title: DDX5 RNA Helicases: Emerging Roles in Viral Infection

text: Asp-Glu-Ala-Asp (DEAD)-box polypeptide 5 (DDX5), also called p68, is a prototypical member of the large ATP-dependent RNA helicases family and is known to participate in all aspects of RNA metabolism ranging from transcription to translation, RNA decay, and miRNA processing. The roles of DDX5 in cell cycle regulation, tumorigenesis, apoptosis, cancer development, adipogenesis, Wnt-β-catenin signaling, and viral infection have been established. Several RNA viruses have been reported to hijack DDX5 to facilitate various steps of their replication cycles. Furthermore, DDX5 can be bounded by the viral proteins of some viruses with unknown functions. Interestingly, an antiviral function of DDX5 has been reported during hepatitis B virus and myxoma virus infection. Thus, the precise roles of this apparently multifaceted protein remain largely obscure. Here, we provide a rapid and critical overview of the structure and functions of DDX5 with a particular emphasis on its role during virus infection.


title: The first clusters of Middle East respiratory syndrome coronavirus in Oman: Time to act

text: Abstract Introduction Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging infectious disease of growing global importance. This review describes the latest MERS-CoV clusters and the first cases of nosocomial transmission within health care facilities in Oman. We have highlighted lessons learned and proposed steps to prevent healthcare-associated infections. Methods A descriptive analysis of MERS-CoV cases was conducted between January 23 and February 16, 2019. The data from officials and other published sources used. Results Thirteen laboratory-confirmed cases of MERS-CoV were reported from three simultaneous clusters from two governorates without an epidemiological link between the clusters. Two clusters were reported from North Al Batinah Governorate, with nine cases (69%) and 1 cluster from South Ash Sharqiyah Governorate with four cases (31%). In total, four deaths were reported (case fatality rate 31%). Four cases (31%) reported were household contacts from the first cluster, 3 (23%) were nosocomial transmission in health care facilities (two for first and one from the second cluster) and 7 (54%) were community-acquired cases. Conclusions The first local clusters of MERS-CoV reported with evidence suggestive of healthcare and household-associated transmission. Early diagnosis and strict implementation of infection control measures remain fundamental in preventing and managing MERS-CoV infection.


title: Expecting the unexpected: nucleic acid-based diagnosis and discovery of emerging viruses

text: Extrapolation from recent disease history suggests that changes in the global environment, including virus, vector and human behavior, will continue to influence the spectrum of viruses to which humans are exposed. In this article, these environmental changes will be enumerated, and their potential impact on target-focused, nucleic acid-based diagnostic tests will be considered, followed by a presentation of some emerging technological responses.


title: The methyltransferase domain of dengue virus protein NS5 ensures efficient RNA synthesis initiation and elongation by the polymerase domain

text: Viral RNA-dependent RNA polymerases (RdRps) responsible for the replication of single-strand RNA virus genomes exert their function in the context of complex replication machineries. Within these replication complexes the polymerase activity is often highly regulated by RNA elements, proteins or other domains of multi-domain polymerases. Here, we present data of the influence of the methyltransferase domain (NS5-MTase) of dengue virus (DENV) protein NS5 on the RdRp activity of the polymerase domain (NS5-Pol). The steady-state polymerase activities of DENV-2 recombinant NS5 and NS5-Pol are compared using different biochemical assays allowing the dissection of the de novo initiation, transition and elongation steps of RNA synthesis. We show that NS5-MTase ensures efficient RdRp activity by stimulating the de novo initiation and the elongation phase. This stimulation is related to a higher affinity of NS5 toward the single-strand RNA template indicating NS5-MTase either completes a high-affinity RNA binding site and/or promotes the correct formation of the template tunnel. Furthermore, the NS5-MTase increases the affinity of the priming nucleotide ATP upon de novo initiation and causes a higher catalytic efficiency of the polymerase upon elongation. The complex stimulation pattern is discussed under the perspective that NS5 adopts several conformations during RNA synthesis.


title: Coronavirus disease pandemic (Covid-19): Challenges and a global perspective

text: The technology-driven world of the 21stcentury is currently confronted with a major threat to humankind, represented by the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2). As of now, COVID-19 has affected more than 6 million confirmed cases and took 0.39 million human lives. SARS-CoV-2 spreads much faster than its two ancestors, SARS-CoV and Middle East respiratory syndrome-CoV (MERS-CoV), but has low fatality rates. Our analyses speculate that the efficient replication and transmission of SARS-CoV-2 might be due to the high-density basic amino acid residues, preferably positioned in close proximity at both the furin-like cleavage sites (S1/S2 and S2’) within the spike protein. Given the high genomic similarities of SARS-CoV-2 to bat SARS-like CoVs, it is likely that bats serve as a reservoir host for its progenitor. Women and children are less susceptible to SARS-CoV-2 infection, while the elderly and people with comorbidities are more prone to serious clinical outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. The cohesive approach amongst researchers across the globe has delivered high-end viral diagnostics. However, home-based point-of-care diagnostics are still under development, which may prove transformative in current COVID-19 pandemic containment. Similarly, vaccines and therapeutics against COVID-19 are currently in the pipeline for clinical trials. In this review, we discuss the noteworthy advancements, focusing on the etiological viral agent, comparative genomic analysis, population susceptibility, disease epidemiology and diagnosis, animal reservoirs, laboratory animal models, disease transmission, therapeutics, vaccine challenges, and disease mitigation measures.


title: A single chain Fv antibody displayed on phage surface recognises conformational group-specific epitope of bluetongue virus

text: Abstract A single chain fragment variable (scFv) antibody gene was isolated from hybridoma cell line secreting monoclonal antibody (MAb) 20E9 that recognises bluetongue virus (BTV) VP7. DNA fragments encoding variable regions of heavy and light chains were amplified by RT-PCR and library of scFv was constructed in phage vector. Two scFv clones that were selected showed specific reactivity with conformational epitope VP7. The N-terminal 22 amino acid residues of 20E9 light chain were identical to that deduced from scFv DNA sequence. An in-frame TAG stop codon was found in the coding sequence and its potential role in regulating the expression and stability of scFv in phage is discussed.


title: The mutual effects of COVID-19 and obesity

text: • The rate of obesity was increased during this era of the COVID-19 epidemic. • Obesity is dangerous in COVID-19 patients.


title: SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

text: BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection.


title: Avian influenza A/H5N1 neuraminidase expressed in yeast with a functional head domain

text: Abstract The study reports heterologous expression in Pichia pastoris of active neuraminidase derived from avian influenza virus A/Viet Nam/DT-036/2005(H5N1). A gene encoding the neuraminidase N1 head domain (residues 63–449) was fused directly in-frame with the Saccharomyces cerevisiae α-factor secretion signal in pPICZ(A vector. Recombinant N1 neuraminidase was expressed in P. pastoris as a 72kDa secreted, soluble protein. Glycopeptidase F treatment generated a 45kDa product, indicating that the secreted recombinant N1 neuraminidase is an N-linked glycoprotein. Kinetic studies and inhibition tests with oseltamivir carboxylate demonstrated that the recombinant N1 neuraminidase has similar K m and K i values to those of the viral N1 neuraminidase. This yeast-based heterologous expression system provided functionally active recombinant N1 neuraminidase that should be useful in anti-influenza drug screening, and also as a potential protein-based vaccine.


title: What did we learn from preparing for cross-border transmission of Ebola virus disease into a complex humanitarian setting – The Republic of South Sudan?

text: BACKGROUND: Following the West Africa Ebola virus disease (EVD) outbreak (2013–2016), WHO developed a preparedness checklist for its member states. This checklist is currently being applied for the first time on a large and systematic scale to prepare for the cross border importation of the ongoing EVD outbreak in the Democratic Republic of Congo hence the need to document the lessons learnt from this experience. This is more pertinent considering the complex humanitarian context and weak health system under which some of the countries such as the Republic of South Sudan are implementing their EVD preparedness interventions. MAIN TEXT: We identified four main lessons from the ongoing EVD preparedness efforts in the Republic South Sudan. First, EVD preparedness is possible in complex humanitarian settings such as the Republic of South Sudan by using a longer-term health system strengthening approach. Second, the Republic of South Sudan is at risk of both domestic and cross border transmission of EVD and several other infectious disease outbreaks hence the need for an integrated and sustainable approach to outbreak preparedness in the country. Third, a phased and well-prioritized approach is required for EVD preparedness in complex humanitarian settings given the costs associated with preparedness and the difficulties in the accurate prediction of outbreaks in such settings. Fourth, EVD preparedness in complex humanitarian settings is a massive undertaking that requires effective and decentralized coordination. CONCLUSION: Despite a very challenging context, the Republic of South Sudan made significant progress in its EVD preparedness drive demonstrating that it is possible to rapidly scale up preparedness efforts in complex humanitarian contexts if appropriate and context-specific approaches are used. Further research, systematic reviews and evaluation of the ongoing preparedness efforts are required to ensure comprehensive documentation and application of the lessons learnt for future EVD outbreak preparedness and response efforts.


title: No slack in diseases threat

text: Summary A new WHO report argues that there should be no let up in efforts to increase global cooperation in the face of still unprecedented threats from new diseases. Nigel Williams reports.


title: A Python based Support Vector Regression Model for prediction of Covid19 cases in India

text: The proposed work utilizes Support Vector Regression model to predict the number of total number of deaths, recovered cases, cumulative number of confirmed cases and number of daily cases. The data is collected for the time period of 1(st) March,2020 to 30(th) April,2020 (61 Days). The total number of cases as on 30(th) April is found to be 35043 confirmed cases with 1147 total deaths and 8889 recovered patients. The model has been developed in Python 3.6.3 to obtain the predicted values of aforementioned cases till 30(th) June,2020. The proposed methodology is based on prediction of values using support vector regression model with Radial Basis Function as the kernel and 10% confidence interval for the curve fitting. The data has been split into train and test set with test size 40% and training 60%. The model performance parameters are calculated as mean square error, root mean square error, regression score and percentage accuracy. The model has above 97% accuracy in predicting deaths, recovered, cumulative number of confirmed cases and 87% accuracy in predicting daily new cases. The results suggest a gaussian decrease of the number of cases and could take another 3 to 4 months to come down the minimum level with no new cases being reported. The method is very efficient and has higher accuracy than linear or polynomial regression.


title: Silver nanoparticles as an effective disinfectant: A review

text: Abstract The paradigm modifications in the metallic crystals from bulky to micro-size to nano-scale have resulted in excellent and amazing properties; which have been the remarkable interests in a wider range of applications. Particularly, Ag NPs have much attention owing to their distinctive optical, chemical, electrical and catalytic properties that can be tuned with surface nature, size, shapes, etc. and hence these crystals have been used in various fields such as catalysis, sensor, electronic components, antimicrobial agents in the health industry etc. Among them, Ag NPs based disinfectants have paid attention due to the practical applications in our daily life. Therefore the Ag NPs have been used in different sectors such as silver-based air/water filters, textile, animal husbandry, biomedical and food packaging etc. In this review, the Ag NPs as a disinfectant in different sectors have been included in detail.


title: Small mammal virology

text: Most viral infections in small mammals are transient and rarely produce clinical signs. When clinical signs do appear, they are often of a multifactorial etiology such as respiratory infection with Sendai virus and the bacteria M. pulmonis in rodents. Diagnosis is generally made based on clinical signs, while therapy involves treatment for concurrent bacterial infections and supportive care. Small mammals may carry zoonotic viruses such as LCMV, but natural infections are uncommon. Viral diseases are rare (or largely unknown) for hedgehogs, chinchillas, and prairie dogs, while no known naturally occurring, clinically relevant viral diseases exist for gerbils and sugar gliders. This article is intended to aid the clinician in identifying viral infections in small mammals and to help determine the significance each virus has during clinical disease.


title: Middle East respiratory syndrome coronavirus on inanimate surfaces: A risk for health care transmission

text: The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care–associated outbreaks. We investigated whether high-touch surfaces in 3 rooms of laboratory-confirmed MERS-CoV patients were contaminated with MERS-CoV RNA. We found 2 out of 51 surfaces were contaminated with MERS-CoV viral genetic material. Hence, environmental contamination may be a potential source of health care transmission and outbreaks. Meticulous environmental cleaning may be important in preventing transmission within the health care setting.


title: Multiplexed Component Analysis to Identify Genes Contributing to the Immune Response during Acute SIV Infection

text: Immune response genes play an important role during acute HIV and SIV infection. Using an SIV macaque model of AIDS and CNS disease, our overall goal was to assess how the expression of genes associated with immune and inflammatory responses are longitudinally changed in different organs or cells during SIV infection. To compare RNA expression of a panel of 88 immune-related genes across time points and among three tissues – spleen, mesenteric lymph nodes (MLN) and peripheral blood mononuclear cells (PBMC) – we designed a set of Nanostring probes. To identify significant genes during acute SIV infection and to investigate whether these genes are tissue-specific or have global roles, we introduce a novel multiplexed component analysis (MCA) method. This combines multivariate analysis methods with multiple preprocessing methods to create a set of 12 “judges”; each judge emphasizes particular types of change in gene expression to which cells could respond, for example, the absolute or relative size of expression change from baseline. Compared to bivariate analysis methods, our MCA method improved classification rates. This analysis allows us to identify three categories of genes: (a) consensus genes likely to contribute highly to the immune response; (b) genes that would contribute highly to the immune response only if certain assumptions are met – e.g. that the cell responds to relative expression change rather than absolute expression change; and (c) genes whose contribution to immune response appears to be modest. We then compared the results across the three tissues of interest; some genes are consistently highly-contributing in all tissues, while others are specific for certain tissues. Our analysis identified CCL8, CXCL10, CXCL11, MxA, OAS2, and OAS1 as top contributing genes, all of which are stimulated by type I interferon. This suggests that the cytokine storm during acute SIV infection is a systemic innate immune response against viral replication. Furthermore, these genes have approximately equal contributions to all tissues, making them possible candidates to be used as non-invasive biomarkers in studying PBMCs instead of MLN and spleen during acute SIV infection experiments. We identified clusters of genes that co-vary together and studied their correlation with regard to other gene clusters. We also developed novel methods to faithfully visualize multi-gene correlations on two-dimensional polar plots, and to visualize tissue specificity of gene expression responses.


Abstract 37. Antibody modulation of coronavirus encephalitis


title: CFD study of exhaled droplet transmission between occupants under different ventilation strategies in a typical office room

text: This paper investigated the transmission of respiratory droplets between two seated occupants equipped with one type of personalized ventilation (PV) device using round movable panel (RMP) in an office room. The office was ventilated by three different total volume (TV) ventilation strategies, i.e. mixing ventilation (MV), displacement ventilation (DV), and under-floor air distribution (UFAD) system respectively as background ventilation methods. Concentrations of particles with aerodynamic diameters of 0.8 μm, 5 μm, and 16 μm as well as tracer gas were numerically studied in the Eulerian frame. Two indexes, i.e. intake fraction (IF) and concentration uniformity index R(C) were introduced to evaluate the performance of ventilation systems. It was found that without PV, DV performed best concern protecting the exposed manikin from the pollutants exhaled by the polluting manikin. In MV when the exposed manikin opened RMP the inhaled air quality could always be improved. In DV and UFAD application of RMP might sometimes, depending on the personalized airflow rate, increase the exposure of the others to the exhaled droplets of tracer gas, 0.8 μm particles, and 5 μm particles from the infected occupants. Application of PV could reduce R(C) for all the three TV systems of 0.8 μm and 5 μm particles. PV enhanced mixing degree of particles under DV and UFAD based conditions much stronger than under MV based ones. PV could increase the average concentration in the occupied zone of the exposed manikin as well as provide clean personalized airflow. Whether inhaled air quality could be improved depended on the balance of pros and cons of PV.


title: The Impact of Respiratory Viral Infection on Wheezing Illnesses and Asthma Exacerbations

text: The etiology and morbidity associated with asthma are thought to stem from both genetic factors and potentially modifiable environmental factors, such as viral infections.[1-7] Although it is unclear whether respiratory viral infections cause asthma, observational studies have demonstrated a high rate of asthma in children with a history of severe viral lower respiratory tract infections during infancy, and viruses are the associated with the majority of asthma exacerbations among both children and adults. This review will discuss the pathogens associated with virus-induced wheezing illnesses during infancy and early childhood, the association of bronchiolitis during infancy with an increased risk of childhood asthma, and the association of respiratory viruses with asthma exacerbations in older children and adults.


title: Detection of pancoronavirus using PCR in Camelus dromedarius in Iran (first report)

text: Coronaviride is a colossal family of viruses that cause a variety of diseases in humans and other animals. As of late, a novel coronavirus, not anterior-optically discerned in humans, has been identified in a denizen of the Middle East. There is growing evidence that the Camelus dromedarius is host species for the virus and plays an important role of a source of human infection. Along these lines, the authors decided to detect coronaviruses in dromedary camels in two high-risk areas of Iran by employing an reverse transcription polymerase chain reaction (RT-PCR) assay. In the present study, nasal swab specimens were collected from 98 camels (C. dromedarius) traditionally reared in southeast and northwest of Iran. The detection of pancoronavirus was carried out, using RT-PCR. Pancoronavirus RNA was observed in seven cases among 98 nasal swab samples. Among these, 4 positive samples belonged to Azerbaijan province located in northwest of Iran and 3 positive samples were taken from southeast of Iran. The results of this study contribute to raising the hypothesis to the extent of transmission and risk factors for human infection and public health in Iran.


title: Treatment of Hepatocellular Carcinoma (HCC) during the COVID‐19 Outbreak: The Working Group Report of JAMTT‐HCC

text: This contingency guide was formulated on the premise that delivering standard treatment for hepatocellular carcinoma (HCC) has come under strain due to the COVID‐19 pandemic. Measures required are likely to vary largely across regions and individual institutions, depending on the level of the strain imposed by the pandemic (e.g., number of inpatients infected with COVID‐19 and the availability of resources, including personal protective equipment and inpatient beds). Also, models suggest that second and third waves of COVID‐19 will occur before effective vaccines and medicines become widely available in Japan (expected time, 2–3 years). This guide should serve as a good reference for best practices in the management of HCC in light of the possible risk of impending collapse of the healthcare system due to a surge in COVID‐19 infections.


Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement regarding COVID-19


title: Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

text: BACKGROUND: Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV) form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP) encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. RESULTS: Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G), were established for Thogoto virus (THOV) GP and Autographa california multiple NPV (AcMNPV) GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. CONCLUSION: These results suggest that proteins in the GP64 superfamily are class III penetrenes.


title: Recommendations for intensive care unit and hospital preparations for an influenza epidemic or mass disaster: summary report of the European Society of Intensive Care Medicine’s Task Force for intensive care unit triage during an influenza epidemic or mass disaster

text: PURPOSE: To provide recommendations and standard operating procedures for intensive care units and hospital preparedness for an influenza pandemic. METHODS: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics. RESULTS: Key recommendations include: Hospitals should increase their ICU beds to the maximal extent by expanding ICU capacity and expanding ICUs into other areas. Hospitals should have appropriate beds and monitors for these expansion areas. Establish a management system with control groups at facility, local, regional and/or national levels to exercise authority over resources. Establish a system of communication, coordination and collaboration between the ICU and key interface departments. A plan to access, coordinate and increase labor resources is required with a central inventory of all clinical and non-clinical staff. Delegate duties not within the usual scope of workers’ practice. Ensure that adequate essential medical equipment, pharmaceuticals and supplies are available. Protect patients and staff with infection control practices and supporting occupational health policies. Maintain staff confidence with reassurance plans for legal protection and assistance. Have objective, ethical, transparent triage criteria that are applied equitably and publically disclosed. ICU triage of patients should be based on the likelihood for patients to benefit most or a ‘first come, first served’ basis. Develop protocols for safe performance of high-risk procedures. Train and educate staff. CONCLUSIONS: Mortality, although inevitable during a severe influenza outbreak or disaster, can be reduced by adequate preparation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-010-1759-y) contains supplementary material, which is available to authorized users.


title: Umifenovir treatment is not associated with improved outcomes in patients with coronavirus disease 2019: A retrospective study

text: Abstract Objectives Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Umifenovir (Arbidol®) is an antiviral drug being used to treat influenza in Russia and China. This study aimed to investigate the effectiveness and safety of umifenovir for COVID-19. Methods A retrospective study was performed in non-ICU Ward in Jinyintan Hospital from February 2, 2020 to March 20, 2020. COVID-19 was confirmed by real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay for pharyngeal swab specimens. The confirmed patients were divided into umifenovir group and control group according to the use of umifenovir. The main outcomes were the negative rate of pharyngeal swab’s test for SARS-CoV-2 within 1 week after admission, as well as the duration for virus turning negative. The negativity time of SARS-CoV-2 was defined as the first day of a negative test if the nucleid acid of SARS-CoV-2 was negative for 2 consecutive tests. Results A total of 81 COVID-19 patients were included, with 45 in umifenovir group and 36 in control group. Baseline clinical, laboratory characteristics were comparable between two groups. 33/45 (73.3%) patients in umifenovir group were tested negative in SARS-CoV-2 within 7 days after admission, the number was 28/36 (77.8%) in control group (p=0.19). The median time from onset of symtoms to SARS-CoV-2 turning negative were 18 days (interquartile range [IQR] 12-21) in umifenovir group and 16 days (IQR, 11-21) in control group (p= 0.42). Patients in umifenovir group had longer hospital stay than patients in control group (13 days [IQR, 9-17] vs 11 days [IQR, 9-14], p=0.04). No deaths or severe adverse reaction were found in both groups. Conclusions Umifenovir might not improve the prognosis or accelerate the SARS-CoV-2 clearance in non-ICU patients. A randomized control clinical trial is needed to assess the efficacy of umifenovir.


title: A Mutation in Myo15 Leads to Usher-Like Symptoms in LEW/Ztm-ci2 Rats

text: The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, an impaired vision can be observed in some animals through behavioral studies. Syndromal deafness as well as retinal degeneration are features of the Usher syndrome in humans. In the present study, the mutation was identified as a base substitution (T->C) in exon 56 of Myo15, leading to an amino acid exchange from leucine (Leu) to proline (Pro) within the carboxy-terminal MyTH4 domain in the proteins' tail region. Myo15 mRNA was expressed in the retina as demonstrated for the first time with the help of in-situ hybridization and PCR. To characterize the visual phenotype, rats were examined by scotopic and photopic electroretinography and, additionally, histological analyses of the retinas were conducted. The complete loss of sight was detected along with a severe degeneration of photoreceptor cells. Interestingly, the manifestation of the disease does not solely depend on the mutation, but also on environmental factors. Since the LEW/Ztm-ci2 rat features the entire range of symptoms of the human Usher syndrome we think that this strain is an appropriate model for this disease. Our findings display that mutations in binding domains of myosin XV do not only cause non-syndromic hearing loss but can also lead to syndromic disorders including retinal dysfunction.


title: Pathogenicity and tissue tropism of infectious bronchitis virus is associated with elevated apoptosis and innate immune responses

text: Abstract To establish a characteristic host response to predict the pathogenicity and tissue tropism of infectious bronchitis viruses (IBV), we investigated innate immune responses (IIR) and apoptosis in chicken embryo kidney cells (CEKC) and tracheal organ cultures (TOC) infected with three IBV strains. Results showed nephropathogenic IBV strains 885 and QX induced greater apoptosis in CEKC than M41, which induced greater apoptosis in TOCs compared to 885 and QX. Elevated IIR is associated with tissue tropism of different IBV strains. Compared to M41, 885 and QX caused greater induction of toll like receptor 3 (TLR3), melanoma differentiation associated protein 5 (MDA5) and interferon beta (IFN-β) in CEKC. In contrast, M41 infection caused greater expression of these genes than 885 or QX in TOCs. In summary, greater levels of apoptosis and elevated levels of TLR3, MDA5 and IFN-β expression are associated with increased pathogenicity of IBV strains in renal and tracheal tissues.


title: Characterization of equine arteritis virus particles and demonstration of their hemolytic activity

text: Equine arteritis virus (EAV), a member of the newly established family Arteriviridae, is a small, positive-stranded RNA virus. It carries two protein complexes in its envelope, gp5/M and the recently described gp2b/gp3/gp4 complex. We report here on several basic features of EAV replication in cell culture and on the protein composition of virus particles. We have also characterized gp2b, gp3, and gp4 expressed using a baculovirus system in insect cells. Finally, we provide evidence that EAV possess hemagglutinating and hemolytic activity. The hemolysis assay might be useful for determining which of the surface proteins carries the receptor-binding and membrane fusion activity of EAV.


title: The swine flu and its impacts on tourism in Brunei

text: Abstract This paper demonstrates how to disentangle the impacts of the swine flu on tourism in Brunei, which overlaps with the continued effects of the 2008 global financial crisis that occurred earlier using the auto regressive integrated moving average and intervention time series analysis methods. Estimating the impacts of the swine flu for the first 12 months' post-swine flu period, we have predicted the number of tourists by fitting two auto regressive integrated moving average models: one for the swine flu and another for the global financial crisis which occurred and affected the number of tourist arrivals; and one intervention time series analysis model. It is shown that the number of tourists have been reduced significantly due to both the swine flu and the global financial crisis, which is reconfirmed by testing the coefficients of the fitted intervention time series analysis model. It is found that a small country like Brunei lost nearly 30, 000 (15%) tourists and B$15 million dollars due to the swine flu during the first twelve months’ post-swine flu period.


title: Syndromic surveillance: A necessary public health tool

text: Abstract Of late much has been said about emerging infectious diseases and the threat of bioterrorism. The focus has been on continuous public health surveillance for early detection of outbreaks and potential threats. Preparedness is the way forward and relevant institutions and organizations need to make the necessary investments early. Familiarity, good coordination, active participation and a change of mindset amongst personnel is crucial to make the system work. We also share a general approach to using electronic Emergency Department data for syndromic surveillance.


title: Aerobiology and Its Role in the Transmission of Infectious Diseases

text: Aerobiology plays a fundamental role in the transmission of infectious diseases. As infectious disease and infection control practitioners continue employing contemporary techniques (e.g., computational fluid dynamics to study particle flow, polymerase chain reaction methodologies to quantify particle concentrations in various settings, and epidemiology to track the spread of disease), the central variables affecting the airborne transmission of pathogens are becoming better known. This paper reviews many of these aerobiological variables (e.g., particle size, particle type, the duration that particles can remain airborne, the distance that particles can travel, and meteorological and environmental factors), as well as the common origins of these infectious particles. We then review several real-world settings with known difficulties controlling the airborne transmission of infectious particles (e.g., office buildings, healthcare facilities, and commercial airplanes), while detailing the respective measures each of these industries is undertaking in its effort to ameliorate the transmission of airborne infectious diseases.


title: Translational control of the subgenomic RNAs of severe acute respiratory syndrome coronavirus

text: The 3′-one-third of the severe acute respiratory syndrome coronavirus (SARS-CoV) genome contains genes for four essential structural proteins and eight virus-specific genes. The expression of this genomic information of SARS-CoV involves synthesis of a nested set of subgenomic RNAs (sgRNAs). In this study, we showed that the translational levels of 10 SARS-CoV sgRNAs including the two low-abundance sgRNAs 2-1 and 3-1 varied considerably in translation reporter assays. We also demonstrated that the initiator AUG codon of sgRNA-8 was silent and the repressive control was most likely positioned in the upstream untranslated region (UTR) of sgRNA-8. The initiator AUG codons of most sgRNAs are in poor Kozak contexts and the translation of truncated proteins from downstream AUG codons by leaky scanning was common in our experimental settings. No significant correlation was found between complexity of 5′-UTR and the sequence context of AUG codon with the level of translation of SARS-CoV sgRNAs. These results will be helpful for further studies to reveal the biological functions and translation regulatory mechanisms of sgRNAs in the coronavirus life cycle and pathogenesis.


Ratified AVA policies July 2011


title: The multifaceted long-term effects of the COVID-19 pandemic on urology

text: The COVID-19 pandemic has resulted in immediate effects on urological practice, in particular the vast reduction in elective surgeries. These changes are likely to have long-term effects for both patients and for urologists, which will persist even after the pandemic resolves. The many facets of COVID-19’s effects on urology remain to be seen, but they might also offer opportunities to reassess and improve patient management in urology and beyond.


title: Isolation and identification of virus-specific mRNAs in cells infected with mouse hepatitis virus (MHV-A59)

text: Abstract We have determined the kinetics of virus production and virus-specific RNA synthesis in Sac(−) cells infected with mouse hepatitis virus strain A59 (MHV-A59). Immunofluorescence showed that all cells became infected at a multiplicity of 10 PFU/cell. The virus was concentrated and purified to obtain the high titered stocks needed for these one-step growth experiments. Release of virus into the culture medium started 4 hr after infection (pi) and was complete at 10 hr pi. Synthesis of virus-specific RNA, measured by the incorporation of [3H]uridine in the presence of 1 μg/ml actinomycin D, also started at 4 hr pi and its maximum rate occurred between 6 and 8 hr pi. RNA labeled during this period was isolated from infected cells. About 50% of this RNA bound to oligo(dT)-cellulose; this material was denatured with glyoxal-dimethyl sulfoxide and analyzed by electrophoresis in 1% agarose gels. Seven RNA species with the following molecular weights were present: 5.6 × 106 (RNA1), 4.0 × 106 (RNA2), 3.0 × 106 (RNA3), 1.4 × 106 (RNA4), 1.2 × 106 (RNA5), 0.9 × 106 (RNA6), and 0.6 × 106 (RNA7). RNA1 comigrated with the viral genome. Artifacts caused by defective interfering particles or breakdown of RNA were excluded. To determine whether these RNA species were functional as messengers in infected cells, virus-specific RNAs present in polyribosomes were analyzed. EDTA treatment was used to discriminate between RNA present in polyribosomes and in EDTA-resistant, presumably ribonucleoprotein, particles. Most (91%) of RNA1 was present in EDTA-resistant particles; the remainder and all other RNAs synthesized between 6 and 8 hr pi were present in polyribosomes. We conclude that MHV-A59 has six subgenomic mRNAs. Since the total molecular mass (11.1 × 106 daltons) of these messengers is about twice that of the viral genome, sequence homologies must exist between the mRNAs. The position of these homologous regions and the translation products of each of the mRNAs remain to be determined.


title: Clinical evaluation methods for new antimicrobial agents to treat respiratory infections: Report of the Committee for the Respiratory System, Japan Society of Chemotherapy

text: Abstract The present report constitutes an attempt to improve and modify the existing clinical evaluation method for new antimicrobial agents to treat respiratory infections. One year ago, a general guideline on the clinical evaluation of antimicrobial agents to treat respiratory infections was drafted in Japanese, leaving scope for critical discussion, and this has been translated into English, as there were no major changes. In this report, respiratory infections have been discussed under the headings “acute respiratory tract infection” and pneumonia and acute exacerbation of chronic pulmonary diseases. Standardized criteria were set for the assessment of severity of infection and effectiveness of the antimicrobial agent in question. Severity was evaluated on the basis of a combined assessment of the severity of infection and severity of the clinical condition of the patients. Clinical effectiveness of the antimicrobial agent used was evaluated on the basis of clinical outcome as well as microbiological outcome of the trial. Body temperature, local pain, cough, change in sputum quality, peripheral white blood cell count, C-reactive protein level, and chest radiograph were used as the parameters for the evaluation. To maintain the quality of specimens to be examined, Geckler's classification of specimens was used. This report was constructed based on the analysis of large amounts of material collected over the years, incorporating internal and external factors concerning the present evaluation methods. The newly suggested standardized criteria for clinical evaluation of the new antimicrobial drugs are expected to be practiced properly hereupon and subjected to further improvement if necessary.


title: Deep learning-based multi-view fusion model for screening 2019 novel coronavirus pneumonia: a multicentre study

text: Abstract Purpose To develop a deep learning-based method to assist radiologists to fast and accurately identify patients with COVID-19 by CT images. Methods We retrospectively collected chest CT images of 495 patients from three hospitals in China. 495 datasets were randomly divided into 395 cases (80%, 294 of COVID-19, 101 of other pneumonia) of the training set, 50 cases (10%, 37 of COVID-19, 13 of other pneumonia) of the validation set and 50 cases (10%, 37 of COVID-19, 13 of other pneumonia) of the testing set. We trained a multi-view fusion model using deep learning network to screen patients with COVID-19 using CT images with the maximum lung regions in axial, coronal and sagittal views. The performance of the proposed model was evaluated by both the validation and testing sets. Results The multi-view deep learning fusion model achieved the area under the receiver-operating characteristics curve (AUC) of 0.732, accuracy of 0.700, sensitivity of 0.730 and specificity of 0.615 in validation set. In the testing set, we can achieve AUC, accuracy, sensitivity and specificity of 0.819, 0.760, 0.811 and 0.615 respectively. Conclusions Based on deep learning method, the proposed diagnosis model trained on multi-view images of chest CT images showed great potential to improve the efficacy of diagnosis and mitigate the heavy workload of radiologists for the initial screening of COVID-19 pneumonia.


title: Diagnostic Testing of Mouse and Rat Colonies for Infectious Agents

text: Rodent health monitoring programs make an essential contribution to biomedical research by identifying the presence of infectious agents that might confound animal research. The authors discuss the types of diagnostic tests available, which agents deserve monitoring, and the appropriate frequency for such interventions.


title: Methods for studying stem cells: Adult stem cells for lung repair

text: Abstract Recent progress in lung biology includes the description of a series of pulmonary stem and progenitor cells involved in homeostasis and regeneration of the respiratory system. Moreover, the contribution of extrapulmonary stem cells to healthy and pathological lung tissue has been observed and the developmental biology of such processes should provide important hints for understanding maintenance and repair of adult lung structure and function. Despite such remarkable advances, the phenotypic and especially the functional characterization of these stem and progenitor cells, and their derivatives, along with an understanding of the molecular cues and pathways underlying differentiation into specific respiratory lineages is still in its infancy. Accordingly, the role of endogenous and extrapulmonary stem cells in normal tissue repair and pathogenesis is still largely mysterious and added basic knowledge is required in order to explore their potential for novel regenerative therapies. This review provides an overview of the current state of the art in adult lung stem cell biology including technical aspects of isolation, characterization and differentiation, and a discussion of perspectives for future regenerative therapies.


title: Acute Care Surgery during the COVID-19 pandemic in Spain: changes in volume, causes and complications. A multicentre retrospective cohort study

text: BACKGROUND: during the COVID-19 pandemic, the number of Acute Care Surgery procedures performed in Spanish hospitals decreased significantly. The aim of this study was to compare Acute Care Surgery activity during the COVID-19 pandemic and during a control period. MATERIAL AND METHODS: a multicenter retrospective cohort study was performed including patients who underwent Acute Care Surgery in three tertiary care hospitals in Spain during a control (11(th) March 2019 to 21(st) April 2019) and a pandemic (16(th) March 2020 to 26(th) April 2020) period. Type of surgical procedures, patients´ features and postoperative complications were compared. RESULTS: two hundred and eighty-five and 117 patients were included in each group. Mean number of patients who underwent Acute Care Surgery during the control and pandemic periods was 2.3 and 0.9 patients per day and hospital (p<0.001), representing a 58.9% decrease in Acute Care Surgery activity. Time from symptoms onset to patient arrival at the Emergency Department was longer during the pandemic (44.6 vs. 71.0 hours, p<0.001). Surgeries due to acute cholecystitis and complications from previous elective procedures decreased (26.7% vs. 9.4%) during the pandemic, while bowel obstructions and abdominal wall hernia surgeries increased (12.3% vs. 22.2%) (p=0.001). Morbidity was higher during pandemic period (34.7% vs. 47.1%, p=0.022), although this difference was not statistically significant in the multivariate analysis. Reoperation rate (17.9% vs. 12.8%, p=0.212) and mortality (6.7% vs. 4.3%, p=0.358) were similar in both groups. CONCLUSION: during the COVID-19 pandemic, a significant reduction in the performance of Acute Care Surgery procedures was observed. Moreso, a longer time from symptoms onset to patient arrival at the Emergency Department was noted. Higher morbidity was observed in patients undergoing Acute Care Surgery during the pandemic period, although there was not any difference in mortality or reoperation rate.


title: Error thresholds and the constraints to RNA virus evolution

text: Abstract RNA viruses are often thought of as possessing almost limitless adaptability as a result of their extreme mutation rates. However, high mutation rates also put a cap on the size of the viral genome by establishing an error threshold, beyond which lethal numbers of deleterious mutations accumulate. Herein, I argue that a lack of genomic space means that RNA viruses will be subject to important evolutionary constraints because specific sequences are required to encode multiple and often conflicting functions. Empirical evidence for these constraints, and how they limit viral adaptability, is now beginning to accumulate. Documenting the constraints to RNA virus evolution has important implications for predicting the emergence of new viruses and for improving therapeutic procedures.


title: Clinical characteristics of COVID-19 patients in three consecutive generations of spread in Zhejiang, China

text: OBJECTIVE: To determine the clinical characteristics of COVID-19 patients as the SARS-CoV-2 virus continues to circulate in the population. METHODS: This is a retrospective, multi-center cohort study. Adult COVID-19 cases from four hospitals in Zhejiang were enrolled and clustered into 3 groups based on epidemiological history. First-generation patients had a travel history to Hubei within 14 days before disease onset; second generation patients had a contact history with first-generation patients; third-generation patients had a contact history with second-generation patients. Demographic, clinical characteristics, clinical outcomes, and duration of viral shedding were analyzed. RESULTS: 171 patients were enrolled, with 83, 44, and 44 patients in the first, second, and third generation, respectively. Compared to first and second generation, third generation patients were older (61.3 vs. 48.3 and 44.0 y, P<0.001), had more coexisting conditions (56.8% vs. 36.1% and 27.3%, P=0.013). At 7±1 days from illness onset, third generation patients had lower lymphocyte (0.6 vs. 0.8 and 0.8×10(9)/L, P=0.007), higher C-reactive protein (29.7 vs. 17.1 and 13.8mg/L, P=0.018) and D-dimer (1066 vs. 412.5 and 549μg/L, P=0.002) and more lesions involving the pulmonary lobes (lobes≥5, 81.8% vs. 53.0% and 34.1%, P<0.001). The proportions of third-generation patients developing severe illness (72.7% vs. 32.5% and 27.3%, P<0.001), critical illness (38.6% vs. 10.8% and 6.8%, P<0.001) and receiving endotracheal intubation (20.5% vs. 3.6% and 2.3%, P=0.002) were higher than the other two groups. CONCLUSION: The third generation patients were older, had more underlying comorbidities and had a higher proportion of severe or critical illness compared to first and second-generation.


title: Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region

text: BACKGROUND: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging. METHODOLOGY/PRINCIPAL FINDINGS: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making.


title: A case of an Infant with SARS‐CoV‐2 hepatitis early after liver transplantation

text: We present a case of a pediatric liver transplant recipient diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection four days after receiving a living donor liver allograft from her mother. The recipient was a 6‐month‐old with end‐stage liver disease due to biliary atresia and failed Kasai. The infant had an uncomplicated implantation, excellent graft function and down‐trending liver enzymes until developing fevers, diarrhea, and moderate respiratory distress requiring non‐invasive respiratory support. SARS‐CoV‐2 testing (nasal swab Polymerase Chain Reaction) was positive on post‐operative day (POD) 4. Liver enzymes peaked ~1000 U/L (5‐fold higher than the previous day) on POD 6. Histology demonstrated a mixed picture of moderate acute hepatitis and classical elements of mild to moderate acute cellular rejection. Her hepatitis and respiratory symptoms improved coincident with completing treatment with hydroxychloroquine, reduced immunosuppression, and intravenous gamma globulin (IVIG).


title: Underlying Diseases and Causative Microorganisms of Recurrent Pneumonia in Children: A 13-Year Study in a University Hospital

text: Pneumonia is a significant cause of death for children, particularly those in developing countries. The records of children who were hospitalized because of pneumonia between January 2003 and December 2015 were retrospectively reviewed, and patients who met the recurrent pneumonia criteria were included in this study. During this 13-year period, 1395 patients were hospitalized with pneumonia; of these, 129 (9.2%) met the criteria for recurrent pneumonia. Underlying diseases were detected in 95 (73.6%) patients, with aspiration syndrome (21.7%) being the most common. Rhinovirus (30.5%), adenovirus (17.2%) and respiratory syncytial virus (13.9%) were the most frequent infectious agents. These results demonstrate that underlying diseases can cause recurrent pneumonia in children. Viruses are also commonly seen in recurrent pneumonia. Appropriate treatments should be chosen based on an analysis of the underlying disease, the patient’s clinical condition and the laboratory and radiological data.


The COVID‐19 pandemic: some lessons learned about crisis preparedness and management, and the need for international benchmarking to reduce deficits


title: Laboratory Diagnosis of Respiratory Tract Infections in Children – the State of the Art

text: In the pediatric population, respiratory infections are the most common cause of physician visits. Although many respiratory illnesses are self-limiting viral infections that resolve with time and supportive care, it can be critical to identify the causative pathogen at an early stage of the disease in order to implement effective antimicrobial therapy and infection control. Over the last few years, diagnostics for respiratory infections have evolved substantially, with the development of novel assays and the availability of updated tests for newer strains of pathogens. Newer laboratory methods are rapid, highly sensitive and specific, and are gradually replacing the conventional gold standards, although the clinical utility of these assays is still under evaluation. This article reviews the current laboratory methods available for testing for respiratory pathogens and discusses the advantages and disadvantages of each approach.


title: Viral etiologies of acute respiratory tract infections among hospitalized children – A comparison between single and multiple viral infections

text: Abstract Background Acute respiratory tract infections are commonly caused by viruses in children. The differences in clinical data and outcome between single and multiple viral infections in hospitalized children were analyzed. Methods We retrospectively reviewed the medical records of hospitalized children who had fever and a xTAG Respiratory Virus Panel (RVP) test over a 2-year period. The clinical data were analyzed and compared between single and multiple viral infections. Viral etiologies in upper and lower respiratory infections were analyzed and compared. Results A total of 442 patients were enrolled. Patients with positive viral detection (N = 311) had a significantly lower rate of leukocytosis (p = 0.03), less evidence of bacterial infection (p = 0.004), and shorter duration of hospitalization (p = 0.019) than those with negative viral detection. The age of patients with multiple viral infections was younger than those with single viral infection; however, there were no significant differences in duration of fever, antibiotics treatment and hospitalization between these two groups. The most commonly identified virus was human rhinovirus. About 27% (n = 83) of patients had multiple viral infections. Overall, the highest percentage of human bocavirus infection was detected in multiple viral infections (79%). Lower respiratory tract infection (LRTI) was independently associated with multiple viral infections (p = 0.022), respiratory syncytial virus (RSV) infection (p = 0.001) and longer hospitalization duration (p = 0.011). Conclusion Multiple viral infections were associated with younger age and a higher risk of developing LRTI. However, multiple viral infections did not predict a worse disease outcome. More studies are needed to unveil the interplay between the hosts and different viruses in multiple viral infections.


title: Determination of the cell tropism of serotype 1 feline infectious peritonitis virus using the spike affinity histochemistry in paraffin‐embedded tissues

text: Unlike for serotype II feline coronaviruses (FCoV II), the cellular receptor for serotype I FCoV (FCoV I), the most prevalent FCoV serotype, is unknown. To provide a platform for assessing the pattern by which FCoV I attaches to its host receptor(s), HEK293 cell lines that stably express the ectodomains of the spike (S) proteins derived from a FCoV I feline enteric coronavirus strain UU7 (FECV UU7) and a feline infectious peritonitis virus strain UU4 (FIPV UU4) were established. Using the recombinant S proteins as probes to perform S protein affinity histochemistry in paraffin‐embedded tissues, although no tissue or enteric binding of FECV UU7 S protein was detected, it was found that by immunohistochemistry that the tissue distribution of FIPV UU4 S protein‐bound cells correlated with that of FIPV antigen‐positive cells and lesions associated with FIP and that the affinity binding of FIPV UU4 S protein on macrophages was not affected by enzymatic removal of host cell‐surface sialic acid with neuraminidase. These findings suggest that a factor(s) other than sialic acid contribute(s) to the macrophage tropism of FIPV strain UU4. This approach allowed obtaining more information about both virus–host cell interactions and the biological characteristics of the unidentified cellular receptor for FCoV I.


title: Molecular characterization of bovine noroviruses and neboviruses in Turkey: detection of recombinant strains

text: To investigate the molecular epidemiology and genetic diversity of bovine enteric caliciviruses, a total of 167 fecal samples from diarrheic calves were screened. Bovine noroviruses (BoNoVs) and neboviruses were detected in 56 (33.5%) and 37 (22.1%) fecal samples, respectively. Sequences of the RdRp and capsid gene of selected BoNoVs showed that the GIII.1 and GIII.2 genotypes were in circulation in Turkey. Two of the BoNoV strains were identified as recombinant strains (GIII.P1/GIII.2). All examined neboviruses possessed a Nebraska-like RdRp gene. The two nebovirus strains were classified into lineage 4 based on phylogenetic analysis of VP1 amino acid sequences. One of them showed evidence of a recombination event within the S domain. This study is thus the first to reveal the presence of the BoNoV GIII.1 genotype and recombinant strains of BoNoV and neboviruses in Turkey. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04186-0) contains supplementary material, which is available to authorized users.


title: ATR-FTIR spectroscopy and spectroscopic imaging for the analysis of biopharmaceuticals

text: Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy is a label-free, non-destructive technique that can be applied to a vast range of biological applications, from imaging cancer tissues and live cells, to determining protein content and secondary structure composition. This review summarises the recent advances in applications of ATR-FTIR spectroscopy to biopharmaceuticals, the application of this technique to biosimilars, and the current uses of FTIR spectroscopy in biopharmaceutical production. We discuss the use of ATR-FTIR spectroscopic imaging to investigate biopharmaceuticals, and finally, give an outlook on the possible future developments and applications of ATR-FTIR spectroscopy and spectroscopic imaging to this field. Throughout the review comparisons will be made between FTIR spectroscopy and alternative analytical techniques, and areas will be identified where FTIR spectroscopy could perhaps offer a better alternative in future studies. This review focuses on the most recent advances in the field of using ATR-FTIR spectroscopy and spectroscopic imaging to characterise and evaluate biopharmaceuticals, both in an industrial and an academic research based environment.


title: StatinImplications of the complex biology and micro-environment of cardiac sarcomeres in the use of high affinity troponin antibodies as serum biomarkers for cardiac disorders

text: Cardiac troponin I (cTnI), the inhibitory-unit, and cardiac troponin T (cTnT), the tropomyosin-binding unit together with the Ca-binding unit (cTnC) of the hetero-trimeric troponin complex signal activation of the sarcomeres of the adult cardiac myocyte. The unique structure and heart myocyte restricted expression of cTnI and cTnT led to their worldwide use as biomarkers for acute myocardial infarction (AMI) beginning more than 30 years ago. Over these years, high sensitivity antibodies (hs-cTnI and hs-cTnT) have been developed. Together with careful determination of history, physical examination, and EKG, determination of serum levels using hs-cTnI and hs-cTnT permits risk stratification of patients presenting in the Emergency Department (ED) with chest pain. With the ability to determine serum levels of these troponins with high sensitivity came the question of whether such measurements may be of diagnostic and prognostic value in conditions beyond AMI. Moreover, the finding of elevated serum troponins in physiological states such as exercise and pathological states where cardiac myocytes may be affected requires understanding of how troponins may be released into the blood and whether such release may be benign. We consider these questions by relating membrane stability to the complex biology of troponin with emphasis on its sensitivity to the chemo-mechanical and micro-environment of the cardiac myocyte. We also consider the role determinations of serum troponins play in the precise phenotyping in personalized and precision medicine approaches to promote cardiac health.


A case of exacerbation of psoriasis after oseltamivir and hydroxychloroquine in a patient with COVID‐19: Will cases of psoriasis increase after COVID‐19 pandemic?


title: Identification of a B-cell antigenic epitope at the N-terminus of SARS-CoV M protein and characterization of monoclonal antibody against the protein

text: To identify the potential B-cell antigenic epitopes within the N-terminus of SARS-CoV (SARS-associated coronavirus, SARS-CoV) M protein and characterize monoclonal antibody (MAb) against the protein as well as its recognizing region, we expressed and purified a portion of SARS-CoV M protein (amino acid 1–43) in Escherichia coli (E. coli). By using Western blot and enzyme-linked immunosorbent assay (ELISA), we showed that the purified recombinant M protein could be recognized by four SARS-CoV-positive human sera even when those sera were 12,800-fold diluted. Furthermore, we characterized one representative IgG2 MAb, 3H9, which exhibited a strong immunoreaction to both recombinant M protein and native viral protein of SARS-CoV. We found a B-cell antigenic epitope located between amino acid 1–15 and defined the MAb recognizing region within amino acid 16–28 of M. These findings not only suggest that both recombinant M protein and its specific MAbs may be used as the diagnostic reagents for SARS, but also provide a potential target site for the design of an epitope-based vaccine against SARS.


title: IFITM Proteins Restrict Antibody-Dependent Enhancement of Dengue Virus Infection

text: Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections.


title: How to deal with the negative psychological impact of COVID-19 for people who pay attention to anxiety and depression

text: BACKGROUND: The fear of insecurity and uncertainty caused by 2019 coronavirus disease (COVID-19), the separation and loss of certain important relationships, and the great changes in lifestyle have awakened strong emotional response, which may cause psychological problems to the general population. However, there are few researches on how the people who pay attention to anxiety and depression coping with negative psychological during the epidemic or major disaster. This study aimed to identify what behaviors can effectively reduce negative emotions during the epidemic. METHODS: From February 1, to March 8 in 2020, we conducted a web-based survey and collected information on general demographic data. The probable depression, anxiety symptoms and coping behaviors was assessed by Patient Health Questionnaire-9 and Generalized anxiety disorder-7 and the self-made Coping Behaviors Questionnaires. RESULT: Among 17249 responders, 7923 and 9326 completed the assessment of depression and anxiety respectively, and all responders finished the assessment of the coping behaviors questionnaires. Our survey population had a high prevalence rate of possible depression disorders and anxiety disorders were34.66% and 56.93%, respectively. Those who are old, female, low education, low income, and cohabiting were more likely to suffer depression and/or anxiety. Students are a high-risk group suffering from depression and/or anxiety. After adjusting for social-demographic factors (e.g. age, sex), depression and anxiety were positively associated with self-injury, doing housework, and having sex or masturbating and negatively associated with singing, drawing, or writing, dating friends online, singing, attending lectures, and doing yoga. CONCLUSION: During the epidemic, our findings identify some spontaneous coping behaviors that can probably relieve the psychological impact of vulnerable groups during the COVID-19 epidemic.


COVID‐19 anticoagulation recommendations in children


title: Should we wait or not? The preferable option for patients with stage IV oral cancer in COVID‐19 pandemic

text: BACKGROUND: The coronavirus infection is rapidly spreading, putting a strain on health care services across the globe. Patients with oral cancer are susceptible often immunosuppressed due to the disease and/or the treatment received. METHODS: We performed a simulation of the currently available data using a multistate and hazards model to provide an objective model for counseling and decision making for health care workers. RESULTS: Stage IV patients with oral cancer who did not receive treatment had progression of disease and an increased mortality rate compared to patients who receive treatment but did not contract COVID‐19. The patients who received treatment and got affected with COVID‐19 had a far worse impact and higher mortality rate than all other groups. CONCLUSION: Isolation and deferring treatment for stage IV patients with oral cancer, so as to avoid hospital visits and contraction of COVID‐19, is an advisable strategy based on this model.


title: Severe Acute Respiratory Syndrome: Developing a Research Response

text: When severe acute respiratory syndrome (SARS) first came to world attention in March 2003, it was immediately perceived to be a global threat with a pandemic potential. To help coordinate international research efforts, the National Institute of Allergy and Infectious Diseases convened a colloquium entitled SARS: Developing a Research Response on 30 May 2003. Breakout sessions intended to identify unmet research needs in 5 areas of SARS research—clinical research, epidemiology, diagnostics, therapeutics, and vaccines—are summarized here. Since this meeting, however, the identified research needs have been only partially met. Needs that have yet to be realized include reliable methods for early identification of individuals with SARS, a full description of SARS pathogenesis and immune response, and animal models that faithfully mimic SARS respiratory symptoms. It is also of the utmost importance that the global scientific community enhance mechanisms for international cooperation and planning for SARS research, as well as for other emerging infectious disease threats that are certain to arise in the future.


Need of the Hour— COVID-19 for Cardiologists


title: Chapter Six T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders

text: Abstract Continuous epidemiological surveillance of existing and emerging viruses and their associated disorders is gaining importance in light of their abilities to cause unpredictable outbreaks as a result of increased travel and vaccination choices by steadily growing and aging populations. Close surveillance of outbreaks and herd immunity are also at the forefront, even in industrialized countries, where previously eradicated viruses are now at risk of re-emergence due to instances of strain recombination, contractions in viral vector geographies, and from their potential use as agents of bioterrorism. There is a great need for the rational design of current and future vaccines targeting viruses, with a strong focus on vaccine targeting of adaptive immune effector memory T cells as the gold standard of immunity conferring long-lived protection against a wide variety of pathogens and malignancies. Here, we review viruses that have historically caused large outbreaks and severe lethal disorders, including respiratory, gastric, skin, hepatic, neurologic, and hemorrhagic fevers. To observe trends in vaccinology against these viral disorders, we describe viral genetic, replication, transmission, and tropism, host-immune evasion strategies, and the epidemiology and health risks of their associated syndromes. We focus on immunity generated against both natural infection and vaccination, where a steady shift in conferred vaccination immunogenicity is observed from quantifying activated and proliferating, long-lived effector memory T cell subsets, as the prominent biomarkers of long-term immunity against viruses and their associated disorders causing high morbidity and mortality rates.


title: Brief historical remarks as an introduction for the international symposium on taeniasis/cysticercosis and echinococcosis

text: Abstract Some historical remarks are made on the background information leading to the international symposium on taeniasis/cysticercosis and echincoccosis with focus on Asia and the Pacific.


title: COVID‐19 in context: Why do people die in emergencies? It’s probably not because of collective psychology

text: Notions of psychological frailty have been at the forefront of debates around the public response to the COVID‐19 pandemic. In particular, there is the argument that collective selfishness, thoughtless behaviour, and over‐reaction would make the effects of COVID‐19 much worse. The same kinds of claims have been made in relation to other kinds of emergencies, such as fires, earthquakes, and sinking ships. We argue that in these cases as well as in the case of the COVID‐19 pandemic, other factors are better explanations for fatalities – namely under‐reaction to threat, systemic or structural factors, and mismanagement. Psychologizing disasters serves to distract from the real causes and thus from who might be held responsible. Far from being the problem, collective behaviour in emergencies – including the solidarity and cooperation so commonly witnessed among survivors – is the solution, one that should be harnessed more effectively in policy and practice.


title: Propagation of bovine rotavirus by young dogs

text: Abstract Ten young dogs were experimentally infected twice with different isolates of bovine rotavirus and 2 uninfected dogs were kept in contact with them. None of the animals developed diarrhoea, but all of them excreted rotavirus in their faeces over a period of up to 10 days after each inoculation, as shown by counterimmunoelectro-osmophoresis and virus isolation. Dogs may thus play a role in the epizootiology of rotavirus diarrhoea in calves. Seroconversion occurred in 6 of the 10 infected dogs but in neither of the 2 contact controls.


title: COVID-19-Cluster-Studie an einem Lehrkrankenhaus: Corona-Pandemie 2020

text: On Mar 11th, 2020, the World Health Organization (WHO) stated in its Situation Report — 51 Coronavirus disease 2019 (COVID-19) as a pandemic. In early April 2020, a teaching hospital underwent shutdown and quarantine due to an outbreak of infection in accordance with Section 6 of the Infection Protection Act (index patient and 5 infected nursing staff). The complete staff (physicians, nurses and nonmedical personnel [NMP]) underwent COVID-19 testing within two phases: (1) between Apr 3rd and 5th, 2020 [n=1170], followed by (2) between Apr 8th and 9th, 2020 [n=953] with COVID-19 silent carrier positivity rates in accordance to testing phases of (1) n=19 (1.6%) and (2) n=25 (2.6%). The cumulative infection rate for NMP (1.6%), doctors (3.8%) and nurses (9.7%) was connected to type and extent of COVID-19 patient contact. Despite COVID-19 positivity of 34.8% (46 of 132 beds), a risk-free management of hospital operation is possible to a certain extent if hygiene regulations and strict patient selection are followed. However, a COVID-19-free clinic cannot be expected due to silent carriers.


title: Cyclophilin polymorphism and virus infection

text: Viruses are obligate intracellular parasites. All stages of their replication cycle depend on support by host-encoded factors. However, sequence variation also exists in host factors mostly in the form of single nucleotide polymorphisms (SNPs). Several coding and non-coding genetic variants in the PPIA gene encoding for CypA have been described, but there is only limited information about their influence on the course of viral infection. This paper reviews PPIA polymorphisms and what is known about their impact on the replication cycle and course of disease for different viral infections.


title: Proactive Prophylaxis With Azithromycin and HydroxyChloroquine in Hospitalised Patients With COVID-19 (ProPAC-COVID): A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: The aim of this randomised GCP-controlled trial is to clarify whether combination therapy with the antibiotic azithromycin and hydroxychloroquine via anti-inflammation/immune modulation, antiviral efficacy and pre-emptive treatment of supra-infections can shorten hospitalisation duration for patients with COVID-19 (measured as "days alive and out of hospital" as the primary outcome), reduce the risk of non- invasive ventilation, treatment in the intensive care unit and death. TRIAL DESIGN: This is a multi-centre, randomised, Placebo-controlled, 2-arm ratio 1:1, parallel group double-blind study. PARTICIPANTS: 226 participants are recruited at the trial sites/hospitals, where the study will take place in Denmark: Aalborg, Bispebjerg, Gentofte, Herlev, Hillerød, Hvidovre, Odense and Slagelse hospitals. Inclusion criteria: • Patient admitted to Danish emergency departments, respiratory medicine departments or internal medicine departments • Age≥ 18 years • Hospitalized ≤48 hours • Positive COVID-19 test / diagnosis during the hospitalization (confirmed). • Men or non-fertile women. Fertile women* must not be pregnant, i.e. negative pregnancy test must be available at inclusion • Informed consent signed by the patient *Defined as after menarche and until postmenopausal (no menstruation for 12 months) Exclusion criteria: • At the time of recruitment, the patient uses >5 LO2/min (equivalent to 40% FiO2 if measured) • Known intolerance/allergy to azithromycin or hydroxychloroquine or hypersensitivity to quinine or 4-aminoquinoline derivatives • Neurogenic hearing loss • Psoriasis • Retinopathy • Maculopathy • Visual field changes • Breastfeeding • Severe liver diseases other than amoebiasis (INR> 1.5 spontaneously) • Severe gastrointestinal, neurological and hematological disorders (investigator-assessed) • eGFR <45 ml/min/1.73 m2 • Clinically significant cardiac conduction disorders/arrhythmias or prolonged QTc interval (QTc (f) of> 480/470 ms). • Myasthenia gravis • Treatment with digoxin* • Glucose-6-phosphate dehydrogenase deficiency • Porphyria • Hypoglycaemia (Blood glucose at any time since hospitalization of <3.0 mmol/L) • Severe mental illness which significantly impedes cooperation • Severe linguistic problems that significantly hinder cooperation • Treatment with ergot alkaloids *The patient must not be treated with digoxin for the duration of the intervention. For atrial fibrillation/flutter, select according to the Cardiovascular National Treatment Guide (NBV): Calcium antagonist, Beta blocker, direct current (DC) conversion or amiodarone. In case of urgent need for digoxin treatment (contraindication for the aforementioned equal alternatives), the test drug should be paused, and ECG should be taken daily. INTERVENTION AND COMPARATOR: Control group: The control group will receive the standard treatment + placebo for both types of intervention medication at all times. If part or all the intervention therapy being investigated becomes standard treatment during the study, this may also be offered to the control group. Intervention group: The patients in the intervention group will also receive standard care. Immediately after randomisation to the intervention group, the patient will begin treatment with: Azithromycin: Day 1-3: 500 mg x 1 Day 4-15: 250 mg x 1 If the patient is unable to take the medication orally by themselves, the medication will, if possible, be administered by either stomach-feeding tube, or alternatively, temporary be changed to clarithromycin 500 mg x 2 (this only in agreement with either study coordinator Pradeesh Sivapalan or principal investigator Jens-Ulrik Stæhr Jensen). This will also be done in the control group if necessary. The patient will switch back to azithromycin when possible. Hydroxychloroquine: Furthermore, the patient will be treated with hydroxychloroquine as follows: Day 1-15: 200 mg x 2 MAIN OUTCOMES: • Number of days alive and discharged from hospital within 14 days (summarises both whether the patient is alive and discharged from hospital) ("Days alive and out of hospital") RANDOMISATION: The sponsor (Chronic Obstructive Pulmonary Disease Trial Network, COP:TRIN) generates a randomisation sequence. Randomisation will be in blocks of unknown size and the final allocation will be via an encrypted website (REDCap). There will be stratification for age (>70 years vs. <=70 years), site of recruitment and whether the patient has any of the following chronic lung diseases: COPD, asthma, bronchiectasis, interstitial lung disease (Yes vs. No). BLINDING (MASKING): Participants and study personnel will both be blinded, i.e. neither will know which group the participant is allocated to. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study requires 226 patients randomised 1:1 with 113 in each group. TRIAL STATUS: Protocol version 1.8, from April 16, 2020. Recruitment is ongoing (first patient recruited April 6, 2020; final patient expected to be recruited October 31, 2020). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04322396 (registered March 26, 2020) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


title: After corona: there is life after the pandemic

text: Abstract The current pandemic of Coronavirus Disease 2019 (COVID-19) has focused the attention of medical-care providers away from non-life-threatening diseases, including infertility. Although infertility does not jeopardize the physical survival of infertile couples, it does jeopardize their future quality of life. Human infertility can be caused by a number of factors, some of which are age-dependent, and their effects may become irreversible if appropriate measures are not taken in time to prevent irreversible childlessness. Accordingly, each case of infertility should be evaluated comprehensively to establish its position of priority. Assisted reproductive technology (ART) makes it possible to separate fertilization and pregnancy in time. Whereas pregnant women infected with coronavirus may have an increased risk of adverse neonatal outcomes, gametes do not transmit COVID-19. Thus, performing ovarian stimulation and fertilization without delay, freezing the resulting embryos and delaying embryo transfer until the end of the pandemic appears to be the best strategy at present.


The COVID‐19 Pandemic


AMPA Position Statement on COVID-19


title: Local RAS

text: The concept of a circulating RAS is well established and known to play an endocrine role in the regulation of fluid homeostasis (see Section 4.1, Chapter 4). However, it is more appropriate to view the RAS in the contemporary notion as an “angiotensin-generating system”, which consists of angiotensinogen, angiotensin-generating enzymes, and angiotensins, as well as their receptors. Some RASs can be termed as “complete”, having renin and ACE involved in the biosynthesis of angiotensin II peptide, i.e. in a renin and/or ACE-dependent manner which is exemplified in the circulating RAS. On the other hand, some RAS can be termed as “partial”, having alternate enzymes to renin and ACE, such as chymase and ACE2 (see Section 4.3, Chapter 4) available for the generation of angiotensin II and other bioactive angiotensin peptides in the biosynthetic cascade, i.e. in a renin and/or ACE-independent manner. Complete vs. partial RASs can be exemplified in the so-called intrinsic angiotensin-generating system or local RAS; for example, a local and functional RAS with renin and ACE-dependent but a renin-independent pathway have been indentified in the pancreas and carotid body, respectively. In the past two decades, local RASs have gained increasing recognition especially with regards to their clinical importance. Distinct from the circulating RAS, these functional local RASs exist in such diverse tissues and organs as the pancreas, liver, intestine, heart, kidney, vasculature, carotid body, and adipose, as well as the nervous, reproductive, and digestive systems. Taken into previous findings from our laboratory and others together, Table 5.1 is a summary of some recently identified local RASs in various levels of tissues and organs.


title: The pathogenesis and treatment of the `Cytokine Storm' in COVID-19

text: Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.


title: Development of a homogeneous screening assay for automated detection of antiviral agents active against severe acute respiratory syndrome-associated coronavirus

text: Abstract The severity and global spread of the 2003 outbreak of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) highlighted the risks to human health posed by emerging viral diseases and emphasized the need for specific therapeutic agents instead of relying on existing broadly active antiviral compounds. The development of rapid screening assays is essential for antiviral drug discovery. Thus, a screening system for anti-SARS-CoV agents was developed, which evaluated compound potency, specificity and cytotoxicity at the initial screening phase. Cell lines were engineered to constitutively express an enhanced green fluorescent protein (EGFP) and used to detect (1) antiviral potency in SARS-CoV infection tests; (2) antiviral specificity in tests using the porcine coronavirus transmissible gastroenteritis virus (TGEV); and (3) cytotoxicity in the same assays without virus challenge. The assay system involves minimal manipulation after assay set-up, facilitates automated read-out and minimizes risks associated with hazardous viruses. The suitability of this assay system in drug discovery was demonstrated by screening of 3388 small molecule compounds. The results show that these assays can be applied to high-throughput screening for identification of inhibitors selectively active against SARS-CoV.


title: Recent advances of protein microarrays

text: Technological innovations and novel applications have greatly advanced the field of protein microarrays. Over the past two years, different types of protein microarrays have been used for serum profiling, protein abundance determinations, and identification of proteins that bind DNA or small compounds. However, considerable development is still required to ensure common quality standards and to establish large content repertoires. Here, we summarize applications available to date and discuss recent technological achievements and efforts on standardization.


title: SARS and MERS: recent insights into emerging coronaviruses

text: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002–2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrmicro.2016.81) contains supplementary material, which is available to authorized users.


title: Association between NO(2)cumulative exposure and influenza prevalence in mountainous regions: A case study from Southwest China

text: While accumulating evidence shows that air pollution exposure is an important risk factor to influenza prevalence, their association has been inadequately investigated in mountainous regions with dense populations and high humidity. We aim to estimate the association and exposure-outcome effects between exposure to nitrogen dioxide (NO(2)) and influenza prevalence in a mountainous region with a dense population and high humidity. We investigated 14,993 patients with confirmed influenza cases from January 2013 to December 2017 in Chongqing, a mountainous city in southwest China. We developed distributed lag non-linear models with quasi-Poisson link to take into account the lag and non-linear effects of NO(2) exposure on influenza prevalence. We estimated that the cumulative effect of a 10 μg/m(3) increase in NO(2) with seven-day lag (i.e., summing all the contributions up to seven days) corresponded to relative risk of 1.24 (95% CI: 1.17-1.31) in daily influenza prevalence. Comparing to annual mean of the World Health Organization air quality guidelines of 40 μg/m(3) for NO(2), we estimated that 14.01% (95% CI: 10.69-17.08%) of the influenza cases were attributable to excessive NO(2) exposure. Our results suggest that NO(2) exposure could worsen the risk of influenza infection in this mountainous city, filling the gap of relevant researches in densely populated and mountainous cities. Our findings provide evidence for developing influenza surveillance and early warning systems.


title: Viruses and endogenous retroviruses in multiple sclerosis: From correlation to causation

text: Multiple sclerosis is an immune‐mediated disease with an environmental component. According to a long‐standing but unproven hypothesis dating to initial descriptions of multiple sclerosis (MS) at the end of the 19th century, viruses are either directly or indirectly implicated in MS pathogenesis. Whether viruses in MS are principally causal or simply contributory remains to be proven, but many viruses or viral elements—predominantly Epstein‐Barr virus, human endogenous retroviruses (HERVs) and human herpesvirus 6 (HHV‐6) but also less common viruses such as Saffold and measles viruses—are associated with MS. Here, we present an up‐to‐date and comprehensive review of the main candidate viruses implicated in MS pathogenesis and summarize how these viruses might cause or lead to the hallmark demyelinating and inflammatory lesions of MS. We review data from epidemiological, animal and in vitro studies and in doing so offer a transdisciplinary approach to the topic. We argue that it is crucially important not to interpret “absence of evidence” as “evidence of absence” and that future studies need to focus on distinguishing correlative from causative associations. Progress in the MS‐virus field is expected to arise from an increasing body of knowledge on the interplay between viruses and HERVs in MS. Such interactions suggest common HERV‐mediated pathways downstream of viral infection that cause both neuroinflammation and neurodegeneration. We also comment on the limitations of existing studies and provide future research directions for the field.


title: A ten-year China-US laboratory collaboration: improving response to influenza threats in China and the world, 2004–2014

text: The emergence of severe acute respiratory syndrome (SARS) underscored the importance of influenza detection and response in China. From 2004, the Chinese National Influenza Center (CNIC) and the United States Centers for Disease Control and Prevention (USCDC) initiated Cooperative Agreements to build capacity in influenza surveillance in China. From 2004 to 2014, CNIC and USCDC collaborated on the following activities: 1) developing human technical expertise in virology and epidemiology in China; 2) developing a comprehensive influenza surveillance system by enhancing influenza-like illness (ILI) reporting and virological characterization; 3) strengthening analysis, utilization and dissemination of surveillance data; and 4) improving early response to influenza viruses with pandemic potential. Since 2004, CNIC expanded its national influenza surveillance and response system which, as of 2014, included 408 laboratories and 554 sentinel hospitals. With support from USCDC, more than 2500 public health staff from China received virology and epidemiology training, enabling > 98% network laboratories to establish virus isolation and/or nucleic acid detection techniques. CNIC established viral drug resistance surveillance and platforms for gene sequencing, reverse genetics, serologic detection, and vaccine strains development. CNIC also built a bioinformatics platform to strengthen data analysis and utilization, publishing weekly on-line influenza surveillance reports in English and Chinese. The surveillance system collects 200,000–400,000 specimens and tests more than 20,000 influenza viruses annually, which provides valuable information for World Health Organization (WHO) influenza vaccine strain recommendations. In 2010, CNIC became the sixth WHO Collaborating Centre for Influenza. CNIC has strengthened virus and data sharing, and has provided training and reagents for other countries to improve global capacity for influenza control and prevention. The collaboration’s successes were built upon shared mission and values, emphasis on long-term capacity development and sustainability, and leadership commitment.


title: Effect of Polyprenyl Immunostimulant on the survival times of three cats with the dry form of feline infectious peritonitis

text: Feline infectious peritonitis (FIP) is considered a fatal disease. Three cats with dry form FIP were treated with Polyprenyl Immunostimulant. Two of the three cats are still on treatment and are alive and well 2 years after diagnosis. The third cat survived 14 months but was treated for only 4.5 months. Further studies are necessary to assess the potential of the Polyprenyl Immunostimulant.


title: Pathogenesis of feline enteric coronavirus infection

text: Fifty-one specific pathogen-free (SPF) cats 10 weeks to 13 years of age were infected with a cat-to-cat fecal–oral passed strain of feline enteric coronavirus (FECV). Clinical signs ranged from unapparent to a mild and self-limiting diarrhea. Twenty-nine of these cats were FECV naïve before infection and followed sequentially for fecal virus shedding and antibody responses over a period of 8–48 months. Fecal shedding, as determined by real-time polymerase chain reaction (RT-PCR) from rectal swabs, appeared within a week and was significantly higher in kittens than older cats. FECV shedding remained at high levels for 2–10 months before eventually evolving into one of three excretion patterns. Eleven cats shed the virus persistently at varying levels over an observation period of 9–24 months. Eleven cats appeared to have periods of virus shedding interlaced with periods of non-shedding (intermittent or recurrent shedders), and seven cats ceased shedding after 5–19 months (average 12 months). There was no change in the patterns of virus shedding among cats that were excreting FECV at the time of a secondary challenge exposure. Four cats, which had ceased shedding, re-manifested a primary type infection when secondarily infected. Cats with higher feline coronavirus (FCoV) antibody titers were significantly more likely to shed virus, while cats with lower titers were significantly less likely to be shedding. Twenty-two kittens born to experimentally infected project queens began shedding virus spontaneously, but never before 9–10 weeks of age. Natural kittenhood infections appeared to be low grade and abortive. However, a characteristic primary type infection occurred following experimental infection with FECV at 12–15 weeks of age. Pregnancy, parturition and lactation had no influence on fecal shedding by queens. Methylprednisolone acetate treatment did not induce non-shedders to shed and shedders to increase shedding.


title: Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis

text: BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24–0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11–0.37) and 47% (OR = 0.53, 95% CI = 0.36–0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.