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potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.human respiratory syncytial virus (rsv) is the main cause of lower respiratory tract infections in young children. the rsv fusion protein (f) is highly conserved and is the only viral membrane protein that is essential for infection. the prefusion conformation of rsv f is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. here, we describe two llama-derived sin ...201728194013
a single dose recombinant piv5 expressing respiratory syncytial virus f and g proteins protected cotton rats and african green monkeys from rsv challenge.human respiratory syncytial virus (rsv) is a common cause of severe respiratory disease among infants, immunocompromised individuals and the elderly. no licensed vaccine is currently available. in this study, we evaluated two parainfluenza virus 5 (piv5)-vectored vaccines expressing rsv f (piv5/f) or g (piv5/g) proteins in the cotton rat and african green monkey models for their replication, immunogenicity and efficacy of protection against rsv challenge. following a single intranasal inoculatio ...201728298602
a rapid, simple, and accurate plaque assay for human respiratory syncytial virus (hrsv).plaque assays of human respiratory syncytial virus (hrsv) are time-consuming, requiring 4 to 7 days for plaque formation and several hours for dye staining. here, we describe a simple method by which rsv plaques can be visualized and counted with the naked eye only 2 days after infection of hep-2 cells. in this assay, the infected cells are stained with monoclonal antibodies and the plaques are developed using diaminobenzidine (dab). we tested the accuracy of this new plaque assay by comparing t ...201728373028
genetic stability of genome-scale deoptimized rna virus vaccine candidates under selective pressure.recoding viral genomes by numerous synonymous but suboptimal substitutions provides live attenuated vaccine candidates. these vaccine candidates should have a low risk of deattenuation because of the many changes involved. however, their genetic stability under selective pressure is largely unknown. we evaluated phenotypic reversion of deoptimized human respiratory syncytial virus (rsv) vaccine candidates in the context of strong selective pressure. codon pair deoptimized (cpd) versions of rsv w ...201728049853
inclusion body fusion of human parainfluenza virus type 3 regulated by acetylated α-tubulin enhances viral replication.viral inclusion bodies (ibs), or replication factories, are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying ib formation and fusion. our previous study demonstrated that the interaction between the nucleoprotein (n) and phosphoprotein (p) of human parainfluenza virus type 3 (hpiv3), an enveloped virus with great medical impact, can form ibs. in this study, we found ...201727881643
utility of assessing cytokine levels for the differential diagnosis of pneumonia in a pediatric population.although pneumonia is easily diagnosed, determining the causative agent is difficult due to low pathogen detection rates. we performed a prospective observational study to evaluate the utility of measuring inflammatory cytokine levels to discriminate between pneumonia caused by typical bacteria, respiratory syncytial virus, or mycoplasma pneumoniae in a pediatric population.201728198756
rage deficiency predisposes mice to virus-induced paucigranulocytic asthma.asthma is a chronic inflammatory disease. although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. the aetiology of paucigranulocytic asthma is unknown. however, both respiratory syncytial virus (rsv) infection and mutations in the receptor for advanced glycation endproducts (rage) are risk factors for asthma development. here, we show that rage def ...201728099113
diagnostic value of nasopharyngeal aspirates in children with lower respiratory tract infections.the accuracy of nasopharyngeal aspirate (npa) specimens in detecting lower respiratory pathogens remains controversial. the objective of this study was to evaluate the diagnostic accuracy of aspirates (npas) specimen in lower respiratory tract infections (lrtis) in children.201728303845
intranasal administration of rsv antigen-expressing mcmv elicits robust tissue-resident effector and effector memory cd8+ t cells in the lung.cytomegalovirus vectors are promising delivery vehicles for vaccine strategies that aim to elicit effector cd8+ t cells. to determine how the route of immunization affects cd8+ t-cell responses in the lungs of mice vaccinated with a murine cytomegalovirus vector expressing the respiratory syncytial virus matrix (m) protein, we infected cb6f1 mice via the intranasal or intraperitoneal route and evaluated the m-specific cd8+ t-cell response at early and late time points. we found that intranasal v ...201727220815
a new hexahydrobenzopyran derivative from the gorgonian-derived fungus eutypella sp.a new hexahydrobenzopyran derivative cytosporin l (1), and another eight known compounds were isolated from the gorgonian-derived fungus eutypella sp. collected from the south china sea. the structure of 1 was elucidated by comprehensive spectroscopic data. the absolute configuration of 1 was determined by a chemical reaction and the modified mosher's method. the isolated secondary metabolites were evaluated for their antibacterial activities. compound 1 showed antibacterial activity towards mic ...201728278631
lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. here we examine the effect of oral lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (rsv) infection. l. johnsonii supplementation reduced airway t helper type 2 cytokines and dendritic cell (dc) function, increased regulatory t cells, and was associated with a reprogrammed circulating meta ...201728295020
[rapid diagnostic test for respiratory infections].acute respiratory infections are the second cause of morbidity and mortality in children and adults worldwide, being viruses, bacteria and fungi involved in their etiology. the rapid diagnosis allows for a better clinical management of the patient, for adopting public health measures and for controlling possible outbreaks. the main etiologic agents can be diagnosed within the first hours after the onset of symptoms with antigen detection techniques, primarily immunochromatography. results are ob ...201728062161
influenza and respiratory syncytial viruses: efficacy of different diagnostic assays.to determine the efficacy of cell culture, immunoflourescence assay (ifa) and real time polymerase chain reaction (rrt-pcr) in relation to diagnosis of influenza and respiratory syncytial virus (rsv).201726430404
diagnostic performance and clinical feasibility of a point-of-care test for respiratory viral infections in primary health care.inappropriately high levels of antibiotics are still prescribed in primary health care for respiratory tract infections (rtis). access to diagnostic point-of-care tests (pocts) for rtis might reduce this over-prescription.201728369370
apoptosis, toll-like, rig-i-like and nod-like receptors are pathways jointly induced by diverse respiratory bacterial and viral pathogens.lower respiratory tract infections are among the top five leading causes of human death. fighting these infections is therefore a world health priority. searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. with this aim, alveolar macrophages were independently infected with three unrelated bacterial (streptococcus pneumoniae, klebsiella pneumoniae, an ...201728298903
[the interactions between microorganisms and the small airways. a paediatric focus].the spectrum of respiratory viruses is expanding and emerging diseases have been described regularly over the last fifteen years. the origin of these emerging respiratory viruses may be zoonotic (by crossing species barrier, after changes to rna viruses such as avian influenza virus type a or coronaviruses), or related to the use of new identification techniques (metapneumovirus, bocavirus). the relationship between bronchiolitis and asthma is now better understood thanks to prospective follow u ...201728262277
glucocorticoid insensitivity in virally infected airway epithelial cells is dependent on transforming growth factor-β activity.asthma and chronic obstructive pulmonary disease (copd) exacerbations are commonly associated with respiratory syncytial virus (rsv), rhinovirus (rv) and influenza a virus (iav) infection. the ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (gcs). viral infection elicits transforming growth factor-β (tgf-β) activity, a growth factor we have previously shown to impair gc action in human airway epithelial cells through the activation of activin-like kin ...201728046097
prevailing genotype distribution and characteristics of human respiratory syncytial virus in northeastern china.although human respiratory syncytial virus (rsv) is one of the most common viruses inducing respiratory tract infections in young children and the elderly, the genotype distribution and characteristics of rsv in northeastern china have not been investigated. here, we identified 25 rsv-a and 8 rsv-b strains from 80 samples of patients with respiratory infections between february 2015 and may 2015. all 25 rsv-a viruses were classified as the on1 genotype, which rapidly spread and became the domina ...201727448044
activation pathway of a nucleoside analog inhibiting respiratory syncytial virus polymerase.human respiratory syncytial virus (rsv) is a negative-sense rna virus and a significant cause of respiratory infection in infants and the elderly. no effective vaccines or antiviral therapies are available for the treatment of rsv. als-8176 is a first-in-class nucleoside prodrug inhibitor of rsv replication currently under clinical evaluation. als-8112, the parent molecule of als-8176, undergoes intracellular phosphorylation, yielding the active 5'-triphosphate metabolite. the host kinases respo ...201728103684
occurrence of human respiratory syncytial virus in summer in japan.in temperate zones, human respiratory syncytial virus (hrsv) outbreaks typically occur in cold weather, i.e. in late autumn and winter. however, recent outbreaks in japan have tended to start during summer and autumn. this study examined associations of meteorological conditions with the numbers of hrsv cases reported in summer in japan. using data from the hrsv national surveillance system and national meteorological data for summer during the period 2007-2014, we utilized negative binomial log ...201727682641
immunological features of respiratory syncytial virus-caused pneumonia-implications for vaccine design.the human respiratory syncytial virus (hrsv) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hrsv. further, t cell immunity plays an important role for v ...201728273842
novel recombinant dna vaccine candidates for human respiratory syncytial virus: preclinical evaluation of immunogenicity and protection efficiency.the development of safe and potent vaccines for human respiratory syncytial virus (hrsv) is still a challenge for researchers worldwide. dna-based immunization is currently a promising approach that has been used to generate human vaccines for different age groups. in this study, novel hrsv dna vaccine candidates were generated and preclinically tested in balb/c mice. three different versions of the codon-optimized hrsv fusion (f) gene were individually cloned into the ppoe vector. the new recom ...201728272978
conidial heads (fruiting bodies) as a hallmark for histopathological diagnosis of angioinvasive aspergillosis.aspergillosis is a mycosis that afflicts immunocompetent and immunocompromised hosts; among the former it exhibits different clinical pictures, and among the latter the infection renders an invasive form of the disease. the histologic diagnosis of invasive aspergillosis is somewhat challenging mostly because of some morphological similarities between other fungi. however, when present, the conidial heads are pathognomonic of aspergillosis. the authors present the case of a 68-year-old woman who ...201726894041
clinical characterization of influenza a and human respiratory syncytial virus among patients with influenza like illness.influenza a and respiratory syncytial virus (rsv) has been recognized as a major cause of acute respiratory tract infection. h1n1 is one of the subtypes of influenza a, pandemic worldwide in july 2009, causing 18,449 deaths globally. to investigate the prevalence and clinical manifestation of the influenza a, h1n1pdm09, and rsv. throat/nasal swab collected from the patients of all age group either outpatients/inpatients having respiratory illness from 2 to 5 days. the clinical data were recorded ...201727329816
estimates of hospitalization attributable to influenza and rsv in the us during 1997-2009, by age and risk status.estimates of influenza and respiratory syncytial virus (rsv) burden must be periodically updated to inform public health strategies. we estimated seasonal influenza- and rsv-attributable hospitalizations in the us from 1997 to 2009 according to age and risk status (nct01599390).201728320361
novel expression of a functional trimeric fragment of human sp-a with efficacy in neutralisation of rsv.respiratory syncytial virus (rsv) is the leading cause of bronchiolitis and hospitalisation of infants in developed countries. surfactant protein a (sp-a) is an important innate immune molecule, localized in pulmonary surfactant. sp-a binds to carbohydrates on the surface of pathogens in a calcium-dependent manner to enable neutralisation, agglutination and clearance of pathogens including rsv. sp-a forms trimeric units and further oligomerises through interactions between its n-terminal domains ...201727793398
peritonsillar abscess: clinical aspects of microbiology, risk factors, and the association with parapharyngeal abscess.pta is a collection of pus located between the tonsillar capsule and the pharyngeal constrictor muscle. it is considered a complication of acute tonsillitis and is the most prevalent deep neck infection (approximately 2000 cases annually in denmark) and cause of acute admission to danish ent departments. teenagers and young adults are most commonly affected and males may predominate over females. however, no studies of age- and gender-stratified incidence rates have previously been published. fu ...201728260599
antiviral activity of aspirin against rna viruses of the respiratory tract-an in vitro study.aspirin (acetylsalicylic acid) has been used for more than 115 years in medicine. research exists to show that aspirin has antiviral effects in vitro, for example, by blocking influenza virus propagation via nf-κb inhibition when used at high concentrations and short-term incubation steps. the aim of this study was to confirm the antiviral activity of aspirin against influenza virus and further elucidate the activity of aspirin against other respiratory viruses.201727542891
antiviral activity of the "virus blocking factor" (vbf) derived i.a. from pelargonium extract and sambucus juice against different human-pathogenic cold viruses in vitro.the in-vitro antiviral activity of the "virus blocking factor" (vbf), a combination of pelargonium extract and sambucus juice with addition of betaglucan 1,3 / 1,6, zincum gluconium, acidum ascorbicum, was studied against human pathogenic viruses: influenza a h1n1 (flua h1n1), rhinovirus b subtype 14 (hrv14), respiratory syncytial virus (rsv), parainfluenzavirus subtype 3 (para 3), and adenovirus c subtype 5 (adeno 5).201727717933
viral infections in neonates with suspected late-onset bacterial sepsis-a prospective cohort study.objective the aim of our study was to evaluate the occurrence of viral infections in infants with suspected late-onset bacterial sepsis in a neonatal intensive care unit. methods in a prospective study, infants with suspected late-onset bacterial sepsis underwent viral testing alongside routine blood culture sampling. using a multiplex reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, nasopharyngeal aspirates were analyzed for adenovirus, respiratory syncytial vi ...201727182999
regional diversification of influenza activity in poland during the 2015/16 epidemic season.the national influenza center (nic) at the department of influenza research of the national institute for public health-national institute of hygiene (niph-nih) participates in the global influenza surveillance and response system (gisrs) and continuously coordinates epidemiological and virological surveillance of influenza in poland. the aim of this study was to determine the regional differences of influenza activity in poland in the 2015/16 epidemic season. the influenza surveillance involved ...201728255914
modulation of antiviral immunity by heme oxygenase-1.heme oxygenase-1 (ho-1) is a stress-inducible, anti-inflammatory, and cytoprotective enzyme expressed in most cell types in the organism. under several stress stimuli, ho-1 expression and activity is up-regulated to catalyze the rate-limiting enzymatic step of heme degradation into carbon monoxide, free iron, and biliverdin. besides its effects on cell metabolism, ho-1 is also capable of modulating host innate and adaptive immune responses in response to sepsis, transplantation, and autoimmunity ...201728082120
biosynthesis of an antiviral compound using a stabilized phosphopentomutase by multipoint covalent immobilization.ribavirin is a synthetic guanosine analogue with a broad-spectrum of antiviral activity. it is clinically effective against several viruses, such as respiratory syncytial virus, several hemorrhagic fever viruses and hcv when combined with pegylated interferon-α. phosphopentomutase (ppm) catalyzes the transfer of intramolecular phosphate (from c1 to c5) on ribose, and is involved in pentose phosphate pathway and in purine metabolism. reactions catalyzed by this enzyme are useful for nucleoside an ...201728347766
a novel benzo-heterocyclic amine derivative n30 inhibits influenza virus replication by depression of inosine-5'-monophospate dehydrogenase activity.influenza virus is still a huge threat to the world-wide public health. host inosine-5'- monophosphate dehydrogenase (impdh) involved in the synthesis of guanine nucleotides, is known to be a potential target to inhibit the replication of viruses. herein, we evaluated antiviral activity of a benzo-heterocyclic amine derivative n30, which was designed to inhibit impdh.201728298229
report from the world health organization's third product development for vaccines advisory committee (pdvac) meeting, geneva, 8-10th june 2016.the third meeting of who's product development for vaccines advisory committee (pdvac) was held in june 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase iii trials of a ...201728262332
diterpenoid alkaloids from delphinium ajacis and their anti-rsv activities.five new diterpenoid alkaloids, ajacisines a-e (1-5), were isolated from delphinium ajacis, along with seven known alkaloids (6-12). on the basis of their spectral data (ir, uv, hr-esi-ms, 1d and 2d nmr) and chemical properties, the structures of compounds 1-12 were identified. all isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus, and compounds 3-5 and 8 exhibited moderate to weak effects with ic50 values of 75.2 ± 1.1, 35.1 ± 0.6, 10. ...201727405107
meeting report: 29th international conference on antiviral research in la jolla, ca, usa.the 29th international conference on antiviral research (icar) was held in la jolla, ca, usa from april 17 to 21, 2016. this report opens with a tribute to the late chris mcguigan, a past-president of isar, then continues with summaries of the principal invited lectures. doug richman (elion award) investigated hiv resistance, bob vince (holý award) showed how carbocyclic nucleoside analogs led to abacavir and jerome deval (prusoff award) explained how his group chose to seek a nucleoside analog ...201727815125
[adult immunisation: general points, hot topics and perspectives].vaccination in immunocompetent adult mainly concerns booster vaccination against diphtheria, tetanus, polio and pertussis. some chronic diseases may also require the achievement of pneumococcal and influenza vaccines. in addition, from the age of 65, annual influenza vaccination as well as one dose of a live attenuated shingles vaccine between 64 and 75 years are recommended. immunocompromised adults, due to the increased risk of serious infections responsible of significant morbidity and mortal ...201728214181
viral encephalitis after haplo-identical hematopoietic stem cell transplantation: causative viral spectrum, characteristics, and risk factors.to retrospectively identify characteristics and risk factors of viral encephalitis (ve) in patients who underwent a haplo-identical hematopoietic stem cell transplant (hsct).201728129450
environmental factor and inflammation-driven alteration of the total peripheral t-cell compartment in granulomatosis with polyangiitis.autoimmune diseases are initiated by a combination of predisposing genetic and environmental factors resulting in self-perpetuating chronic inflammation and tissue damage. autoantibody production and an imbalance of effector and regulatory t-cells are hallmarks of autoimmune dysregulation. while expansion of circulating effector memory t-cells is linked to disease pathogenesis and progression, the causes driving alterations of the peripheral t-cell compartment have remained poorly understood so ...201728040323
a comparison of host gene expression signatures associated with infection in vitro by the makona and ecran (mayinga) variants of ebola virus.the ebola virus (ebov) variant makona (which emerged in 2013) was the causative agent of the largest outbreak of ebola virus disease recorded. differences in virus-host interactions between viral variants have potential consequences for transmission, disease severity and mortality. a detailed profile of the cellular changes induced by the makona variant compared with other ebola virus variants was lacking. in this study, a549 cells, a human cell line with a robust innate response, were infected ...201728240256
excess respiratory viral infections and low antibody responses among hiv-exposed, uninfected infants.hiv-exposed uninfected (heus) infants have frequent severe infection, hospitalization, and death. we performed a serologic investigation to determine the role of common childhood respiratory pathogens in the excess incidence of infections in heus.201728060016
systems biology from virus to humans.natural infection and then recovery are considered to be the most effective means for hosts to build protective immunity. thus, mimicking natural infection of pathogens, many live attenuated vaccines such as influenza virus, and yellow fever vaccine 17d were developed and have been successfully used to induce protective immunity. however, humans fail to generate long-term protective immunity to some pathogens after natural infection such as influenza virus, respiratory syncytial virus (rsv), and ...201726269748
human coronavirus in the 2014 winter season as a cause of lower respiratory tract infection.during the late autumn to winter season (october to december) in the republic of korea, respiratory syncytial virus (rsv) is the most common pathogen causing lower respiratory tract infections (lrtis). interestingly, in 2014, human coronavirus (hcov) caused not only upper respiratory infections but also lrtis more commonly than in other years. therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with hcov infections at a sin ...201727873511
patterns of human respiratory viruses and lack of mers-coronavirus in patients with acute upper respiratory tract infections in southwestern province of saudi arabia.we undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between november 2013 and january 2014 (winter time). nasal swabs were collected from 182 patients and screened for mers-cov as well as other respiratory viruses using rt-pcr and multiplex microarray. a total of 75 (41.2%) of these patients had positive viral infection. mers-cov was not detected in any of the samples. human rhinovirus (hrv) was the mo ...201728348590
comparison of different methods for extraction of cinnamomi ramulus: yield, chemical composition and in vitro antiviral activities.hydrodistillation (hd), supercritical fluid extraction (sfe) and reflux extraction (re) were applied to obtain cinnamomi ramulus extracts. the yields, chemical compositions and antiviral activities of the extracts were investigated. extracts were analysed using gas chromatography-mass spectrometry and the antiviral activities were evaluated using cytopathic effect inhibition assay. hd, sfe and re afforded 0.376, 1.227 and 5.914% yields, respectively. cinnamaldehyde (ca), sfe and ethanol extracts ...201728322072
acute viral respiratory infections among children in mers-endemic riyadh, saudi arabia, 2012-2013.the emergence of the middle east respiratory syndrome (mers) in saudi arabia has intensified focus on acute respiratory infections [aris]. this study sought to identify respiratory viruses (rvs) associated with aris in children presenting at a tertiary hospital. children (aged ≤13) presenting with ari between january 2012 and december 2013 tested for 15 rvs using the seeplex(r) rv15 kit were retrospectively included. epidemiological data was retrieved from patient records. of the 2235 children t ...201727430485
matrix metalloproteinase 9 facilitates hepatitis b virus replication through binding with type i interferon (ifn) receptor 1 to repress ifn/jak/stat signaling.hepatitis b virus (hbv) infection may cause acute hepatitis b, chronic hepatitis b (chb), liver cirrhosis, and hepatocellular carcinoma (hcc). however, the mechanisms by which hbv evades host immunity and maintains chronic infection are largely unknown. here, we revealed that matrix metalloproteinase 9 (mmp-9) is activated in peripheral blood mononuclear cells (pbmcs) of hbv-infected patients, and hbv stimulates mmp-9 expression in macrophages and pbmcs isolated from healthy individuals. mmp-9 p ...201728122987
sb 9200, a novel agonist of innate immunity, shows potent antiviral activity against resistant hcv variants.sb 9200 is a novel, first-in-class oral modulator of innate immunity that is believed to act via the activation of the rig-i and nod2 pathways. sb 9200 has broad-spectrum antiviral activity against rna viruses including hepatitis c virus (hcv), norovirus, respiratory syncytial virus and influenza and has demonstrated activity against hepatitis b virus (hbv) in vitro and in vivo. in phase i clinical trials in chronically infected hcv patients, sb 9200 has been shown to reduce hcv rna by up to 1.9 ...201728303593
throat swabs in children with respiratory tract infection: associations with clinical presentation and potential targets for point-of-care testing.diagnostic uncertainty over respiratory tract infections (rtis) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. if symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. this study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs.201728334924
enteric helminth-induced type i interferon signaling protects against pulmonary virus infection through interaction with the microbiota.helminth parasites have been reported to have beneficial immunomodulatory effects in patients with allergic and autoimmune conditions and detrimental consequences in patients with tuberculosis and some viral infections. their role in coinfection with respiratory viruses is not clear.201728196762
influenza in poland in 2013 and 2013/2014 epidemic seasonanalysis of epidemiological situation of influenza in poland in 2013 and 2013/14 epidemic season in reference to previous years and seasons.201727883286
microrna-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase-mediated suppression of histone deacetylase 2.severe steroid-insensitive asthma is a substantial clinical problem. effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. however, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. the mechanisms that underpin ...201727448447
respiratory viruses in acute exacerbations of chronic obstructive pulmonary disease.acute exacerbations of chronic obstructive pulmonary disease (aecopd) cause significant morbidity, mortality, and an inexorable decline of lung function. data from developed countries have shown viruses to be important causes of aecopd, but data from developing countries like india are scant. we set out to determine the contribution of viruses in the causation of hospitalized patients with aecopd.201728144057
microrna-146a induction during influenza h3n2 virus infection targets and regulates traf6 levels in human nasal epithelial cells (hnecs).we have previously shown that human nasal epithelial cells (hnecs) are highly permissive cells for respiratory viruses including influenza a virus (iav) and respiratory syncytial virus. recent studies have indicated that micrornas (mirnas) are involved in virus-host relationship, and this led us to investigate its essential roles in the in vitro hnecs model derived from multiple donors. by comparing the differential expression of mirnas upon iav infection among animal and cell line studies, cand ...201728131813
single- and multiple viral respiratory infections in children: disease and management cannot be related to a specific pathogen.the number of viral pathogens associated with pediatric acute respiratory tract infection (ari) has grown since the introduction of reverse transcription real-time polymerase chain reaction (rt-pcr) assays. multiple viruses are detected during a single ari episode in approximately a quarter of all cases. the clinical relevance of these multiple detections is unclear, as is the role of the individual virus. we therefore investigated the correlation between clinical data and rt-pcr results in chil ...201728077074
a recombinant subunit vaccine for bovine rsv and histophilus somni protects calves against dual pathogen challenge.bovine respiratory syncytial virus (brsv) and histophilus somni synergize to cause respiratory disease in cattle. these pathogens cause enhanced disease during dual-infection and an ige response to antigens of h. somni in dual-infected but not singly infected calves. vaccines containing whole inactivated brsv or h. somni have been associated with ige responses a vaccine strategy that avoids stimulation of ige antibodies would provide superior protection from dual infection. we hypothesized that ...201728274639
pathogens, patterns of pneumonia, and epidemiologic risk factors associated with respiratory disease in recently weaned cattle in ireland.we examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (brd) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in ireland. a standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneu ...201728074713
agreement among 4 sampling methods to identify respiratory pathogens in dairy calves with acute bovine respiratory disease.four sampling techniques commonly are used for antemortem identification of pathogens from cattle with bovine respiratory disease (brd): the nasal swab (ns), guarded nasopharyngeal swab (nps), bronchoalveolar lavage (bal), and transtracheal wash (ttw). agreement among these methods has not been well characterized.201728295570
structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.bovine respiratory disease (brd) is an economically important disease of cattle and continues to be an intensely studied topic. however, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. a structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common brd viral and bacterial pathog ...201725929158
immortalized sheep microglial cells are permissive to a diverse range of ruminant viruses.ruminants, including sheep and goats (small ruminants), are key agricultural animals in many parts of the world. infectious diseases, including many viral diseases, are significant problems to efficient production of ruminants. unfortunately, reagents tailored to viruses of ruminants, and especially small ruminants, are lacking compared to other animals more typically used for biomedical research.201728293985
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
simultaneous antibiofilm and antiviral activities of an engineered antimicrobial peptide during virus-bacterium coinfection.antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. the us ...201727303744
plant-based vaccines against respiratory diseases: current status and future prospects.respiratory infections have an enormous, worldwide epidemiologic impact on humans and animals. among the prophylactic measures, vaccination has the potential to neutralize this impact. new technologies for vaccine production and delivery are of importance in this field since they offer the potential to develop new immunization approaches overriding the current limitations that comprise high cost, safety issues, and limited efficacy. areas covered: in the present review, the state of the art in d ...201727599605
mycoplasma bovis arthritis and pneumonia in calves.mycoplasma bovis arthritis and pneumonia in six-month-old calvessudden deaths in housed suckler cows due to hypomagnesaemiabovine respiratory syncytial virus infection in two-year-old heifersbovine abortion associated with parachlamydia speciesfibrinous pericarditis due to aeromonas hydrophila in weaner pigsthese are among matters discussed in the disease surveillance report for december 2016 from sac consulting: veterinary services (sac c vs).201728302886
disease complexity in a declining alaskan muskox (ovibos moschatus) population.the muskox ( ovibos moschatus ) population inhabiting the eastern north slope (ens) of alaska, us declined dramatically during 1999-2006, whereas populations in western alaska (wa) were stable or increasing. to understand morbidity and mortality factors contributing to the decline, alaska department of fish and game conducted pathologic investigations of carcasses from 2005 until 2008. additionally, archived sera from both ens and wa muskoxen collected during 1984-92, before the documented begin ...201728099077
development of a one-run real-time pcr detection system for pathogens associated with bovine respiratory disease complex.bovine respiratory disease complex (brdc) is frequently found in cattle worldwide. the etiology of brdc is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. here, we developed a detection system by applying taqman real-time pcr (dembo respiratory-pcr) to screen a broad range of microbes associated with brdc in a single run. we selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza vi ...201728070089
the role of nod-like receptors in pulmonary infection.pneumonia is caused by both viral and bacterial pathogens and is responsible for a significant health burden in the unites states. the innate immune system is the human body's first line of defense against these pathogens. the recognition of invading pathogens via pattern recognition receptors (prrs) leads to proinflammatory cytokine and chemokine production followed by recruitment and activation of effector immune cells. the nonspecific inflammatory nature of the innate immune response can resu ...201728157451
antibody response to paramyxoviruses in paget's disease of bone.paget's disease of bone (pdb) is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover. genetic factors play a central role in the pathogenesis of pdb but environmental factors also contribute. measles virus (mv), respiratory syncytial virus (rsv) and canine distemper virus (cdv) have all been implicated as potential disease triggers but the data are conflicting. since chronic paramyxovirus infection with measles is known to be accompanied by ...201728361207
multiplexed metagenomic deep sequencing to analyze the composition of high-priority pathogen reagents.laboratories studying high-priority pathogens need comprehensive methods to confirm microbial species and strains while also detecting contamination. metagenomic deep sequencing (mds) inventories nucleic acids present in laboratory stocks, providing an unbiased assessment of pathogen identity, the extent of genomic variation, and the presence of contaminants. double-stranded cdna mds libraries were constructed from rna extracted from in vitro-passaged stocks of six viruses (la crosse virus, ebol ...201727822544
the bovine paranasal sinuses: bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens.the bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. while lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (brd) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. the par ...201728282443
animal models of respiratory syncytial virus infection.human respiratory syncytial virus (hrsv) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. there is no licensed hrsv vaccine or effective therapeutic agent. however, there are a growing number of hrsv vaccine candidates that have been developed targeting different populations at risk of hrsv infection. animal models of hrsv play an important role in the preclinical testi ...201727908639
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