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https://www.readbyqxmd.com/read/28735047/sesamol-exhibits-potent-antimycobacterial-activity-underlying-mechanisms-and-impact-on-virulence-traits
#1
Sandeep Hans, Sharda Sharma, Saif Hameed, Zeeshan Fatima
OBJECTIVES: Novel strategies to overcome multidrug resistance (MDR) in Tuberculosis (TB) still remain a concern. Usage of natural compounds nowadays to surmount the increasing burden of MDR-TB has shown promising results. The aim of this study was to evaluate the antimycobacterial potential of sesamol (Ses) a natural phenolic compound against Mycobacterium smegmatis, a surrogate for MTB and its underlying mechanism of action along with its effect on mycobacterial virulence traits. METHODS: Cell surface phenotypes were estimated microscopically and spectrophotometrically respectively...
July 19, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28734205/identification-of-mycobacterium-tuberculosis-enoyl-acyl-carrier-protein-reductase-inhibitors-a-combined-in-silico-and-in-vitro-analysis
#2
Mohsin Y Lone, Mohd Athar, Vivek K Gupta, Prakash C Jha
Mycobacterium tuberculosis (Mtb), had developed evolutionary changes in its genome to adapt for survival and thereby generated multi-drug resistant strains. However, novel drug targets that remained unchanged for their biochemical role has impressed the research community to target such proteins. The comprehensive analysis of multiple protein targets has influenced us to make a consensus structural rule exploited by pharmacophore and other allied techniques from a large repository of protein structures. In this pursuit, we made a retrospective analysis of pharmacophores mapped from the tuberculosis structural proteome and identified unique patterns that can be employed for the novel molecules design...
July 14, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28733605/genexpert-mtb-rif-assay-in-the-diagnosis-of-urinary-tuberculosis-from-urine-specimens
#3
Yu Pang, Yuanyuan Shang, Jie Lu, Qian Liang, Lingling Dong, Yunxu Li, Liping Zhao, Guanglu Jiang, Hairong Huang
Conventional bacteriological methods are not generally helpful in diagnosing urinary tuberculosis (UTB). GeneXpert is endorsed for the detection of pulmonary tuberculosis, whereas the data on its utility for urine specimens is limited. In this study, we aimed to evaluate its performance on urine specimens in a country with high TB incidence. A total of 163 suspected UTB patients were consecutively enrolled in the analysis, including 37 (22.7%) culture-positive and 44 (27.0%) clinically diagnosed UTB cases. Compared with conventional culture, the sensitivity of GeneXpert (94...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728275/-changes-and-differences-of-dna-methylation-in-human-macrophages-infected-with-virulent-and-avirulent-mycobacterium-tuberculosis
#4
L N Lyu, H Y Jia, Z H Li, Z Q Liu, Z D Zhang
Objective: To profile DNA methylation and compare differentially methylated region (DMR) of macrophages infected with virulent and avirulent strains of Mycobacterium tuberculosis (MTB). Methods: PMA(50 ng/ml) treated THP-1 macrophages were left uninfected or infected with the virulent H37Rv(THP-1/Rv) or avirulent H37Ra(THP-1/Ra). The genomic DNA was then extracted and DNA methylation was profiled via Reduced Representation Bisulfite Sequencing (RRBS). The DNA methylation pattern and DMRs between the tested samples were indentified...
July 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28727491/impact-of-point-of-care-xpert-mtb-rif-on-tuberculosis-treatment-initiation-a-cluster-randomised-trial
#5
Richard J Lessells, Graham S Cooke, Nuala McGrath, Mark P Nicol, Marie-Louise Newell, Peter Godfrey-Faussett
RATIONALE: Point-of-care (POC) diagnostics have potential to reduce pre-treatment loss to follow-up and delays to initiation of appropriate TB treatment. OBJECTIVE: To evaluate the effect of a POC diagnostic strategy on initiation of appropriate TB treatment. METHODS: A cluster randomised trial of adults with cough who were HIV positive and/or at high risk of drug-resistant TB. Two-week time blocks were randomised to two strategies (i) Xpert performed at district hospital laboratory (ii) POC Xpert performed at primary health care clinic...
July 20, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28723785/asymptomatic-congenital-tuberculosis-a-case-report
#6
Patrick M Meyer Sauteur, Ewerton Marques-Maggio, Christa Relly, Peter M Keller, Christian F Clarenbach, Christoph Berger
RATIONALE: Congenital tuberculosis (TB) is described as a rare, but severe disease. In contrast to the cases with severe symptoms reported so far, we describe a child with asymptomatic congenital TB. PATIENT CONCERNS: An 8-week-old girl was investigated because of newly diagnosed TB in her mother, which complained about cough since 21 weeks gestation. Lung biopsy tissue specimens of the mother revealed necrotizing granuloma with a single acid-fast bacillus (AFB) and Mycobacterium tuberculosis (MTB) was detected by polymerase chain reaction...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723242/interspecific-and-intraspecific-hybrid-epichlo%C3%A3-species-symbiotic-with-the-north-american-native-grass-poa-alsodes
#7
Tatsiana Shymanovich, Nikki D Charlton, Ashleigh M Musso, Jonathan Scheerer, Nadja B Cech, Stanley H Faeth, Carolyn A Young
The endophyte presence and diversity in natural populations of Poa alsodes were evaluated along a latitudinal transect from the southern distribution range in North Carolina to New York. Two distinct Epichloë hybrid taxa were identified from 23 populations. Each taxon could easily be distinguished by polymerase chain reaction (PCR) genotyping with primers designed to mating type genes and alkaloid biosynthesis genes that encode key pathway steps for ergot alkaloids, indole-diterpenes, lolines, and peramine...
June 26, 2017: Mycologia
https://www.readbyqxmd.com/read/28720766/predicting-susceptibility-to-tuberculosis-based-on-gene-expression-profiling-in-dendritic-cells
#8
John D Blischak, Ludovic Tailleux, Marsha Myrthil, Cécile Charlois, Emmanuel Bergot, Aurélien Dinh, Gloria Morizot, Olivia Chény, Cassandre Von Platen, Jean-Louis Herrmann, Roland Brosch, Luis B Barreiro, Yoav Gilad
Tuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the world's population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720502/design-synthesis-and-in-vitro-anti-mycobacterial-evaluation-of-gatifloxacin-1h-1-2-3-triazole-isatin-hybrids
#9
Zhi Xu, Shu Zhang, Xufeng Song, Min Qiang, Zaosheng Lv
A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-l was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12μg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but were much more toxic (CC50: 7.8-62.5μg/mL) than the parent gatifloxacin (GTFX) (CC50: 125μg/mL). Among them, 61 (MIC: 0.025μg/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28719821/bcg-old-workhorse-new-skills
#10
REVIEW
M Gengenbacher, N E Nieuwenhuizen, She Kaufmann
Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1(Mmar), Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4(+) T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination...
July 15, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28717766/practice-and-impact-of-multidisciplinary-tumor-boards-on-patient-management-a-prospective-study
#11
Raghid N Charara, Firas Y Kreidieh, Rania A Farhat, Karine A Al-Feghali, Katia E Khoury, Ali Haydar, Lara Nassar, Ghina Berjawi, Ali Shamseddine, Nagi S El Saghir
PURPOSE: Multidisciplinary tumor boards (MTBs) have become commonplace. The use, attendance, and function of MTBs need continued assessment and improvement. METHODS: We prospectively recorded and assessed all cases presented at MTBs between October 2013 and December 2014. Data were collected before and during each MTB. Data were analyzed using SPSS for Windows version 23 (SPSS, Chicago, IL). RESULTS: Five hundred three cases were presented: 234 cases (46%) at GI cancer MTBs, 149 cases (29...
June 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28717600/implementation-of-the-xpert-mtb-rif-assay-for-tuberculosis-in-mongolia-a-qualitative-exploration-of-barriers-and-enablers
#12
Nicole L Rendell, Solongo Bekhbat, Gantungalag Ganbaatar, Munkhjargal Dorjravdan, Madhukar Pai, Claudia C Dobler
OBJECTIVE: The aim of our study was to identify barriers and enablers to implementation of the Xpert MTB/RIF test within Mongolia's National Tuberculosis Program. METHODS: Twenty-foursemi-structured interviews were conducted between June and September 2015 with laboratory staff and tuberculosis physicians in Mongolia's capital Ulaanbaatar and regional towns where Xpert MTB/RIF testing had been implemented. Interviews were recorded, transcribed, translated and analysed thematically using NVIVO qualitative analysis software...
2017: PeerJ
https://www.readbyqxmd.com/read/28716809/determining-clinical-decision-thresholds-for-hiv-positive-patients-suspected-of-having-tuberculosis
#13
Tom Boyles, Isabella Locatelli, Nicolas Senn, Mark Ebell
Clinical decision thresholds may aid the evaluation of diagnostic tests but have rarely been determined for tuberculosis (TB). We presented clinicians with six web-based clinical scenarios, describing patients with HIV and possible TB at various sites and with a range of clinical stability. The probability of disease was varied randomly and clinicians asked to make treatment decisions; threshold curves and therapeutic thresholds were calculated. Test and treatment thresholds were calculated using Bayes theorem and the diagnostic accuracy of Xpert MTB/RIF...
July 17, 2017: Evidence-based Medicine
https://www.readbyqxmd.com/read/28716462/rapid-identification-of-a-mycobacterium-tuberculosis-full-genetic-drug-resistance-profile-through-whole-genome-sequencing-directly-from-sputum
#14
Camus Nimmo, Ronan Doyle, Carrie Burgess, Rachel Williams, Rebecca Gorton, Timothy D McHugh, Mike Brown, Stephen Morris-Jones, Helen Booth, Judith Breuer
INTRODUCTION: Resistance to second line tuberculosis drugs is common, but slow to diagnose with phenotypic drug sensitivity testing. Rapid molecular tests speed up diagnosis, but can only detect limited mutations. Whole genome sequencing (WGS) of culture isolates can generate a complete genetic drug resistance profile, but is delayed by the initial culture step. We previously successfully achieved WGS directly from sputum using targeted enrichment. CASE REPORT: A 29-year-old Nigerian lady was diagnosed with tuberculosis...
July 14, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28715935/new-findings-of-toll-like-receptors-involved-in-mycobacterium-tuberculosis-infection
#15
Majid Faridgohar, Hassan Nikoueinejad
Tuberculosis (TB), an important issue in the present age, affects millions of people each year. The infectious agent of TB, Mycobacterium tuberculosis (Mtb), interacts with the immune system which prevents the development of this bacterium as much as possible. In fact, the receptors on the surface of immune cells identify the bacteria, one of which is Toll-like receptors (TLRs). Different TLRs including 2, 4, 9 and 8 play critical roles in tuberculosis infection. In this paper, we focused on the role of TLRs which interact with different components of Mtb and, consequently, prevent the entrance and influence of bacteria on the body...
July 17, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28713838/role-of-interferons-in-the-development-of-diagnostics-vaccines-and-therapy-for-tuberculosis
#16
REVIEW
Kai Ling Chin, Fadhilah Zulkipli Anis, Maria E Sarmiento, Mohd Nor Norazmi, Armando Acosta
Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28711989/striking-the-right-immunological-balance-prevents-progression-of-tuberculosis
#17
REVIEW
Shachi Pranjal Vyas, Ritobrata Goswami
INTRODUCTION: 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...
July 15, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28710410/combining-molecular-typing-and-spatial-pattern-analysis-to-identify-areas-of-high-tuberculosis-transmission-in-a-moderate-incidence-county-in-taiwan
#18
Yih-Yuan Chen, Jia-Ru Chang, Chih-Da Wu, Yen-Po Yeh, Shiu-Ju Yang, Chih-Hao Hsu, Ming-Ching Lin, Ching-Fang Tsai, Ming-Shian Lin, Ih-Jen Su, Horng-Yunn Dou
In total, 303 randomly selected clinical Mycobacterium tuberculosis (MTB) isolates from 303 patients (collected January to December 2012) in central Taiwan were examined. The major lineages found were Beijing (N = 114, 37.62%), Haarlem (N = 76, 25.08%) and East African-Indian (EAI) (N = 42, 13.86%). Notably, younger persons (≤30 years old) were 6.58 times more likely to be infected with a Beijing genotype compared to older persons (>70 years) (p < 0.05). Combining molecular typing methods and geographical information system (GIS) analysis, we uncovered a twofold higher incidence of Beijing strains in a hotspot area (33%) compared to non-hotspot areas (17%)...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709488/endobronchial-ultrasound-experience-in-a-high-tuberculosis-prevalence-setting
#19
Balamugesh Thangakunam, Barney Thomas Jesudason Isaac, Devasahayam Jesudas Christopher
BACKGROUND: Most of the published endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) data are from the western countries, establishing the role of EBUS-TBNA in the diagnosis and staging of lung cancer. The etiology of mediastinal lymphadenopathy may be different in an ethnic group with a high prevalence of tuberculosis (TB). OBJECTIVE: To assess the etiology of mediastinal adenopathy in a high TB prevalence setting and to determine the performance of various tests in the diagnosis of tuberculous mediastinal lymphadenitis...
July 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28708968/rv3723-luca-coordinates-fatty-acid-and-cholesterol-uptake-in-mycobacterium-tuberculosis
#20
Evgeniya V Nazarova, Christine R Montague, Thuy La, Kaley M Wilburn, Neelima Sukumar, Wonsik Lee, Shannon Caldwell, David G Russell, Brian C VanderVen
Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb were previously unknown. Here, we identify and determine that the previously uncharacterized protein Rv3723/LucA, functions to integrate cholesterol and fatty acid uptake in Mtb. Rv3723/LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters by maintaining their stability...
June 27, 2017: ELife
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