The consequences of the COVID‐19 pandemic for self‐care in patients supported with a Left Ventricular Assist Device


Science news top 25


title: The Response in Air Quality to the Reduction of Chinese Economic Activities during the COVID‐19 Outbreak

text: During the COVID‐19 outbreak that took place in early 2020, the economic activities in China were drastically reduced and accompanied by a strong reduction in the emission of primary air pollutants. On the basis of measurements made at the monitoring stations operated by the China National Environmental Monitoring Center, we quantify the reduction in surface PM(2.5), NO(2), CO and SO(2) concentrations in northern China during the lockdown, which started on 23 January 2020. We find that, on the average, the levels of surface PM(2.5) and NO(2) have decreased by approximately 35 and 60 percent, respectively, between the period 1‐22 January 2020 and the period 23 January‐29 February 2020. At the same time, the mean ozone concentration has increased by a factor 1.5–2. In urban area of Wuhan, where drastic measures were adopted to limit the spread of the coronavirus, similar changes in the concentrations of PM(2.5), NO(2) and ozone are found.


Violence against women, children, and adolescents during the COVID-19 pandemic: overview, contributing factors, and mitigating measures.


title: Current Situation and Perspectives of Clinical Study in Integrative Medicine in China

text: Integrative medicine is not only an innovative China model in clinical practice, but also the bridge for TCM toward the world. In the past thirty years, great achievements have been made in integrative medicine researches, especially in clinical practice. The clinical achievements mainly include the following three: innovating methodology of disease-syndrome combination, excavating the classical theory in traditional Chinese medicine (TCM), preventing and curing refractory diseases. The development ideas and strategies of integrative medicine for future mainly include (a) standing on frontier field of international medicine and improving the capability of preventing and curing refractory diseases; (b) moving prevention and control strategy forward and improving the curative effect of common and frequent disease; (c) excavating the classical theory of TCM and broadening the treatment system of modern medicine; (d) improving the innovation level of new high effective drugs on the basis of classical prescriptions and herbs in TCM; (e) rerecognizing the theory of formula corresponding to syndrome in TCM and enhancing the level of clinical research evidence based on evidence-based medicine. Integrative medicine will do obtain greater achievements in creating new medicine and pharmacology and make more tremendous contributions for the great rejuvenation of the Chinese nation and human health care.


title: Psychological impact of healthcare workers in China during COVID-19 pneumonia epidemic: a multi-center cross-sectional survey investigation

text: BACKGROUND: : Since the outbreak of 2019 new coronavirus (COVID-19) pneumonia, healthcare workers (HCW) have suffered psychological stress. The present study is to examine the prevalence of stress, anxiety and depression of HCW in China during the COVID-19 epidemic, and to determine the risk factors predicting psychological morbidities that can be used as psychological intervention targets. METHODS: : A cross-sectional survey was conducted to investigate the psychological levels of HCW in multiple centers in China. The prevalence of stress, anxiety and depression were determined by using Perceived Stress Scale (PSS-14) and Hospital Anxiety / Depression scale (HAD). Psychology related factors were evaluated and correlation between job title and contact history was analyzed. RESULTS: : We received 958 of effective responses, 73.6% of which were from Wuhan and 67.2% were female participants. 55.1% of respondents had psychological stress that is higher than that of HCW during SARS. 54.2% and 58% of participants had symptoms of anxiety and depression. Stress levels of HCW were different in job titles and years of work experience. Anxiety and depression levels were different between different gender, job titles, degrees of protective measures and levels of contact history. Gender, intermediate title, protective measures and contact history were the independent risk factors for anxiety. Protective measures and contact history were the independent risk factors for depression. CONCLUSIONS: : The COVID-19 epidemic has induced stress levels for HCW, and high percentages of HCW have anxiety and depression. The situation of HCW is worrying and intervention service is urgent.


title: Unpacking the black box: How to promote citizen engagement through government social media during the COVID-19 crisis

text: Abstract During times of public crises, governments must act swiftly to communicate crisis information effectively and efficiently to members of the public; failure to do so will inevitably lead citizens to become fearful, uncertain and anxious in the prevailing conditions. This pioneering study systematically investigates how Chinese central government agencies used social media to promote citizen engagement during the COVID-19 crisis. Using data scraped from ‘Healthy China’, an official Sina Weibo account of the National Health Commission of China, we examine how citizen engagement relates to a series of theoretically relevant factors, including media richness, dialogic loop, content type and emotional valence. Results show that media richness negatively predicts citizen engagement through government social media, but dialogic loop facilitates engagement. Information relating to the latest news about the crisis and the government's handling of the event positively affects citizen engagement through government social media. Importantly, all relationships were contingent upon the emotional valence of each Weibo post.


title: Orthopedic healthcare in the time of COVID-19: Experience of the orthopedic surgery department at Mustapha Bacha Hospital, Algeria

text: In response to the global health emergency, which has been raised to its highest level as a consequence of the coronavirus disease 2019 (COVID-19), urgent and aggressive actions were taken by health institutions across the world to stop the spread of the disease while ensuring continuity of vital care. This article outlines the urgent measures put in place by the orthopedic surgery department at Mustapha Bacha Hospital in response to the COVID-19 pandemic.


title: The Potential Impacts of Pandemic Policing on Police Legitimacy: Planning Past the COVID-19 Crisis

text: One of the biggest challenges facing modern policing in recent years has been the lack of police legitimacy. The tipping point of this phenomenon is often attributed to the Rodney King incident in Los Angeles in 1991, where Los Angeles Police Department (LAPD) officers were videoed assaulting a lone black male. They were arrested and charged but eventually all were acquitted, thereby etching deep distrust between communities and police. Now the Rodney King example is an extreme and criminal act by police but it was the beginning of communities and media focusing on what the police were doing and how they were doing it. This lack of legitimacy coupled with what is referred to as the militarization of policing have lasting consequences and impacts on police–community relations and how interactions between police and community shape society today. In the wake of pandemic policing due to COVID-19, there are tales of two eventualities for police legitimacy that will be explored in this article: (1) The police response to the pandemic results in further militarization and draws deeper divides between police and communities or (2) the police response is compassionate and build on procedurally just operations resulting in the rebuilding of police legitimacy post-pandemic.


title: Hygienic and ecological risks connected with utilization of animal manures and biosolids in agriculture

text: Abstract In recent years the fate of human and animal pathogen microorganisms as a potential pollutant of the environment has been paid increased attention. Substantial quantities of these compounds and their metabolites are excreted, flushed down the drain, discarded as waste, or left over in animal feedlots. After passing to the sewer, several of these compounds are not adequately eliminated by the methods that are currently used in sewage treatment. Substantial quantities of biosolids and livestock manure end up on agricultural land. Effective sanitation of the environment, particularly of some of its special parts, which can be a source of spreading of diseases, plays an important role in prevention of infectious diseases. In this respect special attention should be paid to the disinfection of infected farm animal excrements. Sanitation of excrements should, on the one hand, ensure effective inhibition of infectious agents and, on the other hand, comply with the requirement of preserving the composition of the manure so it can be used in agricultural production.


title: A GeXP-Based Assay for Simultaneous Detection of Multiple Viruses in Hospitalized Children with Community Acquired Pneumonia

text: The GeXP-based assay has recently been developed for simultaneous detection of multiple pathogens. So far, the application of the GeXP assay to test larger clinical samples has hardly been reported. Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. Rapid and accurate diagnosis of virus infection is important for the clinical management of CAP. In this study, we explored the GeXP assay for simultaneous detection of 20 types/subtypes of viruses in hospitalized children with CAP. A total of 1699 nasopharyngeal swabs were prospectively collected and viral nucleic acid was extracted and assayed. Using viral genomic DNA or RNA as template, we showed that at the concentration of 10(4) copies of DNA or RNA of each virus/μl, all 20 target viruses were simultaneously identified by the GeXP assay. Fifteen control microorganisms, in contrast, failed to be amplified by the assay. About 65% of cases tested in this study had viral infection, with patients aged <3 years having a 70% positive rate, significantly higher than that in patients aged > 3 years (40%). The most frequently detected virus was RSV followed by PIV3, HRV, ADV and HBoV. Seasonal distribution analysis revealed that RSV was the most predominant in autumn and winter, while in spring and summer PIV3 and RSV were the most frequently identified with similar positive percentages. One hundred twenty randomly-chosen samples tested by the GeXP assay were re-evaluated by mono-RT-PCR, the results showed 97.5% diagnosis agreement between these 2 methods. Our findings suggest that the GeXP assay could be a valuable diagnostic tool for virus infection in pediatric patients with CAP.


title: Do or die—Strategic decision-making following a shock event

text: Little attention has been directed towards investigating how senior managers and boards approach strategic decision-making when dealing with shock events as compared to strategic decision-making in a stable environment. This paper presents evidence to suggest that strategic decision-making following a shock event involves a more intuitive, less analytical and less consultative approach, while decision-making in a stable environment is characterised by a more cooperative, formal and analytical process. Decision-making following a shock event tends to be simplified and fast, whereas decision-making in a stable environment tends to be comprehensive and slow. Furthermore, the strategic role of the board transforms following a shock event from a limited involvement in strategy setting to a strong involvement in the setting of strategy. This research has important management implications signifying that crisis management must increasingly focus on building an organisation's ability to reach swift decisions in crisis situations and avoid analysis paralysis.


title: Skin Reactions to Non‐glove Personal Protective Equipment: An Emerging Issue in the COVID‐19 Pandemic

text: Protecting healthcare workers (HCWs) is crucial during Corona Virus Disease 2019 pandemic and requires wearing personal protective equipment (PPE) [1]. While most of the studies have focused on the skin reactions caused by gloves, other PPE such as gowns, respirator masks, face shields and goggles are also worn by HCWs for long hours during the current epidemic and skin irritations caused by these equipment may cause discouragement of health workers from using them [2]. In this letter we have focused on the reaction caused by non‐glove PPE.


title: A dynamic model for infectious diseases: The role of vaccination and treatment

text: Abstract Understanding dynamics of an infectious disease helps in designing appropriate strategies for containing its spread in a population. Recent mathematical models are aimed at studying dynamics of some specific types of infectious diseases. In this paper we propose a new model for infectious diseases spread having susceptible, infected, and recovered populations and study its dynamics in presence of incubation delays and relapse of the disease. The influence of treatment and vaccination efforts on the spread of infection in presence of time delays are studied. Sufficient conditions for local stability of the equilibria and change of stability are derived in various cases. The problem of global stability is studied for an important special case of the model. Simulations carried out in this study brought out the importance of treatment rate in controlling the disease spread. It is observed that incubation delays have influence on the system even under enhanced vaccination. The present study has clearly brought out the fact that treatment rate even in presence of time delays would contain the disease as compared to popular belief that eradication can only be done through vaccination.


title: Emergency Medicine Manual, Sixth Edition

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title: Structure and Intracellular Targeting of the SARS-Coronavirus Orf7a Accessory Protein

text: Summary The open reading frame (ORF) 7a of the SARS-associated coronavirus (SARS-CoV) encodes a unique type I transmembrane protein of unknown function. We have determined the 1.8 Å resolution crystal structure of the N-terminal ectodomain of orf7a, revealing a compact seven-stranded β sandwich unexpectedly similar in fold and topology to members of the Ig superfamily. We also demonstrate that, in SARS-CoV- infected cells, the orf7a protein is expressed and retained intracellularly. Confocal microscopy studies using orf7a and orf7a/CD4 chimeras implicate the short cytoplasmic tail and transmembrane domain in trafficking of the protein within the endoplasmic reticulum and Golgi network. Taken together, our findings provide a structural and cellular framework in which to explore the role of orf7a in SARS-CoV pathogenesis.


title: Precautionary Behavior in Response to Perceived Threat of Pandemic Influenza

text: Faced with an epidemic of an infectious disease, persons may take precautionary actions to try to reduce their risk. Such actions include avoiding situations that persons perceive to be risky, which can have negative health and economic effects. Therefore, we conducted a population-based survey of persons’ precautionary actions in response to a hypothetical influenza pandemic. For the 5 European and 3 Asian regions that had been affected by severe acute respiratory syndrome, the pattern of reported precautionary action was broadly similar across the regions; ≈75% of respondents reported that they would avoid public transportation and 20%–30% would try to stay indoors. Some regional differences were noted; Europeans were more likely than Asians to avoid places of entertainment, and Asians were more likely to avoid seeing physicians. This international survey provides insight into what might be expected during an influenza pandemic.


title: Zur antimikrobiellen und viruziden Wirkung eines Hals- und Rachensprays auf der Basis von Hexamidin

text: Antiseptika zur Anwendung auf den Schleimhäuten des Rachenraums dienen nicht nur der Behandlung akuter Symptome bei mikrobiellen oder viralen Infektionen. Zunehmend ist die Anwendung von Antiseptika die einzige noch verbleibende Alternative, wenn auf die Verwendung von Antibiotika verzichtet werden soll oder muss. Dies gilt insbesondere für die Sanierung von MRSA-Trägern. Die Auswahl an geeigneten Wirkstoffen wie auch an verfügbaren Präparaten zur Anwendung auf Schleimhautoberflächen ist begrenzt, und viele von ihnen weisen nicht die erforderliche antimikrobielle oder viruzide Wirksamkeit auf. Ziel der vorgestellten Untersuchung war daher die Überprüfung der antibakteriellen und viruziden Wirkung eines kommerziellen Präparats, basierend auf der Substanz Hexamidindiisetionat. Die Ergebnisse haben gezeigt, dass die Substanz, in einer Dosierung von 1 mg /1 g Lösung und konfektioniert als Rachenspray, eine gute mikrobiostatische und levurostatische Wirksamkeit aufweist. Eine viruzide oder antivirale Wirkung konnte dagegen bei dieser Dosierung nicht gefunden werden.


title: Evaluation of Measles Vaccine Virus as a Vector to Deliver Respiratory Syncytial Virus Fusion Protein or Epstein-Barr Virus Glycoprotein gp350

text: Live attenuated recombinant measles vaccine virus (MV) Edmonston-Zagreb (EZ) strain was evaluated as a viral vector to express the ectodomains of fusion protein of respiratory syncytial virus (RSV F) or glycoprotein 350 of Epstein-Barr virus (EBV gp350) as candidate vaccines for prophylaxis of RSV and EBV. The glycoprotein gene was inserted at the 1(st) or the 3(rd) position of the measles virus genome and the recombinant viruses were generated. Insertion of the foreign gene at the 3(rd) position had a minimal impact on viral replication in vitro. RSV F or EBV gp350 protein was secreted from infected cells. In cotton rats, EZ-RSV F and EZ-EBV gp350 induced MV- and insert-specific antibody responses. In addition, both vaccines also induced insert specific interferon gamma (IFN-γ) secreting T cell response. EZ-RSV F protected cotton rats from pulmonary replication of RSV A2 challenge infection. In rhesus macaques, although both EZ-RSV F and EZ-EBV gp350 induced MV specific neutralizing antibody responses, only RSV F specific antibody response was detected. Thus, the immunogenicity of the foreign antigens delivered by measles vaccine virus is dependent on the nature of the insert and the animal models used for vaccine evaluation.


title: Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan, China

text: BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. METHODS: Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. RESULTS: A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. CONCLUSIONS: A period of 7–13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.


Role of Ultrasound Guided Evaluation of Dyspnea in Coronavirus Disease 2019 Pandemic


Research round-up


title: Redox Biology of Respiratory Viral Infections

text: Respiratory viruses cause infections of the upper or lower respiratory tract and they are responsible for the common cold—the most prevalent disease in the world. In many cases the common cold results in severe illness due to complications, such as fever or pneumonia. Children, old people, and immunosuppressed patients are at the highest risk and require fast diagnosis and therapeutic intervention. However, the availability and efficiencies of existing therapeutic approaches vary depending on the virus. Investigation of the pathologies that are associated with infection by respiratory viruses will be paramount for diagnosis, treatment modalities, and the development of new therapies. Changes in redox homeostasis in infected cells are one of the key events that is linked to infection with respiratory viruses and linked to inflammation and subsequent tissue damage. Our review summarizes current knowledge on changes to redox homeostasis, as induced by the different respiratory viruses.


title: Coronaviruses and SARS-COV-2

text: Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19’s first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.


title: Studies of nonhuman primates: key sources of data on zoonoses and microbiota

text: The genetic and morphologic similarities between primates and humans means that much information obtained from primates may be applied to humans, and vice versa. However, habitat loss, hunting and the continued presence of humans have a negative effect on the biology and behaviour of almost all nonhuman primates. Noninvasive methods such as stool collection are among the safest alternative ways to study the multiple aspects of the biology of primates. Many epidemiologic issues (e.g. pathogen detection, microbiota studies) may be easily studied using stool samples from primates. Primates are undoubtedly among the first candidates suspected of becoming the source of one of the next emerging epidemic of zoonotic origin, as has already been observed with HIV, malaria and monkeypox. The Institut Hospitalo-Universitaire Méditerranée Infection in Marseille actively participates in the study, mostly epidemiologic, of nonhuman primates, using mostly stool samples.


title: Beyond Channel Activity: Protein-Protein Interactions Involving Viroporins

text: Viroporins are short polypeptides encoded by viruses. These small membrane proteins assemble into oligomers that can permeabilize cellular lipid bilayers, disrupting the physiology of the host to the advantage of the virus. Consequently, efforts during the last few decades have been focused towards the discovery of viroporin channel inhibitors, but in general these have not been successful to produce licensed drugs. Viroporins are also involved in viral pathogenesis by engaging in critical interactions with viral proteins, or disrupting normal host cellular pathways through coordinated interactions with host proteins. These protein-protein interactions (PPIs) may become alternative attractive drug targets for the development of antivirals. In this sense, while thus far most antiviral molecules have targeted viral proteins, focus is moving towards targeting host proteins that are essential for virus replication. In principle, this largely would overcome the problem of resistance, with the possibility of using repositioned existing drugs. The precise role of these PPIs, their strain- and host- specificities, and the structural determination of the complexes involved, are areas that will keep the fields of virology and structural biology occupied for years to come. In the present review, we provide an update of the efforts in the characterization of the main PPIs for most viroporins, as well as the role of viroporins in these PPIs interactions.


title: SAFETY IN DIGESTIVE ENDOSCOPY PROCEDURES IN THE COVID ERA RECOMMENDATIONS IN PROGRES OF THE ITALIAN SOCIETY OF DIGESTIVE ENDOSCOPY

text: The new corona virus disease has started in Wuhan - China at the end of 2019 and quickly spread with a pandemic trend across the rest of the world. The scientific community is making an extraordinary effort to study and control the situation, but the results are just partial. Based on the most recent scientific literature and strong statements by the most prestigious international health institutions, the Italian Society of Digestive Endoscopy has drawn up some recommendations about the use of personal protective equipment, the correct way of dressing and undressing of endoscopists and nurses, before and after digestive endoscopy procedures. In addition, some other important indications are given to reduce the risk of contamination of healthcare providers during endoscopic activities, in the setting of a pandemic. Nevertheless, because of the very quick evolution of our knowledge on this issue, these recommendations must be considered as evolving, because they could change in a short time.


title: Dendritic Cell-Specific Antigen Delivery by Coronavirus Vaccine Vectors Induces Long-Lasting Protective Antiviral and Antitumor Immunity

text: Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8(+) T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity.


title: Effects of human activities on concentrations of culturable bioaerosols in indoor air environments

text: Abstract We studied the effects of human activity on concentrations of fungal and bacterial bioaerosols in indoor air environments. We conducted measurement experiments for concentrations of bioaerosols and aerosol particles in test chambers with people performing various activities inside. We found that the number of people and human activities had positive correlations with the concentrations of bacterial bioaerosols. However, the concentration of fungal bioaerosols was not influenced by human presence or activities. The findings regarding the concentrations of fungal and bacterial bioaerosols and the effects of human presence and activities will be useful for studying control methods against bioaerosols.


title: A novel method to produce armored double-stranded DNA by encapsulation of MS2 viral capsids

text: With the rapid development of molecular diagnostic techniques, there is a growing need for quality controls and standards with favorable properties to monitor the entire detection process. In this study, we describe a novel method to produce armored hepatitis B virus (HBV) and human papillomavirus (HPV) DNA for use in nucleic acid tests, which was confirmed to be stable, homogeneous, noninfectious, nuclease resistant, and safe for shipping. We demonstrated that MS2 bacteriophage could successfully package double-stranded DNA of 1.3-, 3-, 3.5-, and 6.5-kb length into viral capsids with high reassembly efficiency. This is the first application of RNA bacteriophage MS2 as a platform to encapsulate double-stranded DNA, forming virus-like particles (VLPs) which were indistinguishable from native MS2 capsids in size and morphology. Moreover, by analyzing the interaction mechanism of pac site and the MS2 coat protein (CP), we found that in addition to the recognized initiation signal TR-RNA, TR-DNA can also trigger spontaneous reassembly of CP dimers, providing a more convenient and feasible method of assembly. In conclusion, this straightforward and reliable manufacturing approach makes armored DNA an ideal control and standard for use in clinical laboratory tests and diagnostics, possessing prospects for broad application, especially providing a new platform for the production of quality controls for DNA viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-015-6664-4) contains supplementary material, which is available to authorized users.


title: Human Torovirus: A New Nosocomial Gastrointestinal Pathogen

text: Studies were undertaken to determine if human torovirus is associated with gastroenteritis and to examine the clinical features of torovirus illness in children. The fecal excretion of torovirus in patients with gastroenteritis was compared with that in matched asymptomatic controls in a case-control study. Toroviruses were identified in 72 (35.0%) of 206 gastroenteritis cases compared with 30 (14.5%) of 206 controls (P < .001). Clinical features of torovirus gastroenteritis in 172 patients positive for torovirus were compared with those of 115 patients infected with rotavirus or astrovirus. Persons infected with torovirus were more frequently immunocompromised (43.0% vs. 15.7%) and nosocomially infected (57.6% vs. 31.3%). They also experienced less vomiting (46.4% vs. 66.7%) but had more bloody diarrhea (11.2% vs. 1.8%). An antibody response to torovirus developed mainly in older, nonimmunocompromised children (P < .01). These studies demonstrate an association between torovirus excretion and gastroenteritis in the pediatric population among immunocompromised hospitalized patients and in previously healthy patients.


title: Possibilities of using ultrasound for diagnosis of invasive pulmonary mucormycosis – A case study

text: Abstract Introduction Mucormycosis is a rare but highly lethal fungal infection, usually affecting immunocompromised patients. Aim To present and analyze the diagnostic capabilities of transthoracic ultrasonography in invasive pulmonary mucormycosis. Case study We present a case involving a 41-year-old female patient with pneumonia complicated by multisystem organ failure, who was diagnosed with invasive pulmonary mucormycosis. Results and discussion Transthoracic ultrasonography (TUS) revealed a consolidation area of heterogeneous echostructure with an abnormal air bronchogram, possibly suggestive of an invasive pulmonary fungal disorder. The presence of lesions observed with TUS was confirmed by computed tomography (CT). The final diagnosis of mucormycosis was possible after Mucor species fungi were detected in bronchoalveolar lavage culture. Conclusions (1) TUS is a widely available and inexpensive diagnostic method that is characterized by the absence of adverse effects, and its applicability in the diagnosis of pulmonary disorders other than invasive fungal infections is well documented. (2) Ultrasonographic analysis of lesions facilitates differentiation between bacterial and fungal pneumonia, and the high sensitivity and specificity of the procedure compared to CT scans as a reference method supports the reliability of ultrasound scans in the diagnosis of invasive pulmonary aspergillosis (IPA). (3) The use of TUS in the diagnosis of invasive pulmonary mucormycosis appears warranted, particularly in cases when it is impossible to obtain a proven diagnosis. (4) Ultrasonographic diagnosis of invasive lung disorders, including mucormycosis, requires further studies.


title: Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines

text: Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use.


title: Docking approaches for modeling multi-molecular assemblies

text: Computational docking approaches aim to overcome the limited availability of experimental structural data on protein–protein interactions, which are key in biology. The field is rapidly moving from the traditional docking methodologies for modeling of binary complexes to more integrative approaches using template-based, data-driven modeling of multi-molecular assemblies. We will review here the predictive capabilities of current docking methods in blind conditions, based on the results from the most recent community-wide blind experiments. Integration of template-based and ab initio docking approaches is emerging as the optimal strategy for modeling protein complexes and multimolecular assemblies. We will also review the new methodological advances on ab initio docking and integrative modeling.


title: Industrial buying during the coronavirus pandemic: A cross-cultural study

text: Abstract With the onset of the 2020 coronavirus pandemic, industrial suppliers are increasingly challenged to close their open sales opportunities and keep generating business. Against this backdrop, the authors of this study investigate which offerings industrial customers are most likely to purchase as the pandemic progresses. Drawing on positive decision theory and empirically investigating 31,353 sales opportunities across 57 countries, the authors show that the coronavirus pandemic significantly decreases industrial customers' purchase probability, especially for high-priced offerings. In countries with low uncertainty avoidance and strong long-term orientation (e.g., China, India, Singapore), purchase probability is less affected by the pandemic. The coronavirus pandemic even increases purchase probability for offerings with low prices in countries where cultures are simultaneously uncertainty-avoidant and short-term oriented (e.g., Argentina, Brazil, Mexico). This is presumably because customers safeguard their operations in the face of impending supply shortages. Consequently, this helps suppliers focus on the right sales opportunities to secure their business during exogenous global shocks such as the coronavirus pandemic.


Proteolysis of Sars-Associated Coronavirus Spike Glycoprotein


Developing countries, markets, and the coronavirus: two challenges


title: The Psychological Impacts of a COVID-19 Outbreak on College Students in China: A Longitudinal Study

text: An outbreak in Wuhan, China in late 2019 of a highly infectious new coronary pneumonia (COVID-19) led to the imposition of countrywide confinement measures from January to March 2020. This is a longitudinal study on changes in the mental health status of a college population before and after their COVID-19 confinement for the first two weeks, focusing on states of psychological distress, depression, anxiety and affectivity. The influence of possible stressors on their mental health were investigated, including inadequate supplies and fears of infection. Five hundred and fifty-five undergraduate students were recruited from Hebei Agricultural University in Baoding, China. The participants completed two online surveys—on anxiety and depression, and on positive and negative affect. One survey was conducted before the confinement and the other was conducted 15–17 days after the start of the confinement. Increases in negative affect and symptoms of anxiety and depression (p-values < 0.001) were observed after 2 weeks of confinement. Inadequate supplies of hand sanitizers, a higher year of study, and higher scores on anxiety and depression were common predictors of increased negative affect, anxiety, and depression across the confinement period. The results suggest that healthcare policymakers should carefully consider the appropriate confinement duration, and ensure adequate supplies of basic infection-control materials.


title: Biological weapons: Hospital preparedness to bioterrorism and other infectious disease emergencies

text: In the last 2 decades, successive outbreaks caused by new, newly recognised and resurgent pathogens, and the risk that high-consequence pathogens might be used as bioterrorism agents amply demonstrated the need to enhance capacity in clinical and public health management of highly infectious diseases. In this article we review these recent and current threats to public health, whether naturally occurring or caused by accidental or intentional release. Moreover, we discuss some components of hospital preparedness for, and response to, infectious disease of the emergencies in developed countries. The issues of clinical awareness and education, initial investigation and management, surge capacity, communication, and caring for staff and others affected by the emergency are discussed. We also emphasise the importance of improving the everyday practice of infection control by healthcare professionals.


COVID-19: an opportunity to restructure surgical education


title: A molecular survey for selected viral enteropathogens revealed a limited role of Canine circovirus in the development of canine acute gastroenteritis

text: Abstract Canine circovirus (CanineCV) is a canine virus, whose pathogenetic role is still uncertain. Based on recent data suggesting its role as entheropathogen, a case-control study was conducted between 2013 and 2016 to investigate the association of CanineCV with gastroenteritis in dogs, alone or in combination with other viral pathogens, including canine parvovirus (CPV), canine coronavirus (CCoV) and canine distemper virus (CDV). A total of 219 dogs suffering from acute gastroenteritis disorders and 67 controls randomly recruited among healthy dogs or patients presenting without enteric signs were screened by a panel of real-time (RT-)PCR assays for CanineCV, CPV, CCoV and CDV. A high prevalence of viral infections was detected in dogs with gastroenteritis (77.16%), with CPV representing the most frequently detected enteropathogen, followed by CanineCV and CCoV. While CPV and CCoV infections displayed a strong association with occurrence of acute gastroenteritis (p< 0.00001), detection of CanineCV in control dogs (28.35%) occurred with prevalence comparable to that of clinical cases (32.42%), so that its correlation with gastrointestinal disease was not statistically supported (p =0.530988). Different from the clinical cases, where co-infections were frequently observed, all positive samples from the control group contained single infections. Noteworthy, a significant association was calculated between co-infections with CanineCV and occurrence of acute gastroenteritis (p< 0.00001). This study supports the role of CanineCV as a co-pathogen in the development of gastrointestinal disease, mainly acting in synergism with other enteric viruses.


title: Chitin nanowhiskers from shrimp shell waste as green filler in acrylonitrile-butadiene rubber: Processing and performance properties

text: In this work, chitin nanowhiskers with high crystallinity index were obtained from shrimp shells waste using acid hydrolysis method and then comprehensively characterized. Subsequently, the impact of chitin nanowhisker content on processing and performance of acrylonitrile-butadiene rubber based nanocomposites was evaluated. The results showed that the addition of chitin nanowhiskers increased tensile strength and tear strength of nanocomposites by 116% and 54%, which was related to suitable dispersion of chitin nanowhiskers in matrix. Reinforcing effect of chitin nanowhiskers in acrylonitrile-butadiene rubber was also confirmed by Wolff activity coefficient, glass transition temperature and equilibrium swelling measurements. Moreover, it was found that higher content chitin nanowhiskers significantly improve the thermal stability of studied nanocomposites. The incorporation of chitin nanowhiskers resulted in increase of 74 °C for onset degradation temperature. This work confirmed that shrimp shell waste can be upcycled into chitin nanowhiskers - promising green filler in NBR for high-performance elastomeric applications.


title: Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid

text: BACKGROUND: Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non-enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. METHODS: A new hand disinfectant was developed based upon 69.39 % w/w ethanol and 3.69 % w/w 2-propanol. Different amounts of citric acid and urea were added in order to create a virucidal claim against poliovirus (PV), adenovirus type 5 (AdV) and polyomavirus SV40 (SV40) as non-enveloped test viruses in the presence of fetal calf serum (FCS) as soil load. The exposure time was fixed to 60 s. RESULTS: With the addition of 2.0 % citric acid and 2.0 % urea an activity against the three test viruses was achieved demonstrating a four log(10) reduction of viral titers. Furthermore, this formulation was able to inactivate PV, AdV, SV40 and murine norovirus (MNV) in quantitative suspension assays according to German and European Guidelines within 60 s creating a virucidal claim. For inactivation of vaccinia virus and bovine viral diarrhea virus 15 s exposure time were needed to demonstrate a 4 log(10) reduction resulting in a claim against enveloped viruses. Additionally, it is the first hand disinfectant passing a carrier test with AdV and MNV. CONCLUSIONS: In conclusion, this new formulation with a low alcohol content, citric acid and urea is capable of inactivating all enveloped and non-enveloped viruses as indicated in current guidelines and thereby contributing as valuable addition to the hand disinfection portfolio.


title: ToGo-WF: prediction of RNA tertiary structures and RNA–RNA/protein interactions using the KNIME workflow

text: Recent progress in molecular biology has revealed that many non-coding RNAs regulate gene expression or catalyze biochemical reactions in tumors, viruses and several other diseases. The tertiary structure of RNA molecules and RNA–RNA/protein interaction sites are of increasing importance as potential targets for new medicines that treat a broad array of human diseases. Current RNA drugs are split into two groups: antisense RNA molecules and aptamers. In this report, we present a novel workflow to predict RNA tertiary structures and RNA–RNA/protein interactions using the KNIME environment, which enabled us to assemble a combination of RNA-related analytical tools and databases. In this study, three analytical workflows for comprehensive structural analysis of RNA are introduced: (1) prediction of the tertiary structure of RNA; (2) prediction of the structure of RNA–RNA complexes and analysis of their interactions; and (3) prediction of the structure of RNA–protein complexes and analysis of their interactions. In an RNA–protein case study, we modeled the tertiary structure of pegaptanib, an aptamer drug, and performed docking calculations of the pegaptanib-vascular endothelial growth factor complex using a fragment of the interaction site of the aptamer. We also present molecular dynamics simulations of the RNA–protein complex to evaluate the affinity of the complex by mutating bases at the interaction interface. The results provide valuable information for designing novel features of aptamer-protein complexes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10822-019-00195-y) contains supplementary material, which is available to authorized users.


title: IRSS: a web-based tool for automatic layout and analysis of IRES secondary structure prediction and searching system in silico

text: BACKGROUND: Internal ribosomal entry sites (IRESs) provide alternative, cap-independent translation initiation sites in eukaryotic cells. IRES elements are important factors in viral genomes and are also useful tools for bi-cistronic expression vectors. Most existing RNA structure prediction programs are unable to deal with IRES elements. RESULTS: We designed an IRES search system, named IRSS, to obtain better results for IRES prediction. RNA secondary structure prediction and comparison software programs were implemented to construct our two-stage strategy for the IRSS. Two software programs formed the backbone of IRSS: the RNAL fold program, used to predict local RNA secondary structures by minimum free energy method; and the RNA Align program, used to compare predicted structures. After complete viral genome database search, the IRSS have low error rate and up to 72.3% sensitivity in appropriated parameters. CONCLUSION: IRSS is freely available at this website . In addition, all source codes, precompiled binaries, examples and documentations are downloadable for local execution. This new search approach for IRES elements will provide a useful research tool on IRES related studies.


title: Medically unexplained symptoms in the times of Covid-19 pandemic: a case-report

text: Abstract In early 2020, a novel coronavirus (SARS-CoV-2) leading to a potentially fatal condition was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread worldwide becoming a pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the psychological impact that COVID-19 may have, especially on vulnerable individuals with pre-existing mental health conditions. Somatic symptom disorder (SSD) is characterized by a dysfunctional preoccupation with physical symptoms leading to excessive and unnecessary healthcare utilization. Despite being quite common, such condition remains underrecognized. We report a detailed clinical case of a 16 years old adolescent, who presented with a history suggestive of COVID-19 infection and associated psychological distress. Despite testing negative for the presence of SARS-CoV-2, his extreme and persisting health preoccupations required an inpatient admission to the Child and Adolescent Neuropsychiatric Unit. He responded rapidly to a low dose of antipsychotic and an antidepressant. Based on his medical history and current presentation, he received a diagnosis of SSD. When COVID-19-like symptoms occur, we highlight the importance of differentially diagnosing a possible exacerbation of a pre-existing SSD, triggered by fear of being infected. This may help preventing further burden to the healthcare system.


title: Canine Coronavirus

text: This chapter provides an overview of the classification and description of the canine coronavirus, its hosts, the key developments regarding the virus, and the diagnostic techniques and reagents. Canine coronavirus causes diarrhea and vomiting in dogs. The hosts that are infected by the canine coronavirus include dogs and coyotes. It is a recognized disease of dogs. Although the virus was first isolated in 1971, the disease entity was reported in 1974. The experimental pathogenesis has been described. Immune electron microscopy (EM) may aid the diagnosis but as transmissible gastro-enteritis (TGE) virus may also react, viral isolation may be necessary for a definitive diagnosis. The diagnostic reagents include routine EM materials and virus isolation in A72 cells.


title: The Time Required to Estimate the Case Fatality Ratio of Influenza Using Only the Tip of an Iceberg: Joint Estimation of the Virulence and the Transmission Potential

text: Estimating the case fatality ratio (CFR) of a novel strain of influenza virus during the early stage of the pandemic is one of key epidemiological tasks to be conducted as rapid research response. Past experience during the epidemics of severe acute respiratory syndrome (SARS) and influenza A (H1N1-2009) posed several technical challenges in estimating the CFR in real time. The present study aimed to develop a simple method to estimate the CFR based on readily available datasets, that is, confirmed cases and deaths, while addressing some of the known technical issues. To assess the reliability and validity of the proposed method, we examined the minimum length of time required for the assigned CFR to be included within the 95% confidence intervals and for the estimated CFR to be below a prespecified cut-off value by means of Monte Carlo simulations. Overall, the smaller the transmission potential was, the longer it took to compare the estimated CFR against the cut-off value. If policymaking and public health response have to be made based on the CFR estimate derived from the proposed method and readily available data, it should be noted that the successful estimation may take longer than a few months.


title: Isolated severe thrombocytopenia in a patient with COVID-19: A case report

text: COVID-19 is known to cause serious respiratory symptoms and involvement of other body systems such as hematopoietic, neurological and the immune system. In this report, we described a case of a COVID-19 patient who presented with no pulmonary involvement but severe thrombocytopenia. She suffered from headache and malaise with no respiratory symptoms, fever or chills. Chest radiological imaging was unremarkable but, the laboratory results showed significant thrombocytopenia associated with relatively decreased lymphocytes. Based on her high-risk work environment, a reverse transcription polymerase chain reaction (RT-PCR) test was performed and SARS-CoV-2 RNA was detected in the nasopharyngeal swab. Complete blood count (CBC) of patient was re-checked during admission and platelet count showed rising trend up to normal levels. A narrow diagnostic approach where only febrile patients with pulmonary symptoms are evaluated for a COVID-19 diagnosis will result in many missed diagnoses; so it is important that physicians are familiar with atypical and rare presentations of COVID-19, such as isolated thrombocytopenia.


title: Interferons induce the expression of IFITM1 and IFITM3 and suppress the proliferation of rat neonatal cardiomyocytes

text: Cardiovascular diseases have been one of the leading killers among the human population worldwide. During the heart development, cardiomyocytes undergo a transition from hyperplastic to hypertrophic growth with an unclear underlying mechanism. In this study, we aim to investigate how interferons differentially stimulate the interferon‐inducible transmembrane (IFITM) family proteins and further be involved in the process of heart development. The expression levels of three IFITM family members, IFITM1, IFITM2, and IFITM3 were investigated during Sprague–Dawley rat myocardial development and differentiation of H9C2 cardiomyocytes. The effects of interferon‐α, ‐β, and ‐γ on DNA synthesis in H9C2 cells were also characterized. Up‐regulation of IFITM1 and IFITM3 were observed during the heart development of Sprague–Dawley rat and the differentiation of H9C2 cells. Moreover, interferon‐α and ‐β induce the expression of IFITM3 while interferon‐γ up‐regulates IFITM1. Finally, interferon‐α and ‐β were demonstrated to inhibit DNA synthesis during H9C2 cell differentiation. Our results indicated interferons are potentially involved in the differentiation and cell proliferation during heart development. J. Cell. Biochem. 113: 841–847, 2012. © 2011 Wiley Periodicals, Inc.


title: Lung Involvement Found on Chest CT Scan in a Pre-Symptomatic Person with SARS-CoV-2 Infection: A Case Report

text: The novel coronavirus SARS-CoV-2 infection is spreading worldwide, and there are many reports of acute respiratory distress syndrome caused by this infection. However, asymptomatic lung involvement has not been reported. We hereby present the case of a 44-year-old health-care worker, who was found to be infected with the SARS-CoV-2 virus after a CT-scan performed for an unrelated condition revealed a lesion in the lung field compatible with COVID-19 infection. His condition deteriorated initially, but eventually improved with supportive treatment and the compassionate use of antivirals and antimalarials and is now in a stable condition.


title: Public health implications of complex emergencies and natural disasters

text: BACKGROUND: During the last decade, conflict or natural disasters have displaced unprecedented numbers of persons. This leads to conditions prone to outbreaks that imperil the health of displaced persons and threaten global health security. Past literature has minimally examined the association of communicable disease outbreaks with complex emergencies (CEs) and natural disasters (NDs). METHODS: To examine this association, we identified CEs and NDs using publicly available datasets from the Center for Research on the Epidemiology of Disasters and United Nations Flash and Consolidated Appeals archive for 2005–2014. We identified outbreaks from World Health Organization archives. We compared findings to identify overlap of outbreaks, including their types (whether or not of a vaccine-preventable disease), and emergency event types (CE, ND, or Both) by country and year using descriptive statistics and measure of association. RESULTS: There were 167 CEs, 912 NDs, 118 events linked to ‘Both’ types of emergencies, and 384 outbreaks. Of CEs, 43% were associated with an outbreak; 24% NDs were associated with an outbreak; and 36% of ‘Both’ types of emergencies were associated with an outbreak. Africa was disproportionately affected, where 67% of total CEs, 67% of ‘Both’ events (CE and ND), and 46% of all outbreaks occurred for the study period. The odds ratio of a vaccine-preventable outbreak occurring in a CE versus an ND was 4.14 (95% confidence limits 1.9, 9.4). CONCLUSIONS: CEs had greater odds of being associated with outbreaks compared with NDs. Moreover, CEs had high odds of a vaccine-preventable disease causing that outbreak. Focusing on better vaccine coverage could reduce CE-associated morbidity and mortality by preventing outbreaks from spreading.


title: Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

text: Microglia are prominent immune cells in the central nervous system (CNS) and are critical players in both neurological development and homeostasis, and in neurological diseases when dysfunctional. Our previous understanding of the phenotypes and functions of microglia has been greatly extended by a dearth of recent investigations. Distinct genetically defined subsets of microglia are now recognized to perform their own independent functions in specific conditions. The molecular profiling of single microglial cells indicates extensively heterogeneous reactions in different neurological disorders, resulting in multiple potentials for crosstalk with other kinds of CNS cells such as astrocytes and neurons. In settings of neurological diseases it could thus be prudent to establish effective cell‐based therapies by targeting entire microglial networks. Notably, activated microglial depletion through genetic targeting or pharmacological therapies within a suitable time window can stimulate replenishment of the CNS niche with new microglia. Additionally, enforced repopulation through provision of replacement cells also represents a potential means of exchanging dysfunctional with functional microglia. In each setting the newly repopulated microglia might have the potential to resolve ongoing neuroinflammation. In this review, we aim to summarize the most recent knowledge of microglia and to highlight microglial depletion and subsequent repopulation as a promising cell replacement therapy. Although glial cell replacement therapy is still in its infancy and future translational studies are still required, the approach is scientifically sound and provides new optimism for managing the neurotoxicity and neuroinflammation induced by activated microglia.


title: The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA

text: The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA binding protein that plays a variety of roles in the viral life cycle including replication, transcription, and genome packaging. Despite its critical and multifunctional nature, the molecular details that underlie how N protein mediates these functions are poorly understood. Here we combine single-molecule spectroscopy with all-atom simulations to uncover the molecular details that contribute to the function of SARS-CoV-2 N protein. N protein contains three intrinsically disordered regions and two folded domains. All three disordered regions are highly dynamic and contain regions of transient helicity that appear to act as local binding interfaces for protein-protein or protein-RNA interactions. The two folded domains do not significantly interact with one another, such that full-length N protein is a flexible and multivalent RNA binding protein. As observed for other proteins with similar molecular features, we found that N protein undergoes liquid-liquid phase separation when mixed with RNA. Polymer models predict that the same multivalent interactions that drive phase separation also engender RNA compaction. We propose a simple model in which symmetry breaking through specific binding sites promotes the formation of metastable single-RNA condensate, as opposed to large multi-RNA phase separated droplets. We speculate that RNA compaction to form dynamic single-genome condensates may underlie the early stages of genome packaging. As such, assays that measure how compounds modulate phase separation could provide a convenient tool for identifying drugs that disrupt viral packaging.


title: The Intestinal Eukaryotic Virome in Healthy and Diarrhoeic Neonatal Piglets

text: Neonatal porcine diarrhoea of uncertain aetiology has been reported from a number of European countries. The aim of the present study was to use viral metagenomics to examine a potential viral involvement in this diarrhoea and to describe the intestinal virome with focus on eukaryotic viruses. Samples from the distal jejunum of 50 diarrhoeic and 19 healthy piglets from 10 affected herds were analysed. The viral fraction of the samples was isolated and nucleic acids (RNA and DNA fractions) were subjected to sequence independent amplification. Samples from diarrhoeic piglets from the same herds were pooled whereas samples from healthy piglets were analysed individually. In total, 29 clinical samples, plus two negative controls and one positive control consisting of a mock metagenome were sequenced using the Ion Torrent platform. The resulting sequence data was subjected to taxonomic classification using Kraken, Diamond and HMMER. In the healthy specimens, eight different mammalian virus families were detected (Adenoviridae, Anelloviridae, Astroviridae, Caliciviridae, Circoviridae, Parvoviridae, Picornaviridae, and Reoviridae) compared to four in the pooled diarrhoeic samples (Anelloviridae, Circoviridae, Picornaviridae, and Reoviridae). It was not possible to associate a particular virus family with the investigated diarrhoea. In conclusion, this study does not support the hypothesis that the investigated diarrhoea was caused by known mammalian viruses. The results do, however, indicate that known mammalian viruses were present in the intestine as early as 24–48 hours after birth, indicating immediate infection post-partum or possibly transplacental infection.


title: Diarrheal Diseases

text: Abstract An estimated 700000 children die annually due to diarrhea with majority of these occurring in children under the age of 5 years. Morbidity from diarrhea includes poor growth and development. The global diarrhea burden is primarily due to infections secondary to rotavirus, cryptosporidium, enterotoxigenic Escherichia coli, and Shigella species. Known interventions to effectively treat and prevent diarrhea include vaccines against rotavirus and cholera, zinc supplementation, and therapy with oral rehydration solution. The achievement of the fourth Millennium Development Goal requires reductions in mortality from diarrhea, and can only be accomplished by implementing evidence-based strategies.


The Evolving Pandemic of COVID‐19 and Interventional Cardiology


title: Emerging and Reemerging Virus Diseases of Vertebrates

text: In the last two decades, a large number of new viruses have been discovered, many of which are pathogenic in humans or other vertebrates. Among the more important causes of virus emergence have been changes in human behavior, population, and increases in travel to distant countries. In addition, the application of new molecular technologies has led to the recognition of many viruses that hitherto went undetected. Many of the new, emerging viruses have an RNA genome, and many are zoonoses. The spread of human immunodeficiency virus, causing acquired immune deficiency syndrome, and the use of immunosuppressive drugs following transplant surgery, have increased the numbers of people in the population that are highly susceptible to emerging virus infections. The threat of a new pandemic of influenza virus in the human population stresses the need for development of better methods for detection, surveillance, and control of emerging virus diseases.


Reply to letter to the editor (HED‐20‐0582) regarding “how to avoid nosocomial spread during tracheostomy for COVID‐19 patients”


title: How the cryptocurrency market has performed during COVID 19? A multifractal analysis

text: Cryptocurrency markets are complex systems based on speculation. Where investors interact using strategies that generate some biases responsible for endogenous instabilities. This paper investigated the herding biases by quantifying the self-similarity intensity of cryptocurrency returns’ during the COVID-19 pandemic. The main purpose of this work was to study the level of cryptocurrency efficiency through multifractal analysis before and after the coronavirus pandemic. The empirical results proved that COVID-19 has a positive impact on the cryptocurrency market efficiency.


title: Autoantibodies against appetite-regulating peptide hormones and neuropeptides: Putative modulation by gut microflora

text: Abstract Objective Peptide hormones synthesized in gastrointestinal and adipose tissues in addition to neuropeptides regulate appetite and body weight. Previously, autoantibodies directed against melanocortin peptides were found in patients with eating disorders; however, it remains unknown whether autoantibodies directed against other appetite-regulating peptides are present in human sera and whether their levels are influenced by gut-related antigens. Methods Healthy women were studied for the presence of immunoglobulin (Ig) G and IgA autoantibodies directed against 14 key appetite-regulating peptides. The concept of molecular mimicry was applied to search in silico whether bacteria, viruses, or fungi contain proteins with amino acid sequences identical to appetite-regulating peptides. In addition, autoantibodies serum levels were studied in germ-free and specific pathogen-free rats. Results We found these IgG and IgA autoantibodies directed against leptin, ghrelin, peptide YY, neuropeptide Y, and other appetite-regulating peptides are present in human sera at levels of 100–900 ng/mL. Numerous cases of sequence homology with these peptides were identified among commensal and pathogenic micro-organisms including Lactobacilli, bacteroides, Helicobacter pylori, Escherichia coli, and Candida species. Decreased levels of IgA autoantibodies directed against several appetite-regulating peptides and increased levels of antighrelin IgG were found in germ-free rats compared with specific pathogen-free rats. Conclusion Healthy humans and rats display autoantibodies directed against appetite-regulating peptide hormones and neuropeptides, suggesting that these autoantibodies may have physiologic implications in hunger and satiety pathways. Gut-related antigens including the intestinal microflora may influence production of theses autoantibodies, suggesting a new link between the gut and appetite control.


title: Metabolite profiling studies in Saccharomyces cerevisiae: an assisting tool to prioritize host targets for antiviral drug screening

text: BACKGROUND: The cellular proteins Pat1p, Lsm1p, and Dhh1p are required for the replication of some positive-strand viruses and therefore are potential targets for new antiviral drugs. To prioritize host targets for antiviral drug screening a comparative metabolome analysis in Saccharomyces cerevisiae reference strain BY4742 Matα his3Δ1 leu2Δ0 lys2Δ0 ura3Δ0 and deletion strains pat1Δ, lsm1Δ and dhh1Δ was performed. RESULTS: GC/MS analysis permitted the quantification of 47 polar metabolites and the identification of 41 of them. Metabolites with significant variation between the strains were identified using partial least squares to latent structures discriminate analysis (PLS-DA). The analysis revealed least differences of pat1Δ to the reference strain as characterized by Euclidian distance of normalized peak areas. The growth rate and specific production rates of ethanol and glycerol were also most similar with this strain. CONCLUSION: From these results we hypothesize that the human analog of yeast Pat1p is most likely the best drug target candidate.


title: Keynote Speaker II Biomedical Engineering Research in the Social Network Analysis Era: Stance Classification for Analysis of Hoax Medical News in Social Media

text: Abstract Biomedical engineering research trend can be healthcare models with unobtrusive smart systems for monitoring vital signs and physical activity. Detecting infant facial cry because of inability to communicate pain, recognizing facial emotion to understand dysfunction mechanisms through micro expression or transform captured human expression with motion device into three-dimensional objects are some of the applied systems. Nowadays, collaborated with biomedical research, mining and analyzing social network can improve public and private health care sectors as well such as research health news shared on social media about pharmaceutical drugs, pandemics, or viral outbreaks. Due to the vast amount of shared news, there is an urgency to select and filter information to prevent the spread of hoax or fake news. We explored in depth some steps to classify hoaxes written as news articles. This discussion also encourages on how technologies of social network analysis could be used to make new kinds improvement in health care sectors. Then close with a description of limitless future possibilities of biomedical engineering research in social media.


Section 3 Clinical Signs


title: Navigating disruptive crises through service-led growth: The impact of COVID-19 on Italian manufacturing firms

text: Abstract This study draws on an extensive survey and interview data collected during the COVID-19 pandemic. The respondents were executives of industrials firms whose factories, warehouses, and headquarters are located in Northern Italy. This is undoubtedly the European region first and most extensively affected by the pandemic, and the government implemented radical lockdown measures, banning nonessential travel and mandating the shutdown of all nonessential businesses. Several major effects on both product and service businesses are highlighted, including the disruption of field-service operations and supply networks. This study also highlights the increased importance of servitization business models and the acceleration of digital transformation and advanced services. To help firms navigate through the crisis and be better positioned after the pandemic, the authors present a four-stage crisis management model (calamity, quick & dirty, restart, and adapt), which provides insights and critical actions that should be taken to cope with the expected short and long-term implications of the crisis. Finally, this study discusses how servitization can enhance resilience for future crises—providing a set of indicators on the presumed role of, and impact on, service operations in relation to what executives expect to be the “next normal.”


Modern Sunni-Shia conflicts and their neglected tropical diseases


title: A systematic review of the prophylactic role of chloroquine and hydroxychloroquine in coronavirus disease‐19 (COVID‐19)

text: OBJECTIVE: The pandemic coronavirus disease‐19 (COVID‐19) has pushed the global healthcare system to a crisis and amounted to a huge economic burden. Different drugs for prophylaxis against COVID‐19 including chloroquine (CQ) or hydroxychloroquine (HCQ) have been tried. This study was performed to systematically review the role of CQ and HCQ in preventing the spread of COVID‐19. METHODS: PubMed, EMBASE, ClinicalTrials.gov, International Clinical Trials Registry Platform and Cochrane Library databases were searched for studies that evaluated the prophylactic role of CQ or HCQ on SARS‐CoV‐2 (pre‐clinical studies) or COVID‐19 (clinical studies) until 30 March 2020. The available literature was critically appraised. RESULTS: A total of 45 articles were screened and 5 (3 in vitro pre‐clinical studies and 2 clinical opinions) were included. The pre‐clinical studies showed the prophylactic effects of CQ and HCQ against SARS‐CoV‐2. On the other hand, the clinical opinions advocated the prophylactic use of CQ and HCQ against COVID‐19. However, no original clinical studies on the prophylactic role of CQ or HCQ on COVID‐19 were available. CONCLUSION: Although pre‐clinical results are promising, to date there is a dearth of evidence to support the efficacy of CQ or HCQ in preventing COVID‐19. Considering potential safety issues and the likelihood of imparting a false sense of security, prophylaxis with CQ or HCQ against COVID‐19 needs to be thoroughly evaluated in observational studies or high‐quality randomized controlled studies.


title: Inequities in access to education: Lessons from the COVID‐19 pandemic

text: The COVID‐19 pandemic has brought attention to the stark inequities in public education worldwide, with the United Nations sharing these statistics: Schools closed in 191 countries, affecting 1.5 billion students and 63 million primary and secondary school teachers. Half of students did not have access to a computer, and 40% did not have internet access. A total of 56 million children live in areas that are not served by mobile networks — for example, in sub‐Saharan Africa. In the United States, about 7 million school‐aged children are in homes without home internet service.


SOGC Committee Opinion – COVID-19 in Pregnancy


title: Le service de soins intensifs (réanimation) adultes à Genève, Suisse

text: Résumé Le complexe hospitalier universitaire de Genève est le plus grand de Suisse et est couplé à la Faculté de Médecine de l’Université de Genève. Le service des soins intensifs adultes est un service médico-chirurgical et comprend 32 lits répartis en trois unités : une unité de neuro-réanimation, une unité de médecine intensive cardiovasculaire et une unité polyvalente s’occupant des malades qui n’ont pas les spécificités des deux autres secteurs. Le service accueille plus de 2200 patients annuellement, en moyenne pour 4 jours. Le taux de mortalité est de 7,5 % en 2019 pour un SAPS2 moyen de 44 points. Une quatrième unité, non-géographique celle-là, s’occupe des besoins spécifiques des patients « long séjour » et de leurs proches ainsi que de la consultation post-réanimation, 6 et 12 mois après l’hospitalisation. Les infirmières sont spécialisées en soins intensifs et s’occupent en moyenne d’1,5 patients la journée et de 2 patients la nuit. Le service est un centre de formation pour les intensivistes suisses et un centre de recherche clinique de qualité. Summary The University Hospitals of Geneva is the largest hospital complex in Switzerland and is coupled to the Faculty of medicine of the University of Geneva. The division of adult intensive care is a 32-bed mixed medical and surgical ICU, made of three different units: one neurocritical care unit, one cardiovascular unit, and one polyvalent unit receiving patients that do not fit into the two previous units. More than 2200 patients are hospitalised yearly in the division of adult intensive care, staying a mean of 4 days. The ICU mortality rate is 7.5% for a mean SAPS2 of 44 points. A fourth non-geographical unit with dedicated doctors and nurses is dedicated to the specific needs of “long-stayers” and their next of kin and to the organisation of post-ICU clinics, 6 and 12 months after ICU discharge. Nurses follow a special ICU training of 2 years, and obtain an ICU nurse certificate. One nurse takes care of 1.5 patients during the day and 2 patients during night shifts. The ICU division is a training centre for doctors to become intensivists and a centre for quality clinical research.


title: Gefitinib sensitization of cisplatin-resistant wild-type EGFR non-small cell lung cancer cells

text: PURPOSE: The usual first-line strategy of wild-type EGFR (wtEGFR) non-small cell lung cancer (NSCLC) remains cisplatin-based chemotherapy. However, cisplatin often loses effectiveness because most tumors acquire drug resistance over time. As EGFR is the most important pro-survival/proliferation signal receptor in NSCLC cells, we aimed at investigating whether cisplatin resistance is related to EGFR activation and further evaluating the combined effects of cisplatin/gefitinib (EGFR-tyrosine kinase inhibitor, EGFR-TKI) on cisplatin-resistant wtEGFR NSCLC cells. MATERIALS AND METHODS: EGFR activation was analysed in parental and cisplatin-resistant wtEGFR NSCLC cell lines (H358 and H358(R), A549 and A549(R)). Cellular proliferation and apoptosis of H358(R)/A549(R) cells treated with cisplatin or gefitinib, alone or in combination were investigated, and the related effector protein was detected by western blot analysis. Anti-tumor effect of two drugs combined was evaluated in animal models of H358(R) xenografts in vivo. RESULTS: EGFR was significantly phosphorylated in cisplatin-resistant wtEGFR NSCLC cells H358(R) and A549(R) than their parental cells. In H358(R) and A549(R) cells, anti-proliferative ability of gefitinib was further improved, and gefitinib combined with cisplatin enhanced inhibition of cellular survive/proliferation, and promotion of apoptosis in vitro. The combined effects were also associated with the inhibition of EGFR downstream effector proteins. Similarly, in vivo, gefitinib and cisplatin in combination significantly inhibited tumor growth of H358(R) xenografts. CONCLUSION: Abnormal activation of EGFR may induce wtEGFR NSCLC cell resistance to cisplatin. The combined effects of cisplatin/gefitinib suggest that gefitinib, as a combination therapy for patients with cisplatin-resistant wtEGFR NSCLC should be considered.


title: Infecciones nosocomiales en pediatría

text: Numerosas son las particularidades de la población pediátrica que deben intervenir, en nuestra opinión, en el control de las infecciones nosocomiales. Los riesgos y los agentes patógenos responsables son diferentes en función del tipo de población (prematuros, recién nacidos, otros). Además, esta población, que comparte los mismos factores de riesgo de infecciones nosocomiales que la población adulta (hospitalización en reanimación, cateterismos, etc.), se distingue no sólo por la inmadurez del sistema inmunitario de los recién nacidos, sino también por la multiplicidad de los participantes, desde los sanitarios hasta los padres, pasando por los educadores y los acompañantes (visitantes de todo tipo, etc.) necesarios para el desarrollo conductual y emocional del niño. Además, es importante subrayar el aumento del riesgo ligado a los contactos frecuentes, cercanos e íntimos que están parcial e incluso totalmente ausentes en el ámbito hospitalario «adulto». Así como existen riesgos de transmisión cruzada a través del principal vector constituido por los sanitarios, el control del riesgo no puede excluir a los educadores, a los acompañantes, a los padres y a los mismos niños. Si el riesgo en la esfera adulta está limitado a las actividades médicas, en la esfera pediátrica se comparte con las demás actividades (juegos, enseñanza, etc.), que con frecuencia son comunes. Todos estos riesgos son todavía mayores debido a la prevalencia de los agentes patógenos como los virus (respiratorios y digestivos), la frecuencia de las antibioticoterapias y la dificultad de los diagnósticos etiológicos, dada la inespecificidad de los signos clínicos y la actitud diagnóstica poco o nada invasiva. De esta manera, el control del riesgo infeccioso nosocomial se resume en los siguientes elementos: un reservorio importante y difícilmente identificable, numerosos vectores potenciales, una población expuesta de manera variable al riesgo, todo ello sin olvidar las necesidades emocionales de los niños y los comportamientos «culturales».


title: S1 Subunit and Host Proteases as Potential Therapeutic Avenues for the Treatment of COVID-19

text: Abstract The novel corona virus (SARS-CoV-2) that causes severe acute respiratory syndrome, now called COVID-19 initially originated in Wuhan city of China and later spread across borders and infected more than two million people and killed over 2.9 lakh people all over the globe. This disease has been announced as pandemic by WHO. So far, there has been not much progress in terms of drug development for fighting against this deadliest virus, also no existing drugs has been reported completely effective for COVID-19 treatment owing to lack of effective therapeutic targets and a broad understanding of the viral behavior in target cell. Some reports have found and confirmed that SARS-CoV-2 like others SARS-CoVs utilizes angiotensin converting enzyme-2 receptor for making entry into target cell by binding to the receptor with its S1 subunit and employing host cell proteases for cleaving S2 subunit at S2′ in order to fuse with cell membrane. Thus, simultaneous blocking of S1 subunit and inactivation of proteases seem to be promising therapeutic targets for the development of effective novel drugs. In current write up we hypothesize that S1 subunit and host proteases as potential therapeutic avenues for the treatment of COVID-19.


title: Knowledge, Attitude and Practice Toward COVID-19 Among the Public in the Kingdom of Saudi Arabia: A Cross-Sectional Study

text: Background: Saudi Arabia has taken unprecedented and stringent preventive and precautionary measures against COVID-19 to control its spread, safeguard citizens and ensure their well-being. Public adherence to preventive measures is influenced by their knowledge and attitude toward COVID-19. This study investigated the knowledge, attitudes, and practices of the Saudi public, toward COVID-19, during the pandemic. Methods: This is a cross-sectional study, using data collected via an online self-reported questionnaire, from 3,388 participants. To assess the differences in mean scores, and identify factors associated with knowledge, attitudes, and practices toward COVID-19, the data were run through univariate and multivariable regression analyses, respectively. Results: The majority of the study participants were knowledgeable about COVID-19. The mean COVID-19 knowledge score was 17.96 (SD = 2.24, range: 3–22), indicating a high level of knowledge. The mean score for attitude was 28.23 (SD = 2.76, range: 6–30), indicating optimistic attitudes. The mean score for practices was 4.34 (SD = 0.87, range: 0–5), indicating good practices. However, the results showed that men have less knowledge, less optimistic attitudes, and less good practice toward COVID-19, than women. We also found that older adults are likely to have better knowledge and practices, than younger people. Conclusions: Our finding suggests that targeted health education interventions should be directed to this particular vulnerable population, who may be at increased risk of contracting COVID-19. For example, COVID-19 knowledge may increase significantly if health education programs are specifically targeted at men.


title: Detection of human coronaviruses in simultaneously collected stool samples and nasopharyngeal swabs from hospitalized children with acute gastroenteritis

text: BACKGROUND: Human coronaviruses (HCoVs) are a well-known cause of respiratory infections but their role in gastrointestinal infections is unclear. The objective of our study was to assess the significance of HCoVs in the etiology of acute gastroenteritis (AGE) in children <6 years of age. METHODS: Stool samples and nasopharyngeal (NP) swabs collected from 260 children hospitalized for AGE (160 also had respiratory symptoms) and 157 otherwise healthy control children admitted for elective surgery were tested for the presence of four HCoVs using real time RT-PCR. Registered at ClinicalTrials.gov (reg. NCT00987519). RESULTS: HCoVs were more frequent in patients with AGE than in controls (23/260, 8.8% versus 4/151, 2.6%; odds ratio, OR 3.3; 95% confidence interval, CI 1.3–10.0; P = 0.01). Three of four HCoV-positive members in the control group, asymptomatic when sampled, recalled gastrointestinal or respiratory symptoms within the previous 14 days. In patients with AGE, HCoVs were present in NP samples more often than in stools (22/256, 8.6%, versus 6/260, 2.3%; P = 0.0004). In 5/6 children with HCoVs detected in stools, the viruses were also detected in NP swabs. Patients had a significantly higher probability of HCoV detection in stool (OR 4; 95% CI 1.4–15.3; P = 0.006) and also in stool and/or NP (OR 3.3, 95% CI 1.3–10.0; P = 0.01) than healthy controls. All four HCoVs species were detected in stool and NP samples. CONCLUSIONS: Although HCoVs were more frequently detected in patients with AGE than in the control group, high prevalence of HCoVs in NP swabs compounded by their low occurrence in stool samples and detection of other viruses in stool samples, indicate that HCoVs probably play only a minor role in causing gastrointestinal illness in children <6 years old.


title: Hybridization Chain Reactions Targeting the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

text: In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coronavirus 2 (SARS–CoV-2) nucleocapsid phosphoproteins gene loci and human RNase P are proposed to provide an isothermal amplification screening tool. The proposed chain reactions target the complementary DNA (cDNA) of SARS–CoV-2, with loci corresponding to gold-standard polymerase chain reaction (PCR) loci. Four hybridization chain reaction reactions are demonstrated herein, targeting N1/N2/N3 loci and human RNase P. The design of the hybridization chain reaction, herein, is assisted with an algorithm. The algorithm helps to search target sequences with low local secondary structure and high hybridization efficiency. The loop domain of the fuel hairpin molecule H1 and H2, which are the tunable segments in such reactions, are used as an optimization parameter to improve the hybridization efficiency of the chain reaction. The algorithm-derived HCR reactions were validated with gel electrophoresis. All proposed reactions exhibit a hybridization complex with a molecular mass >1.5k base pairs, which is clear evidence of chain reaction. The hybridization efficiency trend revealed by gel electrophoresis corresponds nicely to the simulated data from the algorithm. The HCR reactions and the corresponding algorithm serve as a basis to further SARS–CoV-2 sensing applications and facilitate better screening strategies for the prevention of on-going pandemics.


title: Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries

text: Abstract From the end of 2019, an unprecedented novel coronavirus, which was named COVID-19 by the World Health Organization (WHO) emerged from Wuhan city, China. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 has continued to rise, with over 4 million confirmed-cases and over 300,000 deaths worldwide until mid-May. This study aims to present the effect of the promulgation of social distancing measures on the spread of COVID-19 in the cases of 10 highly infected countries. The authors focus on the statistics of the COVID-19 confirmed-cases and deaths in 10 highly infected countries, including The U.S., Spain, Italy, The U.K., France, Germany, Russia, Turkey, Iran and China, and the response to the pandemic of these countries in the period from January 11 to May 2, 2020. The relationships between the social distancing measures and the statistics of COVID-19 confirmed-cases and deaths were analyzed in order to elucidate the effectiveness of the social distancing measures on the spread of COVID-19 in 10 highly infected countries. The results showed it took1–4 weeks since the highest level of social distancing measures promulgation until the daily confirmed-cases and deaths showed signs of decreasing. The effectiveness of the social distancing measures on the spread of COVID-19 was different between the 10 focused countries. This variation is due to the difference in the levels of promulgated social distancing measures, as well as the difference in the COVID-19 spread situation at the time of promulgation between the countries.


title: Comparative features of infections of two Massachusetts (Mass) infectious bronchitis virus (IBV) variants isolated from Western Canadian layer flocks

text: BACKGROUND: Infectious bronchitis virus (IBV) is one of the leading causes of mortality and morbidity in chickens. There are numerous serotypes and variants, which do not confer cross protection resulting in failure of currently used IBV vaccines. Although variant IBV isolates with major genetic differences have been subjected to comparative studies, it is unknown whether minor genetic differences in IBV variants within a serotype are different in terms of pathogenesis and eliciting host responses. Two Massachusetts (Mass) variant IBV isolates recovered from commercial layer flocks in the Western Canadian provinces of Alberta (AB) and Saskatchewan (SK) were compared genetically and evaluated for their pathogenicity, tissue distribution and ability to recruit and replicate in macrophages. RESULTS: Although whole genome sequencing of these two Mass IBV isolates showed low similarity with the M41 vaccinal strain, they had an identical nucleotide sequence at open reading frames (ORFs) 3a, 3b, envelop (E), matrix (M), 5a and 5b. The rest of the ORFs of these 2 IBV isolates showed 99.9% nucleotide similarity. However, upon experimental infection, we found that the IBV isolate originating from AB was different to the one that originated in SK due to higher tracheal lesion scores and lower lung viral replication and lower genome loads in cecal tonsils. Nevertheless, both IBV isolates elicited host responses characterized by significant macrophage recruitment to the respiratory tract and there was evidence that both IBV isolates replicated within tracheal and lung macrophages. CONCLUSIONS: Overall, this study shows that Mass variant IBV isolates, although possessing minor genetic variations, can lead to significant differences in pathogenicity in young chickens. Further studies are required to investigate the pathogenicity of these two Mass variant IBV isolates in laying hens. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12917-018-1720-9) contains supplementary material, which is available to authorized users.


title: Proteinase‐activated receptor 1 (PAR1): A target for repurposing in the treatment of COVID‐19?

text: In the search to rapidly identify effective therapies that will mitigate the morbidity and mortality of COVID‐19, attention has been directed towards the repurposing of existing drugs. Candidates for repurposing include drugs that target COVID‐19 pathobiology, including agents that alter angiotensin signaling. Recent data indicate that key findings in COVID‐19 patients include thrombosis and endothelitis. Activation of PAR1 (Proteinase‐activated receptor 1), in particular by the serine protease thrombin, is a critical element in platelet aggregation and coagulation. PAR1 activation also impacts on the actions of other cell types involved in COVID‐19 pathobiology, including endothelial cells, fibroblasts and pulmonary alveolar epithelial cells. Vorapaxar is an approved inhibitor of PAR1, used for treatment of patients with myocardial infarction or peripheral arterial disease. Here, we discuss evidence implying a possible beneficial role for vorapaxar in the treatment of COVID‐19 patients and in addition, other as‐yet non‐approved antagonists of PAR1 and PAR4.


title: “Amantadine disrupts lysosomal gene expression; a hypothesis for COVID19 treatment “

text: Abstract SARS-coronavirus 2 is the causal agent of the COVID-19 outbreak. SARS-Cov-2 entry into a cell is dependent upon binding of the viral spike (S) protein to cellular receptor and on cleavage of the spike protein by the host cell proteases such as Cathepsin L and Cathepsin B. CTSL/B are crucial elements of lysosomal pathway and both enzymes are almost exclusively located in the lysosomes. CTSL disruption offers potential for CoVID-19 therapies. The mechanisms of disruption include: decreasing expression of CTSL, direct inhibition of CTSL activity and affecting the conditions of CTSL environment (increase pH in the lysosomes). We have conducted a high throughput drug screen gene expression analysis to identify compounds that would downregulate the expression of CTSL/CTSB. One of the top significant results shown to downregulate the expression of the CTSL gene is amantadine (10uM). Amantadine was approved by the US Food and Drug Administration in 1968 as a prophylactic agent for influenza and later for Parkinson's disease. It is available as a generic drug. Amantadine in addition to downregulating CTSL appears to further disrupt lysosomal pathway, hence, interfering with the capacity of the virus to replicate. It acts as a lysosomotropic agent altering the CTSL functional environment. We hypothesize that amantadine could decrease the viral load in SARS-CoV-2 positive patients and as such it may serve as a potent therapeutic decreasing the replication and infectivity of the virus likely leading to better clinical outcomes. Clinical studies will be needed to examine the therapeutic utility of amantadine in COVID-19 infection.


title: Use of Simple Laboratory Features to Distinguish the Early Stage of Severe Acute Respiratory Syndrome from Dengue Fever

text: Background. The diagnosis of severe acute respiratory syndrome (SARS) is difficult early in the illness, because its presentation resembles that of other nonspecific viral fevers, such as dengue. Dengue fever is endemic in many of the countries in which the large SARS outbreaks occurred in early 2003. Misdiagnosis may have serious public health consequences. We aimed to determine simple laboratory features to differentiate SARS from dengue. Methods. We compared the laboratory features of 55 adult patients with SARS at presentation (who were all admitted before radiological changes had occurred) and 147 patients with dengue. Features independently predictive of dengue were modeled by multivariate logistic regression to create a diagnostic tool with 100% specificity for dengue. Results. Multivariate analysis identified 3 laboratory features that together are highly predictive of a diagnosis of dengue and able to rule out the possibility of SARS: platelet count of <140 × 10(9) platelets/L, white blood cell count of <5 × 10(9)cells/L, and aspartate aminotransferase level of >34 IU/L. A combination of these parameters has a sensitivity of 75% and a specificity of 100%. Conclusions. Simple laboratory data may be helpful for the diagnosis of disease in adults admitted because of fever in areas in which dengue is endemic when the diagnosis of SARS needs to be excluded. Application of this information may help to optimize the use of isolation rooms for patients presenting with nonspecific fever.


title: Recommendations of the coronavirus study group for the nomenclature of the structural proteins, mRNAs, and genes of coronaviruses

text: Abstract We propose a nomenclature to replace the various systems currently in use to designate coronavirus structural proteins, mRNAs, and genes/open reading frames. The nonstructural proteins have not been addressed.


title: Latent viral infections of the nervous system: Role of the host immune response

text: Abstract Viruses that infect the nervous system may cause acute, chronic or latent infections. Despite the so-called immunoprivileged status of the nervous system, immunosurveillance plays an important role in the fate of viral infection of the brain. Herpes simplex virus 1 (HSV-1) persists in the nervous system for the life of the host with periodic stress induced reactivation that produces progeny viruses. Prevention of reactivation requires a complex interplay between virus neurons, and immune response. New evidence supports the view that CD8+T cells employing both lytic granule- and IFN-gamma-dependent effectors are essential in setting up and maintaining HSV-1 latency. HSV-1 infection of the nervous system can be seen as a parasitic invasion which leaves the individual at risk for subsequent reactivation and disease. The recent observation that herpes virus latency may confer protection against experimental bacterial infection suggests that unexpected symbiosis may exist between latent viruses and the infected nervous system of its host.


“The King of Terrors” Revisited: The Smallpox Vaccination Campaign and Its Lessons for Future Biopreparedness(1)


title: Uptake of Recommended Vaccines and Its Associated Factors Among Malaysian Pilgrims During Hajj and Umrah 2018

text: This study aimed to assess the uptake of recommended vaccines and to identify the factors associated with the vaccines' uptake among Malaysian Hajj and Umrah pilgrims. A cross-sectional survey among Malaysian Hajj and Umrah pilgrims in 2018. The uptake of the recommended vaccines was surveyed through an anonymous self-administered questionnaire to pilgrims attending a pre-departure Hajj/Umrah orientation course. Descriptive statistics were used for elaborating the demographic characteristics and vaccines uptake of the respondents. Multiple logistic regression was used for predicting the factors associated with the vaccines' uptake. A total of 1,274 pilgrims participated in the study with a mean age (standard deviation) of 42.42 (15.6). A total of 833 (65.4%) participants were females and 232 of the participants (18.2%) had at least more than one chronic disease. The uptake of influenza and pneumococcal vaccines were 28.6% (364/1,274) and 25.4% (324/1,274), respectively. Among the 527 pilgrims who were “at increased risk” of infections, 168 (31.9%) and 184 (34.9%) received influenza and pneumococcal vaccines, respectively. Gender, marital status and occupation were the common predictors associated with vaccines uptake. The vaccination uptake among Malaysian Hajj and Umrah pilgrims is low and declining from previous years. Educating the pilgrims toward vaccine uptake is essential and exploring the barriers for vaccination.