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https://www.readbyqxmd.com/read/29243549/how-primary-care-reforms-influenced-health-indicators-in-manisa-district-in-turkey-lessons-for-general-practitioners
#1
Celalettin Cevik, Kaan Sozmen, Bulent Kilic
BACKGROUND: Turkish health reforms began in 2003 and brought some significant changes in primary care services. Few studies in Turkey compare the shift from health centres (HC) to family physicians (FP) approach, which was initiated by reforms. OBJECTIVES: This study compares health status indicators during the HC period before reforms (2003-2007) and the FP period after reforms (2008-2012) in Turkey. METHODS: This study encompasses time series data consisting of the results of a 10-year assessment (2003-2012) in Manisa district...
December 15, 2017: European Journal of General Practice
https://www.readbyqxmd.com/read/29243495/the-recombinant-fusion-protein-cfp10-esat6-difn-has-protective-effect-against-tuberculosis-in-guinea-pigs
#2
Natalya V Permyakova, Pavel A Belavin, Dariya S Pirozhkova, Elena G Ufimtseva, Sergey M Rozov, Sergey R Mursalimov, Yuriy V Sidorchuk, Elena A Uvarova, Alla A Zagorskaya, Tatiana V Marenkova, Svetlana V Bannikova, Evgeniy A Demidov, Konstantin V Starostin, Marionella A Kravchenko, Diana V Vakhrusheva, Roman B Berdnikov, Natalya I Eremeeva, Sergey N Skornyakov, Sergey E Peltek, Elena V Deineko
Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10-ESAT6-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response...
December 15, 2017: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/29242198/an-attenuated-quadruple-gene-mutant-of-mycobacterium-tuberculosis-imparts-protection-against-tuberculosis-in-guinea-pigs
#3
Ritika Kar Bahal, Shubhita Mathur, Priyanka Chauhan, Anil K Tyagi
Previously we had developed a triple gene mutant of M. tuberculosis (MtbΔmms) harbouring disruption in three genes namely mptpA, mptpB and sapM Though vaccination with MtbΔmms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with MtbΔmms resulted in some pathological damage to the spleens in the early phase of infection. In order to generate a strain that overcomes the pathology caused by MtbΔmms in spleen of guinea pigs and controls dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain...
December 14, 2017: Biology Open
https://www.readbyqxmd.com/read/29241819/cyclophostin-and-cyclipostins-analogs-new-promising-molecules-to-treat-mycobacterial-related-diseases
#4
Phuong Chi Nguyen, Abdeldjalil Madani, Pierre Santucci, Benjamin P Martin, Rishi R Paudel, Sandrine Delattre, Jean-Louis Herrmann, Christopher D Spilling, Laurent Kremer, Stéphane Canaan, Jean-François Cavalier
The progression of mycobacterial diseases requires the development of new therapeutics. Here, we evaluated the efficacy and selectivity of a panel of Cyclophostin and Cyclipostins analogs (CyCs) against various bacteria and mycobacteria. The activity of these 26 CyCs was first assayed using the agar plate method. Compounds exhibiting a 50-100% growth inhibition rate were then selected to determine their MIC using the REMA assay. The best drug candidate was further tested against mycobacterial clinical isolates and bacteria responsible for nosocomial infections...
December 11, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29236768/autophagy-induction-by-mycobacterium-indicus-pranii-promotes-mycobacterium-tuberculosis-clearance-from-raw-264-7-macrophages
#5
Bindu Singh, Mohd Saqib, Ananya Gupta, Pawan Kumar, Sangeeta Bhaskar
Mycobacterium indicus pranii (MIP) is a potent vaccine candidate against tuberculosis (TB) as it has demonstrated significant protection in animal models of tuberculosis as well as in clinical trials. Higher protective efficacy of MIP against TB as compared to BCG provoked the efforts to gain insight into the molecular mechanisms underlying MIP mediated protection against Mycobacterium tuberculosis (M.tb). Autophagy, initially described as a cell survival mechanism during starvation, also plays a key role in host resistance to M...
2017: PloS One
https://www.readbyqxmd.com/read/29234108/mother-to-newborn-transmission-of-mycobacterial-l-forms-and-v%C3%AE-2-t-cell-response-in-placentobiome-of-bcg-vaccinated-pregnant-women
#6
T Dimova, A Terzieva, L Djerov, V Dimitrova, A Nikolov, P Grozdanov, N Markova
The ability of bacteria to exist as a population of self-replicating forms with defective or entirely missing cell wall (L-forms) is an adaptive mechanism for their survival and reproduction under unfavorable conditions. Bacterial mother-to-fetus transfer is a universal phenomenon in the animal kingdom. However, data about vertical transfer of L bacterial forms are extremely scarce. Bacille Calmette-Guérin is an attenuated strain of M. bovis and the only licensed vaccine used for tuberculosis prevention. We already have shown that filterable L-forms of BCG exist freely in the vaccine and are able to reproduce and to form colonies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233822/hematopoietic-stem-cell-gene-therapy-for-ifn%C3%AE-r1-deficiency-protects-mice-from-mycobacterial-infections
#7
Miriam Hetzel, Adele Mucci, Patrick Blank, Ariane Hai Ha Nguyen, Jan Schiller, Olga Halle, Mark-Philipp Kühnel, Sandra Billig, Robert Meineke, Daniel Brand, Vanessa Herder, Wolfgang Baumgärtner, Franz-Christoph Bange, Ralph Goethe, Danny Jonigk, Reinhold Förster, Bernhard Gentner, Jean-Laurent Casanova, Jacinta Bustamante, Axel Schambach, Ulrich Kalinke, Nico Lachmann
Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare primary immunodeficiency, characterized by severe infections caused by weakly virulent mycobacteria. Bi-allelic null mutations in genes encoding interferon gamma (IFNγ) receptor 1 or -2 (IFNGR1, IFNGR2) result in a life-threatening disease phenotype in early childhood. Recombinant IFNγ therapy is inefficient and hematopoietic stem cell transplantation (HSCT) has a poor prognosis. Thus, we developed a HSC gene therapy approach using lentiviral vectors expressing Ifnγr1 either constitutively or myeloid-specifically...
December 12, 2017: Blood
https://www.readbyqxmd.com/read/29230214/exome-sequencing-identifies-a-novel-map3k14-mutation-in-recessive-atypical-combined-immunodeficiency
#8
Nikola Schlechter, Brigitte Glanzmann, Eileen Garner Hoal, Mardelle Schoeman, Britt-Sabina Petersen, Andre Franke, Yu-Lung Lau, Michael Urban, Paul David van Helden, Monika Maria Esser, Marlo Möller, Craig Kinnear
Primary immunodeficiency disorders (PIDs) render patients vulnerable to infection with a wide range of microorganisms and thus provide good in vivo models for the assessment of immune responses during infectious challenges. Priming of the immune system, especially in infancy, depends on different environmental exposures and medical practices. This may determine the timing and phenotype of clinical appearance of immune deficits as exemplified with early exposure to Bacillus Calmette-Guérin (BCG) vaccination and dissemination in combined immunodeficiencies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29230211/evaluation-of-aggregated-ag85b-antigen-for-its-biophysical-properties-immunogenicity-and-vaccination-potential-in-a-murine-model-of-tuberculosis-infection
#9
Faraz Ahmad, Swaleha Zubair, Pushpa Gupta, Umesh Datta Gupta, Rakesh Patel, Mohammad Owais
Protein aggregates have been reported to act as a reservoir that can release biologically active, native form of precursor protein. Keeping this fact into consideration, it is tempting to exploit protein aggregate-based antigen delivery system as a functional vaccine to expand desirable immunological response in the host. Herein, we explored the capacity of aggregated Ag85B of Mycobacterium tuberculosis (Mtb) to act as a prophylactic vaccine system that releases the precursor antigen in slow and sustained manner...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29230061/boosting-with-recombinant-mva-expressing-m-tuberculosis-%C3%AE-crystallin-antigen-augments-the-protection-imparted-by-bcg-against-tuberculosis-in-guinea-pigs
#10
Prachi Nangpal, Ritika Kar Bahal, Anil K Tyagi
Tuberculosis (TB) is one of the major causes of mortality all over the globe. BCG, the only vaccine available against this disease has been successful in preventing the severe forms of childhood TB. However, the unsatisfactory performance of BCG in controlling the adult pulmonary tuberculosis has made the development of an effective vaccine against M. tuberculosis a prime objective of the TB research. In this study, a genetically stable, marker-free recombinant MVA expressing α-crystallin of M. tuberculosis (rMVA...
December 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29228220/the-burden-of-presumed-tuberculosis-in-hospitalized-children-in-a-resource-limited-setting-in-papua-new-guinea-a-prospective-observational-study
#11
Villa Watch, Jimmy Aipit, Tina Kote-Yarong, Allanie Rero, John W Bolnga, Elvin Lufele, Moses Laman
Background: In Papua New Guinea, TB is considered to be a major public health problem, but little is known about the prevalence and prognosis of presumed TB in children. Methods: As part of a prospective hospital-based surveillance on the northern coast of mainland Papua New Guinea, the authors investigated the admission prevalence and case fatality rate associated with presumed TB over a 6-year period (2011-2016). All children admitted who were diagnosed with TB were followed-up until discharge or death...
December 8, 2017: International Health
https://www.readbyqxmd.com/read/29223317/sequential-strategy-for-the-ltbi-screening-of-newly-arrived-immigrants-in-vulnerable-social-situations
#12
Núria Serre-Delcor, Begoña Treviño-Maruri, M Teresa Tórtola, Manuel Fernández-Quevedo, Antoni Soriano-Arandes, Inés Oliveira-Souto, Mateu Espasa, Israel Molina, Carlos Ascaso
INTRODUCTION: Some studies indicate high prevalences of latent tuberculosis infection (LTBI) in the immigrant population, which is relevant because 5-10% of cases will develop active tuberculosis. The objective of this study is to describe the results of a sequential strategy in the newly-arrived immigrant population for the diagnosis of LTBI using the tuberculin skin test (TST) and IGRAs. METHODS: A retrospective descriptive study was carried out with immigrants between 6 and 35years of age from shelters, referred to an international health unit between July 2013 and June 2016...
December 6, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/29219122/towards-the-use-of-breath-for-detecting-mycobacterial-infection-a-case-study-in-a-murine-model
#13
Flavio Antonio Franchina, Theodore Robert Mellors, Minara Aliyeva, Jeffrey Wagner, Nirav Daphtary, Lennart Lundblad, Sarah M Fortune, Eric J Rubin, Jane E Hill
In the present research, the potential of breath analysis by comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GC×GC-MS) was investigated for the discrimination between healthy and infected mice. A pilot study employing a total of 16 animals was used to develop a method for breath analysis in a murine model for studying MTBC (Mycobacterium tuberculosis complex) using the M. bovis BCG (Bacillus Calmette-Guérin). Breath was collected in Tedlar bags and concentrated onto thermal desorption tubes for the subsequent analysis by GC×GC-MS...
December 8, 2017: Journal of Breath Research
https://www.readbyqxmd.com/read/29216358/rapid-protective-effects-of-early-bcg-on-neonatal-mortality-among-low-birth-weight-boys-observations-from-randomised-trials
#14
Sofie Biering-Sørensen, Kristoffer Jarlov Jensen, Ivan Monterio, Henrik Ravn, Peter Aaby, Christine Stabell Benn
Background: Three randomised trials (RCTs) in low-weight (LW, <2.5 kg) infants have shown that Bacille Calmette-Guérin (BCG) vaccine non-specifically reduces all-cause mortality in the neonatal period. Methods: Using data from three RCTs of early BCG (N=6,583) we examined potential sex-differences in the timing of the mortality reduction in the neonatal period, presenting meta-estimates of the main outcome mortality rate ratios (MRR) for BCG-vaccinated and controls...
December 5, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29215373/mangiferin-prevents-the-growth-of-gastric-carcinoma-by-blocking-the-pi3k-akt-signalling-pathway
#15
Min Du, Gang Wen, Juan Jin, Yuanguang Chen, Jun Cao, Aman Xu
The aim of the present study was to investigate the effects of mangiferin on gastric carcinoma cells and to determine the possible mechanisms underlying such effects. The MTT assay was performed to evaluate the antiproliferative effect of mangiferin. Following treatment, apoptosis rates of SGC-7901 were established by flow cytometry and laser confocal microscopy, and western blot analysis was used to detect the expression of apoptosis-related proteins. The MTT assay showed that mangiferin inhibited the proliferation of SGC-7901 and BCG-823 cells in a dose-dependent and time-dependent manner...
December 5, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29215013/allosteric-pyruvate-kinase-based-logic-gate-synergistically-senses-energy-and-sugar-levels-in-mycobacterium-tuberculosis
#16
Wenhe Zhong, Liang Cui, Boon Chong Goh, Qixu Cai, Peiying Ho, Yok Hian Chionh, Meng Yuan, Abbas El Sahili, Linda A Fothergill-Gilmore, Malcolm D Walkinshaw, Julien Lescar, Peter C Dedon
Pyruvate kinase (PYK) is an essential glycolytic enzyme that controls glycolytic flux and is critical for ATP production in all organisms, with tight regulation by multiple metabolites. Yet the allosteric mechanisms governing PYK activity in bacterial pathogens are poorly understood. Here we report biochemical, structural and metabolomic evidence that Mycobacterium tuberculosis (Mtb) PYK uses AMP and glucose-6-phosphate (G6P) as synergistic allosteric activators that function as a molecular "OR logic gate" to tightly regulate energy and glucose metabolism...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29214786/itpkc-and-slc11a1-gene-polymorphisms-and-gene-gene-interactions-in-korean-patients-with-kawasaki-disease
#17
Kyu Yeun Kim, Yoon Sun Bae, Woohyuk Ji, Dongjik Shin, Ho Seong Kim, Dong Soo Kim
PURPOSE: Kawasaki disease (KD) is an acute systemic vasculitis. Both the etiology of KD and the erythema of Bacille Calmette-Guérin (BCG) injection sites observed in the disease are poorly understood. We investigated the association between KD and single nucleotide polymorphisms (SNPs) in two candidate genes: inositol 1,4,5-triphosphate 3-kinase (ITPKC), a well-studied KD-associated gene, and solute carrier 11a1 (SLC11A1), which is associated with the hypersensitive reaction to the BCG strain in Koreans...
January 2018: Yonsei Medical Journal
https://www.readbyqxmd.com/read/29212486/emerging-concepts-and-spectrum-of-renal-injury-following-intravesical-bcg-for-non-muscle-invasive-bladder-cancer
#18
Azharuddin Mohammed, Zubair Arastu
BACKGROUND: Intravesical Bacilli Calmette-Guerin (IVBCG) therapy for non-muscle invasive bladder cancer (NMIBC) has long been in use successfully. Albeit rarely, we still face with its safety concerns more than 25 years on since its approval by US Food and Drug Agency in 1990. Local and systemic infection following intravesical BCG is widely reported as compared to immune mediated local or systemic hypersensitivity reactions involving kidneys; acute kidney injury (AKI) and other renal manifestations are well reported but not of chronic kidney disease (CKD)...
December 6, 2017: BMC Urology
https://www.readbyqxmd.com/read/29210987/prophylactic-sublingual-immunization-with-mycobacterium-tuberculosis-subunit-vaccine-incorporating-the-natural-killer-t-cell-agonist-alpha-galactosylceramide-enhances-protective-immunity-to-limit-pulmonary-and-extra-pulmonary-bacterial-burden-in-mice
#19
Arshad Khan, Shailbala Singh, Gloria Galvan, Chinnaswamy Jagannath, K Jagannadha Sastry
Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer), a potent natural killer T (NKT) cell agonist...
December 6, 2017: Vaccines
https://www.readbyqxmd.com/read/29209984/intravesical-thalidomide-boosts-bacillus-calmette-gu%C3%A3-rin-bcg-in-non-muscle-invasive-bladder-cancer-treatment
#20
Gabriela R Passos, Juliana A Camargo, Karen L Ferrari, Mário J A Saad, Amilcar C de Mattos, Leonardo O Reis
The aim of this study was to explore the efficacy of intravesical Thalidomide (immunomodulatory, anti-inflammatory and anti-angiogenic) added to BCG using an immune competent autochthonous orthotopic NMIBC animal model. Female Fischer 344 rats, 7 weeks of age, received every 2 weeks for four times, a dose of 1.5 mg/kg of N-methyl-N-nitrosourea (MNU) intravesically. The rats were randomized into four groups (n = 10 per group) to receive intravesical treatment once a week for 6 weeks as follows: control (0...
December 4, 2017: Medical Oncology
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