title: Gargling for Oral Hygiene and the Development of Fever in Childhood: A Population Study in Japan

text: BACKGROUND: Fever is one of the most common symptoms among children and is usually caused by respiratory infections. Although Japanese health authorities have long recommended gargling to prevent respiratory infections, its effectiveness among children is not clear. METHODS: The children in this observational study were enrolled from 145 nursery schools in Fukuoka City, Japan. Children in the exposure group were instructed to gargle at least once a day. The endpoints of this study were incidence of fever during the daytime and incidence of sickness absence. Differences among gargling agents for each endpoint were also analyzed. RESULTS: A total of 19 595 children aged 2 to 6 years were observed for 20 days (391 900 person-days). In multivariate logistic regression, the overall odds ratio (OR) for fever onset in the gargling group was significantly lower (OR = 0.68). In age-stratified analysis, ORs were significantly lower at age 2 (OR = 0.67), 4 (OR = 0.46), and 5 (OR = 0.41) years. Regarding sickness absence, the overall OR was 0.92 (not significant) in the gargling group. In age-stratified analysis, ORs were significantly lower at age 4 (OR = 0.68), 5 (OR = 0.59), and 6 (OR = 0.63) years. In subgroup analysis, significantly lower ORs for fever onset were observed for children who gargled with green tea (OR = 0.32), functional water (OR = 0.46), or tap water (OR = 0.70). However, the ORs were not significant for sickness absence. CONCLUSIONS: Gargling might be effective in preventing febrile diseases in children.


title: The effect of severe acute respiratory syndrome (SARS) on emergency airway management

text: Summary From early March 2003 to late May 2003, severe acute respiratory syndrome (SARS) was detected in Singapore. The increase in workload and new infection control procedures were thought to affect resuscitation and airway management. Our aim was to study the effects of wearing of personal protective equipment (PPE) and powered air-purifying respirator (PAPR) and the restriction in the number of resuscitation personnel on airway management during the SARS crisis. Data was collected prospectively through an ongoing emergency airway registry. The data was divided into three periods: (1) before PPE was instituted from 1 November 2002 to 31 March 2003; (2) during SARS (when PPE use was mandatory) from 1 April to 31 July 2003; (3) post-SARs (when PPE use was non-mandatory but encouraged) from 1 August to 31 March 2004. There was no change in patient demographics during the three periods. There were significant increases in the proportion of resuscitation cases and airway interventions during the SARS period compared to the pre-SARS period. The resident medical officer intubation rate decreased from 45.1% pre-SARS to 35.2% during SARS and 17.7% post-SARS. The complication rates were 10.5%, 9.9% and 9.4% in periods 1–3, respectively. Restriction in the number of healthcare staff attending to each patient may have influenced the department's decision to allow only the most confident or experienced personnel to manage the airway. The exposure of junior medical officers in emergency airway management during SARS and the immediate post-SARS period was decreased. This trend should be monitored further and intervention may be necessary should it continue to decline.


title: Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque

text: Development of therapeutic agents for severe acute respiratory syndrome (SARS) viral infection using short interfering RNA (siRNA) inhibitors exemplifies a powerful new means to combat emerging infectious diseases. Potent siRNA inhibitors of SARS coronavirus (SCV) in vitro were further evaluated for efficacy and safety in a rhesus macaque (Macaca mulatta) SARS model using clinically viable delivery while comparing three dosing regimens. Observations of SARS-like symptoms, measurements of SCV RNA presence and lung histopathology and immunohistochemistry consistently showed siRNA-mediated anti-SARS efficacy by either prophylactic or therapeutic regimens. The siRNAs used provided relief from SCV infection–induced fever, diminished SCV viral levels and reduced acute diffuse alveoli damage. The 10–40 mg/kg accumulated dosages of siRNA did not show any sign of siRNA-induced toxicity. These results suggest that a clinical investigation is warranted and illustrate the prospects for siRNA to enable a massive reduction in development time for new targeted therapeutic agents. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1280) contains supplementary material, which is available to authorized users.


title: X-ray Structure of Main Protease of the Novel Coronavirus SARS-CoV-2 Enables Design of α-Ketoamide Inhibitors

text: A novel coronavirus has been identified as the causative agent of a massive outbreak of atypical pneumonia originating at Wuhan, Hubei province, China. Involved in the formation of the coronavirus replication complex, the viral main protease (Mpro, also called 3CLpro) represents an attractive target for therapy. We determined the crystal structure of the unliganded Mpro at 1.75 Å resolution and used this structure to guide optimization of a series of alpha-ketoamide inhibitors. The main goal of the optimization efforts was improvement of the pharmacokinetic properties of the compounds. We further describe 1.95- and 2.20-Å crystal structures of the complex between the enzyme and the most potent alpha-ketoamide optimized this way. These structures will form the basis for further development of these compounds to antiviral drugs.


title: Modelling the skip-and-resurgence of Japanese encephalitis epidemics in Hong Kong

text: Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne virus, persisting in pigs, Ardeid birds and Culex mosquitoes. It is endemic to China and Southeastern Asia. The case-fatality ratio (CFR) or the rate of permanent psychiatric sequelae is 30% among symptomatic patients. There were no reported local JEV human cases between 2006 and 2010 in Hong Kong, but it was followed by a resurgence of cases from 2011 to 2017. The mechanism behind this “skip-and-resurgence” patterns is unclear. This work aims to reveal the mechanism behind the “skip-and-resurgence” patterns using mathematical modelling and likelihood-based inference techniques. We found that pig-to-pig transmission increases the size of JEV epidemics but is unlikely to maintain the same level of transmission among pigs. The disappearance of JEV human cases in 2006–2010 could be explained by a sudden reduction of the population of farm pigs as a result of the implementation of the voluntary “pig-rearing licence surrendering” policy. The resurgence could be explained by of a new strain in 2011, which increased the transmissibility of the virus or the spill-over ratio from reservoir to host or both.


title: Comparison of the prevalence of enteric viruses in healthy dogs and those with acute haemorrhagic diarrhoea by electron microscopy

text: Objectives: To evaluate prevalence of enteric viruses in healthy dogs and to compare it with prevalences in dogs with acute haemorrhagic diarrhoea. Methods: Faecal samples were collected from 200 healthy dogs and examined by electron microscopy for presence of viral particles. Data were compared with viral prevalences that had been determined retrospectively by electron microscopy for 936 dogs with acute haemorrhagic diarrhoea. Results: There were significantly more negative faecal samples among the healthy dogs (82·0 per cent) compared with 55·8 per cent in dogs with acute haemorrhagic diarrhoea (P<0·001). With a prevalence of 17·5 per cent, significantly more healthy dogs were shedding coronavirus compared with 11·6 per cent in dogs with acute haemorrhagic diarrhoea (P=0·034). Parvovirus was only detected in one healthy dog (0·5 per cent), thus with a prevalence that was significantly lower than 16·0 per cent detected in the dogs with acute haemorrhagic diarrhoea (P<0·001). Paramyxovirus was not found in any of the healthy dogs but was found in 9·3 per cent of dogs with acute haemorrhagic diarrhoea (P<0·001). Clinical Significance: Results suggest that shedding of parvovirus and paramyxovirus is strongly associated with acute haemorrhagic diarrhoea. However, coronavirus seems to be even more prevalent among healthy dogs, raising the need for further studies to investigate the strain‐associated pathogenicity of this virus.


title: Sharing of fake news on social media: Application of the honeycomb framework and the third-person effect hypothesis

text: Abstract Sharing of fake news on social media platforms is a global concern, with research offering little insight into the motives behind such sharing. This study adopts a mixed-method approach to explore fake-news sharing behaviour. To begin with, qualitative data from 58 open-ended essays was analysed to identify six behavioural manifestations associated with sharing fake news. Thereafter, research model hypothesizing the association between these behaviours was proposed using the honeycomb framework and the third-person effect hypothesis. Age and gender were the control variables. Two data sets obtained from cross-sectional surveys with 471 and 374 social media users were utilized to test the proposed model. The study results suggest that instantaneous sharing of news for creating awareness had positive effect on sharing fake news due to lack of time and religiosity. However, authenticating news before sharing had no effect on sharing fake news due to lack of time and religiosity. The study results also suggest that social media users who engage in active corrective action are unlikely to share fake news due to lack of time. These results have significant theoretical and practical implications.


Challenges and issues about organising a hospital to respond to the COVID-19 outbreak: experience from a French reference centre


title: Viroporin activity of murine hepatitis virus E protein

text: The viroporin activity of the E protein from murine hepatitis virus (MHV), a member of the coronaviruses, was analyzed. Viroporins are a growing family of viral proteins able to enhance membrane permeability, promoting virus budding. Initially, the MHV E gene was inducibly expressed in Escherichia coli cells, leading to the arrest of bacterial growth, cell lysis and permeabilization to different compounds. Thus, exit of labeled nucleotides from E. coli cells to the cytoplasm was apparent upon expression of MHV E. In addition, enhanced entry of the antibiotic hygromycin B occurred at levels comparable to those observed with the viroporin 6K from Sindbis virus. Mammalian cells are also readily permeabilized by the expression of MHV E protein. Finally, brefeldin A powerfully blocks the viroporin activity of the E protein in BHK cells, suggesting that an intact vesicular system is necessary for this coronavirus to permeabilize mammalian cells.


title: Use of National Pneumonia Surveillance to Describe Influenza A(H7N9) Virus Epidemiology, China, 2004–2013

text: In mainland China, most avian influenza A(H7N9) cases in the spring of 2013 were reported through the pneumonia of unknown etiology (PUE) surveillance system. To understand the role of possible underreporting and surveillance bias in assessing the epidemiology of subtype H7N9 cases and the effect of live-poultry market closures, we examined all PUE cases reported from 2004 through May 3, 2013. Historically, the PUE system was underused, reporting was inconsistent, and PUE reporting was biased toward A(H7N9)-affected provinces, with sparse data from unaffected provinces; however, we found no evidence that the older ages of persons with A(H7N9) resulted from surveillance bias. The absolute number and the proportion of PUE cases confirmed to be A(H7N9) declined after live-poultry market closures (p<0.001), indicating that market closures might have positively affected outbreak control. In China, PUE surveillance needs to be improved.


title: Emergence of Novel Human Infections: New Insights and New Challenges

text: Abstract Novel human infections have continued to emerge over the past decade. Their presentation, epidemiology, and microbiology have shifted the paradigms of traditional science. In particular insights into nongenetic or paragenetic mechanisms (plasmid mediated), modes of infection have challenged biology. In reviewing the new challenges posed by these emergent events, new technologies promise some answers; however, global health security against pandemic threats, particularly given the uneven distribution of global resources for prevention, detection, and response, remains a critical area of challenge.


title: Épidémiologie des pneumopathies communautaires de l'enfant. Données actuelles

text: Summary Viruses, particularly syncitial respiratory virus, are the main aetiology of community-acquired lower respiratory tract infections in infants, while bacterial agents are more frequently responsible in children older than 3 years. Antimicrobial therapy must take into account the development of reduced susceptibility of penicillin to strains of Straptoccocus pneumoniae and Haemophilus influenzae with β-lactamase, and high frequency of Mycoplasma pneumoniae and Chlamydia pneumoniae infections. Although the mortality rate has remained low in France, the morbidity appeared to increase in recent years.


title: Sustainability research in business-to-business markets: An agenda for inquiry

text: Abstract Corporate interest in the topic of sustainability has increased in prominence. Most of the research on sustainability has a business-to-consumer focus, with limited research emphasizing sustainability in the context of business-to-business marketing. The paper examines research on sustainability, published in the journal Industrial Marketing Management, where thirty-eight articles have appeared in the past twenty-seven years, the majority on supply-chain research. Research on sustainability in business-to-business markets is sparse, and some of the fundamental research questions in this area have gone unaddressed. This paper addresses three interrelated research issues associated with sustainability in business-to-business markets. First, what research is available to researchers and practitioners? Second, what framework can be used to examine sustainability research in business-to-business markets? Third, what subareas of sustainability research need focus and deeper examination, and what are the associated research questions? Overall, the findings from this paper suggest the need for additional research in the area because of its substantial implications for theory, research, and practice.


title: Sialic acid-specific lectins: occurrence, specificity and function

text: Sialic acids consist of a family of acidic ninecarbon sugars that are typically located at the terminal positions of a variety of glycoconjugates. Naturally occurring sialic acids show an immense diversity of structure, and this reflects their involvement in a variety of biologically important processes. One such process involves the direct participation of sialic acids in recognition events through specific interactions with lectins, a family of proteins that recognise and bind sugars. This review will present a detailed overview of our current knowledge regarding the occurrence, specificity and function of sialic acid-specific lectins, particularly those that occur in viruses, bacteria and non-vertebrate eukaryotes.


title: Virus-based vectors for gene expression in mammalian cells: Coronavirus

text: Publisher Summary The coronavirus and the torovirus genera form the Coronaviridae family, which is closely related to the Arteriviridae family. Both families are included in the Nidovirales order. Recently, a new group of invertebrate viruses, the Roniviridae, with a genetic structure and replication strategy similar to those of coronaviruses, has been described. This new virus family has been included within the Nidovirales. Coronaviruses have several advantages as vectors over other viral expression systems: (1) coronaviruses are single-stranded RNA viruses that replicate within the cytoplasm without a DNA intermediary, making integration of the virus genome into the host cell chromosome unlikely, (2) these viruses have the largest RNA virus genome and, in principle, have room for the insertion of large foreign genes, (3) a pleiotropic secretory immune response is best induced by the stimulation of gut-associated lymphoid tissues, (4) the tropism of coronaviruses may be modified by manipulation of the spike (S) protein allowing engineering of the tropism of the vector, (5) non-pathogenic coronavirus strains infecting most species of interest (human, porcine, bovine, canine, feline, and avian) are available to develop expression systems, and (6) infectious coronavirus cDNA clones are available to design expression systems. Within the coronavirus two types of expression vectors have been developed: one requires two components (helper–dependent expression system) and the other a single genome that is modified either by targeted recombination or by engineering a cDNA encoding an infectious RNA. This chapter focuses on the advantages and limitations of these coronavirus expression systems, the attempts to increase their expression levels by studying the transcription-regulating sequences (TRSs), and the proven possibility of modifying their tissue and species-specificity.


title: Real-time RT-PCR detection of Bovine Viral Diarrhoea virus in whole blood using an external RNA reference

text: Abstract A novel two-step real-time RT-PCR assay using SYBR® Green I was developed for the detection of acute Bovine Viral Diarrhoea virus (BVDV) infection in whole blood from cattle. During infection animals experience a characteristic transient leucopenia and the number of cells per volume of blood changes over time; so quantitation of viral load by reference to a cellular housekeeping gene is not ideal as this may hide significant animal to animal variation. Therefore, to facilitate comparison of different samples, an external RNA reference was used for normalisation whereby each sample was spiked with the RNA virus, Canine Enteric Coronavirus (CECov), prior to RNA extraction, for comparative purposes. Real-time RT-PCR was carried out with two primer sets designed to amplify either a 156bp region of the BVDV 5′-UTR or a 280bp region of the CECov nucleocapsid protein gene. Linearity and efficiency of the assay was established and the method assessed using samples from BVDV-challenged calves. Viral RNA was quantified on days 6 and 14 post-challenge by real-time RT-PCR. Infectious virus isolation by traditional cell culture was negative after day 7. This study demonstrates encouraging results for rapid, sensitive and reliable detection of acute BVDV infection and provides an alternative real-time RT-PCR method for use on whole blood samples or samples where suitable housekeeping genes are not available.


title: Structural polypeptides of the enteropathogenic bovine coronavirus strain LY-138

text: The bovine coronavirus strain LY-138 was purified by differential as well as velocity and isopycnic centrifugation in sucrose or CsCl gradients. The substrate for purification was contents of the small intestine of experimentally inoculated calves. This strain is highly enteropathogenic, but it could not yet be propagated in cultured cells. Intact virions had a density of 1.245 g/cm(3) in CsCl and 1.185 g/cm(3) in sucrose. A spherical core-like structure with an average diameter of 82 nm remaining after treatment with chloroform had a density of 1.299 g/cm(3) in CsCl and 1.201 g/cm(3) in sucrose. Seven distinct bands of polypeptides and 4 shoulders were detected after electrophoresis of SDS-solubilized virions in polyacrylamide gels. The approximate molecular weights ranged from 110,000 to 36,000. Four of the bands gave a PAS positive reaction. These 4 glycoproteins and an additional protein with an approximate molecular weight of 70,000 were removed by chloroform treatment. The remaining core-like structure contained the 2 polypeptides VP3 and VP7.


Can COVID-19 related mental health issues be measured?: Assessment options for mental health professionals


title: Anti-infective monoclonal antibodies: perils and promise of development

text: So far, most monoclonal antibodies have been developed for treating cancer or immunological diseases. However, the global spread of infections such as West Nile and corona viruses, and the need to address the potential threat of bioterrorism, has boosted public interest in, and government support of, counter-measures for infectious diseases. The attractive features of monoclonal antibodies, such as high specificity and effective recruitment of the immune system, would seem to make them excellent candidates as anti-infective agents. Here, we analyse trends in the development and approval of anti-infective monoclonal antibodies, and discuss factors that influence their success.


title: SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine “storm” and risk factor for damage of hematopoietic stem cells

text: The scientific community faces an unexpected and urgent challenge related to the SARS-CoV-2 pandemic and is investigating the role of receptors involved in entry of this virus into cells as well as pathomechanisms leading to a cytokine “storm,” which in many cases ends in severe acute respiratory syndrome, fulminant myocarditis and kidney injury. An important question is if it may also damage hematopoietic stem progenitor cells?


title: Identification of an indol-based derivative as potent and selective varicella zoster virus (VZV) inhibitor

text: We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the indole nucleus. Modifications of this template through Mannich and Friedel-Crafts reactions, coupled with nucleophilic displacement and reductive aminations led to 23 final derivatives, which were pharmacologically tested. Tryptamine derivative 17a was found to have a selective inhibitory activity against human varicella zoster virus (VZV) replication in vitro, being inactive against a variety of other DNA and RNA viruses. A structure-activity relationship (SAR) study showed that the presence of a biphenyl ethyl moiety and the acetylation at the amino group of tryptamine are a prerequisite for anti-VZV activity. The novel compound shows the same activity against thymidine kinase (TK)-competent (TK(+)) and TK-deficient (TK(−)) VZV strains, pointing to a novel mechanism of antiviral action.


title: Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients

text: BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-017-0672-0) contains supplementary material, which is available to authorized users.


title: A Decentralized Molecular Diagnostic Testing Plan for Pandemic Influenza in the Ontario Public Health Laboratory System

text: The Ontario Public Health Laboratories system (OPHL) is in the midst of a six-year plan to implement molecular tools for pandemic influenza diagnostics in one central and three regional public health laboratories. This plan has been formulated as a consequence of: 1) experiences gained through severe acute respiratory syndrome (SARS), and comments of the members of the Expert Panel on SARS and Infectious Disease Control (i.e., the Walker report); 2) a review of pandemic preparedness literature; 3) historical and epidemiologic discussions about previous pandemics; and 4) suggestions made by various pandemic working committees. The OPHL plan includes: 1) an aggressive restructuring of the overall molecular microbiology testing capacity of the OPHL; 2) the ability to shift influenza testing of samples between designated OPHL laboratories; and 3) the development of screening tools for pandemic influenza diagnostic tests. The authors believe that investing in increased molecular testing capacity for regional laboratories outside the greater Toronto area will be beneficial to the OPHL system whether or not an influenza pandemic occurs. Well-trained technologists and microbiologists, and the introduction of new technologies, will facilitate the development of a wide variety of molecular tests for other infectious diseases at public health laboratories geographically distant from Toronto, thus enhancing overall laboratory testing capacity in the province of Ontario.


title: Suppression of PmRab11 inhibits YHV infection in Penaeus monodon

text: Abstract Yellow head virus (YHV) is one of the most serious pathogens that causes worldwide shrimp production loss. It enters the cells via clathrin-mediated endocytosis and utilizes small GTPase Rab proteins such as PmRab5 and PmRab7 for intracellular trafficking. In this study, molecular cloning and functional analysis of Rab11 during YHV infection were investigated. PmRab11 cDNA was cloned by Rapid amplification of cDNA ends (RACEs). It contained two forms of sizes 1200 and 1050 bp distinct at the 5ʹ UTR. The coding region of PmRab11 was 645 bp, encoding 214 amino acids. It also demonstrated the characteristics of Rab11 proteins containing five GTP-binding domains, five Rab family domains, four Rab subfamily domains and a prenylation site at the C-terminus. Suppression of PmRab11 using dsRNA-PmRab11 either before or after YHV-challenge resulted in significant inhibition of YHV levels in the hemocytes and viral release in the supernatant in both mRNA and protein levels. In addition, the silencing effect of PmRab11 in YHV-infected shrimps resulted in a delay in shrimp mortality for at least 2 days. Immunofluorescence study showed co-localization between PmRab11 and YHV at 24–72 h post YHV-challenge. In contrast, the co-localization signals were absence in the PmRab11 knockdown hemocytes and the YHV signals accumulated at the perinuclear region at 24 h post YHV-challenge. Then, accumulation of YHV was hardly observed after 48–72 h. These results suggested that PmRab11 is required for YHV infection in shrimp.


title: Melatonin modulates the autophagic response in acute liver failure induced by the rabbit hemorrhagic disease virus

text: Autophagy is an important survival pathway and participates in the host response to infection. Beneficial effects of melatonin have been previously reported in an animal model of acute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). This study was aimed to investigate whether melatonin protection against liver injury induced by the RHDV associates to modulation of autophagy. Rabbits were infected with 2 × 10(4) hemagglutination units of a RHDV isolate and received 20 mg/kg melatonin at 0, 12, and 24 hr postinfection. RHDV induced autophagy, with increased expression of beclin‐1, ubiquitin‐like autophagy‐related (Atg)5, Atg12, Atg16L1 and sequestrosome 1 (p62/SQSTM1), protein 1 light chain 3 (LC3) staining, and conversion of LC3‐I to autophagosome‐associated LC3‐II. These effects reached a maximum at 24 hr postinfection, in parallel to extensive colocalization of LC3 and lysosome‐associated membrane protein (LAMP)‐1. The autophagic response induced by RHDV infection was significantly inhibited by melatonin administration. Melatonin treatment also resulted in decreased immunoreactivity for RHDV viral VP60 antigen and a significantly reduction in RHDV VP60 mRNA levels, oxidized to reduced glutathione ratio (GSSG/GSH), caspase‐3 activity, and immunoglobulin‐heavy‐chain‐binding protein (BiP) and CCAAT/enhancer‐binding protein homologous protein (CHOP) expression. Results indicate that, in addition to its antioxidant and antiapoptotic effects, and the suppression of ER stress, melatonin induces a decrease in autophagy associated with RHDV infection and inhibits RHDV RNA replication. Results obtained reveal novel molecular pathways accounting for the protective effect of melatonin in this animal model of ALF.


title: Paulownia C-geranylated flavonoids: their structural variety, biological activity and application prospects

text: Paulownia species, especially their flowers and fruits, are traditionally used in Chinese herbal medicines for the treatment of infectious diseases. C-geranylated flavonoids were found to be the major special metabolites in Paulownia flowers and fruits, and 76 C-geranylated flavonoids had been isolated and characterized thus far. Structural variations in Paulownia C-geranylated flavonoids are mainly due to the complicated structural modifications in their geranyl substituents. These natural compounds have attracted much attention because of their various biological activities, including antioxidation, anti-inflammation, cytotoxic activity and various enzymatic inhibitions, etc. Among them, diplacone, a major Paulownia component, was considered to have promise for applications in medicine. This paper summarizes the information from current publications on Paulownia C-geranylated flavonoids, with a focus on their structural variety, key spectroscopic characteristics, biological activity with structure–activity relationships and application prospects. We hope that this paper will stimulate further investigations of Paulownia species and this kind of natural product.


Chapter 1 Rational Approach to Diagnosing and Managing Infectious Causes of Diarrhea in Kittens


title: Appropriate Use and Future Directions of Molecular Diagnostic Testing

text: PURPOSE OF REVIEW: Major technologic advances in two main areas of molecular infectious disease diagnostics have resulted in accelerated adoption or ordering, outpacing implementation, and clinical utility studies. Physicians must understand the limitations to and appropriate utilization of these technologies in order to provide cost-effective and well-informed care for their patients. RECENT FINDINGS: Rapid molecular testing and, to a lesser degree, clinical metagenomics are now being routinely used in clinical practice. While these tests allow for a breadth of interrogation not possible with conventional microbiology, they pose new challenges for diagnostic and antimicrobial stewardship programs. This review will summarize the most recent literature on these two categories of technologic advances and discuss the few studies that have looked at utilization and stewardship approaches. This review also highlights the future directions for both of these technologies. SUMMARY: The appropriate utilization of rapid molecular testing and clinical metagenomics has not been well established. More studies are needed to assess their prospective impacts on patient management and antimicrobial stewardship efforts as the future state of infectious disease diagnostics will see continued expansion of these technologic advances.


title: Cerebral Microhemorrhage and Purpuric Rash in COVID-19: The Case for a Secondary Microangiopathy

text: INTRODUCTION: Since the emergence of Coronavirus Disease 19 (COVID-19) pandemic, multiple neurologic complications in infected patients have been reported. Despite these reports, the mechanism of COVID-19 nervous system injury is not well understood. We report the case of a COVID-19 patient with diffuse microhemorrhages on brain MRI, positive anticardiolipin antibodies, and purpuric rash with biopsy showing a thrombotic vasculopathy, all features suggestive of secondary microangiopathy. CASE REPORT: A 69-year-old male with history of hypertension, chronic kidney disease, and hypothyroidism presented with one week of dyspnea, cough, diarrhea, and fevers. Chest x-ray demonstrated bibasilar consolidations and nasopharyngeal reverse transcriptase polymerase chain reaction confirmed SARS-CoV-2 infection. He had subsequent respiratory decline requiring intubation the day after admission. He developed a truncal morbilliform rash and diffuse purpura, a biopsy of which showed small dermal blood vessels with intraluminal microthrombi consistent with thrombotic vasculopathy. He was found to have elevated aCL IgM and IgG and equivocal lupus anticoagulant study. Brain MRI obtained for persistent encephalopathy showed innumerable areas of susceptibility weighted imaging changes throughout the bilateral juxtacortical white matter, corpus callosum, basal ganglia, and brainstem, as well as multiple small areas of FLAIR hyperintensities, consistent with microhemorrhage DISCUSSION: While there have been several reported cases of neurologic manifestations of COVID-19, the pathophysiology may not be related to neurotropism of the virus itself. The new development of antiphospholipid antibodies and thrombotic vasculopathy in dermal blood vessels in this patient suggest a secondary microangiopathy potentially related to a virally-induced inflammatory state.


title: COVID-19 in people with multiple sclerosis: A global data sharing initiative

text: BACKGROUND: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. OBJECTIVES: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. METHODS: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. RESULTS: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. CONCLUSIONS: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.


title: Next-generation direct-acting influenza therapeutics

text: Influenza viruses are a major threat to human health globally. In addition to further improving vaccine prophylaxis, disease management through antiviral therapeutics constitutes an important component of the current intervention strategy to prevent advance to complicated disease and reduce case-fatality rates. Standard-of-care is treatment with neuraminidase inhibitors that prevent viral dissemination. In 2018, the first mechanistically new influenza drug class for the treatment of uncomplicated seasonal influenza in 2 decades was approved for human use. Targeting the PA endonuclease subunit of the viral polymerase complex, this class suppresses viral replication. However, the genetic barrier against viral resistance to both drug classes is low, pre-existing resistance is observed in circulating strains, and resistant viruses are pathogenic and transmit efficiently. Addressing the resistance problem has emerged as an important objective for the development of next-generation influenza virus therapeutics. This review will discuss the status of influenza therapeutics including the endonuclease inhibitor baloxavir marboxil after its first year of clinical use and evaluate a subset of direct-acting antiviral candidates in different stages of preclinical and clinical development.


title: Exploring the Active Compounds of Traditional Mongolian Medicine in Intervention of Novel Coronavirus (COVID-19) Based on Molecular Docking Method

text: OBJECTIVE: This article intends to use molecular docking technology to find potential inhibitors that can respond to COVID-19 from active compounds in Mongolian medicine. METHODS: Mongolian medicine with anti-inflammatory and antiviral effects is selected from Mongolian medicine prescription preparations. TCMSP, ETCM database and document mining methods were used to collect active compounds. Swiss TargetPrediction and SuperPred server were used to find targets of compounds with smiles number. Drugbank and Genecard database were used to collect antiviral drug targets. Then the above targets were compared and analyzed to screen out antiviral targets of Mongolia medicine. Metascape database platform was used to enrich and analyze the GO (Gene ontology) annotation and KEGG pathway of the targets. In view of the high homology of gene sequences between SARS-CoV-2 S-protein RBD domain and SARS virus, as well as their similarities in pathogenesis and clinical manifestations, we established SARS-CoV-2 S-protein model using Swiss-Model. The ZDOCK protein docking software was applied to dock the S-protein with the human angiotensin ACE2 protein to find out the key amino acids of the binding site. Taking ACE2 as the receptor, the molecular docking between the active ingredients and the target protein was studied by AutoDock molecular docking software. The interaction between ligand and receptor is applied to provide a choice for screening anti-COVID-19 drugs. RESULTS: A total of 253 active components were predicted. Metascape analysis showed that key candidate targets were significantly enriched in multiple pathways related to different toxins. These key candidate targets were mainly derived from phillyrin and chlorogenic acid. Through the protein docking between S-protein and ACE2, it is found that Glu329/Gln325 and Gln42/Asp38 in ACE2 play an important role in the binding process of the two. The results of molecular docking virtual calculation showed that phillyrin and chlorogenic acid could stably combine with Gln325 and Gln42/Asp38 in ACE2, respectively, which hindered the combination between S- protein and ACE2. CONCLUSION: Phillyrin and chlorogenic acid can effectively prevent the combination of SARS-CoV-2 S-protein and ACE2 at the molecular level. Phillyrin and chlorogenic acid can be used as potential inhibitors of COVID-19 for further research and development.


BACKGROUND: A variety of in-service emergency care training courses are currently being promoted as a strategy to improve the quality of care provided to seriously ill newborns and children in low-income countries. Most courses have been developed in high-income countries. However, whether these courses improve the ability of health professionals to provide appropriate care in low-income countries remains unclear. This is the first update of the original review. OBJECTIVES: To assess the effects of in-service emergency care training on health professionals' treatment of seriously ill newborns and children in low-income countries. SEARCH METHODS: For this update, we searched the Cochrane Database of Systematic Reviews, part of The Cochrane Library (http://www.cochranelibrary.com); MEDLINE, Ovid SP; EMBASE, Ovid SP; the Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library (http://www.cochranelibrary.com) (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register); Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Knowledge/Science and eight other databases. We performed database searches in February 2015. We also searched clinical trial registries, websites of relevant organisations and reference lists of related reviews. We applied no date, language or publication status restrictions when conducting the searches. SELECTION CRITERIA: Randomised trials, non-randomised trials, controlled before and after studies and interrupted-time-series studies that compared the effects of in-service emergency care training versus usual care were eligible for inclusion. We included only hospital-based studies and excluded community-based studies. Two review authors independently screened and selected studies for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study risk of bias and confidence in effect estimates (certainty of evidence) for each outcome using GRADE (Grades of Recommendation, Assessment, Development and Evaluation). We described results and presented them in GRADE tables. MAIN RESULTS: We identified no new studies in this update. Two randomised trials (which were included in the original review) met the review eligibility criteria. In the first trial, newborn resuscitation training compared with usual care improved provider performance of appropriate resuscitation (trained 66% vs usual care 27%, risk ratio 2.45, 95% confidence interval (CI) 1.75 to 3.42; moderate certainty evidence) and reduced inappropriate resuscitation (trained mean 0.53 vs usual care 0.92, mean difference 0.40, 95% CI 0.13 to 0.66; moderate certainty evidence). Effect on neonatal mortality was inconclusive (trained 28% vs usual care 25%, risk ratio 0.77, 95% CI 0.40 to 1.48; N = 27 deaths; low certainty evidence). Findings from the second trial suggest that essential newborn care training compared with usual care probably slightly improves delivery room newborn care practices (assessment of breathing, preparedness for resuscitation) (moderate certainty evidence). AUTHORS' CONCLUSIONS: In-service neonatal emergency care courses probably improve health professionals' treatment of seriously ill babies in the short term. Further multi-centre randomised trials evaluating the effects of in-service emergency care training on long-term outcomes (health professional practice and patient outcomes) are needed. PLAIN LANGUAGE SUMMARY: In-service training for health professionals to improve care of seriously ill newborns and children in low-income countries WHAT QUESTION WAS THE REVIEW ASKING? This is the first update of the original Cochrane review, whose objective was to find out whether additional emergency care training programmes can improve the ability of health workers in poor countries to care for seriously ill newborns and children admitted to hospitals. Researchers at The Cochrane Collaboration searched for all studies that could answer this question and found two relevant studies. WHAT ARE THE KEY MESSAGES? The review authors suggest that giving health professionals in poor countries additional training in emergency care probably improves their ability to care for seriously ill newborns. We need additional high-quality studies, including studies in which health professionals are trained to care for seriously ill older children. BACKGROUND: TRAINING HEALTH PROFESSIONALS TO CARE FOR SERIOUSLY ILL BABIES AND CHILDREN: In poor countries, many babies and children with serious illnesses die even though they have been cared for in hospitals. One reason for this may be that health workers in these countries often are not properly trained to offer the care that these children need. In poor countries, children often become seriously ill because of conditions such as pneumonia, meningitis and diarrhoea, and may need emergency care. For newborn babies, the most common reason for emergency care is too little oxygen to the baby during birth. If this goes on for too long, the person delivering the baby has to help the baby breathe, and sometimes has to get the baby's heart rate back to normal. This is called neonatal resuscitation. Neonatal resuscitation is a skilled task, and the health worker needs proper training. As babies need to be resuscitated quickly, the health worker needs to know how to prepare for this before the baby is born. For instance, he or she needs to know how to prepare the room and proper equipment. Health workers in poor countries often do not have these skills, and these babies are likely to die. Babies can also be harmed if the health worker does not resuscitate the baby correctly. Several training programmes have been developed to teach health workers how to give emergency care to seriously ill babies and children. But most of these have been developed and tested in wealthy countries, and we don't know whether they would work in poor countries. WHAT HAPPENS WHEN HEALTH PROFESSIONALS IN POOR COUNTRIES ARE GIVEN EXTRA TRAINING? The review authors found two relevant studies. These studies compared the practices of health professionals who had been given extra training in the care of newborns with the practices of health professionals who did not receive extra training. In the first study, nurses at a maternity hospital in Kenya completed a one-day training course on how to resuscitate newborn babies. This course was adapted from the UK Resuscitation Council, and it included lectures and practical training. The study suggests that after these training courses: health professionals are probably more likely to resuscitate newborn babies correctly (moderate certainty of the evidence); and newborn babies may be less likely to die while being resuscitated (low certainty of the evidence). In the second study, doctors, nurses and midwives in five Sri Lankan hospitals were given a four-day training course on how to prepare for and provide care for newborns. This course was adapted from the World Health Organization (WHO) Training Modules on Essential Newborn Care and Breastfeeding, and included lectures, demonstrations, hands-on training and small group discussions. This study suggests that after these training courses: health professionals probably are more likely to be well prepared to resuscitate newborn babies (moderate certainty of the evidence). Unfortunately, the two studies followed up with health professionals for only two to three months after they received training. We therefore don't know if the benefits of the training courses lasted over time. The review authors found no studies that looked at the effects of training programmes on the care of older children. HOW UP-TO-DATE IS THIS REVIEW? Review authors searched for studies that had been published up to February 2015.


title: The Use of Non‐Immune Plasma Powder in the Prophylaxis of Neonatal Escherichia coli Diarrhoea in Calves

text: The protective use of plasma powder from cattle and swine against experimentally induced neonatal E. coli diarrhoea in colostrum‐deprived calves was examined. Diarrhoea was induced with a strain expressing F5(+) fimbriae and a strain expressing F17(+) fimbriae. In all groups supplemented with bovine plasma powder, diarrhoea and fever were less severe than in the control groups. For the groups infected with the F5(+) E. coli strain, a reduction in excretion of the challenge strain by 2–4 orders of magnitude and by 1–2 orders of magnitude was seen when supplemented with bovine plasma powder at a dose of 25 g/l milk and 10 g/l milk, respectively. The bovine plasma powder showed also beneficial effects in the F17(+) infected groups. No mortality, no septicaemia and no severe clinical signs were observed. Concerning the excretion of the E. coli F17(+) strain in the faeces, no significant difference with the control group was found. Swine plasma powder showed little beneficial effect on E. coli diarrhoea in calves in this study.


title: Middle East Respiratory Syndrome coronavirus (MERS CoV): Update 2013

text: Middle East Respiratory Syndrome coronavirus (MERS CoV) came to attention as an emerging pathogen causing severe respiratory illness in patients from the Middle East in September 2012. As of 14 June 2013, 58 human cases of MERS CoV infection have been confirmed, including 33 deaths (case fatality rate of 57%). MERS CoV is a beta-coronavirus, in the same family as SARS-CoV, and shares a probable origin from bats. No animal reservoir or intermediates have been definitely implicated in transmission. Limited human-to-human transmission has occurred within several clusters, as individuals without a recent travel history have become infected after exposure to an ill returned traveler.


title: Doubling Time of the COVID-19 Epidemic by Chinese Province

text: COVID-19 epidemic doubling time by Chinese province was increasing from January 20 through February 9, 2020. The harmonic mean of the arithmetic mean doubling time estimates ranged from 1.4 (Hunan, 95% CI, 1.2–2.0) to 3.1 (Xinjiang, 95% CI, 2.1–4.8), with an estimate of 2.5 days (95% CI, 2.4–2.6) for Hubei.


Infection à SARS-CoV-2/COVID 19 et cancers solides : synthèse des recommandations à l’attention des professionnels de santé


title: TN curve: A novel 3D graphical representation of DNA sequence based on trinucleotides and its applications

text: Abstract In this paper, a novel 3D graphical representation of DNA sequence based on trinucleotides is proposed. This representation allows direct inspection of composition as well as distribution of trinucleotides in DNA sequence for the first time and avoids loss of information, from which one can obtain more information. Based on this novel model, six numerical descriptors of DNA sequence are deduced without complicated calculations, and the applications in similarities/dissimilarities analysis of coding sequences and conserved genes discrimination illustrate their utilities. In addition, two simple methods for similarities/dissimilarities analysis of coding sequences among different species are exploited by using two vectors composed of 64 and six components, respectively, which can provide convenient sequence alignment tools for both computational scientists and molecular biologists.


title: Systematic analysis of bicistronic reporter assay data

text: Bicistronic reporter assay systems have become a mainstay of molecular biology. While the assays themselves encompass a broad range of diverse and unrelated experimental protocols, the numerical data garnered from these experiments often have similar statistical properties. In general, a primary dataset measures the paired expression of two internally controlled reporter genes. The expression ratio of these two genes is then normalized to an external control reporter. The end result is a ‘ratio of ratios’ that is inherently sensitive to propagation of the error contributed by each of the respective numerical components. The statistical analysis of this data therefore requires careful handling in order to control for the propagation of error and its potentially misleading effects. A careful survey of the literature found no consistent method for the statistical analysis of data generated from these important and informative assay systems. In this report, we present a detailed statistical framework for the systematic analysis of data obtained from bicistronic reporter assay systems. Specifically, a dual luciferase reporter assay was employed to measure the efficiency of four programmed −1 frameshift signals. These frameshift signals originate from the L-A virus, the SARS-associated Coronavirus and computationally identified frameshift signals from two Saccharomyces cerevisiae genes. Furthermore, these statistical methods were applied to prove that the effects of anisomycin on programmed −1 frameshifting are statistically significant. A set of Microsoft Excel spreadsheets, which can be used as templates for data generated by dual reporter assay systems, and an online tutorial are available at our website (http://dinmanlab.umd.edu/statistics). These spreadsheets could be easily adapted to any bicistronic reporter assay system.


title: Asymmetric Primaquine and Halogenaniline Fumardiamides as Novel Biologically Active Michael Acceptors

text: Novel primaquine (PQ) and halogenaniline asymmetric fumardiamides 4a–f, potential Michael acceptors, and their reduced analogues succindiamides 5a–f were prepared by simple three-step reactions: coupling reaction between PQ and mono-ethyl fumarate (1a) or mono-methyl succinate (1b), hydrolysis of PQ-dicarboxylic acid mono-ester conjugates 2a,b to corresponding acids 3a,b, and a coupling reaction with halogenanilines. 1-[bis(Dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) was used as a coupling reagent along with Hünig′s base. Compounds 4 and 5 were evaluated against a panel of bacteria, several Mycobacterium strains, fungi, a set of viruses, and nine different human tumor cell lines. p-Chlorofumardiamide 4d showed significant activity against Staphylococcus aureus, Streptococcus pneumoniae and Acinetobacter baumannii, but also against Candida albicans (minimum inhibitory concentration (MIC) 6.1–12.5 µg/mL). Together with p-fluoro and p-CF(3) fumardiamides 4b,f, compound 4d showed activity against Mycobacterium marinum and 4b,f against M. tuberculosis. In biofilm eradication assay, most of the bacteria, particularly S. aureus, showed susceptibility to fumardiamides. m-CF(3) and m-chloroaniline fumardiamides 4e and 4c showed significant antiviral activity against reovirus-1, sindbis virus and Punta Toro virus (EC(50) = 3.1–5.5 µM), while 4e was active against coxsackie virus B4 (EC(50) = 3.1 µM). m-Fluoro derivative 4a exerted significant cytostatic activity (IC(50) = 5.7–31.2 μM). Acute lymphoblastic leukemia cells were highly susceptible towards m-substituted derivatives 4a,c,e (IC(50) = 6.7–8.9 μM). Biological evaluations revealed that fumardiamides 4 were more active than succindiamides 5 indicating importance of Michael conjugated system.


title: Experimental Data-Mining Analyses Reveal New Roles of Low-Intensity Ultrasound in Differentiating Cell Death Regulatome in Cancer and Non-cancer Cells via Potential Modulation of Chromatin Long-Range Interactions

text: Background: The mechanisms underlying low intensity ultrasound (LIUS) mediated suppression of inflammation and tumorigenesis remain poorly determined. Methods: We used microarray datasets from NCBI GEO Dataset databases and conducted a comprehensive data mining analyses, where we studied the gene expression of 299 cell death regulators that regulate 13 different cell death types (cell death regulatome) in cells treated with LIUS. Results: We made the following findings: (1) LIUS exerts a profound effect on the expression of cell death regulatome in cancer cells and non-cancer cells. Of note, LIUS has the tendency to downregulate the gene expression of cell death regulators in non-cancer cells. Most of the cell death regulator genes downregulated by LIUS in non-cancer cells are responsible for mediating inflammatory signaling pathways; (2) LIUS activates different cell death transcription factors in cancer and non-cancer cells. Transcription factors TP-53 and SRF- were induced by LIUS exposure in cancer cells and non-cancer cells, respectively; (3) As two well-accepted mechanisms of LIUS, mild hyperthermia and oscillatory shear stress induce changes in the expression of cell death regulators, therefore, may be responsible for inducing LIUS mediated changes in gene expression patterns of cell death regulators in cells; (4) LIUS exposure may change the redox status of the cells. LIUS may induce more of antioxidant effects in non-cancer cells compared to cancer cells; and (5) The genes modulated by LIUS in cancer cells have distinct chromatin long range interaction (CLRI) patterns to that of non-cancer cells. Conclusions: Our analysis suggests novel molecular mechanisms that may be utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.


title: Isolation and Identification of Porcine Deltacoronavirus and Alteration of Immunoglobulin Transport Receptors in the Intestinal Mucosa of PDCoV-Infected Piglets

text: Porcine deltacoronavirus (PDCoV) is a porcine enteropathogenic coronavirus that causes watery diarrhea, vomiting, and frequently death in piglets, causing serious economic losses to the pig industry. The strain CHN-JS-2017 was isolated and identified by cytopathology, immunofluorescence assays, transmission electron microscopy, and sequence analysis. A nucleotide sequence alignment showed that the whole genome of CHN-JS-2017 is 97.4%–99.6% identical to other PDCoV strains. The pathogenicity of the CHN-JS-2017 strain was investigated in orally inoculated five-day-old piglets; the piglets developed acute, watery diarrhea, but all recovered and survived. CHN-JS-2017 infection-induced microscopic lesions were observed, and viral antigens were detected mainly by immunohistochemical staining in the small intestine. The neonatal Fc receptor (FcRn) and polymeric immunoglobulin receptor (pIgR) are crucial immunoglobulin (Ig) receptors for the transcytosis ofimmunoglobulin G (IgG), IgA, or IgM. Importantly, CHN-JS-2017 infected five-day-old piglets could significantly down-regulate the expression of FcRn, pIgR, and nuclear factor-kappa B (NF-κB)in the intestinal mucosa. Note that the level of FcRn mRNA in the intestinal mucosa of normal piglets is positively correlated with pIgR and NF-κB. At the same time, the expressions of FcRn, pIgR, and NF-κB mRNA are also positively correlated in infected piglets. These results may help explain the immunological and pathological changes associated with porcine deltacorononirus infection.


“COVID-19 and Obesity: Postoperative Risk in Patients Who Have Undergone Bariatric Surgery. Preliminary Report from High Volume Center in Italy (Lombardy)”


title: Use of Rapid Online Surveys to Assess People's Perceptions During Infectious Disease Outbreaks: A Cross-sectional Survey on COVID-19

text: BACKGROUND: Given the extensive time needed to conduct a nationally representative household survey and the commonly low response rate of phone surveys, rapid online surveys may be a promising method to assess and track knowledge and perceptions among the general public during fast-moving infectious disease outbreaks. OBJECTIVE: This study aimed to apply rapid online surveying to determine knowledge and perceptions of coronavirus disease 2019 (COVID-19) among the general public in the United States and the United Kingdom. METHODS: An online questionnaire was administered to 3000 adults residing in the United States and 3000 adults residing in the United Kingdom who had registered with Prolific Academic to participate in online research. Prolific Academic established strata by age (18-27, 28-37, 38-47, 48-57, or ≥58 years), sex (male or female), and ethnicity (white, black or African American, Asian or Asian Indian, mixed, or “other”), as well as all permutations of these strata. The number of participants who could enroll in each of these strata was calculated to reflect the distribution in the US and UK general population. Enrollment into the survey within each stratum was on a first-come, first-served basis. Participants completed the questionnaire between February 23 and March 2, 2020. RESULTS: A total of 2986 and 2988 adults residing in the United States and the United Kingdom, respectively, completed the questionnaire. Of those, 64.4% (1924/2986) of US participants and 51.5% (1540/2988) of UK participants had a tertiary education degree, 67.5% (2015/2986) of US participants had a total household income between US $20,000 and US $99,999, and 74.4% (2223/2988) of UK participants had a total household income between £15,000 and £74,999. US and UK participants’ median estimate for the probability of a fatal disease course among those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 5.0% (IQR 2.0%-15.0%) and 3.0% (IQR 2.0%-10.0%), respectively. Participants generally had good knowledge of the main mode of disease transmission and common symptoms of COVID-19. However, a substantial proportion of participants had misconceptions about how to prevent an infection and the recommended care-seeking behavior. For instance, 37.8% (95% CI 36.1%-39.6%) of US participants and 29.7% (95% CI 28.1%-31.4%) of UK participants thought that wearing a common surgical mask was “highly effective” in protecting them from acquiring COVID-19, and 25.6% (95% CI 24.1%-27.2%) of US participants and 29.6% (95% CI 28.0%-31.3%) of UK participants thought it was prudent to refrain from eating at Chinese restaurants. Around half (53.8%, 95% CI 52.1%-55.6%) of US participants and 39.1% (95% CI 37.4%-40.9%) of UK participants thought that children were at an especially high risk of death when infected with SARS-CoV-2. CONCLUSIONS: The distribution of participants by total household income and education followed approximately that of the US and UK general population. The findings from this online survey could guide information campaigns by public health authorities, clinicians, and the media. More broadly, rapid online surveys could be an important tool in tracking the public’s knowledge and misperceptions during rapidly moving infectious disease outbreaks.


title: Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic

text: BACKGROUND: To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic. METHODS: A survey conducted in 21 intensive care units in 17 provinces in China. RESULTS: Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001). CONCLUSION: Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.


title: Characterization of the nasopharyngeal viral microbiome from children with community‐acquired pneumonia but negative for Luminex xTAG respiratory viral panel assay detection

text: In the present study, 50 nasopharyngeal swabs from children with community‐acquired pneumonia (CAP) but negative for 18 common respiratory viruses, as measured by the Luminex xTAG Respiratory Viral Panel Assay, were subjected to multiplex metagenomic analyses using a next‐generation sequencing platform. Taxonomic analysis showed that all sequence reads could be assigned to a specific species. An average of 95.13% were assigned to the Bacteria kingdom, whereas, only 0.72% were potentially virus derived. This snapshot of the respiratory tract virome revealed most viral reads to be respiratory tract related, classified into four known virus families: Paramyxoviridae, Herpesviridae, Anelloviridae, and Polyomaviridae. Importantly, we detected a novel human parainfluenza virus 3 (HPIV 3) strain with a 32‐bp insertion in the haemagglutinin‐neuraminidase (HN) gene that produced a negative result in the Luminex assay, highlighting the strength of virome metagenomic analysis to identify not only novel viruses but also viruses likely to be missed by ordinary clinical tests. Thus, virome metagenomic analysis could become a viable clinical diagnostic method.


title: COVID-19 trials in Italy: A call for simplicity, top standards and global pooling

text: The novel coronavirus disease, affecting ~9 million people in the past five months and causing >460,000 deaths worldwide, is completely new to mankind. More than 2,000 research projects registered at ClinTrials.gov are aiming at finding effective preventive or curative treatments for rapid transfer to clinical practice.


title: Detection of Respiratory Viruses in Nasopharyngeal Swab and Adenoid Tissue from Children Submitted to Adenoidectomy: Pre- and Postoperative Analysis

text: Introduction The presence of respiratory viruses in lymphoid tissues of the nasopharynx and oropharynx and its impact on recurrent infections and hypertrophy of these tissues are not yet fully understood. Objective To identify and determine the prevalence of major respiratory viruses in nasopharyngeal secretions and adenoid tissue pre- and postoperatively of children undergoing adenoidectomy. Methods A prospective observational study was conducted in 36 patients under 12 years of age with upper airway lymphoid hypertrophy who were undergoing adenoidectomy, in which various respiratory viruses were investigated using real-time polymerase chain reaction in adenoid tissue and nasopharyngeal secretions collected preoperatively and 30 days postoperatively. Results At least 1 viral agent was isolated in any of the samples collected in 58.3% of children and 25.9% of total samples. Respiratory viruses were identified in 33.8% of preoperative nasopharyngeal specimens and in 19.8% of postoperative secretion. Of the 21 patients with positive results for any respiratory virus, 6 (28.6%) had more than 1 virus. Considering all 36 respiratory viruses found, the main agent isolated was rhinovirus (27.8%), followed by bocavirus (22.2%). Conclusion The virus found more frequently in all samples was rhinovirus. After removal of adenoid tissue, there was a decrease in the prevalence of the virus contained in nasopharyngeal secretion 30 days after surgery.


title: Effective block by pirfenidone, an antifibrotic pyridone compound (5-methyl-1-phenylpyridin-2[H-1]-one), on hyperpolarization-activated cation current: An additional but distinctive target

text: Pirfenidone (PFD), a pyridone compound, is well recognized as an antifibrotic agent tailored for the treatment of idiopathic pulmonary fibrosis. Recently, through its anti-inflammatory and anti-oxidant effects, PFD based clinical trial has also been launched for the treatment of coronavirus disease (COVID-19). To what extent this drug can perturb membrane ion currents remains largely unknown. Herein, the exposure to PFD was observed to depress the amplitude of hyperpolarization-activated cation current (I(h)) in combination with a considerable slowing in the activation time of the current in pituitary GH(3) cells. In the continued presence of ivabradine or zatebradine, subsequent application of PFD decreased I(h) amplitude further. The presence of PFD resulted in a leftward shift in I(h) activation curve without changes in the gating charge. The addition of this compound also led to a reduction in area of voltage-dependent hysteresis evoked by long-lasting inverted triangular (downsloping and upsloping) ramp pulse. Neither the amplitude of M-type nor erg-mediated K(+) current was altered by its presence. In whole-cell potential recordings, addition of PFD reduced the firing frequency, and this effect was accompanied by the depression in the amplitude of sag voltage elicited by hyperpolarizing current stimulus. Overall, this study highlights evidence that PFD is capable of perturbing specific ionic currents, revealing a potential additional impact on functional activities of different excitable cells.


title: Revisiting ‘The Plague’ by Camus: Shaping the ‘Social Absurdity’ of the COVID-19 Pandemic

text: COVID-19 has emerged as a global health threat. The catastrophic reaction to a pandemic in spite of knowing the deadly outcomes, has been referred to as the 'social absurdity’. Such reaction creates a negativistic outlook with regard to the infection, thus contributing to chaos and preventing containment. In this article, the current pandemic of COVID-19 is revisited through the lens of Camus' ‘La Peste, 1947’. The philosophical roots of social ‘absurdity’ during a pandemic are critically discussed in the context of death anxiety. Subsequently, ways of reshaping it are highlighted, borrowing from the theories of existentialism and positive psychology.


title: Intracellular processing of the N-terminal ORF 1a proteins of the coronavirus MHV-A59 requires multiple proteolytic events

text: Abstract Several polypeptide products of MHV-A59 ORF 1a were characterized in MHV-A59 infected DBT cells, using antisera directed against fusionn roteins encoded in the first 6.5 kb of ORF1a. These included the previously identified N-terminal ORF 1a product, p28, as well as 290-, 240-, and 50-kDa polypeptides. P28 was always detected as a discrete band without larger precursors, suggesting rapid cleavage of p28 immediately after its synthesis. Once p28 was cleaved there was little degradation of the protein over a 2-hr period. The intracellular cleavage of p28 was not inhibited by the protease inhibitor leupeptin, in contrast to results obtained during in vitro translation of genome RNA (Denison and Perlman, 1986). These data suggest that different protease activities may be responsible for the cleavage of p28 in vitro and in vivo. The 290-kDa protein was an intermediate cleavage product derived from a precursor of greater than 400 kDa. The 290-kDa product was subsequently cleaved into secondary products of 50 and 240 kDa. The intracellular cleavage of the 290-kDa polypeptide was inhibited by leupeptin at concentrations which did not inhibit the early cleavage of p28 or the cleavage of the 290-kDa product from its larger polyprotein precursor. In the presence of zinc chloride, a product of >320 kDa was detected, which appears to incorporate p28 at its amino terminus. This suggests that at least two protease activities may be necessary for processing of ORF1a proteins, one of which cleaves p28 and is sensitive to zinc chloride but resistant to leupeptin, and the other which cleaves the 290-kDa precursor and is sensitive to both inhibitors. Both the 290- and 240-kDa proteins should contain sequences predicted to encode two papain-like protease activities.


title: Hyperpyrexia in COVID‐19 patients

text: Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a global health emergency, in which its effective treatment and prevention remain obscured. Hyperpyrexia is an elevation of body temperature (BT) above 106.7 °F (41.5 °C) due to an abnormally increased hypothalamic thermo‐regulatory set. The pathophysiology, impact, and outcomes of hyperpyrexia in COVID‐19 patients have not yet been studied. Herein, we present clinical features and outcomes of six COVID‐19 patients who had developed hyperpyrexia during hospitalization. All patients expired shortly after the onset of hyperpyrexia. Hyperpyrexia seems to adversely impact the outcomes and mortality in patients with COVID‐19. The underlying mechanisms of developing hyperpyrexia in COVID‐19 are mysterious. We propose it may be caused by SARS‐CoV‐2 related brain injury, exuberant immune response, and thrombus formation. More research is needed to verify our results. Understanding the association between hyperpyrexia and SARS‐CoV‐2 will help to elucidate the COVID‐19 pathogenesis, which is mandatory for developing effective treatment strategies. This article is protected by copyright. All rights reserved.


title: Viral and bacterial upper respiratory tract infection in hospital health care workers over time and association with symptoms

text: BACKGROUND: Bacterial colonisation of the respiratory tract is commonly described and usually thought to be of no clinical significance. The aim of this study was to examine the presence and significance of bacteria and viruses in the upper respiratory tract of healthcare workers (HCWs), and association with respiratory symptoms. METHODS: A prospective cohort study was conducted in China and 223 HCWs were recruited from fever clinics and respiratory, paediatric, emergency/Intensive medication wards. Participants were followed over 4 weeks (7th May 2015 to 4th June 2015) for development of clinical respiratory illness (CRI). Nasopharyngeal swabs were obtained at baseline and at the end of the study. The primary endpoints were laboratory-confirmed bacterial colonisation and viral respiratory infection. Rates of the following infections in symptomatic and asymptomatic participants were compared at the start or end of the study; 1) all bacterial/viral infections, 2) bacterial infection and bacterial-viral co-infections, excluding virus only infections, and 3) only bacterial infections. RESULTS: Bacterial colonisation was identified in 88% (196/223) of participants at the start or end of the study. Among these participants, 66% (148/223) had only bacterial colonisation while 22% (48/223) had co-infection with a virus. Bacteria were isolated from 170 (76.2%) participants at baseline and 127 (57%) participants at the end of the study. Laboratory confirmed viral infections were identified in 53 (23.8%) participants - 35 (15.7%) at the baseline and 20 (9.0%) at the end of the study. CRI symptoms were recorded in 12 participants (4.5%) and all had a positive bacterium isolation at baseline (n = 11) or end of the study (n = 1). Among asymptomatic participants, 187 (87%) had bacterial colonisation or bacterial/viral co-infection at baseline or end of the study. Viruses were also isolated from 5 (2.4%) asymptomatic cases. Rates of all infection outcomes were higher in symptomatic participants, however differences were not statistically significant. CONCLUSION: We isolated high rates of bacteria and viruses in the upper respiratory tract of hospital HCWs, which may reflect greater exposure to respiratory infections in the hospital. Although respiratory infections are mostly symptomatic, the association between bacterial colonization and symptomatic illness is not clear. In the healthcare setting, HCWs may acquire and transmit infection to patients and other HCWs around them. Larger studies are required to explore ongoing occupational risk of respiratory infection in hospitals HCWs.


title: Synthesis and biological evaluation of nucleoside analogues having 6-chloropurine as anti-SARS-CoV agents

text: Abstract Nucleoside analogues that have 6-chloropurine as the nucleobase were synthesized and evaluated for anti-SARS-CoV activity by plaque reduction and yield reduction assays in order to develop novel anti-SARS-CoV agents. Among these analogues, two compounds, namely, 1 and 11, exhibited promising anti-SARS-CoV activity that was comparable to those of mizoribine and ribavirin, which are known anti-SARS-CoV agents. Moreover, we observed several SAR trends such as the antiviral effects of the 6-chloropurine moiety, unprotected 5′-hydroxyl group and benzoylated 5′-hydroxyl group.


title: Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2

text: Abstract Cholesterol present in the plasma membrane of target cells has been shown to be important for the infection by SARS-CoV. We show that cholesterol depletion by treatment with methyl-β-cyclodextrin (mβCD) affects infection by SARS-CoV to the same extent as infection by vesicular stomatitis virus-based pseudotypes containing the surface glycoprotein S of SARS-CoV (VSV-ΔG-S). Therefore, the role of cholesterol for SARS-CoV infection can be assigned to the S protein and is unaffected by other coronavirus proteins. There have been contradictory reports whether or not angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV, is present in detergent-resistant membrane domains. We found that ACE2 of both Vero E6 and Caco-2 cells co-purifies with marker proteins of detergent-resistant membranes supporting the notion that cholesterol-rich microdomains provide a platform facilitating the efficient interaction of the S protein with the cellular receptor ACE2. To understand the involvement of cholesterol in the initial steps of the viral life cycle, we applied a cell-based binding assay with cells expressing the S protein and cells containing angiotensin-converting enzyme 2 (ACE2). Alternatively, we used a soluble S protein as interaction partner. Depletion of cholesterol from the ACE2-expressing cells reduced the binding of S-expressing cells by 50% whereas the binding of soluble S protein was not affected. This result suggests that optimal infection requires a multivalent interaction between viral attachment protein and cellular receptors.


title: Epidemical features of HAdV-3 and HAdV-7 in pediatric pneumonia in Chongqing, China

text: Human adenoviruses (HAdV) of species B, C, and E (HAdV-B, -C, -E) are frequent causative agents of acute respiratory infections worldwide. No specific analysis has been done on the epidemiological and clinical features of HAdV in pediatric pneumonia in China. Nasopharyngeal aspirates were collected from hospitalized children with pneumonia from June 2009 to May 2014. All samples that tested positive for HAdV were typed by sequencing the hexon and fiber genes. From a total of 3089 samples, 208 (6.7 %) were positive for HAdV, identified as belonging to HAdV-B (186, 89.4 %), HAdV-C (9, 4.3 %) and HAdV-E (1, 0.5 %). HAdV-7 (104, 50.0 %) and HAdV-3 (78, 37.5 %) were the two major types, followed by HAdV-1, HAdV-55 and HAdV-14. There were 87 (41.8 %) single HAdV infections, of which 80 % were HAdV-7 infections. Multivariate analysis showed that single infections with HAdV-7 were associated with a higher prevalence of severe pneumonia. Temporal patterns showed that, except for a simultaneous outbreak of HAdV-3 and HAdV-7 during the years 2010–2011, HAdV-7 and HAdV-3 were alternately predominant, and the dominance shifted to HAdV-3 after 2014. Identification of the predominant HAdV genotypes and their epidemical features is useful for determining preventive strategies. HAdV-7 associated severe pneumonia needs to be considered with high priority in clinical practice.


title: MG132 Attenuates the Replication of Classical Swine Fever Virus in vitro

text: The 26S proteasome, in charge of intracellular protein degradation, plays significant roles in the modulation of various cellular activities as well as in the interplay between virus and host. However, studies about the relationship between 26S proteasome and classical swine fever virus (CSFV) is limited up to now. MG132 is a proteasome inhibitor and has been extensively used in studies about replication of many viruses. Herein, we investigated the role of MG132 in CSFV replication and results showed that MG132 significantly decreased virus titers and viral RNA copies in CSFV-infected PK-15 cells. Further studies demonstrated that MG132 upregulated the expression of several interferon-stimulated genes (ISGs), in CSFV-infected cells. Since the activation of ISGs is controlled by the JAK-STAT signal pathway, we next examined the effect of MG132 on the expression and localization of key molecular STAT1 in the infected cells using Western blot and confocal laser scanning microscopy, respectively. Results showed that CSFV infection and viral NS4A protein decreased the protein level of STAT1, and MG132 promoted the accumulation of STAT1 in the nucleus of cells adjacent to the CSFV-infected cells. Besides, MG132 did not affect the expressions of IFN-α, STAT1, Mx1, OAS1, and PKR genes in cells without CSFV. In conclusion, we identify that MG132 significantly inhibits CSFV replication in vitro, in which the activation of the JAK-STAT pathway and the subsequent upregulation of expressions of ISGs might play significant roles, providing a potential preventive method for CSF.


Production and Characterization of Monoclonal Antibodies Against the Nucleocapsid Protein of SARS-COV


title: Serum YKL-40 levels may help distinguish exacerbation of post-infectious bronchiolitis obliterans from acute bronchiolitis in young children

text: Children with post-infectious bronchiolitis obliterans (PIBO) are frequently hospitalized with acute exacerbation, but clinical differentiation of PIBO exacerbation from acute bronchiolitis is often challenging, which may result in treatment delay and chronic lung function impairment. We aimed to examine whether serum YKL-40 and growth factors could be markers for PIBO exacerbation. Thirty-seven children admitted with acute exacerbation of PIBO were enrolled and studied retrospectively. Diagnosis of PIBO was based on clinical history of acute respiratory infection followed by persistent airway obstruction and characteristic findings in high-resolution computed tomography. Serum levels of YKL-40, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, and platelet-derived growth factor (PDGF)-BB were measured on admission. The biomarkers were also examined in children admitted with acute bronchiolitis serving as positive controls (N = 30) and in age-matched controls (N = 20). Only YKL-40 levels were found to be significantly higher in PIBO patients with exacerbation compared with that in bronchiolitis patients and showed a positive correlation with the severity of disease before diagnosis of PIBO. Conclusion: Our results suggest that measuring serum YKL-40 levels might help distinguish exacerbation of PIBO from acute bronchiolitis in young children.


title: Incidence and seasonality of respiratory viruses causing acute respiratory infections in the Northern United Arab Emirates

text: BACKGROUND: The data on the seasonality of respiratory viruses helps to ensure the optimal vaccination period and to monitor the possible outbreaks of variant type. OBJECTIVES: This study was designed to describe the molecular epidemiology and seasonality of acute respiratory infection (ARI)‐related respiratory viruses in the United Arab Emirates (UAE). METHODS: Both upper and lower respiratory specimens were collected for the analysis from all the patients who visited the Sheikh Khalifa Specialty Hospital (SKSH) with ARI for over 2 years. The multiplex real‐time reverse transcription polymerase chain reaction (rRT‐PCR) test was used to detect respiratory viruses, which include human adenovirus, influenza virus (FLU) A and B, respiratory syncytial virus, parainfluenza viruses, human rhinovirus (HRV), human metapneumovirus, human enterovirus, human coronavirus, and human bocavirus. RESULTS: A total of 1,362 respiratory samples were collected from 733 (53.8%) male and 629 (46.2%) female patients with ARI who visited the SKSH between November 2015 and February 2018. The rRT‐PCR test revealed an overall positivity rate of 37.2% (507/1362). The positive rate increased during winter; it was highest in December and lowest in September. FLU was the most frequently detected virus (273/1362 [20.0%]), followed by human rhinovirus (146/1362 [10.7%]). The FLU positivity rate showed two peaks, which occurred in August and December. The peak‐to‐low ratio for FLU was 2.26 (95% confidence interval: 1.52‐3.35). CONCLUSIONS: The pattern of FLU in the UAE parallels to that of temperate countries. The trend of the small peak of FLU in the summer suggests a possibility of semi‐seasonal pattern in the UAE.


title: How Blockchain can impact financial services – The overview, challenges and recommendations from expert interviewees

text: FinTech (Financial Technology) and Blockchain are prevalent topics among technology leaders in finance today. This article describes the impact and revolution of FinTech and Blockchain in the financial industry and demonstrates the main characteristics of such technology. Then, we present three critical challenges as well as three ethical issues about using Blockchain technology. Next, we discuss the development of Blockchain for the financial sector. In addition, we describe the real motivations for banks to explore Blockchain, and problems they face. In order to have a good understanding of the industry, a qualitative method was adopted, and sixteen experts were interviewed. It was identified that knowledge hiding in Blockchain was common and the rationale behind was analyzed using the TPB (Theory of Planned Behavior) approach. The analysis results suggested that knowledge hiding was due to affective, behavioral and cognitive evaluations. The interviewees also provided several recommendations and success factors to overcome current issues in Blockchain adoption. Therefore, four important propositions have been developed. Finally, this article suggests how financial services should respond to this new technology and how to manage knowledge sharing in a more structured way. This article contributes to the literature related to the current entrepreneurial finance landscape for Blockchain.


Year in review in Intensive Care Medicine, 2006. II. Infections and sepsis, haemodynamics, elderly, invasive and noninvasive mechanical ventilation, weaning, ARDS


title: Infections respiratoires aiguës à métapneumovirus humain chez l’enfant : études descriptive et comparative avec le virus respiratoire syncytial

text: Résumé Objectif. – Un nouveau paramyxovirus, le métapneumovirus humain, a été récemment isolé. Nous rapportons les premiers cas pédiatriques français d’infection respiratoire à ce virus, détectés entre 2000 et 2002. Matériel et méthodes. – Les prélèvements ont été obtenus par aspirations nasales chez des enfants hospitalisés pour infections respiratoires dans les services de pédiatrie du centre hospitalier universitaire de Caen et de l’hôpital de Flers. La recherche du métapneumovirus humain a été effectuée par polymerase chain reaction sur les prélèvements négatifs pour les virus respiratoire syncytial, virus influenza A et B, virus para-influenza (1, 2 et 3), adénovirus, entérovirus, coronavirus et rhinovirus. La comparaison de la morbidité des infections à métapneumovirus et virus respiratoire syncytial a été effectuée après appariement des sexe, âge et mois d’infection. Résultats. – Vingt-six cas d’infection à métapneumovirus humain ont été identifiés. L’étude comparative avec une cohorte appariée de nourrissons infectés par le virus respiratoire syncytial n’a retrouvé aucune différence significative en ce qui concerne les motifs d’hospitalisation, les signes cliniques et la prise en charge thérapeutique. Conclusion. – Le métapneumovirus humain est responsable d’un tableau typique de bronchiolite aiguë du nourrisson. Abstract Background. – A new paramyxovirus, the human metapneumovirus was recently isolated. We report the first French cases collected between 2000 and 2002. Material and methods. – Samples were obtained from nasopharyngeal aspirates from children hospitalised for acute respiratory tract infection in hospitals of Caen and Flers in Basse-Normandie. Human metapneumovirus was studied by polymerase chain reaction on negative samples for respiratory syncytial virus, influenza A and B virus, parainfluenza (1, 2 and 3) virus, adenovirus, coronavirus and rhinovirus. Comparison between metapneumovirus virus and respiratory syncytial virus infections was done after matching sex, age and infection month. Results. – Twenty-six human metapneumovirus infections were identified. A comparative study of a matched group of children infected by respiratory syncytial virus found no significative difference for hospitalisation motive, clinical criteria and treatment. Conclusion. – The human metapneumovirus is responsible for typical acute bronchiolitis in children.


Lung ultrasound as an extension of medical examination for COVID-19 pneumonia: much more than an imaging technique


title: Rapid and Real-time Detection of Human Viral Infections: Current Trends and Future Perspectives

text: The development of technologies with rapid and sensitive detection capabilities and increased throughput have become crucial for responding to greater number of threats posed by emerging and re-emerging viruses in the recent past. The conventional identification methods require time-consuming culturing, and/or detection of antibodies, which are not very sensitive and specific. The recent advances in molecular biology techniques in the field of genomics and proteomics greatly facilitate the rapid identification with more accuracy. The real-time assays viz; SYBR green I based real time RT-PCR and RT-LAMP have been developed for rapid detection as well as typing of some of the emerging arboviruses of biomedical importance viz; Dengue, Japanese Encephalitis, Chikungunya, West Nile, SARS and Swine Flu etc. Both these techniques are capable of detection and differentiation as well as quantifying viral load with higher sensitivity, rapidity and specificity. One of the most important advantages of RT-LAMP is its field applicability, without requirement of any sophisticated equipments. The establishment of these real time molecular assays will certainly facilitate the rapid detection of viruses with high degree of precision and accuracy in future.


Do Black Lives Matter to Consultation Liaison Psychiatry?


title: Residues on the Dimer Interface of SARS Coronavirus 3C-like Protease: Dimer Stability Characterization and Enzyme Catalytic Activity Analysis

text: 3C-like protease (3CL(pro)) plays pivotal roles in the life cycle of severe acute respiratory syndrome coronavirus (SARS-CoV) and only the dimeric protease is proposed as the functional form. Guided by the crystal structure and molecular dynamics simulations, we performed systematic mutation analyses to identify residues critical for 3CL(pro) dimerization and activity in this study. Seven residues on the dimer interface were selected for evaluating their contributions to dimer stability and catalytic activity by biophysical and biochemical methods. These residues are involved in dimerization through hydrogen bonding and broadly located in the N-terminal finger, the α-helix A′ of domain I, and the oxyanion loop near the S1 substrate-binding subsite in domain II. We revealed that all seven single mutated proteases still have the dimeric species but the monomer–dimer equilibria of these mutants vary from each other, implying that these residues might contribute differently to the dimer stability. Such a conclusion could be further verified by the results that the proteolytic activities of these mutants also decrease to varying degrees. The present study would help us better understand the dimerization-activity relationship of SARS-CoV 3CL(pro) and afford potential information for designing anti-viral compounds targeting the dimer interface of the protease.


title: Urology surgical activity and COVID‐19: Risk assessment at the epidemic peak the parisian multicenter experience

text: OBJECTIVES: To evaluate the risk of contracting severe COVID‐19, defined as COVID‐19 specific intensive care unit (ICU) admission or death, for patients undergoing urological surgery during the epidemic. To define consequences of receiving surgery for COVID‐19 patients. PATIENTS AND METHODS: This is a multicenter observational cohort study. Every patient receiving a urological procedure in Paris academic urological centers during the 4 initial weeks of surgical restrictions were included. Their status was updated minimum 3 weeks after the procedure. The main outcomes were the COVID‐19 specific ICU admission and death. Statistics were mostly descriptive. The Post‐operative COVID‐19 confirmed group was compared with non‐COVID patients using Chi‐square tests for categorical and Wilcoxon test tests for continuous variables. RESULTS: During the 4‐week period, 552 patients received surgery within 8 centers. At follow‐up, 57 (10%) patients were lost. Among the 11 preoperative COVID‐19 cases, one remained in ICU, no new admission, and no death. For the non‐COVID patients, 57 (12%) developed COVID‐related symptoms; only one case (0.2%) required COVID‐19 specific ICU and 3 (0.6%) patients died of COVID‐19 after surgery. CONCLUSIONS: Performing urological surgery during the COVID‐19 epidemic peak has a limited impact on ICU admissions but presents a real (0.6%) risk of specific mortality. Surgical activities should be maintained according to this risk.


title: Management-supportive measures for managers of healthcare organizations during the COVID-19 epidemic

text: Contagious or infectious diseases are one of the major causes of death.(1) Epidemics are a serious threat to public health and a global challenge (2)and management the of these epidemics is very difficult. In these conditions, economic, social and health factors of the country are of great worry, therefore, healthcare managers must properly manage and support health care centers (3)and use management-supportive measures for the organization and staff to provide best healthcare services. Presenting a scientific framework for managing health centers can be very helpful.The most important management-supportive practices at healthcare centers during outbreaks are listed below:1.Engage Leadership: Leadership affects the performance of physicians and nurses. Maintain effective communication with employees, pay attention to them, and listen to them effectively.2.Choose Wise Motivations: Talk about the importance of staff work, appreciate their work, and provide encouragement.3.Note to Work-life Balance: Note that you define a proper and balanced workload for employees. Say that optimal performance depends on enough rest and emphasize the need to re-energize.4.Encourage Peer Support: Protect your staff from external pressures, illogical or uncertain demands from patients and individuals, and promote support among colleagues.5.Provide Resources to Protect Employees and Their Mental Health: Minimize risky conditions in the organization and minimize workplace stress to ensure that staff are not exposed to additional stressors.6.Build A Good Community: Build the right teamwork and improve working relationships.7.Increase Employee Control Over Their Work: Clarify your expectations of employees and create an environment for team members to perform important tasks without interruption.8.Review Your Achievements Regularly: Talk to staff about your progress and successes.9.Cancel Unnecessary Meetings: Try to avoid unnecessary gatherings at work. Use video conferencing if a meeting needs to be held.


title: Surface displayed expression of a neutralizing epitope of spike protein from a Korean strain of porcine epidemic diarrhea virus

text: The neutralizing epitope (K-COE) of the spike protein from a Korean strain of porcine epidemic diarrhea virus (PEDV) has been shown to prevent and foster an immune response to PED, when orally adjusted. The cell surface of the budding yeast,Saccharomyces cerevisiae, was engineered to anchor the K-COE on the outer layer of the cell, and consequently, the altered yeast was applied as a dietary complement for animal feed, with immunogenic functions. In this study, the K-COE gene (K-COE) of the Korean strain of PEDV with the signal peptide of rice amylase 1A (Ramy 1A), was fused with the gene encoding the carboxyterminal half (320 amino acid residues from the C terminus) of yeast α-agglutinin, a mating associated protein that is anchored covalently to the cell wall. The glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter was selected in order to direct the expression of the fusion construct, and the resulting recombinant plasmid was then introduced intoS. cerevisiae. The surface display of K-COE was visualized via confocal microscopy using a polyclonal antibody against K-COE as the primary antibody, and FITC (fluorescein isothiocyanate)-conjugated goat anti-mouse IgG as the secondary antibody. The display of the K-COE on the cell surface was further verified via Western blot analysis using the cell wall fraction after the administration of α-1,3-glucanase/PNGase F/β-mannosidase treatment.