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design, synthesis, and in vitro biological evaluation of novel 6-methyl-7-substituted-7-deaza purine nucleoside analogs as anti-influenza a agents.among many subtypes of influenza a viruses, influenza a(h1n1) and a(h3n2) subtypes are currently circulating among humans (who report 2014-15). therapeutically, the emergence of viral resistance to currently available drugs (adamantanes and neuraminidase inhibitors) has heightened alarms for developing novel drugs that could address diverse targets in the viral replication cycle in order to improve treatment outcomes. to this regard, the design and synthesis of nucleoside analog inhibitors as po ...201626802557
incidence and clinical course of respiratory viral coinfections in children aged 0-59 months.clinical data available on coinfections are contradictory concerning both the number of viruses involved and the severity of the condition. a total of 114 patients aged 0-59 months with symptoms of respiratory tract infection were enrolled into the study. nasal and pharyngeal swabs were tested using the pcr method for the following 12 viruses: influenza a, influenza b, respiratory syncytial virus a (rsv a), respiratory syncytial virus b (rsv b), adenovirus, metapneumovirus, coronavirus 229e/nl63 ...201626801151
antibiotic prescription practices among children with influenza.the important factor in the development of resistance to antibiotics is their overuse, especially for viral respiratory infections. the aim of the study was to find out the frequency of the antibiotic therapy administrated to children with influenza. a total of 114 children younger than 59 months seeking care for the acute respiratory tract infection was enrolled into the study. the patients had influenza-like symptoms: fever > 38 °c, cough, and sore throat of less than 4 days duration. nasal an ...201626801146
an individualized predictor of health and disease using paired reference and target samples.consider the problem of designing a panel of complex biomarkers to predict a patient's health or disease state when one can pair his or her current test sample, called a target sample, with the patient's previously acquired healthy sample, called a reference sample. as contrasted to a population averaged reference this reference sample is individualized. automated predictor algorithms that compare and contrast the paired samples to each other could result in a new generation of test panels that ...201626801061
platform technology to generate broadly cross-reactive antibodies to α-helical epitopes in hemagglutinin proteins from influenza a viruses.we have utilized a de novo designed two-stranded α-helical coiled-coil template to display conserved α-helical epitopes from the stem region of hemagglutinin (ha) glycoproteins of influenza a. the immunogens have all the surface-exposed residues of the native α-helix in the native ha protein of interest displayed on the surface of the two-stranded α-helical coiled-coil template. this template when used as an immunogen elicits polyclonal antibodies which bind to the α-helix in the native protein. ...201626799790
design and evaluation of novel interferon lambda analogs with enhanced antiviral activity and improved drug attributes.type iii interferons (ifns) (also called ifn-λ: ifn-λ1, ifn-λ2, ifn-λ3, and ifn-λ4) are critical players in the defense against viral infection of mucosal epithelial cells, where the activity of type i ifns is weak, and unlike type i ifns that are associated with severe and diverse side effects, type iii ifns cause minimal side effects due to the highly restricted expression of their receptors, and thus appear to be promising agents for the treatment and prevention of respiratory and gastrointes ...201626792983
the semi-synthesis of novel andrographolide analogues and anti-influenza virus activity evaluation of their derivatives.two novel andrographolide analogues with the structural motif of δ(8,17)-alkene exo-to-endo isomerization, ai78 and ai89, were semi-synthesized firstly. two series of derivatives were designed and synthesized based on the synthetic pathway (including series i: olefin isomerizing to endocyclic δ(8,9) and series ii: olefin isomerizing to endocyclic δ(7,8)). the anti-influenza virus activity in vitro for all derivatives was evaluated. among the compounds synthesized, compound 38 with benzyl amino g ...201626791013
antiviral action of methylated β-lactoglobulin on the human influenza virus a subtype h3n2.antiviral activity of methylated β-lactoglobulin (met-blg) against h3n2 infected into mdck cell lines depended on concentration of met-blg, viral load, and duration of infection. ic50% of the hemagglutination activity for 1 and 0.2 moi (multiplicity of infection) after 24 h of incubation at 37 °c in the presence of 5% co2 were 20 ± 0.8 and 17 ± 0.7 μg ml(-1) met-blg, respectively. longer incubation period (4 days) was associated with low ic50% of the hemagglutination activity (7.1 ± 0.3 μg ml(-1 ...201026781119
discovery of influenza a virus sequence pairs and their combinations for simultaneous heterosubtypic targeting that hedge against antiviral resistance.the multiple circulating human influenza a virus subtypes coupled with the perpetual genomic mutations and segment reassortment events challenge the development of effective therapeutics. the capacity to drug most rnas motivates the investigation on viral rna targets. 123,060 segment sequences from 35,938 strains of the most prevalent subtypes also infecting humans-h1n1, 2009 pandemic h1n1, h3n2, h5n1 and h7n9, were used to identify 1,183 conserved rna target sequences (≥15-mer) in the internal ...201626771381
ultrasensitive detection of influenza viruses with a glycan-based impedimetric biosensor.an ultrasensitive impedimetric glycan-based biosensor for reliable and selective detection of inactivated, but intact influenza viruses h3n2 was developed. such glycan-based approach has a distinct advantage over antibody-based detection of influenza viruses since glycans are natural viral receptors with a possibility to selectively distinguish between potentially pathogenic influenza subtypes by the glycan-based biosensors. build-up of the biosensor was carefully optimized with atomic force mic ...201626765527
influenza in the emergency department: vaccination, diagnosis, and treatment: clinical practice paper approved by american academy of emergency medicine clinical guidelines committee.influenza is an acute respiratory virus that results in significant worldwide morbidity and mortality each year. as emergency physicians, we are often the first to encounter patients with seasonal influenza. it is therefore critical that we draw on the most recent and relevant research when we make clinical decisions regarding the diagnosis, treatment, and prophylaxis of this disease.201626763858
correlates of protection against influenza in the elderly: results from an influenza vaccine efficacy trial.although a number of studies have investigated and quantified immune correlates of protection against influenza in adults and children, data on immune protection in the elderly are sparse. a recent vaccine efficacy trial comparing standard-dose with high-dose inactivated influenza vaccine in persons 65 years of age and older provided the opportunity to examine the relationship between values of three immunologic assays and protection against community-acquired a/h3n2 influenza illness. the high- ...201626762363
accelerating influenza research: vaccines, antivirals, immunomodulators and monoclonal antibodies. the manufacture of a new wild-type h3n2 virus for the human viral challenge model.influenza and its associated diseases are a major cause of morbidity and mortality. the united states advisory committee on immunization practices recommends influenza vaccination for everyone over 6 months of age. the failure of the flu vaccine in 2014-2015 demonstrates the need for a model that allows the rapid development of novel antivirals, universal/intra-seasonal vaccines, immunomodulators, monoclonal antibodies and other novel treatments. to this end we manufactured a new h3n2 influenza ...201626761707
isolation of a novel h3n2 influenza virus containing a gene of h9n2 avian influenza in a dog in south korea in 2015.we isolated a serotype h3n2 influenza virus from a dog with severe respiratory distress in an animal clinic in south korea in 2015 and characterized the sequences of its eight genes. the following seven genes were derived from canine influenza virus: pb2, pb1, ha, np, na, m, and ns. however, the pa gene was derived from avian h9n2 influenza virus that is circulating in poultry in korea. these findings suggest that the continued surveillance of the influenza virus in dogs is warranted because hum ...201626757941
characterization of viral load, viability and persistence of influenza a virus in air and on surfaces of swine production facilities.indirect transmission of influenza a virus (iav) in swine is poorly understood and information is lacking on levels of environmental exposure encountered by swine and people during outbreaks of iav in swine barns. we characterized viral load, viability and persistence of iav in air and on surfaces during outbreaks in swine barns. iav was detected in pigs, air and surfaces from five confirmed outbreaks with 48% (47/98) of oral fluid, 38% (32/84) of pen railing and 43% (35/82) of indoor air sample ...201626757362
are plasma mineral levels related to antibody response to influenza vaccination in older adults?an effective immune response to vaccination may be related to nutritional status. this study examined the association of plasma mineral levels with hemagglutination inhibition (hi) titers produced in response to influenza vaccine in older adults.201626751915
prevalence of influenza a virus in exhibition swine during arrival at agricultural fairs.the exhibition swine at agricultural fairs provides a critical human-swine interface that allows for the bidirectional transmission of influenza a virus (iav). previous iav surveillance at the end of fairs has resulted in frequent detection of iav-infected swine; little is known, however, about the frequency with which swine arrive at fairs already infected with iav. we investigated the iav prevalence among exhibition swine entering fairs to better understand the epidemiology of iav in this uniq ...201626750204
targeting host calpain proteases decreases influenza a virus infection.influenza a viruses (iav) trigger contagious acute respiratory diseases. a better understanding of the molecular mechanisms of iav pathogenesis and host immune responses is required for the development of more efficient treatments of severe influenza. calpains are intracellular proteases that participate in diverse cellular responses, including inflammation. here, we used in vitro and in vivo approaches to investigate the role of calpain signaling in iav pathogenesis. calpain expression and acti ...201626747784
epidemiology of human coronavirus nl63 infection among hospitalized patients with pneumonia in taiwan.human coronavirus (hcov) nl63 is recognized in association with upper or lower respiratory tract illnesses in children. this study surveyed the prevalence of hcov-nl63 and influenza viruses in patients with influenza-like illness in taiwan during 2010-2011.201526746130
the pb1 segment of an influenza a virus h1n1 2009pdm isolate enhances the replication efficiency of specific influenza vaccine strains in cell culture and embryonated eggs.influenza vaccine strains (ivss) contain the haemagglutinin (ha) and neuraminidase (na) genome segments of relevant circulating strains in the genetic background of influenza a/pr/8/1934 virus (pr8). previous work has shown that the nature of the pb1 segment may be a limiting factor for the efficient production of ivss. here, we showed that the pb1 segment (pb1gi) from the 2009 pandemic influenza a virus (iav) a/giessen/06/2009 (gi wt, h1n1pdm) may help to resolve (some of) these limitations. we ...201626743314
deep sequencing reveals potential antigenic variants at low frequencies in influenza a virus-infected humans.influenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (ha). the rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. we used deep sequencing to characterize the between- and within-host genetic diversity of influenza viruses in a cohort of patients that i ...201626739054
multiplex rt-pcr detection of h3n2 influenza a virus in dogs.a multiplex rt-pcr (mrt-pcr) assay to detect h3n2 civ genomic segments was developed as a rapid and cost-effective method. its performance was evaluated with forty-six influenza a viruses from different hosts using three primer sets which amplify four segments of h3n2 civ simultaneously. the mrt-pcr has been successful in detecting the viral segments, indicating that it can improve the speed of diagnosis for h3n2 civ and its reassortants.201626738688
evolution of 2014/15 h3n2 influenza viruses circulating in us: consequences for vaccine effectiveness and possible new pandemic.a key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. here we propose a new bioinformatics approach for analysis of influenza viruses which could be used as an efficient tool for selection of vaccine viruses, assessment of the effectiveness of seasonal influenza vaccines, and prediction of the epidemic/pandemic potential of novel influenza viruses.201526733989
ring test evaluation of the detection of influenza a virus in swine oral fluids by real-time reverse-transcription polymerase chain reaction and virus isolation.the probability of detecting influenza a virus (iav) in oral fluid (of) specimens was calculated for each of 13 assays based on real-time reverse-transcription polymerase chain reaction (rrt-pcr) and 7 assays based on virus isolation (vi). the of specimens were inoculated with h1n1 or h3n2 iav and serially diluted 10-fold (10(-1) to 10(-8)). eight participating laboratories received 180 randomized of samples (10 replicates × 8 dilutions × 2 iav subtypes plus 20 iav-negative samples) and performe ...201626733728
quantifying influenza virus diversity and transmission in humans.influenza a virus is characterized by high genetic diversity. however, most of what is known about influenza evolution has come from consensus sequences sampled at the epidemiological scale that only represent the dominant virus lineage within each infected host. less is known about the extent of within-host virus diversity and what proportion of this diversity is transmitted between individuals. to characterize virus variants that achieve sustainable transmission in new hosts, we examined withi ...201626727660
imidazole-based pinanamine derivatives: discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza a virus.we previously reported potent hit compound 4 inhibiting the wild-type influenza a virus a/hk/68 (h3n2) and a/m2-s31n mutant viruses a/ws/33 (h1n1), with its latter activity quite weak. to further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. among them, 33 ...201626722757
characterization of the localized immune response in the respiratory tract of ferrets following infection with influenza a and b viruses.the burden of infection with seasonal influenza viruses is significant. each year is typically characterized by the dominance of one (sub)type or lineage of influenza a or b virus, respectively. the incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. to improve our understanding of the impacts of seasonal influenza viruses, w ...201526719259
ineffectiveness of the 2014-2015 h3n2 influenza vaccine.the seasonal influenza vaccine is currently the most effective preventive modality against influenza infection. nasopharyngeal samples of vaccinated and non-vaccinated patients presenting with influenza-like-illness (ili) were collected from over 20 outpatient clinics located in different geographic parts of israel and were tested for the presence of influenza viruses (influenza a and influenza b). here we show, that in the 2014-2015 season, the vaccine that included the a/texas/50/2012 h3n2 vir ...201626716420
quercetin as an antiviral agent inhibits influenza a virus (iav) entry.influenza a viruses (iavs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-iav agents. the glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including a/puerto rico/8/34 (h1n1), a/fm-1/47/1 (h1n1), and a/aichi/2/68 (h3n ...201526712783
recombinant influenza virus with a pandemic h2n2 polymerase complex has a higher adaptive potential than one with seasonal h2n2 polymerase complex.the reassortment of influenza viral gene segments plays a key role in the genesis of pandemic strains. all of the last three pandemic viruses contained reassorted polymerase complexes with subunits derived from animal viruses, suggesting that the acquisition of a reassorted polymerase complex might have a role in generating these pandemic viruses. here, we studied polymerase activities of the pandemic h2n2, seasonal h2n2 and pandemic h3n2 viruses. we observed that the viral ribonucleoprotein (vr ...201626703222
discovery of influenza a virus neuraminidase inhibitors using support vector machine and naïve bayesian models.neuraminidase (na) is a critical enzyme in the life cycle of influenza virus, which is known as a successful paradigm in the design of anti-influenza agents. however, to date there are no classification models for the virtual screening of na inhibitors. in this work, we built support vector machine and naïve bayesian models of na inhibitors and non-inhibitors, with different ratios of active-to-inactive compounds in the training set and different molecular descriptors. four models with sensitivi ...201626689205
pentacyclic triterpenes grafted on cd cores to interfere with influenza virus entry: a dramatic multivalent effect.multivalent effect plays an important role in biological processes, particularly in the specific recognition of virus with its host cell during the first step of infection. here we report the synthesis of multivalent pentacyclic triterpene grafted on cyclodextrin core and potency of against influenza entry activity. nine star-shaped compounds containing six, seven and eight pentacyclic triterpene pharmacophore on cyclodextrin scaffold were prepared by way of copper-catalyzed azide-alkyl cycloadd ...201626686050
generation and characterization of monoclonal antibodies specific to avian influenza h5n1 hemagglutinin protein.highly pathogenic avian influenza (hpai) h5n1 virus has in the past breached the species barrier from infected domestic poultry to humans in close contact. although human-to-human transmission has previously not been reported, hpai h5n1 virus has pandemic potential owing to gain of function mutation(s) and/or genetic reassortment with human influenza a viruses. monoclonal antibodies (mabs) have been used for diagnosis as well as specific therapeutic candidates in several disease conditions inclu ...201526683184
prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of human influenza viruses in faecal samples: what do we know?this review provides for the first time an assessment of the current understanding about the occurrence and the clinical significance of gastrointestinal (gi) symptoms in influenza patients, and their correlation with the presence of human influenza viruses in stools of patients with confirmed influenza virus infection. studies exploring how human influenza viruses spread to the patient's gi tract after a primary respiratory infection have been summarized. we conducted a systematic search of pub ...201526651485
indole alkaloid glucosides from the roots of isatis indigotica.five new indole alkaloid glucosides named isatindigotindolosides a-e (1-5), along with three known analogs (6-8), were isolated from an aqueous extract of the isatis indigotica roots. their structures including the absolute configurations were determined based on comprehensive spectroscopic data analysis, combined with chemical methods and electronic circular dichroism spectra calculations. in the preliminary assays, compounds 1, 6 and 7 showed antiviral activity against influenza virus a/hanfan ...201626651370
transcription factor runx3 is induced by influenza a virus and double-strand rna and mediates airway epithelial cell apoptosis.influenza a virus (iav) targets airway epithelial cells and exploits the host cell machinery to replicate, causing respiratory illness in annual epidemics and pandemics of variable severity. the high rate of antigenic drift (viral mutation) and the putative antigenic shift (reassortant strains) have raised the need to find the host cell inducible factors modulating iav replication and its pathogenesis to develop more effective antiviral treatment. in this study, we found for the first time that ...201526643317
outcomes of influenza infections in hematopoietic cell transplant recipients: application of an immunodeficiency scoring index.hematopoietic cell transplant (hct) recipients have lower immune response to influenza vaccination and are susceptible to lower respiratory tract infection (lri) and death. we determined clinical characteristics and outcomes of laboratory-confirmed influenza, including 2014/h3n2 infection, in 146 hct recipients. an immunodeficiency scoring index (isi) was applied to identify patients at high risk for lri and death. thirty-three patients (23%) developed lri and 7 (5%) died within 30 days of diagn ...201626638804
[analysis of the neuraminidase amino acid sequences of influenza a/h1n1pdm09, a/h3n2, and b viruses isolated from influenza patients in the 2013/14 japanese influenza season].neuraminidase (na) is an essential surface protein for influenza virus replication. na inhibitors are commonly used for the treatment of influenza patients in japan. several mutations that reduce the effect of na inhibitors have been reported. we sequenced the whole na segment of isolated virus from influenza patients and investigated the relation between the na amino acid sequence and the 50% inhibitory concentration (ic50) of four na inhibitors.201526630841
historical and recent cases of h3 influenza a virus in turkeys in minnesota.subtype h3 influenza a viruses (iavs) are abundant in wild waterfowl and also infect humans, pigs, horses, dogs, and seals. in minnesota, turkeys are important and frequent hosts of iav from wild waterfowl and from pigs. over 48 yr of surveillance history, 11 hemagglutinin (ha) subtypes of iav from waterfowl, as well as two ha subtypes from swine, h1 and h3, have infected turkeys in minnesota. however, there have only been two cases of avian-origin h3 iav infections in turkeys during this 48-yr ...201526629625
protection against influenza a virus by vaccination with a recombinant fusion protein linking influenza m2e to human serum albumin (hsa).the highly conserved extracellular domain of m2 protein (m2e) of influenza a viruses has limited immunogenicity on its own. hence, aiming to enhance immunogenicity of m2e protein, optimal approaches remain to be established. in this study, we created recombinant fusion protein vaccines by linking m2e consensus sequence of influenza a viruses with c-terminal domain of human serum albumin (hsa). then hsa/m2e recombinant fusion protein was studied. our results showed that hsa/m2e could induce stron ...201626615805
genome-wide analysis of evolutionary markers of human influenza a(h1n1)pdm09 and a(h3n2) viruses may guide selection of vaccine strain candidates.here we analyzed whole-genome sequences of 3,969 influenza a(h1n1)pdm09 and 4,774 a(h3n2) strains that circulated during 2009-2015 in the world. the analysis revealed changes at 481 and 533 amino acid sites in proteins of influenza a(h1n1)pdm09 and a(h3n2) strains, respectively. many of these changes were introduced as a result of random drift. however, there were 61 and 68 changes that were present in relatively large number of a(h1n1)pdm09 and a(h3n2) strains, respectively, that circulated dur ...201526615216
distinct functional determinants of influenza hemagglutinin-mediated membrane fusion.membrane fusion is the critical step for infectious cell penetration by enveloped viruses. we have previously used single-virion measurements of fusion kinetics to study the molecular mechanism of influenza-virus envelope fusion. published data on fusion inhibition by antibodies to the 'stem' of influenza virus hemagglutinin (ha) now allow us to incorporate into simulations the provision that some has are inactive. we find that more than half of the has are unproductive even for virions with no ...201526613408
prediction of the next highly pathogenic avian influenza pandemic that can cause illness in humans.in recent years, avian influenza viruses (aivs) have seriously threatened human health. questions such as: why do aivs infect humans?, how quickly can an aiv become pandemic?, and which virus is the most dangerous? cannot be sufficiently answered using current bioinformatic studies.201526612517
assessment of influenza vaccine effectiveness in a sentinel surveillance network 2010-13, united states.influenza vaccines are now widely used to reduce the burden of annual epidemics of influenza virus infections. influenza vaccine effectiveness (ve) is monitored annually to determine ve against each season's circulating influenza strains in different groups such as children, adults and the elderly. few prospective surveillance programs are available to evaluate influenza ve against medically attended illness for patients of all ages in the united states.201626611200
labdisk with complete reagent prestorage for sample-to-answer nucleic acid based detection of respiratory pathogens verified with influenza a h3n2 virus.portable point-of-care devices for pathogen detection require easy, minimal and user-friendly handling steps and need to have the same diagnostic performance compared to centralized laboratories. in this work we present a fully automated sample-to-answer detection of influenza a h3n2 virus in a centrifugal labdisk with complete prestorage of reagents. thus, the initial supply of the sample remains the only manual handling step. the self-contained labdisk automates by centrifugal microfluidics al ...201626610171
zanamivir-resistant influenza viruses with q136k or q136r neuraminidase residue mutations can arise during mdck cell culture creating challenges for antiviral susceptibility monitoring.surveillance of circulating influenza strains for antiviral susceptibility is important to ensure patient treatment guidelines remain appropriate. influenza a(h3n2) and a(h1n1)pdm09 virus isolates containing mutations at the q136 residue of the neuraminidase (na) that conferred reduced susceptibility to the na inhibitor (nai) zanamivir were detected during antiviral susceptibility monitoring. interestingly, the mutations were not detectable in the viruses from respective clinical specimens, only ...201526608955
substantial influenza vaccine effectiveness in households with children during the 2013-2014 influenza season, when 2009 pandemic influenza a(h1n1) virus predominated.we examined the influenza vaccine effectiveness (ve) during the 2013-2014 influenza season, in which 2009 pandemic influenza a(h1n1) virus (influenza a[h1n1]pdm09) predominated. in 2 previous years when influenza a(h3n2) virus predominated, the ve was low and negatively affected by prior year vaccination.201626597255
identification of a small-molecule inhibitor of influenza virus via disrupting the subunits interaction of the viral polymerase.assembly of the heterotrimeric influenza virus polymerase complex from the individual subunits pb1, pa, and pb2 is a prerequisite for viral replication, in which the interaction between the c terminal of pa (pac) and the n-terminal of pb1 (pb1n) may be a desired target for antiviral development. in this study, we compared the feasibility of high throughput screening by enzyme-linked immunosorbent assay (elisa) and fluorescence polarization assay. among the two, elisa was demonstrated to own broa ...201626593979
natural co-infection of influenza a/h3n2 and a/h1n1pdm09 viruses resulting in a reassortant a/h3n2 virus.despite annual co-circulation of different subtypes of seasonal influenza, co-infections between different viruses are rarely detected. these co-infections can result in the emergence of reassortant progeny.201526590689
surveillance for severe acute respiratory infections in southern arizona, 2010-2014.the binational border infectious disease surveillance program began surveillance for severe acute respiratory infections (sari) on the us-mexico border in 2009. here, we describe patients in southern arizona.201626590069
partial protection induced by 2011-2012 influenza vaccine against serologically evidenced a(h3n2) influenza virus infections in elderly institutionalized people.ninety-two institutionalized elderly subjects were vaccinated with trivalent influenza inactivated vaccine available for the 2011-2012 season, characterized by a prevalent circulation of a(h3n2) influenza viruses (a/victoria/208-clade) presenting antigenic and genetic patterns different from the a(h3n2) vaccine component (a/perth/16/2009-clade). haemagglutination inhibiting (hi) antibody titers were determined in sera collected before, 1 and 6 months after vaccination and patients were considere ...201626577530
analytical sensitivity comparison between singleplex real-time pcr and a multiplex pcr platform for detecting respiratory viruses.multiplex pcr methods are attractive to clinical laboratories wanting to broaden their detection of respiratory viral pathogens in clinical specimens. however, multiplexed assays must be well optimized to retain or improve upon the analytic sensitivity of their singleplex counterparts. in this experiment, the lower limit of detection (lod) of singleplex real-time pcr assays targeting respiratory viruses is compared to an equivalent panel on a multiplex pcr platform, the genmark esensor rvp. lods ...201526569120
the clinical usefulness of lymphocyte:monocyte ratios in differentiating influenza from viral non-influenza-like illnesses in hospitalized adults during the 2015 influenza a (h3n2) epidemic: the uniqueness of hpiv-3 mimicking influenza a.during influenza epidemics, influenza-like illnesses (ilis) viruses cocirculate with influenza strains. if positive, rapid influenza diagnostic tests (ridts) identify influenza a/b, but false-negative ridts require retesting by viral polymerase chain reaction (pcr). patient volume limits testing during influenza epidemics, and non-specific laboratory findings have been used for presumptive diagnosis pending definitive viral testing. in adults, the most useful laboratory abnormalities in influenz ...201626563893
influenza surveillance in russia based on epidemiological and laboratory data for the period from 2005 to 2012.exchange of information on and sharing of influenza viruses through the gisrs network has great significance for understanding influenza virus evolution, recognition of a new pandemic virus emergence and for preparing annual who recommendations on influenza vaccine strain composition. influenza surveillance in russia is based on collaboration of two nics with 59 regional bases. most epidemiological and laboratory data are entered through the internet into the electronic database at the research ...201726561480
topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial.pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. we aimed to clarify its effect in a younger age group.201626559482
antiviral activities of several oral traditional chinese medicines against influenza viruses.influenza is still a serious threat to human health with significant morbidity and mortality. the emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. traditional chinese medicines (tcms) may be an alternative to overcome the challenge. here, 10 oral proprietary chinese medicines were selected to evaluate their anti-influenza activities. these drugs exhibit potent inhibitory effects against influenza a h1n1, influenza a h3n2, and influenza b virus. i ...201526557857
detection of influenza a(h3n2) clade 3c.2a viruses in patients with suspected mumps in british columbia, canada, during the 2014/15 influenza season. 201526536131
impact of a large deletion in the neuraminidase protein identified in a laninamivir-selected influenza a/brisbane/10/2007 (h3n2) variant on viral fitness in vitro and in ferrets.viral fitness of a laninamivir-selected influenza a/brisbane/10/2007-like (h3n2) isolate (lrvp9) containing a 237-amino acid neuraminidase deletion and a p194l hemagglutinin mutation was evaluated in vitro and in ferrets. lrvp9 and the wild-type (wt) virus showed comparable replication kinetics in mdck-st6gali cells. cultured virus was recovered between days 2 and 5 post-infection in nasal washes (nw) from the 4 wt-infected ferrets whereas no virus was recovered from the lrvp9-infected animals. ...201626526406
human micrornas profiling in response to influenza a viruses (subtypes ph1n1, h3n2, and h5n1).micrornas (mirnas) play an important role in regulation of gene silencing and are involved in many cellular processes including inhibition of infected viral replication. this study investigated cellular mirna expression profiles operating in response to influenza virus in early stage of infection which might be useful for understanding and control of viral infection. a549 cells were infected with different subtypes of influenza virus (ph1n1, h3n2 and h5n1). after 24 h post-infection, mirnas were ...201626518627
differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.exposure to influenza virus triggers a complex cascade of events in the human host. in order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza a/wisconsin/67/2005 (h3n2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. nine of 17 (53%) inoculated subjects developed symptomatic influenza infection. individuals who will go on to become symptomatic demonstrate inc ...201626506932
icam-1 regulates the survival of influenza virus in lung epithelial cells during the early stages of infection.intercellular cell adhesion molecule-1 (icam-1) is an inducible cell surface glycoprotein that is expressed on many cell types. influenza virus infection enhanced icam-1 expression and messenger rna levels. human bronchial epithelial cells (hbepc) and nasal epithelial cells, on exposure to different strains of influenza virus (h1n1, h3n2, and h9n1) showed significant increase in icam-1 gene expression (p<0.001) along with the icam-1 protein levels (surface and secreted). depleting icam-1 in hbep ...201626499045
[child and adolescent interepydemic immunity to influenza viruses].our aim was to evaluate the child and adolescent population immunity to influenza a viruses (iav) and influenza b virus (ibv).201526495719
ceftiofur hydrochloride affects the humoral and cellular immune response in pigs after vaccination against swine influenza and pseudorabies.cephalosporins are a class of antibiotics that are active against many gram-positive and some gram-negative bacteria. beyond their antibacterial activity, they are reported to have various immunomodulatory properties. it has been shown that they reduce the secretion of cytokines as well as influence the humoral and cellular immune response. in the field conditions antibiotics are frequently administered at the same time as vaccines in pigs and, in the view of their potential immunomodulatory pro ...201526493336
identification of a novel viral protein expressed from the pb2 segment of influenza a virus.over the past 2 decades, several novel influenza virus proteins have been identified that modulate viral infections in vitro and/or in vivo. the pb2 segment, which is one of the longest influenza a virus segments, is known to encode only one viral protein, pb2. in the present study, we used reverse transcription-pcr (rt-pcr) targeting viral mrnas transcribed from the pb2 segment to look for novel viral proteins encoded by spliced mrnas. we identified a new viral protein, pb2-s1, encoded by a nov ...201526491155
identification of the ifn-β response in h3n2 canine influenza virus infection.canine influenza viruses (civs) circulate continuously in the dog population, providing opportunities for exposure to humans and other species. although the dog genome has been sequenced, innate immunity in dogs is not well characterized, which limits the understanding of h3n2 canine influenza virus pathogenesis. equally, how this virus evades the canine host innate immune response to successfully establish infection remains unclear. to analyse the ifn-β response to civ infection in madin-darby ...201626490006
serological evidence of pandemic h1n1 influenza virus infections in greek swine.the introduction of the 2009 pandemic h1n1 (ph1n1) influenza virus in pigs changed the epidemiology of influenza a viruses (iavs) in swine in europe and the rest of the world. previously, three iav subtypes were found in the european pig population: an avian-like h1n1 and two reassortant h1n2 and h3n2 viruses with human-origin haemagglutinin (ha) and neuraminidase proteins and internal genes of avian decent. these viruses pose antigenically distinct has, which allow the retrospective diagnosis o ...201626477456
h3n2 mismatch of 2014-15 northern hemisphere influenza vaccines and head-to-head comparison between human and ferret antisera derived antigenic maps.the poor performance of 2014-15 northern hemisphere (nh) influenza vaccines was attributed to mismatched h3n2 component with circulating epidemic strains. using human serum samples collected from 2009-10, 2010-11 and 2014-15 nh influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (hai) antibody responses against recent h3 epidemic isolates. all three populations (children, adults, and older adults) vaccinated with the 2014-15 nh egg- or cell-based vaccine, showe ...201526472175
pb1-f2 protein does not impact the virulence of triple-reassortant h3n2 swine influenza virus in pigs but alters pathogenicity and transmission in turkeys.pb1-f2 protein, the 11th influenza a virus (iav) protein, is considered to play an important role in primary influenza virus infection and postinfluenza secondary bacterial pneumonia in mice. the functional role of pb1-f2 has been reported to be a strain-specific and host-specific phenomenon. its precise contribution to the pathogenicity and transmission of influenza virus in mammalian host, such as swine, and avian hosts, such as turkeys, remain largely unknown. in this study, we explored the r ...201526468540
aureonitol, a fungi-derived tetrahydrofuran, inhibits influenza replication by targeting its surface glycoprotein hemagglutinin.the influenza virus causes acute respiratory infections, leading to high morbidity and mortality in groups of patients at higher risk. antiviral drugs represent the first line of defense against influenza, both for seasonal infections and pandemic outbreaks. two main classes of drugs against influenza are in clinical use: m2-channel blockers and neuraminidase inhibitors. nevertheless, because influenza strains that are resistant to these antivirals have been described, the search for novel compo ...201526462111
oseltamivir population pharmacokinetics in the ferret: model application for pharmacokinetic/pharmacodynamic study design.the ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic h5n1 viruses. rigorous pharmacokinetics/pharmacodynamics (pk/pd) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir pk. here, based on pk data from several studies on both uninfected and influenza-infected groups (i.e., with influenza a viruses of h5n1 and h3n2 subtypes and an inf ...201526460484
the coexistence or replacement of two subtypes of influenza.a pandemic subtype of influenza a sometimes replaces but sometimes coexists with the previous seasonal subtype. for example, the 1957 pandemic subtype h2n2 replaced the seasonal subtype h1n1; whereas after 1977 subtypes h1n1 (from the pandemic) and h3n2 continue to coexist. in an attempt to understand these alternatives, a hybrid model for the dynamics of influenza a is formulated. during an epidemic season the model takes into account cross-immunity of strains depending on the most recent seaso ...201526453807
lipid composition of viral envelope of three strains of influenza virus - not all viruses are created equal.while differences in the rate of virus fusion and budding from the host cell membrane have been correlated with pathogenicity, no systematic study of the contribution of differences in viral envelope composition has previously been attempted. using rigorous virus purification, marked differences between virions and host were observed. over 125 phospholipid species have been quantitated for three strains of influenza (hkx31- h3n2, pr8- h1n1, and vn1203- h5n1) grown in eggs. the glycerophospholipi ...201526448476
development of single-chain variable fragments (scfv) against influenza virus targeting hemagglutinin subunit 2 (ha2).influenza a viruses (iav) are widespread in birds and domestic poultry, occasionally causing severe epidemics in humans and posing health threats. hence, the need to develop a strategy for prophylaxis or therapy, such as a broadly neutralizing antibody against iav, is urgent. in this study, single-chain variable fragment (scfv) phage display technology was used to select scfv fragments recognizing influenza envelope proteins. the tomlinson i and j scfv phage display libraries were screened again ...201626446888
influenza virus reassortment is enhanced by semi-infectious particles but can be suppressed by defective interfering particles.a high particle to infectivity ratio is a feature common to many rna viruses, with ~90-99% of particles unable to initiate a productive infection under low multiplicity conditions. a recent publication by brooke et al. revealed that, for influenza a virus (iav), a proportion of these seemingly non-infectious particles are in fact semi-infectious. semi-infectious (si) particles deliver an incomplete set of viral genes to the cell, and therefore cannot support a full cycle of replication unless co ...201526440404
assessing antigenic drift of seasonal influenza a(h3n2) and a(h1n1)pdm09 viruses.under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (ha) have continually evolved to escape antibody recognition, termed antigenic drift. we analyzed the genomes of influenza a(h3n2) and a(h1n1)pdm09 virus strains circulating in thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemisphere matched them. we amplified and sequenced the ha gene of 120 a(h3n2) and 81 a(h1n1)pdm09 influenza ...201526440103
epidemiology of influenza viruses from 2009 to 2013 - a sentinel surveillance report from union territory of puducherry, india.to report the findings of influenza surveillance programme from union territory of puducherry and to document the clinical and epidemiological data of influenza viruses over a five year period from 2009 to 2013.201526433657
addition of n-glycosylation sites on the globular head of the h5 hemagglutinin induces the escape of highly pathogenic avian influenza a h5n1 viruses from vaccine-induced immunity.highly pathogenic avian influenza a h5n1 viruses remain endemic in poultry in several countries and still constitute a pandemic threat. since the early 20th century, we experienced four influenza a pandemics. h3n2 and h1n1pdm09 viruses that respectively emerged during 1968 and 2009 pandemics are still responsible for seasonal epidemics. these viruses evolve regularly by substitutions in antigenic sites of the hemagglutinin (ha), which prevent neutralization by antibodies directed against previou ...201526433051
detection and isolation of swine influenza a virus in spiked oral fluid and samples from individually housed, experimentally infected pigs: potential role of porcine oral fluid in active influenza a virus surveillance in swine.the lack of seasonality of swine influenza a virus (swiav) in combination with the capacity of swine to harbor a large number of co-circulating iav lineages, resulting in the risk for the emergence of influenza viruses with pandemic potential, stress the importance of swiav surveillance. to date, active surveillance of swiav worldwide is barely done because of the short detection period in nasal swab samples. therefore, more sensitive diagnostic methods to monitor circulating virus strains are r ...201526431039
quantifying protection against influenza virus infection measured by hemagglutination-inhibition assays in vaccine trials.correlations between hemagglutination-inhibition titers (hereafter "titers") and protection against infection have been identified in historical studies. however, limited information is available about the dynamics of how titer influences protection.201626427723
interim estimates of divergence date and vaccine strain match of human influenza a(h3n2) virus from systematic influenza surveillance (2010-2015) in hangzhou, southeast of china.in the post-pandemic period 2010-2015, seasonal influenza a(h3n2) virus predominated in hangzhou, southeast of china, with an increased activity and semi-annual seasons. this study utilized ha virus gene segment sequences to analyze the divergence date and vaccine strain match of human influenza a(h3n2) virus from systematic influenza surveillance in hangzhou.201526417878
diversity in compartmental dynamics of gene regulatory networks: the immune response in primary influenza a infection in mice.current approaches to study transcriptional profiles post influenza infection typically rely on tissue sampling from one or two sites at a few time points, such as spleen and lung in murine models. in this study, we infected female c57/bl6 mice intranasally with mouse-adapted h3n2/hong kong/x31 avian influenza a virus, and then analyzed the gene expression profiles in four different compartments (blood, lung, mediastinal lymph nodes, and spleen) over 11 consecutive days post infection. these dat ...201526413862
influenza virus survival in aerosols and estimates of viable virus loss resulting from aerosolization and air-sampling.using a collison nebulizer, aerosols of influenza (a/udorn/307/72 h3n2) were generated within a controlled experimental chamber, from known starting virus concentrations. air samples collected after variable suspension times were tested quantitatively using both plaque and polymerase chain reaction assays, to compare the proportion of viable virus against the amount of detectable viral rna. these experiments showed that whereas influenza rna copies were well preserved, the number of viable virus ...201526412395
clinical outcome of laninamivir octanoate hydrate for influenza in the 2013-2014 japanese season.the clinical outcome of laninamivir octanoate hydrate (laninamivir) in the japanese 2013-2014 influenza season was investigated. a total of 235 patients were enrolled, of whom 222 were evaluated for the duration of fever and other symptoms. the types/subtypes were 101 a(h1n1)pdm09 (45.5%), 37 a(h3n2) (16.7%), and 84 b (37.8%). the median durations of fever were 32.0, 41.0, and 50.0 h, and the median durations of symptoms were 74.5, 85.0, and 95.0 h for a(h1n1)pdm09, a(h3n2), and b, respectively. ...201526410550
cross-protection against european swine influenza viruses in the context of infection immunity against the 2009 pandemic h1n1 virus: studies in the pig model of influenza.pigs are natural hosts for the same influenza virus subtypes as humans and are a valuable model for cross-protection studies with influenza. in this study, we have used the pig model to examine the extent of virological protection between a) the 2009 pandemic h1n1 (ph1n1) virus and three different european h1 swine influenza virus (siv) lineages, and b) these h1 viruses and a european h3n2 siv. pigs were inoculated intranasally with representative strains of each virus lineage with 6- and 17-wee ...201526404790
influenza virus surveillance in coordinated swine production systems, united states.to clarify the epidemiology of influenza a viruses in coordinated swine production systems to which no animals from outside the system are introduced, we conducted virologic surveillance during september 2012-september 2013. animal age, geographic location, and farm type were found to affect the prevalence of these viruses.201526402228
identification of conserved peptides comprising multiple t cell epitopes of matrix 1 protein in h1n1 influenza virus.cell mediated immune response plays a key role in combating viral infection and thus identification of new vaccine targets manifesting t cell mediated response may serve as an ideal approach for influenza vaccine. the present study involves the application of an immunoinformatics-based consensus approach for epitope prediction (three epitope prediction tools each for cd4+ and cd8+ t cell epitopes) and molecular docking to identify peptide sequences containing t cell epitopes using the conserved ...201526398199
new functionally-enhanced soy proteins as food ingredients with anti-viral activity.respiratory viruses are a major public health problem because of their prevalence and high morbidity rate leading to considerable social and economic implications. cranberry has therapeutic potential attributed to a comprehensive list of phytochemicals including anthocyanins, flavonols, and unique a-type proanthocyanidins. soy flavonoids, including isoflavones, have demonstrated anti-viral effects in vitro and in vivo. recently, it was demonstrated that edible proteins can efficiently sorb and c ...201526396978
update: influenza activity--united states and worldwide, may 24-september 5, 2015.during may 24–september 5, 2015, the united states experienced typical low levels of seasonal influenza activity. influenza a (h1n1)pdm09 (ph1n1), influenza a (h3n2), and influenza b viruses were detected worldwide and were identified sporadically in the united states. all of the influenza viruses collected from u.s. states and other countries during that time have been characterized antigenically and/or genetically as being similar to the influenza vaccine viruses recommended for inclusion in t ...201526390411
diagnostic potential of recombinant scfv antibodies generated against hemagglutinin protein of influenza a virus.human influenza a viruses have been the cause of enormous socio-economic losses worldwide. in order to combat such a notorious pathogen, hemagglutinin protein (ha) has been a preferred target for generation of neutralizing-antibodies as potent therapeutic/diagnostic agents. in the present study, recombinant anti-ha single chain variable fragment antibodies were constructed using the phage-display technology to aid in diagnosis and treatment of human influenza a virus infections. spleen cells of ...201526388868
sexual diergism in antibody response to whole virus trivalent inactivated influenza vaccine in outbred mice.an outbred mouse model was used to determine if antibody response to immunization with whole-virus trivalent inactivated influenza vaccine (tiv) differs between the sexes. the antibody response was examined one (serum titer of igm antibodies), and three and six weeks post-immunization (serum titer of neutralizing and total igg antibodies and igg subclass profile). compared with male in female mice was found (i) the more robust igm response against all influenza strains included in tiv and (ii) m ...201526382601
attenuated recombinant influenza a virus expressing hpv16 e6 and e7 as a novel therapeutic vaccine approach.persistent infection with high-risk human papillomavirus (hpv) types, most often hpv16 and hpv18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. two prophylactic virus-like particle (vlps)-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. we have generated recombinant live-attenuated influenza a v ...201526381401
role of substitutions in the hemagglutinin in the emergence of the 1968 pandemic influenza virus.hemagglutinin (ha) of h3n2/1968 pandemic influenza viruses differs from the putative avian precursor by seven amino acid substitutions. substitutions q226l and g228s are known to be essential for adaptation of avian ha to mammals. we found that introduction of avian-virus-like amino acids at five other ha positions (positions 62, 81, 92, 144, and 193) of a/hong kong/1/1968 virus decreased viral replication in human cells and transmission in pigs. thus, substitutions at some of these positions fa ...201526378170
rig-i signaling is essential for influenza b virus-induced rapid interferon gene expression.influenza b virus causes annual epidemics and, along with influenza a virus, accounts for substantial disease and economic burden throughout the world. influenza b virus infects only humans and some marine mammals and is not responsible for pandemics, possibly due to a very low frequency of reassortment and a lower evolutionary rate than that of influenza a virus. influenza b virus has been less studied than influenza a virus, and thus, a comparison of influenza a and b virus infection mechanism ...201526378160
insight flu005: an anti-influenza virus hyperimmune intravenous immunoglobulin pilot study.hemagglutination inhibition (hai) antibody responses to anti-influenza virus hyperimmune intravenous immunoglobulin (hivig) were characterized. thirty-one patients with influenza during the 2013-2014 season were randomly assigned to receive 0.25 g/kg of hivig (n = 16) or placebo (n = 15). for hivig recipients, the ratio of geometric mean titers (1 hour after infusion/before infusion) was 4.00 (95% confidence interval [ci], 2.61-6.13) for 2009 pandemic influenza a(h1n1) and 1.76 (95% ci, 1.33-2.3 ...201626374911
cross protection against influenza a virus by yeast-expressed heterologous tandem repeat m2 extracellular proteins.the influenza m2 ectodomain (m2e) is well conserved across human influenza a subtypes, but there are few residue changes among avian and swine origin influenza a viruses. we expressed a tandem repeat construct of heterologous m2e sequences (m2e5x) derived from human, swine, and avian origin influenza a viruses using the yeast expression system. intramuscular immunization of mice with as04-adjuvanted m2e5x protein vaccines was effective in inducing m2e-specific antibodies reactive to m2e peptide ...201526366729
evaluation of commercial diagnostic assays for the specific detection of avian influenza a (h7n9) virus rna using a quality-control panel and clinical specimens in china.a novel avian influenza a h7n9-subtype virus emerged in china in 2013 and threatened global public health. commercial kits that specifically detect avian influenza a (h7n9) virus rna are urgently required to prepare for the emergence and potential pandemic of this novel influenza virus. the safety and effectiveness of three commercial molecular diagnostic assays were evaluated using a quality-control panel and clinical specimens collected from over 90 patients with confirmed avian influenza a (h ...201526361351
in vitro validation of self designed "universal human influenza a sirna".the genomic variability of influenza a virus (iav) makes it difficult for the existing vaccines or anti-influenza drugs to control. the sirna targeting viral gene induces rnai mechanism in the host and silent the gene by cleaving mrna. in this study, we developed an universal sirna and validated its efficiency in vitro. the sirna was designed rationally, targeting the most conserved region (delineated with the help of multiple sequence alignment) of m gene of iav strains. three level screening m ...201526349314
[analysis of the mechanism of a three-wave epidemic influenza a virus cvcle].a three-wave epidemic cycle caused by a new serotype agent is simulated. the mechanism of stepwise recession in a stratum of the susceptible persons is examined. a group of asymptomatic infected individuals as well as an antigen activity index, which regulates the intensity of input streams into the groups of infected patients, are introduced into the model. morbidity rate is additionally regulated by the virulence. the model is identified according to the observations of the three-wave passage ...201526349219
recommendations for prevention and control of influenza in children, 2015-2016.the purpose of this statement is to update recommendations for routine use of seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. the american academy of pediatrics recommends annual seasonal influenza immunization for all people 6 months and older, including all children and adolescents. highlights for the upcoming 2015-2016 season include the following: 1. annual universal influenza immunization is indicated with either a trivalent or ...201526347430
in silico identification of highly conserved epitopes of influenza a h1n1, h2n2, h3n2, and h5n1 with diagnostic and vaccination potential.the unpredictable, evolutionary nature of the influenza a virus (iav) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. in this study, we completed an in silico analysis of the reported epitopes of the 4 iav proteins that are antigenically most significant (ha, na, np, and m2) in the 3 strains with the greatest world circulation in the last century (h1n1, h2n2, and h3n2) and in one ...201526346523
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