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the enigma ml fluab-rsv assay: a fully automated molecular test for the rapid detection of influenza a, b and respiratory syncytial viruses in respiratory specimens.the enigma(®) ml fluab-rsv assay (enigma diagnostics, porton down, salisbury, uk) is a ce-ivd marked multiplex molecular panel for the detection of influenza a, b and respiratory syncytial viruses in nasopharyngeal swabs. the assay runs on the fully automated enigma ml platform without further specimen manipulation and provides a sample-to-answer result within 95 min. the reported sensitivity and specificity for influenza a are 100% (95% ci: 98.2-100) and 98.3% (95% ci: 95.5-99.4), respectively, ...201525399865
quantitative investigation of the affinity of human respiratory syncytial virus phosphoprotein c-terminus binding to nucleocapsid protein.there are no approved small molecule drug therapies for human respiratory syncytial virus (hrsv), a cause of morbidity and mortality in at-risk newborns, the immunocompromised, and the elderly. we have investigated as a potential novel hrsv drug target the protein-protein interaction between the c-terminus of the viral phosphoprotein (p) and the viral nucleocapsid protein (n), components of the ribonucleoprotein complex that contains, replicates, and transcribes the viral rna genome. earlier wor ...201425407889
imaging analysis of human metapneumovirus-infected cells provides evidence for the involvement of f-actin and the raft-lipid microdomains in virus morphogenesis.due to difficulties of culturing human metapneumovirus (hmpv) much of the current understanding of hmpv replication can be inferred from other closely related viruses. the slow rates of virus replication prevent many biochemical analyses of hmpv particles. in this study imaging was used to examine the process of hmpv morphogenesis in individually infected llc-mk2 cells, and to better characterise the sites of hmpv assembly. this strategy has circumvented the problems associated with slow replica ...201425408253
associations between co-detected respiratory viruses in children with acute respiratory infections.viruses are the major etiological agents of acute respiratory infections (aris) in young children. although respiratory virus co-detections are common, analysis of combinations of co-detected viruses has never been conducted in japan. nineteen respiratory viruses or subtypes were surveyed using multiplex real-time pcr on 1,044 pediatric (patient age < 6 years) ari specimens collected in osaka city, japan between january 2010 and december 2011. in total, 891 specimens (85.3%) were virus positive ...201425410563
dual proinflammatory and antiviral properties of pulmonary eosinophils in respiratory syncytial virus vaccine-enhanced disease.human respiratory syncytial virus (rsv) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. previous studies in humans and animal models have shown that vaccination with formalin-inactivated rsv (fi-rsv) leads to prominent airway eosinophilic inflammation following rsv challenge; however, the roles of pulmonary eosinophilia in the antiviral response ...201525410867
haemophilus influenzae increases the susceptibility and inflammatory response of airway epithelial cells to viral infections.nontypeable haemophilus influenzae (nthi), a common colonizer of lungs of patients with chronic obstructive pulmonary disease (copd), can enhance expression of the cellular receptor intercellular adhesion molecule 1 (icam-1), which in turn can be used by major group human rhinoviruses (hrvs) for attachment. here, we evaluated the effect of nthi-induced up-regulation of icam-1 on viral replication and inflammatory responses toward different respiratory viruses. therefore, human bronchial epitheli ...201525411435
is there still room for novel viral pathogens in pediatric respiratory tract infections?viruses are the most frequent cause of respiratory disease in children. however, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. in this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by pcr. nasal washings from 25 children (ou ...201425412469
respiratory syncytial virus human experimental infection model: provenance, production, and sequence of low-passaged memphis-37 challenge virus.respiratory syncytial virus (rsv) is the leading cause of lower respiratory tract infections in children and is responsible for as many as 199,000 childhood deaths annually worldwide. to support the development of viral therapeutics and vaccines for rsv, a human adult experimental infection model has been established. in this report, we describe the provenance and sequence of rsv memphis-37, the low-passage clinical isolate used for the model's reproducible, safe, experimental infections of heal ...201425415360
anti-respiratory syncytial virus prenylated dihydroquinolone derivatives from the gorgonian-derived fungus aspergillus sp. xs-20090b15.two new prenylated dihydroquinolone derivatives, 22-o-(n-me-l-valyl)aflaquinolone b (1) and 22-o-(n-me-l-valyl)-21-epi-aflaquinolone b (2), and two known analogues, aflaquinolones a (3) and d (or a diastereomer of d, 4), were isolated from the mycelia of a gorgonian-derived aspergillus sp. fungus. the structures of the new compounds were elucidated by spectroscopic methods, ecd spectra, marfey's method, and chemical conversion. compounds 1 and 2 display an unusual esterification of n-me-l-val to ...201425420212
respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the united states and finland.we investigated whether children with a higher respiratory syncytial virus (rsv) genomic load are at a higher risk of more-severe bronchiolitis.201425425699
occurrence of virus-induced copd exacerbations during four seasons.in this study, we investigated the occurrence of viral infections in acute exacerbations of chronic obstructive pulmonary disease (copd) during four seasons. viral infections were detected by the use of real-time reverse transcriptase polymerase chain reaction on pharyngeal swabs. during a 12-month period pharyngeal swabs were obtained in 136 exacerbations of 63 patients. in 35 exacerbations (25.7%) a viral infection was detected. most viral infections occurred in the winter (n = 14, 40.0%), fol ...201525426994
clinical performance evaluation of the sofia rsv fia rapid antigen test for diagnosis of respiratory syncytial virus infection.a recently introduced sofia respiratory syncytial virus (rsv) fluorescent immunoassay (fia) was evaluated against the binaxnow rsv card and the sd bioline rsv test using 348 respiratory samples. the sofia, binaxnow, and sd bioline kits showed sensitivities of 66%, 65%, and 64%, respectively, for detecting rsv-a, and 71%, 63%, and 65% for detecting rsv-b, respectively.201525428155
viperin protein expression inhibits the late stage of respiratory syncytial virus morphogenesis.we examined the effect of respiratory syncytial virus (rsv) infection on viperin protein expression in the permissive hep2 and non-permissive raw 264.7 macrophage cell lines. in rsv-infected hep2 cells low levels of the viperin protein was localized to the virus-induced inclusion bodies and did not impair virus transmission in these cells. in contrast, rsv-infected raw 264.7 cells increased expression of the stat1 protein occurred at between 6 and 12h post-infection, which coincided with the app ...201525433308
screening for respiratory syncytial virus and isolation strategies in children hospitalized with acute respiratory tract infection.nosocomial infection with respiratory syncytial virus (rsv) is an important health risk in pediatric care but is largely preventable by efficient infection control measures. commonly applied rapid antigen detection tests (radts) miss a considerable number of rsv-infected patients. the objective of our analysis was to evaluate whether readily available host parameters are associated with false-negative radt, and to assess how these parameters could be applied in an optimized rsv isolation strateg ...201425437026
infection-related asthma.the role of infection in asthma is varied in that it may exacerbate established asthma or contribute to the initial development of the clinical onset of asthma. mounting evidence implicates both roles with particular viral pathogens, namely human rhinovirus and respiratory syncytial virus, among the most likely culprits in asthma inception. once asthma is present, infection, particularly viral infection, is a common precipitant of asthma exacerbations. bacterial infections and colonization also ...201425439354
risk of respiratory syncytial virus infection in infants with congenital cystic lung disease.congenital cystic lung disease (ccld), which includes congenital cystic adenomatoid malformation, bronchopulmonary sequestration, and congenital lobar emphysema, has been reported to increase the risk of recurrent respiratory infection. in particular, respiratory syncytial virus (rsv) causes severe lower respiratory tract disease in high-risk infants. the objective of this study was to investigate the risk of severe rsv infection in infants with ccld.201525441859
risk factors associated with death in patients with severe respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection is an important cause of viral respiratory tract infection in children. this retrospective study describes the clinical characteristics of severe rsv infection and determines the risk factors for death.201625442868
the first wheezing episode: respiratory virus etiology, atopic characteristics, and illness severity.susceptibility to early rhinovirus-induced wheezing has been recognized as an important risk factor for childhood asthma, but data on the first wheezing episode are limited. the aim of this selected population study was to investigate virus etiology, atopic characteristics, and illness severity, as well as their interrelation, among first-time wheezing children.201425444257
[vrs bronchiolitis with severe hyponatremia leading to acute seizures: a report of three cases].acute bronchiolitis due to respiratory syncytial virus (rsv) can present with extrapulmonary manifestations, notably severe hyponatremia. hyponatremia is caused by excess secretion of antidiuretic hormone and can be exacerbated by intravenous infusion of hypotonic solutions. we report three cases of infants admitted for acute bronchiolitis and hyponatremia leading to acute seizures. we describe how hyponatremia was corrected and analyze the management aspects that might have worsened the magnitu ...201425445128
measles-mumps-rubella vaccination and respiratory syncytial virus-associated hospital contact.the live measles vaccine has been associated with lower non-measles mortality and admissions in low-income countries. the live measles-mumps-rubella vaccine has also been associated with lower rate of admissions with any type of infection in danish children; the association was strongest for admissions with lower respiratory infections.201525446818
mechanism of action for respiratory syncytial virus inhibitor rsv604.respiratory syncytial virus (rsv) is the leading cause of acute lower respiratory tract infections in young children and other high-risk populations. rsv nucleoprotein (n) is essential for virus assembly and replication as part of the viral ribonucleoprotein (rnp) complex. rsv604 was a putative n inhibitor in phase 2 clinical trials whose molecular mechanism of action (moa) was not well understood. this study investigated the cell line-dependent potency of rsv604 and demonstrated its direct bind ...201525451060
galectin-9 ameliorates respiratory syncytial virus-induced pulmonary immunopathology through regulating the balance between th17 and regulatory t cells.respiratory syncytial virus (rsv) infections are characterized by lung inflammation, mucus hypersecretion, and hyperresponsiveness. cd4+ t cells play a pivotal role in the development of rsv-induced lung pathology. thus targeting the activation of cd4+ t cell subsets and enhancing regulatory functions of cd4+ t cells could be an effectively therapeutic approach. in the present study, we showed that rsv-induced lung inflammation can be suppressed by lectin family member galectin-9 (gal-9), which ...201525451068
[management of copd exacerbations: from primary care to hospitalization].the société de pneumologie de langue française defines acute exacerbation of chronic obstructive pulmonary disease (ae copd) as an increase in daily respiratory symptoms, basically duration ≥ 48h or need for treatment adjustment. etiology of ea copd are mainly infectious, viral (rhinovirus, influenzae or parainfluenzae virus, coronavirus, adenovirus and respiratory syncytial virus) or bacterial (haemophilus influenzae, streptococcus pneumoniae, or moraxella catarrhalis). pollutant exposure can a ...201425451635
editorial: rsv: a new box of delights for an old enemy. 201425452617
respiratory syncytial virus infection and bronchiolitis. 201425452661
[update of recommendations on the use of palivizumab as prophylaxis in rsv infections].the standards committee of the spanish neonatology society (seneo) considers that the new document from the american academy of pediatrics, including recommendations for palivizumab use to prevent serious infections produced by the respiratory syncytial virus (rsv), provides no new scientific evidence which would justify the modification of the current recommendations of the seneo. however, some adjustments to the criteria of the existing recommendations are proposed to reduce the cost of the dr ...201525453311
many respiratory viruses have temporal association with meningococcal disease.previous ecological studies have shown a temporal and spatial association between influenza epidemics and meningococcal disease (mng); however, none have examined more than two respiratory viruses.201525456529
infantile systemic hyalinosis complicated with right atrial thrombus and pericardial effusion in an infant.infantile systemic hyalinosis (ish) is a rare multisystem fatal autosomal recessive disorder that involves widespread deposition of hyaline on connective tissues and certain internal organs. the major manifestations include painful articular contractures, hyperpigmentation, subcutaneous nodules, gingival hypertrophy, failure to thrive secondary to protein-losing enteropathy, and osteolytic bone lesions. in this paper, we report a 12-month-old girl with ish presenting with recurrent diarrhea, fai ...201725458638
randomized trial to evaluate azithromycin's effects on serum and upper airway il-8 levels and recurrent wheezing in infants with respiratory syncytial virus bronchiolitis.respiratory syncytial virus (rsv) bronchiolitis in infancy is a major risk factor for recurrent wheezing and asthma. because azithromycin attenuated neutrophilic airway inflammation in a murine viral bronchiolitis model, demonstration of similar effects in human subjects might provide a strategy for the prevention of postbronchiolitis recurrent wheezing.201525458910
[incidence and severity of pertussis in infants with a respiratory syncytial virus infection].pertussis is a re-emerging disease that mostly affects infants. at this age, the severity can be affected by intercurrent infections such as respiratory syncytial virus (rsv).201725459193
a patient self-collection method for longitudinal monitoring of respiratory virus infection in solid organ transplant recipients.methods for the longitudinal study of respiratory virus infections are cumbersome and limit our understanding of the natural history of these infections in solid organ transplant (sot) recipients.201525464966
control of pathogenic effector t-cell activities in situ by pd-l1 expression on respiratory inflammatory dendritic cells during respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection is a leading cause of severe lower respiratory tract illness in young infants, the elderly and immunocompromised individuals. we demonstrate here that the co-inhibitory molecule programmed cell death 1 (pd-1) is selectively upregulated on t cells within the respiratory tract during both murine and human rsv infection. importantly, the interaction of pd-1 with its ligand pd-l1 is vital to restrict the pro-inflammatory activities of lung effector t cells ...201525465101
respiratory syncytial virus--united states, july 2012-june 2014.respiratory syncytial virus (rsv) causes lower respiratory infection among infants and young children worldwide. annually in the united states, rsv infection has been associated with an estimated 57,527 hospitalizations and 2.1 million outpatient visits among children aged <5 years. in temperate climate zones, rsv generally circulates during the fall, winter, and spring. however, the exact timing and duration of rsv seasons vary by region and from year-to-year. knowing the start of the rsv seaso ...201425474034
sendai virus recombinant vaccine expressing a secreted, unconstrained respiratory syncytial virus fusion protein protects against rsv in cotton rats.the respiratory syncytial virus (rsv) is responsible for as many as 199000 annual deaths worldwide. currently, there is no standard treatment for rsv disease and no vaccine. sendai virus (sev) is an attractive pediatric vaccine candidate because it elicits robust and long-lasting virus-specific b cell and t cell activities in systemic and mucosal tissues. the virus serves as a gene delivery system as well as a jennerian vaccine against its close cousin, human parainfluenza virus type 1. here we ...201525477211
inhibition of priming for bovine respiratory syncytial virus-specific protective immune responses following parenteral vaccination of passively immune calves.the effect of maternal antibodies (matab) on immunological priming by neonatal parenteral vaccination for bovine respiratory syncytial virus (brsv) was addressed for the first time in experimental infection in 34 holstein calves. both vaccinated and control calves developed moderate to severe respiratory disease characteristic of acute brsv infection. there were no differences in clinical signs, brsv shed, arterial oxygen concentrations, or mortality between vaccinated and control calves after b ...201425477547
the eukaryotic elongation factor 1a is critical for genome replication of the paramyxovirus respiratory syncytial virus.the eukaryotic translation factor eef1a assists replication of many rna viruses by various mechanisms. here we show that down-regulation of eef1a restricts the expression of viral genomic rna and the release of infectious virus, demonstrating a biological requirement for eef1a in the respiratory syncytial virus (rsv) life cycle. the key proteins in the replicase/transcriptase complex of rsv; the nucleocapsid (n) protein, phosphoprotein (p) and matrix (m) protein, all associate with eef1a in rsv ...201425479059
bacterial lysates improve the protective antibody response against respiratory viruses through toll-like receptor 4.respiratory viruses cause significant morbidity and mortality in infants and young children worldwide. current strategies to modulate the immune system and prevent or treat respiratory viral infections in this age group have shown limited success. here, we demonstrate that a lysate derived from gram-positive and gram-negative organisms positively modulates protective antibody responses against both respiratory syncytial virus (rsv) and influenza virus in murine models of infection. interestingly ...201425483455
a population-weighted, condition-adjusted estimate of palivizumab efficacy in preventing rsv-related hospitalizations among us high-risk children.preterm infants ≤ 35 weeks' gestational age (ga), and children ≤ 24 months of age with bronchopulmonary dysplasia (bpd) or hemodynamically significant congenital heart disease (hschd) are at high risk for developing severe respiratory syncytial virus (rsv) disease. in 3 previous randomized, placebo-controlled trials, palivizumab efficacy varied significantly based on these underlying conditions, and trial enrollment was not proportional to condition prevalence. this analysis provides the first e ...201425483483
viral etiology of mumps-like illnesses in suspected mumps cases reported in catalonia, spain.we investigated the etiology of reported sporadic suspected mumps cases with a negative rt-pcr result for the mumps virus in the barcelona-south region in 2007-2011. samples from mumps virus-negative patients presenting unilateral or bilateral parotitis or other salivary gland swelling were tested for epstein-barr virus (ebv) by real-time pcr and for respiratory viruses by two multiplex-pcr-based assays to detect parainfluenza virus (piv) 1-4, influenza virus (inv) a, b and c, respiratory syncyt ...201525483547
meeting report vlpnpv: session 8: vaccines i.in session 8 of the recent conference "virus-like particle and nano-particle vaccines" held at the salk institute in la jolla, california (05 june 2014), four scientists described new virus-like particle (vlp) approaches, progress, and early-stage plans for vaccines against significant human pathogens including hpv, malaria, hiv, dengue, and rsv. a unifying theme was that displaying epitopes in an array on a virus-like particle can be a powerful approach for achieving a strong immune response. v ...201425483643
serum palivizumab level is associated with decreased severity of respiratory syncytial virus disease in high-risk infants.monthly doses of palivizumab, an rsv-specific monoclonal antibody, reduce rsv-related hospitalizations (rsvh) in high-risk children; however, no specific palivizumab level has been correlated with disease severity in humans. a post hoc analysis of a previous randomized, placebo-controlled trial evaluated the relationship between serum palivizumab level at the time of rsvh and disease severity. pediatric intensive care unit (picu) admission was the primary severity marker. relationships were eval ...201425483663
raman spectroscopy characterization of antibody phases in serum.when administered in serum, an efficacious therapeutic antibody should be homogeneous to minimize immune reactions or injection site irritation during administration. monoclonal antibody (mab) phase separation is one type of inhomogeneity observed in serum, and thus screening potential phase separation of mabs in serum could guide lead optimization. however, serum contains numerous components, making it difficult to resolve mab/serum mixtures at a scale amenable to analysis in a discovery settin ...201425484036
neurally adjusted ventilator assist (nava) reduces asynchrony during non-invasive ventilation for severe bronchiolitis.to determine the prevalence of main inspiratory asynchrony events during non-invasive intermittent positive-pressure ventilation (niv) for severe bronchiolitis. ventilator response time and asynchrony were compared in neurally adjusted ventilator assist (nava) and in pressure assist/control (pac) modes.201525488197
respiratory syncytial virus-associated mortality in hospitalized infants and young children.respiratory syncytial virus (rsv) is a common cause of pediatric hospitalization, but the mortality rate and estimated annual deaths are based on decades-old data. our objective was to describe contemporary rsv-associated mortality in hospitalized infants and children aged <2 years.201525489019
clinical evaluation of viral acute respiratory tract infections in children presenting to the emergency department of a tertiary referral hospital in the netherlands.the relative incidence and clinical impact of individual respiratory viruses remains unclear among children presenting to the hospital emergency department with acute respiratory tract infection (arti).201425491885
[simultaneous detection of respiratory viruses and influenza a virus subtypes using multiplex pcr].this study was conducted to investigate the respiratory viruses and subtyping of influenza a virus when positive by multiplex pcr in patients with flu-like symptoms, after the pandemic caused by influenza a (h1n1)pdm09. nasopharyngeal swab samples collected from 700 patients (313 female, 387 male; age range: 24 days-94 yrs, median age: 1 yr) between december 2010 - january 2013 with flu-like symptoms including fever, headache, sore throat, rhinitis, cough, myalgia as defined by the world health ...201425492660
respiratory syncytial virus infection-associated hospitalization in adults: a retrospective cohort study.once considered primarily a pediatric concern, respiratory syncytial virus (rsv) infection is gaining recognition as a cause of significant morbidity and mortality in adults. a better understanding of rsv epidemiology and disease in adults is needed to guide patient management and to assess the need for prophylaxis, vaccines, and treatments.201425494918
evaluation of respiratory syncytial virus (rsv) direct antigen detection assays for use in point-of-care testing.rsv infections cause lower respiratory tract infections and result in surges in physician's office, emergency department visits and hospitalizations, especially in infants and toddlers. point-of-care (poc) testing reduces healthcare costs and permits informed decisions on treatment, however, optimal poc assays must be sensitive, easy to perform and provide rapid results. a prospective study tested 230 patient nasopharyngeal specimens using 4 rsv direct antigen detection assays (directigen, quick ...201525500182
rapid and generic identification of influenza a and other respiratory viruses with mass spectrometry.the rapid identification of existing and emerging respiratory viruses is crucial in combating outbreaks and epidemics. matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) is a rapid and reliable identification method in bacterial diagnostics, but has not been used in virological diagnostics. mass spectrometry systems have been investigated for the identification of respiratory viruses. however, sample preparation methods were laborious and time-consuming. ...201525500183
hospitalizations associated with influenza and respiratory syncytial virus among patients attending a network of private hospitals in south africa, 2007-2012.influenza and respiratory syncytial virus (rsv) infection are common causes of lower respiratory tract illness. data on their burden in low and middle-income settings and from africa are scarce. we aimed to estimate age-specific rates of hospitalization attributable to influenza and rsv among patients attending private hospitals in south africa during 2007-2012.201425510622
recombinant influenza virus expressing a fusion protein neutralizing epitope of respiratory syncytial virus (rsv) confers protection without vaccine-enhanced rsv disease.respiratory syncytial virus (rsv) is the leading cause of viral bronchiolitis in both children and the elderly. there is no vaccine available for the prevention of rsv infection. here, we generated recombinant influenza virus (pr8/rsv.ha-f) expressing an rsv f243-294 neutralizing epitope in the hemagglutinin (ha) as a chimeric protein. neutralizing antibodies specific for both rsv and influenza virus were induced by a single intranasal immunization of mice with pr8/rsv.ha-f. mice that were immun ...201525513755
modulation of host adaptive immunity by hrsv proteins.globally, the human respiratory syncytial virus (hrsv) is the major cause of lower respiratory tract infections (lrtis) in infants and children younger than 2 years old. furthermore, the number of hospitalizations due to lrtis has shown a sustained increase every year due to the lack of effective vaccines against hrsv. thus, this virus remains as a major public health and economic burden worldwide. the lung pathology developed in hrsv-infected humans is characterized by an exacerbated inflammato ...201425513775
importance of viruses in acute otitis media.acute otitis media occurs as a complication of viral upper respiratory tract infection. bacterial otopathogens and respiratory viruses interact and play important roles in acute otitis media development. a better understanding of viral and bacterial interactions may lead to innovative ways to lessen the burden of this common childhood disease.201525514574
multiplex pcr analysis of clusters of unexplained viral respiratory tract infection in cambodia.fevers of unknown origin constitute a substantial disease burden in southeast asia. in majority of the cases, the cause of acute febrile illness is not identified.201425514971
clinical characteristics and risk factors of severe respiratory syncytial virus-associated acute lower respiratory tract infections in hospitalized infants.to investigate the clinical characteristics and analyze risk factors for severe respiratory syncytial virus (rsv) infection in hospitalized infants with acute lower respiratory tract infections (alris).201425515808
systematic review and meta-analysis of the effectiveness of commercially available vaccines against bovine herpesvirus, bovine viral diarrhea virus, bovine respiratory syncytial virus, and parainfluenza type 3 virus for mitigation of bovine respiratory disease complex in cattle.to evaluate and analyze data from controlled studies on the effectiveness of vaccinating cattle with commercially available viral antigen vaccines for mitigation of the effects of bovine respiratory disease complex (brdc).201525517335
ataxia telangiectasia mutated kinase mediates nf-κb serine 276 phosphorylation and interferon expression via the irf7-rig-i amplification loop in paramyxovirus infection.respiratory syncytial virus (rsv) is a primary etiological agent of childhood lower respiratory tract disease. molecular patterns induced by active infection trigger a coordinated retinoic acid-inducible gene i (rig-i)-toll-like receptor (tlr) signaling response to induce inflammatory cytokines and antiviral mucosal interferons. recently, we discovered a nuclear oxidative stress-sensitive pathway mediated by the dna damage response protein, ataxia telangiectasia mutated (atm), in cytokine-induce ...201525520509
[roles of cd4+cd25+foxp3+ regulatory t cells and il-33 in the pathogenesis of asthma in children].to study the roles of cd4(+)cd25(+)foxp3(+) regulatory t cells (treg) and il-33 in the pathogenesis of asthma in children.201425523567
estimation of nasal shedding and seroprevalence of organisms known to be associated with bovine respiratory disease in australian live export cattle.the prevalence of organisms known to be associated with bovine respiratory disease (brd) was investigated in cattle prior to export. a quantitative reverse transcription polymerase chain reaction assay was used to detect nucleic acids from the following viruses and bacteria in nasal swab samples: bovine coronavirus (bocv; betacoronavirus 1), bovine herpesvirus 1 (bohv-1), bovine viral diarrhea virus 1 (bvdv-1), bovine respiratory syncytial virus (brsv), bovine parainfluenza virus 3 (bpiv-3), his ...201525525134
in silico approach towards designing virtual oligopeptides for hrsv.hrsv (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. in the present study, in silico docking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-hrsv agents. additional simulations were conducted to study the conformational ...201425525622
pulmonary immunity during respiratory infections in early life and the development of severe asthma.asthma affects 10% of the population in westernized countries, being most common in children. it is a heterogeneous condition characterized by chronic allergic airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (ahr) to normally innocuous antigens. combination therapies with inhaled corticosteroids and bronchodilators effectively manage mild to moderate asthma, but there are no cures, and patients with severe asthma do not respond to these treatments. the inception of asth ...201425525736
risk factors for requiring intensive care among children admitted to ward with bronchiolitis.to examine risk factors for transfer of bronchiolitis patients from the ward to the intensive care unit (icu) and/or initiation of critical care interventions.201625528126
meeting report vlpnpv: session 3: immune responses.virus-like particles (vlps) and nano-particles (np) are increasingly considered for both prophylactic and therapeutic vaccines for a wide variety of human and animal diseases. indeed, 2 vlps have already been licensed for use in humans, the human papilloma virus vaccine and the hepatitis b virus vaccine. (1) reflecting this increased interest, a second international conference with a specific focus on vlps and np was held at the salk institute for biological studies in la jolla, california, in j ...201425529229
proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.the aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (hrsv), a major cause of paediatric illness.201525533920
[impact of a targeted educational intervention on respiratory syncytial virus bronchiolitis prevention in full-term and preterm infants].palivizumab, a humanized monoclonal antibody directed against respiratory syncytial virus (rsv), is the only existent immunoprophylaxis therapy for prevention of serious lower respiratory tract disease caused by rsv in infants (up to 2 years of age), particularly in those who meet high-risk criteria (preterm infants and/or those with bronchopulmonary or congenital heart disease). in our region, the monthly injections are not given at the hospital but by private pediatricians during the epidemic ...201525534557
evidence for an intranasal immune response to human respiratory syncytial virus infection in cynomolgus macaques.there is no large-scale therapy available against human respiratory syncytial virus (hrsv), a major pathogen responsible for acute respiratory diseases. macaques represent an interesting animal model to evaluate potential treatments because of their genetic, anatomical and immunological proximity with humans. however, the parameters that influence hrsv growth and control in this model are still poorly understood. we have documented in the following study the influence of age as well as repeated ...201525537374
recombinant subgroup b human respiratory syncytial virus expressing enhanced green fluorescent protein efficiently replicates in primary human cells and is virulent in cotton rats.human respiratory syncytial virus (hrsv) is the most important viral cause of severe respiratory tract disease in infants. two subgroups (a and b) have been identified, which cocirculate during, or alternate between, yearly epidemics and cause indistinguishable disease. existing in vitro and in vivo models of hrsv focus almost exclusively on subgroup a viruses. here, a recombinant (r) subgroup b virus (rhrsv(b05)) was generated based on a consensus genome sequence obtained directly from an unpas ...201525540371
blood mxa protein as a marker for respiratory virus infections in young children.type i interferon induced mxa response can differentiate viral from bacterial infections, but mxa responses in rhinovirus or asymptomatic virus infections are not known.201525542463
characterization of novel respiratory syncytial virus inhibitors identified by high throughput screen.respiratory syncytial virus (rsv) is a major cause of lower respiratory tract infections with no effective treatment available. finding novel inhibitors of rsv is an important first step towards developing an efficacious rsv therapy. here we report the characterization of three novel classes of rsv replication inhibitors identified through a high throughput rsv replicon screen of ∼1million compounds in the astrazeneca compound collection. these inhibitors, cpd 1, 2, and 3, specifically targeted ...201525542974
intrapulmonary recombinant factor viia for diffuse alveolar hemorrhage in children.diffuse alveolar hemorrhage (dah) is a life-threatening pulmonary complication in patients with hematologic malignancies or autoimmune disorders, and it has a high mortality rate. the current treatment options of corticosteroids, transfusions, and immunosuppressants have been limited and largely unsuccessful, and they can be accompanied by multiple complications. intrapulmonary administration of recombinant activated factor vii (rfviia) has been reported in adults, but there are scarce data on i ...201525548333
effectiveness of palivizumab in preventing rsv hospitalization in high risk children: a real-world perspective.infection with respiratory syncytial virus (rsv) is one of the major causes globally of childhood respiratory morbidity and hospitalization. palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe rsv-associated respiratory illness. this recommendation is based on evidence of efficacy when used under clinical trial conditions. however the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is no ...201425548575
epidemiology of pathogen-specific respiratory infections among three us populations.diagnostic tests for respiratory infections can be costly and time-consuming. improved characterization of specific respiratory pathogens by identifying frequent signs, symptoms and demographic characteristics, along with improving our understanding of coinfection rates and seasonality, may improve treatment and prevention measures.201425549089
effect of cleaning and disinfection of toys on infectious diseases and micro-organisms in daycare nurseries.the rising number of children in daycare nurseries increases opportunities for the transmission of infectious diseases. pathogens may be transmitted directly from child to child via sneezing, coughing and touching, or indirectly via the environment. toys are among the fomites with the highest pathogen load, but their role in disease transmission is unknown.201525549827
recombinant influenza virus carrying the conserved domain of respiratory syncytial virus (rsv) g protein confers protection against rsv without inflammatory disease.respiratory syncytial virus (rsv) is one of the most important causes for viral lower respiratory tract disease in humans. there is no licensed rsv vaccine. here, we generated recombinant influenza viruses (pr8/rsv.ha-g) carrying the chimeric constructs of hemagglutinin (ha) and central conserved-domains of the rsv g protein. pr8/rsv.ha-g virus showed lower pathogenicity without compromising immunogenicity in mice. single intranasal inoculation of mice with pr8/rsv.ha-g induced igg2a isotype dom ...201525553517
immunology of bovine respiratory syncytial virus in calves.bovine respiratory syncytial virus (brsv) is an important cause of respiratory disease in young calves. the virus is genetically and antigenically closely related to human (h)rsv, which is a major cause of respiratory disease in young infants. as a natural pathogen of calves, brsv infection recapitulates the pathogenesis of respiratory disease in man more faithfully than semi-permissive, animal models of hrsv infection. with the increasing availability of immunological reagents, the calf can be ...201525553595
tlr4 genotype and environmental lps mediate rsv bronchiolitis through th2 polarization.while 30%-70% of rsv-infected infants develop bronchiolitis, 2% require hospitalization. it is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and th2 bias are proposed explanations. while tlr4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (rsv) pathogenesis is controversial. here, we evaluated the interaction between tlr4 and environmental factors in rsv disease and defined the ...201525555213
new host factors important for respiratory syncytial virus (rsv) replication revealed by a novel microfluidics screen for interactors of matrix (m) protein.although human respiratory syncytial virus (rsv) is the most common cause of bronchiolitis and pneumonia in infants and elderly worldwide, there is no licensed rsv vaccine or effective drug treatment available. the rsv matrix protein plays key roles in virus life cycle, being found in the nucleus early in infection in a transcriptional inhibitory role, and later localizing in viral inclusion bodies before coordinating viral assembly and budding at the plasma membrane. in this study, we used a no ...201525556234
a cost-benefit analysis of the immunisation of children against respiratory syncytial virus (rsv) using the english hospital episode statistics (hes) data set.respiratory syncytial virus (rsv) is a common cause of respiratory infection that is highly prevalent in infants, particularly those with underlying medical conditions. severe cases of rsv require hospitalisation as well as admission to intensive care and may even result in death. the objective of the study was to measure the net benefits that could arise from an immunisation programme of infants that may well eradicate rsv to a high degree and save the direct and indirect medical care costs fro ...201525557555
surveillance of acute respiratory infections in mumbai during 2011-12.acute respiratory infections (aris) are a leading cause of morbidity and mortality in individuals aged less than 5 years. ari often leads to hospitalisation, and it has been indicated that causative viral and bacterial infections go undetermined and results in the occurrence of resistant strains. the objective of the study was to assess the prevalence of various viral and bacterial infections in patients with aris.201525560001
phosphatidylinositol inhibits respiratory syncytial virus infection.respiratory syncytial virus (rsv) infects nearly all children under age 2, and reinfection occurs throughout life, seriously impacting adults with chronic pulmonary diseases. recent data demonstrate that the anionic pulmonary surfactant lipid phosphatidylglycerol (pg) exerts a potent antiviral effect against rsv in vitro and in vivo. phosphatidylinositol (pi) is also an anionic pulmonary surfactant phospholipid, and we tested its antiviral activity. pi liposomes completely suppress interleukin-8 ...201525561461
association between respiratory syncytial virus activity and pneumococcal disease in infants: a time series analysis of us hospitalization data.the importance of bacterial infections following respiratory syncytial virus (rsv) remains unclear. we evaluated whether variations in rsv epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (pcv7) were associated with changes in the rate of hospitalizations coded as rsv.201525562317
[palivizumab: four seasons in russia].in 2010, the russian federation (rf) registered palivizumab--innovative drug, based on monoclonal antibodies for passive immunization of seasonal respiratory syncytial virus (rsv) infection in children of disease severe progress risk group, which include primarily premature infants, children with bronchopulmonary dysplasia and hemodynamically significant congenital heart disease. currently, palivizumab is included in the list of recommended medicines and medical care standards of different count ...201425563005
use of palivizumab is underestimated in the swedish prescribed drug register - implications for register-based drug studies.register studies are a valuable tool, when monitoring the safety of drugs. the swedish prescribed drug register (pdr) was established in 2005 and keeps records of all prescribed drugs dispensed in community pharmacies. drugs prescribed in-hospital are not registered on an individual level, which may hamper the validity of register-based studies on drugs potentially administered in-hospital.201525565893
identification and characterization of the binding site of the respiratory syncytial virus phosphoprotein to rna-free nucleoprotein.the rna genome of respiratory syncytial virus (rsv) is constitutively encapsidated by the viral nucleoprotein n, thus forming a helical nucleocapsid. polymerization of n along the genomic and antigenomic rnas is concomitant to replication and requires the preservation of an unassembled monomeric nucleoprotein pool. to this end, and by analogy with paramyxoviridae and rhabdoviridae, it is expected that the viral phosphoprotein p acts as a chaperone protein, forming a soluble complex with the rna- ...201525568210
environmental drivers of the spatiotemporal dynamics of respiratory syncytial virus in the united states.epidemics of respiratory syncytial virus (rsv) are known to occur in wintertime in temperate countries including the united states, but there is a limited understanding of the importance of climatic drivers in determining the seasonality of rsv. in the united states, rsv activity is highly spatially structured, with seasonal peaks beginning in florida in november through december and ending in the upper midwest in february-march, and prolonged disease activity in the southeastern us. using data ...201525569275
a passive quantitative measurement of airway resistance using depth data.the respiratory syncytial virus (rsv) is the most common cause of serious lower respiratory tract infections in infants and young children. rsv often causes increased airway resistance, clinically detected as wheezing by chest auscultation. in this disease, expiratory flows are significantly reduced due to the high resistance in patient's airway passages. a quantitative method for measuring resistance can have a great benefit to diagnosis and management of children with rsv infections as well as ...201425571300
the role of tlr4 and cd14 polymorphisms in the pathogenesis of respiratory syncytial virus bronchiolitis in greek infants.clinical manifestations of respiratory syncytial virus (rsv) infection vary from minimal disease to severe acute bronchiolitis. the structural complex of tlr4/cd14 participates in the virus recognition as a component of natural immune response. genetic variations of tlr4/cd14 may explain great variations in disease severity. the aim of this study was to investigate the possible role of polymorphisms of tlr4, asp299gly and thr399ile and cd14, c-159t and c-550t in the development of rsv bronchioli ...201525572736
discovery of an oral respiratory syncytial virus (rsv) fusion inhibitor (gs-5806) and clinical proof of concept in a human rsv challenge study.gs-5806 is a novel, orally bioavailable rsv fusion inhibitor discovered following a lead optimization campaign on a screening hit. the oral absorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. a mean ec50 = 0.43 nm was found toward a panel of 75 rsv a and b clinical isolates and dose-dependent antiviral efficacy in the co ...201525574686
recent advances in the management of acute bronchiolitis.acute bronchiolitis is characterized by acute wheezing in infants or children and is associated with signs or symptoms of respiratory infection; it is rarely symptomatic in adults and the most common etiologic agent is respiratory syncytial virus (rsv). usually it does not require investigation, treatment is merely supportive and a conservative approach seems adequate in the majority of children, especially for the youngest ones (<3 months); however, clinical scoring systems have been proposed a ...201425580257
vaccines 'on demand': science fiction or a future reality.self-amplifying mrna vaccines are being developed as a platform technology with potential to be used for a broad range of targets. the synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. preclinical proof of concept has so far been achieved for influenza, respiratory syncytial virus, rabies, ebola, cytomegalovirus, human immunodeficiency virus and ...201525582273
bovine respiratory syncytial virus and bovine coronavirus in swedish organic and conventional dairy herds.infections with bovine respiratory syncytial virus (brsv) and bovine coronavirus (bocv) are endemic to the cattle populations in most countries, causing respiratory and/or enteric disease. it has been demonstrated that herds can remain free from these infections for several years also in high prevalence areas. organically managed (om) dairy herds have been shown to have lower seroprevalence of both viruses compared to conventionally managed (cm) herds. the objective of this study was to challeng ...201525582919
evaluation of novel second-generation rsv and influenza rapid tests at the point of care.acute respiratory infections represent common pediatric emergencies. infection control warrants immediate and accurate diagnoses. in the past, first-generation respiratory syncytial virus (rsv) rapid tests (strip tests) have shown suboptimal sensitivities. in 2013, the food and drug administration licensed a second-generation rsv rapid test providing user-independent readouts (sofia™-rsv) using automated fluorescence assay technology known to yield superior results with influenza rapid testing. ...201525583129
respiratory viral infections and subversion of cellular antioxidant defenses.reactive oxygen species (ros) formation is part of normal cellular aerobic metabolism, due to respiration and oxidation of nutrients in order to generate energy. low levels of ros are involved in cellular signaling and are well controlled by the cellular antioxidant defense system. elevated levels of ros generation due to pollutants, toxins and radiation exposure, as well as infections, are associated with oxidative stress causing cellular damage. several respiratory viruses, including respirato ...201425584194
synthesis and biological evaluation of strictosamide derivatives with improved antiviral and antiproliferative activities.a series of novel derivatives of strictosamide were synthesized and biologically evaluated. most of the new compounds exhibited improved activities than the parent compound strictosamide. among them, compounds ib and if possessed antiviral activities against influenza a virus (a/jinan/15/90) with ic50 values of 4.12 and 12.35 μg/ml, respectively. compound ie possessed antiviral activity against respiratory syncytial virus (rsv) with an ic50 value of 9.58 μg/ml. both compounds iic and iid had mod ...201525589048
demographic buffering: titrating the effects of birth rate and imperfect immunity on epidemic dynamics.host demography can alter the dynamics of infectious disease. in the case of perfectly immunizing infections, observations of strong sensitivity to demographic variation have been mechanistically explained through analysis of the susceptible-infected-recovered (sir) model that assumes lifelong immunity following recovery from infection. when imperfect immunity is incorporated into this framework via the susceptible-infected-recovered-susceptible (sirs) model, with individuals regaining full susc ...201525589567
relationships among dissemination of primary parainfluenza virus infection in the respiratory tract, mucosal and peripheral immune responses, and protection from reinfection: a noninvasive bioluminescence-imaging study.respiratory paramyxoviruses such as respiratory syncytial virus (rsv) and human parainfluenza virus type 1 (hpiv1) to hpiv4 infect virtually all children by the age of 2 to 5 years, leading to partial but incomplete protection from reinfection. here, we used luciferase-expressing reporter sendai viruses (the murine counterpart of hpiv1) to noninvasively measure primary infection, immune responses, and protection from reinfection by either a lethal challenge or natural transmission in living mice ...201525589649
relationship between meteorological conditions and respiratory syncytial virus in a tropical country.this study aimed to determine which meteorological conditions are associated with respiratory syncytial virus (rsv) isolates in a population of children hospitalized with acute lower respiratory infection (alri) in bogota, colombia. in an analytical cross-sectional study, links were examined between the number of monthly rsv infections and monthly average climatic variation (temperature, relative humidity, rainfall, wind speed, solar radiation) between 1 january 2010 and 30 april 2011 in a popul ...201525591796
antiviral effects of jinxin oral liquid against respiratory syncytial virus infection in the balb/c mice model.jinxin oral liquid (jol) is used in traditional chinese medicine (tcm) to treat influenza, cough, asthma, and viral pneumonia, on the basis of ma xing shi gan tang (mxsgt) and the clinical experience of professor wang shouchuan, one of the most prestigious pediatricians in china.201525593018
the discovery of 1,2,3,9b-tetrahydro-5h-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (rsv) fusion inhibitors. part 1.respiratory syncytial virus (rsv) is a major cause of respiratory tract infections in infants, young children and adults. compound 1a (9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-1,2,3,9b-tetrahydro-5h-imidazo[2,1-a]isoindol-5-one) was identified as an inhibitor of a and b strains of rsv targeting the fusion glycoprotein. sar was developed by systematic exploration of the phenyl (r(1)) and benzoyl (r(2)) groups. furthermore, introduction of a nitrogen at the 8-position of the tricyclic core resulted ...201525595682
1,2,3,9b-tetrahydro-5h-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (rsv) fusion inhibitors. part 2: identification of bta9881 as a preclinical candidate.respiratory syncytial virus (rsv) is a major cause of respiratory tract infections in infants, young children and adults. 1,2,3,9b-tetrahydro-5h-imidazo[2,1-a]isoindol-5-ones with general structure 1 were previously identified as promising inhibitors of rsv targeting the fusion glycoprotein. in particular, the introduction of a nitrogen at the 8-position of the tricyclic core yielded lead compounds 2 and 3. extensive exploration of the r(2) group established that certain heterocyclic amides conf ...201525595685
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