niryuu/sni-each-converted huggingface dataset:
Background: Molecular assays for diagnosis of Flu A, Flu B, and RSV with short turn-around-time (TAT) are of considerable clinical importance. In addition, rapid and accurate diagnosis of a large panel of viral and atypical pathogens can be crucial in immunocompromised patients. Objectives: First, to evaluate the performance of the Simplexa™ Direct assay system in comparison with direct fluorescent antibody (DFA) and customized Taqman® Array Card (TAC) testing for RSV, Flu A, and Flu B in immunocompromised patients. Second, to evaluate different algorithms for the detection of respiratory pathogens in terms of cost, turn-around-time (TAT) and diagnostic yield. Study design: We collected 125 nasopharyngeal swabs (NTS) and 25 BAL samples from symptomatic immunocompromised patients. Samples for which Simplexa™ and TAC results were discordant underwent verification testing. The TAC assay is based on singleplex RT-PCR, targeting 24 viruses, 8 bacteria and 2 fungi simultaneously. Results: The overall sensitivity was significantly lower for DFA testing than for the two molecular methods (p < 0.05). Performance characteristics of Simplexa™ testing were not significantly different compared to TAC testing (p > 0.1). For BAL samples only, the sensitivity and specificity of the Simplexa™ assay was 100%. In total, 6.7, 16 and 18% of samples were positive for Flu A, Flu B or RSV by DFA, Simplexa™ and TAC testing, respectively. When considering not only these pathogens but also all results for TAC, the method identified 93 samples with one or more respiratory pathogens (62%). A co-infection rate of 15.3% was found by TAC. The estimated costs and TAT were 8.2€ and 2 h for DFA, 31.8€ and 1.5 h for Simplexa™ and 55€ and 3 h for TAC testing. Conclusions: Performing the Simplexa™ test 24 h a day/7 days a week instead of DFA would considerably improve the overall sensitivity and time-to-result, albeit at a higher cost generated in the laboratory. Performing the TAC would increase the diagnostic yield and detection of co-infections significantly.
Output: Performance evaluation of direct fluorescent antibody, Focus Diagnostics Simplexa™ Flu A/B & RSV and multi-parameter customized respiratory Taqman® array card in immunocompromised patients
To examine the relationship of impairments of the liver and kidney with viral load after nephropathogenic infectious bronchitis virus (NIBV) infection in embryonic chickens, 120 specific-pathogenfree Leghorn embryonated chicken eggs were randomly divided into two groups (infected and control), with three replicates per group and 20 eggs in each replicate. The eggs in the infected and control groups were challenged with 0.2 mL of 10 5.5 ELD 50 NIBV and sterile saline solution, respectively. The embryonic chickens' plasma and liver and kidney tissues were collected at 1, 3, and 5 days post-inoculation (dpi), the liver and kidney functional parameters were quantified, and the tissue viral loads were determined with real-time PCR. The results showed that plasma potassium, sodium, chlorine, magnesium, calcium, and phosphorus levels were increased. The infected group exhibited significantly higher plasma uric acid, blood urea nitrogen, and creatinine levels than the control group at 3 dpi. The plasma concentrations of aspartate aminotransferase and alanine aminotransferase were significantly increased in the infected group. The total protein, albumin, and globulin levels in the infected group were significantly lower than those in the control group. The liver-kidney viral load in the infected group peaked at 3 dpi, at which time the kidney viral load was significantly higher than that of the liver. Our results indicated that NIBV infection caused liver and kidney damage in the embryonic chickens, and the results also demonstrated that the liver and kidney damage was strongly related to the tissue viral load following NIBV infection in embryonic chickens.
Output: The relationship between liver-kidney impairment and viral load after nephropathogenic infectious bronchitis virus infection in embryonic chickens
we conducted a cross-sectional survey of 1,295 undergraduate students in Guangzhou, China, where the population of immigrants from Africa is high (online Technical Appendix, http://wwwnc.cdc.gov/EID/article/22/1/15-0898-Techapp1.pdf). Our aim was to measure students' anticipated negative emotional responses and avoidance activities (dependent variables) to a possible outbreak of EVD (5). We constructed scales for the dependent and independent variables to assess EVD-related perceptions: 1) misconceptions/knowledge about transmission modes, 2) scenarios of an EVD outbreak in Guangzhou (chances, severity, control), 3) efficacy of preventive measures and self-protection, and 4) public stigma toward EVD survivors. MLwiN 2.30 (Centre for Multilevel Modeling, University of Bristol, Bristol, UK) was used for multilevel regression analyses (online Technical Appendix). We analyzed data from 1,155 (89.2%) students who had heard of EVD. To the example of 2-3 EVD cases detected in Guangzhou, 31.0% showed >4 types of anticipated negative emotions (e.g., fear, panic, worry); 59.5% showed >3 types of anticipated unnecessary avoidance. Most (80.0%) indicated >1 misconception regarding transmission mode (e.g., believed it was droplet or waterborne) but knew that direct contact with the corpse of an infected person (69.0%) and body fluids (81.4%) could lead to infection and perceived EVD as fatal (85.6%,) and highly infectious (81.6%). About half of respondents believed that effective treatment and a vaccine were unavailable (51.9% and 59.1%, respectively); 22.2% anticipated EVD outbreaks among Africans in Guangzhou (during the next 12 months). Many students perceived severe consequences if a small EVD outbreak occurred in Guangzhou and believed an outbreak would have a high fatality rate (70.5%), EVD is highly infectious (65.4%), an outbreak would be of long duration (47.5%), and the number of infected persons would be high (
Output: Anticipated Negative Responses by Students to Possible Ebola Virus Outbreak, Guangzhou, China
Backgrounds: An ongoing outbreak of a novel coronavirus (2019-nCoV) pneumonia hit a major city of China, Wuhan, December 2019 and subsequently reached other provinces/regions of China and countries. We present estimates of the basic reproduction number, R0, of 2019-nCoV in the early phase of the outbreak. Accounting for the impact of the variations in disease reporting rate, we modelled the epidemic curve of 2019-nCoV cases time series, in mainland China from January 10 to January 24, 2020, through the exponential growth. With the estimated intrinsic growth rate (γ), we estimated R0 by using the serial intervals (SI) of two other well-known coronavirus diseases, MERS and SARS, as approximations for the true unknown SI. The early outbreak data largely follows the exponential growth. We estimated that the mean R0 ranges from 2.24 (95%CI: 1.96-2.55) to 3.58 (95%CI: 2.89-4.39) associated with 8-fold to 2-fold increase in the reporting rate. We demonstrated that changes in reporting rate substantially affect estimates of R0.
Output: Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak
National evidence-based guidelines for preventing healthcare-associated infections (HCAI) in National Health Service (NHS) hospitals in England were commissioned by the Department of Health (DH) and developed during 1998-2000 by a nurse-led multi-professional team of researchers and specialist clinicians. Following extensive consultation, they were published in January 2001. 1 These guidelines describe the precautions healthcare workers should take in three areas: standard principles for preventing HCAI, which include hospital environmental hygiene, hand hygiene, the use of personal protective equipment, and the safe use and disposal of sharps; preventing infections associated with the use of short-term indwelling urethral catheters; and preventing infections associated with central venous catheters. The evidence for these guidelines was identified by multiple systematic reviews of experimental and nonexperimental research and expert opinion as reflected in systematically identified professional, national and international guidelines, which were formally assessed by a validated appraisal process. In 2003, we developed complementary national guidelines for preventing HCAI in primary and community care on behalf of the National Collaborating Centre for Nursing and Supportive Care (National Institute for Health and Clinical Excellence). 2 A cardinal feature of evidence-based guidelines is that they are subject to timely review in order that new research evidence and technological advances can be identified, appraised and, if shown to be effective in preventing HCAI, incorporated into amended guidelines. Periodically updating the evidence base and guideline recommendations is essential in order to maintain their validity and authority. Consequently, the DH commissioned a review of new evidence published following the last systematic reviews. We have now updated the evidence base for making infection prevention and control recommendations. A critical assessment of the updated evidence indicated that the original epic guidelines published in 2001 remain robust, relevant and appropriate but that adjustments need to be
Output: epic2: National Evidence-Based Guidelines for Preventing Healthcare-Associated Infections in NHS Hospitals in England 1 Introductory section 1.1 Guideline Development Team
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. The term is derived from the Greek word for "alternative"-para and for "mucus"-myxo. 2. Syncytium A syncytium (pl., syncytia) refers to a multinucleated cell that can result from multiple cell fusions of uninuclear cells. The term is derived from the Greek word for "together"-syn and for "box (cell)"-kytos.
Output: Molecular Virology of Human Pathogenic Viruses
Uniform polymeric nanoparticles with various morphologies of projection coronas like the viruses in the coronavirus group have been formed by the self-organization of macromolecular chains polymerizing in a dispersion system of styrene (St), acrylonitrile (AN) and poly(ethylene glycol) monomethoxymonomethacrylate (PEGm) in a polar solvent (water/ethanol). An increase in the water composition reduced the crystallization degree of AN units, resulting in a variety of the nanoparticle morphology such as the increased particle size, the reduced projection size, the increased projection number, and the decreased inter-projection distance. The difference in the projection morphology strongly affected a dispersibility in water. q
Output: One-step nanomorphology control of self-organized projection coronas in uniform polymeric nanoparticles *
Background: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood. Methods: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/-11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/-11.8 yrs.) who fulfilled criteria for fibromyalgia. Results: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post-SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms. Conclusions: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.
Output: Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post- SARS syndrome; a case-controlled study
Human rhinovirus type C is a recently discovered species that has been associated with respiratory tract infections of unusual severity in some cases. However, the precise type of diseases associated with this new human rhinovirus needs to be investigated. In the present report, we used adapted real-time PCR assays to screen different clinical specimens collected from a 14-month-old boy presenting an acute lower respiratory tract disease complicated by a severe pericarditis. RT-PCR identified picornavirus RNA in the bronchoalveolar lavage (BAL) specimen, pericardial fluid, plasma and stools. This supported the existence of a disseminated viral infection that extended to the pericardial space. 5 UTR and VP1 sequence analysis performed directly from the BAL sample allowed genotyping of the virus as a human rhinovirus C. This observation highlights the need for adapted diagnostic tools and the potential for the new rhinovirus species C to cause complications, including pericarditis.
Output: Pneumonia and pericarditis in a child with HRV-C infection: A case report
The study of epidemic spreading on populations of networked individuals has seen recently a great deal of significant progresses. A common point in many of past studies is, however, that there is only one peak of infected density in each single epidemic spreading episode. At variance, real data from different cities over the world suggest that, besides a major single peak trait of infected density, a finite probability exists for a pattern made of two (or multiple) peaks. We show that such a latter feature is distinctive of a multilayered network of interactions, and reveal that a two peaks pattern may emerge from different time delays at which the epidemic spreads in between the two layers. Further, we show that the essential ingredient is a weak coupling condition between the layers themselves, while different degree distributions in the two layers are also helpful. Moreover, an edge-based theory is developed which fully explains all numerical results. Our findings may therefore be of significance for protecting secondary disasters of epidemics, which are definitely undesired in real life.
Output: Multiple peaks patterns of epidemic spreading in multi-layer networks
The prevention of airborne infections in emergency departments is a very important issue. This study investigated the effects of architectural features on airborne pathogen dispersion in emergency departments by using a CFD (computational fluid dynamics) simulation tool. The study included three architectural features as the major variables: increased ventilation rate, inlet and outlet diffuser positions, and partitions between beds. The most effective method for preventing pathogen dispersion and reducing the pathogen concentration was found to be increasing the ventilation rate. Installing partitions between the beds and changing the ventilation system's inlet and outlet diffuser positions contributed only minimally to reducing the concentration of airborne pathogens.
Output: Case Study of Airborne Pathogen Dispersion Patterns in Emergency Departments with Different Ventilation and Partition Conditions
The feasibility of developing a prophylactic vaccine against SARS was assessed by comparing the immune responses elicited by immunizing mice with a recombinant SARS spike glycoprotein (S-protein) formulated with different adjuvants, given by different routes. In both young and aged mice, an intranasal Protollin-formulated S-protein vaccine elicited high levels of antigen-specific IgG in serum, comparable to those elicited by an intramuscular Alum-adsorbed S-protein vaccine. Serum antibodies were shown to be virus neutralizing. Intranasal immunization of young mice with the Protollin-formulated vaccine elicited significant levels of antigen-specific lung IgA in contrast to mice immunized with the intramuscular vaccine in which no antigen-specific lung IgA was detected. Following live virus challenge of aged mice, no virus was detected in the lungs of intranasally immunized mice, in contrast to intramuscularly immunized mice whose lung virus titers were comparable to those observed in control mice.
Output: Intranasal Protollin-formulated recombinant SARS S-protein elicits respiratory and serum neutralizing antibodies and protection in mice
PRRSV live vaccines are widely used in pig farming practice and are usually not adjuvanted. For safety issues, it would be useful to reduce the antigenic load of such vaccines while preserving their efficacy. In this study we show that the addition of polymer or oil adjuvants in a PRRS live vaccine enhanced the protection to challenge of vaccinated animals compared to a non-adjuvanted commercial reference. Moreover, for both types of adjuvants, despite lower antibody titers, the protection to challenge given by the adjuvanted vaccine containing only 50% of the antigen load was equivalent to the protection given by the non-adjuvanted vaccine. These results demonstrate that the addition of relevant adjuvants can enhance the efficacy of the protection conferred to animals by live vaccines.
Output: of the 5th vaccine conference organizing committee. of the 5th vaccine conference organizing committee
Estimating the case fatality ratio (CFR) of a novel strain of influenza virus during the early stage of the pandemic is one of key epidemiological tasks to be conducted as rapid research response. Past experience during the epidemics of severe acute respiratory syndrome (SARS) and influenza A (H1N1-2009) posed several technical challenges in estimating the CFR in real time. The present study aimed to develop a simple method to estimate the CFR based on readily available datasets, that is, confirmed cases and deaths, while addressing some of the known technical issues. To assess the reliability and validity of the proposed method, we examined the minimum length of time required for the assigned CFR to be included within the 95% confidence intervals and for the estimated CFR to be below a prespecified cut-off value by means of Monte Carlo simulations. Overall, the smaller the transmission potential was, the longer it took to compare the estimated CFR against the cut-off value. If policymaking and public health response have to be made based on the CFR estimate derived from the proposed method and readily available data, it should be noted that the successful estimation may take longer than a few months.
Output: The Time Required to Estimate the Case Fatality Ratio of Influenza Using Only the Tip of an Iceberg: Joint Estimation of the Virulence and the Transmission Potential
Knowledge of protein-protein interactions and their binding sites is indispensable for in-depth understanding of the networks in living cells. With the avalanche of protein sequences generated in the postgenomic age, it is critical to develop computational methods for identifying in a timely fashion the protein-protein binding sites (PPBSs) based on the sequence information alone because the information obtained by this way can be used for both biomedical research and drug development. To address such a challenge, we have proposed a new predictor, called iPPBS-Opt, in which we have used: (1) the K-Nearest Neighbors Cleaning (KNNC) and Inserting Hypothetical Training Samples (IHTS) treatments to optimize the training dataset; (2) the ensemble voting approach to select the most relevant features; and (3) the stationary wavelet transform to formulate the statistical samples. Cross-validation tests by targeting the experiment-confirmed results have demonstrated that the new predictor is very promising, implying that the aforementioned practices are indeed very effective. Particularly, the approach of using the wavelets to express protein/peptide sequences might be the key in grasping the problem's essence, fully consistent with the findings that many important biological functions of proteins can be elucidated with their low-frequency internal motions. To maximize the convenience of most experimental scientists, we have provided a step-by-step guide on how to use the predictor's web server (http://www.jci-bioinfo.cn/iPPBS-Opt) to get the desired results without the need to go through the complicated mathematical equations involved.
Output: molecules iPPBS-Opt: A Sequence-Based Ensemble Classifier for Identifying Protein-Protein Binding Sites by Optimizing Imbalanced Training Datasets
Background: Acute ischemic stroke (AIS) in pediatric populations accounts for more than half of pediatric strokes and is associated with significant morbidity and mortality. Pediatric AIS can present with nonspecific symptoms or symptoms that mimic alternate pathology. Case Report: A 4-month-old female presented to the emergency department for fever, decreased oral intake, and ''limp'' appearance after antibiotic administration. She was febrile, tachypneic, and hypoxic. Her skin was mottled with 3-s capillary refill, her anterior fontanelle was tense, and she had mute Babinski reflex bilaterally but was moving all extremities. The patient was hyponatremic, thrombocytopenic, and tested positive for influenza A. A computed tomography scan of the brain revealed an acute infarction involving the right frontal, parietal, temporal, and occipital lobes in addition to hyperdensities concerning for thrombosed cortical veins. The patient was transferred for specialty evaluation and was discharged 2 weeks later on levetiracetam. Why Should an Emergency Physician be Aware of This?: Pediatric AIS can present with nonspecific symptoms that mimic alternate pathology. A high level of suspicion is needed so as not to miss the diagnosis of pediatric AIS in the emergency department. A thorough neurologic assessment is warranted, and subtle abnormalities should be investigated further. Ó
Output: Clinical Communications: Pediatrics CEREBROVASCULAR ACCIDENT IN A PEDIATRIC PATIENT PRESENTING WITH INFLUENZA
In Western Europe, gastrointestinal nematodes are widespread in dairy cattle. This study was carried out to evaluate the relationship between optical density ratio (ODR) measured on bulk tank milk with an indirect Ostertagia ostertagi ELISA and reproduction/mortality parameters. Data were collected between 2008 and 2010 from monitoring carried out on 1643 dairy herds (Normandy, Western France). ODR values of 3 samples from each farm taken from November 2008 to 2010 were averaged and then transformed into a categorical variable. Reproductive and mortality data were obtained from 1444 herds using cow records from government databases. Statistical analysis was carried out using ordinary logistic regression (OLR). The outcome variables were the case-control status of a herd for reproductive factors, age at first calving and inter-calving intervals, and mortality ratios of various age classes. The effect of the categorical ODR variable was studied and several potential confounder herd factors were used to improve the model fit. A significant relationship was found between high Ostertagia ODR levels and a late age at the first calving (>34.5 months) (odds ratio (OR) = 1.94, p < 0.001). No significant relationship was observed with OLR for inter-calving intervals although bivariate analysis showed that herds with high ODR levels had longer inter-calving intervals than herds with low ODR level (first intercalving interval in herds with low vs. high ODR levels = 412 days vs. 422 days, p < 0.001; other inter-calving intervals = 408 days vs. 413 days, p < 0.01). A high ODR level was also associated with high mortality of calves between 0 and 30 days of life (mortality ratio > 6%) (OR = 1.43, p < 0.05) and between 91 and 365 days (ratio > 3%) (OR = 1.72, p < 0.01). No significant relationship was observed with multivariate approach for mortalities in other classes by age, but bivariate analysis showed that herds with high ODR level had higher mortalities than herds with low ODR levels (mortality between 31 and 90 days in herds with low vs. high ODR levels = 1.89% vs. 2.91%, p < 0.001; mortality after 365 days = 1.67% vs. 2.93%, p < 0.001). In conclusion, our results confirm the usefulness of ELISA as an indicator for production losses in dairy herds. This inexpensive tool could be advantageous, used to aid farmers and veterinarians to carry out appropriate control measures.
Output: The association between Ostertagia ostertagi antibodies in bulk tank milk samples and parameters linked to cattle reproduction and mortality
The relative bioavailability of nicotine from a nasal spray was assessed in 15 smokers suffering a common cold and rhinitis according to generally accepted criteria. The patients were given a single dose of 2 mg nicotine from the nasal spray with and without concurrent administration of a nasal vasoconstrictor decongestant, xylometazoline, in randomised order. Control session measurements were made in the disease-free state. Applying strict bioequivalence criteria, we found that common cold/rhinitis slightly reduced the bioavailability of nicotine, both in its rate and extent; the geometric mean of the ratio of Crnax , AUC and tma x were 0.81, 0.93 and 1.36, respectively. The nasal vasoconstrictor, xylometazoline, normalised the extent of the bioavailability of nicotine, but further prolonged the time for absorption to almost twice that measured in the disease-free state, increasing the tma x ratio to 1.72. The results suggest that a minor proportion of people stopping smoking with the help of a nicotine nasal spray may experience a minor reduction in the effect of the spray during common cold/rhinitis. However, the nicotine self-titration behaviour found with most smoking cessation products (except the nicotine patch) will automatically lead to an adjustment of the dosage to achieve the desired effect.
Output: Relative bioavailability of nicotine from a nasal spray in infectious rhinitis and after use of a topical decongestant
Twenty TGEV isolates were compared by sequencing a 393±414 nucleotide stretch near the 5 H end of the S gene, after ampli®cation by RT-PCR. This part of the S gene is known to show considerable variation between porcine, canine and feline coronaviruses and is completely deleted from porcine respiratory coronaviruses. The discrimination achieved by nucleotide sequence analysis was compared with that obtained by monoclonal antibody typing. The viruses could be split into several clusters, and recent isolates of TGEV from England, The Netherlands and Belgium showed the greatest differences compared to earlier reference types. However, not all viruses with unique isolation histories were distinct, suggesting either genetic stability over many years, laboratory cross-contaminations or repeated introductions of similar viruses into the ®eld. Firm conclusions on evolutionary trends cannot be drawn without obtaining a larger number of isolates, preferably from outbreaks with known epidemiological links. The sequences of some ®eld isolates from the 1980s contained both nucleotide deletions and insertions. The latter included a short sequence of fourteen nucleotides with identity to a region of the TGEV polymerase gene. Transmissible gastroenteritis (TGE) is a highly contagious pig disease that may cause serious losses, especially in unweaned piglets [17] . The causative virus, TGEV, is a member of the Coronaviridae, and has a large, single-stranded, positive sense RNA genome. The virion is enveloped, and covered in projections caused by a glycosylated spike protein (S), of approximately 200 kDa. The S protein is a major target for antibodies, and monoclonal antibodies (mAbs) have helped to de®ne four principal antigenic sites, one of which
Output: Discrimination between transmissible gastroenteritis virus isolates Brief Report
Bacterial and viral pathogens affect their eukaryotic host partly by interacting with proteins of the host cell. Hence, to investigate infection from a systems' perspective we need to construct complete and accurate host-pathogen protein-protein interaction networks. Because of the paucity of available data and the cost associated with experimental approaches, any construction and analysis of such a network in the near future has to rely on computational predictions. Specifically, this challenge consists of a number of sub-problems: First, prediction of possible pathogen interactors (e.g. effector proteins) is necessary for bacteria and protozoa. Second, the prospective host binding partners have to be determined and finally, the impact on the host cell analyzed. This review gives an overview of current bioinformatics approaches to obtain and understand host-pathogen interactions. As an application example of the methods covered, we predict host-pathogen interactions of Salmonella and discuss the value of these predictions as a prospective for further research.
Output: Computational analysis of interactomes: Current and future perspectives for bioinformatics approaches to model the host-pathogen interaction space
ForceÀdistance measurements have been used to examine differences in the interaction of the dendritic cell glycan-binding receptor DC-SIGN and the closely related endothelial cell receptor DC-SIGNR (L-SIGN) with membranes bearing glycan ligands. The results demonstrate that upon binding to membraneanchored ligand, DC-SIGNR undergoes a conformational change similar to that previously observed for DC-SIGN. The results also validate a model for the extracellular domain of DC-SIGNR derived from crystallographic studies. Force measurements were performed with DC-SIGNR variants that differ in the length of the neck that result from genetic polymorphisms, which encode different numbers of the 23-amino acid repeat sequences that constitute the neck. The findings are consistent with an elongated, relatively rigid structure of the neck repeat observed in crystals. In addition, differences in the lengths of DC-SIGN and DC-SIGNR extracellular domains with equivalent numbers of neck repeats support a model in which the different dispositions of the carbohydrate-recognition domains in DC-SIGN and DC-SIGNR result from variations in the sequences of the necks.
Output: Geometry and Adhesion of Extracellular Domains of DC-SIGNR Neck Length Variants Analyzed by ForceÀDistance Measurements
Recent studies have shown that gamma interferon (IFN-γ) synergizes with IFN-α/β to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. Since IFN response represents an early host defense event against viral infection and the fact that treatment with meliacine, a plant antiviral, ameliorate the severity of the herpetic infection in female mice infected intravaginally with HSV-2, we wanted to investigate whether the administration of meliacine to HSV-2 infected mice could altered the homoestasis of IFNs host response. For this purpose we studied the effect of the compound 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), which is the responsible for meliacine antiviral action, on the HSV-2 inhibition exerted by IFN α, IFN-γ or their combination. We have found that like HSV-1, IFN-γ synergizes with IFN-α to inhibit HSV-2 replication in Vero cells. While treatment with IFN-α or IFN-γ alone has weak antiviral action, HSV-2 plaque formation, viral replication and the onset of viral CPE in Vero cells are synergistically inhibited by interferon combination. In addition, CDM treatment contributes to protect cells from virus cytopathic effect and causes a strong inhibition of HSV-2 titer. Moreover, the presence of CDM for 2 h before IFN induction, during the 16 h induction period, only for 24 h after infection or during the complete IFN treatment period, reduces virus yields in an additive way without affecting IFN antiviral action. The results reported here indicated that the presence of CDM did not alter the antiviral activity of IFN-α, IFN-γ or the synergism exerted by their combination. As a result we can envision that the administration of CDM in vivo could not affect the biological activity of IFNs, which are so important mediators of the innate resistance to HSV-2 infection.
Output: Virology Journal The synergistic effect of IFN-α and IFN-γ against HSV-2 replication in Vero cells is not interfered by the plant antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin
Understanding the environmental drivers of zoonotic reservoir and human interactions is crucial to understanding disease risk, but these drivers are poorly predicted. We propose a mechanistic understanding of human-reservoir interactions, using hantavirus pulmonary syndrome as a case study. Crucial processes underpinning the disease's incidence remain poorly studied, including the connectivity among natural and peridomestic deer mouse host activity, virus transmission, and human exposure. We found that disease cases were greatest in arid states and declined exponentially with increasing precipitation. Within arid environments, relatively rare climatic conditions (e.g., El Niño) are associated with increased rainfall and reservoir abundance, producing more frequent virus transmission and host dispersal. We suggest that deer mice increase their occupancy of peridomestic structures during spring-summer, amplifying intraspecific transmission and human infection risk. Disease incidence in arid states may increase with predicted climatic changes. Mechanistic approaches incorporating reservoir behavior, reservoir-human interactions, and pathogen spillover could enhance our understanding of global hantavirus ecology, with applications to other directly transmitted zoonoses.
Output: Toward a Mechanistic Understanding of Environmentally Forced Zoonotic Disease Emergence: Sin Nombre Hantavirus
Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a novel coronavirus and causing worldwide outbreaks. SARS coronavirus (SARS-CoV) is an enveloped RNA virus, which contains several structural proteins. Among these proteins, spike (S) protein is responsible for binding to specific cellular receptors and is a major antigenic determinant, which induces neutralizing antibody. In order to analyze the antigenicity and receptor-binding ability of SARS-CoV S protein, we expressed the S protein in Escherichia coli using a pET expression vector. After the isopropyl-b-D D -thiogalactoside induction, S protein was expressed in the soluble form and purified by nickel-affinity chromatography to homogeneity. The amount of S protein recovered was 0.2-0.3 mg/100 ml bacterial culture. The S protein was recognized by sera from SARS patients by ELISA and Western blot, which indicated that recombinant S protein retained its antigenicity. By biotinylated ELISA and Western blot using biotinlabeled S protein as the probe, we identified 130-kDa and 140-kDa proteins in Vero cells that might be the cellular receptors responsible for SARS-CoV infection. Taken together, these results suggested that recombinant S protein exhibited the antigenicity and receptor-binding ability, and it could be a good candidate for further developing SARS vaccine and anti-SARS therapy.
Output: Antigenicity and receptor-binding ability of recombinant SARS coronavirus spike protein
Treatment guidelines for acute rhinosinusitis (RS) recommend the use of intranasal corticosteroids (INSs) as monotherapy or adjunctive therapy. However, the adverse event (AE) profiles of oral glucocorticoids, which result largely from the systemic absorption of those agents, have engendered concerns about the safety of INSs. These concerns persist for INSs despite significant or marked clinical differences between them and systemic corticosteroids in systemic absorption and among the INSs in bioavailability, mechanism of action, and lipophilicity, which may contribute to differences in AEs. For example, the systemic bioavailability of the INSs as a percentage of the administered drug is less than 0.1% for mometasone furoate, less than 1% for fluticasone propionate, 46% for triamcinolone acetonide, and 44% for beclomethasone dipropionate. A review of the safety profiles of INSs, as reported in clinical trials in acute and chronic RS and allergic rhinitis, shows primarily local AEs (eg, epistaxis and headache) that are generally classified as mild to moderate, with occurrence rates that are similar to those with placebo. Studies of the safety of mometasone furoate, fluticasone propionate, budesonide, and triamcinolone acetonide did not identify any evidence of systemic AEs, such as growth retardation in children due to suppression of the hypothalamicpituitary-adrenal axis, bone mineral density loss, or cataracts, which suggests that INSs can be safely administered in patients with acute RS without concern for systemic AEs.
Output: Current review Safety of intranasal corticosteroids in acute rhinosinusitis
High-density lipoproteins (HDL) are nanoparticles with >80 associated proteins, phospholipids, cholesterol and cholesteryl esters. A comprehensive genetic analysis of the regulation of proteome of HDL isolated from a panel of 100 diverse inbred strains of mice, Hybrid Mouse Diversity Panel (HMDP), revealed widely varied HDL protein levels across the strains. Some of this variation was explained by local, cis-acting regulation, termed cis-protein quantitative trait loci. Variations in apolipoprotein A-II and apolipoprotein C-3 affected the abundance of multiple HDL proteins indicating a coordinated regulation. We identified modules of co-varying proteins and define a protein-protein interaction network describing the protein composition of the naturally occurring subspecies of HDL in mice. Sterol efflux capacity varied up to 3-fold across the strains and HDL proteins displayed distinct correlation patterns with macrophage and ABCA1 specific cholesterol efflux capacity and cholesterol exchange, suggesting that subspecies of HDL participate in discrete functions. The baseline and stimulated sterol efflux capacity phenotypes associated with distinct QTLs with smaller effect size suggesting a multi genetic regulation. Our results highlight the complexity of HDL particles by revealing high degree of heterogeneity and intercorrelation, some of which is associated with functional variation, supporting the concept that HDL-cholesterol alone is not an accurate measure of HDL's properties such as protection against CAD.
Output: Genetic control of the HDL proteome
as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K d ) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs. Hepatitis E virus (HEV) is the causative pathogen of Hepatitis E disease, a major form of acute viral hepatitis worldwide. Four different genotypes are known in various geographical regions 1 : genotype 1 (Asia), genotype 2 (Africa and Mexico), genotype 3 (Europe and North America) and genotype 4 (Asia). The global burden of genotype 1 and 2 infections is substantial and the number of infections is estimated at 20 million per year, leading to 70,000 deaths and 3,000 stillbirths 2 . The Hepatitis E virus is a single strand plus RNA virus belonging to the family Hepeviridae. Approximately 7,200 nucleotides encode for three open reading frames (Fig. 1 ). ORF1 is a nonstructural, functional poly-protein with several defined functions 3,4 . The first functional domain encodes a methyltransferase (Met), which is required for capping the 5′ end of the HEV RNA. Next, ORF1 contains a so-called Y domain which shows significant similarities to sequences of Rubella virus and Beet necrotic yellow vein virus but whose function in the viral context remains unknown. Further downstream ORF1 contains a papain-like cysteine protease (Plp) domain. The functionality of the protease domain was often questioned but recently the processing of the ORF1 poly-protein and ORF2 capsid protein by the Plp protease has been confirmed 5 . Next, a hypervariable (V) proline-rich region is located between the putative protease domain and the subsequent so-called X domain (X). For the proline-rich domain an important role in the fine tuning of viral replication through protein-protein interactions (PPIs) has been postulated 6 . The above mentioned X domain is also known as macro-domain or ADP-Ribose binding domain and has been exclusively associated with viral protease domains in other viruses. Towards the 3′ end, ORF1 encodes for the well characterized helicase
Output: The Hepatitis E virus intraviral interactome
Pathogens that spill over between species cause a significant human and animal health burden. Here, we describe characteristics of animal reservoirs that are required for pathogen spillover. We assembled and analyzed a database of 330 disease systems in which a pathogen spills over from a reservoir of one or more species. Three-quarters of reservoirs included wildlife, and 84% included mammals. Further, 65% of pathogens depended on a community of reservoir hosts, rather than a single species, for persistence. Among mammals, the most frequently identified reservoir hosts were rodents, artiodactyls, and carnivores. The distribution among orders of mammalian species identified as reservoirs did not differ from that expected by chance. Among disease systems with high priority pathogens and epidemic potential, we found birds, primates, and bats to be overrepresented. We also analyzed the life history traits of mammalian reservoir hosts and compared them to mammals as a whole. Reservoir species had faster life history characteristics than mammals overall, exhibiting traits associated with greater reproductive output rather than long-term survival. Thus, we find that in many respects, reservoirs of spillover pathogens are indeed special. The described patterns provide a useful resource for studying and managing emerging infectious diseases.
Output: Are disease reservoirs special? Taxonomic and life history characteristics
Background. Annually, Saudi Arabia is the host of the Hajj mass gathering. We aimed to determine the Middle East respiratory syndrome coronavirus (MERS-CoV) nasal carriage rate among pilgrims performing the 2013 Hajj and to describe the compliance with the Saudi Ministry of Health vaccine recommendations. Method. Nasopharyngeal samples were collected from 5235 adult pilgrims from 22 countries and screened for MERS-CoV using reverse transcriptase-polymerase chain reaction. Information regarding the participants' age, gender, country of origin, medical conditions, and vaccination history were obtained. Results. The mean age of the screened population was 51.8 years (range, 18-93 years) with a male/female ratio of 1.17:1. MERS-CoV was not detected in any of the samples tested (3210 pre-Hajj and 2025 post-Hajj screening). According to the vaccination documents, all participants had received meningococcal vaccination and the majority of those from at-risk countries were vaccinated against yellow fever and polio. Only 22% of the pilgrims (17.5% of those ≥65 years and 36.3% of diabetics) had flu vaccination, and 4.4% had pneumococcal vaccination. Conclusion. There was no evidence of MERS-CoV nasal carriage among Hajj pilgrims. While rates of compulsory vaccinations uptake were high, uptake of pneumococcal and flu seasonal vaccinations were low, including among the high-risk population.
Output: Ministry of Health, Jeddah, 4 Saudi Aramco Medical Services Organization, Dhahran, Kingdom of Saudi Arabia; 5 Indiana University School of Medicine, Indianapolis; 6 Special Infectious Diseases Unit
The genome sequence of Catopsilia pomona nucleopolyhedrovirus (CapoNPV) was determined by the Roche 454 sequencing system. The genome consisted of 128,058 bp and had an overall G+C content of 40%. There were 130 hypothetical open reading frames (ORFs) potentially encoding proteins of more than 50 amino acids and covering 92% of the genome. Among all the hypothetical ORFs, 37 baculovirus core genes, 23 lepidopteran baculovirus conserved genes and 10 genes conserved in Group I alphabaculoviruses were identified. In addition, the genome included regions of 8 typical baculoviral homologous repeat sequences (hrs). Phylogenic analysis showed that CapoNPV was in a distinct branch of clade "a" in Group I alphabaculoviruses. Gene parity plot analysis and overall similarity of ORFs indicated that CapoNPV is more closely related to the Group I alphabaculoviruses than to other baculoviruses. Interesting, CapoNPV lacks the genes encoding the fibroblast growth factor (fgf) and ac30, which are conserved in most lepidopteran and Group I baculoviruses, respectively. Sequence analysis of the F-like protein of CapoNPV showed that some amino acids were inserted into the fusion peptide region and the pre-transmembrane region of the protein. All these unique features imply that CapoNPV represents a member of a new baculovirus species. 4 / 12 Fig 4. Sequence alignment of CapoNPV hrs. Black background shows greater than 80% identity among compared regions, dark gray and light gray shows greater than 50% and 30% identity, respectively. Palindromes are indicated below the alignments. * The CapoNPV hypothetical unique genes (capo31, capo35, capo78 and capo106) are not included.
Output: Genome Sequencing and Analysis of Catopsilia pomona nucleopolyhedrovirus: A Distinct Species in Group I Alphabaculovirus