niryuu/sni-each-converted huggingface dataset:
Background: Antimicrobial resistance is an under-appreciated threat to public health in nations around the globe. With globalization booming, it is important to understand international patterns of resistance. If countries already experience similar patterns of resistance, it may be too late to worry about international spread. If large countries or groups of countries that are likely to leap ahead in their integration with the rest of the world -China being the standout case -have high and distinctive patterns of resistance, then a coordinated response could substantially help to control the spread of resistance. The literature to date provides only limited evidence on these issues. We study the recent patterns of antibiotic resistance in three geographically separated, and culturally and economically distinct countries -China, Kuwait and the United States -to gauge the range and depth of this global health threat, and its potential for growth as globalization expands. Our primary measures are the prevalence of resistance of specific bacteria to specific antibiotics. We also propose and illustrate methods for aggregating specific "bug-drug" data. We use these aggregate measures to summarize the resistance pattern for each country and to study the extent of correlation between countries' patterns of drug resistance. We find that China has the highest level of antibiotic resistance, followed by Kuwait and the U.S. In a study of resistance patterns of several most common bacteria in China in 1999 and 2001, the mean prevalence of resistance among hospital-acquired infections was as high as 41% (with a range from 23% to 77%) and that among community-acquired infections was 26% (with a range from 15% to 39%). China also has the most rapid growth rate of resistance (22% average growth in a study spanning 1994 to 2000). Kuwait is second (17% average growth in a period from 1999 to 2003), and the U.S. the lowest (6% from 1999 to 2002). Patterns of resistance across the three countries are not highly correlated; the most correlated were China and Kuwait, followed by Kuwait and the U.S., and the least correlated pair was China and the U.S. Antimicrobial resistance is a serious and growing problem in all three countries. To date, there is not strong international convergence in the countries' resistance patterns. This finding may change with the greater international travel that will accompany globalization. Future research on the determinants of drug resistance patterns, and their international convergence or divergence, should be a priority.
Output: Globalization and Health Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States
Host-pathogen interactions provide a fascinating example of two or more active genomes directly exerting mutual influence upon each other. These encounters can lead to multiple outcomes from symbiotic homeostasis to mutual annihilation, undergo multiple cycles of latency and lysogeny, and lead to coevolution of the interacting genomes. Such systems pose numerous challenges but also some advantages to modeling, especially in terms of functional, mathematical genome representations. The main challenges for the modeling process start with the conceptual definition of a genome for instance in the case of hostintegrated viral genomes. Furthermore, hardly understood influences of the activity of either genome on the other(s) via direct and indirect mechanisms amplify the needs for a coherent description of genome activity. Finally, genetic and local environmental heterogeneities in both the host's cellular and the pathogen populations need to be considered in multiscale modeling efforts. We will review here two prominent examples of host-pathogen interactions at the genome level, discuss the current modeling efforts and their shortcomings, and explore novel ideas of representing active genomes which promise being particularly adapted to dealing with the modeling challenges posed by host-pathogen interactions.
Output: Critical Dynamics in Host-Pathogen Systems
The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and 78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003 (9.40 ± 7.83)% to 2004 (3.20 ± 4.78)% (P < 0.001) and remained stable thereafter until 2018 (4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio (FEV 1 /FVC %, t = 2.21, P = 0.04) and mid-flow of maximum expiration (FEF 25%-75% , t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003 (38.83 ± 21.01)% to 2005 (30.38 ± 20.23)% (P = 0.000 2), then declined slowly from 2005 to 2013 (28.99 ± 20.59)% and plateaued until 2018 (25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible. Bone Research (2020) 8:8 ; https://doi.
Output: Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study
Ethnopharmacological relevance: Pelargonium sidoides DC. (Geraniaceae), a popular medicinal plant used in traditional medicine in the treatment of gastrointestinal ailments has been transformed into a phytopharmaceutical (EPs s 7360) for treating respiratory tract infections. The increasing international demand for Pelargonium sidoides has led to localised overexploitation of its wild populations in southern Africa. The aim of the review is to provide a synthesis of the current state of scientific knowledge on the phytochemical, pharmacological and toxicological properties of Pelargonium sidoides as well as the potential role of plant biotechnology in its conservation. The review highlights knowledge gaps in these research areas. Materials and Methods: A comprehensive literature search involving mainly electronic and library sources of information were used to collate and synthesise published data. Results: Experimental results from in vitro studies indicate that bioactive phytochemical constituents of Pelargonium sidoides may not possess a direct antimicrobial effect, but instead act by interfering with microbial binding to host cell receptors, inhibition of key enzymes and the production of antimicrobial effector molecules such as nitric oxide and interferons (IFNs) by the host cells. Furthermore, clinical evaluations in randomised, double-blind, placebo-controlled trials have demonstrated the beneficial effect of Pelargonium sidoides in the treatment of respiratory tract infections with few side effects. However, there is lack of adequate information on the safety evaluation of the plant. On the other hand, the increasing demand for Pelargonium sidoides has led to localised illegal harvesting of wild plants. Conclusions: Pharmacological data reported in literature suggest that Pelargonium sidoides shows a beneficial effect in the treatment of respiratory tract infections. However, more studies are required to elucidate the mode of action of the active constituents exhibited in the treatment of respiratory tract infections and other health conditions caused by microbial attack. Furthermore, the pharmacological usefulness of Pelargonium sidoides must take cognisance of the broader context involving the need for conservation-friendly approaches in its utilisation. In this regard, plant biotechnology applications can play a meaningful role in a holistic conservation strategy.
Output: Medicinal properties and conservation of Pelargonium sidoides DC
Common marmoset (Callithrix jacchus) is emerging as a clinically relevant nonhuman primate model for various diseases, but is hindered by the availability of marmoset cell lines, which are critical for understanding the disease pathogenesis and drug/toxicological screening prior to animal testing. Here we describe the generation of immortalized marmoset hepatic progenitor cells (MHPCs) by lentivirus-mediated transfer of the simian virus 40 large T antigen gene in fetal liver polygonal cells. MHPCs proliferate indefinitely in vitro without chromosomal alteration and telomere shortening. These cells possess hepatic progenitor cell-specific gene expression profiles with potential to differentiate into both hepatocytic and cholangiocytic lineages in vitro and in vivo and also can be genetically modified. Importantly, injected MHPCs repopulated the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice with hepatocyte-like cells. MHPCs also engraft as cholangiocytes into bile ducts of 3,5-diethoxycarbonyl-1,4dihydrocollidine (DDC)-induced bile ductular injured mice. MHPCs provide a tool to enable efficient derivation and genetic modification of both hepatocytes and cholangiocytes for use in disease modeling, tissue engineering, and drug screening.
Output: Immortalized common marmoset (Callithrix jacchus) hepatic progenitor cells possess bipotentiality in vitro and in vivo
In order to predict pathogen emergence, we must distinguish between emergence phenomena that occur via different processes. Focusing on the appearance of viral pathogens in new host species, I outline a framework that uses specific molecular characteristics to rank virus families by their expected a priori ability to complete each of three steps in the emergence process (encounter, infection, and propagation). I then discuss the degree to which the patterns expected, based solely on molecular-level structural characteristics, agree with observations regarding the ability of animal viruses to infect humans. This approach yields predictions consistent with empirical observations regarding the ability of specific viral families to infect novel host species but highlights the need for consideration of other factors, such as the ecology of host interactions and the determinants of cellular susceptibility and permissivity to specific virus groups, when trying to predict the frequency with which a virus will encounter a novel host species or the probability of propagation within a novel host species once infection has occurred.
Output: Viral Host Jumps: Moving toward a Predictive Framework
Canine Monocytic Ehrlichiosis (CME) is a serious tick-borne rickettsial disease affecting canine populations globally. Besides few reports from stray and pet dogs from localised geographical regions (cities/towns/small states), a comprehensive study on prevalence of Ehrlichia canis (E. canis) among working dogs from different geoclimatic zones of India was pertinently lacking. Study of CME among these dog populations was thus carried out, encompassing clinical aspects and different diagnostic methodologies viz., microscopy, serology and molecular biology. During the two-year study period, clinical specimens from 225 cases suspected of canine ehrlichiosis were examined for clinical pathology and presence of the haemoparasites. Overall prevalence of ehrlichiosis by microscopic examination, commercial dot-ELISA kit and nested PCR assay was estimated to be 1.3%, 19.1% and 5.8%, respectively, which were found to be statistically significant by McNemar Chi squared test (p < 0.05). It was also observed that possibly due to widespread use of doxycycline therapy in field, CME presently does not remain a potential threat which it uses to pose earlier. However, concurrent infections of E. canis and Babesia gibsoni were found to be mostly fatal. Keeping in view of high number of apparently healthy dogs (24) out of total positive cases (46) observed during the study, it is recommended that prevalence studies on CME should also involve screening of apparently healthy dogs. Phylogenetic analysis carried on partial sequencing of 16S rRNA of E. canis strains revealed that all of the Indian strains clustered in a single clade with other E. canis species from India and rest of the world. Molecular divergence was observed among the sequences of Brazilian and American isolates which were also included in the present study. These findings have thus opened a new paradigm for planning of pragmatic control strategies against CME.
Output: Canine Monocytic Ehrlichiosis among working dogs of organised kennels in India: A comprehensive analyses of clinico-pathology, serological and molecular epidemiological approach
Coronaviruses are the etiological agents of respiratory and enteric diseases in humans and livestock, exemplified by the life-threatening severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV). However, effective means for combating coronaviruses are still lacking. The interaction between nonstructural protein (nsp) 10 and nsp16 has been demonstrated and the crystal structure of SARS-CoV nsp16/10 complex has been revealed. As nsp10 acts as an essential trigger to activate the 2 -O-methyltransferase activity of nsp16, short peptides derived from nsp10 may have inhibitory effect on viral 2 -O-methyltransferase activity. In this study, we revealed that the domain of aa 65-107 of nsp10 was sufficient for its interaction with nsp16 and the region of aa 42-120 in nsp10, which is larger than the interaction domain, was needed for stimulating the nsp16 2 -O-methyltransferase activity. We further showed that two short peptides derived from the interaction domain of nsp10 could inhibit the 2 -O-methyltransferase activity of SARS-CoV nsp16/10 complex, thus providing a novel strategy and proof-of-principle study for developing peptide inhibitors against SARS-CoV.
Output: Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2 -O-methyltransferase activity of nsp10/nsp16 complex
Many acute infectious pulmonary diseases have incubation periods that are long enough for travelers to have symptoms after returning home to a health-care system that is not familiar with "foreign" infections. Respiratory infections have a relatively limited repertoire of clinical manifestations, so that there is often nothing characteristic enough about a specific infection to make the diagnosis obvious. Thus, the pathway to the diagnosis of infections that are not endemic in a region relies heavily on taking a thorough history of both itinerary and of specific exposures. One important caveat is that on occasion, the history of a recent trip creates an element of "tunnel vision" in the evaluating health-care provider. It is tempting to relate a person's problem to that recent trip; however, when evaluating recent returnees, it is always important to remember that the travel may have nothing to do with the patient's presentation. Recent travel may add diagnostic considerations to the list of possibilities, but an astute clinician must not disregard the possibility that the patient's illness has nothing to do with the recent trip. (CHEST 2008; 134:163-171) 
Output: Acute Respiratory Infections in a Recently Arrived Traveler to Your Part of the World*
A new Molecularly Imprinted Solid Phase Extraction (MISPE) protocol was developed for the selective extraction and purification of glycyrrhizic acid (GL) from liquorice roots. Non-covalent MIP were synthesized using methacrylic acid (MAA), 2-(dimethylamino)ethyl methacrilate (DMAEM) or 2-hydroxyethylmetacrylate (HEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. After the evaluation of the selectivity of the GL imprinted polymers, the performance of these materials as Solid Phase Extraction (SPE) sorbents was investigated. MIP having HEMA as functional monomer were found to be able to selectively extract almost 80% of GL content in liquorice roots. The proposed MISPE-HPLC procedure has good precision, thus it can be successfully used for the purification of GL from natural sources.
Output: Molecularly imprinted polymers for the selective extraction of glycyrrhizic acid from liquorice roots
Virus attachment to host cells is mediated by dedicated virion proteins, which specifically recognize one or, at most, a limited number of cell surface molecules. Receptor binding often involves protein-protein interactions, but carbohydrates may serve as receptor determinants as well. In fact, many different viruses use members of the sialic acid family either as their main receptor or as an initial attachment factor. Sialic acids (Sias) are 9-carbon negativelycharged monosaccharides commonly occurring as terminal residues of glycoconjugates. They come in a large variety and are differentially expressed in cells and tissues. By targeting specific Sia subtypes, viruses achieve host cell selectivity, but only to a certain extent. The Sia of choice might still be abundantly present on non-cell associated molecules, on non-target cells (including cells already infected) and even on virus particles themselves. This poses a hazard, as high-affinity virion binding to any of such "false" receptors would result in loss of infectivity. Some enveloped RNA viruses deal with this problem by encoding virionassociated receptor-destroying enzymes (RDEs). These enzymes make the attachment to Sia reversible, thus providing the virus with an escape ticket. RDEs occur in two types: neuraminidases and sialate-O-acetylesterases. The latter, originally discovered in influenza C virus, are also found in certain nidoviruses, namely in group 2 coronaviruses and in toroviruses, as well as in infectious salmon anemia virus, an orthomyxovirus of teleosts. Here, the structure, function and evolution of viral sialate-O-acetylesterases is re-R.J.d. Groot ( ) Virology Section,
Output: Structure, function and evolution of the hemagglutinin-esterase proteins of corona-and toroviruses
Accumulating evidence suggests that extracellular α-synuclein (eSNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) or related synucleinopathies by inducing neurotoxicity directly or indirectly via microglial or astroglial activation. However, the mechanisms by which this occurs remain to be characterized. To explore these mechanisms, we combined three biochemical techniques -Stable Isotope Labeling of Amino acid in Cell cultures (SILAC); biotin labeling of plasma membrane proteins followed by affinity purification; and analysis of unique proteins binding to SNCA peptides on membrane arrays. The SILAC proteomic analysis identified 457 proteins, of which, 245 or 172 proteins belonged to membrane or membrane associated proteins, depending on the various bioinformatics tools used for interpretation. In dopamine neuronal cells treated with eSNCA, the levels of 86 membrane proteins were increased and 35 were decreased compared with untreated cells. In peptide array analysis, 127 proteins were identified as possibly interacting with eSNCA. Of those, seven proteins were overlapped with the membrane proteins that displayed alterations in relative abundance after eSNCA treatment. One was ciliary neurotrophic factor receptor alpha (CNTFRα), which appeared to modulate eSNCA-mediated neurotoxicity via mechanisms related to JAK1/ STAT3 signaling but independent of eSNCA endocytosis.
Output: Identification of ciliary neurotrophic factor receptor alpha as a mediator of neurotoxicity induced by α-synuclein
Several polypeptide products of MHV-A59 ORF 1 a were characterized in MHV-A59 infected DBT cells, using antisera directed against fusion proteins encoded in the first 6.5 kb of ORFla. These included the previously identified N-terminal ORF 1 a product, ~28, as well as 290-, 240-, and 50-kDa polypeptides. P28 was always detected as a discrete band without larger precursors, suggesting rapid cleavage of p28 immediately after its synthesis. Once p28 was cleaved there was little degradation of the protein over a 2-hr period. The intracellular cleavage of p28 was not inhibited by the protease inhibitor leupeptin, in contrast to results obtained during in vitro translation of genome RNA (Denison and Perlman, 1986). These data suggest that different protease activities may be responsible for the cleavage of p28 in vitro and in Go. The 290-kDa protein was an intermediate cleavage product derived from a precursor of greater than 400 kDa. The 290-kDa product was subsequently cleaved into secondary products of 50 and 240 kDa. The intracellular cleavage of the 290-kDa polypeptide was inhibited by leupeptin at concentrations which did not inhibit the early cleavage of p28 or the cleavage of the 290-kDa product from its larger polyprotein precursor. In the presence of zinc chloride, a product of >320 kDa was detected, which appears to incorporate p28 at its amino terminus. This suggests that at least two protease activities may be necessary for processing of ORFl a proteins, one of which cleaves p28 and is sensitive to zinc chloride but resistant to leupeptin, and the other which cleaves the 290-kDa precursor and is sensitive to both inhibitors. Both the 290-and 240-kDa proteins should contain sequences predicted to encode two papain-like prOtesS? activities. 0 1992 Academic PVE.S. Inc.
Output: Intracellular Processing of the N-Terminal ORF la Proteins of the Coronavirus MHV-A59 Requires Multiple Proteolytic Events
Insults to the alveoli usually lead to inefficient gas exchange or even respiratory failure, which is difficult to model in animal studies. Over the past decade, stem cell-derived self-organizing three-dimensional organoids have emerged as a new avenue to recapitulate respiratory diseases in a dish. Alveolar organoids have improved our understanding of the mechanisms underlying tissue homeostasis and pathological alterations in alveoli. From this perspective, we review the state-of-the-art technology on establishing alveolar organoids from endogenous lung epithelial stem/progenitor cells or pluripotent stem cells, as well as the use of alveolar organoids for the study of respiratory diseases, including idiopathic pulmonary fibrosis, tuberculosis infection, and respiratory virus infection. We also discuss challenges that need to be overcome for future application of alveolar organoids in individualized medicine.
Output: Organoids as a Powerful Model for Respiratory Diseases
The lion Panthera leo is one of the world's most charismatic carnivores and is one of Africa's key predators. Here, we used a large dataset from 357 lions comprehending 1.13 megabases of sequence data and genotypes from 22 microsatellite loci to characterize its recent evolutionary history. Patterns of molecular genetic variation in multiple maternal (mtDNA), paternal (Y-chromosome), and biparental nuclear (nDNA) genetic markers were compared with patterns of sequence and subtype variation of the lion feline immunodeficiency virus (FIV Ple ), a lentivirus analogous to human immunodeficiency virus (HIV). In spite of the ability of lions to disperse long distances, patterns of lion genetic diversity suggest substantial population subdivision (mtDNA W ST = 0.92; nDNA F ST = 0.18), and reduced gene flow, which, along with large differences in seroprevalence of six distinct FIV Ple subtypes among lion populations, refute the hypothesis that African lions consist of a single panmictic population. Our results suggest that extant lion populations derive from several Pleistocene refugia in East and Southern Africa (,324,000-169,000 years ago), which expanded during the Late Pleistocene (,100,000 years ago) into Central and North Africa and into Asia. During the Pleistocene/Holocene transition (,14,000-7,000 years), another expansion occurred from southern refugia northwards towards East Africa, causing population interbreeding. In particular, lion and FIV Ple variation affirms that the large, well-studied lion population occupying the greater Serengeti Ecosystem is derived from three distinct populations that admixed recently. This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Output: The Evolutionary Dynamics of the Lion Panthera leo Revealed by Host and Viral Population Genomics
The recent coronavirus pandemic follows in its early stages an almost exponential expansion, with the number of cases as a function of time reasonably well fit by N (t) ∝ e αt , in many countries. We analyze the rate α in different countries, choosing as a starting point in each country the first day with 30 cases and fitting for the following 12 days, capturing thus the early exponential growth in a rather homogeneous way. We look for a link between the rate α and the average temperature T of each country, in the month of the epidemic growth. We analyze a base set of 42 countries, which developed the epidemic earlier, and an extended set of 88 countries, which developed the epidemic more recently. Fitting with a linear behavior α(T ), we find evidence in both datasets for a decreasing growth rate as a function of T , at 99.66%C.L. and 99.86%C.L. in the base and extended dataset, respectively. In the base set, going beyond a linear model, a peak at about (7.7 ± 3.6) • C seems to be present in the data. Our findings give hope that, for northern hemisphere countries, the growth rate should significantly decrease as a result of both warmer weather and lockdown policies. In general the propagation should be hopefully stopped by strong lockdown, testing and tracking policies, before the arrival of the next cold season. I.
Output: Temperature dependence of COVID-19 transmission
Transmissible gastroenteritis virus (TGEV) replicates in the small intestine and induces enteritis and watery diarrhea. Establishment of local immunity in the intestine would thus prevent TGEV transmission. CpG DNA has been reported as a promising mucosal adjuvant in some animals. The effects of oral immunization of CpG DNA together with inactivated TGEV (ITGEV) were investigated in this study. Pigs (6 weeks old) were orally immunized with ITGEV plus CpG DNA. The TGEV-specific IgA level in the intestinal tract and the TGEV-specific IgG level in serum significantly increased following immunization with ITGEV plus CpG DNA (P ≤ 0.05). Moreover, populations of IgA-secreting cells, CD3+ T lymphocytes and intraepithelial lymphocytes (IELs), in the intestine increased significantly after immunization with ITGEV plus CpG DNA (P ≤ 0.05). Furthermore, the expression of IL-6, IL-12 and interferon-␥ (IFN-␥) in ligated intestine segments increased significantly after injection with ITGEV plus CpG DNA (P ≤ 0.05). Taken together, these data suggest that oral immunization of ITGEV plus CpG DNA elicits a local immune response. Further studies are required to determine whether this immunity provides protection against TGEV in pigs.
Output: CpG DNA facilitate the inactivated transmissible gastroenteritis virus in enhancing the local and systemic immune response of pigs via oral administration
Background: To our knowledge, no studies to date demonstrate potential spread of microbes during actual emergency medical service (EMS) activities. Our study introduces a novel approach to identification of contributors to EMS environment contamination and development of infection control strategies, using a bacteriophage surrogate for pathogenic organisms. Methods: Bacteriophage FX174 was used to trace cross-contamination and evaluate current disinfection practices and a hydrogen peroxide (H 2 O 2 ) wipe intervention within emergency response vehicles. Prior to EMS calls, 2 surfaces were seeded with FX174. On call completion, EMS vehicle and equipment surfaces were sampled before decontamination, after decontamination per current practices, and after implementation of the intervention. Results: Current decontamination practices did not significantly reduce viral loads on surfaces (P ¼ .3113), but H 2 O 2 wipe intervention did (P ¼ .0065). Bacteriophage spread to 56% (27/48) of sites and was reduced to 54% (26/48) and 40% (19/48) with current decontamination practices and intervention practices, respectively. Conclusion: Results suggest firefighters' hands were the main vehicles of microbial transfer. Current practices were not consistently applied or standardized and minimally reduced prevalence and quantity of microbial contamination on EMS surfaces. Although use of a consistent protocol of H 2 O 2 wipes significantly reduced percent prevalence and concentration of viruses, training and promotion of surface disinfection should be provided.
Output: Spread of infectious microbes during emergency medical response
Background: Bacterial colonisation of the respiratory tract is commonly described and usually thought to be of no clinical significance. The aim of this study was to examine the presence and significance of bacteria and viruses in the upper respiratory tract of healthcare workers (HCWs), and association with respiratory symptoms. Methods: A prospective cohort study was conducted in China and 223 HCWs were recruited from fever clinics and respiratory, paediatric, emergency/Intensive medication wards. Participants were followed over 4 weeks (7th May 2015 to 4th June 2015) for development of clinical respiratory illness (CRI). Nasopharyngeal swabs were obtained at baseline and at the end of the study. The primary endpoints were laboratory-confirmed bacterial colonisation and viral respiratory infection. Rates of the following infections in symptomatic and asymptomatic participants were compared at the start or end of the study; 1) all bacterial/viral infections, 2) bacterial infection and bacterial-viral co-infections, excluding virus only infections, and 3) only bacterial infections. Results: Bacterial colonisation was identified in 88% (196/223) of participants at the start or end of the study. Among these participants, 66% (148/223) had only bacterial colonisation while 22% (48/223) had co-infection with a virus. Bacteria were isolated from 170 (76.2%) participants at baseline and 127 (57%) participants at the end of the study. Laboratory confirmed viral infections were identified in 53 (23.8%) participants -35 (15.7%) at the baseline and 20 (9.0%) at the end of the study. CRI symptoms were recorded in 12 participants (4.5%) and all had a positive bacterium isolation at baseline (n = 11) or end of the study (n = 1). Among asymptomatic participants, 187 (87%) had bacterial colonisation or bacterial/viral co-infection at baseline or end of the study. Viruses were also isolated from 5 (2.4%) asymptomatic cases. Rates of all infection outcomes were higher in symptomatic participants, however differences were not statistically significant. Conclusion: We isolated high rates of bacteria and viruses in the upper respiratory tract of hospital HCWs, which may reflect greater exposure to respiratory infections in the hospital. Although respiratory infections are mostly symptomatic, the association between bacterial colonization and symptomatic illness is not clear. In the healthcare setting, HCWs may acquire and transmit infection to patients and other HCWs around them. Larger studies are required to explore ongoing occupational risk of respiratory infection in hospitals HCWs.
Output: Viral and bacterial upper respiratory tract infection in hospital health care workers over time and association with symptoms
The increased number of outbreaks of H5 and H7 LPAI and HPAI viruses in poultry has major public and animal health implications. The continuous rapid evolution of these subtypes and the emergence of new variants influence the ability to undertake effective surveillance. Retroviral pseudotypes bearing influenza haemagglutinin (HA) and neuraminidase (NA) envelope glycoproteins represent a flexible platform for sensitive, readily standardized influenza serological assays. We describe a multiplex assay for the study of neutralizing antibodies that are directed against both influenza H5 and H7 HA. This assay permits the measurement of neutralizing antibody responses against two antigenically distinct HAs in the same serum/plasma sample thus increasing the amount and quality of serological data that can be acquired from valuable sera. Sera obtained from chickens vaccinated with a monovalent H5N2 vaccine, chickens vaccinated with a bivalent H7N1/H5N9 vaccine, or turkeys naturally infected with an H7N3 virus were evaluated in this assay and the results correlated strongly with data obtained by HI assay. We show that pseudotypes are highly stable under basic cold-chain storage conditions and following multiple rounds of freeze-thaw. We propose that this robust assay may have practical utility for in-field serosurveillance and vaccine studies in resource-limited regions worldwide.
Output: Multiplex Evaluation of Influenza Neutralizing Antibodies with Potential Applicability to In-Field Serological Studies
Executive summary Suicide mortality Suicide attempts Health system and societal risk factors Community and relationship risk factors What protects people from the risks of suicide? The current situation in suicide prevention What are countries doing about suicide prevention now? Current legal status of suicide around the world and perspectives for change How can countries create a comprehensive national strategy and why is it useful? How can progress be tracked when evaluating a national suicide prevention strategy? The cost and cost-effectiveness of suicide prevention efforts The way forward for suicide prevention What can be done and who needs to be involved? Forging a way forward What does success look like? Key messages REFERENCES ANNEXES Annex 1. Estimated numbers and rates of suicide by sex and age, 2000 and 2012 Annex 2: WHO Member States grouped by WHO Region and average income per capita
Output: WHO Library Cataloguing-in-Publication Data CONCEPTUALIZATION AND GUIDANCE
The next influenza pandemic may be imminent. Because antiviral agents and vaccines will be unavailable to people in most countries, we need to determine whether other agents could offer clinical benefits. Influenza is associated with an increase in acute cardiovascular diseases, and influenza viruses induce proinflammatory cytokines. Statins are cardioprotective and have anti-inflammatory and immunomodulatory effects, and they thus might benefit patients with influenza. This hypothesis should be evaluated by using administrative databases to search for reduced rates of hospitalization and death due to influenzarelated conditions among people taking statins. These studies should be followed by laboratory studies of statins in animal and cell-based models of influenza virus infection and, later, by clinical trials. Positive results from such studies would provide physicians in all countries with something to offer patients for treatment and prophylaxis of pandemic influenza. Generic statins will be widely distributed and inexpensive. They might be the only agents that could alter the course of a global pandemic.
Output: Pandemic Influenza: A Potential Role for Statins in Treatment and Prophylaxis
Toroviruses are emergent viruses, belonging to the Nidovirales order, that remain mostly ignored, despite they are able to infect different species of domestic animals and humans, causing enteric diseases and diarrhea. Thus far, only five variants of porcine torovirus (PToV) have been identified. In this report we describe the identification and partial characterization of a new strain of porcine torovirus (PToV-BRES) that was detected by RT-PCR in a swine faecal specimen from a farm in Brescia (Italy). The complete genes coding for the nucleocapsid (N), hemagglutinin-esterase (HE) and membrane (M) proteins were amplified, and sequence analysis showed that PToV-BRES is a new PToV strain that, based on the HE gene sequence, is phylogenetically related to P4 strain, that was up to now the only member of a distinct PToV lineage. The nucleocapsid protein from PToV-BRES was expressed in insect cells as a his-tagged protein, purified by affinity chromatography and used to develop an ELISA method to detect antibodies against PToV. This assay was evaluated using a serum collection including 45 samples from three commercial farms from Spain. High antibody prevalence against PToV was observed in the three farms, both in adult animals and in piglets, which could suggest that PToV might be endemic in Spanish porcine population. The ELISA method developed in this work could be useful in future epidemiological surveys about toroviruses.
Output: Molecular characterization of a new PToV strain. Evolutionary implications
The increasing incidence and prevalence of asthma in many parts of the world continue to make it a global health concern. The heterogeneous nature of the clinical manifestations and therapeutic responses of asthma in both adult and pediatric patients indicate that it may be more of a syndrome rather than a specific disease entity. Numerous triggering factors including viral infections, allergen and irritant exposure, and exercise, among others, complicate both the acute and chronic treatment of asthma. Therapeutic intervention has focused on the appreciation that airway obstruction in asthma is composed of both bronchial smooth muscle spasm and variable degrees of airway inflammation characterized by edema, mucus secretion, and the influx of a variety of inflammatory cells. The presence of only partial reversibility of airflow obstruction in some patients indicates that structural remodeling of the airways may also occur over time. Choosing appropriate medications depends on the disease severity (intermittent, mild persistent, moderate persistent, severe persistent), extent of reversibility, both acutely and chronically, patterns of disease activity (exacerbations related to viruses, allergens, exercise, etc), and the age of onset (infancy, childhood, adulthood). (J Allergy Clin Immunol 2003;111:S502-19.)
Output: Allergic disorders 6. Asthma
Background: Although primary and established human hepatoma cell lines have been evaluated for hepatitis C virus (HCV) infection in vitro, thus far only Huh7 cells have been found to be highly permissive for infectious HCV. Since our understanding of the HCV lifecycle would benefit from the identification of additional permissive cell lines, we assembled a panel of hepatic and non-hepatic cell lines and assessed their ability to support HCV infection. Here we show infection of the human hepatoma cell lines PLC/PRF/5 and Hep3B with cell culturederived HCV (HCVcc), albeit to lower levels than that achieved in Huh7 cells. To better understand the reduced permissiveness of PLC and Hep3B cells for HCVcc infection, we performed studies to evaluate the ability of each cell line to support specific steps of the viral lifecycle (i.e. entry, replication, egress and spread). Results: We found that while the early events in HCV infection (i.e. entry plus replication initiation) are cumulatively equivalent or only marginally reduced in PLC and Hep3B cells, later steps of the viral life cycle such as steady-state replication, de novo virus production and/or spread are impaired to different degrees in PLC and Hep3B cultures compared to Huh7 cell cultures. Interestingly, we also observed that interferon stimulated gene (i.e. ISG56) expression was significantly and differentially up-regulated in PLC and Hep3B cells following viral infection. Conclusions: We conclude that the restrictions observed later during HCV infection in these cell lines could in part be attributed to HCV-induced innate signaling. Nevertheless, the identification of two new cell lines capable of supporting authentic HCVcc infection, even at reduced levels, expands the current repertoire of cell lines amendable for the study of HCV in vitro and should aid in further elucidating HCV biology and the cellular determinants that modulate HCV infection.
Output: Permissiveness of human hepatoma cell lines for HCV infection
Introduction: Migratory birds act as hosts for a number of zoonotic viruses, and have the ability to disperse these viruses to distant geographic locations. Coronaviruses (CoVs) represent a family of zoonotic viruses with wide variety of animal hosts, including birds and humans. The infections caused by coronaviruses vary from mild to severe, depending on the viral species and the host. Since the coronaviruses exhibit extraordinary large RNA genome, also the rate of homologous recombination is high, which in turn contributes to the genetic diversity and interspecies host-switches of CoVs. The emergence of novel CoVs has been rich during the last decades, and wild birds seem to serve as reservoirs for a variety of CoV strains. We examined the CoVs circulating among wild birds in Finland. Materials and methods: Samples (cloacal swab, tracheal swab, oropharyngeal swab, or tissue) representing 61 bird species were collected during 2010-2013, and examined by RT-PCR targeting the RdRp gene for the presence of CoV RNA. Results: Altogether 51/939 (5.4%) of the examined birds were found positive by RT-PCR. Diverse gamma-and deltacoronavirus sequences were detected. Discussion: Gamma-and deltacoronaviruses circulate among wild birds in Finland. The number of CoV-positive birds detected each year varies greatly. ARTICLE HISTORY
Output: Prevalence and genetic diversity of coronaviruses in wild birds, Finland
A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n ‫؍‬ 8) but was not detected in healthy pythons or other snakes (n ‫؍‬ 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease. IMPORTANCE Ball pythons are popular pets because of their diverse coloration, generally nonaggressive behavior, and relatively small size. Since the 1990s, veterinarians have been aware of an infectious respiratory disease of unknown cause in ball pythons that can be fatal. We used unbiased shotgun sequencing to discover a novel virus in the order Nidovirales that was present in cases but not controls. While nidoviruses are known to infect a variety of animals, this is the first report of a nidovirus recovered from any reptile. This report will enable diagnostics that will assist in determining the role of this virus in the causation of disease, which would allow control of the disease in zoos and private collections. Given its evolutionary divergence from known nidoviruses and its unique host, the study of reptile nidoviruses may further our understanding of related diseases and the viruses that cause them in humans and other animals. DeRisi JL. 2014. Ball python nidovirus: a candidate etiologic agent for severe respiratory disease in Python regius. mBio 5(5):e01484-14.
Output: Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius
# Contributed equally J o u r n a l P r e -p r o o f Highlights  We reviewed discovery and development process of broad-spectrum antiviral agents.  We summarized the information on 119 safe-in-man agents in freely accessible database.  Further studies will increase the number of broad-spectrum antivirals, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections. : Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and reemerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 119 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.
Output: Journal Pre-proof Discovery and development of safe-in-man broad-spectrum antiviral agents Discovery and Development of Safe-in-man Broad-Spectrum Antiviral Agents
BALB/c male mice were mated with either Swiss-Webster or MF1 females to produce first generation cross-bred offspring. Hybridoma cell lines, from the fusion of P3-NS1-Ag4/1 myeloma cells with spleen cells sensitised to the porcine coronavirus causing transmissible gastroenteritis, were injected intraperitoneally into these mice to produce ascitic fluid containing monoclonal antibodies. Mice of 11 weeks of age weighing between 26 and 34 g were used. The volume of ascites produced by mice injected with four of the five hybrid cell lines tested was greater in the cross-bred offspring than in the BALB/c parent. The fifth cell line gave comparable volumes in the MF1 cross-breed and BALB/c parent but a lesser volume in the Swiss-Webster cross-breed. The antibody titres of the ascites as determined by virus neutralisation, radioimmune and indirect immune fluorescence assays, did not differ significantly between mouse types. The ability to use all offspring from a litter of cross-bred mice, irrespective of sex, and the increased volume of ascitic fluid formed in each mouse, permits fewer animals to be used for the production of ascites in these strains, thereby offering considerable economic and ethical advantages over the use of BALB/c mice.
Output: Comparison of ascites production for monoclonal antibodies in BALB/c and BALB/c-derived cross-bred mice