title: The cytotoxicity to leukemia cells and antiviral effects of Isatis indigotica extracts on pseudorabies virus

text: Abstract Aim of the study Isatis indigotica (I. indigotica), Cruciferae, has been used in Chinese medicine for anti-leukemia and anti-severe acute respiratory syndrome (SARS). The aim of this study was to evaluate the cytotoxicity of Isatis indigotica extracts on human leukemia cell line (HL-60) and the antiviral activity on swine pseudorabies virus (PrV) in in vitro assays. Materials and methods Extracts and derived fractions of Isatis indigotica were prepared from root (R) and leaf (L) using methanol (M), ethyl acetate (E) and distilled water (D). The cytotoxic effect of extracts on swine peripheral blood mononuclear cells (PBMCs) and HL-60 was assessed by MTT method. The cytopathic effect (CPE) reduction, plaque reduction and inhibition assays on viral replication, and virucidal activity were further conducted to investigate the anti-PrV activity. Results Indirubin, one of the biological active compounds of Isatis indigotica, had the most significant cytotoxicity on HL-60 cells and inhibitory effect on PrV replication. Extracts from roots and leaves of Isatis indigotica also presented CPE inhibition either before or after infection of PrV on porcine kidney (PK-15) cells. Leaf extracts had better virucidal activity than roots, and ethyl acetate extracts exhibited the highest efficacy among extracts tested. Conclusion Isatis indigotica posses a valuable virucidal effect in disease control of pseudorabies virus infection in swine.


docid: kcatqzgs

title: An emerging novel goose astrovirus associated with gosling gout disease, China

text: Since the first isolation from human, astroviruses have been detected in many species. Wide host range and occasional cross-transmission of astrovirus pose a risk for zoonotic infection. Here, novel astroviruses were identified from goslings with recent epidemic gout disease in China. A virus, designated as GD, was efficiently isolated from a diseased gosling using LMH cells. Genome of GD amplified using 5′ and 3′ RACE was 7183nt in full length. Sequence analysis revealed the genome of GD was <60.8% homology with others deposited in Genbank. Moreover, GD could be neutralized by goose convalescent sera, and the gout associated symptom in goslings could be reproduced by GD infection. Our data demonstrated the goose astrovirus could be one of the causative agents of the ongoing gosling gout disease in China. The identification of the goose astrovirus not only diversified the astrovirus species, but also broadened the disease patterns caused by astroviruses.


title: ¿Es esperable que haya cuadros neurológicos por la pandemia por SARS-CoV-2?

text: INTRODUCTION: There is growing evidence that SARS-CoV-2 can gain access to the central nervous system (CNS). We revise the literature on coronavirus infection of the CNS associated with neurological diseases. DEVELOPMENT: Neurological symptoms were rarely reported in the SARS-CoV and MERS-CoV epidemics, although isolated cases were described. There are also reports of cases of neurological symptoms associated with CoV-OC43 and CoV-229E infection. The presence of neurological lesions, especially demyelinating lesions in the mouse hepatitis virus model, may explain the mechanisms by which coronaviruses enter the CNS, particularly those related with the immune response. This may explain the presence of coronavirus in patients with multiple sclerosis. We review the specific characteristics of SARS-CoV-2 and address the question of whether the high number of cases may be associated with greater CNS involvement. CONCLUSION: Although neurological symptoms are not frequent in coronavirus epidemics, the high number of patients with SARS-CoV-2 infection may explain the presence of the virus in the CNS and increase the likelihood of early- or delayed-onset neurological symptoms. Follow-up of patients affected by the SARS-CoV-2 epidemic should include careful assessment of the CNS.


title: COVID-19 in Older People: A Rapid Clinical Review

text: INTRODUCTION: The COVID-19 pandemic poses a high risk to older people. The aim of this paper is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: We searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20th and 24th March 2020, respectively. RESULTS: Screening of over 1100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral-PCR and serology are the mainstays of testing but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: Given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.


docid: tntugqub

title: Anthropocenic war: coronavirus and total demobilization

text: This paper argues that the covid-19 coronavirus pandemic of 2019–2020 constituted the first Anthropocenic war: as an anthropogenic virus and biological attack on the human body and as the first global pandemic requiring a truly global response since our recognition of the Anthropocene. The paper explores how each nation was forced by the virus into a pause of global connections and relationships and a war against the human body, with the ‘total demobilization’ and bunkerization of their domestic populations. With space cut-off, this became a war of time and of endurance, with relations reduced, as Virilio suggests, to those of the connected ‘terminal citizen’. Beyond the civil war against the body, however, there was also the civil war within the domestic populations who were active participants in this imploded home front line, producing and sharing both feel-good and disciplinary propaganda and engaging in debates around politics, conspiracy theories and disinformation. The paper explores the problems governments face in remobilization, the new data regime of informational totalitarianism remobilization will help produce and the likely instability of the post-covid-19 international order. It concludes that this ‘war’ was only the beginning and that anthropogenic environmental factors will play an increasing role in human conflicts in coming years.


title: Griffithsin binds to the glycosylated proteins (E and prM) of Japanese encephalitis virus and inhibit its infection

text: Abstract Griffithsin (GRFT) is a broad-spectrum antiviral protein against several glycosylated viruses. In our previous publication, we have shown that GRFT exerted antiviral activity against Japanese encephalitis virus (JEV) infection. Herein, we further elucidated the mechanism by which GRFT inhibits JEV infection in BHK-21 cells. In vitro experiments using Pull-down assay and Co-immunoprecipitation (CO-IP) assay showed that GRFT binds to the JEV glycosylated viral proteins, specifically the enveloped (E) and premature (prM) glycoproteins. The binding of GRFT to the JEV was competitively inhibited by increasing concentrations of mannose; in turns abolished anti-JEV activity of GRFT. We suggested that, the binding of GRFT to the glycosylated viral proteins may contribute to its anti-JEV activity. Collectively, our data indicated a possible mechanism by which GRFT exerted its anti-JEV activity. This observation suggests GRFT's potentials in the development of therapeutics against JEV or other flavivirus infection.


The Neuroinvasive Potential of Severe Acute Respiratory Syndrome Coronavirus 2


Stability of Middle East Respiratory Syndrome Coronavirus in Milk


title: Human coronavirus NL63: a clinically important virus?

text: Respiratory tract infection is a leading cause of morbidity and mortality worldwide, especially among young children. Human coronaviruses (HCoVs) have only recently been shown to cause both lower and upper respiratory tract infections. To date, five coronaviruses (HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63 and HCoV HKU-1) that infect humans have been identified, four of which (HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU-1) circulate continuously in the human population. Human coronavirus NL63 (HCoV-NL63) was first isolated from the aspirate from a 7-month-old baby in early 2004. Infection with HCoV-NL63 has since been shown to be a common worldwide occurrence and has been associated with many clinical symptoms and diagnoses, including severe lower respiratory tract infection, croup and bronchiolitis. HCoV-NL63 causes disease in children, the elderly and the immunocompromised, and has been detected in 1.0–9.3% of respiratory tract infections in children. In this article, the current knowledge of human coronavirus HCoV-NL63, with special reference to the clinical features, prevalence and seasonal incidence, and coinfection with other respiratory viruses, will be discussed.


title: Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus

text: It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (−)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (−)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (−)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−)-strand sgmRNA. (3) Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (−1) of sgmRNA 7 is correlated to the efficiency of (−)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−)-strand sgmRNA synthesis in BCoV.


title: Antiviral Effects of Lactococcus lactis on Feline Calicivirus, A Human Norovirus Surrogate

text: Foodborne viruses, particularly human norovirus (NV) and hepatitis virus type A, are a cause of concern for public health making it necessary to explore novel and effective techniques for prevention of foodborne viral contamination, especially in minimally processed and ready-to-eat foods. This study aimed to determine the antiviral activity of a probiotic lactic acid bacterium (LAB) against feline calicivirus (FCV), a surrogate of human NV. Bacterial growth medium filtrate (BGMF) of Lactococcus lactis subsp. lactis LM0230 and its bacterial cell suspension (BCS) were evaluated separately for their antiviral activity against FCV grown in Crandell–Reese feline kidney (CRFK) cells. No significant antiviral effect was seen when CRFK cells were pre-treated with either BGMF (raw or pH 7-adjusted BGMF) or BCS. However, pre-treatment of FCV with BGMF and BCS resulted in a reduction in virus titers of 1.3 log(10) tissue culture infectious dose (TCID)(50) and 1.8 log(10) TCID(50), respectively. The highest reductions in FCV infectivity were obtained when CRFK cells were co-treated with FCV and pH 7-adjusted BGMF or with FCV and BCS (7.5 log(10) TCID(50) and 6.0 log(10) TCID(50), respectively). These preliminary results are encouraging and indicate the need for continued studies on the role of probiotics and LAB on inactivation of viruses in various types of foods.


docid: cfktjerw

title: SARS‐CoV‐2 virus and liver expression of host receptors: Putative mechanisms of liver involvement in COVID‐19

text: Zhang et al. showed that COVID‐19 affected patients’ present liver biochemistry abnormalities, including elevation of aminotransferases, gamma‐glutamyl transferase, and alkaline phosphatase (1). Hence, several possible clinical scenarios in the setting of liver diseases have been postulated. First, patients with chronic liver disease may be more vulnerable to the severe clinical consequences of COVID‐19, including oxygen desaturation and hypoxemia due to severe pneumonia or the cytokine storm (1;2). Second, liver biochemistry abnormalities are the consequence of drug toxicity.


Letter to the Editor - Impactful Policy Action to Reduce Drug Costs in Managing Critically Ill Patients with COVID19


title: A tripartite ssDNA mycovirus from a plant pathogenic fungus is infectious as cloned DNA and purified virions

text: Here, we describe a tripartite circular single-stranded (ss) DNA mycovirus, named Fusarium graminearum gemytripvirus 1 (FgGMTV1). The genome of FgGMTV1 comprises three circular ssDNA segments (DNA-A, DNA-B, and DNA-C). Sequence alignments and phylogenetic analyses showed that FgGMTV1 is nested within the family Genomoviridae. We also constructed the first infectious DNA clones of a DNA mycovirus. Our results show that DNA-A and DNA-B are mutually interdependent for their replication and are associated with severely reduced colony growth and hypovirulence. DNA-C relies on DNA-A and DNA-B for replication and is necessary for the recovery of abnormal fungal phenotypes. DNA-C also enhances the accumulation of viral DNA in infected fungi and permits stable colonization and easy transmission via conidia. This is the first multipartite DNA virus isolated from a fungus. Our phylogenetic analyses also suggest that the multipartite genome of FgGMTV1 may have evolved from a monopartite genome of an ancient genomovirus.


title: Chapter 22 Issues on Source, Access, Extent, and Quality of Information Available Among Pharmacists and Pharmacy Personnel to Practice Effectively

text: Abstract This chapter describes the source, access, extent, and quality of information available among pharmacists and pharmacy personnel in developing countries to practice effectively. Our world today witnesses huge advancements in the information-related technologies and in the amount of medicines information available and accessible by all healthcare providers as well as the public. Remaining in the front line as medicines information providers represents great challenge for pharmacists. Scientific biomedical journals represent the core source of our knowledge about medicines. Textbooks and books represent the cornerstone for a user who has no or little basic information about certain topic. Today, the Internet is the most commonly used source of information for a variety of uses and topics. The literature available in our hand indicates the presence of medicines information centers in a variety of countries from the developing world. Manufacturers of medicines usually represent an important source of information on medicines specifically about the labeled and off-label indications. Every source of medicines information is having its specific points of strengths and weaknesses and an information user should be aware of that.


title: Practical insights for paediatric otolaryngology surgical cases and performing microlaryngobronchoscopy during the COVID-19 pandemic

text: Abstract Paediatric otolaryngology practice involves examining and operating in anatomical locations with high levels of aerosol generation and transmission of COVID-19 to treating clinicians, especially from the asymptomatic patient populations including children. During the COVID-19 pandemic all emergent otolaryngological conditions affecting the airway, oral, and nasal cavities should be managed medically where possible and any operating deferred. We present guidelines for operating on paediatric otolaryngological patients when necessary during the COVID-19 pandemic, and incorporate experience gathered during microlaryngobronchoscopy on a COVID-19 positive infant at our institution.


title: Myocardial injury in patients with COVID-19

text: In patients with COVID-19, myocardial injury is prevalent and is associated with an adverse prognosis and increased mortality, according to two retrospective cohort studies from China and the USA.


title: Discovery of novel non-competitive inhibitors of mammalian neutral M1 aminopeptidase (APN)

text: Abstract Neutral metallo-aminopeptidase (APN) catalyzes the cleavage of neutral and basic amino acids from the N-terminus of protein or peptide substrates. APN expression is dysregulated in inflammatory diseases as well as in several types of cancer. Therefore, inhibitors of APN may be effective against cancer and inflammation. By virtual screening and enzymatic assays, we identified three non-competitive inhibitors (α > 1) of the porcine and human APN with Ki values in the μM range. These non-peptidic compounds lack the classical zinc-binding groups (ZBG) present in most of the APN inhibitors. Molecular docking simulations suggested the novel inhibitors suppress APN activity by an alternative mechanism to Zn coordination: they interacted with residues comprising the S1 and S5′ subsites of APN. Of note, these compounds also inhibited the porcine aminopeptidase A (pAPA) using a competitive inhibition mode. This indicated differences in the binding mode of these compounds with APN and APA. Based on sequence and structural analyses, we predicted the significance of targeting human APN residues: Ala-351, Arg-442, Ala-474, Phe-896 and Asn-900 for improving the selectivity of the identified compounds. Remarkably, the intraperitoneal injection of compounds BTB07018 and JFD00064 inhibited APN activity in rat brain, liver and kidney indicating good bio-distribution of these inhibitors in vivo. These data reinforce the idea of designing novel APN inhibitors based on lead compounds without ZBG.


title: Atención al ictus agudo durante la pandemia por COVID-19. Recomendaciones Plan Ictus Madrid

text: RESUMEN Introducción: La pandemia por COVID-19 ha obligado a una reorganización de los sistemas sanitarios y una saturación excepcional de sus recursos. En este contexto es vital asegurar la atención al ictus agudo y optimizar los procesos asistenciales del código ictus para reducir el riesgo de contagios y racionalizar el uso de recursos hospitalarios. Para ello desde el Grupo multidisciplinar Ictus Madrid proponemos una serie de recomendaciones. Métodos: Revisión bibliográfica no sistemática de las publicaciones disponibles con los términos “stroke” y “covid-19” o “coronavirus” o “SARS-COV-2”, así como otras conocidas por los autores. En base a ésta se redacta un documento de recomendaciones que es sometido a consenso por el Grupo multidisciplinar Ictus Madrid y su Comité de Neurología. Resultados: Las recomendaciones se estructuran en cinco líneas fundamentales: (1) Coordinar la actuación para garantizar el acceso a la asistencia hospitalaria de los pacientes con ictus, (2) Reconocer a los pacientes con ictus potencialmente infectados por COVID-19, (3) Organización adecuada para garantizar la protección de los profesionales sanitarios frente al riesgo de contagio por COVID-19, (4) la realización de Neuroimagen y otros procedimientos que conlleven contactos de riesgo de infección COVID-19 hay que procurar reducirlos y asegurar la protección, y (5) alta y seguimiento seguros procurando optimizar la ocupación hospitalaria. Resumimos el procedimiento de forma esquemática con el acrónimo CORONA (COordinar, Reconocer, Organizar, Neuroimagen, Alta). Conclusiones: Estas recomendaciones pueden servir de apoyo para la organización del sistema sanitario en la atención al ictus agudo y la optimización de sus recursos, garantizando la protección de sus profesionales. ABSTRACT Background: The COVID-19 pandemic has forced a reorganization of healthcare systems and an exceptional saturation of their resources. In this context, it is vital to ensure acute stroke care and optimize the care processes of the stroke code to reduce the risk of contagion and rationalize the use of hospital resources. To do this, the Ictus Madrid multidisciplinary group proposes a series of recommendations. Methods: Non-systematic bibliographic review of the available publications with the terms “stroke” and “covid-19” or “coronavirus” or “SARS-COV-2”, as well as other already known for the authors. We provide a document of recommendations as a result of the consensus of the Ictus Madrid multidisciplinary group and its Neurology Committee. Results: Our recommendations are structured on five lines: (1) Coordinate to guarantee the access to hospital care for stroke patients, (2) Recognize potentially COVID-19 infected stroke patients, (3) Organize to ensure the protection of healthcare professionals from COVID-19 infections, (4) Neuroimaging and other procedures potentially associated to risks for COVID-19 infection should be reduced and secured to avoid contagion, and (5) At home as soon as possible and supported follow-up to optimize hospital occupancy. The procedure is shown summarized under the acronym CORONA (Coordinate, Recognize, Organize, Neuroimaging, At home). Conclusions: These recommendations can support the organization of healthcare services for acute stroke care and the optimization of their resources, guaranteeing the protection of healthcare professionals.


title: COVID-19, una emergencia de salud pública mundial

text: Resumen Un nuevo brote de coronavirus surgió el pasado 31 de diciembre de 2019 en Wuhan, China, causando conmoción entre la comunidad médica y el resto del mundo. Esta nueva especie de coronavirus fue denominada como 2019-nCoV, causante de un gran número de casos y fallecimientos en China y en cantidad creciente fuera de ella, convirtiéndose en una emergencia de salud pública a nivel mundial. 2019-nCoV es un virus con alta homología con otros coronavirus patogénicos, como los originados por zoonosis con murciélagos (SARS-CoV) causantes de aproximadamente 646 muertes en China a principios de la década. Su tasa de mortalidad no es tan elevada (aproximadamente del 2-3%), pero su rápida propagación ha propiciado la activación de protocolos para detener su diseminación. Este patógeno tiene el potencial para convertirse en pandemia, por lo que es vital seguir las recomendaciones de cuidado personal dictadas por la Organización Mundial de la Salud. Abstract A new coronavirus outbreak emerged on the 31st of December 2019 in Wuhan, China, causing commotion among the medical community and the rest of the world. This new species of coronavirus has been termed 2019-nCoV and has caused a considerable number of cases of infection and deaths in China and, to a growing degree, beyond China, becoming a worldwide public health emergency. 2019-nCoV has high homology to other pathogenic coronaviruses, such as those originating from bat-related zoonosis (SARS-CoV), which caused approximately 646 deaths in China at the start of the decade. The mortality rate for 2019-nCoV is not as high (approximately 2-3%), but its rapid propagation has resulted in the activation of protocols to stop its spread. This pathogen has the potential to become a pandemic. It is therefore vital to follow the personal care recommendations issued by the World Health Organisation.


title: Maladie de Kawasaki de l’adulte : un cas d’évolution chronique et d’issue fatale avec une spondylarthropathie sensible au traitement par immunoglobulines intraveineuses

text: Résumé Nous rapportons l’observation inhabituelle d’un homme âgé de 40 ans, d’origine caucasienne, qui présentait une atteinte clinique sévère évocatrice de maladie de Kawasaki. La maladie évoluait depuis sept années avant que n’apparaissent des anévrismes coronariens multiples qui ont entraîné le décès malgré un traitement par immunoglobulines intraveineuses polyvalentes (IgIV). Le patient souffrait aussi d’une atteinte invalidante du rachis qui avait débuté en même temps que la maladie de Kawasaki. Alors que ni les anti-inflammatoires non stéroïdiens, ni la corticothérapie à forte dose, ni les agents anti-TNF n’avaient eu d’efficacité probante, les signes cliniques d’inflammation rachidienne ont été très sensibles au traitement par IgIV et ont été attribués de manière certaine à une spondylarthrite axiale HLA B27 négative sur les données de la scintigraphie osseuse et de l’imagerie par résonance magnétique qui avaient mis en évidence des enthésites des deux talons et une sacro-iliite bilatérale.


title: ORION-VIRCAT: a tool for mapping ICTV and NCBI taxonomies

text: Viruses, viroids and prions are the smallest infectious biological entities that depend on their host for replication. The number of pathogenic viruses is considerably large and their impact in human global health is well documented. Currently, the International Committee on the Taxonomy of Viruses (ICTV) has classified ∼4379 virus species while the National Center for Biotechnology Information Viral Genomes Resource (NCBI-VGR) database has mapped 617 705 proteins to eight large taxonomic groups. Despite these efforts, an automated approach for mapping the ICTV master list and its officially accepted virus naming to the NCBI-VGR’s taxonomical classification is not available. Due to metagenomic sequencing, it is likely that the discovery and naming of new viral species will increase by at least ten fold. Unfortunately, existing viral databases are not adequately prepared to scale, maintain and annotate automatically ultra-high throughput sequences and place this information into specific taxonomic categories. ORION-VIRCAT is a scalable and interoperable object-relational database designed to serve as a resource for the integration and verification of taxonomical classifications generated by the ICTV and NCBI-VGR. The current release (v1.0) of ORION-VIRCAT is implemented in PostgreSQL and it has been extended to ORACLE, MySQL and SyBase. ORION-VIRCAT automatically mapped and joined 617 705 entries from the NCBI-VGR to the viral naming of the ICTV. This detailed analysis revealed that 399 095 entries from the NCBI-VGR can be mapped to the ICTV classification and that one Order, 10 families, 35 genera and 503 species listed in the ICTV disagree with the the NCBI-VGR classification schema. Nevertheless, we were eable to correct several discrepancies mapping 234 000 additional entries. Database URL: http://www.orionbiosciences.com/research/orion-vircat.html


title: COVID‐19: a lever for the recognition of obesity as a disease? The French experience

text: Despite repeated efforts by the international scientific community, academic societies and the combined actions of patient associations, public authorities have difficulties in admitting that obesity is not just a risk factor but a disease. Could our current experience with the COVID‐19 pandemic be a lever to advance the cause of people with obesity? In this crisis, it seems pertinent to report on the French experience with the actions of stakeholders that were able to challenge the status quo in this field.


title: Implementation Guide for Rapid Integration of an Outpatient Telemedicine Program during the COVID-19 Pandemic

text: Abstract: Objective In the novel coronavirus disease (COVID-19) pandemic, social distancing has been necessary to help prevent disease transmission. As a result, medical practices have limited access to in-person visits. This poses a challenge to maintain appropriate patient care while preventing a significant backlog of patients once stay-at-home restrictions are lifted. In practices that are naive to telehealth as an alternative option, providers and staff are experiencing challenges with telemedicine implementation. We aim to provide a comprehensive guide on how to rapidly integrate telemedicine into practice during a pandemic. Methods We built a toolkit that details 8 essential components to successful implementation of a telemedicine platform: Provider and staff training, patient education, an existing electronic medical record system, patient and provider investment in hardware, billing and coding integration, information technology support, audiovisual platforms, and patient and caregiver participation. Results Rapid integration of telemedicine in our practice was required to be compliant with our institution’s COVID-19 Taskforce. Within 3 days of this declaration, our large specialty-care clinic converted to a telemedicine platform and we completed 638 visits within the first month of implementation. Conclusions Effective and efficient integration of a telemedicine program requires extensive staff and patient education, accessory platforms to facilitate video and audio communication, and adoption of new billing codes that are outlined in this toolkit.


title: Porcine reproductive and respiratory syndrome virus and Haemophilus parasuis antigen distribution in dually infected pigs

text: Abstract Immunohistochemical, viral and bacterial isolation techniques were used to study the distribution and localization of porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus (H.) parasuis in experimentally infected pigs. Thirty pigs seronegative to PRRSV and H. parasuis were divided into four groups. Group A pigs (10 animals) were inoculated with both virus and bacteria; group B pigs (10 animals) were inoculated with bacteria, group C pigs (five animals) were inoculated with virus and group D pigs (five animals) were kept as negative controls. All pigs of groups A and C became infected with PRRSV, according to virological techniques used (immunohistochemistry, virus isolation and virus serology). Lung, heart and tonsils were the most frequently immunolabeled tissues, and monocyte/macrophage lineage cells were the target for PRRSV in all tissues. All pigs in groups A and B also became infected with H. parasuis based on immunohistochemical and bacterial isolation results. Serosal surfaces, lung and tonsils were the most frequently immunolabeled tissues, and bacteria were found in monocyte/macrophage lineage cells as well as within neutrophil cytoplasm. No differences in terms of bacterial distribution or localization in tissues of pigs of groups A and B were detected. These results suggest that there is no influence of the previous infection with PRRSV in the occurrence of H. parasuis infection.


title: Évolution des techniques de préparation des produits sanguins labiles (PSL) : inactivation des pathogènes dans les PSL

text: Résumé Les techniques d’inactivation des agents pathogènes dans les produits sanguins labiles (PSL) apparaissent comme la nouvelle stratégie permettant d’augmenter la sécurité transfusionnelle face aux risques de transmission d’agents pathogènes par les PSL. Différentes techniques sont en cours de développement ou déjà validées et utilisées en France. Ces dernières ne s’appliquent que pour le plasma ou les concentrés plaquettaires. Les mécanismes d’action ainsi que l’efficacité d’inactivation et d’atténuation des agents pathogènes varient en fonction des différentes techniques. Chacune d’elles constitue un procédé de préparation composé d’opérations unitaires dont il faut s’assurer de la maîtrise dans le but de garantir la qualité et l’efficacité transfusionnelle du produit traité. Abstract The techniques for inactivation of pathogens in labile blood products (LBP) would appear to be the new strategy which will permit us to increase transfusion safety in the face of the risks of transmission of pathogenic agents by LBP. Various methods are in the course of development or already validated and used in France. The latter only apply however to plasma or platelet concentrates. The mechanisms of action and the efficacy of inactivation and attenuation of pathogenic agents vary with the different techniques. Each of these constitutes a preparative procedure composed of unit steps which have to be fully mastered in order to ensure the quality and transfusion efficacy of the treated product.


title: IR35 changes postponed

text: In light of the COVID-19 pandemic, changes to the implementation of the Off-Payroll (IR35) Tax is now due to be reintroduced in April 2021 The decision was taken following significant pressure from many who warned that the inevitable loss of work due to the virus for contractors deemed 'inside IR35' and effectively forced into 'zero rights employment' would prove catastrophic


title: Art of prevention: Life in the time of coronavirus

text: Abstract The novel coronavirus disease 2019 (COVID-19) has continued to progress since its discovery in December 2019. A cluster of patients with atypical pneumonia identified in Wuhan, China, served as the epicenter of this recent epidemic. This family of viruses is responsible for the common cold along with the infamous severe acute respiratory syndrome epidemic in 2002 and Middle East respiratory syndrome in 2012. The Southern China Wholesale Market reportedly has connections to the original 27 cases in Wuhan, China. The worldwide confirmed case total has eclipsed 1,450,000, with more than 83,000 deaths. Patient presentation ranges from mild respiratory illness to acute respiratory distress syndrome and subsequent death. Early epidemiologic studies of viral spread support the hypothesis that COVID-19 can remain latent with an extended and infectious incubation period. The U.S. government has issued level 3 precautions for most international travel, along with prohibiting entry to foreign nationals traveling from China, Iran, the United Kingdom, the Republic of Ireland, and the European Schengen area (e.g., France, Italy, Germany). Prevention remains the mainstay in treating and defeating the COVID-19 epidemic. Anyone infected or suspected of being infected should self-quarantine at home or admit themselves to a specified hospital with infrastructure to handle the situation. The combination of prevention and containment provides the best opportunity to stall the spread of COVID-19.


title: Quantifying the prevalence of SARS-CoV-2 long-term shedding among non-hospitalized COVID-19 patients

text: With anecdotal reports of viral shedding from COVID-19 patients for several weeks, there is a need to quantify the prevalence of long-term SARS-CoV-2 shedding. Here, we characterize the temporal distribution of diagnostic SARS-CoV-2 PCR outcomes from nasopharyngeal swabs and associated EHR-derived features over two months for 874 COVID-19 patients with longitudinal data. Among a cohort of 379 COVID-19 patients with at least one positive follow-up SARS-CoV-2 PCR test, 53 patients remain SARS-CoV-2-positive after four weeks of initial diagnosis. Surprisingly, a majority of COVID-19 patients with long-term viral shedding are not hospitalized (40 of 53 patients), and have no enrichments among symptoms, demographics, or medical history. In a cohort of 370 COVID-19 patients that transition to a confirmed negative status, the upper bound of viral shedding duration has a mean of 21.2 days with standard deviation of 9.3 days. Of the 81 PCR-confirmed COVIDpos patients who have undergone serologic testing, 68 patients have developed anti-SARS-CoV-2 IgG to date, with a mean upper bound of time to seroconversion of 38.1 days (95% C.I. = 35.2-41.1 days). Given that SARS-CoV-2 PCR testing may detect replication incompetent virus and that serologic tests do not imply neutralizing immunity, we suggest that the development of novel assays for measuring infectious viral load in non-hospitalized long-term shedders may help mitigate community transmission. This study motivates a platform that can link longitudinal diagnostic and serologic testing with real-time epidemiological data, towards proactively identifying and managing emerging hotspots of COVID-19.


title: Respiratory Management in Critical Care Respiratory Management in Critical Care. A. J. D. Griffiths and T. W. Evans (editors). Published by BMJ Books, London. Pp. 137; indexed; illustrated. Price £27.50. ISBN 0-7279-1729-3.

text: Unknown


title: Rabies virus glycoprotein as a carrier for anthrax protective antigen

text: Abstract Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule, we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems.


title: Modeling the Spread of COVID-19 Infection Using a Multilayer Perceptron

text: Coronavirus (COVID-19) is a highly infectious disease that has captured the attention of the worldwide public. Modeling of such diseases can be extremely important in the prediction of their impact. While classic, statistical, modeling can provide satisfactory models, it can also fail to comprehend the intricacies contained within the data. In this paper, authors use a publicly available dataset, containing information on infected, recovered, and deceased patients in 406 locations over 51 days (22nd January 2020 to 12th March 2020). This dataset, intended to be a time-series dataset, is transformed into a regression dataset and used in training a multilayer perceptron (MLP) artificial neural network (ANN). The aim of training is to achieve a worldwide model of the maximal number of patients across all locations in each time unit. Hyperparameters of the MLP are varied using a grid search algorithm, with a total of 5376 hyperparameter combinations. Using those combinations, a total of 48384 ANNs are trained (16128 for each patient group—deceased, recovered, and infected), and each model is evaluated using the coefficient of determination (R2). Cross-validation is performed using K-fold algorithm with 5-folds. Best models achieved consists of 4 hidden layers with 4 neurons in each of those layers, and use a ReLU activation function, with R2 scores of 0.98599 for confirmed, 0.99429 for deceased, and 0.97941 for recovered patient models. When cross-validation is performed, these scores drop to 0.94 for confirmed, 0.781 for recovered, and 0.986 for deceased patient models, showing high robustness of the deceased patient model, good robustness for confirmed, and low robustness for recovered patient model.


title: Detection of infectious bronchitis virus strains similar to Japan in Taiwan

text: A total of 1,320 tracheal samples from 66 broiler flocks sent to slaughterhouses and 42 tracheal samples from 42 flocks of local chickens in the field were collected for infectious bronchitis virus (IBV) gene detection by reverse transcription polymerase chain reaction using nucleocapsid-specific primers and spike-specific primers. Prevalence in broiler flocks was 39.4% (26/66) and in local chicken flocks was 11.9% (5/42). Several IBVs similar to Japan were detected in Taiwan. One-direction neutralization revealed that the reference antisera did not offer protection against the IBVs similar to those from Japan.


docid: quryxghj

title: COVID‐19 pandemic: a large boulder on the head of stoma patients


title: Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection

text: Abstract A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4–12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity.


title: An Epidemic in the Midst of a Pandemic: Opioid Use Disorder and COVID-19

text: The COVID-19 pandemic is a particularly grave risk to the millions of Americans with opioid use disorder, who—already vulnerable and marginalized—are heavily dependent on face-to-face health care delivery. These authors propose rapid and coordinated action on the part of clinicians and policymakers to mitigate risks of disrupted care for these patients.


title: Increased Risk of Noninfluenza Respiratory Virus Infections Associated With Receipt of Inactivated Influenza Vaccine

text: We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.


title: Framework for Manufacturing in Post-Covid-19 World Order: An Indian Perspective

text: Covid-19 pandemic has created a colossal disruption all over the globe, especially in Europe, the USA, China, India, and many developed economies. The production supply chains have been massively disturbed. It is estimated that a significant number of Fortune 1000 firms have been severely affected by the pandemic. Manufacturing companies operating in and through India are also affected by Covid-19. However, Covid-19 also offers an opportunity to revisit the competitiveness of Indian manufacturing. Traditionally, India’s manufacturing growth has been based mostly on its domestic market. The disruptions due to Covid-19 are likely to offer new models of working and at the same time, opportunities to build capabilities and explore new international markets. The paper gives a perspective on Indian manufacturing involving various stakeholders such as industry associations, professional bodies, academic institutes, and industry to tackle the issue of enhancing manufacturing competitiveness. In a post-Covid-19, India will have to decide a mix of conventional manufacturing facilities, the automated special purpose, and industry 4.0. One perspective is to have an increased level of automation and implementation of Industry 4.0, with localized skills and global aspirations and another view is to have traditional manufacturing facilities that can ramp up its capabilities to satisfy increased demand of products. This paper presents a conceptual framework to assess Indian manufacturing.


docid: wgodcsav

title: Infections in the Immunocompromised

text: Infections in the immunocompromised differ significantly from those in the immunocompetent. They can be more serious, more often life threatening, more difficult to diagnose and are caused by more unusual organisms. Children can be immunocompromised for a variety of reasons and the numbers, worldwide, are growing.


title: Red cell alloimmunisation in patients with different types of infections

text: Red cell alloantigen exposure can cause alloantibody‐associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case–control study within a source population of patients receiving their first and subsequent red cell transfusions during an 8‐year follow‐up period. Patients developing a first transfusion‐induced red cell alloantibody (N = 505) were each compared with two similarly exposed, but non‐alloimmunised controls (N = 1010) during a 5‐week ‘alloimmunisation risk period’ using multivariate logistic regression analysis. Transfusions during ‘severe’ bacterial (tissue‐invasive) infections were associated with increased risks of alloantibody development [adjusted relative risk (RR) 1·34, 95% confidence interval (95% CI) 0·97–1·85], especially when these infections were accompanied with long‐standing fever (RR 3·06, 95% CI 1·57–5·96). Disseminated viral disorders demonstrated a trend towards increased risks (RR 2·41, 95% CI 0·89–6·53), in apparent contrast to a possible protection associated with Gram‐negative bacteraemia (RR 0·58, 95% CI 0·13–1·14). ‘Simple’ bacterial infections, Gram‐positive bacteraemia, fungal infections, maximum C‐reactive protein values and leucocytosis were not associated with red cell alloimmunisation. These findings are consistent with murine models. Confirmatory research is needed before patients likely to develop alloantibodies may be identified based on their infectious conditions at time of transfusion.


title: Re The source of elevated plasma D‐dimer levels in COVID‐19 infection

text: Markedly elevated levels D-dimers are seen in severe COVID-19 infection and have been related to a poor prognosis 1-2 . D-dimers are elevated alongside other acute inflammatory plasma markers such as fibrinogen, CRP and serum ferritin 1 . The elevation of plasma D-dimers has been taken to indicate there is a coagulopathy2 , and the assumption has been made that the increased fibrinolysis is secondary (due to thrombin generation) indeed an indication of disseminated intravascular coagulation (DIC).


title: Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

text: The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.


title: Invasive alien plant species: Their impact on environment, ecosystem services and human health

text: Abstract Ecological perturbations caused by biotic invasion have been identified as a growing threat to global sustainability. Invasive alien plants species (IAPS) are considered to be one of the major drivers of biodiversity loss and thereby altering the ecosystem services and socio-economic conditions through different mechanisms. Although the ecological impacts of IAPS are well documented, there is a dearth of studies regarding their economic quantification, livelihood considerations, biotechnological prospects (phytoremediation, bioenergy, phyto-synthesis of nanoparticles, biomedical, industrial applications etc.) and human health risk assessments of IAPS. In this context, the current panoramic review aimed to investigate the environmental, socio-ecological and health risks posed by IAPS as well as the compounded impact of IAPS with habitat fragmentation, climate and land use changes. To this end, the need of an integrated trans-disciplinary research is emphasized for the sustainable management of IAPS. The management prospects can be further strengthened through their linkage with geo-spatial technologies (remote sensing and GIS) by mapping and monitoring the IAPS spread. Further, the horizon of IAPS management is expanded to ecological indicator perspectives of IAPS, biosecurity, and risk assessment protocols with critical discussion. Moreover, positive as well as negative implications of the IAPS on environment, health, ecosystem services and socio-economy (livelihood) are listed so that a judicious policy framework could be developed for the IAPS management in order to mitigate the human health implications.


title: Observation of high recombination occurrence of Porcine Reproductive and Respiratory Syndrome Virus in field condition

text: Abstract Recombination in Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a well-documented phenomenon. A high recombination frequency has been reported in experimental conditions both in vitro and in vivo, and its role in driving viral evolution has been postulated by several authors. However field evidences are rare, mainly obtained from large-scale sampling and typically represented by single sequences rather than by groups of circulating “recombinant progenies”. The present work was aimed to investigate the gray area between experimental studies and large-scale epidemiological investigations. The study was performed on ORF5, ORF7 and concatenated sequences obtained in our laboratory or available in GenBank collected between 2009 and 2012 in northern Italy. Six independent recombinant strains out of 66 concatenated sequences (∼9%) were found, demonstrating a high recombination frequency respect to previous field studies but comparable to in vitro experiments. In silico analysis let speculate that this new strain displayed physicochemical features diverse enough to potentially alter its immunological properties. Taken altogether, the results of our study support previous experimental evidences that depict PRRSV to be extremely prone to recombination. The limited temporal and geographical spread of recombinant strains however states in favor of a limited fitness of the recombinant progeny compared to parental strains and the marginal role of this phenomenon in PRRSV evolution.


Does Hydroxychloroquine Combat COVID-19? A Timeline of Evidence


title: Mycoplasma pneumoniae detection in children with respiratory tract infections and influence on management – a retrospective cohort study in Switzerland

text: AIM: To evaluate the frequency of Mycoplasma pneumoniae in nasopharyngeal specimens from children with respiratory tract infections (RTIs) and to detail clinical characteristics and management. METHODS: The study was designed as a retrospective cohort study. All children with RTI and nucleic acid amplification testing from nasopharyngeal specimens were analysed. Clinical data were extracted from electronic health records for all M. pneumoniae‐positive cases. Stored samples of cases and a random selection of matched controls were retested using a M. pneumoniae‐specific nucleic acid amplification test. RESULTS: Of 4460 children, 70 (1.6%) were positive for M. pneumoniae with a median age of 6.4 (IQR: 2.7–9.7). M. pneumoniae was the only organism identified in 50/64 (78%) cases. Macrolide treatment was prescribed in 52/65 (80%); prescription was empirical in 29/52 (56%) and targeted in 23/52 (44%) with no difference regarding patient age, oxygen requirement or duration of hospitalisation. CONCLUSION: The prevalence of M. pneumoniae in nasopharyngeal specimens of children with RTI was low. The detection of M. pneumoniae influenced antibiotic prescriptions, but the benefit of early empirical versus targeted treatment remains unclear.


title: The Serendipitous Impact of COVID-19 Pandemic: A Rare Opportunity for Research and Practice

text: In this opinion paper, I argue that the Covid-19 pandemic, as tragic and disastrous as it undoubtedly is, has also given us a rare opportunity to deeply examine the research and practice of information management in particular and information systems in general. To cope with the pandemic, we have retreated to the digital world and drastically changed the way we work. Yet these very practices can well shape the way we work in the post-pandemic world. Moreover, the pandemic is also a sharp lens through which we can study deep-rooted theoretical issues that otherwise would not have surfaced, or at least remained in the background. My call to the research community is to seize this rare opportunity.


title: A model for COVID-19 transmission in Connecticut

text: To support public health policymakers in Connecticut as they begin phased lifting of social distancing restrictions, we developed a county-structured compartmental SEIR-type model of SARS-CoV-2 transmission and COVID-19 disease progression. We calibrated this model to the local dynamics of deaths and hospitalizations and the exact timing of state interventions, including school closures and stay-at-home order. In this technical report, we describe the details of the model design, implementation and calibration, and show projections of epidemic development through the Summer of 2020 under different assumptions about the increase in contact rates following partial state reopening. Our model results are consistent with high effectiveness of state lockdown measures, but changes in human interaction patterns during the coming months are unknown. In addition, a lot of uncertainty remains with respect to several key epidemiological parameters and the effectiveness of increased testing and contact tracing capacity. As more information becomes available, we will update the projections presented in this report.


title: A Novel Dynamic Model Describing the Spread of the MERS-CoV and the Expression of Dipeptidyl Peptidase 4

text: The Middle East respiratory syndrome (MERS) coronavirus, a newly identified pathogen, causes severe pneumonia in humans. MERS is caused by a coronavirus known as MERS-CoV, which attacks the respiratory system. The recently defined receptor for MERS-CoV, dipeptidyl peptidase 4 (DPP4), is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells. In this paper, a class of novel four-dimensional dynamic model describing the infection of MERS-CoV is given, and then global stability of the equilibria of the model is discussed. Our results show that the spread of MERS-CoV can also be controlled by decreasing the expression rate of DPP4.


Remote Respiratory Monitoring in the Time of COVID-19


title: Modeling and public health emergency responses: Lessons from SARS

text: Abstract Modelers published thoughtful articles after the 2003 SARS crisis, but had limited if any real-time impact on the global response and may even have inadvertently contributed to a lingering misunderstanding of the means by which the epidemic was controlled. The impact of any intervention depends on its efficiency as well as efficacy, and efficient isolation of infected individuals before they become symptomatic is difficult to imagine. Nonetheless, in exploring the possible impact of quarantine, the product of efficiency and efficacy was varied over the entire unit interval. Another mistake was repeatedly fitting otherwise appropriate gamma distributions to times to event regardless of whether they were stationary or not, particularly onset-isolation intervals whose progressive reduction evidently contributed to SARS control. By virtue of their unknown biology, newly-emerging diseases are more challenging than familiar human scourges. Influenza, for example, recurs annually and has been modeled more thoroughly than any other infectious disease. Moreover, models were integrated into preparedness exercises, during which working relationships were established that bore fruit during the 2009 A/H1N1 pandemic. To provide the most accurate and timely advice possible, especially about the possible impact of measures designed to control diseases caused by novel human pathogens, we must appreciate the value and difficulty of policy-oriented modeling. Effective communication of insights gleaned from modeling SARS will help to ensure that policymakers involve modelers in future outbreaks of newly-emerging infectious diseases. Accordingly, we illustrate the increasingly timely care-seeking by which, together with increasingly accurate diagnoses and effective isolation, SARS was controlled via heuristic arguments and descriptive analyses of familiar observations.


title: Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients

text: Abstract The role of cell-mediated immunity in human SARS-CoV infection is still not well understood. In this study, we found that memory T-cell responses against the spike (S) protein were persistent for more than 1 year after SARS-CoV infection by detecting the production of IFN-γ using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4+ and CD8+ T cells were involved in cellular responses against SARS-CoV infection. Interestingly, most of SARS-CoV S-specific memory CD4+ T cells were central memory cells expressing CD45RO+ CCR7+ CD62L−. However, the majority of memory CD8+ T cells revealed effector memory phenotype expressing CD45RO− CCR7− CD62L−. Thus, our study provides the evidence that SARS-CoV infection in humans can induce cellular immune response that is persistent for a long period of time. These data may have an important implication in the possibility of designing effective vaccine against SARS-CoV infection, specifically in defining T-cell populations that are implicated in protective immunity.


title: Isolation and characterization of a highly pathogenic strain of Porcine enteric alphacoronavirus causing watery diarrhoea and high mortality in newborn piglets

text: Porcine enteric alphacoronavirus (PEAV) was first discovered in China in February 2017, and the origin and virulence of this novel porcine coronavirus were not fully characterized. Here, we isolated a strain of PEAV, named GDS04 that is identified by immunofluorescence and typical crown‐shaped particles observed with electron microscopy. Genomic analysis reveals that PEAV GDS04 shares a close relationship with SADS‐CoV and SeACoV. Furthermore, newborn piglets orally challenged with PEAV GDS04 developed typical clinical symptoms as watery diarrhoea in neonatal piglets. Viral RNA was detected in faeces and various tissues of the infected piglets. Moreover, macroscopic and microscopic lesions in whole intestinal tract were observed, and viral antigen could be detected in the small intestines by immunohistochemical staining and electron microscopy. Importantly, the mortality rate of inoculated‐newborn piglets was 100% and half of the cohabiting piglets died. Collectively, we demonstrate that PEAV is highly pathogenic in newborn piglets.


Classic paper: Fenner on the exanthemata


title: Neutralizing antibody responses to enterovirus and adenovirus in healthy adults in China

text: Hand, foot and mouth disease (HFMD) is an important public health problem that has emerged over the past several years. HFMD predominantly infects children under seven years old and occasionally causes severe disease in adults. Among the enteroviruses, enterovirus 71 (EV71) and coxsackievirus 16 (CA16) are the major causative agents of HFMD. In addition, adenovirus cocirculates with enterovirus and has become a possible additional pathogenic factor for HFMD in some cases. Here, we have investigated the neutralizing antibody responses to both enterovirus and adenovirus in adults, with the aim of exploring the prevalence trends of these viruses and the nature of protective immunity in humans to these viral infections. Sera from 391 healthy adults from 21 provinces and cities in China were tested for the presence of antibodies against EV71, CA16, adenovirus human serotype 5 (AdHu5) and chimpanzee adenovirus pan7 (AdC7) using neutralization tests. High seroprevalence rates of EV71, CA16 and AdHu5 were found in the population (85.7%, 58.8% and 74.2%, respectively). The coseropositivity rate of these three viruses was 39.4% (154 of 391), with median neutralizing antibody titers of 80, 40 and 640, respectively, and the neutralizing antibody titer for EV71 was found to be correlated with those of CA16 and AdHu5. AdC7 was found to be a rare adenovirus serotype in the human population, with a seropositivity rate of 11.8%, suggesting that it could be a good choice for a vaccine carrier that could be used in vaccine development.


docid: tdlqliuw

title: Possible application of H(2)S-producing compounds in therapy of coronavirus (COVID-19) infection and pneumonia


title: Epidemiological and clinical features of human coronavirus infections among different subsets of patients

text: BACKGROUND: Epidemiological and clinical data of human coronaviruses (HCoVs) infections are restricted to span 1–3 years at most. We conducted a comprehensive 9‐year study on HCoVs by analyzing 1137 respiratory samples from four subsets of patients (asymptomatic, general community, with comorbidities, and hospitalized) in São Paulo, Brazil. METHODS: A pan‐coronavirus RT‐PCR screening assay was performed, followed by species‐specific real‐time RT‐PCR monoplex assays. RESULTS: Human coronaviruses were detected in 88 of 1137 (7.7%) of the samples. The most frequently detected HCoV species were NL63 (50.0%) and OC43 (27.3%). Patients with comorbidities presented the highest risk of acquiring coronavirus infection (odds ratio = 4.17; 95% confidence interval = 1.9–9.3), and children with heart diseases revealed a significant HCoV infection presence. Dyspnea was more associated with HCoV‐229E infections (66.6%), and cyanosis was reported only in HCoV‐OC43 infections. There were interseasonal differences in the detection frequencies, with HCoV‐229E being predominant in the year 2004 (61.5%) and HCoV‐NL63 (70.8%) in 2008. CONCLUSIONS: Our data provide a novel insight into the epidemiology and clinical knowledge of HCoVs among different subsets of patients, revealing that these viruses may cause more than mild respiratory tract disease.


Gastrointestinal and Hepatic Manifestations of 2019 Novel Coronavirus Disease in a Large Cohort of Infected Patients From New York: Clinical Implications.


title: The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries

text: Abstract Background Coronavirus disease 2019 (COVID-19) has associated cutaneous manifestations. Objective To characterize the diversity of cutaneous manifestations of COVID-19, and facilitate understanding of underlying pathophysiology. Methods Case series from an international registry from the American Academy of Dermatology and International League of Dermatological Societies. Results The registry collected 716 cases of new-onset dermatologic symptoms in patients with confirmed/suspected COVID-19. Of the 171 patients in the registry with laboratory-confirmed COVID-19, the most common morphologies were morbilliform (22%), pernio-like (18%), urticarial (16%), macular erythema (13%), vesicular (11%), papulosquamous (9.9%), and retiform purpura (6.4%). Pernio-like lesions were common in patients with mild disease, while retiform purpura presented exclusively in ill, hospitalized patients. Limitations We cannot estimate incidence or prevalence. Confirmation bias is possible. Conclusion This study highlights the array of cutaneous manifestations associated with COVID-19. Many morphologies were non-specific, while others may provide insight into potential immune or inflammatory pathways in COVID-19 pathophysiology.


title: CHAPTER 6 CROCODILIANS

text: Publisher Summary This chapter presents a general overview of the anatomy, physiology, and treatment methodology for crocodilians. Most crocodilians grow to be larger than other reptile species and, therefore, have significant space requirements. Like most animals requiring an aquatic environment, crocodilians need water that is clean and free of disease. Crocodilians have a true hard palate in the roof of the mouth that ends caudally in a soft palate. This soft palate has a ventral flap which is referred to as the velum palati. The respiratory system of crocodilians consists of well-developed lungs benefiting from a very effective inspiration aided by the intercostal muscles and the septum post hepaticum. Crocodilians have a four-chambered heart as opposed to the three-chambered heart found in other reptiles and amphibians. The temperature and humidity requirements for crocodilians in captivity vary with the species. An understanding of crocodilian biology and natural history is needed to try and duplicate their natural environment. An important consideration is the allowance of circadian variations in light cycle and temperatures to mimic their natural environment. This is not the case in many commercial operations, where they are maintained at a fairly constant temperature and humidity to achieve faster growth.


title: Cytokine Responses in the Common Cold and Otitis Media

text: Cytokines are a group of diverse molecules that influence the function of every organ system. They are most well studied in their effects on the immune system and their integral role in mediating inflammation. The common cold and otitis media are two such disease states, and much has been learned about the various effects of cytokines in each disease. Most often the viruses isolated include rhinovirus (RV), respiratory syncytial virus (RSV), adenovirus, coronavirus, and picornavirus. Otitis media, sinusitis, bronchiolitis, pneumonia, and asthma exacerbation are commonly accepted as complications of viral upper respiratory tract infections. Furthermore, otitis media and upper respiratory infections are inextricably linked in that the majority (>70 %) of cases of acute otitis media occur as complications of the common cold. Cytokine polymorphisms have been associated with the severity of colds as well as the frequency of otitis media. This article attempts to update the reader on various studies that have recently been published regarding the role of cytokines in these two disease entities.


title: Predictors of Viral Pneumonia in Patients with Community-Acquired Pneumonia

text: BACKGROUND: Viruses are increasingly recognized as major causes of community-acquired pneumonia (CAP). Few studies have investigated the clinical predictors of viral pneumonia, and the results have been inconsistent. In this study, the clinical predictors of viral pneumonia were investigated in terms of their utility as indicators for viral pneumonia in patients with CAP. METHODS: Adult patients (≥18 years old) with CAP, tested by polymerase chain reaction (PCR) for respiratory virus, at two teaching hospitals between October 2010 and May 2013, were identified retrospectively. Demographic and clinical data were collected by reviewing the hospital electronic medical records. RESULTS: During the study period, 456 patients with CAP were identified who met the definition, and 327 (72%) patients were tested using the respiratory virus PCR detection test. Viral pneumonia (n = 60) was associated with rhinorrhea, a higher lymphocyte fraction in the white blood cells, lower serum creatinine and ground-glass opacity (GGO) in radiology results, compared to non-viral pneumonia (n = 250) (p<0.05, each). In a multivariate analysis, rhinorrhea (Odd ratio (OR) 3.52; 95% Confidence interval (CI), 1.58–7.87) and GGO (OR 4.68; 95% CI, 2.48–8.89) were revealed as independent risk factors for viral pneumonia in patients with CAP. The sensitivity, specificity, positive- and negative-predictive values (PPV and NPV) of rhinorrhea were 22, 91, 36 and 83%: the sensitivity, specificity, PPV and NPV of GGO were and 43, 84, 40 and 86%, respectively. CONCLUSION: Symptom of rhinorrhea and GGO predicted viral pneumonia in patients with CAP. The high specificity of rhinorrhea and GGO suggested that these could be useful indicators for empirical antiviral therapy.


title: The Swedish breeding cat: population description, infectious diseases and reproductive performance evaluated by a questionnaire

text: The questionnaire based study gives a combined description of management, infectious diseases and reproductive performance in breeding catteries during 1 year. The mean number of cats per cattery was 6.1, and 25% of the breeders let some of their cats have free access to outdoors. Breeders reported that infection with feline panleukopenia virus, feline immunodeficiency virus or feline leukaemia virus was uncommon, but 8% of the breeders had sold or had themselves owned a cat that died of feline infectious peritonitis. Presence of conjunctivitis was reported by 33.3% of the breeders. Mean litter size was 3.7±1.5, with 9.7% stillbirths and 8.3% kitten mortality week 1–12. The percentage of stillborn kittens increased with the age of the queen and litter size, and also differed among breeds. Kitten mortality differed among breeds, but did not increase with age of the queen. Seven percent of the litters were delivered by caesarean section, significantly more during winter and positively associated with presence of stillborn kittens.


title: Actualización de las infecciones respiratorias en Urgencias

text: Resumen Las infecciones respiratorias agudas (IRA) constituyen uno de los motivos de consulta más frecuentes en los Servicios de Urgencias (SU) y se encuentran entre las primeras causas de morbimortalidad en los países en vías de desarrollo, según la Organización Mundial de la Salud (OMS). De manera general, se pueden definir como un deterioro clínico agudo caracterizado por la presencia de tos, expectoración, disnea, fiebre, cambios en las características del esputo y alteraciones radiológicas; todas estas mani- festaciones pueden comprometer de manera significativa la salud de los pacientes. Realizar un buen diagnóstico y tratamiento de las IRA es primordial en la práctica diaria, tanto en Atención Primaria como a nivel hospitalario, para evitar complicaciones y mortalidad relacionadas con estas enfermedades. En esta actualización, hablaremos de las infecciones respiratorias más frecuentes en el SU, la bronquitis aguda, las agudizaciones de la EPOC o bronquiectasias y las neumonías. Abstract Acute respiratory infections (ARI) are among leading causes of emergency department (ER) consultancy and, according with World Health Organization (WHO) is one of the first causes of morbimortality in developing countries. ARI is defined as an acute clinical deterioration characterized by cough, spitting, dyspnea, fever and sputum and radiological changes, which can endanger patient's health significantly. In order to prevent clinical complications and death, proper diagnosis and treatment are mandatory in both Primary and Hospital Care. In the current update, most common respiratory infections in ER (acute bronchitis, COPD exacerbations or bronchiectasis and pneumonia) will be analyzed


title: Drosophila melanogaster as a model for studying the function of animal viral proteins

text: Studies in which Drosophila melanogaster individuals carrying transgenes of animal viruses were used to analyze the action of animal viral proteins on the cell are reviewed. The data presented suggest that host specificity of viruses is determined by their proteins responsible for the penetration of the virus into the cell, while viral proteins responsible for interactions with the host cell are much less host-specific. Due to this, the model of Drosophila with its developed system of searching for genetic interactions can be used to find intracellular targets for the action of viral proteins of the second group.


title: Rousettus aegyptiacus Bats Do Not Support Productive Nipah Virus Replication

text: Nipah virus (NiV) is a bat-borne zoonotic pathogen that can cause severe respiratory distress and encephalitis upon spillover into humans. Nipah virus is capable of infecting a broad range of hosts including humans, pigs, ferrets, dogs, cats, hamsters, and at least 2 genera of bats. Little is known about the biology of NiV in the bat reservoir. In this study, we evaluate the potential for the Egyptian fruit bat (EFB), Rousettus aegyptiacus, to serve as a model organism for studying NiV in bats. Our data suggest that NiV does not efficiently replicate in EFBs in vivo. Furthermore, we show a lack of seroconversion against NiV glycoprotein and a lack of viral replication in primary and immortalized EFB-derived cell lines. Our data show that despite using a conserved target for viral entry, NiV replication is limited in some bat species. We conclude that EFBs are not an appropriate organism to model NiV infection or transmission in bats.


docid: hhusdjel

title: Microgravimetric immunosensor for direct detection of aerosolized influenza A virus particles

text: Abstract The development and characterization of a quartz crystal microbalance (QCM) sensor for the direct detection of aerosolized influenza A virions is reported. Self-assembled monolayers (SAMs) of mercaptoundecanoic acid (MUA) are formed on QCM gold electrodes to provide a surface amenable for the immobilization of anti-influenza A antibodies using NHS/EDC coupling chemistry. The surface-bound antibody provides a selective and specific sensing interface for the capture of influenza virions. A nebulizer is used to create aerosolized samples and is directly connected to a chamber housing the antibody-modified crystal (“immunochip”). Upon exposure to the aerosolized virus, the interaction between the antibody and virus leads to a dampening of the oscillation frequency of the quartz crystal. The magnitude of frequency change is directly related to virus concentration. Control experiments using aerosols from chicken egg allantoic fluid and an anti-murine antibody based immunosensor confirm that the observed signal originates from specific viral binding on the chip surface. Step-by-step surface modification of MUA assembly, antibody attachment, and antibody–virus interaction are characterized by atomic force microscopy (AFM) imaging analysis. Using the S/N =3 principle, the limit of detection is estimated to be 4 virus particles/mL. The high sensitivity and real-time sensing scheme presented here can play an important role in the public health arena by offering a new analytical tool for identifying bio-contaminated areas and assisting in timely patient diagnosis.


title: The broad-spectrum antiviral functions of IFIT and IFITM proteins

text: Over the past few years, several groups have identified novel genes downstream of type I interferon (IFN) signaling that inhibit infection by individual or multiple families of viruses. Among these IFN stimulated genes (ISGs) with antiviral activity are two genetically and functionally distinct families — IFN-induced proteins with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane proteins (IFITM). This review focuses on recent advances in identifying the unique mechanisms of action of IFIT and IFITM genes, which explain their broad-spectrum activity against replication, spread, and disease pathogenesis of a range of human viruses.


title: Subtypes of Depression: Latent Class Analysis in Spanish Old People with Depressive Symptoms

text: Major depressive disorder (MDD) is one of the most disabling disorders and the one that most contributes to disability. When it occurs in older people, it is an additional burden to their potential physical and cognitive deficiencies, making MDD an important public health problem that supposes a large investment in health. There is a clear lack of consistency between the subtypes of depression found in the literature, ranging from two to seven classes, with three being the most commonly found non-melancholic, melancholic and psychotic, or putative psychotics. The aim of this research is to add knowledge to the profiles of depressive symptoms in a representative sample of older Spanish people, and to study the possible relationship of these symptom profiles with variables that have traditionally been related to depression. Spanish data from the sixth wave of SHARE were used, with 612 Spanish older adults living in Spain. A routine of several LCAs with a different number of classes was performed to answer this first aim to classify Spanish adults with depression symptoms. The results pointed out the presence of three different classes among the participants in the study: psychosomatic (11.12%), melancholic (14.21%), and anhedonic (74.67%). This work represents a step forward to understand the heterogeneity of major depressive disorder, facilitating the diagnosis, and subsequent treatment of older adults.


title: Structure of the SARS-Unique Domain C From the Bat Coronavirus HKU4

text: Coronaviruses (CoVs) that cause infections such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome phylogenetically originate from bat CoVs. The coronaviral nonstructural protein 3 (nsp3) has been implicated in viral replication, polyprotein cleavage, and host immune interference. We report the structure of the C domain from the SARS-Unique Domain of bat CoV HKU4. The protein has a frataxin fold, consisting of 5 antiparallel β strands packed against 2 α helices. Bioinformatics analyses and nuclear magnetic resonance experiments were conducted to investigate the function of HKU4 C. The results showed that HKU4 C engages in protein-protein interactions with the nearby M domain of nsp3. The HKU4 C residues involved in protein-protein interactions are conserved in group 2c CoVs, indicating a conserved function.


title: Characterization of Dak Nong virus, an insect nidovirus isolated from Culex mosquitoes in Vietnam

text: In this study, we isolated and characterized an insect nidovirus from the mosquito Culex tritaeniorhynchus Giles (Diptera: Culicidae) in Vietnam, as an additional member of the new family Mesoniviridae in the order Nidovirales. The virus, designated “Dak Nong virus (DKNV),” shared many characteristics with Cavally virus and Nam Dinh virus, which have also been discovered recently in mosquitoes, and these viruses should be considered members of a single virus species, Alphamesonivirus 1. DKNV grew in cultured mosquito cells but could not replicate in the cultured vertebrate cells tested. N-terminal sequencing of the DKNV structural proteins revealed two posttranslational cleavage sites in the spike glycoprotein precursor. DKNV is assumed to be a new member of the species Alphamesonivirus 1, and the current study provides further understanding of viruses belonging to the new family Mesoniviridae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-013-1741-4) contains supplementary material, which is available to authorized users.


title: Molecular characteristics and successful management of a respiratory syncytial virus outbreak among pediatric patients with hemato-oncological disease

text: BACKGROUND: Respiratory syncytial virus (RSV) is responsible for upper and lower respiratory tract infection in adults and children. Especially immunocompromised patients are at high risk for a severe course of infection, and mortality is increased. Moreover RSV can spread in healthcare settings and can cause outbreaks. Herein we demonstrate the successful control and characteristics of a RSV outbreak that included 8 patients in our Department of Pediatric Hematology and Oncology. METHODS: We performed an epidemiologic investigation and a molecular analysis of the outbreak strains. Moreover we present the outbreak control bundle and our concept for RSV screening in the winter season. RESULTS: RSV A and B strains caused the outbreak. RSV B strains affected 3 patients, 2 of whom were co-infected with RSV A. Exactly this RSV A strain was detected in another 5 patients. Our multimodal infection control bundle including prophylactic RSV screening was able to rapidly stop the outbreak. CONCLUSION: An infection control bundle in RSV outbreaks should address all potential transmission pathways. In pediatric settings the restriction of social activities might have a temporal negative impact on quality of life but helps to limit transmission opportunities. Molecular analysis allows better understanding of RSV outbreaks and, if done in a timely manner, might be helpful for guidance of infection control measures.


title: The Detection and Genetic Characterization Based on the S1 Gene Region of BCoVs from Respiratory and Enteric Infections in Turkey

text: We investigated bovine coronavirus (BCoV) as an etiological agent in cattle with clinical respiratory and digestive signs using 147 feces and 199 nasal swab samples. A total of 18 test samples (16 feces and 2 nasal swap samples) were detected positive by ELISA and/or RT‐PCR targeting the BCoV N gene. The partial S1 gene regions of BCoVs (An‐4 and An‐11) detected in feces samples from two herd‐mate dairy calves were compared. Virological and serological results indicated that BCoVs are widespread in Turkey and are likely etiological agents in diarrhea cases in calves.


title: Differential virological diagnosis of acute respiratory infections in suspect SARS patients

text: Abstract The NIC in Lyon has been involved in the virological diagnosis of suspect severe acute respiratory syndrome (SARS) patients. In March, the French medical authorities organized a medical surveillance of the medical staff who had returned from the French hospital in Hanoi. Each person presenting or not with respiratory symptoms was sampled systematically by the nearest general practitioner (GP) belonging to the influenza network surveillance in the community called GROG and the samples were sent to the NICs located either in Paris or in Lyon. We also received samples from patients hospitalized in the south of France suffering from acute respiratory infection soon after a journey in Asia. We implemented a PCR diagnosis for the human respiratory viruses: influenza A and B, Parainfluenza (Type 1 to Type 4), Metapneumovirus, RSV, Rhinovirus, Enterovirus, Adenovirus. In April, we set up the PCR detection of the SARS-associated coronavirus Urbani strain. The practitioners performed respiratory samples. From 14 March to 15 May we received and tested 88 respiratory samples, respectively, 19 were realized by GPs from the community network and 69 came from hospitalized patients. We never detected the urbani coronavirus strain. However, we detected respiratory viruses in 24% of the cases: the most frequent virus was influenza A H3N2 (11%) and Parainfluenza type 3 (8%). RSV, influenza A H1N1 and Rhinovirus were also detected 2, 1 and 1 cases, respectively. All the positive samples except the rhinovirus came from hospitalized patients. The patients were sampled once and all of them recovered rapidly.


docid: bpfarowa

title: Chapter 2 Anatomical Uniqueness of the Mucosal Immune System (GALT, NALT, iBALT) for the Induction and Regulation of Mucosal Immunity and Tolerance

text: Abstract Mucosal surfaces lining the lung and the gut are constantly exposed to environmental antigens, commensal organisms, and pathogens. Consequently, the host’s immune system devotes enormous resources to the defense of these tissues. Although mucosal immune responses must be sufficiently strong to eliminate pathogens, they must also have mechanisms to prevent excessive inflammation and initiate epithelial repair. Importantly, mucosal immune responses are initiated and regulated by a variety of mucosal lymphoid tissues, collectively known as mucosa-associated lymphoid tissue (MALT). This chapter describes the unique developmental, architectural, and functional features of the MALT and how those features facilitate the local immune response at each site.


title: Exotic Viral Diseases: A Global Guide Stephen A. Berger Charles H. Calisher

text: Unknown


title: Inhibition of white spot syndrome virus in Litopenaeus vannamei shrimp by sequence-specific siRNA

text: Abstract RNA interference (RNAi) is a sequence-specific, post-transcriptional process of mRNA degradation. Here, we described specific silencing of five white spot syndrome virus (WSSV) genes in Litopenaeus vannamei in vivo with sequence-specific siRNAs. These genes included DNA polymerase (dnapol), ribonucleotide reductase small subunit (rr2), thymidine kinase and thymidylate kinase (tk-tmk), vp24 and vp28. At 6 days post-challenged, the relative survival rates of shrimp injected with siDNApol, siRR2, siTK-TMK, siVP24 and siVP28 (siRNAs for dnapol, rr2, tk-tmk, vp24 and vp28 genes) reached 50%, 50%, 66%, 33% and 33%, respectively. Specific siRNAs of the five WSSV genes could result in suppression of the target genes and a significant reduction in the viral proliferation. In negative controls, sequence-independent siRNA (mutant siRNA) could not inhibit expression of these five genes or viral replication. Consequently, injection of sequence-dependent siRNA could induce anti-WSSV activity in shrimp. These results suggest that siRNA can suppress WSSV efficiently in shrimp, and it may provide a potential approach to the therapy of aquaculture viral disease.


title: Structural and mutational analysis of the interaction between the Middle-East respiratory syndrome coronavirus (MERS-CoV) papain-like protease and human ubiquitin

text: The papain-like protease (PL(pro)) of Middle-East respiratory syndrome coronavirus (MERS-CoV) has proteolytic, deubiquitinating, and deISGylating activities. The latter two are involved in the suppression of the antiviral innate immune response of the host cell. To contribute to an understanding of this process, we present here the X-ray crystal structure of a complex between MERS-CoV PL(pro) and human ubiquitin (Ub) that is devoid of any covalent linkage between the two proteins. Five regions of the PL(pro) bind to two areas of the Ub. The C-terminal five residues of Ub, RLRGG, are similar to the P5–P1 residues of the polyprotein substrates of the PL(pro) and are responsible for the major part of the interaction between the two macromolecules. Through sitedirected mutagenesis, we demonstrate that conserved Asp165 and non-conserved Asp164 are important for the catalytic activities of MERS-CoV PL(pro). The enzyme appears not to be optimized for catalytic efficiency; thus, replacement of Phe269 by Tyr leads to increased peptidolytic and deubiquitinating activities. Ubiquitin binding by MERS-CoV PL(pro) involves remarkable differences compared to the corresponding complex with SARS-CoV PL(pro). The structure and the mutational study help understand common and unique features of the deubiquitinating activity of MERS-CoV PL(pro). ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s12250-016-3742-4 and is accessible for authorized users.


title: Neurologic Characteristics in Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

text: Importance: Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease that has caused a global pandemic. The presenting symptoms are mainly respiratory symptom, yet studies have reported nervous system involvement in the disease. A systematic review and meta-analysis of these studies are required to understanding the neurologic characteristic of the disease and help physicians with early diagnosis and management. Objective: To conduct a systematic review and meta-analysis on the neurologic characteristics in patients with COVID-19. Evidence Review: Authors conducted a literature search through PubMed from January 1st, 2020 to April 8th, 2020. Furthermore, the authors added additional sources by reviewing related references. Studies presenting the neurologic features of COVID-19 patients in their data were included. Case reports and case series were also included in this review. The quality of the studies was assessed based on the Oxford Center for Evidence-Based Medicine guidelines. Selected studies were included in the meta-analysis of proportion and the heterogeneity test. Finding: From 280 identified studies, 33 were eligible, with 7,559 participants included. Most of the included studies were from China (29 [88%]). Muscle injury or myalgia was the most common (19.2%, 95%CI 15.4–23.2%) neurologic symptom of COVID-19, followed by headache (10.9%, 95%CI 8.62–13.51%); dizziness (8.7%, 95%CI 5.02–13.43%); nausea with or without vomiting (4.6%, 95%CI 3.17–6.27%); concurrent cerebrovascular disease (4.4%, 95%CI 1.92–7.91%); and impaired consciousness (3.8%, 95%CI 0.16–12.04%). Underlying cerebrovascular disease was found in 8.5% (95%CI 4.5–13.5%) of the studies. Conclusion: Neurologic findings vary from non-specific to specific symptoms in COVID-19 patients. Some severe symptoms or diseases can present in the later stage of the disease. Physicians should be aware of the presence of neurologic signs and symptoms as a chief complaint of COVID-19, in order to improve management and prevent a worsening outcome of the patients.


title: Treatment strategy for gastrointestinal tumor under the outbreak of novel coronavirus pneumonia in China

text: The outbreak of the novel coronavirus pneumonia (NCP) has become a public health emergency in China. Chinese authorities and health agencies had devoted great efforts to control this disease. As surgeons specialized in the treatment of gastrointestinal tumors, we should always be aware of the prevention for NCP and incorporate this awareness into every detail of clinical practice. For the patients with gastrointestinal tumors, pre-admission screening should be done in order to rule out NCP. Real-time RT-PCR panel and chest CT scan should be conducted for patients with fever (>37.3℃), travel history to Hubei Province within 14 days, or contact history with residents from Wuhan district within 14 days. Prevention measures for both medical staffs and the screen-negative admitted patients should also be enhanced because false negative is possible. Medical instruments should be properly discarded or disinfected according to standardized procedures established by the local center for disease control and prevention (CDC). Surgical operation should be reduced at a minimal level to prevent cross infection in this special period.Surgical intervention for benign tumor should be postponed. For malignant tumor, multidisciplinary therapy (MDT) is recommended and non-surgical anti-tumor therapy should be selected with higher priority. Neoadjuvant therapy is highly recommended for gastrointestinal cancer at advanced stages that meet the indications of NCCN guideline (gastric cancer T stage ≥ 2/rectal cancer T stage ≥ 3/unresectable colon cancer). Gastric or esophagogastricjunction (EGJ) malignant tumor with obstruction can be managed with gastric tube decompression or stent placement to relieve the symptoms. Transnasal enteral feeding tube intubation/percutaneous endoscopic gastrostomy could be adopted to ensure enteral nutrition supply. For colorectal malignancy with simple intestinal obstruction, stent placement can achieve a high success rate, which not only helps avoid emergency surgery, but also creates a better condition for subsequent surgery. Transcatheter arterial embolization for hemostasis is an alternative choice for gastrointestinal tumor with bleeding. However, emergency operation still must be performed for patients with acute uncontrolled bleeding, obstruction or after other alternative treatment measures fail. All cases with suspicious or confirmed with NCP must be reported to the local CDC department. All invasive intervention must be performed in a designated isolation area. Tertiary prevention measure must be adopted for all anesthetists with additional face mask or medical goggle protection to prevent respiratory droplet transmission. Preventive enterostomy is preferable in lower digestive tract surgery. Thoroughly disinfecting the operating room after surgery is necessary. Fever after surgery must be carefully differentiated whether it's caused by post-surgery abdominal infection/inflammation or NCP. Single-room isolation and related examinations should be performed according to the standard procedures. We believe that with the unprecedentedly joint efforts of doctors and patients, we will eventually win this war against NCP.


Public Health Literacy for Lawyers


title: Experimental co-infection of infectious bronchitis and low pathogenic avian influenza H9N2 viruses in commercial broiler chickens

text: Abstract In this study, commercial broilers were experimentally infected with single (classical IBV, variant IBV or AIV-H9N2) or mixed AIV-H9N2 with classical, variant or vaccine strains of IBV. Birds were monitored for clinical and pathological outcomes and virus shedding for 10days post infection (DPI). Clinical signs were limited to the respiratory tract in all challenged groups and varied from mild to moderate mouth breathing to severe respiratory signs with snorting sound and extended head. Mortalities were only recorded in mixed AIV-H9N2/variant IBV challenge group. AIV-H9N2 challenge caused tracheal petechial hemorrhage that progressed to tracheal congestion and caseation. In mixed AIV-H9N2/IBV vaccine challenge, severe tracheitis with bronchial cast formation was observed. In mixed AIV-H9N2/variant IBV challenge severe congestion of the tracheal mucosa and excessive exudates with a tendency to form tubular casts were observed. Kidney ureate deposition was only observed in variant IBV challenge group. Histopathologically, tracheal congestion, severe degeneration, and deciliation were noticed in all groups of mixed infection. Interestingly, hemorrhage and atrophy were observed in thymus gland of birds challenged with single AIV-H9N2 or mixed AIV-H9N2/IBV. There was no difference in the tracheal shedding level of variant IBV between single and mixed infected groups while classical IBV shedding increased in mixed infection group. Interestingly, the AIV-H9N2 showed constantly high shedding titers till 7DPI with variant or vaccine IBV co-infection. In conclusion, co-infection of IBV and AIV-H9N2 induced severe clinical outcome and high mortality. Also, IBV co-infection increased the shedding of AIV-H9N2 in experimentally infected birds.


China's shift in HIV/AIDS policy marks turnaround on health


title: Novel Viruses, Zoonotic Infections, and Travel Health

text: Novel viruses and zoonotic infections pose global health risks.


title: Simultaneous detection and differentiation of canine parvovirus and feline parvovirus by high resolution melting analysis

text: BACKGROUND: Canine parvovirus (CPV) and feline parvovirus (FPV) are causative agents of diarrhea in dogs and cats, which manifests as depression, vomiting, fever, loss of appetite, leucopenia, and diarrhea in young animals. CPV and FPV can single or mixed infect cats and cause disease. To diagnose sick animals effectively, an effective virus diagnostic and genome typing method with high sensitivity and specificity is required. RESULTS: In this study, a conserved segment containing one SNP A4408C of parvovirus was used for real-time PCR amplification. Subsequently, data were auto-analyzed and plotted using Applied Biosystems® High Resolution Melt Software v3.1. Results showed that CPV and FPV can be detected simultaneously in a single PCR reaction. No cross-reactions were observed with canine adenovirus, canine coronavirus, and canine distemper virus. The assay had a detection limit of 4.2 genome copies of CPV and FPV. A total of 80 clinical samples were subjected to this assay, as well as to conventional PCR-sequence assay and virus isolation. Results showed that the percentage of agreement of the assay and other methods are high. CONCLUSIONS: In short, we have developed a diagnostic test for the accurate detection and differentiation of CPV and FPV in fecal samples, which is also cost effective.


title: COVID-19 and the Fears of Italian Senior Citizens

text: Italy has been hit very hard by the severe acute respiratory syndrome—coronavirus-2 (SARS-CoV-2) pandemic. This brief report highlights some of the peculiarities manifested by its older adult population, with particular reference to those living in nursing institutions and at home. Mortality data (as of 26 April) are reported, together with reactions to forced isolation, loneliness, and fear of contracting the disease, which represent big challenges for all, especially for frail elderly people.