docid: dytfoyiz

title: Group B Betacoronavirus in Rhinolophid Bats, Japan

text: We report group B Betacoronavirus infection in little Japanese horseshoe bats in Iwate prefecture. We then used reverse-transcription PCR to look for the coronavirus RNA-dependent RNA polymerase gene in fecal samples collected from 27 little Japanese horseshoe bats and found eight were provisionally positive. We had a success in the nucleotide sequencing of six of the eight positive samples and compared them with those of authentic coronaviruses. We found that these six samples were positive in coronavirus infection, and they belonged to the group B Betacornavirus by phylogenetic analysis. Virus isolation using the Vero cell culture was unsuccessful. Pathogenic trait of these bat coronaviruses remained unexplored.


title: Inducibility of Ia antigen on astrocytes by murine coronavirus JHM is rat strain dependent

text: Inducibility of Ia molecules on cultivated astrocytes by JHM virus correlates with demyelinating disease susceptibility of animals from which these astrocytes are derived. On the contrary, class I induction of both astrocytes and oligodendrocytes occurs as a consequence of normal cultivation procedures in both susceptible and resistant strains. Increased expression of class I antigens on rat astrocytes and oligodendrocytes is not related to JHM viral infection as it is in the mouse. These data indicate that strain differences in Ia inducibility, rather than inducibility of class I antigens, by JHM virus may explain higher levels of T cell-mediated damage to myelin during infection in susceptible rat strains compared with resistant strains.


title: Does Circulating Antibody Play a Role in the Protection of Piglets against Porcine Epidemic Diarrhea Virus?

text: The contribution of circulating antibody to the protection of naïve piglets against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive antibody transfer model. Piglets (n = 62) derived from 6 sows were assigned to one of 6 different treatments using a randomized block design which provided for allocation of all treatments to all sows' litters. Each treatment was designed to achieve a different level of circulating anti-PEDV antibody via intraperitoneally administration of concentrated serum antibody. Piglets were orally inoculated with PEDV (USA/IN/2013/19338E, 1 x 10(3) TCID(50) per piglet) 24 hours later and then monitored for 14 days. Piglets remained with their dam throughout the experiment. Sow milk samples, piglet fecal samples, and data on piglet clinical signs, body weight, and body temperature were collected daily. Fecal samples were tested by PEDV real-time reverse transcriptase PCR. Serum, colostrum, and milk were tested for PEDV IgG, IgA, and virus-neutralizing antibody. The data were evaluated for the effects of systemic PEDV antibody levels on growth, body temperature, fecal shedding, survival, and antibody response. The analysis showed that circulating antibody partially ameliorated the effect of PEDV infection. Specifically, antibody-positive groups returned to normal body temperature faster and demonstrated a higher rate of survivability than piglets without PEDV antibody. When combined with previous literature on PEDV, it can be concluded that both systemic antibodies and maternal secretory IgA in milk contribute to the protection of the neonatal pig against PEDV infections. Overall, the results of this experiment suggested that passively administered circulating antibodies contributed to the protection of neonatal piglets against PEDV infection.


title: Severe Community-Acquired Pneumonia

text: Severe community-acquired pneumonia necessitating intensive care unit admission is associated with high morbidity, mortality, and health-care cost. This review article serves to summarize the epidemiology, diagnosis, treatment, and prognosis of this common life-threatening condition. Current practice guidelines as well as the role of several scoring systems (such as the PSI, CURB-65, and IDSA/ATS criteria) used to predict CAP severity, prognosis, and site of care are reviewed. In addition, common complications and prevention strategies are discussed.


The effect on the prehospital system with Out-of-Hospital Cardiac Arrest patients during the Covid-19 Outbreak in one city of China


title: Immunoprophylaxis against important virus diseases of horses, farm animals and birds

text: Since the refinement of tissue culture techniques for virus isolation and propagation from the mid 1960s onwards, veterinary virology has received much academic and industrial interest, and has now become a major global industry largely centred on vaccine development against economically important virus diseases of food animals. Bio-tech approaches have been widely used for improved vaccines development. While many viral diseases are controlled through vaccination, many still lack safe and efficacious vaccines. Additional challenges faced by academia, industry and governments are likely to come from viruses jumping species and also from the emergence of virulent variants of established viruses due to natural mutations. Also viral ecology is changing as the respective vectors adapt to new habitats as has been shown in the recent incursion by bluetongue virus into Europe. In this paper the current vaccines for livestock, horses and birds are described in a species by species order. The new promising bio-tech approaches using reverse genetics, non-replicating viral vectors, alpha virus vectors and genetic vaccines in conjunction with better adjuvants and better ways of vaccine delivery are discussed as well.


title: Cheetah Paradigm Revisited: MHC Diversity in the World's Largest Free-Ranging Population

text: For more than two decades, the cheetah (Acinonyx jubatus) has been considered a paradigm of disease vulnerability associated with low genetic diversity, particularly at the immune genes of the major histocompatibility complex (MHC). Cheetahs have been used as a classic example in numerous conservation genetics textbooks as well as in many related scientific publications. However, earlier studies used methods with low resolution to quantify MHC diversity and/or small sample sizes. Furthermore, high disease susceptibility was reported only for captive cheetahs, whereas free-ranging cheetahs show no signs of infectious diseases and a good general health status. We examined whether the diversity at MHC class I and class II-DRB loci in 149 Namibian cheetahs was higher than previously reported using single-strand conformation polymorphism analysis, cloning, and sequencing. MHC genes were examined at the genomic and transcriptomic levels. We detected ten MHC class I and four class II-DRB alleles, of which nine MHC class I and all class II-DRB alleles were expressed. Phylogenetic analyses and individual genotypes suggested that the alleles belong to four MHC class I and three class II-DRB putative loci. Evidence of positive selection was detected in both MHC loci. Our study indicated that the low number of MHC class I alleles previously observed in cheetahs was due to a smaller sample size examined. On the other hand, the low number of MHC class II-DRB alleles previously observed in cheetahs was further confirmed. Compared with other mammalian species including felids, cheetahs showed low levels of MHC diversity, but this does not seem to influence the immunocompetence of free-ranging cheetahs in Namibia and contradicts the previous conclusion that the cheetah is a paradigm species of disease vulnerability.


title: A Filippov system describing media effects on the spread of infectious diseases

text: Abstract A Filippov epidemic model with media coverage is proposed to describe the real characteristics of media/psychological impact in the spread of an infectious disease. We extend the existing models by incorporating a piecewise continuous transmission rate to describe that the media coverage exhibits its effect once the number of infected individuals exceeds a certain critical level. Mathematical and bifurcation analyses with regard to the local, global stability of equilibria and local sliding bifurcations are performed. Our main results show that the system stabilizes at either the equilibrium points of the two subsystems or the new endemic state induced by the on–off media effect, depending on the threshold levels. The finding suggests that a previously chosen level of the desired number of infected individuals can be reached when the threshold policy and other parameters are chosen properly.


Management of Patients with Crohn’s Disease and Ulcerative Colitis During the COVID-19 Pandemic: Results of an International Meeting


title: An insightful recollection since the distorted key theory was born about 23 years ago

text: Abstract During the last three decades or so, many efforts have been made to study the protein cleavage sites by some disease-causing enzyme, such as HIV (human immunodeficiency virus) protease and SARS (severe acute respiratory syndrome) coronavirus main proteinase. It has become increasingly clear via this minireview that the motivation driving the aforementioned studies is quite wise, and that the results acquired through these studies are very rewarding, particularly for developing peptide drugs.


title: Symptom Criteria for COVID‐19 Testing of Heath Care Workers

text: BACKGROUND: Limitations on testing availability has been a challenge during the COVID‐19 pandemic. An evidence based symptom criteria for identifying heath care workers (HCW) for testing, based on the probability of positive COVID‐19 test results, would allow for a more appropriate use of testing resources. METHODS: This was an observational study of outpatient COVID‐19 testing of HCW. Prior to testing, HCW were asked about the presence of 10 symptoms. Their responses were then compared to their subsequent pharyngeal swab COVID‐19 Polymerase Chain Reaction test results. These data were used to derive and evaluate a symptom based testing criteria. RESULTS: 961 HCW were included in the analysis, of which 225 (23%) had positive test results. Loss of taste or smell was the symptom with the largest positive likelihood ratio (3.33). Dry cough, regardless of the presence or absence of other symptoms, was the most sensitive (74%) and the least specific (32%) symptom. The existing testing criteria consisting of any combination of one or more of three symptoms (fever, shortness of breath, dry cough) was 93% sensitive and 9% specific (AUC = 0.63, 95% CI: 0.59 – 0.67). The derived testing criteria consisting of any combination of one or more of two symptoms (fever, loss of taste or smell) was 89% sensitive and 48% specific (AUC = 0.75, 95% CI: 0.71 – 0.78). The hybrid testing criteria consisting of any combination of one or more of four symptoms (fever, shortness of breath, dry cough, loss of taste or smell) was 98% sensitive and 8% specific (AUC = 0.77, 95% CI: 0.73 – 0.80). CONCLUSION: An evidence based approach to COVID‐19 testing which at least includes fever and loss of taste or smell should be utilized when determining which HCW should be tested.


Impact of the COVID‐19 pandemic on surgical services: early experiences at a nominated COVID‐19 centre


title: Smart polyhydroxyalkanoate nanobeads by protein based functionalization

text: Abstract The development of innovative medicines and personalized biomedical approaches calls for new generation easily tunable biomaterials that can be manufactured applying straightforward and low-priced technologies. Production of functionalized bacterial polyhydroxyalkanoate (PHA) nanobeads by harnessing their natural carbon-storage granule production system is a thrilling recent development. This branch of nanobiotechnology employs proteins intrinsically binding the PHA granules as tags to immobilize recombinant proteins of interest and design functional nanocarriers for wide range of applications. Additionally, the implementation of new methodological platforms regarding production of endotoxin free PHA nanobeads using Gram-positive bacteria opened new avenues for biomedical applications. This prompts serious considerations of possible exploitation of bacterial cell factories as alternatives to traditional chemical synthesis and sources of novel bioproducts that could dramatically expand possible applications of biopolymers. From the Clinical Editor In the 21st century, we are coming into the age of personalized medicine. There is a growing use of biomaterials in the clinical setting. In this review article, the authors describe the use of natural polyhydroxyalkanoate (PHA) nanoparticulates, which are formed within bacterial cells and can be easily functionalized. The potential uses would include high-affinity bioseparation, enzyme immobilization, protein delivery, diagnostics etc. The challenges of this approach remain the possible toxicity from endotoxin and the high cost of production.


title: Children Infected With SARS-CoV-2 From Family Clusters

text: Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing globally. Limited data are available for children with SARS-CoV-2 infection. Methods: A retrospective case study was conducted in one designated hospital for children with SARS-CoV-2 infection in Wuhan. Results: Out of the 74 children with laboratory-confirmed SARS-CoV-2 infection, the median age was 5.8 years, with no notable variation based on gender. All of the children had had direct exposure to at least one family member with confirmed SARS-CoV-2 infection. The most common symptoms were cough in 41 (55.4%) and fever in 38 (51.4%). Typical CT patterns of viral pneumonia were exhibited in 40 (54.1%) children, including ground-glass opacity and interstitial abnormalities. However, 17 (23.0%) children were classified as asymptomatic carriers, with neither symptoms nor radiological findings. Also, 68 (91.9%) children recovered fully and showed negative results on RT-PCR assay by nasopharyngeal swabs during our observation period. In contrast to the negative result for nasopharyngeal swab, 34% of the anal swabs showed a continued positive result. The mean hospitalization days of the children discharged after full recovery was 10.0 days. Conclusion: Within family clusters that had SARS-CoV-2 infection, children had mild or even asymptomatic illness. Although CT is highly sensitive, it should be avoided in follow-up of the disease in consideration of the radiological hazards and limited clinical benefits for mild illness in children. Furthermore, it is advocated that both nasopharyngeal and anal swabs should be confirmed negative for viral load prior to declaring full recovery so as to avoid oral-fecal transmission. Asymptomatic children with family clusters are potentially a little-known source of COVID-19. This therefore warrants an urgent reassessment of the transmission dynamics of the current outbreak.


title: Utilizing poxviral vectored vaccines for antibody induction—Progress and prospects

text: Over the last decade, poxviral vectors emerged as a mainstay approach for the induction of T cell-mediated immunity by vaccination, and their suitability for human use has led to widespread clinical testing of candidate vectors against infectious intracellular pathogens and cancer. In contrast, poxviruses have been widely perceived in the vaccine field as a poor choice of vector for the induction of humoral immunity. However, a growing body of data, from both animal models and recent clinical trials, now suggests that these vectors can be successfully utilized to prime and boost B cells and effective antibody responses. Significant progress has been made in the context of heterologous prime–boost immunization regimes, whereby poxviruses are able to boost responses primed by other vectors, leading to the induction of high-titre antigen-specific antibody responses. In other cases, poxviral vectors have been shown to stimulate humoral immunity against both themselves and encoded transgenes, in particular viral surface proteins such as influenza haemagglutinin. In the veterinary field, recombinant poxviral vectors have made a significant impact with numerous vectors licensed for use against a variety of animal viruses. On-going studies continue to explore the potential of poxviral vectors to modulate qualitative aspects of the humoral response, as well as their amenability to adjuvantation seeking to improve quantitative antibody immunogenicity. Nevertheless, the underlying mechanisms of B cell induction by recombinant poxviruses remain poorly defined, and further work is necessary to help guide the rational optimization of future poxviral vaccine candidates aiming to induce antibodies.


title: Child with liver transplant recovers from COVID-19 infection. A case report

text: Abstract We present the case of a 55-month-old girl who recovered from coronavirus disease 2019 (COVID-19) infection 5 months after undergoing liver transplantation; she had a co-infection with Epstein–Barr virus (EBV). To the best of our knowledge, this is the first case report of a COVID-19 infection in a pediatric patient with liver transplantation. Additionally, this is also the first report of confirmed co-infection between COVID-19 and EBV. On the basis of this case, we suggest that liver transplantation is not associated with COVID-19 symptom severity and development. Moreover, COVID-19 and EBV co-infections do not seem to aggravate the clinical outcome.


title: Analysis of Codon Usage and Nucleotide Bias in Middle East Respiratory Syndrome Coronavirus Genes

text: The Middle East Respiratory Syndrome (MERS) is an emerging disease caused by a recently identified human coronavirus (CoV). Over 2494 laboratory-confirmed cases and 858 MERS-related deaths have been reported from 27 countries. MERS-CoV has been associated with a high case fatality rate, especially in patients with pre-existing conditions. Despite the fatal nature of MERS-CoV infection, a comprehensive study to explore its evolution and adaptation in different hosts is lacking. We performed codon usage analyses on 4751 MERS-CoV genes and determined underlying forces that affect the codon usage bias in the MERS-CoV genome. The current analyses revealed a low but highly conserved, gene-specific codon usage bias in the MERS-CoV genome. The codon usage bias is mainly shaped by natural selection, while mutational pressure emerged as a minor factor affecting codon usage in some genes. Other contributory factors included CpG dinucleotide bias, physical and chemical properties of encoded proteins and gene length. Results reported in this study provide considerable insights into the molecular evaluation of MERS-CoV and could serve as a theoretical basis for optimizing MERS-CoV gene expression to study the functional relevance of various MERS-CoV proteins. Alternatively, an attenuated vaccine strain containing hundreds of silent mutations could be engineered. Codon de-optimization will not affect the amino acid sequence or antigenicity of a vaccine strain, but the sheer number of mutations would make viral reversion to a virulent phenotype extremely unlikely.


title: Exploiting genes and functional diversity of chlorogenic acid and luteolin biosyntheses in Lonicera japonica and their substitutes

text: Abstract Chlorogenic acids (CGAs) and luteolin are active compounds in Lonicera japonica, a plant of high medicinal value in traditional Chinese medicine. This study provides a comprehensive overview of gene families involved in chlorogenic acid and luteolin biosynthesis in L. japonica, as well as its substitutes Lonicera hypoglauca and Lonicera macranthoides. The gene sequence feature and gene expression patterns in various tissues and buds of the species were characterized. Bioinformatics analysis revealed that 14 chlorogenic acid and luteolin biosynthesis-related genes were identified from the L. japonica transcriptome assembly. Phylogenetic analyses suggested that the function of individual gene could be differentiation and induce active compound diversity. Their orthologous genes were also recognized in L. hypoglauca and L. macranthoides genomic datasets, except for LHCHS1 and LMC4H2. The expression patterns of these genes are different in the tissues of L. japonica, L. hypoglauca and L. macranthoides. Results also showed that CGAs were controlled in the first step of biosynthesis, whereas both steps controlled luteolin in the bud of L. japonica. The expression of LJFNS2 exhibited positive correlation with luteolin levels in L. japonica. This study provides significant information for understanding the functional diversity of gene families involved in chlorogenic acid and the luteolin biosynthesis, active compound diversity of L. japonica and its substitutes, and the different usages of the three species.


title: Detection of antibodies to the SARS-CoV-2 spike glycoprotein in both serum and saliva enhances detection of infection

text: BACKGROUND: Detecting antibody responses during and after SARS-CoV-2 infection is essential in determining the seroepidemiology of the virus and the potential role of antibody in disease. Scalable, sensitive and specific serological assays are essential to this process. The detection of antibody in hospitalized patients with severe disease has proven straightforward; detecting responses in subjects with mild disease and asymptomatic infections has proven less reliable. We hypothesized that the suboptimal sensitivity of antibody assays and the compartmentalization of the antibody response may contribute to this effect. METHODS: We systemically developed an ELISA assay, optimising different antigens and amplification steps, in serum and saliva from symptomatic and asymptomatic SARS-CoV-2-infected subjects. RESULTS: Using trimeric spike glycoprotein, rather than nucleocapsid enabled detection of responses in individuals with low antibody responses. IgG1 and IgG3 predominate to both antigens, but more antispike IgG1 than IgG3 was detectable. All antigens were effective for detecting responses in hospitalized patients. Anti-spike, but not nucleocapsid, IgG, IgA and IgM antibody responses were readily detectable in saliva from non-hospitalized symptomatic and asymptomatic individuals. Antibody responses in saliva and serum were largely independent of each other and symptom reporting. CONCLUSIONS. Detecting antibody responses in both saliva and serum is optimal for determining virus exposure and understanding immune responses after SARS-CoV-2 infection. FUNDING. This work was funded by the University of Birmingham, the National Institute for Health Research (UK), the NIH National Institute for Allergy and Infectious Diseases, the Bill and Melinda Gates Foundation and the University of Southampton.


title: International Turbulence and Russia

text: Using a multidisciplinary approach, this report analyzes the current transformation of the world-order architecture. It is noted that the speed and depth of this transformation is unprecedented for peacetime over the past 200 years. One of the most important indicators of turbulence is a certain deglobalization of the world economy. A study of the technological, social, economic, and political variables of social change has revealed that the traditional (for developed countries) social contract between government, business, and civil society has come to a crisis. This social contract has been in effect for more than half a century, since the times before globalization, the times of an industrial and bipolar world. Its inconsistency with modern realities, coupled with the inability of the old political center to offer convincing approaches to its modernization, has polarized societies and weakened social cohesion in the developed part of the world. As a result, populist and isolationist political forces have come to power. It is these forces that have started the dismantling of the existing system of global governance and its norms and institutions. The main contradiction of the current transformation in the world order is an attempt to bring back the polycentric world to a unipolar architecture with the dominance of the United States. The most likely scenario for resolving this contradiction is to create a new bipolarity. The author of the report expresses his views on the possible outlines of Russia’s foreign policy, which would enable the country to adapt to the bipolarity of the 21st century and to a new role as a balance-keeper. A new design of global architecture is proposed, which is based on multilateral responsible leadership.


title: Comparison of ascites production for monoclonal antibodies in BALB/c and BALB/c-derived cross-bred mice

text: Abstract BALB/c male mice were mated with either Swiss-Webster or MF1 females to produce first generation cross-bred offspring. Hybridoma cell lines, from the fusion of P3-NS1-Ag4/1 myeloma cells with spleen cells sensitised to the porcine coronavirus causing transmissible gastroenteritis, were injected intraperitoneally into these mice to produce ascitic fluid containing monoclonal antibodies. Mice of 11 weeks of age weighing between 26 and 34 g were used. The volume of ascites produced by mice injected with four of the five hybrid cell lines tested was greater in the cross-bred offspring than in the BALB/c parent. The fifth cell line gave comparable volumes in the MF1 cross-breed and BALB/c parent but a lesser volume in the Swiss-Webster cross-breed. The antibody titres of the ascites as determined by virus neutralisation, radioimmune and indirect immune fluorescence assays, did not differ significantly between mouse types. The ability to use all offspring from a litter of cross-bred mice, irrespective of sex, and the increased volume of ascitic fluid formed in each mouse, permits fewer animals to be used for the production of ascites in these strains, thereby offering considerable economic and ethical advantages over the use of BALB/c mice.


Severe Acute Respiratory Syndrome: SARS: One Toronto Hospital Experience


title: Residues involved in the antigenic sites of transmissible gastroenteritis coronavirus S glycoprotein

text: Abstract The S glycoprotein of transmissible gastroenteritis virus (TGEV) has been shown to contain four major antigenic sites (A, B, C, and D). Site A is the main inducer of neutralizing antibodies and has been previously subdivided into the three subsites Aa, Ab, and Ac. The residues that contribute to these sites were localized by sequence analysis of 21 mutants that escaped neutralization or binding by TGEV-specific monoclonal antibodies (MAbs), and by epitope scanning (PEPSCAN). Site A contains the residues 538, 591, and 543, which are essential in the formation of subsites Aa, Ab, and Ac, respectively. In addition, mar mutant 1B.H6 with residue 586 changed had partially altered both subsite Aa and Ab, indicating that these subsites overlap in residue 586; i.e. this residue also is part of site A. The peptide 537-MKSGYGQPIA-547 represents, at least partially, subsite Ac which is highly conserved among coronaviruses. This site is relevant for diagnosis and could be of interest for protection. Other residues contribute to site B (residues 97 and 144), site C (residues 50 and 51), and site D (residue 385). The location of site D is in agreement with PEPSCAN results. Site C can be represented by the peptide 48-P-P/S-N-S-D/E-52 but is not exposed on the surface of native virus. Its accessibility can be modulated by treatment at pH >11 (at 4°) and temperatures >45°. Sites A and B are fully dependent on glycosylation for proper folding, while sites C and D are fully or partially independent of glycosylation, respectively. Once the S glycoprotein has been assembled into the virion, the carbohydrate moiety is not essential for the antigenic sites.


title: The influence of social behaviour on competition between virulent pathogen strains

text: Abstract Infectious disease interventions like contact precautions and vaccination have proven effective in disease control and elimination. The priority given to interventions can depend strongly on how virulent the pathogen is, and interventions may also depend partly for their success on social processes that respond adaptively to disease dynamics. However, mathematical models of competition between pathogen strains with differing natural history profiles typically assume that human behaviour is fixed. Here, our objective is to model the influence of social behaviour on the competition between pathogen strains with differing virulence. We couple a compartmental Susceptible-Infectious-Recovered model for a resident pathogen strain and a mutant strain with higher virulence, with a differential equation of a population where individuals learn to adopt protective behaviour from others according to the prevalence of infection of the two strains and the perceived severity of the respective strains in the population. We perform invasion analysis, time series analysis and phase plane analysis to show that perceived severities of pathogen strains and the efficacy of infection control against them can greatly impact the invasion of more virulent strain. We demonstrate that adaptive social behaviour enables invasion of the mutant strain under plausible epidemiological scenarios, even when the mutant strain has a lower basic reproductive number than the resident strain. Surprisingly, in some situations, increasing the perceived severity of the resident strain can facilitate invasion of the more virulent mutant strain. Our results demonstrate that for certain applications, it may be necessary to include adaptive social behaviour in models of the emergence of virulent pathogens, so that the models can better assist public health efforts to control infectious diseases.


title: Two RT-PCR based assays to detect human metapneumovirus in nasopharyngeal aspirates

text: Abstract Two sensitive and specific RT-PCR assays were standardised for testing the presence of human metapneumovirus. A total of 300 nasopharyngeal aspirates collected from infants suffering from bronchiolitis since October 2000 to June 2003 and shown previously as negative to common respiratory viruses were examined. Matrix and polymerase viral genes, which show a low rate of variation, were chosen to design amplification assays to ensure that any genotype of the human metapneumovirus could be detected. A RT-PCR followed by a reverse line blotting hybridisation was developed for viral polymerase gene. For the matrix gene, after the RT-PCR assay, a subsequent nested PCR was carried out. Both assays had similar sensitivity, equivalent to 0.1 TCID50 of human metapneumovirus strain NL/1/99 which was used as the positive control. The human metapneumovirus was present in 16.6% of the specimens studied. The approaches described below are not only a robust method for rapid diagnosis of the human metapneumovirus, but also to establish an etiological surveillance tool for epidemiological studies. Based on the results obtained, human metapneumovirus infections in Madrid followed a seasonal pattern, with most of the infections occurring between February and April.


title: Foodborne viral illness - status in Australia

text: Abstract Norwalk-like virus contamination of oysters and orange juice, and hepatitis A virus contamination of oysters have been responsible for large outbreaks of foodborne viral disease in Australia. Rotavirus, adenovirus, astrovirus, parvovirus and other enteroviruses also contribute to the incidence of gastroenteritis in this country but the role of foods and waters in transmitting these viruses is unclear. Protocols for the investigation, surveillance and reporting of foodborne viral illness require further development to enable a more accurate description of the problem. Few laboratories have the capability to analyse foods for viruses and specific training in this technology is needed. Management of food safety in Australia largely relies on the implementation of HACCP principles, but these need to be adapted to address the specific risks from viruses.


title: Infection nosocomiale à SARS-Cov-2 dans les services de Chirurgie Digestive

text: RESUME Introduction: La pandémie de COVID-19 a imposé une diminution radicale de l’activité chirurgicale afin de répondre à l’afflux de patients hospitalisés et protéger les patients non infectés en leur évitant une hospitalisation. Toutefois, le risque d’infection lors de l’hospitalisation et ses conséquences sont encore très peu connus. Le but de ce travail était de rapporter une série de patients hospitalisés en chirurgie digestive chez qui une infection nosocomiale à SARS-Cov-2 a été diagnostiquée. Méthodes: Etude rétrospective non-interventionnelle réalisée au sein de 3 services de chirurgie digestive. Les données cliniques, biologiques et radiologiques des patients ayant développé une infection nosocomiale au SARS-Cov-2 ont été collectées à partir des dossiers informatisés. Résultats: Du 1er Mars 2020 au 5 Avril 2020, parmi 305 patients admis en chirurgie digestive, 15 (4.9%) ont présenté une infection nosocomiale à SARS-Cov-2. Il s’agissait de 9 hommes et 6 femmes, d’un âge médian de 62 ans (35-68 ans). Tous les patients présentaient une comorbidité. Les motifs d’hospitalisation étaient : traitement chirurgical d’un cancer (n=5), urgences complexes (n=5), traitement de complications liées au cancer ou à son traitement (n=3), reconstruction par gastroplastie (n=1), fermeture de stomie (n=1). Le délai médian entre l’admission et le diagnostic d’infection à SARS-Cov-2 était de 34 jours (5-61 jours). Chez 12 (80%) patients, le diagnostic a été posé après une durée d’hospitalisation de plus de 14 jours (15-63 jours). A l’issue du suivi, 2 patients sont décédés, 7 étaient hospitalisés dont 2 sous assistance respiratoire et 6 patients étaient sortis d’hospitalisation. Conclusions: Le risque d’infection au SARS-Cov-2 au cours d’une hospitalisation ou dans les suites d’une intervention de chirurgie digestive est un risque réel et potentiellement grave. Des mesures sont nécessaires afin de minimiser ce risque dans la perspective d’une reprise de l’activité chirurgicale en toute sécurité. SUMMARY Introduction: The COVID-19 pandemic imposed a drastic reduction in surgical activity in order to respond to the influx of hospital patients and to protect uninfected patients by avoiding hospitalization. However, little is known about the risk of infection during hospitalization or its consequences. The aim of this work was to report a series of patients hospitalized on digestive surgery services who developed a nosocomial infection with SARS-Cov-2 virus. Methods: This is a non-interventional retrospective study carried out within three departments of digestive surgery. The clinical, biological and radiological data of the patients who developed a nosocomial infection with SARS-Cov-2 were collected from the computerized medical record. Results: From March 1, 2020 to April 5, 2020, among 305 patients admitted to digestive surgery services, 15 (4.9%) developed evident nosocomial infection with SARS-Cov-2. There were nine men and six women, with a median age of 62 years (35-68 years). All patients had co-morbidities. The reasons for hospitalization were: surgical treatment of cancer (n = 5), complex emergencies (n = 5), treatment of complications linked to cancer or its treatment (n = 3), gastroplasty (n = 1), and stoma closure (n = 1). The median time from admission to diagnosis of SARS-Cov-2 infection was 34 days (5-61 days). In 12 patients (80%), the diagnosis was made after a hospital stay of more than 14 days (15-63 days). At the end of the follow-up, two patients had died, seven were hospitalized with two of them on respiratory assistance, and six patients were discharged post-hospitalization. Conclusions: The risk of SARS-Cov-2 infection during hospitalization or following digestive surgery is a real and potentially serious risk. Measures are necessary to minimize this risk in order to return to safe surgical activity.


Leading a COVID‐19 cohort ward without blades: a surgeon's perspectives


title: Clinical study of transcutaneous vaccination using a hydrogel patch for tetanus and diphtheria

text: Transcutaneous immunization (TCI) is a non-invasive and easy-to-use vaccination method. We demonstrated the efficacy and safety of a transcutaneous vaccine formulation using a hydrogel patch in animal experiments. In the present study, we performed a clinical study to apply our TCI formulation for vaccination against tetanus and diphtheria in human. The TCI device was a hydrogel patch (antigen-free) applied to the left brachial medial skin of 22 healthy volunteers for 48 h. Next, the hydrogel patch, containing 2 mg tetanus toxoid (TT) and 2 mg diphtheria toxoid (DT) as the TCI formulation, was applied to 27 healthy volunteers for 24 h and some volunteers were vaccinated again by TCI formulation. For safety assessment, the patch application site was observed to assess local adverse events, and systemic adverse events were determined by a blood test. The antigen-free hydrogel patch and TCI formulation containing TT and DT did not induce local or systemic severe adverse events. For vaccine efficacy estimation, toxoid-specific serum antibody titers were determined by ELISA and the toxin-neutralizing activity of the induced antibody was evaluated in a passive-challenge experiment. The anti-TT IgG titer and the anti-DT IgG titer increased, and a significant effect was detected by paired t-test. The antibody titers were maintained at higher level than that before vaccination for at least 1 year. Moreover, toxoid-specific antibodies were produced by the second vaccination in some subjects. Antibodies induced by application of the TCI formulation neutralized the toxin and prevented toxic death in mice. In addition, changes in the skin condition due to application of the TCI formulation were observed under in vivo confocal Raman spectroscopy. The amount of water and patch components in the stratum corneum increased after application of the TCI formulation, suggesting that the change in the skin condition was related to antigen penetration. These data indicate that this easy-to-use TCI system induces an immune response without severe adverse reactions in humans. This easy-to-use and safe TCI formulation enables mass treatment in an outbreak setting and increased vaccination rates in developing countries, and will greatly contribute to worldwide countermeasures against infectious diseases.


title: SRAS et SDRA : l’évolution radiologique est la même J.Y.H. Hui D.H.Y. Cho

text: Unknown


Shenzhen’ Experience on Containing 2019 Novel Coronavirus-Infected Pneumonia Transmission


docid: tndzsxce

title: Strengthening the US Medical Countermeasure Enterprise for Biological Threats


title: COVID‐19 pandemic: Effects and evidence‐based recommendations for otolaryngology and head and neck surgery practice

text: The 2019 novel coronavirus disease (COVID‐19) is a highly contagious zoonosis produced by SARS‐CoV‐2 that is spread human‐to‐human by respiratory secretions. It was declared by the WHO as a public health emergency. The most susceptible populations, needing mechanical ventilation, are the elderly and people with associated comorbidities. There is an important risk of contagion for anesthetists, dentists, head and neck surgeons, maxillofacial surgeons, ophthalmologists, and otolaryngologists. Health workers represent between 3.8% and 20% of the infected population; some 15% will develop severe complaints and among them, many will lose their lives. A large number of patients do not have overt signs and symptoms (fever/respiratory), yet pose a real risk to surgeons (who should know this fact and must therefore apply respiratory protective strategies for all patients they encounter). All interventions that have the potential to aerosolize aerodigestive secretions should be avoided or used only when mandatory. Health workers who are: pregnant, over 55 to 65 years of age, with a history of chronic diseases (uncontrolled hypertension, diabetes mellitus, chronic obstructive pulmonary diseases, and all clinical scenarios where immunosuppression is feasible, including that induced to treat chronic inflammatory conditions and organ transplants) should avoid the clinical attention of a potentially infected patient. Health care facilities should prioritize urgent and emergency visits and procedures until the present condition stabilizes; truly elective care should cease and discussed on a case‐by‐case basis for patients with cancer. For those who are working with COVID‐19 infected patients' isolation is compulsory in the following settings: (a) unprotected close contact with COVID‐19 pneumonia patients; (b) onset of fever, cough, shortness of breath, and other symptoms (gastrointestinal complaints, anosmia, and dysgeusia have been reported in a minority of cases). For any care or intervention in the upper aerodigestive tract region, irrespective of the setting and a confirmed diagnosis (eg, rhinoscopy or flexible laryngoscopy in the outpatient setting and tracheostomy or rigid endoscopy under anesthesia), it is strongly recommended that all health care personnel wear personal protective equipment such as N95, gown, cap, eye protection, and gloves. The procedures described are essential in trying to maintain safety of health care workers during COVID‐19 pandemic. In particular, otolaryngologists, head and neck, and maxillofacial surgeons are per se exposed to the greatest risk of infection while caring for COVID‐19 positive subjects, and their protection should be considered a priority in the present circumstances.


title: Review colleagues’ lessons learned for managing impact of COVID‐19 crisis

text: The COVID‐19 crisis sent student affairs hurtling into a whole new realm. And it happened so completely out of the blue that there was little time to prepare, and nothing to compare it to. But student affairs professionals have always excelled at adapting, even thriving, under stressful conditions, while making sure to lead their students and staff to succeed right along with them. And that's proven true once again during this crisis.


title: Bioterrorism—Types of epidemics, new epidemiological paradigm and levels of prevention

text: Summary Biological attacks can cause both an epidemic of infectious disease and of fear and panic. Epidemiological triangle chain models can be used to present both these types of epidemic. By merging these two triangles we suggest a new four-sided pyramidal model of bioterrorism attack and appropriate levels of prevention. Primordial prevention of biological attacks should comprise the impeding of access of both terrorists and biological agents to the territory. The primary prevention level should comprise internal surveillance of potential sources of agents and terrorists. Secondary prevention activities should be directed toward breaking both the epidemic of infectious disease and that of fear and panic. Tertiary prevention should include measures for repair following the attack. This is a task mainly for mental health professionals, curing and rehabilitating those affected by the epidemic of fear and panic. The suggested epidemiological model can be implemented into training programmes for detecting and responding to bioterrorist attacks around the world.


title: Extraction and characterization of the rhesus macaque T cell receptor β-chain genes

text: Rhesus macaque models have been instrumental for the development and testing of vaccines prior to human studies and have provided fundamental insights into the determinants of immune efficacy in a variety of infectious diseases. However, the characterization of antigen-specific T cell receptor (TCR) repertoires during adaptive immune responses in these models has previously relied on human TCR gene assignments. Here, we extracted and characterized TCR β-chain (TRB) genes from the recently sequenced rhesus macaque genome that are homologous to the human TRB genes. Comparison of the rhesus macaque TRB genes with the human TRB genes revealed an average best-match similarity of 92.9%. Furthermore, we confirmed the usage of most rhesus macaque TRB genes by expressed TCRβ sequences within epitope-specific TCR repertoires. This primary description of the rhesus macaque TRB genes will provide a standardized nomenclature and enable better characterization of TCR usage in studies that utilize this species.


title: Longitudinal association between markers of liver injury and mortality in COVID‐19 in China

text: Coronavirus disease 2019 (COVID‐19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID‐19 pneumonia in Hubei Province. We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non‐severe and the severe group. AST abnormality was associated with the highest mortality risk compared to other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID‐19‐associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.


title: Remaining Questions about Clinical Variola Major

text: After the recent summary of World Health Organization–authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate.


title: Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

text: BACKGROUND: Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. METHODS: We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. RESULTS: Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. CONCLUSION: Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis.


docid: arrhvqwa

title: Identification and characterization of novel neutralizing epitopes in the receptor-binding domain of SARS-CoV spike protein: Revealing the critical antigenic determinants in inactivated SARS-CoV vaccine

text: The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) is considered as a major antigen for vaccine design. We previously demonstrated that the receptor-binding domain (RBD: residues 318–510) of S protein contains multiple conformation-dependent neutralizing epitopes (Conf I to VI) and serves as a major target of SARS-CoV neutralization. Here, we further characterized the antigenic structure in the RBD by a panel of novel mAbs isolated from the mice immunized with an inactivated SARS-CoV vaccine. Ten of the RBD-specific mAbs were mapped to four distinct groups of conformational epitopes (designated Group A to D), and all of which had potent neutralizing activity against S protein-pseudotyped SARS viruses. Group A, B, C mAbs target the epitopes that may overlap with the previously characterized Conf I, III, and VI respectively, but they display different capacity to block the receptor binding. Group D mAb (S25) was directed against a unique epitope by its competitive binding. Two anti-RBD mAbs recognizing the linear epitopes (Group E) were mapped to the RBD residues 335–352 and 442–458, respectively, and none of them inhibited the receptor binding and virus entry. Surprisingly, most neutralizing epitopes (Groups A to C) could be completely disrupted by single amino acid substitutions (e.g., D429A, R441A or D454A) or by deletions of several amino acids at the N-terminal or C-terminal region of the RBD; however, the Group D epitope was not sensitive to the mutations, highlighting its importance for vaccine development. These data provide important information for understanding the antigenicity and immunogenicity of SARS-CoV, and this panel of novel mAbs can be used as tools for studying the structure of S protein and for guiding SARS vaccine design.


title: Complete genome sequence and recombination analysis of infectious bronchitis virus attenuated vaccine strain H120

text: The strain H120 of infectious bronchitis virus (IBV) is one of the earliest and representative attenuated live Infectious Bronchitis vaccine strains. To investigate the genomic feature of H120 and further understand its role in the epidemiology of IBV, complete genome of H120 was sequenced and compared with sequences of other IBV strains by phylogenetic and recombination analysis. The complete genome of H120 is 27631 nucleotides in length and has a similar structure with that of Beaudette strain. We found that strain ZJ971 is probably a virulence revertant of H120. Nine amino acids changes and a three-nucleotide deletion were identified in ZJ971. Besides, potential recombination events associated with H120 were found in five IBV strains including H52, KQ6, SAIBK, Ark DPI 11, and Ark DPI 101. This study suggested that H120 might have contributed to the emergence of new IBV variants through both virulence reversion and recombination.


title: The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry

text: Vesicle-membrane-protein-associated protein A (VAPA) and oxysterol-binding protein (OSBP) regulate intracellular cholesterol homeostasis, which is required for many virus infections. During entry, viruses or virus-containing vesicles can fuse with endosomal membranes to mediate the cytosolic release of virions, and alterations in endosomal cholesterol can inhibit this invasion step. We show that the antiviral effector protein Interferon-inducible transmembrane protein 3 (IFITM3) interacts with VAPA and prevents its association with OSBP, thereby disrupting intracellular cholesterol homeostasis and inhibiting viral entry. By altering VAPA-OSBP function, IFITM3 induces a marked accumulation of cholesterol in multivesicular bodies and late endosomes, which inhibits the fusion of intraluminal virion-containing vesicles with endosomal membranes and thereby blocks virus release into the cytosol. Consequently, ectopic expression or depletion of the VAPA gene profoundly affects IFITM3-mediated inhibition of viral entry. Thus, IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry, further underscoring the importance of cholesterol in virus infection.


docid: cdxlhgud

title: Pre-emptive contact precautions for intubated patients reduced healthcare-associated meticillin-resistant Staphylococcus aureus transmission and infection in an intensive care unit

text: Summary Healthcare-associated infection by meticillin-resistant Staphylococcus aureus (MRSA) is still a great concern in an intensive care unit (ICU). Our surveillance data in the ICU revealed that intubated patients were at eight times higher risk of acquiring MRSA than non-intubated patients, so we hypothesised that pre-emptive contact precautions for all intubated patients would prevent healthcare-associated infection by MRSA in the ICU. Patients staying in our ICU for >2 days were included in this study. The study period was divided into two periods. During 2004 (1st period), contact precautions were performed only for patients with MRSA. During 2005–2007 (2nd period), contact precautions were applied to all intubated patients regardless of MRSA infection status. Patients were defined as MRSA-positive on admission when MRSA was detected by surveillance or clinical culture on enrolment. Other MRSA-positive results were defined as healthcare-associated MRSA (HA-MRSA) transmission. HA-MRSA infection was diagnosed according to the National Nosocomial Infections Surveillance Manual. The 1st period comprised 415 patients, and the 2nd period comprised 1280 patients. In intubated patients, HA-MRSA infection rate decreased significantly in the 2nd period (1st period 12.2%, 2nd period 5.6%; P =0.015). HA-MRSA infection of all patients decreased from 3.6 to 2.3 incidents per 1000 patient-days (P <0.05), despite a significant increase in the rate of patients MRSA positive on admission in the 2nd period (1st period 2.9%; 2nd period 6.1%). Pre-emptive contact precautions for intubated patients would be helpful in reducing HA-MRSA infection in ICU.


title: Respiratory Viruses

text: Respiratory viruses are the most frequent causative agents of disease in humans, with significant impact on morbidity and mortality worldwide. Common respiratory agents from several virus families are well adapted to efficient person-to-person transmission and circulate in a global scale, and community-based studies conducted over the past five decades or so confirm that these viruses are the predominant etiological agents of acute respiratory infections (ARIs). The respiratory viruses that most commonly circulate in all continents as endemic or epidemic agents are influenza virus, respiratory syncytial virus, parainfluenza viruses, metapneumovirus, rhinovirus, coronaviruses, adenoviruses, and bocaviruses. Although vaccines and effective antiviral drugs are not yet available for most of these viruses, much progress has been made in the understanding of their biology and fundamental issues of host–parasite relationship. This article is a summary of the current knowledge about these viruses.


title: Transmissible gastroenteritis virus infection induces apoptosis through FasL- and mitochondria-mediated pathways

text: Abstract Transmissible gastroenteritis virus (TGEV) has been reported to induce apoptosis in swine testis (ST) cells. However, the mechanisms underlying TGEV-induced apoptosis are still unclear. In this study we observed that TGEV infection induced apoptosis in porcine kidney (PK-15) cells in a time- and dose-dependent manner. TGEV infection up-regulated FasL, activated FasL-mediated apoptotic pathway, leading to activation of caspase-8 and cleavage of Bid. In addition, TGEV infection down-regulated Bcl-2, up-regulated Bax expression, promoted translocation of Bax to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c and the activation of caspase-9. Both extrinsic and intrinsic pathways activated downstream effector caspase-3, followed by the cleavage of PARP, resulting in cell apoptosis. Moreover, TGEV infection did not induce significant DNA fragmentation in ammonium chloride (NH4Cl) pretreated PK-15 cells or cells infected with UV-inactivated TGEV. In turn, block of caspases activation also did not affect TGEV replication. Taken together, this study demonstrates that TGEV-induced apoptosis is dependent on viral replication in PK-15 cells and occurs through activation of FasL- and mitochondria-mediated apoptotic pathways.


Letter to the Editor on “Disaster Rehabilitation Response Plan: Now or Never”


title: Inactivation of surrogate coronaviruses on hard surfaces by health care germicides

text: BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.


title: The role of hand-held ultrasound for cardiopulmonary assessment during a pandemic

text: During the COVID-19 pandemic, we are likely to see a significant increase in the requests for rapid assessment of cardiac function, due to the frequent pre-existence of cardiac pathologies in patients admitted to hospital, and to the emergence of specific cardiac manifestations of this infection, such as myocarditis, sepsis related cardiomyopathy, stress induced cardiomyopathy and acute coronary syndromes. Hand-held, point-of-care ultrasound (HH-POCUS) is particularly suited for the provision of rapid, focused, integrated assessments of the heart and lungs. We present a review of the indications and protocols for focused HH-POCUS use in an acute setting and formulate proposals for streamlining their application in the COVID-19 context towards guiding optimum management of these patients while at the same time allowing adherence to robust infection control measures to provide safety to both the patient and our clinical staff.


title: Asymptomatic infection and atypical manifestations of COVID-19: comparison of viral shedding duration

text: • More than 25% of patients with COVID-19 were asymptomatic. • Among patients with COVID-19, 26.1% presented anosmia, and 22.6% complained of ageusia with median duration of 7 days. • Mean duration of SARS-CoV-2 viral shedding was 24.5 days. • Irrespective of clinical manifestations, all patients with COVID-19 showed prolonged viral shedding.


title: Cathepsin L is required for ecotropic murine leukemia virus infection in NIH3T3 cells

text: Abstract Recently it has been reported that a cathepsin B inhibitor, CA-074Me, attenuates ecotropic murine leukemia virus (Eco-MLV) infection in NIH3T3 cells, suggesting that cathepsin B is required for the Eco-MLV infection. However, cathepsin B activity was negative or extremely low in NIH3T3 cells. How did CA-074Me attenuate the Eco-MLV infection? The CA-074Me treatment of NIH3T3 cells inhibited cathepsin L activity, and a cathepsin L specific inhibitor, CLIK148, attenuated the Eco-MLV vector infection. These results indicate that the suppression of cathepsin L activity by CA-074Me induces the inhibition of Eco-MLV infection, suggesting that cathepsin L is required for the Eco-MLV infection in NIH3T3 cells. The CA-074Me treatment inhibited the Eco-MLV infection in human cells expressing the exogenous mouse ecotropic receptor and endogenous cathepsins B and L, but the CLIK148 treatment did not, showing that only the cathepsin L suppression by CLIK148 is not enough to prevent the Eco-MLV infection in cells expressing both of cathepsins B and L, and CA-074Me inhibits the Eco-MLV infection by suppressing both of cathepsins B and L. These results suggest that either cathepsin B or L is sufficient for the Eco-MLV infection.


title: Survival-Convolution Models for Predicting COVID-19 Cases and Assessing Effects of Mitigation Strategies

text: Countries around the globe have implemented unprecedented measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic. We aim to predict COVID-19 disease course and compare effectiveness of mitigation measures across countries to inform policy decision making. We propose a robust and parsimonious survival-convolution model for predicting key statistics of COVID-19 epidemics (daily new cases). We account for transmission during a pre-symptomatic incubation period and use a time-varying effective reproduction number (R(t)) to reflect the temporal trend of transmission and change in response to a public health intervention. We estimate the intervention effect on reducing the infection rate and quantify uncertainty by permutation. In China and South Korea, we predicted the entire disease epidemic using only data in the early phase (two to three weeks after the outbreak). A fast rate of decline in R(t) was observed and adopting mitigation strategies early in the epidemic was effective in reducing the infection rate in these two countries. The lockdown in Italy did not further accelerate the speed at which the infection rate decreases. The effective reproduction number has staggered around R(t) = 1.0 for more than 2 weeks before decreasing to below 1.0, and the epidemic in Italy is currently under control. In the US, R(t) significantly decreased during a 2-week period after the declaration of national emergency, but afterwards the rate of decrease is substantially slower. If the trend continues after May 1, the first wave of COVID-19 may be controlled by July 26 (CI: July 9 to August 27). However, a loss of temporal effect on infection rate (e.g., due to relaxing mitigation measures after May 1) could lead to a long delay in controlling the epidemic (November 19 with less than 100 daily cases) and a total of more than 2 million cases.


title: Two simple comments regarding coronavirus

text: Abstract Two thought provoking comments related to understanding the problems with the coronavirus are presented.


title: Molecular characterization of PL97-1, the first Korean isolate of the porcine reproductive and respiratory syndrome virus

text: Abstract We determined the complete nucleotide and predicted amino acid sequence of the genomic RNA of PL97-1, the first Korean strain of porcine reproductive and respiratory syndrome virus (PRRSV), which was isolated from the serum of an infected pig in 1997. We found that the 15411-nucleotide genome of PL97-1 consisted of a 189-nucleotide 5′ noncoding region (NCR), a 15071-nucleotide protein-coding region, and a 151-nucleotide 3′NCR, followed by a poly (A) tail. The 5′-end of PL97-1 began with 1 ATG ACG TAT AGG12. Comparison of the PL97-1 genome with the 11 fully sequenced PRRSV genomes currently available revealed sequence divergence ranging from 0.3% (the VR-2332-derived vaccine MLV RespPRRS/Repro strain) to 38% (the Dutch Lelystad strain). To better understand the genetic relationships between these different strains, phylogenetic analyses were performed on the full-length PRRSV genomes. Significantly, the phylogenetic tree based on the ORF1b or ORF7 genes most closely resembled the tree based on the full-length genomes. Thus, these single genes will be the most useful in revealing the genetic relationships between the different strains relative to their geographical distribution. Extensive phylogenetic analyses using the ORF7 sequences of 111 PRRSV isolates available revealed that PL97-1 is most closely related to the North American genotype VR-2332, a VR-2332-derived vaccine strain, and Chinese BJ-4. It is distantly related to the European genotype Lelystad. This study provides the largest full-length genome phylogenetic analysis of PRRSV that has been published to date, and supports an earlier genetic grouping of the many temporally and geographically diverse PRRSV strains currently isolated.


docid: evlkmngy

title: Programas de reabilitação cardíaca para doentes com insuficiência cardíaca durante o período do COVID-19


title: Quantitative analysis and chromatographic fingerprinting for the quality evaluation of Scutellaria baicalensis Georgi using capillary electrophoresis

text: Abstract Quantitative analysis and chromatographic fingerprinting for the quality evaluation of a Chinese herb Scutellaria baicalensis Georgi using capillary electrophoresis (CE) technique was developed. The separation was performed with a 50.0cm (42.0cm to the detector window)×75μm i.d. fused-silica capillary, and the CE fingerprint condition was optimized using the combination of central composite design and multivariate analysis. The optimized buffer system containing 15mM borate, 40mM phosphate, 15mM SDS, 15% (v/v) acetonitrile and 7.5% (v/v) 2-propanol was employed for the method development, and the baseline separation was achieved within 15min. The determination of the major active components (Baicalin, Baicalein and Wogonin) was carried out using the optimized CE condition. Good linear relationships were provided over the investigated concentration ranges (the values of R 2: 0.9997 for Baicalin, 0.9992 for Baicalein, and 0.9983 for Wogonin, respectively). The average recoveries of these target components ranged between 96.1–105.6%, 98.6–105.2%, and 96.3–105.0%, respectively. CE fingerprints combined with the quantitative analysis can be used for the quality evaluation of S. baicalensis.


docid: htwlfqos

title: miRNA-200c-3p is crucial in acute respiratory distress syndrome

text: Influenza infection and pneumonia are known to cause much of their mortality by inducing acute respiratory distress syndrome (ARDS), which is the most severe form of acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2), which is a negative regulator of angiotensin II in the renin–angiotensin system, has been reported to have a crucial role in ALI. Downregulation of ACE2 is always associated with the ALI or ARDS induced by avian influenza virus, severe acute respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis. However, the molecular mechanism of the decreased expression of ACE2 in ALI is unclear. Here we show that avian influenza virus H5N1 induced the upregulation of miR-200c-3p, which was then demonstrated to target the 3′-untranslated region of ACE2. Then, we found that nonstructural protein 1 and viral RNA of H5N1 contributed to the induction of miR-200c-3p during viral infection. Additionally, the synthetic analog of viral double-stranded RNA (poly (I:C)), bacterial lipopolysaccharide and lipoteichoic acid can all markedly increase the expression of miR-200c-3p in a nuclear factor-κB-dependent manner. Furthermore, markedly elevated plasma levels of miR-200c-3p were observed in severe pneumonia patients. The inhibition of miR-200c-3p ameliorated the ALI induced by H5N1 virus infection in vivo, indicating a potential therapeutic target. Therefore, we identify a shared mechanism of viral and bacterial lung infection-induced ALI/ARDS via nuclear factor-κB-dependent upregulation of miR-200c-3p to reduce ACE2 levels, which leads increased angiotensin II levels and subsequently causes lung injury.


title: Mitigating the Psychological Impact of COVID-19 on Healthcare Workers: A Digital Learning Package

text: The coronavirus pandemic (COVID-19) will undoubtedly have psychological impacts for healthcare workers, which could be sustained; frontline workers will be particularly at risk. Actions are needed to mitigate the impacts of COVID-19 on mental health by protecting and promoting the psychological wellbeing of healthcare workers during and after the outbreak. We developed and evaluated a digital learning package using Agile methodology within the first three weeks of UK outbreak. This e-package includes evidence-based guidance, support and signposting relating to psychological wellbeing for all UK healthcare employees. A three-step rapid development process included public involvement activities (PPIs) (STEP 1), content and technical development with iterative peer review (STEP 2), and delivery and evaluation (STEP 3). The package outlines the actions that team leaders can take to provide psychologically safe spaces for staff, together with guidance on communication and reducing social stigma, peer and family support, signposting others through psychological first aid (PFA), self-care strategies (e.g., rest, work breaks, sleep, shift work, fatigue, healthy lifestyle behaviours), and managing emotions (e.g., moral injury, coping, guilt, grief, fear, anxiety, depression, preventing burnout and psychological trauma). The e-package includes advice from experts in mental wellbeing as well as those with direct pandemic experiences from the frontline, as well as signposting to public mental health guidance. Rapid delivery in STEP 3 was achieved via direct emails through professional networks and social media. Evaluation included assessment of fidelity and implementation qualities. Essential content was identified through PPIs (n = 97) and peer review (n = 10) in STEPS 1 and 2. The most important messages to convey were deemed to be normalisation of psychological responses during a crisis, and encouragement of self-care and help-seeking behaviour. Within 7 days of completion, the package had been accessed 17,633 times, and healthcare providers had confirmed immediate adoption within their health and wellbeing provisions. Evaluation (STEP 3, n = 55) indicated high user satisfaction with content, usability and utility. Assessment of implementation qualities indicated that the package was perceived to be usable, practical, low cost and low burden. Our digital support package on ‘psychological wellbeing for healthcare workers’ is free to use, has been positively evaluated and was highly accessed within one week of release. It is available here: Supplementary Materials. This package was deemed to be appropriate, meaningful and useful for the needs of UK healthcare workers. We recommend provision of this e-package to healthcare workers alongside wider strategies to support their psychological wellbeing during and after the COVID-19 pandemic.


title: Primary and Repeated Respiratory Viral Infections Among Infants in Rural Nepal

text: BACKGROUND: Respiratory viruses cause significant morbidity and death in infants; 99% of such deaths occur in resource-limited settings. Risk factors for initial and repeated respiratory viral infections in young infants in resource-limited settings have not been well described. METHODS: From 2011 to 2014, a birth cohort of infants in rural Nepal was enrolled and followed with weekly household-based active surveillance for respiratory symptoms until 6 months of age. Respiratory illness was defined as having any of the following: fever, cough, wheeze, difficulty breathing, and/or a draining ear. We tested nasal swabs of infants with respiratory illness for multiple respiratory viruses by using a reverse transcription polymerase chain reaction assay. The risk of primary and repeated infections with the same virus was evaluated using Poisson regression. RESULTS: Of 3528 infants, 1726 (49%) had a primary infection, and 419 (12%) had a repeated infection. The incidences of respiratory viral infection in infants were 1816 per 1000 person-years for primary infections and 1204 per 1000 person-years for repeated infection with the same virus. Exposure to other children and male sex were each associated with an increased risk for primary infection (risk ratios, 1.13 [95% confidence interval (CI), 1.06–1.20] and 1.14 [95% CI, 1.02–1.27], respectively), whereas higher maternal education was associated with a decreased risk for both primary and repeated infections (risk ratio, 0.96 [95% CI, 0.95–0.98]). The incidence of subsequent infection did not change when previous infection with the same or another respiratory virus occurred. Illness duration and severity were not significantly different in the infants between the first and second episodes for any respiratory virus tested. CONCLUSIONS: In infants in rural Nepal, repeated respiratory virus infections were frequent, and we found no decrease in illness severity with repeated infections and no evidence of replacement with another virus. Vaccine strategies and public health interventions that provide durable protection in the first 6 months of life could decrease the burden of repeated infections by multiple respiratory viruses, particularly in low-resource countries.


title: Light and Ultrastructural Pathologic Changes in Intestinal Coronavirus Infection of Newborn Calves

text: SUMMARY: Seven conventional newborn calves were inoculated orally with the coronavirus strain LY‐138, originally recovered from naturally‐infected diarrheic calves. All calves developed diarrhea during the first 24 h after inoculation. The presence and excretion of virus was monitored by electron microscopy. Grossly, the changes were subtle and not striking. The intestinal tract was distended and contained a yellow clear fluid. The small intestinal wall was thin and transparent. Histologic changes were characterized by atrophy and fusion of the villi, decreased height and vacuolation of the intestinal epithelial cells, by a reduced number of goblet cells, crypt hypertrophy and dilatation, and by edema and increased cellularity of the lamina propria mucosae. Ultrastructurally the viral agent infected the intestinal absorptive epithelial cells, undifferentiated epithelial cells and goblet cells of the villi, and occasionally fibroblasts and endothelial cells of the lamina propria mucosae. Morphologic evidence indicated that virus multiplication occurred only in the cytoplasm of infected cells. The rough and smooth endoplasmic reticulum became dilated, and electron‐dense, granulo‐fibrillar material filled their cysternae to form smooth membrane‐bounded viral factories in the supranuclear cytoplasm of infected intestinal epithelial cells. Ultrastructural cytologic changes in this viral infection consisted of dilation of the endoplasmic reticulum network, cellular ribosome depletion, extensive endoplasmic vacuolation and vesiculation of Golgi elements of intestinal epithelial cells, swelling and degeneration of mitochondria, loss of normal nuclear polarity with pyknosis and karyolysis of the nuclei, loss of cytoplasmic matrix, and a broad spectrum of pathologic changes involving the microvilli and terminal web. ZUSAMMENFASSUNG: Lichtmikroskopische und Ultrastrukturelle pathologische Veränderungen bei intestinaler Coronavirusinfektion neugeborener Kälber Sieben konventionelle neugeborene Kälber wurden oral mit dem Coronavirus‐Stamm LY‐138, der ursprünglich von natürlich infizierten Kälbern mit Diarrhoe stammt, infiziert. Alle Kälber entwickelten Durchfall während der ersten 24 Stunden nach Inokulation. Vorhandensein und die Ausscheidung des Virus wurden elektronenoptisch verfolgt. Sichtbare Veränderungen waren gering und wenig auffallend. Der Darmtrakt war erweitert und enthielt eine gelbe, klare Flüssigkeit. Die Dünndarmwand war dünn und durchscheinend. Histologische Veränderungen waren charakterisiert durch Atrophie und Verschmelzung der Zotten, verminderte Höhe und Vakuolisierung der intestinalen Epithelzellen, durch eine reduzierte Anzahl von Gobletzellen, Kryptenhypertrophie und ‐erweiterung, sowie Ödematisierung und erhöhte Zellularität der lamina propria mucusae. Ultrastrukturell infizierte das Virus die intestinalen absorptiven Epithelzellen, nichtdifferenzierte Epithelzellen und Gobletzellen der Zotten, und gelegentlich Fibroblasten sowie Endothelzellen der Lamina propria mucosae. Die morphologischen Veränderungen weisen darauf hin, daß die Virusvermehrung nur im Zytoplasma infizierter Zellen stattfand. Das rauhe und glatte endoplasmatische Retikulum war erweitert, und elektronendichtes, granulo‐fibrilläres Material füllte die Zisternen aus, die feine Membran‐gebundene Virusvermehrungsfabriken in dem supranukleären Zytoplasmabereich infizierter intestinaler Epithelzellen bildeten. Ultrastrukturelle zytologische Veränderungen bestanden bei dieser Virusinfektion aus Erweiterung des endoplasmatischen Retikulumnetzwerks, zellulärem Ribosomenverlust, extensiver endoplasmatischer Vakuolisierung der Golgielemente der intestinalen Epithelzellen, Schwellung und Degeneration von Mitochondrien, Verlust der normalen nukleären Polarität mit Pyknose und Karyolyse der Zellkerne, Verlust der Zytoplasmamatrix, und aus einem breiten Spektrum pathologischer Veränderungen an den Mikrozotten und der terminalen Netzstruktur. RÉSUMÉ: Lésions pathologiques ultrastructurelles et au microscope optique lors d'infection intestinale à Coronavirus chez des veaux nouveau‐nés Sept veaux nouveau‐nés conventionnels ont été infectés oralement par la souche LY‐138 de Coronavirus, isolée précédement chez des veaux naturellement infectés présentant une diarrhée. Tous les veaux développèrent une diarrhée durant les premières 24 heures suivant l'inovulation. La présence et la sécrétion du virus ont été suivies au microscope électronique. Les lésions apparentes furent faibles et peu apparentes. Le tractus digestif fut élargi et contenait un liquide jaune et clair. La paroi de l'intestin grêle était mince et transparente. Les lésions histologiques furent caractérisées par une atrophie et une fusion des villi, une hauteur diminuée et une vacuolisation des cellules épithéliales de l'intestin, par un nombre réduit des cellules caliciformes, une hypertrophie et un élargissement des cryptes ainsi qu'un oedème et un nombre de cellules augmenté de Lamina propria mucosae. Le virus a infecté ultrastructurellement les cellules épithéliales absorbantes de l'intestin, des cellules épithéliales non différenciées et des cellules caliciformes des villi, de temps en temps des fibroblastes et des cellules endothéliales de Lamina propria mucosae. Les lésions morphologiques ont montré que la multiplication du virus n'avait lieu que dans le cytoplasme des cellules infectées. Le Reticulum endoplasmique grossier et fin fut élargi et un matériel granuleux et fibrillaire remplissait les citernes qui formaient de fines régions de réplication virale liées à la membrane dans le voisinage cytoplasmique supranucléaire des cellules épithéliales infectées de l'intestin. Les lésions cytologiques ultrastructurelles lors de cette infection virale consistèrent en un élargissement du réseau endoplasmique, une perte des ribosomes cellulaires, une vacuolisation endoplasmique extensive des éléments de Golgi dans les cellules épithéliales de l'intestin, une enflure et une dégénérescence des mitochondries, une perte de la polarité nucléaire normale avec une picnose et une carylolyse des noyaux cellulaires, une perte de la matrice cytoplasmique et un large éventail de lésions pathologiques des microvilli et des tissus terminaux. RESUMEN: Modificaciones patológicas fotomicroscópicas y ultraestructurales en la infección intestinal de terneros recién nacidos por virus Corona Se infectaron por vía oral siete terneros convencionales con la estirpe de virus Corona LY‐138, la cual es originaria de terneros, infectados naturalmente, con diarrea. Todos los terneros manifestaban diarrea durante las 24 horas primeras después de la inoculación. Se seguía electrónicoópticamente la presencia y eliminación de virus. Las modificaciones visibles eran escasas y se destacaban poco. El tracto intestinal se hallaba dilatado, conteniendo un líquido amarillo claro. La pared del intestino delgado era tenue y translúcida. Las modificaciones histopatológicas se caracterizaban por atrofia y soldadura de las villosidades, altura reducida y vacuolización de las células epiteliales intestinales, por una cantidad reducida de células caliciformes, hipertrofia y ensanchamiento de las criptas, y por edematización y celularidad aumentada de la lámina propia mucosa. El virus infectaba ultraestructuralmente las células epiteliales intestinales absortivas, células epiteliales no diferenciadas y células caliciformes de las villosidades, y, en ocasiones fibroblastos y células endoteliales de la lámina propia mucosa. Las modificaciones morfológicas señalan que la multiplicación de virus solo tuvo lugar en el citoplasma de las células infectadas. El retículo endoplasmático basto y fino se hallaba dilatado y material granulosofibrilar, opaco a los electrones, ocupaba las cisternas, las cuales formaban lugares finos de replicación antiviral, ligados a las membranas en el ámbito citoplasmático supranuclear de células epiteliales intestinales infectadas. Las modificaciones citológicas ultraestructurales consistían en esta infección a virus en dilatación del retículo endoplasmático, pérdida celular de ribosomas, vacuolización endoplasmática extensiva de los elementos de Golgi de las células epiteliales intestinales, tumefacción y degeneración de mitocondrias, pérdida de la polaridad nuclear normal con picnosis y cariolisis de los núcleos celulares, pérdida de la matriz citoplasmática, y en un espectro amplio de modificaciones patológicas en las microvillosidades y tejidos terminales.


Mobile phones of paediatric senior physicians are highly contaminated with viral genomes of several epidemic viruses during the winter season


title: Monoclonal Antibody as a Potential Anti-COVID-19

text: Coronavirus disease 2019 (COVID-19) is expanding rapidly, which made it as one of top priorities for scientists to develop novel treatment strategies. Researchers are racing to develop treatments based on antibodies to block and/or neutralize the coronavirus in affected patients. Initially, the genetic and structural similarity of the virus to severe acute respiratory syndrome coronavirus (SARS-CoV) created the potential for understanding disease pathogenesis. Researchers have published reports of specific monoclonal antibodies against to COVID-19 (B38, H4, 47D11) and hope that this method is effective. As well as studies on patients who are plasma therapy, the patient's condition shows improvement. The evidence for these studies is very promising and demonstrates the potential of monoclonal antibody therapy as a therapeutic approach and prevention of covid-19 infection.


title: Could human coronavirus OC43 have co-evolved with early humans?

text: This paper reports on an investigation of the role of codon usage evolution on the suggested bovine-to-human spillover of Bovine coronavirus (BCoV), an enteric/respiratory virus of cattle, resulting in the emergence of the exclusively respiratory Human coronavirus OC43 (HCoV-OC43). Analyses based on full genomes of BCoV and HCoV-OC43 and on both human and bovine mRNAs sequences of cholecystokinin (CCK) and surfactant protein 1 A (SFTP1-A), representing the enteric and respiratory tract codon usage, respectively, have shown natural selection leading to optimization or deoptimization of viral codon usage to the human enteric and respiratory tracts depending on the virus genes under consideration. A higher correlation was found for the nucleotide distance at the 3(rd) nucleotide position of codons and codon usage optimization to the human respiratory tract when BCoV and HCoV-OC43 were compared. An MCC tree based on relative synonymous codon usage (RSCU) data integrating data from both viruses and hosts into a same analysis indicated three putative host/virus contact dates ranging from 1.54E8 to 2.44E5 years ago, suggesting that an ancestor coronavirus might have followed human evolution.


A Post-Truth Proactionary Look at the Pandemic


title: The role of type-2 turkey astrovirus in poult enteritis syndrome

text: ABSTRACT An experimental study was conducted to determine the comparative pathogenicity of type-2 turkey astrovirus (TAstV-2) obtained from turkey flocks afflicted with poult enteritis syndrome (PES) and from turkey flocks displaying no apparent signs of infection. In total, ninety 7-d-old poults, which tested negative for the presence of astrovirus, rotavirus, coronavirus, and reovirus by reverse transcriptase (RT) PCR, were divided evenly into 3 groups: A, B, and C. Birds in group A were inoculated orally with turkey astrovirus-positive intestinal contents from birds affected with PES. Group B received turkey astrovirus-containing intestinal contents from apparently healthy flocks. Group C served as a negative control and was given PBS. Clinical signs of diarrhea, depression, and dullness were observed in group A. Birds in group B also showed clinical signs similar to those in group A, although the signs were milder in nature. Birds in group C did not show any clinical signs. At 16 d postinoculation, the BW of birds in group A was significantly lower than that of birds in groups B or C. In addition, the bursa size was reduced in group A, but not in groups B or C. Birds in groups A and B, but not in group C, were found to shed turkey astrovirus in their feces, as detected by RT-PCR. These results provide a preliminary indication that TAstV-2 from PES birds may be more pathogenic than TAstV-2 from apparently healthy poults. Further studies are needed to determine if pathogenic and nonpathogenic strains of TAstV-2 exist in the environment. These results also reinforce our previous observations that astrovirus is involved in PES, causing significant retardation in growth and weight gain.


title: Outcome of coronavirus‐associated severe acute respiratory syndrome using a standard treatment protocol

text: Objective: There is so far no consensus on the optimal treatment strategy for the coronavirus‐associated severe acute respiratory syndrome (SARS). We aimed to analyse the outcomes of a standard treatment strategy comprising antibiotics, a combination of ribavirin, a 3‐week step‐down course of corticosteroids, and the possibility of pulsed methylprednisolone rescue in the event of deterioration. Methodology: This was a prospective cohort study performed at a major public‐funded hospital in Hong Kong. Eighty‐eight World Health Organisation/Centers for Disease Control and Prevention probable cases of SARS (97% laboratory‐confirmed) were treated with a standard protocol previously reported. Seventy‐one patients treated de novo were analysed in detail with regard to time to clinical stabilization after combination treatment, requirement of additional therapy (pulsed methylprednisolone; assisted ventilation); and final outcomes (recovery, mortality). Results: The mean age was 42. Twenty‐one patients (24%) had comorbidities. Three of 71 treated de novo recovered with antibiotics alone. The remaining 68 received combination treatment at a mean of 5.8 days after symptom onset, of whom 30 subsequently required pulsed methylprednisolone rescue (independent predictors: older age and higher LDH) and 18 required assisted ventilation (independent predictors: older age, higher oxygen requirement and creatinine level). Their median time to clinical stabilization was 8.0 days after combination treatment (independent predictor for longer time to stabilization: median age of 41 or above). Common complications were hyperglycaemia (58%), pneumo‐mediastinum/thoraces (13%), psychiatric manifestations (7%) and ventilator‐associated pneumonia (2%). One patient (1%) died of SARS‐related respiratory failure. All‐cause mortality was 3.4%, occurring in patients aged > 65 years only. None of the discharged survivors required continuation of oxygen therapy. Conclusions: This standard treatment protocol resulted in overall satisfactory outcomes. Randomized controlled trial is suggested to confirm its efficacy.


title: Neglected Zoonotic Diseases—The Long and Winding Road to Advocacy

text: BACKGROUND: Years of advocacy for the neglected tropical diseases (NTDs) have focused the world's attention on these diseases of the poor, resulting most recently in the 2012 “London Declaration” and the recent World Health Assembly Resolution WHA66.12 on NTDs in May 2013. Control of the endemic neglected zoonotic diseases (NZDs) would benefit from a similar campaign, which needs the support of a global community. METHODOLOGY/PRINCIPAL FINDINGS: The resolutions from all 66 World Health Assembly (WHA) meetings held between 1948 and 2013 were examined to determine how many contain a specific focus on any of the following eight NZDs as defined by the World Health Organisation (WHO): anthrax, bovine tuberculosis (TB), brucellosis, Taenia solium cysticercosis, cystic echinococcosis (hydatidosis), leishmaniasis, rabies, and zoonotic human African trypanosomiasis (HAT or sleeping sickness). Twenty-one resolutions adopted in the 16 assemblies between 1948 and 2013 targeted one or more of these eight NZDs, representing 4% of the total resolutions on infectious diseases passed to date. The 2013 adoption of Resolution WHA66.12 targeting all 17 NTDs marks a change in approach by the WHA. Whereas previous resolutions have targeted the NTDs as separate entities, the new approach of the combined resolution will help increase the overall momentum to target these ancient diseases as coendemic clusters in endemic countries. However, three major NZDs remain outside this recent resolution: anthrax, brucellosis, and bovine TB. CONCLUSIONS AND SIGNIFICANCE: The recent adoption of a specific resolution at the WHA in 2013 that emphasises a One Health approach for the successful control of 17 NTDs is a major development in advocacy. However, recognition of the importance of three major NZDs to public health in endemic countries—anthrax, brucellosis, and bovine tuberculosis—is still lacking despite being prioritised by the WHA as early as the 1950s. Global advocacy for control of the NZDs as a whole would similarly benefit from adoption of a One Health approach as is promoted for the NTDs under WHA66.12.


title: Factors associated with changing indications for adenotonsillectomy: A population-based longitudinal study

text: OBJECTIVE: Adenotonsillectomy (AT) is one of the most common surgical procedures performed in children and adults. We aim to assess the factors associated with changes in the incidence of and indications for AT using population-level data. STUDY DESIGN: This retrospective cohort study investigated patients who underwent AT between 1997 and 2010 by using data from the Taiwan National Health Insurance Research Database. We examined surgical rates and indications by the calendar year as well as age, sex, hospital level, and insured residence areas for the correlating factors. RESULTS: The average annual incidence rate of AT was 14.7 per 100,000 individuals during 1997–2010. Pediatric (<18 years) patients represented 48.2% of the total AT population. More than 99% of the patients underwent the AT procedures as an inpatient intervention. Longitudinal data demonstrated an increasing trend in the pediatric AT rates from 1997 (4.3/100,000) to 2010 (5.7/100,000) (p = 0.029). In the adult subgroup, a decreasing prevalence of infectious indications (p = 0.014) coincided with an increasing neoplastic indications (p = 0.001). In the pediatric subgroup, the prevalence of obstructive indications increased (p = 0.002). The logistic regression analyses indicated that the significant factors associated with the changing surgical indications for AT were the age in the adult subgroup and hospital level in the pediatric subgroup. CONCLUSIONS: This study revealed a low AT rate in Taiwan than that in other countries. Pediatric AT incidence increased during 1997–2010. Although a rising prevalence of obstructive and neoplastic indications was noted, infection remained the most common indications for AT. Age in the adult subgroup and hospital level in the pediatric subgroup were factors associated with the changing indications for AT.


title: Male mortality and the German response: lessons from COVID‐19

text: The current COVID‐19 outbreak has raised many questions, amongst them the higher mortality rates in men and the low overall mortality rates in Germany compared to other European countries. Here the authors explore some of the reasons behind both these phenomena and outline what we can learn from them for the future.


title: Feline herpes dermatitis treated with interferon omega

text: This case report describes the diagnosis, demonstration and treatment of feline herpes virus‐induced facial dermatitis in a cat. The cat was successfully treated with interferon omega (IFN‐ω).


title: Niclosamide induced cell apoptosis via upregulation of ATF3 and activation of PERK in Hepatocellular carcinoma cells

text: BACKGROUND: Hepatocellular carcinoma (HCC) is one of most common and aggressive human malignancies in the world, especially, in eastern Asia, and its mortality is very high at any phase. We want to investigate mechanism of niclosamide inducing cell apoptosis in HCC. METHODS: Two hepatoma cell lines were used to evaluate activity of niclosamide inducing cell apoptosis and study its mechanism. Quantitative real-time PCR and western blotting were used in analysis of genes expression or protein active regulated by niclosamide. RESULTS: Niclosamide remarkably induced cell apoptosis in hepatoma cells. Furthermore, our study revealed that RNA-dependent protein kinase-like kinase (PERK) is activated and its expression is up-regulated in HCC cells which are exposed to niclosamide. niclosamide also significantly increase activating transcription factor 3 (ATF3), activating transcription factor 4 (ATF4) and CCAAT/enhancer-binding protein-homologous protein (CHOP) expression in HCC cells. It’s suggested that the function of niclosamide was abrogated by PERK inhibitor or absent ATF3. Expression of PERK and CHOP is correlated with ATF3 level in the cells. CONCLUSION: Taken together, our results indicate that ATF3 plays an integral role in ER stress activated and cell apoptosis induced by niclosamide in HCC cells. In this study, the new mechanism of niclosamide as anti-cancer we investigated, too.


title: Molecular characterization of the S proteins of two enterotropic murine coronavirus strains

text: Abstract Enterotropic strains of murine coronaviruses (MHV-Y and MHV-RI) differ extensively in their pathogenesis from the prototypic respiratory strains of murine coronaviruses. In an effort to determine which viral proteins might be determinants of enterotropism, immunoblots of MHV-Y and MHV-RI virions using anti-S, -N and -M protein-specific antisera were performed. The uncleaved MHV-Y and MHV-RI S proteins migrated slightly faster than the MHV-A59 S protein. The MHV-Y S protein was inefficiently cleaved. The MHV-Y, MHV-RI and MHV-A59 N and M proteins showed only minor differences in their migration. The S genes of MHV-Y and MHV-RI were cloned, sequenced and found to encode 1361 and 1376 amino acid long proteins, respectively. The presence of several amino acids changes upstream from the predicted cleavage site of the MHV-Y S protein may contribute its inefficient cleavage. A high degree of homology was found between the MHV-RI and MHV-4 S proteins, whereas the homology between the MHV-Y S protein and the S proteins of other MHV strains was much lower. These results indicate that the enterotropism of MHV-RI and MHV-Y may be determined by different amino acid changes in the S protein and/or by changes in other viral proteins.


Uncertainty and the risk for occupational exposure to Severe Acute Respiratory Syndrome-Coronavirus-2


title: Identification of GBF1 as a cellular factor required for hepatitis E virus RNA replication

text: The hepatitis E virus (HEV) genome is a single‐stranded, positive‐sense RNA that encodes three proteins including the ORF1 replicase. Mechanisms of HEV replication in host cells are unclear, and only a few cellular factors involved in this step have been identified so far. Here, we used brefeldin A (BFA) that blocks the activity of the cellular Arf guanine nucleotide exchange factors GBF1, BIG1, and BIG2, which play a major role in reshuffling of cellular membranes. We showed that BFA inhibits HEV replication in a dose‐dependent manner. The use of siRNA and Golgicide A identified GBF1 as a host factor critically involved in HEV replication. Experiments using cells expressing a mutation in the catalytic domain of GBF1 and overexpression of wild type GBF1 or a BFA‐resistant GBF1 mutant rescuing HEV replication in BFA‐treated cells, confirmed that GBF1 is the only BFA‐sensitive factor required for HEV replication. We demonstrated that GBF1 is likely required for the activity of HEV replication complexes. However, GBF1 does not colocalise with the ORF1 protein, and its subcellular distribution is unmodified upon infection or overexpression of viral proteins, indicating that GBF1 is likely not recruited to replication sites. Together, our results suggest that HEV replication involves GBF1‐regulated mechanisms.