title: siRNA targeting the Leader sequence of SARS-CoV inhibits virus replication

text: SARS-CoV (the SARS-Associated Coronavirus) was reported as a novel virus member in the coronavirus family, which was the cause of severe acute respiratory syndrome. Coronavirus replication occurs through a unique mechanism employing Leader sequence in the transcripts when initiating transcription from the genome. Therefore, we cloned the Leader sequence from SARS-CoV(BJ01), which is identical to that identified from SARS-CoV(HKU-39849), and constructed specific siRNA targeting the Leader sequence. Using EGFP and RFP reporter genes fused with the cloned SARS-CoV Leader sequence, we demonstrated that the siRNA targeting the Leader sequence decreased the mRNA abundance and protein expression levels of the reporter genes in 293T cells. By stably expressing the siRNA in Vero E6 cells, we provided data that the siRNA could effectively and specifically decrease the mRNA abundance of SARS-CoV genes as analyzed by RT-PCR and Northern blot. Our data indicated that the siRNA targeting the Leader sequence inhibited the replication of SARS-CoV in Vero E6 cells by silencing gene expression. We further demonstrated, via transient transfection experiments, that the siRNA targeting the Leader sequence had a much stronger inhibitory effect on SARS-CoV replication than the siRNAs targeting the Spike gene or the antisense oligodeoxynucleotides did. This report provides evidence that targeting Leader sequence using siRNA could be a powerful tool in inhibiting SARS-CoV replication.


title: Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

text: G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding–unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA–RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.


An international physical activity and public health research agenda to inform COVID-19 policies and practices


title: Exit and Entry Screening Practices for Infectious Diseases among Travelers at Points of Entry: Looking for Evidence on Public Health Impact

text: A scoping search and a systematic literature review were conducted to give an insight on entry and exit screening referring to travelers at points of entry, by analyzing published evidence on practices, guidelines, and experiences in the past 15 years worldwide. Grey literature, PubMed. and Scopus were searched using specific terms. Most of the available data identified through the systematic literature review concerned entry screening measures at airports. Little evidence is available about entry and exit screening measure implementation and effectiveness at ports and ground crossings. Exit screening was part of the World Health Organisation’s (WHO) temporary recommendations for implementation in certain points of entry, for specific time periods. Exit screening measures for Ebola Virus Disease (EVD) in the three most affected West African countries did not identify any cases and showed zero sensitivity and very low specificity. The percentages of confirmed cases identified out of the total numbers of travelers that passed through entry screening measures in various countries worldwide for Influenza Pandemic (H1N1) and EVD in West Africa were zero or extremely low. Entry screening measures for Severe Acute Respiratory Syndrome (SARS) did not detect any confirmed SARS cases in Australia, Canada, and Singapore. Despite the ineffectiveness of entry and exit screening measures, authors reported several important concomitant positive effects that their impact is difficult to assess, including discouraging travel of ill persons, raising awareness, and educating the traveling public and maintaining operation of flights from/to the affected areas. Exit screening measures in affected areas are important and should be applied jointly with other measures including information strategies, epidemiological investigation, contact tracing, vaccination, and quarantine to achieve a comprehensive outbreak management response. Based on review results, an algorithm about decision-making for entry/exit screening was developed.


title: The process by which perceived autonomy support predicts motivation, intention, and behavior for seasonal influenza prevention in Hong Kong older adults

text: BACKGROUND: This study examined the effectiveness of a theoretical framework that integrates self-determination theory (SDT) and the theory of planned behavior (TPB) in explaining the use of facemasks to prevent seasonal influenza among Hong Kong older adults. METHODS: Data were collected at two time points in the winter in Hong Kong, during which influenza is most prevalent. At Time 1, older adults (N = 141) completed self-report measures of SDT (perceived autonomy support from senior center staff, autonomous motivation for influenza prevention) and TPB (attitude, subjective norm, perceived behavioral control, and intention for influenza prevention) constructs with respect to facemask used to prevent infection. Two weeks later, at Time 2, participants’ acceptance of a facemask to prevent influenza in the presence of an experimenter with flu-like symptoms was recorded. RESULTS: Path analysis found that perceived autonomy support of senior center staff was positively and significantly linked to autonomous motivation for facemask use, which, in turn, was positively related to intentions to wear facemasks through the mediation of attitude, subjective norm, and perceived behavioral control. However, the effect of intention on facemask use was not significant. CONCLUSIONS: Results generally support the proposed framework and the findings of previous studies with respect to intention, but the non-significant intention-behavior relationship may warrant future research to examine the reasons for older adults not to wear facemasks to prevent seasonal influenza despite having positive intentions to do so.


title: Transmissible Gastroenteritis Virus Papain-Like Protease 1 Antagonizes Production of Interferon-β through Its Deubiquitinase Activity

text: Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus- (SeV-) induced interferon (IFN-β) production. Recently, the crystal structure of transmissible gastroenteritis virus (TGEV) PL1 has been solved, which was similar to that of SARS-CoV PL2(pro), which may antagonize host innate immunity. However, very little is known about whether TGEV PL1 can antagonize host innate immune response. Here, we presented evidence that TGEV PL1 encoded by the replicase gene could suppress the IFN-β expression and inhibit the nuclear translocation of interferon regulatory factor 3 (IRF3). The ability to antagonize IFN-β production was dependent on the intact catalytic activity of PL1. Furthermore, TGEV PL1 exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I- (RIG-1-) and stimulator of interferon gene- (STING-) dependent IFN expression. Our data collectively suggest that TGEV PL1 can inhibit the IFN-β expression and interfere with RIG-1- and STING-mediated signaling through a viral DUB activity. Our study has yielded strong evidence for the TGEV PL1 mechanisms that counteract the host innate immunity.


title: Transient hyperglycosylation of rhodopsin with galactose

text: Abstract Rhodopsin's oligosaccharide chains contain predominantly two types of sugar residues: mannose and N-acetylglucosamine. In the present work, bovine and rat rhodopsin were analysed biochemically for the presence of a third sugar, galactose. Treatment of bovine rod outer segments (ROS) with galactose oxidase followed by reduction with tritium-labeled sodium borohydride revealed the presence of existing molecules of galactose on rhodopsin. Rats injected intravitreally with [3H]galactose and [14C]leucine and maintained in darkness were killed 1 hr, 6 hr, 1, 3, or 5 days following the injection. Retinas were collected for subcellular fractionation and rhodopsin from each of the fractions was purified by ConA sepharose chromatography and SDS-PAGE. During the first 6 hr, galactose selectively labeled rhodopsin in the Golgi-enriched fraction resulting in increased [3H] [14C] ratios in both Golgi and ROS. The data suggested that trimming was occurring at the transition from Golgi to ROS. Furthermore, a decrease in isotope ratio in the ROS between 6 hr and 1 day suggested further trimming of rhodopsin after membrane assembly in the ROS. Additional in vivo experiments demonstrated existing molecules of galactose on rhodopsin's oligosaccharide chain using lectin affinity chromatography. Rats injected intravitreally with [35S]methionine were dark-adapted for 2 hr. Following subcellular fractionation of retinas, ConA purified rhodopsin from ROS was applied to one of two additional lectin columns: Ricinus communis agglutinin (RCA) or Griffonia simplicifolia I (GSA). Eight to nine per cent of the labeled rhodopsin was bound to and eluted from RCA, whereas none bound to GSA, indicating the presence of a β-galactoside. The RCA agarose eluted protein co-electrophoresed with a rhodopsin standard and was light sensitive. Galactose was shown to be the terminal sugar on this subset of rhodopsin and was not capped by neuraminic acid. Binding of rhodopsin's oligosaccharide to RCA was abolished by pre-treatment with β-galactosidase. Decreased binding of rhodopsin to RCA was observed following intravitreal injection of castanospermine but not swainsonine. Of those two inhibitors of glycoprotein trimming, only castanospermine would be expected to prevent the addition of galactose to the oligosaccharide. The association of galactose with rat rhodopsin appeared to be a transient one. At 2 hr, 8–9% of rhodopsin contained galactose, at 6 hr only 2·2% had galactose and by 24 hr less than 1% did. The galactose was trimmed from rhodopsin's oligosaccharide presumably after its role was complete. Separation of rhodopsin of the plasma membranes from rhodopsin of discs indicated that 75% of the galactose-containing rhodopsin was in the plasma membrane and only 25% was in the discs. These findings suggested a possible role for galactose in new disc formation with subsequent removal after the discs are sealed.


title: Viral Interplay with the Host Sumoylation System

text: Viruses have evolved elaborate means to regulate diverse cellular pathways in order to create a cellular environment that facilitates viral survival and reproduction. This includes enhancing viral macromolecular synthesis and assembly, as well as preventing antiviral responses, including intrinsic, innate, and adaptive immunity. There are numerous mechanisms by which viruses mediate their effects on the host cell, and this includes targeting various cellular post-translational modification systems, including sumoylation. The wide-ranging impact of sumoylation on cellular processes such as transcriptional regulation, apoptosis, stress response, and cell cycle control makes it an attractive target for viral dysregulation. To date, proteins from both RNA and DNA virus families have been shown to be modified by SUMO conjugation, and this modification appears critical for viral protein function. More interestingly, members of the several viral families have been shown to modulate sumoylation, including papillomaviruses, adenoviruses, herpesviruses, orthomyxoviruses, filoviruses, and picornaviruses. This chapter will focus on mechanisms by which sumoylation both impacts human viruses and is used by viruses to promote viral infection and disease.


title: Respiratory Tract Infections Due to Human Metapneumovirus in Immunocompromised Children

text: BACKGROUND: The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood. METHODS: We performed a retrospective evaluation of pediatric patients with laboratory-confirmed hMPV infections and underlying hematologic malignancy, solid tumors, solid organ transplant, rheumatologic disease, and/or receipt of chronic immunosuppressants. Data were analyzed using t tests and Fisher's exact tests. RESULTS: Overall, 55 patients (median age: 5 years; range: 5 months–19 years) with hMPV infection documented between 2006 and 2010 were identified, including 24 (44%) with hematologic malignancy, 9 (16%) undergoing hematopoietic stem cell transplant, 9 (16%) with solid tumors, and 8 (15%) with solid organ transplants. Three (5%) presented with fever alone, 35 (64%) presented with upper respiratory tract infections, and 16 (29%) presented with lower respiratory tract infections (LRTI). Twelve (23%) patients required intensive care unit admission and/or supplemental oxygen ≥28% FiO(2). Those with severe disease were more likely to be neutropenic (P = .02), but otherwise did not differ by age (P = .27), hematopoietic stem cell transplant recipient status (P = .19), or presence of lymphopenia (P = .09). Nine (16%) patients received treatment with ribavirin, intravenous immunoglobulin, or both. Three children (5%) died of hMPV pneumonia. CONCLUSIONS: Immunocompromised pediatric patients with hMPV infection have high rates of LRTI and mortality. The benefits of treatment with ribavirin and intravenous immunoglobulin in this patient population require further evaluation.


title: CT features of novel coronavirus pneumonia (COVID-19) in children

text: ABSTRACT: A serious epidemic of COVID-19 broke out in Wuhan, Hubei Province, China, and spread to other Chinese cities and several countries now. As the majority of patients infected with COVID-19 had chest CT abnormality, chest CT has become an important tool for early diagnosis of COVID-19 and monitoring disease progression. There is growing evidence that children are also susceptible to COVID-19 and have atypical presentations compared with adults. This review is mainly about the differences in clinical symptom spectrum, diagnosis of COVID-19, and CT imaging findings between adults and children, while highlighting the value of radiology in prevention and control of COVID-19 in pediatric patients. KEY POINTS: • Compared with adults, pediatric patients with COVID-19 have the characteristics of lower incidence, slighter clinical symptoms, shorter course of disease, and fewer severe cases. • The chest CT characteristics of COVID-19 in pediatric patients were atypical, with more localized GGO extent, lower GGO attenuation, and relatively rare interlobular septal thickening. • Chest CT should be used with more caution in pediatric patients with COVID-19 to protect this vulnerable population from risking radiation.


title: Patients With Cancer and COVID-19: A WhatsApp Messenger-Based Survey of Patients’ Queries, Needs, Fears, and Actions Taken

text: PURPOSE: This descriptive investigation was undertaken at three oncology units to report queries, needs, and fears related to severe acute respiratory syndrome coronavirus 2 (COVID-19) of patients with cancer and to avoid uncontrolled treatment delays or withdrawal, behavioral mistakes, and panic. PATIENTS AND METHODS: All queries spontaneously delivered through the WhatsApp instant messaging system commonly used by patients to communicate with oncology units were collected and grouped by homology in five categories. Responses to the queries were given according to recommendations by the Italian Association of Medical Oncology through WhatsApp and by subsequent phone calls. Patients were also classified according to the site of the primary tumor, stage of disease, and current treatments. Analysis of the association between these data and queries was carried out. RESULTS: The social scenario in Italy is a nationwide lockdown except for hospitals, pharmacies, and food supplies. Overall, 446 different patients’ WhatsApp conversations were analyzed between March 1 and March 13 and comprised the following: requirement of visit delay by patients undergoing oral therapies or in follow-up, delays in chemotherapy or immunotherapy administration, queries about possible immunosuppression, and changes in lifestyle or daily activities. Delay requirements were statistically more frequent among patients with prostate or breast cancer compared with those with lung or pancreatic cancer. Actions taken by oncologists are also reported. CONCLUSION: To our knowledge, the WhatsApp instant messaging system has been occasionally used in other medical settings with controversial results. In our experience, WhatsApp turned out to be adequate to give a rapid answer to most queries from patients with cancer in the COVID-19 pandemic scenario.


title: The COVID‐19 pandemic and agriculture – Short and long run implications for international trade relations

text: The COVID‐19 pandemic has put unprecedented strain on food supply chains. Given the ever‐increasing degree of globalization, those supply chains very often stretch across international borders. In the short run, countries have largely been working to keep those supply chains intact and operating efficiently so that panic buying is cooled and shifts in consumption habits arising from personal isolation can be accommodated. Once the crisis has passed, based on what has been learned regarding the international food system's resilience, governments may wish to strengthen institutions that govern international trade. On the other hand, based on their COVID‐19 experience, governments may feel that they are too dependent on foreign sources of supply and may wish to reverse the impacts of globalization on their food systems. As a result, they may become increasingly isolationist, eschewing international cooperation. Which of these opposing forces will prevail may depend on the paths economies follow after the disequilibrium precipitated by the pandemic. This article is protected by copyright. All rights reserved


title: Chapter 9 Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus in Workers in the Food Industry

text: Abstract Staphylococcus aureus is part of the common flora on the skin and mucous membranes of mammals and approximately 20–30% of humans are persistently colonized, mainly by mostly susceptible human-adapted isolates. In contrast, colonization with methicillin-resistant S. aureus is rare (approximately 1%), predominantly transient and associated with prior contact to the health care system. Additionally, in recent years livestock-associated S. aureus clones contributed to colonization in humans, especially in those working in close contact to farm animals. A considerable percentage of colonizing S. aureus isolates is equipped with enterotoxin genes. Humans carrying enterotoxigenic isolates represent a contamination source when handling food, thus generating a continuous risk of S. aureus food intoxication. Molecular characterization of isolates colonizing humans and obtained from food, respectively, enables the tracing of food-related outbreaks back to the source of food intoxication. We will summarize current knowledge about the S. aureus population colonizing humans, including those in close contact to animals and food, respectively. Additionally, we will review data on the molecular characterization of S. aureus isolates related to staphylococcal foodborne disease and the elucidation of staphylococcal foodborne outbreaks. Staphylococcal food poisoning is a common foodborne disease, mediated by the ingestion of enterotoxins produced by enterotoxigenic strains of S. aureus. For several outbreaks of foodborne S. aureus disease, colonized personnel could be identified as the source of food contamination. However, because of the widespread occurrence of enterotoxigenic strains as human colonizers and the often transient nature of colonization, the source of contamination cannot always be identified unambiguously. Therefore, compliance with hygiene measures is the most important requirement to prevent food contamination by both human colonization and environmental S. aureus reservoirs.


title: Sequence and Structure Analysis of Distantly-Related Viruses Reveals Extensive Gene Transfer between Viruses and Hosts and among Viruses

text: The origin and evolution of viruses is a subject of ongoing debate. In this study, we provide a full account of the evolutionary relationships between proteins of significant sequence and structural similarity found in viruses that belong to different classes according to the Baltimore classification. We show that such proteins can be found in viruses from all Baltimore classes. For protein families that include these proteins, we observe two patterns of the taxonomic spread. In the first pattern, they can be found in a large number of viruses from all implicated Baltimore classes. In the other pattern, the instances of the corresponding protein in species from each Baltimore class are restricted to a few compact clades. Proteins with the first pattern of distribution are products of so-called viral hallmark genes reported previously. Additionally, this pattern is displayed by the envelope glycoproteins from Flaviviridae and Bunyaviridae and helicases of superfamilies 1 and 2 that have homologs in cellular organisms. The second pattern can often be explained by horizontal gene transfer from the host or between viruses, an example being Orthomyxoviridae and Coronaviridae hemagglutinin esterases. Another facet of horizontal gene transfer comprises multiple independent introduction events of genes from cellular organisms into otherwise unrelated viruses.


Quand le sénat juge sévèrement la gestion du Covid-19


title: Emerging Infectious Diseases: a 10-Year Perspective from the National Institute of Allergy and Infectious Diseases

text: Although optimists once imagined that serious infectious disease threats would by now be conquered, newly emerging (e.g., severe acute respiratory syndrome [SARS]), reemerging (e.g., West Nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax bioterrorism) continue to appear throughout the world. Over the past decade, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive measures and treatments for many of the world's most dangerous pathogens has resulted in considerable progress. Intramural and extramural investigators supported by the National Institute of Allergy and Infectious Diseases (NIAID) have contributed substantially to this effort. This overview highlights selected NIAID-sponsored research advances over the past decade, with a focus on progress in combating HIV/AIDS, malaria, tuberculosis, influenza, SARS, West Nile virus, and potential bioterror agents. Many basic research discoveries have been translated into novel diagnostics, antiviral and antimicrobial compounds, and vaccines, often with extraordinary speed.


Identifying a Capability Framework That Could Mitigate the Coronavirus Disease 2019 Pandemic in a Global Health Community


title: Play or not to play—An analysis of the mechanism of the zero-commission Chinese outbound tours through a game theory approach

text: The purpose of this study is to demystify the mechanism of the so-called zero-commission tours that have become synonymous with the booming Chinese outbound tourism market in the past decade. Two models of game theory are applied to identify nine proposed key factors that constitute the “zero-tour” phenomenon. These involve interactions in both the temporal and spatial dimensions of all of the stakeholders concerned with such tours, from outbound tourists and outbound and inbound operators to local guides and governments both within and beyond the Chinese border. It is concluded that zero-commission tours, underpinned by the proposed factors and notwithstanding their current legal and practical viability, have a tremendous negative impact on all of the stakeholders. This study may serve as a reference for the drafting and implementation of both policy and business countermeasures to curb zero-commission tours, thus facilitating more positive contributions from Chinese outbound tourism to the development of world tourism.


title: Factors Affecting Intestinal Health in Poultry

text: Abstract The gastrointestinal (GI) tract has the most extensive exposed surface in the body and is constantly exposed to a wide variety of potentially harmful substances. The GI tract acts as a selective barrier between the tissues of the bird and its luminal environment. This barrier is composed of physical, chemical, immunological, and microbiological components. A wide range of factors associated with diet and infectious disease agents can negatively affect the delicate balance among the components of the chicken gut and, as a result, affect health status and production performance of birds in commercial poultry operations. Phasing out of antibiotic growth promoters from poultry diets in Europe and recent moves toward reduction or removal of these compounds in other parts of the world including North America will likely change the microbial profile of the GI tract environment in commercial poultry. This paper reviews the GI tract from developmental, immunological, and microbial standpoints and then discusses factors that can affect health status of this system. Necrotic enteritis and coccidiosis and their interactions, and possible consequences of antibiotic growth promoter removal from poultry diets with respect to these diseases, are discussed in more detail.


title: Viral nanoparticles and virus‐like particles: platforms for contemporary vaccine design

text: Current vaccines that provide protection against infectious diseases have primarily relied on attenuated or inactivated pathogens. Virus‐like particles (VLPs), comprised of capsid proteins that can initiate an immune response but do not include the genetic material required for replication, promote immunogenicity and have been developed and approved as vaccines in some cases. In addition, many of these VLPs can be used as molecular platforms for genetic fusion or chemical attachment of heterologous antigenic epitopes. This approach has been shown to provide protective immunity against the foreign epitopes in many cases. A variety of VLPs and virus‐based nanoparticles are being developed for use as vaccines and epitope platforms. These particles have the potential to increase efficacy of current vaccines as well as treat diseases for which no effective vaccines are available. WIREs Nanomed Nanobiotechnol 2011 3 174–196 DOI: 10.1002/wnan.119 1.. Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.


title: A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature

text: Abstract The spike (S) glycoprotein of coronavirus is responsible for receptor binding and membrane fusion. A number of variants with deletions and mutations in the S protein have been isolated from naturally and persistently infected animals and tissue cultures. Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. The complete sequences of wild type (wt) virus, two ts mutants, and the revertant were compared and variations linked to phenotypes were mapped. A single amino acid reversion (L294-to-Q) in the S protein is sufficient to abrogate the ts phenotype. Interestingly, unlike wt virus, the revertant grows well at and below 32 °C, the permissive temperature, as it carries other mutations in multiple genes that might be associated with the cold-adaptation phenotype. If the two ts mutants were allowed to enter cells at 32 °C, the S protein was synthesized, core-glycosylated and at least partially modified at 40 °C. However, compared with wt virus and the revertant, no infectious particles of these ts mutants were assembled and released from the ts mutant-infected cells at 40 °C. Evidence presented demonstrated that the Q294-to-L294 mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. Consequently, some essential functions of the S protein, including mediation of cell-to-cell fusion and its incorporation into virions, were completely abolished.


title: CXCL10 contributes to p38-mediated apoptosis in primary T lymphocytes in vitro

text: Abstract CXCL10 is part of the group of interferon-stimulated genes and it plays an important role during different viral infections by inducing cell activation, chemotaxis and lymphocyte priming toward the Th1 phenotype. In this study, we investigated in vitro the effects of CXCL10 in activated human primary T lymphocytes in terms of apoptosis or survival, and delineated the signaling pathways that are involved. CXCL10, in combination with IL-2 and/or IFNα, induces apoptosis in T lymphocytes. Moreover, CXCL10-induced activation of CXCR3 also triggers pro-survival signals that can be blocked by pertussis toxin. The analysis of the downstream signaling kinases shows that apoptosis is p38 MAPK-dependent and the pro-survival signals rely on the sustained activation of PI3K and the transient activation of Akt. On the other hand, the transient activation of p44/p42 ERK did not have an impact on T lymphocyte survival. We propose an immunological model in which CXCL10, together with other co-stimulating cytokines, participates in the activation of T lymphocytes, promotes survival and expansion of certain lymphocyte subsets, and induces chemotaxis toward the infected tissues. On the other hand, CXCL10 might contribute to the triggering of apoptosis in other subsets of T lymphocytes, including those lymphocytes that were transiently activated but later lacked the appropriate sets of specific co-stimulating signals to ensure their survival.


title: Altered pro-inflammatory cytokine mRNA levels in chickens infected with infectious bronchitis virus

text: Abstract Infectious bronchitis virus (IBV) replicates primarily in the respiratory tract and grows in various organs in chickens, with or without pathological effects. The diversity of this virus has been verified by sequence analysis of the S1 glycoprotein gene, but this method must be supplemented with further analysis for characterization of the agent. To increase our understanding of the pathogenesis of the disease caused by this virus, we investigated the response of chickens to 2 IBV with different genotypes, KIIa and ChVI. The clinical signs induced by the viruses were observed. In addition, the mRNA levels of the pro-inflammatory cytokines, IL-6, IL-1β, and lipopolysaccharide-induced tumor necrosis factor-α factor and the serum levels of α1-acid glycoprotein, which is a major acute phase protein, were measured. The KIIa genotype (Kr/ADL110002/2011) induced clinical signs accompanied by the excessive production of pro-inflammatory cytokines and a higher viral load. In chickens infected with this isolate, simultaneous peaks in the viral copy number and cytokine production were observed at 7 dpi in the trachea and 9 d postinoculation in the kidney. On the other hand, the chickens infected with the ChVI genotype (Kr/ADL120003/2012) did not show a response other than a mild upregulation of cytokines at 1 d postinoculation, which appears to indicate the invasion of the virus. In summary, we confirmed a differential innate response following infection with distinct IBV. We hypothesize that an excessive innate response contributes to the scale of the pathophysiologic effect in chickens.


title: Evaluation of real-time RT-PCR for the quantification of FCoV shedding in the faeces of domestic cats

text: Faecal samples were taken from cats living in multi-cat households with endemic feline coronavirus (FCoV) infection. Total RNA was extracted from faecal suspensions and FCoV RNA was quantified using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The real-time RT-PCR threshold cycle (C(T)) values were consistently high suggesting that the samples contained very little viral RNA. However, experiments in which RNA extracted from FCoV-infected cell culture supernatants was combined with RNA extracted from faecal suspensions revealed the presence of faecal factors that significantly inhibited the reverse transcription reaction. Consequently, three methods of RNA extraction were investigated and RNA dilution was undertaken to investigate whether the effects of the faecal inhibitors could be reduced. Our results show that using the QIAgen RNA mini kit for RNA extraction and dilution of the RNA samples helps to reduce the inhibitory effects. However, because the extent of the inhibitory effects varied between faecal samples, accurate quantification proved difficult. We, therefore, conclude that although real-time RT-PCR provides an excellent method for detecting the presence of viral shedding, quantification of FCoV RNA in faecal material has to take into account the possible effects of RT-PCR inhibitors. It is, therefore, essential that all new assays, and the methods of sample preparation, are carefully evaluated before being used in a clinical setting.


title: Emerging Infections, the International Health Regulations, and Macro-Economy

text: Abstract When breaches in the species barrier between animals and humans result in crossover of animal infections to humans, the result is an emerging infectious disease. Emerging infections have the potential to cause severe human illness and death, and to spread among human populations and across geographic borders. Direct costs associated with emerging infections are often high, caused by prolonged patient management, hospitalization, and convalescence. Indirect costs are caused by absenteeism from work, death, and permanent removal from the workforce. There may be additional costs if precautionary prevention measures are required, based on the known or potential risk. These costs result from culling and prohibited trade in animals and animal-based products if infected animals are a continuing threat to humans; or from postponement or cancellation of travel and tourism if transmission in the general population is uncontrolled. Emerging infections sometimes cause panic and/or fear because of misunderstanding of the risk, and can lead to actions that result in economic loss similar to that caused by legitimate public health precautionary measures. They include reactions such as avoiding animal-based foods mistakenly thought to be the source of infection; unnecessary cancelling travel plans to avoid geographic areas where there is a perception of risk of infection; and/or unwarranted culling of animals or destruction of animal-based foods. If the misunderstanding is transmitted widely by the press or through social media networks, the negative economic impact can be amplified. Economic loss caused by these perceived risks can generally not be disentangled from the losses causes by public health measures that may be in place, but it is thought that at times they add significantly to the economic burden. The International Health Regulations (IHR) were designed to respond to the international spread of infectious disease outbreaks in a manner that prevents unnecessary negative economic impacts. Agreed by all Member States of the World Health Organization in 2005, they are a legally binding global agreement with the specific purpose of ensuring maximum security against the international spread of diseases, with a minimum interference in world traffic and trade. They reflect current understanding of infectious disease risks, especially those that emerge at the animal/human interface; the realization that infectious diseases cannot be stopped from entering countries at borders; the vast increase in access to information through the internet; and globalization that increases the speed with which infectious diseases spread. Under the IHR, countries are able to work transparently with WHO and its scientific experts and collaborating laboratories to conduct joint risk assessments of public health events such as outbreaks of infectious diseases; to make evidence-based recommendations to help prevent or control their international spread; and, by providing valid and transparent information to national focal points, to help prevent unnecessary panic and misunderstanding about risk.


title: Chapter 3 Immunobiological aspects of vaccines in pregnancy: Maternal perspective

text: Abstract Immunization during pregnancy is an efficient strategy to protect both the mother and the newborn infant against infectious pathogens. Pregnant women have an increased susceptibility to severe infections caused by some pathogens, but the mechanisms involved remain poorly understood. Pregnancy is associated with dynamic changes in maternal immune system that are critical for tolerance of the fetus. These changes could also play an important role in shaping maternal immune components that are transferred to the newborn infant following natural infection or vaccination to prevent infectious diseases in early life. As the momentum for maternal immunization is growing, there is a need to increase our understanding of the immunobiology of maternal immunization in order to better prevent infectious diseases in the pregnant women and the young infant.


title: Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical Cancer Patients

text: We investigated whether circulating osteopontin (OPN) could be used as a biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659) specific for the unique and intact thrombin-sensitive site in OPN using an inhibition ELISA. We found significantly higher levels of OPN in 33 cervical cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum (424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31 plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P = 0.0002), respectively]. Similar results were obtained when the plasma from a bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL) were compared with the same plasma samples of the healthy individuals (P = 0.0014). More significantly, the OPN level was highest in stage III-IV disease (614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non-discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318). No such discrimination was found when a mAb of a different specificity (mAb 446) was used in a similar inhibition ELISA to compare the two groups in the first study; a commercial capture ELISA also failed. The possibility that the target epitope recognized by the antibody probe in these assays was absent from the circulating OPN due to protein truncation was supported by gel fractionation of the OPN found in patients’ plasma: 60–64 kDa fragments were found instead of the presumably full-length OPN (68 kDa) seen in healthy people. How these fragments are generated and what possible role they play in cancer biology remain interesting questions.


title: Collateral damage: the impact on outcomes from cancer surgery of the COVID-19 pandemic

text: BACKGROUND: Cancer diagnostics and surgery have been disrupted by the response of healthcare services to the COVID-19 pandemic. Progression of cancers during delay will impact on patient long-term survival. METHODS: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of three months and six months and periods of disruption of one year and two years. Using healthcare resource costing, we contextualise attributable lives saved and life-years gained from cancer surgery to equivalent volumes of COVID-19 hospitalisations. FINDINGS: Per year, 94,912 resections for major cancers result in 80,406 long-term survivors and 1,717,051 life years gained. Per-patient delay of three/six months would cause attributable death of 4,755/10,760 of these individuals with loss of 92,214/208,275 life-years. For cancer surgery, average life-years gained (LYGs) per patient are 18.1 under standard conditions and 17.1/15.9 with a delay of three/six months (an average loss of 0.97/2.19 LYG per patient). Taking into account units of healthcare resource (HCRU), surgery results on average per patient in 2.25 resource-adjusted life-years gained (RALYGs) under standard conditions and 2.12/1.97 RALYGs following delay of three/six months. For 94,912 hospital COVID-19 admissions, there are 482,022 LYGs requiring of 1,052,949 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.08 LYG and 0.46 RALYGs. INTERPRETATION: Modest delays in surgery for cancer incur significant impact on survival. Delay of three/six months in surgery for incident cancers would mitigate 19%/43% of life-years gained by hospitalisation of an equivalent volume of admissions for community-acquired COVID-19. This rises to 26%/59% when considering resource-adjusted life-years gained. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued.


title: Porcine Transmissible Gastroenteritis Virus

text: Publisher Summary This chapter provides an overview of porcine transmissible gastroenteritis virus (TGE). This virus is a species that belongs to the family Coronaviridae and the genus Coronavirus. The virus causes severe fatal diarrhea in young piglets and usually a mild disease in adult pigs. Pigs, foxes, dogs, and cats are the hosts to the virus. TGE was first described in 1946 in the United States. Subsequently, it was found to be in many other countries. Live vaccines have been used for porcine transmissible gastroenteritis. Epizootiological studies that have been made on the disease reveal that it is possible that birds are involved as carriers of the disease. A profusion of methods of diagnosis has been reported in the literature for the disease. Agar gel immunodiffusion (AGID), virus neutralisation (VN), indirect immunofluorescent assay (IFA), complement fixation (CF), microneutralization, and enzyme-linked immunosorbent assay (ELISA) are some diagnostic techniques for the disease.


Conducting clinical research in the era of Covid-19


Quelling an innate response to dsRNA


title: A microarray of ubiquitylated proteins for profiling deubiquitylase activity reveals the critical roles of both chain and substrate

text: Abstract Substrate ubiquitylation is a reversible process critical to cellular homeostasis that is often dysregulated in many human pathologies including cancer and neurodegeneration. Elucidating the mechanistic details of this pathway could unlock a large store of information useful to the design of diagnostic and therapeutic interventions. Proteomic approaches to the questions at hand have generally utilized mass spectrometry (MS), which has been successful in identifying both ubiquitylation substrates and profiling pan-cellular chain linkages, but is generally unable to connect the two. Interacting partners of the deubiquitylating enzymes (DUBs) have also been reported by MS, although substrates of catalytically competent DUBs generally cannot be. Where they have been used towards the study of ubiquitylation, protein microarrays have usually functioned as platforms for the identification of substrates for specific E3 ubiquitin ligases. Here, we report on the first use of protein microarrays to identify substrates of DUBs, and in so doing demonstrate the first example of microarray proteomics involving multiple (i.e., distinct, sequential and opposing) enzymatic activities. This technique demonstrates the selectivity of DUBs for both substrate and type (mono- versus poly-) of ubiquitylation. This work shows that the vast majority of DUBs are monoubiquitylated in vitro, and are incapable of removing this modification from themselves. This work also underscores the critical role of utilizing both ubiquitin chains and substrates when attempting to characterize DUBs. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.


title: Implications of nonlinearity, confounding, and interactions for estimating exposure concentration-response functions in quantitative risk analysis

text: Recent advances in understanding of biological mechanisms and adverse outcome pathways for many exposure-related diseases show that certain common mechanisms involve thresholds and nonlinearities in biological exposure concentration-response (C-R) functions. These range from ultrasensitive molecular switches in signaling pathways, to assembly and activation of inflammasomes, to rupture of lysosomes and pyroptosis of cells. Realistic dose-response modeling and risk analysis must confront the reality of nonlinear C-R functions. This paper reviews several challenges for traditional statistical regression modeling of C-R functions with thresholds and nonlinearities, together with methods for overcoming them. Statistically significantly positive exposure-response regression coefficients can arise from many non-causal sources such as model specification errors, incompletely controlled confounding, exposure estimation errors, attribution of interactions to factors, associations among explanatory variables, or coincident historical trends. If so, the unadjusted regression coefficients do not necessarily predict how or whether reducing exposure would reduce risk. We discuss statistical options for controlling for such threats, and advocate causal Bayesian networks and dynamic simulation models as potentially valuable complements to nonparametric regression modeling for assessing causally interpretable nonlinear C-R functions and understanding how time patterns of exposures affect risk. We conclude that these approaches are promising for extending the great advances made in statistical C-R modeling methods in recent decades to clarify how to design regulations that are more causally effective in protecting human health.


title: Consistently Unreliable: Oil Spill Data and Transparency Discourse

text: Abstract Our recent research reveals enormous discrepancies in oil spill data disclosed by regulatory institutions and corporate sources in Nigeria. Federal agencies as well as major international oil corporations publish inconsistent and sometimes contradictory figures, often employing different spatial or regional categorizations. Uncertainties pertaining to data veracity in the Niger Delta, alongside the thin scientific record inflect deeply contentious debates regarding the country's oil industry. For advocacy organizations, the result is that those seeking to monitor oil spills may spend hours trying to square and cross-reference uneven information, time that could otherwise be spent assessing the scale of impacts and analyzing the complex structural causes surrounding them. Scholarly work in other jurisdictions indicates that the staging of non-transparent, incoherent and/or intentionally misleading data on oil spill risks is not unique to Nigeria, leading to a kind of epistemological vertigo in studying this sector.


title: Imported Episodic Rabies Increases Patient Demand for and Physician Delivery of Antirabies Prophylaxis

text: BACKGROUND: Imported cases threaten rabies reemergence in rabies-free areas. During 2000–2005, five dog and one human rabies cases were imported into France, a rabies-free country since 2001. The Summer 2004 event led to unprecedented media warnings by the French Public Health Director. We investigated medical practice evolution following the official elimination of rabies in 2001; impact of subsequent episodic rabies importations and national newspaper coverage on demand for and delivery of antirabies prophylaxis; regular transmission of epidemiological developments within the French Antirabies Medical Center (ARMC) network; and ARMC discussions on indications of rabies post-exposure prophylaxis (RPEP). METHODOLOGY/PRINCIPAL FINDINGS: Annual data collected by the National Reference Center for Rabies NRCR (1989–2006) and the exhaustive database (2000–2005) of 56 ARMC were analyzed. Weekly numbers of patients consulting at ARMC and their RPEP- and antirabies-immunoglobulin (ARIG) prescription rates were determined. Autoregressive integrated moving-average modeling and regression with autocorrelated errors were applied to examine how 2000–2005 episodic rabies events and their related national newspaper coverage affected demand for and delivery of RPEP. A slight, continuous decline of rabies-dedicated public health facility attendance was observed from 2000 to 2004. Then, during the Summer 2004 event, patient consultations and RPEP and ARIG prescriptions increased by 84%, 19.7% and 43.4%, respectively. Moreover, elevated medical resource use persisted in 2005, despite communication efforts, without any secondary human or animal case. CONCLUSIONS: Our findings demonstrated appropriate responsiveness to reemerging rabies cases and effective newspaper reporting, as no secondary case occurred. However, the ensuing demand on medical resources had immediate and long-lasting effects on rabies-related public health resources and expenses. Henceforth, when facing such an event, decision-makers must anticipate the broad impact of their media communications to counter the emerging risk on maintaining an optimal public health organization and implement a post-crisis communication strategy.


title: Complete Genome Sequences of Four Novel Human Coronavirus OC43 Isolates Associated with Severe Acute Respiratory Infection

text: We report here the complete genome sequences of four human coronavirus (HCoV) OC43 isolates generated using targeted viral nucleic acid capture and next-generation sequencing; the isolates were collected in New Mexico and Arkansas, USA, in February (HCoV-OC43/USA/TCNP_0070/2016) and March (HCoV-OC43/USA/ACRI_0052/2016) 2016 and January 2017 (HCoV-OC43/USA/TCNP_00204/2017 and HCoV-OC43/USA/TCNP_00212/2017).


title: High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses

text: Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing Renilla luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs in vitro. We screened 56 hits from the HTS data and validated 36 compounds in vitro using wild-type HCoV-OC43. Furthermore, we identified seven compounds (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) as broad-spectrum inhibitors according to their strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations. Additionally, we found that emetine blocked MERS-CoV entry according to pseudovirus entry assays and that lycorine protected BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This represents the first demonstration of in vivo real-time bioluminescence imaging to monitor the effect of lycorine on the spread and distribution of HCoV-OC43 in a mouse model. These results offer critical information supporting the development of an effective therapeutic strategy against CoV infection. IMPORTANCE Currently, there is no approved therapy to treat coronavirus infection; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are needed. Based on our high-throughput screening assay using a compound library, we identified seven compounds with broad-spectrum efficacy against the replication of four CoVs in vitro. Additionally, one compound (lycorine) was found to protect BALB/c mice against HCoV-OC43-induced lethality by decreasing viral load in the central nervous system. This inhibitor might offer promising therapeutic possibilities for combatting novel CoV infections in the future.


title: The dipeptidyl peptidase-4 expression in some MERS-CoV naturally infected dromedary camels in Saudi Arabia 2018–2019

text: MERS-CoV usually causes respiratory and renal failure in some patients, which may be the underlying cause of death. Dromedary camels are the only known reservoir of the virus until now. They shed the virus in their body secretions thus potentiate a risk for human infection. MERS-CoV tropism and replication is mainly affected by the presence of certain receptor ligands on the target tissues. The dipeptidyl peptidase-4 (DPP-4) is believed to act as receptors for MERS-CoV. The main objective of this study was to determine the expression levels of the DPP-4 in various organs of some naturally infected camels. We conducted a surveillance study to identify some positive MERS-CoV infected camels. Three positive animals identified by the Real time PCR. Our results are clearly showing the high level of expression of the DPP-4 in various organs of these animals’ particularly nasal turbinate, trachea, and lungs. The expression level may explain at least in part the pathogenesis of MERS-CoV in these organs. These findings confirm the pivotal roles of the DPP4 in the context of the MER-CoV infection in dromedary camels. Further studies are needed for a better understanding of the molecular pathogenesis of MER-CoV infection.


title: Impact of crisis events on Chinese outbound tourist flow: A framework for post-events growth()

text: International tourism is highly susceptible to external political, economic and environmental crisis events. This paper consists of two studies. Study 1 uses time-series monthly data and the TRAMO/SEATS model to detect and estimate the impact of a range of political, economic and environmental crisis events on the tourist flows from China to Japan and South Korea during the period of 2005–2017. Study 2 uses in-depth interviews to investigate the factors intensifying or alleviating the negative impacts of these crisis events on tourism as well as factors contributing to post-events tourism recovery and growth. Results identify the varying levels of impacts caused by event type and other causative factors for negative impacts. The paper discusses the influence of these factors to provide references to relevant stakeholders for strategic planning, policy making and recovery and growth scheme development.


title: Medicinal properties and conservation of Pelargonium sidoides DC.

text: Abstract Ethnopharmacological relevance Pelargonium sidoides DC. (Geraniaceae), a popular medicinal plant used in traditional medicine in the treatment of gastrointestinal ailments has been transformed into a phytopharmaceutical (EPs® 7360) for treating respiratory tract infections. The increasing international demand for Pelargonium sidoides has led to localised overexploitation of its wild populations in southern Africa. The aim of the review is to provide a synthesis of the current state of scientific knowledge on the phytochemical, pharmacological and toxicological properties of Pelargonium sidoides as well as the potential role of plant biotechnology in its conservation. The review highlights knowledge gaps in these research areas. Materials and Methods A comprehensive literature search involving mainly electronic and library sources of information were used to collate and synthesise published data. Results Experimental results from in vitro studies indicate that bioactive phytochemical constituents of Pelargonium sidoides may not possess a direct antimicrobial effect, but instead act by interfering with microbial binding to host cell receptors, inhibition of key enzymes and the production of antimicrobial effector molecules such as nitric oxide and interferons (IFNs) by the host cells. Furthermore, clinical evaluations in randomised, double-blind, placebo-controlled trials have demonstrated the beneficial effect of Pelargonium sidoides in the treatment of respiratory tract infections with few side effects. However, there is lack of adequate information on the safety evaluation of the plant. On the other hand, the increasing demand for Pelargonium sidoides has led to localised illegal harvesting of wild plants. Conclusions Pharmacological data reported in literature suggest that Pelargonium sidoides shows a beneficial effect in the treatment of respiratory tract infections. However, more studies are required to elucidate the mode of action of the active constituents exhibited in the treatment of respiratory tract infections and other health conditions caused by microbial attack. Furthermore, the pharmacological usefulness of Pelargonium sidoides must take cognisance of the broader context involving the need for conservation-friendly approaches in its utilisation. In this regard, plant biotechnology applications can play a meaningful role in a holistic conservation strategy.


COVID-19 protection guidelines in outpatient medical imaging centers


title: The clinical implication of dynamic neutrophil to lymphocyte ratio and D-dimer in COVID-19: A retrospective study in Suzhou China

text: Abstract Objective To investigate the clinical features of COVID-19 cases in Suzhou China. Biomarkers were screened out of hematological parameters for risk stratification. Method Confirmed COVID-19 adult patients in Suzhou were included. The patient data was collected, and the results of laboratory examinations were compared between the mild/moderate and severe COVID-19 groups. A ROC was calculated to compare the diagnostic performance of candidate indexes, and dynamic levels of hematological indexes were compared between the two groups. Result 75 patients were enrolled, with a mean age of 46.6 ± 14 years, and 45 patients were male. All patients were classified into two groups: the mild/moderate group and the severe group. WBC, neutrophil to lymphocyte ratio (NLR), D-dimer, and fibrinogen levels of the severe group were significantly higher (P < 0.05) than the mild/moderate, and the lymphocyte was lower. The ROC test showed that the hematological parameters had a larger AUC than that of inflammatory factors. There was a significant difference in lymphocyte and fibrinogen levels between the two groups on day 1 (P < 0.05). However, NLR of the severe group was higher than the mild/moderate on days 1, 4 and 14 (P < 0.01), and so was D-dimer on days 1, 7 and 14 (P < 0.05). Conclusion The common COVID-19 abnormal hematological indexes on admission included hyperfibrinogenemia, lymphopenia, the elevation of D-dimer, and leukopenia, which were significantly different between the mild/moderate and severe COVID-19 groups. Furthermore, the dynamic change of NLR and D-dimer level can distinguish severe COVID-19 cases from the mild/moderate.


title: A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell

text: Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage.


title: Heterogeneidad de criterios en el diagnóstico de bronquiolitis aguda en España

text: Resumen Introducción La bronquiolitis vírica aguda (BA) es una de las enfermedades respiratorias más frecuentes en los lactantes. Sin embargo, los criterios utilizados para su diagnóstico son heterogéneos e insuficientemente conocidos. Objetivo Identificar los criterios de diagnóstico de BA empleados en España, tanto por expertos como por pediatras clínicos. Métodos Estudio de metodología Delphi con expertos españoles en BA, buscando los puntos de consenso sobre el diagnóstico de BA. Posteriormente se realizó un estudio transversal mediante encuesta on-line dirigida a todos los pediatras españoles, contactados a través de mensajes de correo electrónico enviados por nueve sociedades científicas pediátricas. Se hizo análisis descriptivo y análisis factorial de los resultados de la encuesta, buscando si los criterios diagnósticos empleados se relacionaban con variables demográficas, geográficas o con la subespecialidad pediátrica. Resultados Los 40 expertos participantes alcanzaron un consenso en muchos aspectos (primer episodio de dificultad respiratoria y aumento de la frecuencia respiratoria, diagnóstico en cualquier estación del año, y utilidad de la identificación de virus para el diagnóstico), pero manteniendo opiniones enfrentadas en cuestiones importantes como la edad máxima aceptable para el diagnóstico. A la encuesta on-line respondieron 1297 pediatras. Los criterios diagnósticos que aplican son heterogéneos y están fuertemente asociados con la subespecialidad pediátrica. Su acuerdo con el consenso de expertos y con estándares internacionales es muy bajo. Conclusiones Los criterios usados en España para el diagnóstico de BA son heterogéneos. Esas diferencias pueden causar variabilidad en la práctica clínica en pacientes con BA. Abstract Introduction Acute viral bronchiolitis (AB) is one of the most common respiratory diseases in infants. However, diagnostic criteria for AB are heterogeneous and not very well known. Objective To identify the diagnostic criteria for AB used by experts and clinical paediatricians in Spain. Methods Delphi study with Spanish AB experts, looking for the points of agreement about AB diagnosis. A subsequent cross-sectional study was conducted by means of an on-line questionnaire addressed to all Spanish paediatricians, reached through electronic mail messages sent by nine paediatric scientific societies. Descriptive and factorial analyses were carried out, looking for any association of diagnostic criteria with demographic or geographic variables, or with paediatric subspecialty. Results Agreement was reached by 40 experts in many issues (first episode of respiratory distress and high respiratory frequency, diagnosis in any season of the year, and usefulness of virus identification in making diagnosis), but opposite views were maintained on key characteristics such as the maximum age for diagnosis. The on-line questionnaire was completed by 1297 paediatricians. Their diagnostic criteria were heterogeneous and strongly associated with their paediatric sub-specialty. Their agreement with the Spanish expert consensus and with international standards was very poor. Conclusions Diagnostic criteria for AB in Spain are heterogeneous. These differences could cause variability in clinical practice with AB patients.


title: An acute febrile outbreak in a refugee community of an Italian asylum seeker center: lessons learned

text: Abstract Objectives The management of infectious outbreaks in closed settings represents an important public health issue. An outbreak of acute febrile syndrome affecting 22 refugees resident at the Asylum Seekers Centre of Castelnuovo di Porto in Rome has been reported, and the preventive and control measures adopted have been described as an example of public health safety. Methods Pharyngeal swab and whole-blood samples were collected from 22 cases observed and analyzed for standard bacterial cultures and respiratory and herpesviruses by qualitative CLART PneumoVir2 and Entherpex microarray. Results A possible respiratory-transmitted etiology and a concomitant reactivation of multiple herpesviruses have been evidenced. The epidemiological investigation showed that the spread of the epidemic was promoted because patients were hosted in neighboring rooms or in the same room, facilitating the rapid spread of infectious disease. Conclusions The potential way of transmission was supposed, and preventive measures for infection control were adopted. The measures adopted are an example of best practice for outbreak management, and the microbiological surveillance is recommended for public health improvement.


title: Evaluation of viremia, proviral load and cytokine profile in naturally feline immunodeficiency virus infected cats treated with two different protocols of recombinant feline interferon omega

text: Abstract This study assesses viremia, provirus and blood cytokine profile in naturally FIV-infected cats treated with two distinct protocols of interferon omega (rFeIFN-ω). Samples from FIV-cats previously submitted to two single-arm studies were used: 7/18 received the licensed/subcutaneous protocol (SC) while 11/18 were treated orally (PO). Viremia, provirus and blood mRNA expression of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12p40, Interferon-γ and Tumor Necrosis Factor-α were monitored by Real-Time qPCR. Concurrent plasma levels of IL-6, IL-12p40 and IL-4 were assessed by ELISA. IL-6 plasma levels decreased in the SC group (p = 0.031). IL-6 mRNA expression (p = 0.037) decreased in the PO group, albeit not sufficiently to change concurrent plasma levels. Neither viremia nor other measured cytokines changed with therapy. Proviral load increased in the SC group (p = 0.031), which can be justified by a clinically irrelevant increase of lymphocyte count. Independently of the protocol, rFeIFN-ω seems to act on innate immunity by reducing pro-inflammatory stimulus.


title: Is it fair to hope that patients with Type 1 Diabetes (autoimmune) may be spared by the infection of Covid-19?

text: The CoV-19 infection appears to be unusual among patients with type 1Diabetes Mellitus, although they are considered a fragile population. We think that this in part due to the peculiar immune condition that leads to the destruction of the Beta cells.


title: Psychological Interventions during COVID-19: Challenges for low and middle income countries

text: Abstract At the start of 2020, the 2019 coronavirus disease (COVID-19), originating from China has spread to the world. There have been increasing numbers of confirmed cases and deaths around the globe. The COVID-19 pandemic has paved the way for considerable psychological and psychosocial morbidity among the general public and health care providers. An array of guidelines has been put forward by multiple agencies for combating mental health challenges. This paper addresses some of the mental health challenges faced by low and middle income countries (LMIC). It is worthwhile to note that these are challenges at the current stage of the pandemic and may change with the course of the pandemic itself.


title: Dual enteric and respiratory tropisms of winter dysentery bovine coronavirus in calves

text: Although winter dysentery (WD), which is caused by the bovine coronavirus (BCoV) is characterized by the sudden onset of diarrhea in many adult cattle in a herd, the pathogenesis of the WD-BCoV is not completely understood. In this study, colostrum-deprived calves were experimentally infected with a Korean WD-BCoV strain and examined for viremia, enteric and nasal virus shedding as well as for viral antigen expression and virus-associated lesions in the small and large intestines and the upper and lower respiratory tract from 1 to 8 days after an oral infection. The WD-BCoV-inoculated calves showed gradual villous atrophy in the small intestine and a gradual increase in the crypt depth of the large intestine. The WD-BCoV-infected animals showed epithelial damage in nasal turbinates, trachea and lungs, and interstitial pneumonia. The WD-BCoV antigen was detected in the epithelium of the small and large intestines, nasal turbinates, trachea and lungs. WD-BCoV RNA was detected in the serum from post-inoculation day 3. These results show that the WD-BCoV has dual tropism and induces pathological changes in both the digestive and respiratory tracts of calves. To our knowledge, this is the first detailed report of dual enteric and respiratory tropisms of WD-BCoV in calves. Comprehensive studies of the dual tissue pathogenesis of the BCoV might contribute to an increased understanding of similar pneumoenteric CoV infections in humans.


(In) visible impact of inadequate WaSH Provision on COVID-19 incidences can be not be ignored in large and megacities of India


title: Clinical Aspects of Feline Retroviruses: A Review

text: Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) are retroviruses with global impact on the health of domestic cats. The two viruses differ in their potential to cause disease. FeLV is more pathogenic, and was long considered to be responsible for more clinical syndromes than any other agent in cats. FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system. Today, FeLV is less commonly diagnosed than in the previous 20 years; prevalence has been decreasing in most countries. However, FeLV importance may be underestimated as it has been shown that regressively infected cats (that are negative in routinely used FeLV tests) also can develop clinical signs. FIV can cause an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors. In most naturally infected cats, however, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems. This article provides a review of clinical syndromes in progressively and regressively FeLV-infected cats as well as in FIV-infected cats.


title: To what extent are Arab pilgrims to Makkah aware of the middle east respiratory syndrome coronavirus and the precautions against it?

text: BACKGROUND: Approximately, 80% of the many cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) confirmed worldwide were diagnosed in the Kingdom of Saudi Arabia (KSA). The risk of the disease spreading internationally is especially worrying given the role of KSA as the home of the most important Islamic pilgrimage sites. This means the need to assess Arab pilgrims' awareness of MERS-CoV is of paramount importance. MATERIALS AND METHODS: A cross-sectional study was carried out during Ramadan 2015 in the Holy Mosque in Makkah, Saudi Arabia. Self-administered questionnaires were distributed to 417 Arab participants at King Fahad Extension, King Abdullah Prayer Extension and, King Abdullah Piazza Extension after Taraweeh and Fajr prayers. RESULTS: The mean MERS-CoV knowledge score was 52.56. Majority of the respondents (91.3%) were familiar with MERS-CoV. Saudis had significantly higher knowledge of MERS-CoV than non-Saudis (56.92 ± 18.55 vs. 44.91 ± 25.46, p = 0.001). Females had significantly more knowledge about consanguineous MERS-CoV than males (55.82 ± 19.35 vs. 49.93 ± 23.66, p = 0.006). The average knowledge was significantly higher in respondents who had received health advice on MERS-CoV (56.08 ± 20.86 vs. 50.65 ± 22.51, p = 0.024). With respect to stepwise linear regression, knowledge of MERS-CoV tended to increase by 14.23 (B = 14.23%, p = 0.001) in participants who were familiar with MERS-CoV, and by 8.50 (B = 8.50, p = 0.001) in those who perceived MERS-CoV as a very serious disease. CONCLUSION: There is a great need for educational programs to increase awareness about MERS-CoV.


title: The novel Chinese coronavirus (2019‐nCoV) infections: Challenges for fighting the storm

text: Since end of December 2019, a cluster of patients with pneumonia of unknown origin was reported from Wuhan, Hubei province, China. They shared a connection with the Huanan South China Seafood Market in Wuhan, and now it has been confirmed that the disease is caused by a novel coronavirus (provisionally named 2019-nCoV). As of today (30 January 2020), 7734 cases have been confirmed in China, and 90 cases have also been cumulatively reported from Taiwan, Thailand, Vietnam, Malaysia, Nepal, Sri Lanka, Cambodia, Japan, Singapore, Republic of Korea, United Arab Emirate, United States, The Philippines, India, Australia, Canada, Finland, France, and Germany (Finland, France and Germany are the only European countries in which cases [n= 1, n = 5, and n = 4, respectively] have been reported up to date). According to the released news, the case rate fatality is 2.2% (170/7824).


title: Vacunación antigripal en personal sanitario

text: Resumen Fundamento y objetivo El objetivo es determinar la tendencia en cobertura vacunal antigripal en trabajadores sanitarios. Método Estudio epidemiológico transversal. Período 1990-2005. Proporciones globales y por categorías profesionales anuales. Análisis: test χ2 y test de tendencia lineal Mantel-Haenszel. Resultados Las mayores coberturas fueron: 2003-2004, 15,9% (IC 95%: 14,8-17) y 2005-2006, 16,3% (IC 95%: 15,3-17,4). Médicos y MIR tienen mayores coberturas, 30,09%. La tendencia fue creciente durante todo el período. Conclusiones Tendencia creciente de inmunización antigripal en personal sanitario. Abstract Background and objective The aim of this study was to determine the trends in yearly vaccination coverage in healthcare workers. Method Cross-sectional epidemiological study over fifteen seasons (1990-2005). Overall vaccination coverage and coverage by professional category was estimated annually. The chi-square test and Mantel-Haenszel test for linear trend were used for the statistical analysis. Results The greatest vaccination coverage was in the 2003-04 season (15.9%; 95% CI: 14.8-17) and the 2005-06 season (16.3%; 95% CI: 15.3-17.4). The medical staff and residents showed the highest coverage (30.1%). A positive trend was observed along the period. Conclusions An increasing trend in influenza vaccination coverage has been observed in healthcare workers.


Ventilators-by-Lottery: The Least Unjust Form of Allocation in the COVID-19 Pandemic


title: Airflow patterns through single hinged and sliding doors in hospital isolation rooms – Effect of ventilation, flow differential and passage

text: Abstract Negative pressure isolation rooms are used to house patients with highly contagious diseases (e.g. with airborne diseases) and to contain emitted pathogens to reduce the risk for cross-infection in hospitals. Airflows induced by door opening motion and healthcare worker passage can, however, transport the potentially pathogen laden air across the doorway. In this study airflow patterns across the isolation room doorway induced by the operation of single hinged and sliding doors with simulated human passage were examined. Smoke visualizations demonstrated that the hinged door opening generated a greater flow across the doorway than the sliding door. Tracer gas measurements showed that the examined ventilation rates (6 and 12 air changes per hour) had only a small effect on the air volume exchange across the doorway with the hinged door. The results were more variable with the sliding door. Supply-exhaust flow rate differential reduced the door motion-induced air transfer significantly with both door types. The experiments showed that the passage induced substantial air volume transport through the doorway with both door types. However, overall, the sliding door performed better in all tested scenarios, because the door-opening motion itself generated relatively smaller air volume exchange across the doorway, and hence should be the preferred choice in the design of isolation rooms.


title: Adenoviral-expressed GP(5) of porcine respiratory and reproductive syndrome virus differs in its cellular maturation from the authentic viral protein but maintains known biological functions

text: The ORFs 5, 6 and 7, encoding for the three major structural proteins, GP(5), M and N, of the IAF-Klop strain of PRRSV were cloned and expressed in 293 cells using replication-defective human type 5 adenoviral vectors (hAdVs). Although the M protein gene could be cloned into hAdVs and expressed constituvely in 293 cells under the control of the hCMV immediate early promotor/enhancer, hAdVs expressing N and GP(5) proteins, which appeared to be toxic or interfered with adenovirus replication, could only be generated by inclusion of a tetracycline-regulatable promotor in the transfer vector pAdTR5. The recombinant (rec) proteins appeared similar to the authentic viral proteins in regards to their M (r)s and antigenicities. However, the recGP(5) apparently possesses different N-linked oligosaccharides residues. Its sensitivity to endo-β-galactosidase digestion indicates that poly-N-acetyllactosamine is present on the individually-expressed protein, but not on the authentic GP(5) anchored into the virion envelope. The recGP(5) apparently accumulates within the ER compartment as a glycoprotein that possesses high-mannose N-linked oligosaccharide side chains sensitive to endo-β-N-acetylglucosaminidase H treatment, by contrast to its viral counterpart for which N-linked oligosaccharide side chains are of both high-mannose and complex types. Coinfection of 293 cells with hAdVs expressing the M and GP(5) did not lead to M-GP(5) heterodimer formation, as demonstrated in PRRSV-infected cells. Moreover, cells infected with inducible hAdV/ORF5 showed that GP(5) of the North American strain is proapoptotic. Indeed, when the expression cassette was turned-on, caspase 3 activity in hAdV/ORF5 infected cells was enhanced and DNA fragmentation could be detected by TUNEL assays. Pigs intradermally injected twice with hAdV/ORF5 developed antibody titers to the authentic viral GP(5) as soon as 10 days following challenge with the homologous virulent PRRSV strain, as revealed by Western blot and virus neutralization tests, suggesting the establishment of a specific immune memory.


Geriatric practice during and after the COVID‐19 pandemic


title: Safety immunopharmacology: Evaluation of the adverse potential of pharmaceuticals on the immune system

text: Abstract The ICH S6R1 and S8 guidelines define a general framework for the immunotoxicity evaluation of biotechnology-derived pharmaceuticals and human pharmaceuticals, respectively. As severe and unpredicted adverse events dramatically showed in the recent years that the immune system is a critical aspect of drug safety, this framework needs to be revisited to enhance the prediction of nonclinical immune safety evaluation. Safety immunopharmacology is deemed to contribute to this awaited improvement by enabling early screening of the potential for drug candidates to induce unexpected immunosuppressive and immunostimulatory effects as well as nonimmune-mediated hypersensitivity reactions. Dedicated safety immunopharmacology can also generate mechanistic data to determine which relevant additional immunotoxicity studies should be conducted. Immunological assays and models that can be considered for use in the context of safety pharmacology studies are presented as well as perspectives for their timely development.


title: New Adenovirus in Bats, Germany

text: We tested 55 deceased vespertilionid bats of 12 species from southern Germany for virus infections. A new adenovirus was isolated from tissue samples of 2 Pipistrellus pipistrellus bats, which represents the only chiropteran virus isolate found in Europe besides lyssavirus (rabies virus). Evidence was found for adenovirus transmission between bats.


title: The persistent prevalence and evolution of cross-family recombinant coronavirus GCCDC1 among a bat population: a two-year follow-up

text: Bats are connected with the increasing numbers of emerging and re-emerging viruses that may break the species barrier and spread into the human population. Coronaviruses are one of the most common viruses discovered in bats, which were considered as the natural source of recent human-susceptible coronaviruses, i.e. SARS-COV and MERS-CoV. Our previous study reported the discovery of a bat-derived putative cross-family recombinant coronavirus with a reovirus gene p10, named as Ro-BatCoV GCCDC1. In this report, through a two-year follow-up of a special bat population in one specific cave of south China, we illustrate that Ro-BatCoV GCCDC1 persistently circulates among bats. Notably, through the longitudinal observation, we identified the dynamic evolution of Ro-BatCoV GCCDC1 in bats represented by continuously recombination events. Our study provides the first glimpse of the virus evolution in one longitudinally observed bat population cohort and underlines the surveillance and pre-warning of potential interspecies transmittable viruses in bats.


COVID-19 and Gynecomastia: What Is the Relationship?


title: Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S-IgA at mucosal surfaces

text: Abstract An explanation of the principles and mechanisms involved in peaceful co-existence between animals and the huge, diverse, and ever-changing microbiota that resides on their mucosal surfaces represents a challenging puzzle that is fundamental in everyday survival. In addition to mechanical barriers and a variety of innate defense factors, mucosal immunoglobulins (Igs) provide protection by two complementary mechanisms: specific antibody activity and innate, Ig glycan-mediated binding, both of which serve to contain the mucosal microbiota in its physiological niche. Thus, the interaction of bacterial ligands with IgA glycans constitutes a discrete mechanism that is independent of antibody specificity and operates primarily in the intestinal tract. This mucosal site is by far the most heavily colonized with an enormously diverse bacterial population, as well as the most abundant production site for antibodies, predominantly of the IgA isotype, in the entire immune system. In embodying both adaptive and innate immune mechanisms within a single molecule, S-IgA maintains comprehensive protection of mucosal surfaces with economy of structure and function.


title: Viral Pneumonia in Older Adults

text: Viruses account for a substantial portion of respiratory illnesses, including pneumonia, in the elderly population. Presently, influenza virus A H3N2 and respiratory syncytial virus are the most commonly identified viral pathogens in older adults with viral pneumonia. As diagnostic tests such as reverse-transcription polymerase chain reaction become more widely used, the relative importance of additional viruses (such as parainfluenza, rhinoviruses, coronaviruses, and human metapneumovirus) will likely increase. Influenza virus should be considered as a cause of pneumonia during the winter months, especially during periods of peak activity. Patients with high-grade fever, myalgias, and cough should arouse the highest suspicion. Respiratory syncytial virus pneumonia should also be suspected during the winter in patients with coryza, wheezing, low-grade fever, and patchy infiltrates, especially if negative for influenza on rapid testing. Because clinical features and periods of activity for many viruses overlap, laboratory confirmation of influenza is recommended for cases involving seriously ill or institutionalized patients.


title: Chicken interferome: avian interferon-stimulated genes identified by microarray and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I interferon (IFN-α)

text: Viruses that infect birds pose major threats—to the global supply of chicken, the major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza viruses H5N1 and H7N9). Controlling these viruses in birds as well as understanding their emergence into, and transmission amongst, humans will require considerable ingenuity and understanding of how different species defend themselves. The type I interferon-coordinated response constitutes the major antiviral innate defence. Although interferon was discovered in chicken cells, details of the response, particularly the identity of hundreds of stimulated genes, are far better described in mammals. Viruses induce interferon-stimulated genes but they also regulate the expression of many hundreds of cellular metabolic and structural genes to facilitate their replication. This study focusses on the potentially anti-viral genes by identifying those induced just by interferon in primary chick embryo fibroblasts. Three transcriptomic technologies were exploited: RNA-seq, a classical 3′-biased chicken microarray and a high density, “sense target”, whole transcriptome chicken microarray, with each recognising 120–150 regulated genes (curated for duplication and incorrect assignment of some microarray probesets). Overall, the results are considered robust because 128 of the compiled, curated list of 193 regulated genes were detected by two, or more, of the technologies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0363-8) contains supplementary material, which is available to authorized users.


title: Successful use of tPA for thrombolysis in COVID related ARDS: a case series

text: We describe successful usage of low dose Tissue plasminogen activator (tPA) (30–50 mg) in three COVID19 critically ill patients, who were in worsening respiratory failure in-spite of being on therapeutic anticoagulation. All patients had respiratory rate > 40; FiO(2) > 0.7(on NIV); PiO(2)/FiO(2) ratio < 100 and D-dimer>1000 ng/ml. C.T. Pulmonary Angiography could not be done in these patients due to poor general condition, but 2D echo was normal and none of the patients was in shock. So there was no conventional indication of thrombolysis in these patients, yet after thrombolysis, we saw dramatic changes in oxygenation. All patients became off oxygen within 3–7 days and were discharged within 2 weeks. The whole idea was to prevent intubation, since mortality rates are very high in intubated COVID19 patients. tPA is associated with <1% risk of fatal bleed. In this unprecedented pandemic with high mortality rates, thrombolysis could be an effective and safe option in carefully selected critically ill patients of COVID19.


title: Occurrence, clinical involvement and zoonotic potential of endoparasites infecting Swiss pigs

text: Abstract In order to estimate the diversity, clinical involvement and zoonotic potential of parasites in pigs submitted for diagnosis to the PathoPig project of the Swiss Federal Food Safety and Veterinary Office, faeces (n =125) from suckling piglets (n =39), weaners (n =60) and piglets beginning fattening (n =26) from 74 Swiss farms were examined by 3 coproscopical methods (i.e. sedimentation/zinc chloride-flotation; SAFC and Ziehl-Neelsen staining). Samples microscopically positive for Cryptosporidium were further tested by PCR/sequencing for species assessment. The most frequently detected parasite was Balantidium coli, a facultative pathogenic ciliate with zoonotic potential, in 5.1, 36.7 and 50.0% of suckling, weaners and fatteners and 43.2% of farms; however, no association with disease was observed. Isospora (syn. Cystoisospora) suis infections were detected in 13.3 and 11.1% of suckling piglets with and without diarrhoea, and in 10.0 and 13.3% of weaners and fatteners with diarrhoea, respectively, and were significant associated with emaciation. Cryptosporidium infections were detected in 10.3, 15.0 and 19.2% of sucklings, weaners and fatteners, respectively, and in 18.9% of the farms. Interestingly, two age-related species were identified: C. suis in younger piglets (2 to 6weeks) and C. scrofarum in older ones (6 to 17weeks). None of the pigs infected with C. scrofarum (n =8), but 3 of 4 piglets infected with C. suis (co-infection with I. suis in 2 cases) had diarrhoea. The zoonotic species C. parvum was not detected, nevertheless, sporadic cases of human infection with the porcine-adapted species have been reported. Ascaris suum, Trichuris suis and Strongylida were rarely detected (<4%) in all age categories.


title: A reverse transcription loop-mediated isothermal amplification method for rapid detection of bovine viral diarrhea virus

text: Abstract A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and optimized to detect bovine viral diarrhea viral (BVDV) RNA. The RT-LAMP assay is highly sensitive and able to detect 4.67×100 copies of BVDV RNA. Additionally, the RT-LAMP method is capable of detecting both genotypes of BVDV. No cross-reaction with other bovine viruses was observed. The ability of RT-LAMP to detect BVDV RNA from bovine fecal swabs was also evaluated. Of the 88 fecal swabs, 38 were found to be positive by RT-LAMP assay, whereas 39 were positive by real-time RT-PCR. Taken together, the BVDV specific RT-LAMP method is highly specific and sensitive and can be used as a rapid and direct diagnostic assay for testing clinical samples.


title: Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections

text: Aim: To determine whether nasopharyngeal aspirates (NPAs) cytokine response is different according to the causative viruses in children with lower respiratory tract infections (LRTI). Methods: NPAs from 277 children with LRTI caused by respiratory virus were evaluated. Based on the proven viral agents, LRTI patients were divided into four groups. Levels of IL‐4, IL‐5 and IFN‐γ were determined by ELISA. Results: Patients with influenza virus infection demonstrated significantly lower IL‐4 and IL‐5 levels than those with other three groups. Patients with respiratory syncytial virus (RSV) infection showed an increase in production of IL‐4 and IL‐5, and a decrease in the IFN‐γ level when compared to patients with influenza virus infection. Interestingly, a similar Th2 response was seen in patients with parainfluenza virus or adenovirus infection. Conclusion: These results demonstrate that respiratory viruses can induce different local cytokine responses. However, Th2 biased responses are not unique for RSV but seem to be predominant in respiratory viruses of young children.


title: A lateral flow dipstick combined with reverse transcription recombinase polymerase amplification for rapid and visual detection of the bovine respirovirus 3

text: Abstract Bovine respirovirus 3 also known as Bovine parainfluenza virus type 3 (BPIV3) is one of the most important viral respiratory agents of both young and adult cattle. Rapid diagnosis could contribute greatly in containing epidemics and thus avoid economic losses. However, the lack of robust isothermal visual method poses difficulty. In this study, a novel isothermal assay for detecting BPIV3 was established. The method includes a lateral flow dipstick (LFD) assay combined with reverse transcription recombinase polymerase amplification (RT-RPA). First, the analytical sensitivity and specificity of BPIV3 LFD RT-RPA were tested. The LFD RT-RPA assay has a detection limit of up to 100 copies per reaction in 30 min at 38 °C. Then the performance of LFD RT-RPA was evaluated using 95 clinical samples. Compared to qPCR, the LFD RT-RPA assay showed a clinical sensitivity of 94.74%, a clinical specificity of 96.05% and 0.8734 kappa coefficient. These results have demonstrated the efficiency and effectiveness of the method to be developed into a point of care protocol for the diagnosis of BPIV3.


title: Impacts of Social and Economic Factors on the Transmission of Coronavirus Disease 2019 (COVID-19) in China

text: This paper examines the role of various socioeconomic factors in mediating the local and cross-city transmissions of the novel coronavirus 2019 (COVID-19) in China. We implement a machine learning approach to select instrumental variables that strongly predict virus transmission among the rich exogenous weather characteristics. Our 2SLS estimates show that the stringent quarantine, massive lockdown and other public health measures imposed in late January significantly reduced the transmission rate of COVID-19. By early February, the virus spread had been contained. While many socioeconomic factors mediate the virus spread, a robust government response since late January played a determinant role in the containment of the virus. We also demonstrate that the actual population flow from the outbreak source poses a higher risk to the destination than other factors such as geographic proximity and similarity in economic conditions. The results have rich implications for ongoing global efforts in containment of COVID-19.


Insights into Ebola and Other Emerging and Re-emerging Infectious Disease Risks


title: Pulmonary Thromboembolism as a Potential Cause of Clinical Deterioration in COVID-19 Patients; a Commentary

text: Although the findings of some studies have been indicative of the direct relationship between the severity of clinical findings and imaging, reports have been published regarding inconsistency of clinical findings with imaging and laboratory evidence. Physicians treating these patients frequently report cases in which patients, sometimes in the recovery phase and despite improvements in imaging indices, suddenly deteriorate and in some instances suddenly expire. This letter aimed to draw attention to the role of pulmonary thromboembolism as a potential and possible cause of clinical deterioration in covid-19 patients.


title: Platelets and Infection – An Emerging Role of Platelets in Viral Infection

text: Platelets are anucleate blood cells that play a crucial role in the maintenance of hemostasis. While platelet activation and elevated platelet counts (thrombocytosis) are associated with increased risk of thrombotic complications, low platelet counts (thrombocytopenia) and several platelet function disorders increase the risk of bleeding. Over the last years, more and more evidence has emerged that platelets and their activation state can also modulate innate and adaptive immune responses and low platelet counts have been identified as a surrogate marker for poor prognosis in septic patients. Viral infections often coincide with platelet activation. Host inflammatory responses result in the release of platelet activating mediators and a pro-oxidative and pro-coagulant environment, which favors platelet activation. However, viruses can also directly interact with platelets and megakaryocytes and modulate their function. Furthermore, platelets can be activated by viral antigen–antibody complexes and in response to some viruses B-lymphocytes also generate anti-platelet antibodies. All these processes contributing to platelet activation result in increased platelet consumption and removal and often lead to thrombocytopenia, which is frequently observed during viral infection. However, virus-induced platelet activation does not only modulate platelet count but also shape immune responses. Platelets and their released products have been reported to directly and indirectly suppress infection and to support virus persistence in response to certain viruses, making platelets a double-edged sword during viral infections. This review aims to summarize the current knowledge on platelet interaction with different types of viruses, the viral impact on platelet activation, and platelet-mediated modulations of innate and adaptive immune responses.