Sun, Chunyan; Ping, Hong; Zhang, Minwei; Li, Hongkun; Guan, Fengrui

2011-11-01

Lanthanide sensitized luminescence and chemiluminescence (CL) are of great importance because of the unique spectral properties, such as long lifetime, large Stokes shifts, and narrow emission bands characteristic to lanthanide ions (Ln(3+)). With the fluoroquinolone (FQ) compounds including enoxacin (ENX), norfloxacin (NFLX), lomefloxacin (LMFX), fleroxacin (FLRX), ofloxacin (OFLX), rufloxacin (RFX), gatifloxacin (GFLX) and sparfloxacin (SPFX), the luminescence and CL properties of Tb(3+)-FQ and Eu(3+)-FQ complexes have been investigated in this contribution. Ce(4+)-SO(3)(2-) in acidic conditions was taken as the CL system and sensitized CL intensities of Tb(3+)-FQ and Eu(3+)-FQ complexes were determined by flow-injection analysis. The luminescence and CL spectra of Tb(3+)-FQ complexes show characteristic peaks of Tb(3+) at 490 nm, 545 nm, 585 nm and 620 nm. Complexes of Tb(3+)-ENX, Tb(3+)-NFLX, Tb(3+)-LMFX and Tb(3+)-FLRX display relatively strong emission intensity compared with Tb(3+)-OFLX, Tb(3+)-RFX, Tb(3+)-GFLX and Tb(3+)-SPFX. Quite weak peaks with unique characters of Eu(3+) at 590 nm and 617 nm appear in the luminescence and CL spectra of Eu(3+)-ENX, but no notable sensitized luminescence and CL of Eu(3+) could be observed when Eu(3+) is added into other FQ. The distinct differences on emission intensity of Tb(3+)-FQ and Eu(3+)-FQ might originate from the different energy gap between the triplet levels of FQ and the excited levels of the Ln(3+). The different sensitized luminescence and CL signals among Tb(3+)-FQ complexes could be attributed to different optical properties and substituents of these FQ compounds. The detailed mechanism involved in the luminescence and CL properties of Tb(3+)-FQ and Eu(3+)-FQ complexes has been investigated by analyzing the luminescence and CL spectra, quantum yields, and theoretical calculation results. Copyright © 2011 Elsevier B.V. All rights reserved.

Is Knowledge Regarding Tuberculosis Associated with Stigmatising and Discriminating Attitudes of General Population towards Tuberculosis Patients? Findings from a Community Based Survey in 30 Districts of India.

PubMed

Sagili, Karuna D; Satyanarayana, Srinath; Chadha, Sarabjit S

2016-01-01

Stigmatising and discriminating attitudes may discourage tuberculosis (TB) patients from actively seeking medical care, hide their disease status, and discontinue treatment. It is expected that appropriate knowledge regarding TB should remove stigmatising and discriminating attitudes. In this study we assessed the prevalence of stigmatising and discriminating attitudes towards TB patients among general population and their association with knowledge regarding TB. A cross-sectional knowledge, attitude and practice survey was conducted in 30 districts of India in January-March 2011. A total of 4562 respondents from general population were interviewed using semi-structured questionnaires which contained items to measure stigma, discrimination and knowledge on TB. Of the 4562 interviewed, 3823 were eligible for the current analysis. Of these, 73% (95% CI 71.4-74.2) had stigmatising and 98% (95% CI 97.4-98.3) had discriminating attitude towards TB patients. Only 17% (95% CI 15.6-18.0) of the respondents had appropriate knowledge regarding TB with even lower levels observed amongst females, rural areas and respondents from low income groups. Surprisingly stigmatising (adjusted OR 1.31 (0.78-2.18) and discriminating (adjusted OR 0.79 (0.43-1.44) attitudes were independent of knowledge regarding TB. Stigmatising and discriminating attitudes towards TB patients remain high among the general population in India. Since these attitudes were independent of the knowledge regarding TB, it is possible that the current disseminated knowledge regarding TB which is mainly from a medical perspective may not be adequately addressing the factors that lead to stigma and discrimination towards TB patients. Therefore, there is an urgent need to review the messages and strategies currently used for disseminating knowledge regarding TB among general population and revise them appropriately. The disseminated knowledge should include medical, psycho-social and economic aspects of TB that not only informs people about medical aspects of TB disease, but also removes stigma and discrimination.

TB control programmes: the challenges for Africa.

PubMed

Harries, T

1996-11-01

Governmental neglect of tuberculosis (TB), inadequately managed and inaccurately designed TB control programs, population growth, and the HIV epidemic account for the resurgence of TB in sub-Saharan Africa. The World Health Organization and the International Union against TB and Lung Disease have developed a TB control strategy that aims to reduce mortality, morbidity, and transmission of TB. It aims for an 85% cure rate among detected new cases of smear-positive TB and a 70% rate of detecting existing smear-positive TB cases. The strategy involves the provision of short-course chemotherapy (SCC) to all identified smear-positive TB cases through directly observed treatment (DOTS). SCC treatment regimens for smear-positive pulmonary TB recommended for sub-Saharan African countries are: initial phase = daily administration over 2 months of streptomycin, rifampicin, isoniazid, and pyrazinamide; continuation phase = 3 doses over 4 months of isoniazid and rifampicin or daily administration of thiacetazone and isoniazid or of ethambutol and isoniazid. A TB control policy must be implemented to bring about effective TB control. The essential elements of this policy include political commitment, case detection through passive case-finding, SCC, a regular supply of essential drugs, and a monitoring and evaluation system. Political commitment involves establishing a National TB Control Program to be integrated into the existing health structure. Increased awareness of TB in the community and among health workers and a reference laboratory are needed to make case finding successful. A distribution and logistics system is needed to ensure uninterrupted intake of drugs throughout treatment. These regimens have been very successful and cost-effective but pose several disadvantages (e.g., heavy workload of recommended 3 sputum smear tests). A simplified approach involves 1 initial sputum smear for 6 months; 6-months, intermittent rifampicin-based therapy, 100% DOTS throughout entire treatment course, and ascertainment of treatment completion rates and mortality rates in all patients.

Political commitment to tuberculosis control in Ghana.

PubMed

Amo-Adjei, Joshua

2014-01-01

As part of expanding and sustaining tuberculosis (TB) control, the Stop TB Partnership of the World Health Organization initiative has called for strong political commitment to TB control, particularly in developing countries. Framing political commitment within the theoretical imperatives of the political economy of health, this study explores the existing and the expected dimensions of political commitment to TB control in Ghana. Semi-structured in-depth interviews were conducted with 29 purposively selected staff members of the Ghana Health Service and some political officeholders. In addition, the study analysed laws, policies and regulations relevant to TB control. Four dimensions of political commitment emerged from the interviews: provision of adequate resources (financial, human and infrastructural); political authorities' participation in advocacy for TB; laws and policies' promulgation and social protection interventions. Particularly in respect to financial resources, donors such as the Global Fund to Fight AIDS, Tuberculosis and Malaria presently give more than 60% of the working budget of the programme. The documentary review showed that laws, policies and regulations existed that were relevant to TB control, albeit they were not clearly linked.

Migrants and tuberculosis: analysing epidemiological data with ethnography.

PubMed

Littleton, Judith; Park, Julie; Thornley, Craig; Anderson, Anneka; Lawrence, Jody

2008-04-01

Media portrayals of tuberculosis (TB) in New Zealand are of immigrants who enter the country with active disease and pose a threat to inhabitants, which fosters a popular perception that border control is the best and only response to disease control. This paper reviews both New Zealand and international data on TB rates, causes and transmission among migrant populations to elucidate the precise nature of the link between immigration and TB rates. Recent information from scholarly journals on immigration and TB was reviewed. Surveillance data from New Zealand and comparable information from other low-incidence countries were reviewed. The importation of active TB is only a minor part of the total TB burden. While effective border control is essential, equally, if not more important, are the circumstances that promote the reactivation of latent TB infection in migrant communities, including migrants' experiences in transit and after arrival, structural conditions, and personal characteristics. For sound prevention strategies, attention needs to be paid to the existence of transnational communities and the conditions for migrants, rather than placing a singular focus on place of birth.

Enhancement of TbIII–CuII Single‐Molecule Magnet Performance through Structural Modification

PubMed Central

Heras Ojea, María José; Milway, Victoria A.; Velmurugan, Gunasekaran; Thomas, Lynne H.; Coles, Simon J.; Wilson, Claire; Wernsdorfer, Wolfgang

2016-01-01

Abstract We report a series of 3d–4f complexes {Ln2Cu3(H3L)2Xn} (X=OAc−, Ln=Gd, Tb or X=NO3 −, Ln=Gd, Tb, Dy, Ho, Er) using the 2,2′‐(propane‐1,3‐diyldiimino)bis[2‐(hydroxylmethyl)propane‐1,3‐diol] (H6L) pro‐ligand. All complexes, except that in which Ln=Gd, show slow magnetic relaxation in zero applied dc field. A remarkable improvement of the energy barrier to reorientation of the magnetisation in the {Tb2Cu3(H3L)2Xn} complexes is seen by changing the auxiliary ligands (X=OAc− for NO3 −). This leads to the largest reported relaxation barrier in zero applied dc field for a Tb/Cu‐based single‐molecule magnet. Ab initio CASSCF calculations performed on mononuclear TbIII models are employed to understand the increase in energy barrier and the calculations suggest that the difference stems from a change in the TbIII coordination environment (C 4v versus Cs). PMID:27484259

Knowledge, attitudes and practices regarding tuberculosis among immigrants of Somalian ethnic origin in London: a cross-sectional study.

PubMed

Shetty, N; Shemko, M; Abbas, A

2004-03-01

The objectives were to study knowledge, attitudes, and practices (KAP) regarding tuberculosis (TB) among Somalian subjects in inner London. We administered structured, fixed response KAP questionnaires to 23 patients (culture proved TB), and two groups of controls: 25 contacts (family members) and 27 lay controls (general Somali immigrant population). Responses were summed on a five-point scale. Most were aware of the infectious nature of TB but uncertain of other risk factors. Many were uncertain about coping with the disease and its effect on lifestyle. Belief in biomedicine for TB was unequivocal with men having a significantly higher belief score than women (p = 0.02); the need to comply with TB medication was unambiguously understood. Somalians interviewed were educated, multilingual, and aware of important health issues. Uncertainties in core TB knowledge need to be addressed with direct educational input, especially in women and recent entrants into the country. Volunteers from the established Somalian community could play a valuable part as links in the community to fight TB.

CARGO: effective format-free compressed storage of genomic information

PubMed Central

Roguski, Łukasz; Ribeca, Paolo

2016-01-01

The recent super-exponential growth in the amount of sequencing data generated worldwide has put techniques for compressed storage into the focus. Most available solutions, however, are strictly tied to specific bioinformatics formats, sometimes inheriting from them suboptimal design choices; this hinders flexible and effective data sharing. Here, we present CARGO (Compressed ARchiving for GenOmics), a high-level framework to automatically generate software systems optimized for the compressed storage of arbitrary types of large genomic data collections. Straightforward applications of our approach to FASTQ and SAM archives require a few lines of code, produce solutions that match and sometimes outperform specialized format-tailored compressors and scale well to multi-TB datasets. All CARGO software components can be freely downloaded for academic and non-commercial use from http://bio-cargo.sourceforge.net. PMID:27131376

Preparation, characterization and luminescence properties of core-shell ternary terbium composites SiO2(600)@Tb(MABA-Si)•L

NASA Astrophysics Data System (ADS)

Ma, Yang-Yang; Li, Wen-Xian; Zheng, Yu-Shan; Bao, Jin-Rong; Li, Yi-Lian; Feng, Li-Na; Yang, Kui-Suo; Qiao, Yan; Wu, An-Ping

2018-03-01

Two novel core-shell structure ternary terbium composites SiO2(600)@Tb(MABA-Si)·L(L:dipy/phen) nanometre luminescence materials were prepared by ternary terbium complexes Tb(MABA-Si)·L2·(ClO4)3·2H2O shell grafted onto the surface of SiO2 microspheres. And corresponding ternary terbium complexes were synthesized using (CONH(CH2)3Si(OCH2CH3)3)2 (denoted as MABA-Si) as first ligand and L as second ligand coordinated with terbium perchlorate. The as-synthesized products were characterized by means of IR spectra, 1HNMR, element analysis, molar conductivity, SEM and TEM. It was found that the first ligand MABA-Si of terbium ternary complex hydrolysed to generate the Si-OH and the Si-OH condensate with the Si-OH on the surface of SiO2 microspheres; then ligand MABA-Si grafted onto the surface of SiO2 microspheres. The diameter of SiO2 core of SiO2(600)@Tb(MABA-Si)·L was approximately 600 nm. Interestingly, the luminescence properties demonstrate that the two core-shell structure ternary terbium composites SiO2(600)Tb(MABA-Si)·L(dipy/phen) exhibit strong emission intensities, which are 2.49 and 3.35 times higher than that of the corresponding complexes Tb(MABA-Si)·L2·(ClO4)3·2H2O, respectively. Luminescence decay curves show that core-shell structure ternary terbium composites have longer lifetime. Excellent luminescence properties enable the core-shell materials to have potential applications in medicine, industry, luminescent fibres and various biomaterials fields.

Influence of annealing temperature on structural and optical properties of Lu{sub 2}O{sub 3}:Eu{sup 3+}, Tb{sup 3+} transparent films

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

Morales-Ramírez, Ángel de Jesús; García-Murillo, Antonieta, E-mail: angarciam@ipn.mx; Carrillo-Romo, Felipe de Jesús

2015-10-15

Highlights: • Lu{sub 2}O{sub 3}:Eu{sup 3+}, Tb{sup 3+} films were synthesized by sol–gel and by dip-coating technique. • Effects of annealing treatment on structural and optical properties were studied. • Optogeometrical characteristics of synthesized films were analyzed. • X-ray diffraction results showed that Lu{sub 2}O{sub 3}:Eu{sup 3+}, Tb{sup 3+} crystallizes at 700 °C. • High reddish emission on transparent films with at least 1 μm thick was observed. - Abstract: High-optical quality Lu{sub 2}O{sub 3}:Eu{sup 3+} 5 mol%, X Tb{sup 3+} (X = 0–0.04 mol%) thin films were prepared by the sol–gel process and dip-coating technique. The procedure was asmore » follows: lutetium, europium and terbium nitrates were used as precursors, and ethanol as a solvent. Etylenglycol (EG) was added as a sol stabilizer, and the pH was adjusted by acetic acid. After 10 dipping-cycles, followed by an annealing process (600–900 °C) for 1 h, transparent, smooth and crack-free films (ra = 8–9 nm) were formed. The X-ray diffraction (XRD) results showed crystallized films into the cubic structure at 800 °C. The ellipsometry results showed that the thickness of the films varied from 1 to 1.4 μm at 1000 and 600 °C, respectively. Finally, the films presented a typical Eu{sup 3+} red emission at 611 nm ({sup 5}D{sub 0} → {sup 7}F{sub 2}); furthermore, the effect of the Tb{sup 3+} content showed that the highest emission intensity corresponded to the lower Tb{sup 3+} content.« less

Preparation, characterization and luminescence properties of core-shell ternary terbium composites SiO2(600)@Tb(MABA-Si)•L.

PubMed

Ma, Yang-Yang; Li, Wen-Xian; Zheng, Yu-Shan; Bao, Jin-Rong; Li, Yi-Lian; Feng, Li-Na; Yang, Kui-Suo; Qiao, Yan; Wu, An-Ping

2018-03-01

Two novel core-shell structure ternary terbium composites SiO 2(600) @Tb(MABA-Si)·L(L:dipy/phen) nanometre luminescence materials were prepared by ternary terbium complexes Tb(MABA-Si)·L 2 ·(ClO 4 ) 3 ·2H 2 O shell grafted onto the surface of SiO 2 microspheres. And corresponding ternary terbium complexes were synthesized using (CONH(CH 2 ) 3 Si(OCH 2 CH 3 ) 3 ) 2 (denoted as MABA-Si) as first ligand and L as second ligand coordinated with terbium perchlorate. The as-synthesized products were characterized by means of IR spectra, 1 HNMR, element analysis, molar conductivity, SEM and TEM. It was found that the first ligand MABA-Si of terbium ternary complex hydrolysed to generate the Si-OH and the Si-OH condensate with the Si-OH on the surface of SiO 2 microspheres; then ligand MABA-Si grafted onto the surface of SiO 2 microspheres. The diameter of SiO 2 core of SiO 2(600) @Tb(MABA-Si)·L was approximately 600 nm. Interestingly, the luminescence properties demonstrate that the two core-shell structure ternary terbium composites SiO 2(600) Tb(MABA-Si)·L(dipy/phen) exhibit strong emission intensities, which are 2.49 and 3.35 times higher than that of the corresponding complexes Tb(MABA-Si)·L 2 ·(ClO 4 ) 3 ·2H 2 O, respectively. Luminescence decay curves show that core-shell structure ternary terbium composites have longer lifetime. Excellent luminescence properties enable the core-shell materials to have potential applications in medicine, industry, luminescent fibres and various biomaterials fields.

Preparation, characterization and luminescence properties of core–shell ternary terbium composites SiO2(600)@Tb(MABA-Si)•L

PubMed Central

Ma, Yang-Yang; Zheng, Yu-Shan; Bao, Jin-Rong; Li, Yi-Lian; Feng, Li-Na; Yang, Kui-Suo; Qiao, Yan; Wu, An-Ping

2018-01-01

Two novel core–shell structure ternary terbium composites SiO2(600)@Tb(MABA-Si)·L(L:dipy/phen) nanometre luminescence materials were prepared by ternary terbium complexes Tb(MABA-Si)·L2·(ClO4)3·2H2O shell grafted onto the surface of SiO2 microspheres. And corresponding ternary terbium complexes were synthesized using (CONH(CH2)3Si(OCH2CH3)3)2 (denoted as MABA-Si) as first ligand and L as second ligand coordinated with terbium perchlorate. The as-synthesized products were characterized by means of IR spectra, 1HNMR, element analysis, molar conductivity, SEM and TEM. It was found that the first ligand MABA-Si of terbium ternary complex hydrolysed to generate the Si–OH and the Si–OH condensate with the Si–OH on the surface of SiO2 microspheres; then ligand MABA-Si grafted onto the surface of SiO2 microspheres. The diameter of SiO2 core of SiO2(600)@Tb(MABA-Si)·L was approximately 600 nm. Interestingly, the luminescence properties demonstrate that the two core–shell structure ternary terbium composites SiO2(600)Tb(MABA-Si)·L(dipy/phen) exhibit strong emission intensities, which are 2.49 and 3.35 times higher than that of the corresponding complexes Tb(MABA-Si)·L2·(ClO4)3·2H2O, respectively. Luminescence decay curves show that core–shell structure ternary terbium composites have longer lifetime. Excellent luminescence properties enable the core–shell materials to have potential applications in medicine, industry, luminescent fibres and various biomaterials fields. PMID:29657773

Application of Tight-Binding Method in Atomistic Simulation of Covalent Materials

NASA Astrophysics Data System (ADS)

Isik, Ahmet

1994-05-01

The primary goal of this thesis is to develop and apply molecular dynamics simulation methods to elemental and binary covalent materials (Si, C, SiC) based on the tight-binding (TB) model of atomic cohesion in studies of bulk and deformation properties far from equilibrium. A second purpose is to compare results with those obtained using empirical interatomic potential functions in order to elucidate the applicability of models of interatomic interactions which do not take into account explicitly electronic structure effects. We have calculated the former by using a basis set consisting of four atomic orbitals, one for the s state and three for the p states, constructing a TB Hamiltonian in the usual Slater-Koster parametrization, and diagonalizing the Hamiltonian matrix at the origin of the Brillouin zone. For the repulsive part of the energy we employ a function in the form of inverse power law with screening which is then fitted to the bulk modulus and lattice parameter of several stable polytypes, results calculated by ab initio methods in the literature. Three types of applications have been investigated to demonstrate the utility of the present TB models and their advantages relative to empirical potentials. In the case of Si we show the calculated cohesive energy agrees to within a few percent with the ab initio local-density approximation (LDA) results. In addition, for clusters up to 10 atoms we find most of the energies and equilibrium structures to be in good agreement with LDA results (the failure of the empirical potential of Stillinger and Weber (SW) is well known). In the case of C clusters our TB model gives ring and chain structures which have been found both experimentally and by LDA calculations. In the second application we have applied our TB model of Si to investigate the core structure and energetics of partial dislocations on the glide plane and reconstruction antiphase defect (APD). For the 90^circ partial we show that the TB description gives the correct asymetric reconstruction previously found by LDA. For the 30^circ partial, TB gives better bond angles in the dislocation core. For the APD we have obtained a binding energy and activation for migration which are somewhat larger than the SW values, but the conclusion remains that APD is a low-energy defect which should be quite mobile. In the third application we formulate a simple TB model for SiC where the coefficients of the two-center integrals in Si-C interactions are taken to be simple averages of Si-Si and C-C integrals. Fitting is done on two polytypes, zincblende and rocksalt structures, and a simulated annealing procedure is used. The TB results are found in good agreement with LDA and experimental results in the cohesive energy, acoustic phonon modes, and elastic constants. (Abstract shortened by UMI.).

Structural basis for catalysis of a tetrameric, class IIa fructose 1,6-bisphosphate aldolase from M. tuberculosis

PubMed Central

Pegan, Scott D.; Rukseree, Kamolchanok; Franzblau, Scott G.; Mesecar, Andrew D.

2009-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), currently infects one third of the world’s population in its latent form. The emergence of multidrug resistant strains, MDR-TB and XDR-TB has highlighted the need for new pharmacological targets within M. tuberculosis. The Class IIa fructose 1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been proposed as one such target since its upregulated in latent TB. Since the structure of MtFBA had not been determined and since there was little information available on its reaction mechanism, we sought to determine the X-ray structure of MtFBA in complex with its substrates. By lowering the pH of the enzyme in the crystalline state, we were able to determine a series of high-resolution X-ray structures of MtFBA bound to dihydroxyacetonephosphate (DHAP), glyceraldehyde-3-phosphate (G3P), and fructose 1,6-bisphosphate (FBP) at 1.5 Å, 2.1 Å, and 1.3 Å respectively. Through these structures it was discovered that MtFBA belongs to a novel tetrameric class of the type IIa FBAs. The molecular details at the interface of the tetramer revealed important information for being able to better predict the quaternary structures among the FBAs based on their primary sequences. These X-ray structures also provide interesting and new details on the reaction mechanism of class II FBAs. Not only were the substrates and products observed in geometries poised for catalysis, but unexpectedly the hydroxyl enolate intermediate of DHAP was also captured and resolved structurally. These concise new details provide a better understanding of the reaction mechanisms for FBAs in general and provide a structural basis for inhibitor design efforts aimed at this class of enzymes. PMID:19167403

Effect of hypoxia on metabolic rate, core body temperature, and c-fos expression in the naked mole rat.

PubMed

Nathaniel, Thomas I; Otukonyong, Effiong; Abdellatif, Ahmed; Soyinka, Julius O

2012-10-01

Recent investigations of hypoxia physiology in the naked mole rat have opened up an interesting line of research into the basic physiological and genomic alterations that accompany hypoxia survival. The extent to which such findings connect the effect of hypoxia to metabolic rate (O₂ consumption), core body temperature (Tb), and transcripts encoding the immediate early gene product (such as c-fos) under a constant ambient temperature (Ta) is not well known. We investigated this issue in the current study. Our first sets of experiments measured Tb and metabolic rates during exposure of naked mole rats to hypoxia over a constant Ta. Hypoxia significantly decreased metabolic rates in the naked mole rat. Although core Tb also decreased during hypoxia, the effect of hypoxia in suppressing core Tb was not significant. The second series of experiments revealed that c-fos protein and mRNA expression in the hippocampus neurons (CA1) increased in naked mole rats that were repeatedly exposed to 3% O₂ for 60 min per day for 5 days when compared to normoxia. Our findings provide evidence for the up-regulation of c-fos and suppression of metabolic rate in hypoxia tolerating naked mole rats under constant ambient temperature. Metabolic suppression and c-fos upregulation constitute part of the physiological complex associated with adaptation to hypoxia. Published by Elsevier Ltd.

Small interfering RNA-producing loci in the ancient parasitic eukaryote Trypanosoma brucei

PubMed Central

2012-01-01

Background At the core of the RNA interference (RNAi) pathway in Trypanosoma brucei is a single Argonaute protein, TbAGO1, with an established role in controlling retroposon and repeat transcripts. Recent evidence from higher eukaryotes suggests that a variety of genomic sequences with the potential to produce double-stranded RNA are sources for small interfering RNAs (siRNAs). Results To test whether such endogenous siRNAs are present in T. brucei and to probe the individual role of the two Dicer-like enzymes, we affinity purified TbAGO1 from wild-type procyclic trypanosomes, as well as from cells deficient in the cytoplasmic (TbDCL1) or nuclear (TbDCL2) Dicer, and subjected the bound RNAs to Illumina high-throughput sequencing. In wild-type cells the majority of reads originated from two classes of retroposons. We also considerably expanded the repertoire of trypanosome siRNAs to encompass a family of 147-bp satellite-like repeats, many of the regions where RNA polymerase II transcription converges, large inverted repeats and two pseudogenes. Production of these newly described siRNAs is strictly dependent on the nuclear DCL2. Notably, our data indicate that putative centromeric regions, excluding the CIR147 repeats, are not a significant source for endogenous siRNAs. Conclusions Our data suggest that endogenous RNAi targets may be as evolutionarily old as the mechanism itself. PMID:22925482

A dehydration-inducible gene in the truffle Tuber borchii identifies a novel group of dehydrins

PubMed Central

Abba', Simona; Ghignone, Stefano; Bonfante, Paola

2006-01-01

Background The expressed sequence tag M6G10 was originally isolated from a screening for differentially expressed transcripts during the reproductive stage of the white truffle Tuber borchii. mRNA levels for M6G10 increased dramatically during fruiting body maturation compared to the vegetative mycelial stage. Results Bioinformatics tools, phylogenetic analysis and expression studies were used to support the hypothesis that this sequence, named TbDHN1, is the first dehydrin (DHN)-like coding gene isolated in fungi. Homologs of this gene, all defined as "coding for hypothetical proteins" in public databases, were exclusively found in ascomycetous fungi and in plants. Although complete (or almost complete) fungal genomes and EST collections of some Basidiomycota and Glomeromycota are already available, DHN-like proteins appear to be represented only in Ascomycota. A new and previously uncharacterized conserved signature pattern was identified and proposed to Uniprot database as the main distinguishing feature of this new group of DHNs. Expression studies provide experimental evidence of a transcript induction of TbDHN1 during cellular dehydration. Conclusion Expression pattern and sequence similarities to known plant DHNs indicate that TbDHN1 is the first characterized DHN-like protein in fungi. The high similarity of TbDHN1 with homolog coding sequences implies the existence of a novel fungal/plant group of LEA Class II proteins characterized by a previously undescribed signature pattern. PMID:16512918

Tuberculosis infection control practices in a high-burden metro in South Africa: A perpetual bane for efficient primary health care service delivery.

PubMed

Engelbrecht, Michelle C; Kigozi, Gladys; Janse van Rensburg, Andre P; Van Rensburg, Dingie H C J

2018-05-30

Tuberculosis (TB) prevention, including infection control, is a key element in the strategy to end the global TB epidemic. While effective infection control requires all health system components to function well, this is an area that has not received sufficient attention inSouth Africa despite the availability of policy and guidelines. To describe the state of implementation of TB infection control measures in a high-burden metro in South Africa. The research was undertaken in a high TB- and HIV-burdened metropolitan area of South Africa. More specifically, the study sites were primary health care facilities (PHC), thatamong other services also diagnosed TB. A cross-sectional survey, focusing on the World Health Organization levels of infection control, which included structured interviews with nurses providing TB diagnosis and treatment services as well as observations, at all 41 PHC facilities in a high TB-burdened and HIV-burdened metro of South Africa. Tuberculosis infection control was poorly implemented, with few facilities scoring 80% and above on compliance with infection control measures. Facility controls: 26 facilities (63.4%) had an infection control committee and 12 (29.3%) had a written infection control plan. Administrative controls: 26 facilities (63.4%) reported separating coughing and noncoughing patients, while observations revealed that only 11 facilities (26.8%) had separate waiting areas for (presumptive) TB patients. Environmental controls: most facilities used open windows for ventilation (n = 30; 73.2%); however, on the day of the visit, only 12 facilities (30.3%) had open windows in consulting rooms. Personal protective equipment: 9 facilities (22%) did not have any disposable respirators in stock and only 9 respondents (22%) had undergone fit testing. The most frequently reported barrier to implementing good TBinfection control practices was lack of equipment (n = 22; 40%) such as masks and disposable respirators, as well as the structure or layout of the PHC facilities. The main recommendation to improve TB infection control was education for patients and health care workers (n = 18; 33.3%). All levels of the health care system should be engaged to address TB prevention and infection control in PHC facilities. Improved infection control will address the nosocomial spread of TB in health facilities and keep health care workers and patients safe from infection.

Tuberculosis: a balanced diet of lipids and carbohydrates.

PubMed

Bhowruth, Veemal; Alderwick, Luke J; Brown, Alistair K; Bhatt, Apoorva; Besra, Gurdyal S

2008-08-01

In spite of effective antibiotics to treat TB (tuberculosis) since the early 1960s, we enter the new millennium with TB currently the leading cause of death from a single infectious agent, killing more than 3 million people worldwide each year. Thus an understanding of drug-resistance mechanisms, the immunobiology of cell wall components to elucidate host-pathogen interactions and the discovery of new drug targets are now required for the treatment of TB. Above the plasma membrane is a classical chemotype IV peptidoglycan to which is attached the macromolecular structure, mycolyl-arabinogalactan via a unique diglycosylphosphoryl bridge. The present review discusses the assembly of the mAGP (mycolyl-arabinogalactan-peptidoglycan) complex and the site of action of EMB (ethambutol), bringing forward a new era in TB research and focus for new drugs to combat multidrug-resistant TB.

CONFLICT IN EASTERN UKRAINE: STRATEGY FOR TUBERCULOSIS.

PubMed

Kuchuloria, T; Akhvlediani, T; Akhvlediani, N

2016-09-01

This root cause analysis concerns the conflict in the Eastern Ukraine and its impact on healthcare delivery in the context of treating internally displaced persons (IDPs). Inadequate treatment of tuberculosis (TB) was selected as a major topic for intervention planning in conflict areas in Ukraine. With respect to treating TB among IDPs, rapid diagnosis and adequate nutrition and shelter are important components of care and disease control. The DOT, supported by trained primary healthcare providers equipped with rapid MDR TB diagnostic capacities, need to provide appropriate shelter and nutrition to IDPs. In addition to active disease management, this paper discusses the important role of ongoing project monitoring and communicating evaluation findings with all the major stakeholders shaping the national TB strategy in Ukraine. A comprehensive strategy is essential for successful transitioning and re-structuring of TB healthcare delivery both during after conflict resolution.

Structure of the MazF-mt9 toxin, a tRNA-specific endonuclease from Mycobacterium tuberculosis.

PubMed

Chen, Ran; Tu, Jie; Liu, Zhihui; Meng, Fanrong; Ma, Pinyun; Ding, Zhishan; Yang, Chengwen; Chen, Lei; Deng, Xiangyu; Xie, Wei

2017-05-06

Tuberculosis (TB) is a severe disease caused by Mycobacterium tuberculosis (M. tb) and the well-characterized M. tb MazE/F proteins play important roles in stress adaptation. Recently, the MazF-mt9 toxin has been found to display endonuclease activities towards tRNAs but the mechanism is unknown. We hereby present the crystal structure of apo-MazF-mt9. The enzyme recognizes tRNA Lys with a central UUU motif within the anticodon loop, but is insensitive to the sequence context outside of the loop. Based on our crystallographic and biochemical studies, we identified key residues for catalysis and proposed the potential tRNA-binding site. Copyright © 2017 Elsevier Inc. All rights reserved.

Photoluminescence and energy transfer process in Gd{sub 2}O{sub 3}:Eu{sup 3+}, Tb{sup 3+}

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

Selvalakshmi, T.; Bose, A. Chandra, E-mail: acbose@nitt.edu

2016-05-23

Variation in photoluminescence (PL) properties of Eu{sup 3+} and Tb{sup 3+} as a function of co-dopant (Tb{sup 3+}) concentration are studied for Gd{sub 2-x-y}O{sub 3}: Eu{sup 3+}{sub x} Tb{sup 3+}{sub y} (x = 0.02, y = 0.01, 0.03, 0.05). The crystal structure analysis is carried out by X-ray Diffraction (XRD). Absence of addition peaks corresponding europium or terbium phase confirms the phase purity. Diffuse reflectance spectroscopy (DRS) reveals the absorption peaks corresponding to host matrix, Eu{sup 3+} and Tb{sup 3+}. The bandgap calculated from Kubelka – Munk function is also reported. PL spectra are recorded at the excitation wavelength ofmore » 307 nm and the emission peak corresponding to Eu{sup 3+} confirms the energy transfer from Tb{sup 3+} to Eu{sup 3+}. The agglomeration of particles acts as quenching centres for energy transfer at higher concentrations.« less

Structural, electronic and optical properties of LiNbO3 using GGA-PBE and TB-mBJ functionals: A DFT study

NASA Astrophysics Data System (ADS)

Arshad Javid, M.; Khan, Zafar Ullah; Mehmood, Zahid; Nabi, Azeem; Hussain, Fayyaz; Imran, M.; Nadeem, Muhammad; Anjum, Naeem

2018-06-01

In the present work, first-principles calculations were performed to obtain the structural, electronic and optical properties of lithium niobate crystal using two exchange-correlation functionals (GGA-PBE and TB-mBJ). The calculated structural parameters were very close to the experimental values. TB-mBJ functional was found to be good when compared to LDA and GGA functionals in case of bandgap energy of 3.715 eV of lithium niobate. It was observed that the upper valence and lower conduction bands consist mainly the O-2p and Nb-4d states, respectively. Furthermore, calculations for real and imaginary parts of frequency-dependent dielectric function 𝜀(ω) of lithium niobate crystal were performed using TD-DFT method. The ordinary refractive index no(ω), extraordinary refractive index ne(ω), its birefringence and absorption peaks in imaginary dielectric function 𝜀2(ω) were also calculated.

Genome-Wide Identification and Characterization of BrrTCP Transcription Factors in Brassica rapa ssp. rapa.

PubMed

Du, Jiancan; Hu, Simin; Yu, Qin; Wang, Chongde; Yang, Yunqiang; Sun, Hang; Yang, Yongping; Sun, Xudong

2017-01-01

The teosinte branched1/cycloidea/proliferating cell factor (TCP) gene family is a plant-specific transcription factor that participates in the control of plant development by regulating cell proliferation. However, no report is currently available about this gene family in turnips ( Brassica rapa ssp. rapa ). In this study, a genome-wide analysis of TCP genes was performed in turnips. Thirty-nine TCP genes in turnip genome were identified and distributed on 10 chromosomes. Phylogenetic analysis clearly showed that the family was classified as two clades: class I and class II. Gene structure and conserved motif analysis showed that the same clade genes have similar gene structures and conserved motifs. The expression profiles of 39 TCP genes were determined through quantitative real-time PCR. Most CIN-type BrrTCP genes were highly expressed in leaf. The members of CYC/TB1 subclade are highly expressed in flower bud and weakly expressed in root. By contrast, class I clade showed more widespread but less tissue-specific expression patterns. Yeast two-hybrid data show that BrrTCP proteins preferentially formed heterodimers. The function of BrrTCP2 was confirmed through ectopic expression of BrrTCP2 in wild-type and loss-of-function ortholog mutant of Arabidopsis. Overexpression of BrrTCP2 in wild-type Arabidopsis resulted in the diminished leaf size. Overexpression of BrrTCP2 in triple mutants of tcp2/4/10 restored the leaf phenotype of tcp2/4/10 to the phenotype of wild type. The comprehensive analysis of turnip TCP gene family provided the foundation to further study the roles of TCP genes in turnips.

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo

PubMed Central

Kaboru, Berthollet Bwira; Ogwang, Brenda. A.; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-01-01

Background: HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. Methods: A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Results: Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases’ control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. Conclusion: HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region. PMID:24596866

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo.

PubMed

Kaboru, Berthollet Bwira; Ogwang, Brenda A; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-09-01

HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases' control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region.

Prevalence of post-traumatic stress symptoms and associated factors in tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa.

PubMed

Peltzer, Karl; Naidoo, Pamela; Matseke, Gladys; Louw, Julia; McHunu, Gugu; Tutshana, Bomkazi

2013-01-01

High rates of tuberculosis (TB) and TB/HIV co-infection is often linked with mental health issues such as post-traumatic stress disorder (PTSD) symptoms, which is further associated with poor health outcomes. In a country such as South Africa where rates of these infectious diseases are high, it is concerning that there is limited/no data on prevalence rates of mental disorders such as PTSD and its associated factors. Therefore, the aim of this study was to establish the prevalence of PTSD symptoms and associated factors in TB, TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa. Brief screening self-report tools were used to measure: PTSD symptoms, psychological distress (anxiety and depression) and alcohol misuse. Other relevant measures, such as adherence to medication, stressful life events and sexual risk-taking behaviours, were obtained through structured questions. A total of 4900 public primary care adult patients from clinics in high TB burden districts from three provinces in South Africa participated. All the patients screened positive for TB (either new or retreatment cases). The prevalence of PTSD symptoms was 29.6%. Patients who screened positive for PTSD symptoms and psychological distress were more likely to be on antidepressant medication. Factors that predicted PTSD symptoms were poverty, residing in an urban area, psychological distress, suicide attempt, alcohol and/or drug use before sex, unprotected sex, TB-HIV co-infected and the number of other chronic conditions. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of TB and HIV.

Alternative medicine: an ethnographic study of how practitioners of Indian medical systems manage TB in Mumbai.

PubMed

McDowell, Andrew; Pai, Madhukar

2016-03-01

Mumbai is a hot spot for drug-resistant TB, and private practitioners trained in AYUSH systems (Ayurveda, yoga, Unani, Siddha and homeopathy) are major healthcare providers. It is important to understand how AYUSH practitioners manage patients with TB or presumptive TB. We conducted semi-structured interviews of 175 Mumbai slum-based practitioners holding degrees in Ayurveda, homeopathy and Unani. Most providers gave multiple interviews. We observed 10 providers in clinical interactions, documenting: clinical examinations, symptoms, history taking, prescriptions and diagnostic tests. No practitioners exclusively used his or her system of training. The practice of biomedicine is frequent, with practitioners often using biomedical disease categories and diagnostics. The use of homeopathy was rare (only 4% of consultations with homeopaths resulted in homeopathic remedies) and Ayurveda rarer (3% of consultations). For TB, all mentioned chest x-ray while 31 (17.7%) mentioned sputum smear as a TB test. One hundred and sixty-four practitioners (93.7%) reported referring TB patients to a public hospital or chest physician. Eleven practitioners (6.3%) reported treating patients with TB. Nine (5.1%) reported treating patients with drug-susceptible TB with at least one second-line drug. Important sources of health care in Mumbai's slums, AYUSH physicians frequently use biomedical therapies and most refer patients with TB to chest physicians or the public sector. They are integral to TB care and control. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Knowledge, care-seeking behavior, and factors associated with patient delay among newly-diagnosed pulmonary tuberculosis patients, Federal Capital Territory, Nigeria, 2010.

PubMed

Biya, Oladayo; Gidado, Saheed; Abraham, Ajibola; Waziri, Ndadilnasiya; Nguku, Patrick; Nsubuga, Peter; Suleman, Idris; Oyemakinde, Akin; Nasidi, Abdulsalami; Sabitu, Kabir

2014-01-01

Early treatment of Tuberculosis (TB) cases is important for reducing transmission, morbidity and mortality associated with TB. In 2007, Federal Capital Territory (FCT), Nigeria recorded low TB case detection rate (CDR) of 9% which implied that many TB cases were undetected. We assessed the knowledge, care-seeking behavior, and factors associated with patient delay among pulmonary TB patients in FCT. We enrolled 160 newly-diagnosed pulmonary TB patients in six directly observed treatment short course (DOTS) hospitals in FCT in a cross-sectional study. We used a structured questionnaire to collect data on socio-demographic variables, knowledge of TB, and care-seeking behavior. Patient delay was defined as > 4 weeks between onset of cough and first hospital contact. Mean age was 32.8 years (± 9 years). Sixty two percent were males. Forty seven percent first sought care in a government hospital, 26% with a patent medicine vendor and 22% in a private hospital. Forty one percent had unsatisfactory knowledge of TB. Forty two percent had patient delay. Having unsatisfactory knowledge of TB (p = 0.046) and multiple care-seeking (p = 0.02) were significantly associated with patient delay. After controlling for travel time and age, multiple care-seeking was independently associated with patient delay (Adjusted Odds Ratio = 2.18, 95% CI = 1.09-4.35). Failure to immediately seek care in DOTS centers and having unsatisfactory knowledge of TB are factors contributing to patient delay. Strategies that promote early care-seeking in DOTS centers and sustained awareness on TB should be implemented in FCT.

Evaluation of whole genome sequencing and software tools for drug susceptibility testing of Mycobacterium tuberculosis.

PubMed

van Beek, J; Haanperä, M; Smit, P W; Mentula, S; Soini, H

2018-04-11

Culture-based assays are currently the reference standard for drug susceptibility testing for Mycobacterium tuberculosis. They provide good sensitivity and specificity but are time consuming. The objective of this study was to evaluate whether whole genome sequencing (WGS), combined with software tools for data analysis, can replace routine culture-based assays for drug susceptibility testing of M. tuberculosis. M. tuberculosis cultures sent to the Finnish mycobacterial reference laboratory in 2014 (n = 211) were phenotypically tested by Mycobacteria Growth Indicator Tube (MGIT) for first-line drug susceptibilities. WGS was performed for all isolates using the Illumina MiSeq system, and data were analysed using five software tools (PhyResSE, Mykrobe Predictor, TB Profiler, TGS-TB and KvarQ). Diagnostic time and reagent costs were estimated for both methods. The sensitivity of the five software tools to predict any resistance among strains was almost identical, ranging from 74% to 80%, and specificity was more than 95% for all software tools except for TGS-TB. The sensitivity and specificity to predict resistance to individual drugs varied considerably among the software tools. Reagent costs for MGIT and WGS were €26 and €143 per isolate respectively. Turnaround time for MGIT was 19 days (range 10-50 days) for first-line drugs, and turnaround time for WGS was estimated to be 5 days (range 3-7 days). WGS could be used as a prescreening assay for drug susceptibility testing with confirmation of resistant strains by MGIT. The functionality and ease of use of the software tools need to be improved. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Identification of the anti‐mycobacterial functional properties of piperidinol derivatives

PubMed Central

Guy, Collette S; Tichauer, Esther; Kay, Gemma L; Phillips, Daniel J; Bailey, Trisha L; Harrison, James; Furze, Christopher M; Millard, Andrew D; Gibson, Matthew I; Pallen, Mark J

2017-01-01

Background and Purpose Tuberculosis (TB) remains a major global health threat and is now the leading cause of death from a single infectious agent worldwide. The current TB drug regimen is inadequate, and new anti‐tubercular agents are urgently required to be able to successfully combat the increasing prevalence of drug‐resistant TB. The purpose of this study was to investigate a piperidinol compound derivative that is highly active against the Mycobacterium tuberculosis bacillus. Experimental Approach The antibacterial properties of the piperidinol compound and its corresponding bis‐Mannich base analogue were evaluated against M. smegmatis and Gram‐negative organisms. Cytotoxicity studies were undertaken in order to determine the selectivity index for these compounds. Spontaneous resistant mutants of M. smegmatis were generated against the piperidinol and corresponding bis‐Mannich base lead derivatives and whole genome sequencing employed to determine the genetic modifications that lead to selection pressure in the presence of these compounds. Key Results The piperidinol and the bis‐Mannich base analogue were found to be selective for mycobacteria and rapidly kill this organism with a cytotoxicity selectivity index for mycobacteria of >30‐fold. Whole genome sequencing of M. smegmatis strains resistant to the lead compounds led to the identification of a number of single nucleotide polymorphisms indicating multiple targets. Conclusion and Implications Our results indicate that the piperidinol moiety represents an attractive compound class in the pursuit of novel anti‐tubercular agents. Linked Articles This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro‐organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc PMID:28195652

Effect of tuberculosis on the survival of HIV-infected men in a country with low TB incidence

PubMed Central

López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP

2010-01-01

Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866

TB infection prevention and control experiences of South African nurses - a phenomenological study

PubMed Central

2011-01-01

Background The tuberculosis (TB) epidemic in South Africa is characterised by one of the highest levels of TB/HIV co-infection and growing multidrug-resistant TB worldwide. Hospitals play a central role in the management of TB. We investigated nurses' experiences of factors influencing TB infection prevention and control (IPC) practices to identify risks associated with potential nosocomial transmission. Methods The qualitative study employed a phenomenological approach, using semi-structured interviews with a quota sample of 20 nurses in a large tertiary academic hospital in Cape Town, South Africa. The data was subjected to thematic analysis. Results Nurses expressed concerns about the possible risk of TB transmission to both patients and staff. Factors influencing TB-IPC, and increasing the potential risk of nosocomial transmission, emerged in interconnected overarching themes. Influences related to the healthcare system included suboptimal IPC provision such as the lack of isolation facilities and personal protective equipment, and the lack of a TB-IPC policy. Further influences included inadequate TB training for staff and patients, communication barriers owing to cultural and linguistic differences between staff and patients, the excessive workload of nurses, and a sense of duty of care. Influences related to wider contextual conditions included TB concerns and stigma, and the role of traditional healers. Influences related to patient behaviour included late uptake of hospital care owing to poverty and the use of traditional medicine, and poor adherence to IPC measures by patients, family members and carers. Conclusions Several interconnected influences related to the healthcare system, wider contextual conditions and patient behavior could increase the potential risk of nosocomial TB transmission at hospital level. There is an urgent need for the implementation and evaluation of a comprehensive contextually appropriate TB IPC policy with the setting and auditing of standards for IPC provision and practice, adequate TB training for both staff and patients, and the establishment of a cross-cultural communication strategy, including rapid access to interpreters. PMID:21518434

Assessing the Consequences of Stigma for Tuberculosis Patients in Urban Zambia

PubMed Central

Cremers, Anne Lia; de Laat, Myrthe Manon; Kapata, Nathan; Gerrets, Rene; Klipstein-Grobusch, Kerstin; Grobusch, Martin Peter

2015-01-01

Background Stigma is one of the many factors hindering tuberculosis (TB) control by negatively affecting hospital delay and treatment compliance. In Zambia, the morbidity and mortality due to TB remains high, despite extended public health attempts to control the epidemic and to diminish stigma. Study Aim To enhance understanding of TB-related stigmatizing perceptions and to describe TB patients’ experiences of stigma in order to point out recommendations to improve TB policy. Methods We conducted a mixed method study at Kanyama clinic and surrounding areas, in Lusaka, Zambia; structured interviews with 300 TB patients, multiple in-depth interviews with 30 TB patients and 10 biomedical health workers, 3 focus group discussions with TB patients and treatment supporters, complemented by participant observation and policy analysis of the TB control program. Predictors of stigma were identified by use of multivariate regression analyses; qualitative analysis of the in-depth interviews, focus group discussions and participant observation was used for triangulation of the study findings. Results We focused on the 138/300 patients that described TB-related perceptions and attitudes, of whom 113 (82%) reported stigma. Stigma provoking TB conceptions were associated with human immunodeficiency virus (HIV)-infection, alleged immoral behaviour, (perceived) incurability, and (traditional) myths about TB aetiology. Consequences of stigma prevailed both among children and adults and included low self-esteem, insults, ridicule, discrimination, social exclusion, and isolation leading to a decreased quality of life and social status, non-disclosure, and/or difficulties with treatment compliance and adherence. Women had significantly more stigma-related problems than men. Conclusions The findings illustrate that many TB patients faced stigma-related issues, often hindering effective TB control and suggesting that current efforts to reduce stigma are not yet optimal. The content and implementation of sensitization programs should be improved and more emphasis needs to be placed on women and children. PMID:25806955

An ontology for factors affecting tuberculosis treatment adherence behavior in sub-Saharan Africa.

PubMed

Ogundele, Olukunle Ayodeji; Moodley, Deshendran; Pillay, Anban W; Seebregts, Christopher J

2016-01-01

Adherence behavior is a complex phenomenon influenced by diverse personal, cultural, and socioeconomic factors that may vary between communities in different regions. Understanding the factors that influence adherence behavior is essential in predicting which individuals and communities are at risk of nonadherence. This is necessary for supporting resource allocation and intervention planning in disease control programs. Currently, there is no known concrete and unambiguous computational representation of factors that influence tuberculosis (TB) treatment adherence behavior that is useful for prediction. This study developed a computer-based conceptual model for capturing and structuring knowledge about the factors that influence TB treatment adherence behavior in sub-Saharan Africa (SSA). An extensive review of existing categorization systems in the literature was used to develop a conceptual model that captured scientific knowledge about TB adherence behavior in SSA. The model was formalized as an ontology using the web ontology language. The ontology was then evaluated for its comprehensiveness and applicability in building predictive models. The outcome of the study is a novel ontology-based approach for curating and structuring scientific knowledge of adherence behavior in patients with TB in SSA. The ontology takes an evidence-based approach by explicitly linking factors to published clinical studies. Factors are structured around five dimensions: factor type, type of effect, regional variation, cross-dependencies between factors, and treatment phase. The ontology is flexible and extendable and provides new insights into the nature of and interrelationship between factors that influence TB adherence.

An ontology for factors affecting tuberculosis treatment adherence behavior in sub-Saharan Africa

PubMed Central

Ogundele, Olukunle Ayodeji; Moodley, Deshendran; Pillay, Anban W; Seebregts, Christopher J

2016-01-01

Purpose Adherence behavior is a complex phenomenon influenced by diverse personal, cultural, and socioeconomic factors that may vary between communities in different regions. Understanding the factors that influence adherence behavior is essential in predicting which individuals and communities are at risk of nonadherence. This is necessary for supporting resource allocation and intervention planning in disease control programs. Currently, there is no known concrete and unambiguous computational representation of factors that influence tuberculosis (TB) treatment adherence behavior that is useful for prediction. This study developed a computer-based conceptual model for capturing and structuring knowledge about the factors that influence TB treatment adherence behavior in sub-Saharan Africa (SSA). Methods An extensive review of existing categorization systems in the literature was used to develop a conceptual model that captured scientific knowledge about TB adherence behavior in SSA. The model was formalized as an ontology using the web ontology language. The ontology was then evaluated for its comprehensiveness and applicability in building predictive models. Conclusion The outcome of the study is a novel ontology-based approach for curating and structuring scientific knowledge of adherence behavior in patients with TB in SSA. The ontology takes an evidence-based approach by explicitly linking factors to published clinical studies. Factors are structured around five dimensions: factor type, type of effect, regional variation, cross-dependencies between factors, and treatment phase. The ontology is flexible and extendable and provides new insights into the nature of and interrelationship between factors that influence TB adherence. PMID:27175067

Genotyping of Mycobacterium tuberculosis: application in epidemiologic studies

PubMed Central

Kato-Maeda, Midori; Metcalfe, John Z.; Flores, Laura

2014-01-01

Genotyping is used to track specific isolates of Mycobacterium tuberculosis in a community. It has been successfully used in epidemiologic research (termed ‘molecular epidemiology’) to study the transmission dynamics of TB. In this article, we review the genetic markers used in molecular epidemiologic studies including the use of whole-genome sequencing technology. We also review the public health application of molecular epidemiologic tools. PMID:21366420

The effects of graded levels of calorie restriction: III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse

PubMed Central

Mitchell, Sharon E.; Delville, Camille; Konstantopedos, Penelope; Derous, Davina; Green, Cara L.; Chen, Luonan; Han, Jing-Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Douglas, Alex; Lusseau, David; Speakman, John R.

2015-01-01

A commonly observed response in mammals to calorie restriction (CR) is reduced body temperature (Tb). We explored how the Tb of male C57BL/6 mice responded to graded CR (10 to 40%), compared to the response to equivalent levels of protein restriction (PR) over 3 months. Under CR there was a dynamic change in daily Tb over the first 30–35 days, which stabilized thereafter until day 70 after which a further decline was noted. The time to reach stability was dependent on restriction level. Body mass negatively correlated with Tb under ad libitum feeding and positively correlated under CR. The average Tb over the last 20 days was significantly related to the levels of body fat, structural tissue, leptin and insulin-like growth factor-1. Some mice, particularly those under higher levels of CR, showed periods of daily torpor later in the restriction period. None of the changes in Tb under CR were recapitulated by equivalent levels of PR. We conclude that changes in Tb under CR are a response only to the shortfall in calorie intake. The linear relationship between average Tb and the level of restriction supports the idea that Tb changes are an integral aspect of the lifespan effect. PMID:26286956

Survey of health care worker knowledge about childhood tuberculosis in high-burden centers in Botswana.

PubMed

Arscott-Mills, T; Masole, L; Ncube, R; Steenhoff, A P

2017-05-01

Quantifying health care workers' (HCWs') knowledge about tuberculosis (TB) informs educational interventions. We assessed HCWs' knowledge about childhood TB in Botswana. Semi-structured interviews were conducted with HCWs at 46 sites around Botswana using a piloted instrument. Transcripts were double-coded using a coding schema. Discrepancies were resolved by consensus and a systematic thematic analysis was performed. The sites (42 clinics and 4 hospitals) were urban (n = 9, 20%), semi-urban (n = 10, 22%) and rural (n = 27, 58%). HCWs included nurses (n = 42, 89%) and nurse assistants (n = 4, 11%). Sixteen (56%) HCWs were the TB focal persons for their site. Themes did not vary by type of site, HCW or TB focal person. Although the level of knowledge about secondary prevention using isoniazid prophylaxis therapy was fair, implementation was poor and contact tracing was not being performed. Barriers to TB diagnosis included poor knowledge about TB in the community, minimal diagnostics at site of care and not receiving test results. However, most HCWs reported that treatment initiation and the calculation of appropriate dosages were easy once the diagnosis had been made. In Botswana, HCWs' levels of knowledge about childhood TB varied greatly. The areas of TB diagnosis, screening and prophylaxis in children need additional attention in TB training courses; however, increased knowledge alone would not overcome all the barriers identified by the HCWs.

Health worker perspectives on barriers to delivery of routine tuberculosis diagnostic evaluation services in Uganda: a qualitative study to guide clinic-based interventions.

PubMed

Cattamanchi, Adithya; Miller, Cecily R; Tapley, Asa; Haguma, Priscilla; Ochom, Emmanuel; Ackerman, Sara; Davis, J Lucian; Katamba, Achilles; Handley, Margaret A

2015-01-22

Studies of the quality of tuberculosis (TB) diagnostic evaluation of patients in high burden countries have generally shown poor adherence to international or national guidelines. Health worker perspectives on barriers to improving TB diagnostic evaluation are critical for developing clinic-level interventions to improve guideline implementation. We conducted structured, in-depth interviews with staff at six district-level health centers in Uganda to elicit their perceptions regarding barriers to TB evaluation. Interviews were transcribed, coded with a standardized framework, and analyzed to identify emergent themes. We used thematic analysis to develop a logic model depicting health system and contextual barriers to recommended TB evaluation practices. To identify possible clinic-level interventions to improve TB evaluation, we categorized findings into predisposing, enabling, and reinforcing factors as described by the PRECEDE model, focusing on potentially modifiable behaviors at the clinic-level. We interviewed 22 health center staff between February 2010 and November 2011. Participants identified key health system barriers hindering TB evaluation, including: stock-outs of drugs/supplies, inadequate space and infrastructure, lack of training, high workload, low staff motivation, and poor coordination of health center services. Contextual barrier challenges to TB evaluation were also reported, including the time and costs borne by patients to seek and complete TB evaluation, poor health literacy, and stigma against patients with TB. These contextual barriers interacted with health system barriers to contribute to sub-standard TB evaluation. Examples of intervention strategies that could address these barriers and are related to PRECEDE model components include: assigned mentors/peer coaching for new staff (targets predisposing factor of low motivation and need for support to conduct job duties); facilitated workshops to implement same day microscopy (targets enabling factor of patient barriers to completing TB evaluation), and recognition/incentives for good TB screening practices (targets low motivation and self-efficacy). Our findings suggest that health system and contextual barriers work together to impede TB diagnosis at health centers and, if not addressed, could hinder TB case detection efforts. Qualitative research that improves understanding of the barriers facing TB providers is critical to developing targeted interventions to improve TB care.

The development of new phosphors of Tb3+/Eu3+ co-doped Gd3Al5O12 with tunable emission

NASA Astrophysics Data System (ADS)

Teng, Xin; Wang, Wenzhi; Cao, Zhentao; Li, Jinkai; Duan, Guangbin; Liu, Zongming

2017-07-01

The gadolinium aluminum garnets Gd3Al5O12 (GdAG) activated with Tb3+/Eu3+ were successfully prepared via co-precipitation method at 1500 °C in this work. The crystal structure stabilization, elements analysis, microphotograph, PL/PLE spectra, decay behavior and quantum efficiency were discussed in detail. The metastable GdAG compounds been effectively stabilized by doping with smaller 10 at.% Tb3+, which then allows the development of new phosphors of (Gd0.9-xTb0.1Eux)3Al5O12 (GdAG:Tb3+/Eu3+, x = 0-0.03) for opto-functionality explorations. The PLE/PL spectra displays that the strongest PLE peak was located at ∼276 nm, which overlaps the 8S7/2 → 6IJ transition of Gd3+. Under 276 nm excitation, the phosphors exhibited both Tb3+ and Eu3+ emissions at 548 nm (green, 5D4 → 7F5 transition of Tb3+) and 592 nm (orange-red, 5D0 → 7F1 transition of Eu3+), respectively. The emission intensities of Tb3+ and Eu3+ remarkably varied with the Eu3+ incorporation. As a consequence, the emission color can be readily tuned from approximately green to orange-red. Fluorescence decay analysis found that the lifetime for the Tb3+ emission rapidly decreased conforming to the Tb3+ → Eu3+ energy transfer, and the energy transfer efficiency was calculated. Owing to the Gd3+ → Eu3+ and Gd3+ → Tb3+ energy transfer, the emission intensities of Tb3+ and Eu3+ in (Gd0.9-xTb0.1Eux)AG phosphor were higher than (Y0.87Tb0.1Eu0.03)AG and (Lu0.87Tb0.1Eu0.03)AG system. The (Gd0.9-xTb0.1Eux)AG garnet phosphors developed in this work may serve as a new type of phosphor which hopefully meets the requirements of various lighting and optical display applications.

A supramolecular Tröger's base derived coordination zinc polymer for fluorescent sensing of phenolic-nitroaromatic explosives in water† †Electronic supplementary information (ESI) available: Spectroscopic (multinuclear NMR, IR HRMS) characterizations, optimized structure, TGA, powder diffraction and fluorescence titration profiles. See DOI: 10.1039/c6sc04367d Click here for additional data file.

PubMed Central

Dabadie, Charlyne; Byrne, Kevin; Savyasachi, Aramballi J.; Umadevi, Deivasigamani; Schmitt, Wolfgang; Kitchen, Jonathan A.

2017-01-01

A V-Shaped 4-amino-1,8-napthalimide derived tetracarboxylic acid linker (L; bis-[N-(1,3-benzenedicarboxylic acid)]-9,18-methano-1,8-naphthalimide-[b,f][1,5]diazocine) comprising the Tröger's base (TB) structural motif was rationally designed and synthesised to access a nitrogen-rich fluorescent supramolecular coordination polymer. By adopting the straight forward precipitation method, a new luminescent nanoscale Zn(ii) coordination polymer (TB-Zn-CP) was synthesized in quantitative yield using Zn(OAc)2·2H2O and tetraacid linker L (1 : 0.5) in DMF at room temperature. The phase-purity of as-synthesised TB-Zn-CP was confirmed by X-ray powder diffraction analysis, infra-red spectroscopy, and elemental analysis. Thermogravimetric analysis suggests that TB-Zn-CP is thermally stable up to 330 °C and the morphological features of TB-Zn-CP was analysed by SEM and AFM techniques. The N2 adsorption isotherm of thermally activated TB-Zn-CP at 77 K revealed a type-II reversible adsorption isotherm and the calculated Brunauer–Emmett–Teller (BET) surface area was found to be 72 m2 g–1. Furthermore, TB-Zn-CP displayed an excellent CO2 uptake capacity of 76 mg g–1 at 273 K and good adsorption selectivity for CO2 over N2 and H2. The aqueous suspension of as-synthesized TB-Zn-CP showed strong green fluorescence (λ max = 520 nm) characteristics due to the internal-charge transfer (ICT) transition and was used as a fluorescent sensor for the discriminative sensing of nitroaromatic explosives. The aqueous suspension of TB-Zn-CP showed the largest quenching responses with high selectivity for phenolic-nitroaromatics (4-NP, 2,4-DNP and PA) even in the concurrent presence of other potentially competing nitroaromatic analytes. The fluorescence titration studies also provide evidence that TB-Zn-CP detects picric acid as low as the parts per billion (26.3 ppb) range. Furthermore, the observed fluorescence quenching responses of TB-Zn-CP towards picric acid were highly reversible. The highly selective fluorescence quenching responses including the reversible detection efficiency make the nanoscale coordination polymer TB-Zn-CP a potential material for the discriminative fluorescent sensing of nitroaromatic explosives. PMID:28572910

Participatory communication for tuberculosis control in prisons in Bolivia, Ecuador, and Paraguay.

PubMed

Waisbord, Silvio

2010-03-01

To assess the challenges in reducing tuberculosis (TB) in prisons in Bolivia, Ecuador, and Paraguay and propose ways to address them through communication interventions. Challenges to two central goals of TB control--early diagnosis of positive cases and successful application of the directly observed treatment, short course (DOTS) strategy--were examined. Data were gathered (through in-depth, structured interviews) and focus groups were conducted in the prisons that housed the largest number of male inmates in each country. Interviewees and focus group participants included program directors, administrative personnel, correctional health and security staff, and incarcerated people who were or had been under treatment for TB and had participated as 'peers' in health services. The findings showed a range of entrenched obstacles for adequate TB control. Stigmatizing attitudes and low knowledge about TB among inmates and key prison personnel discouraged people living in prisons from seeking diagnosis and treatment. Systemic problems in prison health services, along with squalid living conditions, lack of coordination between national TB programs and prison health systems, and insufficient allocation of resources to health prevented the provision of adequate TB prevention and care. In addressing the barriers to effective TB control in prison systems in Bolivia, Ecuador, and Paraguay, a participatory approach to communication is necessary.

Towards the development of new phosphors with reduced content of rare earth elements: Structural and optical characterization of Ce:Tb: Al{sub 2}SiO{sub 5}

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

Chiriu, D.; Stagi, L.; Carbonaro, C.M.

2016-05-15

Highlights: • A new promising inert matrix as host of luminescent ions is proposed. • Al2SiO5 matrix is free from Rare earths (critical raw materials). • Doping the matrix with Ce and Tb we obtain an efficient green emitter. • Cerium acts as sensitizer for Terbium emission. - Abstract: A new promising inert matrix as host of luminescent ions is proposed. Al2SiO5 samples, doped with rare earths (Ce, Tb single doped and co-doped) are proposed as good prospect for the development of new UV–vis converter with reduced content of rare earths elements. Structural characterization by Raman, XRD spectroscopy and TEMmore » imaging reveals the sillimanite phase and nano sized dimension of the investigated powders. Optical characterization by steady time and time resolved emission spectroscopy for the single doped and co-doped samples allows to identify an efficient energy transfer from Ce to Tb ions under near UV excitation wavelength. The intense green emission observed in the Ce:Tb co-doped Al2SiO5 system suggests its potential application as efficient blue pumped green emitter phosphor to be exploited for white LED: to this purpose we tested the compound in combination with a red emitting doping ion recording for Ce:Tb:Cr:ASO system a correlated color temperature of 6720 K.« less

Terbium(III) Modified Fluorescent Carbon Dots for Highly Selective and Sensitive Ratiometry of Stringent.

PubMed

Chen, Bin Bin; Liu, Meng Li; Zhan, Lei; Li, Chun Mei; Huang, Cheng Zhi

2018-03-20

Highly selective and sensitive detection of guanosine 3'-diphosphate-5'-diphosphate (ppGpp), namely, the stringent in plants or microorganisms responding to strict or extreme environmental conditions such as stress and starvation, which plays an important role in gene expression, rRNA and antibiotics production, regulations of virulence of bacteria, and growth of plants, faces a great challenge owing to its extreme similarity to normal nucleotides. By modifying the surface groups of a facile two-step hydrothermal route prepared carbon dots (CDs) with terbium ions (Tb 3+ ) in this contribution, a novel fluorescent probe with excellent properties such as highly physical and chemical stability, narrow emission and excitation wavelength-independent emission was prepared. The Tb 3+ ions on the surface of CDs cannot only preserve the intrinsic fluorescence (FL) of CDs but also keep its own coordination capacity with rare earth complex, and thus the clamp structure (four phosphate groups) of ppGpp can specific binding with Tb 3+ ions on the surface of CDs to produce antenna effect. Therefore, a highly selective and sensitive fluorescent ratiometry of ppGpp was developed by terbium-modified carbon dots (CDs-Tb) with the limit of detection as low as 50 nM based on the synergistic effect of antenna effect of Tb 3+ ions and specific recognition capacity of CDs. The applicability of this assay was demonstrated by CDs-Tb-based paper sensor for high distinguishing ppGpp from other nucleotides with similar structure.

Identification and mapping of two powdery mildew resistance genes in Triticum boeoticum L.

PubMed

Chhuneja, Parveen; Kumar, Krishan; Stirnweis, Daniel; Hurni, Severine; Keller, Beat; Dhaliwal, Harcharan S; Singh, Kuldeep

2012-04-01

Powdery mildew (PM) caused by Blumeria graminis f. sp. tritici (Bgt), is one of the important foliar diseases of wheat that can cause serious yield losses. Breeding for cultivars with diverse resources of resistance is the most promising approach for combating this disease. The diploid A genome progenitor species of wheat are an important resource for new variability for disease resistance genes. An accession of Triticum boeoticum (A(b)A(b)) showed resistance against a number of Bgt isolates, when tested using detached leaf segments. Inheritance studies in a recombinant inbred line population (RIL), developed from crosses of PM resistant T. boeoticum acc. pau5088 with a PM susceptible T. monococcum acc. pau14087, indicated the presence of two powdery mildew resistance genes in T. boeoticum acc. pau5088. Analysis of powdery mildew infection and molecular marker data of the RIL population revealed that both powdery mildew resistance genes are located on the long arm of chromosome 7A. Mapping was conducted using an integrated linkage map of 7A consisting of SSR, RFLP, STS, and DArT markers. These powdery mildew resistance genes are tentatively designated as PmTb7A.1 and PmTb7A.2. The PmTb7A.2 is closely linked to STS markers MAG2185 and MAG1759 derived from RFLP probes which are linked to powdery mildew resistance gene Pm1. This indicated that PmTb7A.2 might be allelic to Pm1. The PmTb7A.1, flanked by a DArT marker wPt4553 and an SSR marker Xcfa2019 in a 4.3 cM interval, maps proximal to PmT7A.2. PmTb7A.1 is putatively a new powdery mildew resistance gene. The powdery mildew resistance genes from T. boeoticum are currently being transferred to cultivated wheat background through marker-assisted backcrossing, using T. durum as bridging species.

Identification and evaluation of the novel immunodominant antigen Rv2351c from Mycobacterium tuberculosis

PubMed Central

Wang, Xuezhi; Chen, Shuangshuang; Xu, Yongjuan; Zheng, Huajun; Xiao, Tongyang; Li, Yuqing; Chen, Xing; Huang, Mingxiang; Zhang, Haifeng; Fang, Xijing; Jiang, Yi; Li, Machao; Liu, Haican; Wan, Kanglin

2017-01-01

There is an urgent need for new immunodominant antigens to improve the diagnosis of tuberculosis (TB) and the efficacy of the TB vaccine to control the disease worldwide. In this study, we evaluated the diagnostic potential of a novel Mycobacterium tuberculosis (MTB)-specific antigen, Rv2351c, from region of difference (RD) 7 of the MTB genome, and investigated the potency of the vaccine by identifying its immunological function in human and animal immunological experiments. Twenty T-cell epitopes were identified using TEpredict and prediction tools from the Immune Epitope Database and Analysis Resource. A total of 159 subjects, including 61 patients with pulmonary TB, 38 patients with no TB and 55 healthy donors, were recruited and analyzed with an enzyme-linked immunospot (ELISpot) assay. The ELISpot assay using Rv2351c to detect TB infection, as compared with bacteriological tests as the gold standard, had a sensitivity and specificity of 61.4% (35/57) and 91.4% (85/93), respectively. The ELISpot assay using Rv2351c had a good conformance (κ=0.554) as compared with the bacteriological test. Rv2351c also elicited a potent cellular immune response with a high expression of cytokines (IFN-γ (4978±596.7 μg/mL) and IL-4 (68.3±15.5 μg/mL)) and a potent humoral immune response with a high concentration of IgG (1:2.2 × 106), IgG1 (1:4.5 × 105) and IgG2a (1:1.6 × 106) in immunized BALB/c mice. In addition, the ratio of IgG2a/IgG1 indicated that Rv2351c induced cellular immunity in the mice. The results of this study indicated that Rv2351c is an antigen with good immunogenicity that may potentially be used to develop diagnostic techniques and new TB vaccines. PMID:28588287

Urine-Based Nested PCR for the Diagnosis of Mycobacterium tuberculosis: A Comparative Study Between HIV-Positive and HIV-Negative Patients.

PubMed

Jamshidi Makiani, Mahin; Davoodian, Parivash; Baghershiroodi, Mahnaz; Nejatizadeh, Abdol Azim; Fakkhar, Farideh; Zangeneh, Mehrangiz; Jahangiri, Nadia

2016-08-01

While tuberculosis (TB) can be diagnosed by microscopy and culture, the sensitivity of Ziehl-Neelsen staining is variable and culture results require 4 - 8 weeks to be determined. Polymerase chain reaction (PCR) and its modifications, including nested PCR, might be promising methods for the rapid diagnosis of TB. This study aimed to evaluate the performance of nested PCR on urine samples of human immunodeficiency virus (HIV)-positive and -negative patients with different manifestations of clinical TB. In a prospective study, three early-morning urine samples from 100 patients with pulmonary TB (PTB) or extrapulmonary TB (EPTB) were evaluated using a molecular target with insertion element IS6110, specific to the Mycobacterium tuberculosis genome, and nested PCR was performed. The results were analyzed with SPSS version 22. A total of 100 patients, including 74 (74%) with PTB and 26 (26%) with EPTB, were enrolled. Positive smears were seen in 38 patients (38%). Lymph nodes were the most commonly involved organ in 14 of the 26 (53.8%) EPTB patients (13.5%). Seven (23.1%) of the EPTB patients were HIV-positive. Urine PCR was positive in only 28 patients (28%). Seven HIV-positive patients with PTB showed positive urine PCR results. Moreover, PCR results were positive in only one of the seven HIV-positive subjects with EPTB. Positive PCR results were found in 20 of the 73 HIV-negative patients (27.4%) and in 8 of the 27 HIV-positive patients (29.6%). Therefore, there was no significant difference between the HIV-negative and HIV-positive patients for urine PCR (sensitivity 29.6%, specificity 72.6%; positive and negative predictive values 28% and 72%, respectively; P = 0.138). Nested PCR showed the same sensitivity in HIV-positive and HIV-negative patients. It can be applied as a rapid technique for the diagnosis of TB.

Cetia pacifica gen. nov., sp. nov., a chemolithoautotrophic, thermophilic, nitrate-ammonifying bacterium from a deep-sea hydrothermal vent.

PubMed

Grosche, Ashley; Sekaran, Hema; Pérez-Rodríguez, Ileana; Starovoytov, Valentin; Vetriani, Costantino

2015-04-01

A thermophilic, anaerobic, chemolithoautotrophic bacterium, strain TB-6(T), was isolated from a deep-sea hydrothermal vent located on the East Pacific Rise at 9° N. The cells were Gram-staining-negative and rod-shaped with one or more polar flagella. Cell size was approximately 1-1.5 µm in length and 0.5 µm in width. Strain TB-6(T) grew between 45 and 70 °C (optimum 55-60 °C), 0 and 35 g NaCl l(-1) (optimum 20-30 g l(-1)) and pH 4.5 and 7.5 (optimum pH 5.5-6.0). Generation time under optimal conditions was 2 h. Growth of strain TB-6(T) occurred with H2 as the energy source, CO2 as the carbon source and nitrate or sulfur as electron acceptors, with formation of ammonium or hydrogen sulfide, respectively. Acetate, (+)-d-glucose, Casamino acids, sucrose and yeast extract were not used as carbon and energy sources. Inhibition of growth occurred in the presence of lactate, peptone and tryptone under a H2/CO2 (80 : 20; 200 kPa) gas phase. Thiosulfate, sulfite, arsenate, selenate and oxygen were not used as electron acceptors. The G+C content of the genomic DNA was 36.8 mol%. Phylogenetic analysis of the 16S rRNA gene of strain TB-6(T) showed that this organism branched separately from the three most closely related genera, Caminibacter , Nautilia and Lebetimonas , within the family Nautiliaceae . Strain TB-6(T) contained several unique fatty acids in comparison with other members of the family Nautiliaceae . Based on experimental evidence, it is proposed that the organism represents a novel species and genus within the family Nautiliaceae , Cetia pacifica, gen. nov., sp. nov. The type strain is TB-6(T) ( = DSM 27783(T) = JCM 19563(T)). © 2015 IUMS.

Structural and functional features of enzymes of Mycobacterium tuberculosis peptidoglycan biosynthesis as targets for drug development.

PubMed

Moraes, Gleiciane Leal; Gomes, Guelber Cardoso; Monteiro de Sousa, Paulo Robson; Alves, Cláudio Nahum; Govender, Thavendran; Kruger, Hendrik G; Maguire, Glenn E M; Lamichhane, Gyanu; Lameira, Jerônimo

2015-03-01

Tuberculosis (TB) is the second leading cause of human mortality from infectious diseases worldwide. The WHO reported 1.3 million deaths and 8.6 million new cases of TB in 2012. Mycobacterium tuberculosis (M. tuberculosis), the infectious bacteria that causes TB, is encapsulated by a thick and robust cell wall. The innermost segment of the cell wall is comprised of peptidoglycan, a layer that is required for survival and growth of the pathogen. Enzymes that catalyse biosynthesis of the peptidoglycan are essential and are therefore attractive targets for discovery of novel antibiotics as humans lack similar enzymes making it possible to selectively target bacteria only. In this paper, we have reviewed the structures and functions of enzymes GlmS, GlmM, GlmU, MurA, MurB, MurC, MurD, MurE and MurF from M. tuberculosis that are involved in peptidoglycan biosynthesis. In addition, we report homology modelled 3D structures of those key enzymes from M. tuberculosis of which the structures are still unknown. We demonstrated that natural substrates can be successfully docked into the active sites of the GlmS and GlmU respectively. It is therefore expected that the models and the data provided herein will facilitate translational research to develop new drugs to treat TB. Copyright © 2015. Published by Elsevier Ltd.

Folic acid-conjugated GdPO4:Tb3+@SiO2 Nanoprobe for folate receptor-targeted optical and magnetic resonance bi-modal imaging

NASA Astrophysics Data System (ADS)

Xu, Xianzhu; Zhang, Xiaoying; Wu, Yanli

2016-11-01

Both fluorescent and magnetic nanoprobes have great potential applications for diagnostics and therapy. In the present work, a folic acid-conjugated and silica-modified GdPO4:Tb3+ (GdPO4:Tb3+@SiO2-FA) dual nanoprobe was strategically designed and synthesized for the targeted dual-modality optical and magnetic resonance (MR) imaging via a facile aqueous method. Their structural, optical, and magnetic properties were determined using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), ultraviolet-visible spectra (UV-Vis), photoluminescence (PL), and superconducting quantum interference device (SQUID). These results indicated that GdPO4:Tb3+@SiO2-FA were uniform monodisperse core-shell structured nanorods (NRs) with an average length of 200 nm and an average width of 25 nm. The paramagnetic property of the synthesized GdPO4:Tb3+@SiO2-FA NRs was confirmed with its linear hysteresis plot (M-H). In addition, the NRs displayed an obvious T1-weighted effect and thus it could potentially serve as a T1-positive contrast agent. The NRs emitted green lights due to the 5D4 → 7F5 transition of the Tb3+. The in vitro assays with NCI-H460 lung cancer cells and human embryonic kidney cell line 293T cells indicated that the GdPO4:Tb3+@SiO2-FA nanoprobe could specifically bind the cells bearing folate receptors (FR). The MTT assay of the NRs revealed that its cytotoxicity was very low. Further in vivo MRI experiments distinctively depict enhanced anatomical features in a xenograft tumor. These results suggest that the GdPO4:Tb3+@SiO2-FA NPs have excellent imaging and cell-targeting abilities for the folate receptor-targeted dual-modality optical and MR imaging and can be potentially used as the nanoprobe for bioimaging.

Interactive Exploration on Large Genomic Datasets.

PubMed

Tu, Eric

2016-01-01

The prevalence of large genomics datasets has made the the need to explore this data more important. Large sequencing projects like the 1000 Genomes Project [1], which reconstructed the genomes of 2,504 individuals sampled from 26 populations, have produced over 200TB of publically available data. Meanwhile, existing genomic visualization tools have been unable to scale with the growing amount of larger, more complex data. This difficulty is acute when viewing large regions (over 1 megabase, or 1,000,000 bases of DNA), or when concurrently viewing multiple samples of data. While genomic processing pipelines have shifted towards using distributed computing techniques, such as with ADAM [4], genomic visualization tools have not. In this work we present Mango, a scalable genome browser built on top of ADAM that can run both locally and on a cluster. Mango presents a combination of different optimizations that can be combined in a single application to drive novel genomic visualization techniques over terabytes of genomic data. By building visualization on top of a distributed processing pipeline, we can perform visualization queries over large regions that are not possible with current tools, and decrease the time for viewing large data sets. Mango is part of the Big Data Genomics project at University of California-Berkeley [25] and is published under the Apache 2 license. Mango is available at https://github.com/bigdatagenomics/mango.

The effects of Tb substitution for La on the magnetic properties of LaFe11.5Si1.5 compound

NASA Astrophysics Data System (ADS)

Imam, H.; Zhang, H. G.; Xu, L.; Zhao, J. L.; Gao, X. X.; Yue, M.

2018-05-01

The structural and magnetic properties of La1-yTbyFe11.5Si1.5 compounds have been investigated. The substituted 5 percent of Tb has remarkably increased the maximum entropy change (-ΔSM) to a value of 25.2 J/kg·K. However, a further increase of Tb leads to a monotonous decrease in the entropy change, mainly due to phase separation. The Tb substitution also can lower the thermal and magnetic hysteresis loss of the system. Another feature of this replacement is that, with Tb content higher than 10 percent, the Curie temperature (TC) starts to increase and reaches 197 K when 30 percent of La is substituted. These results indicate that La1-yTbyFe11.5Si1.5 may be a promising candidate for magnetic refrigeration material in certain temperature range.

Barriers to the treatment of childhood tuberculous infection and tuberculosis disease: a qualitative study.

PubMed

Chiang, S S; Roche, S; Contreras, C; Del Castillo, H; Canales, P; Jimenez, J; Tintaya, K; Becerra, M C; Lecca, L

2017-02-01

In 2012, Peru's National TB Program (NTP) reported approximately 2400 incident cases of tuberculosis (TB) disease in children aged <15 years. Peru's TB burden is concentrated in the Lima metropolitan area, particularly in poor districts such as El Agustino and La Victoria, where this study was conducted. To identify barriers to the treatment of childhood tuberculous infection and TB disease in Lima from the perspective of front-line providers and patients' families. We conducted 10 semi-structured focus groups with 53 purposefully sampled primary care providers, community health workers, and parents/guardians of pediatric TB patients. We also completed nine in-depth interviews with National TB Program administrators and pulmonologists specializing in TB. Two authors performed inductive thematic analysis and identified emerging themes. Four main treatment barriers emerged from the data: 1) dosing errors, 2) time- and labor-intensive preparation and administration of medications, 3) provider concern that isoniazid preventive therapy (IPT) generates isoniazid resistance, and 4) poor adherence to IPT. Our findings highlight the urgent need for child-friendly formulations, provider and parent/guardian education about IPT, and strategies to promote adherence to IPT, including support and supervision by health workers and/or regimens with fewer doses.

Luminescence of Tb-doped Ca 3Y 2(Si 3O 9) 2 oxide upon UV and VUV synchrotron radiation excitation

NASA Astrophysics Data System (ADS)

Dobrowolska, Anna; Zych, Eugeniusz

2011-07-01

Powders of calcium yttrium silicate, Ca 3Y 2(Si 3O 9) 2, containing 0.1-3% Tb 3+ were prepared using a sol-gel method and characterized with XRD, IR, UV-vis and UV-VUV spectroscopies at room temperature and 10 K. Structural analysis revealed pure monoclinic phase of Ca 3Y 2(Si 3O 9) 2 after heat-treatment at 1000 °C. Infrared spectroscopy showed that between 800 and 900 °C a short-range structural organization of the components proceeded, yet without crystallization. A strong emission of Tb 3+ had been observed both in the green part of the spectrum due to the 5D4→ 7FJ transitions and in the blue-violet region owing to the 5D3→ 7FJ radiative relaxation. The color of the light could be tuned from yellowish-green to bluish-white both by means of the dopant content and the temperature of synthesis. Efficient luminescence of Tb 3+-doped Ca 3Y 2(Si 3O 9) 2 phosphors could also be obtained upon stimulation with vacuum ultraviolet synchrotron radiation demonstrating that an energy transfer from the host to the Tb 3+ ions takes place.

The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

PubMed

Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB susceptibility in parental populations may contribute to variation in disease susceptibility in the region.

The Effects of Socioeconomic Status, Clinical Factors, and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

PubMed Central

Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB susceptibility in parental populations may contribute to variation in disease susceptibility in the region. PMID:24728409

Evaluating the electronic tuberculosis register surveillance system in Eden District, Western Cape, South Africa, 2015.

PubMed

Mlotshwa, Mandla; Smit, Sandra; Williams, Seymour; Reddy, Carl; Medina-Marino, Andrew

2017-01-01

Tuberculosis (TB) surveillance data are crucial to the effectiveness of National TB Control Programs. In South Africa, few surveillance system evaluations have been undertaken to provide a rigorous assessment of the platform from which the national and district health systems draws data to inform programs and policies. Evaluate the attributes of Eden District's TB surveillance system, Western Cape Province, South Africa. Data quality, sensitivity and positive predictive value were assessed using secondary data from 40,033 TB cases entered in Eden District's ETR.Net from 2007 to 2013, and 79 purposively selected TB Blue Cards (TBCs), a medical patient file and source document for data entered into ETR.Net. Simplicity, flexibility, acceptability, stability and usefulness of the ETR.Net were assessed qualitatively through interviews with TB nurses, information health officers, sub-district and district coordinators involved in the TB surveillance. TB surveillance system stakeholders report that Eden District's ETR.Net system was simple, acceptable, flexible and stable, and achieves its objective of informing TB control program, policies and activities. Data were less complete in the ETR.Net (66-100%) than in the TBCs (76-100%), and concordant for most variables except pre-treatment smear results, antiretroviral therapy (ART) and treatment outcome. The sensitivity of recorded variables in ETR.Net was 98% for gender, 97% for patient category, 93% for ART, 92% for treatment outcome and 90% for pre-treatment smear grading. Our results reveal that the system provides useful information to guide TB control program activities in Eden District. However, urgent attention is needed to address gaps in clinical recording on the TBC and data capturing into the ETR.Net system. We recommend continuous training and support of TB personnel involved with TB care, management and surveillance on TB data recording into the TBCs and ETR.Net as well as the implementation of a well-structured quality control and assurance system.

Is Knowledge Regarding Tuberculosis Associated with Stigmatising and Discriminating Attitudes of General Population towards Tuberculosis Patients? Findings from a Community Based Survey in 30 Districts of India

PubMed Central

Sagili, Karuna D.; Satyanarayana, Srinath; Chadha, Sarabjit S.

2016-01-01

Background Stigmatising and discriminating attitudes may discourage tuberculosis (TB) patients from actively seeking medical care, hide their disease status, and discontinue treatment. It is expected that appropriate knowledge regarding TB should remove stigmatising and discriminating attitudes. In this study we assessed the prevalence of stigmatising and discriminating attitudes towards TB patients among general population and their association with knowledge regarding TB. Method A cross-sectional knowledge, attitude and practice survey was conducted in 30 districts of India in January-March 2011. A total of 4562 respondents from general population were interviewed using semi-structured questionnaires which contained items to measure stigma, discrimination and knowledge on TB. Result Of the 4562 interviewed, 3823 were eligible for the current analysis. Of these, 73% (95% CI 71.4–74.2) had stigmatising and 98% (95% CI 97.4–98.3) had discriminating attitude towards TB patients. Only 17% (95% CI 15.6–18.0) of the respondents had appropriate knowledge regarding TB with even lower levels observed amongst females, rural areas and respondents from low income groups. Surprisingly stigmatising (adjusted OR 1.31 (0.78–2.18) and discriminating (adjusted OR 0.79 (0.43–1.44) attitudes were independent of knowledge regarding TB. Conclusion Stigmatising and discriminating attitudes towards TB patients remain high among the general population in India. Since these attitudes were independent of the knowledge regarding TB, it is possible that the current disseminated knowledge regarding TB which is mainly from a medical perspective may not be adequately addressing the factors that lead to stigma and discrimination towards TB patients. Therefore, there is an urgent need to review the messages and strategies currently used for disseminating knowledge regarding TB among general population and revise them appropriately. The disseminated knowledge should include medical, psycho-social and economic aspects of TB that not only informs people about medical aspects of TB disease, but also removes stigma and discrimination. PMID:26829713

Cellular Architecture of Spinal Granulomas and the Immunological Response in Tuberculosis Patients Coinfected with HIV.

PubMed

Bhattacharya, Debapriya; Danaviah, Siva; Muema, Daniel M; Akilimali, Ngomu Akeem; Moodley, Prashini; Ndung'u, Thumbi; Das, Gobardhan

2017-01-01

Mycobacterium tuberculosis ( M.tb ) and HIV are individually responsible for the most deaths worldwide among all infectious agents, and coinfection with M.tb and HIV is a significant public health challenge in the developing world. Although the lung is the primary target organ for tuberculosis (TB), M.tb can also cause extrapulmonary tuberculosis (EPTB) such as in the bones and joints. Treatment of EPTB is much more challenging than treatment of pulmonary TB. The hallmark of the host immune response against TB is the formation of organized structures called granulomas that are infiltrated with immune cells and are rich in cytokines and chemokines. Inside granulomas, the host confines the M.tb bacteria to a particular region of the organ and avoids dispersion. In this study, we analyzed immune cells in bone granulomas of patients with EPTB that are also coinfected with HIV. We found that HIV-infected TB patients have dispersed bone granulomas, with reduced T cell numbers and a concomitant increase in plasma cells. Additionally, HIV-infected patients exhibited dramatically increased serum levels of IgM and IgG1 antibodies, which is indicative of T-cell-independent B-cell activation and mucosal T-cell activation, respectively. Interestingly, we also observed that CD29 + stem cells are increased in HIV-TB coinfection, suggesting a link with HIV infection. Therefore, our work provides new insights into the architecture of spinal TB granulomas and the role of B-cells and humoral immunity against a highly infectious intracellular pathogen. We propose that our findings will inform biomarker identification for EPTB and possibly the development of related therapeutics and/or vaccines to protect HIV-infected patients against disseminated TB.

A survey to assess the extent of public-private mix DOTS in the management of tuberculosis in Zambia

PubMed Central

Kapata, Nathan; Maboshe, Mwendaweli; Michelo, Charles; Babaniyi, Olusegun

2015-01-01

Background Involving all relevant healthcare providers in tuberculosis (TB) management through public-private mix (PPM) approaches is a vital element in the World Health Organization's (WHO) Stop TB Strategy. The control of TB in Zambia is mainly done in the public health sector, despite the high overall incidence rates. Aim We conducted a survey to determine the extent of private-sector capacity, participation, practices and adherence to national guidelines in the control of TB. Setting This survey was done in the year 2012 in 157 facilities in three provinces of Zambia where approximately 85% of the country's private health facilities are found. Methods We used a structured questionnaire to interview the heads of private health facilities to assess the participation of the private health sector in TB diagnosis, management and prevention activities. Results Out of 157 facilities surveyed, 40.5% were from the Copperbelt, 4.4% from Central province and 55.1% from Lusaka province. Only 23.8% of the facilities were able to provide full diagnosis and management of TB patients. Although 47.4% of the facilities reported that they do notify their cases to the National TB control programme, the majority (62.7%) of these facilities did not show evidence of notifications. Conclusion Our results show that the majority of the facilities that diagnose and manage TB in the private sector do not report their TB activities to the National TB Control Programme (NTP). There is a need for the NTP to improve collaboration with the private sector with respect to TB control activities and PPM for Directly Observed Treatment, Short Course (DOTS). PMID:26245591

Team approach to manage difficult-to-treat TB cases: Experiences in Europe and beyond.

PubMed

D'Ambrosio, L; Bothamley, G; Caminero Luna, J A; Duarte, R; Guglielmetti, L; Muñoz Torrico, M; Payen, M C; Saavedra Herrera, N; Salazar Lezama, M A; Skrahina, A; Tadolini, M; Tiberi, S; Veziris, N; Migliori, G B

As recommended by the World Health Organization (WHO), optimal management of MDR-TB cases can be ensured by a multi-speciality consultation body known as 'TB Consilium'. This body usually includes different medical specialities, competences and perspectives (e.g., clinical expertise both for adults and children; surgical, radiological and public health expertise; psychological background and nursing experience, among others), thus lowering the risk of making mistakes - or managing the patients inappropriately, in order to improve their clinical outcomes. At present, several high MDR-TB burden countries in the different WHO regions (and beyond) have introduced TB Consilium-like bodies at the national or subnational level to reach consensus on the best treatment approach for their patients affected by TB. In addition, in countries/settings where a formal system of consultation does not exist, specialized staff from MDR-TB reference centres or international organizations usually spend a considerable amount of their working time responding to phone or e-mail clinical queries on how to manage M/XDR-TB cases. The aim of this manuscript is to describe the different experiences with the TB Consilia both at the international level (European Respiratory Society - ERS/WHO TB Consilium) and in some of the countries where this experience operates successfully in Europe and beyond. The Consilium experiences are described around the following topics: (1) history, aims and focus; (2) management and funding; (3) technical functioning and structure; (4) results achieved. In addition a comparative analysis of the TB Consilia in the different countries has been performed. Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Early Whole Blood Transcriptional Signatures Are Associated with Severity of Lung Inflammation in Cynomolgus Macaques with Mycobacterium tuberculosis Infection.

PubMed

Gideon, Hannah P; Skinner, Jason A; Baldwin, Nicole; Flynn, JoAnne L; Lin, Philana Ling

2016-12-15

Whole blood transcriptional profiling offers great diagnostic and prognostic potential. Although studies identified signatures for pulmonary tuberculosis (TB) and transcripts that predict the risk for developing active TB in humans, the early transcriptional changes immediately following Mycobacterium tuberculosis infection have not been evaluated. We evaluated the gene expression changes in the cynomolgus macaque model of TB, which recapitulates all clinical aspects of human M. tuberculosis infection, using a human microarray and analytics platform. We performed genome-wide blood transcriptional analysis on 38 macaques at 11 postinfection time points during the first 6 mo of M. tuberculosis infection. Of 6371 differentially expressed transcripts between preinfection and postinfection, the greatest change in transcriptional activity occurred 20-56 d postinfection, during which fluctuation of innate and adaptive immune response-related transcripts was observed. Modest transcriptional differences between active TB and latent infection were observed over the time course with substantial overlap. The pattern of module activity previously published for human active TB was similar in macaques with active disease. Blood transcript activity was highly correlated with lung inflammation (lung [ 18 F]fluorodeoxyglucose [FDG] avidity) measured by positron emission tomography and computed tomography at early time points postinfection. The differential signatures between animals with high and low lung FDG were stronger than between clinical outcomes. Analysis of preinfection signatures of macaques revealed that IFN signatures could influence eventual clinical outcomes and lung FDG avidity, even before infection. Our data support that transcriptional changes in the macaque model are translatable to human M. tuberculosis infection and offer important insights into early events of M. tuberculosis infection. Copyright © 2016 by The American Association of Immunologists, Inc.

MCM-BP Is Required for Repression of Life-Cycle Specific Genes Transcribed by RNA Polymerase I in the Mammalian Infectious Form of Trypanosoma brucei

PubMed Central

Kim, Hee-Sook; Park, Sung Hee; Günzl, Arthur; Cross, George A. M.

2013-01-01

Trypanosoma brucei variant surface glycoprotein (VSG) expression is a classic example of allelic exclusion. While the genome of T. brucei contains >2,000 VSG genes and VSG pseudogenes, only one allele is expressed at the surface of each infectious trypanosome and the others are repressed. Along with recombinatorial VSG switching, allelic exclusion provides a major host evasion mechanism for trypanosomes, a phenomenon known as antigenic variation. To extend our understanding of how trypanosomes escape host immunity by differential expression of VSGs, we attempted to identify genes that contribute to VSG silencing, by performing a loss-of-silencing screen in T. brucei using a transposon-mediated random insertional mutagenesis. One identified gene, which we initially named LOS1, encodes a T. brucei MCM-Binding Protein (TbMCM-BP). Here we show that TbMCM-BP is essential for viability of infectious bloodstream-form (BF) trypanosome and is required for proper cell-cycle progression. Tandem affinity purification of TbMCM-BP followed by mass spectrometry identified four subunits (MCM4-MCM7) of the T. brucei MCM complex, a replicative helicase, and MCM8, a subunit that is uniquely co-purified with TbMCM-BP. TbMCM-BP is required not only for repression of subtelomeric VSGs but also for silencing of life-cycle specific, insect-stage genes, procyclin and procyclin-associated genes (PAGs), that are normally repressed in BF trypanosomes and are transcribed by RNA polymerase I. Our study uncovers a functional link between chromosome maintenance and RNA pol I-mediated gene silencing in T. brucei. PMID:23451133

[Cloning expression and serological evaluation on Mycobacterium tuberculosis four new antigens].

PubMed

Luo, Q; Li, S J; Xiao, T Y; Li, M C; Liu, H C; Lou, Y L; Wan, K L

2018-04-10

Objective: To evaluate the serological diagnostic value of Mycobacterium (M.) tuberculosis four new antigens Rv0432, Rv0674, Rv1566c and Rv1547. Methods: Rv0432, Rv0674, Rv1566c and Rv1547 were amplified from M. tuberculosis strain H37Rv genomic DNA by using PCR, among which Rv1547 was divided into two segments for amplification ( Rv1547-1 and Rv1547-2 ). The segments were cloned into expression vector PET-32a while the recombinant proteins were purified by affinity chromatography. Serums were incubated with BL21 (DE3) proteins. Antibodies IgG against M. tuberculosis were tested with 151 serum samples (41 healthy people and 110 TB patients) by using ELISA. The diagnostic efficiency of antigens was analyzed by means of receiver operating characteristic curve. Difference of the objective proteins in TB patients and healthy controls was compared by t -test. Results: Recombinant antigens Rv0432, Rv0674, Rv1566c, Rv1547-1 and Rv1547-2 were successfully expressed and purified. Results from ELISA showed that the sensitivity, specificity, positive predictive value, negative predictive value, Youden index and area under the curve of Rv0432, Rv0674, Rv1566c, Rv1547-1 and Rv1547-2, as 43.64%-92.73%, 80.49%-92.68%, 0.92-0.94, 0.38-0.80, 0.363-0.732 and 0.649-0.915. All the objective proteins showed significantly higher antibody levels in TB patients, when compared to the healthy controls ( P <0.000 1). Conclusion: The newly identified antigens Rv0432, Rv0674, Rv1566c, Rv1547-1 and Rv1547-2 all performed well when being used for TB serological diagnosis, thus were expected to be new candidate antigens used for TB diagnosis.

Assessment of changes in knowledge and stigmatization following tuberculosis training workshops in taiwan.

PubMed

Wu, Ping-Sheng; Chou, Pesus; Chang, Nien-Tzu; Sun, Wen-Jung; Kuo, Hsu-Sung

2009-05-01

There is little understanding of the depth of knowledge of health workers involved in tuberculosis (TB) control programs, and even less is known about health workers attaching stigma to TB patients. This study surveyed health workers enrolled in TB training workshops prior to the execution of the directly observed treatment, short course (DOTS) program. All participants attended the training course and completed structured questionnaires before (pre-test) and after training (post-test). The questionnaires were collected immediately following completion and the scores were analyzed. Pair comparison of knowledge scores revealed that all participants made statistically significant improvements in level of TB knowledge, except those who had a history of TB (p = 0.331). Pair comparison of stigmatization scores revealed a reduction in stigmatization, with the DOTS workers attaching less stigma to TB patients. After training, caregivers, including women (p = 0.012), public health workers (p = 0.028), 40-49-year-old subjects (p = 0.035), those with an education of < 12 years (p = 0.024), those who had been a volunteer (p = 0.018), and those who had a history of TB and those who did not (p = 0.034, p = 0.036), were significantly less likely to stigmatize patients. TB knowledge was not found to be significantly correlated with stigmatization (pre-test, p = 0.298; post-test, p = 0.821). Training workshops in TB control were effective for promotion of knowledge and elimination of stigmatization in first-line caregivers. DOTS workers attached less stigma to TB patients than public health workers, and older workers who had been volunteers attached the least stigma.

Quantitative imaging of peripheral trabecular bone microarchitecture using MDCT.

PubMed

Chen, Cheng; Zhang, Xiaoliu; Guo, Junfeng; Jin, Dakai; Letuchy, Elena M; Burns, Trudy L; Levy, Steven M; Hoffman, Eric A; Saha, Punam K

2018-01-01

Osteoporosis associated with reduced bone mineral density (BMD) and microarchitectural changes puts patients at an elevated risk of fracture. Modern multidetector row CT (MDCT) technology, producing high spatial resolution at increasingly lower dose radiation, is emerging as a viable modality for trabecular bone (Tb) imaging. Wide variation in CT scanners raises concerns of data uniformity in multisite and longitudinal studies. A comprehensive cadaveric study was performed to evaluate MDCT-derived Tb microarchitectural measures. A human pilot study was performed comparing continuity of Tb measures estimated from two MDCT scanners with significantly different image resolution features. Micro-CT imaging of cadaveric ankle specimens (n=25) was used to examine the validity of MDCT-derived Tb microarchitectural measures. Repeat scan reproducibility of MDCT-based Tb measures and their ability to predict mechanical properties were examined. To assess multiscanner data continuity of Tb measures, the distal tibias of 20 volunteers (age:26.2±4.5Y,10F) were scanned using the Siemens SOMATOM Definition Flash and the higher resolution Siemens SOMATOM Force scanners with an average 45-day time gap between scans. The correlation of Tb measures derived from the two scanners over 30% and 60% peel regions at the 4% to 8% of distal tibia was analyzed. MDCT-based Tb measures characterizing bone network area density, plate-rod microarchitecture, and transverse trabeculae showed good correlations (r∈0.85,0.92) with the gold standard micro-CT-derived values of matching Tb measures. However, other MDCT-derived Tb measures characterizing trabecular thickness and separation, erosion index, and structure model index produced weak correlation (r<0.8) with their micro-CT-derived values. Most MDCT Tb measures were found repeatable (ICC∈0.94,0.98). The Tb plate-width measure showed a strong correlation (r = 0.89) with experimental yield stress, while the transverse trabecular measure produced the highest correlation (r = 0.81) with Young's modulus. The data continuity experiment showed that, despite significant differences in image resolution between two scanners (10% MTF along xy-plane and z-direction - Flash: 16.2 and 17.9 lp/cm; Force: 24.8 and 21.0 lp/cm), most Tb measures had high Pearson correlations (r > 0.95) between values estimated from the two scanners. Relatively lower correlation coefficients were observed for the bone network area density (r = 0.91) and Tb separation (r = 0.93) measures. Most MDCT-derived Tb microarchitectural measures are reproducible and their values derived from two scanners strongly correlate with each other as well as with bone strength. This study has highlighted those MDCT-derived measures which show the greatest promise for characterization of bone network area density, plate-rod and transverse trabecular distributions with a good correlation (r ≥ 0.85) compared with their micro-CT-derived values. At the same time, other measures representing trabecular thickness and separation, erosion index, and structure model index produced weak correlations (r < 0.8) with their micro-CT-derived values, failing to accurately portray the projected trabecular microarchitectural features. Strong correlations of Tb measures estimated from two scanners suggest that image data from different scanners can be used successfully in multisite and longitudinal studies with linear calibration required for some measures. In summary, modern MDCT scanners are suitable for effective quantitative imaging of peripheral Tb microarchitecture if care is taken to focus on appropriate quantitative metrics. © 2017 American Association of Physicists in Medicine.

Human Genomic Loci Important in Common Infectious Diseases: Role of High-Throughput Sequencing and Genome-Wide Association Studies

PubMed Central

Sserwadda, Ivan; Amujal, Marion; Namatovu, Norah

2018-01-01

HIV/AIDS, tuberculosis (TB), and malaria are 3 major global public health threats that undermine development in many resource-poor settings. Recently, the notion that positive selection during epidemics or longer periods of exposure to common infectious diseases may have had a major effect in modifying the constitution of the human genome is being interrogated at a large scale in many populations around the world. This positive selection from infectious diseases increases power to detect associations in genome-wide association studies (GWASs). High-throughput sequencing (HTS) has transformed both the management of infectious diseases and continues to enable large-scale functional characterization of host resistance/susceptibility alleles and loci; a paradigm shift from single candidate gene studies. Application of genome sequencing technologies and genomics has enabled us to interrogate the host-pathogen interface for improving human health. Human populations are constantly locked in evolutionary arms races with pathogens; therefore, identification of common infectious disease-associated genomic variants/markers is important in therapeutic, vaccine development, and screening susceptible individuals in a population. This review describes a range of host-pathogen genomic loci that have been associated with disease susceptibility and resistant patterns in the era of HTS. We further highlight potential opportunities for these genetic markers. PMID:29755620

Effect of pH value on structural and photoluminescence properties of Tb3+ -doped Lu2O3 nanopowders synthesized by sol-gel route

NASA Astrophysics Data System (ADS)

Mendoud, A.; Guerbous, L.; Boukerika, A.; Boudine, B.; Benrekaa, N.

2018-01-01

Tb3+-doped Lu2O3 nanophosphors were prepared via simple sol-gel method, at different pH value of solution (2, 5, 8 and 11), using diethanolamine (DEA) as polymerization agent. The nanopowder samples were characterized by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, room temperature steady and time resolved photoluminescence spectroscopy. The structural analysis reveals that all samples mainely crystallized in the cubic bixbyite structure with Ia3 space group. Also, it was found that the pH value of solution strongly influences the crystallite size, the vibrational frequency modes and the surface morphology of Lu2O3:Tb3+ nanocrystals. All samples show blue-greenish emissions, corresponding to 5D4 → 7FJ (J = 3, 4, 5 and 6) intraconfigurationnelles transitions. The intense green emission peak situated at 542 nm is assigned to 5D4 → 7F5 transition. The 4f8 → 4f75d1 spin-allowed and forbidden transitions, the charge transfer band (CTB) O2- → Tb3+ and the host absorption bands were observed and their dependence on pH value is discussed.

The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats

PubMed Central

Mohamed, Norazlina; Gwee Sian Khee, Sharon; Shuid, Ahmad Nazrun; Muhammad, Norliza; Suhaimi, Farihah; Othman, Faizah; Babji, Abdul Salam; Soelaiman, Ima-Nirwana

2012-01-01

Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women. PMID:22924056

The Effects of Cosmos caudatus on Structural Bone Histomorphometry in Ovariectomized Rats.

PubMed

Mohamed, Norazlina; Gwee Sian Khee, Sharon; Shuid, Ahmad Nazrun; Muhammad, Norliza; Suhaimi, Farihah; Othman, Faizah; Babji, Abdul Salam; Soelaiman, Ima-Nirwana

2012-01-01

Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.

A Target-Based High Throughput Screen Yields Trypanosoma brucei Hexokinase Small Molecule Inhibitors with Antiparasitic Activity

PubMed Central

Sharlow, Elizabeth R.; Lyda, Todd A.; Dodson, Heidi C.; Mustata, Gabriela; Morris, Meredith T.; Leimgruber, Stephanie S.; Lee, Kuo-Hsiung; Kashiwada, Yoshiki; Close, David; Lazo, John S.; Morris, James C.

2010-01-01

Background The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK), an enzyme essential to the parasite that transfers the γ-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay. Methodology/Principal Findings Exploiting optimized high throughput screening assay procedures, we interrogated 220,233 unique compounds and identified 239 active compounds from which ten small molecules were further characterized. Computation chemical cluster analyses indicated that six compounds were structurally related while the remaining four compounds were classified as unrelated or singletons. All ten compounds were ∼20-17,000-fold more potent than lonidamine, a previously identified TbHK1 inhibitor. Seven compounds inhibited T. brucei blood stage form parasite growth (0.03≤EC50<3 µM) with parasite specificity of the compounds being demonstrated using insect stage T. brucei parasites, Leishmania promastigotes, and mammalian cell lines. Analysis of two structurally related compounds, ebselen and SID 17387000, revealed that both were mixed inhibitors of TbHK1 with respect to ATP. Additionally, both compounds inhibited parasite lysate-derived HK activity. None of the compounds displayed structural similarity to known hexokinase inhibitors or human African trypanosomiasis therapeutics. Conclusions/Significance The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome. PMID:20405000

Magnetostructural phase transitions and magnetocaloric effect in Tb-Dy-Ho-Co-Al alloys with a Laves phase structure

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

Tereshina, I. S., E-mail: irina-tereshina@mail.ru; Baikov Institute of Metallurgy and Material Sciences, Russian Academy of Sciences, Moscow 119991; International Laboratory of High Magnetic Fields and Low Temperatures, Wroclaw 53-421

2016-07-07

The influence of simultaneous substitution within the rare earth (R) and Co sublattices on the structural, magnetic, and magnetocaloric properties of the Laves phase RCo{sub 2}-type compounds is studied. Main attention is devoted to the studies of the magnetostructural phase transitions and the transition types with respect to the alloy composition. Multicomponent alloys Tb{sub x}(Dy{sub 0.5}Ho{sub 0.5}){sub 1−x}Co{sub 2} and Tb{sub x}(Dy{sub 0.5}Ho{sub 0.5}){sub 1−x}Co{sub 1.75}Al{sub 0.25} were prepared with the use of high purity metals. Majority of the Tb{sub x}(Dy{sub 0.5}Ho{sub 0.5}){sub 1−x}Co{sub 2} alloys exhibit magnetic transitions of the first-order type and a large magnetocaloric effect. The substitutionmore » of Al for Co in Tb{sub x}(Dy{sub 0.5}Ho{sub 0.5}){sub 1−x}Co{sub 2} increases the Curie temperature (T{sub C}) but changes the transition type from first-to the second-order. The discussion of the physical mechanisms behind the observed phenomena is given on the basis of the first principles electronic-structure calculations taking into account both the atomic disorder and the magnetic disorder effects at finite temperatures. The advantage of Al-containing materials is that sufficiently high magnetocaloric effect values are preserved at T > T{sub C}.« less

A self-assembling luminescent lanthanide molecular nanoparticle with potential for live cell imaging.

PubMed

Yang, Xiaoping; Wang, Shiqing; Zhang, Yali; Liang, Guang; Zhu, Ting; Zhang, Lijie; Huang, Shaoming; Schipper, Desmond; Jones, Richard A

2018-05-28

Four luminescent 32-metal Cd-Tb nanoclusters, [Tb 8 Cd 24 (L 1 ) 12 (OAc) 48 ] ( 1 ), [Tb 8 Cd 24 (L 2 ) 12 (OAc) 48 ] ( 2 ), [Tb 8 Cd 24 (L 3 ) 12 (OAc) 48 ] ( 3 ) and [Tb 8 Cd 24 (L 2 ) 12 (1,4-BDC) 4 (OAc) 38 (OH) 2 ] ( 4 ), were constructed from three specially designed chain-like Schiff base ligands H 2 L 1-3 with flexible carbon-carbon backbones containing 5, 6 and 10 methylene units, respectively. The clusters exhibit drum-like structures and can be imaged using transmission electron microscopy (TEM). In addition to the Schiff base ligands (the primary energy transfer donors), four 1,4-BDC bridging units were successfully introduced into the structure of 4 . In addition to providing increased structural stability, the 1,4-BDC units act as secondary energy transfer donors providing extra energy for lanthanide luminescence, which results in improved luminescence properties when compared to those of the related Cd-Ln nanoclusters without 1,4-BDC units. In vitro investigations on 4 with SGC and PANC cancer cells revealed an accumulation of the molecular nanoparticles in the cells, as confirmed by confocal microscopy. The cytotoxicity of 4 toward the SGC and PANC cells is moderate (IC 50 values of 4 lie in the range of 15-60 μM). ICP-MS analysis reveals that cellular uptakes of 4 in 1000 SGC and PANC cells after treatment for 3 hours are 0.0094 pmol and 0.015 pmol, respectively.

Developing a customised approach for strengthening tuberculosis laboratory quality management systems toward accreditation

PubMed Central

Trollip, Andre; Erni, Donatelle; Kao, Kekeletso

2017-01-01

Background Quality-assured tuberculosis laboratory services are critical to achieve global and national goals for tuberculosis prevention and care. Implementation of a quality management system (QMS) in laboratories leads to improved quality of diagnostic tests and better patient care. The Strengthening Laboratory Management Toward Accreditation (SLMTA) programme has led to measurable improvements in the QMS of clinical laboratories. However, progress in tuberculosis laboratories has been slower, which may be attributed to the need for a structured tuberculosis-specific approach to implementing QMS. We describe the development and early implementation of the Strengthening Tuberculosis Laboratory Management Toward Accreditation (TB SLMTA) programme. Development The TB SLMTA curriculum was developed by customizing the SLMTA curriculum to include specific tools, job aids and supplementary materials specific to the tuberculosis laboratory. The TB SLMTA Harmonized Checklist was developed from the World Health Organisation Regional Office for Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation checklist, and incorporated tuberculosis-specific requirements from the Global Laboratory Initiative Stepwise Process Towards Tuberculosis Laboratory Accreditation online tool. Implementation Four regional training-of-trainers workshops have been conducted since 2013. The TB SLMTA programme has been rolled out in 37 tuberculosis laboratories in 10 countries using the Workshop approach in 32 laboratories in five countries and the Facility-based approach in five tuberculosis laboratories in five countries. Conclusion Lessons learnt from early implementation of TB SLMTA suggest that a structured training and mentoring programme can build a foundation towards further quality improvement in tuberculosis laboratories. Structured mentoring, and institutionalisation of QMS into country programmes, is needed to support tuberculosis laboratories to achieve accreditation. PMID:28879165

Co-evolution of Mycobacterium tuberculosis and Homo sapiens

PubMed Central

Brites, Daniela; Gagneux, Sebastien

2015-01-01

The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future ‘genome-to-genome’ studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines. PMID:25703549

Cross-border outbreak of extensively drug-resistant tuberculosis linked to a university in Romania.

PubMed

Popovici, O; Monk, Ph; Chemtob, D; Chiotan, D; Freidlin, P J; Groenheit, R; Haanperä, M; Homorodean, D; Mansjö, M; Robinson, E; Rorman, E; Smith, G; Soini, H; Van Der Werf, M J

2018-05-01

Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases. These investigations increased the total number of cases to seven. All confirmed cases shared a very similar WGS profile. Two more cases were epidemiologically linked, but no laboratory confirmation exists. Despite all the efforts done, the source of the outbreak was not identified, but the transmission was controlled. The investigation was conducted by a team including epidemiologists and microbiologists from five countries (Finland, Israel, Romania, Sweden and the UK) and from the European Centre for Disease Prevention and Control. Our report shows how countries can collaborate to control the spread of XDR TB by exchanging information about cases and their contacts to enable identification of additional cases and transmission and to perform the source investigation.

Photoluminescence properties and energy transfer of color tunable MgZn₂(PO₄)₂:Ce³⁺,Tb³⁺ phosphors.

PubMed

Xu, Mengjiao; Wang, Luxiang; Jia, Dianzeng; Zhao, Hongyang

2015-11-21

A series of Ce(3+)/Tb(3+) co-doped MgZn2(PO4)2 phosphors have been synthesized by the co-precipitation method. Their structure, morphology, photoluminescence properties, decay lifetime, thermal stability and luminous efficiency were investigated. The possible energy transfer mechanism was proposed based on the experimental results and detailed luminescence spectra and decay curves of the phosphors. The critical distance between Ce(3+) and Tb(3+) ions was calculated by both the concentration quenching method and the spectral overlap method. The energy transfer mechanism from the Ce(3+) to Tb(3+) ion was determined to be dipole-quadrupole interaction, and the energy transfer efficiency was 85%. By utilizing the principle of energy transfer and appropriate tuning of Ce(3+)/Tb(3+) contents, the emission color of the obtained phosphors can be tuned from blue to green light. The MgZn2(PO4)2:Ce(3+),Tb(3+) phosphor is proved to be a promising UV-convertible material capable of green light emitting in UV-LEDs due to its excellent thermal stability and luminescence properties.

Tuberculosis management practices by private practitioners in Andhra Pradesh, India.

PubMed

Achanta, Shanta; Jaju, Jyoti; Kumar, Ajay M V; Nagaraja, Sharath Burugina; Shamrao, Srinivas Rao Motta; Bandi, Sasidhar Kumar; Kumar, Ashok; Satyanarayana, Srinath; Harries, Anthony David; Nair, Sreenivas Achutan; Dewan, Puneet K

2013-01-01

Private medical practitioners in Visakhapatnam district, Andhra Pradesh, India. To evaluate self-reported TB diagnostic and treatment practices amongst private medical practitioners against benchmark practices articulated in the International Standards of Tuberculosis Care (ISTC), and factors associated with compliance with ISTC. Cross- sectional survey using semi-structured interviews. Of 296 randomly selected private practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and treatment standards in TB management. Only 11 (6%) followed a combination of 6 diagnostic standards together and only 1 followed a combination of all seven treatment standards together. There were 28 (14%) private practitioners who complied with a combination of three core ISTC (cough for tuberculosis suspects, sputum smear examination and use of standardized treatment). Higher ISTC compliance was associated with caring for more than 20 TB patients annually, prior sensitization to TB control guidelines, and practice of alternate systems of medicine. Few private practitioners in Visakhapatnam, India reported TB diagnostic and treatment practices that met ISTC. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance.

UNIX NSW Front End Enhancements. Volume I.

DTIC Science & Technology

1981-06-01

scenario number */ int pi pcod ; /* value of us pcod in US entry */ int pi-mlen; /* length of following message */1; In both structures, the fields are...inst; /* cqde for kind of info stored -- is ipptr->ipinst */ int tb_pcod; /* value of us_pcod for this buffer */1; It is necessary to store tb pcod in

Experimental and theoretical study of pure and doped crystals: Gd2O2S, Gd2O2S:Eu3+ and Gd2O2S:Tb3+

NASA Astrophysics Data System (ADS)

Wang, Fei; Chen, Xiumin; Liu, Dachun; Yang, Bin; Dai, Yongnian

2012-08-01

Quantum chemistry and experimental method were used to study on pure and doped Gd2O2S crystals in this paper. The band structure and DOS diagrams of pure and doped Gd2O2S crystals which calculated by using DFT (Density Functional Theory) method were illustrated to explain the luminescent properties of impurities in crystals. The calculations of the crystal structure were finished by using the program of CASTEP (Cambridge Sequential Total Energy Package). The samples showed the characteristic emissions of Tb3+ ions with 5D4-7FJ transitions and Eu3+ ions with 5D0-7FJ transitions which emit pure green luminescence and red luminescence respectively. The experimental excitation spectra of Tb3+ and Eu3+ doped Gd2O2S are in agreement of the DOS diagrams over the explored energy range, which has allowed a better understanding of different luminescence mechanisms of Tb3+ and Eu3+ in Gd2O2S crystals.

Interfacial exchange coupling and magnetization reversal in perpendicular [Co/Ni]N/TbCo composite structures.

PubMed

Tang, M H; Zhang, Zongzhi; Tian, S Y; Wang, J; Ma, B; Jin, Q Y

2015-06-15

Interfacial exchange coupling and magnetization reversal characteristics in the perpendicular heterostructures consisting of an amorphous ferrimagnetic (FI) TbxCo(100-x) alloy layer exchange-coupled with a ferromagnetic (FM) [Co/Ni]N multilayer have been investigated. As compared with pure TbxCo(100-x) alloy, the magnetization compensation composition of the heterostructures shift to a higher Tb content, implying Co/Ni also serves to compensate the Tb moment in TbCo layer. The net magnetization switching field Hc⊥ and interlayer interfacial coupling field Hex, are not only sensitive to the magnetization and thickness of the switched TbxCo(100-x) or [Co/Ni]N layer, but also to the perpendicular magnetic anisotropy strength of the pinning layer. By tuning the layer structure we achieve simultaneously both large Hc⊥ = 1.31 T and Hex = 2.19 T. These results, in addition to the fundamental interest, are important to understanding of the interfacial coupling interaction in the FM/FI heterostructures, which could offer the guiding of potential applications in heat-assisted magnetic recording or all-optical switching recording technique.

Effect of different surfactants on structural and optical properties of Ce3+ and Tb3+ co-doped BiPO4 nanostructures

NASA Astrophysics Data System (ADS)

Lakshminarayana, G.; Dao, T. D.; Chen, K.; Sharma, Manoj; Takeda, T.; Brik, M. G.; Kityk, I. V.; Singh, Sarabjot; Nagao, T.

2015-01-01

In this paper we report on the Ce3+ and Tb3+ ions co-doped bismuth phosphate (BiPO4) nanostructures that were synthesized by a simple precipitation method using different surfactants such as glycerol/H2O, glycerol/ethylene glycol, oleic acid, and ethylene glycol. The structural (X-ray diffraction, scanning electron microscopy, tunneling electron microscopy), functional groups analysis (Fourier transform infrared and Raman spectroscopy), thermal (thermogravimetry and differential thermal analysis), and optical (photoluminescence, photoluminescence-excitation) properties were investigated. The structural and morphological analysis confirms the pure hexagonal crystal structure of the synthesized nanostructures. From the measured Fourier transform infrared (FTIR) and Raman spectra various functional groups such as υ3 stretching vibration of the PO4 group, and δ(O-P-O) and υ4 (PO4) vibrations including the υ2 and υ1 bending modes of the PO4 units are identified. Based on the thermal analysis, for all the studied samples an exothermic peak between 680 °C and 700 °C was observed due to phase transition from hexagonal to high temperature monoclinic. The Ce3+and Tb3+ codoped samples show spectrally broad 5d → 4f luminescence in the blue (centered at 459 nm) wavelength region under the direct optical excitation of Ce3+ at 417 nm. Similarly, Tb3+ has revealed four main emission bands (5D4 → 7F6, 5, 4 and 3) at 490 nm, 545 nm, 585 nm and 621 nm with 378 nm (7F6 → 5G6) as the excitation wavelength, including three more weak emission bands at 647 nm, 669 nm, and 681 nm which could be assigned to 5D4 → 7F2, 1, 0 emission transitions. Among them, 545 nm (5D4 → 7F5) has shown bright green emission. The Ce3+ and Tb3+ codoped sample synthesized with pure oleic acid have shown relatively high green emission intensity for Tb3+, and relatively weak blue emission intensity for Ce3+ under their respective optical excitation wavelengths.

Population genomics reveals the origin and asexual evolution of human infective trypanosomes

PubMed Central

Weir, William; Capewell, Paul; Foth, Bernardo; Clucas, Caroline; Pountain, Andrew; Steketee, Pieter; Veitch, Nicola; Koffi, Mathurin; De Meeûs, Thierry; Kaboré, Jacques; Camara, Mamadou; Cooper, Anneli; Tait, Andy; Jamonneau, Vincent; Bucheton, Bruno; Berriman, Matt; MacLeod, Annette

2016-01-01

Evolutionary theory predicts that the lack of recombination and chromosomal re-assortment in strictly asexual organisms results in homologous chromosomes irreversibly accumulating mutations and thus evolving independently of each other, a phenomenon termed the Meselson effect. We apply a population genomics approach to examine this effect in an important human pathogen, Trypanosoma brucei gambiense. We determine that T.b. gambiense is evolving strictly asexually and is derived from a single progenitor, which emerged within the last 10,000 years. We demonstrate the Meselson effect for the first time at the genome-wide level in any organism and show large regions of loss of heterozygosity, which we hypothesise to be a short-term compensatory mechanism for counteracting deleterious mutations. Our study sheds new light on the genomic and evolutionary consequences of strict asexuality, which this pathogen uses as it exploits a new biological niche, the human population. DOI: http://dx.doi.org/10.7554/eLife.11473.001 PMID:26809473

Striking the right immunological balance prevents progression of tuberculosis.

PubMed

Vyas, Shachi Pranjal; Goswami, Ritobrata

2017-12-01

Tuberculosis (TB) caused by infection with Mycobacterium tuberculosis (Mtb) is a major burden for human health worldwide. Current standard treatments for TB require prolonged administration of antimycobacterial drugs leading to exaggerated inflammation and tissue damage. This can result in the reactivation of latent TB culminating in TB progression. Thus, there is an unmet need to develop therapies that would shorten the duration of anti-TB treatment and to induce optimal protective immune responses to control the spread of mycobacterial infection with minimal lung pathology. Granulomata is the hallmark structure formed by the organized accumulation of immune cells including macrophages, natural killer cells, dendritic cells, neutrophils, T cells, and B cells to the site of Mtb infection. It safeguards the host by containing Mtb in latent form. However, granulomata can undergo caseation and contribute to the reactivation of latent TB, if the immune responses developed to fight mycobacterial infection are not properly controlled. Thus, an optimal balance between innate and adaptive immune cells might play a vital role in containing mycobacteria in latent form for prolonged periods and prevent the spread of Mtb infection from one individual to another. Optimal and well-regulated immune responses against Mycobacterium tuberculosis may help to prevent the reactivation of latent TB. Moreover, therapies targeting balanced immune responses could help to improve treatment outcomes among latently infected TB patients and thereby limit the dissemination of mycobacterial infection.

Strain-induced modification of magnetic structure and new magnetic phases in rare-earth epitaxial films

NASA Astrophysics Data System (ADS)

Dufour, C.; Dumesnil, K.; Mangin, Ph

2006-07-01

Rare earths exhibit complex magnetic phase diagrams resulting from the competition between various contributions to the magnetic energy: exchange, anisotropy and magnetostriction. The epitaxy of a rare-earth film on a substrate induces (i) a clamping to the substrate and (ii) pseudomorphic strains. Both these effects are shown to lead to modifications of the magnetic properties in (0 0 1)Dy, (0 0 1)Tb and (1 1 0)Eu films. In Dy and Tb films, spectacular variations of the Curie temperature have been evidenced. Additionally, Tb films exhibit a new large wavelength magnetic modulation. In Eu films, one of the helical magnetic domains disappears at low temperature whereas the propagation vectors of the other helices are tilted. The link between structural and magnetic properties is underlined via magnetoelastic models. Moreover, molecular beam epitaxy permits the growth of Sm in a metastable dhcp phase. The magnetic structure of dhcp Sm has been elucidated for the first time. In this review, neutron scattering is shown to be a powerful technique to reveal the magnetic structures of rare-earth films.

Risk factors of tuberculosis among health care workers in Sabah, Malaysia.

PubMed

Jelip, Jenarun; Mathew, George G; Yusin, Tanrang; Dony, Jiloris F; Singh, Nirmal; Ashaari, Musa; Lajanin, Noitie; Shanmuga Ratnam, C; Yusof Ibrahim, Mohd; Gopinath, Deyer

2004-01-01

Tuberculosis (TB) is one of the main public health problems in Sabah; 30% of the total number of TB cases reported in Malaysia every year occur in Sabah. The average incidence of TB among health care workers over the past 5 years is 280.4 per 100,000 population (1, Annual Report of Sabah State TB Control Programme, 1998). At present, there are no specific measures for the prevention of TB transmission in health care facilities. A case-control study was conducted among health care workers in Sabah in 2000-2001. Cases were health care workers with TB diagnosed between January 1990 and June 2000. Controls were health care workers without TB and working in the same facility as cases during the disease episode. The study attempted to identify risk factors for TB among the study population. Data were collected through structured interviews and review of patients' records. The notification rate of TB among health care workers was significantly higher than that to the general population (Z=4.893, p<0.01). The average notification rate of TB among health care workers over the last 5 years was two times higher than in the general population (280.4/100,000 compared to 153.9/100,000). Regression results showed that ethnicity, designation, family contact and TB related knowledge did not significantly contribute to the risk of contracting TB in this study. However, after controlling for the above factors, age, gender, history of TB contact outside the workplace (other than family contact), duration of service and failure to use respiratory protection when performing high-risk procedures, were the main risk factors of TB among health care workers. This study succeeded in identifying some of the risk factors of TB among health care workers. We managed to include the large ratio of controls to case (3:1) and those cases spanned over a period of 10 years. However, the findings from the study have to be applied with caution due to the limitations of this study, which include recall bias, dropouts, and small sample size. Based on the study findings, we recommend that health care workers in the first 10 years of service should take extra precautions, such as using respiratory protection when performing procedures that are considered to be of high risk with respect to TB infection. They should also undergo TB screening at least once every 2 years and, if symptomatic, offered prophylactic treatment. The Respiratory Protection Programme should be fully implemented to help reduce the risk of TB among health care workers in Sabah.

Cloning, expression, and purification of recombinant protein MPT-64 from a virulent strain of Mycobacterium bovis in a prokaryotic system.

PubMed

Tashakkori, Maryam Mohammadi; Tebianian, Majid; Tabatabaei, Mohammad; Mosavari, Nader

2016-12-01

Tuberculosis (TB) is a zoonotic infectious disease common to humans and animals that is caused by the rod-shaped acid-fast bacterium Mycobacterium bovis. Rapid and sensitive detection of TB is promoted by specific antigens. Virulent strains of the TB complex from M. bovis contain 16 regions of difference (RD) in their genome that encode important proteins, including major protein of Mycobacterium Tuberculosis 64 (MBT-64, which is a primary immune-stimulating antigen encoded by RD-2. In this study, we cloned, expressed, and purified MPT-64 as a potent M. bovis antigen in a prokaryotic system for use in future diagnostic studies. The antigenic region of the Mpt64 gene was investigated by bioinformatics methods, cloned into the PQE-30 plasmid, and expressed in Escherichia coli M15 cells, followed by isopropyl β-d-1-thiogalactopyranoside induction. The expressed protein was analyzed sodium dodecyl sulfate polyacrylamide gel electrophoresis and purified using a nickel-affinity column. Biological activity was confirmed by western blot using specific antibodies. Our data verified the successful cloning of the Mpt64 gene (687-bp segment) via the expression vector and purification of recombinant MPT-64 as a 24-kDa protein. These results indicated successful expression and purification of recombinant MPT-64 protein in a prokaryotic system. This protein can be used for serological diagnosis, improved detection of pathogenicity and non-pathogenicity between infected cattle, and for verification of suspected cases of bovine TB. Copyright © 2016.

Structural and magnetic properties of two branches of the tripod-kagome-lattice family A2R3Sb3O14 (A = Mg, Zn; R = Pr, Nd, Gd, Tb, Dy, Ho, Er, Yb)

NASA Astrophysics Data System (ADS)

Dun, Z. L.; Trinh, J.; Lee, M.; Choi, E. S.; Li, K.; Hu, Y. F.; Wang, Y. X.; Blanc, N.; Ramirez, A. P.; Zhou, H. D.

2017-03-01

We present a systematic study of the structural and magnetic properties of two branches of the rare-earth tripod-kagome-lattice (TKL) family A2R3Sb3O14 (A = Mg, Zn; R = Pr, Nd, Gd, Tb, Dy, Ho, Er, Yb; here, we use abbreviation A-R, as in MgPr for Mg2Pr3Sb3O14 ), which complements our previously reported work on MgDy, MgGd, and MgEr [Z. L. Dun et al., Phys. Rev. Lett. 116, 157201 (2016), 10.1103/PhysRevLett.116.157201]. The present susceptibility (χdc, χac) and specific-heat measurements reveal various magnetic ground states, including the nonmagnetic singlet state for MgPr, ZnPr; long-range orderings (LROs) for MgGd, ZnGd, MgNd, ZnNd, and MgYb; a long-range magnetic charge ordered state for MgDy, ZnDy, and potentially for MgHo; possible spin-glass states for ZnEr, ZnHo; the absence of spin ordering down to 80 mK for MgEr, MgTb, ZnTb, and ZnYb compounds. The ground states observed here bear both similarities as well as striking differences from the states found in the parent pyrochlore systems. In particular, while the TKLs display a greater tendency towards LRO, the lack of LRO in MgHo, MgTb, and ZnTb can be viewed from the standpoint of a balance among spin-spin interactions, anisotropies, and non-Kramers nature of single-ion state. While substituting Zn for Mg changes the chemical pressure, and subtly modifies the interaction energies for compounds with larger R ions, this substitution introduces structural disorder and modifies the ground states for compounds with smaller R ions (Ho, Er, Yb).

Comparative analysis of different joining techniques to improve the passive fit of cobalt-chromium superstructures.

PubMed

Barbi, Francisco C L; Camarini, Edevaldo T; Silva, Rafael S; Endo, Eliana H; Pereira, Jefferson R

2012-12-01

The influence of different joining techniques on passive fit at the interface structure/abutment of cobalt-chromium (Co-Cr) superstructures has not yet been clearly established. The purpose of this study was to compare 3 different techniques of joining Co-Cr superstructures by measuring the resulting marginal misfit in a simulated prosthetic assembly. A specially designed metal model was used for casting, sectioning, joining, and measuring marginal misfit. Forty-five cast bar-type superstructures were fabricated in a Co-Cr alloy and randomly assigned by drawing lots to 3 groups (n=15) according to the joining method used: conventional gas-torch brazing (G-TB), laser welding (LW), and tungsten inert gas welding (TIG). Joined specimens were assembled onto abutment analogs in the metal model with the 1-screw method. The resulting marginal misfit was measured with scanning electron microscopy (SEM) at 3 different points: distal (D), central (C), and mesial (M) along the buccal aspect of both abutments: A (tightened) and B (without screw). The Levene test was used to evaluate variance homogeneity and then the Welsch ANOVA for heteroscedastic data (α=.05). Significant differences were found on abutment A between groups G-TB and LW (P=.013) measured mesially and between groups G-TB and TIG (P=.037) measured centrally. On abutment B, significant differences were found between groups G-TB and LW (P<.001) and groups LW and TIG (P<.001) measured mesially; groups G-TB and TIG (P=.007) measured distally; and groups G-TB and TIG (P=.001) and LW and TIG (P=.007) measured centrally. The method used for joining Co-Cr prosthetic structures had an influence on the level of resulting passive fit. Structures joined by the tungsten inert gas method produced better mean results than did the brazing or laser method. Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

One-step solvothermal synthesis, a worm-shaped morphology and luminescence properties of green-emitting Y2O2S:Tb3+ nanophosphors

NASA Astrophysics Data System (ADS)

Liu, Fan; Lian, Jingbao; Wu, Nianchu; He, Jiao; Zhang, Xue; Liu, Feng

2018-02-01

The worm-shaped Y2O2S:Tb3+ nanophosphors have been successfully prepared via one-step solvothermal synthesis, using ethanediamine as the main solvent and sublimed sulfur powder as the source of sulfur without adding additional structure-directing reagents. XRD, FT-IR, FESEM, PL and CIE chromaticity diagram were used to characterize the obtained products. XRD results demonstrate that all diffraction peaks of the sample can be well indexed to pure hexagonal phase of Y2O2S with optimal condition, i.e. the molar ration of S/Y3+m = 10, solvothermal temperature T = 220 °C and synthetic time t = 24 h. When t varies from 2 h to 24 h, the morphology of Y2O2S transforms from cauliflower-like structure to worm-shaped nanoparticles with the length of ∼80 nm. The formation mechanism depending on t has also been proposed. Upon 250 nm ultraviolet (UV) light excitation, the worm-shaped Y2O2S:Tb3+ nanophosphors exhibit green emissions, corresponding to the 5D4 → 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ions. The quenching concentration is 7% and its corresponding lifetime is 1216 μs. The CIE chromaticity coordinates show the tuneable emission shifting from yellow green to yellowish green with increasing concentration of Tb3+ions from 1% to 7%. Those results suggest that the worm-shaped Y2O2S:Tb3+ nanophosphors may have potential applications in X-ray intensifying screens, fluorescence and biomedical fields.

Multiple-decker phthalocyaninato dinuclear lanthanoid(III) single-molecule magnets with dual-magnetic relaxation processes.

PubMed

Katoh, Keiichi; Horii, Yoji; Yasuda, Nobuhiro; Wernsdorfer, Wolfgang; Toriumi, Koshiro; Breedlove, Brian K; Yamashita, Masahiro

2012-11-28

The SMM behaviour of dinuclear Ln(III)-Pc multiple-decker complexes (Ln = Tb(3+) and Dy(3+)) with energy barriers and slow-relaxation behaviour were explained by using X-ray crystallography and static and dynamic susceptibility measurements. In particular, interactions among the 4f electrons of several dinuclear Ln(III)-Pc type SMMs have never been discussed on the basis of the crystal structure. For dinuclear Tb(III)-Pc complexes, a dual magnetic relaxation process was observed. The relaxation processes are due to the anisotropic centres. Our results clearly show that the two Tb(3+) ion sites are equivalent and are consistent with the crystal structure. On the other hand, the mononuclear Tb(III)-Pc complex exhibited only a single magnetic relaxation process. This is clear evidence that the magnetic relaxation mechanism depends heavily on the dipole-dipole (f-f) interactions between the Tb(3+) ions in the dinuclear systems. Furthermore, the SMM behaviour of dinuclear Dy(III)-Pc type SMMs with smaller energy barriers compared with that of Tb(III)-Pc and slow-relaxation behaviour was explained. Dinuclear Dy(III)-Pc SMMs exhibited single-component magnetic relaxation behaviour. The results indicate that the magnetic relaxation properties of dinuclear Ln(III)-Pc multiple-decker complexes are affected by the local molecular symmetry and are extremely sensitive to tiny distortions in the coordination geometry. In other words, the spatial arrangement of the Ln(3+) ions (f-f interactions) in the crystal is important. Our work shows that the SMM properties can be fine-tuned by introducing weak intermolecular magnetic interactions in a controlled SMM spatial arrangement.

Electrode modified with toluidine blue-doped silica nanoparticles, and its use for enhanced amperometric sensing of hemoglobin.

PubMed

Liu, Meichuan; Shi, Guoyue; Zhang, Li; Zhao, Guohua; Jin, Litong

2008-07-01

Three-dimensionally structured, silica based, organic-inorganic hybrid nanoparticles (NPs) were prepared by a simple and feasible water-in-oil (W/O) microemulsion method and a promising platform for bioelectrochemical analysis was obtained. The commonly used phenathiazine organic compound, toluidine blue (TB) was readily captured in the three-dimensional cage of the inorganic SiO(2) network, which was considered to serve as a protective "shell" toward the embedded TB. A TEM image indicated the size of the thus prepared TB-doped SiO(2) (TB@SiO(2)) NPs was 21 +/- 3 nm. UV-visible and IR spectroscopy confirmed successful formation of the organic-inorganic composite and possible interaction between TB and SiO(2), which favored enhanced stability of the hybrid. A sensitive amperometric sensor for hemoglobin (Hb) biomolecules based on TB@SiO(2) NPs conjugated with a biopolymer chitosan (CHIT) membrane was then developed. The surface of the silica NPs was highly biocompatible and the TB captured inside maintained its high electron-transfer efficiency. Dye leakage of TB from the TB@SiO(2) hybrid was proved to be minimal, owing to the inorganic SiO(2) network and the force of interaction between TB and SiO(2). The amperometric sensor had a detection limit of 2.5 x 10(-9) mol L(-1) (S/N = 3) with a linear range from 5.0 x 10(-9) to 3.0 x 10(-6) mol L(-1) for Hb. When it was applied to determine the concentration of a clinical blood sample, satisfactory results were obtained which were in good agreement with those obtained by the standard method.

Noncollinear spin structure in SmxTb1-x[Cr(CN)6]•4H2O having orthogonal single-ion anisotropies

NASA Astrophysics Data System (ADS)

Hozumi, Toshiya; Hashimoto, Kazuhito; Ohkoshi, Shin-Ichi

2006-03-01

A series of SmxIIITb1-xIII[CrIII(CN)6]•4H2O magnets, in which SmIII and TbIII have different magnetic single-ion anisotropies, was prepared. Magnetic ordering temperatures (Tc) decreased from 12.0K (x=0) to 7.4K (x=0.55) and then increased to 10.2K (x=1) with increasing x . The magnetization (Ms) values at 5K gradually decreased from 3.0μB (x=0) to 1.6μB (x=1) . These trends of experimental Tc and Ms values suggest that the present series takes a noncollinear spin structure, in which the directions of the SmIII and TbIII sublattice magnetizations are perpendicular, from the analysis of the molecular-field model.

The binding of terbium ions to tubulin induces ring formation.

PubMed

Monasterio, O; Acoria, M; Díaz, M A; Lagos, R

1993-02-01

The intrinsic fluorescence excitation and emission spectra of chicken brain tubulin showed the characteristic tryptophan fluorescence. The emission spectrum of Tb3+ in the presence of tubulin and GTP excited at 295 nm, showed four peaks, with the maxima at 490, 545, and 586 nm and a minor peak around 620 nm. Titration of tubulin with Tb3+ was followed by the increment in luminescence at 545 nm and showed a sigmoidal curve where the initial lag interval and the maximal luminescence intensity depended on tubulin concentration. The presence of Mg2+, Co2+, and Zn2+ diminished both the sigmoidicity of the curve and the maximal luminescence intensity. Titration of tubulin with Tb3+ also produced a sigmoidal increase in turbidity, which was shifted to the left with respect to the luminescence curve. The dependence of turbidity on the wavelength of the Tb(3+)-induced polymers revealed that the large structures formed were not microtubules. Electron microscopy of the aggregates induced by Tb3+ showed mainly a lattice of double rings with side-by-side contacts. These results indicate that Tb3+ induces principally double ring formation and that these rings (33 +/- 2 nm external diameter) aggregate in large-ordered arrays. The luminescence of Tb3+ seems to be induced mainly by the aggregation of rings.

Assessing infection control practices to protect health care workers and patients in Malawi from nosocomial transmission of Mycobacterium tuberculosis.

PubMed

Flick, Robert J; Munthali, Adamson; Simon, Katherine; Hosseinipour, Mina; Kim, Maria H; Mlauzi, Lameck; Kazembe, Peter N; Ahmed, Saeed

2017-01-01

Transmission of Mycobacterium tuberculosis (TB) in health settings threatens health care workers and people living with HIV in sub-Saharan Africa. Nosocomial transmission is reduced with implementation of infection control (IC) guidelines. The objective of this study is to describe implementation of TB IC measures in Malawi. We conducted a cross-sectional study utilizing anonymous health worker questionnaires, semi-structured interviews with facility managers, and direct observations at 17 facilities in central Malawi. Of 592 health care workers surveyed, 34% reported that all patients entering the facility were screened for cough and only 8% correctly named the four most common signs and symptoms of TB in adults. Of 33 managers interviewed, 7 (21%) and 1 (3%) provided the correct TB screening questions for use in adults and children, respectively. Of 592 health workers, only 2.4% had been screened for TB in the previous year. Most (90%) reported knowing their HIV status, 53% were tested at their facility of employment, and half reported they would feel comfortable receiving ART or TB treatment at their facility of employment. We conclude that screening is infrequently conducted and knowledge gaps may undercut its effectiveness. Further, health care workers do not routinely access TB and HIV diagnostic and treatment services at their facility of employment.

Public health nihilism vs pragmatism: history, politics, and the control of tuberculosis.

PubMed Central

Fairchild, A L; Oppenheimer, G M

1998-01-01

Tuberculosis (TB) began to decline in the Western world in the mid- to late 1800s. In the United States, the disease receded until the mid-1980s, when that trend was reversed. Although the TB epidemic in the United States subsided in response to public health interventions, it sparked a controversy regarding the relative value of targeted public health measures vs broad social reform. That controversy, which echoed earlier debates calling for structural reform over public health programs, was further strengthened by the historical and demographic studies of Thomas McKeown. His influential thesis maintains that clinical and primary prevention efforts had little effect on TB mortality. In this paper, the historical literature is used to examine whether public health had a significant impact on the decline of TB mortality rates in several countries. Specifically, the paper describes the arguments for and data affirming the efficacy of 2 major public health interventions over time: segregation of those infected with pulmonary TB and eradication of bovine TB. This review finds support for the hypothesis that public health measures, along with other factors, led to falling rates of TB mortality beginning in the late 19th century. Images FIGURE 3 p1112-a p1113-a PMID:9663166

Perpendicular exchange coupling effects in ferrimagnetic TbFeCo/GdFeCo hard/soft structures

NASA Astrophysics Data System (ADS)

Wang, Ke; Wang, Yahong; Ling, Fujin; Xu, Zhan

2018-04-01

Bilayers consisting of magnetically hard TbFeCo and soft GdFeCo alloy were fabricated. Exchange-spring and sharp switching in a step-by-step fashion were observed in the TbFeCo/GdFeCo hard/soft bilayers with increasing GdFeCo thickness. A perpendicular exchange bias field of several hundred Oersteds is observed from the shift of minor loops pinned by TbFeCo layer. The perpendicular exchange energy is derived to be in the range of 0.18-0.30 erg/cm2. The exchange energy is shown to increase with the thickness of GdFeCo layer in the bilayers, which can be attributed to the enhanced perpendicular anisotropy of GdFeCo layer in our experimental range.

Structure, thermal and luminescence properties of Eu/Tb(BA)3phen/PAN fibers fabricated by electrospinning

NASA Astrophysics Data System (ADS)

Wang, Shiwei; Xie, Guangbo; Zhang, Jingjing; Zhang, Sen; Li, Tingju

2018-04-01

Novel high luminescence fibers often exhibit potential applications in the fields of color displays and sensor systems. In this study, Eu(BA)3phen and Tb(BA)3phen powders was successfully synthesized by solvothermal reactions, firstly. Then, three kinds of novel flexible Eu(BA)3phen/PAN, Tb(BA)3phen/PAN and Eu/Tb(BA)3phen/PAN (BA = benzoic acid, phen = phenanthroline, PAN = Polyacrylonitrile) fibers had been successfully prepared by electrospinning technology. The characterizations of the final products have been investigated in detail. It was found that the diameter of the as-prepared fibers were almost uniform with the fabricated complexes doping into PAN successfully. Thermogravimetric analysis indicates that the thermal stability of the pure PAN fiber could be improved by the incorporation of the complex, although only 1 wt % was added. Furthermore, in Eu/Tb(BA)3phen complex, the fluorescence intensity of Eu3+ ions was remarkably increased by adding Tb3+ ions. This is primarily due to an energy transfer from the 5D4 level of Tb (III) to the 5D0 level of Eu (III) ions, where Tb3+ acted as sensitizer. The corresponding luminescent fibers displayed the same regularity as the complexes. Moreover, with the increasing of the incorporation of complexes into PAN, the fluorescence intensities were significantly enhanced and reached its maximum value at 2.5 wt % for Eu(BA)3phen/PAN fibers and 2.0 wt% for Tb(BA)3phen/PAN fibers. The further intensity decreased with the increasing content of the complexes because of typical emission concentration quenching.

Children's difficulty with true belief tasks: Competence deficit or performance problem?

PubMed

Oktay-Gür, Nese; Rakoczy, Hannes

2017-09-01

According to the standard picture of explicit theory of mind (ToM) development, children begin to (explicitly) ascribe beliefs to others and themselves from around age 4. The empirical basis of this picture comes from numerous studies consistently showing that children master verbal false belief (FB) tasks from around age 4 while children much younger have no difficulty in mastering structurally analogous true belief (TB) tasks. The standard picture, though, has come under serious attack from recent studies using TB tasks with wider age ranges. These studies have found that, paradoxically, children begin to fail TB tasks once they master FB tasks. Such findings cast doubt on the standard picture and suggest, instead, that FB tasks may be solved by much simpler strategies than proper belief reasoning. In the present study, we tested for the development of FB and TB performance in comprehensive and systematic ways. In particular, we tested the competing predictions of competence accounts (according to which TB failure reflects lack of conceptual competence) versus performance limitation accounts (according to which the standard picture is true yet children from around age 4 fail TB tasks due to performance factors). Studies 1 and 2 showed that performance in a variety of novel TB tasks showed a clear U-shaped curve, with children until age 3 and from age 10 performing competently and children in between failing, with strong negative correlations between TB and FB. Crucially, these patterns were found for various kinds of TB tasks, including those for which existing competence limitation accounts would not even predict any difficulty. Study 3, therefore, directly tested performance limitation accounts in terms of pragmatic and related factors and found that these patterns (failure in TB and negative TB-FB correlations) disappear once the relevant performance factors have been removed from the TB tasks. Taken together, these findings suggest that previous TB findings constitute false negatives, clearly speak for performance limitation accounts and thus corroborate the standard picture of the development of explicit theory of mind. Copyright © 2017 Elsevier B.V. All rights reserved.

Monomer and metallopolymer compounds of Tb(III) as precursors for OLEDs

NASA Astrophysics Data System (ADS)

Irina, Savchenko; Oleksandra, Berezhnytska; Olena, Trunova; Yaroslav, Fedorov; Sergiy, Smola; Nataliya, Rusakova

2018-03-01

The Terbium (III) complexes [Tb(III)-water, mixed-ligand complex Tb(III)-phenanthroline] with 2-methyl-5-phenyl-1-pentene-3,5-dione were synthesized. The polycomplex was obtained by free-radical polymerization. The results of above studies have shown that the configuration of the chelate unit is unchanged during the polymerization. As a result, the type of coordination was determined and the structure of coordination polyhedra was assumed. The luminescence spectra of obtained metallocomplexes and polymer were investigated and analyzed. The solubilization of terbium complex with phenanthroline, was shown to change luminescence intensity in this complex.

A self-consistency approach to improve microwave rainfall rate estimation from space

NASA Technical Reports Server (NTRS)

Kummerow, Christian; Mack, Robert A.; Hakkarinen, Ida M.

1989-01-01

A multichannel statistical approach is used to retrieve rainfall rates from the brightness temperature T(B) observed by passive microwave radiometers flown on a high-altitude NASA aircraft. T(B) statistics are based upon data generated by a cloud radiative model. This model simulates variabilities in the underlying geophysical parameters of interest, and computes their associated T(B) in each of the available channels. By further imposing the requirement that the observed T(B) agree with the T(B) values corresponding to the retrieved parameters through the cloud radiative transfer model, the results can be made to agree quite well with coincident radar-derived rainfall rates. Some information regarding the cloud vertical structure is also obtained by such an added requirement. The applicability of this technique to satellite retrievals is also investigated. Data which might be observed by satellite-borne radiometers, including the effects of nonuniformly filled footprints, are simulated by the cloud radiative model for this purpose.

Free tuberculosis diagnosis and treatment are not enough: patient cost evidence from three continents.

PubMed

Mauch, V; Bonsu, F; Gyapong, M; Awini, E; Suarez, P; Marcelino, B; Melgen, R E; Lönnroth, K; Nhung, N V; Hoa, N B; Klinkenberg, E

2013-03-01

The National Tuberculosis Programs of Ghana, Viet Nam and the Dominican Republic. To assess the direct and indirect costs of tuberculosis (TB) diagnosis and treatment for patients and households. Each country translated and adapted a structured questionnaire, the Tool to Estimate Patients' Costs. A random sample of new adult patients treated for at least 1 month was interviewed in all three countries. Across the countries, 27-70% of patients stopped working and experienced reduced income, 5-37% sold property and 17-47% borrowed money due to TB. Hospitalisation costs (US$42-118) and additional food items formed the largest part of direct costs during treatment. Average total patient costs (US$538-1268) were equivalent to approximately 1 year of individual income. We observed similar patterns and challenges of TB-related costs for patients across the three countries. We advocate for global, united action for TB patients to be included under social protection schemes and for national TB programmes to improve equitable access to care.

Whole genome sequencing reveals mycobacterial microevolution among concurrent isolates from sputum and blood in HIV infected TB patients.

PubMed

Ssengooba, Willy; de Jong, Bouke C; Joloba, Moses L; Cobelens, Frank G; Meehan, Conor J

2016-08-05

In the context of advanced immunosuppression, M. tuberculosis is known to cause detectable mycobacteremia. However, little is known about the intra-patient mycobacterial microevolution and the direction of seeding between the sputum and blood compartments. From a diagnostic study of HIV-infected TB patients, 51 pairs of concurrent blood and sputum M. tuberculosis isolates from the same patient were available. In a previous analysis, we identified a subset with genotypic concordance, based on spoligotyping and 24 locus MIRU-VNTR. These paired isolates with identical genotypes were analyzed by whole genome sequencing and phylogenetic analysis. Of the 25 concordant pairs (49 % of the 51 paired isolates), 15 (60 %) remained viable for extraction of high quality DNA for whole genome sequencing. Two patient pairs were excluded due to poor quality sequence reads. The median CD4 cell count was 32 (IQR; 16-101)/mm(3) and ten (77 %) patients were on ART. No drug resistance mutations were identified in any of the sequences analyzed. Three (23.1 %) of 13 patients had SNPs separating paired isolates from blood and sputum compartments, indicating evidence of microevolution. Using a phylogenetic approach to identify the ancestral compartment, in two (15 %) patients the blood isolate was ancestral to the sputum isolate, in one (8 %) it was the opposite, and ten (77 %) of the pairs were identical. Among HIV-infected patients with poor cellular immunity, infection with multiple strains of M. tuberculosis was found in half of the patients. In those patients with identical strains, whole genome sequencing indicated that M. tuberculosis intra-patient microevolution does occur in a few patients, yet did not reveal a consistent direction of spread between sputum and blood. This suggests that these compartments are highly connected and potentially seed each other repeatedly.

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

Pani, M., E-mail: marcella@chimica.unige.it; Institute SPIN-CNR, Corso Perrone 24, 16152 Genova; Morozkin, A.V.

The title compounds have been synthesized and characterized both from the structural and magnetic point of view. Both crystallize in a new monoclinic structure strictly related to the tetragonal BaCd{sub 11} type. The structure was solved by means of X-ray single-crystal techniques for GdNi{sub 8}Si{sub 3} and confirmed for TbNi{sub 8}Si{sub 3} on powder data; the corresponding lattice parameters (obtained from Guinier powder patterns) are a=6.3259(2), b=13.7245(5), c=7.4949(3) Å, β=113.522(3)°, V{sub cell}=596.64(3) Å{sup 3} and a=6.3200(2), b=13.6987(4), c=7.4923(2) Å, β=113.494(2)°, V{sub cell}=594.88(2) Å{sup 3}. The symmetry relationship between the tI48-I4{sub 1}/amd BaCd{sub 11} aristotype and the new ordered mS48-C2/c GdNi{submore » 8}Si{sub 3} derivative is described via the Bärnighausen formalism within the group theory. The large Gd–Gd (Tb–Tb) distances, mediated via Ni–Si network, likely lead to weak magnetic interactions. Low-field magnetization vs temperature measurements indicate weak and field-sensitive antiferromagnetic ground state, with ordering temperatures of 3 K in GdNi{sub 8}Si{sub 3} and about 2–3 K in TbNi{sub 8}Si{sub 3}. On the other hand, the isothermal field-dependent magnetization data show the presence of competing interactions in both compounds, with a field-induced ferromagnetic behavior for GdNi{sub 8}Si{sub 3} and a ferrimagnetic-like behavior in TbNi{sub 8}Si{sub 3} at the ordering temperature T{sub C/N} of about (or slightly higher than) 3K. The magnetocaloric effect, quantified in terms of isothermal magnetic entropy change ΔS{sub m}, has the maximum values of –19.8 J(kg K){sup −1} (at 4 K for 140 kOe field change) and −12.1 J(kg K){sup −1} (at 12 K for 140 kOe field change) in GdNi{sub 8}Si{sub 3} and TbNi{sub 8}Si{sub 3}, respectively. - Graphical abstract: GdNi{sub 8}Si{sub 3} and TbNi{sub 8}Si{sub 3} compounds are isostructural, and crystallize in a new monoclinic type strictly related to the tetragonal BaCd{sub 11} structure. The large R–R interatomic distances mediated via Ni–Si network lead to a weak magnetism in both compounds. - Highlights: • Novel RNi{sub 8}Si{sub 3} (R=Gd, Tb) compounds have been synthesized and characterized. • GdNi{sub 8}Si{sub 3} and TbNi{sub 8}Si{sub 3} are isostructural compounds, belonging to a new monoclinic structure type. • The monoclinic GdNi{sub 8}Si{sub 3} type is an ordered derivative of the tetragonal BaCd{sub 11} type. • The large R–R interatomic distances mediated via Ni–Si network lead to a weak magnetism. • Both compounds GdNi{sub 8}Si{sub 3} and TbNi{sub 8}Si{sub 3} show antiferromagnetic-like order around 3 K.« less

Structural and chemical characterization of terbia thin films grown on hexagonally close packed metal substrates

NASA Astrophysics Data System (ADS)

Cartas, William

Rare earth oxides (REOs) exhibit favorable catalytic performance for a diverse set of chemical transformations, including both partial and complete oxidation reactions. I will discuss our efforts to develop thin film systems of terbia for model surface science investigations of a REO that is effectively reducible, and which is thus expected to promote complete oxidation chemistry of adsorbed species. The growth of terbia on Cu(111) is shown to produce a complex surface that exhibits multiple phases of the oxide as well as exposed substrate. Growing the film on Pt(111) results in more uniform, single phase, and closed film. We used low energy electron diffraction (LEED) and scanning tunneling microscopy (STM) to characterize the structural properties of terbia thin films grown on Pt(111) in ultrahigh vacuum (UHV) using physical vapor deposition. We find that the REO grows as a high quality Tb2O 3(111) film, and adopts oxygen-deficient fluorite structures wherein the metal cations form a hexagonal lattice in registry with the Pt(111) substrate, while oxygen vacancies are randomly distributed within the film. The Tb 2O3(111) films are thermally stable when heated to 1000 K in UHV. LEED and STM show that a fraction of the Tb2O3 forms hexagonal islands when first deposited, and further depositions typically result in three dimensional growth of the film. The Tb2O3 (111) / Pt(111) system produces a coincidence structure, seen very clearly in LEED images. We have also found that Tb2O3(111) films can be oxidized in UHV by exposure to plasma-generated atomic oxygen beams. The oxidized films have an estimated TbO2 stoichiometry and decompose to Tb2O3 during heating, with O2 desorption starting at about 500 K. Terbia films oxidized at 90 K show a weakly bound state of oxygen that is likely chemisorbed. Temperature programmed reaction spectroscopy (TPRS) studies using methanol show that increased oxygen in the film does not modify the chemical selectivity of the film; however, the increased oxygen content does increase the activity of the film toward methanol dehydrogenation. We have found that when methanol is adsorbed onto the terbia-Pt(111) system, it reacts to form formaldehyde and water and reduces the surface. The development of high-quality terbia thin films on Pt(111) provides new opportunities to investigate oxidation chemistry on an REO that has distinct reduction and oxidation properties.

Deposition-temperature dependence of structural anisotropy in amorphous Tb-Fe films

NASA Astrophysics Data System (ADS)

Harris, V. G.; Elam, W. T.; Koon, N. C.; Hellman, F.

1994-02-01

The anisotropic local structure in a series of amorphous Tb26Fe74 films deposited at different deposition temperatures and having different magnetic anisotropy energies have been investigated using polarization-dependent extended x-ray-absorption fine-structure measurements. Samples deposited at temperatures >=300 K exhibit anisotropic pair correlations where like atomic pairs are favored in plane and unlike pairs are favored out of plane. Both the anisotropic pair correlations and the perpendicular magnetic anisotropy increase with increasing deposition temperature. In contrast, a sample deposited at 77 K was found to have isotropic pair correlations, low perpendicular magnetic anisotropy, and a large (~=1%) in-plane compression.

Predictions of thermomagnetic properties of Laves phase compounds: TbAl2, GdAl2 and SmAl2 performed with ATOMIC MATTERS MFA computation system

NASA Astrophysics Data System (ADS)

Michalski, Rafał; Zygadło, Jakub

2018-04-01

Recent calculations of properties of TbAl2 GdAl2 and SmAl2 single crystals, performed with our new computation system called ATOMIC MATTERS MFA are presented. We applied localized electron approach to describe the thermal evolution of Fine Electronic Structure of Tb3+, Gd3+ and Sm3+ ions over a wide temperature range and estimate Magnetocaloric Effect (MCE). Thermomagnetic properties of TbAl2, GdAl2 and SmAl2 were calculated based on the fine electronic structure of the 4f8, 4f7 and 4f5 electronic configuration of the Tb3+ and Gd3+ and Sm3+ ions, respectively. Our calculations yielded: magnetic moment value and direction; single-crystalline magnetization curves in zero field and in external magnetic field applied in various directions m(T,Bext); the 4f-electronic components of specific heat c4f(T,Bext); and temperature dependence of the magnetic entropy and isothermal entropy change with external magnetic field - ΔS(T,Bext). The cubic universal CEF parameters values used for all CEF calculations was taken from literature and recalculated for universal cubic parameters set for the RAl2 series: A4 = +7.164 Ka04 and A6 = -1.038 Ka06. Magnetic properties were found to be anisotropic due to cubic Laves phase C15 crystal structure symmetry. These studies reveal the importance of multipolar charge interactions when describing thermomagnetic properties of real 4f electronic systems and the effectiveness of an applied self-consistent molecular field in calculations for magnetic phase transition simulation.

The association between multiple sources of information and risk perceptions of tuberculosis, Ntcheu district, Malawi.

PubMed

Chizimba, Robert; Christofides, Nicola; Chirwa, Tobias; Singini, Isaac; Ozumba, Chineme; Sikwese, Simon; Banda, Hastings T; Banda, Rhoda; Chimbali, Henry; Ngwira, Bagrey; Munthali, Alister; Nyasulu, Peter

2015-01-01

Tuberculosis (TB) is one of the main causes of death in developing countries. Awareness and perception of risk of TB could influence early detection, diagnosis and care seeking at treatment centers. However, perceptions about TB are influenced by sources of information. This study aimed to determine the association between multiple sources of information, and perceptions of risk of TB among adults aged 18-49 years. A cross-sectional study was conducted in Ntcheu district in Malawi. A total of 121 adults were sampled in a three-stage simple random sampling technique. Data were collected using a structured questionnaire. Perceptions of risk were measured using specific statements that reflected common myths and misconceptions. Low risk perception implied a person having strong belief in myths and misconceptions about TB and high risk perception meant a person having no belief in myths or misconceptions and demonstrated understanding of the disease. Females were more likely to have low risk perceptions about TB compared to males (67.7% vs. 32.5%, p = 0.01). The higher the household asset index the more likely an individual had higher risk perceptions about TB (p = 0.006). The perception of risk of TB was associated with sources of information (p = 0.03). Use of both interpersonal communication and mass media was 2.8 times more likely to be associated with increased perception of risk of TB (Odds Ratio [OR] = 2.8; 95% Confidence interva1[CI]: 3.1-15. 6; p = 0.01). After adjusting for sex and asset ownership, use of interpersonal communication and mass media were more likely to be associated with higher perception of risk of TB (OR, 2.0; 95% CI: 1.65-10.72; p = 0.003) compared with interpersonal communication only (OR 1.6, 95%; CI: 1.13-8.98, p = 0.027). The study found that there was association between multiple sources of information, and higher perceptions of risk of TB among adults aged 18-49 years.

A novel blue-greenish emitting phosphor Ba{sub 3}LaK(PO{sub 4}){sub 3}F:Tb{sup 3+} with high thermal stability

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

Zeng, Chao; Huang, Hongwei, E-mail: hhw@cugb.edu.cn; Hu, Yingmo, E-mail: huyingmo@cugb.edu.cn

Highlights: • The Ba{sub 3}LaK(PO{sub 4}){sub 3}F:Tb{sup 3+} phosphors exhibit a broad excitation band. • The Ba{sub 3}LaK(PO{sub 4}){sub 3}F:Tb{sup 3+} emission color adjust from blue to green. • The Ba{sub 3}LaK(PO{sub 4}){sub 3}F:Tb{sup 3+} show superior thermal stability. - Abstract: Ba{sub 3}La{sub 1−m}K(PO{sub 4}){sub 3}F:mTb{sup 3+}(m = 0.01–0.50) phosphors have been prepared by a traditional high temperature solid-state reaction. XRD analysis verified the apatite-type phase structure of the as-prepared samples, and the morphology has been checked by the Scanning electron microscope (SEM). The emission spectrum of Ba{sub 3}LaK(PO{sub 4}){sub 3}F:Tb{sup 3+} phosphor consists of two regions, blue emission bandmore » from 380 to 470 nm and green emission band from 470 to 650 nm. With increasing Tb{sup 3+} ions doped concentration (m), the color hue of Ba{sub 3}La{sub 1−m}K(PO{sub 4}){sub 3}F:mTb{sup 3+}adjusts from blue to green. On the basis of concentration quenching method, the critical distance between Tb{sup 3+} ions is calculated to be 7.98 Å, suggesting that multipolar interaction predominate in quenching process. In addition, the temperature-dependence PL spectra of Ba{sub 3}LaK(PO{sub 4}){sub 3}F:0.01Tb{sup 3+} and Ba{sub 3}LaK(PO{sub 4}){sub 3}F:0.40Tb{sup 3+} phosphor are given,which exhibit superior thermal stability.« less

Tuberculosis in HIV-infected Tanzanian children below 14 years.

PubMed

Njau, J C; Aboud, S

2010-09-01

Tuberculosis (TB)-human immunodeficiency virus (HIV) co-infection is an important public health problem. Diagnosis of TB in children usually follows discovery of an adult case, and relies on clinical presentation, sputum examination and chest radiograph. However, clinical features are non-specific, chest radiographs are difficult to interpret, and routine laboratory tests are not helpful. The aim of the current study was to determine the prevalence of TB in HIV-infected children below 14 years attending a tertiary hospital. A cross-sectional study was conducted in HIV-infected children below 14 years of age at Muhimbili National Hospital, in Dar es Salaam, Tanzania, between July 2008 and January 2009. Information on socio-demographic and anthropometric characteristics was collected using a structured questionnaire. Following assessment of clinical presentation, physical examination, tuberculin skin test, and chest radiograph were performed for each child. Two consecutive sputum specimens and blopd sample were collected for microscopy and culture, and CD4 T-lymphocyte percentage test, respectively. Chi-square test was used to compare differences in proportions. Odds ratio (OR) and their 95% confidence interval (CI) are presented as the risk estimator. Of 182 HIV-infected children enrolled in the study, 104 (57.1%) were males. Overall, thirty-seven (20.3%) children had TB. The prevalence of TB was highest in males (78.4%) compared to females (p = 0.003). There was a higher proportion of TB (45.9%) in the age group below 24 months compared to other age groups (p = 0.001). Male gender, history of positive TB contact and severe immunosuppression were found to be significant risk factors for TB while use of antiretroviral therapy was found to be associated with decreased risk for TB. One-fifth of children had TB/HIV co-infection. Presence of four or more clinical manifestations and a low CD4+ T-lymphocyte percentage can be used to predict active TB in HIV-infected children.

Influence of meniscus on cartilage and subchondral bone features of knees from older individuals: A cadaver study

PubMed Central

Touraine, Sébastien; Bouhadoun, Hamid; Engelke, Klaus; Laredo, Jean Denis; Chappard, Christine

2017-01-01

Objective Cartilage and subchondral bone form a functional unit. Here, we aimed to examine the effect of meniscus coverage on the characteristics of this unit in knees of older individuals. Methods We assessed the hyaline cartilage, subchondral cortical plate (SCP), and subchondral trabecular bone in areas covered or uncovered by the meniscus from normal cadaver knees (without degeneration). Bone cores harvested from the medial tibial plateau at locations uncovered (central), partially covered (posterior), and completely covered (peripheral) by the meniscus were imaged by micro-CT. The following were measured on images: cartilage volume (Cart.Vol, mm3) and thickness (Cart.Th, mm); SCP thickness (SCP.Th, μm) and porosity (SCP.Por, %); bone volume to total volume fraction (BV/TV, %); trabecular thickness (Tb.Th, μm), spacing (Tb.Sp, μm), and number (Tb.N, 1/mm); structure model index (SMI); trabecular pattern factor (Tb.Pf); and degree of anisotropy (DA). Results Among the 28 specimens studied (18 females) from individuals with mean age 82.8±10.2 years, cartilage and SCP were thicker at the central site uncovered by the meniscus than the posterior and peripheral sites, and Cart.Vol was greater. SCP.Por was highest in posterior samples. In the upper 1–5 mm of subchondral bone, central samples were characterized by higher values for BV/TV, Tb.N, Tb.Th, and connectivity (Tb.Pf), a more plate-like trabecular structure and lower anisotropy than with other samples. Deeper down, at 6–10 mm, the differences were slightly higher for Tb.Th centrally, DA peripherally and SMI posteriorly. Conclusions The coverage or not by meniscus in the knee of older individuals is significantly associated with Cart.Th, SCP.Th, SCP.Por and trabecular microarchitectural parameters in the most superficial 5 mm and to a lesser extent the deepest area of subchondral trabecular bone. These results suggest an effect of differences in local loading conditions. In subchondral bone uncovered by the meniscus, the trabecular architecture resembles that of highly loaded areas. PMID:28797093

Assessment of current practices in management of childhood TB among frontline clinicians in Southern Nigeria.

PubMed

Chukwu, Joseph N; Ukwaja, Kingsley N; Ekeke, Ngozi; Nwafor, Charles C; Meka, Anthony O; Madichie, Nelson O; Anyim, Moses C; Ogbudebe, Chidubem; Adegbesan, Julie; Ikebudu, Joy; Oshi, Daniel C

2016-07-01

Poor competence of clinicians may be a critical factor responsible for the under-diagnosis of childhood TB in high-burden settings. Our objective was to assess the current practices of management of childhood TB among clinicians in Nigeria. A cross-sectional survey was conducted among clinicians recruited through a three-stage sampling technique from 76 health facilities in Southern Nigeria. A semi-structured questionnaire was administered to all participants. Of 106 clinicians who completed the survey, 73 (68.9%) were <40 years and 67 (63.2%) were males. Also, 14 (13.2%) were paediatricians, 22 (20.8%) were paediatric specialist trainees and 70 (66%) were medical officers in primary and secondary care health facilities. About 94% of the respondents perceived diagnosis of childhood TB a challenge in Nigeria. The overall mean (SD) knowledge score was 3.8±0.9 (maximum 5), and 68 (64.2%) had good knowledge of childhood TB. The mean (SD) appropriate practice score was 4.0±1.7 (maximum 10) and, only 8 (7.5%) of them were considered to have adopted appropriate practices regarding childhood TB care. There are gaps in practices adopted by frontline clinicians in the management of childhood TB in Nigeria. Focused training of health workers on childhood TB care is urgently recommended. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Self-assembled 3D sphere-like SrMoO4 and SrMoO4:Ln3+ (Ln=Eu, Sm, Tb, Dy) microarchitectures: facile sonochemical synthesis and optical properties.

PubMed

Zhang, Junjun; Li, Ruiqing; Liu, Lu; Li, Linlin; Zou, Lianchun; Gan, Shucai; Ji, Guijuan

2014-09-01

Three-dimensional (3D) well-defined SrMoO4 and SrMoO4:Ln(3+) (Ln=Eu, Sm, Tb, Dy) hierarchical structures of obvious sphere-like shape have been successfully synthesized using a large-scale and facile sonochemical route without using any catalysts or templates. X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), and photoluminescence (PL) spectra were used to characterize the samples. The intrinsic structural feature of SrMoO4 and external factor, namely the ultrasonic time and the pH value, are responsible for the ultimate shape evolutions of the product. The possible formation mechanism for the product is presented. Additionally, the PL properties of SrMoO4 and SrMoO4:Ln(3+) (Ln=Eu, Sm, Tb, Dy) hierarchical structures were investigated in detail. The Ln(3+) ions doped SrMoO4 samples exhibit respective bright red-orange, yellow, green and white light of Eu(3+), Sm(3+), Tb(3+) and Dy(3+) under ultraviolet excitation, and have potential application in the field of color display. Simultaneously, this novel and efficient pathway could open new opportunities for further investigating about the properties of molybdate materials. Copyright © 2014 Elsevier B.V. All rights reserved.

The relationship between dental implant stability and trabecular bone structure using cone-beam computed tomography

PubMed Central

2016-01-01

Purpose The objective of this study was to investigate the relationships between primary implant stability as measured by impact response frequency and the structural parameters of trabecular bone using cone-beam computed tomography(CBCT), excluding the effect of cortical bone thickness. Methods We measured the impact response of a dental implant placed into swine bone specimens composed of only trabecular bone without the cortical bone layer using an inductive sensor. The peak frequency of the impact response spectrum was determined as an implant stability criterion (SPF). The 3D microstructural parameters were calculated from CT images of the bone specimens obtained using both micro-CT and CBCT. Results SPF had significant positive correlations with trabecular bone structural parameters (BV/TV, BV, BS, BSD, Tb.Th, Tb.N, FD, and BS/BV) (P<0.01) while SPF demonstrated significant negative correlations with other microstructural parameters (Tb.Sp, Tb.Pf, and SMI) using micro-CT and CBCT (P<0.01). Conclusions There was an increase in implant stability prediction by combining BV/TV and SMI in the stepwise forward regression analysis. Bone with high volume density and low surface density shows high implant stability. Well-connected thick bone with small marrow spaces also shows high implant stability. The combination of bone density and architectural parameters measured using CBCT can predict the implant stability more accurately than the density alone in clinical diagnoses. PMID:27127692

Synthesis, characterization and heterogeneous base catalysis of amino functionalized lanthanide metal-organic frameworks

NASA Astrophysics Data System (ADS)

Huang, Jinping; Li, Chunmei; Tao, Lingling; Zhu, Huilin; Hu, Gang

2017-10-01

Lanthanide metal-organic frameworks (Ln-MOFs) are featured by their tolerance to water and dense structure. In this work, an amine-functionalized Ln-MOF was facilely synthesized by coordination of terbium with 2-aminoterephthalic acid under the condition of microwave irradiation. The crystal structure was characterized by single crystal X-ray diffraction, FT-IR, Raman, TG-DTA and XPS analysis. The basic catalytic activity of the NH2-Tb-MOF was evaluated for Knoevenagel condensation and Henry reactions. Apart from the high activity and 100% selectivity to the condensation product, the NH2-Tb-MOF catalyst could be easily recycled and reused owing to the high stability of the MOF framework formed by coordination of Tb3+ with carboxylic groups. Remarkably, the NH2-Tb-MOF exhibited size-selective catalysis to substrates. For the small-sized reactants, it displayed comparable activity to the homogeneous catalyst of aniline owing to the high dispersion of NH2- active sites and the low diffusion limits. However, in the same reaction system, extremely poor activity in Knoevenagel condensation and Henry reaction for the bulky substrate 4-(tert-butyl) benzaldehyde was observed due to the both effects of substitute and inhibition of diffusion into the micropores. Crystal structure analysis provided a mechanistic evidence that the heterogeneous base catalysis arose from the amino groups densely distributed inside the micropores.

High fluorescence emission of carboxylic acid functionalized polystyrene/BaTiO{sub 3} nanocomposites and rare earth metal complexes: Preparation and characterization

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

Cao, X. T.; Showkat, A. M.; Wang, Z.

2015-03-30

Noble fluorescence nanocomposite compound based on barium titanate nanoparticles (BTO), polystyrene (PSt), and terbium ion (Tb{sup 3+}) was synthesized by a combination of surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization, Friedel-Crafts alkylation reaction and coordinate chemistry. Initially, a modification of surface of BTO was conducted by an exchange process with S-benzyl S’-trimethoxysilylpropyltrithiocarbonate to create macro-initiator for polymerization of styrene. Subsequently, aryl carboxylic acid functionalized polystyrene grafted barium titanate (BTO-g-PSt-COOH) was generated by substitution reaction between 4-(Chloromethyl) benzoic acid and PSt chains. The coordination of the nanohybrids with Tb{sup 3+} ions afforded fluorescent Tb{sup 3+} tagged aryl carboxylic acid functionalized polystyrenemore » grafted barium titanate (BTO-g-PSt-Tb{sup 3+}) complexes. Structure, morphology, and fluorescence properties of nanohybrid complexes were investigated by respective physical and spectral studies. FT-IR and SEM analyses confirmed the formation of BTO-g-PSt-Tb{sup 3+}nanohybrids. Furthermore, TGA profiles demonstrated the grafting of aryl carboxylic acid functionalized polystyrene on BTO surface. Optical properties of BTO-g-PSt-Tb{sup 3+} complexes were investigated by fluorescence spectroscopy.« less

The influence of interface on spin pumping effect in Ni{sub 80}Fe{sub 20} /Tb bilayer

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

Yue, Jinjin; Jiang, Sheng; Zhang, Dong

2016-05-15

Focusing on the interface effect of the Ni{sub 80}Fe{sub 20} (Py)/terbium (Tb) bilayer, the influence of interface on the magnetization dynamic damping is investigated systematically. Two series of Py (12 nm)/Tb (d nm) films with and without copper (Cu) (1 nm) interlayer are deposited on silicon (Si) substrates by DC magnetron sputtering at room temperature. From vibrating sample magnetometer (VSM) measurements, the saturation magnetization (M{sub s}) decreases with increasing Tb thickness in Py/Tb bilayer while the decrease of M{sub s} is suppressed efficiently by inserting a Cu layer with even 1 nm of thickness. From the frequency dependence of ferromagneticmore » resonance (FMR) linewidth, we can obtain the Gilbert damping coefficient (α), α is found to exhibit an extreme enhancement in comparison to the single Py layer and shows an increasing trend with increasing Tb thickness. By inserting the Cu layer, α decreases significantly. From theoretical fitting, the spin diffusion length (λ{sub SD}) and spin mixing conductance (g{sup ↑↓}) are determined. It shows that the interface structure influences the spin mixing conductance but not the spin diffusion length.« less

Understanding private retail drug outlet dispenser knowledge and practices in tuberculosis care in Tanzania.

PubMed

Rutta, E; Tarimo, A; Delmotte, E; James, I; Mwakisu, S; Kasembe, D; Konduri, N; Silumbe, R; Kakanda, K; Valimba, R

2014-09-01

Private sector accredited drug dispensing outlets in Morogoro and pharmacies in Dar es Salaam, Tanzania. To assess 1) the level of knowledge about tuberculosis (TB) among dispensers in Tanzania's retail pharmaceutical sector; 2) practices related to identification of patients with suspected TB; 3) the availability of educational materials and training; and 4) the availability of first- and second-line anti-tuberculosis treatment in retail drug outlets. A cross-sectional descriptive study involving the administration of a structured questionnaire among drug dispensers in 122 pharmacies and 173 accredited drug dispensing outlets. Private retail drug outlets are convenient; most are open at least 12 h per day, 7 days/week. Although 95% of dispensers identified persistent cough as a symptom of TB, only 1% had received TB-related training in the previous 3 years; 8% of outlets stocked first-line anti-tuberculosis medicines, which are legally prohibited from being sold at retail outlets. The majority of respondents reported seeing clients with TB-like symptoms, and of these 95% reported frequently referring clients to nearby health facilities. Private retail pharmaceutical outlets can potentially contribute to TB case detection and treatment; however, a coordinated effort is needed to train dispensers and implement appropriate referral procedures.

Tuberculosis Management Practices by Private Practitioners in Andhra Pradesh, India

PubMed Central

Achanta, Shanta; Jaju, Jyoti; Kumar, Ajay M. V.; Nagaraja, Sharath Burugina; Shamrao, Srinivas Rao Motta; Bandi, Sasidhar Kumar; Kumar, Ashok; Satyanarayana, Srinath; Harries, Anthony David; Nair, Sreenivas Achutan; Dewan, Puneet K.

2013-01-01

Setting Private medical practitioners in Visakhapatnam district, Andhra Pradesh, India. Objectives To evaluate self-reported TB diagnostic and treatment practices amongst private medical practitioners against benchmark practices articulated in the International Standards of Tuberculosis Care (ISTC), and factors associated with compliance with ISTC. Design Cross- sectional survey using semi-structured interviews. Results Of 296 randomly selected private practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and treatment standards in TB management. Only 11 (6%) followed a combination of 6 diagnostic standards together and only 1 followed a combination of all seven treatment standards together. There were 28 (14%) private practitioners who complied with a combination of three core ISTC (cough for tuberculosis suspects, sputum smear examination and use of standardized treatment). Higher ISTC compliance was associated with caring for more than 20 TB patients annually, prior sensitization to TB control guidelines, and practice of alternate systems of medicine. Conclusion Few private practitioners in Visakhapatnam, India reported TB diagnostic and treatment practices that met ISTC. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance. PMID:23967158

Cultural concepts of tuberculosis and gender among the general population without tuberculosis in rural Maharashtra, India.

PubMed

Atre, Sachin R; Kudale, Abhay M; Morankar, Sudhakar N; Rangan, Sheela G; Weiss, Mitchell G

2004-11-01

Gender-specific patterns of experience, meaning, and behaviour for tuberculosis (TB) require consideration to guide control programmes. To clarify concepts of gender, culture, and TB in a rural endemic population of Maharashtra, India, this study of 80 men and 80 women employed qualitative and quantitative methods of cultural epidemiology, using a locally adapted semi-structured Explanatory Model Interview Catalogue (EMIC) interviews are instruments for cultural epidemiological study of the distribution of illness-related experiences, meanings, and behaviours. This interview queried respondents without active disease about vignettes depicting a man and woman with typical features of TB. Emotional and social symptoms were frequently reported for both vignettes, but more often considered most distressing for the female vignette; specified problems included arranging marriages, social isolation, and inability to care for children and family. Job loss and reduced income were regarded most troubling for the male vignette. Men and women typically identified sexual experience as the cause of TB for opposite-sex vignettes. With wider access to information about TB, male respondents more frequently recommended allopathic doctors and specialty services. Discussion considers the practical significance of gender-specific cultural concepts of TB.

Synthesis, structure, luminescence, and magnetic properties of a single-ion magnet "mer"-[tris(N-[(imidazol-4-yl)-methylidene]-DL-phenylalaninato)terbium(III) and related "fac"-DL-alaninato derivative.

PubMed

Yamauchi, Suguru; Fujinami, Takeshi; Matsumoto, Naohide; Mochida, Naotaka; Ishida, Takayuki; Sunatsuki, Yukinari; Watanabe, Masayuki; Tsuchimoto, Masanobu; Coletti, Cecilia; Re, Nazzareno

2014-06-16

Two Tb(III) complexes with the same N6O3 donor atoms but different coordination geometries, "fac"-[Tb(III)(HL(DL-ala))3]·7H2O (1) and "mer"-[Tb(III)(HL(DL-phe))3]·7H2O (2), were synthesized, where H2L(DL-ala) and H2L(DL-phe) are N-[(imidazol-4-yl)methylidene]-DL-alanine and -DL-phenylalanine, respectively. Each Tb(III) ion is coordinated by three electronically mononegative NNO tridentate ligands to form a coordination geometry of a tricapped trigonal prism. Compound 1 consists of enantiomers "fac"-[Tb(III)(HL(D-ala))3] and "fac"-[Tb(III)(HL(L-ala))3], while 2 consists of "mer"-[Tb(III)(HL(D-phe))2(HL(L-phe))] and "mer"-[Tb(III)(HL(D-phe))(HL(L-phe))2]. Magnetic data were analyzed by a spin Hamiltonian including the crystal field effect on the Tb(III) ion (4f(8), J = 6, S = 3, L = 3, gJ = 3/2, (7)F6). The Stark splitting of the ground state (7)F6 was evaluated from magnetic analysis, and the energy diagram pattern indicated easy-plane and easy-axis (Ising type) magnetic anisotropies for 1 and 2, respectively. Highly efficient luminescences with Φ = 0.50 and 0.61 for 1 and 2, respectively, were observed, and the luminescence fine structure due to the (5)D4 → (7)F6 transition is in good accordance with the energy diagram determined from magnetic analysis. The energy diagram of 1 shows an approximate single-well potential curve, whereas that of 2 shows a double- or quadruple-well potential within the (7)F6 multiplets. Complex 2 displayed an onset of the out-of-phase signal in alternating current (ac) susceptibility at a direct current bias field of 1000 Oe on cooling down to 1.9 K. A slight frequency dependence was recorded around 2 K. On the other hand, 1 did not show any meaningful out-of-phase ac susceptibility. Pulsed-field magnetizations of 1 and 2 were measured below 1.6 K, and only 2 exhibited magnetic hysteresis. This finding agrees well with the energy diagram pattern from crystal field calculation on 1 and 2. DFT calculation allowed us to estimate the negative charge distribution around the Tb(III) ion, giving a rationale to the different magnetic anisotropies of 1 and 2.

Positron annihilation response and broadband dielectric spectroscopy: salol.

PubMed

Bartoš, J; Iskrová, M; Köhler, M; Wehn, R; Sauša, O; Lunkenheimer, P; Krištiak, J; Loidl, A

2011-09-01

A phenomenological analysis of the ortho-positronium (o-Ps) annihilation from positron annihilation lifetime spectroscopy (PALS) and the dynamics from broadband dielectric spectroscopy (BDS) are reported on a small molecular glass former of intermediate H-bonding and fragility: salol. The dielectric spectra extend over a very broad frequency range of about 2 × 10(-2)-3.5 × 10(11) Hz, providing information on the α-relaxation, the secondary relaxation giving rise to the excess wing, and the shallow high-frequency minimum in the micro- to milli-meter wave range. A number of empirical correlations between the o-Ps lifetime, τ(3)(T), and the various spectral and relaxation features have been observed. Thus, the phenomenological evaluation of the τ(3)(T) dependence of the PALS response of the amorphous sample reveals three characteristic PALS temperatures: T(g)(PALS), T(b1)(L) = 1.15T(g)(PALS) and T(b2)(L) = 1.25T(g)(PALS), which are discussed in relation to similar findings for some typical small molecular vdW- and H-bonded glass formers. A slighter change of the slope at T(b1)(L) appears to be related to the transition from excess wing to the primary α-process-dominated behavior, with the secondary process dominating in the deeply supercooled liquid state below T(b1)(L). The high-temperature plateau effect in the τ (3)(T) plot occurs at T(b2)(L) and agrees with the characteristic Stickel temperature, T(B)(ST), marking a qualitative change of the primary α process, but it does not follow the relation T(b2)(L) < T(α) [τ(3)(T(b2)) < τ(α)]. Both effects at T(b1)(L) and T(b2)(L) correlate with two crossovers in the spectral shape and related non-exponentiality parameter of the structural relaxation, β (KWW). Finally, the application of the two-order parameter (TOP) model to the structural relaxation as represented by the primary α relaxation times from BDS leads to the characteristic TOP temperature, T(m)(c), close to T(b1) from PALS. Within this model the phenomenological interpretation is offered based on changes in the probability of occurrence of solid-like and liquid-like domains to explain the dynamic as well as PALS responses. In summary, all the empirical correlations support further very close connections between the PALS response and the dielectric relaxation behavior in small molecule glass formers.

TB questions, East Kwaio answers: community-based participatory research in a remote area of Solomon Islands.

PubMed

Massey, P D; Wakageni, J; Kekeubata, E; Maena'adi, J; Laete'esafi, J; Waneagea, J; Fangaria, G; Jimuru, C; Houaimane, M; Talana, J; MacLaren, D; Speare, R

2012-01-01

East Kwaio is a remote region on the island of Malaita, Solomon Islands. Atoifi Adventist Hospital (the Hospital) is the only hospital and tuberculosis (TB) services provider in the region. If people come to the Hospital with TB, they are usually admitted for the two-month intensive phase of treatment as there are no community-based TB services. Most people walk or travel by canoe to the Hospital as there are no roads. East Kwaio is known to have high rates of TB; however, it has a low case detection rate and low treatment completion. The aims of this study were to explore why people with TB, especially from the mountain areas, present to the Hospital so late in their illness or do not present at all. The study was part of a larger project to strengthen the research capacity of local health workers and community leaders, supported by visiting researchers from Australia. Semi-structured interviews with TB patients, a focus group of key informants and direct interaction with a community with a history of TB were used to explore reasons why people present to the Hospital late in their TB illness. Four interviews and a focus group of 12 key informants were conducted and a mountain hamlet with a history of TB was visited. The results represent the data from the interviews and the focus group. The time delay in presenting to the Hospital from when participants first became unwell ranged between two and three years. In the mountain hamlet, two additional people with probable TB were seen who had not presented to the Hospital during illnesses of five and nine months. Reasons for delays included: seeking care from traditional healers; the challenge of accessing health services due to distance, cost and cultural issues different from the Hospital's worldview; social isolation when in hospital; and being old so not having long to live. Delays in diagnosis of people with TB will increase the risk of transmission to family and through hamlets and villages. This study has led to plans being developed to build a more culturally appropriate TB ward and community treatment program. The study has identified TB questions that need East Kwaio answers. It has shown that a small project can inform the development of important changes to TB services, such as the redevelopment and relocation of the TB ward. To enable TB control, the local health services need to develop an understanding of, and appropriately engage with, traditional beliefs that influence how people interact with Hospital TB treatment and management. This is the case even if the beliefs are based on a worldview different than that of the health service providers. Ongoing operational research is required into TB diagnosis and treatment services and the many factors that contribute to the high TB burden in this remote area.

Suppression of the cooperative Jahn-Teller distortion and its effect on the Raman octahedra-rotation modes of TbM n1 -xF exO3

NASA Astrophysics Data System (ADS)

Vilarinho, R.; Passos, D. J.; Queirós, E. C.; Tavares, P. B.; Almeida, A.; Weber, M. C.; Guennou, M.; Kreisel, J.; Moreira, J. Agostinho

2018-04-01

This work reports the changes in structure and lattice dynamics induced by substituting the Jahn-Teller-active M n3 + ion by the Jahn-Teller-inactive F e3 + in TbM n1 -xF exO3 over the full composition range. The structural analysis reveals that the amplitude of the cooperative Jahn-Teller distortion decreases linearly from x =0 (pure TbMn O3 ) to x =0.5 , where it is completely suppressed. We then correlate this evolution with the behavior of the Raman modes across the solid solution. In particular, we show that the Raman modes associated with the rotation of octahedra, whose wave number is commonly considered to scale linearly with the tilt angles in orthorhombic Pnma perovskites, are also sensitive to the amplitude of the Jahn-Teller distortion.

Radio- and photoluminescence properties of Ce/Tb co-doped glasses with huntite-like composition

NASA Astrophysics Data System (ADS)

Lorenzi, Roberto; Golubev, Nikita V.; Ziaytdinova, Mariyam Z.; Jarý, Vítězslav; Babin, Vladimir; Malashkevich, Georgii E.; Paleari, Alberto; Sigaev, Vladimir N.; Fasoli, Mauro; Nikl, Martin

2018-04-01

Optical properties of yttria-aluminoborate (YAB) glasses with general composition 10(CexTbyY(1-x-y))-30Al2O3-60B2O3 are investigated and compared with data available on YAB crystals with huntite-like structure. Ce doped samples show optical features ascribable to preferential location of rare earth ions in sites with specific geometry similar to that observed in crystalline structures. Samples prepared with Tb ions as emission activator and Ce ions as sensitizer have been studied within the framework of non-radiative energy transfer. The resulting Förster radius is of 4.6 ± 0.5 Å comparable with that observed in Ce/Tb co-doped YAl3(BO3)4 crystals. The investigated materials possess radio- and photoluminescence emission efficiencies and performances comparable to that of crystalline counterparts with the advantage of having easiness of preparation and workability typical of glassy systems.

Magnetic and thermal property studies of RCrTeO6 (R=trivalent lanthanides) with layered honeycomb sublattices

NASA Astrophysics Data System (ADS)

Narsinga Rao, G.; Sankar, R.; Panneer Muthuselvam, I.; Chou, F. C.

2014-12-01

We have investigated the magnetic ordering of the RCrTeO6 (R=Y, La, Tb and Er) samples comprising Cr3+ (S=3/2). The X-ray diffraction structure analysis revealed that all samples are a hexagonal structure with the space group P 3bar. The magnetic susceptibility χ(T) and heat capacity CP(T) measurement results reveal that both short range and long range antiferromagnetic (AFM) orderings exist in non-magnetic rare earth R=Y and La compounds. For isostructural compounds of R=Tb and Er, CP(T) curves show long range ordering at the same temperature as non-magnetic R=Y, which indicates that the super-super exchange of Cr spins dominates. For R elements of Tb and Er with large spins sitting between honeycomb sublattices composed of CrO6-TeO6 octahedra, the two sublattices of R and Cr appear to be independently magnetic.

Giant magnetostriction in nanoheterogeneous Fe-Al alloys

NASA Astrophysics Data System (ADS)

Han, Yongjun; Wang, Hui; Zhang, Tianli; He, Yangkun; Jiang, Chengbao

2018-02-01

As a potential magnetostrictive material, Fe-Al alloys exhibit excellent mechanical properties, low cost, and moderate magnetostriction, but the magnetostriction mechanism is still a mystery. Here, we elucidate the structural origin of magnetostriction in Fe-Al alloys and further improve the magnetostriction five-fold via Tb doping. Nanoinclusions with a size of 3-5 nm were found dispersed in the A2 matrix in Fe82Al18 ribbons. The structure of the nanoinclusions is identified to be tetragonally modified-D03 (L60), which are considered to create the tetragonal distortion of the matrix, leading to the enhanced magnetostriction. Furthermore, a drastic enhancement of the magnetostriction up to 5 times was achieved by trace Tb doping (0.2 at. %). Synchrotron X-ray diffraction directly revealed the increased tetragonal distortion of the matrix caused by these Tb dopants. The results further enrich the heterogeneous magnetostriction and guide the development of magnetostrictive materials.

Organization of a tumor bank: the experience of the National Cancer Institute of Mexico.

PubMed

Ruíz-Godoy, L; Meneses-García, A; Suárez-Roa, L; Enriquez, V; Lechuga-Rojas, R; Reyes-Lira, E

2010-01-01

A tumor bank (TB) is an ordered collection of neoplastic samples, normal tissue, and/or fluids preserved under optimal conditions, as well as storing patients' clinical information. The objective of this article is to outline the planning and logistics necessary for the functioning of the Instituto Nacional de Cancerología (INCan) TB in Mexico City. For the planning and logistics of a TB, several technical, legal, medical, structural, and physical aspects were considered, which can be grouped under four headings: (1) design and structure, (2) equipping the area and informatics, (3) ethical-legal aspects, and (4) sample collection, preservation, and quality control. One crucial element of interinstitutional interest will be the transfer of these concepts to the different oncological centers, integrating in this manner a network that enables the exploration of the different pathologies from therapeutic, epidemiological, and molecular points of view. 2010 S. Karger AG, Basel.

Effective lattice Hamiltonian for monolayer tin disulfide: Tailoring electronic structure with electric and magnetic fields

NASA Astrophysics Data System (ADS)

Yu, Jin; van Veen, Edo; Katsnelson, Mikhail I.; Yuan, Shengjun

2018-06-01

The electronic properties of monolayer tin dilsulfide (ML -Sn S2 ), a recently synthesized metal dichalcogenide, are studied by a combination of first-principles calculations and tight-binding (TB) approximation. An effective lattice Hamiltonian based on six hybrid s p -like orbitals with trigonal rotation symmetry are proposed to calculate the band structure and density of states for ML -Sn S2 , which demonstrates good quantitative agreement with relativistic density-functional-theory calculations in a wide energy range. We show that the proposed TB model can be easily applied to the case of an external electric field, yielding results consistent with those obtained from full Hamiltonian results. In the presence of a perpendicular magnetic field, highly degenerate equidistant Landau levels are obtained, showing typical two-dimensional electron gas behavior. Thus, the proposed TB model provides a simple way in describing properties in ML -Sn S2 .

A survey of knowledge, attitude, and practices of private retail pharmacies staff in tuberculosis care: study from Dera Ismail Khan City, Pakistan.

PubMed

Mustafa, Tehmina; Shahzad, Yasir; Kiani, Ayyaz

2018-01-01

In order to engage pharmacies in tuberculosis (TB) care, a survey was conducted in the Dera Ismail (DI) Khan City of the Khyber Pakhtoon Khwa province, Pakistan. The objectives were to; 1) characterize the retail pharmacies; 2) determine knowledge of the staff on various aspects of pulmonary TB; 3) determine practices related to the sale of anti-TB drugs, and referrals of presumptive TB patient, and willingness to participate in the National Tuberculosis Control Programme's (NTP) Directly Observed Treatment Short-Course (DOTS) strategy. A cross-sectional survey was conducted by using a structured questionnaire to collect data from pharmacy staff at all the private retail pharmacies of the DI khan city. All the interviewed staff ( n  = 82) were males, only 38% had formal training as pharmacist (5%) or as a pharmacy assistant (33%). Pharmacies established for a longer period were better staffed and had high customer load. About 92% of the interviewed staff knew that persistent cough is a symptom for TB, 82% knew that TB is diagnosed by examination of sputum. Almost 66% of the pharmacy staff did not know multi-drug resistance TB as a consequence of improper treatment. Those with formal training and longer experience in retail pharmacy had better knowledge of various aspects of TB as compared to the staff with no formal pharmacy training and lesser experience ( p  < 0.01). Only 57% were aware of NTP while only 30% had heard of the DOTS strategy. All reported sale of first-line TB drugs as fixed dose combinations. The majority (80%) referred presumptive TB patients to chest physicians and no patient was referred to the NTP. Nearly 83% of the interviewed staff was willing to be involved in TB control efforts by getting training and referring patients to the DOTS facility. There was shortage of professionally qualified and female staff in private retail pharmacies. Knowledge of professionally qualified staff about TB seemed sufficient to identify presumptive TB patients; however, their knowledge about NTP and DOTS was poor, and referral practices to NTP and DOTS centers were suboptimal. Majority of staff was willing to be involved in TB control efforts.

Phase transition of intermetallic TbPt at high temperature and high pressure

NASA Astrophysics Data System (ADS)

Qin, Fei; Wu, Xiang; Yang, Ke; Qin, Shan

2018-04-01

Here we present synchrotron-based x-ray diffraction experiments combined with diamond anvil cell and laser heating techniques on the intermetallic rare earth compound TbPt (Pnma and Z  =  4) up to 32.5 GPa and ~1800 K. The lattice parameters of TbPt exhibit continuous compression behavior up to 18.2 GPa without any evidence of phase transformation. Pressure-volume data were fitted to a third-order Birch-Murnaghan equation of state with V 0  =  175.5(2) Å3, {{K}{{T0}}}   =  110(5) GPa and K{{T0}}\\prime   =  3.8(7). TbPt exhibits anisotropic compression with β a   >  β b   >  β c and the ratio of axial compressibility is 2.50:1.26:1.00. A new monoclinic phase of TbPt assigned to the Pc or P2/c space group was observed at 32.5 GPa after laser heating at ~1800 K. This new phase is stable at high pressure and presented a quenchable property on decompression to ambient conditions. The pressure-volume relationship is well described by the second-order Birch-Murnaghan equation of state, which yields V 0  =  672(4) Å3, {{K}{{T0}}}   =  123(6) GPa, which is about ~14% more compressible than the orthorhombic TbPt. Our results provide more information on the structure and elastic property view, and thus a better understanding of the physical properties related to magnetic structure in some intermetallic rare earth alloys.

Soy protein is beneficial but high-fat diet and voluntary running are detrimental to bone structure in mice.

PubMed

Yan, Lin; Graef, George L; Nielsen, Forrest H; Johnson, LuAnn K; Cao, Jay

2015-06-01

Physical activity and soy protein isolate (SPI) augmentation have been reported to be beneficial for bone health. We hypothesized that combining voluntary running and SPI intake would alleviate detrimental changes in bone induced by a high-fat diet. A 2 × 2 × 2 experiment was designed with diets containing 16% or 45% of energy as corn oil and 20% SPI or casein fed to sedentary or running male C57BL/6 mice for 14 weeks. Distal femurs were assessed for microstructural changes. The high-fat diet significantly decreased trabecular number (Tb.N) and bone mineral density (BMD) and increased trabecular separation (Tb.Sp). Soy protein instead of casein, regardless of fat content, in the diet significantly increased bone volume fraction, Tb.N, connectivity density, and BMD and decreased Tb.Sp. Voluntary running, regardless of fat content, significantly decreased bone volume fraction, Tb.N, connectivity density, and BMD and increased Tb.Sp. The high-fat diet significantly decreased osteocalcin and increased tartrate-resistant acid phosphatase 5b (TRAP 5b) concentrations in plasma. Plasma concentrations of osteocalcin were increased by both SPI and running. Running alleviated the increase in TRAP 5b induced by the high-fat diet. These findings demonstrate that a high-fat diet is deleterious, and SPI is beneficial to trabecular bone properties. The deleterious effect of voluntary running on trabecular structural characteristics indicates that there may be a maximal threshold of running beyond which beneficial effects cease and detrimental effects occur. Increases in plasma osteocalcin and decreases in plasma TRAP 5b in running mice suggest that a compensatory response occurs to counteract the detrimental effects of excessive running. Published by Elsevier Inc.

The politics of tuberculosis and HIV service integration in Ghana.

PubMed

Amo-Adjei, Joshua; Kumi-Kyereme, Akwasi; Fosuah Amo, Hannah; Awusabo-Asare, Kofi

2014-09-01

The need to integrate TB/HIV control programmes has become critical due to the comorbidity regarding these diseases and the need to optimise the use of resources. In developing countries such as Ghana, where public health interventions depend on donor funds, the integration of the two programmes has become more urgent. This paper explores stakeholders' views on the integration of TB/HIV control programmes in Ghana within the remits of contingency theory. With 31 purposively selected informants from four regions, semi-structured interviews and observations were conducted between March and May 2012, and the data collected were analysed using the inductive approach. The results showed both support for and opposition to integration, as well as some of the avoidable challenges inherent in combining TB/HIV control. While those who supported integration based their arguments on clinical synergies and the need to promote the efficient use of resources, those who opposed integration cited the potential increase in workload, the clinical complications associated with joint management, the potential for a leadership crisis, and the "smaller the better" propositions to support their stance. Although a policy on TB/HIV integration exists, inadequate 'political will' from the top management of both programmes has trickled down to lower levels, which has stifled progress towards the comprehensive management of TB/HIV and particularly leading to weak data collection and management structures and unsatisfactory administration of co-trimoxazole for co-infected patients. It is our view that the leadership of both programmes show an increased commitment to protocols involving the integration of TB/HIV, followed by a commitment to addressing the 'fears' of frontline service providers to encourage confidence in the process of service integration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sociocultural dimensions of tuberculosis: an overview of key concepts.

PubMed

Mason, P H; Degeling, C; Denholm, J

2015-10-01

Biomedical innovations are unlikely to provide effective and ethical tuberculosis (TB) control measures without complementary social science research. However, a strong interest in interdisciplinary work is often undermined by differences in language and concepts specific to each disciplinary approach. Accordingly, biological and social scientists need to learn how to communicate with each other. This article will outline key concepts relating to TB from medical anthropology and health sociology. Distilling these concepts in an introductory framework is intended to make this material accessible to researchers in laboratory, clinical and fieldwork settings, as well as to encourage more social scientists to engage with TB research among target groups critical for successful programmatic interventions. For pedagogical purposes, the relevant concepts are grouped into three categories: 1) structures and settings, which includes overarching themes such as syndemics, local biologies, medicalisation, structural violence and surveillance; 2) practices and processes, encompassing gender, stigma, taboo, and victim blaming; and 3) experience and enculturation, which includes illness narratives, biographical disruption and dynamic nominalism. By helping to navigate this literature, we hope to foster more cross-disciplinary conversations between qualitative and quantitative researchers. TB, a quintessential social disease, will be controlled more effectively using a multistranded research approach.

Dy-V magnetic interaction and local structure bias on the complex spin and orbital ordering in Dy₁₋ xTb xVO₃ (x=0 and 0.2)

DOE PAGES

Yan, J.-Q.; Cao, H. B.; McGuire, M. A.; ...

2013-06-10

The spin and orbital ordering in Dy₁₋ xTb xVO₃ (x=0 and 0.2) was studied by measuring x-ray powder diffraction, magnetization, specific heat, and neutron single-crystal diffraction. The results show that G-OO/C-AF and C-OO/G-AF phases coexist in Dy 0.8Tb 0.20VO 3 in the temperature range 2–60 K, and the volume fraction of each phase is temperature and field dependent. The ordering of Dy moments at T* = 12 K induces a transition from G-OO/C-AF to a C-OO/G-AF phase. Magnetic fields suppress the long-range order of Dy moments and thus the C-OO/G-AF phase below T*. The polarized moments induced at the Dymore » sublattice by external magnetic fields couple to the V 3d moments, and this coupling favors the G-OO/C-AF state. Also discussed is the effect of the Dy-V magnetic interaction and local structure distortion on the spin and orbital ordering in Dy₁₋ xTb xVO₃.« less

Multiple competing interactions and reentrant ferrimagnetism in Tb 0.8Nd 0.2Mn 6Ge 6

NASA Astrophysics Data System (ADS)

Schobinger-Papamantellos, P.; André, G.; Rodríguez-Carvajal, J.; Duong, N. P.; Buschow, K. H. J.

2001-06-01

The magnetic ordering of the hexagonal compound Tb 0.8Nd 0.2Mn 6Ge 6 has been studied by neutron diffraction and magnetic measurements in the temperature range 1.5-800 K. This compound was found to undergo consecutive magnetic transitions with temperature. The magnetic phase diagram comprises four distinct regions and requires the wave vectors: q1=(0, 0, qz) and q2=0 for its description. The low temperature range (LT): 1.5 K< T< T1=85 K, is characterised by a triple ferrimagnetic conical (spiral) structure with qz=0.128 r.l.u and a net moment along the c direction ( q2=0). The intermediate temperature range displays two transitions: At T1=85 K the conical structure transforms to a simple triple (flat) spiral persisting in range (ITa) 85 K< T< T2≈340 K, with a small thermal variation of the wave vector. Above T2 in range (ITb) T2< T< TS≈390 K the destabilised spiral transforms to a FAN-like structure with a fast decrease of the wave vector length towards zero while a ferrimagnetic planar structure ( q2=0) develops at the cost of the spiral. The planar ferrimagnetic magnetic structure ( q2=0) dominates the high temperature range (HT) 390 K< T< Tc=450 K. The onset of re-entrant ferrimagnetism reflects the interplay of multiple competing inter- and intra- sublattice interactions of the three types of magnetic ions with different crystal field anisotropies. The Nd and Tb sublattices are coupled antiferromagnetically while the Tb-Mn and Nd-Mn interactions are negative and positive, respectively.

Persistence of collective behavior at high spin in the N = 88 nucleus Tb 153

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

Hartley, D. J.; Riley, M. A.; Wang, X.

Excited states in the N = 88 nucleus Tb-153 were observed up to spin similar to 40 in an experiment utilizing the Gammasphere array. The Tb-153 states were populated in a weak alpha 4n evaporation channel of the Cl-37 + Sn-124 reaction. Two previously known sequences were extended to higher spins, and a new decoupled structure was identified. The pi h(11/2) band was observed in the spin region where other N = 88 isotopes exhibit effects of prolate to oblate shape changes leading to band termination along the yrast line, whereas Tb-153 displays a persistent collective behavior. However, minor perturbationsmore » of the very highest state in both signatures of this h(11/2) band are observed, which perhaps signal the start of the transition towards band termination.« less

Genome-Wide Identification of TCP Family Transcription Factors in Medicago truncatula Reveals Significant Roles of miR319-Targeted TCPs in Nodule Development

PubMed Central

Wang, Hongfeng; Wang, Hongwei; Liu, Rong; Xu, Yiteng; Lu, Zhichao; Zhou, Chuanen

2018-01-01

TCP proteins, the plant-specific transcription factors, are involved in the regulation of multiple aspects of plant development among different species, such as leaf development, branching, and flower symmetry. However, thus far, the roles of TCPs in legume, especially in nodulation are still not clear. In this study, a genome-wide analysis of TCP genes was carried out to discover their evolution and function in Medicago truncatula. In total, 21 MtTCPs were identified and classified into class I and class II, and the class II MtTCPs were further divided into two subclasses, CIN and CYC/TB1. The expression profiles of MtTCPs are dramatically different. The universal expression of class I MtTCPs was detected in all organs. However, the MtTCPs in CIN subclass were highly expressed in leaf and most of the members in CYC/TB1 subclass were highly expressed in flower. Such organ-specific expression patterns of MtTCPs suggest their different roles in plant development. In addition, most MtTCPs were down-regulated during the nodule development, except for the putative MtmiR319 targets, MtTCP3, MtTCP4, and MtTCP10A. Overexpression of MtmiR319A significantly reduced the expression level of MtTCP3/4/10A/10B and resulted in the decreased nodule number, indicating the important roles of MtmiR319-targeted MtTCPs in nodulation. Taken together, this study systematically analyzes the MtTCP gene family at a genome-wide level and their possible functions in nodulation, which lay the basis for further explorations of MtmiR319/MtTCPs module in association with nodule development in M. truncatula.

Whole genome sequencing of Mycobacterium tuberculosis for detection of drug resistance: a systematic review.

PubMed

Papaventsis, D; Casali, N; Kontsevaya, I; Drobniewski, F; Cirillo, D M; Nikolayevskyy, V

2017-02-01

We conducted a systematic review to determine the diagnostic accuracy of whole genome sequencing (WGS) of Mycobacterium tuberculosis for the detection of resistance to first- and second-line anti-tuberculosis (TB) drugs. The study was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews group. A total of 20 publications were included. The sensitivity, specificity, positive-predictive value and negative-predictive value of WGS using phenotypic drug susceptibility testing methods as a reference standard were determined. Anti-TB agents tested included all first-line drugs, a variety of reserve drugs, as well as new drugs. Polymorphisms in a total of 53 genes were tested for associations with drug resistance. Pooled sensitivity and specificity values for detection of resistance to selected first-line drugs were 0.98 (95% CI 0.93-0.98) and 0.98 (95% CI 0.98-1.00) for rifampicin and 0.97 (95% CI 0.94-0.99) and 0.93 (95% CI 0.91-0.96) for isoniazid, respectively. Due to high heterogeneity in study designs, lack of data, knowledge of resistance mechanisms and clarity on exclusion of phylogenetic markers, there was a significant variation in analytical performance of WGS for the remaining first-line, reserved drugs and new drugs. Whole genome sequencing could be considered a promising alternative to existing phenotypic and molecular drug susceptibility testing methods for rifampicin and isoniazid pending standardization of analytical pipelines. To ensure clinical relevance of WGS for detection of M. tuberculosis complex drug resistance, future studies should include information on clinical outcomes. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Element specific determination of the magnetic properties of two macrocyclic tetranuclear 3d-4f complexes with a Cu3Tb core by means of X-ray magnetic circular dichroism (XMCD).

PubMed

Balinski, K; Schneider, L; Wöllermann, J; Buling, A; Joly, L; Piamonteze, C; Feltham, H L C; Brooker, S; Powell, A K; Delley, B; Kuepper, K

2018-06-20

We apply X-ray magnetic circular dichroism to study the internal magnetic structure of two very promising star shaped macrocyclic complexes with a CuII3TbIII core. These complexes are rare examples prepared with a macrocyclic ligand that show indications of SMM (Single Molecule Magnet) behavior, and they differ only in ring size: one has a propylene linked macrocycle, [CuII3TbIII(LPr)(NO3)2(MeOH)(H2O)2](NO3)·3H2O (nickname: Cu3Tb(LPr)), and the other has the butylene linked analogue, [CuII3TbIII(LBu)(NO3)2(MeOH)(H2O)](NO3)·3H2O (nickname: Cu3Tb(LBu)). We analyze the orbital and spin contributions to the Cu and Tb ions quantitatively by applying the spin and orbital sum rules concerning the L2 (M4)/L3 (M5) edges. In combination with appropriate ligand field simulations, we demonstrate that the Tb(iii) ions contribute with high orbital magnetic moments to the magnetic anisotropy, whereas the ligand field determines the easy axis of magnetization. Furthermore, we confirm that the Cu(ii) ions in both molecules are in a divalent valence state, the magnetic moments of the three Cu ions appear to be canted due to 3d-3d intramolecular magnetic interactions. For Cu3Tb(LPr), the corresponding element specific magnetization loops reflect that the Cu(ii) contribution to the overall magnetic picture becomes more important as the temperature is lowered. This implies a low value for the 3d-4f coupling.

TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.

PubMed

Houben, R M G J; Lalli, M; Sumner, T; Hamilton, M; Pedrazzoli, D; Bonsu, F; Hippner, P; Pillay, Y; Kimerling, M; Ahmedov, S; Pretorius, C; White, R G

2016-03-24

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact.

Spatial patterns of multidrug resistant tuberculosis and relationships to socio-economic, demographic and household factors in northwest Ethiopia.

PubMed

Alene, Kefyalew Addis; Viney, Kerri; McBryde, Emma S; Clements, Archie C A

2017-01-01

Understanding the geographical distribution of multidrug-resistant tuberculosis (MDR-TB) in high TB burden countries such as Ethiopia is crucial for effective control of TB epidemics in these countries, and thus globally. We present the first spatial analysis of multidrug resistant tuberculosis, and its relationship to socio-economic, demographic and household factors in northwest Ethiopia. An ecological study was conducted using data on patients diagnosed with MDR-TB at the University of Gondar Hospital MDR-TB treatment centre, for the period 2010 to 2015. District level population data were extracted from the Ethiopia National and Regional Census Report. Spatial autocorrelation was explored using Moran's I statistic, Local Indicators of Spatial Association (LISA), and the Getis-Ord statistics. A multivariate Poisson regression model was developed with a conditional autoregressive (CAR) prior structure, and with posterior parameters estimated using a Bayesian Markov chain Monte Carlo (MCMC) simulation approach with Gibbs sampling, in WinBUGS. A total of 264 MDR-TB patients were included in the analysis. The overall crude incidence rate of MDR-TB for the six-year period was 3.0 cases per 100,000 population. The highest incidence rate was observed in Metema (21 cases per 100,000 population) and Humera (18 cases per 100,000 population) districts; whereas nine districts had zero cases. Spatial clustering of MDR-TB was observed in districts located in the Ethiopia-Sudan and Ethiopia-Eritrea border regions, where large numbers of seasonal migrants live. Spatial clustering of MDR-TB was positively associated with urbanization (RR: 1.02; 95%CI: 1.01, 1.04) and the percentage of men (RR: 1.58; 95% CI: 1.26, 1.99) in the districts; after accounting for these factors there was no residual spatial clustering. Spatial clustering of MDR-TB, fully explained by demographic factors (urbanization and percent male), was detected in the border regions of northwest Ethiopia, in locations where seasonal migrants live and work. Cross-border initiatives including options for mobile TB treatment and follow up are important for the effective control of MDR-TB in the region.

Ten years' experience of Directly Observed Treatment Short-course (DOTS) in Gambella Regional State, Ethiopia: An evaluation of tuberculosis control program.

PubMed

Sisay, Solomon; Mengistu, Belete; Erku, Woldargay; Woldeyohannes, Desalegne

2016-12-01

World Health Organization (WHO) declared tuberculosis (TB) as a global public health emergency and recommended DOTS as a standard strategy for controlling the disease. TB is one of the major causes of infectious diseases in the world, and 25% of all avoidable deaths in developing countries. About a third of the world's population is estimated to be infected with tubercle bacilli, and hence at risk of developing active disease. The objective of the study was, therefore, to evaluate the impact of DOTS strategy on smear-positive pulmonary tuberculosis case finding and their treatment outcomes in Gambella Regional State, Ethiopia. A retrospective health facility-based descriptive study was employed. Quarterly data were collected by using WHO structured reporting format for TB case finding and treatment outcome from all DOTS implementing health facilities in the region. A total of 10,024 TB cases (all forms) were registered and reported between the periods from 2003 up to 2012. Out of these, 4100 (40.9%) were smear-positive pulmonary TB, 3164 (31.6%) were smear-negative pulmonary TB and 2760 (27.5%) had extra-pulmonary TB. An average case detection rate (CDR) 1 of 40.9% (SD=0.1) and treatment success rate (TSR) 2 of 55.7% (SD=0.28) for smear-positive pulmonary TB including other forms of TB were reported for the specified years period. Additionally, the average mean values of treatment defaulter and treatment failure rates were 4.2% and 0.3%, respectively. The recommended TSR set by WHO was achieved as it was already been fulfilled more than 85% from 2009 up to 2011 in the region and the reported CDR was far below (40.9%) for smear-positive pulmonary TB including other forms of TB from the target. Therefore, extensive efforts should be established to maintain the achieved TSR and to increase the low level of CDR for all forms of TB cases through implementing alternative case finding strategies. Copyright © 2016.

Spatiotemporal Clustering of Mycobacterium tuberculosis Complex Genotypes in Florida: Genetic Diversity Segregated by Country of Birth

PubMed Central

Séraphin, Marie Nancy; Lauzardo, Michael; Morris, J. Glenn; Blackburn, Jason K.

2016-01-01

Background Tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). Although the MTBC is highly clonal, between-strain genetic diversity has been observed. In low TB incidence settings, immigration may facilitate the importation of MTBC strains with a potential to complicate TB control efforts. Methods We investigated the genetic diversity and spatiotemporal clustering of 2,510 MTBC strains isolated in Florida, United States, between 2009 and 2013 and genotyped using spoligotyping and 24-locus MIRU-VNTR. We mapped the genetic diversity to the centroid of patient residential zip codes using a geographic information system (GIS). We assessed transmission dynamics and the influence of immigration on genotype clustering using space-time permutation models adjusted for foreign-born population density and county-level HIV risk and multinomial models stratified by country of birth and timing of immigration in SaTScan. Principal Findings Among the 2,510 strains, 1,245 were reported among foreign-born persons; including 408 recent immigrants (<5 years). Strain allelic diversity (h) ranged from low to medium in most locations and was most diverse in urban centers where foreign-born population density was also high. Overall, 21.5% of cases among U.S.-born persons and 4.6% among foreign-born persons clustered genotypically and spatiotemporally and involved strains of the Haarlem family. One Haarlem space-time cluster identified in the mostly rural northern region of Florida included US/Canada-born individuals incarcerated at the time of diagnosis; two clusters in the mostly urban southern region of Florida were composed predominantly of foreign-born persons. Both groups had HIV prevalence above twenty percent. Conclusions/Significance Almost five percent of TB cases reported in Florida during 2009–2013 were potentially due to recent transmission. Improvements to TB screening practices among the prison population and recent immigrants are likely to impact TB control. Due to the monomorphic nature of available markers, whole genome sequencing is needed to conclusively delineate recent transmission events between U.S. and foreign-born persons. PMID:27093156

Public Health Implications and Risk Factors Assessment of Mycobacterium bovis Infections among Abattoir Personnel in Bauchi State, Nigeria

PubMed Central

Sa'idu, A. S.; Okolocha, E. C.; Dzikwi, A. A.; Gamawa, A. A.; Ibrahim, S.; Kwaga, J. K. P.; Usman, A.; Maigari, S. A.

2015-01-01

Bovine tuberculosis (bTB) is a chronic infectious and contagious zoonotic disease of domestic animals, wild animals, and humans. It poses a public health threat and economic losses due to abattoir condemnation of infected carcasses during meat inspection of slaughtered animals. Bovine tuberculosis is widespread in Africa including Nigeria affecting both cattle and humans, particularly Northern Nigeria. A prospective survey was conducted from June to August 2013 in the three Zonal abattoirs of Bauchi State, Nigeria. A total of 150 structured close-ended questionnaires were administered to abattoir personnel to assess their level of awareness of bTB. This study was aimed at determining the level of public health awareness, attitude, and practices of abattoir workers of bTB in Bauchi State, Nigeria. There was a statistically significant association between respondents' awareness of bTB and their occupational status, age, and duration of exposure to cattle carcasses (P < 0.05); the odds of being aware of bTB were 9.4, 7.3, and 2.1, respectively. In conclusion, these demonstrate the urgent need for public health authorities to intervene in bTB control. The risk of bTB transmission as indicated by the personnel's practices and awareness levels in Bauchi State could be prevented through the use of protective clothing (PPEs). PMID:26464954

Assessing infection control practices to protect health care workers and patients in Malawi from nosocomial transmission of Mycobacterium tuberculosis

PubMed Central

Simon, Katherine; Hosseinipour, Mina; Kim, Maria H.; Mlauzi, Lameck; Kazembe, Peter N.; Ahmed, Saeed

2017-01-01

Transmission of Mycobacterium tuberculosis (TB) in health settings threatens health care workers and people living with HIV in sub-Saharan Africa. Nosocomial transmission is reduced with implementation of infection control (IC) guidelines. The objective of this study is to describe implementation of TB IC measures in Malawi. We conducted a cross-sectional study utilizing anonymous health worker questionnaires, semi-structured interviews with facility managers, and direct observations at 17 facilities in central Malawi. Of 592 health care workers surveyed, 34% reported that all patients entering the facility were screened for cough and only 8% correctly named the four most common signs and symptoms of TB in adults. Of 33 managers interviewed, 7 (21%) and 1 (3%) provided the correct TB screening questions for use in adults and children, respectively. Of 592 health workers, only 2.4% had been screened for TB in the previous year. Most (90%) reported knowing their HIV status, 53% were tested at their facility of employment, and half reported they would feel comfortable receiving ART or TB treatment at their facility of employment. We conclude that screening is infrequently conducted and knowledge gaps may undercut its effectiveness. Further, health care workers do not routinely access TB and HIV diagnostic and treatment services at their facility of employment. PMID:29211793

Household ventilation and tuberculosis transmission in Kampala, Uganda.

PubMed

Chamie, G; Wandera, B; Luetkemeyer, A; Bogere, J; Mugerwa, R D; Havlir, D V; Charlebois, E D

2013-06-01

To test the feasibility of measuring household ventilation and evaluate whether ventilation is associated with tuberculosis (TB) in household contacts in Kampala, Uganda. Adults with pulmonary TB and their household contacts received home visits to ascertain social and structural household characteristics. Ventilation was measured in air changes per hour (ACH) in each room by raising carbon dioxide (CO₂) levels using dry ice, removing the dry ice, and measuring changes in the natural log of CO₂ (lnCO2) over time. Ventilation was compared in homes with and without co-prevalent TB. Members of 61 of 66 (92%) households approached were enrolled. Households averaged 5.4 residents/home, with a median of one room/home. Twelve homes (20%) reported co-prevalent TB in household contacts. Median ventilation for all rooms was 14 ACH (interquartile range [IQR] 10-18). Median ventilation was 12 vs. 15 ACH in index cases' sleeping rooms in households with vs. those without co-prevalent TB (P = 0.12). Among smear-positive indexes not infected by the human immunodeficiency virus (HIV), median ventilation was 11 vs. 17 ACH in index cases' sleeping rooms in homes with vs. those without co-prevalent TB (P = 0.1). Our findings provide evidence that a simple CO₂ decay method used to measure ventilation in clinical settings can be adapted to homes, adding a novel tool and a neglected variable, ventilation, to the study of household TB transmission.

Priority-Setting for Novel Drug Regimens to Treat Tuberculosis: An Epidemiologic Model

PubMed Central

Cohen, Ted; Nuermberger, Eric; Dooley, Kelly E.; Gonzalez-Angulo, Lice; Churchyard, Gavin J.; Nahid, Payam; Rich, Michael L.; Bansbach, Cathy; Forissier, Thomas; Dowdy, David W.

2017-01-01

Background Novel drug regimens are needed for tuberculosis (TB) treatment. New regimens aim to improve on characteristics such as duration, efficacy, and safety profile, but no single regimen is likely to be ideal in all respects. By linking these regimen characteristics to a novel regimen’s ability to reduce TB incidence and mortality, we sought to prioritize regimen characteristics from a population-level perspective. Methods and Findings We developed a dynamic transmission model of multi-strain TB epidemics in hypothetical populations reflective of the epidemiological situations in India (primary analysis), South Africa, the Philippines, and Brazil. We modeled the introduction of various novel rifampicin-susceptible (RS) or rifampicin-resistant (RR) TB regimens that differed on six characteristics, identified in consultation with a team of global experts: (1) efficacy, (2) duration, (3) ease of adherence, (4) medical contraindications, (5) barrier to resistance, and (6) baseline prevalence of resistance to the novel regimen. We compared scale-up of these regimens to a baseline reflective of continued standard of care. For our primary analysis situated in India, our model generated baseline TB incidence and mortality of 157 (95% uncertainty range [UR]: 113–187) and 16 (95% UR: 9–23) per 100,000 per year at the time of novel regimen introduction and RR TB incidence and mortality of 6 (95% UR: 4–10) and 0.6 (95% UR: 0.3–1.1) per 100,000 per year. An optimal RS TB regimen was projected to reduce 10-y TB incidence and mortality in the India-like scenario by 12% (95% UR: 6%–20%) and 11% (95% UR: 6%–20%), respectively, compared to current-care projections. An optimal RR TB regimen reduced RR TB incidence by an estimated 32% (95% UR: 18%–46%) and RR TB mortality by 30% (95% UR: 18%–44%). Efficacy was the greatest determinant of impact; compared to a novel regimen meeting all minimal targets only, increasing RS TB treatment efficacy from 94% to 99% reduced TB mortality by 6% (95% UR: 1%–13%, half the impact of a fully optimized regimen), and increasing the efficacy against RR TB from 76% to 94% lowered RR TB mortality by 13% (95% UR: 6%–23%). Reducing treatment duration or improving ease of adherence had smaller but still substantial impact: shortening RS TB treatment duration from 6 to 2 mo lowered TB mortality by 3% (95% UR: 1%–6%), and shortening RR TB treatment from 20 to 6 mo reduced RR TB mortality by 8% (95% UR: 4%–13%), while reducing nonadherence to the corresponding regimens by 50% reduced TB and RR TB mortality by 2% (95% UR: 1%–4%) and 6% (95% UR: 3%–10%), respectively. Limitations include sparse data on key model parameters and necessary simplifications to model structure and outcomes. Conclusions In designing clinical trials of novel TB regimens, investigators should consider that even small changes in treatment efficacy may have considerable impact on TB-related incidence and mortality. Other regimen improvements may still have important benefits for resource allocation and outcomes such as patient quality of life. PMID:28045934

Prevalence of drug-resistant pulmonary tuberculosis in India: systematic review and meta-analysis.

PubMed

Goyal, Vishal; Kadam, Vijay; Narang, Prashant; Singh, Vikram

2017-10-17

Drug-resistant pulmonary tuberculosis (DR-TB) is a significant public health issue that considerably deters the ongoing TB control efforts in India. The purpose of this review was to investigate the prevalence of DR-TB and understand the regional variation in resistance pattern across India from 1995 to 2015, based on a large body of published epidemiological studies. A systematic review of published studies reporting prevalence of DR-TB from biomedical databases (PubMed and IndMed) was conducted. Meta-analysis was performed using random effects model and the pooled prevalence estimate (95% confidence interval [CI]) of DR-TB, multidrug resistant (MDR-) TB, pre-extensively drug-resistant (pre-XDR) TB and XDR-TB were calculated across two study periods (decade 1: 1995 to 2005; decade 2: 2006 to 2015), countrywide and in different regions. Heterogeneity in this meta-analysis was assessed using I 2 statistic. A total of 75 of 635 screened studies that fulfilled the inclusion criteria were selected. Over 40% of 45,076 isolates suspected for resistance to any first-line anti-TB drugs tested positive. Comparative analysis revealed a worsening trend in DR-TB between the two study decades (decade 1: 37.7% [95% CI = 29.0; 46.4], n = 25 vs decade 2: 46.1% [95% CI = 39.0; 53.2], n = 36). The pooled estimate of MDR-TB resistance was higher in previously treated patients (decade 1: 29.8% [95% CI = 20.7; 39.0], n = 13; decade 2: 35.8% [95% CI = 29.2; 42.4], n = 24) as compared with the newly diagnosed cases (decade 1: 4.1% [95% CI = 2.7; 5.6], n = 13; decade 2: 5.6% [95% CI = 3.8; 7.4], n = 17). Overall, studies from Western states of India reported highest prevalence of DR-TB (57.8% [95% CI = 37.4; 78.2], n = 6) and MDR-TB (39.9% [95% CI = 21.7; 58.0], n = 6) during decade 2. Prevalence of pre-XDR TB was 7.9% (95% CI = 4.4; 11.4, n = 5) with resistance to fluoroquinolone (66.3% [95% CI = 58.2; 74.4], n = 5) being the highest. The prevalence of XDR-TB was 1.9% (95% CI = 1.2; 2.6, n = 14) over the 20-year period. The alarming increase in the trend of anti-TB drug resistance in India warrants the need for a structured nationwide surveillance to assist the National TB Control Program in strengthening treatment strategies for improved outcomes.

Multifaceted remodeling by vitamin C boosts sensitivity of Mycobacterium tuberculosis subpopulations to combination treatment by anti-tubercular drugs.

PubMed

Sikri, Kriti; Duggal, Priyanka; Kumar, Chanchal; Batra, Sakshi Dhingra; Vashist, Atul; Bhaskar, Ashima; Tripathi, Kritika; Sethi, Tavpritesh; Singh, Amit; Tyagi, Jaya Sivaswami

2018-05-01

Bacterial dormancy is a major impediment to the eradication of tuberculosis (TB), because currently used drugs primarily target actively replicating bacteria. Therefore, decoding of the critical survival pathways in dormant tubercle bacilli is a research priority to formulate new approaches for killing these bacteria. Employing a network-based gene expression analysis approach, we demonstrate that redox active vitamin C (vit C) triggers a multifaceted and robust adaptation response in Mycobacterium tuberculosis (Mtb) involving ~ 67% of the genome. Vit C-adapted bacteria display well-described features of dormancy, including growth stasis and progression to a viable but non-culturable (VBNC) state, loss of acid-fastness and reduction in length, dissipation of reductive stress through triglyceride (TAG) accumulation, protective response to oxidative stress, and tolerance to first line TB drugs. VBNC bacteria are reactivatable upon removal of vit C and they recover drug susceptibility properties. Vit C synergizes with pyrazinamide, a unique TB drug with sterilizing activity, to kill dormant and replicating bacteria, negating any tolerance to rifampicin and isoniazid in combination treatment in both in-vitro and intracellular infection models. Finally, the vit C multi-stress redox models described here also offer a unique opportunity for concurrent screening of compounds/combinations active against heterogeneous subpopulations of Mtb. These findings suggest a novel strategy of vit C adjunctive therapy by modulating bacterial physiology for enhanced efficacy of combination chemotherapy with existing drugs, and also possible synergies to guide new therapeutic combinations towards accelerating TB treatment. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Longitudinal whole genome analysis of pre and post drug treatment Mycobacterium tuberculosis isolates reveals progressive steps to drug resistance.

PubMed

Datta, Gargi; Nieto, Luisa M; Davidson, Rebecca M; Mehaffy, Carolina; Pederson, Caroline; Dobos, Karen M; Strong, Michael

2016-05-01

Tuberculosis (TB) is one of the leading causes of death due to an infectious disease in the world. Understanding the mechanisms of drug resistance has become pivotal in the detection and treatment of newly emerging resistant TB cases. We have analyzed three pairs of Mycobacterium tuberculosis strains pre- and post-drug treatment to identify mutations involved in the progression of resistance to the drugs rifampicin and isoniazid. In the rifampicin resistant strain, we confirmed a mutation in rpoB (S450L) that is known to confer resistance to rifampicin. We discovered a novel L101R mutation in the katG gene of an isoniazid resistant strain, which may directly contribute to isoniazid resistance due to the proximity of the mutation to the katG isoniazid-activating site. Another isoniazid resistant strain had a rare mutation in the start codon of katG. We also identified a number of mutations in each longitudinal pair, such as toxin-antitoxin mutations that may influence the progression towards resistance or may play a role in compensatory fitness. These findings improve our knowledge of drug resistance progression during therapy and provide a methodology to monitor longitudinal strains using whole genome sequencing, polymorphism comparison, and functional annotation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lanthanide-based coordination polymers assembled by a flexible multidentate linker: design, structure, photophysical properties, and dynamic solid-state behavior.

PubMed

Marchal, Claire; Filinchuk, Yaroslav; Chen, Xiao-Yan; Imbert, Daniel; Mazzanti, Marinella

2009-01-01

Four picolinate building blocks were implemented into the multidentate linker N,N',N'-tetrakis[(6-carboxypyridin-2-yl)methyl]butylenediamine (H(4)tpabn) with a linear flexible spacer to promote the assembly of lanthanide-based 1D coordination polymers. The role of the linker in directing the geometry of the final assembly is evidenced by the different results obtained in the presence of Htpabn(3-) and tpabn(4-) ions. The tpabn(4-) ion leads to the desired 1D polymer {[Nd(tpabn)]H(3)O x 6 H(2)O}(infinity) (12). The Htpabn(3-) ion leads to the assembly of Tb(III) and Er(III) ions into 1D zigzag chains of the general formula {[M(Htpabn)] x xH(2)O}(infinity) (M = Tb, x = 14 (1); M = Tb, x = 8 (11); M = Er, x = 14 (2); M = Er, x = 5.5 (4)), a 2D network is formed by the Eu(III) ion (i.e., {[Eu(Htpabn)] x 10 H(2)O}(infinity) (7)), and both supramolecular isomers (1D and 2D) are obtained by the Tb(III) ion. The high flexibility of the polymeric chains results in a dynamic behavior with a solvent-induced reversible structural transition. The Tb(III)- and Eu(III)-containing polymers display high-luminescence quantum yields (38 and 18%, respectively). A sizeable near-IR luminescence emission is observed for the Er(III)- and Nd(III)-containing polymers when lattice water molecules are removed.

Role of the ancillary ligand N,N-dimethylaminoethanol in the sensitization of Eu(III) and Tb(III) luminescence in dimeric beta-diketonates.

PubMed

Eliseeva, Svetlana V; Kotova, Oxana V; Gumy, Frédéric; Semenov, Sergey N; Kessler, Vadim G; Lepnev, Leonid S; Bünzli, Jean-Claude G; Kuzmina, Natalia P

2008-04-24

Two types of dimeric complexes [Ln2(hfa)6(mu2-O(CH2)2NHMe2)2] and [Ln(thd)2(mu2,eta2-O(CH2)2NMe2)]2 (Ln = YIII, EuIII, GdIII, TbIII, TmIII, LuIII; hfa- = hexafluoroacetylacetonato, thd- = dipivaloylmethanato) are obtained by reacting [Ln(hfa)3(H2O)2] and [Ln(thd)3], respectively, with N,N-dimethylaminoethanol in toluene and are fully characterized. X-ray single crystal analysis performed for the TbIII compounds confirms their dimeric structure. The coordination mode of N,N-dimethylaminoethanol depends on the nature of the beta-diketonate. In [Tb2(hfa)6(mu2-O(CH2)2NHMe2)2], eight-coordinate TbIII ions adopt distorted square antiprismatic coordination environments and are O-bridged by two zwitterionic N,N-dimethylaminoethanol ligands with a Tb1...Tb2 separation of 3.684(1) A. In [Tb(thd)2(mu2,eta2-O(CH2)2NMe2)]2, the N,N-dimethylaminoethanol acts as chelating-bridging O,N-donor anion and the TbIII ions are seven-coordinate; the Tb1...Tb1A separation amounts to 3.735(2) A within centrosymmetric dimers. The dimeric complexes are thermally stable up to 180 degrees C, as shown by thermogravimetric analysis, and their volatility is sufficient for quantitative sublimation under reduced pressure. The EuIII and TbIII dimers display metal-centered luminescence, particularly [Eu2(hfa)6(O(CH2)2NHMe2)2] (quantum yield Q(L)Ln = 58%) and [Tb(thd)2(O(CH2)2NMe2)]2 (32%). Consideration of energy migration paths within the dimers, based on the study of both pure and EuIII- or TbIII-doped (0.01-0.1 mol %) LuIII analogues, leads to the conclusion that both the beta-diketone and N,N-dimethylaminoethanol ligands contribute significantly to the sensitization process of the EuIII luminescence. The ancillary ligand increases considerably the luminescence of [Eu2(hfa)6(O(CH2)2NHMe2)2], compared to [Ln(hfa)3(H2O)2], through the formation of intra-ligand states while it is detrimental to TbIII luminescence in both beta-diketonates. Thin films of the most luminescent compound [Eu2(hfa)6(O(CH2)2NHMe2)2] obtained by vacuum sublimation display photophysical properties analogous to those of the solid-state sample, thus opening perspectives for applications in electroluminescent devices.

Knowledge of tuberculosis (TB) and human immunodeficiency virus (HIV) and perception about provider initiated HIV testing and counselling among TB patients attending health facilities in Harar town, Eastern Ethiopia.

PubMed

Seyoum, Ayichew; Legesse, Mengistu

2013-02-08

Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infection is one of the major health problems in Ethiopia. The national TB and HIV control guideline in Ethiopia recommends provider initiated HIV testing and counselling (PITC) as a routine care for TB patients. However, the impact of this approach on the treatment seeking of TB patients has not been well studied. In this study, we assessed knowledge of TB and HIV, and perception about PITC among TB patients attending health facilities in Harar town, Eastern Ethiopia. In a health facilities based cross-sectional study, a total of 415 study participants were interviewed about knowledge of TB and HIV as well as the impact of HIV testing on their treatment seeking behavior using a semi-structured questionnaires. Multivariable logistic regression analysis showed the association of distance > 10 km from health facility [adjusted odds ratio (AOR)=0.48, 95% CI: 0.24 - 0.97, P=0.042] with low knowledge of TB. Distance > 10 km from health facility (AOR= 0.12, 95% CI: 0.06 -0.23, P < 0.001) was also associated with low knowledge of HIV testing. Delay in treatment seeking was associated with female participants (AOR = 0.11, 95% CI: 0.05-0.25, <0.001), single marital status (AOR =0.001, 95% CI: 0.00 - 0.01, P< 0.001) and distance > 10 km from health facility (AOR =0.46, 95% CI: 0.28 - 0.75, P=0.002). Most of the study participants (70%) believed that there is no association between TB and HIV/AIDS. On the other hand, two thirds (66.5%) of the participants thought that HIV testing has importance for TB patients. However, the majority (81.6%) of the study participants in the age category less than 21 years believed that fear of PITC could cause delay in treatment seeking. The study showed the association of low knowledge of the study participants about TB and HIV testing with distance > 10 km from health facility. Study participants in the age category less than 21 years thought that fear of PITC could cause treatment delay of TB patients. Hence, emphasis should be given to improve knowledge of TB and HIV among residents far away from health facility, and attention also needs to be given to improve the perception of individuals in the age group less than 21 years about PITC in the present study area.

Structural measurements and cell line studies of the copper-PEG-Rifampicin complex against Mycobacterium tuberculosis.

PubMed

Manning, Thomas; Mikula, Rachel; Wylie, Greg; Phillips, Dennis; Jarvis, Jackie; Zhang, Fengli

2015-02-01

The bacterium responsible for tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, LC-MS and UV/Vis are used to study the copper-Rifampicin-Polyethylene glycol (PEG-3350) complex. The copper (II) cation is a carrier for the antibiotic Rifampicin as well as nutrients for the bacterium. The NIH-NIAID cell line containing several Tb strains (including antibiotic resistant strains) is tested against seven copper-PEG-RIF complex variations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multi-q crystal and magnetic structure in TbMnO3: Evidence for a Soliton-lattice

NASA Astrophysics Data System (ADS)

Aliouane, N.; Strempfer, J.; Caliebe, W.

2005-03-01

In TbMnO3, Mn-spins order with a sinusoidal antiferromagnetic (AF) propagation wave vector QMn=[0,k+/-q,l] (q˜0.288b^*) at TN(Mn)=41K. The propagation vector QMn varies with temperature on cooling until TLock(Mn) ˜30K, which coincides with a ferroelectric transition. In addition to QMn reflections we find magnetic reflections at 3QMn. Our X-ray measurements show that the magneto-elastic coupling gives rise to a structural modulation at twice the magnetic wavevector (2QMn). Field cooling the sample under a magnetic field oriented along the a-direction with H>9T shows that all magnetic wavevectors for Mn and Tb collapse to a single q structure with Q=[0,1/4,0], an up-up, down-down phase, and coincide with anomalies in the polarization. We argue that the temperature and field dependence of the magnetic and superlattice reflections are consistent with a soliton formalism which predicts a stable commensurate single q=1/4 phase [1]. [1] Kimura et al., PRB 68, 60403(2003).

Structural studies of a green-emitting terbium doped calcium zinc phosphate phosphor

NASA Astrophysics Data System (ADS)

Ramesh, B.; Dillip, G. R.; Rambabu, B.; Joo, S. W.; Raju, B. Deva Prasad

2018-03-01

In this study, a new green emitting CaZn2(PO4)2:Tb3+ phosphors were synthesized through solid-state reaction route. The phosphors were characterized structurally by X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). All the synthesized phosphors were crystallized in triclinic crystal structure with P 1 bar space group. The phosphate groups in the phosphors were confirmed by FTIR analysis. The surface elements O 1s, P 2p, Ca 2p, Zn 2p and Tb 3d were studied by high-resolution XPS spectra. Upon excitation at 378 nm, the dominant green emission of CaZn2(PO4)2:Tb3+ phosphors at 542 nm were noticed in the emission spectra. For various emission wavelengths (at 435 and 489 nm) and constant excitation wavelength (at 378 nm), the decay curves have shown two different decay dynamics of phosphors. The lighting properties such as Commission International de l'Eclairage (x = 0.319, y = 0.398) and color temperature (5995 K) were calculated.

FadA5 a thiolase from Mycobacterium tuberculosis - a unique steroid-binding pocket reveals the potential for drug development against tuberculosis

PubMed Central

Schaefer, Christin M.; Lu, Rui; Nesbitt, Natasha M.; Schiebel, Johannes; Sampson, Nicole S.; Kisker, Caroline

2014-01-01

Summary With the exception of HIV, tuberculosis (TB) is the leading cause of mortality among infectious diseases. The urgent need to develop new anti-tubercular drugs is apparent due to the increasing number of drug resistant Mycobacterium tuberculosis (Mtb) strains. Proteins involved in cholesterol import and metabolism have recently been discovered as potent targets against TB. FadA5, a thiolase from Mtb, is catalyzing the last step of the β-oxidation reaction of the cholesterol side-chain degradation under release of critical metabolites and was shown to be of importance during the chronic stage of TB infections. To gain structural and mechanistic insight on FadA5 we characterized the enzyme in different stages of the cleavage reaction and with a steroid bound to the binding pocket. Structural comparisons to human thiolases revealed that it should be possible to target FadA5 specifically and the steroid-bound structure provides a solid basis for the development of inhibitors against FadA5. PMID:25482540

Milestone in the NTB phase investigation and beyond: direct insight into molecular self-assembly.

PubMed

Ivšić, Trpimir; Vinković, Marijana; Baumeister, Ute; Mikleušević, Ana; Lesac, Andreja

2014-12-14

Although liquid-crystalline materials are most widely exploited for flat-panel displays, their ability to self-organize into periodically ordered nanostructures gives rise to a broad variety of additional applications. The recently discovered low-temperature nematic phase (N(TB)) with unusual characteristics generated considerable attention within the scientific community: despite the fact that the molecules from which the phase is composed are not chiral, the helicoidal structure of the phase is strongly implicated. Here we report on combined experimental, computational and spectroscopic studies of the structural aspects influencing formation of the N(TB) phase as well as on the molecular organization within the phase. In an extensive DFT study, the structure-property prerequisite was traced to a "bent-propeller" shape of the molecule. We also demonstrate the first utilization of liquid state NMR for direct analysis of intermolecular interactions within thermotropic liquid-crystalline phases, providing new insight into molecular packing that can lead towards design of novel chiral functional materials. The synergy of experimental, computational and NMR studies suggests a syn-parallel helical molecular organization within the N(TB) phase.

Sol-hydrothermal synthesis and optical properties of Eu3+, Tb(3+)-codoped one-dimensional strontium germanate full color nano-phosphors.

PubMed

Lin, Liangwu; Sun, Xinyuan; Jiang, Yao; He, Yuehui

2013-12-21

Novel near-UV and blue excited Eu(3+), Tb(3+)-codoped one dimensional strontium germanate full-color nano-phosphors have been successfully synthesized by a simple sol-hydrothermal method. The morphologies, internal structures, chemical constitution and optical properties of the resulting samples were characterized using FE-SEM, TEM, HRTEM, EDS, XRD, FTIR, XPS, PL and PLE spectroscopy and luminescence decay curves. The results suggested that the obtained Eu(3+), Tb(3+)-codoped strontium germanate nanowires are single crystal nanowires with a diameter ranging from 10 to 80 nm, average diameter of around 30 nm and the length ranging from tens to hundreds micrometers. The results of PL and PLE spectra indicated that the Eu(3+), Tb(3+)-codoped single crystal strontium germanate nanowires showed an intensive blue, blue-green, green, orange and red or green, orange and red light emission under excitation at 350-380 nm and 485 nm, respectively, which may attributed to the coexistent Eu(3+), Eu(2+) and Tb(3+) ions, and the defects located in the strontium germanate nanowires. A possible mechanism of energy transfer among the host, Eu(3+) and Tb(3+) ions was proposed. White-emission can be realized in a single-phase strontium germanate nanowire host by codoping with Tb(3+) and Eu(3+) ions. The Eu(3+), Tb(3+)-codoped one-dimensional strontium germanate full-color nano-phosphors have superior stability under electron bombardment. Because of their strong PL intensity, good CIE chromaticity and stability, the novel 1D strontium germanate full-color nano-phosphors have potential applications in W-LEDs.

Tune color of single-phase LiGd(MoO4)2-X(WO4)X: Sm3+, Tb3+ via adjusting the proportion of matrix and energy transfer to create white-light phosphor

NASA Astrophysics Data System (ADS)

Wu, Hongyue; Yang, Junfeng; Wang, Xiaoxue; Gan, Shucai; Li, Linlin

2018-03-01

A series of LiGd(MO4)2: Sm3+, Tb3+ (M = Mo, W) phosphors was prepared by a conventional solid state reaction method. Powder X-Ray diffraction (XRD) analysis reveals that the compounds are of the same structure type. Their luminescent properties have been studied. The optimal doping concentrations are 8% for Sm3+ and 18% for Tb3+ in the LiGd(MoO4)2 host. Sm3+ and Tb3+ have different sensitivity to the Mo/W ratio. For LiGd(MoO4)2-X(WO4)X: Sm3+ (X = 0, 0.4, 0.8, 1.2, 1.6, 2.0), the strongest emission intensity is 1.766 times than that of the weakest, while 171 times for LiGd(MoO4)2-X(WO4)X: Tb3+. The experimental results show that Mo/W ratio strong influences on the properties of LiGd(MoO4)2-X(WO4)X: Tb3+. With the increasing of WO42- groups concentration, the shape of characteristic excitation peaks of Tb3+ is almost the same and the excitation intensity gradually increase. Moreover, the energy transfer from Tb3+ to Sm3+ has been realized in the co-doped phosphors. The experimental analysis and theoretical calculations reveal that the quadrupole-quadrupole interaction is the dominant mechanism for the Tb3+→Sm3+ energy transfer. Therefore, luminous intensity can be adjusted by different sensitivities to matrix composition and energy transfer from Tb3+→Sm3+. By this tuning color method, white-light-emitting phosphor has been prepared. The excitation wavelength is 378 nm, and this indicates that the white-light-emitting phosphor could be pumped by near-UV light.

Direct biomechanical modeling of trabecular bone using a nonlinear manifold-based volumetric representation

NASA Astrophysics Data System (ADS)

Jin, Dakai; Lu, Jia; Zhang, Xiaoliu; Chen, Cheng; Bai, ErWei; Saha, Punam K.

2017-03-01

Osteoporosis is associated with increased fracture risk. Recent advancement in the area of in vivo imaging allows segmentation of trabecular bone (TB) microstructures, which is a known key determinant of bone strength and fracture risk. An accurate biomechanical modelling of TB micro-architecture provides a comprehensive summary measure of bone strength and fracture risk. In this paper, a new direct TB biomechanical modelling method using nonlinear manifold-based volumetric reconstruction of trabecular network is presented. It is accomplished in two sequential modules. The first module reconstructs a nonlinear manifold-based volumetric representation of TB networks from three-dimensional digital images. Specifically, it starts with the fuzzy digital segmentation of a TB network, and computes its surface and curve skeletons. An individual trabecula is identified as a topological segment in the curve skeleton. Using geometric analysis, smoothing and optimization techniques, the algorithm generates smooth, curved, and continuous representations of individual trabeculae glued at their junctions. Also, the method generates a geometrically consistent TB volume at junctions. In the second module, a direct computational biomechanical stress-strain analysis is applied on the reconstructed TB volume to predict mechanical measures. The accuracy of the method was examined using micro-CT imaging of cadaveric distal tibia specimens (N = 12). A high linear correlation (r = 0.95) between TB volume computed using the new manifold-modelling algorithm and that directly derived from the voxel-based micro-CT images was observed. Young's modulus (YM) was computed using direct mechanical analysis on the TB manifold-model over a cubical volume of interest (VOI), and its correlation with the YM, computed using micro-CT based conventional finite-element analysis over the same VOI, was examined. A moderate linear correlation (r = 0.77) was observed between the two YM measures. This preliminary results show the accuracy of the new nonlinear manifold modelling algorithm for TB, and demonstrate the feasibility of a new direct mechanical strain-strain analysis on a nonlinear manifold model of a highly complex biological structure.

Preparation, structure, and luminescence of dinuclear lanthanide complexes of a novel imine-amine phenolate macrocycle

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

Matthews, K.D.; Kahwa, I.A.; Williams, D.J.

1994-03-30

Metal-free condensation of 2,6-diformyl-p-cresol with 3,6-dioxa-1,8-octanediamine followed by reduction with sodium tetrahydroborate and addition of lanthanide(III) nitrate salts, in that order, yield (slowly) crystalline dinuclear complexes of a novel imine-amine phenolate macrocycle 2. The decacoordination geometry of the identical Pr[sup 3+] ions in a C[sub 2v] 4A,6B-extended dodecahedron made up of two bidentate NO[sub 3]-ions, two phenolate and two either oxygens, and one imine and one amine nitrogens. Dinuclear lanthanide complexes of 2 appear to be more stable than those of the totally reduced chelate 2 in alcoholic media. The Tb[sub 2]2(NO[sub 3])[sub 4][center dot]1.2CH[sub 3]-OH and (La[sub 0.97]Tb[sub 0.03])[submore » 2]2(NO[sub 3])[sub 4][center dot]1.2CH[sub 3]OH compounds exhibit strong Tb[sup 3+] ([sup 5]D[sub 4] [yields] [sup 7]F[sub J]) emission sensitized by the single state of 2 at both 77 and 295 K. No Tb[sup 3+]-Tb[sup 3+] self-quenching or N-H trapping effects are observed at 77 K (decay rate is 598 s[sup [minus]1]); the coordination cavities of 2 are therefore potentially good hosts for Tb[sup 3+] in luminescent diagnostic agents. At room temperature the complex decay kinetics of Tb[sup 3+] in Tb[sub 2]2(NO[sub 3])[sub 4][center dot]1.2CH[sub 3]OH are similar to those of Tb[sub 2]1(NO[sub 3])[sub 4][center dot]H[sub 2]O. But for the dilute complex, (La[sub 0.97]-Tb[sub 0.03])[sub 2]2(NO[sub 3])[sub 4][center dot]1.35CH[sub 3]OH, unusual thermal equilibration of the ligand triplet and Tb[sup 3+] [sup 5]D[sub 4] states occurs at room temperature; the ligand-to-Tb[sup 3+] energy-transfer rate is [approx]4.36 x 10[sup 4] s[sup [minus]1], while Tb[sup 3+]-to-ligand back-energy-transfer is [approx]7.1 x 10[sup 4] s[sup [minus]1].« less

Luminescence and energy transfer properties of Ca2Ba3(PO4)3Cl and Ca2Ba3(PO4)3Cl:A (A = Eu2+/Ce3+/Dy3+/Tb3+) under UV and low-voltage electron beam excitation.

PubMed

Shang, Mengmeng; Geng, Dongling; Yang, Dongmei; Kang, Xiaojiao; Zhang, Yang; Lin, Jun

2013-03-18

Pure Ca2Ba3(PO4)3Cl and rare earth ion (Eu(2+)/Ce(3+)/Dy(3+)/Tb(3+)) doped Ca2Ba3(PO4)3Cl phosphors with the apatite structure have been prepared via a Pechini-type sol-gel process. X-ray diffraction (XRD) and structure refinement, photoluminescence (PL) spectra, cathodoluminescence (CL) spectra, absolute quantum yield, as well as lifetimes were utilized to characterize samples. Under UV light excitation, the undoped Ca2Ba3(PO4)3Cl sample shows broad band photoluminescence centered near 480 nm after being reduced due to the defect structure. Eu(2+) and Ce(3+) ion doped Ca2Ba3(PO4)3Cl samples also show broad 5d → 4f transitions with cyan and blue colors and higher quantum yields (72% for Ca2Ba3(PO4)3Cl:0.04Eu(2+); 67% for Ca2Ba3(PO4)3Cl:0.016Ce(3+)). For Dy(3+) and Tb(3+) doped Ca2Ba3(PO4)3Cl samples, they give strong line emissions coming from 4f → 4f transitions. Moreover, the Ce(3+) ion can transfer its energy to the Tb(3+) ion in the Ca2Ba3(PO4)3Cl host, and the energy transfer mechanism has been demonstrated to be a resonant type, via a dipole-quadrupole interaction. However, under the low voltage electron beam excitation, Tb(3+) ion doped Ca2Ba3(PO4)3Cl samples present different luminescence properties compared with their PL spectra, which is ascribed to the different excitation mechanism. On the basis of the good PL and CL properties of the Ca2Ba3(PO4)3Cl:A (A = Ce(3+)/Eu(2+)/Tb(3+)/Dy(3+)), Ca2Ba3(PO4)3Cl might be promising for application in solid state lighting and field-emission displays.

The Genotypic Population Structure of Mycobacterium tuberculosis Complex from Moroccan Patients Reveals a Predominance of Euro-American Lineages

PubMed Central

Lahlou, Ouafae; Millet, Julie; Chaoui, Imane; Sabouni, Radia; Filali-Maltouf, Abdelkarim; Akrim, Mohammed; El Mzibri, Mohammed; Rastogi, Nalin; El Aouad, Rajae

2012-01-01

Background Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level. Methodology/Principal Findings Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004–2006). It identified 129 patterns: 105 (n = 568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1– ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2– modern/TbD1−/PGG1 group (Beijing, CAS), group 3– evolutionary recent/TbD1−/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n = 5, CAS n = 1), and 3 strains (BOV_1 n = 2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n = 114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the “evolutionary recent” TbD1−/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco. PMID:23077552

Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines.

PubMed

Ellrott, Kyle; Bailey, Matthew H; Saksena, Gordon; Covington, Kyle R; Kandoth, Cyriac; Stewart, Chip; Hess, Julian; Ma, Singer; Chiotti, Kami E; McLellan, Michael; Sofia, Heidi J; Hutter, Carolyn; Getz, Gad; Wheeler, David; Ding, Li

2018-03-28

The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls for the TCGA data to enable robust cross-tumor-type analyses. Our approach accounts for variance and batch effects introduced by the rapid advancement of DNA extraction, hybridization-capture, sequencing, and analysis methods over time. We present best practices for applying an ensemble of seven mutation-calling algorithms with scoring and artifact filtering. The dataset created by this analysis includes 3.5 million somatic variants and forms the basis for PanCan Atlas papers. The results have been made available to the research community along with the methods used to generate them. This project is the result of collaboration from a number of institutes and demonstrates how team science drives extremely large genomics projects. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

[Tuberculosis: steady dynamics between past and present to imagine the future].

PubMed

Cabello C, Felipe

2011-07-01

Progress in understanding the biological processes that allow Mycobacterium tuberculosis to be a successful parasite have accelerated in the last twenty years. This progress has been stimulated by the return of tuberculosis (TB) as an important disease in industrialized countries, by its increase in emergent nations in the tail of population increases and poverty and by the spread of multiple drug resistant (MDR) and extensively drug resistant (XDR) M. tuberculosis as a result of treatment failures. Progress on M. tuberculosis biology has also been fueled by advances in microbiology and molecular biology, including molecular genetics, genomics, proteomics and in vitro and in vivo models of infection. The study of latency or dormancy, a phenomenon central to understanding the persistence of M. tuberculosis and the development of TB in individuals, its spread in human populations and the emergence of antibiotic-resistant/tolerant organisms, has been preferred targets for investigators in this area. In this manner, factors that trigger M. tuberculosis latency (e. g, hypoxia, nutrient starvation, NO exposure) have been characterized and the metabolic shifts to host lipid utilization, tolerance to antimicrobials and resistance to host immune mechanisms involved in latency have been determined. Similarly, genetic changes and the resulting antimicrobial mechanisms mediating the MDR and XDR states have been characterized and potential new vaccines that avoid reactivation from latency and infection are being developed. Despite this progress, and given the fact that effective anti tuberculosis therapy was developed and first introduced clinically at the end of the 1940s, there are now more cases of latent and active TB worldwide than ever before. This reinforces the concept of TB as a bacterial disease with strong social and economical! determinants which are presently stimulating increased transmission in many human groups, undermining diagnostics, treatment and prevention. It suggests that in a scenario of global economical crisis the struggle against TB will be weakened, unless efforts are included to alleviate poverty, decrease economic inequality, improve public health and allow democracy and political organization.

Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs

PubMed Central

Seifert, Marva; Garfein, Richard S.; Rodwell, Timothy C.

2017-01-01

ABSTRACT Rapid molecular diagnostics have great potential to limit the spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis genome that confer phenotypic drug resistance. However, there have been few data published regarding the relationships between the detected M. tuberculosis resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological, and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between M. tuberculosis resistance mutations and patient mortality. The presence of an rrs 1401G mutation was associated with significantly higher odds of patient mortality (adjusted odds ratio [OR] = 5.72; 95% confidence interval [CI], 1.65 to 19.84]) after adjusting for relevant patient clinical characteristics and all other resistance mutations. Further analysis of mutations, categorized by the associated resistance level, indicated that the detection of mutations associated with high-level fluoroquinolone (OR, 3.99 [95% CI, 1.10 to 14.40]) and kanamycin (OR, 5.47 [95% CI, 1.64 to 18.24]) resistance was also significantly associated with higher odds of patient mortality, even after accounting for clinical site, patient age, reported smoking history, body mass index (BMI), diabetes, HIV, and all other resistance mutations. Specific gyrA and rrs resistance mutations, associated with high-level resistance, were associated with patient mortality as identified in clinical M. tuberculosis isolates from a diverse M/XDR-TB patient population at three high-burden clinical sites. These results have important implications for the interpretation of molecular diagnostics, including identifying patients at increased risk for mortality during treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT02170441.) PMID:28404672

Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs.

PubMed

Georghiou, Sophia B; Seifert, Marva; Catanzaro, Donald G; Garfein, Richard S; Rodwell, Timothy C

2017-06-01

Rapid molecular diagnostics have great potential to limit the spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis genome that confer phenotypic drug resistance. However, there have been few data published regarding the relationships between the detected M. tuberculosis resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological, and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between M. tuberculosis resistance mutations and patient mortality. The presence of an rrs 1401G mutation was associated with significantly higher odds of patient mortality (adjusted odds ratio [OR] = 5.72; 95% confidence interval [CI], 1.65 to 19.84]) after adjusting for relevant patient clinical characteristics and all other resistance mutations. Further analysis of mutations, categorized by the associated resistance level, indicated that the detection of mutations associated with high-level fluoroquinolone (OR, 3.99 [95% CI, 1.10 to 14.40]) and kanamycin (OR, 5.47 [95% CI, 1.64 to 18.24]) resistance was also significantly associated with higher odds of patient mortality, even after accounting for clinical site, patient age, reported smoking history, body mass index (BMI), diabetes, HIV, and all other resistance mutations. Specific gyrA and rrs resistance mutations, associated with high-level resistance, were associated with patient mortality as identified in clinical M. tuberculosis isolates from a diverse M/XDR-TB patient population at three high-burden clinical sites. These results have important implications for the interpretation of molecular diagnostics, including identifying patients at increased risk for mortality during treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT02170441.). Copyright © 2017 American Society for Microbiology.

Factors that influence treatment adherence of tuberculosis patients living in Java, Indonesia.

PubMed

Widjanarko, Bagoes; Gompelman, Michelle; Dijkers, Maartje; van der Werf, Marieke J

2009-11-03

Due to nonadherence of tuberculosis (TB) patients to treatment, complications may arise and if remaining infectious, these patients may infect other people with TB. To obtain information about factors associated with nonadherence, we performed a study comparing adherent and nonadherent TB patients. Adherent and nonadherent patients randomly selected from hospital records in one urban and two rural districts were interviewed using semi-structured questionnaires. Key informant interviews were done with TB nurses and doctors. The most frequently mentioned reason for nonadherence to treatment was feeling better. Although the drugs were given free of charge, many patients were nonadherent because of lack of money. Social support was considered very important for adherence. The study indicated that some patients had a negative image about the health care staff, treatment, and quality of medication. Treatment adherence of TB patients receiving treatment in hospitals in Central Java might be improved by providing health education about treatment duration and side effects, facilitating procedures for receiving treatment free of charge and reducing costs of transportation and consultation. Qualified friendly health care staff able to motivate patients might further improve adherence.

Fabrication and characterization of Gd2O2SO4:Tb3+ phosphors by sol-gel method

NASA Astrophysics Data System (ADS)

Aritman, I.; Yildirim, S.; Kisa, A.; Guleryuz, L. F.; Yurddaskal, M.; Dikici, T.; Celik, E.

2017-02-01

The objective of the innovative approaches of the scintillation materials to be used in the digital portal imaging systems in the radiotherapy applications is to research the GOS material production that has been activated with the rare earth elements (RE), to produce the scintillation detectors that have a rapid imaging process with a lesser radiation and higher image quality from these materials and to apply the radiographic imaging systems. The GOS: Tb3+ showed high emission peak and high x-ray absorption properties which have been determined for application to mammography and dental radiography. In this study, Gd2O2SO4:Tb3+ phosphors were fabricated by the sol-gel method that is a unique technique and not previously applied. Besides, the structural characterization of GOS: Tb3+ has been investigated. The strongest emission peak located at 549 nm under 312 nm UV light excitation was appeared on the GOS: Tb3+ phosphor particles. The characterization processing optimized by using FTIR, DTA-TG, XRD, XPS, SEM and the luminescence spectroscopy.

PA-Tb-Cu MOF as luminescent nanoenzyme for catalytic assay of hydrogen peroxide.

PubMed

Qi, Zewan; Wang, Li; You, Qi; Chen, Yang

2017-10-15

Metal organic frameworks (MOFs) with flexible structures and components have aroused great interest in designing functional materials. In this work, we designed and made a kind of PA-Tb-Cu MOF nanoenzyme capable of emitting fluorescence for the catalytic reaction of hydrogen peroxide (H 2 O 2 ). Luminescent Tb 3+ , catalytic Cu 2+ and bridging ligand were assembled and integrated into a single material nanoenzyme. This PA-Tb-Cu MOF nanoenzyme not only possessed excellent catalytic activity comparable to horseradish peroxidase but also can real-time fluorescently indicate the concentration of H 2 O 2 as low as 0.2µM during catalysis. Luminescent PA-Tb-Cu MOF nanoenzyme did not need a common combined use of natural/artificial enzymes and chromogenic reactions for the quantification of H 2 O 2 in widely-used enzyme-catalytic reactions. The present strategy assembled directly from functional ions/molecules provides a new way for the design and development of smart, multifunctional artificial enzymes for wide applications in biocatalysis, bioassays and nano-biomedicine. Copyright © 2017 Elsevier B.V. All rights reserved.

[Management of cases of active pulmonary tuberculosis in diagnostic radiology departments in Italy: proposal of a checklist and role of radiology technicians].

PubMed

Giorgini, Giulia; Mesto, Anna; Soardo, Vincenzo

2013-01-01

Tuberculosis (TB) affects more than two billion people worldwide. In hospitals, the presence of suspect cases of infectious TB should be reported as quickly as possible. An anonymous questionnaire was administered to a sample of radiology technicians employed by several local health departments in Italy. The questionnaire contained questions regarding workplace characteristics, knowledge about precautions for preventing disease transmission, degree of collaboration between health professionals and departments regarding communicable diseases. Study results point to the presence of structural and organizational weaknesses as well as inadequate communication between healthcare workers and units. Eighty percent of surveyed technicians stated that patients with suspected TB may arrive in diagnostic radiology wards devoid of surgical mask. The authors suggest the adoption of a checklist to aid healthcare professionals and specifically X-Ray technicians in adopting a behavioral model for the management of patients with infectious TB.

Understanding spin configuration in the geometrically frustrated magnet TbB 4: A resonant soft X-ray scattering study

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

Huang, H.; Jang, H.; Kang, B. Y.

The frustrated magnet has been regarded as a system that could be a promising host material for the quantum spin liquid (QSL). However, it is difficult to determine the spin configuration and the corresponding mechanism in this system, because of its geometrical frustration ( i.e., crystal structure and symmetry). Herein, we systematically investigate one of the geometrically frustrated magnets, the TbB 4 compound. Using resonant soft x-ray scattering (RSXS), we explored its spin configuration, as well as Tb's quadrupole. Comprehensive evaluations of the temperature and photon energy/polarization dependences of the RSXS signals reveal the mechanism of spin reorientation upon coolingmore » down, which is the sophisticated interplay between the Tb spin and the crystal symmetry rather than its orbit (quadrupole). Here, our results and their implications would further shed a light on the search for possible realization of QSL.« less

Understanding spin configuration in the geometrically frustrated magnet TbB 4: A resonant soft X-ray scattering study

DOE PAGES

Huang, H.; Jang, H.; Kang, B. Y.; ...

2018-05-05

The frustrated magnet has been regarded as a system that could be a promising host material for the quantum spin liquid (QSL). However, it is difficult to determine the spin configuration and the corresponding mechanism in this system, because of its geometrical frustration ( i.e., crystal structure and symmetry). Herein, we systematically investigate one of the geometrically frustrated magnets, the TbB 4 compound. Using resonant soft x-ray scattering (RSXS), we explored its spin configuration, as well as Tb's quadrupole. Comprehensive evaluations of the temperature and photon energy/polarization dependences of the RSXS signals reveal the mechanism of spin reorientation upon coolingmore » down, which is the sophisticated interplay between the Tb spin and the crystal symmetry rather than its orbit (quadrupole). Here, our results and their implications would further shed a light on the search for possible realization of QSL.« less

Enhanced rare earth photoluminescence in inverse opal photonic crystals and its application for pH sensing.

PubMed

Zhu, Yongsheng; Cui, Shaobo; Wang, Yinhua; Liu, Mao; Lu, Cheng; Mishra, Abhinay; Xu, Wen

2016-10-07

Concentration quenching effects of identical rare earth (RE) activator ions and energy transfer (ET) between different RE ions often compromise the photoluminescence (PL) quantum efficiency in RE based luminescence materials. Here, we demonstrate that in NaGd(WO4)2:Tb(3+), Eu(3+) inverse opal photonic crystals (IOPCs), the suppression of the emission line located in the photonic stop band (PSB) and a dramatic increase of the lifetimes of Eu(3+) and Tb(3+) ions are observed. More interestingly, the concentration quenching among Eu(3+) ions and ET from Tb(3+) to Eu(3+) is significantly relieved owing to the periodic empty cavity structure of IOPCs. As a consequence, the luminescent quantum efficiency (QE) of the NaGd(WO4)2:Tb(3+), Eu(3+) IOPCs increases ∼2 times more than that of crushed NaGd(WO4)2:Tb(3+), Eu(3+) powder. In addition, a reusable pH sensor with good linear response (pH 5-10) has been designed based on the high surface-to-volume ratio, high connectivity, and enhanced luminescence of NaGd(WO4)2:Tb(3+), Eu(3+)IOPCs, which could be applied to the dynamical detection of pH value.

Synthesis, Structure, White-Light Emission, and Temperature Recognition Properties of Eu/Tb Mixed Coordination Polymers.

PubMed

An, Ran; Zhao, Hui; Hu, Huai-Ming; Wang, Xiaofang; Yang, Meng-Lin; Xue, Ganglin

2016-01-19

Two series of Eu(III)/Tb(III) coordination polymers, [LnL(glu)]n·2nH2O (Ln = Eu (1), Tb (2)) and [LnL(glu)(H2O)]n (Ln = Eu (3), Tb (4)) [HL = (2-(2-sulfophenyl)imidazo(4,5-f)(1,10)-phenanthroline, H2glu = glutaric acid] have been hydrothermally synthesized by controlling the pH values and characterized by elemental analysis, infrared spectra, and single-crystal X-ray diffraction. Isomorphic compounds 1 and 2 exhibit 6-connected 3D network with the pcu topological net, containing left- and right-handed helical chains. Isomorphic compounds 3 and 4 show 3,4-connected 2D new topology with the point symbol of (4(2)·6(3)·8)(4(2)·6). Multicolor luminescence can be tailored from red to green regions by singly varying the mixing molar ratio of Eu(III)/Tb(III) cations. The mixing component of 1Eu/2Tb = 4:6 not only achieves white-light emission with the CIE coordinate of (0.323, 0.339) upon excitation at 405 nm but also presents a temperature recognition property with the significantly high sensitivity of 0.68% per K in the 50-225 K temperature range upon excitation at 370 nm.

Prominent blue emission through Tb3+ doped La2O3 nano-phosphors for white LEDs

NASA Astrophysics Data System (ADS)

Jain, Neha; Singh, Rajan Kr; Srivastava, Amit; Mishra, S. K.; Singh, Jai

2018-06-01

In this article, we report the tunable luminescence emission of Tb3+ doped La2O3 nanophosphors synthesized by a facile and effective Polyol method. The structural and surface morphological studies have been carried out by employing X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The XRD studies elucidate the proper phase formation and the results emanate from Raman spectroscopy of the as synthesized nanophosphor affirms it. The optical properties of the as fabricated nanoparticles have been investigated by Raman and photoluminescence (PL) spectroscopy. The PL spectroscopy shows the occurrence of excitation peaks at 305, 350 and 375 nm for 543 nm emissions, correspond to transition 5D4 →7F5. Emission spectra with 305 nm excitation exhibits characteristic emission peaks of Tb3+ion at 472, 487, 543 and 580 nm. The intensity of emission increases with Tb3+ concentration and is most prominent for 7 at% Tb3+ ion. The characteristic emissions of Tb3+ ion owes to the transition in which intensities of blue and green emission are prominent. The dominant intensity has been found for 472 nm (for blue emission). Commission international d 'Eclairage (CIE) co-ordinates have found in the light blue to green region. The research work provides a new interesting insight dealing with tunable properties with Tb3+ doping in La2O3 nanophosphors, to be useful for display devices, solar cells, LEDs and optoelectronic devices.

Structural variations in terbium(III) complexes with 1,3-adamantanedicarboxylate and diverse co-ligands

NASA Astrophysics Data System (ADS)

Thuéry, Pierre

2015-07-01

Terbium nitrate was reacted with 1,3-adamantanedicarboxylic acid (LH2) under solvo-hydrothermal conditions with either N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMA) as organic solvents. Hydrolysation of the latter co-solvents resulted in the formation of formate or acetate ions, which are present as co-ligands in the 1D coordination polymer [Tb(L)(HCOO)(H2O)2] (1) and the 2D assembly [Tb(L)(CH3COO)(H2O)] (2). The increase in dimensionality in the latter arises from the higher connectivity provided by acetate versus formate, the L2- ligand being bis-chelating in both cases. The complex [Tb2(L)3(H2O)5][Tb2(L)3(H2O)4]·3H2O (3), another 1D species, crystallizes alongside crystals of 2. Further addition of cucurbit[6]uril (CB6), with DMF as co-solvent, gave the two complexes [Tb2(L)2(CB6)(H2O)6](NO3)2·6H2O (4) and [H2NMe2]2[Tb(L)(HCOO)2]2·CB6·3H2O (5). Complex 4 crystallizes as a 3D framework in which Tb(L)+ chains are connected by tetradentate CB6 molecules, while 5 unites a carboxylate-bridged anionic 2D planar assembly and layers of CB6 molecules with counter-cations held at both portals.

Controllable synthesis of Ln3+ (Ln = Tb, Eu) doped zinc phosphate nano-/micro-structured materials: phase, morphology and luminescence properties

NASA Astrophysics Data System (ADS)

Yue, Dan; Lu, Wei; Li, Chunyang; Zhang, Xinlei; Liu, Chunxia; Wang, Zhenling

2014-01-01

Ln3+ (Ln = Tb, Eu) doped zinc phosphate tetrahydrate (ZPT:Ln3+) and ammonium zinc phosphate (AZP:Ln3+) nano-/micro-structured materials were synthesized in aqueous solution without the addition of any structure-directing agent. The phase structures, morphologies and luminescence properties of the as-synthesized samples were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), photoluminescence (PL) spectroscopy and lifetime. These investigations indicate that different phosphate sources MnH(3-n)PO4 (M = NH4+ or Na+, n = 1, 2, 3) can lead to the altering of morphology from nanosheet to microflower, but have no significant effect on the phase structure of the samples. The microlump, nanosheet, and microflower (constructed by the primary microlumps or nanosheets) of orthorhombic ZPT:Ln3+ could be selectively prepared by adjusting the pH value from 3.5 to 7.0. A mixture of orthorhombic ZPT:Ln3+ and monoclinic AZP:Ln3+ with a microflower morphology was obtained when the pH value was adjusted to 8.0. Monoclinic AZP:Ln3+ microplate, microcube and nanoparticle morphologies were obtained at pH values of 8.5, 9.0 and 11.0 respectively. The phase transformation and growth mechanism of the diverse morphologies were proposed, and ZPT:Ln3+ (Ln3+ = Eu or Tb) samples exhibit red or green emission under the excitation of UV light.Ln3+ (Ln = Tb, Eu) doped zinc phosphate tetrahydrate (ZPT:Ln3+) and ammonium zinc phosphate (AZP:Ln3+) nano-/micro-structured materials were synthesized in aqueous solution without the addition of any structure-directing agent. The phase structures, morphologies and luminescence properties of the as-synthesized samples were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), photoluminescence (PL) spectroscopy and lifetime. These investigations indicate that different phosphate sources MnH(3-n)PO4 (M = NH4+ or Na+, n = 1, 2, 3) can lead to the altering of morphology from nanosheet to microflower, but have no significant effect on the phase structure of the samples. The microlump, nanosheet, and microflower (constructed by the primary microlumps or nanosheets) of orthorhombic ZPT:Ln3+ could be selectively prepared by adjusting the pH value from 3.5 to 7.0. A mixture of orthorhombic ZPT:Ln3+ and monoclinic AZP:Ln3+ with a microflower morphology was obtained when the pH value was adjusted to 8.0. Monoclinic AZP:Ln3+ microplate, microcube and nanoparticle morphologies were obtained at pH values of 8.5, 9.0 and 11.0 respectively. The phase transformation and growth mechanism of the diverse morphologies were proposed, and ZPT:Ln3+ (Ln3+ = Eu or Tb) samples exhibit red or green emission under the excitation of UV light. Electronic supplementary information (ESI) available: Additional XRD patterns, EDX, SEM and TEM images, dependence of the average lifetimes on the different doping concentrations of Eu3+ and Tb3+. See DOI: 10.1039/c3nr03749e

Highly aqueous soluble CaF2:Ce/Tb nanocrystals: effect of surface functionalization on structural, optical band gap, and photoluminescence properties.

PubMed

Ansari, Anees A; Parchur, Abdul K; Kumar, Brijesh; Rai, S B

2016-12-01

The design of nanostructured materials with highly stable water-dispersion and luminescence efficiency is an important concern in nanotechnology and nanomedicine. In this paper, we described the synthesis and distinct surface modification on the morphological structure and optical (optical absorption, band gap energy, excitation, emission, decay time, etc.) properties of highly crystalline water-dispersible CaF 2 :Ce/Tb nanocrystals (core-nanocrystals). The epitaxial growth of inert CaF 2 and silica shell, respectively, on their surface forming as CaF 2 :Ce/Tb@CaF 2 (core/shell) and CaF 2 :Ce/Tb@CaF 2 @SiO 2 (core/shell/SiO 2 ) nanoarchitecture. X-ray diffraction and transmission electron microscope image shows that the nanocrystals were in irregular spherical phase, highly crystalline (~20 nm) with narrow size distribution. The core/shell nanocrystals confirm that the surface coating is responsible in the change of symmetrical nanostructure, which was determined from the band gap energy and luminescent properties. It was found that an inert inorganic shell formation effectively enhances the luminescence efficiency and silica shell makes the nanocrystals highly water-dispersible. In addition, Ce 3+ /Tb 3+ -co-doped CaF 2 nanocrystals show efficient energy transfer from Ce 3+ to Tb 3+ ion and strong green luminescence of Tb 3+ ion at 541 nm( 5 D 4 → 7 F 5 ). Luminescence decay curves of core and core/shell nanocrystals were fitted using mono and biexponential equations, and R 2 regression coefficient criteria were used to discriminate the goodness of the fitted model. The lifetime values for the core/shell nanocrystals are higher than core-nanocrystals. Considering the high stable water-dispersion and intensive luminescence emission in the visible region, these luminescent core/shell nanocrystals could be potential candidates for luminescent bio-imaging, optical bio-probe, displays, staining, and multianalyte optical sensing. A newly designed CaF 2 :Ce/Tb nanoparticles via metal complex decomposition rout shows high dispersibility in aqueous solvents with enhanced photoluminescence. The epitaxial growth of inert CaF 2 shell and further amorphous silica, respectively, enhanced their optical and luminescence properties, which is highly usable for luminescent biolabeling, and optical bioprobe etc.

The interplay of long-range magnetic order and single-ion anisotropy in rare earth nickel germanides

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

Islam, Z.

1999-05-10

This dissertation is concerned with the interplay of long-range order and anisotropy in the tetragonal RNi{sub 2}Ge{sub 2} (R = rare earth) family of compounds. Microscopic magnetic structures were studied using both neutron and x-ray resonant exchange scattering (XRES) techniques. The magnetic structures of Tb, Dy, Eu and Gd members have been determined using high-quality single-crystal samples. This work has correlated a strong Fermi surface nesting to the magnetic ordering in the RNi{sub 2}Ge{sub 2} compounds. Generalized susceptibility, {chi}{sub 0}(q), calculations found nesting to be responsible for both incommensurate ordering wave vector in GdNi{sub 2}Ge{sub 2}, and the commensurate structuremore » in EuNi{sub 2}Ge{sub 2}. A continuous transition from incommensurate to commensurate magnetic structures via band filling is predicted. The surprisingly higher T{sub N} in EuNi{sub 2}Ge{sub 2} than that in GdNi{sub 2}Ge{sub 2} is also explained. Next, all the metamagnetic phases in TbNi{sub 2}Ge{sub 2} with an applied field along the c axis have been characterized with neutron diffraction measurements. A mixed phase model for the first metamagnetic structure consisting of fully-saturated as well as reduced-moment Tb ions is presented. The moment reduction may be due to moment instability which is possible if the exchange is comparable to the low-lying CEF level splitting and the ground state is a singlet. In such a case, certain Tb sites may experience a local field below the critical value needed to reach saturation.« less

A supramolecular Tröger's base derived coordination zinc polymer for fluorescent sensing of phenolic-nitroaromatic explosives in water.

PubMed

Shanmugaraju, Sankarasekaran; Dabadie, Charlyne; Byrne, Kevin; Savyasachi, Aramballi J; Umadevi, Deivasigamani; Schmitt, Wolfgang; Kitchen, Jonathan A; Gunnlaugsson, Thorfinnur

2017-02-01

A V-Shaped 4-amino-1,8-napthalimide derived tetracarboxylic acid linker ( L ; bis-[ N -(1,3-benzenedicarboxylic acid)]-9,18-methano-1,8-naphthalimide-[ b , f ][1,5]diazocine) comprising the Tröger's base (TB) structural motif was rationally designed and synthesised to access a nitrogen-rich fluorescent supramolecular coordination polymer. By adopting the straight forward precipitation method, a new luminescent nanoscale Zn(ii) coordination polymer ( TB-Zn-CP ) was synthesized in quantitative yield using Zn(OAc) 2 ·2H 2 O and tetraacid linker L (1 : 0.5) in DMF at room temperature. The phase-purity of as-synthesised TB-Zn-CP was confirmed by X-ray powder diffraction analysis, infra-red spectroscopy, and elemental analysis. Thermogravimetric analysis suggests that TB-Zn-CP is thermally stable up to 330 °C and the morphological features of TB-Zn-CP was analysed by SEM and AFM techniques. The N 2 adsorption isotherm of thermally activated TB-Zn-CP at 77 K revealed a type-II reversible adsorption isotherm and the calculated Brunauer-Emmett-Teller (BET) surface area was found to be 72 m 2 g -1 . Furthermore, TB-Zn-CP displayed an excellent CO 2 uptake capacity of 76 mg g -1 at 273 K and good adsorption selectivity for CO 2 over N 2 and H 2 . The aqueous suspension of as-synthesized TB-Zn-CP showed strong green fluorescence ( λ max = 520 nm) characteristics due to the internal-charge transfer (ICT) transition and was used as a fluorescent sensor for the discriminative sensing of nitroaromatic explosives. The aqueous suspension of TB-Zn-CP showed the largest quenching responses with high selectivity for phenolic-nitroaromatics (4-NP, 2,4-DNP and PA) even in the concurrent presence of other potentially competing nitroaromatic analytes. The fluorescence titration studies also provide evidence that TB-Zn-CP detects picric acid as low as the parts per billion (26.3 ppb) range. Furthermore, the observed fluorescence quenching responses of TB-Zn-CP towards picric acid were highly reversible. The highly selective fluorescence quenching responses including the reversible detection efficiency make the nanoscale coordination polymer TB-Zn-CP a potential material for the discriminative fluorescent sensing of nitroaromatic explosives.

Screening of health-care workers for latent tuberculosis infection in a Tertiary Care Hospital.

PubMed

Janagond, Anand Bimari; Ganesan, Vithiya; Vijay Kumar, G S; Ramesh, Arunagiri; Anand, Prem; Mariappan, M

2017-01-01

Health-care workers (HCWs) are at increased risk of acquiring tuberculosis (TB) than the general population. While national-level data on the burden of TB in general population is available from reliable sources, nationally representative data on latent tuberculosis infection (LTBI) burden in HCWs in the high burden countries is lacking. A prospective study was carried out to assess the risk of TB infection among HCWs who directly engage in medical duties. HCWs were recruited between January 2014 and December 2015. A structured questionnaire was used for risk assessment of TB infection among HCWs, including sociodemographic characteristics (e.g., age, gender, period of professional work, and employed position), knowledge of TB prevention and control, and history of professional work. A single-step tuberculin skin test (TST) using 5 international units (IU; 0.1 ml) of tuberculin (purified protein derivative from Mycobacterium bovis Bacillus Calmette-Guérin [BCG]). TB infection was determined using a TST induration ≥10 mm as a cutoff point for TST positivity. TST-positive participants were further subjected to detailed clinical evaluation and chest radiography to rule out active TB. The associations between TB infection and the sociodemographic characteristics, duration of possible exposure to TB while on medical duties, BCG vaccination, and knowledge about TB were estimated using Chi-square test. A two-sided P < 0.05 indicated statistical significance. A total of 206 eligible HCWs signed the informed consent and completed the questionnaires between January 2014 and December 2015. The age of the participants ranged from 18 to 71 years, with a mean age of 27.13 years. TST induration size (mean 6.37 mm) the TST results suggested that 36.8% (76/206) were infected with TB using a TST induration ≥10 mm as a cut-off point. All 76 TST-positive HCWs showed no evidence of active TB in clinical evaluation and chest radiography. However, during the study, two HCWs developed pulmonary TB (both TST baseline test negative). Statistical analysis suggested that age, duration of employment as a health-care professional, literacy status, and working in medical wards/OP/Intensive Care Unit were significantly associated with TB infection. Many studies propose serial tests of LTBI as effective occupational protection strategies. However, practically, it is not feasible because it has to be done at frequent intervals, but how frequently to be done is not clear. Another concern is even if found to have LTBI, there are no clear consensus guidelines about the treatment in high prevalence settings. The prevalence of LTBI is so high in countries like India that affected HCWs could not be exempted from working in high-risk areas. The depth of knowledge of TB prevention and control among HCWs should be improved by regular infection control training.

Prisons as a source of tuberculosis in Russia.

PubMed

Sarang, Anya; Platt, Lucy; Vyshemirskaya, Inna; Rhodes, Tim

2016-01-01

The purpose of this paper is to analyze poor management of tuberculosis (TB) prevention and treatment and explore parameters and causes of this problem drawing on qualitative interviews with former prisoners and medical specialists in Kaliningrad Oblast in Russia. The authors undertook a qualitative study, to explore access to HIV and TB treatment for people who inject drugs in Kaliningrad. The authors interviewed (outside of prisons) 15 patients and eight health specialists using a semi-structured guide. The authors analyzed the accounts thematically and health consequences of imprisonment emerged as a major theme. Prisons are overcrowded and lack basic hygiene and infection control. Demand for medical services outstrip supply, HIV and TB prevention lacking, HIV and TB treatment is patchy, with no second-line drugs available for resistant forms. The prison conditions are generally degrading and unhealthy and many respondents perceived surviving prisons as a miracle. Cooperation with medical services in the community is poor. The authors used qualitative research methods, which do not rely on a representative sample. However, many of the structural barriers preventing effective TB treatment and prevention highlighted in this paper have been noted elsewhere, suggesting that findings are likely to reflect conditions elsewhere in Russia. The authors tried to include all possible points of view, as of the medical staff and the patients. However, due to resistance of the officials the authors were unable to conduct interviews with employees of the FCS. Since all the interviews are recalling past experience, the situation may have changed. This does not undermine importance of the findings, as they shed light on particular treatment experiences, and development of prison health system. The paper contributes to the literature on prisons as a contributor to TB epidemic, including drug resistant forms. An urgent penitentiary reform in Russia should focus on HIV and TB prevention, case detection, availability of medications and effective treatments. Key to decreasing prison population and improving health is political reform aimed at introduction of effective drug treatment, de-penalization and de-criminalization of drug users and application of alternatives to incarceration.

Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population.

PubMed

Torres-García, Diana; Cruz-Lagunas, Alfredo; García-Sancho Figueroa, Ma Cecilia; Fernández-Plata, Rosario; Baez-Saldaña, Renata; Mendoza-Milla, Criselda; Barquera, Rodrigo; Carrera-Eusebio, Aida; Ramírez-Bravo, Salomón; Campos, Lizeth; Angeles, Javier; Vargas-Alarcón, Gilberto; Granados, Julio; Gopal, Radha; Khader, Shabaana A; Yunis, Edmond J; Zuñiga, Joaquin

2013-09-21

The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. We carried out a case-control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR= 2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected. Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians.

Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population

PubMed Central

2013-01-01

Background The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. Methods We carried out a case–control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. Results We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR= 2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected. Conclusions Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians. PMID:24053111

Concentration and wavelength dependent frequency downshifting photoluminescence from a Tb3+ doped yttria nano-phosphor: A photochromic phosphor

NASA Astrophysics Data System (ADS)

Yadav, Ram Sagar; Rai, Shyam Bahadur

2018-03-01

In this article, the Tb3+ doped Y2O3 nano-phosphor has been synthesized through solution combustion method. The structural measurements of the nano-phosphor have been carried out by X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques, which reveal nano-crystalline nature. The Fourier transform infrared (FTIR) measurements reveal the presence of different molecular species in the nano-phosphor. The UV-Vis-NIR absorption spectrum of the nano-phosphor shows large number of bands due to charge transfer band (CTB) and 4f-4f electronic transitions of Tb3+ ion. The Tb3+ doped Y2O3 nano-phosphor emits intense green downshifting photoluminescence centered at 543 nm due to 5D4 → 7F5 transition on excitation with 350 nm. The emission intensity of the nano-phosphor is optimized at 1.0 mol% concentration of Tb3+ ion. When the as-synthesized nano-phosphor is annealed at higher temperature the emission intensity of the nano-phosphor enhances upto 5 times. The enhancement in the emission intensity is due to an increase in crystallinity of the nano-phosphor, reduction in surface defects and optical quenching centers. The CIE diagram reveals that the Tb3+ doped nano-phosphor samples show the photochromic nature (color tunability) with a change in the concentration of Tb3+ ion and excitation wavelength. The lifetime measurement indicates an increase in the lifetime for the annealed sample. Thus, the Tb3+ doped Y2O3 nano-phosphor may be used in photochromic displays and photonic devices.

Polyvinylpyrrolidone (PVP)-assisted solvothermal synthesis of flower-like SrCO{sub 3}:Tb{sup 3+} phosphors

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

Xue, Yannan; Ren, Xiaolei; Zhai, Xuefeng

Graphical abstract: A simple solvothermal method for the synthesis of flower-like SrCO{sub 3}:Tb{sup 3+} phosphors with the assistance of polyvinylpyrrolidone (PVP, K30). Highlights: Black-Right-Pointing-Pointer Well-crystallized flower-like SrCO{sub 3}:Tb{sup 3+} phosphors could be easily prepared by a simple solvothermal method with the assistance of polyvinylpyrrolidone (PVP). Black-Right-Pointing-Pointer The amount of PVP and the reaction time have a strong effect on controlling the morphology and optical properties of SrCO{sub 3}:Tb{sup 3+} particles. Black-Right-Pointing-Pointer The main synthesizing process and the growth mechanism for the formation of final samples were proposed. -- Abstract: Well-crystallized flower-like SrCO{sub 3}:Tb{sup 3+} phosphors have been synthesized by anmore » inexpensive and friendly solvothermal process using polyvinylpyrrolidone (PVP, K30) as an additive without further annealing treatment. X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), and field emission scanning electron microscopy (FESEM) as well as photoluminescence spectroscopy (PL) were used to characterize the resulting samples. The amount of PVP and the reaction time have strong effect on the morphology of the SrCO{sub 3}:Tb{sup 3+} particles. The results of XRD confirm the formation of a well-crystallized SrCO{sub 3} phase with an orthorhombic structure. The possible formation mechanism for flower-like SrCO{sub 3}:Tb{sup 3+} phosphor is proposed. The SrCO{sub 3}:Tb{sup 3+} phosphors show the characteristic {sup 5}D{sub 4}-{sup 7}F{sub J} (J = 6, 5, 4, 3) emission lines with green emission {sup 5}D{sub 4}-{sup 7}F{sub 5} (544 nm) as the most prominent group under ultraviolet excitation.« less

Development and Psychometric Properties of a Tuberculosis-Specific Multidimensional Health-Related Quality-of-Life Measure for Patients with Pulmonary Tuberculosis.

PubMed

Abdulelah, Juman; Sulaiman, Syed Azhar Syed; Hassali, Mohamed A; Blebil, Ali Q; Awaisu, Ahmed; Bredle, Jason M

2015-05-01

Various generic instruments exist to assess health-related quality of life (HRQOL) in patients with tuberculosis (TB), but a psychometrically sound disease-specific instrument is lacking. The present study aimed to develop and psychometrically validate a multidimensional TB-specific HRQOL instrument relevant to the value of patients with pulmonary TB in Iraq with an eye toward cross-cultural application. The core general HRQOL questionnaire is composed of the Functional Assessment of Cancer Therapy-General items. A modular approach was followed for the development of the Functional Assessment of Chronic Illness Therapy-Tuberculosis (FACIT-TB) questionnaire in which a set of items assessing quality-of-life (QOL) issues not sufficiently covered by the core Functional Assessment of Cancer Therapy-General items, but considered to be relevant to the target population, was added. Moreover, principal-component analysis was used to determine the new subscale structure of the questionnaire. In addition to the 27 items of the core questionnaire, a set of 20 items referring to disease symptoms related to the site of infection, adverse effects, and additional QOL dimensions such as fatigue, social stigma, and economic burden of the illness was included. Factor analysis demonstrated that the FACIT-TB construct comprised five domains. A rigorous method was applied in the development of the FACIT-TB measure to fully understand the impact of TB on patients' QOL. The instrument is psychometrically sound and portrays multiple important dimensions of HRQOL. FACIT-TB is relatively brief, is easy to administer and score, and is appropriate for use in clinical trials and practice. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Internal and external factors in the structural organization in cocrystals of the mixed-metal endohedrals (GdSc2N@Ih-C80, Gd2ScN@Ih-C80, and TbSc2N@Ih-C80) and nickel(II) octaethylporphyrin.

PubMed

Stevenson, Steven; Chancellor, Christopher J; Lee, Hon Man; Olmstead, Marilyn M; Balch, Alan L

2008-03-03

Structural characterizations of three new mixed-metal endohedrals, GdSc 2N@ I h -C80, Gd 2ScN@ I h -C80, and TbSc 2@ I h -C80, have been obtained by single-crystal X-ray diffraction on GdSc 2N@ I h -C80 x Ni (II)(OEP) x 2C 6H 6, Gd 2ScN@ I h -C 80 x Ni(II)(OEP) x 2C6H6, and TbSc 2N@ I h -C80 x Ni (II)(OEP) x 2C6H6. All three have I h -C 80 cages and planar MM' 2N units. The central nitride ion is positioned further from the larger Gd3+ or Tb3+ ions and closer to the smaller Sc3+ ions. The MM' 2N units show a remarkable degree of orientational order in these and related compounds in which the endohedral fullerene is cocrystallized with a metalloporphyrin. The MM' 2N units are oriented perpendicularly to the porphyrin plane and aligned along one of the N-Ni-N axes of the porphyrin. The smaller Sc3+ ions show a marked preference to lie near the porphyrin plane. The larger Gd3+ or Tb3+ ions assume positions further from the plane of the porphyrin. The roles of dipole forces and electrostatic forces in ordering these cocrystals of endohedral fullerenes and metalloporphyrins are considered.

Highly structured genetic diversity of the Mycobacterium tuberculosis population in Djibouti.

PubMed

Godreuil, S; Renaud, F; Choisy, M; Depina, J J; Garnotel, E; Morillon, M; Van de Perre, P; Bañuls, A L

2010-07-01

Djibouti is an East African country with a high tuberculosis incidence. This study was conducted over a 2-month period in Djibouti, during which 62 consecutive patients with pulmonary tuberculosis (TB) were included. Genetic characterization of Mycobacterium tuberculosis, using mycobacterial interspersed repetitive-unit variable-number tandem-repeat typing and spoligotyping, was performed. The genetic and phylogenetic analysis revealed only three major families (Central Asian, East African Indian and T). The high diversity and linkage disequilibrium within each family suggest a long period of clonal evolution. A Bayesian approach shows that the phylogenetic structure observed in our sample of 62 isolates is very likely to be representative of the phylogenetic structure of the M. tuberculosis population in the total number of TB cases.

Structural and functional characterization of Mycobacterium tuberculosis triosephosphate isomerase

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

Connor, Sean E.; Capodagli, Glenn C.; Deaton, Michelle K.

Tuberculosis (TB) is a major infectious disease that accounts for over 1.7 million deaths every year. Mycobacterium tuberculosis, the causative agent of tuberculosis, enters the human host by the inhalation of infectious aerosols. Additionally, one third of the world's population is likely to be infected with latent TB. The incidence of TB is on the rise owing in part to the emergence of multidrug-resistant strains. As a result, there is a growing need to focus on novel M. tuberculosis enzyme targets. M. tuberculosis triosephosphate isomerase (MtTPI) is an essential enzyme for gluconeogenetic pathways, making it a potential target for futuremore » therapeutics. In order to determine its structure, the X-ray crystal structure of MtTPI has been determined, as well as that of MtTPI bound with a reaction-intermediate analog. As a result, two forms of the active site were revealed. In conjunction with the kinetic parameters obtained for the MtTPI-facilitated conversion of dihydroxyacetone phosphate (DHAP) to D-glyceraldehyde-3-phosphate (D-GAP), this provides a greater structural and biochemical understanding of this enzyme. Additionally, isothermal titration calorimetry was used to determine the binding constant for a reaction-intermediate analog bound to the active site of MtTPI.« less

Charge-transfer-based terbium MOF nanoparticles as fluorescent pH sensor for extreme acidity.

PubMed

Qi, Zewan; Chen, Yang

2017-01-15

Newly emerged metal organic frameworks (MOFs) have aroused the great interest in designing functional materials by means of its flexible structure and component. In this study, we used lanthanide Tb 3+ ions and small molecular ligands to design and assemble a kind of pH-sensitive MOF nanoparticle based on intramolecular-charge-transfer effect. This kind of made-to-order MOF nanoparticle for H + is highly specific and sensitive and could be used to fluorescently indicate pH value of strong acidic solution via preset mechanism through luminescence of Tb 3+ . The long luminescence lifetime of Tb 3+ allows eliminating concomitant non-specific fluorescence by time-revised fluorescence techniques, processing an advantage in sensing H + in biological media with strong autofluorescence. Our method showed a great potential of MOF structures in designing and constructing sensitive sensing materials for specific analytes directly via the assembly of functional ions/ligands. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation of Structure of Gd and Tb Nuclei using STARS and LiBerACE

NASA Astrophysics Data System (ADS)

Bonniwell, Cain; Pauerstein, Ben; Allmond, J. M.; Beausang, C. W.

2009-10-01

This experiment, performed at Livermore Berkeley National Lab as a collaboration of Livermore, Berkeley, and the University of Richmond, was designed to investigate the structure of gadolinium and terbium nuclei using the P + 156Gd reaction at E beam = 27 MeV. The experimental design included use of the STARS system for detecting charged particles as well as the LiBerACE clover array for detecting gamma rays. The master gate was set to record particle-gamma as well as gamma-gamma coincidences. The data is currently being analyzed using the RADWARE escl8r software package which has allowed the creation of extensive level schemes for several Gd and Tb nuclei. So far the data suggests new gamma ray transitions as well as new energy states in 154Gd and 155Tb. The project is ongoing, and the results will be presented. This work was supported by the US Department of Energy under grant numbers DE-FG52NA26206 and DE-FG02-05ER41379.

Effect of cooling rate on magnetic domain structure and magnetic properties of Tb0.27Dy0.73Fe1.95 alloys solidified in high magnetic field

NASA Astrophysics Data System (ADS)

Liu, Tie; Dong, Meng; Gao, Pengfei; Xiao, Yubao; Yuan, Yi; Wang, Qiang

2018-05-01

In this work, Tb0.27Dy0.73Fe1.95 alloys were solidified in a high magnetic field of 4.4 T at various cooling rates. Changes in the magnetostriction, crystal orientation, magnetization, and magnetic domain of the solidified alloys were investigated. The application of the magnetic field can induce <111> orientation of (Tb, Dy)Fe2 phase. However, the effect of the magnetic field is strongly dependent on the cooling rate. The alloy solidified at 5 °C/min shows the highest magnetostriction, strongest <111> orientation, best contrast of light and dark in the domain image, and fastest magnetization, and followed in descending order by the alloys solidified at 1.5 °C/min and 60 °C/min. The change in the magnetostriction of the alloys can be attributed to the changes in crystal orientation and magnetic domain structure caused by both the magnetic field and cooling rate.

Synthesis and characterization of a BaGdF5:Tb glass ceramic as a nanocomposite scintillator for x-ray imaging.

PubMed

Lee, Gyuhyon; Struebing, Christian; Wagner, Brent; Summers, Christopher; Ding, Yong; Bryant, Alex; Thadhani, Naresh; Shedlock, Daniel; Star-Lack, Josh; Kang, Zhitao

2016-05-20

Transparent glass ceramics with embedded light-emitting nanocrystals show great potential as low-cost nanocomposite scintillators in comparison to single crystal and transparent ceramic scintillators. In this study, cubic structure BaGdF5:Tb nanocrystals embedded in an aluminosilicate glass matrix are reported for potential high performance MeV imaging applications. Scintillator samples with systematically varied compositions were prepared by a simple conventional melt-quenching method followed by annealing. Optical, structural and scintillation properties were characterized to guide the design and optimization of selected material systems, aiming at the development of a system with higher crystal volume and larger crystal size for improved luminosity. It is observed that enhanced scintillation performance was achieved by tuning the glass matrix composition and using GdF3 in the raw materials, which served as a nucleation agent. A 26% improvement in light output was observed from a BaGdF5:Tb glass ceramic with addition of GdF3.

Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs

PubMed Central

Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica; Dunfield, Peter F.; Hedlund, Brian P.; Dekas, Anne E.; Grasby, Stephen E.; Brady, Allyson L.; Dong, Hailiang; Briggs, Brandon R.; Li, Wen-Jun; Goudeau, Danielle; Malmstrom, Rex; Pati, Amrita; Pett-Ridge, Jennifer; Rubin, Edward M.; Woyke, Tanja; Kyrpides, Nikos C.; Ivanova, Natalia N.

2016-01-01

Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum (‘Candidatus Kryptonia') found exclusively in high-temperature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic ‘blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery. PMID:26814032

Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs.

PubMed

Eloe-Fadrosh, Emiley A; Paez-Espino, David; Jarett, Jessica; Dunfield, Peter F; Hedlund, Brian P; Dekas, Anne E; Grasby, Stephen E; Brady, Allyson L; Dong, Hailiang; Briggs, Brandon R; Li, Wen-Jun; Goudeau, Danielle; Malmstrom, Rex; Pati, Amrita; Pett-Ridge, Jennifer; Rubin, Edward M; Woyke, Tanja; Kyrpides, Nikos C; Ivanova, Natalia N

2016-01-27

Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum ('Candidatus Kryptonia') found exclusively in high-temperature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic 'blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestyle with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery.

Global metagenomic survey reveals a new bacterial candidate phylum in geothermal springs

DOE PAGES

Eloe-Fadrosh, Emiley A.; Paez-Espino, David; Jarett, Jessica; ...

2016-01-27

Analysis of the increasing wealth of metagenomic data collected from diverse environments can lead to the discovery of novel branches on the tree of life. Here we analyse 5.2 Tb of metagenomic data collected globally to discover a novel bacterial phylum (' Candidatus Kryptonia') found exclusively in higherature pH-neutral geothermal springs. This lineage had remained hidden as a taxonomic 'blind spot' because of mismatches in the primers commonly used for ribosomal gene surveys. Genome reconstruction from metagenomic data combined with single-cell genomics results in several high-quality genomes representing four genera from the new phylum. Metabolic reconstruction indicates a heterotrophic lifestylemore » with conspicuous nutritional deficiencies, suggesting the need for metabolic complementarity with other microbes. Co-occurrence patterns identifies a number of putative partners, including an uncultured Armatimonadetes lineage. The discovery of Kryptonia within previously studied geothermal springs underscores the importance of globally sampled metagenomic data in detection of microbial novelty, and highlights the extraordinary diversity of microbial life still awaiting discovery.« less

[Health examination in future at the era of low tuberculosis incidence--from contacts examination toward active epidemiological studies].

PubMed

Maeda, Hideo; Shirai, Chika

2013-03-01

Japan is still "intermediate burden" country as medium-incidence of tuberculosis (TB). But the incidence of TB varies by public health units. The priority for TB control would be lowering in the areas where the incidence of TB is relatively low. In addition, younger age groups get low prevalence of TB infection than elderly persons. As a result, fewer experiences for TB diagnosis and treatment in the hospital and the medical facility would cause the delay in the detection of TB patients which eventually cause outbreaks. Although there are differences in population density and population mobility between urban and rural areas, the socially economic vulnerable patients and foreign patients are the common risks. Any public health units' policies of TB should correspond to the individual situation. At the era of low tuberculosis incidence, the infection risk is to be "From ubiquitous to the uneven distribution". This makes TB detection much more difficult. At this symposium, each speaker presented the case for actually experienced with QFT test and/or VNTR analysis. They mainly focused on the paradigm shift in TB control which is indispensable for resolving the gaps in regional differences and the differences in diagnostic capability. Although the cases in this symposium were not for the low incidence situation, the pioneering approaches presented here would boost the future application of QFT and VNTR analysis nationwide. The discussions also partially covered the technical infrastructure for molecular epidemiology which covers the whole country. By making full use of QFT test and VNTR analysis as a contact screening tool, we can appropriately understand the risk of TB infection in the region from a buildup of bacteria and patient information. Now is the time to prepare for. Active surveillance of TB by this way would clarify the risk of the disease and lead to the advocacy essential for the resolution. 1. Current situation and challenge of contact survey by using QFT test in Tokyo: Hideo MAEDA (Bureau of Social Welfare and Public Health, Tokyo Metropolitan Government). 2. Contact investigation of a tuberculosis outbreak: Kenichi MIYAMOTO (Takaido Community Health Center). We have experienced a TB outbreak in integrated junior and senior high school in Tokyo. Index patient was a student with persistent respiratory symptoms for six months before diagnosis of sputum smear-positive TB. Public health center started contact investigation immediately. QFT-positive rates were high in close contacts, especially in classmates. Additionally, a student outside of contact investigation was diagnosed as TB and considered to be infected from the first patient by VNTR analysis. Therefore, public health center expanded QFT-tests to all students and teachers in this school. Finally, 9 students and 2 teachers in this school were diagnosed as sputum smear-negative TB by contact investigation. 3. Utilization of molecular epidemiological procedure in contact investigation in Kyoto City: Masahiro ITO (Public Health Center of Kyoto City) Molecular epidemiological procedure using VNTR analysis has been used for contact investigation of tuberculosis since January 2011 in Kyoto City. One hundred forty four strains of Mycobacterium tuberculosis from patients with tuberculosis were investigated and 130 strains were fully analyzed. Fourteen clusters were found and the number of strains included in the cluster was ranged from two to 11. Epidemiological relationship between patients in one cluster was found, however, significant relationship in another clusters was not demonstrated. It was suggested that VNTR analysis is useful for molecular epidemiological analysis of tuberculosis. 4. The population based molecular epidemiological studies and QFT test in a contact examination: Riyo FUJIYAMA, Keisuke MATSUBAYASHI, Setsuko MIZUSHIRI, Junko HIGUCHIL Chika SHIRAI, Yuko KATAGAMI, Mieko CHIHARA, Akihiro IJICHI (Kobe City Public Health Center), Kentaro ARIKAWA, Noriko NAKANISHI, Tomotada IWAMOTO (Kobe Institute of Health). The population based molecular epidemiological studies should be made good use of contacts examination. In future, we expect the tuberculosis molecular epdimiological study improve search for the process of tuberculosis infection. The QFT positive rates correlated well with closeness of contact. QFT test is considered useful for diagnosing tuberculosis infection. However, in the judgment of tuberculosis infection, we should consider the total result of contact investigation not only QFT test but also the contact situation. 5. Insights into the TB epidemiology through population based molecular epidemiological studies: Tomotada IWAMOTO (Kobe Institute of Health) The population based molecular epidemiological studies unveiled the transmission dynamics of tuberculosis at bacterial clone level. This provides scientific evidences for achieving better TB control programs. In the advanced stage of the tuberculosis molecular epidemiological study, we expect to change the current geno-typing based molecular epidemiology to whole genome-typing based molecular epidemiology on the basis of the rapid innovation of next-generation sequencing technology.

Improved Optical Transmittance and Crystal Characteristics of ZnS:TbOF Thin Film on Bi4Ti3O12/Indium Tin Oxide/Glass Substrate by Using a SiO2 Buffer Layer

NASA Astrophysics Data System (ADS)

Chia, Wei‑Kuo; Yokoyama, Meiso; Yang, Cheng‑Fu; Chiang, Wang‑Ta; Chen, Ying‑Chung

2006-07-01

Bi4Ti3O12 thin films are deposited on indium tin oxide (ITO)/glass substrates using RF magnetron sputtering technology and are annealed at 675 °C in a rapid thermal annealing furnace in an oxygen atmosphere. The resulting films have high optical transmittances and good crystalline characteristics. ZnS:TbOF films are then deposited on the Bi4Ti3O12 films, causing the originally highly transparent specimens to blacken and to resemble a glass surface coated with carbon powder. The optical transmittance of the specimen is less than 15% under the visible wavelength range, and neither a crystalline phase nor a distinct ZnS grain structure is evident in X-ray diffractometer (XRD) and scanning electronic microscope (SEM). Secondary ion mass spectrometer (SIMS) analysis reveals the occurrence of interdiffusion between the ZnS and Bi4Ti3O12 layers. This suggests that one or more unknown chemical reactions take place among the elements Bi, S, and O at the interface during the deposition of ZnS:TbOF film on a Bi4Ti3O12/ITO/glass substrate. These reactions cause the visible transmittance of the specimens to deteriorate dramatically. To prevent interdiffusion, a silicon dioxide (SiO2) buffer layer 100 nm thick was grown on the Bi4Ti3O12/ITO/glass substrate using plasma-enhanced chemical vapor deposition (PECVD), then the ZnS:TbOF film was grown on the SiO2 buffer layer. The transmittance of the resulting specimen is enhanced approximately 8-fold in the visible region. XRD patterns reveal the ZnS(111)-oriented phase is dominant. Furthermore, dense, crack-free ZnS:TbOF grains are observed by SEM. The results imply that the SiO2 buffer layer sandwiched between the ZnS:TbOF and Bi4Ti3O2 layers effectively separates the two layers. Therefore, interdiffusion and chemical reactions are prevented at the interface of the two layers, and the crystalline characteristics of the ZnS:TbOF layer and the optical transmittance of the specimen are improved as a result. Finally, the dielectric constant of the stacked structure is lower than that of the single layer structure without SiO2, but the dielectric breakdown strength is enhanced.

Host-sensitized luminescence properties in CaNb2O6:Ln(3+) (Ln(3+) = Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+)) phosphors with abundant colors.

PubMed

Li, Kai; Liu, Xiaoming; Zhang, Yang; Li, Xuejiao; Lian, Hongzhou; Lin, Jun

2015-01-05

A series of Ln(3+) (Ln(3+) = Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+)) ion doped CaNb2O6 (CNO) phosphors have been prepared via the conventional high-temperature solid-state reaction route. The X-ray diffraction (XRD) and structure refinement, diffuse reflection, photoluminescence (PL), and fluorescent decay curves were used to characterize the as-prepared samples. Under UV radiation, the CNO host present a broad emission band from about 355 to 605 nm centered around 460 nm originating from the NbO6 octahedral groups, which has spectral overlaps with the excitation of f-f transitions of Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) in CNO:Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) samples. They show both host emission and respective emission lines derived from the characteristic f-f transitions of activators, which present different emission colors owing to the energy transfer from the NbO6 group in the host to Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) with increasing activator concentrations. The decreases of decay lifetimes of host emissions in CNO:Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+) demonstrate the energy transfer from the hosts to Eu(3+)/Tb(3+)/Dy(3+)/Sm(3+). The energy transfer mechanisms in CNO:Eu(3+)/Tb(3+)/Dy(3+) phosphors have been determined to be a resonant type via dipole-dipole mechanisms. For CNO:Sm(3+), the metal-metal charge transfer transition (MMCT) might contribute to the different variations of decay lifetimes and emission intensity from CNO:Eu(3+)/Tb(3+)/Dy(3+) samples. The best quantum efficiency is 71.2% for CNO:0.01/0.02Dy(3+). The PL properties of as-prepared materials indicate the promising application in UV-pumped white-emitting lighting diodes field.

Understanding the role played by Fe on the tuning of magnetocaloric effect in Tb5Si2Ge2

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

Pereira, Andre; Moreira Dos Santos, Antonio F; Magen Dominguez, Cesar

2011-01-01

In this work, it is shown that when replacing Ge by Fe in Tb5Si2Ge2 the structural transition still occurs and enhances the Magnetocaloric effect (up to 66%) with maximum of MCE at a critical Fe amount where the magnetic and structural transitions become fully coupled. It is observed that Fe concentration is able to mimic the e?ect of external pressure as it induces a complex microstructure, that tunes long range strain ?elds. This knowledge is crucial for the development of strategies towards materials with improved performance for e?cient magnetic refrigeration applications.

An environment-dependent semi-empirical tight binding model suitable for electron transport in bulk metals, metal alloys, metallic interfaces, and metallic nanostructures. I. Model and validation

NASA Astrophysics Data System (ADS)

Hegde, Ganesh; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy; Klimeck, Gerhard

2014-03-01

Semi-empirical Tight Binding (TB) is known to be a scalable and accurate atomistic representation for electron transport for realistically extended nano-scaled semiconductor devices that might contain millions of atoms. In this paper, an environment-aware and transferable TB model suitable for electronic structure and transport simulations in technologically relevant metals, metallic alloys, metal nanostructures, and metallic interface systems are described. Part I of this paper describes the development and validation of the new TB model. The new model incorporates intra-atomic diagonal and off-diagonal elements for implicit self-consistency and greater transferability across bonding environments. The dependence of the on-site energies on strain has been obtained by appealing to the Moments Theorem that links closed electron paths in the system to energy moments of angular momentum resolved local density of states obtained ab initio. The model matches self-consistent density functional theory electronic structure results for bulk face centered cubic metals with and without strain, metallic alloys, metallic interfaces, and metallic nanostructures with high accuracy and can be used in predictive electronic structure and transport problems in metallic systems at realistically extended length scales.

Preparation and photocatalytic performance of fibrous Tb3+-doped TiO2 using collagen fiber as template

NASA Astrophysics Data System (ADS)

Luo, Ting; Wan, Xiang-Jun; Jiang, Shang-Xuan; Zhang, Li-Yuan; Hong, Zheng-Qu; Liu, Jiao

2018-04-01

Fibrous Tb3+-doped TiO2 were prepared using collagen fiber as template. Morphology, crystalline structure, surface area, element content, chemical composition and elemental chemical status, microstructure and element distribution of the prepared samples were characterized by using scanning electron microscopy, X-ray diffraction, specific surface area analysis, inductively coupled plasma atomic emission spectrometer, X-ray photoelectron spectroscopy, transmission electron microscope and element mapping, respectively. The photocatalytic activities were evaluated by following degradation of methyl orange. The results showed that the fiber structure of collagen template was fully preserved when the calcination temperature was 500-800 °C. However, with the increase of calcination temperature, crystallinity and average particle size were increased, and the photocatalytic performance was decreased. For 2% Tb3+-TiO2 calcined at 500 °C, the degradation rate of methyl orange reached 93.87% after 6 h when a high-pressure mercury lamp (150 W) was used as the light source for photocatalytic degradation. Titanium tanning agent performance was excellent, the yield of TiO2 was high, and the fiber structure was presented when 0.2 mol/L citric acid/sodium citrate buffer solution was used.

A multi-responsive luminescent sensor based on a super-stable sandwich-type terbium(iii)-organic framework.

PubMed

Wen, Guo-Xuan; Han, Min-Le; Wu, Xue-Qian; Wu, Ya-Pan; Dong, Wen-Wen; Zhao, Jun; Li, Dong-Sheng; Ma, Lu-Fang

2016-10-04

A super-stable multifunctional terbium(iii)-organic framework, namely {[Tb(TATAB) (H 2 O) 2 ]·NMP·H 2 O} n (Tb-MOF, H 3 TATAB = 4,4',4''-s-triazine-1,3,5-triyltri-m-aminobenzoic acid, NMP = N-methyl-2-pyrrolidone) was synthesized. Tb-MOF exhibits a 2D sql structure with binuclear [Tb 2 (COO) 4 (H 2 O) 4 ] 2+ units as 4-connected nodes, and free water and NMP molecules are inserted between 2D layers through hydrogen-bonding interactions, forming a sandwich-type architecture. Observably, such a framework remains intact in a remarkable variety of environments such as common solvents and aqueous solutions with metal cations and inorganic anions, as well as with a pH ranging from 1 to 13. In particular, Tb-MOF can not only detect small organic molecules, metal cations and inorganic anions with high sensitivity and high selectivity, but also can accurately detect explosive 2-nitrophenol, 3-nitrophenol, 4-nitrophenol and 2,4,6-trinitrophenol in water. Its luminescence quenching response to Fe 3+ and Cr 2 O 7 2- ions can be explained in terms of the competitive absorption mechanism. In addition, the luminescence intensity of Tb-MOF is strongly correlated with the pH value in a pH range from 1 to 13. Thus, this material can be potentially used as a multi-responsive luminescent sensor.

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

Paul, Nibedita; Deka, Amrita; Mohanta, Dambarudhar, E-mail: best@tezu.ernet.in

The present work reports on the effect of Tb³⁺ doping on the luminescence and photocatalytic performance of nano-structured titania derived through a sol-gel route. X-ray diffraction patterns have revealed the existence of anatase phase with and without Tb³⁺ doping and with an improved orientation factor along (004) and (200) planes. Transmission electron microscopy and selective area electron diffraction studies, while exhibiting ample poly-crystallinity feature, have predicted an average particle size of ~9 nm and ~6 nm for the un-doped and 5% Tb³⁺ doped nano-titania samples; respectively. Apart from emissions accompanied by different types of defects, Tb³⁺ related transitions, such as,more » ⁵D₃ → ⁷F₅, ⁵D₃ → ⁷F₄, and ⁵D₄ → ⁷F₆ were identified in the photoluminescence spectra. Brunauer-Emmett-Teller surface area analysis, as carried out on a Tb³⁺ doped nano-titania system, has demonstrated a more-open hysteretic loop owing to significant difference of N₂ adsorption/desorption rates. The photocatalytic activity of nano-titania, as evaluated from the nature of degradation of methyl orange under UV illumination, exhibited the highest efficiency for a Tb³⁺ doping level of 2.5%. The augmented photocatalytic degradation has also been discussed in the light of a model based on pseudo first-order kinetics.« less

Revealing the transport properties of the spin-polarized β‧-Tb2(MoO4)3: DFT+U

NASA Astrophysics Data System (ADS)

Reshak, A. H.

2017-11-01

The thermoelectric properties of the spin-polarized β‧-Tb2(MoO4)3 phase are calculated using first-principles and second-principles methods to solve the semi-classical Bloch-Boltzmann transport equations. It is interesting to highlight that the calculated electronic band structure reveals that the β‧-Tb2(MoO4)3 has parabolic bands in the vicinity of the Fermi level (EF); therefore, the carriers exhibit low effective mass and hence high mobility. The existence of strong covalent bonds between Mo and O in the MoO4 tetrahedrons is more favorable for the transport of the carriers than the ionic bond. It has been found that the carrier concentration of spin-up (↑) and spin-down (↓) increases linearly with increasing the temperature and exhibits a maximum carrier concentration at EF. The calculations reveal that the β‧-Tb2(MoO4)3 exhibits maximum electrical conductivity, minimum electronic thermal conductivity, a large Seebeck coefficient and a high power factor at EF for (↑) and (↓). Therefore, the vicinity of EF is the area where the β‧-Tb2(MoO4)3 is expected to show maximum efficiency.

Peculiarities of tuberculosis control in a scenario of urban violence in a disadvantaged community in Rio de Janeiro, Brazil.

PubMed

Souza, Fabiana Barbosa Assumpção de; Villa, Tereza Cristina Scatena; Cavalcante, Solange Cesar; Ruffino Netto, Antonio; Lopes, Luciane Blanco; Conde, Marcus Barreto

2007-01-01

To describe the difficulties and peculiarities encountered by health professionals during the treatment and investigation of contacts of tuberculosis (TB) patients in disadvantaged communities. A qualitative study carried out at health care facilities in Health Programming Area 1.0, located in the city of Rio de Janeiro, Brazil, which has a TB incidence rate of 240/100,000 inhabitants. From among the professionals responsible for visiting and treating TB cases and their contacts, two home visit agents and one clinical nurse were selected to be interviewed for the study. Data were transcribed and structured in the form of quotations, emphasizing the predominant ideas. The central ideas focus on the issue of violence, one significant facet of which is the set of rules imposed by narcotraffickers, and on the barriers to the movement of patients/health professionals for TB treatment, as well as on public safety (police). This study provides public health officials, as well as institutions that graduate health professionals, data for reflection and analysis of the difficulties that urban violence creates for the control of TB in a disadvantaged community.

Magnetism of Ho 1-xTb xAl₂ alloys: Critical dependence of a first-order transition on Tb concentration

DOE PAGES

Khan, Mahmud; Mudryk, Ya.; Gschneidner, K. A.; ...

2011-12-27

HoAl₂ exhibits a first-order spin reorientation transition at 20 K, which is manifested as a sharp peak in the heat capacity. When Ho is partially replaced by only 5% of Tb, the sharp heat-capacity peak in Ho 1-xTb xAl₂ (x = 0.05) disappears, and then reappears again for x ≥ 0.07. For x = 0.05, the anomaly corresponding to the spin reorientation transition is barely seen in the heat capacity, but as x exceeds 0.07 the weak anomaly transforms to a sharp peak. The spin reorientation transition temperature increases to 29 K for x = 0.05, and as x increasesmore » further the transition shifts to lower temperature and returns to ~20 K for x = 0.25. The transition is no longer observed when x exceeds 0.60. Temperature-dependent x-ray powder-diffraction data confirm the first-order nature of the spin reorientation transition for the alloy with x = 0.40, and indicate that the compound retains the room-temperature cubic structure within the sensitivity of the technique. Experimental observations are discussed considering the easy magnetization directions of HoAl₂ and TbAl₂.« less

New tetragonal derivatives of cubic NaZn13-type structure: RNi6Si6 compounds, crystal structure and magnetic ordering (R=Y, La, Ce, Sm, Gd-Yb)

NASA Astrophysics Data System (ADS)

Pani, M.; Manfrinetti, P.; Provino, A.; Yuan, Fang; Mozharivskyj, Y.; Morozkin, A. V.; Knotko, A. V.; Garshev, A. V.; Yapaskurt, V. O.; Isnard, O.

2014-02-01

Novel RNi6Si6 compounds adopt the new CeNi6Si6-type structure for R=La-Ce (tP52, space group P4/nbm N 125-1) and new YNi6Si6-type structure for R=Y, Sm, Gd-Yb (tP52, space group P4barb2N 117) that are tetragonal derivative of NaZn13-type structure, like LaCo9Si4-type. The CeNi6Si6, GdNi6Si6, TbNi6Si6, DyNi6Si6 and HoNi6Si6 compounds are Curie-Weiss paramagnets down to ~30 K, and do not order magnetically down to 5 K. However, the inverse paramagnetic susceptibility of LaNi6Si6 does not follow Curie-Weiss law. The DyNi6Si6 shows ferromagnetic-like saturation behaviour at 5 K in applied fields of 50 kOe, giving rise to a magnetic moment value of 6.5 μB/f.u. in 50 kOe. The powder neutron diffraction study in zero applied filed indicates square modulated the c-collinear antiferromagnetic ordering of TbNi6Si6 with K=[±1/4, ±1/4, 0] wave vector below ~10 K. The CeNi6Si6, GdNi6Si6, TbNi6Si6, DyNi6Si6 and HoNi6Si6 compounds are Curie-Weiss paramagnets down to ~30 K, and do not order magnetically down to 4.2 K. The powder neutron diffraction study in zero applied filed indicates square modulated the c-collinear antiferromagnetic ordering of TbNi6Si6 with K=[±1/4, ±1/4, 0] wave vector below ~10 K.

A rapid assessment and response approach to review and enhance Advocacy, Communication and Social Mobilisation for Tuberculosis control in Odisha state, India

PubMed Central

2011-01-01

Background Tuberculosis remains a major public health problem in India with the country accounting for 1 in 5 of all TB cases reported globally. An advocacy, communication and social mobilisation project for Tuberculosis control was implemented and evaluated in Odisha state of India. The purpose of the study was to identify the impact of project interventions including the use of 'Interface NGOs' and involvement of community groups such as women's self-help groups, local government bodies, village health sanitation committees, and general health staff in promoting TB control efforts. Methods The study utilized a rapid assessment and response (RAR) methodology. The approach combined both qualitative field work approaches, including semi-structured interviews and focus group discussions with empirical data collection and desk research. Results Results revealed that a combination of factors including the involvement of Interface NGOs, coupled with increased training and engagement of front line health workers and community groups, and dissemination of community based resources, contributed to improved awareness and knowledge about TB in the targeted districts. Project activities also contributed towards improving health worker and community effectiveness to raise the TB agenda, and improved TB literacy and treatment adherence. Engagement of successfully treated patients also assisted in reducing community stigma and discrimination. Conclusion The expanded use of advocacy, communication and social mobilisation activities in TB control has resulted in a number of benefits. These include bridging pre-existing gaps between the health system and the community through support and coordination of general health services stakeholders, NGOs and the community. The strategic use of 'tailored messages' to address specific TB problems in low performing areas also led to more positive behavioural outcomes and improved efficiencies in service delivery. Implications for future studies are that a comprehensive and well planned range of ACSM activities can enhance TB knowledge, attitudes and behaviours while also mobilising specific community groups to build community efficacy to combat TB. The use of rapid assessments combined with other complementary evaluation approaches can be effective when reviewing the impact of TB advocacy, communication and social mobilisation activities. PMID:21663623

A rapid assessment and response approach to review and enhance advocacy, communication and social mobilisation for tuberculosis control in Odisha state, India.

PubMed

Kamineni, Vishnu Vardhan; Turk, Tahir; Wilson, Nevin; Satyanarayana, Srinath; Chauhan, Lakbir Singh

2011-06-10

Tuberculosis remains a major public health problem in India with the country accounting for 1 in 5 of all TB cases reported globally. An advocacy, communication and social mobilisation project for Tuberculosis control was implemented and evaluated in Odisha state of India. The purpose of the study was to identify the impact of project interventions including the use of 'Interface NGOs' and involvement of community groups such as women's self-help groups, local government bodies, village health sanitation committees, and general health staff in promoting TB control efforts. The study utilized a rapid assessment and response (RAR) methodology. The approach combined both qualitative field work approaches, including semi-structured interviews and focus group discussions with empirical data collection and desk research. Results revealed that a combination of factors including the involvement of Interface NGOs, coupled with increased training and engagement of front line health workers and community groups, and dissemination of community based resources, contributed to improved awareness and knowledge about TB in the targeted districts. Project activities also contributed towards improving health worker and community effectiveness to raise the TB agenda, and improved TB literacy and treatment adherence. Engagement of successfully treated patients also assisted in reducing community stigma and discrimination. The expanded use of advocacy, communication and social mobilisation activities in TB control has resulted in a number of benefits. These include bridging pre-existing gaps between the health system and the community through support and coordination of general health services stakeholders, NGOs and the community. The strategic use of 'tailored messages' to address specific TB problems in low performing areas also led to more positive behavioural outcomes and improved efficiencies in service delivery. Implications for future studies are that a comprehensive and well planned range of ACSM activities can enhance TB knowledge, attitudes and behaviours while also mobilising specific community groups to build community efficacy to combat TB. The use of rapid assessments combined with other complementary evaluation approaches can be effective when reviewing the impact of TB advocacy, communication and social mobilisation activities.

Structure based drug discovery for designing leads for the non-toxic metabolic targets in multi drug resistant Mycobacterium tuberculosis.

PubMed

Kaur, Divneet; Mathew, Shalu; Nair, Chinchu G S; Begum, Azitha; Jainanarayan, Ashwin K; Sharma, Mukta; Brahmachari, Samir K

2017-12-21

The problem of drug resistance and bacterial persistence in tuberculosis is a cause of global alarm. Although, the UN's Sustainable Development Goals for 2030 has targeted a Tb free world, the treatment gap exists and only a few new drug candidates are in the pipeline. In spite of large information from medicinal chemistry to 'omics' data, there has been a little effort from pharmaceutical companies to generate pipelines for the development of novel drug candidates against the multi drug resistant Mycobacterium tuberculosis. In the present study, we describe an integrated methodology; utilizing systems level information to optimize ligand selection to lower the failure rates at the pre-clinical and clinical levels. In the present study, metabolic targets (Rv2763c, Rv3247c, Rv1094, Rv3607c, Rv3048c, Rv2965c, Rv2361c, Rv0865, Rv0321, Rv0098, Rv0390, Rv3588c, Rv2244, Rv2465c and Rv2607) in M. tuberculosis, identified using our previous Systems Biology and data-intensive genome level analysis, have been used to design potential lead molecules, which are likely to be non-toxic. Various in silico drug discovery tools have been utilized to generate small molecular leads for each of the 15 targets with available crystal structures. The present study resulted in identification of 20 novel lead molecules including 4 FDA approved drugs (droxidropa, tetroxoprim, domperidone and nemonapride) which can be further taken for drug repurposing. This comprehensive integrated methodology, with both experimental and in silico approaches, has the potential to not only tackle the MDR form of Mtb but also the most important persister population of the bacterium, with a potential to reduce the failures in the Tb drug discovery. We propose an integrated approach of systems and structural biology for identifying targets that address the high attrition rate issue in lead identification and drug development We expect that this system level analysis will be applicable for identification of drug candidates to other pathogenic organisms as well.

Defining and Mapping Mammalian Coat Pattern Genes: Multiple Genomic Regions Implicated in Domestic Cat Stripes and Spots

PubMed Central

Eizirik, Eduardo; David, Victor A.; Buckley-Beason, Valerie; Roelke, Melody E.; Schäffer, Alejandro A.; Hannah, Steven S.; Narfström, Kristina; O'Brien, Stephen J.; Menotti-Raymond, Marilyn

2010-01-01

Mammalian coat patterns (e.g., spots, stripes) are hypothesized to play important roles in camouflage and other relevant processes, yet the genetic and developmental bases for these phenotypes are completely unknown. The domestic cat, with its diversity of coat patterns, is an excellent model organism to investigate these phenomena. We have established three independent pedigrees to map the four recognized pattern variants classically considered to be specified by a single locus, Tabby; in order of dominance, these are the unpatterned agouti form called “Abyssinian” or “ticked” (Ta), followed by Spotted (Ts), Mackerel (TM), and Blotched (tb). We demonstrate that at least three different loci control the coat markings of the domestic cat. One locus, responsible for the Abyssinian form (herein termed the Ticked locus), maps to an ∼3.8-Mb region on cat chromosome B1. A second locus controls the Tabby alleles TM and tb, and maps to an ∼5-Mb genomic region on cat chromosome A1. One or more additional loci act as modifiers and create a spotted coat by altering mackerel stripes. On the basis of our results and associated observations, we hypothesize that mammalian patterned coats are formed by two distinct processes: a spatially oriented developmental mechanism that lays down a species-specific pattern of skin cell differentiation and a pigmentation-oriented mechanism that uses information from the preestablished pattern to regulate the synthesis of melanin profiles. PMID:19858284

Defining and mapping mammalian coat pattern genes: multiple genomic regions implicated in domestic cat stripes and spots.

PubMed

Eizirik, Eduardo; David, Victor A; Buckley-Beason, Valerie; Roelke, Melody E; Schäffer, Alejandro A; Hannah, Steven S; Narfström, Kristina; O'Brien, Stephen J; Menotti-Raymond, Marilyn

2010-01-01

Mammalian coat patterns (e.g., spots, stripes) are hypothesized to play important roles in camouflage and other relevant processes, yet the genetic and developmental bases for these phenotypes are completely unknown. The domestic cat, with its diversity of coat patterns, is an excellent model organism to investigate these phenomena. We have established three independent pedigrees to map the four recognized pattern variants classically considered to be specified by a single locus, Tabby; in order of dominance, these are the unpatterned agouti form called "Abyssinian" or "ticked" (T(a)), followed by Spotted (T(s)), Mackerel (T(M)), and Blotched (t(b)). We demonstrate that at least three different loci control the coat markings of the domestic cat. One locus, responsible for the Abyssinian form (herein termed the Ticked locus), maps to an approximately 3.8-Mb region on cat chromosome B1. A second locus controls the Tabby alleles T(M) and t(b), and maps to an approximately 5-Mb genomic region on cat chromosome A1. One or more additional loci act as modifiers and create a spotted coat by altering mackerel stripes. On the basis of our results and associated observations, we hypothesize that mammalian patterned coats are formed by two distinct processes: a spatially oriented developmental mechanism that lays down a species-specific pattern of skin cell differentiation and a pigmentation-oriented mechanism that uses information from the preestablished pattern to regulate the synthesis of melanin profiles.

A hybrid computational strategy to address WGS variant analysis in >5000 samples.

PubMed

Huang, Zhuoyi; Rustagi, Navin; Veeraraghavan, Narayanan; Carroll, Andrew; Gibbs, Richard; Boerwinkle, Eric; Venkata, Manjunath Gorentla; Yu, Fuli

2016-09-10

The decreasing costs of sequencing are driving the need for cost effective and real time variant calling of whole genome sequencing data. The scale of these projects are far beyond the capacity of typical computing resources available with most research labs. Other infrastructures like the cloud AWS environment and supercomputers also have limitations due to which large scale joint variant calling becomes infeasible, and infrastructure specific variant calling strategies either fail to scale up to large datasets or abandon joint calling strategies. We present a high throughput framework including multiple variant callers for single nucleotide variant (SNV) calling, which leverages hybrid computing infrastructure consisting of cloud AWS, supercomputers and local high performance computing infrastructures. We present a novel binning approach for large scale joint variant calling and imputation which can scale up to over 10,000 samples while producing SNV callsets with high sensitivity and specificity. As a proof of principle, we present results of analysis on Cohorts for Heart And Aging Research in Genomic Epidemiology (CHARGE) WGS freeze 3 dataset in which joint calling, imputation and phasing of over 5300 whole genome samples was produced in under 6 weeks using four state-of-the-art callers. The callers used were SNPTools, GATK-HaplotypeCaller, GATK-UnifiedGenotyper and GotCloud. We used Amazon AWS, a 4000-core in-house cluster at Baylor College of Medicine, IBM power PC Blue BioU at Rice and Rhea at Oak Ridge National Laboratory (ORNL) for the computation. AWS was used for joint calling of 180 TB of BAM files, and ORNL and Rice supercomputers were used for the imputation and phasing step. All other steps were carried out on the local compute cluster. The entire operation used 5.2 million core hours and only transferred a total of 6 TB of data across the platforms. Even with increasing sizes of whole genome datasets, ensemble joint calling of SNVs for low coverage data can be accomplished in a scalable, cost effective and fast manner by using heterogeneous computing platforms without compromising on the quality of variants.

Possible misdiagnosis of HIV associated lymphoma as tuberculosis among patients attending Uganda Cancer Institute.

PubMed

Buyego, Paul; Nakiyingi, Lydia; Ddungu, Henry; Walimbwa, Stephen; Nalwanga, Damalie; Reynolds, Steven J; Parkes-Ratanshi, Rosalind

2017-03-14

Early diagnosis of HIV associated lymphoma is challenging because the definitive diagnostic procedure of biopsy, requires skills and equipment that are not readily available. As a consequence, diagnosis may be delayed increasing the risk of mortality. We set out to determine the frequency and risk factors associated with the misdiagnosis of HIV associated lymphoma as tuberculosis (TB) among patients attending the Uganda Cancer Institute (UCI). A retrospective cohort study design was used among HIV patients with associated lymphoma patients attending the UCI, Kampala, Uganda between February and March 2015. Eligible patient charts were reviewed for information on TB treatment, socio-demographics, laboratory parameters (Hemoglobin, CD4cells count and lactate dehydrogenase) and clinical presentation using a semi structured data extraction form. A total of 183 charts were reviewed; 106/183 were males (57.9%), the median age was 35 (IQR, 28-45). Fifty six (30.6%) patients had a possible misdiagnosis as TB and their median time on TB treatment was 3.5 (1-5.3) months. In multivariate analysis the presence of chest pain had an odd ratio (OR) of 4.4 (95% CI 1.89-10.58, p < 0.001) and stage III and IV lymphoma disease had an OR of 3.22 (95% CI 1.08-9.63, p < 0.037) for possible misdiagnosis of lymphoma as TB. A high proportion of patients with HIV associated lymphoma attending UCI are misdiagnosed and treated as TB. Chest pain and stage III and IV of lymphoma were associated with an increased risk of a possible misdiagnosis of lymphoma as TB.

Surface and Atmospheric Contributions to Passive Microwave Brightness Temperatures for Falling Snow Events

NASA Technical Reports Server (NTRS)

Skofronick-Jackson, Gail; Johnson, Benjamin T.

2011-01-01

Physically based passive microwave precipitation retrieval algorithms require a set of relationships between satellite -observed brightness temperatures (TBs) and the physical state of the underlying atmosphere and surface. These relationships are nonlinear, such that inversions are ill ]posed especially over variable land surfaces. In order to elucidate these relationships, this work presents a theoretical analysis using TB weighting functions to quantify the percentage influence of the TB resulting from absorption, emission, and/or reflection from the surface, as well as from frozen hydrometeors in clouds, from atmospheric water vapor, and from other contributors. The percentage analysis was also compared to Jacobians. The results are presented for frequencies from 10 to 874 GHz, for individual snow profiles, and for averages over three cloud-resolving model simulations of falling snow. The bulk structure (e.g., ice water path and cloud depth) of the underlying cloud scene was found to affect the resultant TB and percentages, producing different values for blizzard, lake effect, and synoptic snow events. The slant path at a 53 viewing angle increases the hydrometeor contributions relative to nadir viewing channels. Jacobians provide the magnitude and direction of change in the TB values due to a change in the underlying scene; however, the percentage analysis provides detailed information on how that change affected contributions to the TB from the surface, hydrometeors, and water vapor. The TB percentage information presented in this paper provides information about the relative contributions to the TB and supplies key pieces of information required to develop and improve precipitation retrievals over land surfaces.

Comparison of Cramer classification between Toxtree, the OECD QSAR Toolbox and expert judgment.

PubMed

Bhatia, Sneha; Schultz, Terry; Roberts, David; Shen, Jie; Kromidas, Lambros; Marie Api, Anne

2015-02-01

The Threshold of Toxicological Concern (TTC) is a pragmatic approach in risk assessment. In the absence of data, it sets up levels of human exposure that are considered to have no appreciable risk to human health. The Cramer decision tree is used extensively to determine these exposure thresholds by categorizing non-carcinogenic chemicals into three different structural classes. Therefore, assigning an accurate Cramer class to a material is a crucial step to preserve the integrity of the risk assessment. In this study the Cramer class of over 1000 fragrance materials across diverse chemical classes were determined by using Toxtree (TT), the OECD QSAR Toolbox (TB), and expert judgment. Disconcordance was observed between TT and the TB. A total of 165 materials (16%) showed different results from the two programs. The overall concordance for Cramer classification between TT and expert judgment is 83%, while the concordance between the TB and expert judgment is 77%. Amines, lactones and heterocycles have the lowest percent agreement with expert judgment for TT and the TB. For amines, the expert judgment agreement is 45% for TT and 55% for the TB. For heterocycles, the expert judgment agreement is 55% for TT and the TB. For lactones, the expert judgment agreement is 56% for TT and 50% for the TB. Additional analyses were conducted to determine the concordance within various chemical classes. Critical checkpoints in the decision tree are identified. Strategies and guidance on determining the Cramer class for various chemical classes are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Coloring the white plague: a syndemic approach to immigrant tuberculosis in Canada.

PubMed

Reitmanova, Sylvia; Gustafson, Diana L

2012-01-01

In this article, we adopt a syndemic approach to immigrant tuberculosis (TB) in Canada as a way of challenging contemporary epidemiological models of infectious diseases that tend to racialize and medicalize the risk of infections in socio-economically disadvantage populations and obscure the role of social conditions in sustaining the unequal distribution of diseases in these populations. A syndemic approach unravels social and biological connections which shape the distribution of infections over space and time and is useful in de-racializing and de-medicalizing these epidemiologic models. The socio-historic framework allows us to examine social factors which, refracted through medical science, were central to the development of TB control in Canada at the beginning of twentieth century. We expose the ideological assumptions about race, immigration, and social status which underpin current policies designed to control TB within the immigrant population. We argue that TB control policies which divert the attention from structural health determinants perpetuate health and social inequities of racialized populations in Canada. Medical screening and surveillance is an ineffective control policy because the proportion of TB cases attributed to immigrants increased from 18 to 66% between 1970 and 2007. More effective TB control policies require shifting the focus from the individual disease carriers toward social inequities which underlie the problem of immigrant TB in Canada. In addition, de-racialization and de-medicalization of the contemporary epidemiological models of infectious diseases entail an in-depth exploration of how the categories of ethnicity, culture, and immigration status are played out in everyday health-related experiences of racialized groups.

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0

PubMed Central

2014-01-01

Background We recently developed a freely available mobile app (TB Mobile) for both iOS and Android platforms that displays Mycobacterium tuberculosis (Mtb) active molecule structures and their targets with links to associated data. The app was developed to make target information available to as large an audience as possible. Results We now report a major update of the iOS version of the app. This includes enhancements that use an implementation of ECFP_6 fingerprints that we have made open source. Using these fingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape. Proposed compounds can also be compared to existing target data, using a näive Bayesian scoring system to rank probable targets. We have curated an additional 60 new compounds and their targets for Mtb and added these to the original set of 745 compounds. We have also curated 20 further compounds (many without targets in TB Mobile) to evaluate this version of the app with 805 compounds and associated targets. Conclusions TB Mobile can now manage a small collection of compounds that can be imported from external sources, or exported by various means such as email or app-to-app inter-process communication. This means that TB Mobile can be used as a node within a growing ecosystem of mobile apps for cheminformatics. It can also cluster compounds and use internal algorithms to help identify potential targets based on molecular similarity. TB Mobile represents a valuable dataset, data-visualization aid and target prediction tool. PMID:25302078

New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0.

PubMed

Clark, Alex M; Sarker, Malabika; Ekins, Sean

2014-01-01

We recently developed a freely available mobile app (TB Mobile) for both iOS and Android platforms that displays Mycobacterium tuberculosis (Mtb) active molecule structures and their targets with links to associated data. The app was developed to make target information available to as large an audience as possible. We now report a major update of the iOS version of the app. This includes enhancements that use an implementation of ECFP_6 fingerprints that we have made open source. Using these fingerprints, the user can propose compounds with possible anti-TB activity, and view the compounds within a cluster landscape. Proposed compounds can also be compared to existing target data, using a näive Bayesian scoring system to rank probable targets. We have curated an additional 60 new compounds and their targets for Mtb and added these to the original set of 745 compounds. We have also curated 20 further compounds (many without targets in TB Mobile) to evaluate this version of the app with 805 compounds and associated targets. TB Mobile can now manage a small collection of compounds that can be imported from external sources, or exported by various means such as email or app-to-app inter-process communication. This means that TB Mobile can be used as a node within a growing ecosystem of mobile apps for cheminformatics. It can also cluster compounds and use internal algorithms to help identify potential targets based on molecular similarity. TB Mobile represents a valuable dataset, data-visualization aid and target prediction tool.

Socioeconomic and Behavioral Factors Associated with Tuberculosis Diagnostic Delay in Lima, Peru.

PubMed

Bonadonna, Lily V; Saunders, Matthew J; Guio, Heinner; Zegarra, Roberto; Evans, Carlton A

2018-06-01

Early detection and diagnosis of tuberculosis (TB) is a global priority. Prolonged symptom duration before TB diagnosis is associated with increased morbidity, mortality, and risk of transmission. We aimed to determine socioeconomic and behavioral factors associated with diagnostic delays among patients with TB. Data were collected from 105 patients with TB using a semi-structured interview guide in Lima, Peru. Factors associated with diagnostic delay were analyzed using negative binomial regression. The median delay from when symptoms commenced and the first positive diagnostic sample in public health facilities was 57 days (interquartile range: 28-126). In multivariable analysis, greater diagnostic delay was independently associated with patient older age, female gender, lower personal income before diagnosis, living with fewer people, and having more visits to professional health facilities before diagnosis (all P < 0.05). Patients who first sought care at a private health facility had more visits overall to professional health facilities before diagnosis than those who first sought care from public or insured employee health facilities and had longer diagnostic delay in analysis adjusted for age and gender. Patients with TB were significantly more likely to first self-medicate than to visit professional health facilities before diagnosis ( P = 0.003). Thus, diagnostic delay was prolonged, greatest among older, low-income women, and varied according to the type of care sought by individuals when their symptoms commenced. These findings suggest that TB case-finding initiatives should target vulnerable groups in informal and private health facilities, where many patients with TB first seek health care.