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h3n2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice.broadly neutralizing antibodies directed against the conserved stalk domain of the viral hemagglutinin have attracted increasing attention in recent years. however, only a limited number of stalk antibodies directed against group 2 influenza hemagglutinins have been isolated so far. also, little is known about the general level of induction of these antibodies by influenza virus vaccination or infection. to characterize the anti-stalk humoral response in the mouse model as well as in humans, chi ...201323408625
detection of positive selection eliminating effects of structural constraints in hemagglutinin of h3n2 human influenza a virus.in the evolutionary studies of proteins, the average effect of natural selection operating on amino acid mutations may be examined by comparing the numbers of synonymous (ds) and nonsynonymous (dn) substitutions that have accumulated during the same time period. in this method, destabilizing mutations occurring across protein molecules may interfere with detection of natural selection, particularly positive selection, operating on other mutations. here an attempt to detect positive selection eli ...201323403095
interim estimates of influenza vaccine effectiveness in 2012/13 from canada's sentinel surveillance network, january 2013.the 2012/13 influenza season in canada has been characterised to date by early and moderately severe activity, dominated (90%) by the a(h3n2) subtype. vaccine effectiveness (ve) was assessed in january 2013 by canada's sentinel surveillance network using a test-negative case-control design. interim adjusted-ve against medically attended laboratory-confirmed influenza a(h3n2) infection was 45% (95% ci: 13-66). influenza a(h3n2) viruses in canada are similar to the vaccine, based on haemagglutinat ...201323399422
short communication: isolation and phylogenetic analysis of an avian-origin h3n2 canine influenza virus in dog shelter, china.a h3n2 canine influenza virus, a/canine/guangdong/3/2011 (h3n2), was isolated from roaming dogs in rural china. sequence and phylogenetic analysis of eight gene segments revealed that the a/canine/guangdong/3/2011 (h3n2) was most similar to a recent h3n2 canine influenza virus isolated in cats from south korea, which originated from an avian strain. to our knowledge, this is the first report of an avian-origin h3n2 civ which was isolated from roaming dogs in china. the epidemiologic information ...201323355070
experimental infection and natural contact exposure of ferrets with canine influenza virus (h3n2).epidemics of h3n2 canine influenza virus (civ) among dogs in south korea and southern china have raised concern over the potential for zoonotic transmission of these viruses. here, we analysed the pathogenesis and transmissibility of h3n2 civ in ferret. h3n2 civ replicated efficiently in the respiratory system of inoculated ferrets and caused acute necrotizing bronchioalveolitis and non-suppurative encephalitis. transmission of h3n2 civ was detected in three of six ferrets co-housed with inocula ...201323329681
the roles of competition and mutation in shaping antigenic and genetic diversity in influenza.influenza a (h3n2) offers a well-studied, yet not fully understood, disease in terms of the interactions between pathogen population dynamics, epidemiology and genetics. a major open question is why the virus population is globally dominated by a single and very recently diverged (2-8 years) lineage. classically, this has been modeled by limiting the generation of new successful antigenic variants, such that only a small subset of progeny acquire the necessary mutations to evade host immunity. a ...201323300455
influenza epidemiology in italy two years after the 2009-2010 pandemic: need to improve vaccination coverage.since 2000, a sentinel surveillance of influenza, influnet, exists in italy. it is coordinated by the ministry of health and is divided into two parts; one of these is coordinated by the national institute of health (nih), the other by the inter-university centre for research on influenza and other transmissible infections (ciri-it). the influenza surveillance system performs its activity from the 42nd week of each year (mid-october) to the 17th week of the following year (late april). only duri ...201323292210
h3n2 homeopathic influenza virus solution modifies cellular and biochemical aspects of mdck and j774g8 cell lines.influenza viruses cause highly contagious acute respiratory illnesses with significant mortality, especially among young children, elderly people, and individuals with serious medical conditions. this encourages the development of new treatments for human flu. biotherapies are diluted solutions prepared from biological products compounded following homeopathic procedures.201323290877
[ability of the influenza viruses and their envelope proteins to stimulates endothelial cells apoptosis in vitro].the ability of the modern epidemic strains of influenza virus type a (subtypes h5n1, h3n2, h1n1pdm) and their surface proteins, hemagglutinin (ha) and neuraminidase to cause the activation of the cellular protein caspase-3 and stimulate the emergence of phosphatidylserine on the membrane of human endothelial cell line eahy926 has been studied. it was questioned how the viruses and their surface proteins that were studied cause the activation of caspase-3 after 0.5 h of exposure that recorded imm ...201325509110
avian-origin h3n2 canine influenza virus circulating in farmed dogs in guangdong, china.since 2006, more and more cases of the infectious h3n2 canine influenza virus (civ) in pet dogs have been reported in southern china. however, little is known about the prevalence situation of h3n2 civ infections in farmed dogs in china. this is the first systematic epidemiological surveillance of civ in different dog populations in southern china. two virus strains a/canine/guangdong/1/2011(h3n2) and a/canine/guangdong/5/2011(h3n2) were isolated from canine nasal swabs collected at one dog farm ...201323261544
retraction. triple reassortant swine influenza a (h3n2) virus in waterfowl. 201323260489
glutathione peroxidase-1 reduces influenza a virus-induced lung inflammation.oxidative stress caused by excessive reactive oxygen species production is implicated in influenza a virus-induced lung disease. glutathione peroxidase (gpx)-1 is an antioxidant enzyme that may protect lungs from such damage. the objective of this study was to determine if gpx-1 protects the lung against influenza a virus-induced lung inflammation in vivo. male wild-type (wt) or gpx-1(-/-) mice were inoculated with hkx31 (h3n2, 1 × 10(4) plaque-forming units), and bronchoalveolar lavage fluid (b ...201323002098
inter- and intraspecies transmission of canine influenza virus (h3n2) in dogs, cats, and ferrets.the emergence of zoonotic viruses in domestic animals is a significant public health concern. canine influenza virus (civ) h3n2 is a virus that can infect companion animals and is, therefore, a potential public health concern.201322616918
neu5acα2,6gal and neu5acα2,3gal receptor specificities on influenza viruses determined by a waveguide-mode sensor.to characterize the differences in the receptor-binding specificities of human and avian influenza viruses with glycan chains, the authors performed binding analyses using an evanescent field-coupled waveguide-mode biosensor. the experiments were performed on intact viruses and hemagglutinin proteins, using gold-nanoparticle-conjugated neu5acα2,6gal and neu5acα2,3gal glycan chains. several influenza viruses belonging to subtypes h3n2 (a/udorn/307/1972, a/shandong/9/1993, a/kiev/301/1994, a/panam ...201323022889
phylogenetic, molecular and drug-sensitivity analysis of ha and na genes of human h3n2 influenza a viruses in guangdong, china, 2007-2011.annual h3n2 subtype influenza outbreaks in guangdong, china are a severe public health issue and require ongoing monitoring of emerging viral variants. the variation and evolution of haemagglutinin (ha) and neuraminidase (na) genes of influenza isolates from guangdong during 2007-2011 and others from genbank were analysed using lasergene 7.1 and mega 5.05, and serological analysis of antigens was determined by haemagglutination inhibition (hi). susceptibility to antiviral drugs was correlated wi ...201322827898
effect of receptor specificity of a/hong kong/1/68 (h3n2) influenza virus variants on replication and transmission in pigs.several arguments plead for an important role of pigs in human influenza ecology, including the similar receptor expression pattern in the respiratory tract of both species. how virus receptor binding specificity affects transmission in pigs, on the other hand, has not been studied so far.201322564359
design of escherichia coli-expressed stalk domain immunogens of h1n1 hemagglutinin that protect mice from lethal challenge.the hemagglutinin protein (ha) on the surface of influenza virus is essential for viral entry into the host cells. the ha1 subunit of ha is also the primary target for neutralizing antibodies. the ha2 subunit is less exposed on the virion surface and more conserved than ha1. we have previously designed an ha2-based immunogen derived from the sequence of the h3n2 a/hk/68 virus. in the present study, we report the design of an ha2-based immunogen from the h1n1 subtype (pr/8/34). this immunogen (h1 ...201223015722
in contrast to conventional inactivated influenza vaccines, 4xm2e.hsp70c fusion protein fully protected mice against lethal dose of h1, h3 and h9 influenza a isolates circulating in iran.ideal vaccines against influenza viruses should elicit not only a humoral response, but also a cellular response. mycobacterium tuberculosis hsp70 (mhsp70) have been found to promote immunogenic apcs function, elicit a strong cytotoxic t lymphocyte (ctl) response, and prevent the induction of tolerance. moreover, it showed linkage of antigens to the c-terminus of mhsp70 (mhsp70c) can represent them as vaccines resulted in more potent, protective antigen specific responses in the absence of adjuv ...201222595444
inhibitory effects of an m2-specific monoclonal antibody on different strains of influenza a virus.new approaches to the treatment of influenza have been designed based on the highly conserved antigenicity of the m2 envelope protein among influenza a virus strains. the present study examined the anti-viral activities of an anti-m2 ectodomain (m2e) monoclonal antibody (clone rm2ss23), which binds to the m2 proteins of the influenza a virus strains a/ aichi/2/68 (h3n2) (aichi) and a/pjr/8/34 (h1n1) (pr8). the results showed that rm2ss23 bound to both aichi and pr8 m2 proteins expressed on the c ...201223094582
immunization with m2e-displaying t7 bacteriophage nanoparticles protects against influenza a virus challenge.considering the emergence of highly pathogenic influenza viruses and threat of worldwide pandemics, there is an urgent need to develop broadly-protective influenza vaccines. in this study, we demonstrate the potential of t7 bacteriophage-based nanoparticles with genetically fused ectodomain of influenza a virus m2 protein (t7-m2e) as a candidate universal flu vaccine. immunization of mice with non-adjuvanted t7-m2e elicited m2e-specific serum antibody responses that were similar in magnitude to ...201223029232
lgp2 downregulates interferon production during infection with seasonal human influenza a viruses that activate interferon regulatory factor 3.lgp2, a member of the rig-i-like receptor family, lacks the amino-terminal caspase activation recruitment domains (cards) required for initiating the activation of interferon regulatory factor 3 (irf3) and interferon (ifn) transcription. the role of lgp2 in virus infection is controversial, and the only lgp2 experiments previously carried out with mammalian influenza a viruses employed an attenuated, mouse-adapted h1n1 a/pr/8/34 (pr8) virus that does not encode the ns1 protein. here we determine ...201222837208
intracytoplasmic trapping of influenza virus by a lipophilic derivative of aglycoristocetin.we report on a new anti-influenza virus agent, sa-19, a lipophilic glycopeptide derivative consisting of aglycoristocetin coupled to a phenylbenzyl-substituted cyclobutenedione. in madin-darby canine kidney cells infected with influenza a/h1n1, a/h3n2, or b virus, sa-19 displayed a 50% antivirally effective concentration of 0.60 μm and a selectivity index (ratio of cytotoxic versus antiviral concentration) of 112. sa-19 was 11-fold more potent than unsubstituted aglycoristocetin and was active i ...201222740402
a novel small molecule inhibitor of influenza a viruses that targets polymerase function and indirectly induces interferon.influenza viruses continue to pose a major public health threat worldwide and options for antiviral therapy are limited by the emergence of drug-resistant virus strains. the antiviral cytokine, interferon (ifn) is an essential mediator of the innate immune response and influenza viruses, like many viruses, have evolved strategies to evade this response, resulting in increased replication and enhanced pathogenicity. a cell-based assay that monitors ifn production was developed and applied in a hi ...201222577360
induction of protective immune responses against ev71 in mice by baculovirus encoding a novel expression cassette for capsid protein vp1.ev71 is a major causative agent of hand, foot and mouth disease (hfmd) and is responsible for large outbreaks in various asian pacific countries. in the present study, we generated the recombinant baculovirus (bac-vp1) encoding vp1 in a novel expression cassette. the transmembrane domain of hemagglutinin of the h3n2 influenza virus was included in the cassette as a minimal membrane anchor for vp1. the protective immunity of bac-vp1 was investigated in a mouse model. the results showed that mice ...201222691220
[development of sybr green i real-time rt-pcr for the detection of ebola virus].in order to establish a rapid and accurate method for the detection of ebola virus (ebov), the primers used in sybr green i real-time rt-pcr were designed based on the ebov np gene sequences published in genbank. the sybr green i real-time rt-pcr was established and optimized for the detection of ebov. the ebov rna that was transcribed in vitro was used as a template. the sensitivity of this method was found to reach 1.0 x 10(2) copies/microl and the detection range was 10(2) - 10(10). no cross ...201223233935
a reduced dose seasonal trivalent influenza vaccine is safe and immunogenic in adult and elderly patients - a randomized controlled trial.background: with the recent pandemic of influenza a (h1n1) and vaccine shortages, there has been a considerable interest of developing influenza vaccines with reduced doses, allowing for increased production capacity.design: here we report a prospective, randomized, double-blind, single-center clinical trial of a reduced-dose whole-virion inactivated, adjuvanted influenza vaccine in adult and elderly volunteers.methods: a total of 234 subjects including 120 adults (18-60 years of age) and 114 el ...201222219315
tracking oseltamivir-resistance in new zealand influenza viruses during a medicine reclassification in 2007, a resistant-virus importation in 2008 and the 2009 pandemic.oseltamivir (tamiflu®) is an important pharmaceutical intervention against the influenza virus. the importance of surveillance for resistance to oseltamivir has been highlighted by two global events: the emergence of an oseltamivir-resistant seasonal influenza a(h1n1) virus in 2008, and emergence of the influenza a(h1n1)pdm09 virus in 2009. oseltamivir is a prescription medicine in new zealand, but more timely access has been provided since 2007 by allowing pharmacies to directly dispense oselta ...201223908945
respiratory virus laboratory pandemic planning and surveillance in central viet nam, 2008-2010.laboratory capacity is needed in central viet nam to provide early warning to public health authorities of respiratory outbreaks of importance to human health, for example the outbreak of influenza a(h1n1) pandemic in 2009. polymerase chain reaction (pcr) procedures established as part of a capacity-building process were used to conduct prospective respiratory surveillance in a region where few previous studies have been undertaken.201223908924
[analysis on pathogen detection for 53 influenza outbreaks].in order to provide a scientific basis for influenza prevention and control, analyzing the epidemic characteristics and laws of influenza outbreaks in xuzhou area during 2005-2011.201223627018
[etiological analysis of influenza surveillance data in xuzhou from 2005 to 2011].to investigate the prevalence and subtypes of influenza viruses in xuzhou city from 2005 to 2011 and to provide the scientific supports for influenza prevention and control in this religion.201223627016
[characterization of influenza virus reassortants based on new donor strain a/hk/1/68/162/35(h3n2)].influenza reassortant viruses a/spb/hk/09(h1n1), a/astana/hk/2009 (h5n1), a/otar/hk/2010(h3n8), and a/perth/ hk/2011(h3n2), carrying surface antigens of different subtypes, were constructed on the basis of new potential unified donor strain a/hk/1/68/162/35(h3n2). the virulence and reproduction activity of the obtained reassortants were tested. the safety of the candidate live and inactivated influenza vaccines produced from the reassortant viruses was demonstrated. the study demonstrates that a ...201223477254
[genetic diversity and molecular evolution of the influenza a viruses in russia during 2006-2012].the results of molecular genetic analysis of more than 280 strains of influenza a virus subtypes h1n1 and h3n2 circulating in russia in 2006-2012 are presented. the genetic changes underlying the evolution of the virus strains and sensitivity to antiviral drugs were analyzed. significant changes in the genetic structure of influenza a viruses circulating in the russian federation and their phylogenetic affiliation are shown to occur within the studied period. the studies identifying codons under ...201223477253
[development of influenza surveillance in russia in the system of the who national influenza center].analysis of development influenza activity season 2010-2011 is presented. significant participation of influenza a(h1n1)pdm09 virus and influenza b of victoria lineage virus in the epidemic morbidity structure with minor participation ofa(h3n2) virus was revealed. the influenza viruses isolated in russia according to antigenic properties were similar to the strains included in the vaccine composition. drift variants of influenza a(h1n1)pdm09 viruses isolated in astrakhan and st.-petersburg were ...201223477249
[characterization of cold-adapted influenza strain a/hongkong/1/68/162/35 as a potential donor of attenuation and high reproduction].live and inactivated vaccines are currently produced using virus reassortants originating from various gene donors of internal proteins. based on the pandemic virus a/hong kong/1/68 (h3n2), a cold-adapted thermo-sensitive strain a/hong kong/1/68/162/35 was generated. it is distinguished for its high reproductive capacity (9-9.5 lg eid50), and hemagglutinating activity (1:1024-1:2048). the strain has ts and ca phenotype: reproductive capacity at t = 39 degrees c is 1.0 lg eid50; at t = 26 degrees ...201223477248
effect of statin treatments on highly pathogenic avian influenza h5n1, seasonal and h1n1pdm09 virus infections in balb/c mice.statins are used to control elevated cholesterol or hypercholesterolemia, but have previously been reported to have antiviral properties. aims: to show efficacy of statins in various influenza virus mouse models. materials & methods: balb/c mice were treated intraperitoneally or orally with several types of statins (simvastatin, lovastatin, mevastatin, pitavastatin, atorvastatin or rosuvastatin) at various concentrations before or after infection with either influenza a/duck/ mn/1525/81 h5n1 vir ...201223420457
genetic analysis of avian influenza viruses: cocirculation of avian influenza viruses with allele a and b nonstructural gene in northern pintail (anas acuta) ducks wintering in japan.the pandemic influenza virus strains of 1918 (h1n1), 1957 (h2n2), 1968 (h3n2), and 2009 (h1n1) have genes related to avian influenza viruses (aivs). the nonstructural (ns) gene of aivs plays a significant role in host-viral interaction. however, little is known about the degree of diversity of this gene in northern pintail (anas acuta) ducks wintering in japan. this study describes characteristics of pintail-originated h1n1, h1n2, h1n3, h5n2, h5n3, h5n9, and h7n7 viruses. most of the viruses wer ...201223320157
replication of swine and human influenza viruses in juvenile and layer turkey hens.since the first reported isolation of swine influenza viruses (sivs) in turkeys in the 1980s, transmission of sivs to turkeys was frequently documented. recently, the 2009 pandemic h1n1 virus, that was thought to be of swine origin, was detected in turkeys with a severe drop in egg production. in this study, we assessed the infectivity of different mammalian influenza viruses including swine, pandemic h1n1 and seasonal human influenza viruses in both juvenile and layer turkeys. in addition, we i ...201223305617
components of selection in the evolution of the influenza virus: linkage effects beat inherent selection.the influenza virus is an important human pathogen, with a rapid rate of evolution in the human population. the rate of homologous recombination within genes of influenza is essentially zero. as such, where two alleles within the same gene are in linkage disequilibrium, interference between alleles will occur, whereby selection acting upon one allele has an influence upon the frequency of the other. we here measured the relative importance of selection and interference effects upon the evolution ...201223300444
phylodynamic inference and model assessment with approximate bayesian computation: influenza as a case study.a key priority in infectious disease research is to understand the ecological and evolutionary drivers of viral diseases from data on disease incidence as well as viral genetic and antigenic variation. we propose using a simulation-based, bayesian method known as approximate bayesian computation (abc) to fit and assess phylodynamic models that simulate pathogen evolution and ecology against summaries of these data. we illustrate the versatility of the method by analyzing two spatial models descr ...201223300420
efficacy of influenza vaccination in patients with cirrhosis and inactive carriers of hepatitis b virus infection.influenza can causes morbidity and mortality that are greatly enhanced in patients with underlying chronic diseases such as cirrhotic patients. this study was performed to assess the immunogenicity of influenza vaccination in patients with cirrhosis and inactive carriers of hepatitis b virus infection.201223285414
robust immunity and heterologous protection against influenza in mice elicited by a novel recombinant np-m2e fusion protein expressed in e. coli.the 23-amino acid extracellular domain of matrix 2 protein (m2e) and the internal nucleoprotein (np) of influenza are highly conserved among viruses and thus are promising candidate antigens for the development of a universal influenza vaccine. various m2e- or np-based dna or viral vector vaccines have been shown to have high immunogenicity; however, high cost, complicated immunization procedures, and vector-specific antibody responses have restricted their applications. immunization with an np- ...201223285063
susceptibility of human h3n2 influenza virus to oseltamivir in south korea, 2009-2011.during the 2009-2011 influenza seasons, 10.26% of the specimens isolated from patients in south korea were subtyped as h3n2 viruses. some oseltamivir-sensitive h3n2 samples exhibited different plaque morphologies, and were found to have novel mutations in the neuraminidase gene. in a subsequent analysis using na mutant viruses, viral compensation against oseltamivir treatment was observed only in the n2 mutant virus. all things considered, these novel mutations may account for the exclusive char ...201223274998
influenza a virus nucleoprotein derived from escherichia coli or recombinant vaccinia (tiantan) virus elicits robust cross-protection in mice.immunity to conserved viral antigens is an attractive approach to develop a universal vaccine against epidemic and pandemic influenza. a nucleoprotein (np)-based vaccine has been explored and preliminary studies have shown promise. however, no study has explored the immunity and cross-protective efficacy of recombinant np derived from escherichia coli compared with recombinant vaccinia virus (tiantan).201223272943
comparative study of pandemic (h1n1) 2009, swine h1n1, and avian h3n2 influenza viral infections in quails.quail has been proposed to be an intermediate host of influenza a viruses. however, information on the susceptibility and pathogenicity of pandemic h1n1 2009 (ph1n1) and swine influenza viruses in quails is limited. in this study, the pathogenicity, virus shedding, and transmission characteristics of ph1n1, swine h1n1 (swh1n1), and avian h3n2 (dkh3n2) influenza viruses in quails was examined. three groups of 15 quails were inoculated with each virus and evaluated for clinical signs, virus sheddi ...201223271181
immune responses and protective efficacy of a recombinant swinepox virus co-expressing ha1 genes of h3n2 and h1n1 swine influenza virus in mice and pigs.the recombinant swine poxvirus rspv/h3-2a-h1 co-expressing ha1 genes of h3n2 and h1n1 subtype siv has been constructed and identified. inoculations of rspv/h3-2a-h1 yielded elisa and neutralization antibodies against siv h1n1 and h3n2, and elicited potent h1n1 and h3n2 siv-specific inf-γ response from t-lymphocytes in mice and pigs in this study. complete protection against siv h1n1 or h3n2 challenge in pigs was observed.201223265244
induction of anti-influenza immunity by modified green fluorescent protein (gfp) carrying hemagglutinin-derived epitope structure.the development of vaccination methods that can overcome the emergence of new types of influenza strains caused by escape mutations is desirable to avoid future pandemics. here, a novel type of immunogen was designed that targeted the conformation of a highly conserved region of influenza a virus hemagglutinin (ha) composed of two separate sequences that associate to form an anti-parallel β-sheet structure. our previous study identified this β-sheet region as the structural core in the epitope o ...201223264630
vaccination with ns1-truncated h3n2 swine influenza virus primes t cells and confers cross-protection against an h1n1 heterosubtypic challenge in pigs.the diversity of contemporary swine influenza virus (siv) strains impedes effective immunization of swine herds. mucosally delivered, attenuated virus vaccines are one approach with potential to provide broad cross-protection. reverse genetics-derived h3n2 siv virus with truncated ns1 (ns1δ126 tx98) is attenuated and immunogenic when delivered intranasally in young pigs. we analyzed t-cell priming and cross-protective efficacy in weanling piglets after intranasal inoculation with ns1δ126 tx98 ve ...201222067263
inefficient splicing of segment 7 and 8 mrnas is an inherent property of influenza virus a/brevig mission/1918/1 (h1n1) that causes elevated expression of ns1 protein.influenza a virus encodes two segments (7 and 8) that produce mrnas that can be spliced. we have investigated if naturally occurring sequence polymorphisms in the influenza a virus family affects splicing of these viral mrnas, as that could potentially alter the ns1/ns2- and/or m1/m2-protein ratios. we compared splicing efficiency of segment 7 and 8 mrnas of a/brevig mission/1918/1 (h1n1) and a/netherlands/178/95 (h3n2), as well as various h5n1 avian strains. results revealed that both segment 7 ...201222036312
Identification of novel virus inhibitors by influenza A virus specific reporter cell based screening.As influenza viruses have developed resistance towards current drugs, it is urgent to find potential novel antiviral inhibitors. Here we generated an influenza virus reporter cell line in which the luciferase gene was driven by the influenza virus promoter and screened a small compound library (NCI Diversity Set II). Ten compounds were identified to have inhibitory activity against influenza A virus H1N1. Among them, four compounds blocked influenza virus replication through inhibiting the activ ...201222057306
Characterization of neutralizing antibodies in adults after intranasal vaccination with an inactivated influenza vaccine.The levels and properties of neutralizing antibodies in nasal wash and serum collected from five healthy adults were examined after intranasal administration of an A/Uruguay/716/2007 (H3N2) split vaccine (45?µg hemagglutinin (HA) per dose; five doses, with an interval of 3 weeks between each dose). Prior to the assays, nasal wash samples were concentrated so that the total amount of antibodies was equivalent to about 1/10 of that found in the natural nasal mucus. Vaccination induced virus-specif ...201222170556
impaired wound healing predisposes obese mice to severe influenza virus infection.(see the editorial commentary by beck, on pages 172-3, and the article by kim et al, on pages 244-51.) for the first time, obesity appeared as a risk factor for developing severe 2009 pandemic influenza infection. given the increase in obesity, there is a need to understand the mechanisms underlying poor outcomes in this population. in these studies, we examined the severity of pandemic influenza virus in obese mice and evaluated antiviral effectiveness. we found that genetically and diet-induce ...201222147799
Boosting Heterosubtypic Neutralization Antibodies in Recipients of 2009 Pandemic H1N1 Influenza Vaccine.Background. A mass vaccination has been implemented to prevent the spread of 2009 pandemic influenza virus in China. Highly limited information is available on whether this vaccine induces cross-reactive neutralization antibodies against other subtypes of influenza viruses. Methods. We employed pseudovirus-based assays to analyze heterosubtypic neutralization responses in serum samples of 23 recipients of 2009 pandemic influenza vaccine. Results. One dose of pandemic vaccine not only stimulated ...201222052887
molecular and antigenic evolution of human influenza a/h3n2 viruses in quebec, canada, 2009-2011.a/h3n2 variability leads to poor vaccine effectiveness when the vaccine strain is not well matched to the circulating virus.201222036039
Antiviral activity of arbidol, a broad-spectrum drug for use against respiratory viruses, varies according to test conditions.The therapeutic activity of arbidol was investigated against representatives of seven different virus families. Its 50% median effective concentration (EC(50) ) was 0.22-11.8?µg/ml (0.41-22?nM). Therapeutic indices of 91 were obtained for type 1 poliovirus and 1.9-8.5 for influenza A and B, human paramyxo-3, avian infectious bronchitis-, and Marek's disease viruses. Arbidol was more inhibitory for influenza A/Aichi/2/68 (H3N2) virus than rimantadine or amantadine (EC(50) 10 vs. >15 and >31.6?µg/ ...201222028179
Intranasal administration of a flagellin-adjuvanted inactivated influenza vaccine enhances mucosal immune responses to protect mice against lethal infection.The influenza virus, a mucosal pathogen that infects the respiratory tract, is a major global health issue. There have been attempts to mucosally administer inactivated influenza vaccines to induce both mucosal and systemic immune responses. However, mucosally administered inactivated influenza vaccine has low immunogenicity, which is partially due to the lack of an effective mucosal adjuvant. The development of a safe and effective mucosal adjuvant is a prerequisite to the practical use of a mu ...201222051136
Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990-2010.Swine influenza viruses (SIV) have been recognized as important pathogens for pigs and occasional human infections with swine origin influenza viruses (SOIV) have been reported. Between1990 and 2010, a total of twenty seven human cases of SOIV infections have been identified in the United States. Six viruses isolated from1990 to 1995 were recognized as classical SOIV (cSOIV) A(H1N1). After 1998, twenty-one SOIV recovered from human cases were characterized as triple reassortant (tr_SOIV) inherit ...201222078166
respiratory syncytial virus (rsv) community-acquired pneumonia (cap) in a hospitalized adult with human immunodeficiency virus (hiv) mimicking influenza a and pneumocystis (carinii) jiroveci pneumonia (pcp).respiratory syncytial virus (rsv) is an important cause of lower respiratory tract infections in young children, the elderly, and immunocompromised hosts, but rsv is a rare cause of community-acquired pneumonia (cap) in hospitalized adults with human immunodeficiency virus (hiv). in patients with hiv, cap is most frequently attributable to the usual bacterial respiratory pathogens that cause cap in immunocompetent hosts, eg, streptococcuspneumoniae or hemophilus influenzae. adults with hiv are a ...201222005289
Host genetic background and the innate inflammatory response of lung to influenza virus.Many studies of influenza severity have focused on viral properties that confer virulence, whereas the contributory role of the host genetic background on infection severity remains largely unexplored. In this study, we measure the impact of inoculation with influenza virus in four strains of inbred mice - BALB/cByJ, C57BL/6J, A/J, and DBA/2J. To evaluate the extent to which responses are inherent to lung per se, as opposed to effects of the systemic response to lung infection, we also measured ...201221920449
Identification of H5N1-Specific T-Cell Responses in a High-risk Cohort in Vietnam Indicates the Existence of Potential Asymptomatic Infections.Background. Most reported human H5N1 viral infections have been severe and were detected after hospital admission. A case ascertainment bias may therefore exist, with mild cases or asymptomatic infections going undetected. We sought evidence of mild or asymptomatic H5N1 infection by examining H5N1-specific T-cell and antibody responses in a high-risk cohort in Vietnam. Methods. Peripheral blood mononuclear cells were tested using interferon-? enzyme-linked immunospot T assays measuring the respo ...201222080094
use of a human influenza challenge model to assess person-to-person transmission: proof-of-concept study.background. influenza transmission in humans remains poorly understood. in particular, the relative contribution of contact, large droplet, and aerosol transmission is unknown. the aims of this proof-of-concept study were to determine whether an experimentally induced influenza infection is transmissible between humans and whether this would form a viable platform for future studies. methods. in a quarantine facility, healthy volunteers ("donors") were inoculated with a/wisconsin/67/2005 (h3n2) ...201222131338
synthesis and biological evaluation of sialic acid derivatives containing a long hydrophobic chain at the anomeric position and their c-5 linked polymers as potent influenza virus inhibitors.conversions of the c-5 acetamide group in sialic acid into two kinds of cc double bond substituents were accomplished under shotten-baumann conditions. the polymerizable glycomonomers also contain a hydrophobic chain or hydroxyl group at the anomeric position. radical polymerizations of the fully protected glycomonomers were carried out with acryl amide in the presence of ammonium persulfate (aps) and n,n,n',n'-tetramethylethylenediamine (temed), followed by deprotection to furnish water-soluble ...201222100261
public health impact of including two lineages of influenza b in a quadrivalent seasonal influenza vaccine.the annual trivalent influenza vaccine (tiv) includes viruses representing three influenza strains - one a/h1n1, one a/h3n2, and one b, although two antigenically distinct lineages of influenza b (victoria and yamagata) co-circulate annually in the united states. predicting which lineage of influenza b will predominate during a season is challenging, and cross-protection by immunization against the other lineage is expected to be low. one proposed alternative is to produce a quadrivalent influen ...201222226861
surveillance in eastern india (2007-2009) revealed reassortment event involving ns and pb1-f2 gene segments among co-circulating influenza a subtypes.abstract: background: influenza a virus encodes for eleven proteins, of which ha, na, ns1 and pb1-f2 have been implicated in viral pathogenicity and virulence. thus, in addition to the ha and na gene segments, monitoring diversity of ns1 and pb1-f2 is also important. methods: 55 out of 166 circulating influenza a strains (31 h1n1 and 24 h3n2) were randomly picked during 2007-2009 and ns and pb1-f2 genes were sequenced. phylogenetic analysis was carried out with reference to the prototype strain ...201222217077
cloned cdna of a/swine/iowa/15/1930 internal genes as a candidate backbone for reverse genetics vaccine against influenza a viruses.reverse genetics viruses for influenza vaccine production usually utilize the internal genes of the egg-adapted a/puerto rico/8/34 (pr8) strain. this egg-adapted strain provides high production yield in embryonated eggs but does not necessarily give the best yield in mammalian cell culture. in order to generate a reverse genetics viral backbone that is well-adapted to high growth in mammalian cell culture, a swine influenza isolate a/swine/iowa/15/30 (h1n1) (rg1930) that was shown to give high y ...201222230579
influenza vaccine: an effective preventive vaccine for developing countries.the influenza virus a, b and c causes disease in humans, birds and animals. the influenza type a causes moderate to severe illness in all age groups in humans while the illness caused by type b is of milder and it is primarily affects children. among many subtypes of influenza a viruses, currently influenza a(h1n1) and a(h3n2) subtypes are circulating among humans. influenza is a serious public health problem that causes severe illnesses and deaths for higher risk populations. influenza virus is ...201222634439
sentinel surveillance for influenza in senegal, 1996-2009.data on influenza in tropical and resource-limited countries are scarce. in this study we present results from 14 years of influenza surveillance in senegal, one of the few tropical countries in africa from which longitudinal data are available.201223169958
induction and maintenance of anti-influenza antigen-specific nasal secretory iga levels and serum igg levels after influenza infection in adults.to determine the induction and changes in anti-influenza virus secretory iga (s-iga) levels in nasal washes and serum igg levels in patients with influenza.201222226319
update: influenza a (h3n2)v transmission and guidelines - five states, 2011.from august 17 to december 23, 2011, cdc received reports of 12 human infections with influenza a (h3n2)v viruses that have the matrix (m) gene from the influenza a (h1n1)pdm09 virus (formerly called swine-origin influenza a [h3n2] and pandemic influenza a [h1n1] 2009 viruses, respectively). the 12 cases occurred in five states (indiana, iowa, maine, pennsylvania, and west virginia), and 11 were in children. six of the 12 patients had no identified recent exposure to swine. three of the 12 patie ...201222217624
the use of antiviral drugs for influenza: guidance for practitioners 2012/2013.the present article addresses the use of antiviral drugs in the management of seasonal influenza illness for the 2012/2013 season. it updates the previous document published in 2011 (1). noteworthy guidance updates since 2011 include the following: seasonal influenza in 2012/2013 is predicted to be caused by two human influenza a and one influenza b strain, all of which are anticipated to remain generally susceptible to oseltamivir.the predicted strains are a/california/7/2009 (h1n1) pdm09-like, ...201224294283
improved sensitivity of influenza a antigen detection using a combined np, m, and ns1 sandwich elisa.a new modified triple-antigen detection test was developed for the direct detection of the influenza a virus. the nucleoprotein (np), matrix (m), and non-structural (ns1) proteins were used as target antigens because they are abundant in infected cells. monoclonal antibodies specific to the np, m, and ns1 proteins were generated. the antibody pairs were selected and evaluated for their reactivity individually and in combination in the triple-antigen detection using sandwich elisa. triple-antigen ...201222677225
multiplex rt-pcr assay for differentiating european swine influenza virus subtypes h1n1, h1n2 and h3n2.in europe, three major swine influenza viral (siv) subtypes (h1n1, h1n2 and h3n2) have been isolated in pigs. developing a test that is able to detect and identify the subtype of the circulating strain rapidly during an outbreak of respiratory disease in the pig population is of essential importance. this study describes two multiplex rt-pcrs which distinguish the haemagglutinin (ha) gene and the neuraminidase (na) gene of the three major subtypes of siv circulating in europe. the ha pcr was abl ...201222664185
influenza m1 vlps containing neuraminidase induce heterosubtypic cross-protection.influenza virus like particles (vlps) containing hemagglutinin were previously demonstrated to induce protection against the homologous strains. however, little information is available on the protective role of neuraminidase (na), the second major glycoprotein. in this study, we developed vlps (na vlps) containing na and m1 derived from a/pr/8/34 (h1n1) influenza virus, and investigated their ability to induce protective immunity. intranasal immunization with na vlps induced serum antibody resp ...201222658901
clinical effectiveness of neuraminidase inhibitors--oseltamivir, zanamivir, laninamivir, and peramivir--for treatment of influenza a(h3n2) and a(h1n1)pdm09 infection: an observational study in the 2010-2011 influenza season in japan.the clinical effectiveness of the newly released neuraminidase inhibitors (nais) laninamivir and peramivir has not been sufficiently evaluated in influenza-infected patients in clinical and practical settings. in this study, we analyzed the clinical data of 211 patients infected with influenza a virus subtype h3n2 (a(h3n2)) and 45 patients infected with influenza a virus subtype h1n1pdm (a(h1n1)pdm09) who received the nais oseltamivir, zanamivir, laninamivir, or peramivir during the 2010-2011 in ...201222644080
the age distribution of mortality due to influenza: pandemic and peri-pandemic.pandemic influenza is said to 'shift mortality' to younger age groups; but also to spare a subpopulation of the elderly population. does one of these effects dominate? might this have important ramifications?201223234604
human monoclonal antibodies to pandemic 1957 h2n2 and pandemic 1968 h3n2 influenza viruses.investigation of the human antibody response to the 1957 pandemic h2n2 influenza a virus has been largely limited to serologic studies. we generated five influenza virus hemagglutinin (ha)-reactive human monoclonal antibodies (mabs) by hybridoma technology from the peripheral blood of healthy donors who were born between 1950 and 1968. two mabs reacted with the pandemic h2n2 virus, two recognized the pandemic h3n2 virus, and remarkably, one reacted with both the pandemic h2n2 and h3n2 viruses. e ...201222457520
influenza viral infections among the iranian hajj pilgrims returning to shiraz, fars province, iran.annually over two million muslims from across the world converge on mecca to perform the hajj pilgrimage. overcrowding at the hajj facilitates spread of communicable diseases, especially respiratory infections. the aim of this study was to determine the attack rate of seasonal and pandemic influenza among returning iranian pilgrims after the 2009 hajj.201222606996
bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus.bovine lactoferrin (blf) is a multifunctional glycoprotein that plays an important role in innate immunity against infections, including influenza. here we have dissected blf into its c- and n-lobes and show that inhibition of influenza virus hemagglutination and cell infection is entirely attributable to the c-lobe and that all major virus subtypes, including h1n1 and h3n2, are inhibited. by far-western blotting and sequencing studies, we demonstrate that blf c-lobe strongly binds to the ha(2) ...201222595270
synthesis and antiviral evaluation of c5-substituted-(1,3-diyne)-2'-deoxyuridines.starting from acetylated 5-ethynyl-2'-deoxyuridine (3), 14 hitherto unknown c5-substituted-(1,3-diyne)-2'-deoxyuridines (with cyclopropyl, hydroxymethyl, methylcyclopentane, p-(substituted)phenyl and disubstituted-phenyl substituents) have been synthesized via a nickel-copper catalyzed c-h activation between two terminal alkynes, in yields ranging from 19% to 67%. their antiviral activities were measured against a large number of dna and rna viruses including herpes simplex virus type 1 and type ...201222578783
a novel pathogenic mechanism of highly pathogenic avian influenza h5n1 viruses involves hemagglutinin mediated resistance to serum innate inhibitors.in this study, the effect of innate serum inhibitors on influenza virus infection was addressed. seasonal influenza a(h1n1) and a(h3n2), 2009 pandemic a(h1n1) (h1n1pdm) and highly pathogenic avian influenza (hpai) a(h5n1) viruses were tested with guinea pig sera negative for antibodies against all of these viruses as evaluated by hemagglutination-inhibition and microneutralization assays. in the presence of serum inhibitors, the infection by each virus was inhibited differently as measured by th ...201222563489
nationwide surveillance of influenza during the pandemic (2009-10) and post-pandemic (2010-11) periods in taiwan.although who declared the world moving into the post-pandemic period on august 10, 2010, influenza a(h1n1) 2009 virus continued to circulate globally. its impact was expected to continue during the 2010-11 influenza season. this study describes the nationwide surveillance findings of the pandemic and post-pandemic influenza periods in taiwan and assesses the impact of influenza a(h1n1) 2009 during the post-pandemic period.201222545158
a sentinel platform to evaluate influenza vaccine effectiveness and new variant circulation, canada 2010-2011 season.during the 2010-2011 winter, a large number of outbreaks due to influenza a/h3n2 at long-term care facilities, including higher-than-expected attack rates among vaccinated staff, were reported in some regions of canada. interim analysis from the community-based sentinel surveillance system showed circulating h3n2 variants and suboptimal vaccine effectiveness (ve), assessed here for the entire season's data set.201222539661
development of a proficiency testing program for molecular diagnosis of influenza viruses.the molecular virology proficiency testing program at the wadsworth center began the assembly and distribution of influenza virus panels to us public health labs (phls) in 2008. the program was created to assist phls in assessing their performance and in meeting clia regulations for mandated proficiency testing (pt).201222538096
the effect of rosuvastatin in a murine model of influenza a infection.hmg-coa reductase inhibitors such as rosuvastatin may have immunomodulatory and anti-inflammatory effects that may reduce the severity of influenza a infection. we hypothesized that rosuvastatin would decrease viral replication, attenuate lung injury, and improve mortality following influenza a infection in mice.201222536437
genetic engineering of live attenuated influenza viruses.the first live attenuated influenza vaccine (laiv) was licensed in the usa in 2003; it is a trivalent vaccine composed of two type a (h1n1 and h3n2) and one type b influenza virus each at 10(7) fluorescent focus units (ffu). each influenza vaccine strain is a reassortant virus that contains the hemagglutinin (ha) and neuraminidase (na) gene segments from a wild-type influenza virus and the six internal protein gene segments from a master donor virus (mdv) of either cold-adapted a/ann arbor/6/60 ...201222528159
the fluorescence neuraminidase inhibition assay: a functional method for detection of influenza virus resistance to the neuraminidase inhibitors.neuraminidase inhibitors (nais) are presently the only effective antiviral drugs for treatment and chemoprophylaxis of influenza a and b infections, due to the high prevalence of resistance to the adamantane class of drugs among influenza a(h3n2) and a(h1n1) viruses, including the 2009 pandemic h1n1 strain. the limited pharmaceutical options currently available for control of influenza infections underscore the critical need for surveillance on nai susceptibility of influenza viruses circulating ...201222528156
in vitro anti-influenza virus and anti-inflammatory activities of theaflavin derivatives.the theaflavins fraction (tf80%, with a purity of 80%) and three theaflavin (tf) derivatives from black tea have been found to exhibit potent inhibitory effects against influenza virus in vitro. they were evaluated with a neuraminidase (na) activity assay, a hemagglutination (ha) inhibition assay, a real-time quantitative pcr (qpcr) assay for gene expression of hemagglutinin (ha) and a cytopathic effect (cpe) reduction assay. the experimental results showed that they all exerted significant inhi ...201222521753
human infections with novel reassortant influenza a(h3n2)v viruses, united states, 2011.during july-december 2011, a variant virus, influenza a(h3n2)v, caused 12 human cases of influenza. the virus contained genes originating from swine, avian, and human viruses, including the m gene from influenza a(h1n1)pdm09 virus. influenza a(h3n2)v viruses were antigenically distinct from seasonal influenza viruses and similar to proposed vaccine virus a/minnesota/11/2010.201222516540
influenza-associated mortality in temperate and subtropical chinese cities, 2003-2008.to estimate influenza-associated mortality in urban china.201222511824
antibodies cross-reactive to influenza a (h3n2) variant virus and impact of 2010-11 seasonal influenza vaccine on cross-reactive antibodies - united states.since august 2011, a total of 12 human infections with influenza a (h3n2) variant viruses with genes from avian, swine, and human viruses (i.e., a [h3n2]v) that had acquired the m gene from influenza a (h1n1)pdm09 virus have been reported to cdc. eleven of the cases occurred in children aged <10 years. in six cases, no history of recent exposure to swine was noted, suggesting that human-to-human transmission had occurred. this new gene constellation for a (h3n2)v viruses and its temporal associa ...201222495226
estimates of influenza vaccine effectiveness for 2007-2008 from canada's sentinel surveillance system: cross-protection against major and minor variants.to estimate influenza vaccine effectiveness (ve) for the 2007-2008 season and assess the sentinel surveillance system in canada for monitoring virus evolution and impact on ve.201222492921
pathogenicity and transmission in pigs of the novel a(h3n2)v influenza virus isolated from humans and characterization of swine h3n2 viruses isolated in 2010-2011.swine influenza virus (siv) h3n2 with triple reassorted internal genes (trig) has been enzootic in unites states since 1998. transmission of the 2009 pandemic h1n1 (ph1n1) virus to pigs in the united states was followed by reassortment with endemic siv, resulting in reassorted viruses that include novel h3n2 genotypes (rh3n2p). between july and december 2011, 12 cases of human infections with swine-lineage h3n2 viruses containing the pandemic matrix (pm) gene [a(h3n2)v] were detected. whole-geno ...201222491461
childhood influenza in the outpatient setting in shanghai, china.influenza is a common cause of outpatient visits in childhood. influenza vaccine has been widely used for children ≥ 6 months of age in developed countries based on accumulating evidence on the substantial socioeconomic burden of influenza in children. however, the data of childhood influenza in china are scarce.201222481425
eps® 7630 (umckaloabo®), an extract from pelargonium sidoides roots, exerts anti-influenza virus activity in vitro and in vivo.a prodelphinidin-rich extract from pelargonium sidoides dc, eps® 7630 (umckaloabo®), which is licensed to treat respiratory tract infections such as acute bronchitis, was investigated for its antiviral effects. eps® 7630 showed dose-dependent anti-influenza activity at non-toxic concentrations against pandemic h1n1, oseltamivir-sensitive and -resistant seasonal h1n1, seasonal h3n2 and the laboratory h1n1 strain a/puerto rico/8/34, while it had no antiviral activity against adenovirus or measles ...201222475498
small molecule inhibitors of influenza a and b viruses that act by disrupting subunit interactions of the viral polymerase.influenza viruses are the cause of yearly epidemics and occasional pandemics that represent a significant challenge to public health. current control strategies are imperfect and there is an unmet need for new antiviral therapies. here, we report the identification of small molecule compounds able to effectively and specifically inhibit growth of influenza a and b viruses in cultured cells through targeting an assembly interface of the viral rna-dependent rna polymerase. using an existing crysta ...201222474359
molecular and antigenic characterization of reassortant h3n2 viruses from turkeys with a unique constellation of pandemic h1n1 internal genes.triple reassortant (tr) h3n2 influenza viruses cause varying degrees of loss in egg production in breeder turkeys. in this study we characterized tr h3n2 viruses isolated from three breeder turkey farms diagnosed with a drop in egg production. the eight gene segments of the virus isolated from the first case submission (fav-003) were all of tr h3n2 lineage. however, viruses from the two subsequent case submissions (fav-009 and fav-010) were unique reassortants with pb2, pa, nucleoprotein (np) an ...201222470427
swine influenza virus infection dynamics in two pig farms; results of a longitudinal assessment.in order to assess the dynamics of influenza virus infection in pigs, serological and virological follow-ups were conducted in two whole batches of pigs from two different farms (f1 and f2), from 3 weeks of age until market age. anti-swine influenza virus (siv) antibodies (measured by elisa and hemagglutination inhibition) and nasal virus shedding (measured by rrt-pcr and isolation in embryonated chicken eggs and mdck cells) were carried out periodically. siv isolates were subtyped and hemagglut ...201222452923
protective effect of ginseng polysaccharides on influenza viral infection.ginseng polysaccharide has been known to have multiple immunomodulatory effects. in this study, we investigated whether panax ginseng polysaccharide (gp) would have a preventive effect on influenza infection. administration of mice with gp prior to infection was found to confer a survival benefit against infection with h1n1 (a/pr/8/34) and h3n2 (a/philippines/82) influenza viruses. mice infected with the 2009 h1n1 virus suspended in gp solution showed moderately enhanced survival rates and lower ...201222442708
identification of a novel compound with antiviral activity against influenza a virus depending on pa subunit of viral rna polymerase.influenza viruses have developed resistance to current drugs, creating a need for new antiviral targets and new drugs to treat influenza virus infections. in this study, computational and experimental screening of an extensive compound library identified thc19, which was able to suppress influenza virus replication. this compound had no cytotoxic effects and did not disrupt cell cycle progression or induce apoptosis in mdck cells as confirmed by wst-1 assays, flow cytometry analysis, and caspase ...201222441116
detecting patches of protein sites of influenza a viruses under positive selection.influenza a viruses are single-stranded rna viruses capable of evolving rapidly to adapt to environmental conditions. examples include the establishment of a virus in a novel host or an adaptation to increasing immunity within the host population due to prior infection or vaccination against a circulating strain. knowledge of the viral protein regions under positive selection is therefore crucial for surveillance. we have developed a method for detecting positively selected patches of sites on t ...201222427709
identification of dual receptor-binding specific strains of human h5n1 viruses in china.both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. the binding preference of avian flu virus h5n1 ha to the 2, 3-linked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. to monitor potential adaptation of h5n1 virus in human population, the surveillance of receptor-binding specificity was undertaken in china.201222424634
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