title: Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins

text: The identification of conserved autophagy-related proteins (ATGs) that mediate bulk degradation of cytosolic material laid the foundation for breakthroughs linking autophagy to a litany of physiological processes and disease conditions. Recent discoveries are revealing that these same ATGs orchestrate processes that are related to, and yet clearly distinct from, classic autophagy. Autophagy-related functions include secretion, trafficking of phagocytosed material, replication and egress of viral particles, and regulation of inflammatory and immune signaling cascades. Here, we define common processes dependent on ATGs, and discuss the challenges in mechanistically separating autophagy from these related pathways. Elucidating the molecular events that distinguish how individual ATGs function promises to improve our understanding of the origin of diseases ranging from autoimmunity to cancer.


title: Structural basis of mercury- and zinc-conjugated complexes as SARS-CoV 3C-like protease inhibitors

text: Five active metal-conjugated inhibitors (PMA, TDT, EPDTC, JMF1586 and JMF1600) bound with the 3C-like protease of severe acute respiratory syndrome (SARS)-associated coronavirus were analyzed crystallographically. The complex structures reveal two major inhibition modes: Hg(2+)-PMA is coordinated to C(44), M(49) and Y(54) with a square planar geometry at the S3 pocket, whereas each Zn(2+) of the four zinc-inhibitors is tetrahedrally coordinated to the H(41)–C(145) catalytic dyad. For anti-SARS drug design, this Zn(2+)-centered coordination pattern would serve as a starting platform for inhibitor optimization.


title: Seroprevalence of antibodies to the influenza A (H1N1) virus among healthcare workers prior to the 2009 pandemic peak

text: OBJECTIVE: Our aim was to study the proportion of healthcare workers with a positive serology for Influenza A(H1N1)2009 without having flu, in a Spanish hospital at the beginning of the pandemic. METHODS: A survey study carried out during August 2009 (before the peak of the pandemic in Spain) in the Hospital Costa del Sol, a second level hospital with almost 300 beds in the South of Spain. The participants were workers in the following hospital units: Emergencies, Medical Area (Internal Medicine, Chest Diseases), Surgical Area (General Surgery and Anaesthesia) of any professional category. A study was made of the proportion of healthcare workers in our hospital with positive serology for the new influenza A (H1N1)2009 virus, as determined by the haemagglutination inhibition technique (≥1/40). The subjects completed a health status questionnaire, and provided a blood sample for serology testing. RESULTS: A total of 239 workers participated, of whom 25.1% had positive serology. The hospital area in which most individuals had positive serology was the Emergency Department (36.6%), while the professional category in which most individuals with a positive serology worked was that of the orderlies (41.7%). CONCLUSION: Around 25% of healthcare workers in our hospital had positive serology before the peak of the pandemic, none of them had received vaccine for Influenza A (H1N1) 2009 or had been diagnosed of influenza previously.


title: Mutated COVID-19 may foretell a great risk for mankind in the future

text: Coronavirus disease 2019 SARS-CoV-2 (COVID-19) is a zoonotic virus causing a variety of severe respiratory diseases. SARS-CoV-2 is closest to SARS-CoV and MERS-CoV in structure. The high prevalence of COVID-19 is a result of a lack of symptoms at onset. Our study aimed to present an overview of the virus in terms of structure, epidemiology, symptoms, treatment and prevention. Whole genome sequences and some viral proteins were investigated to determine gaps and changes in alternation of nucleotides and amino acid sequences. We evaluate 11 complete genome sequences of different coronaviruses using BAST and MAFFT software. We also selected seven types of structural proteins. We conclude that COVID-19 might produce new mutations, specifically in glycoproteins, so caution and complete preparation by health authorities is required.


title: A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

text: Neutralizing antibodies could be antivirals against COVID-19 pandemics. Here, we report isolation of four human-origin monoclonal antibodies from a convalescent patient, all of which display neutralization abilities. B38 and H4 block the binding between virus S-protein RBD and cellular receptor ACE2. A competition assay indicates their different epitopes on the RBD, making them a potential virus-targeting MAb-pair to avoid immune escape in future clinical applications. Moreover, a therapeutic study in a mouse model validated that these antibodies can reduce virus titers in infected lungs. The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity. Our results highlight the promise of antibody-based therapeutics and provide a structural basis for rational vaccine design.


Community health workers reveal COVID-19 disaster in Brazil


title: Evaluation of a protocol to reduce the incidence of neonatal calf diarrhoea on dairy herds

text: Abstract Calf diarrhoea causes substantial economic losses in cattle herds worldwide. Neonatal calves are particularly sensitive to infections with enteropathogens. The present study focused on prevention against the main infectious causes of neonatal calf diarrhoea i.e. Escherichia coli, rota- and coronavirus, and Cryptosporidium parvum. Dairy herds (n =24) with a high percentage of neonatal calves scouring (>10%) were included and calves were sampled for the presence of these four enteropathogens. To decrease diarrhoea problems among neonatal calves, a standard protocol was tested on 13 herds (treatment group) where both C. parvum and either E. coli or rota- or coronavirus were identified as being involved, the other 11 herds served as control group. The protocol consisted of 2 points of action: preventive vaccination of dams against E. coli, rota- and coronavirus, and preventive administration of halofuginone lactate to newborn calves. The average percentage of calves suffering from neonatal diarrhoea (39.7% versus 14.3%, P <0.01) and the average percentage of faecal samples positive for C. parvum (34% versus 11%, P <0.05) differed significantly between control herds and treatment herds after implementation of the protocol. No significant differences between control and treatment group were observed in the percentage of calves excreting E. coli, rotavirus and coronavirus, both before and at the end of the trial. Furthermore, risk factors potentially associated with the development of neonatal calf scours were determined. Non-significant results were obtained for the effect of the protocol on duration of diarrhoea and the effect of the colostral IgG quantity on the risk of diarrhoea. Passive immunity transfer status of the calves, measured both before the onset and at the end of the study, were non-significant between groups.


title: Ultraviolet irradiation of spray-dried porcine plasma does not affect the growth performance of nursery pigs when compared with nonirradiated bovine plasma

text: Ultraviolet light irradiation of spray-dried porcine plasma (SDPP) decreases the risk of disease transmission, but it may decrease the activity of bioactive components in SDPP. Therefore, the objectives of this study were to determine growth performance, morbidity, and mortality responses of nursery pigs fed UV-irradiated SDPP (UV-SDPP) compared with nonirradiated spray-dried bovine plasma (SDBP). Pigs (n = 480; 6.09 ± 2.4 kg initial BW) were blocked by initial BW, and blocks were assigned to pens. the sex ratio was equalized within blocks and pens. Pens were randomly assigned to 1 of 5 dietary treatments (8 pigs/pen and 12 replicates/treatment) in a 3-phase feeding program (phase 1 = d 0 to 13, phase 2 = d 14 to 27, and phase 3 = d 28 to 55). Dietary treatments included a control diet without UV-SDPP or SDBP and diets containing 3% UV-SDPP, 3% SDBP, 6% UV-SDPP, or 6% SDBP during phase 1. Diets were formulated to meet or exceed nutrient requirements and contained the same concentrations of standardized ileal digestible Lys and Lys:ME ratio within phases. Pigs were provided ad libitum access to diets throughout the 55-d experiment. Dietary inclusion rates during phase 2 were reduced to 1.5% UV-SDPP, 1.5% SDBP, 3% UV-SDPP, and 3% SDBP, and all pigs were fed a common diet without UV-SDPP or SDBP during phase 3. Growth performance data were analyzed as a 2 × 2 factorial arrangement of treatments with a control within a completely randomized block design to evaluate the main effects of plasma processing (UV irradiated vs. nonirradiated) and dietary inclusion level, and block, room, and pen were random effects. In phase 1, there were no differences in G:F among treatments, but pigs fed 6% UV-SDPP and 6% SDBP had greater (P < 0.01) ADG (0.11 vs. 0.08 kg/d) and ADFI (0.17 vs. 0.15 kg/d) than pigs fed the control, 3% SDBP, and 3% UV-SDPP diets. After phase 1 (d13), feeding UV-SDPP or SDBP increased (P = 0.02) the BW of pigs. In phases 2 and 3 and the overall feeding period (d 0 to 55), there were no differences in ADG, ADFI, and G:F among dietary treatments. There was a linear decrease (P < 0.01) in mortality of nursery pigs as dietary inclusion rate of SDBP and UV-SDPP increased. In conclusion, feeding SDBP or UV-SDPP diets improved ADG and ADFI during the first 2 wk after weaning due to improved feed consumption, and UV irradiation appeared to have no detrimental effects on the feeding value of SDPP.


title: Spike protein assembly into the coronavirion: exploring the limits of its sequence requirements

text: Abstract The coronavirus spike (S) protein, required for receptor binding and membrane fusion, is incorporated into the assembling virion by interactions with the viral membrane (M) protein. Earlier we showed that the ectodomain of the S protein is not involved in this process. Here we further defined the requirements of the S protein for virion incorporation. We show that the cytoplasmic domain, not the transmembrane domain, determines the association with the M protein and suffices to effect the incorporation into viral particles of chimeric spikes as well as of foreign viral glycoproteins. The essential sequence was mapped to the membrane-proximal region of the cytoplasmic domain, which is also known to be of critical importance for the fusion function of the S protein. Consistently, only short C-terminal truncations of the S protein were tolerated when introduced into the virus by targeted recombination. The important role of the about 38-residues cytoplasmic domain in the assembly of and membrane fusion by this approximately 1300 amino acids long protein is discussed.


title: Ethics and Social Value Judgments in Public Health

text: Abstract The exercise of government powers for the health of its population raises ethical issues, such as public welfare, individual autonomy and freedom, privacy and confidentiality, just distribution of benefits and burdens, transparency, and public accountability. Conflicts among these values often arise and how they should be balanced will vary on a case-by-case basis, weighing costs against benefits. This entry discusses justifications for government action in public health, the tension between individual freedom and public health, issues of distributive justice in public health, and ethical guidelines for public health policymaking.


title: Manejo Seguro De La Ropa E Higiene De La Piel En Pacientes Y Profesionales Sanitarios Frente Al Covid-19: Scoping Review

text: Resumen Introducción: En enero de 2020 aparece en China un brote de neumonía causada por un virus zoonótico(SARS-CoV-2). Se considera que la ruta principal de transmisión es por inhalación de grandes gotas respiratorias, por deposición en las mucosas y las manos o los fómites contaminados. El objetivo es identificar las intervenciones a realizar durante la hospitalización para un manejo correcto y seguro de la ropa e higiene de los pacientes y profesionales sanitarios. Método: Scoping review realizada sin delimitación cronológica ni de idioma en las bases de datos PUBMED y Cochrane. Rastreo de normas y recomendaciones de entidades gubernamentales nacionales e internacionales para responder a la pregunta de investigación sobre el manejo seguro de la ropa y la higiene de la piel en pacientes y en profesionales sanitarios para evitar el contagio por Covid-19. El análisis de los datos fue realizado en dos etapas: en la primera, identificación y categorización de los estudios, y en la segunda, análisis de contenido como criterio informativo y clasificatorio. Resultados: Se han seleccionado 14 documentos, principalmente de entidades gubernamentales. Las recomendaciones se estructuran en 5 epígrafes sobre manejo de ropa e higiene de la piel de pacientes infectados y profesionales sanitarios en el ámbito hospitalario. Conclusión: La ropa de los pacientes y del personal sanitario son vehículos transmisores de la enfermedad. Su correcto tratamiento ayuda a mejorar el control de la misma y a una correcta utilización de los recursos disponibles en estos momentos. La adecuada higiene de la piel, en especial la limpieza de las manos, constituye uno de los pilares básicos para la prevención y el control de la infección. Destacamos la semejanza de algunas de las pautas recogidas y proporcionadas por los diferentes organismos consultados Abstract Introduction: In January 2020, an outbreak of pneumonia caused by a zoonotic virus (SARS-CoV-2) appeared in China. The main route of transmission is considered to be the inhalation of large respiratory drops, by deposition in the mucosa and hands or contaminated fomites. The objective is to identify the interventions to be performed during hospitalization for the correct and safe handling of clothing and hygiene of patients and health professionals. Method: Scoping review carried out without chronological or language delimitation in the PUBMED and Cochrane databases. Tracking standards and recommendations of national and international government entities to answer the research question on the safe handling of clothing and skin hygiene in patients and in health professionals to avoid Covid-19 infection. The data analysis was carried out in two stages: in the first, identification and categorization of the studies, and in the second, content analysis as an informative and classifying criterion. Results: 14 documents have been selected, mainly from government entities. The recommendations are structured in 5 sections on the management of clothing and skin hygiene of infected patients and health professionals in the hospital setting. Conclusion: The clothing of patients and healthcare personnel are transmitting vehicles of the disease. Its correct treatment helps to improve the control of the same and the correct use of the resources available at the moment. Proper skin hygiene, especially hand cleansing, is one of the basic pillars for infection prevention and control. We highlight the similarity of some of the guidelines collected and provided by the different agencies consulted.


title: An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

text: The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low‐to‐sub‐micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex‐bases) has been successfully coupled to both ribose and 2′‐deoxyribose sugars by using the N‐deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno‐expanded tricyclic heterocyclic base, as well as several distal and proximal flex‐bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.


title: SARS in Taiwan: an overview and lessons learned

text: Summary Objectives: This report aims to describe the epidemiology of severe acute respiratory syndrome (SARS) in Taiwan between March and July 2003, and to examine the public health response. Methods: Surveillance for SARS was initiated on 14 March 2003. Response activities are described for the isolation of patients; contact tracing; quarantine of contact persons; fever screening for inbound and outbound passengers at the airport; and hospital infection control as assessed by mobile SARS containment teams. Results: Between 14 March and 30 July 2003 a total of 668 probable cases of SARS were reported. Of the 668 cases, 181 (27%) were fatal. Compared to the survivors, fatal cases were more likely to be older (p <0.001), male (p <0.05), exposed through hospital contact (p <0.001), and have a coexisting medical disorder (p <0.001). Between 28 March and 30 July a total of 151,270 persons were quarantined. Among them, 46 (3.0/10,000) were subsequently classified as being probable SARS cases. At the time of the mobile team assessments, 46 (53%) hospitals had implemented WHO infection control recommendations. Conclusions: In this outbreak, an emergency plan consisted of patient isolation and strict hospital infection control.


This editorial aims to summarize the nine scientific papers that contributed to the Special Issue entitled ‘Nanoparticles to Improve the Efficacy of Vaccines’.


title: Island blues: indigenous knowledge of indigo-yielding plant species used by Hainan Miao and Li dyers on Hainan Island, China

text: BACKGROUND: Historically, indigo-yielding plant species were important cash crops from Central Asia to the southern United States and Central America. Indigo-dyed textiles were widely traded along the legendary Silk Road that linked China to Europe. Today, due to the labor-intensive nature of indigo extraction at the household level, lifestyle changes and the widespread availability of commercially produced indigo paste, traditional indigo extraction methods have declined in villages. Yet Li textile weavers on Hainan Island are internationally recognized as producers of indigo-dyed textile using warp ikat techniques. In contrast, Hainan Miao weavers produce indigo-dyed textiles using batik (wax resist) techniques. The aim of this study was to document the indigenous knowledge on indigo-yielding plant species used by both Hainan Miao and Li people on Hainan Island, China. METHOD: Ethnic uses were documented during three field surveys, through a questionnaire survey of 193 respondents, comprising 144 Hainan Miao and 49 Li traditional dyers. Mention index (QI), Availability index (AI), and Preference ranking (PR) of each indigo-yielding plant species were calculated to screen out plant resources with potential development value. RESULTS: Five indigo-yielding plant species (from four plant families and four genera) were historically used by Hainan Miao and Li dyers. However, just four species are still in use. Strobilanthes cusia was the main indigo source for Hainan Miao dyers. Li dyers also commonly use Indigofera species (I. tinctoria and I. suffruticosa) for indigo extraction. Wrightia laevis is less commonly used as a contemporary indigo source. Indigo extraction by steeping in water to which lime is added to increase the pH is sharing by the five indigo-yielding plant species. Strobilanthes cusia had the highest QI, AI and PR values in Hainan Miao villages. Indigofera tinctoria had the highest QI and AI values, but Indigofera suffruticosa was preferred by Li dyers. CONCLUSION: In the process of modernization and urbanization, some Hainan Miao and Li dyers retain the traditional indigo extraction methods. We found that Strobilanthes cusia and Indigofera tinctoria have the most potential for sustainable indigo production in the future. Furthermore, this study documents the details of extraction method from Wrightia laevis for the first time and the use of Ricinus communis seeds in that process. As one of the last places globally where Wrightia laevis is still used for indigo production, the may also be a nice market among textile collectors and museums that keeps the tradition of Wrightia laevis production and use for indigo extraction alive.


title: Inferring population-level contact heterogeneity from common epidemic data

text: Models of infectious disease spread that incorporate contact heterogeneity through contact networks are an important tool for epidemiologists studying disease dynamics and assessing intervention strategies. One of the challenges of contact network epidemiology has been the difficulty of collecting individual and population-level data needed to develop an accurate representation of the underlying host population's contact structure. In this study, we evaluate the utility of common epidemiological measures (R(0), epidemic peak size, duration and final size) for inferring the degree of heterogeneity in a population's unobserved contact structure through a Bayesian approach. We test the method using ground truth data and find that some of these epidemiological metrics are effective at classifying contact heterogeneity. The classification is also consistent across pathogen transmission probabilities, and so can be applied even when this characteristic is unknown. In particular, the reproductive number, R(0), turns out to be a poor classifier of the degree heterogeneity, while, unexpectedly, final epidemic size is a powerful predictor of network structure across the range of heterogeneity. We also evaluate our framework on empirical epidemiological data from past and recent outbreaks to demonstrate its application in practice and to gather insights about the relevance of particular contact structures for both specific systems and general classes of infectious disease. We thus introduce a simple approach that can shed light on the unobserved connectivity of a host population given epidemic data. Our study has the potential to inform future data-collection efforts and study design by driving our understanding of germane epidemic measures, and highlights a general inferential approach to learning about host contact structure in contemporary or historic populations of humans and animals.


title: The Medicine and Public Health Initiative Ten Years Later

text: Abstract The Medicine and Public Health Initiative (MPHI) was created jointly 10 years ago by the American Medical Association and the American Public Health Association to bridge the nearly century-wide gulf between the respective disciplines. We review the history of MPHI and its growing significance in light of recent terrorism events. We report on current MPHI activities by examining three bellwether states—California, Florida, and Texas—as well as international sites. Upon its inception, MPHI was rapidly embraced and nationally disseminated. Sustainability 10 years later in the post-911 world requires renewed commitment by all collaborators. In order to meet the numerous health challenges facing our nation, from terrorism to chronic disease, and for MPHI to be successful, medicine and public health must work in tandem.


title: Complement and viral pathogenesis

text: Abstract The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection.


title: Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site

text: Epstein-Barr virus (EBV) represents a major global health problem. Though it is associated with infectious mononucleosis and over 200,000 cancers annually worldwide, a vaccine is not available. The major target of immunity is EBV glycoprotein 350/220 (gp350) that mediates attachment to B cells through complement receptor 2 (CR2/CD21). Here, we created self-assembling nanoparticles that displayed different domains of gp350 in a symmetric array. By focusing presentation of the CR2-binding domain on nanoparticles, potent neutralizing antibodies were elicited in mice and non-human primates. The structurally designed nanoparticle vaccine improved vaccine-induced protection in a mouse model by targeting a functionally conserved site of vulnerability with 10- to 100-fold increased neutralization compared to soluble gp350. This rational approach to EBV vaccine design elicited potent neutralizing antibody responses by focusing on a conserved viral entry domain, a strategy that can be applied to other viruses.


COVID-19, Clinical Trials and QT-Prolonging Prophylactic Therapy in Healthy Subjects: First, Do No Harm


title: Whole-genome characterization of Uruguayan strains of avian infectious bronchitis virus reveals extensive recombination between the two major South American lineages

text: Abstract Infectious bronchitis virus (Gammacoronavirus, Coronaviridae) is a genetically variable RNA virus that causes one of the most persistent respiratory diseases in poultry. The virus is classified in genotypes and lineages with different epidemiological relevance. Two lineages of the GI genotype (11 and 16) have been widely circulating for decades in South America. GI-11 is an exclusive South American lineage while the GI-16 lineage is distributed in Asia, Europe and South America. Here, we obtained the whole genome of two Uruguayan strains of the GI-11 and GI-16 lineages using Illumina high-throughput sequencing. The strains here sequenced are the first obtained in South America for the infectious bronchitis virus and provide new insights into the origin, spreading and evolution of viral variants. The complete genome of the GI-11 and GI-16 strains have 27,621 and 27,638 nucleotides, respectively, and possess the same genomic organization. Phylogenetic incongruence analysis reveals that both strains have a mosaic genome that arose by recombination between Euro Asiatic strains of the GI-16 lineage and ancestral South American GI-11 viruses. The recombination occurred in South America and produced two viral variants that have retained the full-length S1 sequences of the parental lineages but are extremely similar in the rest of their genomes. These recombinant virus have been extraordinary successful, persisting in the continent for several years with a notorious wide geographic distribution. Our findings reveal a singular viral dynamics and emphasize the importance of complete genomic characterization to understand the emergence and evolutionary history of viral variants.


title: How Could This Happen?: Narrowing Down the Contagion of COVID-19 and Preventing Acute Respiratory Distress Syndrome (ARDS)

text: In this rapid commentary, a mini-review is given of the present state-of-knowledge regarding the etiology and epidemiology of the new coronavirus 2019-nCoV and the risks for developing Acute respiratory distress syndrome (ARDS). The available knowledge on the viral genomics, molecular biology and pathogenicity of viruses of the Coronaviridae family and other Nidovirales, forms a helpful template for understanding the present pandemic outbreak. However, important questions remain unanswered about the underlying mechanism causing the very high case fatality ratios (CFR) and mechanisms regarding severe reactions like ARDS, fatal cardiac and renal failures, associated with a number of important comorbidity factors. Immunological reactions to lung alveoles in particular (involving lung macrophages and alveolar epithelial cell damage) in late phase ARDS in SARS-like CoV diseases, so far may not have received enough attention. Finally a shortlist of questions for high priority further research is suggested.


title: Replicable and recombinogenic RNAs

text: Abstract This paper summarizes results of the 40-year studies on replication and recombination of RNA molecules in the cell-free amplification system of bacteriophage Qβ. Special attention is paid to the molecular colony technique that has provided for the discovery of the nature of “spontaneous” RNA synthesis by Qβ replicase and of the ability of RNA molecules to spontaneously rearrange their sequences under physiological conditions. Also discussed is the impact of these data on the concept of RNA World and on the development of new in vitro cloning and diagnostic tools.


title: Effect of genomic drift of influenza PCR tests

text: Abstract Background Nucleic acid amplification assays have become the method of choice for influenza (Flu) testing due to superior accuracy and faster turnaround time. Although assays are designed to detect highly conserved genomic targets, mutations can influence test sensitivity. Most of the circulating viruses in the United States during the 2014–2015 season were associated with significant genetic drift; however, the effect on testing was unknown. Objectives and study design We compared the performance of Prodesse ProFlu+/ProFAST+ (PFlu/PFAST), FilmArray Respiratory Panel (RP), cobas® Influenza A/B test (cIAB), and Xpert® Flu (Xpt) in a retrospective analysis of consecutive nasopharyngeal specimens received for a two-week period during the winter of 2015. Furthermore, limits of detection (LOD) were determined with six isolates of Flu. Results Of the 275 specimens, 63 were positive for FluA by PFAST, 60 were positive by RP, 58 were positive by cIAB and 52 were positive by Xpt. Only a subset of 135 specimens was tested by PFlu, of which 32 were positive. The sensitivity/specificity for PFAST, RP, cIAB, Xpt and PFlu was 100/99.1%, 96.7/99.5%, 91.8/99.1%, 85.2%/100%, and 75.6%/98.9%, respectively. LOD analyses demonstrated assay performance variations were strain associated. Specifically, PFlu’s and cIAB’s LODs were higher with A/Texas/50/2012-like and A/Switzerland/9715293/2013-like strains, while Xpt’s highest LOD was with the Swiss strain. Conclusions Strain-associated assay performance variation is known to occur with other Flu test methods; hence, it is not surprising that such variation would be observed with molecular tests. Careful monitoring and reporting for strain-associated variances are warranted for all test methods.


Conducting Research in Disease Outbreaks


Taxonomy


title: The relevance of psychosocial variables and working conditions in predicting nurses’ coping strategies during the SARS crisis: An online questionnaire survey

text: Abstract Objectives The purpose of this investigation was to examine the relationship between psychosocial variables and working conditions, and nurses’ coping methods and distress in response to the severe acute respiratory syndrome (SARS) crisis in Canada. Participants and procedure The sample consisted of 333 nurses (315 women, 18 men) who completed an Internet-mediated questionnaire that was posted on the Registered Nurses’ Association of Ontario (RNAO) website between March and May 2004. The questionnaire was restricted to respondents who had to authenticate their RNAO membership with a valid username and password before accessing the questionnaire. This served a dual purpose: to ensure that only RNAO nurses completed the questionnaire and thereby safeguarding the generalizability of the findings; and second, to prevent any one nurse from contributing more than once to the overall sample. Results Correlational analysis yielded several significant relationships between psychosocial variables and working conditions, and the traditional correlates of burnout and stress. Three multiple regression analysis revealed that the model we evolved—including higher levels of vigor, organizational support, and trust in equipment/infection control initiative; and lower levels of contact with SARS patients, and time spent in quarantine—predicted to lower levels of avoidance behavior, emotional exhaustion, and state anger. Conclusions By employing models of stress and burnout that combine psychosocial variables and working conditions, researchers can account for significant amounts of variance in outcomes related to burnout. These findings highlight the importance of vigor and perceived organizational support in predicting nurses’ symptoms of burnout. For healthcare administrators, this means that a likely strategy for assuaging the negative outcomes of stress should address nurses’ psychosocial concerns and the working conditions that they face during novel times of crisis.


title: Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA and neutralization assay against viral spike pseudotyped virus

text: Abstract Background Human coronavirus HKU1 (HCoV-HKU1) is a recently identified coronavirus with a global distribution and known to cause mainly respiratory infections. Objectives To investigate the seroepidemiology of HKU1 infections in our local population. Study design An ELISA-based IgG antibody detection assay using recombinant HCoV-HKU1 nucleocapsid and spike (S) proteins (genotype A) were developed for the diagnosis of CoV-HKU1 infections, Additionally, a neutralization antibody assay using the HCoV-HKU1 pseudotyped virus was developed to detect the presence of neutralizing antibodies in serum with antibody positivity in an S protein-based ELISA. Results Results of the recombinant S protein-based ELISA were validated with Western blot, immunofluorescence analysis and flow cytometry. The coupled results demonstrated good correlation with Spearmen's coefficient of 0.94. Seroepidemiological study in a local hospital-based setting using this newly developed ELISA showed steadily increasing HCoV-HKU1 seroprevalence in childhood and early adulthood, from 0% in the age group of <10 years old to a plateau of 21.6% in the age group of 31–40 years old. Conclusions Our study demonstrated the usefulness of the S-based ELISA which could be applied to future epidemiological studies of HCoV-HKU1 in other localities.


Clearing up the obesity paradox in cardiac surgery


title: Evaluating the virucidal efficacy of hydrogen peroxide vapour

text: Summary Background Surface contamination has been implicated in the transmission of certain viruses, and surface disinfection can be an effective measure to interrupt the spread of these agents. Aim To evaluate the in-vitro efficacy of hydrogen peroxide vapour (HPV), a vapour-phase disinfection method, for the inactivation of a number of structurally distinct viruses of importance in the healthcare, veterinary and public sectors. The viruses studied were: feline calicivirus (FCV, a norovirus surrogate); human adenovirus type 1; transmissible gastroenteritis coronavirus of pigs (TGEV, a severe acute respiratory syndrome coronavirus [SARS-CoV] surrogate); avian influenza virus (AIV); and swine influenza virus (SwIV). Methods The viruses were dried on stainless steel discs in 20- or 40-μL aliquots and exposed to HPV produced by a Clarus L generator (Bioquell, Horsham, PA, USA) in a 0.2-m3 environmental chamber. Three vaporized volumes of hydrogen peroxide were tested in triplicate for each virus: 25, 27 and 33mL. Findings No viable viruses were identified after HPV exposure at any of the vaporized volumes tested. HPV was virucidal (>4-log reduction) against FCV, adenovirus, TGEV and AIV at the lowest vaporized volume tested (25mL). For SwIV, due to low virus titre on the control discs, >3.8-log reduction was shown for the 25-mL vaporized volume and >4-log reduction was shown for the 27-mL and 33-mL vaporized volumes. Conclusion HPV was virucidal for structurally distinct viruses dried on surfaces, suggesting that HPV can be considered for the disinfection of virus-contaminated surfaces.


Filtration Group switches part of German production to face masks


title: Fifty years of the bottleneck model: A bibliometric review and future research directions

text: Abstract The bottleneck model introduced by Vickrey in 1969 has been recognized as a benchmark representation of the peak-period traffic congestion due to its ability to capture the essence of congestion dynamics in a simple and tractable way. This paper aims to provide a 50th anniversary review of the bottleneck model research since its inception. A bibliometric analysis approach is adopted for identifying the distribution of all journal publications, influential papers, top contributing authors, and leading topics in the past half century. The literature is classified according to recurring themes into travel behavior analysis, demand-side strategies, supply-side strategies, and joint strategies of demand and supply sides. For each theme, typical extended models developed to date are surveyed. Some potential directions for further studies are discussed.


title: Bioproduction of Therapeutic Proteins in the 21st Century and the Role of Plants and Plant Cells as Production Platforms

text: abstract: In the last decade, the technique to genetically modify crop plants has gained more and more interest in terms of bioproduction of heterologous proteins. Plants have been discovered as a possible source for large amounts of cost effective recombinant protein. Main application fields are therapeutics for use in animal and human health, diagnostics, and technical enzymes. This review is focused on the recent progress in this field of molecular farming. After a comparison with hitherto established protein production systems, the advantages of plants as an alternative production system are discussed. An overview about the different host plants and possible expression strategies is given and the progress in commercialization of the techniques is highlighted. Finally, the role of plant cell cultures for the production of recombinant proteins is discussed.


title: Molecular detection of CF lung pathogens: Current status and future potential

text: Abstract Molecular diagnostic tests, based on the detection and identification of nucleic acids in human biological samples, are increasingly employed in the diagnosis of infectious diseases and may be of future benefit to CF microbiology services. Our growing understanding of the complex polymicrobial nature of CF airway infection has highlighted current and likely future shortcomings in standard diagnostic practices. Failure to detect fastidious or slow growing microbes and misidentification of newly emerging pathogens could potentially be addressed using culture-independent molecular technologies with high target specificity. This review considers existing molecular diagnostic tests in the context of the key requirements for an envisaged CF microbiology focussed assay. The issues of assay speed, throughput, detection of multiple pathogens, data interpretation and antimicrobial susceptibility testing are discussed.


title: Snapshot PCR Surveillance for SARS-CoV-2 in Hospital Staff in England

text: BACKGROUND: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. METHODS: Cross-sectional ‘snapshot’ survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. FINDINGS: Point prevalence of SARS-CoV-2 carriage across the sites was 2•0% (23/1152 participants), median cycle threshold value 35•70 (IQR:32•42-37•57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3•46, 95%CI 1•38-8•67; p=0•008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. INTERPRETATION: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. FUNDING: Public Health England.


title: Reported Direct and Indirect Contact with Dromedary Camels among Laboratory-Confirmed MERS-CoV Cases

text: Dromedary camels (Camelus dromedarius) are now known to be the vertebrate animal reservoir that intermittently transmits the Middle East respiratory syndrome coronavirus (MERS-CoV) to humans. Yet, details as to the specific mechanism(s) of zoonotic transmission from dromedaries to humans remain unclear. The aim of this study was to describe direct and indirect contact with dromedaries among all cases, and then separately for primary, non-primary, and unclassified cases of laboratory-confirmed MERS-CoV reported to the World Health Organization (WHO) between 1 January 2015 and 13 April 2018. We present any reported dromedary contact: direct, indirect, and type of indirect contact. Of all 1125 laboratory-confirmed MERS-CoV cases reported to WHO during the time period, there were 348 (30.9%) primary cases, 455 (40.4%) non-primary cases, and 322 (28.6%) unclassified cases. Among primary cases, 191 (54.9%) reported contact with dromedaries: 164 (47.1%) reported direct contact, 155 (44.5%) reported indirect contact. Five (1.1%) non-primary cases also reported contact with dromedaries. Overall, unpasteurized milk was the most frequent type of dromedary product consumed. Among cases for whom exposure was systematically collected and reported to WHO, contact with dromedaries or dromedary products has played an important role in zoonotic transmission.


title: Pulmonary Infections Following Lung Transplantation

text: Infectious complications are a major cause of morbidity and mortality in solid organ transplant recipients. Infections with viruses, bacteria, and fungi have all been associated with the development of bronchiolitis obliterans syndrome (chronic allograft rejection) in lung transplant recipients. Lung transplant recipients have a higher risk of infectious complications than recipients of other solid organs because of the intensity of immunosuppression, blunted cough mechanism, and constant exposure to the environment. This review provides a broad overview of the infectious complications encountered in caring for patients who have undergone lung transplantation.


title: Immunity and age: living in the past?

text: Increasing age is associated with a decreasing ability to mediate effective immune responses to newly encountered antigens. It is generally believed that this reflects the age-associated decline in the number, repertoire and function of available naive T cells. Here, we propose that naive T cells become increasingly irrelevant to the immune system, and that responses to newly encountered antigens are progressively dominated by cross-reactive memory T cells as the individual ages. In addition, we propose that the majority, if not all, of the response to newly encountered antigens in the elderly is mediated by cross-reactive memory T cells. This predicts highly stochastic responses to new infections that should vary between individuals, and has important implications for vaccination strategies in the elderly.


title: The infodemics of COVID-19 amongst healthcare professionals in India

text: BACKGROUND: There is a deluge of information and misinformation about COVID-19. The present survey was conducted to explore the sources of information /misinformation for healthcare professionals from India. METHODS: A cross-sectional online survey using snowballing technique was conducted from 24 Mar to 10 Apr 2020. The questionnaire was pretested and developed using standard techniques. It was circulated among medical students and physicians. Data were analysed using the STATA software. RESULTS: Data of 758 participants were analysed. A total of 255 (33.6%) medical students, 335 (44.2%) nonspecialists and 168 (22.1%) specialists participated. The most common source of formal and informal information was official government websites and online news, respectively. A total of 517 (68.2%) participants accepted receiving misinformation. Social media and family and friends were the most common sources of misinformation. Seventy-two percent of participants agreed that spread of information helped to contain COVID-19, but more than that 75% agreed to having received inaccurate information. Seventy-four percent of respondents felt the need for regulation of information during such times; 26% and 33% felt that information about COVID-19 made them feel uncomfortable and distracts routine decision-making, respectively, and 50% felt it was difficult to differentiate correct from incorrect information about COVID-19. CONCLUSION: The study explored the sources of information and misinformation and found a high prevalence of misinformation, especially from social media. We suggest the need to better manage the flow of information so that it can be an effective weapon against SARS-CoV2. There is a need for doctors to adapt to the changing times of infodemics accompanying pandemics.


title: Evaluating MERS-CoV Entry Pathways

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic pathogen with a broad host range. The extent of MERS-CoV in nature can be traced to its adaptable cell entry steps. The virus can bind host-cell carbohydrates as well as proteinaceous receptors. Following receptor interaction, the virus can utilize diverse host proteases for cleavage activation of virus-host cell membrane fusion and subsequent genome delivery. The fusion and genome delivery steps can be completed at variable times and places, either at or near cell surfaces or deep within endosomes. Investigators focusing on the CoVs have developed several methodologies that effectively distinguish these different cell entry pathways. Here we describe these methods, highlighting virus-cell entry factors, entry inhibitors, and viral determinants that specify the cell entry routes. While the specific methods described herein were utilized to reveal MERS-CoV entry pathways, they are equally suited for other CoVs, as well as other protease-dependent viral species.


title: Factors affecting stability and infectivity of SARS-CoV-2

text: BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20∼25(o)C). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.


Reply to: ‘No evidence for an increased liver uptake of SARS-CoV-2 in metabolic associated fatty liver disease’


Fighting COVID-19 Hypoxia with One Hand Tied Behind Our Back: Blanket Prohibition of High Flow Oxygen and Non-Invasive Positive End-Expiratory Pressure in United States Hospitals


title: Characterization of the porcine epidemic diarrhea virus codon usage bias

text: Abstract Porcine epidemic diarrhea virus (PEDV) has been responsible for several recent outbreaks of porcine epidemic diarrhea (PED) and has caused great economic loss in the swine-raising industry. Considering the significance of PEDV, a systemic analysis was performed to study its codon usage patterns. The relative synonymous codon usage value of each codon revealed that codon usage bias exists and that PEDV tends to use codons that end in T. The mean ENC value of 47.91 indicates that the codon usage bias is low. However, we still wanted to identify the cause of this codon usage bias. A correlation analysis between the codon compositions (A3s, T3s, G3s, C3s, and GC3s), the ENC values, and the nucleotide contents (A%, T%, G%, C%, and GC%) indicated that mutational bias plays role in shaping the PEDV codon usage bias. This was further confirmed by a principal component analysis between the codon compositions and the axis values. Using the Gravy, Aroma, and CAI values, a role of natural selection in the PEDV codon usage pattern was also identified. Neutral analysis indicated that natural selection pressure plays a more important role than mutational bias in codon usage bias. Natural selection also plays an increasingly significant role during PEDV evolution. Additionally, gene function and geographic distribution also influence the codon usage bias to a degree.


title: Interferon and cytokine responses to Crimean Congo hemorrhagic fever virus; an emerging and neglected viral zonoosis

text: Abstract Crimean Congo hemorrhagic fever virus (CCHFV) causes an acute disease with the potential of a fatal outcome. The virus is prevalent in about 30 countries. Clinical symptoms of infection commonly include fever, myalgia, and hemorrhages. Levels of liver enzymes are raised, and bleeding markers are often increased. A role of inflammatory cytokines in the pathogenesis has been suggested, and CCHFV employs a range of passive and active mechanisms to avoid induction of the antiviral type I interferons. Here, we review the most recent findings on the molecular pathogenesis and the interaction of CCHFV with the type I interferon and cytokine responses and discuss implications for pathogenesis.


title: Codon usage pattern and its influencing factors in different genomes of hepadnaviruses

text: Codon usage bias (CUB) arises from the preference for a codon over codons for the same amino acid. The major factors contributing to CUB are evolutionary forces, compositional properties, gene expression, and protein properties. The present analysis was performed to investigate the compositional properties and the extent of CUB across the genomes of members of the family Hepadnaviridae, as previously no work using bioinformatic tools has been reported. The viral genes were found to be AT rich with low CUB. Analysis of relative synonymous codon usage (RSCU) was used to identify overrepresented and underrepresented codons for each amino acid. Correlation analysis of overall nucleotide composition and its composition at the third codon position suggested that mutation pressure might influence the CUB. A highly significant correlation was observed between GC12 and GC3 (r = 0.910, p < 0.01), indicating that directional mutation affected all three codon positions across the genome. Translational selection (P2) and mutational responsive index (MRI) values of genes suggested that mutation plays a more important role than translational selection in members of the family Hepadnaviridae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04533-6) contains supplementary material, which is available to authorized users.


title: Fatal HBoV-1 infection in adult female cystic fibrosis patient

text: Abstract A clinical case of fatal HBoV infection in an adult cystic-fibrosis patient awaiting lung transplantation is reported. The case is important as the genetic background of the underlying disease is congruent with the background of the sole permissive permanent cell culture CuFi-8 which originates also from a CF patient donor.


title: An experimental vaccine for calf pneumonia caused by Mycoplasma bovis: clinical, cultural, serological and pathological findings

text: A single dose of vaccine for Mycoplasma bovis pneumonia, inactivated with saponin, was inoculated subcutaneously into 3–4 week-old calves. The calves were challenged 3 weeks later with a virulent strain of M. bovis on two occasions within 24 h using the aerosol route. The calves were monitored for clinical signs and serological responses then post mortemed 3 weeks after challenge. The vaccine was shown to be highly immunogenic in calves and did not cause adverse effects. Vaccinated calves showed few clinical signs while all unvaccinated calves developed signs of pneumonia. There was a significant decrease in body weight gain in unvaccinated calves compared to vaccinates and a significant increase in lung lesions and rectal temperatures in unvaccinated calves. The vaccine also reduced the spread of M. bovis to internal organs. In conclusion the M. bovis vaccine produced a significant level of protection against a large virulent challenge.


title: Home Medical Nutrition during SARS-CoV-2 pandemic – a position paper

text: Summary Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a worldwide rapidly spreading illness, Coronavirus Disease 2019 (COVID-19). Patients fed enterally and parenterally at home are exposed to the same risk of infection as the general population, but more prone to complications than others. Therefore the guidance for care-givers and care-takers of these patients is needed. Methods The literature search identified no relevant systematic reviews or studies on the subject. Therefore a panel of 21 experts from 13 home medical nutrition (HMN) centres in Poland was formed. Twenty-three key issues relevant to the management of SARS-CoV-2 infection or COVID-19 in the HMN settings were identified and discussed. Some statements diverge from the available nutrition, surgical or ICU guidelines, some are based on the best available experience. Each topic was discussed and assessed during two Delphi rounds subsequently. Statements were graded strong or weak based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Results the panel issued 23 statements, all of them were graded strong. Two scored 85.71% agreement, eleven 95.23%, and ten 100%. The topics were: infection control, enrolment to HMN, logistics and patient information. Conclusions the position paper present pragmatic statements for HMN to be implemented in places without existing protocols for SARS-CoV-2 pandemic. They represent the state of knowledge available at the moment and may change should new evidence occurs.


title: SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon

text: SARS-CoV is a pathogenic coronavirus that emerged from a zoonotic reservoir, leading to global dissemination of the virus. The association SARS-CoV with aberrant cytokine, chemokine, and Interferon Stimulated Gene (ISG) responses in patients provided evidence that SARS-CoV pathogenesis is at least partially controlled by innate immune signaling. Utilizing models for SARS-CoV infection, key components of innate immune signaling pathways have been identified as protective factors against SARS-CoV disease, including STAT1 and MyD88. Gene transcription signatures unique to SARS-CoV disease states have been identified, but host factors that regulate exacerbated disease phenotypes still remain largely undetermined. SARS-CoV encodes several proteins that modulate innate immune signaling through the antagonism of the induction of Interferon and by avoidance of ISG effector functions.


title: Mosaic Structure of Human Coronavirus NL63, One Thousand Years of Evolution

text: Abstract Before the SARS outbreak only two human coronaviruses (HCoV) were known: HCoV-OC43 and HCoV-229E. With the discovery of SARS-CoV in 2003, a third family member was identified. Soon thereafter, we described the fourth human coronavirus (HCoV-NL63), a virus that has spread worldwide and is associated with croup in children. We report here the complete genome sequence of two HCoV-NL63 clinical isolates, designated Amsterdam 57 and Amsterdam 496. The genomes are 27,538 and 27,550 nucleotides long, respectively, and share the same genome organization. We identified two variable regions, one within the 1a and one within the S gene, whereas the 1b and N genes were most conserved. Phylogenetic analysis revealed that HCoV-NL63 genomes have a mosaic structure with multiple recombination sites. Additionally, employing three different algorithms, we assessed the evolutionary rate for the S gene of group Ib coronaviruses to be ∼3×10−4 substitutions per site per year. Using this evolutionary rate we determined that HCoV-NL63 diverged in the 11th century from its closest relative HCoV-229E.


title: Vanadium: History, chemistry, interactions with α-amino acids and potential therapeutic applications

text: Abstract In the last 30 years, since the discovery that vanadium is a cofactor found in certain enzymes of tunicates and possibly in mammals, different vanadium-based drugs have been developed targeting to treat different pathologies. So far, the in vitro studies of the insulin mimetic, antitumor and antiparasitic activity of certain compounds of vanadium have resulted in a great boom of its inorganic and bioinorganic chemistry. Chemical speciation studies of vanadium with amino acids under controlled conditions or, even in blood plasma, are essential for the understanding of the biotransformation of e.g. vanadium antidiabetic complexes at the physiological level, providing clues of their mechanism of action. The present article carries out a bibliographical research emphaticizing the chemical speciation of the vanadium with different amino acids and reviewing also some other important aspects such as its chemistry and therapeutical applications of several vanadium complexes.


Case Report of Leishmaniasis in Four Cats


title: Modulation of immune-associated surface markers and cytokine production by murine retinal glial cells

text: Abstract Murine retinal glia are normally negative for major histocompatibility complex (MHC) Class II antigens and express low levels of MHC Class I and intercellular adhesion molecule-1 (ICAM-1) as detected by avidin-biotin-peroxidase immunohistochemistry. These surface molecules associated with immune function were either induced (Class II) or upregulated (Class I and ICAM-1) on cultured retinal glial cells in a dose- and time-dependent manner following exposure to recombinant Interferonγ (rIFN-γ). MHC Class I and II expression by passaged and primary cells was maximal (> 90% positive) after incubation with 100 U/ml of rlFN-y for 48 h. ICAM-1 expression by primary and passaged cells tripled between 48 and 72 h after exposure to 25 or 50 U/ml of rIFN-γ. By 72 h after exposure to 100 U/ml of rIFN-y, 62% of the retinal glia were positive for ICAM-1, whereas under normal culture conditions these molecules were detected on < 3% of the retinal glia. Bacterial lipopolysaccharide (LPS), a known stimulator of central nervous system (CMS) astrocytes, increased ICAM-1 expression only 3-fold to 9% of cells staining positively, but neither MHC Class I nor Class II expression was altered from baseline levels. Surface expression of ICAM-1, MHC Class I, and MHC Class II was unaffected by exposure to either rTNF-α (1000 U/ml) or rIL-6 (100 U/ml) for 24 h. Under normal culture conditions, intracellular interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected immunohistochemically. Exposure to either rIFN-γ or LPS induced more intense staining which correlated with increased secreted levels of both cytokines in culture supernatants. Levels of secreted TNF-α increased 6-fold after stimulation with LPS for 24 h, while secreted IL-6 increased over 9-fold. These results support the hypothesis that retinal glia may participate in intraretinal immune processes following stimulation during inflammatory and infectious processes via either cell surface- or soluble mediator-dependent mechanisms or a combination of both.


title: Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc

text: Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses.


title: Comparison of initial high resolution computed tomography features in viral pneumonia between metapneumovirus infection and severe acute respiratory syndrome

text: Abstract Objective To review and compare initial high resolution computed tomography (HRCT) findings in patients with metapneumovirus pneumonia and severe acute respiratory syndrome (SARS-Coronovirus). Materials and methods 4 cases of metapneumovirus pneumonia (mean age of 52.3years) in an institutional outbreak (Castle Peak Hospital) in 2008 and 38 cases of SARS-coronovirus (mean age of 39.6years) admitted to Tuen Mun hospital during an epidemic outbreak in 2003 were included. HRCT findings of the lungs for all patients were retrospectively reviewed by two independent radiologists. Results In the metapneumovirus group, common HRCT features were ground glass opacities (100%), consolidation (100%), parenchymal band (100%), bronchiectasis (75%). Crazy paving pattern was absent. They were predominantly subpleural and basal in location and bilateral involvement was observed in 50% of patients. In the SARS group, common HRCT features were ground glass opacities (92.1%), interlobular septal thickening (86.8%), crazy paving pattern (73.7%) and consolidation (68%). Bronchiectasis was not seen. Majority of patient demonstrated segmental or lobar in distribution and bilateral involvement was observed in 44.7% of patients. Pleural effusion and lymphadenopathy were of consistent rare features in both groups. Conclusion Ground glass opacities, interlobular septal thickening and consolidations were consistent HRCT manifestations in both metapneumovirus infection and SARS. The presence of bronchiectasis (0% in SARS) may point towards metapneumovirus while crazy paving pattern is more suggestive of SARS.


title: Mechanisms of action of ribavirin against distinct viruses

text: The nucleoside analogue ribavirin has antiviral activity against many distinct viruses both in vitro and in vivo. Five distinct mechanisms have been proposed to explain the antiviral properties of ribavirin. These include both indirect mechanisms (inosine monophosphate dehydrogenase inhibition, immunomodulatory effects) and direct mechanisms (interference with RNA capping, polymerase inhibition, lethal mutagenesis). Recent concerns about bioterrorism have renewed interest in exploring the antiviral activity of ribavirin against unique viruses. In this paper, we review the proposed mechanisms of action with emphasis on recent discoveries, as well as the implications of ribavirin resistance. Evidence exists to support each of the five proposed mechanisms of action, and distinct virus/host combinations may preferentially favour one or more of these mechanisms during antiviral therapy. Copyright © 2005 John Wiley & Sons, Ltd.


title: Global Epidemiology of Bat Coronaviruses

text: Bats are a unique group of mammals of the order Chiroptera. They are highly diversified and are the group of mammals with the second largest number of species. Such highly diversified cell types and receptors facilitate them to be potential hosts of a large variety of viruses. Bats are the only group of mammals capable of sustained flight, which enables them to disseminate the viruses they harbor and enhance the chance of interspecies transmission. This article aims at reviewing the various aspects of the global epidemiology of bat coronaviruses (CoVs). Before the SARS epidemic, bats were not known to be hosts for CoVs. In the last 15 years, bats have been found to be hosts of >30 CoVs with complete genomes sequenced, and many more if those without genome sequences are included. Among the four CoV genera, only alphaCoVs and betaCoVs have been found in bats. As a whole, both alphaCoVs and betaCoVs have been detected from bats in Asia, Europe, Africa, North and South America and Australasia; but alphaCoVs seem to be more widespread than betaCoVs, and their detection rate is also higher. For betaCoVs, only those from subgenera Sarbecovirus, Merbecovirus, Nobecovirus and Hibecovirus have been detected in bats. Most notably, horseshoe bats are the reservoir of SARS-CoV, and several betaCoVs from subgenus Merbecovirus are closely related to MERS-CoV. In addition to the interactions among various bat species themselves, bat–animal and bat–human interactions, such as the presence of live bats in wildlife wet markets and restaurants in Southern China, are important for interspecies transmission of CoVs and may lead to devastating global outbreaks.


title: Mining association rules with multiple minimum supports: a new mining algorithm and a support tuning mechanism

text: Abstract Mining association rules with multiple minimum supports is an important generalization of the association-rule-mining problem, which was recently proposed by Liu et al. Instead of setting a single minimum support threshold for all items, they allow users to specify multiple minimum supports to reflect the natures of the items, and an Apriori-based algorithm, named MSapriori, is developed to mine all frequent itemsets. In this paper, we study the same problem but with two additional improvements. First, we propose a FP-tree-like structure, MIS-tree, to store the crucial information about frequent patterns. Accordingly, an efficient MIS-tree-based algorithm, called the CFP-growth algorithm, is developed for mining all frequent itemsets. Second, since each item can have its own minimum support, it is very difficult for users to set the appropriate thresholds for all items at a time. In practice, users need to tune items' supports and run the mining algorithm repeatedly until a satisfactory end is reached. To speed up this time-consuming tuning process, an efficient algorithm which can maintain the MIS-tree structure without rescanning database is proposed. Experiments on both synthetic and real-life datasets show that our algorithms are much more efficient and scalable than the previous algorithm.


title: The SARS-CoV-2 outbreak: What we know

text: Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.


title: Phylogenetic analysis of porcine astrovirus in domestic pigs and wild boars in South Korea

text: Porcine astrovirus (PAstV) belongs to genetically divergent lineages within the genus Mamastrovirus. In this study, 25/129 (19.4 %) domestic pig and 1/146 (0.7 %) wild boar fecal samples tested in South Korea were positive for PAstV. Positive samples were mainly from pigs under 6 weeks old. Bayesian inference (BI) tree analysis for RNA-dependent RNA polymerase (RdRp) and capsid (ORF2) gene sequences, including Mamastrovirus and Avastrovirus, revealed a relatively geographically divergent lineage. The PAstVs of Hungary and America belong to lineage PAstV 4; those of Japan belong to PAstV 1; and those of Canada belong to PAstV 1, 2, 3, and 5, but not to 4. This study revealed that the PAstVs of Korea belong predominantly to lineage PAstV 4 and secondarily to PAstV 2. It was also observed that PAstV infections are widespread in South Korea regardless of the disease state in domestic pigs and in wild boars as well.


title: Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex

text: Abstract Analysis of virus–host interactions has revealed a variety of ways in which viruses utilize and/or alter host functions in an effort to facilitate efficient replication. Recent work has suggested that certain RNA viruses that replicate in the cytoplasm disrupt the normal trafficking of cellular RNAs and proteins within the host cell. This review will examine the recent evidence showing that poliovirus and vesicular stomatitis virus (VSV) can inhibit nucleo-cytoplasmic transport within cells. Interestingly, the data indicate that inhibition by both viruses involves targeting components of the nuclear pore complex (NPC). Following this, several possible explanations for why viruses might disrupt nucleo-cytoplasmic transport are discussed. Finally, the possibility that disruption of nucleo-cytoplasmic trafficking may be a more common feature of RNA virus–host interactions than previously thought is examined.


title: Prostaglandin E(2) stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis

text: BACKGROUND: Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)), a bioactive eicosanoid, has been implicated in many biological processes including reproduction, inflammation and tumor growth. We previously showed that PGE(2) stimulated lung cancer cell growth and progression through PGE(2) receptor EP2/EP4-mediated kinase signaling pathways. However, the role of PGE(2) in controlling lung airway epithelial cell phenotype remains unknown. We evaluated the effects of c-Jun and 3-phosphoinositede dependent protein kinase-1 (PDK1) in mediating epithelial cell hyperplasia induced by PGE(2). METHOD: The bronchial epithelial cell lines BEAS-2B and HBEc14-KT were cultured and then treated with PGE(2). PDK1 small interfering RNA (siRNA) and a PDK1 inhibitor, an antagonist of the PGE(2) receptor subtype EP4 and EP4 siRNA, c-Jun siRNA, and overexpressions of c-Jun and PDK1 have been used to evaluate the effects on cell proliferation. RESULTS: We demonstrated that PGE(2) increased normal bronchial epithelial cell proliferation through induction of PDK1, an ankyrin repeat-containing Ser/Thr kinase implicated in the induction of apoptosis and the suppression of tumor growth. PDK1 siRNA and a PDK1 inhibitor blocked the effects of PGE(2) on normal cell growth. The PGE(2)-induced PDK1 expression was blocked by an antagonist of the PGE(2) receptor subtype EP4 and by EP4 siRNA. In addition, we showed that induction of PDK1 by PGE(2) was associated with induction of the transcription factor, c-Jun protein. Silencing of c-Jun using siRNA and point mutations of c-Jun sites in the PDK1 gene promoter resulted in blockade of PDK1 expression and promoter activity induced by PGE(2). In contrast, overexpression of c-Jun induced PDK1 gene promoter activity and expression followed increased cell proliferation. CONCLUSION: PGE(2) increases normal bronchial epithelial cell proliferation through increased PDK1 gene expression that is dependent on EP4 and induction of c-Jun. Therewith, our data suggest a new role of c-Jun and PDK1 in mediating epithelial cell hyperplasia induced by PGE(2).


title: Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia

text: The immune system of patients infected by SARS-CoV-2 is severely impaired. Detailed investigation of T cells and cytokine production in patients affected by COVID-19 pneumonia are urgently required. Here we show that, compared with healthy controls, COVID-19 patients’ T cell compartment displays several alterations involving naïve, central memory, effector memory and terminally differentiated cells, as well as regulatory T cells and PD1(+)CD57(+) exhausted T cells. Significant alterations exist also in several lineage-specifying transcription factors and chemokine receptors. Terminally differentiated T cells from patients proliferate less than those from healthy controls, whereas their mitochondria functionality is similar in CD4(+) T cells from both groups. Patients display significant increases of proinflammatory or anti-inflammatory cytokines, including T helper type-1 and type-2 cytokines, chemokines and galectins; their lymphocytes produce more tumor necrosis factor (TNF), interferon-γ, interleukin (IL)-2 and IL-17, with the last observation implying that blocking IL-17 could provide a novel therapeutic strategy for COVID-19.


title: Immune responses with DNA vaccines encoded different gene fragments of severe acute respiratory syndrome coronavirus in BALB/c mice

text: Abstract To analyze the immune responses of DNA vaccine encoded different gene fragments of severe acute respiratory syndrome coronavirus (SARS-Cov), SARS-Cov gene fragments of membrane (M), nucleocapsid (N), spike a (Sa), and spike b (Sb) proteins were cloned into pcDNA3.1 (Invitrogen) vector to form plasmids pcDNAM, pcDNAN, pcDNASa, and pcDNASb, respectively. After mice were immunized intramuscularly with pcDNAM, pcDNAN or pcDNASa–pcDNASb plasmid, blood was collected and serum was separated. Humoral immune response was detected with the enzyme-linked immunosorbent assay, and cellular immune response of SARS-Cov DNA vaccines was detected with lymphoproliferation assay and cytotoxic T lymphocyte assay. Results show that cellular and humoral immune responses can be detected after immunization with pcDNAM, pcDNAN or pcDNASa–pcDNASb plasmids in BALB/c mice. However, pcDNAM stimulated the highest cellular immune response than other plasmids, and pcDNASa–pcDNASb stimulated the highest humoral immune response in week 12. The present results not only suggest that DNA immunization with pcDNAM, pcDNAN or pcDNASa–pcDNASb could be used as potential DNA vaccination approaches to induce antibody in BALB/c mice, but also to illustrate that gene immunization with these SARS DNA vaccines different immune response characters.


Will Ebola change the game? Ten essential reforms before the next pandemic. The report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola


title: Structure, function and metabolism of sialic acids

text: Sialic acids represent a family of sugar molecules with an unusual and highly variable chemical structure that are found mostly in the terminal position of oligosaccharide chains on the surface of cells and molecules. These special features enable them to fulfil several important and even diametrical biological functions. Because of the great importance of sialic acids, it is also worth having a look at their metabolism in order to get an idea of the intimate connection between structure and function of these fascinating molecules and the often serious consequences that result from disturbances in the balance of metabolic reactions. The latter can be due to genetic disorders that result in the absence of certain enzyme activity, leading to severe illness or even to death.


title: D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19

text: A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies, the other is for identifying lead compounds against potential drug targets via docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 Å(3) on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easily to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.


title: Coronavirus disease 2019 (COVID-19) pneumonia presentations in chest computed tomography: a pictorial review

text: Despite imaging not being a tool for novel coronavirus disease 2019 (COVID-19) diagnosis, there has been an increased number of chest computed tomography (CT) scans done worldwide. There are no pathognomonic CT features for COVID-19 pneumonia, as findings are also common in other infectious diseases and noninfectious aetiologies. Nonetheless, point-of-care physicians should be familiarized with the most common imaging presentations of the COVID-19. In this pictorial review, we have summarized the most reported imaging features of COVID-19 pneumonia, including possible differential diagnosis according to the CT finding.


title: Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition).

text: Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.


title: Effect of Substance P and Receptor Antagonists on Secretion of Lingual Lipase and Amylase from Rat von Ebner's Gland

text: Field, R. B., S. J. Chirtel and R. S. Redman. Effect of substance P and receptor antagonists on secretion of lingual lipase and amylase from rat von Ebner's gland. Peptides 18(2) 277–285, 1997.— Substance P (SP, 1 μM) when incubated with minced von Ebner's glands for 15, 30, and 60 min, stimulated secretion of lingual lipase (12.14%±0.90) and amylase (8.30%±0.42). Only 10 μM of the SP receptor antagonist CP-96,345 significantly inhibited SP-evoked secretion. d-Pro(2)-d-Phe(7)-d-Trp(9)-SP (Ia), d-Pro(2)-d-Trp(7,9)-SP (Ib), d-Arg(1)-d-Trp(7,9)-d-Leu(11)-SP (Ic), or 1 μM CP-96,345 were not effective, suggesting that the SP receptor of von Ebner's gland might be an isoform. Propranolol and timolol, β(1)/β(2)-adrenergic receptor antagonists were not effective and the cholinergic receptor antagonist, atropine, was effective in only slightly reducing amylase secretion but not lingual lipase. Differential secretion of the two enzymes was observed for basal and stimulated secretion. Thus, exocytosis may not be the only pathway involved in SP-evoked protein secretion.


title: User acceptance of reusable respirators in health care

text: BACKGROUND: Inclusion of reusable respirators, such as elastomeric half-face respirators (EHFRs) and powered air-purifying respirators (PAPRs), in hospital respiratory protection inventories may represent 1 solution to the problem of N95 respirator shortages experienced during pandemics. User acceptance of these devices is 1 potential barrier to implementing such a strategy in respiratory protection programs. METHODS: To assess user attitudes toward various respirators, health care workers enrolled in respiratory protection programs in a medical system using EHFRs, N95s, and PAPRs and completed an online questionnaire that addressed attitudes, beliefs, and respirator preferences under different risk scenarios. Responses were compared between user groups. RESULTS: Of 1,152 participants, 53% currently used N95s, 24% used EHFRs, and 23% used PAPRs. N95 users rated their respirators more favorably compared with EHFR and PAPR users (P < .001) regarding comfort and communication, however, EHFR users rated their respirators much more highly regarding sense of protection (P < .001). For all user groups, reusable respirators were significantly more likely (odds ratios 2.3-7.7) to be preferred over N95 filtering facepiece respirators in higher risk scenarios compared to “usual circumstance” scenarios. CONCLUSIONS: Despite somewhat less favorable ratings on comfort and communication, experienced EHFR and PAPR users still prefer reusable respirators over N95s in certain higher risk scenarios. This suggests that reusable respirators are an acceptable alternative to N95 respirators in health care and offer 1 viable solution to prevent pandemic-generated respirator shortages.


title: The Covid‐19 ‘infodemic’: a new front for information professionals

text: The virus, commonly known as COVID‐19 which emerged in Wuhan, China, in December 2019, has spread in 213 countries, areas or territories around the globe, with nearly 144 683 deaths worldwide on 18 April 2020. In the wake of this pandemic, we have witnessed a massive infodemic with the public being bombarded with vast quantities of information, much of which is not scientifically correct. Fighting fake news is now the new front in the COVID‐19 battle. This regular feature comments on the role of health sciences librarians and information professionals in combating the COVID‐19 infodemic. To support their work, it draws attention to the myth busters, fact‐checkers and credible sources relating to COVID‐19. It also documents the guides that libraries have put together to help the general public, students and faculty recognise fake news.


title: Antiviral and cytotoxic activities of aminoarylazo compounds and aryltriazene derivatives

text: Abstract Twelve aminoarylazocompounds (A–C) and 46 aryltriazene 7 derivatives (D–G) have been synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against a panel of 10 RNA and DNA viruses. Eight aminoazocompounds and 27 aryltriazene derivatives exhibited antiviral activity, sometimes of high level, against one or more viruses. A marked activity against BVDV and YFV was prevailing among the former compounds, while the latter type of compounds affected mainly CVB-2 and RSV. None of the active compounds inhibited the multiplication of HIV-1, VSV and VV. Arranged in order of decreasing potency and selectivity versus the host cell lines, the best compounds are the following; BVDV: 1 > 7 > 8 > 4; YFV: 7 > 5; CVB-2: 25 > 56 > 18; RSV: 14 > 20 > 55 > 38 > 18 > 19; HSV-1: 2. For these compounds the EC50 ranged from 1.6μM (1) to 12μM (18), and the S. I. from 19.4 (1) to 4.2 (2). Thus the aminoarylazo and aryltriazene substructures appear as interesting molecular component for developing antiviral agents against ss RNA viruses, particularly against RSV and BVDV, which are important human and veterinary pathogens. Finally, molecular modeling investigations indicated that compounds of structure A–C, active against BVDV, could work targeting the viral RNA-dependent RNA-polymerase (RdRp), having been observed a good agreement between the trends of the estimated IC50 and the experimental EC50 values.


title: Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

text: Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.


title: Decentralization and collaborative disaster governance: Evidence from South Korea

text: Decentralized disaster governance has been gaining much attention with the rising global urbanization rate and the complex nature of the disasters occurring in densely urbanized areas today. This paper studies the case of South Korea, a highly urbanized country with relatively recent decentralization reforms, in order to analyze the evolution of its disaster management system and to draw out implications from its experience. Specifically, it traces the national-level institutional changes in its disaster management, and then closely examines a hydrofluoric gas leakage in the industrial city of Gumi. The finding is that South Korea simultaneously carried out both centralization and decentralization of disaster management, which are not contradictory but rather complementary. Nevertheless, while the country successfully set up an integrated and comprehensive national-level management system, from which disaster governance can successfully be decentralized to localities, it still requires much more developed and consolidated multilevel (vertical) and broader (horizontal) collaboration, which are the preconditions for decentralized disaster governance.


title: PLP2, a potent deubiquitinase from murine hepatitis virus, strongly inhibits cellular type I interferon production

text: Infections by coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) result in very little type I interferon (IFN) production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNβ reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase (DUB) activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/cr.2008.294) contains supplementary material, which is available to authorized users.


title: Evaluation of envelope glycoprotein Erns of an atypical bovine pestivirus as antigen in a microsphere immunoassay for the detection of antibodies against bovine viral diarrhea virus 1 and atypical bovine pestivirus

text: Abstract Atypical bovine pestiviruses are related antigenically and phylogenetically to bovine viral diarrhea viruses (BVDV-1 and BVDV-2), and may cause the same clinical manifestations in animals. Glycoprotein Erns of an atypical bovine pestivirus Th/04_KhonKaen was produced in a baculovirus expression system and was purified by affinity chromatography. The recombinant Erns protein was used as an antigen in a microsphere immunoassay for the detection of antibodies against BVDV-1 and atypical bovine pestivirus. The diagnostic performance of the new method was evaluated by testing a total of 596 serum samples, and the assay was compared with enzyme-linked immunosorbent assay (ELISA). Based on the negative/positive cut-off median fluorescence intensity (MFI) value of 2800, the microsphere immunoassay had a sensitivity of 100% and specificity of 100% compared to ELISA. The immunoassay was able to detect antibodies against both BVDV-1 and the atypical pestivirus. This novel microsphere immunoassay has the potential to be multiplexed for simultaneous detection of antibodies against different bovine pathogens in a high-throughput and economical way.


Old and new faces of the nucleolus. Workshop on the Nucleolus and Disease


title: Une maladie cardio-vasculaire et un diabète sont des facteurs de mortalité au cours du SRAS J.W.M. Chan C.K.

text: Unknown


title: Support students’ changing needs throughout the pandemic

text: The COVID‐19 pandemic has meant new challenges for Disability Services Offices, and colleges and universities will likely experience the impacts for months, if not years. Members of Disability Compliance for Higher Education’s Advisory Board participated in a conference call to discuss what's been happening at their institutions, how they have addressed the challenges, and what they plan for the future.


title: Toward a collaborative model of pandemic preparedness and response: Taiwan's changing approach to pandemics

text: Abstract Background Over time, as newly emerging infectious diseases have become increasingly common and more easily spread, it has become clear that traditional response mechanisms have proven inadequate to the task of prevention and control. Purpose To explore whether enhanced cooperation with local government and community institutions can effectively supplement traditional state-centric public health epidemic responses. Methods Drawing on Taiwan as a case study, we assess the role of the whole-of-society approach to epidemic response as arises from the collaborative governance literature. The approach calls for enhanced cooperation, trust building, resource sharing and consensus-oriented decision making among multiple levels of government, business, non-profits, and the public in general. Results The Taiwan case illustrates the benefits of the whole-of-society approach. Enhanced cooperation between state, local government and non-state institutions, particularly neighborhood committees, has resulted in a strengthened, holistic epidemic preparedness and response infrastructure. Conclusion The Taiwan case provides evidence that by implementing the whole-of-society approach to pandemic preparedness and response governments can enhance their ability to manage future outbreaks. We recommend that governments beyond Taiwan's borders seriously consider adopting this approach.


title: A Systematic Approach to Novel Virus Discovery in Emerging Infectious Disease Outbreaks

text: The discovery of novel viruses is of great importance to human health—both in the setting of emerging infectious disease outbreaks and in disease syndromes of unknown etiology. Despite the recent proliferation of many efficient virus discovery methods, careful selection of a combination of methods is important to demonstrate a novel virus, its clinical associations, and its relevance in a timely manner. The identification of a patient or an outbreak with distinctive clinical features and negative routine microbiological workup is often the starting point for virus hunting. This review appraises the roles of culture, electron microscopy, and nucleic acid detection–based methods in optimizing virus discovery. Cell culture is generally slow but may yield viable virus. Although the choice of cell line often involves trial and error, it may be guided by the clinical syndrome. Electron microscopy is insensitive but fast, and may provide morphological clues to choice of cell line or consensus primers for nucleic acid detection. Consensus primer PCR can be used to detect viruses that are closely related to known virus families. Random primer amplification and high-throughput sequencing can catch any virus genome but cannot yield an infectious virion for testing Koch postulates. A systematic approach that incorporates carefully chosen combinations of virus detection techniques is required for successful virus discovery.


title: Participatory epidemiology at the neotropics: study of diseases of backyard livestock and description of hunting patterns in Uaxactún, Maya Reserve Biosphere, Guatemala

text: BACKGROUND: The intention of the following study was to describe the interrelationship between villagers, domestic animals and wildlife at the Community Forestry Concession of Uaxactún, Guatemala by means of participatory epidemiological methods. The main focus was generating information regarding different livestock diseases considered important by villagers and their relevance, as well as obtaining knowledge concerning hunting activities and cooking methods to gain a better understanding of the interrelationship of people and animals and the diseases of their animals. RESULTS: For poultry, an overall prevalence of 41 % of Newcastle disease was found by means of the ELISA test by antibody detection, chicken being the most affected species in the village. No samples were positive to avian influenza with the HI test. No virus was isolated by means of the tracheal or cloaca swabbing of ducks. FOR HUNTING: All species could be hunted by chance at any time of the year. There was a difference in species hunted between seasons, peccaries being more frequently hunted during the dry season and in contrast, deer and wild avian during the rainy season. FOR COOKING: Villagers did not consume any raw meat. The cooking methods depended on the species. Stewing was the most favoured method for peccaries, wild birds, tepezcuintle and domestic poultry, whereas grilling was preferable for deer, roasting for armadillos and marinating for pork. CONCLUSION: According to the generated information, the most important domestic livestock species in the village are chickens and pigs, chickens being the most affected by diseases. No evident health problems on pigs were observed in this study. Hunting was shown as an activity enhanced by poverty and the lack of employment opportunities in the village and was mostly directed at larger species such as deer and peccaries. From the viewpoint of a transmission of zoonoses from animals to humans cooking methods mostly reflected a protective factor as no raw meat was eaten, stews and broths being the most common forms of cooking, involving an exposure of meat to high temperatures. Nonetheless, both agricultural and hunting activities represent a risk factor for the spread of diseases as hunters may act as mechanical vectors for different pathogens within domestic and wild animal populations.


title: Correction to Investigation into SARS-CoV-2 Resistance of Compounds in Garlic Essential Oil

text: [This corrects the article DOI: 10.1021/acsomega.0c00772.].