# ent

id: cord-002889-fie121ns
type: CELL_LINE
entity:
  murine pancreatic adenocarcinoma Panc02 cell line 7 Female C57BL 6 mice Charles River 10 14 weeks of age n 4 8 per group were injected s c


id: cord-003243-u744apzw
type: WORK_OF_ART
entity:
  Sequential Modelling of the Effects of Mass Drug Treatments on Anopheline Mediated Lymphatic Filariasis Infection


id: cord-270286-76mrzaxi
type: PROTEIN
entity:
  contaminants coagulase negative Staphylococcus Bacillus species Micrococcus species Corynebacterium species


id: cord-298032-3zlu8g8y
type: PROTEIN
entity:
  ORF50 transcription activator RTA ORF57 ORF59 ORF40 ORF6 ORF9 ORF K8 ORF K9 vIRF 1 ORF K2 viral interleukin 6 vIL 6 ORF74 viral G protein


id: cord-281403-yl7jdarm
type: ORG
entity:
  the National Association of Medical Examiners NAME Ad Hoc Committee for Bioterrorism and Infectious Disease


id: cord-281403-yl7jdarm
type: ORG
entity:
  Regional Offices Hospital Respiratory Protection Program Toolkit Resources for Respirator Program Administrators


id: cord-298805-ntpm68cg
type: ORG
entity:
  the European Organization for Research and Treatment of Cancer Invasive Fungal Infections Cooperative Group


id: cord-265679-7gzont7l
type: DNA
entity:
  Virus date 2018 09 18 journal Viruses DOI 10 3390 v10090507 sha dce34f36e8a1d8b4692c1e54852d6942da5d065a doc_id 265679 cord_uid 7gzont7l Porcine epidemic diarrhea PED


id: cord-333639-usgpe1cz
type: PROTEIN
entity:
  2R 3R 4R 5R 3 4 bis tert butyldimethylsilyl oxy 5 3 carbamoyl 1H 1 2 4 triazol 1 yl tetrahydrofuran 2


id: cord-333639-usgpe1cz
type: CHEMICAL
entity:
  2R 3R 4R 5R 3 4 bis tert butyldimethylsilyl oxy 5 3 carbamoyl 1H 1 2 4 triazol 1 yl tetrahydrofuran 2 yl methyl 4nitrophenyl carbonate 4 11 g 6 25 mmol 1 equiv


id: cord-289026-v09m2fzw
type: PROTEIN
entity:
  S1 subunits S1 CTDs 17 19 20 Human coronavirus 229E HCoV 229E 21 22 and TGEV 23 24 utilize aminopeptidase N APN


id: cord-289026-v09m2fzw
type: CELL_LINE
entity:
  Henan Agricultural University China Vero cell line African green monkey kidney epithelial cell line Drosophila S2 cell line pMT BiP V5 His A vector


id: cord-289026-v09m2fzw
type: PROTEIN
entity:
  recombinant pAPN ectodomain residues 63 963 PEDV S1 protein residues 21 793 and S1 truncated variants residues 21 249 253 638 and 505 629


id: cord-289026-v09m2fzw
type: DISEASE
entity:
  coronaviruses severe acute respiratory syndrome coronavirus SARS CoV 2 3 4 5 6 and Middle East respiratory syndrome coronavirus MERS CoV


id: cord-348660-qnbgywgy
type: LAW
entity:
  title Production of Recombinant N Protein of Infectious Bronchitis Virus Using the Baculovirus Expression System and Its Assessment as a Diagnostic Antigen date 2018


id: cord-003244-abs3tc3r
type: GPE
entity:
  the People s Republic of China on Prevention and Treatment of Infectious Diseases Database of Laws and Regulations Definition


id: cord-003244-abs3tc3r
type: LAW
entity:
  Different Epidemic Curves for Severe Acute Respiratory Syndrome Reveal Similar Impacts of Control Measures Projecting


id: cord-319871-qnijw08y
type: CELL_TYPE
entity:
  activated B cells NKG2D Natural Killer Group 2D receptor Nod2 Nucleotide binding oligomerization domain


id: cord-319871-qnijw08y
type: CHEBI
entity:
  Oxygen Species S aureus Staphylococcus aureus SEA Staphylococcal Enterotoxin A SEB Staphylococcal Enterotoxin B


id: cord-319871-qnijw08y
type: DISEASE
entity:
  respiratory syncytial virus RSV bronchiolitis Nasopharyngeal bacterial burden and antibiotics influence on inflammatory markers and disease


id: cord-330296-706hf4qw
type: CHEMICAL
entity:
  Fooks A R Bardsley M Carroll M Drosten C Drexler J F Günther S Klempa B Pinschewer D Klimkait T Avsic


id: cord-006892-n2ncamqh
type: PROTEIN
entity:
  norovirus GI I GII 4 bivalent virus like particle VLP vaccine in adults NCT03039790 Takeda Safety and immunogenicity of norovirus GI 1 GII 4 bivalent virus like particle vaccine


id: cord-006892-n2ncamqh
type: PROTEIN
entity:
  Chimeric GII 4 Norovirus Virus Like Particle Based Vaccines Induce Broadly Blocking Immune Responses Chimeric bivalent virus like particle vaccine


id: cord-307543-piust0s6
type: CHEMICAL
entity:
  HH 6 2 1 0 and B9 What importance do patients attach to the fact that you perform optimal HH 6 2 1 0 The self reported HAI


id: cord-319729-6lzjhn8j
type: ORG
entity:
  Lab Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by


id: cord-307547-7n3f3wrz
type: CELL_TYPE
entity:
  human acute B and T lymphoblastic leukemia cervix carcinoma and larynx carcinoma the cytotoxicity of Questiomycin A is up to three orders of magnitude lower IC 50 1 3 μM


id: cord-003171-z22ekgtv
type: DISEASE
entity:
  influenza A H1N1 2009 virus where are we Complex patterns of human antisera reactivity to novel 2009


id: cord-275162-2239dk45
type: DISEASE
entity:
  respiratory syncytial virus RSV parainfluenza virus PIV Types 1 4 rhinovirus human metapneumovirus coronavirus


id: cord-262205-ax3i3d7f
type: GGP
entity:
  ceremonies 8 9 10 11 12 13 The dates of religious ceremonies like Hajj and Arbaeen are decided using the lunar calendar the Islamic or Hijri calendar which is not only shorter than the Gregorian calendar meaning that these events occur 10 days earlier each year and can synchronize with different seasons and season associated diseases Accordingly planners and policy makers of public health are faced with changing goals


id: cord-273324-xhpv783y
type: WORK_OF_ART
entity:
  Mapping the Landscape of Diagnostics for Sexually Transmitted Infections Key Findings and Recommandations


id: cord-003270-vu9b5a14
type: PROTEIN
entity:
  epitopes 109 FAFRDLCIVY 110 CYSLYGTTL 111 VYDFAFRDL 111 112 KFYSKISEY 113 KLPQLCTEL 114 115 116 ISEYRHYCY 117 EYRHYCYSL 111 KLPDLCTEL 116 118 119 120 FAFKDLFVV 119 120


id: cord-017463-repm1vw9
type: WORK_OF_ART
entity:
  A Emerging Infectious Diseases World Health Organization The International Health Regulations World Health Organization


id: cord-003219-iryb3v0z
type: PRODUCT
entity:
  APACHE II Acute Physical and Chronic Health Evaluation SOFA Sequential Organ Function Assessment PSI


id: cord-003219-iryb3v0z
type: ORG
entity:
  Thoracic Society European Society of Intensive Care Medicine Society of Critical Care Medicine Clinical Practice Guideline Mechanical Ventilation


id: cord-290861-5bxvenue
type: PROTEIN
entity:
  interleukin IL 1α IL 1ß IL 2 IL 4 IL 6 IL 8 IL 10 IL 12 IL 18 interferon gamma IF g transforming growth factor beta TGFß


id: cord-290861-5bxvenue
type: PROTEIN
entity:
  beta actin ACTB beta 2 microglobulin B2M beta glucuronidase GUSB hydroxymethylbilane synthase HMBS tyrosine 3 monooxygenase tryptophan 5 monooxygenase activation protein zeta polypeptide YWHAZ and ribosomal proteins L17 RPL17 L30 RPL30 S7 RPS7 S9 RPS9


id: cord-290861-5bxvenue
type: PROTEIN
entity:
  XI NAV1 9 nerve growth factor NGF tachykinin receptor 1 NK1R substance P TAC1 tumor necrosis factor alpha


id: cord-290861-5bxvenue
type: GGP
entity:
  beta actin ACTB beta 2 microglobulin B2M beta glucuronidase GUSB hydroxymethylbilane synthase HMBS tyrosine 3 monooxygenase tryptophan 5 monooxygenase activation protein zeta polypeptide YWHAZ


id: cord-002932-5e7xrd1y
type: PERCENT
entity:
  6 7 8 1 Division of Virology Department of Microbiology and Immunology Institute of Medical Science University of Tokyo


id: cord-314340-ltx4w9zh
type: PROTEIN
entity:
  Histone H3 rabbit mAb Cat 4499 1 1000 Acetyl Histone H3 Lys9 rabbit mAb Cat 9649 1 1000 Acetyl Histone H3 Lys18 rabbit mAb Cat 13998 1 1000 ubiquitin Mouse mAb Cat 3936 1


id: cord-354904-7gq2e6f0
type: ORG
entity:
  the Museum of Strains of the Laboratory of Virology Scientific Research Veterinary Institute Russian Academy of Sciences Saratov


id: cord-280374-yj0r4rwt
type: ORG
entity:
  the European Group for Blood and Marrow Transplantation European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party


id: cord-301767-1jv20em8
type: CL
entity:
  enterohemorrhagic Escherichia coli O157 H7 in soil and on leaf lettuce and parsley grown in fields treated with contaminated manure composts or irrigation water


id: cord-301767-1jv20em8
type: DISEASE
entity:
  enteroviruses echovirus type 7 strain Wallace coxsackievirus B3 strain Nancy and poliovirus type 1 strain LSc


id: cord-296992-2vp35fwv
type: DISEASE
entity:
  influenza A H1N1 pandemic in the Netherlands Optimizing the precision of case fatality ratio estimates under the surveillance pyramid


id: cord-003138-9r1hg7ld
type: DNA
entity:
  Roche Fast Start Essential DNA Green Master Mix Cat No 06 402 712 001 10 μM of each primer Table 2 and 1 μL


id: cord-003138-9r1hg7ld
type: CHEMICAL
entity:
  chloroquine dihydroartemisinin piperaquine lumefantrine amodiaquine atovaquone pyronaridine mefloquine quinine


id: cord-254747-vox5xsgd
type: WORK_OF_ART
entity:
  An Old Protein with A New Story Coronavirus Endoribonuclease Is Important for Evading Host Antiviral Defenses


id: cord-325525-d1hsguds
type: DISEASE
entity:
  considérée indemne mais des épizooties peuvent apparaître suite à l introduction d animaux malades d objets


id: cord-325525-d1hsguds
type: CHEMICAL
entity:
  localisée Les symptômes sont donc divers lésions cutanées sous forme de plaques d urticaire rectangulaires


id: cord-268149-narre5e7
type: CELL_LINE
entity:
  Zegie Peninsula Northwestern Ethiopia Ethnoveterinary remedies of diseases among milk yielding animals in Kathua Ethnoveterinary plants


id: cord-268149-narre5e7
type: ORG
entity:
  the Department of Botany Shaheed Benazir Bhuto University Sheringal District Dir Upper Khyber Pakhtunkhwa Pakistan Species


id: cord-268149-narre5e7
type: ORG
entity:
  biocontainment Institute of Medicine Microbial Threats to Health Emergence Detection and Response Medicinal


id: cord-268149-narre5e7
type: CHEMICAL
entity:
  camaldulensis Ficus carica Melia azedarach Morus indica Morus nigra Olea ferruginea Pinus roxburghii Quercus baloot and Rumex hastatus


id: cord-268149-narre5e7
type: CHEMICAL
entity:
  Acacia modesta Wall Allium cepa L Allium sativum L B rapa Calotropis procera Aiton Dryand Cannabis sativa L Chenopodium album L C longa F vulgare Juglans regia L Nicotiana tabacum L Peganum harmala L Quercus oblongata D Don Trachyspermum ammi L


id: cord-318181-xxc7vdnt
type: GGP
entity:
  Sameera Alghamdi Mohammed G title Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus


id: cord-318181-xxc7vdnt
type: GGP
entity:
  sex p 0 079 and age p 0 220 were similar in the two groups The risk of MERS CoV infection was similar in patients with and without fever p 0 267 respiratory symptoms p 0 080 or gastrointestinal symptoms p 0 382 Severe illness p 0 001 contact


id: cord-353553-adaow2w7
type: GGP
entity:
  Staphylococcus aureus 11 y Klebsiella pneumoniae 10 En la neumonía precoz el patógeno más frecuente es Staphylococcus aureus y


id: cord-327202-2um6jmhk
type: WORK_OF_ART
entity:
  A New Approach to Evaluating the Risk Benefit Equation for Dual Use and Gain of Function Research of Concern


id: cord-330942-x238hq9b
type: DISEASE
entity:
  rhinovirus coronavirus respiratory syncytial virus RSV influenza virus Para influenza virus and metapneumo virus CARV infections


id: cord-009997-oecpqf1j
type: DNA
entity:
  t 12 21 p13 q22 11q23 rearrangements KMT2A iAmp21 t 1 19 q23 p13 1 t 9 22 q34 q11 hypodiploidy hyperdiploidy


id: cord-009997-oecpqf1j
type: CELL_LINE
entity:
  California San Diego La Jolla California United States Background Clinical outcomes after allogeneic hematopoietic stem cell transplantation HSCT


id: cord-009997-oecpqf1j
type: GGP
entity:
  Asmaa Salama Eman D El Desouky Lobna Shalaby National Cancer Institute Cairo Cairo Egypt Background Hodgkin lymphoma HL


id: cord-009997-oecpqf1j
type: ORG
entity:
  the SIOP International Society of Paediatric Oncology PODC Paediatric Oncology in Developing Countries Abandonment of Treatment Working Group


id: cord-009997-oecpqf1j
type: WORK_OF_ART
entity:
  OS Children s Mercy Hospital Kansas City Kansas City Missouri United States Background Post Consolidation


id: cord-009997-oecpqf1j
type: DISEASE
entity:
  B cell lymphoma posttransplant lymphoproliferative disease Wilms tumor rhabdomyosarcoma Ewings sarcoma osteosarcoma neuroblastoma


id: cord-009997-oecpqf1j
type: DISEASE
entity:
  rhabdomyosarcoma RMS n 2 alveolar histology primary site nasopharynx n 1 and lower extremity n 1 Ewing s sarcoma


# bib

id: cord-002889-fie121ns
title: Development of improved therapeutic mesothelin-based vaccines for pancreatic cancer
author: White, Michael
date: 2018-02-23
txt: ./txt/cord-002889-fie121ns.txt
cache: ./cache/cord-002889-fie121ns.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825036/
doi: 10.1371/journal.pone.0193131
summary:
  Human and mouse mesothelin share sequence similarity, expression patterns, and biochemical characteristics, [7] , and the homeostatic function of mesothelin in mammals is unknown: the gene can be deleted without apparent effect in mice PLOS C57Bl6 mice and thus can be grown in syngeneic mice to allow for study of an anti-tumor immune response in an immunocompetent mouse model. In order to create a putative therapeutic anti-mesothelin vaccine, we inserted the mouse mesothelin gene into the poxvirus MVA genome under a viral promoter so that mesothelin would be expressed in any cells infected with the recombinant virus. To determine whether the viruses expressing mesothelin protein were able to induce an immune response in mice, we first attempted to measure anti-mesothelin antibody in vaccinated mouse sera. In comparison, there were very few spots (1-3) in response to stimulation with Lewis Lung cells that do not express mouse mesothelin, and mice vaccinated with MVA, MVAmeso and MVAmesoA35Del viruses all had good responses to restimulation with vaccinia virus (124, 147, and 148 spots respectively).

abstract:
  Pancreatic cancer is the 5(th) leading cause of cancer deaths, and there are no effective treatments. We developed a poxvirus platform vaccine with improved immunogenicity and inserted the mesothelin gene to create an anti-mesothelin cancer vaccine. Mesothelin expression is mostly restricted to tumors in adult mammals and thus may be a good target for cancer treatment. We show here that the modified vaccinia virus Ankara (MVA) virus expressing mesothelin and the enhanced MVA virus missing the immunosuppressive A35 gene and expressing mesothelin were both safe in mice and were able to induce IFN-gamma secreting T cells in response to mesothelin expressing tumor cells. In addition, the MVA virus has oncolytic properties in vitro as it can replicate in and kill Panc02 pancreatic adenocarcinoma cell line tumor cells, even though it is unable to replicate in most mammalian cells. Deletion of the A35 gene in MVA improved T cell responses as expected. However, we were unable to demonstrate inhibition of Panc02 tumor growth in immunocompetent mice with pre-vaccination of mice, boosts, or even intratumoral injections of the recombinant viruses. Vaccine efficacy may be limited by shedding of mesothelin from tumor cells thus creating a protective screen from the immune system.


id: cord-002932-5e7xrd1y
author: Watanabe, Tokiko
date: 2018-03-19
txt: ./txt/cord-002932-5e7xrd1y.txt
cache: ./cache/cord-002932-5e7xrd1y.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859186/
doi: 10.1038/s41598-018-23022-0
summary:
  In the ferret model, these studies demonstrated that the inoculation of animals with highly pathogenic avian influenza H5N1 virus via the aerosol route led to higher nasal wash virus titers, earlier onset of clinical signs, and/or a broader spectrum of disease compared with infection via intranasal inoculation despite no difference in lethality [9] [10] [11] . On day 3 post-infection, VN3040 virus was recovered from nasal swabs of two and three animals in the conventional and aerosol method groups, respectively, and the mean virus titers were comparable between the two groups. Cynomolgus macaques were inoculated with 4 ml of a 10 7 PFU/ml solution of the highly pathogenic H5N1 avian influenza virus A/Vietnam/ UT3040/2004 strain (VN3040) through the aerosol route by using the ultrasonic nebulizer NE-U17 (defined as "the aerosol method group"). In contrast, VN3040 replicated well in the right-and left-lower lung lobes of the infected animals in the conventional method group [the virus mean titers were 3.51 and 4.75 log 10 (PFU/g), respectively].

title:
  Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route

abstract:
  Several animal models are used to study influenza viruses. Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. Aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (NHP) model. Here, we performed the experimental infection of NHPs with a highly pathogenic H5N1 influenza virus via the aerosol route and demonstrated that aerosol infection had no effect on clinical outcome, but caused broader infection throughout all of the lobes of the lung compared with a non-aerosolized approach. Aerosol infection therefore represents an option for inoculation of NHPs in future studies.


id: cord-003018-qrt07zmz
author: Miyakawa, Kei
date: 2018-05-04
txt: ./txt/cord-003018-qrt07zmz.txt
cache: ./cache/cord-003018-qrt07zmz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955094/
doi: 10.18632/oncotarget.25348
summary:
  Using a www.oncotarget.com flow cytometer-based screening assay with Dox-treated and untreated iNTCP cells, we identified a hybridoma clone producing anti-NTCP mAb, clone 9A8 ( Figure 2B ). To test whether the 9A8 antibody can inhibit HBV infection, we pretreated iNTCP cells and primary human hepatocytes with 9A8 mAb and subsequently infected cells with wild type HBV and HBV encoding a luciferase reporter gene (HBV-NL) [21] . iNTCP cells (G) and primary human hepatocytes (H) were infected with HBV or its reporter virus (HBV-NL) respectively, in the presence of 9A8 mAb. Anti-HBs mAb (clone 33A4, which recognizes the PreS1 domain) was used as a control. In this study, we generated iNTCP cells, which have high NTCP expression and high susceptibility to HBV infection, and also developed a monoclonal antibody (mAb) that recognizes cell-surface NTCP. Although primary hepatocytes express NTCP at low levels for the uptake of bile acids, endogenous NTCP in hepatocellular carcinoma cell lines is not sufficient to achieve successful infection with HBV in vitro.

title:
  Development of a cell-based assay to identify hepatitis B virus entry inhibitors targeting the sodium taurocholate cotransporting polypeptide

abstract:
  Sodium taurocholate cotransporting polypeptide (NTCP) is a major entry receptor of hepatitis B virus (HBV) and one of the most attractive targets for anti-HBV drugs. We developed a cell-mediated drug screening method to monitor NTCP expression on the cell surface by generating a HepG2 cell line with tetracycline-inducible expression of NTCP and a monoclonal antibody that specifically detects cell-surface NTCP. Using this system, we screened a small molecule library for compounds that protected against HBV infection by targeting NTCP. We found that glabridin, a licorice-derived isoflavane, could suppress viral infection by inducing caveolar endocytosis of cell-surface NTCP with an IC(50) of ~40 μM. We also found that glabridin could attenuate the inhibitory effect of taurocholate on type I interferon signaling by depleting the level of cell-surface NTCP. These results demonstrate that our screening system could be a powerful tool for discovering drugs targeting HBV entry.


id: cord-003092-3owcqt3d
author: Iketani, Sho
date: 2018-07-03
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030562/
doi: 10.1128/mbio.00898-18
title:
  Viral Entry Properties Required for Fitness in Humans Are Lost through Rapid Genomic Change during Viral Isolation

abstract:
  Human parainfluenza viruses cause a large burden of human respiratory illness. While much research relies upon viruses grown in cultured immortalized cells, human parainfluenza virus 3 (HPIV-3) evolves in culture. Cultured viruses differ in their properties compared to clinical strains. We present a genome-wide survey of HPIV-3 adaptations to culture using metagenomic next-generation sequencing of matched pairs of clinical samples and primary culture isolates (zero passage virus). Nonsynonymous changes arose during primary viral isolation, almost entirely in the genes encoding the two surface glycoproteins—the receptor binding protein hemagglutinin-neuraminidase (HN) or the fusion protein (F). We recovered genomes from 95 HPIV-3 primary culture isolates and 23 HPIV-3 strains directly from clinical samples. HN mutations arising during primary viral isolation resulted in substitutions at HN’s dimerization/F-interaction site, a site critical for activation of viral fusion. Alterations in HN dimer interface residues known to favor infection in culture occurred within 4 days (H552 and N556). A novel cluster of residues at a different face of the HN dimer interface emerged (P241 and R242) and imply a role in HPIV-3-mediated fusion. Functional characterization of these culture-associated HN mutations in a clinical isolate background revealed acquisition of the fusogenic phenotype associated with cultured HPIV-3; the HN-F complex showed enhanced fusion and decreased receptor-cleaving activity. These results utilize a method for identifying genome-wide changes associated with brief adaptation to culture to highlight the notion that even brief exposure to immortalized cells may affect key viral properties and underscore the balance of features of the HN-F complex required for fitness by circulating viruses.


id: cord-003099-a0acr28o
author: Koch, R. M.
date: 2018-07-05
txt: ./txt/cord-003099-a0acr28o.txt
cache: ./cache/cord-003099-a0acr28o.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033844/
doi: 10.1186/s40635-018-0182-5
summary:
  In vitro studies in which influenza-infected alveolar macrophages were subsequently stimulated with bacterial lipopolysaccharide (LPS), a bacterial compound that induces a profound innate immune response, revealed increased levels of pro-inflammatory cytokines tumor necrosis factor (TNF) α, interleukin (IL)-1β, and IL-6 [4] [5] [6] [7] [8] , indicative of a priming effect on these cells by influenza. Likewise, murine influenza infection resulted in increased levels of pro-inflammatory cytokines in both plasma and lungs, and enhanced pulmonary neutrophil influx upon pneumococcal infection 7 days later [10] . In the present study, we demonstrate that a systemic LPS challenge in the acute phase of influenza infection (4 days post-infection) results in an enhanced pulmonary, but not systemic pro-inflammatory cytokine response. Our results are in accordance with in vitro data reporting a cellular priming effect of influenza observed upon secondary stimulation with LPS [4] [5] [6] [7] [8] , as well as with other murine in vivo studies that report increased inflammation and pulmonary neutrophil influx or sequestration upon a secondary bacterial infection or LPS challenge in the acute phase of influenza infection [9, 10] .

title:
  The endotoxin-induced pulmonary inflammatory response is enhanced during the acute phase of influenza infection

abstract:
  BACKGROUND: Influenza infections are often complicated by secondary infections, which are associated with high morbidity and mortality, suggesting that influenza profoundly influences the immune response towards a subsequent pathogenic challenge. However, data on the immunological interplay between influenza and secondary infections are equivocal, with some studies reporting influenza-induced augmentation of the immune response, whereas others demonstrate that influenza suppresses the immune response towards a subsequent challenge. These contrasting results may be due to the use of various types of live bacteria as secondary challenges, which impedes clear interpretation of causal relations, and to differences in timing of the secondary challenge relative to influenza infection. Herein, we investigated whether influenza infection results in an enhanced or suppressed innate immune response upon a secondary challenge with bacterial lipopolysaccharide (LPS) in either the acute or the recovery phase of infection. METHODS: Male C57BL/6J mice were intranasally inoculated with 5 × 10(3) PFU influenza virus (pH1N1, strain A/Netherlands/602/2009) or mock treated. After 4 (acute phase) or 10 (recovery phase) days, 5 mg/kg LPS or saline was administered intravenously, and mice were sacrificed 90 min later. Cytokine levels in plasma and lung tissue, and lung myeloperoxidase (MPO) content were determined. RESULTS: LPS administration 4 days after influenza infection resulted in a synergistic increase in TNF-α, IL-1β, and IL-6 concentrations in lung tissue, but not in plasma. This effect was also observed 10 days after influenza infection, albeit to a lesser extent. LPS-induced plasma levels of the anti-inflammatory cytokine IL-10 were enhanced 4 days after influenza infection, whereas a trend towards increased pulmonary IL-10 concentrations was found. LPS-induced increases in pulmonary MPO content tended to be enhanced as well, but only at 4 days post-infection. CONCLUSIONS: An LPS challenge in the acute phase of influenza infection results in an enhanced pulmonary pro-inflammatory innate immune response. These data increase our insight on influenza-bacterial interplay. Combing data of the present study with previous findings, it appears that this enhanced response is not beneficial in terms of protection against secondary infections, but rather damaging by increasing immunopathology.


id: cord-003138-9r1hg7ld
author: Pawliw, Rebecca
date: 2018-08-06
txt: ./txt/cord-003138-9r1hg7ld.txt
cache: ./cache/cord-003138-9r1hg7ld.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080485/
doi: 10.1186/s12936-018-2435-x
summary:
  title: A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial BACKGROUND: Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor. falciparum in tissue culture flasks for in vitro production of Good Manufacturing Practice (GMP) grade blood stage malaria cell banks was recently described [8] . Development of cultured Plasmodium falciparum blood-stage malaria cell banks for early phase in vivo clinical trial assessment of anti-malaria drugs and vaccines

title:
  A bioreactor system for the manufacture of a genetically modified Plasmodium falciparum blood stage malaria cell bank for use in a clinical trial

abstract:
  BACKGROUND: Although the use of induced blood stage malaria infection has proven to be a valuable tool for testing the efficacy of vaccines and drugs against Plasmodium falciparum, a limiting factor has been the availability of Good Manufacturing Practice (GMP)—compliant defined P. falciparum strains for in vivo use. The aim of this study was to develop a cost-effective method for the large-scale production of P. falciparum cell banks suitable for use in clinical trials. METHODS: Genetically-attenuated parasites (GAP) were produced by targeted deletion of the gene encoding the knob associated histidine rich protein (kahrp) from P. falciparum strain 3D7. A GAP master cell bank (MCB) was manufactured by culturing parasites in an FDA approved single use, closed system sterile plastic bioreactor. All components used to manufacture the MCB were screened to comply with standards appropriate for in vivo use. The cryopreserved MCB was subjected to extensive testing to ensure GMP compliance for a phase 1 investigational product. RESULTS: Two hundred vials of the GAP MCB were successfully manufactured. At harvest, the GAP MCB had a parasitaemia of 6.3%, with 96% of parasites at ring stage. Testing confirmed that all release criteria were met (sterility, absence of viral contaminants and endotoxins, parasite viability following cryopreservation, identity and anti-malarial drug sensitivity of parasites). CONCLUSION: Large-scale in vitro culture of P. falciparum parasites using a wave bioreactor can be achieved under GMP-compliant conditions. This provides a cost-effective methodology for the production of malaria parasites suitable for administration in clinical trials.


id: cord-003171-z22ekgtv
author: Babu, Tara M
date: 2018-10-01
txt: ./txt/cord-003171-z22ekgtv.txt
cache: ./cache/cord-003171-z22ekgtv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107991/
doi: 10.1093/infdis/jiy291
summary:
  title: Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment METHODS: Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A(H2N2) viruses were performed across age groups in Rochester, New York, and Hong Kong, China. In this study, we evaluated population immunity using HAI assays against human and avian H2N2 influenza strains in different age groups in the United States and Hong Kong. The prevalence of titers ≥1:40 against the test viruses is shown for sera from Rochester and Hong Kong in persons born before the 1957 H2N2 pandemic, during the years that H2N2 circulated (1957-1968), or after 1968 is shown in Figure 1 . The comparability of data from 2 geographically separated areas of the world, Rochester and Hong Kong, argues for the representativeness and generalizability of such studies that aim to assess population immunity to viruses of pandemic concern.

title:
  Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment

abstract:
  BACKGROUND: Influenza A pandemics cause significant mortality and morbidity. H2N2 viruses have caused a prior pandemic, and are circulating in avian reservoirs. The age-related frequency of current population immunity to H2 viruses was evaluated. METHODS: Hemagglutinin inhibition (HAI) assays against historical human and recent avian influenza A(H2N2) viruses were performed across age groups in Rochester, New York, and Hong Kong, China. The impact of existing cross-reactive HAI immunity on the effective reproduction number was modeled. RESULTS: One hundred fifty individual sera from Rochester and 295 from Hong Kong were included. Eighty-five percent of patients born in Rochester and Hong Kong before 1968 had HAI titers ≥1:40 against A/Singapore/1/57, and >50% had titers ≥1:40 against A/Berkeley/1/68. The frequency of titers ≥1:40 to avian H2N2 A/mallard/England/727/06 and A/mallard/Netherlands/14/07 in subjects born before 1957 was 62% and 24%, respectively. There were no H2 HAI titers >1:40 in individuals born after 1968. These levels of seroprevalence reduce the initial reproduction number of A/Singapore/1/1957 or A/Berkeley/1/68 by 15%–20%. A basic reproduction number (R(0)) of the emerging transmissible virus <1.2 predicts a preventable pandemic. CONCLUSIONS: Population immunity to H2 viruses is insufficient to block epidemic spread of H2 virus. An H2N2 pandemic would have lower impact in those born before 1968.


id: cord-003219-iryb3v0z
author: Kao, Kuo-Chin
date: 2018-09-24
txt: ./txt/cord-003219-iryb3v0z.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153196/
doi: 10.1186/s13613-018-0440-4
summary:
  title: Predictors of survival in patients with influenza pneumonia-related severe acute respiratory distress syndrome treated with prone positioning CONCLUSIONS: In the present study, in evaluating the effect of prone positioning in patients with influenza pneumonia-related ARDS, pneumonia severity index, renal replacement therapy and increase in dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning. After multivariate Cox regression analysis, PSI, renal replacement therapy and increased dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning. The present study in influenza pneumonia-related ARDS patients receiving prone positioning also found that increased dynamic driving pressure (hazard ratio 1.372, 95% confidence interval 1.095-1.718; p = 0.006) was identified as After multivariate Cox regression analysis, it was found that PSI, renal replacement therapy and increased dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumoniarelated ARDS receiving prone positioning.

title:
  Predictors of survival in patients with influenza pneumonia-related severe acute respiratory distress syndrome treated with prone positioning

abstract:
  BACKGROUND: Patients with influenza complicated with pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ARDS). Prone positioning with longer duration and lung-protective strategies might reduce the mortality level in ARDS. The aim of this study is to investigate the survival predictors of prone positioning in patients with ARDS caused by influenza pneumonia. METHODS: This retrospective study was conducted by eight tertiary referral centers in Taiwan. From January 1 to March 31 in 2016, all of the patients in intensive care units with virology-proven influenza pneumonia were collected, while all of those patients with ARDS and receiving prone positioning were enrolled. Demographic data, laboratory examinations, management records, ventilator settings and clinical outcomes were collected for analysis. RESULTS: During the study period, 336 patients with severe influenza pneumonia were screened and 263 patients met the diagnosis of ARDS. Totally, 65 patients receiving prone positioning were included for analysis. The 60-day survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score, pneumonia severity index (PSI), creatinine level and lower rate of receiving renal replacement therapy than non-survivors (22.4 ± 8.5 vs. 29.2 ± 7.4, p = 0.003; 106.6 ± 40.9 vs. 135.3 ± 48.6, p = 0.019; 1.2 ± 0.9 mg/dL vs. 3.1 ± 3.6 mg/dL, p = 0.040; and 4% vs. 42%, p < 0.005). Multivariate Cox regression analysis identified PSI (hazard ratio 1.020, 95% confidence interval 1.009–1.032; p < 0.001), renal replacement therapy (hazard ratio 6.248, 95% confidence interval 2.245–17.389; p < 0.001), and increase in dynamic driving pressure (hazard ratio 1.372, 95% confidence interval 1.095–1.718; p = 0.006) which were independent predictors associated with 60-day mortality. CONCLUSIONS: In the present study, in evaluating the effect of prone positioning in patients with influenza pneumonia-related ARDS, pneumonia severity index, renal replacement therapy and increase in dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13613-018-0440-4) contains supplementary material, which is available to authorized users.


id: cord-003243-u744apzw
author: Michael, Edwin
date: 2018-10-08
txt: ./txt/cord-003243-u744apzw.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175292/
doi: 10.1371/journal.pntd.0006674
summary:
  METHODOLOGY AND PRINCIPAL FINDINGS: We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations. We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYM-FASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations.

title:
  Quantifying the value of surveillance data for improving model predictions of lymphatic filariasis elimination

abstract:
  BACKGROUND: Mathematical models are increasingly being used to evaluate strategies aiming to achieve the control or elimination of parasitic diseases. Recently, owing to growing realization that process-oriented models are useful for ecological forecasts only if the biological processes are well defined, attention has focused on data assimilation as a means to improve the predictive performance of these models. METHODOLOGY AND PRINCIPAL FINDINGS: We report on the development of an analytical framework to quantify the relative values of various longitudinal infection surveillance data collected in field sites undergoing mass drug administrations (MDAs) for calibrating three lymphatic filariasis (LF) models (EPIFIL, LYMFASIM, and TRANSFIL), and for improving their predictions of the required durations of drug interventions to achieve parasite elimination in endemic populations. The relative information contribution of site-specific data collected at the time points proposed by the WHO monitoring framework was evaluated using model-data updating procedures, and via calculations of the Shannon information index and weighted variances from the probability distributions of the estimated timelines to parasite extinction made by each model. Results show that data-informed models provided more precise forecasts of elimination timelines in each site compared to model-only simulations. Data streams that included year 5 post-MDA microfilariae (mf) survey data, however, reduced each model’s uncertainty most compared to data streams containing only baseline and/or post-MDA 3 or longer-term mf survey data irrespective of MDA coverage, suggesting that data up to this monitoring point may be optimal for informing the present LF models. We show that the improvements observed in the predictive performance of the best data-informed models may be a function of temporal changes in inter-parameter interactions. Such best data-informed models may also produce more accurate predictions of the durations of drug interventions required to achieve parasite elimination. SIGNIFICANCE: Knowledge of relative information contributions of model only versus data-informed models is valuable for improving the usefulness of LF model predictions in management decision making, learning system dynamics, and for supporting the design of parasite monitoring programmes. The present results further pinpoint the crucial need for longitudinal infection surveillance data for enhancing the precision and accuracy of model predictions of the intervention durations required to achieve parasite elimination in an endemic location.


id: cord-003244-abs3tc3r
title: Monitoring the age-specificity of measles transmissions during 2009-2016 in Southern China
author: Chong, Ka Chun
date: 2018-10-08
txt: ./txt/cord-003244-abs3tc3r.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175510/
doi: 10.1371/journal.pone.0205339
summary:
  In 1978, the national Expanded Program on Immunization (EPI) in China started to implement a standard schedule for the routine administration of one dose of measles-containing vaccine (MCV1) among children between 8 and 24 months of age. In the present study, we compared the age-specific R of measles infections between different age groups by using laboratory and clinically confirmed data collected from 2009 to 2016. The R values estimated for children aged 7-15 years were low across the study period in general, even though the values also increased since 2012, indicating that primary and secondary school students had a limited contribution to measles transmissions. In this study, we compared the age-specific R of measles infections between different age groups, using laboratory and clinically confirmed data from 2009 to 2016 for Guangdong Province.

abstract:
  BACKGROUND: Despite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable for planning adequate disease control strategies. We compared the age-specific effective reproductive numbers (R) of measles during 2009–2016 in Guangdong, China. METHODS: We estimated the age-specific R values for 7 age groups: 0–8 months, 9–18 months, 19 months to 6 years, 7–15 years, 16–25 years, 26–45 years, and ≥46 years adapting the contact matrix of China. The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used. RESULTS: The peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population. In general, children aged 0–6 years and adults aged 26–45 years had larger values of R when comparing with other age groups after 2012. While the peaks of R values for children aged 0–6 years dropped steadily after 2013, the peaks of R values for adults aged 26–45 years kept at a high range every year. CONCLUSIONS: Although the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0–6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived. In addition, the transmissions from adults aged between 26 and 45 years increased over time. Disease control strategies should target children and adult groups that carry high potential for measles transmission.


id: cord-003261-fz8ucwwm
title: Innate Immune Detection of Cardioviruses and Viral Disruption of Interferon Signaling
author: Freundt, Eric C.
date: 2018-10-12
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194174/
doi: 10.3389/fmicb.2018.02448
abstract:
  Cardioviruses are members of the Picornaviridae family and infect a variety of mammals, from mice to humans. Replication of cardioviruses produces double stranded RNA that is detected by helicases in the RIG-I-like receptor family and leads to a signaling cascade to produce type I interferon. Like other viruses within Picornaviridae, however, cardioviruses have evolved several mechanisms to inhibit interferon production. In this review, we summarize recent findings that have uncovered several proteins enabling efficient detection of cardiovirus dsRNA and discuss which cell types may be most important for interferon production in vivo. Additionally, we describe how cardiovirus proteins L, 3C and L(∗) disrupt interferon production and antagonize the antiviral activity of interferon effector molecules.


id: cord-003270-vu9b5a14
author: Panahi, Heidar Ali
date: 2018-10-24
txt: ./txt/cord-003270-vu9b5a14.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200245/
doi: 10.1371/journal.pone.0205933
summary:
  In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens'' analyses were carried out successively by different tools. For the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and for the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens analyses were considered. In this study, the binding ability of the first step selected peptides to human and mouse MHC molecules, was analyzed by CABS-dock (http://biocomp.chem.uw.edu.pl/CABSdock/) server. In cancer immunotherapy, the CTL-mediated responses play the central role in eradication of malignant cells, and the binding of epitopes to MHC-I molecules is an essential step for antigen presentation to CTLs. Thus, in this study, predicted epitopes were primarily selected by their MHC-I binding and processing scores.

title:
  A comprehensive in silico analysis for identification of therapeutic epitopes in HPV16, 18, 31 and 45 oncoproteins

abstract:
  Human papillomaviruses (HPVs) are a group of circular double-stranded DNA viruses, showing severe tropism to mucosal tissues. A subset of HPVs, especially HPV16 and 18, are the primary etiological cause for several epithelial cell malignancies, causing about 5.2% of all cancers worldwide. Due to the high prevalence and mortality, HPV-associated cancers have remained as a significant health problem in human society, making an urgent need to develop an effective therapeutic vaccine against them. Achieving this goal is primarily dependent on the identification of efficient tumor-associated epitopes, inducing a robust cell-mediated immune response. Previous information has shown that E5, E6, and E7 early proteins are responsible for the induction and maintenance of HPV-associated cancers. Therefore, the prediction of major histocompatibility complex (MHC) class I T cell epitopes of HPV16, 18, 31 and 45 oncoproteins was targeted in this study. For this purpose, a two-step plan was designed to identify the most probable CD8+ T cell epitopes. In the first step, MHC-I and II binding, MHC-I processing, MHC-I population coverage and MHC-I immunogenicity prediction analyses, and in the second step, MHC-I and II protein-peptide docking, epitope conservation, and cross-reactivity with host antigens’ analyses were carried out successively by different tools. Finally, we introduced five probable CD8+ T cell epitopes for each oncoprotein of the HPV genotypes (60 epitopes in total), which obtained better scores by an integrated approach. These predicted epitopes are valuable candidates for in vitro or in vivo therapeutic vaccine studies against the HPV-associated cancers. Additionally, this two-step plan that each step includes several analyses to find appropriate epitopes provides a rational basis for DNA- or peptide-based vaccine development.


id: cord-003377-9vkhptas
author: Wu, Tong
date: 2018-12-19
txt: ./txt/cord-003377-9vkhptas.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300203/
doi: 10.1371/journal.pone.0208197
summary:
  title: The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN). The indicator for wild bird habitat used in this study was the set of "Important Bird and Biodiversity Areas" (IBAs) for "migratory and congregatory waterbirds" identified by BirdLife The live poultry trade poses different avian influenza risks in different regions of the world Table 1 . Our first specification (Model 1) included a number of factors related to disease risk but excluded both live poultry imports and biosecurity measures.

title:
  The live poultry trade and the spread of highly pathogenic avian influenza: Regional differences between Europe, West Africa, and Southeast Asia

abstract:
  In the past two decades, avian influenzas have posed an increasing international threat to human and livestock health. In particular, highly pathogenic avian influenza H5N1 has spread across Asia, Africa, and Europe, leading to the deaths of millions of poultry and hundreds of people. The two main means of international spread are through migratory birds and the live poultry trade. We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN). Across all three regions, we found per-capita GDP (a proxy for modernization, general biosecurity, and value-at-risk) to be risk reducing. A more specific biosecurity measure–general surveillance–was also found to be mitigating at the all-regions level. However, there were important inter-regional differences. For the EU and ASEAN, intra-bloc live poultry imports were risk reducing while extra-bloc imports were risk increasing; for ECOWAS the reverse was true. This is likely due to the fact that while the EU and ASEAN have long-standing biosecurity standards and stringent enforcement (pursuant to the World Trade Organization’s Agreement on the Application of Sanitary and Phytosanitary Measures), ECOWAS suffered from a lack of uniform standards and lax enforcement.


id: cord-003571-upogtny6
title: The 1918 Influenza Pandemic: Looking Back, Looking Forward
author: Viboud, Cécile
date: 2018-10-20
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454441/
doi: 10.1093/aje/kwy207
summary:
  In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. age patterns; history of epidemiology; influenza; mortality; pandemic; prior immunity One hundred years after the fact, the 1918 influenza pandemic remains one of the most important epidemics of the modern medical era; it was significant for its impact on both human health and the development of epidemiology and other medical sciences.

abstract:
  In commemoration of the centennial of the 1918 influenza pandemic, the American Journal of Epidemiology has convened a collection of 12 articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge again. In the present commentary, we place these 12 articles in the context of a growing body of work on the archeo-epidemiology of past pandemics, the socioeconomic and geographic drivers of influenza mortality and natality impact, and renewed interest in immune imprinting mechanisms and the development of novel influenza vaccines. We also highlight persisting mysteries in the origins and severity of the 1918 pandemic and the need to preserve rapidly decaying information that may provide treasure troves for future generations.


id: cord-003655-uo0hdrgc
title: Paramyxovirus Infections in Ex Vivo Lung Slice Cultures of Different Host Species
author: de Vries, Rory D.
date: 2018-03-27
txt: ./txt/cord-003655-uo0hdrgc.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526457/
doi: 10.3390/mps1020012
summary:
  Here, we describe a protocol for the preparation and ex vivo infection of lung slices from different mammalian host species with various respiratory paramyxoviruses expressing fluorescent reporter proteins, and suggest follow-up experiments including immunohistochemistry, flow cytometry and confocal microscopy. The combination of these viable lung slices with recombinant viruses expressing fluorescent reporter proteins [7] [8] [9] allows for accurate, sensitive and reproducible assessment of respiratory virus infection and dissemination over time. We have validated this technique by infecting lung slices of multiple host species (cotton rats, ferrets, dogs and macaques) with various paramyxoviruses expressing fluorescent reporter proteins (measles virus (MV), canine distemper virus (CDV), human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV)) [10] . Using a (blunt-end) needle or flexible catheter, the fresh lungs are inflated through the trachea (or primary bronchus, if inflation of a half lung or single lobe is desired) with low-melting point agarose mixed with culture medium.

abstract:
  In vivo experiments in animal models of disease are of crucial importance for viral tropism and pathogenesis studies. However, these experiments must be complemented with in vitro and ex vivo experiments. Here, we describe a protocol for the preparation and ex vivo infection of lung slices from different mammalian host species with various respiratory paramyxoviruses expressing fluorescent reporter proteins, and suggest follow-up experiments including immunohistochemistry, flow cytometry and confocal microscopy.


id: cord-006039-vbq9izw3
title: Tissue-specific immunopathology during malaria infection
author: Coban, Cevayir
date: 2018-01-15
txt: ./txt/cord-006039-vbq9izw3.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097228/
doi: 10.1038/nri.2017.138
summary:
  In this Review, we emphasize the need to focus on host interactions with Plasmodium parasites at various tissue levels and the importance of targeting local and specific organ failure and/or pathologies during, as well as long after, infection. Overall, while the process of sequestration is not completely understood, it is known to cause obstruction of blood flow in small capillaries and post-capillary venules (PCVs), endothelial cell activation and inflammation and severe pathology in many organs including lung, adipose tissue, spleen and brain 52, 53, 65, 66 (FIG. This unique brain pathology, known as cerebral malaria, involves convulsions, coma and high fever and develops with the presence of mostly ring-stage infected erythrocytes in the periphery (suggesting a sequestration of late-stage parasites in the organs) [69] [70] [71] . Malaria is a serious disease with acute life-threatening and long-term complications, all of which can be attributed to local but specific organs in which Plasmodium Figure 4 | Infected red blood cells in gut and bone marrow niches.

abstract:
  Systemic inflammation mediated by Plasmodium parasites is central to malaria disease and its complications. Plasmodium parasites reside in erythrocytes and can theoretically reach all host tissues via the circulation. However, actual interactions between parasitized erythrocytes and host tissues, along with the consequent damage and pathological changes, are limited locally to specific tissue sites. Such tissue specificity of the parasite can alter the outcome of malaria disease, determining whether acute or chronic complications occur. Here, we give an overview of the recent progress that has been made in understanding tissue-specific immunopathology during Plasmodium infection. As knowledge on tissue-specific host–parasite interactions accumulates, better treatment modalities and targets may emerge for intervention in malaria disease. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nri.2017.138) contains supplementary material, which is available to authorized users.


id: cord-006325-3no74e74
title: Microorganisms associated with respiratory syncytial virus pneumonia in the adult population
author: Jeannoël, M.
date: 2018-10-23
txt: ./txt/cord-006325-3no74e74.txt
cache: ./cache/cord-006325-3no74e74.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101617/
doi: 10.1007/s10096-018-3407-3
summary:
  A more severe outcome was observed for RSV-bacteria-associated pneumonia compared with RSV pneumonia: length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). In conclusion, we did not observe major differences in the epidemiology of bacterial superinfections in RSV-positive pneumonia compared to reports on post-influenza pneumonia. RSV and bacteria coinfection was statistically associated with a more severe outcome than RSV-positive pneumonia as length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). It is probably due to the systematic testing strategy associated to a Species distribution of pathogenic bacteria involved in RSV-positive pneumonia (CAP) and hospital-acquired pneumonia (HAP) sampling bias toward influenza-like illness. Clinical characteristics and outcome of respiratory syncytial virus infection among adults hospitalized with influenza-like illness in France

abstract:
  Respiratory syncytial virus (RSV) has been recognized as responsible for severe respiratory illness in adults, especially in the elderly. While pneumonia is commonly observed during RSV infection, the burden and epidemiology of bacterial superinfection is poorly understood. The aim of this study was to identify microorganisms associated with RSV-positive pneumonia in adults. A retrospective study was conducted during three consecutive winters (October to April 2013–2016) in the University Hospital of Lyon, France. During RSV circulation periods, a systematic RSV screening was performed by reverse-transcription PCR on all respiratory samples collected from adults. Records of RSV-positive patients were subsequently analyzed to identify radiologically confirmed pneumonia cases. Bacteria were identified by standard bacteriology cultures or urinary antigen screening and classified as potentially causative of pneumonia if quantification was above the specific threshold as defined by the European Manual of Clinical Microbiology. Overall, 14,792 adult respiratory samples were screened for RSV detection by PCR. In total, 292 had a positive RSV detection (2.0%) among which 89 presented with pneumonia including 27 bacterial superinfections (9.3%) with Streptococcus pneumonia, Haemophilus influenza, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis. Most patients were elderly (55.6%) and patients with comorbidities (77.8%). A more severe outcome was observed for RSV-bacteria-associated pneumonia compared with RSV pneumonia: length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). In conclusion, we did not observe major differences in the epidemiology of bacterial superinfections in RSV-positive pneumonia compared to reports on post-influenza pneumonia.


id: cord-006892-n2ncamqh
title: Virus-like particle vaccines: immunology and formulation for clinical translation
author: Donaldson, Braeden
date: 2018-09-19
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103734/
doi: 10.1080/14760584.2018.1516552
abstract:
  Introduction: Virus-like particle (VLP) vaccines face significant challenges in their translation from laboratory models, to routine clinical administration. While some VLP vaccines thrive and are readily adopted into the vaccination schedule, others are restrained by regulatory obstacles, proprietary limitations, or finding their niche amongst the crowded vaccine market. Often the necessity to supplant an existing vaccination regimen possesses an immediate obstacle for the development of a VLP vaccine, despite any preclinical advantages identified over the competition. Novelty, adaptability and formulation compatibility may prove invaluable in helping place VLP vaccines at the forefront of vaccination technology. Areas covered: The purpose of this review is to outline the diversity of VLP vaccines, VLP-specific immune responses, and to explore how modern formulation and delivery techniques can enhance the clinical relevance and overall success of VLP vaccines. Expert commentary: The role of formation science, with an emphasis on the diversity of immune responses induced by VLP, is underrepresented amongst clinical trials for VLP vaccines. Harnessing such diversity, particularly through the use of combinations of select excipients and adjuvants, will be paramount in the development of VLP vaccines.


id: cord-009997-oecpqf1j
title: 2018 ASPHO ABSTRACTS
author: nan
date: 2018-03-31
txt: ./txt/cord-009997-oecpqf1j.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167873/
doi: 10.1002/pbc.27057
abstract: nan
summary:
  Completed cranial radiation and proceeded to allogeneic stem cell transplant with unrelated cord marrow donor and is disease free at approximately day +200.Case 2: 5 year-old female diagnosed with FLT3 and MLL negative AML and completed treatment per COG AAML1031 study on the low risk arm without Bortezomib. Design/Method: This study was a retrospective chart review that included patients 3 to 23 years old with sickle cell disease type SS and S 0 followed at St. Christopher''s Hospital for Children. Background: Hydroxyurea, chronic blood transfusion, and bone marrow transplantation can reduce complications, and improve survival in sickle cell disease (SCD), but are associated with a significant decisional dilemma because of the inherent risk-benefit tradeoffs, and the lack of comparative studies. Brown University -Hasbro Children''s Hospital, Providence, Rhode Island, United States Background: Despite clinical advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant source of disease-related morbidity.


id: cord-017137-6pmts7ui
title: Microbial Forensics: Beyond a Fascination
author: Nema, Vijay
date: 2018-07-12
txt: ./txt/cord-017137-6pmts7ui.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121623/
doi: 10.1007/978-981-13-1583-1_17
summary:
  When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—"microbial forensics." Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Herein the microbial forensics could be defined as "the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes" [21] . Microbial forensics has a role in such cases by applying scientific methods for the analysis of evidence from such a bioterrorism attack. The most reliable technique till date for microbial forensics is metagenomics-a culture-independent approach for identifying and enumerating microbes.

abstract:
  Microbiology has seen a great transition from culture-based identification of microbes using various biochemical and microscopic observations to identify and functionally characterize the microbes by just collecting the DNA and sequencing it. This advancement has not only moved in and around microbiology but has found its applications in fields which were earlier considered to be the remote ones. Forensics is one such field, where tracing the leftover evidence on a crime scene can lead to the identification and prosecution of the culprit. When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—“microbial forensics.” Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Studies have supported the assumption that skin or surface microflora of an individual is somewhat related with the microflora found on the objects used by that individual and efforts are ongoing to see if this is found consistently in various surroundings and with different individuals. Once established, this technique would facilitate accurate identification and differentiation of an individual or suspect to guide investigations along with conventional evidence. Legal investigations are not only the field where microbial forensic could help. Agriculture, defense, public health, tourism, etc. are the fields wherein microbial forensics with different names based on the fields are helping out and have potential to further support other fields.


id: cord-017272-r5en82s1
title: Health Impact of Urban Physicochemical Environment Considering the Mobility of the People
author: Watanabe, Chiho
date: 2018-08-14
txt: ./txt/cord-017272-r5en82s1.txt
cache: ./cache/cord-017272-r5en82s1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121789/
doi: 10.1007/978-981-13-2526-7_2
summary:
  [11] pointed out that due to the accumulation of highly sophisticated spatial and spatiotemporal technology like GIS, GPS, remote sensing, and computer cartography, collectively termed as geographic information science, it becomes possible to model the disease process involving multiple spatiotemporal data obtained in different disciplines. Also, mobility has been one of a classical topic in the area of human ecology since it is associated with the question of how a population utilizes the environment spatially as well as temporally (time allocation studies). Time allocation studies observe the individuals in the targeted field and record the location and type of activity for a given period, which is useful to answer some of the basic questions in human Unlikely Large ecology or other related fields as noted above. A relatively large spatial scale study has been conducted covering approximately 80 × 200 km area in Belgium [3] , which compared regional exposure estimates for two representative air pollutants, NOx and ozone, under two alternative assumptions.

abstract:
  Most of the current environmental health researches assumes that exposure to the environmental agents occurs either in the residence or workplace, neglecting the mobility of the people due to commuting and daily activities. Mobility of the people varies in terms of spatial and temporal range, that is, from momentary short ones to generation-scale long ones. Focusing on the daily movement of the people, various methods for grasping the mobility, which also range from simple observational methods like time allocation to methods with advanced technology like global navigation satellite systems, will be reviewed. Referring environmental health studies examining the health effects of either air pollution or heat, importance of the mobility of the people is discussed. Assessing the mobility will open a new research avenue for the study of infectious diseases as well as noncommunicable diseases.


id: cord-017463-repm1vw9
title: Public Health Surveillance: A Vital Alert and Response Function
author: Ungchusak, Kumnuan
date: 2018-07-27
txt: ./txt/cord-017463-repm1vw9.txt
cache: ./cache/cord-017463-repm1vw9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122032/
doi: 10.1057/978-1-137-54984-6_10
summary:
  We examine networks that contribute to global surveillance systems and highlight the role of social media and information technology in providing data to monitor new events of international importance. The IHR 2005 require countries to develop core capacities in public health, including surveillance systems and epidemiology services, that can analyse and act on surveillance information to detect and respond to diseases where and when they occur so that their potential to spread internationally is decreased. Surveillance and response teams detect early stage public health threats while control programmes gather disease (or condition) specific information to plan activities. These networks depend on cooperation of governments, public health workers and scientists to report cases, provide specimens and share information so that specific diseases can be controlled globally.

abstract:
  Ungchusak, Heymann and Pollack address the critical global issue of public health surveillance. They describe how epidemiologists collect and use surveillance data to detect unusual events or outbreaks and to guide control programmes. Drawing on their combined international experience, the authors explain the vital role that data play in alerting authorities to respond to outbreaks such as Severe Acute Respiratory Syndrome, Ebola, Zika virus and Avian influenza. They point to the importance of sharing information globally while ensuring equal benefits to providers of data, coordinating surveillance activities across sectors, building capacity for surveillance and coordinating national surveillance activities. The authors emphasise the need for enhanced global cooperation to prepare for future public health emergencies of international concern.


id: cord-018066-s0zk9l6a
title: Refugee Crisis As a Potential Threat to Public Health
author: Mihaylova-Garnizova, Raynichka
date: 2018-03-23
txt: ./txt/cord-018066-s0zk9l6a.txt
cache: ./cache/cord-018066-s0zk9l6a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122854/
doi: 10.1007/978-94-024-1263-5_4
summary:
  In order to achieve this, the article analyses the case of the refugee camp in city of Harmanly, close to the Bulgarian-Turkish border, and assesses the public health risks related to this specific situation. The purpose of our article is to collect, summarize and present epidemiological data related to migrants in Bulgaria and, on the basis of this information, to analyze the potential risks to public health (including risks to migrants) and to assess the capacity of Bulgaria''s healthcare system to cope with the refugee crisis. Following the 2012-2013 crisis, in February 2015 a WHO assessment mission to Bulgaria took place to access the country''s capacity to address the public health implications of sudden large-scale influxes of migrants [27] . Public health needs of migrants, refugees and asylum seekers in Europe, 2015: infectious disease aspects

abstract:
  The refugee crisis in Europe continues to persist despite recent data, showing a drop in the number of refugees seeking asylum. The EU has called this as “an unprecedented displacement crisis” and has aimed at devising a comprehensive approach to tackle it, which has been widely criticized. Concerns about public healthcare aspects of the crisis have permanently entered the media and policy discourse even though no systematic association between migration and the importation of infectious diseases has been recorded. In this context, the literature has not filled the existing gap between discourse and evidence, and almost no publications with reliable empirical data exist, both thematic (epidemiology) and geographical (Eastern Europe and Bulgaria). Among the existing publications, the focus has been on TB and HIV (Odone et al., Euro J Public Health 25(3):506–512, 2015). In light of this, the aim of this research is to contribute to the debate by providing an overview of the refugee situation in Bulgaria, as a primary entry-point for refugees entering the EU. In order to achieve this, the article analyses the case of the refugee camp in city of Harmanly, close to the Bulgarian-Turkish border, and assesses the public health risks related to this specific situation. Based on a study of 128 patients with different symptoms we aim to draw wider implications about the linkages between public health and migration. The in-depth review of this specific case shows that both the probability and impact of migration on public health increases when the hosting country is relatively poor, the domestic public healthcare system is not efficient, and there is lack of trust in the government and public services. The study contributes to understanding better these risks in order to identify potential mitigation strategies in the region and the EU as a whole.


id: cord-020750-zvwy7bgt
author: Chapman, Christie
date: 2018-10-11
txt: ./txt/cord-020750-zvwy7bgt.txt
cache: ./cache/cord-020750-zvwy7bgt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147233/
doi: 10.1016/j.nursi.2018.10.010
abstract: nan
summary:
  En la intersección entre el ser humano y los microbios hay un cuadrado que representa la convergencia de los factores que conducen a la aparición de una enfermedad infecciosa. Esto todavía no es realidad, pero grupos como el Global Disease Detection Program (GDD) de los CDC y la Global Outbreak Alert and Response Network de la OMS están vigilando sin descanso la evolución de la interacción entre microbios y seres humanos en todo el planeta, creando tecnología de seguimiento y respondiendo a los informes sobre el aumento de enfermedades y otras emergencias sanitarias 14 . Las enfermedades infecciosas emergentes son una amenaza para todos y cada uno de los habitantes del planeta y todo el mundo puede desempeñar un papel, ya sea en el retraso de la transmisión o la prevención.

title:
  Convergencia mundial de las enfermedades infecciosas emergentes: a tan solo un viaje en avión de distancia


id: cord-021894-lq8yr710
title: Bronchiolitis
author: Cunningham, Steve
date: 2018-03-13
txt: ./txt/cord-021894-lq8yr710.txt
cache: ./cache/cord-021894-lq8yr710.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152174/
doi: 10.1016/b978-0-323-44887-1.00024-9
summary:
  Globally there are an estimated 33.8 million cases of RSV lower respiratory tract infection each year in children under 5 years of age, resulting in 3.4 million admissions to the hospital and 66 to 199 thousand deaths (with the majority in low-and middle-income countries). 42, 43 Severity of disease is associated with both infant risk factors (including lack of adaptive T cell response), 26,44 but also RSV virus specific factors (viral antigen load and direct cytotoxic effects). Respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the United States and Finland Respiratory syncytial virus load, viral dynamics, and disease severity in previously healthy naturally infected children The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection High incidence of pulmonary bacterial co-infection in children with severe respiratory syncytial virus (RSV) bronchiolitis

abstract:
  Acute viral bronchiolitis is a common viral lower respiratory tract infection in young children. Most typically caused by respiratory syncytial virus in 70% of cases, the condition lasts for 4 to 7 days, with a prolonged cough in many. Children with comorbidity, particularly those born prematurely or with significant congenital heart disease, are at risk of more severe disease. Nasal obstruction progresses over 3 to 4 days to difficulty with feeding and increased work of breathing with hypoxemia. Crackles and/or wheeze may be auscultated. Apnoea may be a presenting sign in those less than 3 months of age. Viral load is highest at peak of symptoms and in those with more severe disease. Approximately 2% to 3% of all children are admitted to hospital with bronchiolitis. The differential diagnosis may include bacterial pneumonia, congenital lesions of the lung or heart, or an interstitial lung disease. There are no effective treatments, and admission is for feeding support (by nasogastric or intravenous fluids) or treatment of hypoxemia. Critical care support is required for some infants experiencing respiratory failure, though mortality rates remain unchanged. Practice within and between countries varies significantly and alignment of practice is a common goal of guidelines. Vaccines for RSV are in advanced development, as are several antiviral therapies for RSV. In most children, acute symptoms improve within 5 to 7 days and cough by 2 weeks. Recurrent wheeze is common following acute bronchiolitis and a good association with a diagnosis of asthma in childhood.


id: cord-022046-q1exf47s
title: An Overview of Middle East Respiratory Syndrome in the Middle East
author: Toosy, Arshad Haroon
date: 2018-09-28
txt: ./txt/cord-022046-q1exf47s.txt
cache: ./cache/cord-022046-q1exf47s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152387/
doi: 10.1016/b978-0-323-55228-8.00042-4
abstract: nan
summary:
  Middle East respiratory syndrome (MERS) is an emerging infectious zoonotic disease caused by a novel coronavirus (CoV). 4 Surveillance of DCs in KSA has shown that MERS-CoV clade B has been enzootic in the camel population in Arabia Genetic deep sequencing methods (i.e., high-throughput sequencing) have been readily available to researchers since the disease was first reported. 8 Nevertheless, given the prevalence of MERS-CoV infection in the Middle East''s DC population and due to the potential for spillover to the human population in direct contact with DCs, the development of a vaccine for use in DCs may be feasible. Middle East respiratory syndrome coronavirus (MERS-CoV): animal to human interaction Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia Detection of the Middle East respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient


id: cord-023200-3caevjvh
title: Membranotropic peptides mediating viral entry
author: Falanga, Annarita
date: 2018-02-13
txt: ./txt/cord-023200-3caevjvh.txt
cache: ./cache/cord-023200-3caevjvh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167733/
doi: 10.1002/pep2.24040
summary:
  The discovery of short, membrane interacting, amphipathic or hydrophobic sequences (known as membranotropic peptides) in both enveloped and non‐enveloped viruses suggests that these small peptides are strongly involved in breaching the host membrane and in the delivery of the viral genome into the host cell. [3, 4] The molecular details of the interactions at the interface of virus and cell surfaces are quite complex and highly variable, but there is a common idea that only a limited number of pathways allowing viruses to reach the sites of penetration exist, with enveloped and non-enveloped viruses presenting different and unrelated processes, but with general principles driving all fusion events. [16, 17] Viral fusion proteins undergo significant rearrangements from the pre-fusion to the post-fusion conformations which are triggered by either receptor binding, proteolytic cleavage or low endosomal pH, and eventually determine the exposure of previously sequestered hydrophobic peptides, loops, or patches, able to interact with and destabilize one or both the opposing membranes.

abstract:
  The means used by enveloped viruses to bypass cellular membranes are well characterized; however, the mechanisms used by non‐enveloped viruses to deliver their genome inside the cell remain unresolved and poorly defined. The discovery of short, membrane interacting, amphipathic or hydrophobic sequences (known as membranotropic peptides) in both enveloped and non‐enveloped viruses suggests that these small peptides are strongly involved in breaching the host membrane and in the delivery of the viral genome into the host cell. Thus, in spite of noticeable differences in entry, this short stretches of membranotropic peptides are probably associated with similar entry‐related events. This review will uncover the intrinsic features of viral membranotropic peptides involved in viral entry of both naked viruses and the ones encircled with a biological membrane with the objective to better elucidate their different functional properties and possible applications in the biomedical field.


id: cord-252355-ol21ofj9
author: Abdul-Cader, Mohamed Sarjoon
date: 2018-02-23
txt: ./txt/cord-252355-ol21ofj9.txt
cache: ./cache/cord-252355-ol21ofj9.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0165242717304464
doi: 10.1016/j.vetimm.2018.02.009
summary:
  title: Low pathogenic avian influenza virus infection increases the staining intensity of KUL01+ cells including macrophages yet decrease of the staining intensity of KUL01+ cells using clodronate liposomes did not affect the viral genome loads in chickens When we infected day 6 chickens with H4N6 low pathogenic avian influenza virus (LPAIV), we observed that H4N6 LPAIV infection increased the staining intensity of KUL01+ cells in trachea, lungs and duodenum of chickens at 3 days post-infection. Then, we used clodronate liposomes intra-abdominally in 5 day-old chickens and found significant reduction of staining intensity of KUL01+ cells in trachea and duodenum but not in lungs at 4 days post-treatment. We also hypothesized that the decrease of the staining intensity of KUL01 marker + cells following intra-abdominal administration of clodronate liposomes will augment replication of low pathogenic avian influenza virus (LPAIV) in respiratory and intestinal tracts of chickens.

title:
  Low pathogenic avian influenza virus infection increases the staining intensity of KUL01+ cells including macrophages yet decrease of the staining intensity of KUL01+ cells using clodronate liposomes did not affect the viral genome loads in chickens

abstract:
  The effect of depletion of macrophages using clodronate liposomes as well as macrophage response following viral infections have been studied in various mouse-virus infection models, but they have not been extensively studied in chickens relevant to virus infections. When we infected day 6 chickens with H4N6 low pathogenic avian influenza virus (LPAIV), we observed that H4N6 LPAIV infection increased the staining intensity of KUL01+ cells in trachea, lungs and duodenum of chickens at 3 days post-infection. Then, we used clodronate liposomes intra-abdominally in 5 day-old chickens and found significant reduction of staining intensity of KUL01+ cells in trachea and duodenum but not in lungs at 4 days post-treatment. When we infected the clodronate liposome and PBS liposome treated chickens with H4N6 LPAIV intra-nasally at day 6, we found no effect on H4N6 LPAIV genome loads in trachea, lungs and duodenum of chickens. This study indicates that although KUL01+ cell intensity are increased in respiratory and gastrointestinal tissues in chickens following H4N6 LPAIV infection, the decrease of KUL01+ cell intensity using clodronate liposomes did not change the H4N6 LPAIV genome loads in any of the examined tissues suggesting that KUL01+ cells may not be critical during H4N6 LPAIV infection in chicken.


id: cord-252600-bvh1o64r
author: Galasiti Kankanamalage, Anushka C.
date: 2018-04-25
txt: ./txt/cord-252600-bvh1o64r.txt
cache: ./cache/cord-252600-bvh1o64r.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29544147/
doi: 10.1016/j.ejmech.2018.03.004
summary:
  We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The structure-guided design of inhibitor (I) encompassed the following steps: (a) we first determined a high resolution X-ray crystal structure of MERS-CoV 3CLpro in complex with GC376 ( Fig. 2/Panel A) . Validation of this idea was obtained by synthesizing extended inhibitor GC813 and determining a high resolution X-ray crystal structure of the MERS-CoV 3CLpro:GC813 complex ( Fig. 2/Panel B) . More importantly, representative aldehyde bisulfite adduct compounds 10a and 10c display potent inhibition toward MERS-CoV in both enzyme and cell-based systems, with low cytotoxicity (CC 50 > 100 mM) ( Table 2 and Fig. 4 ).

title:
  Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element

abstract:
  Abstract There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography.


id: cord-252894-c02v47jz
title: Predicting Infectious Disease Using Deep Learning and Big Data
author: Chae, Sangwon
date: 2018-07-27
txt: ./txt/cord-252894-c02v47jz.txt
cache: ./cache/cord-252894-c02v47jz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/ijerph15081596
doi: 10.3390/ijerph15081596
summary:
  This study predicts infectious diseases by optimizing the parameters of deep learning algorithms while considering big data including social media data. The performance of the deep neural network (DNN) and long-short term memory (LSTM) learning models were compared with the autoregressive integrated moving average (ARIMA) when predicting three infectious diseases one week into the future. Therefore, the aim of this study is to design a model that uses the infectious disease occurrence data provided by the KCDC, search query data from search engines that are specialized for South Korea, Twitter social media big data, and weather data such as temperature and humidity. Figure 1 shows the overall framework of the model used in this study including the data collection process and the comparison of models designed using the deep neural network (DNN) method, the long-short term memory (LSTM) method, the autoregressive integrated moving average (ARIMA) method, and the ordinary least squares (OLS) method.

abstract:
  Infectious disease occurs when a person is infected by a pathogen from another person or an animal. It is a problem that causes harm at both individual and macro scales. The Korea Center for Disease Control (KCDC) operates a surveillance system to minimize infectious disease contagions. However, in this system, it is difficult to immediately act against infectious disease because of missing and delayed reports. Moreover, infectious disease trends are not known, which means prediction is not easy. This study predicts infectious diseases by optimizing the parameters of deep learning algorithms while considering big data including social media data. The performance of the deep neural network (DNN) and long-short term memory (LSTM) learning models were compared with the autoregressive integrated moving average (ARIMA) when predicting three infectious diseases one week into the future. The results show that the DNN and LSTM models perform better than ARIMA. When predicting chickenpox, the top-10 DNN and LSTM models improved average performance by 24% and 19%, respectively. The DNN model performed stably and the LSTM model was more accurate when infectious disease was spreading. We believe that this study’s models can help eliminate reporting delays in existing surveillance systems and, therefore, minimize costs to society.


id: cord-254747-vox5xsgd
author: Deng, Xufang
date: 2018-04-01
txt: ./txt/cord-254747-vox5xsgd.txt
cache: ./cache/cord-254747-vox5xsgd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29307596/
doi: 10.1016/j.virol.2017.12.024
summary:
  Overall, current evidence indicates that the EndoU activity of CoV nsp15 is dispensable for viral RNA synthesis and virus replication in cell culture. It was first discovered that the EndoU activity of nsp15 mediates the evasion of host recognition of viral dsRNA by infecting primary macrophages with EndoU-deficient CoVs (Deng et al., 2017; Kindler et al., 2017) . Moreover, treatment with the PKR inhibitor did not affect IFN induction or RNase L-mediated ribosomal RNA degradation in the EndoU-deficient CoV infected-macrophages (Deng et al., unpublished data) . Macrophages infected by the EndoU-deficient CoVs exhibited an early, RNase L-mediated degradation of ribosomal RNA, demonstrating that the OAS-RNase L system was activated (Deng et al., 2017; Kindler et al., 2017) . Lack of MDA5 expression or treatment with the PKR inhibitor did not affect virus-induced RNA degradation (Deng et al., 2017; Kindler et al., 2017) , suggesting that the nsp15-mediated blockage of OAS-RNase L activation is independent of the MDA5-IFN and PKR pathways.

title:
  An “Old” Protein with A New Story: Coronavirus Endoribonuclease Is Important for Evading Host Antiviral Defenses

abstract:
  Here we review the evolving story of the coronavirus endoribonuclease (EndoU). Coronavirus EndoU is encoded within the sequence of nonstructural protein (nsp) 15, which was initially identified as a component of the viral replication complex. Biochemical and structural studies revealed the enzymatic nature of nsp15/EndoU, which was postulated to be essential for the unique replication cycle of viruses in the order Nidovirales. However, the role of nsp15 in coronavirus replication was enigmatic as EndoU-deficient coronaviruses were viable and replicated to near wild-type virus levels in fibroblast cells. A breakthrough in our understanding of the role of EndoU was revealed in recent studies, which showed that EndoU mediates the evasion of viral double-stranded RNA recognition by host sensors in macrophages. This new discovery of nsp15/EndoU function leads to new opportunities for investigating how a viral EndoU contributes to pathogenesis and exploiting this enzyme for therapeutics and vaccine design against pathogenic coronaviruses.


id: cord-256903-8lyw27gh
title: Contributions of Farm Animals to Immunology
author: Guzman, Efrain
date: 2018-12-06
txt: ./txt/cord-256903-8lyw27gh.txt
cache: ./cache/cord-256903-8lyw27gh.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30574508/
doi: 10.3389/fvets.2018.00307
summary:
  Dendritic cells (DC) as such, and their role in immunity were first described in the 1970s and in 1995 Ralph Steinman published a series of papers describing that a cellular receptor called "DEC-205" (now CD205) was expressed on mouse DC, was involved in antigen processing (58, 59) and was detected by the monoclonal antibody NLDC-145. Studies in mice, for example, have shown the efficacy of vaccines against FMDV, however these efficacy studies have failed to be translated to the target species (cattle and pigs), presumably due to fundamental differences in the immune systems of model organisms and target species and the ability of the virus to mutate in these animals (112) . The role of bovine γδ T cells and their WC1 co-receptor in response to bacterial pathogens and promoting vaccine efficacy: a model for cattle and humans

abstract:
  By their very nature, great advances in immunology are usually underpinned by experiments carried out in animal models and inbred lines of mice. Also, their corresponding knock-out or knock-in derivatives have been the most commonly used animal systems in immunological studies. With much credit to their usefulness, laboratory mice will never provide all the answers to fully understand immunological processes. Large animal models offer unique biological and experimental advantages that have been and continue to be of great value to the understanding of biological and immunological processes. From the identification of B cells to the realization that γδ T cells can function as professional antigen presenting cells, farm animals have contributed significantly to a better understanding of immunity.


id: cord-258052-y9pzsoqa
title: Biothreat Agents and Emerging Infectious Disease in the Emergency Department
author: Adalja, Amesh A.
date: 2018-09-06
txt: ./txt/cord-258052-y9pzsoqa.txt
cache: ./cache/cord-258052-y9pzsoqa.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0733862718300634
doi: 10.1016/j.emc.2018.06.011
summary:
  A key method for detecting the presence of an emerging infectious disease syndrome or a biological weapons exposure in an ED patient is to develop a general approach that seeks out key historical and physical examination clues. Any suspicion of smallpox should prompt infectious disease consultation, airborne isolation procedures, and notification of local, state, and national public health authorities. Any suspicion of a VHF should prompt immediate consultation with an infectious disease physician and state and local health authorities. 20 There are several experimental treatments and vaccines (which can be used for postexposure prophylaxis) that are available for filovirus infections and arenavirus infections that would likely be used in any domestic VHF cases caused by these groups of viruses. 22 MERS should be suspected in individuals with upper or lower respiratory infection after travel to the Middle East in the prior 2 weeks, and confirmatory molecular testing can be done in conjunction with state and local health authorities.

abstract:
  The challenges faced by the emergency physician with recognizing and treating category A biothreat agents and emerging infectious disease are summarized and reviewed.


id: cord-261962-sfa9d1ux
author: Lei, H.
date: 2018-01-06
txt: ./txt/cord-261962-sfa9d1ux.txt
cache: ./cache/cord-261962-sfa9d1ux.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/ina.12445
doi: 10.1111/ina.12445
summary:
  In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. • Our identification of the dominated routes, that is the close contact route (large droplet) for influenza, the fomite route for norovirus, and all 3 routes for SARS CoV, suggested the relative importance of different environment intervention for different infectious diseases in air cabins and probably also in other indoor environments. F I G U R E 1 Spatial distribution for 3 in-flight infection outbreaks, (A) norovirus, 26 (B) SARS CoV, 27 and (C) influenza A H1N1 28 of infectious pathogens from the index source passenger, which is also sometimes termed indirect contact route.

title:
  Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses

abstract:
  Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%‐72%) in the in‐flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5‐121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%‐23%), 29% (95% CI: 27%‐31%), and 50% (95% CI: 48%‐53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%‐87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2‐77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.


id: cord-262205-ax3i3d7f
author: Karampourian, Arezou
date: 2018-09-11
txt: ./txt/cord-262205-ax3i3d7f.txt
cache: ./cache/cord-262205-ax3i3d7f.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.12688/f1000research.15290.1
doi: 10.12688/f1000research.15290.1
summary:
  The aim of this study is to explore stakeholders'' experiences on the health system''s preparedness and challenges, and to provide suggestions for preventing infectious diseases during the Arbaeen mass gathering. Health infrastructure defects in Iraq has three sub-themes (health abandonment in Iraq, the weaknesses in health culture and problems related to the health system); poor control of the causative factors of infectious diseases has three sub-themes (the underlying factors of the prevalence of contagious diseases, health system response to communicable diseases and ignoring the risks of the Arbaeen ceremony); the low perception of risk in pilgrims has three sub-themes (lack of awareness in pilgrims, fatalism in pilgrims and unhygienic belief in pilgrims); and the ineffectiveness of health education has two sub-themes (training shortage in the targeted group and educational content problems) that shows participant''s experiences of the health system''s challenges for coping with infectious diseases during the Arbaeen ceremony.

title:
  Exploring challenges of health system preparedness for communicable diseases in Arbaeen mass gathering: a qualitative study

abstract:
  Background: Infectious diseases are common problems in mass gatherings, especially when there is a lack of health system preparedness. Since Iran is one of the most important countries on the walking path of Arbaeen and has a vital role in providing health services to pilgrims, the experiences of health challenges by participants is of key importance. The aim of this study is to explore stakeholders’ experiences on the health system's preparedness and challenges, and to provide suggestions for preventing infectious diseases during the Arbaeen mass gathering. Methods: A qualitative research method was used with a conventional content analysis approach. The number of participants was 17, including 13 executive managers and 4 health policymakers who entered the study among participants. Semi-structured interviews were used to generate the data. Interviews were analyzed by means of content analysis after face-to-face interviews. Results: Data analysis resulted in the extraction of four main themes and 11 sub-themes. Health infrastructure defects in Iraq has three sub-themes (health abandonment in Iraq, the weaknesses in health culture and problems related to the health system); poor control of the causative factors of infectious diseases has three sub-themes (the underlying factors of the prevalence of contagious diseases, health system response to communicable diseases and ignoring the risks of the Arbaeen ceremony); the low perception of risk in pilgrims has three sub-themes (lack of awareness in pilgrims, fatalism in pilgrims and unhygienic belief in pilgrims); and the ineffectiveness of health education has two sub-themes (training shortage in the targeted group and educational content problems) that shows participant’s experiences of the health system's challenges for coping with infectious diseases during the Arbaeen ceremony. Conclusion: Pilgrim-based training, planning and controlling other challenges may change these threats to opportunities and improve the health of participants of the mass gathering of Arbaeen in the region.


id: cord-265282-v3n9ff16
author: Ahn, Inkyung
date: 2018-01-21
txt: ./txt/cord-265282-v3n9ff16.txt
cache: ./cache/cord-265282-v3n9ff16.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jtbi.2017.10.004
doi: 10.1016/j.jtbi.2017.10.004
summary:
  For the SIQ based ordinary differential equation (ODE) model, we perform the task of parameter estimation, and apply optimal control theory to the controlled SIQ model, with the goal of minimizing the infectious compartment population and the cost of implementing the quarantine and isolation strategies. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach.

title:
  Investigation of nonlinear epidemiological models for analyzing and controlling the MERS outbreak in Korea

abstract:
  Abstract Much concern has arisen regarding serious epidemics due to the Middle East Respiratory Syndrome (MERS) coronavirus. The first MERS case of Korea was reported on 20 May 2015, and since then, the MERS outbreak in Korea has resulted in hundreds of confirmed cases and tens of deaths. Deadly infectious diseases such as MERS have significant direct and indirect social impacts, which include disease-induced mortality and economic losses. Also, a delayed response to the outbreak and underestimating its danger can further aggravate the situation. Hence, an analysis and establishing efficient strategies for preventing the propagation of MERS is a very important and urgent issue. In this paper, we propose a class of nonlinear susceptible-infectious-quarantined (SIQ) models for analyzing and controlling the MERS outbreak in Korea. For the SIQ based ordinary differential equation (ODE) model, we perform the task of parameter estimation, and apply optimal control theory to the controlled SIQ model, with the goal of minimizing the infectious compartment population and the cost of implementing the quarantine and isolation strategies. Simulation results show that the proposed SIQ model can explain the observed data for the confirmed cases and the quarantined cases in the MERS outbreak very well, and the number of the MERS cases can be controlled reasonably well via the optimal control approach.


id: cord-265679-7gzont7l
author: Guo, Nan
date: 2018-09-18
txt: ./txt/cord-265679-7gzont7l.txt
cache: ./cache/cord-265679-7gzont7l.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30231560/
doi: 10.3390/v10090507
summary:
  In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. Vero cells cultured in 24-well plates were washed with PBS for 3 times and inoculated respectively with single medium, or single PEDV, or PEDV pre-incubated with different concentrations of Caerin1.1. PEDV suspensions containing different concentrations of Caerin1.1 were pre-incubated for 1 h at 37 • C, and were serially diluted before they were inoculated on the 80% confluent Vero cell monolayers grown in the 96-well plates, followed by washing 3 times with PBS. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1. As shown in Figure 4 , Vero cells were infected with PEDV (200 pfu) pre-incubated with different concentrations of Caerin1.1.

title:
  Caerin1.1 Suppresses the Growth of Porcine Epidemic Diarrhea Virus In Vitro via Direct Binding to the Virus

abstract:
  Porcine epidemic diarrhea (PED) has re-emerged in recent years and has already caused huge economic losses to the porcine industry all over the world. Therefore, it is urgent for us to find out efficient ways to prevent and control this disease. In this study, the antiviral activity of a cationic amphibian antimicrobial peptide Caerin1.1 against porcine epidemic diarrhea virus (PEDV) was evaluated by an in vitro system using Vero cells. We found that even at a very low concentration, Caerin1.1 has the ability to destroy the integrity of the virus particles to block the release of the viruses, resulting in a considerable decrease in PEDV infections. In addition, Caerin1.1 showed powerful antiviral activity without interfering with the binding progress between PEDV and the receptor of the cells, therefore, it could be used as a potential antiviral drug or as a microbicide compound for prevention and control of PEDV.


id: cord-268149-narre5e7
author: Aziz, Muhammad Abdul
date: 2018-01-29
url: https://doi.org/10.1186/s13002-018-0212-0
doi: 10.1186/s13002-018-0212-0
title:
  Traditional uses of medicinal plants used by Indigenous communities for veterinary practices at Bajaur Agency, Pakistan

abstract:
  BACKGROUND: The pastoral lifestyle of Indigenous communities of Bajaur Agency is bringing them close to natural remedies for treating their domestic animals. Several studies have been conducted across the globe describing the importance of traditional knowledge in veterinary care. Therefore, this study was planned with the aim to record knowledge on ethnoveterinary practices from the remote areas and share sit with other communities through published literature. METHODS: Data was gathered from community members through semi-structured interviews and analyzed through informant consensus factor (Fic) to evaluate the consent of current ethnoveterinary practices among the local people. RESULTS: In total, 73 medicinal plants were recorded under the ethnoveterinary practices. Most widely used medicinal plants with maximum use reports (URs) were Visnaga daucoides Gaertn., Foeniculum vulgare Mill., Solanum virginianum L., Withania somnifera (L.) Dunal, Glycyrrhiza glabra L., and Curcuma longa L. New medicinal values were found with confidential level of citations for species including Heracleum candicans and Glycerhiza glabra. Family Apiaceae was the utmost family with high number (7 species) of medicinal plants. Maximum number of medicinal plants (32) was used for gastric problems. High Fic was recorded for dermatological (0.97) followed by reproductive (0.93) and gastrointestinal disorders (0.92). The main route of remedies administration was oral. CONCLUSIONS: Current study revealed that the study area has sufficient knowledge on ethnoveterinary medicinal plants. This knowledge is in the custody of nomadic grazers, herders, and aged community members. Plants with new medicinal uses need to be validated phytochemically and pharmacologically for the development of new alternative drugs for veterinary purposes.


id: cord-270286-76mrzaxi
title: Impact of bacteremia prediction rule in CAP: Before and after study
author: Kim, Byunghyun
date: 2018-05-31
txt: ./txt/cord-270286-76mrzaxi.txt
cache: ./cache/cord-270286-76mrzaxi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28988847/
doi: 10.1016/j.ajem.2017.10.005
summary:
  We also compared 30-day mortality, emergency department (ED) length of stay, time-interval to initial antibiotics after ED arrival, and any changes to the antibiotics regimen as results of the blood cultures. In our time series analysis study, we reported that the implementation of the bacteremia prediction rule successfully reduced the blood culture rate without any significant 30-day mortality and antibiotics regimen changes. Finally the target population only included patients with CAP and this would limit the broad application of the Table 4 Blood culture results with contamination and antibiotics regimen changes before and after implementation of bacteremia prediction model. In conclusion, the implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30day mortality and antibiotics regimen. In conclusion, the implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30day mortality and antibiotics regimen.

abstract:
  Abstract Objective In cases of community acquired pneumonia (CAP), it has been known that blood cultures have low yields and rarely affect clinical outcomes. Despite many studies predicting the likelihood of bacteremia in CAP patients, those results have been rarely implemented in clinical practice, and use of blood culture in CAP is still increasing. This study evaluated impact of implementing a previously derived and validated bacteremia prediction rule. Methods In this registry-based before and after study, we used piecewise regression analysis to compare the blood culture rate before and after implementation of the prediction rule. We also compared 30-day mortality, emergency department (ED) length of stay, time-interval to initial antibiotics after ED arrival, and any changes to the antibiotics regimen as results of the blood cultures. In subgroup analysis, we compared two groups (with or without the use of the prediction rule) after implementation period, using propensity score matching. Results Following the implementation, the blood culture rate declined from 85.5% to 78.1% (P =0.003) without significant changes in 30-day mortality and antibiotics regimen. The interval to initial antibiotics (231min vs. 221min, P =0.362) and length of stay (1019min vs. 954min, P =0.354) were not significantly changed. In subgroup analysis, the group that use the prediction rule showed 25min faster antibiotics initiation (P =0.002) and 48min shorter length of stay (P =0.007) than the group that did not use the rule. Conclusion Implementation of the bacteremia prediction rule in CAP patients reduced the blood culture rate without affecting the 30-day mortality and antibiotics regimen.


id: cord-273324-xhpv783y
author: Land, Kevin J.
date: 2018-12-13
txt: ./txt/cord-273324-xhpv783y.txt
cache: ./cache/cord-273324-xhpv783y.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30546093/
doi: 10.1038/s41564-018-0295-3
summary:
  For example, as POC technologies for HIV viral load and early infant diagnosis were being developed, there was tremendous emphasis on quality, given the complexity of the test and lessons learned from HIV RDTs. Malaria is estimated to be the cause of at least a million deaths a year worldwide, most of which are in sub-Saharan Africa. Although national TB programmes provide a robust architecture for the implementation of new technologies, challenges associated with the near-POC NAT assay remain as barriers -affordability (molecular assays are device-based and costly, even with subsidy), expertise (more technically demanding than lateral flow RDTs) and sustainability 46 , in addition to power and per-test time. Such tests can only be created by forming strong collaborative partnerships across many disciplinary boundaries, and we look toward a future when data connectivity linking cost-effective ASSURED diagnostics to laboratory systems will form the backbone of health care systems and provide real-time data for evidence-based disease control and prevention strategies, more efficient health systems and improved patient outcomes.

title:
  REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes

abstract:
  Lack of access to quality diagnostics remains a major contributor to health burden in resource-limited settings. It has been more than 10 years since ASSURED (affordable, sensitive, specific, user-friendly, rapid, equipment-free, delivered) was coined to describe the ideal test to meet the needs of the developing world. Since its initial publication, technological innovations have led to the development of diagnostics that address the ASSURED criteria, but challenges remain. From this perspective, we assess factors contributing to the success and failure of ASSURED diagnostics, lessons learnt in the implementation of ASSURED tests over the past decade, and highlight additional conditions that should be considered in addressing point-of-care needs. With rapid advances in digital technology and mobile health (m-health), future diagnostics should incorporate these elements to give us REASSURED diagnostic systems that can inform disease control strategies in real-time, strengthen the efficiency of health care systems and improve patient outcomes.


id: cord-275162-2239dk45
title: Course of Illness after Viral Infection in Indian Children with Cystic Fibrosis
author: Gulla, Krishna Mohan
date: 2018-06-09
txt: ./txt/cord-275162-2239dk45.txt
cache: ./cache/cord-275162-2239dk45.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/tropej/fmy033
doi: 10.1093/tropej/fmy033
summary:
  On follow-up, children with viral infection (Group I) had adverse outcome in form of greater worsening of Shwachman clinical scores, number of pulmonary exacerbations requiring antibiotic usage [4 (2.1%)] and [2.8 (1.7%)], need for intravenous antibiotics 30.4% vs. CONCLUSION: Acute viral infection in children with CF affected course of illness on follow-up, including frequent and severe pulmonary exacerbations requiring hospitalization, intravenous antibiotics, decline in CF scores and increased mortality over next 12–18 months. This retrospective cohort study demonstrated that CF children who had suffered a viral respiratory infection had worse outcome in follow-up in the form of lower CF scores, higher use of intravenous antibiotics, higher rate of hospitalization and higher mortality as compared with matched controls who did not have viral respiratory infection. C O N C L U S I O N Following the viral respiratory infections in children with CF who were already nutritionally compromised, there were frequent and severe pulmonary exacerbations requiring hospitalization, intravenous antibiotics, decline in CF scores and increased mortality over next 12-18 months.

abstract:
  OBJECTIVE: To study the clinical impact of respiratory viral infection in children with cystic fibrosis (CF). DESIGN: Retrospective cohort study. SETTING: Tertiary care referral centre for CF in India. PARTICIPANTS/PATIENTS: Children with CF attending a pediatric chest clinic. METHODS: Case records of the children with CF who had a pulmonary exacerbation with documented acute respiratory viral infection between October 2013 and December 2014 (Group I) and an equal number of controls (Group II) with pulmonary exacerbation in absence of acute respiratory viral infection were reviewed. OUTCOME MEASURES: The two groups were compared for the following outcomes over a period of 12–18 months: bacterial colonization, antibiotics usage, pulmonary exacerbations, numbers of outpatient visits, hospitalization and oxygen therapy and spirometric parameters. RESULTS: In total, 46 children [23 each with viral infection (Group I) and without viral infection (Group II)] of age 7–264 months were enrolled; baseline clinical status and pulmonary function tests were comparable. Mean (SD) follow-up duration in those who had viral infection and who had no viral infection was 15.7 (7.1) and 17.5 (5.4) months, respectively. On follow-up, children with viral infection (Group I) had adverse outcome in form of greater worsening of Shwachman clinical scores, number of pulmonary exacerbations requiring antibiotic usage [4 (2.1%)] and [2.8 (1.7%)], need for intravenous antibiotics 30.4% vs. 8.7%, hospitalization rates 31.8% vs. 4.3% and mortality 30.4% vs. 4.7%, respectively. CONCLUSION: Acute viral infection in children with CF affected course of illness on follow-up, including frequent and severe pulmonary exacerbations requiring hospitalization, intravenous antibiotics, decline in CF scores and increased mortality over next 12–18 months.


id: cord-275719-ru33ubss
author: Roingeard, Philippe
date: 2018-11-09
txt: ./txt/cord-275719-ru33ubss.txt
cache: ./cache/cord-275719-ru33ubss.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/rmv.2019
doi: 10.1002/rmv.2019
summary:
  Despite the lack of established methods of biological sample preparation for transmission electron microscopy (TEM) at this time, Helmut Ruska was able to characterize the morphology of several viruses and he developed a rough viral classification based on the size and shape of the viral particles. 4 TEM was rapidly adopted for its first major use in clinical virology: the differential diagnosis of smallpox, caused by the variola virus Abbreviations: ELISA, enzyme-linked immunosorbent assay; EM, electron microscopy; EMEA, European Medicines Agency; FDA, Food and Drug Administration; FPERT, fluorescent product-enhanced reverse transcription; LCMV, lymphocytic choriomeningitis virus; PCR, polymerase chain reaction; SARS, severe acute respiratory syndrome; SFTS, severe fever with thrombocytopenia syndrome; TEM, transmission electron microscopy from the poxvirus family, and chickenpox, caused by the varicellazoster virus of the herpes family, based on investigations of fluid samples from the vesicles on the patients'' skin. Detection of retrovirus-like particles by transmission electron microscopy (TEM) with negative staining in bulk harvests of rodent cells used for the production of biological products.

title:
  Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety

abstract:
  Transmission electron microscopy (TEM) is the only imaging technique allowing the direct visualization of viruses, due to its nanometer‐scale resolution. Between the 1960s and 1990s, TEM contributed to the discovery of many types of viruses and served as a diagnostic tool for identifying viruses directly in biological samples, either in suspension or in sections of tissues or mammalian cells grown in vitro in contact with clinical samples. The diagnosis of viral infections improved considerably during the 1990s, with the advent of highly sensitive techniques, such as enzyme‐linked immunosorbent assay (ELISA) and PCR, rendering TEM obsolete for this purpose. However, the last 20 years have demonstrated the utility of this technique in particular situations, due to its “catch‐all” nature, making diagnosis possible through visualization of the virus, without the need of prior assumptions about the infectious agent sought. Thus, in several major outbreaks in which molecular techniques failed to identify the infectious agent, TEM provided the answer. TEM is also still occasionally used in routine diagnosis to characterize infections not diagnosed by molecular assays. It is also used to check the microbiological safety of biological products. Many biopharmaceuticals are produced in animal cells that might contain little‐known, difficult‐to‐detect viruses. In this context, the “catch‐all” properties of TEM make it possible to document the presence of viruses or virus‐like particles in these products.


id: cord-280374-yj0r4rwt
author: Jain, Richa
date: 2018-01-04
txt: ./txt/cord-280374-yj0r4rwt.txt
cache: ./cache/cord-280374-yj0r4rwt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28984258/
doi: 10.1007/s13312-017-1172-5
summary:
  title: Hepatic sinusoidal-obstruction syndrome and busulfan-induced lung injury in a post-autologous stem cell transplant recipient He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. In our case other bacterial infections typically seen in an immunocompromised child are also unlikely in view of sterile cultures, complete absence of fever and normal Creactive protein (CRP).Though this clinical presentation can be caused by infection with PCJ, it is an uncommon infection. The non-infective etiologies causing respiratory symptoms in a post-transplant setting can be pulmonary GvHD, Idiopathic pneumonia syndrome (IPS), Bronchiolitis obliterans syndrome (BOS), Cryptogenic organising pneumonia (COP) and SOS. The final diagnosis is neuroblastoma stage IV, day + 68 post auto-SCT (Bu-Mel) with pneumonitis, ARDS and multi-organ failure; likely etiology being fungal pneumonia or CMV pneumonia and hepatitis secondary to ischemia with underlying SOS. Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation

title:
  Hepatic sinusoidal-obstruction syndrome and busulfan-induced lung injury in a post-autologous stem cell transplant recipient

abstract:
  Veno-occlusive disease of the liver is mostly encountered as a complication of hematopoietic stem cell transplantation with myeloablative regimens with an incidence estimated to be 13.7%. It is clinically characterized by tender hepatomegaly, jaundice, weight gain and ascites. Strong clinical suspicion and an early recognition of clinical signs are essential to establish the diagnosis and institute effective regimen. Another complication of cytotoxic drugs given for cancers, is development of busulfan-induced lung injury. A strong index of suspicion is needed for its diagnosis, especially in setting where opportunistic fungal and viral infections manifest similarly. We illustrate the clinical and autopsy finings in a 2½-year-old boy who received autologous stem-cell transplantation following resection of stage IV neuroblastoma. He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. The autopsy findings are remarkable for their rarity.


id: cord-281403-yl7jdarm
title: U.S. Medical Examiner/Coroner capability to handle highly infectious decedents
author: Le, Aurora B.
date: 2018-11-06
txt: ./txt/cord-281403-yl7jdarm.txt
cache: ./cache/cord-281403-yl7jdarm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30402743/
doi: 10.1007/s12024-018-0043-2
summary:
  Select results were: less than half of respondents (44%) stated that their office had been involved in handling a suspected or confirmed highly infectious remains case and responses indicated medical examiners. Survey questions included: demographic information (e.g. title, population served, state), personal protective equipment (PPE) worn in different infectious scenarios, procedures performed in different infectious scenarios, duration of training received, biosafety level (BSL) capabilities, and jurisdictional handling of highly infectious remains. Slightly more than half of respondents (56%; 61/108) stated their office staff had received training on donning and doffing PPE in suspected or confirmed cases of highly infectious remains; nearly one-third (32%) (18/56) reported the amount of cumulative training in hours per person, on average per year, was 1 h or less while 29% (16/56) spent between 1 and 2 h of training. 3. This survey, with respondents from nearly every U.S. state, revealed current levels of Medical Examiner/ Coroner training and education to address suspected or confirmed highly infectious remains.

abstract:
  In the United States of America, Medical Examiners and Coroners (ME/Cs) investigate approximately 20% of all deaths. Unexpected deaths, such as those occurring due to a deceased person under investigation for a highly infectious disease, are likely to fall under ME/C jurisdiction, thereby placing the ME/C and other morgue personnel at increased risk of contracting an occupationally acquired infection. This survey of U.S. ME/Cs′ capabilities to address highly infectious decedents aimed to determine opportunities for improvement at ME/C facilities serving a state or metropolitan area. Data for this study was gathered via an electronic survey. Of the 177 electronic surveys that were distributed, the overall response rate was N = 108 (61%), with 99 of those 108 respondents completing all the questions within the survey. At least one ME/C responded from 47 of 50 states, and the District of Columbia. Select results were: less than half of respondents (44%) stated that their office had been involved in handling a suspected or confirmed highly infectious remains case and responses indicated medical examiners. Additionally, ME/C altered their personal protective equipment based on suspected versus confirmed highly infectious remains rather than taking an all-hazards approach. Standard operating procedures or guidelines should be updated to take an all-hazards approach, best-practices on handling highly infectious remains could be integrated into a standardized education, and evidence-based information on appropriate personal protective equipment selection could be incorporated into a widely disseminated learning module for addressing suspected or confirmed highly infectious remains, as those areas were revealed to be currently lacking.


id: cord-282322-ywwqnw74
author: Tomar, Jasmine
date: 2018-10-09
txt: ./txt/cord-282322-ywwqnw74.txt
cache: ./cache/cord-282322-ywwqnw74.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30312742/
doi: 10.1016/j.ejpb.2018.10.008
summary:
  Our previous study in chickens has shown that inhalation of a non-adjuvanted dry powder influenza vaccine formulation during normal breathing results in partial protection against lethal influenza challenge. Upon passive inhalation of dry influenza vaccine formulations in an optimized set-up, BLP and Advax/BLP adjuvanted formulations induced significantly higher systemic immune responses than the non-adjuvanted formulation. In a previous study, we have shown that pulmonary immunization by dispersion of a dry powder influenza vaccine directly at the syrinx of chickens (active administration) was able to completely protect these animals against lethal viral challenge [11] . For this, we initially tested whether (a) BLP or Advax could be co-formulated with influenza vaccine into dry powder formulations that are suitable for pulmonary immunization; (b) the adjuvants have the potential to boost systemic and mucosal immune responses to influenza; (c) passive administration with either non-adjuvanted or adjuvanted influenza formulations would protect chickens against a lethal HPAIV challenge.

title:
  Passive inhalation of dry powder influenza vaccine formulations completely protects chickens against H5N1 lethal viral challenge

abstract:
  Bird to human transmission of high pathogenicity avian influenza virus (HPAIV) poses a significant risk of triggering a flu pandemic in the human population. Therefore, vaccination of susceptible poultry during an HPAIV outbreak might be the best remedy to prevent such transmissions. To this end, suitable formulations and an effective mass vaccination method that can be translated to field settings needs to be developed. Our previous study in chickens has shown that inhalation of a non-adjuvanted dry powder influenza vaccine formulation during normal breathing results in partial protection against lethal influenza challenge. The aim of the present study was to improve the effectiveness of pulmonary vaccination by increasing the vaccine dose deposited in the lungs and by the use of suitable adjuvants. Two adjuvants, namely, Bacterium-like Particles (BLP) and Advax, were spray freeze dried with influenza vaccine into dry powder formulations. Delivery of dry formulations directly at the syrinx revealed that BLP and Advax had the potential to boost either systemic or mucosal immune responses or both. Upon passive inhalation of dry influenza vaccine formulations in an optimized set-up, BLP and Advax/BLP adjuvanted formulations induced significantly higher systemic immune responses than the non-adjuvanted formulation. Remarkably, all vaccinated animals not only survived a lethal influenza challenge, but also did not show any shedding of challenge virus except for two out of six animals in the Advax group. Overall, our results indicate that passive inhalation is feasible, effective and suitable for mass vaccination of chickens if it can be adapted to field settings.


id: cord-287853-cob7ur35
title: The expanding role of mass spectrometry in the field of vaccine development
author: Sharma, Vaneet Kumar
date: 2018-05-31
txt: ./txt/cord-287853-cob7ur35.txt
cache: ./cache/cord-287853-cob7ur35.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1002/mas.21571
doi: 10.1002/mas.21571
summary:
  As illustrated in the following section and in Table 1 , mass spectrometry-based techniques have been used to perform the structural characterization, glycosylation profiling and antigen quantitation during the development of the HIV, influenza, Dengue, Ebola, Meningococcal, and other vaccines. The review also highlights that mass spectrometry-based methods such as glycan analysis has been used to analyze a specific envelope glycoproteins (Env) and has broad applicability to any other glycoprotein-based vaccines. 91 To improve on the conventional approaches for absolute quantitation of GP1 in Ebola virus-like particles (eVLPs), an isotope dilution full-scan liquid chromatography-high-resolution mass spectrometry method was developed using an UltiMate 3000 HPLC and an Development of a liquid chromatography high resolution mass spectrometry method for the quantitation of viral envelope glycoprotein in Ebola virus-like particle vaccine preparations Development and application of a reversed-phase high-performance liquid chromatographic method for quantitation and characterization of a Chikungunya virus-like particle vaccine

abstract:
  Biological mass spectrometry has evolved as a core analytical technology in the last decade mainly because of its unparalleled ability to perform qualitative as well as quantitative profiling of enormously complex biological samples with high mass accuracy, sensitivity, selectivity and specificity. Mass spectrometry‐based techniques are also routinely used to assess glycosylation and other post‐translational modifications, disulfide bond linkage, and scrambling as well as for the detection of host cell protein contaminants in the field of biopharmaceuticals. The role of mass spectrometry in vaccine development has been very limited but is now expanding as the landscape of global vaccine development is shifting towards the development of recombinant vaccines. In this review, the role of mass spectrometry in vaccine development is presented, some of the ongoing efforts to develop vaccines for diseases with global unmet medical need are discussed and the regulatory challenges of implementing mass spectrometry techniques in a quality control laboratory setting are highlighted.


id: cord-288332-y15g1yak
title: Clinical and laboratory profiles of hospitalized children with acute respiratory virus infection
author: Choi, Eunjin
date: 2018-06-25
txt: ./txt/cord-288332-y15g1yak.txt
cache: ./cache/cord-288332-y15g1yak.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3345/kjp.2018.61.6.180
doi: 10.3345/kjp.2018.61.6.180
summary:
  PURPOSE: Despite the availability of molecular methods, identification of the causative virus in children with acute respiratory infections (ARIs) has proven difficult as the same viruses are often detected in asymptomatic children. METHODS: Multiplex reverse transcription polymerase chain reaction assays were performed to detect 15 common respiratory viruses in children under 15 years of age who were hospitalized with ARI between January 2013 and December 2015. Nasopharyngeal aspirates from all patients were obtained within 48 hours of admission for multiplex RT-PCR assay to detect the following 15 common respiratory viruses: influenza virus A and B (IFA, IFB), respiratory syncytial virus A and B (RSV A, RSV B), parainfluenza virus 1-4 (PIV 1, PIV 2, PIV 3, PIV 4), human coronavirus 229E and OC43 (hCV-229E, hCV-OC43), human rhinovirus (hRV), human enterovirus (hEV), adenovirus (AdV), human bocavirus (hBV), and human metapneumovirus (hMPV).

abstract:
  PURPOSE: Despite the availability of molecular methods, identification of the causative virus in children with acute respiratory infections (ARIs) has proven difficult as the same viruses are often detected in asymptomatic children. METHODS: Multiplex reverse transcription polymerase chain reaction assays were performed to detect 15 common respiratory viruses in children under 15 years of age who were hospitalized with ARI between January 2013 and December 2015. Viral epidemiology and clinical profiles of single virus infections were evaluated. RESULTS: Of 3,505 patients, viruses were identified in 2,424 (69.1%), with the assay revealing a single virus in 1,747 cases (49.8%). While major pathogens in single virus-positive cases differed according to age, human rhinovirus (hRV) was common in patients of all ages. Respiratory syncytial virus (RSV), influenza virus (IF), and human metapneumovirus (hMPV) were found to be seasonal pathogens, appearing from fall through winter and spring, whereas hRV and adenovirus (AdV) were detected in every season. Patients with ARIs caused by RSV and hRV were frequently afebrile and more commonly had wheezing compared with patients with other viral ARIs. Neutrophil-dominant inflammation was observed in ARIs caused by IF, AdV, and hRV, whereas lymphocyte-dominant inflammation was observed with RSV A, parainfluenza virus, and hMPV. Monocytosis was common with RSV and AdV, whereas eosinophilia was observed with hRV. CONCLUSION: In combination with viral identification, recognition of virus-specific clinical and laboratory patterns will expand our understanding of the epidemiology of viral ARIs and help us to establish more efficient therapeutic and preventive strategies.


id: cord-289026-v09m2fzw
author: Sun, Yan-gang
date: 2018-10-01
txt: ./txt/cord-289026-v09m2fzw.txt
cache: ./cache/cord-289026-v09m2fzw.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0141813018305300
doi: 10.1016/j.ijbiomac.2018.05.167
summary:
  Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Based on the results above, recombinant pAPN ectodomain was obtained as dimers, and PEDV S1 or S1t protein existed as monomers, which showed similar natures of mammalian APN [43] and other coronavirus S proteins [48] [49] [50] as previously reported. In the current study, three canonical assays were carried out to characterize the interaction between pAPN ectodomain and PEDV S1 or S1t protein since these functional target proteins were successfully prepared. Identification and comparison of receptor binding characteristics of the spike protein of two porcine epidemic diarrhea virus strains

title:
  Characterization of the interaction between recombinant porcine aminopeptidase N and spike glycoprotein of porcine epidemic diarrhea virus

abstract:
  Porcine epidemic diarrhea (PED) has caused huge economic losses to the global pork industry. Infection by its causative agent PED virus (PEDV), an Alpha-coronavirus, was previously proven to be mediated by its spike (S) glycoprotein and a cellular receptor porcine aminopeptidase N (pAPN). Interestingly, some recent studies have indicated that pAPN is not a functional receptor for PEDV. To date, there is a lack of a direct evidence for the interaction between pAPN and PEDV S protein in vitro. Here, we prepared pAPN ectodomain and the truncated variants of PEDV S protein in Drosophila S2 cells. These recombinant proteins were homogeneous after purification by metal-affinity and size-exclusion chromatography. We then assayed the purified target proteins through immunogenicity tests, PEDV binding interference assays, circular dichroism (CD) measurements, pAPN activity assay and structural determination, demonstrating that they were biologically functional. Finally, we characterized their interactions by gel filtration chromatography, native-polyacrylamide gel electrophoresis (PAGE) and surface plasmon resonance (SPR) analyses. The results showed that their affinities were too low to form complexes, which suggest that pAPN may be controversial as the genuine receptor for PEDV. Therefore, further research needs to be carried out to elucidate the interaction between PEDV and its genuine receptor.


id: cord-290861-5bxvenue
author: Ashwell, M.
date: 2018-11-19
txt: ./txt/cord-290861-5bxvenue.txt
cache: ./cache/cord-290861-5bxvenue.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1090023318307524
doi: 10.1016/j.tvjl.2018.11.008
summary:
  Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). After the most stable reference genes were identified, a selection of genes previously associated with nociception in rodent models, and of interest to the authors, were examined using qPCR in the same samples to allow us to start characterizing the neurobiological signature of pain associated with DJD in cats. After a set of stable reference genes were identified for each tissue type, 13 genes associated with pain in rodents were selected (based on current knowledge of genes involved in pain states (Foulkes and Wood, 2008) and their expression levels compared in the DRG from DJD-affected and healthy samples.

title:
  Characterization of gene expression in naturally occurring feline degenerative joint disease-associated pain

abstract:
  Degenerative joint disease (DJD) associated-pain is a clinically relevant and common condition affecting domesticated cats and other species including humans. Identification of the neurobiological signature of pain is well developed in rodent pain models, however such information is lacking from animals or humans with naturally occurring painful conditions. In this study, identification of housekeeping genes (HKG) for neuronal tissue and expression levels of genes considered associated with chronic pain in rodent models were explored in cats with naturally occurring osteoarthritic pain. Fourteen adult cats were evaluated — seven without clinical signs of osteoarthritic pain, and seven with hind limb radiographic DJD and pain. Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). HKG identified as the most stable across all tissue samples were many of the ribosomal protein genes, such as RPL30 and RPS19. qPCR results showed ATF3 and CX3CL1 up-regulated in DJD-affected dorsal root ganglia compared to clinically healthy controls. In spinal cord, CX3CL1 was up-regulated and NGF was down-regulated when DJD-affected samples were compared to healthy samples. Further work is needed to understand the neurobiology of pain in naturally occurring disease and what rodent models are predictive of these changes in more heterogeneous populations such as domestic cats.


id: cord-292830-gcfx1095
title: Novel activities of safe-in-human broad-spectrum antiviral agents
author: Ianevski, Aleksandr
date: 2018-04-23
txt: ./txt/cord-292830-gcfx1095.txt
cache: ./cache/cord-292830-gcfx1095.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29698664/
doi: 10.1016/j.antiviral.2018.04.016
summary:
  Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. Here, we hypothesised that some of the identified safe-in-human BSAs could possess novel antiviral activities and, therefore, could be used for treatment of many different viral infections. Fig. 1 shows BSAs and other approved antiviral drugs linked to viral and host targets through viruses they inhibit. Thus, we tested several known BSA agents against (−)ssRNA, (+) ssRNA, ssRNA-RT and dsDNA viruses and identified novel activities for dalbavancin against EV1, ezetimibe against ZIKV and HIV-1, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against RVFV. We identified novel antiviral activities for dalbavancin (against EV1), ezetimibe (against HIV-1 and ZIKV), azacitidine, cyclosporine, minocycline, oritavancin and ritonavir (against RVFV) (Fig. 4) .

abstract:
  According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.


id: cord-295491-zlah6u5s
author: Günther, Sonja
date: 2018-03-11
txt: ./txt/cord-295491-zlah6u5s.txt
cache: ./cache/cord-295491-zlah6u5s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29540320/
doi: 10.1016/j.jviromet.2018.03.003
summary:
  The aim of this study was to test two commercially available reaction mixtures in a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect feline Coronavirus (FCoV) in body cavity effusions of cats with and without FIP, in order to minimize the time from sampling to obtaining results. The aim of this study was to test specificity and sensitivity of two commercially available reaction mixtures in a reverse transcription LAMP (RT-LAMP) to detect FCoV in body cavity effusions of cats with and without FIP, and to minimize the time from sampling to obtaining results. The FIP group (n = 34) included cats with a definitive diagnosis of FIP by one or more methods: All effusions of cats with FIP tested positive for FCoV by RT-PCR by a commercial laboratory, and in 26/34 samples putative disease-causing mutations could be detected.

title:
  Detection of feline Coronavirus in effusions of cats with and without feline infectious peritonitis using loop-mediated isothermal amplification

abstract:
  Feline infectious peritonitis (FIP) is a fatal disease in cats worldwide. The aim of this study was to test two commercially available reaction mixtures in a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect feline Coronavirus (FCoV) in body cavity effusions of cats with and without FIP, in order to minimize the time from sampling to obtaining results. RNA was extracted from body cavity effusion samples of 71 cats, including 34 samples from cats with a definitive diagnosis of FIP, and 37 samples of control cats with similar clinical signs but other confirmed diseases. Two reaction mixtures (Isothermal Mastermix, OptiGene Ltd.and PCRun™ Molecular Detection Mix, Biogal) were tested using the same primers, which were designed to bind to a conserved region of the FCoV membrane protein gene. Both assays were conducted under isothermal conditions (61 °C–62 °C). Using the Isothermal Mastermix of OptiGene Ltd., amplification times ranged from 4 and 39 min with a sensitivity of 35.3% and a specificity of 94.6% for the reported sample group. Using the PCRun™ Molecular Detection Mix of Biogal, amplification times ranged from 18 to 77 min with a sensitivity of 58.8% and a specificity of 97.3%. Although the RT-LAMP assay is less sensitive than real time reverse transcription PCR (RT-PCR), it can be performed without the need of expensive equipment and with less hands-on time. Further modifications of primers might lead to a suitable in-house test and accelerate the diagnosis of FIP.


id: cord-295878-pd9elo4l
author: Luo, Wei
date: 2018-11-30
txt: ./txt/cord-295878-pd9elo4l.txt
cache: ./cache/cord-295878-pd9elo4l.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0198971517303551
doi: 10.1016/j.compenvurbsys.2018.06.008
summary:
  Based on the location-based network, we simulate influenza transmission dynamics and evaluate the efficacy of different vaccination strategies according to the identified geo-social interaction patterns. Second, the design of control strategies based on individualbased networks (e.g., vaccinate the individual with a large number of contacts) is challenging because it is infeasible to keep track of all social contacts of infections (Cohen, Havlin, & Ben-Avraham 2003; Gómez-Gardenes, Echenique, & Moreno 2006; Holme 2004 ), but the information to estimate population flows among locations based on intra-and inter-community travelers is widely available in the existing census data and travel survey reports (Mao & Bian 2010) . Thus, location-based human interaction network models are required to easily represent explicitly spatial dynamics of the disease transmission and design control strategies to target certain critical locations first rather than prioritizing individuals.

title:
  A large-scale location-based social network to understanding the impact of human geo-social interaction patterns on vaccination strategies in an urbanized area

abstract:
  Abstract Cities play an important role in fostering and amplifying the transmission of airborne diseases (e.g., influenza) because of dense human contacts. Before an outbreak of airborne diseases within a city, how to determine an appropriate containment area for effective vaccination strategies is unknown. This research treats airborne disease spreads as geo-social interaction patterns, because viruses transmit among different groups of people over geographical locations through human interactions and population movement. Previous research argued that an appropriate scale identified through human geo-social interaction patterns can provide great potential for effective vaccination. However, little work has been done to examine the effectiveness of such vaccination at large scales (e.g., city) that are characterized by spatially heterogeneous population distribution and movement. This article therefore aims to understand the impact of geo-social interaction patterns on effective vaccination in the urbanized area of Portland, Oregon. To achieve this goal, we simulate influenza transmission on a large-scale location-based social network to 1) identify human geo-social interaction patterns for designing effective vaccination strategies, and 2) and evaluate the efficacy of different vaccination strategies according to the identified geo-social patterns. The simulation results illustrate the effectiveness of vaccination strategies based on geo-social interaction patterns in containing the epidemic outbreak at the source. This research can provide evidence to inform public health approaches to determine effective scales in the design of disease control strategies.


id: cord-296992-2vp35fwv
title: Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic
author: Simonsen, Lone
date: 2018-05-08
txt: ./txt/cord-296992-2vp35fwv.txt
cache: ./cache/cord-296992-2vp35fwv.txt
extension: .txt
mime: text/plain
url: https://academic.oup.com/cid/article-pdf/67/3/341/25156461/ciy088.pdf
doi: 10.1093/cid/ciy088
summary:
  We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. Since 2009, INSIGHT has undertaken 2 cohort studies-1 outpatient (FLU002) and 1 inpatient (FLU003)-specifically to address gaps in clinical research on the emerging influenza pandemic, including factors linked to disease progression and severe outcomes [24] . To underscore the importance of having baseline data, we compared the estimated pH1N1 clinical severity to that of seasonal influenza types and subtypes and noninfluenza respiratory patients in the post-pandemic period (2012) (2013) (2014) (2015) . Our analysis combining data from inpatient and outpatient INSIGHT cohorts demonstrates how preestablished global research networks could immediately begin rigorous studies to estimate the CFR, a key parameter of clinical severity of an emerging pandemic.

abstract:
  BACKGROUND: Early clinical severity assessments during the 2009 influenza A H1N1 pandemic (pH1N1) overestimated clinical severity due to selection bias and other factors. We retrospectively investigated how to use data from the International Network for Strategic Initiatives in Global HIV Trials, a global clinical influenza research network, to make more accurate case fatality ratio (CFR) estimates early in a future pandemic, an essential part of pandemic response. METHODS: We estimated the CFR of medically attended influenza (CFR(MA)) as the product of probability of hospitalization given confirmed outpatient influenza and the probability of death given hospitalization with confirmed influenza for the pandemic (2009–2011) and post-pandemic (2012–2015) periods. We used literature survey results on health-seeking behavior to convert that estimate to CFR among all infected persons (CFR(AR)). RESULTS: During the pandemic period, 5.0% (3.1%–6.9%) of 561 pH1N1-positive outpatients were hospitalized. Of 282 pH1N1-positive inpatients, 8.5% (5.7%–12.6%) died. CFR(MA) for pH1N1 was 0.4% (0.2%–0.6%) in the pandemic period 2009–2011 but declined 5-fold in young adults during the post-pandemic period compared to the level of seasonal influenza in the post-pandemic period 2012–2015. CFR for influenza-negative patients did not change over time. We estimated the 2009 pandemic CFR(AR) to be 0.025%, 16-fold lower than CFR(MA). CONCLUSIONS: Data from a clinical research network yielded accurate pandemic severity estimates, including increased severity among younger people. Going forward, clinical research networks with a global presence and standardized protocols would substantially aid rapid assessment of clinical severity. CLINICAL TRIALS REGISTRATION: NCT01056354 and NCT010561.


id: cord-298032-3zlu8g8y
title: Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds
author: Nan, Yuchen
date: 2018-04-20
url: https://doi.org/10.3389/fmicb.2018.00750
doi: 10.3389/fmicb.2018.00750
abstract:
  Phosphorodiamidate morpholino oligomers (PMO) are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD) has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.


id: cord-298805-ntpm68cg
title: Non-culture based assays for the detection of fungal pathogens
author: Otašević, S.
date: 2018-03-29
url: https://api.elsevier.com/content/article/pii/S1156523318300076
doi: 10.1016/j.mycmed.2018.03.001
abstract:
  Traditional, culture based methods for the diagnosis of fungal infections are still considered as gold standard, but they are time consuming and low sensitive. Therefore, in order to overcome the limitations, many researchers have focused on the development of new immunological and molecular based rapid assays that could enable early diagnosis of infection and accurate identification of fungal pathogens causing superficial and invasive infection. In this brief review, we highlighted the advantages and disadvantages of conventional diagnostic methods and possibility of non-culture based assays in diagnosis of superficial fungal infections and presented the overview on currently available immunochromatographic assays as well as availability of biomarkers detection by immunodiagnostic procedures in prompt and accurate diagnosis of invasive fungal infections. In addition, we presented diagnostic efficiency of currently available molecular panels and researches in this area.


id: cord-300459-tu2xrt9x
author: Li, Cui
date: 2018-05-01
url: https://api.elsevier.com/content/article/pii/S2211124718305345
doi: 10.1016/j.celrep.2018.04.005
title:
  A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos

abstract:
  Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, an emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. There is now an urgent need for prophylactic and therapeutic agents. To address this, we investigated six human monoclonal antibodies with ZIKV epitope specificity and neutralizing activity in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine.


id: cord-301767-1jv20em8
author: Alegbeleye, Oluwadara Oluwaseun
date: 2018-02-03
txt: ./txt/cord-301767-1jv20em8.txt
cache: ./cache/cord-301767-1jv20em8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29526204/
doi: 10.1016/j.fm.2018.01.003
summary:
  Primarily, pathogens may contaminate produce ''on-field'' via various routes including; atmospheric deposition, uptake from contaminated soils and groundwater (Harris et al., 2003; Lynch et al., 2009; Mei Soon et al., 2012) , use of raw (or poorly treated) manure and compost, exposure to contaminated water (irrigation or flooding), transfer by insects, or by fecal contamination generated by livestock or wild Table 1 The most commonly implicated etiological agents in fresh produce borne illnesses (Brackett, 1994; Buck et al., 2003; Heaton and Jones, 2008; Jung et al., 2014; Callej on et al., 2015) . Epidemiological investigations of food poisoning outbreaks, experimental studies examining pathogen contamination of fruits and vegetables as well as observations of increased incidence of disease in areas practicing wastewater irrigation with little or no wastewater treatment indicate that contaminated irrigation water might indeed be a source of foodborne pathogens on fresh produce (Norman and Kabler, 1953; Hern andez et al., 1997; Steele and Odumeru, 2004) .

title:
  Sources and contamination routes of microbial pathogens to fresh produce during field cultivation: A review

abstract:
  Foodborne illness resulting from the consumption of contaminated fresh produce is a common phenomenon and has severe effects on human health together with severe economic and social impacts. The implications of foodborne diseases associated with fresh produce have urged research into the numerous ways and mechanisms through which pathogens may gain access to produce, thereby compromising microbiological safety. This review provides a background on the various sources and pathways through which pathogenic bacteria contaminate fresh produce; the survival and proliferation of pathogens on fresh produce while growing and potential methods to reduce microbial contamination before harvest. Some of the established bacterial contamination sources include contaminated manure, irrigation water, soil, livestock/ wildlife, and numerous factors influence the incidence, fate, transport, survival and proliferation of pathogens in the wide variety of sources where they are found. Once pathogenic bacteria have been introduced into the growing environment, they can colonize and persist on fresh produce using a variety of mechanisms. Overall, microbiological hazards are significant; therefore, ways to reduce sources of contamination and a deeper understanding of pathogen survival and growth on fresh produce in the field are required to reduce risk to human health and the associated economic consequences.


id: cord-305936-tdswzj7r
author: Freitas, André Ricardo Ribas
date: 2018-01-08
txt: ./txt/cord-305936-tdswzj7r.txt
cache: ./cache/cord-305936-tdswzj7r.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2017.01903
doi: 10.3389/fimmu.2017.01903
summary:
  Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. We analyzed particularly the most predominant variants (AH1N1 and AH3N2) on excess of mortality in the adults and elderly of different age groups in a region with marked seasonality of respiratory diseases in Brazil. Among adults (24-59 years), we observe a large excess of deaths rates during the 2009 pandemic (953 obits), which correspond to 7.1 excess deaths from all causes, and 99 excess mortality from respiratory diseases associated with viral infection in every 100,000 individuals of the age group. Although the elderly are the most vulnerable group to viral respiratory infections, we found relative small excess of deaths in years of circulating AH1N1 pre pandemic (2002 and 2008) .

title:
  Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil

abstract:
  PURPOSE: In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with different predominant virus strains. METHODS: We performed a time trend study to evaluated excess of mortality for pneumonia and influenza, respiratory disease, and all-causes in southern region of Brazil, from 2002 to 2015. After considering other models, we opted for Serfling regression. Excess of death rates per 100,000 inhabitants were analyzed in specific age groups (24–59, 60–69, 70–79, ≥80 years) and by year of occurrence. Mortality information were taken from Brazilian Mortality Information System and etiological data were accessed in Sentinel Virological Surveillance database, getting the weekly positivity of the immunofluorescence tests for influenza A (H1N1, H3N2), and B. RESULTS: In southern Brazil, there is an evident seasonal pattern of all death outcomes among different age groups in the dry and cold season (April–September). The highest excess mortality rates occurs among older, particularly in years of circulation of influenza AH3N2, especially among people ≥80 years, in 2003 and 2007—years of great severity of influenza activity. After 2009, with the introduction of the pandemic influenza AH1N1, we observed a lower impact on the mortality of the elderly compared to <60 years. DISCUSSION: A cross reactivity antibody response from past exposure probably provided protection against disease in the elderly. Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. CONCLUSION: The reduced immune response to infection, and to vaccination, and presence of comorbidities recommend a special attention to this age group in Brazil. Besides medical assistance, the timeliness of vaccine campaigns, its composition, and etiological surveillance of respiratory diseases are some of the preventive and public health measures.


id: cord-307543-piust0s6
author: Oh, Hyang Soon
date: 2018-05-14
txt: ./txt/cord-307543-piust0s6.txt
cache: ./cache/cord-307543-piust0s6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3961/jpmph.17.188
doi: 10.3961/jpmph.17.188
summary:
  title: Knowledge, Perceptions, and Self-reported Performance of Hand Hygiene Among Registered Nurses at Community-based Hospitals in the Republic of Korea: A Cross-sectional Multi-center Study OBJECTIVES: To assess the nurses'' hand hygiene (HH) knowledge, perception, attitude, and self-reported performance in smalland medium-sized hospitals after Middle East Respiratory Syndrome outbreak. The questionnaire included 4 domains: (A) HH knowledge, (B) HH perceptions, (C) HH attitudes and role models, and (D) participant demographics and hospital characteristics. The attitudes and role models domain (C) was adapted from Hand Hygiene Knowledge and Performance a previous study [8] . The regression model for performance was calculated as Y4 =18.302+0.247X41 (perceptions)+0.232X42 (attitudes)+ 0.875X42 (role model); the coefficients were statistically signifiIn terms of infection control infrastructure [16] , ICDs and ICNs were not fully allocated across the hospitals analysed in this study. Consistently with previous studies [13, 21, 22, 25] , our participants'' self-reported HH performance rate of self was positively correlated with their scores for perceptions, attitudes, and role models.

title:
  Knowledge, Perceptions, and Self-reported Performance of Hand Hygiene Among Registered Nurses at Community-based Hospitals in the Republic of Korea: A Cross-sectional Multi-center Study

abstract:
  OBJECTIVES: To assess the nurses’ hand hygiene (HH) knowledge, perception, attitude, and self-reported performance in small- and medium-sized hospitals after Middle East Respiratory Syndrome outbreak. METHODS: The structured questionnaire was adapted from the World Health Organization’s survey. Data were collected between June 26 and July 14, 2017. RESULTS: Nurses showed scores on knowledge (17.6±2.5), perception (69.3±0.8), self-reported HH performance of non-self (86.0±11.0), self-reported performance of self (88.2±11.0), and attitude (50.5±5.5). HH performance rate of non-self was Y(1)=36.678+ 0.555X1 (HH performance rate of self) (adjusted R(2)=0.280, p<0.001). The regression model for performance was Y(4)=18.302+0.247X(41) (peception)+0.232X(42) (attitude)+0.875X(42) (role model); coefficients were significant statistically except attitude, and this model significant statistically (adjusted R(2)=0.191, p<0.001). CONCLUSIONS: Advanced HH education program would be developed and operated continuously. Perception, attitude, role model was found to be a significant predictors of HH performance of self. So these findings could be used in future HH promotion strategies for nurses.


id: cord-307547-7n3f3wrz
author: Węglarz-Tomczak, Ewelina
date: 2018-06-29
txt: ./txt/cord-307547-7n3f3wrz.txt
cache: ./cache/cord-307547-7n3f3wrz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.18632/oncotarget.25532
doi: 10.18632/oncotarget.25532
summary:
  Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with potencies similar to the non-competitive macrocyclic parent compound (K(i) in the micromolar range). Elimination of the cyclic peptide fragments from the structure of Actinomycin D/X 2 allowed the resulting Actinocin to penetrate much further into the active sites of the studied metallopeptidases and to act as a classical competitive ligand by interacting with the metal ions (Figures 5 and 6 ). Actinomycin D is a long-known drug that was developed as an anticancer agent years before apoptosis and other cell death mechanisms and cancer progression were elucidated. Blocking the activity of MetAP2 and APN with Actinomycin D or its analogs seems to be promising for the development of new generations of potent anticancer agents that would be implicated in different mechanisms of action and directed against multiple molecular targets.

title:
  Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs

abstract:
  The potent transcription inhibitor Actinomycin D is used with several cancers. Here, we report the discovery that this naturally occurring antibiotic inhibits two human neutral aminopeptidases, the cell-surface alanine aminopeptidase and intracellular methionine aminopeptidase type 2. These metallo-containing exopeptidases participate in tumor cell expansion and motility and are targets for anticancer therapies. We show that the peptide portions of Actinomycin D and Actinomycin X(2) are not required for effective inhibition, but the loss of these regions changes the mechanism of interaction. Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with potencies similar to the non-competitive macrocyclic parent compound (K(i) in the micromolar range). The mode of action for all four compounds and both enzymes was demonstrated by molecular modeling and docking in the corresponding active sites. This knowledge gives new perspectives to Actinomycin D's action on tumors and suggests new avenues and molecules for medical applications.


id: cord-309565-8syjr6k8
title: A long-term animal experiment indicating persistent infection of bovine coronavirus in cattle
author: KANNO, Toru
date: 2018-05-18
txt: ./txt/cord-309565-8syjr6k8.txt
cache: ./cache/cord-309565-8syjr6k8.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1292/jvms.18-0050
doi: 10.1292/jvms.18-0050
summary:
  A long-term animal experiment involving inoculation with bovine coronavirus (BCoV) was conducted to verify its persistent infection in cattle. Until the end of the experiment (1,085, 700 and 280 days, respectively), viral RNAs were detected sporadically by RT-PCR and nested PCR from plasma, nasal discharge, and feces. Samples of nasal discharge, feces, plasma, and sera were collected daily until 10 days post inoculation (dpi), followed by weekly collection until 141 dpi and then twice-weekly collection until the end of the experiment (1,085 dpi). The virus in the digestive tract might have been quickly inactivated and excreted; therefore, viral RNAs were not detected from nasal discharge and feces at 421 dpi, 10 days after the onset. This study showed that the BCoV RNA was long-lasting, having been detected from the nasal discharge of cattle that had been maintained in an isolated room of a high-containment facility to prevent virus intrusion from outside.

abstract:
  A long-term animal experiment involving inoculation with bovine coronavirus (BCoV) was conducted to verify its persistent infection in cattle. Three colostrum-deprived Holstein calves were housed separately in individual rooms of a high-containment facility and inoculated with the BCoV strain Kumamoto/1/07. Until the end of the experiment (1,085, 700 and 280 days, respectively), viral RNAs were detected sporadically by RT-PCR and nested PCR from plasma, nasal discharge, and feces. Seroconversion and titer changes were validated by hemagglutination inhibition tests and neutralization tests. Among the samples, nasal discharge showed a higher viral positivity than feces, which seemed to be associated with positive detection in the plasma. These data demonstrate the existence of persistent infection of BCoV in the respiratory tissues of cattle.


id: cord-310240-otf9ruvj
title: Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy
author: Prohaska, Stefanie
date: 2018-02-26
txt: ./txt/cord-310240-otf9ruvj.txt
cache: ./cache/cord-310240-otf9ruvj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s40560-018-0278-8
doi: 10.1186/s40560-018-0278-8
summary:
  METHODS: ARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n = 29) or without (control group; n = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively. CONCLUSION: We conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support. Although this treatment was omitted in recent sepsis guidelines due to a lack of supporting evidence in high-quality trials [8] , several studies, including one meta-analysis, describe beneficial effects of immunoglobulins in acute pneumonia induced by drug-resistant bacterial infections [9] [10] [11] . Based on these data, we treated patients with ARDS requiring ECMO therapy with IgM-enriched immunoglobulins immediately after intensive care unit (ICU) admission. The purpose of this analysis was to systematically investigate the potential effect of IgM-enriched immunoglobulins on the outcomes of ARDS patients requiring ECMO therapy.

abstract:
  BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with high mortality rates. ARDS patients suffer from severe hypoxemia, and extracorporeal membrane oxygenation (ECMO) therapy may be necessary to ensure oxygenation. ARDS has various etiologies, including trauma, ischemia-reperfusion injury or infections of various origins, and the associated immunological responses may vary. To support the immunological response in this patient collective, we used intravenous IgM immunoglobulin therapy to enhance the likelihood of pulmonary recovery. METHODS: ARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n = 29) or without (control group; n = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively. RESULTS: The baseline characteristics did not differ between the groups, although the IVIG group showed a significantly reduced oxygenation index compared to the control group. We found no differences in the length of ICU stay or ventilation parameters. We did not find a significant difference between the groups for the extent of inflammation or for overall survival. CONCLUSION: We conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support. TRIAL REGISTRATION: Clinical Trials: NCT02961166; retrospectively registered.


id: cord-314340-ltx4w9zh
title: The Involvement of Histone H3 Acetylation in Bovine Herpesvirus 1 Replication in MDBK Cells
author: Zhu, Liqian
date: 2018-09-27
txt: ./txt/cord-314340-ltx4w9zh.txt
cache: ./cache/cord-314340-ltx4w9zh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v10100525
doi: 10.3390/v10100525
summary:
  During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). Indeed, 5 µM of AA treatment could inhibit histone H3 acetylation as demonstrated by the reduced levels of H3K9ac relative to the control, but AA increased the levels of H3K9ac in the context of virus infection in comparison to the mock treated but infected cells ( Figure 3E ,F).

abstract:
  During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). The depletion of GCN5L2 promoted by virus infection was partially mediated by ubiquitin-proteasome pathway. Interestingly, the viral replication was enhanced by HAT (histone acetyltransferase) activator CTPB [N-(4-Chloro-3-trifluoromethylphenyl)-2-ethoxy-6-pentadecylbenzamide], and vice versa, inhibited by HAT inhibitor Anacardic acid (AA), suggesting that BoHV-1 may take advantage of histone acetylation for efficient replication. Taken together, we proposed that the HAT-dependent histone H3 acetylation plays an important role in BoHV-1 replication in MDBK (Madin-Darby bovine kidney) cells.


id: cord-317688-mr851682
title: Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea
author: Oh, Myoung-don
date: 2018-02-27
txt: ./txt/cord-317688-mr851682.txt
cache: ./cache/cord-317688-mr851682.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3904/kjim.2018.031
doi: 10.3904/kjim.2018.031
summary:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in September 2012 [1] . The first patient (index case) with MERS-CoV infection was a 68-year-old Korean man returning from the Middle East. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications Risk factors for transmission of Middle East respiratory syndrome coronavirus infection during the 2015 outbreak in South Korea Clinical implications of 5 cases of Middle East respiratory syndrome coronavirus infection in a South Korean outbreak Renal complications and their prognosis in Korean patients with Middle East respiratory syndrome-coronavirus from the central MERS-CoV designated hospital Successful treatment of suspected organizing pneumonia in a patient with Middle East respiratory syndrome coronavirus infection: a case report

abstract:
  Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first isolated from a patient with severe pneumonia in 2012. The 2015 Korea outbreak of MERSCoV involved 186 cases, including 38 fatalities. A total of 83% of transmission events were due to five superspreaders, and 44% of the 186 MERS cases were the patients who had been exposed in nosocomial transmission at 16 hospitals. The epidemic lasted for 2 months and the government quarantined 16,993 individuals for 14 days to control the outbreak. This outbreak provides a unique opportunity to fill the gap in our knowledge of MERS-CoV infection. Therefore, in this paper, we review the literature on epidemiology, virology, clinical features, and prevention of MERS-CoV, which were acquired from the 2015 Korea outbreak of MERSCoV.


id: cord-318181-xxc7vdnt
author: Ahmed, Anwar E.
date: 2018-03-14
txt: ./txt/cord-318181-xxc7vdnt.txt
cache: ./cache/cord-318181-xxc7vdnt.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29550445/
doi: 10.1016/j.ijid.2018.03.005
summary:
  A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. Nineteen predictive variables were included: age, sex, fever (temperature !38 C), one composite respiratory symptom (the presence of cough, bloody cough, shortness of breath, or chest pain), one composite gastrointestinal symptoms (the presence of diarrhea, vomiting, or nausea), seven MERS-CoV potential risk factors (contact with sick patients or camels, severe illness (defined according to the patient''s clinical status, ''yes/no'', which is based on clinical judgment), diabetes, lung disease, liver disease, renal disease, and heart disease), and seven laboratory measurements (white blood cell (WBC) count (Â10 9 /l), platelets (Â10 9 /l), creatinine (mmol/l), bilirubin (mmol/l), alanine aminotransferase (ALT; U/l), aspartate aminotransferase (AST; U/l), and albumin (g/ l)).

title:
  Early identification of pneumonia patients at increased risk of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

abstract:
  BACKGROUND: The rapid and accurate identification of individuals who are at high risk of Middle East respiratory syndrome coronavirus (MERS-CoV) infection remains a major challenge for the medical and scientific communities. The aim of this study was to develop and validate a risk prediction model for the screening of suspected cases of MERS-CoV infection in patients who have developed pneumonia. METHODS: A two-center, retrospective case–control study was performed. A total of 360 patients with confirmed pneumonia who were evaluated for MERS-CoV infection by real-time reverse transcription polymerase chain reaction (rRT-PCR) between September 1, 2012 and June 1, 2016 at King Abdulaziz Medical City in Riyadh and King Fahad General Hospital in Jeddah, were included. According to the rRT-PCR results, 135 patients were positive for MERS-CoV and 225 were negative. Demographic characteristics, clinical presentations, and radiological and laboratory findings were collected for each subject. RESULTS: A risk prediction model to identify pneumonia patients at increased risk of MERS-CoV was developed. The model included male sex, contact with a sick patient or camel, diabetes, severe illness, low white blood cell (WBC) count, low alanine aminotransferase (ALT), and high aspartate aminotransferase (AST). The model performed well in predicting MERS-CoV infection (area under the receiver operating characteristics curves (AUC) 0.8162), on internal validation (AUC 0.8037), and on a goodness-of-fit test (p = 0.592). The risk prediction model, which produced an optimal probability cut-off of 0.33, had a sensitivity of 0.716 and specificity of 0.783. CONCLUSIONS: This study provides a simple, practical, and valid algorithm to identify pneumonia patients at increased risk of MERS-CoV infection. This risk prediction model could be useful for the early identification of patients at the highest risk of MERS-CoV infection. Further validation of the prediction model on a large prospective cohort of representative patients with pneumonia is necessary.


id: cord-319729-6lzjhn8j
author: Tian, Bin
date: 2018-01-19
txt: ./txt/cord-319729-6lzjhn8j.txt
cache: ./cache/cord-319729-6lzjhn8j.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2017.02011
doi: 10.3389/fimmu.2017.02011
summary:
  title: Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. To assess innate immune responses in astrocytes, cells were infected with DRV or B2c at an MOI of 0.1 and the expression of several proteins involved in the MAVS signaling pathway, namely, RIG-I, p-IRF7, STAT1 and IFIT1 (ISG56), was measured by Western blot.

title:
  Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway

abstract:
  Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV), evades the host immune response and infects the host central nervous system (CNS) has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt), RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA) than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5). Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS.


id: cord-319871-qnijw08y
author: Morgene, M. Fedy
date: 2018-08-26
txt: ./txt/cord-319871-qnijw08y.txt
cache: ./cache/cord-319871-qnijw08y.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30058450/
doi: 10.1080/21505594.2018.1504561
summary:
  title: Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms S. aureus expresses a wide repertoire of surface proteins that recognize cellular adhesive molecules and it is therefore able to adhere to and internalize into lung epithelial cells, which protects the bacteria from the host immune system and facilitate chronic infection [20] . A recent prospective study investigated the differences in the nasopharyngeal microbiome during acute respiratory tract infections due to human rhinovirus or RSV in 135 infants aged less than 6 months [38] . Several potential mechanisms through which rhinovirus increases susceptibility to bacterial infection have been demonstrated in vitro in epithelial cells of the upper and lower airways. aureus carriage and non-influenza respiratory virus infections, as well as deeper insights into mechanisms of interactions between these different pathogens.

title:
  Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

abstract:
  Viral infections of the respiratory tract can be complicated by bacterial superinfection, resulting in a significantly longer duration of illness and even a fatal outcome. In this review, we focused on interactions between S. aureus and non-influenza viruses. Clinical data evidenced that rhinovirus infection may increase the S. aureus carriage load in humans and its spread. In children, respiratory syncytial virus infection is associated with S. aureus carriage. The mechanisms by which some non-influenza respiratory viruses predispose host cells to S. aureus superinfection can be summarized in three categories: i) modifying expression levels of cellular patterns involved in S. aureus adhesion and/or internalization, ii) inducing S. aureus invasion of epithelial cells due to the disruption of tight junctions, and iii) decreasing S. aureus clearance by altering the immune response. The comprehension of pathways involved in S. aureus-respiratory virus interactions may help developing new strategies of preventive and curative therapy.


id: cord-320107-wels9wt7
title: Community-Acquired Respiratory Viruses
author: Gottlieb, Jens
date: 2018-03-26
txt: ./txt/cord-320107-wels9wt7.txt
cache: ./cache/cord-320107-wels9wt7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29579772/
doi: 10.1055/s-0037-1615799
summary:
  Resolution of respiratory virus infection requires not only the elimination of the Keywords ► lung transplantation ► community-acquired respiratory viruses ► ribavirin ► bronchiolitis obliterns syndrome The incidence of community-acquired respiratory viruses (CARVs) is $15 cases per 100 patient-years after lung transplantation (LTx). The incidence of community-acquired respiratory viruses (CARVs) is $15 cases per 100 patient-years after lung transplantation (LTx). 8 In contrast to the nonimmunosuppressed host, CARV infection usually leads to more severe illness in the lung transplanted recipient with a higher incidence of respiratory failure. ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients Incidence and outcomes of respiratory viral infections in lung transplant recipients: a prospective study Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study

abstract:
  The incidence of community-acquired respiratory viruses (CARVs) is ∼15 cases per 100 patient-years after lung transplantation (LTx). Paramyxoviruses account for almost 50% of the cases of CARV infection in LTx. Most patients will be symptomatic with a mean decline of 15 to 20% in forced expiratory volume in 1 second. The attributable death rate is low in recent years 15 to 25% CARV infected LTx patients will develop chronic lung allograft dysfunction within a year after CARV infection. This risk seems to be increased in comparison to the noninfected LTx recipient. Detection rate of CARV dependent on clinical awareness, sampling, and diagnostic method with nucleic acid testing by polymerase chain reaction in bronchoalveolar lavage is the gold standard after LTx. There is no approved treatment for paramyxoviruses, most centers use ribavirin by various routes. Toxicity of systemic ribavirin is of concern and some patients will have contraindication to this treatment modality. Treatment may reduce the risk to develop chronic lung allograft dysfunction and respiratory failure. Agents under development are inhibiting viral attachment and use silencing mechanisms of viral replication.


id: cord-322201-5laifjgz
title: Bactericidal assessment of nano-silver on emerging and re-emerging human pathogens
author: Anuj, Samir A.
date: 2018-04-24
txt: ./txt/cord-322201-5laifjgz.txt
cache: ./cache/cord-322201-5laifjgz.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0946672X18301275
doi: 10.1016/j.jtemb.2018.04.028
summary:
  To explore the action of nano-silver on emerging Bacillus megaterium MTCC 7192 and re-emerging Pseudomonas aeruginosa MTCC 741 pathogenic bacteria, the study includes an analysis of the bacterial membrane damage through Scanning Electron Microscope (SEM) as well as alternation of zeta potential and intracellular leakages. The comparative antibacterial activities of nano-silver and broad spectrum antibiotics was effectively accessed against emerging pathogens Bacillus megaterium MTCC 7192 and re-emerging pathogens Pseudomonas aeruginosa MTCC 741 using agar well diffusion assay method [13] . Samples from bacterial cultures (Bacillus megaterium MTCC 7192 and Pseudomonas aeruginosa MTCC 741), mixed with 100 μg/ml of nano-silver, were collected at 3 h and pre-fixed with 2.5% glutaraldehyde for 30 min; these were then washed two times in the same buffer and post-fixed for 2 h in 1% osmium tetroxide. The inhibition zones of nano-silver obtained in this study indicated that a nano-silver has potential to control emerging and re-emerging multidrug-resistant pathogens compared to tested antibiotics.

abstract:
  With the threat of the growing number of bacteria resistant to antibiotics, the re-emergence of previously deadly infections and the emergence of new infections, there is an urgent need for novel therapeutic agent. Silver in the nano form, which is being used increasingly as antibacterial agents, may extend its antibacterial application to emerging and re-emerging multidrug-resistant pathogens, the main cause of nosocomial diseases worldwide. In the present study, a completely bottom up method to prepare green nano-silver was used. To explore the action of nano-silver on emerging Bacillus megaterium MTCC 7192 and re-emerging Pseudomonas aeruginosa MTCC 741 pathogenic bacteria, the study includes an analysis of the bacterial membrane damage through Scanning Electron Microscope (SEM) as well as alternation of zeta potential and intracellular leakages. In this work, we observed genuine bactericidal property of nano-silver as compare to broad spectrum antibiotics against emerging and re-emerging mode. After being exposed to nano-silver, the membrane becomes scattered from their original ordered arrangement based on SEM observation. Moreover, our results also suggested that alternation of zeta potential enhanced membrane permeability, and beyond a critical point, it leads to cell death. The leakages of intracellular constituents were confirmed by Gas Chromatography-Mass Spectrometry (GC–MS). In conclusion, the combine results suggested that at a specific dose, nano-silver may destroy the structure of bacterial membrane and depress its activity, which causes bacteria to die eventually.


id: cord-323700-5awng7h1
title: Comparative Viral Sampling in the Sinonasal Passages; Different Viruses at Different Sites
author: Goggin, Rachel K.
date: 2018-09-19
txt: ./txt/cord-323700-5awng7h1.txt
cache: ./cache/cord-323700-5awng7h1.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fcimb.2018.00334
doi: 10.3389/fcimb.2018.00334
summary:
  The aim of the study here presented was to establish differences in viral detection and species sampled from different sinonasal sites, in an effort to validate and standardise viral collection techniques, and facilitate further investigation of the sinonasal virome. All DNA extracts first underwent an endogenous retrovirus 3 (ERV3) assay (present as two copies per human diploid cell) in order to confirm respiratory sample collection quality. Nasal swab samples and real-time polymerase chain reaction assays in community-based, longitudinal studies of respiratory viruses: the importance of sample integrity and quality control High rates of detection of respiratory viruses in the nasal washes and mucosae of patients with chronic rhinosinusitis Detection of herpesviruses 1-6 and community-acquired respiratory viruses in patients with chronic rhinosinusitis with nasal polyposis Real-time RT-PCR detection of 12 respiratory viral infections in four triplex reactions Real-time quantitative PCR assays for detection and monitoring of pathogenic human viruses in immunosuppressed pediatric patients

abstract:
  Background: With the emergence of the microbiome as an important factor in health and disease in the respiratory tract standardised, validated techniques are required for its accurate characterisation. No standardised technique has been reported specifically for viral sampling in the sinonasal passages. Aim: To optimise viral sampling techniques from the sinonasal cavity. Methods: Sterile cytology brushes were used under endoscopic guidance to sample the sinonasal mucosa at time of endoscopic sinus surgery at both the middle and inferior meatuses (MM and IM). DNA and RNA were extracted from the samples and underwent PCR or RT-PCR testing, respectively, for a panel of 15 common upper respiratory tract viruses. Results: Twenty-four adult patients were recruited for this study. 18/24 (75%) patients were positive for virus in at least one site, while 8/24 (33%) were positive for virus at both sites. The mean number of viruses identified at the two sites were similar (0.875 ± 0.899 at the MM vs. 0.750 ± 1.032 at the IM). 6/24 (25%) of patients showed no virus at either site, while 3/24 (12.5%) demonstrated the same viral species at both sites. Conclusion: Although the number of viruses present at different sites with the nasal cavity are similar, discord exists in the viral species between sites. It is therefore recommended that both sites are sampled in the clinical and research setting better to characterise the viral species within the nasal cavity.


id: cord-324432-k0g3r1lw
title: Seasonality and clinical impact of human parainfluenza viruses
author: Maykowski, Philip
date: 2018-08-29
txt: ./txt/cord-324432-k0g3r1lw.txt
cache: ./cache/cord-324432-k0g3r1lw.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/irv.12597
doi: 10.1111/irv.12597
summary:
  PATIENTS/METHODS: This retrospective study was performed from January 2013 to December 2015 in children and adults with HPIV, detected by multiplex reverse transcription polymerase chain reaction, participating in a community surveillance study of acute respiratory infections (ARIs) in New York City and patients admitted to a tertiary care center in the same neighborhood. The community cohort was derived from the Mobile Surveillance for Acute Respiratory Infections (ARIs) and Influenza-like Illness (ILI) in the Community (MoSAIC) study, a 5-year community-based surveillance ordinal logistic regression demonstrated that increased severity of illness was significantly associated with HPIV-4 and chronic cardiovascular and respiratory conditions in children and with age ≥65 years and chronic respiratory conditions in adults. epidemiology, parainfluenza, respiratory, seasonality, viruses F I G U R E 1 Flowcharts depicting the overall number of respiratory viral panel (RVP) tests ordered which yielded the final number of human parainfluenza virus (HPIV) types in the community cohort (1A) and in hospitalized patients (1B) study in New York City (NYC) that includes 250 households annually.

abstract:
  BACKGROUND: Widespread availability of rapid diagnostic testing for respiratory viruses allows more in‐depth studies of human parainfluenza viruses (HPIV). OBJECTIVES: This study aimed to assess seasonality of HPIV types 1‐4, clinical outcomes by HPIV type, and risk factors for illness severity. PATIENTS/METHODS: This retrospective study was performed from January 2013 to December 2015 in children and adults with HPIV, detected by multiplex reverse transcription polymerase chain reaction, participating in a community surveillance study of acute respiratory infections (ARIs) in New York City and patients admitted to a tertiary care center in the same neighborhood. Seasonality trends by HPIV type were compared between the community and hospital groups. The associations between HPIV type, demographics, clinical characteristics, and illness severity were assessed. RESULTS: HPIV was detected in 69 (4%) of 1753 community surveillance participants (median age 9.2 years) and 680 hospitalized patients (median age 6.8 years). Seasonality for HPIV types 1‐3 agreed with previously described patterns; HPIV‐4 occurred annually in late summer and fall. In the community cohort, 22 (32%) participants sought medical care, 9 (13%) reported antibiotic use, and 20 (29%) reported ≥1 day of missed work or school. Among hospitalized patients, 24% had ≥4 chronic conditions. Multivariable ordinal logistic regression demonstrated that increased severity of illness was significantly associated with HPIV‐4 and chronic cardiovascular and respiratory conditions in children and with age ≥65 years and chronic respiratory conditions in adults. CONCLUSIONS: HPIV‐4 presented late summer and early fall annually and was associated with increased severity of illness in hospitalized children.


id: cord-324674-yd7idp90
author: Zhang, Chengfei
date: 2018-08-22
url: https://doi.org/10.1093/jmcb/mjy045
doi: 10.1093/jmcb/mjy045
title:
  IFN-stimulated P2Y(13) protects mice from viral infection by suppressing the cAMP/EPAC1 signaling pathway

abstract:
  Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y(13) and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y(13), as a typical interferon-stimulated gene, is induced together with extracellular ADP during viral infection. Most importantly, extracellular ADP restricts the replication of different kinds of viruses, including vesicular stomatitis virus, Newcastle disease virus, herpes simplex virus 1, and murine leukemia virus. This kind of protection is dependent on P2Y(13) but not P2Y(1) or P2Y(12), which are also considered as receptors for ADP. Furthermore, cyclic adenosine monophosphate and EPAC1 are downregulated by extracellular ADP through the P2Y(13)-coupled Gi alpha subunit. Accordingly, inhibition or deletion of EPAC1 significantly eliminates ADP/P2Y(13)-mediated antiviral activities. Taken together, our results show that P2Y(13) and ADP play pivotal roles in the clearance of invaded virus and have the potential as antiviral targets.


id: cord-325525-d1hsguds
title: Les principales maladies du porc
author: Coudert, Pascal
date: 2018-11-30
txt: ./txt/cord-325525-d1hsguds.txt
cache: ./cache/cord-325525-d1hsguds.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0515370018303410
doi: 10.1016/j.actpha.2018.09.012
summary:
  À l''inverse, des pathologies, comme la maladie de Glässer, sont encore susceptibles d''engendrer d''importantes pertes économiques dans des élevages à haut niveau sanitaire. En 2018, six maladies et infections à déclaration obligatoire (encéphalite à virus Nipah, gastro-entérite transmissible, cysticercose, peste porcine classique et africaine, syndrome dysgénésique et respiratoire) ont été recensées par l''Organisation mondiale de la santé animale pour les suidés 1 . Peste porcine ✦ Causée par un virus de la famille des Flaviridae, la peste porcine classique n''est actuellement plus présente en France tant dans les cheptels porcins domestiques que sauvages. Aucun traitement spécifique n''est disponible et la vaccination préventive des cheptels porcins n''est plus autorisée dans l''Union européenne depuis 1988 suite à la mise en place d''un programme d''éradication de la maladie. Cette affection, pour laquelle il n''existe ni traitement ni vaccin, résulte d''une infection par des entérovirus de la famille des Picornaviridae.

abstract:
  Résumé Plusieurs pathologies autrefois mortelles au sein des élevages porcins ont disparu de notre territoire, mais de nombreuses maladies polysystémiques subsistent. Si l’antibiothérapie s’avère parfois efficace, la vaccination permet de prévenir un certain nombre de pathologies alors qu’il n’existe aucun traitement préventif ni curatif pour d’autres. Par ailleurs, tous les organes du porc sont susceptibles d’être la cible d’agents pathogènes. Là encore, des vaccins et des traitements antibiotiques sont disponibles. Summary Several pathologies which were once mortal within pig farms have disappeared from our territory, numerous polysystemic diseases remain. If antibiotherapy is sometimes effective, vaccination can prevent a certain number of pathologies while there is no preventive of curative treatment for others. Moreover, all the pig's organs are susceptible to being targeted by pathogenic agents. Here again, vaccines and antibiotic treatments are available.


id: cord-327202-2um6jmhk
author: Imperiale, Michael J.
date: 2018-03-08
txt: ./txt/cord-327202-2um6jmhk.txt
cache: ./cache/cord-327202-2um6jmhk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/29568736/
doi: 10.3389/fbioe.2018.00021
summary:
  The conundrum of dual use research of concern was crystallized by the so-called "gain-of-function" type of experiments in which avian influenza viruses were endowed with new properties in the laboratory such as increased virulence and the capacity for mammalian transmission. The major outcome of the great GOF controversy of 2012 is that it defined and crystallized some of the issues of dual-use research in biology by providing clear examples of experiments that were of great scientific value while also raising biosecurity and biosafety concerns. Consequently, when faced with GOF papers containing information that could conceivably be used to enhance the pathogenicity or transmissibility of a virus, editors and journals have almost always opted for full publication, usually requiring more details from the authors about biosafety and biosecurity methods, and often publishing an accompanying editorial emphasizing the scientifically useful aspects of the research [for examples, see Dermody et al.

title:
  A New Approach to Evaluating the Risk–Benefit Equation for Dual-Use and Gain-of-Function Research of Concern

abstract:
  In the twenty-first century, biology faces a problem that has previously vexed other disciplines such as physics, namely the prospect that its knowledge domain could be used to generate biological agents with altered properties that enhanced their weapon potential. Biological weapons bring the additional dimension that these could be self-replicating, easy to manufacture and synthesized with commonly available expertise. This resulted in increasing concern about the type of research done and communicated, despite the fact that such research often has direct societal benefits, bringing the dual-use dilemma to biology. The conundrum of dual use research of concern was crystallized by the so-called “gain-of-function” type of experiments in which avian influenza viruses were endowed with new properties in the laboratory such as increased virulence and the capacity for mammalian transmission. After more than a decade of intensive discussion and controversy involving biological experiments with dual-use potential, there is no consensus on the issue except for the need to carry out such experiments in the safest conditions possible. In this essay, we review the topic with the hindsight of several years and suggest that instead of prescribing prohibitions and experimental limitations the focus should be on the importance of scientific questions at hand. We posit that the importance of a scientific question for medical and scientific progress provides a benchmark to determine the acceptable level of risk in biological experimentation.


id: cord-328086-ji2emajn
author: Zhou, Jie‐ying
date: 2018-01-11
txt: ./txt/cord-328086-ji2emajn.txt
cache: ./cache/cord-328086-ji2emajn.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/irv.12535
doi: 10.1111/irv.12535
summary:
  BACKGROUND: Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited. OBJECTIVES: Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). Clinical disease and viral load in children infected with respiratory syncytial virus or human metapneumovirus Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection High viral load of human bocavirus correlates with duration of wheezing in children with severe lower respiratory tract infection High prevalence of human bocavirus detected in young children with severe acute lower respiratory tract disease by use of a standard PCR protocol and a novel real-time PCR protocol Clinical significance of different virus load of human bocavirus in patients with lower respiratory tract infection

title:
  Human bocavirus and human metapneumovirus in hospitalized children with lower respiratory tract illness in Changsha, China

abstract:
  BACKGROUND: Lower respiratory tract illness is a major cause of morbidity and mortality in children worldwide, however, information about the epidemiological and clinical characteristics of LRTIs caused by HMPV and HBoV in China is limited. OBJECTIVES: Human bocavirus (HBoV) and human metapneumovirus (HMPV) are two important viruses for children with lower respiratory tract infections (LRTI). We aimed to assay the correlation between viral load and clinical characteristics of HBoV and HMPV with LRTI in Changsha, China. METHODS: Nasopharyngeal aspirates (NPAs) from children with LRTI were collected. Real‐time PCR was used to screen HBoV and HMPV. Analyses were performed using SPSS 16.0 software. RESULTS: Pneumonia was the most frequent diagnosis. There was no significant difference between HBoV‐ and HMPV‐positive patients in age (P = .506) or hospitalization duration (P = .280); 24.1% and 18.2% were positive for HBoV and HMPV. HBoV infections peaked in summer (32.2%), and HMPV infections peaked in winter (28.9%). The HBoV‐positive patients had a shorter hospitalization duration than the HBoV‐negative patients (P = .021), and the HMPV‐positive patients had a higher prevalence of fever than the HMPV‐negative patients (P = .002). The HBoV viral load was significantly higher among patients aged <1 year (P = .006). The mean HBoV and HMPV viral loads were not significantly different between patients with single infections and coinfections. Patients infected with HBoV only were older than those coinfected with HBoV and other respiratory viruses (P = .005). No significant difference was found in the clinical characteristics of patients infected with HMPV only and those coinfected with HMPV and other respiratory viruses. CONCLUSION: Pneumonia was the most frequent diagnosis caused by HBoV and HMPV. Neither HBoV nor HMPV viral load was correlated with disease severity.


id: cord-328525-80xk3gln
author: Baier, Claas
date: 2018-09-24
txt: ./txt/cord-328525-80xk3gln.txt
cache: ./cache/cord-328525-80xk3gln.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3205/dgkh000314
doi: 10.3205/dgkh000314
summary:
  Methods: To strengthen the existing infection control concept, a PCR-based screening for RSV and influenza virus was implemented for all patients lacking respiratory symptoms (asymptomatic patients) who were hospitalized on an adult and a pediatric hemato-oncological ward. Conclusion: The seasonal screening program expanded our existing infection control concept in terms of patients lacking respiratory symptoms who shed influenza virus or RSV. To strengthen our existing infection control measures in hematology and oncology, we subsequently implemented a systematic influenza and RSV screening of patients lacking respiratory symptoms on a pediatric and an adult hemato-oncological ward as a prophylactic infection control measure in the following winter (2016/2017). To extend our existing standard infection control measures, we introduced a prophylactic screening program for asymptomatic patients targeting RSV and influenza on an adult and a pediatric hemato-oncological ward.

title:
  Influenza and respiratory syncytial virus screening for the detection of asymptomatically infected patients in hematology and oncology

abstract:
  Introduction: Respiratory syncytial virus (RSV) and influenza virus infections are a significant healthcare risk for immunocompromised patients. In addition to community onset, nosocomial acquisition and transmission may also occur. Detection of asymptomatic shedders (e.g., patients in the incubation period or immunosuppressed long term shedders) facilitates control of nosocomial transmission. Methods: To strengthen the existing infection control concept, a PCR-based screening for RSV and influenza virus was implemented for all patients lacking respiratory symptoms (asymptomatic patients) who were hospitalized on an adult and a pediatric hemato-oncological ward. Laboratory results of this screening were analyzed retrospectively. Results: 665 respiratory specimens were obtained for screening from 251 patients (26% were 18 years and younger) from December 2016 to April 2017. In 23 patients without respiratory symptoms, either influenza virus or RSV infection was found, resulting in a detection rate of about 9%. In 6 patients, the infection was presumably detected during the incubation period, because an increase of viral load was observed in subsequent specimens. Positive screening results facilitated timely implementation of adequate infection control precautions. Nosocomial clusters of RSV or influenza were not detected during the screening period on the two wards. Conclusion: The seasonal screening program expanded our existing infection control concept in terms of patients lacking respiratory symptoms who shed influenza virus or RSV. It enabled us to identify 23 RSV or influenza infections in patients lacking respiratory symptoms in a 4-month period and thus to rapidly take isolation precautions.


id: cord-329227-sqetz7h6
author: Hou, Yixuan
date: 2018-11-07
txt: ./txt/cord-329227-sqetz7h6.txt
cache: ./cache/cord-329227-sqetz7h6.txt
extension: .txt
mime: text/plain
url: https://jvi.asm.org/content/jvi/93/2/e01758-18.full.pdf
doi: 10.1128/jvi.01758-18
summary:
  The amounts of PEDV S proteins in the ERGIC, in other organelles, or on the cell surface are likely regulated by two nearby motifs in its cytoplasmic tail (CT): a tyrosine-based motif, Yxx⌽ (x is any residue and ⌽ is a bulky hydrophobic residue: F, M, I, L, or V), and an ER retrieval signal (ERRS), KVHVQ (10) (11) (12) (13) , as well as other viral and cellular proteins. One study demonstrated that a single amino acid substitution in this motif (KVHVQ to KVRVQ) weakens the intracellular retention function of the S proteins of the 10th passage of a murine-adapted PEDV variant, MK-P10 (18) , resulting in enhanced syncytium formation in Vero cells. In this study, we evaluated the phenotypes of transiently expressed S mutants containing mutations or deletions in these two motifs in mammalian cells and the virulence of three representative recombinant PEDVs in gnotobiotic piglets.

title:
  Deletion of both the Tyrosine-Based Endocytosis Signal and the Endoplasmic Reticulum Retrieval Signal in the Cytoplasmic Tail of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Pigs

abstract:
  Porcine epidemic diarrhea virus (PEDV) causes high mortality in neonatal piglets. The PEDV spike (S) protein contains two intracellular sorting motifs, YxxΦ (tyrosine-based motif YEVF or YEAF) and KVHVQ at the cytoplasmic tail, yet their functions have not been fully elucidated. Some Vero cell-adapted and/or attenuated PEDV variants contain ablations in these two motifs. We hypothesized that these motifs contribute to viral pathogenicity. By transiently expressing PEDV S proteins with mutations in the motifs, we confirmed that the motif KVHVQ is involved in retention of the S proteins in the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC). In addition, we showed that the YxxΦ motif triggers endocytosis of S proteins. These two motifs synergistically regulate the level of S expressed on the cell surface. To investigate their role in viral pathogenicity, we generated three recombinant PEDVs by introducing deletions or a mutation in the two motifs of the infectious clone of PEDV PC22A strain (icPC22A): (i) icΔ10aa (ΔYxxΦEKVHVQ), (ii) icΔ5aa (ΔKVHVQ), and (iii) icYA (Y1378A, to an inactivated motif, AEVF). Infection of Vero cells with icΔ10aa resulted in larger syncytia and more virions, with reduced numbers of S protein projections on the surface compared with icPC22A. Furthermore, we orally inoculated five groups of 5-day-old gnotobiotic piglets with the three mutants, icPC22A, or a mock treatment. Mutant icΔ10aa caused less severe diarrhea rate and significantly milder intestinal lesions than icPC22A, icΔ5aa, and icYA. These data suggest that the deletion of both motifs can reduce the virulence of PEDV in piglets. IMPORTANCE Many coronaviruses (CoVs) possess conserved motifs YxxΦ and/or KxHxx/KKxx in the cytoplasmic tail of the S protein. The KxHxx/KKxx motif has been identified as the ER retrieval signal, but the function of the YxxΦ motif in the intracellular sorting of CoV S proteins remains controversial. In this study, we showed that the YxxΦ of PEDV S protein is an endocytosis signal. Furthermore, using reverse genetics technology, we evaluated its role in PEDV pathogenicity in neonatal piglets. Our results explain one attenuation mechanism of Vero cell-adapted PEDV variants lacking functional YxxΦ and KVHVQ motifs. Knowledge from this study may aid in the design of efficacious live attenuated vaccines against PEDV, as well as other CoVs bearing the same motif in their S protein.


id: cord-329429-ur8g68vp
title: Coronaviruses in Avian Species – Review with Focus on Epidemiology and Diagnosis in Wild Birds
author: Miłek, Justyna
date: 2018-12-10
txt: ./txt/cord-329429-ur8g68vp.txt
cache: ./cache/cord-329429-ur8g68vp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30584600/
doi: 10.2478/jvetres-2018-0035
summary:
  Within the gamma-CoVs the main representative is avian coronavirus, a taxonomic name which includes the highly contagious infectious bronchitis viruses (IBVs) in chickens and similar viruses infecting other domestic birds such as turkeys, guinea fowls, or quails. The methods adopted in monitoring studies of CoVs in different avian species are mainly based on detection of conservative regions within the viral replicase, nucleocapsid genes, and 3''UTR or 5''UTR. The purpose of this review is to summarise recent discoveries in the areas of epidemiology and diagnosis of CoVs in avian species and to understand the role of wild birds in the virus distribution. This taxonomic name includes IBV which causes a highly contagious disease of chickens, and genetically similar viruses isolated from other domestic galliformes: turkey coronavirus (TCoV), responsible for turkey enteritis, and the more recently detected guinea fowl coronavirus (GfCoV), the aetiological factor of fulminating disease in this species (2, 6, 27) .

abstract:
  Coronaviruses (CoVs) are a large group of enveloped viruses with a single-strand RNA genome, which continuously circulate in mammals and birds and pose a threat to livestock, companion animals, and humans. CoVs harboured by avian species are classified to the genera gamma- and deltacoronaviruses. Within the gamma-CoVs the main representative is avian coronavirus, a taxonomic name which includes the highly contagious infectious bronchitis viruses (IBVs) in chickens and similar viruses infecting other domestic birds such as turkeys, guinea fowls, or quails. Additionally, IBVs have been detected in healthy wild birds, demonstrating that they may act as the vector between domestic and free-living birds. Moreover, CoVs other than IBVs, are identified in wild birds, which suggests that wild birds play a key role in the epidemiology of other gammaCoVs and deltaCoVs. Development of molecular techniques has significantly improved knowledge of the prevalence of CoVs in avian species. The methods adopted in monitoring studies of CoVs in different avian species are mainly based on detection of conservative regions within the viral replicase, nucleocapsid genes, and 3’UTR or 5’UTR. The purpose of this review is to summarise recent discoveries in the areas of epidemiology and diagnosis of CoVs in avian species and to understand the role of wild birds in the virus distribution.


id: cord-330296-706hf4qw
title: The European Virus Archive goes global: A growing resource for research
author: Romette, J. L.
date: 2018-10-31
txt: ./txt/cord-330296-706hf4qw.txt
cache: ./cache/cord-330296-706hf4qw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30059721/
doi: 10.1016/j.antiviral.2018.07.017
summary:
  Abstract The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry. The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry (Gould et al., 2012) . In fact, besides the EVAg, we are unaware of any non-profit organization that is concerned with facilitating reliable access globally to viruses and associated reagents from individual virus collections for research and/or diagnostic laboratories, teaching centres or industries involved in the production of diagnostic reagents, pharmaceuticals and vaccines solely for the benefit of science, in a safe and carefully regulated manner.

abstract:
  Abstract The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry. Within three years, it developed from a consortium of nine European laboratories to encompass associated partners in Africa, Russia, China, Turkey, Germany and Italy. In 2014, the H2020 Research and Innovation Framework Programme (INFRAS projects) provided support for the transformation of the EVA from a European to a global organization (EVAg). The EVAg now operates as a non-profit consortium, with 26 partners and 20 associated partners from 21 EU and non-EU countries. In this paper, we outline the structure, management and goals of the EVAg, to bring to the attention of researchers the wealth of products it can provide and to illustrate how end-users can gain access to these resources. Organisations or individuals who would like to be considered as contributors are invited to contact the EVAg coordinator, Jean-Louis Romette, at jean-louis.romette@univmed.fr.


id: cord-330942-x238hq9b
author: Versluys, Anne Birgitta
date: 2018-11-21
txt: ./txt/cord-330942-x238hq9b.txt
cache: ./cache/cord-330942-x238hq9b.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fmicb.2018.02795
doi: 10.3389/fmicb.2018.02795
summary:
  The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Recent studies however, suggest that hRV may be a clinically significant pathogen with the potential to cause serious pulmonary disease in HCT recipients (Campbell et al., 2015; Seo et al., 2015 Seo et al., , 2017 Versluys et al., 2017) with risk of progression to LRTI of 9-24% (Shah et al., 2012; Campbell et al., 2015; Fisher et al., 2017) and hRV related mortality of 4-33% (Shah et al., 2012; Campbell et al., 2015; Fisher et al., 2017) . In 2016 a joint working group in the UK (Dignan et al., 2016) has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with hematological malignancies or those undergoing hematopoietic stem cell transplantation.

title:
  Morbidity and Mortality Associated With Respiratory Virus Infections in Allogeneic Hematopoietic Cell Transplant: Too Little Defense or Harmful Immunity?

abstract:
  The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Here we give an overview of the current literature on the incidence and chance of progression to severe disease in this highly immune compromised population. We discuss the issue whether it is predominantly direct viral damage that causes clinical deterioration, or that it is in fact the allogeneic immuneresponse to the virus that is most important. This is an important question as it will guide therapeutic decision making. It asks for further collaborative studies focusing on sensitive surveillance with PCR techniques and relating clinical data with parameters of immune reconstitution.


id: cord-333639-usgpe1cz
author: Zuwala, Kaja
date: 2018-04-10
txt: ./txt/cord-333639-usgpe1cz.txt
cache: ./cache/cord-333639-usgpe1cz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.jconrel.2018.02.012
doi: 10.1016/j.jconrel.2018.02.012
summary:
  title: Macromolecular prodrugs of ribavirin: Polymer backbone defines blood safety, drug release, and efficacy of anti-inflammatory effects We focus on the choice of the macromolecular backbone as a carrier for the conjugated drug and analyze blood coagulation, binding to albumin, albumin aggregation, inhibitory activity on polymerases, and cytotoxicity for polymers differed by their anionic charge (carboxylates, phosphates and phosphonates, sulfonates). As a result, we identify polymers and macromolecular prodrugs that are devoid of blood anti-coagulation activity but are strong as inhibitors of polymerases and efficacious as delivery vehicles for ribavirinthus being attractive for the development of broad-spectrum antiviral agents. This observation echoes our recent findings on the apparent unique pairing of negative character and hydrophobicity of the polymer backbone that renders PEAA an efficacious inhibitor of e.g. hepatitis C virus intracellular replication [55] and a lead polymer with broad-spectrum antiviral activity [21] . Polyanionic macromolecular prodrugs of ribavirin: antiviral agents with a broad Spectrum of activity

title:
  Macromolecular prodrugs of ribavirin: Polymer backbone defines blood safety, drug release, and efficacy of anti-inflammatory effects

abstract:
  Macromolecular (pro)drugs hold much promise as broad-spectrum antiviral agents as either microbicides or carriers for intracellular delivery of antiviral drugs. Intriguing opportunity exists in combining the two modes of antiviral activity in the same polymer structure such that the same polymer acts as a microbicide and also serves to deliver the conjugated drug (ribavirin) into the cells. We explore this opportunity in detail and focus on the polymer backbone as a decisive constituent of such formulations. Fourteen polyanions (polycarboxylates, polyphosphates and polyphosphonates, and polysulfonates) were analyzed for blood pro/anti coagulation effects, albumin binding and albumin aggregation, inhibitory activity on polymerases, cytotoxicity, and anti-inflammatory activity in stimulated macrophages. Ribavirin containing monomers were designed to accommodate the synthesis of macromolecular prodrugs with disulfide-exchange triggered drug release. Kinetics of drug release was fast in all cases however enhanced hydrophobicity of the polymer significantly slowed release of ribavirin. Results of this study present a comprehensive view on polyanions as backbone for macromolecular prodrugs of ribavirin as broad-spectrum antiviral agents.


id: cord-339871-jso21mbx
author: Lee, Sunhee
date: 2018-05-16
txt: ./txt/cord-339871-jso21mbx.txt
cache: ./cache/cord-339871-jso21mbx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/tbed.12904
doi: 10.1111/tbed.12904
summary:
  To investigate the diversity of PEDVs responsible for the ongoing outbreaks in South Korea, in this study, we determined the full-length sequences of the S proteins of field isolates and complete genome sequences of representative strains identified throughout 2017. Based on the S gene sequences, therefore, PEDV can be genetically separated into two genogroup clusters, genogroup 1 (G1, classical and recombinant: low-pathogenic) and genogroup 2 (G2, field epizootic or panzootic: high-pathogenic), which are further divided into subgroups 1a and F I G U R E 1 Phylogenetic analysis based on nucleotide sequences of the spike genes (a) and full-length genomes (b) of porcine epidemic diarrhoea virus strains. Molecular characterization and phylogenetic analysis of membrane protein genes of porcine epidemic diarrhea virus isolates in China Full-genome sequence analysis of a variant strain of porcine epidemic diarrhea virus in South Korea Genomic and antigenic characterization of Porcine epidemic diarrhoea virus strains isolated from South Korea

title:
  Genomic and antigenic characterization of porcine epidemic diarrhoea virus strains isolated from South Korea, 2017

abstract:
  Porcine epidemic diarrhoea virus (PEDV) is a globally emerging and re‐emerging enteric coronavirus in pigs causing serious economic threats to the world swine industry. Since the re‐emergence of massive PEDV outbreaks in South Korea in 2013−2014, domestic pig farms have continued to experience PED epidemics or endemics. This study represents the molecular characterization of PEDV isolates identified in diarrhoeic animals collected across the country in 2017. Initial sequencing analysis of the full‐length S genes revealed that 70% of the 2017 isolates (7/10) belong to the G2b subgroup, while the remaining isolates were classified as G1b. The data indicated that both variant G1b and global epidemic G2b strains were responsible for current PED outbreaks in South Korea. The 2017 G1b and G2b isolates shared 98.7%–99.4% and 98.1%–99.2% amino acid sequence identity at the S gene level and 99.3% and 99.0%–99.6% nucleotide sequence homology at the genome level compared to the corresponding Korean prototype G1b and G2b strains, respectively. In an interesting manner, one G2b‐like KNU‐1705 strain was found to possess a large 39‐nucleotide deletion in the ORF1a region theoretically encoding nonstructural protein 3. Phylogenetic analysis based on the entire genome and spike protein sequences indicated that the 2017 isolates were most closely related to other global G1b or G2b strains but formed different branches within the same genogroup. These results indicate that PEDVs undergo continuous evolution in the field. In addition, one 2017 PEDV strain, KOR/KNU‐1705/2017, was successfully isolated and propagated in Vero cells. The antisera raised against the Korean prototype 2014 G2b strain efficiently neutralized KNU‐1705 virus infection, suggesting antigenic homology between the 2014 and 2017 PEDV strains. Our data advance the understanding of the molecular epidemiology and antigenicity of PEDV circulating in South Korea.


id: cord-343390-y903mxcj
author: Hoppe, Ingrid Bortolin Affonso Lux
date: 2018-06-27
txt: ./txt/cord-343390-y903mxcj.txt
cache: ./cache/cord-343390-y903mxcj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/s12917-018-1535-8
doi: 10.1186/s12917-018-1535-8
summary:
  title: Bovine respiratory syncytial virus seroprevalence and risk factors in non-vaccinated dairy cattle herds in Brazil This study aimed to characterize the epidemiology of BRSV infection in dairy cattle herds of São Paulo State, Brazil, using serological and risk factors analyses. The analysis of risk factors indicated that the age group and the occurrence of coinfection with bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should be associated with a higher prevalence of BRSV, while natural suckling was considered a protective factor. Due to this, the current study aimed to determine antibody prevalence against BRSV and investigate some risk factors associated with BRSV seroprevalence in herds of an important milk producing region in São Paulo State, Brazil. Bovine respiratory syncytial virus seroprevalence and risk factors in endemic dairy cattle herds Prevalence of and risk factors for bovine respiratory syncytial virus (BRSV) infection in non-vaccinated dairy and dual-purpose cattle herds in Ecuador

title:
  Bovine respiratory syncytial virus seroprevalence and risk factors in non-vaccinated dairy cattle herds in Brazil

abstract:
  BACKGROUND: The cattle industry is one of the most important Brazilian agribusiness sectors and is a strong contributor to the national economy. Annually about 44.6 million calves are bred, which makes the optimal management of these animals extremely important. Several diseases can affect the initial stages of the bovine production chain, being the bovine respiratory syncytial virus (BRSV) one of the most relevant pathogens. This study aimed to characterize the epidemiology of BRSV infection in dairy cattle herds of São Paulo State, Brazil, using serological and risk factors analyses. For that, 1243 blood samples were collected of animals from 26 farms and a questionnaire about possible risk factors for BRSV prevalence was performed. The obtained blood sera were analyzed using virus neutralization test (VNT). RESULTS: VNT results showed high BRSV prevalence in dairy cattle herds, reaching 79.5% of seropositivity. The BRSV seroprevalence among studied farms ranged from 40 to 100%. The analysis of risk factors indicated that the age group and the occurrence of coinfection with bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus 1 (BVDV-1) should be associated with a higher prevalence of BRSV, while natural suckling was considered a protective factor. CONCLUSIONS: The study showed that adult animals over 1 year old are an important risk factor for the high seroprevalence of BRSV in herds. The high BRSV prevalence associated with BoHV-1 and BVDV-1 suggests that biosecurity measures should be applied in order to reduce viral dissemination. Additionally, the natural suckling may be an important management to protect calves from high BRSV seroprevalence.


id: cord-344227-rdlinzrn
title: Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis
author: Gralinski, Lisa E.
date: 2018-10-09
txt: ./txt/cord-344227-rdlinzrn.txt
cache: ./cache/cord-344227-rdlinzrn.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1128/mbio.01753-18
doi: 10.1128/mbio.01753-18
summary:
  As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Mice deficient in C3 (C3 -/-), the central protein of the complement signaling pathway, were protected from SARS-CoV-induced weight loss and had reduced pathology, improved respiratory function, and lower levels of inflammatory cytokines/chemokines in the lung and periphery. Immunohistochemical staining revealed that SARS-CoV MA15 infection induced complement deposition in the lung (Fig. 4) , similar to that associated with pathogenesis in Ross River virus-infected mice (41) and some influenza virus infections (34) , and it is likely that complement deposition contributes to pulmonary disease and inflammatory cell recruitment.

abstract:
  Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3(–/–)), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3(–/–) mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3(–/–) mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3(–/–) mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic.


id: cord-346586-fxxceffl
author: Razanajatovo, Norosoa Harline
date: 2018-11-21
txt: ./txt/cord-346586-fxxceffl.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/30462659/
doi: 10.1371/journal.pone.0205124
summary:
  CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Following the A/H1N1/2009 influenza pandemic that was associated with a high morbidity and an increased risk of mortality among particular groups [13] , a number of countries have strengthened vigilance for the surveillance of severe diseases and deaths in order to rapidly detect new viruses and to provide information in assessing the impact on the population and having operational preparedness plans. A meta-analysis of data from Africa reported that the incidence of RSV in lower acute respiratory infections that required hospitalization ranged from 10-18 per 1000 person year for infants and 3-9 per 1000 person year for children under 5 years of age [26] .

title:
  Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013

abstract:
  BACKGROUND: Few comprehensive data exist regarding the epidemiology of severe acute respiratory infections (SARI) in low income countries. This study aimed at identifying etiologies and describing clinical features of SARI-associated hospitalization in Madagascar. METHODS: It is a prospective surveillance of SARI in 2 hospitals for 3 years. Nasopharyngeal swabs, sputum, and blood were collected from SARI patients enrolled and tested for viruses and bacteria. Epidemiological and clinical information were obtained from case report forms. RESULTS: Overall, 876 patients were enrolled in the study, of which 83.1% (728/876) were tested positive for at least one pathogen. Viral and bacterial infections occurred in 76.1% (667/876) and 35.8% (314/876) of tested samples, respectively. Among all detected viruses, respiratory syncytial virus (RSV) was the most common (37.7%; 348/924) followed by influenza virus A (FLUA, 18.4%; 170/924), rhinovirus (RV, 13.5%; 125/924), and adenovirus (ADV, 8.3%; 77/924). Among bacteria, Streptococcus pneumoniae (S. pneumoniae, 50.3%, 189/370) was the most detected followed by Haemophilus influenzae type b (Hib, 21.4%; 79/370), and Klebsiella (4.6%; 17/370). Other Streptococcus species were found in 8.1% (30/370) of samples. Compared to patients aged less than 5 years, older age groups were significantly less infected with RSV. On the other hand, patients aged more than 64 years (OR = 3.66) were at higher risk to be infected with FLUA, while those aged 15–29 years (OR = 3.22) and 30–64 years (OR = 2.39) were more likely to be infected with FLUB (influenza virus B). CONCLUSION: The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Amongst young children, the demonstrated burden of RSV should guide clinicians for a better case management of children. These findings reveal the need to develop point-of-care tests to avoid overuse of antibiotics and to promote vaccine that could reduce drastically the RSV hospitalizations.


id: cord-348660-qnbgywgy
author: Yilmaz, Huseyin
date: 2018-07-09
txt: ./txt/cord-348660-qnbgywgy.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/29987628/
doi: 10.1007/s12010-018-2815-2
summary:
  Following optimization of the ELISA protocol, 18 test sera were obtained from broiler chickens exposed to natural wild-type IBV infection, 18 test sera from broiler chickens vaccinated with a live-attenuated commercial IBV vaccine, and sera obtained at different time-points from chicks immunized with recombinant IBV N protein (described above) were analyzed to detect IBV N-specific antibodies. To assess the reliability of the performance of our in-house indirect IBV N ELISA, a panel of sera was obtained from chickens naturally infected with local wild-type IBV strains, chickens vaccinated with live-attenuated commercial IBV vaccine, and chickens immunized with recombinant IBV N protein (expressed in a baculovirus expression system). This represents the first study in Turkey that expressed recombinant IBV N protein in baculovirus and examined its reactivity against antisera obtained from Turkish chickens for potential use as antigen Fig. 5 Detection of IBV N specific antibodies in sera obtained from naturally infected chicken (a) and vaccinated chickens (b) using an in-house IBV-N ELISA and a commercial ELISA.

title:
  Production of Recombinant N Protein of Infectious Bronchitis Virus Using the Baculovirus Expression System and Its Assessment as a Diagnostic Antigen

abstract:
  The avian coronavirus-infectious bronchitis virus (AvCoV-IBV) is recognized as an important avian pathogen, and new viral variants are a continuous threat to the poultry industry worldwide. Sensitive diagnostics and efficacious vaccines are necessary to combat IBV infections in chickens. The aim of this study was to produce recombinant N protein of IBV in the baculovirus system to use in ELISA diagnostic tests in order to enable the assessment of the sero-prevalence and risk of IBV infections in chickens in Turkey. For this, the gene encoding the N protein of the Beaudette strain of IBV was expressed using a recombinant baculovirus expression system. The recombinant N protein was purified using Ni-NTA affinity chromatography. An estimated 50-kDa recombinant protein corresponding to the expected molecular weight of IBV N including the 6xHis tag was detected using an anti-His monoclonal antibody. Specific immunoreactivity of the recombinant protein was confirmed by Western blot using antiserum obtained from vaccinated and naturally infected chicken from Turkey as well as using a monoclonal antibody raised against the N protein of the IBV Massachusetts strain. The results obtained with the in-house ELISA had high agreement with a commercial ELISA. Immunoreactivity analysis using antisera in Western blotting and the in-house ELISA suggests that the recombinant IBV N protein could be broadly cross-reactive with antisera produced against different IBV strains. We conclude that the recombinant baculovirus expressed IBV N protein could serve as a useful diagnostic antigen for detection of IBV infections in chickens by ELISA.


id: cord-351760-698voi9y
author: Han, Hui-Ju
date: 2018-11-30
txt: ./txt/cord-351760-698voi9y.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/30513619/
doi: 10.3390/v10120680
summary:
  The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. In vivo study demonstrated that prophylaxis with m336 reduced virus titers in the lung of rabbits infected with MERS-CoV [15] , and m336 also provided transgenic mice expressing human DPP4 with full prophylactic and therapeutic protection from MERS-CoV [16] . A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in Middle East Respiratory Syndrome Coronavirus Spike Protein Prophylaxis with a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection Passive Transfer of a Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV

title:
  Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection

abstract:
  Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) is an effective prophylactic and therapeutic reagent against emerging viruses. In this article, we review current advances in neutralizing mAbs against MERS-CoV. The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. A major problem with neutralizing mAb therapy is mutant escape under selective pressure, which can be solved by combination of neutralizing mAbs targeting different epitopes. Neutralizing mAbs are currently under preclinical evaluation, and they are promising candidate therapeutic agents against MERS-CoV infection.


id: cord-353553-adaow2w7
title: Infecciones en el paciente crítico
author: Asensio Martín, M. J.
date: 2018-04-30
url: https://www.sciencedirect.com/science/article/pii/S0304541218300647
doi: 10.1016/j.med.2018.03.014
abstract:
  Resumen Introducción Las infecciones son muy frecuentes en los pacientes que se encuentran ingresados en los servicios de medicina intensiva, siendo unas veces motivo de ingreso y en otras la infección se adquiere durante el ingreso. Epidemiologia Las causas más frecuentes de infección adquirida en la comunidad que precisa ingreso en la UCI son las infecciones respiratorias, infecciones urinarias y las infecciones del sistema nervioso central. Dentro de las infecciones adquiridas en la UCI, las asociadas a dispositivos son las más frecuentes. Etiología Los gérmenes más frecuentes en la UCI son los Gram negativos. Etiopatogenia. En el paciente crítico se aúnan factores, haciéndolos especialmente vulnerables a las infecciones. Manifestaciones clínicas Dependerán de la localización de la infección. Diagnóstico Debe ser precoz dada su alta mortalidad. Pronóstico Las infecciones nosocomiales se asocian con un aumento de la mortalidad y la estancia. Tratamiento El retraso en el tratamiento se asocia con un aumento de la mortalidad. Abstract Introduction Infections are very frequent in patients who are admitted to Intensive Care Units, sometimes being a reason for admission and in others the infection is acquired during ICU stay. Epidemiology The most frequent causes of acquired infection in the community that require admission to the ICU are respiratory infections, urinary tract infections and infections of the central nervous system. Among the infections acquired in the ICU, devices-associated infections are the most frequent. Etiology The most frequent in ICU are Gram negative pathogens. Etiopathogenesis In the critical patient, several factors are combined making them especially vulnerable to infections. Clinical manifestations Depends on the location of the infection. Diagnosis It must be early due to its increased mortality. Prognosis Nosocomial infections are associated with an increase in mortality and in the length of stay. Treatment The delay in treatment is associated with an increase in mortality.


id: cord-354664-mzzvmyea
author: Shumilak, Geoffrey
date: 2018-09-06
txt: ./txt/cord-354664-mzzvmyea.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/30191333/
doi: 10.1007/s11908-018-0651-8
summary:
  While population-based studies have historically suggested improved clinical outcomes with the routine use of macrolide combination therapy in hospitalized patients with CAP, emerging evidence from recent randomized controlled trials has challenged this practice. Last updated in 2007, the joint Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) guidelines for CAP recommend empiric combination therapy with a beta-lactam plus macrolide or monotherapy with a respiratory fluoroquinolone (e.g., moxifloxacin) for adult patients hospitalized with CAP in a non-ICU setting [21] . The body of evidence used to support current IDSA/ATS guideline recommendations that advocate for combination therapy with a beta-lactam plus macrolide in the management of hospitalized adult patients with CAP originates from a series of large, retrospective cohort studies that showed improved clinical outcomes in patients treated with combination therapy. Based on the findings of these large observational studies, many clinical practice guidelines recommend combination therapy with a beta-lactam plus macrolide or monotherapy with a respiratory fluoroquinolone as first-line therapy for hospitalized adult patients with CAP.

title:
  Moving Past the Routine Use of Macrolides—Reviewing the Role of Combination Therapy in Community-Acquired Pneumonia

abstract:
  PURPOSE OF REVIEW: Despite advances in diagnostic microbiology and sepsis management, community-acquired pneumonia (CAP) remains a significant cause of morbidity and mortality. Current recommendations regarding the use of beta-lactams in combination with macrolides published in clinical practice guidelines are variable and based on low-quality evidence that is frequently retrospective, observational, and heterogeneous in nature. While population-based studies have historically suggested improved clinical outcomes with the routine use of macrolide combination therapy in hospitalized patients with CAP, emerging evidence from recent randomized controlled trials has challenged this practice. In this article, we discuss the historical rationale and current evidence for combination macrolide therapy in the management of CAP. RECENT FINDINGS: Recent randomized controlled trials have assessed the non-inferiority of beta-lactam monotherapy compared to beta-lactam/macrolide combination therapy in adult patients hospitalized with CAP. Beta-lactam monotherapy was associated with equivalent clinical outcomes in patients with mild to moderate CAP. Patients with severe CAP managed with beta-lactam monotherapy have demonstrated worse clinical outcomes when compared to patients treated with combination therapy. In addition, previous beta-lactam exposure prior to hospitalization has not been shown to negatively impact outcomes in patients managed with beta-lactam monotherapy in the hospital. SUMMARY: Current evidence supports the use of beta-lactam monotherapy in adult patients hospitalized with mild to moderate CAP. While existing evidence supports the use of combination therapy in patients with severe pneumonia, further large-scale randomized controlled trials are urgently needed to clarify the role of combination therapy in this population.


id: cord-354700-bdpp3qmf
title: Dissecting human antibody responses: useful, basic and surprising findings
author: Lanzavecchia, Antonio
date: 2018-01-23
txt: ./txt/cord-354700-bdpp3qmf.txt
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url: https://doi.org/10.15252/emmm.201808879
doi: 10.15252/emmm.201808879
summary:
  I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host–pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. I will discuss how a target-agnostic approach based on highthroughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host-pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response.

abstract:
  Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target‐agnostic approach based on high‐throughput screening of antibodies produced by cultured B cells and plasma cells has not only provided potent and broadly neutralizing antibodies against a range of pathogens, but has also advanced our understanding of basic aspects of the immune response, from host–pathogen interaction to the role of somatic mutations in affinity maturation and in the diversification of the antibody response. Most surprisingly, this approach has also revealed a new mechanism of diversification based on templated insertion of non‐Ig DNA into antibody genes that we discovered in the context of the immune response to malaria infection.


id: cord-354904-7gq2e6f0
title: Prospects for the use of spherical gold nanoparticles in immunization
author: Staroverov, Sergey A.
date: 2018-11-06
txt: ./txt/cord-354904-7gq2e6f0.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30402771/
doi: 10.1007/s00253-018-9476-5
summary:
  We used spherical gold nanoparticles (average diameter, 15 nm) as a platform for the antigen for swine transmissible gastroenteritis virus (TGEV). The literature data demonstrate that immunization of animals with the TGEV antigen coupled to gold nanoparticles (GNPs) not only activates antigen-presenting cells but also increases the proliferative activity of splenic lymphoid (antibody-forming) cells. Immunization with the TGEV antigen conjugated to GNPs as a carrier activates the respiratory activity of lymphoid cells and peritoneal macrophages, which is directly related to their transforming activity and to the activation of antibody generation. After the virus''s nucleic acid was inactivated with ribonuclease, the resultant antigen (a mixture of viral capsid proteins) was used for conjugation with GNPs and for subsequent animal immunization. A study of the respiratory activity of splenic lymphoid cells (Fig. 5) showed that after immunization with the conjugate, the activity increased 2.2-fold, as compared to the control, whereas after immunization with TGEV antigen alone, it did not change much.

abstract:
  Recent years have seen extremely fast development of new viral nanovaccines and diagnostic agents using nanostructures prepared by biological and chemical synthesis. We used spherical gold nanoparticles (average diameter, 15 nm) as a platform for the antigen for swine transmissible gastroenteritis virus (TGEV). The literature data demonstrate that immunization of animals with the TGEV antigen coupled to gold nanoparticles (GNPs) not only activates antigen-presenting cells but also increases the proliferative activity of splenic lymphoid (antibody-forming) cells. The contents of γ-IFN, IL-1β, and IL-6 in animals immunized with GNP-antigen conjugates were found to be higher than those in intact animals or in animals given the antigen alone. The increased concentration of IL-1β in the immunized animals directly correlated with the activity of macrophages and stimulated B cells, which produce this cytokine when activated. The increased concentration of IL-6 indicates that the injected preparations are stimulatory to cellular immunity. Immunization with the TGEV antigen conjugated to GNPs as a carrier activates the respiratory activity of lymphoid cells and peritoneal macrophages, which is directly related to their transforming activity and to the activation of antibody generation. Furthermore, the use of this conjugate allows marked improvement of the structure of the animals’ immune organs and restores the morphological–functional state of these organs. The microanatomical changes (increased number of follicles) indicate the activation of the B-dependent zone of the spleen and, consequently, the development of a humoral-type immunological reaction. The degradative processes observed in the animals immunized with TGEV antigen alone are evidence of weak resistance to pathogen attack. These results can be used to develop vaccines against this infection by employing TGEV antigen coupled to gold nanoparticles as a carrier.


