niryuu/sni-each-converted huggingface dataset:
Background. The common cold or upper respiratory infection (URI) is highly prevalent among young children and often results in otitis media (OM). The incidence and characteristics of OM complicating URI due to specific viruses have not been well studied. Methods. We performed a prospective, longitudinal cohort study of 294 healthy children (age range, 6 months to 3 years). Each child was observed for 1 year to assess the occurrence of URI, acute OM (AOM), and OM with effusion (OME) complicating URI due to specific viruses. Results. We documented 1295 URI episodes (5.06 episodes per child-year) and 440 AOM episodes (1.72 episodes per child-year). Virus studies were performed for 864 URI episodes; 63% were virus positive. Rhinovirus and adenovirus were most frequently detected during URI. The overall incidence of OM that complicated URI was 61%, including a 37% incidence of AOM and a 24% incidence of OME. Young age was the most important predictor of AOM that complicated URI. AOM occurred in approximately one-half of children with URI due to adenovirus, respiratory syncytial virus, or coronavirus and in approximately one-third of those with URI due to influenza virus, parainfluenza virus, enterovirus, or rhinovirus. Conclusions. More than 60% of episodes of symptomatic URI among young children were complicated by AOM and/or OME. Young age and specific virus types were predictors of URI complicated by AOM. For young children, the strategy to prevent OM should involve prevention of viral URI. The strategy may be more effective if the priority is given to development of means to prevent URI associated with adenovirus and respiratory syncytial virus. The common cold or upper respiratory infection (URI), a disease caused by a variety of viruses, is a universal illness. Particularly susceptible to URI are young children, especially those who attend day care centers [1] [2] [3] . URI in young children is often complicated by otitis media (OM) [4, 5] . The high prevalence of URI has made OM one of the most common diseases seen in pediatric practice and the emergency department [6, 7] . OM leads to widespread use of antibiotics and per-
Output: Viral Upper Respiratory Tract Infection and Otitis Media Complication in Young Children
Background: Although modified live virus (MLV) vaccines are commonly used for porcine reproductive and respiratory syndrome virus (PRRSV) control, there have been safety concerns due to the quick reversion of MLV to virulence during replication in pigs. Previous studies have demonstrated that mutant viruses emerged from lethal mutagenesis driven by antiviral mutagens and that those viruses had higher genetic stability compared to their parental strains because they acquired resistance to random mutation. Thus, this strategy was explored to stabilize the PRRSV genome in the current study. Results: Four antiviral mutagens (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated for their antiviral effects against VR2332, a prototype of type 2 PRRSV. Among the mutagens, ribavirin and 5-fluorouracil had significant antiviral effects against VR2332. Consequently, VR2332 was serially passaged in MARC-145 cells in the presence of ribavirin at several concentrations to facilitate the emergence of ribavirin-resistant mutants. Two ribavirin-resistant mutants, RVRp13 and RVRp22, emerged from serial passages in the presence of 0.1 and 0.2 mM ribavirin, respectively. The genetic stability of these resistant mutants was evaluated in MARC-145 cells and compared with VR2332. As expected, the ribavirin-resistant mutants exhibited higher genetic stability compared to their parental virus. Conclusions: In summary, ribavirin and 5-fluorouracil effectively suppressed PRRSV replication in MARC-145 cells. However, ribavirin-resistant mutants emerged when treated with low concentrations (≤0.2 mM) of ribavirin, and those mutants were genetically more stable during serial passages in cell culture.
Output: Effects of ribavirin on the replication and genetic stability of porcine reproductive and respiratory syndrome virus
An antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) method was developed for the efficient detection of the UL24 antigen of the duck enteritis virus (DEV) using polyclonal antibodies. Ducks and rabbits were immunized, respectively, with expressed UL24 recombinant protein. The IgG antibodies against UL24 from ducks and rabbits were purified and used as the capture antibodies. The specificity of the optimized AC-ELISA was evaluated by use of DEV, duck hepatitis virus (DHV), duck hepatitis B virus (DHBV), gosling plague virus (GPV), Riemerella anatipestifer (R.A.), Escherichia coli (E. coli), Pasteurella multocida (P.M.) and Salmonella Enteritidis (S.E.). Only DEV specimens yielded a specific and strong signal. The limit of the sensitivity of this method for the detection of DEV was 46 ng/100 l. Compared with PCR and virus isolation, the rate of agreement for the detection of experimentally infected sera was 100%. A comparative test used on clinical specimens between the neutralization test and the AC-ELISA showed that the proportions of true positives and true negatives by the AC-ELISA were 0.90 and 0.67 respectively. These results indicated that the AC-ELISA approach is rapid, sensitive, and reliable for specific detection of DEV antigen.
Output: Development and evaluation of an antigen-capture ELISA for detection of the UL24 antigen of the duck enteritis virus, based on a polyclonal antibody against the UL24 expression protein
Vaccination programs against infectious bronchitis virus (IBV) in Egypt depend on both classical and/or imported variant IBV strain vaccines. However, many IBV outbreaks associated with respiratory distress, nephropathy, and high mortalities were attributed to the circulation of both classical and new nephropathogenic IBV variant 2 strains. In the present study, we report the development of attenuated IBV candidate vaccines using the classic IBV strains (IBM41 and IB2) and a nephropathogenic strain (IBvar2). The wild-type (WT) viruses were attenuated through serial passages in embryonated specific pathogen free (SPF) chicken eggs. Virulence of the attenuated viruses was then tested via the ocular route inoculation and the in vivo back passage in day-old SPF chickens. Efficacy against homologous challenge was investigated also in day-old SPF chickens. Results showed that the viruses were successfully adapted to the embryo by the 100th (IBM41 and IB2) and 110th passages (IBvar2). The attenuated viruses were safe and showed no change of virulence in day-old SPF chickens up to the 10th back passages. The efficacy experiment showed that the attenuated vaccines showed 90 to 100% protection against the homologous challenge based on ciliostasis score and protection percent. The att-IBM41 and att-IB2 vaccines were able to reduce the shedding of the challenge at 3 days post-infection (DPI) and no virus shedding was detected in both vaccinated groups by 5 DPI. In the att-IBvar2 vaccinated birds, only 20% of vaccinated birds shed the challenge virus with low titers (10 2.10±0.3 EID 50 /mL) at 3 DPI. In conclusion, the attenuated strains IBM41, IB2, and IBvar2 are efficient vaccine candidates against currently circulating classic and variant IB viruses, respectively. Further studies to evaluate the field efficacy and combining these attenuated IBV strains to induce a wider protection against heterologous IBV challenge are suggested.
Output: Safety and efficacy of attenuated classic and variant 2 infectious bronchitis virus candidate vaccines
Porcine epidemic diarrhea virus (PEDV) is an emerging pathogenic coronavirus that causes a significant economic burden to the swine industry. The virus infects the intestinal epithelium and causes villous atrophy, resulting in diarrhea and dehydration. Interaction of the viral spike (S) surface glycoprotein − through its S1 subunit − with the host cell receptor is the first step in infection and the main determinant for virus tropism. As for several other alphacoronaviruses including the porcine transmissible gastroenteritis virus (TGEV) and the human coronavirus 229E (HCoV-229E), the aminopeptidase N (APN) protein was reported to be a functional receptor for PEDV. In this study we examined the role of APN as a receptor. We show that overexpression of porcine APN renders MDCK cells susceptible to TGEV, but not to PEDV. Consistently, unlike TGEV-S1, PEDV-S1 exhibited no binding to cell-surface expressed APN or to a soluble version of APN. Moreover, preincubation of these viruses with soluble APN or pretreatment of APN expressing ST cells with soluble TGEV-S1 blocked TGEV infection, but had no effect on infection by PEDV. The combined observations indicated that APN is not required for PEDV infection. To definitively prove this conclusion, we applied CRISPR/Cas9 genome engineering to knock out APN expression in PEDV-susceptible porcine (ST) and human cell lines (Huh7 and HeLa). As a consequence these cells no longer bound TGEV-S1 and HCoV-229E-S1 at their surface and were resistant to infection by the corresponding viruses. However, genetic ablation of APN expression had no effect on their infectability by PEDV, demonstrating that APN is not essential for PEDV cell entry.
Output: Aminopeptidase N is not required for porcine epidemic diarrhea virus cell entry
Oxidative stress and chronic low-grade inflammation in the lungs are associated with aging and may contribute to age-related immune dysfunction. To maintain lung homeostasis, chronic inflammation is countered by enhanced expression of proresolving/antiinflammatory factors. Here, we show that age-dependent increases of one such factor in the lungs, a phospholipase A 2 (PLA 2 ) group IID (PLA 2 G2D) with antiinflammatory properties, contributed to worse outcomes in mice infected with severe acute respiratory syndrome-coronavirus (SARS-CoV). Strikingly, infection of mice lacking PLA 2 G2D expression (Pla2g2d / mice) converted a uniformly lethal infection to a nonlethal one (>80% survival), subsequent to development of enhanced respiratory DC migration to the draining lymph nodes, augmented antivirus T cell responses, and diminished lung damage. We also observed similar effects in influenza A virus-infected middle-aged Pla2g2d / mice. Furthermore, oxidative stress, probably via lipid peroxidation, was found to induce PLA 2 G2D expression in mice and in human monocyte-derived macrophages. Thus, our results suggest that directed inhibition of a single inducible phospholipase, PLA 2 G2D, in the lungs of older patients with severe respiratory infections is potentially an attractive therapeutic intervention to restore immune function.
Output: Article Critical role of phospholipase A 2 group IID in age-related susceptibility to severe acute respiratory syndrome-CoV infection
Background: In a high-throughput environment, to PCR amplify and sequence a large set of viral isolates from populations that are potentially heterogeneous and continuously evolving, the use of degenerate PCR primers is an important strategy. Degenerate primers allow for the PCR amplification of a wider range of viral isolates with only one set of pre-mixed primers, thus increasing amplification success rates and minimizing the necessity for genome finishing activities. To successfully select a large set of degenerate PCR primers necessary to tile across an entire viral genome and maximize their success, this process is best performed computationally. Results: We have developed a fully automated degenerate PCR primer design system that plays a key role in the J. Craig Venter Institute's (JCVI) high-throughput viral sequencing pipeline. A consensus viral genome, or a set of consensus segment sequences in the case of a segmented virus, is specified using IUPAC ambiguity codes in the consensus template sequence to represent the allelic diversity of the target population. PCR primer pairs are then selected computationally to produce a minimal amplicon set capable of tiling across the full length of the specified target region. As part of the tiling process, primer pairs are computationally screened to meet the criteria for successful PCR with one of two described amplification protocols. The actual sequencing success rates for designed primers for measles virus, mumps virus, human parainfluenza virus 1 and 3, human respiratory syncytial virus A and B and human metapneumovirus are described, where >90% of designed primer pairs were able to consistently successfully amplify >75% of the isolates. Conclusions: Augmenting our previously developed and published JCVI Primer Design Pipeline, we achieved similarly high sequencing success rates with only minor software modifications. The recommended methodology for the construction of the consensus sequence that encapsulates the allelic variation of the targeted population and is a key step prior to designing degenerate primers is also formally described.
Output: Automated degenerate PCR primer design for high-throughput sequencing improves efficiency of viral sequencing
Background: There is limited literature on the frequency of face-touching behavior as a potential vector for the self-inoculation and transmission of Staphylococcus aureus and other common respiratory infections. Methods: A behavioral observation study was undertaken involving medical students at the University of New South Wales. Their face-touching behavior was observed via videotape recording. Using standardized scoring sheets, the frequency of hand-to-face contacts with mucosal or nonmucosal areas was tallied and analyzed. Results: On average, each of the 26 observed students touched their face 23 times per hour. Of all face touches, 44% (1,024/2,346) involved contact with a mucous membrane, whereas 56% (1,322/2,346) of contacts involved nonmucosal areas. Of mucous membrane touches observed, 36% (372) involved the mouth, 31% (318) involved the nose, 27% (273) involved the eyes, and 6% (61) were a combination of these regions. Conclusion: Increasing medical students' awareness of their habituated face-touching behavior and improving their understanding of self-inoculation as a route of transmission may help to improve hand hygiene compliance. Hand hygiene programs aiming to improve compliance with before and after patient contact should include a message that mouth and nose touching is a common practice. Hand hygiene is therefore an essential and inexpensive preventive method to break the colonization and transmission cycle associated with self-inoculation. Crown
Output: Face touching: A frequent habit that has implications for hand hygiene
The equilibrium solubility of ribavirin in solvent mixtures of {methanol (1) + water (2)}, {n-propanol (1) + water (2)}, {acetonitrile (1) + water (2)} and {1,4-dioxane (1) + water (2)} was determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1 kPa). At the same temperature and mass fraction of methanol (n-propanol, acetonitrile or 1,4-dioxane), the mole fraction solubility of ribavirin is greater in (methanol + water) than in the other three solvent mixtures. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood-Buff integrals. The preferential solvation parameters for methanol, n-propanol, acetonitrile or 1,4-dioxane (dx 1,3 ) were negative in the four solvent mixtures with a very wide compositions, which indicated that ribavirin was preferentially solvated by water. Temperature had little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behaviour of water interacting with the Lewis basic groups of the ribavirin. Besides, the solubility of the drugs was mathematically represented by using the Jouyban-Acree model, van't Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.57% for correlative studies. It is noteworthy that the solubility data presented in this work contribute to expansion of the physicochemical information about the solubility of drugs in binary solvent mixtures and also allows the thermodynamic analysis of the respective dissolution and specific solvation process.
Output: Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n-propanol, acetonitrile or 1,4-dioxane) + water
Background: Noncontact forehead temperature measurement by handheld infrared thermometer was used as a screening tool for fever. However, the accuracy data and normal range of forehead temperature determined by this method were not available. Methods: The temperature readings from 3 handheld infrared thermometers were validated against an electronic thermometer. Normal range of forehead temperature was determined by measuring the forehead temperature in 1000 apparently healthy subjects. Results: Significant differences were detected in readings obtained by the 3 different handheld infrared thermometers (analysis of covariance, P , .001) The most accurate one was chosen, and the normal range of forehead temperature in 1000 subjects detected by this method was 31.0°C to 35.6°C. Conclusions: Our study shows that commercially available, handheld infrared thermometers require individual validation. Forehead temperature in excess of 35.6°C is suggestive of fever. Further studies are required to confirm accuracy of this value in detecting fever. (Am J Infect Control 2005;33:227-9.) 
Output: A brief report on the normal range of forehead temperature as determined by noncontact, handheld, infrared thermometer
Through a prospective cohort study the relationship between travellers' awareness of MERS-CoV, and compliance with preventive measures and exposure to camels was evaluated among Australian Hajj pilgrims who attended Hajj in 2015. Only 28% of Australian Hajj pilgrims were aware of MERS-CoV in Saudi Arabia. Those who were aware of MERS-CoV were more likely to receive recommended vaccines [odds ratio (OR) 3.1, 95% confidence interval (CI): 1.5-5.9, P < 0.01], but there was no significant difference in avoiding camels or their raw products during Hajj between those who were aware of MERS-CoV and those who were not (OR 1.2, 95% CI: 0.3-5.2, P ¼ 0.7). Hajj pilgrims' awareness is reflected in some of their practices but not in all.
Output: Association between Australian Hajj Pilgrims' awareness of MERS-CoV, and their compliance with preventive measures and exposure to camels
Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.
Output: Review Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group
Tacaribe virus (TCRV) is a mammalian arenavirus that was first isolated from artibeus bats in the 1950s. Subsequent experimental infection of Jamaican fruit bats (Artibeus jamaicensis) caused a disease similar to that of naturally infected bats. Although substantial attention has focused on bats as reservoir hosts of viruses that cause human disease, little is known about the interactions between bats and their pathogens. We performed a transcriptome-wide study to illuminate the response of Jamaican fruit bats experimentally infected with TCRV. Differential gene expression analysis of multiple tissues revealed global and organ-specific responses associated with innate antiviral responses, including interferon alpha/beta and Toll-like receptor signaling, activation of complement cascades, and cytokine signaling, among others. Genes encoding proteins involved in adaptive immune responses, such as gamma interferon signaling and costimulation of T cells by the CD28 family, were also altered in response to TCRV infection. Immunoglobulin gene expression was also elevated in the spleens of infected bats, including IgG, IgA, and IgE isotypes. These results indicate an active innate and adaptive immune response to TCRV infection occurred but did not prevent fatal disease. This de novo assembly provides a highthroughput data set of the Jamaican fruit bat and its host response to TCRV infection, which remains a valuable tool to understand the molecular signatures involved in antiviral responses in bats.
Output: Transcriptomic Signatures of Tacaribe Virus-Infected Jamaican Fruit Bats
An assay for the microsomal hydroxylation of lauric acid (LA), based on HPLC with flowthrough radiochemical detection, has been developed. Conditions were optimized for resolution and quantitation of three microsomal metabolites of LA, one of which has not been reported previously as a metabolite of LA in mammalian microsomal incubations. These products, 12-(w)-hydroxy-LA, 1 1-(w-1)-hydroxy-LA, and a novel metabolite, IO-(o-2)-hydroxy-LA, were isolated by HPLC and identified by gas chromatography/mass spectrometry. In the presence of NADPH, the formation of all three metabolites was linear with time and microsomal protein concentration. Hydrogen peroxide also supported the microsomal metabolism of LA, although the ratio of metabolites was substantially different than that produced by NADPH-supported microsomes. Several biochemical probes (metyrapone, a-naphthoflavone, 2diethylaminoethyl-2,2diphenylvalerate hydrochloride, and lo-undecynoic acid) were used to dissociate the three LA hydroxylase activities. These experiments suggest that the site-specific hydroxylation [w-, (w-l)-, (w-2)-] of LA may be catalyzed by different isozymes of cytochrome P-450.
Output: Determination of Microsomal Laurie Acid Hydroxylase Activity by HPLC with Flow-Through Radiochemical Quantitation
Introduction. Cytosolic pattern recognition receptors (PRR) have been shown to detect nucleic acids from RNA and DNA viruses in order to launch a type I interferon mediated antiviral state [1]. Here we show that RNA of the facultative intracellular bacterium Salmonella typhimurium is a ligand for RIG-I, triggers production of type-I interferons and contributes to pathogenicity in vivo. Methods. We use RIG-IÀ/À MEFs [2] or human epithelial cells depleted of RIG-I by lentiviral shRNA transduction for transfection and infection experiments. IFNbeta production was measured by 293T IFNbeta-reporter cells or qPCR. Intracellular bacterial titers were determined by gentamycin protection assay. In vivo infection experiments were performed as described [3] using SL1344 or SL1344 aroA deficient Salmonella strains in RIG-I+/+ and RIG-IÀ/À mice [4]. Results. Infection of fibroblasts and epithelial cells with S. typhimurium, but not with non-invasive E. coli, triggers IFNbeta transcription, suggesting that intracellular replication is required. RIG-I dependent recognition of bacterial RNA is dominant in non-phagocytic cells, as shown in RIG-I knockout and knockdown model cells. Despite presence of other pathogen-associated patterns (PAMP), like LPS or flagellin, no IFNbeta was produced in fibroblasts and epithelial cells lacking RIG-I upon S. typhimurium infection. In contrast, in macrophages TLR dependent recognition of bacterial PAMPs through TRIF/Myd88 overcomes RIG-I deficiency and leads to robust induction of type I interferon. We observed higher bacterial titers at early time points after infection in the cecum of S. typhimurium infected RIG-IÀ/À mice, when compared to wild type animals. However, at later stages of infection, S. typhimurium overcomes the innate response leading to similar weight loss and mortality in wildtype and RIG-IÀ/À mice. Conclusion. In summary, our data implicate a role of RIG-I mediated innate immune recognition of bacterial RNA in early control of bacterial replication, most likely mediated by non-phagocytic intestinal epithelial cells targeted by S. typhimurium. Disclosure of interest: None declared. Combined action of type I and type III IFN restricts initial replication of SARScoronavirus in the lung but fails to inhibit systemic virus spread
Output: P133 RIG-I mediates recognition of Salmonella RNA in non-phagocytic cells and con- tributes to early bacterial replication in vivo P135 Defining the intracellular innate immune synapse
Highlights d Viral infection leads to redox dysregulation including the downregulation of SOD1 d Sod1 À/À mice exhibit aggravated viral hepatitis, which is rescued by antioxidants d IFN-I signaling via STAT1 drives SOD1 downregulation and early liver damage d Ablation of IFN-I signaling ameliorates viral hepatitis in Sod1 À/À and WT mice Correspondence abergthaler@cemm.oeaw.ac.at Bergthaler and colleagues show that superoxide dismutase 1 protects the liver from type I interferon-driven oxidative damage in viral hepatitis. Liver damage was mediated by hepatocyte-intrinsic IFNAR1-STAT1 signaling.
Output: Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage Accession Number Article Superoxide Dismutase 1 Protects Hepatocytes from Type I Interferon-Driven Oxidative Damage
Fibroblasts play a pivotal role in cardiac remodeling and the development of heart failure through the deposition of extra-cellular matrix (ECM) proteins and also by affecting cardiomyocyte growth and function. The renin-angiotensin system (RAS) is a key regulator of the cardiovascular system in health and disease and many of its effects involve cardiac fibroblasts. Levels of angiotensin II (Ang II), the main effector molecule of the RAS, are elevated in the failing heart and there is a substantial body of evidence indicating that this peptide contributes to changes in cardiac structure and function which ultimately lead to progressive worsening in heart failure. A pathway involving angiotensin converting enzyme 2 (ACE2) has the capacity to break down Ang II while generating angiotensin-(1-7) (Ang- (1-7) , a heptapeptide, which in contrast to Ang II, has cardioprotective and anti-remodeling effects. Many Ang-(1-7) actions involve cardiac fibroblasts and there is information indicating that it reduces collagen production and also may protect against cardiac hypertrophy. This report describes the effects of ACE2 and Ang-(1-7) that appear to be relevant in cardiac remodeling and heart failure and explores potential therapeutic strategies designed to increase ACE2 activity and Ang-(1-7) levels to treat these conditions.
Output: Targeting the ACE2-Ang-(1-7) Pathway in Cardiac Fibroblasts to Treat Cardiac Remodeling and Heart Failure
The response to the novel coronavirus outbreak in China suggests that many of the lessons from the 2003 SARS epidemic have been implemented and the response improved as a consequence. Nevertheless some questions remain and not all lessons have been successful. The national and international response demonstrates the complex link between public health, science and politics when an outbreak threatens to impact on global economies and reputations. The unprecedented measures implemented in China are a bold attempt to control the outbreakwe need to understand their effectiveness to balance costs and benefits for similar events in the future.
Output: Epidemiology and Infection SARS to novel coronavirus -old lessons and new lessons
To evaluate the contribution of antimicrobial use in human and veterinary medicine to the emergence and spread of resistant bacteria, the use of these substances has to be accurately monitored in each setting. Currently, various initiatives collect sales data of veterinary antimicrobials, thereby providing an overview of quantities on the market. However, sales data collected at the level of wholesalers or marketing authorization holders are of limited use to associate with the prevalence of bacterial resistances at species level. We converted sales data to the number of potential treatments of calves and pigs in Switzerland for the years 2011 to 2015 using animal course doses (ACD). For each authorized product, the number of potential therapies was derived from the sales at wholesaler's level and the ACD in mg per kg. For products registered for use in multiple species, a percentage of the sales was attributed to each authorized species according to their biomass distribution. We estimated a total of 5,914,349 therapies for pigs and 1,407,450 for calves in 2015. Using the number of slaughtered animals for that year as denominator, we calculated a treatment intensity of 2.15 therapies per pig and 5.96 per calf. Between 2011 and 2015, sales of veterinary antimicrobials decreased by 30%. The calculated number of potential therapies decreased by 30% for pigs and 15% for calves. An analysis of treatment intensity at antimicrobial class level showed a decrease of 64% for colistin used in pigs, and of 7% for macrolides used in both pigs and calves. Whereas the use of 3rd and 4th generation cephalosporins in calves decreased by 15.8%, usage of fluoroquinolones increased by 10.8% in the same period. Corresponding values for pigs were −16.4 and +0.7%. This is the first extrapolation of antimicrobial usage at product level for pigs and calves in Switzerland. It shows that calves were more frequently treated than pigs with a decreasing trend for both number of therapies and use of colistin, macrolides and cephalosporins 3rd and 4th generations. Nonetheless, we calculated an increase in the usage of fluoroquinolones. Altogether, this study's outcomes allow for trend analysis and can be used to assess the relationship between antimicrobial use and resistance at the national level.
Output: Extrapolating Antibiotic Sales to Number of Treated Animals: Treatments in Pigs and Calves in Switzerland, 2011-2015
The NS5A protein of classical swine fever virus (CSFV) is involved in the RNA synthesis and viral replication. However, the NS5A-interacting cellular proteins engaged in the CSFV replication are poorly defined. Using yeast two-hybrid screen, the eukaryotic elongation factor 1A (eEF1A) was identified to be an NS5A-binding partner. The NS5A-eEF1A interaction was confirmed by coimmunoprecipitation, glutathione S-transferase (GST) pulldown and laser confocal microscopy assays. The domain I of eEF1A was shown to be critical for the NS5A-eEF1A interaction. Overexpression of eEF1A suppressed the CSFV growth markedly, and conversely, knockdown of eEF1A enhanced the CSFV replication significantly. Furthermore, eEF1A, as well as NS5A, was found to reduce the translation efficiency of the internal ribosome entry site (IRES) of CSFV in a dose-dependent manner, as demonstrated by luciferase reporter assay. Streptavidin pulldown assay revealed that eEF1A could bind to the CSFV IRES. Collectively, our results suggest that eEF1A interacts with NS5A and negatively regulates the growth of CSFV. Viruses 2015, 7 4564 Keywords: classical swine fever virus; virus-host interactions; NS5A; eukaryotic elongation factor 1A; internal ribosome entry site
Output: eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus
Background: Newcastle Disease virus (NDV) causes severe and economically significant disease in almost all birds. However, factors that affect NDV replication in host cells are poorly understood. NDV generates long double-stranded RNA (dsRNA) molecules during transcription of single-stranded genomic RNA. Protein kinase R (PKR) is activated by dsRNA. The aim of this study was to elucidate the role of PKR in NDV infection. Results: NDV infection led to the activation of dsRNA-dependent PKR and phosphorylation of its substrate, translation initiation factor eIF2α, in a dose-dependent manner by either the lentogenic strain LaSota or a velogenic strain Herts/33. PKR activation coincided with the accumulation of dsRNA induced by NDV infection. PKR knockdown remarkably decreased eIF2α phosphorylation as well as IFN-β mRNA levels, leading to the augmentation of extracellular virus titer. Furthermore, siRNA knockdown or phosphorylation of eIF2α or okadaic acid treatment significantly impaired NDV replication, indicating the critical role of the PKR/eIF2α signaling cascade in NDV infection. Conclusion: PKR is activated by dsRNA generated by NDV infection and inhibits NDV replication by eIF2α phosphorylation. This study provides insight into NDV-host interactions for the development of candidate antiviral strategies.
Output: Activation of the PKR/eIF2α signaling cascade inhibits replication of Newcastle disease virus
Causative pathogens of pneumonia in children can be diffi cult to identify. Streptococcus pneumoniae is the most common bacterial cause of pneumonia in children. Tachypnea is the most reliable clinical predictor of pneumonia in children. Laboratory and radiologic testing offers limited diagnostic benefi t. Probably the greatest challenge in the approach to children with pneumonia is that the microbiologic etiology is diffi cult to identify. This is primarily due to limitations of diagnostic testing modalities: blood cultures, antigen testing and antibody titers, and the need for invasive means to retrieve specimens. 1,4 Two studies illustrate our limited ability to diagnose the etiology of pneumonia in children. In a prospective study of 168 ambulatory children with CAP, an etiologic agent was identifi ed in only 43% of cases. 5 These included Streptococcus pneumoniae (27%), Mycoplasma pneumoniae (7%) and Chlamydia pneumoniae (6%). Patients with S. pneumoniae frequently had a mixed infection (40%). Of 157 patients tested for viral infection, 20% were positive by culture and/or direct fl uorescent antibody test. Viral etiologies identifi ed included respiratory syncytial virus (RSV), infl uenza viruses A and B, parainfl uenza viruses 1 and 3, adenovirus, enterovirus, cytomegalovirus, and herpes simplex virus. All viral isolates were identifi ed in children less than 8 years of age. 5 A similar study, in 254 hospitalized children with CAP, identifi ed a potential causative agent in 85% of cases. 6 Extensive diagnostic testing accounted for the relatively high yield in this study. Similar etiologies identifi ed, in decreasing frequency of occurrence, included S. pneumoniae, Haemophilus infl uenzae, M. pneumoniae, Moraxella catarrhalis, C. pneumoniae, Streptococcus pyogenes, and Chlamydia trachomatis. Viral etiologies included (most common to least common) RSV, rhinovirus, parainfl uenza viruses 1 through 3, adenovirus, infl uenza virus A and B, coronavirus, human herpesvirus 6, Epstein-Barr virus, and varicella-zoster virus. Mixed viralbacterial infections were detected in 30% of patients, and 41% of patients had more than one microbiologic agent identifi ed. Of interest, of 93 patients with S. pneumoniae, only one had a positive blood culture. The remaining 92 patients were diagnosed based solely on serologic evidence. 6 A prospective analysis seeking to identify etiologic agents via a pneumolysin-based polymerase chain reaction assay identifi ed a respiratory pathogen in 79% of 154 pediatric patients with lower respiratory tract infection. The most common etiologic agent was S. pneumoniae (44%). Of 68 patients with S. pneumoniae infection, 18% had a coinfection with another bacteria and 31% had a co-infection with a virus. Atypical agents (M. pneumoniae and C. pneumoniae) accounted for 22% of all infections (14% and 9%, respectively). The most common viral etiologies included
Output: Pneumonia Key Points
Infections caused by respiratory viruses can have different clinical symptoms, while specific set of symptoms can be induced by different viruses. Despite usually mild course of disease, some viruses causing certain disease entity can result in serious complications. Therefore, quick and appropriate diagnostic is crucial for administering proper treatment. In the epidemic season 2013/2014, 2,497 specimens were tested. Infections caused by influenza viruses were confirmed in 9.8 %, while infections caused by influenza-like viruses (ILI) in 13.2 %. The co-domination of A/H1N1/pdm09 (29.4 %) with A/H3N2/ (30.6 %) was observed among circulating subtypes of influenza virus type A. Analysis of positive specimens categorized into 7 age groups indicated that most of morbidity to influenza was noted in the age intervals: 26-44 (22.9 %) and 45-64 years old (21.6 %). Considering infections caused by influenza-like viruses, the highest amount of positive cases was registered in the age group 0-4 years old (92.7 %) with the highest ratio of RSV (87.9 %) and PIV-3 (10.5 %). Judging by the epidemiological and virological indicators, the 2013/14 influenza season was mild and only low virus activity was reported in Poland as well as in most European countries. Still, 9,000 hospitalizations and 17 deaths were registered in Poland during this epidemic season.
Output: Evaluation of the Activity of Influenza and Influenza-Like Viruses in the
Acoustic trauma was recently shown to induce an inflammatory response in the ear characterized by rapid entry of macrophages in the spiral ligament. The current study seeks to elucidate the mechanisms involved in summoning macrophages to the cochlear lateral wall and the role macrophages play in noiseinduced injury or repair. CCL2 and its primary receptor, CCR2, are the most widely validated effectors of monocyte chemotaxis in vivo. CCL2 -/and CCR2 -/mice have been used extensively in studies of monocyte activation in neuronal injury. However, the function of CCL2 and CCR2 in the cochlea has not been studied. The present study examines the role of CCL2 and CCR2 in acoustic injury. CCL2 -/and CCR2 -/mice on a CX3CR1 +/GFP background were exposed to octave band noise (8-16 kHz) for 2 h to determine the effect of CCL2 and CCR2 on monocyte migration into the cochlea, threshold shift, and cell survival. We found that threshold shift was unchanged in the two knockout mouse strains when compared to the background strain (CX3CR1 +/GFP ). Surprisingly, we found that monocyte migration was also unchanged, despite the absence of CCL2 or CCR2. However, there was a dramatic increase in noise-induced hair cell death in the CCR2 -/strain. This observation suggests that CCR2, independent of CCL2, plays a protective role in the cochlea after noise, and neither ligand nor receptor is necessary for monocyte migration. Possible mechanisms of neuroprotection by CCR2 are discussed.
Output: CC Chemokine Receptor 2 is Protective Against Noise-Induced Hair Cell Death: Studies in CX3CR1 +/GFP Mice
The Alberta Johne's Disease Initiative (AJDI) is a Johne's disease (JD) control program with the goal of reducing the spread of Mycobacterium avium ssp. paratuberculosis (MAP) through implementation of best management practices. The objective was to estimate the economic benefit of participation in the AJDI. A decision tree was constructed in which disease prevalence, test characteristics, and probabilities for implementation of best management practices suggested by herd veterinarians were implemented. Analysis was performed using a Markov analysis, and input data were assigned using estimates from the AJDI and published data. A cost-effectiveness analysis was performed and the net benefit of participation (from the perspective of a dairy farmer) in the AJDI compared with no participation was calculated. A series of 1-way sensitivity analyses were used to control for uncertainty. Farms participating in the AJDI were estimated to have a net benefit of Can$74 per cow over the course of 10 yr. If project costs were covered by the participating farm, the net benefit was Can$27. In addition to the effects on MAP infection, a reduction in calf diarrhea was modeled for farms that improved their calf management through the use of pasteurizers. In that case, the additional costs outweighed additional revenues compared with the baseline analysis, resulting in a reduced net benefit of Can$19. Participation would not be cost effective if cows in early stages of MAP infection did not have decreased production and if prevalence of MAP infection did not increase on farms with poor management. A limitation of the study, despite high uncertainty in some input parameters, was the lack of knowledge regarding changes in prevalence on farms with various management strategies. In conclusion, participation in the AJDI was cost effective for the average Alberta dairy farm.
Output: ECONOMICS OF A PARATUBERCULOSIS CONTROL PROGRAM 2823 2834 WOLF ET AL
This study describes a novel blocking microsphere-based immunoassay for highly sensitive and specific detection of antibodies against bovine viral diarrhoea virus (BVDV). The intra-and inter-assay variability are 4.9% and less than 7%, respectively, and variability of bead conjugations is less than 6.6%. The diagnostic performance of the assay was evaluated by testing a total of 509 serum samples. Based on a negative/positive cut-off value of 30.3%, the assay has a sensitivity of 99.4% and a specificity of 98.3% relative to ELISA. The new microsphere immunoassay provides an alternative to conventional ELISA systems and can be used for high-throughput screening in the BVD control programmes.
Output: A microsphere-based immunoassay for rapid and sensitive detection of bovine viral diarrhoea virus antibodies
Previous studies have suggested that mass media's reports of new suicide methods will increase suicides using the same method. The same pattern seems not to apply to a conventional suicide method, unless it was used by a celebrity. Objective 1) to examine media effects on both new and non-new suicide methods during 1998 and 2005 in Hong Kong (HK), when a new method by burning charcoal (CB suicide) was spreading in the region. 2) to examine how CB competed with non-CB methods in terms of media coverage and "recruiting" suicidal persons in the socio-economic context. A self-and mutual-exciting process model was fitted to the data, adjusting for divorce rate, unemployment rate, and property price index. Breaking the whole period into onset, peak, and post-peak stages, the model was fitted again to examine the differences. Comparable copycat effects were found on both CB and non-CB suicide news. The only cross-method media effects were found in the onset stage when non-CB suicide news showed suppressing effect on CB suicides. CB suicides reported a significant self-excitation effect. A higher divorce rate and lower property price index were associated with significantly more suicides incidences and more suicide news. The emerging of CB suicide method did not substitute media coverage of non-CB suicide in HK. Media effects in this case were not limited to new suicide method or celebrity suicide. The effects were further fueled by adverse socio-economic conditions.
Output: Media effects on suicide methods: A case study on Hong Kong 1998-2005
After the 2019 novel coronavirus (2019-nCoV) outbreak, we estimated the distribution and scale of more than 5 million migrants residing in Wuhan after they returned to their hometown communities in Hubei Province or other provinces at the end of 2019 by using the data from the 2013-2018 China Migrants Dynamic Survey (CMDS). We found that the distribution of Wuhan's migrants is centred in Hubei Province (approximately 75%) at a provincial level, gradually decreasing in the surrounding provinces in layers, with obvious spatial characteristics of circle layers and echelons. The scale of Wuhan's migrants, whose origins in Hubei Province give rise to a gradient reduction from east to west within the province, and account for 66% of Wuhan's total migrants, are from the surrounding prefectural-level cities of Wuhan. The distribution comprises 94 districts and counties in Hubei Province, and the cumulative percentage of the top 30 districts and counties exceeds 80%. Wuhan's migrants have a large proportion of middle-aged and high-risk individuals. Their social characteristics include nuclear family migration (84%), migration with families of 3-4 members (71%), a rural household registration (85%), and working or doing business (84%) as the main reason for migration. Using a quasi-experimental analysis framework, we found that the size of Wuhan's migrants was highly correlated with the daily number of confirmed cases. Furthermore, we compared the epidemic situation in different regions and found that the number of confirmed cases in some provinces and cities in Hubei Province may be underestimated, while the epidemic situation in some regions has increased rapidly. The results are conducive to monitoring the epidemic prevention and control in various regions.
Output: Prediction of Epidemic Spread of the 2019 Novel Coronavirus Driven by Spring Festival Transportation in China: A Population-Based Study
A swine-origin H1N1 triple-reassortant influenza A virus found to be a distant relative of the 1918 "Spanish flu" virus emerged in April 2009 to give rise to the first influenza pandemic of the 21st century. Although disease was generally mild and similar to seasonal influenza, severe manifestations including respiratory failure were noted in some, particularly those with underlying conditions such as asthma, pregnancy and immunosuppression. Children and younger adults accounted for most cases, hospitalizations and deaths. A reverse transcriptase-polymerase chain reaction assay was superior to antigenbased rapid tests for diagnosis. All 2009 H1N1 pandemic influenza strains were susceptible to 1 or more neuraminidase inhibitors. Monovalent, unadjuvanted 2009 H1N1 vaccines were licensed in the United States in September 2009 and initially targeted to younger individuals, pregnant women, caretakers of infants and healthcare providers. The 2009 H1N1 pandemic highlights the need for modernization of influenza vaccines, improved diagnostics and more rigorous evaluation of mitigation strategies.
Output: 2009 H1N1 Influenza: A Twenty-First Century Pandemic With Roots in the Early Twentieth Century
Changes occurred in the patterns of utilization of emergency medical services during the Middle East respiratory syndrome (MERS) outbreak. The purpose of this study was to analyze the patterns of adult and pediatric patients who visited the emergency department (ED) during the outbreak. This retrospective study was conducted by analyzing changes in the patterns of visits among adult and pediatric patients in the ED at one tertiary teaching hospital in Korea. The study was performed from June 1, 2013 to July 31, 2015. The MERS outbreak period was from June 1 to July 31, 2015, and we compared that period to the same periods in 2013 and 2014. We compared and analyzed the patients' characteristics, emergency severity index (ESI) level at the visit, cause of visit, diagnosis, final dispositions, injury/non-injury, length of stay at the ED (EDLOS), and hospitalization rate. A total of 9,107 patients visited the ED during this period. Of these patients, 2,572 (28.2%) were pediatric patients and 6,535 (71.8%) were adult patients. The most common cause of an ED visit was fever (adult patients: 21.6%, pediatric patients: 56.2%). The proportion of non-urgent visits involving an ESI level of 4 or 5 and the EDLOS decreased significantly in pediatric and adult patients in comparison to that during the past two years. This change was significant in pediatric patients. Among adult patients, the rate of injury decreased, whereas it increased among pediatric patients. During the MERS outbreak period, pediatric ED visits due to non-urgent cases decreased significantly and there were more pronounced differences in ED utilization patterns in pediatric patients than in adult patients.
Output: The Impact of Middle East Respiratory Syndrome Outbreak on Trends in Emergency Department Utilization Patterns