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Riti Sharan, Hee-Jeong Yang, Preeti Sule, Jeffrey D Cirillo
Reporter enzyme fluorescence (REF) utilizes substrates that are specific for enzymes present in target organisms of interest for imaging or detection by fluorescence or bioluminescence. We utilize BlaC, an enzyme expressed constitutively by all M. tuberculosis strains. REF allows rapid quantification of bacteria in lungs of infected mice. The same group of mice can be imaged at many time points, greatly reducing costs, enumerating bacteria more quickly, allowing novel observations in host-pathogen interactions, and increasing statistical power, since more animals per group are readily maintained...
February 26, 2018: Journal of Visualized Experiments: JoVE
Karuna D Sagili, Srinath Satyanarayana, Sarabjit S Chadha, Nevin C Wilson, Ajay M V Kumar, Patrick K Moonan, John E Oeltmann, Vineet K Chadha, Sharath Burugina Nagaraja, Smita Ghosh, Terrence Q Lo, Tyson Volkmann, Matthew Willis, Kalpita Shringarpure, Ravichandra Chinnappa Reddy, Prahlad Kumar, Sreenivas A Nair, Raghuram Rao, Mohammed Yassin, Perry Mwangala, Rony Zachariah, Jamhoih Tonsing, Anthony D Harries, Sunil Khaparde
BACKGROUND: The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices. OBJECTIVES: To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice...
2018: Global Health Action
Kirstin Harling, Ernest Adankwah, Alptekin Güler, Anthony Afum-Adjei Awuah, Louis Adu-Amoah, Ertan Mayatepek, Ellis Owusu-Dabo, Norman Nausch, Marc Jacobsen
T-cells critically contribute to protection against Mycobacterium tuberculosis infection, and impaired T-cell responses can lead to disease progression. Pro-inflammatory and immunosuppressive cytokines affect T-cells, and fine-tuned regulation of cytokine signaling via the Jak/STAT signaling pathways is crucial for appropriate T-cell function. Constitutive STAT3 phosphorylation as a consequence of aberrant cytokine signaling has been described to occur in pathognomonic T-cell responses in inflammatory and autoimmune diseases...
March 19, 2018: Cellular & Molecular Immunology
Nitin Gupta, Animesh Ray, Sudeshna Ghosh, Sundeep Malla, Surabhi Vyas
Tropical pulmonary eosinophilia (TPE) is a rare allergic manifestation to the filarial nematode. A 38-year old male and a 15-year old female presented with cough and breathlessness. Their complete blood count showed eosinophilia. This finding was overshadowed by the radiological findings suggestive of tuberculosis. The diagnosis of TPE was confirmed by filarial antigen detection test and both the patients were successfully treated with diethylcarbamazine. TPE presents with cough and breathlessness and can be often confused with tuberculosis, especially in endemic settings...
2018: Drug Discoveries & Therapeutics
Saahir Khan, Audrey Nakasone, Minoo Ghajar, Mariam Zhowandai, Sunita Prabhu, Rick Alexander, Julie Low, Ellena Peterson, Lauri Thrupp
For 94 patients with culture-positive pulmonary tuberculosis, time-to-detection (TTD), acid-fast bacilli (AFB) smear, and nucleic acid amplification test (NAAT) results were reviewed. All 12 patients whose first specimen was negative by AFB smear and NAAT had prolonged TTD, indicating low transmissibility and supporting discontinuing isolation for low-risk patients. Infect Control Hosp Epidemiol 2018;1-3.
March 19, 2018: Infection Control and Hospital Epidemiology
Jale Moradi, Maryam Izad, Mina Tabrizi, Nader Mosavari, Behnaz Esmaeili, Mohammad Mehdi Feizabadi
One third of the world population are latently infected with Mycobacterium tuberculosis and are at the risk of reactivation of tuberculosis (TB). The most effective strategy for control of TB worldwide is the development of a vaccine that inhibits progression of latent TB to active infection. In this study, two optimized constructs consisting of multi-epitopes DNA derived from three latency antigens Rv2029c, Rv2031c, and Rv2627c fused with or without light chain 3 (LC3) are synthetized. The immunogenicity effectiveness of two DNA constructs was evaluated in the mouse model...
March 19, 2018: Acta Microbiologica et Immunologica Hungarica
Ricardo Carrasco-Garcia, Patricia Barroso, Javier Perez-Olivares, Vidal Montoro, Joaquín Vicente
Understanding the role that facultative scavenger species may play in spreading infectious pathogens, and even becoming reservoirs for humans, domestic and wild ungulates or, on the contrary, preventing the spread of disease, requires a prior understanding of the pattern of carrion scavenging in specific scenarios. The objectives of this paper are (i) to describe the guild of vertebrate scavengers and (ii) to study the species-specific, habitat, and management-related factors involved in the usage of gut piles in South Central Spain (SCS), a tuberculosis (TB) endemic area...
2018: Frontiers in Veterinary Science
Raja Kalaiarasi, Chellappa Vijayakumar, Ramalingam Archana, Ramalingam Natarajan
Tuberculosis (TB) is a worldwide public health problem; however, primary tuberculous osteomyelitis involving the mandible is extremely rare. Here, we report a 14-year-old boy who presented with a recurrent, generalized swelling of the cheek in the right side, mimicking parotitis. Fine needle aspiration cytology (FNAC) from the swelling was inconclusive. Contrast-enhanced computed tomography (CECT) of the head and neck revealed an osteolytic lesion of the mandible with a surrounding abscess. An intraoral incisional biopsy of the tissue showed a granulomatous lesion...
January 15, 2018: Curēus
Peter Greaves
The aim of this study was to examine the impact of regional diets on the health of the poor in mid-Victorian Britain. Contemporary surveys of regional diets and living condition were reviewed. This information was compared with mortality data from Britain over the same period. Although there was an overall improvement in life expectancy during the latter part of the 19th century, there were large regional differences in lifestyle, diet and mortality rates. Dietary surveys showed that the poor labouring population in isolated rural areas of England, in the mainland and islands of Scotland and in the west of Ireland enjoyed the most nutritious diets...
March 2018: JRSM Open
Mistire Wolde, Alemayehu Fereja
Background: Determining burden of pulmonary tuberculosis (PTb) may be associated with success of directly observed theraphy (DOT) services in high PTb areas, such as Gambella, Ethiopia. Objective: To assess burden of sputum smear positive SSP-PTb reports in Gambella Regional Hospital, in two consecutive years: mid 2013 to 2015. Methods: From March 2013 to February 2015, PTb suspected patients' sputum Acid Fast Bacilli test results were collected from laboratory registration book of Gambella Regional Hospital, western Ethiopia...
2018: International Journal of Microbiology
Kartikeya Tiwari, Vikash Kumar Dubey
Asparaginase, a pivotal enzyme of the aspartate metabolic pathway is present as two variants in Leishmania donovani, causative agent of visceral leishmaniasis (VL). Our microscopy based analysis revealed that the green fluorescent protein tagged asparaginase variants were localized in the cytosol of the parasite. The finding was also supported by the in silico analysis of the L. donovani asparaginase variants. This finding is in strike contrast with other parasitic species such as M. tuberculosis where asparaginase is secreted out of the parasite...
March 15, 2018: International Journal of Biological Macromolecules
Shalini, Albertus Viljoen, Laurent Kremer, Vipan Kumar
The success in exploring anti-tubercular potency of nitroimidazole and quinoline, the core moieties of recently approved anti-tubercular drugs instigated us to synthesize a series of alkylated/aminated 2-methyl-5-nitroimidazoles and nitroimidazole-7-chloroquinoline conjugates and to evaluate them for their activities against Mycobacterium tuberculosis as well as for their cytotoxicity towards the J774 murine macrophage cell line. Although the synthesized compounds did not surpass the activity of the standard drug Isoniazid, they have appreciable activities with minimal cytotoxicity...
March 8, 2018: Bioorganic & Medicinal Chemistry Letters
Mitchell E Menezes, Praveen Bhoopathi, Anjan K Pradhan, Luni Emdad, Swadesh K Das, Chunqing Guo, Xiang-Yang Wang, Devanand Sarkar, Paul B Fisher
Subtraction hybridization identified genes displaying differential expression as metastatic human melanoma cells terminally differentiated and lost tumorigenic properties by treatment with recombinant fibroblast interferon and mezerein. This approach permitted cloning of multiple genes displaying enhanced expression when melanoma cells terminally differentiated, called melanoma differentiation associated (mda) genes. One mda gene, mda-7, has risen to the top of the list based on its relevance to cancer and now inflammation and other pathological states, which based on presence of a secretory sequence, chromosomal location, and an IL-10 signature motif has been named interleukin-24 (MDA-7/IL-24)...
2018: Advances in Cancer Research
Jana Amlerova, Ibrahim Bitar, Jaroslav Hrabak
Tuberculosis (TB) is considered one of the most serious infectious diseases worldwide. Effective control of tuberculosis infection involves multiple steps, such as reliable detection, treatment, an epidemiological control as a part of case management, and further surveillance and monitoring of TB spread in the human population. Due to the accelerating advances in molecular biology, especially in DNA sequencing, in the past decade, the application of these methods has become crucial for TB evolution studies, differentiation of Mycobacterium tuberculosis genotypes, and their distribution...
March 17, 2018: Folia Microbiologica
Kunal C Shah, Akshay Gadia, Premik Nagad, Shekhar Bhojraj, Abhay Nene
Buckling collapse is the term typically used to describe severe kyphosis more than 100 degrees, characteristically seen in thoracolumbar tuberculosis. Neurofibromatosis is rarely associated with severe cervical kyphosis. Dystrophic changes in vertebra make surgical correction and fusion challenging. Single stage cervical osteotomies (pedicle subtraction osteotomy, vertebral column resection etc) are commonly done in cervico-thoracic junction. However it is technically challenging and associated with high risk of vertebral artery injury, neural injury etc when performed in higher cervical spine...
March 14, 2018: World Neurosurgery
Cristian Alfredo Segura-Cerda, Michel de Jesús Aceves-Sánchez, Brenda Marquina-Castillo, Dulce Mata-Espinoza, Jorge Barrios-Payán, Perla Jazmín Vega-Domínguez, César Pedroza-Roldán, Jorge Bravo-Madrigal, Alba Adriana Vallejo-Cardona, Rogelio Hernández-Pando, Mario Alberto Flores-Valdez
Pellicles, a type of biofilm, have gathered a renewed interest in the field of tuberculosis as a structure that mimics some characteristics occurring during M. tuberculosis infection, such as antibiotic recalcitrance and chronicity of infection, and as a source of antigens for humoral response in infected guinea pigs. In other bacteria, it has been well documented that the second messenger c-di-GMP modulates the transition from planktonic cells to biofilm formation. In this work, we used the live vaccine Mycobacterium bovis BCG to determine whether deletion of genes involved in c-di-GMP metabolism would affect interaction with macrophages, capacity to induce immune response in a murine cell line and mice, and how the protein profile was modified when grown as surface pellicles...
March 14, 2018: Vaccine
André Campaniço, Rui Moreira, Francisca Lopes
Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy...
March 9, 2018: European Journal of Medicinal Chemistry
Suman K Paine, Analabha Basu, Rajib Gon Choudhury, Basudev Bhattacharya, Sidhartha Chatterjee, Chandra Bhattacharya
AIM: Genital tuberculosis (GTB) is a potent contributor to irreversible damage to the reproductive system and infertility in females. As no gold standard diagnostic tool is yet available, clinical suspicion and relatively insensitive approaches such as histopathology, laparoscopy and hysterosalpingogram are currently critical determinants in the diagnosis of GTB. Although a polymerase chain reaction (PCR)-based assay using endometrial tissue seems promising, sampling does require an invasive procedure...
March 16, 2018: Molecular Diagnosis & Therapy
R J Orton, M Deason, P R Bessell, D M Green, R R Kao, L C M Salvador
Bovine tuberculosis (bTB) is a chronic zoonosis with major health and economic impact on the cattle industry. Despite extensive control measures in cattle and culling trials in wildlife, the reasons behind the expansion of areas with high incidence of bTB breakdowns in Great Britain remain unexplained. By balancing the importance of cattle movements and local transmission on the observed pattern of cattle outbreaks, we identify areas at elevated risk of infection from specific Mycobacterium bovis genotypes...
March 1, 2018: Epidemics
Helen Cox, Jennifer Hughes, John Black, Mark P Nicol
Treatment for drug-resistant tuberculosis is largely delivered through standardised, empirical combination regimens in low-resource, high-burden settings. However, individualised treatment, guided by detailed drug susceptibility testing, probably results in improved individual outcomes and is the standard of care in well-resourced settings. Driven by the urgent need to scale up treatment provision, new tuberculosis drugs, incorporated into standardised regimens, are being tested. Although standardised regimens are expected to improve access to treatment in high-burden settings, they are also likely to contribute to the emergence of resistance, even with good clinical management...
March 13, 2018: Lancet Infectious Diseases
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