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https://www.readbyqxmd.com/read/28926428/dna-methyltransferase-inhibitors-in-myeloid-cancer-clonal-eradication-or-clonal-differentiation
#1
Andreas Due Ørskov, Kirsten Grønbæk
DNA methyltransferase inhibitors, so-called hypomethylating agents (HMAs), are the only drugs approved for the treatment of higher-risk myelodysplastic syndromes and are widely used in this context. However, it is still unclear why some patients respond to HMAs, whereas others do not. Recent sequencing efforts have identified molecular disease entities that may be specifically sensitive to these drugs, and many attempts are being made to clarify how HMAs affect the malignant clone during treatment. Here, we review the most recent data on the clinical effects of HMAs in myeloid malignancies...
September 2017: Cancer Journal
https://www.readbyqxmd.com/read/28926399/natural-killer-cells-in-hiv-1-infection-and-therapy
#2
Joanna Mikulak, Ferdinando Oriolo, Elisa Zaghi, Clara Di Vito, Domenico Mavilio
: Natural killer (NK) cells are important effectors of innate immunity playing a key role in the eradication and clearance of viral infections. Over the recent years, several studies have shown that HIV-1 pathologically changes NK cell homeostasis and hampers their antiviral effector functions. Moreover, high levels of chronic HIV-1 viremia markedly impair those NK cell regulatory features that normally regulate the cross-talks between innate and adaptive immune responses. These pathogenic events take place early in the infection and are associated with a pathologic redistribution of NK cell subsets that includes the expansion of anergic CD56 NK cells with an aberrant repertoire of activating and inhibitory receptors...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926080/polio-n%C3%A3-rmar-sig-utrotning
#3
Erling Norrby, Ingrid Uhnoo, Mia Brytting, Katherina Zakikhany, Tiia Lepp, Patrick Olin
Polio close to eradication The WHO Global Polio Eradication Initiative has been highly successful. With a dramatic decrease in polio since it started in 1988, the number of globally reported cases reached a record low of 37 in 2016. This article describes the WHO Endgame Strategic Plan including milestones that have been reached and challenges that have to be overcome in order to reach the goal of polio eradication by 2020. Efforts to strengthen immunizations systems and to detect and interrupt polio virus transmission focus on the three remaining endemic countries, namely Pakistan, Afghanistan and Nigeria...
September 19, 2017: Läkartidningen
https://www.readbyqxmd.com/read/28926033/working-towards-consensus-the-need-for-coordinated-policies-to-assist-control-of-foot-and-mouth-disease-and-emerging-disease-threats-in-south-east-asia
#4
I W Patrick, S Sovann, S Socheat
Foot and mouth disease (FMD) is an important transboundary disease in South-East Asia. Its control has been a priority in the region for at least 20 years, with extensive institutional support and capacity-building being provided by the international community through the World Organisation for Animal Health. This paper describes the FMD control and eradication programme in the Mekong region (Myanmar, Thailand, the Lao People's Democratic Republic, Cambodia and Vietnam) of South-East Asia and evaluates the FMD control programme in one of the region's countries, namely Cambodia...
April 2017: Revue Scientifique et Technique
https://www.readbyqxmd.com/read/28926013/insights-for-the-assessment-of-the-economic-impact-of-endemic-diseases-specific-adaptation-of-economic-frameworks-using-the-case-of-bovine-viral-diarrhoea
#5
A W Stott, G J Gunn
Generic frameworks for the economic analysis of farm animal disease are now well established. The paper, therefore, uses bovine viral diarrhoea (BVD) as an example to explore how these frameworks need to be adapted to fit the characteristics of a particular disease and the specific objectives of the analysis. In the case of BVD, given the relative strength of tests available to correctly identify virus-positive animals, thus enabling them to be culled, the emphasis has been on cost-benefit analysis of regional and national certification/eradication schemes...
April 2017: Revue Scientifique et Technique
https://www.readbyqxmd.com/read/28926004/where-to-next-with-animal-health-in-latin-america-the-transition-from-endemic-to-disease-free-status
#6
H Rojas, J R Romero
The Latin American and Caribbean region (LAC) is a leading global producer and exporter of animal products. Its livestock production systems are diverse, ranging from large-scale commercial enterprises to family farms. Countries in this region have sought to improve their animal health status through both public and private efforts. Despite significant advances in eradicating such diseases as foot and mouth disease and classical swine fever, other animal health challenges remain; constraining exports, causing negative economic impacts and threatening food security...
April 2017: Revue Scientifique et Technique
https://www.readbyqxmd.com/read/28925992/efficacy-of-combining-ing4-and-trail-genes-in-cancer-targeting-gene-virotherapy-strategy-first-evidence-in-preclinical-hepatocellular-carcinoma
#7
A G El-Shemi, A M Ashshi, E Oh, B-K Jung, M Basalamah, A Alsaegh, C-O Yun
Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4); as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL); as potent-apoptosis inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono-and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC...
September 19, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28924294/meatal-obstruction-following-canal-wall-down-mastoidectomy
#8
Nazim Bozan, Ufuk Duzenli, Pinar Kundi, Mahfuz Turan, Ahmet Faruk Kiroglu
Chronic otitis media (COM) is completely treated with a single procedure in most patients but may require multiple surgeries in some cases. The main goals of open cavity mastoidectomy are to completely eradicate the disease, create a large enough meatus for examination and mastoid air cells, and provide a self-cleaning epithelized dry cavity, and achieve maximum hearing. In this report, we present a very rare case of COM who underwent revision mastoidectomy in our clinic due to meatal obstruction in the right ear, total sensorineural hearing loss, and pain and tenderness in the postauricular region...
September 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28924108/proton-pump-inhibitor-induction-of-gastric-cobblestone-like-lesions-in-the-stomach
#9
Kosuke Takahari, Ken Haruma, Hiroshi Ohtani, Sho Kiyoto, Akifumi Watanabe, Tomoari Kamada, Noriaki Manabe, Yu Hatano
Objective The long-term use of proton pump inhibitors (PPIs) may induce adverse events in many organs, including the stomach. The chronic use of PPIs has been associated with the growth of fundic gland polyps (FGPs) and of gastric black spots. This study assessed the incidence of gastric lesions with cobblestone-like appearance in PPI users. Methods The clinical characteristics and endoscopic findings of patients who underwent upper gastrointestinal endoscopy after using PPIs for at least six months were analyzed...
September 15, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28923920/microrna-dysregulation-to-identify-therapeutic-target-combinations-for-chronic-lymphocytic-leukemia
#10
Laura Z Rassenti, Veronica Balatti, Emanuela M Ghia, Alexey Palamarchuk, Luisa Tomasello, Paolo Fadda, Yuri Pekarsky, George F Widhopf, Thomas J Kipps, Carlo M Croce
Loss of miR-15/16 is the most common genetic lesion in chronic lymphocytic leukemia (CLL), promoting overexpression of BCL2, which factors in leukemia pathogenesis. Indeed, an inhibitor of Bcl2, venetoclcax, is highly active in the treatment of patients with CLL. However, single-agent venetoclcax fails to eradicate minimal residual disease in most patients. Accordingly, we were interested in other genes that may be regulated by miR-15/16, which may target other drivers in CLL. We found that miR-15/16 targets ROR1, which encodes an onco-embryonic surface protein expressed on the CLL cells of over 90% of patients, but not on virtually all normal postpartum tissues...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923873/an-anti-persister-strategy-for-the-treatment-of-chronic-pseudomonas-aeruginosa-infections
#11
Martina Koeva, Alina D Gutu, Wesley Hebert, Jeffrey D Wager, Lael M Yonker, George A O'Toole, Frederick M Ausubel, Samuel M Moskowitz, Diane Joseph-McCarthy
Bacterial persisters are a quasi-dormant sub-population of cells that are tolerant to antibiotic treatment. The combination of the aminoglycoside tobramycin with fumarate as an antibacterial potentiator utilizes an anti-persister strategy that is aimed at reducing recurrent Pseudomonas aeruginosa infections by enhancing the killing of P. aeruginosa persisters. Stationary phase cultures of P. aeruginosa were used to generate persister cells. A range of tobramycin concentrations was tested with a range of metabolite concentrations to determine the potentiation effect of the metabolite under a variety of conditions, including a range of pH values and in the presence of azithromycin or cystic fibrosis (CF) patient sputum...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28922967/contemporary-hiv-aids-research-insights-from-knowledge-management-theory
#12
Chris William Callaghan
Knowledge management as a field is concerned with the management of knowledge, including the management of knowledge in research processes. Knowledge management theory has the potential to support research into problems such as HIV, antibiotic resistance and others, particularly in terms of aspects of scientific research related to the contribution of social science. To date, however, these challenges remain with us, and theoretical contributions that can complement natural science efforts to eradicate these problems are needed...
December 2017: SAHARA J: Journal of Social Aspects of HIV/AIDS Research Alliance
https://www.readbyqxmd.com/read/28922704/direct-acting-antivirals-for-chronic-hepatitis-c
#13
REVIEW
Janus C Jakobsen, Emil Eik Nielsen, Joshua Feinberg, Kiran Kumar Katakam, Kristina Fobian, Goran Hauser, Goran Poropat, Snezana Djurisic, Karl Heinz Weiss, Milica Bjelakovic, Goran Bjelakovic, Sarah Louise Klingenberg, Jian Ping Liu, Dimitrinka Nikolova, Ronald L Koretz, Christian Gluud
BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence...
September 18, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28922635/fucoidan-coated-ciprofloxacin-loaded-chitosan-nanoparticles-for-the-treatment-of-intracellular-and-biofilm-infections-of-salmonella
#14
Elbi S, Nimal T R, Rajan V K, Gaurav Baranwal, Raja Biswas, Jayakumar R, Sathianarayanan S
Salmonella infections and their gallstone associated biofilm infections are difficult to treat due to poor penetration of antibiotics into the intracellular compartments of macrophages and within biofilms. Here we developed ciprofloxacin loaded chitosan nanoparticles (cCNPs) and fucoidan (Fu) coated cCNPs (Fu-cCNPs). Characterizations of these nanoparticles were carried out using Dynamic Light Scattering‎, Transmission electron microscopy and Fourier transform infrared spectroscopy. The prepared cCNPs and Fu-cCNPs have the size range of 124±7nm and 320±18nm, respectively...
September 5, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28922433/bismuth-based-quadruple-therapy-following-h-pylori-eradication-failures-a-multicenter-study-in-clinical-practice
#15
Angelo Zullo, Vincenzo De Francesco, Annamaria Bellesia, Roberto Vassallo, Audenzio D'Angelo, Giuseppe Scaccianoce, Rodolfo Sacco, Giampaolo Bresci, Annarita Eramo, Anna Tanzilli, Lorenzo Ridola, Domenico Alvaro, Claudio Londoni, Gianfranco Brambilla, Raffaele Manta, Agostino Di Ciaula, Piero Portincasa
BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice. METHODS: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy...
September 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28921621/-but-we-want-to-work-the-movement-of-child-workers-in-peru-and-the-actions-for-reducing-child-labor
#16
Isidro Maya Jariego
The program Edúcame Primero (Educate Me First) is an evidence-based practice for eradicating child labor that has been applied with positive results in Colombia, Peru, and several Central American countries. In this article, we describe the difficulties of implementing the program in two poor areas of Lima (Peru) between 2014 and 2016. Specifically, we discuss three ethical challenges faced during the implementation of the program: (a) the existence of a movement of working children that defends the right of children to work; (b) the polarization of some community-based associations and government institutions on how to deal with the problems of working children; and (c) the use of network indicators in the evaluation of the community's level of cohesion...
September 18, 2017: American Journal of Community Psychology
https://www.readbyqxmd.com/read/28921309/lung-cancer-associated-brain-metastasis-molecular-mechanisms-and-therapeutic-options
#17
REVIEW
Meysam Yousefi, Tayyeb Bahrami, Arash Salmaninejad, Rahim Nosrati, Parisa Ghaffari, Seyed H Ghaffari
BACKGROUND: Lung cancer is the most common cause of cancer-related mortality in humans. There are several reasons for this high rate of mortality, including metastasis to several organs, especially the brain. In fact, lung cancer is responsible for approximately 50% of all brain metastases, which are very difficult to manage. Understanding the cellular and molecular mechanisms underlying lung cancer-associated brain metastasis brings up novel therapeutic promises with the hope to ameliorate the severity of the disease...
September 18, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#18
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28920920/er-associated-degradation-is-required-for-vasopressin-prohormone-processing-and-systemic-water-homeostasis
#19
Guojun Shi, Diane Somlo, Geun Hyang Kim, Cristina Prescianotto-Baschong, Shengyi Sun, Nicole Beuret, Qiaoming Long, Jonas Rutishauser, Peter Arvan, Martin Spiess, Ling Qi
Peptide hormones are crucial regulators of many aspects of human physiology. Mutations that alter these signaling peptides are associated with physiological imbalances that underlie diseases. However, the conformational maturation of peptide hormone precursors (prohormones) in the ER remains largely unexplored. Here, we report that conformational maturation of proAVP, the precursor for the antidiuretic hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28920918/mice-deficient-for-erad-machinery-component-sel1l-develop-central-diabetes-insipidus
#20
Daniel G Bichet, Yoann Lussier
Deficiency of the antidiuretic hormone arginine vasopressin (AVP) underlies diabetes insipidus, which is characterized by the excretion of abnormally large volumes of dilute urine and persistent thirst. In this issue of the JCI, Shi et al. report that Sel1L-Hrd1 ER-associated degradation (ERAD) is responsible for the clearance of misfolded pro-arginine vasopressin (proAVP) in the ER. Additionally, mice with Sel1L deficiency, either globally or specifically within AVP-expressing neurons, developed central diabetes insipidus...
September 18, 2017: Journal of Clinical Investigation
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