Bacteriophage therapy as an alternative treatment for human infections. A comprehensive review

Author: Kakasis, Athanasios; Panitsa, Gerasimia Description: Bacteriophages, or phages, are viruses that infect bacteria. They were discovered around a century ago and have been used ever since for therapeutic purposes, particularly in former Soviet Union countries. Their use in Western countries was abandoned after the discovery and broad use of penicillin. The rising problem of antimicrobial resistance has revived interest in bacteriophage therapy. The aim of this article is to provide a comprehensive review of all aspects of natural phage therapy. Subject headings: Animals; Bacteria; Bacterial Infections; Bacteriophages; Humans; Phage…

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Bacteriophage resistance mechanisms

Author: Labrie, Simon J.; Samson, Julie E.; Moineau, Sylvain Description: Phages are now acknowledged as the most abundant microorganisms on the planet and are also possibly the most diversified. This diversity is mostly driven by their dynamic adaptation when facing selective pressure such as phage resistance mechanisms, which are widespread in bacterial hosts. When infecting bacterial cells, phages face a range of antiviral mechanisms, and they have evolved multiple tactics to avoid, circumvent or subvert these mechanisms in order to thrive in most environments. In this Review, we highlight the…

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Diabetes and climate change: current evidence and implications for people with diabetes, clinicians and policy stakeholders

Author: Ratter-Rieck, Jacqueline M.; Roden, Michael; Herder, Christian Description: Climate change will be a major challenge for the world’s health systems in the coming decades. Elevated temperatures and increasing frequencies of heat waves, wildfires, heavy precipitation and other weather extremes can affect health in many ways, especially if chronic diseases are already present. Impaired responses to heat stress, including compromised vasodilation and sweating, diabetes-related comorbidities, insulin resistance and chronic low-grade inflammation make people with diabetes particularly vulnerable to environmental risk factors, such as extreme weather events and air pollution. Additionally,…

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Psychotropic medications and HIV

Author: Thompson, Alex; Silverman, Benjamin; Dzeng, Liz; Treisman, Glenn Description: Patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome have high rates of psychiatric illness. The effective management of these psychiatric conditions can improve a patient’s quality of life and may improve antiretroviral adherence. Care providers for patients with HIV infection frequently encounter clinical situations in which psychotropic medications are needed or are being used. Those clinical situations require familiarity with the broad category of medications termed “psychotropic.” That familiarity should include a basic understanding of indications,…

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TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss

Author: Kassem, A.; Henning, P.; Kindlund, B.; Lindholm, C.; Lerner, U.H. Description: Accumulating evidence points to the importance of the innate immune system in inflammation-induced bone loss in infectious and autoimmune diseases. TLRs are well known for being activated by ligands expressed by bacteria, viruses, and fungi. Recent findings indicate that also endogenous ligands in inflammatory processes are important, one being a TLR5 agonist present in synovial fluid from patients with rheumatoid arthritis (RA). We found that activation of TLR5 by its specific ligand, flagellin, caused robust osteoclast formation and…

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SHERLOCK: nucleic acid detection with CRISPR nucleases

Author: Kellner, Max J.; Koob, Jeremy G.; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Zhang, Feng Description: Rapid detection of nucleic acids is integral to applications in clinical diagnostics and biotechnology. We have recently established a CRISPR-based diagnostic platform that combines nucleic acid pre-amplification with CRISPR-Cas enzymology for specific recognition of desired DNA or RNA sequences. This platform, termed specific high-sensitivity enzymatic reporter unlocking (SHERLOCK), allows multiplexed, portable, and ultra-sensitive detection of RNA or DNA from clinically relevant samples. Here, we provide step-by-step instructions for setting up SHERLOCK assays with recombinase-mediated…

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Preclinical Assessment of CD171-Directed CAR T-cell Adoptive Therapy for Childhood Neuroblastoma: CE7 Epitope Target Safety and Product Manufacturing Feasibility

Author: Kunkele, A.; Taraseviciute, A.; Finn, L.S.; Johnson, A.J.; Berger, C.; Finney, O.; Chang, C.A.; Rolczynski, L.S.; Brown, C.; Mgebroff, S.; Berger, M.; Park, J.R.; Jensen, M.C. Description: PURPOSE: The identification and vetting of cell surface tumor-restricted epitopes for chimeric antigen receptor (CAR)-redirected T-cell immunotherapy is the subject of intensive investigation. We have focused on CD171 (L1-CAM), an abundant cell surface molecule on neuroblastomas and, specifically, on the glycosylation-dependent tumor-specific epitope recognized by the CE7 monoclonal antibody. EXPERIMENTAL DESIGN: CD171 expression was assessed by IHC using CE7 mAb in tumor…

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Fecal Bacteria, Bacteriophage, and Nutrient Reductions in a Full-Scale Denitrifying Woodchip Bioreactor

Author: Rambags, F.; Tanner, C.C.; Stott, R.; Schipper, L.A. Description: Denitrifying bioreactors using woodchips or other slow-release carbon sources can be an effective method for removing nitrate (NO) from wastewater and tile drainage. However, the ability of these systems to remove fecal microbes from wastewater has been largely uninvestigated. In this study, reductions in fecal indicator bacteria and viruses (F-specific RNA bacteriophage [FRNA phage]) were analyzed by monthly sampling along a longitudinal transect within a full-scale denitrifying woodchip bioreactor receiving secondary-treated septic tank effluent. Nitrogen, phosphorus, 5-d carbonaceous biochemical oxygen…

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A lanthipeptide library used to identify a protein-protein interaction inhibitor

Author: Yang, X.; Lennard, K.R.; He, C.; Walker, M.C.; Ball, A.T.; Doigneaux, C.; Tavassoli, A.; van der Donk, W.A. Description: In this article we describe the production and screening of a genetically encoded library of 10(6) lanthipeptides in Escherichia coli using the substrate-tolerant lanthipeptide synthetase ProcM. This plasmid-encoded library was combined with a bacterial reverse two-hybrid system for the interaction of the HIV p6 protein with the UEV domain of the human TSG101 protein, which is a critical protein-protein interaction for HIV budding from infected cells. Using this approach, we…

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Revenge of the phages: defeating bacterial defences

Author: Samson, J.E.; Magadan, A.H.; Sabri, M.; Moineau, S. Description: Bacteria and their viral predators (bacteriophages) are locked in a constant battle. In order to proliferate in phage-rich environments, bacteria have an impressive arsenal of defence mechanisms, and in response, phages have evolved counter-strategies to evade these antiviral systems. In this Review, we describe the various tactics that are used by phages to overcome bacterial resistance mechanisms, including adsorption inhibition, restriction-modification, CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems and abortive infection. Furthermore, we consider how these observations have…

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