title: Chapter 3 Features of Host Cells Cellular and Molecular Biology Review

text: Abstract As obligate intracellular parasites, viruses are completely dependent upon a host cell for their replication. They use energy generated by the host cell, and they exploit the host's machinery to manufacture viral proteins. Many of the cell's organelles, as well as the plasma membrane, are involved in viral replication processes. The organelles involved in protein synthesis, processing, and transport—namely the ribosome, rough endoplasmic reticulum, and Golgi complex—are utilized in the manufacture of viral proteins, as well, and viruses use ATP generated by the host cell's mitochondria. The plasma membrane, made of a phospholipid bilayer, is the cell's primary zone of contact with the extracellular world. As such, it is the first obstacle that a virus must overcome for entry into a cell. The Central Dogma of Molecular Biology states that DNA is replicated to create more DNA, DNA is transcribed into mRNA, and mRNA is translated by ribosomes to create proteins. All viruses are dependent upon the host's translation machinery, and many viruses will use other portions of the cell's replication and transcription mechanisms. DNA polymerase is the major enzyme involved in DNA replication, while RNA polymerase creates messenger RNA. Host ribosomes translate the messenger RNA into proteins, composed of amino acids. Viruses also have many unique strategies to ensure the translation of their proteins over host proteins.


docid: vxqgzvxe

title: La consulta telemática para el cardiólogo clínico en tiempos de la COVID-19: presente y futuro. Documento de consenso de la Sociedad Española de Cardiología

text: RESUMEN La pandemia producida por la infección por el coronavirus SARS-CoV-2 (COVID-19) ha cambiado la forma de entender nuestras consultas. Para reducir el riesgo de contagio de los pacientes más vulnerables (aquellos con cardiopatías) y del personal sanitario, se han suspendido la mayoría de las consultas presenciales y se han puesto en marcha las consultas telemáticas. Este cambio se ha implementado en muy poco tiempo, pero parece que ha venido para quedarse. No obstante, hay grandes dudas sobre aspectos organizativos, legales, posibilidades de mejora, etc. En este documento de consenso de la Sociedad Española de Cardiología, tratamos de dar las claves para mejorar la calidad asistencial en nuestras nuevas consultas telemáticas, revisando las afecciones que el cardiólogo clínico atiende con más frecuencia en su consulta ambulatoria y proponiendo unos mínimos en ese proceso asistencial. Estas enfermedades son la cardiopatía isquémica, la insuficiencia cardiaca y las arritmias. En los 3 escenarios tratamos de clarificar los aspectos fundamentales que hay que revisar en la entrevista telefónica, a qué pacientes habrá que atender en una consulta presencial y cuáles serán los criterios para su seguimiento en atención primaria. El documento también recoge distintas mejoras que pueden introducirse en la consulta telemática para mejorar la asistencia de nuestros pacientes. ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care.


title: The psychological impact of COVID-19 pandemic on the general population of Saudi Arabia

text: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging infection causing a widely spread pandemic of Coronavirus disease 2019 (COVID-19). The current COVID-2019 pandemic is prompting fear of falling sick, dying, helplessness and stigma, urgent and timely understanding of mental health status is needed to help the community. Our investigation designed to survey the general population in Saudi Arabia to assess the degree of psychological impact during the pandemic. METHODS: During the early stage of the outbreak, we conducted an online-based survey using a snowballing sample technique. The surveys collected data about several aspects of participant sociodemographic, knowledge, concerns, psychological impact, and mental health status. We assessed the psychological impact and mental health status using the Impact of Event Scale-Revised (IES-R), and the Depression, Anxiety, and Stress Scale (DASS-21). RESULTS: Our survey recruited 1160 respondents of the general public of Saudi Arabia. Of them, 23.6% reported moderate or severe psychological impact of the outbreak, 28.3%,24%, and 22.3% reported moderate to severe depressive, anxiety, and stress symptoms, respectively. Females reported IES-R (B: 5.46, 95% CI: 3.61 to 7.31) and DASS subscales B coefficient ranged from 1.65 to 2.63, along with high-school students, working in the medical field, and poor self-reported health status was significantly associated with a high level of IES-R and DASS scales (p < .05). Experiencing breathing difficulty and dizziness showed a stronger association with higher IES-R and DASS subscales than other somatic symptoms (e.g., headache and fever);(p < .001). Respondents who practiced specific preventative measures (e.g., hand washing, social distancing) demonstrated a protective effect against stress, anxiety, and depression symptoms. Social distancing appeared to be protective on stress and anxiety subscales (B: -1.49, 95% CI: −2.79 to −0.19),(B: -1.53, 95% CI: −2.50 to −0.57),respectively; and hand hygiene on depression subscale (B: -2.43, 95% CI: −4.44 to −0.42). CONCLUSION: Throughout the early stage of the COVID-19 outbreak in Saudi Arabia, the results showed that nearly one-fourth of the sampled general population experienced moderate to severe psychological impact. Following specific precautionary measures appeared to have a protective effect on the individual's mental health. Our findings can be used to construct psychological interventions directed toward vulnerable populations and to implement public mental health strategies in the early stages of the outbreak.


title: Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment

text: Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication, thus is a candidate anti-HFMD drug.


title: Analysis of international tourist arrivals in China: The role of World Heritage Sites

text: This paper analyzes the determinants of international tourist arrivals in China, especially for World Heritage Sites and various kinds of travel spots. Utilizing annual provincial panel data over the 2000–2005 period, the empirical results suggest that key determinants include the relative income, population in the original country, cost of travel, and tourism infrastructure. In addition, World Heritage Sites are also found to be significant in explaining the numbers of international tourists and have a greater tourist-enhancing effect. Other famous tourist sites rated 4A- and 3A-class are also attractive to foreign tourism. Moreover, cultural rather than natural sites attract more interest among foreign tourists, because China is internationally renowned for its long-standing historical and cultural assets. Finally, the importance of the determinants of the demand for tourism varies from country to country.


title: Non-Molecular-Clock-Like Evolution following Viral Origins in Homo sapiens

text: Researchers routinely adopt molecular clock assumptions in conducting sequence analyses to estimate dates for viral origins in humans. We used computational methods to examine the extent to which this practice can result in inaccurate ‘retrodiction.’ Failing to account for dynamic molecular evolution can affect greatly estimating index case dates, resulting in an overestimated age for the SARS-CoV-human infection, for instance.


title: Co‐chaperone BAG3 and adenovirus penton base protein partnership

text: The BAG family of Hsp70/Hsc70 co‐chaperones is characterised by the presence of a conserved BAG domain at the carboxyl‐terminus. BAG3 protein is the only member of this family containing also the N‐terminally located WW domain. We describe here the identification of adenovirus (Ad) penton base protein as the first BAG3 partner recognising BAG3 WW domain. Ad penton base is the viral capsid constituent responsible for virus internalisation. It contains in the N‐terminal part two conserved PPxY motifs, known ligands of WW domains. In cells producing Ad penton base protein, cytoplasmic endogenous BAG3 interacts with it and co‐migrates to the nucleus. Preincubation of BAG3 with Ad base protein results in only slight modulation of BAG3 co‐chaperone activity, suggesting that this interaction is not related to the classical BAG3 co‐chaperone function. However, depletion of BAG3 impairs the cell entry of the virus and viral progeny production in Ad‐infected cells, suggesting that the interaction between virus penton base protein and cellular co‐chaperone BAG3 positively influences virus life cycle. These results thus demonstrate a novel host–pathogen interaction, which contributes to the successful infectious life cycle of adenoviruses. In addition, these data enrich our knowledge about the multifunctionality of the BAG3 co‐chaperone. J. Cell. Biochem. 111: 699–708, 2010. © 2010 Wiley‐Liss, Inc.


title: The potential danger of suboptimal antibody responses in COVID-19

text: There is a desperate need for effective therapies and vaccines for SARS-CoV-2 to mitigate the growing economic crisis that has ensued from societal lockdown. Vaccines are being developed at an unprecedented speed and are already in clinical trials, without preclinical testing for safety and efficacy. Yet, safety evaluation of candidate vaccines must not be overlooked.


docid: gzvtcgyd

title: What does ‘leave no one behind’ mean for humanitarian crises-affected populations in the COVID-19 pandemic?


title: Models of cytokine dynamics in the inflammatory response of viral zoonotic infectious diseases

text: Inflammatory responses to an infection from a zoonotic pathogen, such as avian influenza viruses, hantaviruses and some coronaviruses, are distinctly different in their natural reservoir versus human host. While not as well studied in the natural reservoirs, the pro-inflammatory response and viral replication appear controlled and show no obvious pathology. In contrast, infection in humans results in an initial high viral load marked by an aggressive pro-inflammatory response known as a cytokine storm. The key difference in the course of the infection between the reservoir and human host is the inflammatory response. In this investigation, we apply a simple two-component differential equation model for pro-inflammatory and anti-inflammatory responses and a detailed mathematical analysis to identify specific regions in parameter space for single stable endemic equilibrium, bistability or periodic solutions. The extensions of the deterministic model to two stochastic models account for variability in responses seen at the cell (local) or tissue (global) levels. Numerical solutions of the stochastic models exhibit outcomes that are typical of a chronic infection in the natural reservoir or a cytokine storm in human infection. In the chronic infection, occasional flare-ups between high and low responses occur when model parameters are in a region of bistability or periodic solutions. The cytokine storm with a vigorous pro-inflammatory response and less vigorous anti-inflammatory response occurs in the parameter region for a single stable endemic equilibrium with a strong pro-inflammatory response. The results of the model analyses and the simulations are interpreted in terms of the functional role of the cytokines and the inflammatory responses seen in infection of the natural reservoir or of the human host.


title: Report of the second international conference on next generation sequencing for adventitious virus detection in biologics for humans and animals()

text: The IABS-EU, in association with PROVAXS and Ghent University, hosted the “2(nd) Conference on Next Generation Sequencing (NGS) for Adventitious Virus Detection in Human and Veterinary Biologics” held on November 13(th) and 14(th) 2019, in Ghent, Belgium. The meeting brought together international experts from regulatory agencies, the biotherapeutics and biologics industries, contract research organizations, and academia, with the goal to develop a scientific consensus on the readiness of NGS for detecting adventitious viruses, and on the use of this technology to supplement or replace/substitute the currently used assays. Participants discussed the progress on the standardization and validation of the technical and bioinformatics steps in NGS for characterization and safety evaluation of biologics, including human and animal vaccines. It was concluded that NGS can be used for the detection of a broad range of viruses, including novel viruses, and therefore can complement, supplement or even replace some of the conventional adventitious virus detection assays. Furthermore, the development of reference viral standards, complete and correctly annotated viral databases, and protocols for the validation and follow-up investigations of NGS signals is necessary to enable broader use of NGS. An international collaborative effort, involving regulatory authorities, industry, academia, and other stakeholders is ongoing toward this goal.


The Clinical Nurse Leader and COVID-19: Leadership and quality at the point of care


title: Securing Internet of Medical Things with Friendly-jamming schemes

text: The Internet of Medical Things (IoMT)-enabled e-healthcare can complement traditional medical treatments in a flexible and convenient manner. However, security and privacy become the main concerns of IoMT due to the limited computational capability, memory space and energy constraint of medical sensors, leading to the in-feasibility for conventional cryptographic approaches, which are often computationally-complicated. In contrast to cryptographic approaches, friendly jamming (Fri-jam) schemes will not cause extra computing cost to medical sensors, thereby becoming potential countermeasures to ensure security of IoMT. In this paper, we present a study on using Fri-jam schemes in IoMT. We first analyze the data security in IoMT and discuss the challenges. We then propose using Fri-jam schemes to protect the confidential medical data of patients collected by medical sensors from being eavesdropped. We also discuss the integration of Fri-jam schemes with various communication technologies, including beamforming, Simultaneous Wireless Information and Power Transfer (SWIPT) and full duplexity. Moreover, we present two case studies of Fri-jam schemes in IoMT. The results of these two case studies indicate that the Fri-jam method will significantly decrease the eavesdropping risk while leading to no significant influence on legitimate transmission.


title: Towards a computational model for −1 eukaryotic frameshifting sites

text: Motivation: Unconventional decoding events are now well acknowledged, but not yet well formalized. In this study, we present a bioinformatics analysis of eukaryotic −1 frameshifting, in order to model this event. Results: A consensus model has already been established for −1 frameshifting sites. Our purpose here is to provide new constraints which make the model more precise. We show how a machine learning approach can be used to refine the current model. We identify new properties that may be involved in frameshifting. Each of the properties found was experimentally validated. Initially, we identify features of the overall model that are to be simultaneously satisfied. We then focus on the following two components: the spacer and the slippery sequence. As a main result, we point out that the identity of the primary structure of the so-called spacer is of great importance. Availability: Sequences of the oligonucleotides in the functional tests are available at http://www.igmors.u-psud.fr/rousset/bioinformatics/ Contact: bekaert@igmors.u-psud.frjpforest@lri.frchris@lri.fr


title: Immunoregulation with mTOR inhibitors to prevent COVID‐19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines

text: Coronavirus disease 2019 (COVID‐19) has become a major global public health concern. The mortality rate for critically ill patients is up to 60%, and, thus, reducing the disease severity and case mortality is a top priority. Currently, cytokine storms are considered as the major cause of critical illness and death due to COVID‐19. After a systematical review of the literature, we propose that cross‐reactive antibodies associated with antibody‐dependent enhancement (ADE) may actually be the cause of cytokine storms. It would be more difficult to develop vaccines for highly pathogenic human coronaviruses (CoVs) if ADE characteristics are taken into consideration. Therefore, it is urgent to find an effective way to prevent the occurrence of severe illness as severe acute respiratory syndrome CoV‐2 specific drugs or vaccines are still in development. If the activation of memory B cells can be selectively inhibited in high‐risk patients at an early stage of COVID‐19 to reduce the production of cross‐reactive antibodies against the virus, we speculate that ADE can be circumvented and severe symptoms can be prevented. The mammalian target of rapamycin (mTOR) inhibitors satisfy such needs and it is recommended to conduct clinical trials for mTOR inhibitors in preventing the severity of COVID‐19.


title: How Is WHO Responding to Global Public Health Threats?

text: The editors discuss two recent WHO initiatives on preparing for and responding to global public health threats: the WHO Rapid Advice Guidelines Group and the new revision of the International Health Regulations.


docid: qbaemfnx

title: Rationale for universal face masks in public against COVID‐19


title: Antibioprophylaxie dans le cadre d'interventions obstétricales

text: OBJECTIF: Analyser les résultats et formuler des recommandations sur le recours à l'antibioprophylaxie dans le cadre d'interventions obstétricales. ISSUES: Parmi les issues évaluées, on trouve la nécessité et l'efficacité du recours à des antibiotiques aux fins de la prévention des infections dans le cadre d'interventions obstétricales. RÉSULTATS: La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans Medline et The Cochrane Library au moyen de la rubrique « antibioprophylaxie dans le cadre d'interventions obstétricales ». Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. Les recherches ont été mises à jour de façon régulière et les articles publiés entre janvier 1978 et juin 2009 ont été incorporés à la directive clinique. Les lignes directrices actuellement publiées par le American College of Obstetrics and Gynecology ont également été incorporées à la directive clinique. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. VALEURS: Les résultats obtenus ont été analysés et évalués par le comité sur les maladies infectieuses de la Société des obstétriciens et gynécologues du Canada sous la gouverne des auteures principales, et les recommandations ont été formulées conformément aux lignes directrices élaborées par le Groupe d'étude canadien sur les soins de santé préventifs (Tableau 1). AVANTAGES, DÉSAVANTAGES ET COÛTS: La mise en œuvre de la présente directive clinique devrait réduire les coûts et les torts attribuables à l’administration d’antibiotiques lorsque celle-ci ne s’avère pas requise, ainsi que les torts attribuables à la non-administration d’antibiotiques lorsque ceux-ci pourraient s’avérer bénéfiques. DÉCLARATIONS SOMMAIRES: 1. Les données disponibles ne soutiennent pas le recours à l'antibioprophylaxie en vue d'atténuer la morbidité infectieuse à la suite d'un accouchement vaginal opératoire. (II-1); 2. Nous ne disposons pas de données suffisantes pour soutenir ou déconseiller le recours à l'antibioprophylaxie en vue d'atténuer la morbidité infectieuse dans les cas de retrait manuel du placenta. (III); 3. Nous ne disposons pas de données suffisantes pour soutenir ou déconseiller le recours à l'antibioprophylaxie au moment de la dilatation-curetage postpartum visant des produits de conception en rétention. (III); 4. Les données disponibles ne soutiennent pas le recours à l'antibioprophylaxie en vue d'atténuer la morbidité infectieuse à la suite d'un cerclage planifié ou d'urgence. (II-3). RECOMMANDATIONS: 1. Toutes les femmes qui subissent une césarienne planifiée ou d'urgence devraient se voir administrer une antibioprophylaxie. (I-A); 2. Une dose unique d'une céphalosporine de première génération devrait constituer l'antibiotique à privilégier pour ce qui est des césariennes. Lorsque la patiente présente une allergie à la pénicilline, on peut avoir recours à la clindamycine ou à l'érythromycine. (I-A); 3. Dans le cas de la césarienne, l'antibioprophylaxie devrait être administrée de 15 à 60 minutes avant l'incision de la peau. Aucune dose additionnelle n'est recommandée. (I-A); 4. Lorsqu'une intervention à abdomen ouvert est de longue durée (>3 heures) ou que la perte sanguine estimée est supérieure à 1 500 ml, une dose additionnelle d'antibiotique prophylactique peut être administrée de 3 à 4 heures à la suite de la dose initiale. (III-L); 5. L'administration d'une antibioprophylaxie peut être envisagée pour atténuer la morbidité infectieuse associée à la réparation d'une lésion périnéale du troisième ou du quatrième degré. (I-B); 6. Chez les patientes massivement obèses (IMC > 35), il est possible d'envisager le doublement de la dose d'antibiotiques. (III-B); 7. L’administration d’antibiotiques aux seules fins de prévenir l’endocardite ne devrait pas être mise en œuvre chez les patientes qui doivent subir une intervention obstétricale, quelle qu’en soit la nature. (III-E).


title: Evaluating the promise of recombinant transmissible vaccines

text: Transmissible vaccines have the potential to revolutionize infectious disease control by reducing the vaccination effort required to protect a population against a disease. Recent efforts to develop transmissible vaccines focus on recombinant transmissible vaccine designs (RTVs) because they pose reduced risk if intra-host evolution causes the vaccine to revert to its vector form. However, the shared antigenicity of the vaccine and vector may confer vaccine-immunity to hosts infected with the vector, thwarting the ability of the vaccine to spread through the population. We build a mathematical model to test whether a RTV can facilitate disease management in instances where reversion is likely to introduce the vector into the population or when the vector organism is already established in the host population, and the vector and vaccine share perfect cross-immunity. Our results show that a RTV can autonomously eradicate a pathogen, or protect a population from pathogen invasion, when cross-immunity between vaccine and vector is absent. If cross-immunity between vaccine and vector exists, however, our results show that a RTV can substantially reduce the vaccination effort necessary to control or eradicate a pathogen only when continuously augmented with direct manual vaccination. These results demonstrate that estimating the extent of cross-immunity between vector and vaccine is a critical step in RTV design, and that herpesvirus vectors showing facile reinfection and weak cross-immunity are promising.


Vitamin D deficiency and co-morbidities in COVID-19 patients – A fatal relationship?


title: Community Epidemiology Framework for Classifying Disease Threats

text: Recent evidence suggests that most parasites can infect multiple host species and that these are primarily responsible for emerging infectious disease outbreaks in humans and wildlife. However, the ecologic and evolutionary factors that constrain or facilitate such emergences are poorly understood. We propose a conceptual framework based on the pathogen's between- and within-species transmission rates to describe possible configurations of a multihost-pathogen community that may lead to disease emergence. We establish 3 dynamic thresholds separating 4 classes of disease outcomes, spillover, apparent multihost, true multihost, and potential emerging infectious disease; describe possible disease emergence scenarios; outline the population dynamics of each case; and clarify existing terminology. We highlight the utility of this framework with examples of disease threats in human and wildlife populations, showing how it allows us to understand which ecologic factors affect disease emergence and predict the impact of host shifts in a range of disease systems.


title: Diagnostic Techniques: Serological and Molecular Approaches☆

text: Abstract Virus laboratory diagnostics has an increasingly important role in modern patient care. Virological methods are needed to investigate the etiology of acute viral infection or the reactivation of a latent infection, as well as to follow virus load in antiviral treatments. Serological assays are also used for screening of blood products for the risk of certain chronic infections, evaluation of the immune status, and need for prophylactic treatments in connection with organ transplantations. For diagnostic purposes the following approaches can be used: demonstration of presence of infectious virus or its structural components directly from a patient's specimens or investigation of specific antibody response in serum specimens. Amplification techniques, most commonly polymerase chain reaction (PCR) is currently the workhorse of nucleic acid testing for the detection and quantitation of virus genomes. Virus isolation is used to demonstrate infectious virus in a patient's specimens, whereas virus antigens are investigated by antigen detection assays. Serological diagnosis is based on either the demonstration of the presence of virus-specific IgM antibodies or a significant increase in the levels and/or avidity of specific IgG antibodies. Immunoassays are the most commonly used serological assays. Point-of-care tests (POC tests), for antigens, antibodies, and also nucleic acids are also becoming more and more common in diagnostic use. In order to reach the best diagnostic efficiency for each patient it is important to select the most suitable method using the right sample collected at the right time.


title: Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients

text: A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients. In addition, small series of patients with coronary, cerebrovascular and peripheral arterial thrombotic events have also been reported, but their true incidence and consequences are not well described, and constitute the objective of this study. From February 1st to April 21st, 2020, 2115 COVID-19 patients were treated at Hospital Universitario Fundación Alcorcón (Madrid, Spain), and 1419 were eventually admitted. Patient characteristics and outcomes were collected by reviewing their electronic medical records. Fourteen patients had a systemic arterial thrombotic event, which represents a 1% incidence in relation to the total number of hospitalized patients. Three patients suffered an acute coronary syndrome, two with persistent ST-segment elevation, one of whom was treated invasively, and one with transient ST-segment elevation. Eight patients had a cerebrovascular event. Six suffered an acute ischemic stroke and two a transient ischemic attack, 50% of them had a Rankin score ≥ 3 at discharge. Three additional patients had a limb thrombotic event, all of them infrapopliteal, and were managed conservatively. All three cases developed necrosis of the toes, two of them with bilateral involvement. The hospitalization death rate of patients with an arterial event was 28.6%. Although COVID-19 may favor the occurrence of thrombotic events, the destabilization and thrombosis of arterial atherosclerotic plaques do not seem to be a frequent mechanism which warrants the need for specific systematic preventive measures.


title: U-08: Gestion des infections à MERS-CoV : expérience au CHRU de Lille

text: Introduction – objectifs Deux patients atteints de MERS-CoV (Middle East Respiratory Syndrome-Coronavirus) ont été hospitalisés en France en 2013. L’un d’eux a été pris en charge dans notre unité de Maladies Infectieuses (UMI). L’objectif de ce travail est de décrire et évaluer l’organisation pratique et les mesures de prévention mises en œuvre en situation d’alerte virus émergent. Matériels et méthodes L’UMI dispose de 20 lits dont 6 pouvant être une aile dédiée en cas d’épidémie ou d’alerte virus émergent. Dans ce travail, nous décrivons rétrospectivement la prise en charge des patients infectés par le MERS-CoV ainsi que des cas « contact » suspects d’infection, en collaboration avec le Service de Gestion des Risques Infectieux (SGRIVI), le laboratoire d’analyse médicale et le service de communication du CHR. Résultats Du 9 au 16 mai 2013, 4 patients ont été accueillis dans notre unité sans nécessité d’équipe dédiée : 1 patient «MERS-CoV positif » et 3 patients « contacts ». Nous avons dû rapidement vérifier les pressions négatives des chambres, adapter les procédures de soin et de prélèvement, organiser les mesures de prévention pour les patients, leur famille et le personnel, définir la gestion et l’acheminement des prélèvements par un circuit dédié et gérer la considérable pression médiatique. Conclusion La gestion de l’alerte a été facilitée par notre expérience de l’épidémie de grippe en 2009–2010. Depuis mai 2013 le CHRU a écrit une procédure spécifique MERS-CoV mise en application lors du retour de pèlerinage en octobre 2013 avec une meilleure réactivité, une collaboration des différents intervenants et la mise en place des mesures dédiées. La diffusion des informations auprès des médias est gérée exclusivement par la cellule de communication du CHRU.


Habitat for Humanity cuts staff amid COVID‐19 pandemic


title: High-level expression of the HIV entry inhibitor griffithsin from the plastid genome and retention of biological activity in dried tobacco leaves

text: KEY MESSAGE: The potent anti-HIV microbicide griffithsin was expressed to high levels in tobacco chloroplasts, enabling efficient purification from both fresh and dried biomass, thus providing storable material for inexpensive production and scale-up on demand. ABSTRACT: The global HIV epidemic continues to grow, with 1.8 million new infections occurring per year. In the absence of a cure and an AIDS vaccine, there is a pressing need to prevent new infections in order to curb the disease. Topical microbicides that block viral entry into human cells can potentially prevent HIV infection. The antiviral lectin griffithsin has been identified as a highly potent inhibitor of HIV entry into human cells. Here we have explored the possibility to use transplastomic plants as an inexpensive production platform for griffithsin. We show that griffithsin accumulates in stably transformed tobacco chloroplasts to up to 5% of the total soluble protein of the plant. Griffithsin can be easily purified from leaf material and shows similarly high virus neutralization activity as griffithsin protein recombinantly expressed in bacteria. We also show that dried tobacco provides a storable source material for griffithsin purification, thus enabling quick scale-up of production on demand. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11103-018-0744-7) contains supplementary material, which is available to authorized users.


docid: tnupplfm

title: Genome sequence and origin analyses of the recombinant novel IBV virulent isolate SAIBK2

text: Recombination between infectious bronchitis viruses (IBVs), together with point mutations, insertions, and deletions, is thought to be responsible for the emergence of new IBV variants. SAIBK2 is a nephropathogenic strain isolated from layer flocks vaccinated with live attenuated H120 vaccine in Sichuan province, China in 2011. SAIBK2 causes severe kidney lesions and results in 50 % mortality in 30-day-old specific-pathogen-free chickens (with a dose of 10(5) EID(50)/0.1 mL SAIBK2 per chicken). The complete genome of SAIBK2 consists of 27669 nucleotides, excluding the poly-A tail at the 3′ end. SAIBK2 has the highest identity to YX10 in terms of complete genome. Phylogenetic analysis of complete sequence showed that SAIBK2 belongs to the most dominant genotype in China. Comparison and recombination analyses with other IBV strains revealed that SAIBK2 may originate from recombination events among a YX10-, a YN-, and a Mass-like strain. Furthermore, whole gene 5 and parts of nsp 3, nsp 4, nsp 16, and N genes are involved in the recombination events, and the uptake of these regions from YN and Mass strains by SAIBK2 may increase its replication efficiency and be responsible for its increased virulence in specific-pathogen-free chickens.


title: Promoter Variation in the DC-SIGN–Encoding Gene CD209 Is Associated with Tuberculosis

text: BACKGROUND: Tuberculosis, which is caused by Mycobacterium tuberculosis, remains one of the leading causes of mortality worldwide. The C-type lectin DC-SIGN is known to be the major M. tuberculosis receptor on human dendritic cells. We reasoned that if DC-SIGN interacts with M. tuberculosis, as well as with other pathogens, variation in this gene might have a broad range of influence in the pathogenesis of a number of infectious diseases, including tuberculosis. METHODS AND FINDINGS: We tested whether polymorphisms in CD209, the gene encoding DC-SIGN, are associated with susceptibility to tuberculosis through sequencing and genotyping analyses in a South African cohort. After exclusion of significant population stratification in our cohort, we observed an association between two CD209 promoter variants (−871G and −336A) and decreased risk of developing tuberculosis. By looking at the geographical distribution of these variants, we observed that their allelic combination is mainly confined to Eurasian populations. CONCLUSIONS: Our observations suggest that the two −871G and −336A variants confer protection against tuberculosis. In addition, the geographic distribution of these two alleles, together with their phylogenetic status, suggest that they may have increased in frequency in non-African populations as a result of host genetic adaptation to a longer history of exposure to tuberculosis. Further characterization of the biological consequences of DC-SIGN variation in tuberculosis will be crucial to better appreciate the role of this lectin in interactions between the host immune system and the tubercle bacillus as well as other pathogens.


title: A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin

text: The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health. Communicated by Ramaswamy H. Sarma


title: Current progress in CRISPR‐based diagnostic platforms

text: The CRISPR‐Cas system is a key technology for genome editing and regulation in a wide range of organisms and cell types. Recently, CRISPR‐Cas–based diagnostic platform has shown idealistic properties for pathogen detection. Integrating the CRISPR‐Cas platform along with lateral flow system allows rapid, sensitive, specific, cheap, and reliable diagnostic. It has the potential to be in frontline for not only pathogen detection during the epidemic outbreak, but also cancer, and genetic diseases.


Cytoplasmic Viruses: Rage against the (Cellular RNA Decay) Machine


title: Detection of Zika virus using reverse-transcription LAMP coupled with reverse dot blot analysis in saliva

text: In recent years, there have been increasing numbers of infectious disease outbreaks that spread rapidly to population centers resulting from global travel, population vulnerabilities, environmental factors, and ecological disasters such as floods and earthquakes. Some examples of the recent outbreaks are the Ebola epidemic in West Africa, Middle East respiratory syndrome coronavirus (MERS-Co) in the Middle East, and the Zika outbreak through the Americas. We have created a generic protocol for detection of pathogen RNA and/or DNA using loop-mediated isothermal amplification (LAMP) and reverse dot-blot for detection (RDB) and processed automatically in a microfluidic device. In particular, we describe how a microfluidic assay to detect HIV viral RNA was converted to detect Zika virus (ZIKV) RNA. We first optimized the RT-LAMP assay to detect ZIKV RNA using a benchtop isothermal amplification device. Then we implemented the assay in a microfluidic device that will allow analyzing 24 samples simultaneously and automatically from sample introduction to detection by RDB technique. Preliminary data using saliva samples spiked with ZIKV showed that our diagnostic system detects ZIKV RNA in saliva. These results will be validated in further experiments with well-characterized ZIKV human specimens of saliva. The described strategy and methodology to convert the HIV diagnostic assay and platform to a ZIKV RNA detection assay provides a model that can be readily utilized for detection of the next emerging or re-emerging infectious disease.


title: Identifying Small Molecules That Promote Quasipalindrome-Associated Template-Switch Mutations in Escherichia coli

text: DNA can assemble into non-B form structures that stall replication and cause genomic instability. One such secondary structure results from an inverted DNA repeat that can assemble into hairpin and cruciform structures during DNA replication. Quasipalindromes (QP), imperfect inverted repeats, are sites of mutational hotspots. Quasipalindrome-associated mutations (QPMs) occur through a template-switch mechanism in which the replicative polymerase stalls at a QP site and uses the nascent strand as a template instead of the correct template strand. This mutational event causes the QP to become a perfect or more perfect inverted repeat. Since it is not fully understood how template-switch events are stimulated or repressed, we designed a high-throughput screen to discover drugs that affect these events. QP reporters were engineered in the Escherichia coli lacZ gene to allow us to study template-switch events specifically. We tested 700 compounds from the NIH Clinical Collection through a disk diffusion assay and identified 11 positive hits. One of the hits was azidothymidine (zidovudine, AZT), a thymidine analog and DNA chain terminator. The other ten were found to be fluoroquinolone antibiotics, which induce DNA-protein crosslinks. This work shows that our screen is useful in identifying small molecules that affect quasipalindrome-associated template-switch mutations. We are currently assessing more small molecule libraries and applying this method to study other types of mutations.


title: The liver injury and gastrointestinal symptoms in patients with Coronavirus Disease 19: a systematic review and meta-analysis

text: Abstract Backgrounds: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. Our study aimed to evaluate the association of liver injury and gastrointestinal symptoms (GIS) with the progression of COVID-19. Methods: A comprehensive search was performed on the PubMed to identify eligible studies that summarized the liver injury and GIS in COVID-19. Results: A total of 21 studies with 3024 patients were included. Up to 53% patients had liver dysfunctions and the degree of liver damage was associated the severity of the disease. The prevalence of diarrhoea, nausea/vomiting or abdominal pain in patients with COVID-19 were 9.1%, 5.2% and 3.5%, respectively. No significant was found in the prevalence of diarrhoea (OR, 1.24; 95%CI, 0.90 to 1.72; I2 = 0%, p = 0.19) and nausea/vomiting (OR, 1.24; 95%CI, 0.57 to 2.69; I2 = 61%, p = 0.58) between severe and non-severe patients. In addition, diarrhoea (OR, 1.22; 95%CI, 0.50 to 2.98; I2 = 0%, p = 0.66) and nausea/vomiting (OR, 1.09; 95%CI, 0.46 to 2.62; I2 = 0%, p = 0.84) were not associated with the prognosis of COVID-19 patients. Conclusions: The incidences of GIS in patients with COVID-19 is relatively low and are not associated with the COVID-19 progression. Gastroenterologists should pay more attention to the liver injury induced by SARS-CoV-2 during the course of infection.


title: Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus

text: Abstract Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of 126-LQxxLxxxGL-135. In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export.


title: Implication of COVID‐19 in oral oncology practices in Brazil, Canada and the United States

text: The newly emerged Coronavirus disease 2019 (COVID‐19) is an infectious disease that has spread rapidly throughout the world. The most common signs and symptoms are fever, dry cough and shortness of breath which can progress to severe viral pneumonia and multi‐organ failure in susceptive patients (Chen et al. 2020, Wang et al. 2020). Droplet transmission and person‐person transmission appear to be the main route of transmission of COVID‐19, however asymptomatic patients are also carriers of the virus (Rothe et al. 2020).


title: Advances in Mast Cell Activation by IL-1 and IL-33 in Sjögren’s Syndrome: Promising Inhibitory Effect of IL-37

text: Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disease that affects primarily older women and is characterized by irreversible damage of the exocrine glands, including tear (xerophthalmia) and salivary glands (xerostomia). Secretory glands lose their functionality due to the infiltration of immune cells, which produce cytokines and cause inflammation. Primary SS is characterized by dry syndrome with or without systemic commitment in the absence of other pathologies. Secondary SS is accompanied by other autoimmune diseases with high activation of B lymphocytes and the production of autoantibodies, including the rheumatoid factor. Other cells, such as CD4(+) T cells and mast cells (MCs), participate in SS inflammation. MCs are ubiquitous, but are primarily located close to blood vessels and nerves and can be activated early in autoimmune diseases to express a wide variety of cytokines and chemokines. In the SS acute phase, MCs react by generating chemical mediators of inflammation, tumor necrosis factor (TNF), and other pro-inflammatory cytokines such as interleukin (IL)-1 and IL-33. IL-33 is the specific ligand for ST2 capable of inducing some adaptive immunity TH2 cytokines but also has pro-inflammatory properties. IL-33 causes impressive pathological changes and inflammatory cell infiltration. IL-1 family members can have paracrine and autocrine effects by exacerbating autoimmune inflammation. IL-37 is an IL-1 family cytokine that binds IL-18Rα receptor and/or Toll-like Receptor (TLR)4, exerting an anti-inflammatory action. IL-37 is a natural inhibitor of innate and acquired immunity, and the level is abnormal in patients with autoimmune disorders. After TLR ligand activation, IL-37 mRNA is generated in the cytoplasm, with the production of pro-IL-37 and later mature IL-37 caspase-1 mediated; both precursor and mature IL-37 are biologically active. Here, we discuss, for the first time, the current knowledge of IL-37 in autoimmune disease SS and propose a new therapeutic role.


title: Computational identification of biologically functional non-hairpin GC-helices in human Argonaute mRNA

text: BACKGROUND: Perfectly formed duplex elements in RNA occur within folding units, often as a part of hairpin motifs which can be reliably predicted by various RNA folding algorithms. Double helices with consecutive Watson-Crick base-pairing may also be formed between distant RNA segments thereby facilitating long-range interactions of long-chain RNA that may be biologically functional. Here we addressed the potential formation of RNA duplex motifs by long-range RNA-RNA interactions of distantly located matching sequence elements of a single long-chain RNA. RESULTS: We generated a Python-based software tool that identifies consecutive RNA duplex elements at any given length and nucleotide content formed by distant sequences. The software tool, dubbed RNAslider, is built on the theoretical RNA structure prediction algorithm Mfold. Source code and sample data sets are available on demand. We found that a small ratio of human genes including the Argonaute (Ago)-like gene family encode mRNAs containing highly GC-rich non-hairpin duplex elements (GC-helix) of equal to or more than 8 base pairs in length and we provide experimental evidence for their biological significance. CONCLUSION: GC-helices are observed preferentially within the 5(′)-region of mRNAs in an evolutionarily conserved fashion indicating their potential biological role. This view is supported experimentally by post-transcriptional regulation of gene expression of a fusion transcript containing 5(′)-sequences of human mRNA(Ago2) harbouring GC-helices and down-stream coding sequences of Renilla luciferase.


Diffuse cutaneous manifestation in a new mother with COVID‐19 (SARS‐Cov‐2)


title: Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study

text: Summary Background We previously showed that small interfering RNAs (siRNAs) targeting the Zaire Ebola virus (ZEBOV) RNA polymerase L protein formulated in stable nucleic acid-lipid particles (SNALPs) completely protected guineapigs when administered shortly after a lethal ZEBOV challenge. Although rodent models of ZEBOV infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. We therefore assessed the efficacy of modified non-immunostimulatory siRNAs in a uniformly lethal non-human primate model of ZEBOV haemorrhagic fever. Methods A combination of modified siRNAs targeting the ZEBOV L polymerase (EK-1 mod), viral protein (VP) 24 (VP24-1160 mod), and VP35 (VP35-855 mod) were formulated in SNALPs. A group of macaques (n=3) was given these pooled anti-ZEBOV siRNAs (2 mg/kg per dose, bolus intravenous infusion) after 30 min, and on days 1, 3, and 5 after challenge with ZEBOV. A second group of macaques (n=4) was given the pooled anti-ZEBOV siRNAs after 30 min, and on days 1, 2, 3, 4, 5, and 6 after challenge with ZEBOV. Findings Two (66%) of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected. The treatment regimen in the second study was well tolerated with minor changes in liver enzymes that might have been related to viral infection. Interpretation This complete postexposure protection against ZEBOV in non-human primates provides a model for the treatment of ZEBOV-induced haemorrhagic fever. These data show the potential of RNA interference as an effective postexposure treatment strategy for people infected with Ebola virus, and suggest that this strategy might also be useful for treatment of other emerging viral infections. Funding Defense Threat Reduction Agency.


title: High-resolution CT features of the COVID-19 infection in Nanchong City: Initial and follow-up changes among different clinical types

text: OBJECTIVE: To discuss the high resolution computed tomography (HRCT) manifestations of coronavirus disease 2019 (COVID-19) patients among different clinical types on initial and follow-up CT. METHODS: Seven COVID-19 patients admitted to the Affiliated Hospital of North Sichuan Medical Collage were enrolled. All patients underwent initial and follow-up chest HRCT. The main CT features and semi-quantitative score which represent disease severity among different clinical types were evaluated. RESULT: On initial CT, the main abnormalities observed in common and severe cases respectively were pure ground glass opacities (GGOs) and patchy consolidation surrounded by GGOs. Critical cases had multiple consolidation surrounded by wide range of GGOs distributed in the whole lung fields. The scope and density score in common (4.5 and 5), severe (9.5 and 9.5) and critical (19 and 12) cases were increased by gradient. On follow-up CT, common and severe types manifested as decreasing density of lesion, absorbed consolidation and GGOs. Critical cases showed progression of the disease. The extent and progression scores in common and severe patients were significantly decreased, while the range score of patients with critical disease reached the highest points, accompanied with an increase in the density score. CONCLUSION: CT scanning can accurately assess the severity of COVID-19, and help to monitor disease transformation during follow-up among different clinical conditions.


Perioperative planning in the COVID-19 pandemic: Cardiovascular perfusion and device-related issues.


title: Methods and approaches to disease mechanisms using systems kinomics

text: All cellular functions, ranging from regular cell maintenance and homeostasis, specialized functions specific to cellular types, or generating responses due to external stimulus, are mediated by proteins within the cell. Regulation of these proteins allows the cell to alter its behavior under different circumstances. A major mechanism of protein regulation is utilizing protein kinases and phosphatases; enzymes that catalyze the transfer of phosphates between substrates [1]. Proteins involved in phosphate signaling are well studied and include kinases and phosphatases that catalyze opposing reactions regulating both structure and function of the cell. Kinomics is the study of kinases, phosphatases and their targets, and has been used to study the functional changes in numerous diseases and infectious diseases with aims to delineate the cellular functions affected. Identifying the phosphate signaling pathways changed by certain diseases or infections can lead to novel therapeutic targets. However, a daunting 518 putative protein kinase genes have been identified [2], indicating that this protein family is very large and complex. Identifying which enzymes are specific to a particular disease can be a laborious task. In this review, we will provide information on large-scale systems biology methodologies that allow global screening of the kinome to more efficiently identify which kinase pathways are pertinent for further study.


title: Clinical presentation, diagnostic findings and outcome in dogs diagnosed withpresumptive spinal‐only meningoen‐cephalomyelitis of unknown origin

text: OBJECTIVES: To summarise clinical presentation, diagnostic findings and long‐term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone. METHODS: Medical records were reviewed for dogs diagnosed with presumptive spinal‐only meningoencephalomyelitis of unknown origin between 2006 and 2015. RESULTS: 21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T3‐L3 myelopathy, and spinal hyperaesthesia was a common finding (71%). A spinal cord lesion was visible in 90% of cases on magnetic resonance imaging. Eighteen lesions (86%) showed parenchymal contrast enhancement and 17 lesions (81%) showed contrast enhancement of overlying meninges. All dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. At time of data capture, 10/21 dogs (48%) had died or been euthanased because of the condition. Overall median survival time was 669 days. CLINICAL SIGNIFICANCE: Meningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. Magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. Overall, long‐term survival is guarded, approximately 50% of dogs will die or be euthanased despite appropriate therapy.


title: ‘Distancers’ and ‘non‐distancers’? The potential social psychological impact of moralizing COVID‐19 mitigating practices on sustained behaviour change

text: COVID‐19 mitigating practices such as ‘hand‐washing’, ‘social distancing’, or ‘social isolating’ are constructed as ‘moral imperatives’, required to avert harm to oneself and others. Adherence to COVID‐19 mitigating practices is presently high among the general public, and stringent lockdown measures supported by legal and policy intervention have facilitated this. In the coming months, however, as rules are being relaxed and individuals become less strict, and thus, the ambiguity in policy increases, the maintenance of recommended social distancing norms will rely on more informal social interactional processes. We argue that the moralization of these practices, twinned with relaxations of policy, may likely cause interactional tension between those individuals who do vs. those who do not uphold social distancing in the coming months: that is, derogation of those who adhere strictly to COVID‐19 mitigating practices and group polarization between ‘distancers’ and ‘non‐distancers’. In this paper, we explore how and why these processes might come to pass, their impact on an overall societal response to COVID‐19, and the need to factor such processes into decisions regarding how to lift restrictions.


title: Determinants of safety-focused product purchasing in the United States at the beginning of the global COVID-19 pandemic

text: Public preparation for the COVID-19 pandemic was widely covered in the media due to its intensity and fast-pace. While some individuals prepared with personal safety supplies such as soap and hand sanitizer, many others did not purchase such preparatory products. There are many health and safety benefits to quick engagement and emergency preparedness in a pandemic, and it is important to identify those who conduct these behaviors. The present study examined who engaged in preparatory purchasing of safety and health care products during the early stages of the spread of COVID-19 and what stimulated this action. Results of a cross-sectional study (N = 344) indicates that possessing, or uncertainty about possessing a COVID-19 risk factor (but not differences in age, gender, race, or income), increased purchasing of preparatory health and safety products. Also, in line with past research on risk, affect, and behavior, worry mediated this relationship. Further, gender moderated the relationship between worry and purchasing, such that worry increased product purchasing for men, who were initially low in worry, but not for women. This study lends additional support to worry as a mediator between risk and safety-related behavior and has implications for understanding factors related to preparatory purchasing of health care products during pandemics.


title: 22 Role of Dynein in Viral Pathogenesis

text: Publisher Summary This chapter describes the state of the art machineries that viruses use from viral infection (entry) to the end stage, when new, progeny virus particles disseminate from cells. The development of drugs that target dynein activities during viral replication rely on the disruption of characterized and specific interactions between viral proteins and dynein. Because viruses are parasitic in nature, great reason exists to fully understand the molecular mechanisms underlying host cell protein function and viruses’ dependence on these for additional rounds of infection. Some viral infections induce the assembly of stress granules, including reovirus and respiratory syncytial virus, but others block their assembly during infection. Considering this dependence on dynein activity for assembly, it is possible that viruses co-opt factors of the dynein motor complex during infection, but as a consequence either induce or silence stress granule assembly. This is an emerging field of endeavor, but stress granules and other silencing ribonucleoprotein bodies may represent “dangerous” areas and structures of the cell that viral replication complexes, proteins, and RNAs/DNAs would need to avoid guaranteeing expression and survival. There is research support for the presence of both dynein and kinesin motors driving viral components toward assembly sites. Several viruses, including poxviruses and the vaccinia virus, replicate in cytoplasmic virus factories. Paradoxically, regulatory genes of various viruses enhance and disrupt microtubule integrity and polarization, but this may directly relate to the timing of the replication cycle. This is an area yet to be explored.


title: Protecting health workers from infectious disease transmission: an exploration of a Canadian-South African partnership of partnerships

text: BACKGROUND: Health workers are at high risk of acquiring infectious diseases at work, especially in low and middle-income countries (LMIC) with critical health human resource deficiencies and limited implementation of occupational health and infection control measures. Amidst increasing interest in international partnerships to address such issues, how best to develop such collaborations is being actively debated. In 2006, a partnership developed between occupational health and infection control experts in Canada and institutions in South Africa (including an institute with a national mandate to conduct research and provide guidance to protect health workers from infectious diseases and promote improved working conditions). This article describes the collaboration, analyzes the determinants of success and shares lessons learned. METHODS: Synthesizing participant-observer experience from over 9 years of collaboration and 10 studies already published from this work, we applied a realist review analysis to describe the various achievements at global, national, provincial and hospital levels. Expectations of the various parties on developing new insights, providing training, and addressing service needs were examined through a micro-meso-macro lens, focusing on how each main partner organization contributed to and benefitted from working together. RESULTS: A state-of-the-art occupational health and safety surveillance program was established in South Africa following successful technology transfer from a similar undertaking in Canada and training was conducted that synergistically benefitted Northern as well as Southern trainees. Integrated policies combining infection control and occupational health to prevent and control infectious disease transmission among health workers were also launched. Having a national (South-South) network reinforced by the international (North–south) partnership was pivotal in mitigating the challenges that emerged. CONCLUSIONS: High-income country partnerships with experience in health system strengthening – particularly in much needed areas such as occupational health and infection control – can effectively work through strong collaborators in the Global South to build capacity. Partnerships are particularly well positioned to sustainably reinforce efforts at national and sub-national LMIC levels when they adopt a “communities of practice” model, characterized by multi-directional learning. The principles of effective collaboration learned in this “partnership of partnerships” to improve working conditions for health workers can be applied to other areas where health system strengthening is needed.


title: How long does Coronavirus survive on different surfaces?

text: Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices


Ontario issues final SARS Commission report


title: Ribosomal frameshifting used in influenza A virus expression occurs within the sequence UCC_UUU_CGU and is in the +1 direction

text: Programmed ribosomal frameshifting is used in the expression of many virus genes and some cellular genes. In eukaryotic systems, the most well-characterized mechanism involves –1 tandem tRNA slippage on an X_XXY_YYZ motif. By contrast, the mechanisms involved in programmed +1 (or −2) slippage are more varied and often poorly characterized. Recently, a novel gene, PA-X, was discovered in influenza A virus and found to be expressed via a shift to the +1 reading frame. Here, we identify, by mass spectrometric analysis, both the site (UCC_UUU_CGU) and direction (+1) of the frameshifting that is involved in PA-X expression. Related sites are identified in other virus genes that have previously been proposed to be expressed via +1 frameshifting. As these viruses infect insects (chronic bee paralysis virus), plants (fijiviruses and amalgamaviruses) and vertebrates (influenza A virus), such motifs may form a new class of +1 frameshift-inducing sequences that are active in diverse eukaryotes.


title: Comparison of Clinical Characteristics of Patients with Asymptomatic vs Symptomatic Coronavirus Disease 2019 in Wuhan, China

text: This case series examines clinical characteristics of patients with asymptomatic vs symptomatic coronavirus disease 2019 in Wuhan, China.


title: The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea

text: BACKGROUND AND AIMS: Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity. METHODS: To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2–12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing. RESULTS AND CONCLUSIONS: In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor.


title: Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6, IL-6 receptor and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome. TRIAL DESIGN: A phase 3 prospective, multi-center, interventional, open label, 6-arm 2x2 factorial design study. PARTICIPANTS: Subjects will be recruited at the specialized COVID-19 wards and/or ICUs at 16 Belgian participating hospitals. Only adult (≥18y old) patients will be recruited with recent (≤16 days) COVID-19 infection and acute hypoxia (defined as PaO2/FiO2 below 350mmHg or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation) and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those, who have not been on mechanical ventilation for more than 24 hours before randomisation. Patients should have had a chest X-ray and/or CT scan showing bilateral infiltrates within the last 2 days before randomisation. Patients with active bacterial or fungal infection will be excluded. INTERVENTION AND COMPARATOR: Patients will be randomized to 1 of 5 experimental arms versus usual care. The experimental arms consist of Anakinra alone (anti-IL-1 binding the IL-1 receptor), Siltuximab alone (anti-IL-6 chimeric antibody), a combination of Siltuximab and Anakinra, Tocilizumab alone (humanised anti-IL-6 receptor antibody) or a combination of Anakinra with Tocilizumab in addition to standard care. Patients treated with Anakinra will receive a daily subcutaneous injection of 100mg for a maximum of 28 days or until hospital discharge, whichever comes first. Siltuximab (11mg/kg) or Tocilizumab (8mg/kg, with a maximum dose of 800mg) are administered as a single intravenous injection immediately after randomization. MAIN OUTCOMES: The primary end point is the time to clinical improvement defined as the time from randomization to either an improvement of two points on a six-category ordinal scale measured daily till day 28 or discharge from the hospital or death. This ordinal scale is composed of (1) Death; (2) Hospitalized, on invasive mechanical ventilation or ECMO; (3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, not requiring supplemental oxygen; (6) Not hospitalized. RANDOMISATION: Patients will be randomized using an Interactive Web Response System (REDCap). A 2x2 factorial design was selected with a 2:1 randomization regarding the IL-1 blockade (Anakinra) and a 1:2 randomization regarding the IL-6 blockade (Siltuximab and Tocilizumab). BLINDING (MASKING): In this open-label trial neither participants, caregivers, nor those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 342 participants will be enrolled: 76 patients will receive usual care, 76 patients will receive Siltuximab alone, 76 patients will receive Tocilizumab alone, 38 will receive Anakinra alone, 38 patients will receive Anakinra and Siltuximab and 38 patients will receive Anakinra and Tocilizumab. TRIAL STATUS: COV-AID protocol version 3.0 (15 Apr 2020). Participant recruitment is ongoing and started on April 4(th) 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 1st, 2020 (ClinicalTrials.gov Identifier: NCT04330638) and on EudraCT on April 3rd 2020 (Identifier: 2020-001500-41). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


title: Aetiology of neonatal conjunctivitis evaluated in a population‐based setting

text: AIM: Our aim was to study prospectively the aetiology of neonatal conjunctivitis in a population‐based setting. METHODS: Altogether 173 neonates with clinical conjunctivitis aged on average 20 (SD 10) days were recruited from child welfare clinics in Oulu, Finland, in 2010–2015. Conjunctival specimens were collected from 167 neonates for multiplex polymerase chain reaction to detect 16 respiratory viruses, from 163 for polymerase chain reaction to detect Chlamydia trachomatis and Neisseria gonorrhoeae and from 160 for bacterial culture studies. The cases were followed up until the age of 18 months. RESULTS: Viral conjunctivitis was diagnosed in 8/167 (4.8%; 95% CI 2.1–9.2%), chlamydial or gonococcal conjunctivitis in 0/163 cases (0%; 95% CI 0–2.2%) and other bacterial conjunctivitis in 58/160 (36%; 95% CI 29–44%). Rhinovirus was found at the ocular site in 4/167 (2.4%) neonates, adenovirus in 3/167 (1.8%) and bocavirus in 1/167 (0.6%). The most commonly isolated bacteria included Staphylococcus aureus (16%), Moraxella catarrhalis (9.4%) and Streptococcus pneumoniae (3.1%). None of these pathogens was associated with the 4/173 (2.3%) cases later operated on for persistent nasolacrimal duct obstruction. CONCLUSION: Chlamydia trachomatis was a rare pathogen in neonatal conjunctivitis in a population‐based setting, but respiratory viruses were detected more frequently than indicated earlier.


title: Localisation and distribution of O-acetylated N-acetylneuraminic acids, the endogenous substrates of the hemagglutinin-esterases of murine coronaviruses, in mouse tissue

text: Infections by mouse hepatitis viruses result in disease of the liver, the gastrointestinal tract, respiratory tract, and the central nervous system. Coronaviruses related to mouse hepatitis virus express a hemagglutinin-esterase surface glycoprotein, which specifically hydrolyses either 5-N-acetyl-4-O-acetyl neuraminic acid (Neu4,5Ac(2)) or 5-N-acetyl-9-O-acetyl neuraminic acid (Neu5,9Ac(2)). Moreover, these sialic acids represent potential cellular receptor determinants for murine coronaviruses. Until now, the distribution of these sialic acids in mouse brain was not thoroughly investigated. Particularly Neu4,5Ac(2) was not yet found in mouse brain. Using a sensitive method of gas chromatography coupled to mass spectrometry in the electron impact mode of ionization this manuscript demonstrates the occurrence of 13 different sialic acids varying in their alkyl and acyl substituents in mouse tissues including 5-N-acetyl-4-O-acetyl-9-O-lactyl-neuraminic acid (Neu4,5Ac(2)9Lt), 5-N-acetyl-9-O-lactyl-neuraminic acid (Neu5Ac9Lt), 5-N-acetyl-8-O-methyl-neuraminic acid (Neu5Ac8Me) and the 1,7-lactone (Neu5Ac1,7L) of neuraminic acid. Neu4,5Ac(2), relatively abundant in the gut, was present as a minor compound in all tissues, including liver, olfactory lobe, telencephalon, metencephalon and hippocampus. Neu5,9Ac(2) was also found in these tissues, except in the liver. It is suggested that these sialic acids represent the endogenous substrate and receptor determinants for murine coronaviruses.


title: Both ADP-Ribosyl-Binding and Hydrolase Activities of the Alphavirus nsP3 Macrodomain Affect Neurovirulence in Mice

text: Macrodomain (MD), a highly conserved protein fold present in a subset of plus-strand RNA viruses, binds to and hydrolyzes ADP-ribose (ADPr) from ADP-ribosylated proteins. ADPr-binding by the alphavirus nonstructural protein 3 (nsP3) MD is necessary for the initiation of virus replication in neural cells, whereas hydrolase activity facilitates replication complex amplification. To determine the importance of these activities for pathogenesis of alphavirus encephalomyelitis, mutations were introduced into the nsP3 MD of Sindbis virus (SINV), and the effects on ADPr binding and hydrolase activities, virus replication, immune responses, and disease were assessed. Elimination of ADPr-binding and hydrolase activities (G32E) severely impaired in vitro replication of SINV in neural cells and in vivo replication in the central nervous systems of 2-week-old mice with reversion to wild type (WT) (G) or selection of a less compromising change (S) during replication. SINVs with decreased binding and hydrolase activities (G32S and G32A) or with hydrolase deficiency combined with better ADPr-binding (Y114A) were less virulent than WT virus. Compared to the WT, the G32S virus replicated less well in both the brain and spinal cord, induced similar innate responses, and caused less severe disease with full recovery of survivors, whereas the Y114A virus replicated well, induced higher expression of interferon-stimulated and NF-κB-induced genes, and was cleared more slowly from the spinal cord with persistent paralysis in survivors. Therefore, MD function was important for neural cell replication both in vitro and in vivo and determined the outcome from alphavirus encephalomyelitis in mice.


Are Surgeons in India prepared for COVID−19?


docid: wrmfxkoa

title: Viral Metagenomics Revealed Sendai Virus and Coronavirus Infection of Malayan Pangolins (Manis javanica)

text: Pangolins are endangered animals in urgent need of protection. Identifying and cataloguing the viruses carried by pangolins is a logical approach to evaluate the range of potential pathogens and help with conservation. This study provides insight into viral communities of Malayan Pangolins (Manis javanica) as well as the molecular epidemiology of dominant pathogenic viruses between Malayan Pangolin and other hosts. A total of 62,508 de novo assembled contigs were constructed, and a BLAST search revealed 3600 ones (≥300 nt) were related to viral sequences, of which 68 contigs had a high level of sequence similarity to known viruses, while dominant viruses were the Sendai virus and Coronavirus. This is the first report on the viral diversity of pangolins, expanding our understanding of the virome in endangered species, and providing insight into the overall diversity of viruses that may be capable of directly or indirectly crossing over into other mammals.


title: Recombinant Chimeric Transmissible Gastroenteritis Virus (TGEV)—Porcine Epidemic Diarrhea Virus (PEDV) Virus Provides Protection against Virulent PEDV

text: Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus causing high morbidity and mortality in porcine herds worldwide. Although both inactivated and live attenuated vaccines have been extensively used, the emergence of highly virulent strains and the recurrent outbreaks even in vaccinated farms highlight the need of effective vaccines. Engineering of genetically defined live attenuated vaccines is a rational approach for novel vaccine development. In this line, we engineered an attenuated virus based on the transmissible gastroenteritis virus (TGEV) genome, expressing a chimeric spike protein from a virulent United States (US) PEDV strain. This virus (rTGEV-RS-SPEDV) was attenuated in highly-sensitive five-day-old piglets, as infected animals did not lose weight and none of them died. In addition, the virus caused very minor tissue damage compared with a virulent virus. The rTGEV-RS-SPEDV vaccine candidate was also attenuated in three-week-old animals that were used to evaluate the protection conferred by this virus, compared with the protection induced by infection with a virulent PEDV US strain (PEDV-NVSL). The rTGEV-RS-SPEDV virus protected against challenge with a virulent PEDV strain, reducing challenge virus titers in jejunum and leading to undetectable challenge virus RNA levels in feces. The rTGEV-RS-SPEDV virus induced a humoral immune response specific for PEDV, including neutralizing antibodies. Altogether, the data indicated that rTGEV-RS-SPEDV is a promising vaccine candidate against virulent PEDV infection.


title: Measures to Limit COVID-19 Outbreak Effects Among Military Personnel: Preliminary Data

text: INTRODUCTION: The COVID-19 outbreak posed a threat to the readiness of military forces as well as their ability to fulfill missions. Seeing that military forces have been encountering similar challenges, we found it eminent to share the Israeli Defense Force (IDF) Northern Command’s (NC) preliminary experience. MATERIALS AND METHODS: We retrospectively summarized the actions that were taken by our team, focusing on 18 battalions at the Israeli NC. These actions included promoting a series of organizational changes in terms of social distancing and medical regulations as well as working to strengthen medical leadership through designated video meetings with medical commanders across our organization. Meetings included relevant clinical education, updates, and leadership building. These actions and others were aimed to increase our influence on the decision-making processes. While we conducted real-time reverse transcriptase polymerase chain reaction SARS-CoV-2 laboratory tests for soldiers who were suspected to have COVID-19 (those presenting with compatible signs and symptoms after having been exposed to a confirmed COVID-19 patient), we were not able to screen healthy populations, nor did we have serum antibody serologic tests available during the study period. We reviewed the COVID-19 outbreak national data, obtained from Ministry of Health publishings and the IDF databases. Data were included from February 26th, 2020 (day 0, first COVID-19 patient in Israel) to April 19th, 2020 (day 53, about 1 month after most of the COVID-19 regulation were issued in the NC). RESULTS: The mean age of the battalion soldiers was 21.29 ± 4.06 (range 18–50), 81.34% male. Most restrictions were issued on day 18. On day 53, 98.85% of the personnel in the battalions were kept active and asymptomatic in their units. CONCLUSIONS: Despite the limited availability of laboratory testing for COVID-19 our actions enabled us to lead a strict risk-management policy while maintaining most of the available workforce.


title: Proposed Modifications in the 6-Minute Walk Test for Potential Application in Patients With Mild COVID-19: A Step to Optimize Triage Guidelines

text: Supplemental Digital Content is available in the text.


title: The effects of COVID-19 pandemic on the provision of urgent surgery: a perspective from the USA

text: Corona virus pandemic has affected all the 50 states in the USA. States such as NY, CA and WA being the most affected. According to the Centers for Disease Control and Prevention (CDC) website, as of 28 March 2020, the total number of cases in the USA is over 103 300 and number of deaths to 1668. In the coming weeks, COVID-19 rates are expected to begin skyrocketing and hit a peak in late April/May/June given lessons learned from China, Italy and others. COVID-19 has been declared a pandemic by the World Health Organization (WHO) as confirmed cases approach 575 444 patients with 26 654 deaths across over 160 countries, as of 28 March 2020. There is a lot of impact on management of the urgent and emergent cases. This article highlights the changes that are being made in delivering urgent and emergent surgical care during the pandemic.


title: Impact of TGEV infection on the pig small intestine

text: BACKGROUND: Pig diarrhea causes high mortality and large economic losses in the swine industry. Transmissible gastroenteritis virus (TGEV) causes pig diarrhea, with 100% mortality in piglets less than 2 weeks old. No investigation has yet been made of the small intestine of piglets that survived infection by TGEV. METHODS: In this study, we evaluated the impact of TGEV infection on the small intestine of recovered pigs. RESULTS: Histological analyses showed that TGEV infection led to villi atrophy, and reduced villous height and crypt depth. The number of SIgA positive cells, CD3(+)T cells, and dendritic cells (DCs) in jejunum decreased after TGEV infection in vivo. In contrast, microfold cell (M cell) numbers and cell proliferation increased in infected pigs. TGEV infection also significantly enhanced the mRNA expression levels of cytokine IL-1β, IL-6, TNF-α, IL-10, and TGF-β. Additionally, lower gene copy numbers of Lactobacillus, and higher numbers of Enterobacteriaceae, were detected in mucosal scraping samples from TGEV-infected pigs. CONCLUSIONS: TGEV infection damages the small intestine, impairs immune functions, and increases pathogenic bacterial loading, all of which may facilitate secondary infections by other pathogens. These findings help quantify the impact of TGEV infection and clarify the pathogenic mechanisms underlying its effects in pigs.


title: ESMO Management and treatment adapted recommendations in the COVID-19 era: Breast Cancer

text: The global preparedness and response to the rapid escalation to severe acute respiratory syndrome coronavirus (SARS-CoV)-2-related disease (COVID-19) to a pandemic proportion has demanded the formulation of a reliable, useful and evidence-based mechanism for health services prioritisation, to achieve the highest quality standards of care to all patients. The prioritisation of high value cancer interventions must be embedded in the agenda for the pandemic response, ensuring that no inconsistency or discrepancy emerge in the health planning processes. The aim of this work is to organise health interventions for breast cancer management and research in a tiered framework (high, medium, low value), formulating a scheme of prioritisation per clinical cogency and intrinsic value or magnitude of benefit. The public health tools and schemes for priority setting in oncology have been used as models, aspiring to capture clinical urgency, value in healthcare, community goals and fairness, while respecting the principles of benevolence, non-maleficence, autonomy and justice. We discuss the priority health interventions across the cancer continuum, giving a perspective on the role and meaning to maintain some services (undeferrable) while temporarily abrogate some others (deferrable). Considerations for implementation and the essential link to pre-existing health services, especially primary healthcare, are addressed, outlining a framework for the development of effective and functional services, such as telemedicine. The discussion covers the theme of health systems strategising, and why oncology care, in particular breast cancer care, should be maintained in parallel to pandemic control measures, providing a pragmatic clinical model within the broader context of public healthcare schemes.


title: Passive Immunotherapy: Assessment of Convalescent Serum Against Ebola Virus Makona Infection in Nonhuman Primates

text: Background. Convalescent serum and blood were used to treat patients during outbreaks of Zaire ebolavirus (ZEBOV) infection in 1976 and 1995, with inconclusive results. During the recent 2013–2016 West African epidemic, serum/plasma from survivors of ZEBOV infection was used to treat patients in the affected countries and several repatriated patients. The effectiveness of this strategy remains unknown. Methods. Nine rhesus monkeys were experimentally infected with ZEBOV-Makona. Beginning on day 3 after exposure (at the onset of viremia), 4 animals were treated with homologous ZEBOV-Makona convalescent macaque sera, 3 animals were treated in parallel with heterologous Sudan ebolavirus (SEBOV) convalescent macaque sera, and 2 animals served as positive controls and were not treated. Surviving animals received additional treatments on days 6 and 9. Results. Both untreated control animals died on postinfection day 9. All 4 ZEBOV-Makona–infected macaques treated with homologous ZEBOV-Makona convalescent sera died on days 8–9. One macaque treated with heterologous SEBOV convalescent sera survived, while the other animals treated with the heterologous SEBOV sera died on days 7 and 9. Conclusions. The findings suggest that convalescent sera alone is not sufficient for providing 100% protection against lethal ZEBOV infection when administered at the onset of viremia.


docid: ohwrcavm

title: Cardiac Valves: Another “Disaster-Hit Area” of COVID-19 Patients?


docid: xjmicuki

title: Whole-genome based Archaea phylogeny and taxonomy: A composition vector approach

text: The newly proposed alignment-free and parameter-free composition vector (CVtree) method has been successfully applied to infer phylogenetic relationship of viruses, chloroplasts, bacteria, and fungi from their whole-genome data. In this study we pay special attention to the phylogenetic positions of 56 Archaea genomes among which 7 species have not been listed either in Bergey’s Manual of Systematic Bacteriology or in Taxonomic Outline of Bacteria and Archaea (TOBA). By inspecting the stable monophyletic branchings in CVTrees reconstructed from a total of 861 genomes (56 Archaea plus 797 Bacteria, using 8 Eukarya as outgroups) definite taxonomic assignments were proposed for these not-fully-classified species. Further development of Archaea taxonomy may verify the predicted phylogenetic results of the CVTree approach.


title: An APN-activated NIR photosensitizer for cancer photodynamic therapy and fluorescence imaging

text: Abstract Photodynamic therapy has been developed as a prospective cancer treatment in recent years. Nevertheless, conventional photosensitizers suffer from lacking recognition and specificity to tumors, which causing severe side effects to normal tissues, while the enzyme-activated photosensitizers are capable of solving these conundrums due to high selectivity towards tumors. APN (Aminopeptidase N, APN/CD13), a tumor marker, has become a crucial targeting substance owing to its highly expressed on the cell membrane surface in various tumors, which has become a key point in the research of anti-tumor drug and fluorescence probe. Based on it, herein an APN-activated near-infrared (NIR) photosensitizer (APN-CyI) for tumor imaging and photodynamic therapy has been firstly developed and successfully applied in vitro and in vivo. Studies showed that APN-CyI could be activated by APN in tumor cells, hydrolyzed to fluorescent CyI-OH, which specifically located in mitochondria in cancer cells and exhibited a high singlet oxygen yield under NIR irradiation, and efficiently induced cancer cell apoptosis. Dramatically, the in vivo assays on Balb/c mice showed that APN-CyI could achieve NIR fluorescence imaging (λem = 717 nm) for endogenous APN in tumors and possessed an efficient tumor suppression effect under NIR irradiation.


title: Le diagnostic rapide des infections à virus respiratoire syncytial (RS) par le titrage des IgM sériques (immunofluorescence indirecte)

text: Summary In January 1981, during an outbreak of respiratory diseases in babies aged between 1 and 3 months, 9 patients with severe bronchiolitis were hospitalized in a Pediatric ward and 11 cases occurred as nosocomial infections. For direct rapid diagnosis, pharyngeal swabs and nasal aspirations were obtained from 10 out of 11 patients at a late stage of the disease. The rapid detection of respiratory syncytial (RS) antigen was positive in only 2 cases and the virus isolation unsuccessful. For serological diagnosis, in 9 out of 16 cases, the “first” serum was collected 5 days or more after the onset of the disease. The indirect immunofluorescence (IF) test allowed us to make the diagnosis in 13/16 cases, while the complement fixation (CF) test remained negative. From November 1980 to January 1981, sera were collected from 32 children aged 2 to 14 years and 13 adults hospitalized for acute respiratory disease (bronchitis, bronchopneumopathis) and 35 adults (kidney grafted) submitted to a systematic survey. The indirect IF test was not found to be more sensitive than the CF test but it enabled us: o 1) to differenciate the primary infections from the reinfections; 2) to show detectable IgM in 11/17 cases of reinfections; 3) to make a rapid diagnosis of RS infection in 60% of the cases on a single serum while the CF test gave either a negative result (1 case) or only presumptive results (10 cases).


title: Identification of the membrane protein of porcine epidemic diarrhea virus

text: Sequence information on the genome of porcine epidemic diarrhea virus (PEDV) has only recently been determined. In contrast, very little is known about the viral proteins. In the present report we have identified the membrane glycoprotein (M) of PEDV by use of rabbit anti-peptide sera and transient expression of the cloned M gene in Vero cells and by expression in the baculovirus system. The native M protein of PEDV is incorporated into virions, is N-glycosylated, and migrates with a relative mobility (Mr) of 27 k in polyacrylamide gels. In contrast, the M protein synthesized by recombinant baculoviruses migrates with a Mr of 23 k, that is, with identical mobility as the deglycosylated product of PEDV. Thus, it appears that M protein specified by the recombinant baculovirus is poorly, if at all, glycosylated. Using monoclonal antibodies and rabbit antipeptide sera specific for the N and C termini of the M protein, we were able to show that a 19 k band detected in PEDV-infected cells but not in virions represented a fragment of M from which the C terminus had been cleaved off. Finally, by electron microscopy and immunogold labelling, the relative orientation of M within the virion envelope was determined as NexoCcyt. In conclusion, all of these data strongly support the hypothesis that PEDV should be classified with the group I coronaviruses.


title: Potentially preventable urinary tract infection in patients with type 2 diabetes – A hospital-based study

text: Abstract Aim To investigate the prevalence of urinary tract infections in hospitalized patients with type 2 diabetes mellitus and identify corresponding risk factors. Methods We conducted a cross-sectional study on 7.347 patients with type 2 diabetes mellitus as the principal diagnosis, using hospitalization discharge summary data from January 1 to December 31, 2015. Disease stages were classified as stages 1, 2, and 3. Results Of 7.347 patients, 16.2% had urinary tract infections. The urinary tract infection prevalence was 24.4% in 428 patients in stage 1 and 4.8% in 2.840 patients in stage 2; it was higher among patients who underwent medical procedures than among those who underwent surgery (24.4% vs 4.8%). In multivariate regression analysis, age (OR = 1.031; 95% CI = 1.02–1.04), length of hospitalization (OR = 1.018; 95% CI = 1.013–1.024), sex (woman) (OR = 2.248; 95% CI = 1.778–2.842), comorbidity of stage 3 cerebrovascular disease (OR = 1.737; 95% CI = 1.111–2.714), and comorbidity of stage 1 colorectal cancer (OR = 2.417; 95% CI = 1.152–5.074) were found to be the risk factors of urinary tract infection in the ten hospitals considered. Conclusions Our findings suggest that urinary tract infection prevalence was higher in women without evidence of organ injury and those receiving medical treatment. Comorbidities (cerebrovascular disease and colorectal cancer) were identified as risk factors.


COVID‐19 and sports medicine research


title: Detection of adenoviruses in faeces and the confirmation of isolates by latex agglutination

text: Abstract An adenovirus (AV) group-specific latex agglutination test (LA) was assessed for its ability to detect AVs in faeces and to confirm the isolation of AVs in cell culture. It detected all of 62 strains belonging to subgenus F (AdF) but only 4 40 non-AdF serotypes. This is possibly due to the concentration of AdF strains in faeces being greater than non-AdF strains. No false positive reactions were found with 55 AV-negative faeces, 42 of which contained other viruses frequently found in faeces. Only one of the 157 specimens examined gave a non-specific reaction, i.e. test and control latexes both agglutinated. All of 14 AV isolates but none of the 12 isolates of other viruses were LA positive. It is concluded that LA would be useful for detecting AdF strain in faeces and for confirmation of AV isolates, especially if electron microscopic facilities were not available.