niryuu/sni-each-converted huggingface dataset:
The project Influenza Vaccine Effectiveness-Monitoring (I-MOVE) is part of the European research carried out by the ECDC (European Center for Disease Prevention and Control), aimed at monitoring the effectiveness of vaccination in Europe during the growing incidence of flu and influenza-like illnesses in the coming epidemic seasons. Laboratory studies using molecular RT-PCR biology methods for detection of genetic material of influenza virus and other respiratory viruses were performed by Voivodeship Sanitary-Epidemiological Stations in Poland. The validation of the results of swabs taken from the nose and throat were carried out in the Department of Influenza Research, National Influenza Center in Warsaw. The study involved 210 samples from patients across Poland. Positive results were recorded for 72.4 % of the samples; influenza virus type A was detected in 43 and type B in 38 cases, whereas in 71 cases other respiratory viruses were detected, which included Human parainfluenza virus type 1-4; Human respiratory syncytial virus type A and B; Human coronavirus 229E/NL63, OC43; Human rhinovirus type A, B, and C; Human enterovirus; and Human adenovirus. The results show that although influenza viruses predominated in the 2010/2011 season in Poland, other flu-like viruses also abounded.
Output: Detection of Influenza and Other Respiratory Viruses Carried Out in the Influenza Project -Monitoring Vaccine Effectiveness (I-MOVE)
GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab. The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation. Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains. Homologies between any two strains ranges from 78.9% to 100% regarding the galT locus. Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations. A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8). Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge. Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group. Anti-GALT antibodies were shown to mediate phagocytosis of neutrophils. After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001). This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes. Wen X, et al. (2018) Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71. PLoS ONE 13(6): e0198207. https://doi.org/10.
Output: Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS
The detection of respiratory viruses from clinical samples is important for patient management, promoting the rational use of antivirals and antibiotics, implementing infection control measures and for epidemiology studies. Respiratory viruses can be identified using a variety of techniques including direct antigen testing (non-immunofluorescent and immunofluorescent methods), conventional and rapid cell culture. This article presents an overview of each method. The most commonly used non-culture methods are the membrane-based enzyme immunoassays (EIAs) and optical
Output: Detection of respiratory viruses using non-molecular based methods
Background. Definite diagnosis of Leishmania infections is based on demonstration of the parasite by microscopic analysis of tissue biopsy specimens or aspirate samples. However, microscopy generally shows low sensitivity and requires invasive sampling. Methods. We describe here the development of a simple and rapid test for the detection of polymerase chain reaction-amplified Leishmania DNA. A phase 1 evaluation of the text was conducted in clinical samples from 60 nonendemic and 45 endemic control subjects and from 44 patients with confirmed cutaneous leishmaniasis (CL), 12 with mucocutaneous leishmaniasis (MCL), and 43 with visceral leishmaniasis (VL) from Peru, Kenya, and Sudan. Results. The lower detection limits of the assay are 10 fg of Leishmania DNA and 1 parasite in 180 L of blood. The specificity was 98.3% (95% confidence interval [CI], 91.1%-99.7%) and 95.6% (95% CI, 85.2%-98.8%) for nonendemic and endemic control samples, respectively, and the sensitivity was 93.2% (95% CI, 81.8%-97.7%), 91.7% (95% CI, 64.6%-98.5%), and 86% (95% CI, 72.7%-93.4%) for lesions from patients with CL or MCL and blood from patients with VL, respectively. Conclusions. The Leishmania OligoC-TesT showed high specificity and sensitivity in clinical samples and was able to detect the parasite in samples obtained by less invasive means, such as blood, lymph, and lesion scrapings. The assay is a promising new tool for simplified and standardized molecular detection of Leishmania parasites.
Output: A Simplified and Standardized Polymerase Chain Reaction Format for the Diagnosis of Leishmaniasis
During the processes of human population dispersal around the world over the past 50 000-100 000 years, along with associated cultural evolution and inter-population contact and conflict, there have been several major transitions in the relationships of Homo sapiens with the natural world, animate and inanimate. Each of these transitions has resulted in the emergence of new or unfamiliar infectious diseases. The three great historical transitions since the initial advent of agriculture and livestock herding, from ca. 10 000 years ago, occurred when: (i) early agrarian-based settlements enabled sylvatic enzootic microbes to make contact with Homo sapiens; (ii) early Eurasian civilizations (such as the Greek and Roman empires, China and south Asia) came into military and commercial contact, ca. 3000-2000 years ago, swapping their dominant infections; and (iii) European expansionism, over the past five centuries, caused the transoceanic spread of often lethal infectious diseases. This latter transition is best known in relation to the conquest of the Americas by Spanish conquistadores, when the inadvertent spread of measles, smallpox and influenza devastated the Amerindian populations. Today, we are living through the fourth of these great transitional periods. The contemporary spread and increased lability of various infectious diseases, new and old, reflect the combined and increasingly widespread impacts of demographic, environmental, behavioural, technological and other rapid changes in human ecology. Modern clinical medicine has, via blood transfusion, organ transplantation, and the use of hypodermic syringes, created new opportunities for microbes. These have contributed to the rising iatrogenic problems of hepatitis C, HIV/AIDS and several other viral infections. Meanwhile, the injudicious use of antibiotics has been a rare instance of human action actually increasing 'biodiversity'. Another aspect of this fourth transition is that modern hyper-hygienic living restricts microbial exposure in early life. This, in the 1950s, may have contributed to an epidemic of more serious, disabling, poliomyelitis, affecting older children than those affected in earlier, more endemic decades. As with previous human-microbe transitions, a new equilibrial state may lie ahead. However, it certainly will not entail a world free of infectious diseases. Any mature, sustainable, human ecology must come to terms with both the need for, and the needs of, the microbial species that help to make up the interdependent system of life on Earth. Humans and microbes are not 'at war'; rather, both parties are engaged in amoral, self-interested, coevolutionary struggle. We need to understand better, and therefore anticipate, the dynamics of that process.
Output: Environmental and social influences on emerging infectious diseases: past, present and future
The envelope spike (S) glycoprotein of the severe acute respiratory syndrome associated coronavirus (SARS-CoV) mediates the entry of the virus into target cells. Recent studies point out to a cell entry mechanism of this virus similar to other enveloped viruses, such as HIV-1. As it happens with other viruses peptidic fusion inhibitors, SARS-CoV S protein HR2-derived peptides are potential therapeutic drugs against the virus. It is believed that HR2 peptides block the six-helix bundle formation, a key structure in the viral fusion, by interacting with the HR1 region. It is a matter of discussion if the HIV-1 gp41 HR2-derived peptide T20 (enfuvirtide) could be a possible SARS-CoV inhibitor given the similarities between the two viruses. We tested the possibility of interaction between both T20 (HIV-1 gp41 HR2-derived peptide) and T-1249 with S protein HR1-and HR2-derived peptides. Our biophysical data show a significant interaction between a SARS-CoV HR1-derived peptide and T20. However, the interaction is only moderate (K B = (1.1 T 0.3) Â 10 5 M À1 ). This finding shows that the reasoning behind the hypothesis that T20, already approved for clinical application in AIDS treatment, could inhibit the fusion of SARS-CoV with target cells is correct but the effect may not be strong enough for application. D
Output: Why are HIV-1 fusion inhibitors not effective against SARS-CoV? Biophysical evaluation of molecular interactions
The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature and diagnostic criteria for nonproliferative and proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and diagnostic criteria for classifying lesions in the digestive system including the salivary glands and the exocrine pancreas of laboratory rats and mice. Most lesions are illustrated by color photomicrographs. The standardized nomenclature, the diagnostic criteria, and the photomicrographs are also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and age related lesions as well as lesions induced by exposure to test items. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature and diagnostic criteria for the digestive system will decrease misunderstandings among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.
Output: Nonproliferative and Proliferative Lesions of the Gastrointestinal Tract, Pancreas and Salivary Glands of the Rat and Mouse
Estimation of the fraction and contagiousness of undocumented novel coronavirus infections is critical for understanding the overall prevalence and pandemic potential of this disease. Many mild infections are typically not reported and, depending on their contagiousness, may support stealth transmission and the spread of documented infection. Here we use observations of reported infection and spread within China in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with the emerging coronavirus, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%-90%]) prior to the Wuhan travel shutdown (January 23, 2020). Per person, these undocumented . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint .
Output: Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (COVID-19)
The objective of this experiment was to investigate the therapeutic efficacy of a supplemental bovine serum protein blend fed to calves challenged with virulent coronavirus. Twelve Holstein bull calves (approximately 3 wk of age) were allocated by initial body weight to Control (n = 5) and treated (n = 7) groups. On d 0, all calves were orally challenged with 1 × 10 7 plaqueforming units of virulent coronavirus isolate. Infection was allowed to progress for 24 h before treatment was started. On d 1, treated calves began receiving 160 g of dry bovine serum powder (16 g IgG) mixed into milk replacer powder (67 g) at both an a.m. and p.m. feeding. Control calves received only milk replacer powder (227 g) at both feedings. Response to coronavirus challenge and dietary treatment was monitored prior to a.m. and p.m. feeding by the collection of multiple clinical measures. Fecal consistency was decreased by coronavirus challenge but was not affected by dietary treatment. Mean daily rectal temperature and heart rate were not affected by dietary treatment. Average packed cell volume was higher in treated calves than in control (35.0 and 27.0%). Coronavirus challenge resulted in an immediate increase in respiration rate, decreasing by d 7. Control calves tended to have a greater average respiration rate compared with treated (28.7 vs. 26.8 breaths/min). Treated calves had a higher average feed intake than control (0.57 vs. 0.44 kg/d). These data suggest that bovine-serum supplemented milk replacer may decrease the severity of disease in young calves exposed to coronavirus. Abbreviation key: BCV = bovine coronavirus, PCV = packed cell volume.
Output: The Use of Bovine Serum Protein as an Oral Support Therapy Following Coronavirus Challenge in Calves 1
Vesicular stomatitis virus (VSV) is a promising vector for vaccine and oncolysis, but it can also produce acute diseases in cattle, horses, and swine characterized by vesiculation and ulceration of the tongue, oral tissues, feet, and teats. In experimental animals (primates, rats, and mice), VSV has been shown to lead to neurotoxicities, such as hind limb paralysis. The virus matrix protein (M) and glycoprotein (G) are both major pathogenic determinants of wild-type VSV and have been the major targets for the production of attenuated strains. Existing strategies for attenuation included: (1) deletion or M51R substitution in the M protein (VSV M51 or VSVM51R, respectively); (2) truncation of the C-terminus of the G protein (G 28). Despite these mutations, recombinant VSV with mutated M protein is only moderately attenuated in animals, whereas there are no detailed reports to determine the pathogenicity of recombinant VSV with truncated G protein at high dose. Thus, a novel recombinant VSV (VSV M51-G 28) as well as other attenuated VSVs (VSV M51, VSV-G 28) were produced to determine their efficacy as vaccine vectors with low pathogenicity. In vitro studies indicated that truncated G protein (G 28) could play a more important role than deletion of M51 ( M51) for attenuation of recombinant VSV. VSV M51-G 28 was determined to be the most attenuated virus with low pathogenicity in mice, with VSV-G 28 also showing relatively reduced pathogenicity. Further, neutralizing antibodies stimulated by VSV-G 28 proved to be significantly higher than in mice treated with VSV M51-G 28. In conclusion, among different attenuated VSVs with mutated M and/or G proteins, recombinant VSV with only truncated G protein (VSV-G 28) demonstrated ideal balance between pathogenesis and stimulating a protective immune response. These properties make VSV-G 28 a promising vaccine vector and vaccine candidate for preventing vesicular stomatitis disease.
Output: Evaluation of attenuated VSVs with mutated M or/and G proteins as vaccine vectors
Albumin and IgG were quantitated in paired cerebrospinal fluid (CSF) and serum samples from dogs with demyelinating canine distemper virus (CDV) infection by means of rocket immunoelectrophoresis. The IgG index as indicator for intrathecal immunoglobulin synthesis was normal in animals with non-inflammatory demyelinating lesions and elevated in dogs with inflammatory myelin lesions. Specific antibodies against CDV and myelin were quantitated in CSF and serum from 8 dogs with an elevated IgG index. Eight of these dogs had significant amounts of antimyelin antibody and 4 dogs had neutralizing anti-CDV antibody in the CSF. Whereas the pathogenetic significance of antimyelin antibodies remains uncertain, the intrathecal antiviral immune response provides a plausible explanation for immunopathologic destruction of myelin in distemper.
Output: Studies on the Intrathecal Humoral Immune Response in Canine Distemper Encephalitis
Background: Community-acquired pneumonia in children is common in China. To understand current clinical characteristics and practice, we conducted a cross-sectional study to analyze quality of care on childhood pneumonia in eight eastern cities in China. Methods: Consecutive hospital records between January 1, 2010 and December 31, 2010 were collected from 13 traditional Chinese medicine (TCM) and western medicine (WM) hospitals in February, May, August, and November (25 cases per season, 100 cases over the year), respectively. A predesigned case report form was used to extract data from the hospital medical records. Results: A total of 1298 cases were collected and analyzed. Symptoms and signs upon admission at TCM and WM hospitals were cough (99.3% vs. 98.6%), rales (84.8% vs. 75.0%), phlegm (83.3% vs. 49.1%), and fever (74.9% vs. 84.0%) in frequency. Patients admitted to WM hospitals had symptoms and signs for a longer period prior to admission than patients admitted to TCM hospitals. Testing to identify etiologic agents was performed in 1140 cases (88.4%). Intravenous antibiotics were administered in 99.3% (595/598) of cases in TCM hospitals and in 98.6% (699/700) of cases in WM hospitals. Besides, Chinese herbal extract injection was used more frequently in TCM hospitals (491 cases, 82.1%) than in WM hospitals (212 cases, 30.3%) (p < 0.01). At discharge, 818 cases (63.0%) were clinically cured, with a significant difference between the cure rates in TCM (87.6%) and WM hospitals (42.0%) (OR = 9.8, 95% confidence interval (CI): 7.3~12.9, p < 0.01). Pathogen and previous medical history were more likely associated with the disappearance of rales (OR = 7.2, 95% CI: 4.8~10.9). Adverse effects were not reported from the medical records. Conclusions: Intravenous use of antibiotics is highly prevalent in children with community-acquired pneumonia regardless of aetiology. There was difference between TCM and WM hospitals with regard to symptom profile and the use of antibiotics. Intravenous use of herbal injection was higher in TCM hospitals than in WM hospitals. Most of the cases were diagnosed based on clinical signs and symptoms without sufficient confirmation of aetiology. Audit of current practice is urgently needed to improve care.
Output: A cross-sectional study of the clinical characteristics of hospitalized children with community-acquired pneumonia in eight eastern cities in China
In order to identify priorities for building integrated surveillance systems that effectively model and predict human risk of zoonotic diseases, there is a need for improved understanding of the practical options for linking surveillance data of animals and humans. We conducted an analysis of the literature and characterized the linkage between animal and human health data. We discuss the findings in relation to zoonotic surveillance and the linkage of human and animal data. The Canary Database, an online bibliographic database of animal-sentinel studies was searched and articles were classified according to four linkage categories. Results: 465 studies were identified and assigned to linkage categories involving: descriptive, analytic, molecular, or no human outcomes of human and animal health. Descriptive linkage was the most common, whereby both animal and human health outcomes were presented, but without quantitative linkage between the two. Rarely, analytic linkage was utilized in which animal data was used to quantitatively predict human risk. The other two categories included molecular linkage, and no human outcomes, which present health outcomes in animals but not humans. We found limited use of animal data to quantitatively predict human risk and listed the methods from the literature that performed analytic linkage. The lack of analytic linkage in the literature might not be solely related to technological barriers including access to electronic database, statistical software packages, and Geographical Information System (GIS). Rather, the problem might be from a lack of understanding by researchers of the importance of animal data as a 'sentinel' for human health. Researchers performing zoonotic surveillance should be aware of the value of animal-sentinel approaches for predicting human risk and consider analytic methods for linking animal and human data. Qualitative work needs to be done in order to examine researchers' decisions in linkage strategies between animal and human data.
Output: BMC Veterinary Research Linkages between animal and human health sentinel data
Naturally occurring feline infectious peritonitis (FIP) is usually fatal, giving the impression that immunity to the FIP virus (FIPV) is extremely poor. This impression may be incorrect, because not all cats experimentally exposed to FIPV develop FIP. There is also a belief that the incidence of FIP may be affected by a number of host, virus, and environmental cofactors. However, the contribution of these cofactors to immunity and disease incidence has not been determined. The present study followed 111 random-bred specific pathogen free (SPF) cats that were obtained from a single research breeding colony and experimentally infected with FIPV. The cats were from several studies conducted over the past 5 years, and as a result, some of them had prior exposure to feline enteric coronavirus (FECV) or avirulent FIPVs. The cats were housed under optimized conditions of nutrition, husbandry, and quarantine to eliminate most of the cofactors implicated in FIPV infection outcome and were uniformly challenge exposed to the same field strain of serotype 1 FIPV. Forty of the 111 (36%) cats survived their initial challenge exposure to a Type I cat-passaged field strains of FIPV. Six of these 40 survivors succumbed to FIP to a second or third challenge exposure, suggesting that immunity was not always sustained. Exposure to non-FIP-inducing feline coronaviruses prior to challenge with virulent FIPV did not significantly affect FIP incidence but did accelerate the disease course in some cats. There were no significant differences in FIP incidence between males and females, but resistance increased significantly between 6 months and 1 or more years of age. Genetic testing was done on 107 of the 111 infected cats. Multidimensional scaling (MDS) segregated the 107 cats into three distinct families based primarily on a common sire(s), and resistant and susceptible cats were equally distributed within each family. Genome-wide association studies (GWAS) on 73 cats that died of FIP after one or more exposures (cases) and 34 cats that survived (controls) demonstrated four significant associations after 100k permutations. When these same cats were analyzed using a sib-pair transmission test, three of the four associations were confirmed although not with genome-wide significance. GWAS was then done on three different age groups of cases to take into account age-related resistance, and different associations were observed.
Output: The influence of age and genetics on natural resistance to experimentally induced feline infectious peritonitis
Understanding thestructure and function of theGolgi comiplex has proved to be among the more challenging probllems in cell biology. The last several years have turned out Ito be particularly exciting in this respect since they have Iyielded new insights and ideas at an increasingly rapid ipace. This period of advance has largely been due to the Idevelopment of powerful new biochemical, morphological, #and genetic approaches to unraveling the complexities of 'this organelle. While much remains to be discovered, the Iproblem now is how to integrate this wealth of information. 'To see if this is possible, we will first summarize how the lslolgi is commonly believed to work and then evaluate the lstrength of the evidence that underlies these views.
Output: The Golgi Complex: In Vitro Veritas? Review
1 g KHCO 3 8.3 g NH 4 Cl 37.2 mg EDTA-Na 2 Adjust volume to 1,000 ml with nano-pure H 2 O and filter through a 0.2 µm filter Store at room temperature CD4 + T cell responses have been shown to be protective in many respiratory virus infections. In the respiratory tract, CD4 + T cells include cells in the airway and parenchyma and cells adhering to the pulmonary vasculature. Here we discuss in detail the methods that are useful for characterizing CD4 + T cells in different anatomic locations in mouse lungs.
Output: HHS Public Access Author manuscript Simultaneous Intranasal/Intravascular Antibody Labeling of CD4 + T Cells in Mouse Lungs
Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) into susceptible mouse strains produces a chronic demyelinating disease in which mononuclear cell-rich infiltrates in the central nervous system (CNS) are prominent. Current evidence strongly supports an immune-mediated basis for myelin breakdown, with an effector role proposed for TMEV-specific, major histocompatibility complex (MHC) class II-restricted delayed-type hypersensitivity (DTH) responses in which lymphokine-activated macrophages mediate bystander demyelination. The present study examined the possibility that concomitant or later-appearing neuroantigen-specific autoimmune T cell responses, such as those demonstrated in chronic-relapsing experimental allergic encephalomyelitis (R-EAE), may contribute to the demyelinating process following TMEV infection. T cell responses against intact, purified major myelin proteins (myelin 10 basic protein (MBP) and proteohpid protein (PLP)), and against altered myelin constituents were readily demonstrable in SJL//J mice with R-EAE, but were not detectable in SJL//J mice with TMEV-induced demyehnating disease. TMEV-infected mice also did not display T cell responses against the peptide fragments of MBP(91-104) and PLP(139-151) recently shown to be encephalitogenic in SJL/J mice. In addition, induction of neuroantigen-specific tolerance to a heterogeneous mixture of CNS antigens, via the i.v. injection of syngeneic SJL//J splenocytes covalently coupled with mouse spinal cord homogenate, resulted in significant suppression of clinical and histologic signs of R-EAE and the accompanying MBPand PLP-specific DTH responses. In contrast, neuroantigen-specific tolerance failed to alter the development of clinical and histologic signs of TMEV-induced demyelinating disease or the accompanying virus-specific DTH and humoral immune responses. These findings demonstrate that TMEV-induced demyelinating disease can occur in the apparent absence of neuroantigen-specific autoimmune responses. The relationship of the present results to the immunopathology of multiple sclerosis is discussed.
Output: Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease III. Failure of neuroantigen-specific immune tolerance to affect the clinical course of demyelination
Chikungunya virus (CHIKV) has caused extensive outbreaks in several countries within the Americas, Asia, Oceanic/Pacific Islands, and Europe. In humans, CHIKV infections cause a debilitating disease with acute febrile illness and long-term polyarthralgia. Acute and chronic symptoms impose a major economic burden to health systems and contribute to poverty in affected countries. An efficacious vaccine would be an important step towards decreasing the disease burden caused by CHIKV infection. Despite no licensed vaccine is yet available for CHIKV, there is strong evidence of effective asymptomatic viral clearance due to neutralising antibodies against the viral structural proteins. We have designed viral-vectored vaccines to express the structural proteins of CHIKV, using the replication-deficient chimpanzee adenoviral platform, ChAdOx1. Expression of the CHIKV antigens results in the formation of chikungunya virus-like particles. Our vaccines induce high frequencies of anti-chikungunya specific T-cell responses as well as high titres of anti-CHIKV E2 antibodies with high capacity for in vitro neutralisation. Our results indicate the potential for further clinical development of the ChAdOx1 vaccine platform in CHIKV vaccinology.
Output: Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus
Infectious bronchitis virus (IBV), the first coronavirus described, has been a continuing problem in poultry for more than 70 years. IBV, causing a highly contagious respiratory disease in chickens, resembles the recently described severe acute respiratory syndrome virus in pathogenesis and genome organization. While previous studies demonstrated that effector and memory CD8 C T lymphocytes are critical in controlling acute IBV infection and disease in chickens, here chicken anti-IBV antibody (IgG) secreting cells (ASC) in both peripheral blood mononuclear cells (PBMC) and spleens collected following IBV Gray infection were evaluated using an ELISPOT assay. The ASC in peripheral blood and spleens can be detected from 3 to 7 days post-infection (p.i.), which is 3-7 days earlier than anti-IBV IgG detected in the serum. The ASC frequency reached a maximum at 7-10 days p.i., and decreased more than 90% in the spleen and 70% in PBMC by 14 days p.i. The ASC levels in the PBMC then decreased gradually to 0.5 ASC/10 6 over the next 8 weeks. The higher concentration of about 20 ASC/10 6 cells in spleens may, at least partially, account for the presence of antibody in the serum although bone marrow ASC were not determined. In vitro stimulation of PBMC and splenocytes with IBV antigen demonstrated that memory B cells can be activated to secrete antibody by 3 weeks p.i. ELISPOT detection of primary B cells could be useful in the early detection of infection following infection with respiratory coronaviruses. q
Output: Specific antibody secreting cells from chickens can be detected by three days and memory B cells by three weeks post-infection with the avian respiratory coronavirus
Despite the recent emergence of enterovirus D68 (EV-D68), its clinical impact on adult population is less well defined. To better define the epidemiology of EV-D68, 6,800 nasopharyngeal aspirates (NPAs) from 2010-2014 were subject to EV-D68 detection by RT-PCR and sequencing of 5′UTR and partial VP1. EV-D68 was detected in 30 (0.44%) NPAs from 22 children and 8 adults/elderlies. Sixteen patients (including five elderly) (53%) had pneumonia and 13 (43%) patients were complicated by small airway disease exacerbation. Phylogenetic analysis of VP1, 2C and 3D regions showed four distinct lineages of EV-D68, clade A1, A2, B1 and B3, with adults/elderlies exclusively infected by clade A2. The potentially new clade, B3, has emerged in 2014, while strains closely related to recently emerged B1 strains in the United States were also detected as early as 2011 in Hong Kong. The four lineages possessed distinct aa sequence patterns in BC and DE loops. Amino acid residues 97 and 140, within BC and DE-surface loops of VP1 respectively, were under potential positive selection. EV-D68 infections in Hong Kong usually peak in spring/summer, though with a delayed autumn/winter peak in 2011. This report suggests that EV-D68 may cause severe respiratory illness in adults/elderlies with underlying co-morbidities.
Output: Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong
KEYWORDS Travel health Travel abroad Pretravel Assessment Posttravel Assessment Primary care providers manage the majority of travel medical care. The purpose of the pretravel visit are risk assessment and mitigation. Encourage travelers to enroll in the Smart Traveler Enrollment Program for travel advisories. The Centers for Disease Control and Prevention travel website offers destination-specific, point-of-care resources for clinicians and travelers. Travelers who are visiting friends and relatives are a high-risk group. The most common syndromes in returning travelers are gastrointestinal, febrile, and dermatologic. Prim Care Clin Office Pract 45 (2018) 541-554
Output: Health Guidelines for Travel Abroad
Objective To examine recent time trends in the incidence of osteonecrosis (ON) in Denmark and to investigate different common comorbidities association with ON in a population-based setting. Methods Using Danish medical databases, we included all patients with a first-time hospital diagnosis of ON during 1995-2012. Each ON case was matched with 10 randomly selected population control subjects from general population. For all participants, we obtained a complete hospital history of comorbidities included in the CharlsonComorbidity Index 5 years preceding the inclusion date. results 4107 ON cases and 41 063 controls were included. The incidence of ON increased from 3.9 in 1995 to 5.5 in 2012 per 100 000 inhabitants. Solid cancer was the most common comorbidity, associated with an adjusted OR (aOR) for ON of 2.0 (95% CI 1.7 to 2.2). For advanced metastatic cancer, leukaemia and lymphoma, aORs of ON were 3.4 (95% CI 2.5 to 4.5), 4.3 (95% CI 2.7 to 7.0) and 5.8 (95% CI 4.3 to 7.8), respectively. Among other chronic conditions, aORs were 3.5 (95% CI 3.0 to 4.1) for connective tissue diseases and 2.3 (95% CI 2.0 to 2.7) for chronic pulmonary diseases. aORs were also increased at 2.8 (95% CI 1.9 to 4.1) and 4.5 (95% CI 2.5 to 8.2) for mild and moderate-to-severe liver disease, respectively, and 4.2 (95% CI 3.4 to 5.2) for renal disease. Conclusion This large population-based study provides evidence for an increasing ON incidence in the general population and documents an association between several common comorbid conditions and risk of ON.
Output: Association of common comorbidities with osteonecrosis: a nationwide population-based case-control study in Denmark
Recent outbreak of 2019-nCoV in Wuhan raised serious public health concerns. By February 15, 2020 in Wuhan, the total number of confirmed infection cases has reached 37,914, and the number of deaths has reached 1123, accounting for 56.9% of the total confirmed cases and 73.7% of the total deaths in China. People are eager to know when the epidemic will be completely controlled and when people's work and life will be on the right track. In this study we analyzed the epidemic dynamics and trend of 2019-nCoV in Wuhan by using the data after the closure of Wuhan city till February 12, 2020 based on the SEIR modeling method. The optimal parameters were estimated as R 0 =1.44 (interquartile range: 1.40-1.47)，TI=14 (interquartile range: 14-14) and TE=3.0 (interquartile range: 2.8-3.
Output: When will the battle against novel coronavirus end in Wuhan: a SEIR modeling analysis
Development of RNA interference (RNAi) technology utilizing the short interfering RNA sequences (siRNA) based 'targeted' therapeutics has focused on creating methods for delivering siRNAs to cells and for enhancing siRNA stability in vitro and in vivo. Here, we describe a novel approach for siRNA cellular delivery using siRNA encapsulated into liposomes additionally bearing arginine octamer (R8) molecules attached to their outer surface (R8-liposomes). The R8-liposomal human double minute gene 2 (HDM2)-siRNA demonstrated a significant stability against degradation in the blood serum (siRNA-loaded R8-liposomes remained intact even after 24-h incubation), and higher transfection efficiency into all three tested lung tumor cell lines. siRNA delivery successfully proceeds in the presence of plasma proteins, and R8-liposomes demonstrate low non-specific toxicity. The mechanism of action of R8-liposome-encapsulated siRNA is associated with the RNAi-mediated degradation of the target mRNA. siRNA in R8-liposomes effectively inhibited the targeted gene and significantly reduced the proliferation of cancer cells. The approach offers the potential for siRNA delivery for various in vitro and in vivo applications.
Output: siRNA-containing liposomes modified with polyarginine effectively silence the targeted gene
Background: Pro-coagulant membrane microvesicles (MV) derived from platelets and leukocytes are shed into the circulation following receptor-mediated activation, cell-cell interaction, and apoptosis. Platelets are sentinel markers of tolllike receptor 4 (TLR4) activation. Experiments were designed to evaluate the time course and mechanism of direct interactions between platelets and leukocytes following acute activation of TLR4 by bacterial lipopolysaccharide (LPS). Methodology/Principal Findings: Blood from age-matched male and female wild type (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS (500 ng/ml) for up to one hour. At designated periods, leukocyte antigen positive platelets, platelet antigen positive leukocytes and cell-derived MV were quantified by flow cytometry. Numbers of platelet-or leukocyte-derived MV did not increase within one hour following in vitro exposure of blood to LPS. However, with LPS stimulation numbers of platelets staining positive for both platelet-and leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. This effect was blocked by inhibition of TLR4 signaling mediated by My88 and TRIF. Seven days after a single intravenous injection of LPS (500 ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for leukocyte antigen. However, granulocytes, monocytes and apoptotic bodies stained positive for platelet antigens. Conclusions/Significance: Within one hour of exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4 activation. In vivo, leukocyte expression of platelet antigen is retained after a single exposure to LPS following turn over of the platelet pool. Acute expression of leukocyte antigen on platelets within one hour of exposure to LPS and the sustained expression of platelet antigen on leukocytes following a single acute exposure to LPS in vivo explains, in part, associations of platelets and leukocytes in response to bacterial infection and changes in thrombotic propensity of the blood.
Output: Leukocyte-and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide
Background: Influenza A(H1N1)pdm09 virus infection in Norwegian pigs was largely subclinical. This study tested the hypothesis that the infection causes negligible impact on pigs' growth performance in terms of feed conversion efficiency, daily feed intake, daily growth, age on reaching 100 kg bodyweight and overall feed intake. A sample of 1955 pigs originating from 43 breeding herds was classified into five infection status groups; seronegative pigs (n = 887); seropositive pigs (n = 874); pigs positive for virus at bodyweight between 33 kg and 60 kg (n = 123); pigs positive for virus at bodyweight between 61 kg and 80 kg (n = 34) and pigs positive for virus at bodyweight between 81 kg and 100 kg (n = 37). Each pig had daily recordings of feed intake and bodyweight from 33 kg to 100 kg. Marginal effects of the virus infection on the outcomes were estimated by multi-level linear regression, which accounted for known fixed effects (breed, birthdate, average daily feed intake and growth phase) and random effects (cluster effects of pig and herd). Results: The seropositive and virus positive pigs had decreased (P value<0.05) growth performance compared to seronegative pigs even though feed intake was not decreased. Reduced feed conversion efficiency led to lower average daily growth, additional feed requirement and longer time needed to reach the 100 kg bodyweight. The effects were more marked (P value<0.03) in pigs infected at a younger age and lasted a longer period. Despite increased feed intake observed, their growth rates were lower and they took more time to reach 100 kg bodyweight compared to the seronegative pigs. Conclusion: Our study rejected the null hypothesis that the virus infection had negligible adverse effects on growth performance of Norwegian pigs.
Output: Adverse effects of Influenza A(H1N1)pdm09 virus infection on growth performance of Norwegian pigs -a longitudinal study at a boar testing station
We found that the anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked alloimmune responses in vitro. Based on pharmacokinetic studies, 6 dogs received a single intravenous injection of 5 mg/kg anti-CD154 antibody (on day ؊5), followed 1 day later by donor PBMCs. On day 0, the dogs were given 1 Gy of TBI and underwent DLA-identical marrow grafts. Postgraft immunosuppression consisted of MMF and CSP. All 6 dogs demonstrated initial engraftment; 3 dogs sustained the engraftment for >26 weeks, whereas 3 dogs rejected their grafts, after 9, 22, and 24 weeks, and survived with autologous recovery. Graft survival was significantly improved over that in 11 historical controls conditioned with 1-Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P ‫؍‬ .03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1-Gy TBI.
Output: CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1-Gy Total Body Irradiation
Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including antiviral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell cultureproduced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.
Output: Antiviral Activity of Glycyrrhizin against Hepatitis C Virus In Vitro
In many hospitals, isolation rooms are used to contain patients who are highly infectious, and the spread of air and bacteria within the isolation room is closely relates to room air distribution. This article uses the computational fluid dynamics (CFD) method to investigate the effects of a moving person and the opening and closing of a sliding door on room air distribution, including velocity, pressure and contaminant fields. Dynamic meshes are employed to simulate the movement of the walking person and sliding door. According to numerical results, the impact of those moving objects on room air distribution is addressed in this study. r
Output: Dynamic airflow simulation within an isolation room
During severe acute respiratory syndrome coronavirus (SARS-CoV) infection, the activity of the replication/ transcription complexes (RTC) quickly peaks at 6 hours post infection (h.p.i) and then diminishes significantly in the late post-infection stages. This "down-up-down" regulation of RNA synthesis distinguishes different viral stages: primary translation, genome replication, and finally viron assembly. Regarding the nsp8 as the primase in RNA synthesis, we confirmed that the proteolysis product of the primase (nsp8) contains the globular domain (nsp8C), and indentified the resectioning site that is notably conserved in all the three groups of coronavirus. We subsequently crystallized the complex of SARS-CoV nsp8C and nsp7, and the 3-D structure of this domain revealed its capability to interfuse into the hexadecamer super-complex. This specific proteolysis may indicate one possible mechanism by which coronaviruses to switch from viral infection to genome replication and viral assembly stages. KEYWORDS nsp8, SARS-CoV, RNA primase, viral life cycle * These authors contributed equally to the work 198
Output: New nsp8 isoform suggests mechanism for tuning viral RNA synthesis
Background: Diagnosis of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae in adults and adolescents is hampered by a lack of rapid and standardized tests for detection. Methods: CAP patients from 12 teaching hospitals were prospectively and consecutively recruited. Basic and clinical information, throat swabs and paired sera were collected. Mycoplasma pneumoniae was detected by IgG and IgM antibody tests, fluorescence quantitative polymerase chain reaction (FQ-PCR) and culture. A comparative study of the diagnostic values of three methods, including sensitivity, specificity, positive and negative predictive values and positive likelihood ratio (PLR) was conducted. A fourfold or greater increase of IgG antibody titers of paired sera was set as the diagnostic "gold standard". Results: One hundred and twenty-five CAP patients (52.8% males, median age 47 years, range 14-85) were enrolled. Twenty-seven (21.6%) patients were diagnosed with acute Mycoplasma pneumoniae infections by the "gold standard". Specificity values of all three methods were around 90%. An increasing trend of sensitivity, positive predictive value and PLR was found, with the lowest in IgM testing (7.4%, 28.6% and 1.45), intermediate in FQ-PCR (40.7%, 50% and 3.63), and highest in culture (55.6%, 75% and 10.9). Conclusions: In the defined group of patients, there was a good agreement between positive rate of MP cultivation of throat swabs and acute M. pneumoniae infection (PLR of 10.9). Since the sensitivity is low in all of the evaluated methods, the logical approach would be to incorporate PCR, culture and serological tests for optimum diagnosis of acute Mycoplasma pneumoniae infections in adults and adolescents.
Output: Accuracy of IgM antibody testing, FQ-PCR and culture in laboratory diagnosis of acute infection by Mycoplasma pneumoniae in adults and adolescents with community-acquired pneumonia for Beijing Network for Adult Community-Acquired Pneumonia (BNACAP)