niryuu/sni-each-converted huggingface dataset:
The 5 and 3 untranslated regions (UTRs) of coxsackievirus B3 (CVB3) RNA form highly ordered secondary structures that have been confirmed to play important regulatory roles in viral cap-independent internal translation initiation and RNA replication. We previously demonstrated that deletions in different regions of the 5 UTR significantly reduced viral RNA translation and infectivity. Such observations suggested strongly that viral RNA translation and replication could be blocked if highly specific antisense oligodeoxynucleotides (AS-ODNs) were applied to target crucial sites within the 5 and 3 UTRs. In this study, seven phosphorothioate AS-ODNs were synthesized, and the antiviral activity was evaluated by Lipofectin transfection of HeLa cells with AS-ODNs followed by infection of CVB3. Analysis by Western blotting, reverse transcription-PCR, and viral plaque assay demonstrated that viral protein synthesis, genome replication, and infectivity of CVB3 were strongly inhibited by the AS-ODNs complementary to different regions of the 5 and 3 UTRs. The most effective sites are located at the proximate terminus of the 5 UTR (AS-1), the proximate terminus of the 3 UTR (AS-7), the core sequence of the internal ribosome entry site (AS-2), and the translation initiation codon region (AS-4). These AS-ODNs showed highly sequence-specific and dose-dependent inhibitory effects on both viral protein synthesis and RNA replication. It is noteworthy that the highest inhibitory activities were obtained with AS-1 and AS-7 targeting the termini of the 5 and 3 UTRs. The percent inhibition values of AS-1 and AS-7 for CVB3 protein VP1 synthesis and RNA replication were 70.6 and 79.6 for AS-1 and 73.7 and 79.7 for AS-7, respectively. These data suggest that CVB3 infectivity can be inhibited effectively by AS-ODNs.
Output: Specific Inhibition of Coxsackievirus B3 Translation and Replication by Phosphorothioate Antisense Oligodeoxynucleotides
A febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) of the Samsung Medical Center in 2015, to screen for patients with contagious diseases requiring isolation. We evaluated the utility of the FRIDU during 1 year of operation. We analyzed 1,562 patients who were hospitalized after FRIDU screening between August 2015 and July 2016. The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis. Of the 1,562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1,170 (75%) were not isolated. While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1,258 patients (81%) did not require isolation. The correlation coefficient for isolation consistency was 0.565 (P < 0.001). The sensitivity and negative predictive value of FRIDU screening for diagnosing contagious disease requiring isolation are 76% and 98%, respectively. No serious nosocomial outbreaks of contagious diseases occurred. During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died. The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units. However, the risks of deterioration during the screening process remain challenges.
Output: The Utility of Preliminary Patient Evaluation in a Febrile Respiratory Infectious Disease Unit outside the Emergency Department
Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses.
Output: Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates
Viruses assemble large macromolecular repeat structures that become part of the infectious particles or virions. Ribonucleocapsids (RNCs) of negative strand RNA viruses are a prime example where repetition of nucleoprotein (NP) along the genome creates a core polymeric helical scaffold that accommodates other nucleocapsid proteins including viral polymerase. The RNCs are transported through the cytosol for packaging into virions through association with viral matrix proteins at cell membranes. We hypothesized that RNC would be ideal targets for crosslinkers engineered to promote aberrant protein-protein interactions, thereby blocking their orderly transport and packaging. Previously, we had generated single-domain antibodies (sdAbs) against Filoviruses that have all targeted highly conserved C-terminal regions of NP known to be repetitively exposed along the length of the RNCs of Marburgvirus (MARV) and Ebolavirus (EBOV). Our crosslinker design consisted of dimeric sdAb expressed intracellularly, which we call Xintrabodies (X-for crosslinking). Electron microscopy of purified NP polymers incubated with purified sdAb constructs showed NP aggregation occurred in a genus-specific manner with dimeric and not monomeric sdAb. A virus-like particle (VLP) assay was used for initial evaluation where we found that dimeric sdAb inhibited NP incorporation into VP40-based VLPs whereas monomeric sdAb did not. Inhibition of NP packaging was genus specific. Confocal microscopy revealed dimeric sdAb was diffuse when expressed alone but focused on pools of NP when the two were coexpressed, while monomeric sdAb showed ambivalent partition. Infection of stable Vero cell lines expressing dimeric sdAb specific for either MARV or EBOV NP resulted in smaller plaques and reduced progeny of cognate virus relative to wild-type Vero cells. Though the impact was marginal at later time-points, the collective data suggest that viral replication can be reduced by crosslinking intracellular NP using relatively small amounts of dimeric sdAb to restrict NP packaging. The stoichiometry and ease of application of the approach would likely benefit from transitioning away from intracellular expression of crosslinking sdAb to exogenous delivery of antibody. By retuning sdAb specificity, the approach of crosslinking highly conserved regions of assembly critical proteins may well be applicable to inhibiting replication processes of a broad spectrum of viruses.
Output: Article 1197 1 Original research Citation: Darling TL, Sherwood LJ and Hayhurst A (2017) Intracellular Crosslinking of Filoviral Nucleoproteins with Xintrabodies Restricts Viral Packaging
We have investigated the role of two polymorphic sites (R190W and N192K) on the binding and activation of the formyl peptide receptor (FPR) by viral and formyl peptides. WEDWVGWI, a peptide with antiviral activity derived from the membrane proximal region of feline immunodeficiency virus, binds with high affinity to FPR. The three tryptophans in the peptide are all essential for FPR binding, just as they were essential for antiviral activity [S. Giannecchini, A. Di Fenza, A.M. D'Ursi, D. Matteucci, P. Rovero, M. Bendinelli, Antiviral activity and conformational features of an octapeptide derived from the membrane-proximal ectodomain of the feline immunodeficiency virus transmembrane glycoprotein, J. Virol. 77 (2003) 3724]. Formyl-NleWEDWVGWI behaved as a weak partial agonist with FPR W190/N192 but a stronger partial agonist with FPR R190/K192 and FPR R190/N192. Formyl-NleNleWEDWVGWI behaved as a full agonist toward all three FPRs but exhibited a much higher EC 50 with W190/N192 FPR (300 ± 45 nM) than for R190/K192 FPR (40 ± 3 nM) or R190/N192 (60 ± 8 nM). Formyl-MYKWPWYVWL preferentially activated R190/K192 and R190/N192 FPRs by N 5 fold compared to W190/N192 FPR. Formyl-MFEDAVAWF, a peptide derived from a protein in Mycobacterium avium subsp. paratuberculosis and formyl-MFTFEPFPTN, a peptide derived from the N-terminus of chemotaxis inhibitory protein of Staphylococcus aureus with an added N-terminal formyl-methionine exhibited the greatest selectivity for R190/K192 and R190/N192 FPRs with ∼10 fold lower EC 50 s than that observed with FPR W190/N192. Thus, individuals with the W190 polymorphism may display a reduced ability to detect certain formyl peptides.
Output: Differential activation of polymorphisms of the formyl peptide receptor by formyl peptides
Leishmaniasis is a parasitic disease that courses with cutaneous or visceral clinical manifestations. The amastigote stage of the parasite infects phagocytes and modulates the effector function of the host cells. Our group has described that the interaction between Leishmania and immature monocyte-derived dendritic cells (DCs) takes place through dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), a C-type lectin that specifically recognizes fungal, viral and bacterial pathogens. The DC-SIGN-mediated recognition of Leishmania amastigotes does not induce DC maturation, and the DC-SIGN ligand/s on Leishmania parasites is/are still unknown. We have also found that the DC-SIGN-related molecule L-SIGN, specifically expressed in lymph node and liver sinusoidal endothelial cells, acts as a receptor for L. infantum, the parasite responsible for visceral leishmaniasis, but does not recognize L. pifanoi, which causes the cutaneous form of the disease. Therefore, DC-SIGN and L-SIGN differ in their ability to interact with Leishmania species responsible for either visceral or cutaneous leishmaniasis. A deeper knowledge of the parasite-Ctype lectin interaction may be helpful for the design of new DC-based therapeutic vaccines against Leishmania infections.
Output: Role of the C-type lectins DC-SIGN and L-SIGN in Leishmania interaction with host phagocytes
Background: Positive controls are an integral component of any sensitive molecular diagnostic tool, but this can be affected, if several mutations are being screened in a scenario of a pandemic or newly emerging disease where it can be difficult to acquire all the necessary positive controls from the host. This work describes the development of a synthetic oligo-cassette for positive controls for accurate and highly sensitive diagnosis of several mutations relevant to influenza virus drug resistance. Results: Using influenza antiviral drug resistance mutations as an example by employing the utility of synthetic paired long oligonucleotides containing complementary sequences at their 3' ends and utilizing the formation of oligonucleotide dimers and DNA polymerization, we generated~170bp dsDNA containing several known specific neuraminidase inhibitor (NAI) resistance mutations. These templates were further cloned and successfully applied as positive controls in downstream assays. Conclusion: This approach significantly improved the development of diagnosis of resistance mutations in terms of time, accuracy, efficiency and sensitivity, which are paramount to monitoring the emergence and spread of antiviral drug resistant influenza strains. Thus, this may have a significantly broader application in molecular diagnostics along with its application in rapid molecular testing of all relevant mutations in an event of pandemic.
Output: Synthetic long oligonucleotides to generate artificial templates for use as positive controls in molecular assays: drug resistance mutations in influenza virus as an example
Bronchiectasis is an increasingly recognised respiratory condition with limited therapeutic options and a complex spectrum of clinical manifestations that invariably includes chronic cough. As the primary presentation of bronchiectasis in most cases, chronic cough and its mechanistic underpinnings are of central importance but remain poorly understood in this setting. Bronchiectasis is also increasingly identified as an underlying cause of chronic cough highlighting the interrelationship between the two conditions that share overlapping clinical features. Several therapeutic approaches have illustrated positive effects on bronchiectasis-associated cough, however, more focused treatment of heterogeneous cough subtypes may yield better outcomes for patients. A current challenge is the identification of bronchiectasis and cough endophenotypes that may allow improved patient stratification and more targeted therapeutic matching of the right treatment to the right patient. Here we discuss the complex disease phenotypes of bronchiectasis and their interrelationship with cough while considering current and emerging treatment options. We discuss some key cough promoters in bronchiectasis including infection, allergy and immune dysfunction.
Output: Bronchiectasis and cough: An old relationship in need of renewed attention Chronic cough Bronchiectasis
In 1981, a new virus (virus 132) was described for the first time with morphological and biochemical similarities to rotaviruses (RVs), but without antigenic similarity to any of the previously known rotavirus groups. Subsequently, it was re-designated as D/132, and formed a new serogroup among rotaviruses, the group D rotavirus (RVD). Since their identification, RVs are the leading cause of enteritis and diarrhea in humans and various animal species, and are also associated with abridged growth, particularly in avian species. Recently, RVD has been suggested to play a role in the pathogenesis of runting and stunting syndrome (RSS), alongside other viruses such as reovirus, astrovirus, coronavirus, and others, all of which cause colossal economic losses to the poultry industry. RVD has been reported from several countries worldwide, and to date, only one complete genome sequence for RVD is available. Neither an immunodiagnostic nor a vaccine is available for the detection and prevention of RVD infection. Despite our growing understanding about this particular group, questions remain regarding its exact prevalence and pathogenecity, and the disease-associated annual losses for the poultry industry. Here, we describe the current knowledge about the identification, epidemiology, diagnosis, and prevention of RVD in poultry.
Output: Avian Group D Rotaviruses: Structure, Epidemiology, Diagnosis, and Perspectives on Future Research Challenges
The Syrian golden hamster (Mesocricetus auratus) is a valuable but under-utilized animal model for studies of human viral pathogens such as bunyaviruses, arenaviruses, flaviviruses, henipaviruses, and SARS-coronavirus. A lack of suitable reagents and specific assays for monitoring host responses has limited the use of this animal model to clinical observations, pathology and humoral immune responses. The objective of this study was to establish and validate assays to monitor host immune responses in the hamster including important proinflammatory, anti-inflammatory and innate immune responses, as well as markers of apoptosis, cell proliferation, cell junction integrity and coagulation. Commercially available mouse and rat ELISA and luminex panels were screened for potential cross-reactivity, but were found to be of limited value for studying host responses in hamsters. Subsequently, quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays for the detection of 51 immune-related and four internal reference genes were developed. To validate the immune-related assays, hamsters were infected with vesicular stomatitis virus (VSV), Indiana species, or treated with lipopolysaccharide (LPS) and host immune responses were monitored in selected organs. Ribosomal protein L18 was identified as the most stable internal reference gene. In conclusion, these new assays will greatly improve the use of the hamster as an important small animal model in infectious disease research. Published by Elsevier B.V.
Output: Validation of assays to monitor immune responses in the Syrian golden hamster (Mesocricetus auratus)
The COVID-19 infections in Pakistan are spreading at an exponential rate and a point may soon be reached where rigorous prevention measures would need to be adopted. Mathematical models can help define the scale of an epidemic and the rate at which an infection can spread in a community. We used an SIR model to predict the magnitude of the COVID-19 epidemic in Pakistan and compared the numbers with the reported cases on the national database. Our results indicate that Pakistan could hit peak number of infectious cases on May 26th, 2020 and by June 24th, 2020, 90% of the population will have become infected with the virus if policy interventions seeking to curb this infection are not adopted aggressively. Since the emergence of COVID-19, several mathematical models have been developed to simulate the rate of infection spread, infections per day and the resolution of the epidemic. The SIR model refers to the number of susceptible, infected and recovered cases during an epidemic at any given time. The model assumes that susceptible cases (S), infected cases (I) and . CC-BY-ND 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: Estimation of the Final Size of the COVID-19 Epidemic in Pakistan
Exosomes are 40-100 nm membrane vesicles secreted into the extracellular space by numerous cell types. These structures can be isolated from body fluids including urine and plasma. Exosomes contain proteins, mRNAs, miRNAs, and signaling molecules that reflect the physiological state of their cells of origin and consequently provide a rich source of potential biomarker molecules. Aside from diagnostic uses, exosome-mediated transfer of proteins, mRNAs, miRNAs, and signaling molecules offer the promise that they may be used for therapeutic purposes. In this review, we integrate new knowledge about exosomes from outside the field of nephrology with recent progress by renal researchers in order to provide a basis for speculation about how the study of exosomes may affect the fields of nephrology and renal physiology in the next few years.
Output: Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases
Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings.
Output: Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset
Intra-vitam diagnosis of feline infectious peritonitis (FIP) is a challenge for veterinary diagnosticians, since there are no highly specific and sensitive assays currently available. With the aim to contribute to fill this diagnostic gap, a total of 61 effusions from cats with suspected effusive FIP were collected intra-vitam for detection of feline coronavirus (FCoV) antibodies and RNA by means of indirect immunofluorescence (IIF) assay and real-time RT-PCR (qRT-PCR), respectively. In 5 effusions there was no evidence for either FCoV RNA or antibodies, 51 and 52 specimens tested positive by IIF and qRT-PCR, respectively, although antibody titres ≥ 1:1600, which are considered highly suggestive of FIP, were detected only in 37 effusions. Three samples with high antibody levels tested negative by qRT-PCR, whereas 18 qRT-PCR positive effusions contained no or low-titre antibodies. qRT-PCR positive samples with low antibody titres mostly contained low FCoV RNA loads, although the highest antibody titres were detected in effusions with C T values > 30. In conclusion, combining the two methods, i.e., antibody and RNA detection would help improving the intra-vitam diagnosis of effusive FIP. Effusions were collected intra-vitam from 61 cats whose FIP diagnosis was highly suspected since the clinical cases fulfilled all, or most, of the criteria for FIP diagnosis given in the European Advisory Board of Cat Disease recommendations (Addie et al., 2009,) , as previously http://dx.
Output: Discrepancies between feline coronavirus antibody and nucleic acid detection in effusions of cats with suspected feline infectious peritonitis
Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-b mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-b promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-b mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa. 81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominantnegative functions for NSs-mediated IFN-b suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.
Output: Functional Analysis of Rift Valley Fever Virus NSs Encoding a Partial Truncation
Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV). There are no effective vaccines or treatment available, and the virus virulence determinants and pathogenesis are not fully understood. Here, we describe the sequencing of RNA extracted from Crandell Rees Feline Kidney (CRFK) cells infected with FIPV using the Illumina next-generation sequencing approach. Bioinformatics analysis, based on Felis catus 2X annotated shotgun reference genome, using CLC bio Genome Workbench is used to map both control and infected cells. Kal's Z test statistical analysis is used to analyze the differentially expressed genes from the infected CRFK cells. In addition, RT-qPCR analysis is used for further transcriptional profi ling of selected genes in infected CRFK cells and Peripheral Blood Mononuclear Cells (PBMCs) from healthy and FIP-diagnosed cats.
Output: Transcriptome Analysis of Feline Infectious Peritonitis Virus Infection
The porcine reproductive and respiratory syndrome virus (PRRSV) has three major structural proteins which designated as GP5, M, and N. Protein GP5 and M have been considered very important to arouse the humoral and cellular immune responses against PRRSV infection and proposed to be the excellent candidate proteins in the design of PRRS bioengineering vaccine. There were some attempts on expressing GP5 or M in DNA vaccine and adenovirus to arouse humoral and cellular immune responses, but few papers have been reported on that the immune response can be difference because of the expression patterns of GP5 and M proteins in the recombinant virus. In this article, four recombinant viruses that expressed GP5 and M proteins of PRRSV in the modified vaccinia virus ankara (MVA) with different expression patterns were made. In these recombinant virus (rMVAs), GP5 and M proteins were expressed in MVA in the same virus but under the control of two promoters (rMVA-GP5/ M), or as a fusion protein under one promoter (rMVA-GP5-M), or separately (rMVA-GP5 and rMVA-M). The humoral and cellular immune responses for the four recombinant viruses were evaluated with mouse model. Every mouse was inoculated with 5 · 10 5 TCID 50 of the different rMVAs and boosted 3 weeks later. Neutralizing antibody titers for each group were detected with virus neutralization test assay weekly after the primary inoculation for 13 weeks to evaluate the humoral immune response. The production of gamma interferon (IFN-c), interleukin-2 (IL-2), and interleukin-4 (IL-4) was detected in splenocytes of rMVA-inoculated mice at 30, 60, and 90 days post inoculation to evaluate the cellular immune response. Results showed that rMVA-GP5 and rMVA-M cannot induce obvious humoral and cellular immune responses; rMVA-GP5-M inoculated group developed better immune responses than rMVA-GP5 and rMVA-M inoculated groups; however, mice inoculated with rMVA-GP5/M maintained the strongest cellular response against PRRS and consistently enhanced the anti-PRRSV humoral responses. The strategy of co-expressing PRRSV GP5 and M protein in MVA under the control of different promoters might be an attractive method for future PRRSV vaccine design.
Output: Co-expressing GP5 and M proteins under different promoters in recombinant modified vaccinia virus ankara (rMVA)-based vaccine vector enhanced the humoral and cellular immune responses of porcine reproductive and respiratory syndrome virus (PRRSV)
Chemokines play a pivotal role in the innate response to both bacterial and viral infections, and in mixed infections. To determine chemokine responses to Sindbis virus (SIN) in a co-infection model, peripheral blood mononuclear cells (PBMCs) derived from healthy volunteers were exposed to SIN in the presence and absence of lipopolysaccharide (LPS). Culture supernatants recovered at 2, 24, and 72 h post-exposure were evaluated for virus replication and analyzed for chemokines by ELISA. None of the PBMC cultures showed new virus release, GFP reporter expression, or viral RNA synthesis. While SIN had little effect on the induction of IL-8 and RANTES, the chemokines MCP-1, MIP1-a ( p < 0.001), and MIP1-b ( p < 0.0004) were drastically upregulated by SIN as well as LPS. Both live and UV-inactivated SIN induced secretion of IP-10 and I-TAC. Although LPS did not induce release of IP-10, it sharply inhibited ( p ¼ 0.004) SIN-mediated IP-10 secretion. On the contrary, the release of SLC was blocked by SIN. The adjuvant activity of IP-10, its antiangiogenic function, and antagonism between SIN and LPS for the release of select chemokines may be useful in understanding the pathogenesis of mixed infections, cross-talk between cellular pathways, and may have applications in cancer and sepsis.
Output: Brief Reports Lipopolysaccharide Inhibits Sindbis Virus-Induced IP-10 Release in Human Peripheral Blood Mononuclear Cells
International Concern (PHEIC) Zika WHO Emergency response Lessons identified Global Health Security a b s t r a c t Objectives: To consider why Zika was declared a Public Health Emergency of International Concern (PHEIC), why it stopped being one and what we can learn from this for the future. Study design: This paper reviews the sequence of events and evidence base for the decision to declare Zika a PHEIC, the global response to this, the challenges in maintaining an evidence-based approach to outbreak response and identifies learning outcomes. Methods: Evidence review, all published articles in reputable UK and international journals were identified. : The association between Zika virus infection and congenital malformations including microcephaly became a PHEIC on 1st February 2016 and was declared to be no longer an emergency in November 2016. This shaped the global response led by WHO in the first global emergency since Ebola in West Africa. Conclusion: The response to Zika highlights important issues and lessons for future outbreaks that might pose an international risk. Particular challenges arose in trying to maintain an evidence-based approach to public risk communication when the evidence is unclear or still evolving. The Zika incident also demonstrates the importance of public health practitioners and agencies understanding the political context in which outbreaks must be managed and understanding the competing factors that shape the political response. Public Health jo urnal homepage: www .e lse vi er.co m/ pu he p u b l i c h e a l t h 1 5 0 ( 2 0 1 7 ) 8 7 e9 2 http://dx.
Output: The rise of Zika infection and microcephaly: what can we learn from a public health emergency?
Waltner-Toews, D., Martin, S.W., Meek, A.H. and McMillan, I., 1986. Dairy calf management, morbidity and mortality in Ontario Holstein herds. I. The Data. Prey. Vet. Med., Heifer calf management practices and clinical outcomes were studied on 104 randomly selected Holstein dairy farms in southwestern Ontario between October 1980 and July 1983. Data were collected at both the farm level (all farms) and the individual calf level (1968 calves, 35 farms). Farm-level management data were collected by means of questionnaires and farm visits. Calf-level management data were recorded by farmers on forms provided. Treatments for disease and mortality data were recorded by the farmers on the calves up to the age of weaning, the age at which calves were no longer fed milk or milk substitutes on a regular basis. Farm size ranged from 23 to 154 calvings per year. Farm-level'mortality rates per sixmonth season (winter/summer) were skewed, with a mean of about 6%, a median of zero, and a range of 67%. Morbidity rates were similarly skewed. Four percent of liveborn heifer calves died, 20% were treated for scours, and 15% were treated for pneumonia before the age of weaning. Stated farm policies on calf rearing were implemented to varying degrees on different farms, as estimated from individual calf data. This posed particular problems for interpreting farm-level data, since the danger of committing an ecologic fallacy was high. The data set described in this paper formed the basis for an observational study of the interrelationships of heifer calf management and clinical outcomes.
Output: DAIRY CALF MANAGEMENT, MORBIDITY AND MORTALITY IN ONTARIO HOLSTEIN HERDS. I. THE DATA
Objectives: No international consensus has been reached on the empirical use of antibiotics with atypical coverage in nursing homeeacquired pneumonia (NHAP). Aspiration is an important cause of NHAP, but it may not require antimicrobial treatment. This study aimed to investigate the prevalence and clinical characteristics of AP infections and review the need for empirical antibiotics with atypical coverage in NHAP. Design: A prospective cohort study. Setting: Four nursing homes with a total number of 772 residents. Participants: Patients were aged ! 65 years, hospitalized for NHAP, which was defined as the presence of respiratory symptoms and abnormal chest radiographs, from April 2006 to March 2007. Measurements: Demographics, clinical parameters, and investigation results were recorded. Microbial investigations comprised sputum routine and mycobacterial cultures, blood and urine cultures, serology, and nasopharyngeal aspirate viral culture and polymerase chain reaction tests. Suspected aspiration pneumonitis was arbitrarily defined as NHAP without pathogens identified. Results: After excluding lone bacteriuria, 108 episodes of NHAP in 94 patients were included. Twelve APs were detected in 11 patients. There was no clinical feature to distinguish between infections caused by APs and other pathogens. The commonest APs were Mycoplasma pneumoniae (6) and Chlamydophila pneumoniae (3). No Legionella pneumophila was detected by urinary antigen test. None of the patients with AP infection received antibiotics indicated for AP infections. However, AP infections did not result in mortality. No pathogen was isolated in 31.5% of cases. Patients without pathogens isolated were less likely to have purulent sputum and crepitations on chest auscultation, compared with those with pneumonia caused by identified pathogens. Conclusions: Atypical pathogens (APs) were not associated with mortality even in cases where the prescribed antibiotics did not cover APs. NHAP may not necessarily be treated with empirical antibiotics covering APs.
Output: Role of Atypical Pathogens in Nursing HomeeAcquired Pneumonia
Normal piglets weaned onto soy-or egg-based diets generated antibody responses to fed protein. Concurrent infection with transmissible gastroenteritis virus (TGEV) did not affect the responses to dietary antigens at weaning, nor did it affect the subsequent development of tolerance. However, TGEV infection did enhance the primary immunoglobulin M (IgM) and IgG1, but not IgG2, antibody responses to injected soy in comparison to those of uninfected animals. Paradoxically, TGEV-infected animals showed an enhanced primary IgG1 antibody response to injected soy at 4 weeks of age, but they subsequently showed a reduced secondary response after an intraperitoneal challenge at 9 weeks of age in comparison to uninfected animals. The results suggest that an enteric virus, either used as a vaccine vector or present as a subclinical infection, may not have significant effects on the development of dietary allergies but may have effects both on the primary response and on the subsequent recall response to systemic antigens to which the animal is exposed concurrently with virus antigens. on March 24, 2020 by guest http://cvi.asm.org/ Downloaded from FIG. 5. Total antigen-nonspecific immunoglobulin levels throughout the experimental period for all groups. (a and b) Piglets weaned onto a soy-based diet. (c and d) Piglets weaned onto an egg-based diet. (e and f) Piglets weaned onto an egg-based diet and injected with soy intramuscularly at weaning. IgG1 levels (a, c, and e) and IgG2 levels (b, d, and f) are shown. Results shown are means Ϯ standard errors. 342 BAILEY ET AL. CLIN. DIAGN. LAB. IMMUNOL. on March 24, 2020 by guest
Output: Effects of Infection with Transmissible Gastroenteritis Virus on Concomitant Immune Responses to Dietary and Injected Antigens
To develop CpG oligodeoxynucleotides (CpG ODNs) based therapy for prevention and treatment of severe acute respiratory syndrome (SARS), we selected a novel CpG ODN (BW001), which displays B-type CpG ODN structure feature at the 5V and A-type CpG ODN structure feature at the 3V, and tested for its anti-SARS-CoV activity. We found that the supernatants of human PBMCs stimulated by BW001 significantly protected Vero cells from SARS-CoV infection. BW001 could stimulate human PBMCs and pDCs to secrete high level of IFN-a and promote human PBMCs and B cells to proliferate. Furthermore, we demonstrated that BW001 could activate CD19 + B cells and CD56 + NK cells in human PBMCs. In addition, BW001 could enhance NK cytotoxicity and IFN-g secretion in human PBMCs. Together, BW001 represents a novel type of CpG ODN and may have potential for the development of treatment and prevention for SARS as well as other viral associated diseases. D
Output: Anti-SARS-CoV immunity induced by a novel CpG oligodeoxynucleotide
Although the importance of eggs as a source of specific antibodies has been well recognised, the generation of egg yolk immunoglobulins (IgY) is rarely chosen due to the peculiar composition of egg yolk and the lack of specific affinity ligands. In this work, we report a novel membrane based two-stage ultrafiltration process to isolate IgY from egg yolk. The effects of solution pH, ionic strength, stirring speed and permeate flux on the transmission of proteins were quantified using the pulsed sample injection technique and parameter scanning ultrafiltration. Under optimised conditions, the purity of immunoglobulin obtained was greater than 93% after the two-stage ultrafiltration process and the recovery of immunoglobulin from the feedstock was close to 87%. The resulting immunoglobulin product was then analysed by Isoelectric Focusing (IEF), SDS-PAGE and Circular Dichroism (CD), to confirm its isoelectric point, molecular weight and molecular secondary structure.
Output: A new membrane based process to isolate immunoglobulin from chicken egg yolk
Background: Hospital-acquired infections such as nosocomial pneumonia are a serious cause of mortality for hospitalized patients, especially for those admitted to intensive care units (ICUs). Despite the number of the studies reported to date, the causative agents of pneumonia are not completely known. Herein, we found by molecular technique that vegetable and tobacco DNA may be detected in the bronchoalveolar lavage from patients with ventilator-associated pneumonia (VAP). In the present study, we studied bronchoalveolar lavage (BAL) from patients admitted to ICUs with ventilator-associated pneumonia. BAL fluids were assessed with molecular tests, culture and blood culture. We successfully identified plant DNA in six patients out of 106 (6%) with ventilator-associated pneumonia. Inhalation was confirmed in four cases and suspected in the other two cases. Inhalation was significantly frequent in patients with plant DNA (four out of six patients) than those without plant DNA (three out of 100 patients) (P,0.001). Nicotiana tabacum chloroplast DNA was identified in three patients who were smokers (cases 2, 3 and 6). Cucurbita pepo, Morus bombycis and Triticum aestivum DNA were identified in cases 1, 4 and 5 respectively. Twenty-three different bacterial species, two viruses and five fungal species were identified from among these six patients by using molecular and culture techniques. Several of the pathogenic microorganisms identified are reported to be food-borne or tobacco plant-associated pathogens. Conclusions/Significance: Our study shows that plants DNA may be identified in the BAL fluid of pneumonia patients, especially when exploring aspiration pneumonia, but the significance of the presence of plant DNA and its role in the pathogenesis of pneumonia is unknown and remains to be investigated. However, the identification of these plants may be a potential marker of aspiration in patients with pneumonia.
Output: Detection of Plant DNA in the Bronchoalveolar Lavage of Patients with Ventilator-Associated Pneumonia
Sato, K., Inaba, Y., Kurogi, H., Takahashi, E., Satoda, K., Omori, T. and Matumoto, M.t 1977. Hemagglutination by calf diarrhea coronavirus. Vet. Microbiol., 2: 83--87. The virus was grown in BEK-1 cells, a stable cell line from bovine embryo kidney, and tested for hemagglutinafion (HA) with erythrocytes of a variety of species at 4°C, room temperature and 37°C. HA was observed at all temperatures with chicken, mouse, rat, and hamste~ erythrocytes but not with erythrocytes of human (O), cattle, horses, ~heep, guinea pigs, geese, duck~, pigeons and l-day-old chicks. Chickens showed a~ individual variation in agglutinability of their erythrocytes, requiring selection of birds to obtain erythrocytes for HA. HA reaction was inhibited by specific antiserum. Some factors involved in HA and HA inhibition (HI) were investigated and standard HA and HI tests were worked out.
Output: Short Communication HEMAGGLUTINATION BY CALF DIARRHEA CORONAVIRUS
Aim: The aim of the study was to examine, among hospital employees exposed to an outbreak of severe acute respiratory syndrome (SARS), post-outbreak levels of depressive symptoms and the relationship between those depressive symptom levels and the types of outbreak event exposures experienced. Methods: In 2006, randomly selected employees (N = 549) of a hospital in Beijing were surveyed concerning their exposures to the city's 2003 SARS outbreak and the ways in which the outbreak had affected their mental health. Subjects were assessed on sociodemographic factors, on types of exposure to the outbreak, and on symptoms of posttraumatic stress disorder and depression. Results: The results of multinomial regression analyses showed that, with other relevant factors controlled for, being single, having been quarantined during the outbreak, having been exposed to other traumatic events before SARS, and perceived SARS-related risk level during the outbreak were found to increase the odds of having a high level of depressive symptoms 3 years later. Altruistic acceptance of risk during the outbreak was found to decrease the odds of high post-outbreak depressive symptom levels. Conclusions: Policy makers and mental health professionals working to prepare for potential disease outbreaks should be aware that the experience of being quarantined can, in some cases, lead to long-term adverse mental health consequences.
Output: Depression after exposure to stressful events: lessons learned from the severe acute respiratory syndrome epidemic
Aryl diketoacids have been identified as the first SARS-CoV NTPase/helicase inhibitors with a distinct pharmacophore featuring an arylmethyl group attached to a diketoacid. In order to search for the pharmacophore space around the diketoacid core, three classes of dihydroxychromone derivatives were prepared. Based on SAR study, an extended feature of the pharmacophore model of SARS-CoV NTPase/ helicase was proposed which is constituted of a diketoacid core, a hydrophobic arylmethyl substituent, and a free catechol unit.
Output: Investigation of the pharmacophore space of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) NTPase/helicase by dihydroxychromone derivatives
Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFNs and cellular anti-proliferative activities. We previously showed that the IFITM3 single nucleotide polymorphisms (SNPs) associated with susceptibility to ulcerative colitis (UC). The present study aimed to investigate whether the polymorphisms in the IFITM1 gene are associated with susceptibility to UC. We also evaluated the expression levels in the putative functional promoter polymorphisms to determine the change of their activity. Gene expression profiles in the tissues obtained from human digestive tracts by RT-PCR, and the possible variation sites and SNPs of IFITM1 were identified by direct sequencing method. Genotype analysis in the IFITM1 SNPs was performed by high resolution melting and TaqMan probe analysis, and the haplotype frequencies of IFITM1 SNPs for multiple loci were estimated using the expectation maximization (EM) algorithm. The expression levels in the putative functional promoter polymorphisms were evaluated by performing a luciferase reporter assay. We identified two SNPs and two variation sites, g.-1920G>A (rs77537847), g.-1547delA (novel) and g.-416C>G (rs11246062) in the promoter region, and g.364delA (rs200576757) in intron 1. The genotype and allele frequencies of the g.-1920G>A polymorphism of IFITM1 gene in the UC patients were significantly different from those of the healthy controls (P = 0.002 and 0.042, respectively). These results suggest that the g.-1920G>A polymorphism in IFITM1 may be associated with susceptibility to UC.
Output: Identification of the polymorphisms in IFITM1 gene and their association in a Korean population with ulcerative colitis
We propose a new four state model for disease transmission and illustrate the model with data from the 2003 SARS epidemic in Hong Kong. The critical feature of this model is that the community is modelled as a small-world network of interconnected nodes. Each node is linked to a fixed number of immediate neighbors and a random number of geographically remote nodes. Transmission can only propagate between linked nodes. This model exhibits two features typical of SARS transmission: geographically localized outbreaks and ''superspreaders''. Neither of these features are evident in standard susceptible-infected-removed models of disease transmission. Our analysis indicates that ''super-spreaders'' may occur even if the infectiousness of all infected individuals is constant. Moreover, we find that nosocomial transmission in Hong Kong directly contributed to the severity of the outbreak and that by limiting individual exposure time to 3-5 days the extent of the SARS epidemic would have been minimal. r
Output: Clustering model for transmission of the SARS virus: application to epidemic control and risk assessment
Background: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB. The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA). Results: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels. Conclusions: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application.
Output: The discovery and identification of a candidate proteomic biomarker of active tuberculosis