title: A Systematic Analysis of Host Factors Reveals a Med23-Interferon-λ Regulatory Axis against Herpes Simplex Virus Type 1 Replication

text: Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome.


title: Neutralizing antibodies against porcine epidemic diarrhea virus block virus attachment and internalization

text: BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is emerging as a pathogenic coronavirus that causes a huge economic burden to the swine industry. Interaction of the viral spike (S) surface glycoprotein with the host cell receptor is recognized as the first step of infection and is the main determinant of virus tropism. The mechanisms by which neutralizing antibodies inhibit PEDV have not been defined. Isolating PEDV neutralizing antibodies are crucial to identifying the receptor-binding domains of the viral spike and elucidating the mechanism of protection against PEDV infection. METHODS: B cell hybridoma technique was used to generate hybridoma cells that secrete specific antibodies. E.coli prokaryotic expression system and Bac-to-Bac expression system were used to identify the target protein of each monoclonal antibody. qPCR was performed to analyze PEDV binding to Vero E6 cells with neutralizing antibody. RESULTS: We identified 10 monoclonal antibodies using hybridoma technology. Remarkably, 4 mAbs (designed 2G8, 2B11, 3D9, 1E3) neutralized virus infection potently, of which 2B11 and 1E3 targeted the conformational epitope of the PEDV S protein. qPCR results showed that both 2B11 and 2G8 blocked virus entry into Vero cells. CONCLUSION: The data suggested that PEDV neutralizing antibody inhibited virus infection by binding to infectious virions, which could work as a tool to find the receptor-binding domains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-1042-3) contains supplementary material, which is available to authorized users.


title: Therapeutic effect of high-flow nasal cannula on severe COVID-19 patients in a makeshift intensive-care unit: A case report

text: INTRODUCTION: Several intensive-care units (ICUs) in Wuhan are nonstandard wards that were repurposed from general wards. Considering the shortage of medical resources and the need to prevent nosocomic infection, the respiratory-treatment strategy in these nonstandard ICUs is different from those in general wards and standard ICUs. High-flow nasal cannula (HFNC) plays an important role in nonstandard ICUs and is beneficial to the patients therein. PATIENT CONCERNS: In this study, we analyzed four cases of HFNC-treated patients with severe coronavirus disease 2019 (COVID-19) in a makeshift ICU and summarized our experience. DIAGNOSES: Four patients diagnosed with COVID-19 according to World Health Organization (WHO) interim guidance were admitted to the makeshift ICU. INTERVENTIONS: All patients had oxygen treatment with HFNC, as well as regular treatment of antivirals and traditional Chinese medicine. OUTCOMES: Two patients survived after treatment, while the other two died from acute respiratory distress syndrome (ARDS) and heart failure, respectively. CONCLUSION: Patients with severe and critical COVID-19 often have poor prognoses after mechanical ventilation, exhibiting corresponding complications such as ventilator-associated pneumonia and deep-vein thrombosis, which significantly prolongs length of stay in the ICU. HFNC could prevent intubation in some patients, thereby avoiding the above complications; however, this needs confirmation in further clinical studies. This treatment reduced difficulty and workloads for healthcare professionals, had good tolerability for patients, might not significantly increase the risk of infection for healthcare professionals, and do not require additional preventive measures against nosocomic infection. HFNC treatment has its advantages in providing oxygen therapy in COVID-19, but healthcare professionals should still pay close attention to changes in patients’ oxygenation rates and respiratory frequency.


title: Rapid transit in the immune cells: the role of mRNA turnover regulation

text: There have been recent, significant advances about the role of mRNA turnover in controlling gene expression in immune cells. Post‐transcriptional regulation of gene expression contributes to the characteristics of many of the processes underlying the immune response by ensuring early, rapid, and transient action. The emphasis of this review is on current work that deals with the regulation of mRNA decay during innate immunity against microbes and T cell activation as a model of the adaptive response.


title: An international survey in Latin America on the practice of interventional cardiology during the COVID-19 pandemic, with a particular focus on myocardial infarction

text: INTRODUCTION: A reduction in the number of interventional cardiology procedures has emerged as a result of the COVID-19 pandemic. A survey was performed to quantify this decrease and the impact on the management of myocardial infarction in Latin America. METHODS: A telematic survey was conducted for all countries in Latin America. Diagnostic catheterisations, coronary and structural interventions, as well as the incidence and delay to reperfusion therapy of myocardial infarction (STEMI), were recorded. Two periods were compared: from 24 February to 8 March 2020 (pre-COVID-19) and another 2‑week period that varied according to country (COVID-19). RESULTS: Responses were obtained from 79 centres in 20 countries. There was a significant decrease in the number of diagnostic procedures (−65.2%), coronary interventions (−59.4%), structural therapeutics (−86.1%) and STEMI care (−51.2%). A decrease was noted in the incidence of STEMI, but also a delay in the time to STEMI reperfusion. While there was a variation in activity in interventional cardiology between countries, patient behaviour was rather homogeneous. CONCLUSIONS: A significant reduction in healthcare activity has been noted during the COVID-19 pandemic, including STEMI care, with the risk of increased mortality and/or morbidity following STEMI. Healthcare providers should encourage patients with suspected symptoms of STEMI to call for emergency care to ensure rapid diagnosis and timely reperfusion treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12471-020-01440-y) contains supplementary material which is available to authorized users.


title: NAMI New Hampshire maintaining community connectedness

text: The National Alliance on Mental Illness New Hampshire (NAMI‐NH) is working to maintain community connectedness in the midst of this pandemic via its education and advocacy programs, now conducted remotely, and its virtual support groups.


title: Design of a Multiepitope-Based Peptide Vaccine against the E Protein of Human COVID-19: An Immunoinformatics Approach

text: BACKGROUND: A new endemic disease has spread across Wuhan City, China, in December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a “public-health emergency of international concern” due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus, the objective of this study is to design a multiepitope peptide vaccine against COVID-19 using an immunoinformatics approach. METHOD: Several techniques facilitating the combination of the immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the envelope protein of 2019-nCoV as a target. RESULTS: Extensive mutations, insertion, and deletion were discovered with comparative sequencing in the COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. CONCLUSION: The T-cell epitope-based peptide vaccine was designed for COVID-19 using the envelope protein as an immunogenic target. Nevertheless, the proposed vaccine rapidly needs to be validated clinically in order to ensure its safety and immunogenic profile to help stop this epidemic before it leads to devastating global outbreaks.


title: Online team‐based learning sessions as interactive methodologies during the pandemic

text: The medical education system is currently facing robust challenges as a consequence of the COVID-19 pandemic. One of them is the maintenance of interactive learning techniques such as Team-Based Learning (TBL). TBL is an interactive teaching method that is learner-centered and instructor-directed. It sequentially involves self-work followed by teamwork. After providing the reading material, students are commonly asked to solve 10-20 multiple choice questions, known as the individual readiness assurance test (iRAT). Students are then assigned to answer the same questions while working together in teams, the team readiness assurance test (tRAT).


title: Airport Exit and Entry Screening for Ebola — August–November 10, 2014

text: In response to the largest recognized Ebola virus disease epidemic now occurring in West Africa, the governments of affected countries, CDC, the World Health Organization (WHO), and other international organizations have collaborated to implement strategies to control spread of the virus. One strategy recommended by WHO calls for countries with Ebola transmission to screen all persons exiting the country for "unexplained febrile illness consistent with potential Ebola infection." Exit screening at points of departure is intended to reduce the likelihood of international spread of the virus. To initiate this strategy, CDC, WHO, and other global partners were invited by the ministries of health of Guinea, Liberia, and Sierra Leone to assist them in developing and implementing exit screening procedures. Since the program began in August 2014, an estimated 80,000 travelers, of whom approximately 12,000 were en route to the United States, have departed by air from the three countries with Ebola transmission. Procedures were implemented to deny boarding to ill travelers and persons who reported a high risk for exposure to Ebola; no international air traveler from these countries has been reported as symptomatic with Ebola during travel since these procedures were implemented.


title: An efficient microwave-assisted synthesis and biological properties of polysubstituted pyrimidinyl- and 1,3,5-triazinylphosphonic acids

text: Abstract Polysubstituted pyrimidinylphosphonic and 1,3,5-triazinylphosphonic acids with potential biological properties were prepared in high yields by the microwave-assisted Michaelis–Arbuzov reaction of trialkyl phosphite with the corresponding halopyrimidines and halo-1,3,5-triazines, respectively, followed by the standard deprotection of the phosphonate group using TMSBr in acetonitrile. 4,6-Diamino-5-chloropyrimidin-2-ylphosphonic acid (7a) was found to exhibit a weak to moderate anti-influenza activity (28–50 μM) and may represent a novel hit for further SAR studies and antiviral improvement.


title: Just the Facts: Protecting frontline clinicians during the COVID-19 pandemic

text: There is no patient emergency more important than protecting health care workers during a pandemic.


title: False‐positive reverse transcriptase polymerase chain reaction screening for SARS‐CoV‐2 in the setting of urgent head and neck surgery and otolaryngologic emergencies during the pandemic: Clinical implications

text: BACKGROUND: No reports describe falsepositive reverse transcriptase polymerase chain reaction (RT‐PCR) for novel coronavirus in preoperative screening. METHODS: Preoperative patients had one or two nasopharyngeal swabs, depending on low or high risk of viral transmission. Positive tests were repeated. RESULTS: Forty‐three of 52 patients required two or more preoperative tests. Four (9.3%) had discrepant results (positive/negative). One of these left the coronavirus disease (COVID) unit against medical advice despite an orbital abscess, with unknown true disease status. The remaining 3 of 42 (7.1%) had negative repeat RT‐PCR. Although ultimately considered falsepositives, one was sent to a COVID unit postoperatively and two had urgent surgery delayed. Assuming negative repeat RT‐PCR, clear chest imaging, and lack of subsequent symptoms represent the “gold standard,” RT‐PCR specificity was 0.97. CONCLUSIONS: If false positives are suspected, we recommend computed tomography (CT) of the chest and repeat RT‐PCR. Validated serum immunoglobulin testing may ultimately prove useful.


Severe community-acquired pneumonia


title: Chapter 5 The GRANCH Techniques for Analysis of DNA, RNA and Protein Sequences

text: Abstract: The very rapid growth in molecular sequence data from the daily accretion of large gene and protein sequencing projects have led to issues regarding viewing and analyzing the massive amounts of data. Graphical representation and numerical characterization of DNA, RNA and protein sequences have exhibited great potential to address these concerns. We review here in brief several different formulations of these representations and examples of applications to diverse problems based on what this author had presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia in 2010. In particular, we note several insights that were gained from such representations, and the applications to the bio-medicinal field.


The dark side of COVID‐19: The need of integrated medicine for children with special care needs


title: Cardiological Society of India: Document on Acute MI care during COVID-19

text: Abstract The unprecedented and rapidly spreading Coronavirus Disease-19 (COVID-19) pandemic has challenged public health care systems globally. Based on worldwide experience, India has initiated a nationwide lockdown to prevent the exponential surge of cases. During COVID-19, management of cardiovascular emergencies like acute Myocardial Infarction (MI) may be compromised. Cardiological Society of India (CSI) has ventured in this moment of crisis to evolve a consensus document for care of acute MI. However, this care should be individualized, based on local expertise and governmental advisories.


title: Coincidence of COVID-19 Infection and Smell—Taste Perception Disorders

text: Many reports by physicians and patients during the 2019 to 2020 pandemic indicate that COVID-19 is associated with elevated levels of odor and taste perception disorders (anosmia, hyposmia, ageusia, and/or dysgeusia). Recent increase in olfactory dysfunction in patients referred to ear nose and throat clinics and COVID-19 infection at the same time encouraged us to examine anosmic/hyposmic patients to establish any association between these signs. It has been shown that the COVID-19 virus exploits the uses angiotensin-converting enzyme 2 receptor to obtain cell entry. This result increases the interest to examine the expression of angiotensin-converting enzyme 2 in neurological tissue, and to assess the possible contribution of damage. This mini review provides fundamental knowledge on coincidence of COVID-19 infection and smell—taste perception disorders from an objective perspective.


title: Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase

text: Abstract The genetically diverse Orthocoronavirinae (CoV) family is prone to cross species transmission and disease emergence in both humans and livestock. Viruses similar to known epidemic strains circulating in wild and domestic animals further increase the probability of emergence in the future. Currently, there are no approved therapeutics for any human CoV presenting a clear unmet medical need. Remdesivir (RDV, GS-5734) is a monophosphoramidate prodrug of an adenosine analog with potent activity against an array of RNA virus families including Filoviridae, Paramyxoviridae, Pneumoviridae, and Orthocoronavirinae, through the targeting of the viral RNA dependent RNA polymerase (RdRp). We developed multiple assays to further define the breadth of RDV antiviral activity against the CoV family. Here, we show potent antiviral activity of RDV against endemic human CoVs OC43 (HCoV-OC43) and 229E (HCoV-229E) with submicromolar EC50 values. Of known CoVs, the members of the deltacoronavirus genus have the most divergent RdRp as compared to SARS- and MERS-CoV and both avian and porcine members harbor a native residue in the RdRp that confers resistance in beta-CoVs. Nevertheless, RDV is highly efficacious against porcine deltacoronavirus (PDCoV). These data further extend the known breadth and antiviral activity of RDV to include both contemporary human and highly divergent zoonotic CoV and potentially enhance our ability to fight future emerging CoV.


title: Does COVID-19 cause axonal GBS?

text: • Recent reports of Guillain-Barré Syndrome associated with COVID-19 have described both the axonal and demyelinating subtypes. • In this letter , I highlight features that suggest a predominantly axonal rather than demyelinating electrophysiology in these cases.


title: The relationship of compassion and self-compassion with personality and emotional intelligence in organizations

text: The two studies presented in this article examine the relationships of personality traits and trait emotional intelligence (EI) with compassion and self-compassion in samples of Italian workers. Study 1 explored the relationship between trait EI and both compassion and self-compassion, controlling for the effects of personality traits in 219 workers of private Italian organizations. Hierarchical regression analyses revealed that trait EI explained variance beyond that accounted for by personality traits in relation to both compassion and self-compassion. Study 2 analyzed the contribution of trait EI in mediating the relationship between personality traits and both compassion and self-compassion of 231 workers from public Italian organizations with results supporting the mediating role of trait EI.


title: Viruses in asthma: The role of viruses in childhood respiratory infections

text: Current evidence suggests that the overall load of infectious agents, including respiratory viruses, encountered early in life is an important factor influencing maturation of the immune system from a type 2 bias at birth towards predominantly type 1 responses, thus avoiding atopic diseases. The ‘hygiene hypothesis’ proposes that the relatively sterile environment present in industrialised Western countries has contributed to the recent epidemic of asthma and atopy. Whether specific infections are of greater or lesser protective value is an important question if strategies are to be derived to mimic the beneficial effects of childhood infection whilst avoiding morbidity and potential mortality of the natural pathogens. Infection by respiratory viruses is a major trigger of wheezing in infants and of exacerbations of asthma in older children. Viruses are detected in up to 85% of such episodes. Rhinovirus is common in all age groups; respiratory syncytial virus (RSV) is most important in infants and young children. Knowledge of the immunopathogenetic mechanisms of virus infection in the asthmatic airway will lead to the development of new treatments for virus-induced asthma.


title: SARS-CoV-2 and COVID-19 in older adults: what we may expect regarding pathogenesis, immune responses, and outcomes

text: SARS-CoV-2 virus, the causative agent of the coronavirus infectious disease-19 (COVID-19), is taking the globe by storm, approaching 500,000 confirmed cases and over 21,000 deaths as of March 25, 2020. While under control in some affected Asian countries (Taiwan, Singapore, Vietnam), the virus demonstrated an exponential phase of infectivity in several large countries (China in late January and February and many European countries and the USA in March), with cases exploding by 30–50,000/day in the third and fourth weeks of March, 2020. SARS-CoV-2 has proven to be particularly deadly to older adults and those with certain underlying medical conditions, many of whom are of advanced age. Here, we briefly review the virus, its structure and evolution, epidemiology and pathogenesis, immunogenicity and immune, and clinical response in older adults, using available knowledge on SARS-CoV-2 and its highly pathogenic relatives MERS-CoV and SARS-CoV-1. We conclude by discussing clinical and basic science approaches to protect older adults against this disease.


title: Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs

text: Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti–SARS-CoV activity. A drug-screening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, β-1b, α-n1, α-n3, and human leukocyte interferon α. These findings support clinical testing of approved interferons for the treatment of SARS.


title: In Situ Tagged nsp15 Reveals Interactions with Coronavirus Replication/Transcription Complex-Associated Proteins

text: Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive. nsp15 localizes to sites of RNA replication, but whether it acts independently or requires additional interactions for its function remains unknown. To begin to address these questions, we created an in situ tagged form of nsp15 using the prototypic CoV, mouse hepatitis virus (MHV). In MHV, nsp15 contains the genomic RNA packaging signal (P/S), a 95-bp RNA stem-loop structure that is not required for viral replication or nsp15 function. Utilizing this knowledge, we constructed an internal hemagglutinin (HA) tag that replaced the P/S. We found that nsp15-HA was localized to discrete perinuclear puncta and strongly colocalized with nsp8 and nsp12, both well-defined members of the RTC, but not the membrane (M) protein, involved in virus assembly. Finally, we found that nsp15 interacted with RTC-associated proteins nsp8 and nsp12 during infection, and this interaction was RNA independent. From this, we conclude that nsp15 localizes and interacts with CoV proteins in the RTC, suggesting it plays a direct or indirect role in virus replication. Furthermore, the use of in situ epitope tags could be used to determine novel nsp-nsp interactions in coronaviruses.


title: COVID-19 and newborn health: systematic review

text: OBJECTIVE. To describe perinatal and neonatal outcomes in newborns exposed to SARS-CoV-2. METHODS. A systematic review was conducted by searching PubMed Central, LILACS, and Google Scholar using the keywords ‘covid ’ AND ‘newborn’ OR ‘child’ OR ‘infant,’ on 18 March 2020, and again on 17 April 2020. One researcher conducted the search and extracted data on demographics, maternal outcomes, diagnostic tests, imaging, and neonatal outcomes. RESULTS. Of 256 publications identified, 20 met inclusion criteria and comprised neonatal outcome data for 222 newborns whose mothers were suspected or confirmed to be SARS-CoV-2 positive perinatally (17 studies) or of newborns referred to hospital with infection/pneumonia (3 studies). Most (12 studies) were case-series reports; all were from China, except three (Australia, Iran, and Spain). Of the 222 newborns, 13 were reported as positive for SARS-CoV-2; most of the studies reported no or mild symptoms and no adverse perinatal outcomes. Two papers among those from newborns who tested positive reported moderate or severe clinical characteristics. Five studies using data on umbilical cord blood, placenta, and/or amniotic fluid reported no positive results. Nine studies reported radiographic imaging, including 5 with images of pneumonia, increased lung marking, thickened texture, or high-density nodular shadow. Minor, non-specific changes in biochemical variables were reported. Studies that tested breast milk reported negative SARS-CoV-2 results. CONCLUSIONS. Given the paucity of studies at this time, vertical transmission cannot be confirmed or denied. Current literature does not support abstaining from breastfeeding nor separating mothers and newborns. Further evidence and data collection networks, particularly in the Americas, are needed for establishing definitive guidelines and recommendations.


title: The Molecular Biology of Coronaviruses

text: Abstract Coronaviruses are large, enveloped RNA viruses of both medical and veterinary importance. Interest in this viral family has intensified in the past few years as a result of the identification of a newly emerged coronavirus as the causative agent of severe acute respiratory syndrome (SARS). At the molecular level, coronaviruses employ a variety of unusual strategies to accomplish a complex program of gene expression. Coronavirus replication entails ribosome frameshifting during genome translation, the synthesis of both genomic and multiple subgenomic RNA species, and the assembly of progeny virions by a pathway that is unique among enveloped RNA viruses. Progress in the investigation of these processes has been enhanced by the development of reverse genetic systems, an advance that was heretofore obstructed by the enormous size of the coronavirus genome. This review summarizes both classical and contemporary discoveries in the study of the molecular biology of these infectious agents, with particular emphasis on the nature and recognition of viral receptors, viral RNA synthesis, and the molecular interactions governing virion assembly.


title: Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health

text: The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.


title: A review of bronchiolitis obliterans syndrome and therapeutic strategies

text: Lung transplantation is an important treatment option for patients with advanced lung disease. Survival rates for lung transplant recipients have improved; however, the major obstacle limiting better survival is bronchiolitis obliterans syndrome (BOS). In the last decade, survival after lung retransplantation has improved for transplant recipients with BOS. This manuscript reviews BOS along with the current therapeutic strategies, including recent outcomes for lung retransplantation.


title: Viral genome sequencing by random priming methods

text: BACKGROUND: Most emerging health threats are of zoonotic origin. For the overwhelming majority, their causative agents are RNA viruses which include but are not limited to HIV, Influenza, SARS, Ebola, Dengue, and Hantavirus. Of increasing importance therefore is a better understanding of global viral diversity to enable better surveillance and prediction of pandemic threats; this will require rapid and flexible methods for complete viral genome sequencing. RESULTS: We have adapted the SISPA methodology [1-3] to genome sequencing of RNA and DNA viruses. We have demonstrated the utility of the method on various types and sources of viruses, obtaining near complete genome sequence of viruses ranging in size from 3,000–15,000 kb with a median depth of coverage of 14.33. We used this technique to generate full viral genome sequence in the presence of host contaminants, using viral preparations from cell culture supernatant, allantoic fluid and fecal matter. CONCLUSION: The method described is of great utility in generating whole genome assemblies for viruses with little or no available sequence information, viruses from greatly divergent families, previously uncharacterized viruses, or to more fully describe mixed viral infections.


title: Evolution of infectious bronchitis virus in the field after homologous vaccination introduction

text: Despite the fact that vaccine resistance has been typically considered a rare phenomenon, some episodes of vaccine failure have been reported with increasing frequency in intensively-raised livestock. Infectious bronchitis virus (IBV) is a widespread avian coronavirus, whose control relies mainly on extensive vaccine administration. Unfortunately, the continuous emergence of new vaccine-immunity escaping variants prompts the development of new vaccines. In the present work, a molecular epidemiology study was performed to evaluate the potential role of homologous vaccination in driving IBV evolution. This was undertaken by assessing IBV viral RNA sequences from the ORF encoding the S1 portion of viral surface glycoprotein (S) before and after the introduction of a new live vaccine on broiler farms in northern-Italy. The results of several biostatistics analyses consistently demonstrate the presence of a higher pressure in the post-vaccination period. Natural selection was detected essentially on sites located on the protein surface, within or nearby domains involved in viral attachment or related functions. This evidence strongly supports the action of vaccine-induced immunity in conditioning viral evolution, potentially leading to the emergence of new vaccine-escape variants. The great plasticity of rapidly-evolving RNA-viruses in response to human intervention, which extends beyond the poultry industry, is demonstrated, claiming further attention due to their relevance for animal and especially human health.


title: Sustainable Designed Pavement Materials

text: This Special Issue “Sustainable Designed Pavement Materials” has been proposed and organized as a means to present recent developments in the field of environmentally-friendly designed pavement materials. For this reason, articles included in this special issue relate to different aspects of pavement materials, from industry solid waste recycling to pavement materials recycling, from pavement materials modification to asphalt performance characterization, from pavement defect detection to pavement maintenance, and from asphalt pavement to cement concrete pavement, as highlighted in this editorial.


title: Rumor Detection Based On Propagation Graph Neural Network With Attention Mechanism

text: Rumors on social media have always been an important issue that seriously endangers social security. Researches on timely and effective detection of rumors have aroused lots of interest in both academia and industry. At present, most existing methods identify rumors based solely on the linguistic information without considering the temporal dynamics and propagation patterns. In this work, we aim to solve rumor detection task under the framework of representation learning. We first propose a novel way to construct the propagation graph by following the propagation structure (who replies to whom) of posts on Twitter. Then we propose a gated graph neural network based algorithm called PGNN, which can generate powerful representations for each node in the propagation graph. The proposed PGNN algorithm repeatedly updates node representations by exchanging information between the neighbor nodes via relation paths within a limited time steps. On this basis, we propose two models, namely GLO-PGNN (rumor detection model based on the global embedding with propagation graph neural network) and ENS-PGNN (rumor detection model based on the ensemble learning with propagation graph neural network). They respectively adopt different classification strategies for rumor detection task, and further improve the performance by including attention mechanism to dynamically adjust the weight of each node in the propagation graph. Experiments on a real-world Twitter dataset demonstrate that our proposed models achieve much better performance than state-of-the-art methods both on the rumor detection task and early detection task.


title: Rapid Identification of the Mediterranean Fruit Fly (Diptera: Tephritidae) by Loop-Mediated Isothermal Amplification

text: The Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), ranks as one of the world’s most destructive agricultural pests. This pest is also widespread and highly invasive; thus, it is a high priority for pest detection and quarantine programs. Although Mediterranean fruit fly adult and third-instar larvae can usually be identified and distinguished from other species by morphological keys, it is often difficult or impossible to identify or distinguish this species from other tephritids by using material from other stages of development. In such situations, use of a molecular technique known as loop-mediated isothermal amplification (LAMP) would be valuable as a rapid and robust alternative species diagnostic tool. This method uses isothermal conditions and requires only relatively inexpensive equipment. In this study we have developed a simple and rapid procedure that combines a Chelex-based DNA extraction procedure with LAMP to rapidly detect the presence of Mediterranean fruit fly DNA and discriminate it from other species, by using material from different stages of development. Amounts of DNA as little as that recovered from a single egg were shown to be adequate for the analysis, and LAMP itself required only 45 min to complete.


title: The polypeptides of human and mouse coronaviruses

text: The polypeptide compositions of two coronaviruses, human coronavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV3), were characterised on polyacrylamide gels. Similar polypeptide patterns were observed for both viruses consisting of large surface projection glycopolypeptides of mol. wt. 160,000 and 105,000 for HCV 229E, and 170,000 and 90,000 for MHV3, two small polypeptides of mol. wt. varying from 24,000 to 20,000, and a polypeptide of mol. wt. 50,000. The results are discussed with respect to previous reports of the polypeptides of these and other coronaviruses.


title: Decrease in Hospital Admissions for Transient Ischemic Attack, Mild, and Moderate Stroke During the COVID-19 Era

text: Since the onset of the coronavirus 2019 (COVID-19) pandemic, doctors and public authorities have demonstrated concern about the reduction in quality of care for other health conditions due to social restrictions and lack of resources. Using a population-based stroke registry, we investigated the impact of the onset of the COVID-19 pandemic in stroke admissions in Joinville, Brazil. METHODS: Patients admitted after the onset of COVID-19 restrictions in the city (defined as March 17, 2020) were compared with those admitted in 2019. We analyzed differences between stroke incidence, types, severity, reperfusion therapies, and time from stroke onset to admission. Statistical tests were also performed to compare the 30 days before and after COVID-19 to the same period in 2019. RESULTS: We observed a decrease in total stroke admissions from an average of 12.9/100 000 per month in 2019 to 8.3 after COVID-19 (P=0.0029). When compared with the same period in 2019, there was a 36.4% reduction in stroke admissions. There was no difference in admissions for severe stroke (National Institutes of Health Stroke Scale score >8), intraparenchymal hemorrhage, and subarachnoid hemorrhage. CONCLUSIONS: The onset of COVID-19 was correlated with a reduction in admissions for transient, mild, and moderate strokes. Given the need to prevent the worsening of symptoms and the occurrence of medical complications in these groups, a reorganization of the stroke-care networks is necessary to reduce collateral damage caused by COVID-19.


title: Ultra-rapid delivery of specialty field hospitals to combat COVID-19: Lessons learned from the Leishenshan Hospital project in Wuhan

text: With the outbreak of the 2019 novel coronavirus (COVID-19) epidemic in Wuhan, China, in January 2020, the escalating number of confirmed and suspected cases overwhelmed the admission capacity of the designated hospitals. Two specialty field hospitals—Huoshenshan and Leishenshan—were designed, built and commissioned in record time (9–12 days) to address the outbreak. This study documents the design and construction of Leishenshan Hospital. Based on data collected from various sources such as the semi-structured interviews of key stakeholders from Leishenshan Hospital, this study found that adhering to a product, organization, and process (POP) modeling approach combined with building information modeling (BIM) allowed for the ultra-rapid creation, management, and communication of project-related information, resulting in the successful development of this fully functional, state-of-the-art infectious disease specialty hospital. With the unfortunate ongoing international COVID-19 outbreak, many countries and regions face similar hospital capacity problems. It is thus expected that the lessons learned from the design, construction and commissioning of Leishenshan Hospital can provide a valuable reference to the development of specialty field hospitals in other countries and regions.


Comment on: COVID‐19 pandemic: perspectives on an unfolding crisis – a UK perspective


title: Acute Life-threatening Cardiac Tamponade in a Mechanically Ventilated Patient with COVID-19 Pneumonia

text: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently evolved as a pandemic disease. Although the respiratory system is predominantly affected, cardiovascular complications have been frequently identified, including acute myocarditis, myocardial infarction, acute heart failure, arrhythmias and venous thromboembolic events. Pericardial disease has been rarely reported. We present a case of acute life-threatening cardiac tamponade caused by a small pericardial effusion in a mechanically ventilated patient with severe COVID-19 associated pneumonia. The patient presented acute circulatory collapse with hemodynamic features of cardiogenic or obstructive shock. Bedside echocardiography permitted prompt diagnosis and life-saving pericardiocentesis. Further investigation revealed no other apparent cause of pericardial effusion except for SARS-CoV-2 infection. Cardiac tamponade may complicate COVID-19 and should be included in the differential diagnosis of acute hemodynamic deterioration in mechanically ventilated COVID-19 patients.


title: Concerns about pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) studies in the new therapeutic area of COVID-19 infection

text: In the context of the COVID-19 pandemic, several drugs have been repurposed as potential candidates for the treatment of COVID-19 infection. While preliminary choices were essentially based on in vitro potency, clinical translation into effective therapies may be challenging due to unfavorable in vivo pharmacokinetic properties at the doses chosen for this new indication of COVID-19 infection. However, available pharmacokinetic and pharmacokinetic-pharmacodynamic studies suffer from severe limitations leading to unreliable conclusions, especially in term of dosing optimization. In this paper we propose to highlight these limitations and to identify some of the major requirements that need to be addressed in designing PK and PK-PD studies in this era of COVID. A special attention should be paid to pre-analytical and analytical requirements and to the proper collection of covariates affecting dose-exposure relationships (co-medications, use of specific organ support techniques and other clinical and para-clinical data). We also promote the development of population PK and PK-PD models specifically dedicated to COVID-19 patients since those previously developed for other diseases (SEL, malaria, HIV) and clinical situations (steady-state, non-ICU patients) are not representative of severe patients. Therefore, implementation of well-designed PK and PD studies targeted to COVID-19 patients is urgently needed. For that purpose we call for multi-institutional collaborative work and involvement of clinical pharmacologists in multidisciplinary research consortia.


title: Surface-displayed porcine reproductive and respiratory syndrome virus from cell culture onto gram-positive enhancer matrix particles

text: Vaccine immunization is now one of the most effective ways to control porcine reproductive and respiratory syndrome virus (PRRSV) infection. Impurity is one of the main factors affecting vaccine safety and efficacy. Here we present a novel innovative PRRSV purification approach based on surface display technology. First, a bifunctional protein PA-GRFT (protein anchor-griffithsin), the crucial factor in the purification process, was successfully produced in Escherichia coli yielding 80 mg/L of broth culture. Then PRRSV purification was performed by incubation of PA-GRFT with PRRSV and gram-positive enhancer matrix (GEM) particles, followed by centrifugation to collect virions loaded onto GEM particles. Our results showed that most of the bulk impurities had been removed, and PA-GRFT could capture PRRSV onto GEM particles. Our lactic acid bacteria-based purification method, which is promising as ease of operation, low cost and easy to scale-up, may represent a candidate method for the large-scale purification of this virus for vaccine production.


title: Precautions and recommendations for orthodontic settings during the COVID-19 outbreak: A review

text: Abstract Introduction Coronavirus disease 2019 (COVID-19) is contagious disease caused by the SARS-CoV-2 virus. It emerged as a global pandemic early in 2020, affecting more than 2000 countries and territories. The infection is highly contagious with disease transmission reported from asymptomatic carriers, including children. It spreads through person-to-person contact, via aerosol and droplets. The practice of social distancing – maintaining a distance of 1 – 2 meters or 6 feet -- between people has been widely recommended to slow or halt the spread. This places orthodontists at high risk of acquiring and transmitting the infection. The objective of this review is to report to orthodontists on the emergence, epidemiology, risks, and precautions during disease crisis. This should help increase awareness, reinforce infection control and prevent cross-transmission within the orthodontic facility. Methods A comprehensive literature review of English and non-English articles was performed in March, 2020 using (CORD-19 2020) dataset, PubMed, MEDLINE, Scopus, and Google Scholar to search for infection control and disease transmission in orthodontics. Results This review emphasizes minimizing aerosol production and reinforcing strict infection control measures. Compliance with highest level of personal protection and restriction of treatment to emergency cases is recommended during the outbreak. Surface disinfection, adequate ventilation, and decontamination of instruments and supplies following the guidelines is required. Conclusion Reinforcing strict infection control measures and minimizing personal contact and aerosol production are keys to prevent contamination within the orthodontic settings. Although no cases of COVID-19 cross-transmission within a dental facility have been reported, the risk exists and the disease is still emerging. Further studies are required.


title: Sektion Pflege zur aktuellen Situation der Intensivpflege in Deutschland: Arbeitsgruppe der Sektion Pflege der Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin (DGIIN)

text: The year 2020 is the year of care on the occasion of the 200th birthday of Florence Nightingale. However, due to current events, the “Year of Corona” will be remembered more. A positive aspect is the attention and appreciation of the nursing profession in the population. Nevertheless, politicians and various professional groups in the hospital limit nursing care almost exclusively to practical activities that are directly necessary for the patients. A clearly noticeable improvement in working conditions for nurses as a result of the political efforts of this legislative period has so far failed to materialise to the same extent as the active involvement of nurses in political decisions and resolutions that directly affect the professional group. The rapid build-up of bed capacities has made it possible to provide the patients concerned with the necessary intensive medical care. In many places, however, this has been at the expense of the nurses and physicians, some of whom have had to work without the necessary training, with insufficient protective equipment and in unfamiliar areas. These problems continue to exist even after months of the covid-19 crisis. The Nursing Section of the DGIIN expressly declares its willingness to actively and constructively participate in any processes in the future and, with the following 5 points, offers initial practical assistance to improve the situation in German intensive care units.


title: Recent advances in peptide chain termination

text: Peptide chain termination occurs when a stop codon is decoded by a release factor. In Escherichia coli two codon‐specific release factors (RF1 and RF2) direct the termination of protein synthesis, while in eukaryotes a single factor is required. The E. coli factors have been purified and their genes isolated. A combination of protein and DNA sequence data reveal that the RFs are structurally similar and that RF2 is encoded in two reading frames. Frame‐shifting from one reading frame to the next occurs at a rate of 50%, is regulated by the RF2‐specific stop codon UGA, and involves the direct interaction of the RF2 mRNA with the 3’end of the 16S rRNA. The RF genes are located in two separate operons, with the RF1 gene located at 26.7 min and the RF2 gene at 62.3 min on the chromosome map. Ribosomal binding studies place the RF‐binding region at the interface between the ribosomal subunits. A possible mechanism of stop‐codon recognition is reviewed.


title: Epidemiological analysis of COVID‐19 and practical experience from China

text: The rapid spread of the epidemic has aroused widespread concern in the international community. Severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) originated from Wuhan's Huanan wholesale seafood market, with bats as the likely original hosts and pangolins as potential intermediate hosts. The current source of the disease is mainly patients infected with SARS‐COV‐2. Patients in the incubation period may also become sources of infection. The virus is mainly transmitted via respiratory droplets and contact, and the population is generally susceptible. The epidemic has progressed through the local outbreak stage and community transmission stage due to exposure at Wuhan's Huanan wholesale seafood market and is now in the stage of large‐scale transmission due to the spread of the epidemic. The basic productive number (R0) at the beginning of the epidemic was 2.2, with an average incubation period of 5.2 days. The proportion of critically ill patients was 23.4%, the mortality rate was lower than those of SARS and Middle East respiratory syndrome, and 96.5% of deaths occurred in Hubei Province, where the outbreak occurred first. Among them, elderly men with underlying diseases had a higher mortality rate. Chinese medical staff have summarized a set of effective strategies and methods in the diagnosis and treatment of this disease that are worthy of reference for their international counterparts. With powerful government intervention and the efforts of Chinese medical staff, China's outbreak has gradually improved.


title: Acute Coronary Syndromes and Covid-19: Exploring the Uncertainties.

text: Since an association between myocardial infarction (MI) and respiratory infections has been described for influenza viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. The initial data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss the pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; and learnings that have emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.


title: Automatically fixing errors in glycoprotein structures with Rosetta

text: Recent advances in single-particle cryo-electron microscopy (cryoEM) have resulted in determination of an increasing number of protein structures with resolved glycans. However, existing protocols for the refinement of glycoproteins at low resolution have failed to keep up with these advances. As a result, numerous deposited structures contain glycan stereochemical errors. Here, we describe a Rosetta-based approach for both cryoEM and X-ray crystallography refinement of glycoproteins which is capable of correcting conformational and configurational errors in carbohydrates. Building upon a previous Rosetta framework, we introduced additional features and score terms enabling automatic detection, setup and refinement of glycan-containing structures. We benchmarked this approach using twelve crystal structures and showed that glycan geometries can be automatically improved while maintaining good fit to the crystallographic data. Finally, we used this method to refine carbohydrates of the human coronavirus NL63 spike glycoprotein and of an HIV envelope glycoprotein, demonstrating its usefulness for cryoEM refinement.


title: State of cat genomics

text: Our knowledge of cat family biology was recently expanded to include a genomics perspective with the completion of a draft whole genome sequence of an Abyssinian cat. The utility of the new genome information has been demonstrated by applications ranging from disease gene discovery and comparative genomics to species conservation. Patterns of genomic organization among cats and inbred domestic cat breeds have illuminated our view of domestication, revealing linkage disequilibrium tracks consequent of breed formation, defining chromosome exchanges that punctuated major lineages of mammals and suggesting ancestral continental migration events that led to 37 modern species of Felidae. We review these recent advances here. As the genome resources develop, the cat is poised to make a major contribution to many areas in genetics and biology.


Development of a Surgical Workforce Access Team (SWAT) in the Battle Against COVID-19


title: Microbiologic Investigations for Head and Neck Infections

text: A variety of methods, including direct examination of stained smears, antigen detection, routine and special cultures, and histopathologic evaluation are available for investigation of head and neck infections. Newer rapid molecular techniques with increased sensitivity and specificity are becoming available at many centers. Evaluation of specific causes in head and neck infections is complicated by the tendency for polymicrobial infections, difficulty in obtaining adequate specimens, and the presence of a diverse endogenous microflora at various mucosal sites that also can include true pathogens. These aspects of laboratory investigation for head and neck infections are reviewed in this article.


title: Foot-and-mouth disease virus replicates independently of phosphatidylinositol 4-phosphate and type III phosphatidylinositol 4-kinases

text: Picornaviruses form replication complexes in association with membranes in structures called replication organelles. Common themes to emerge from studies of picornavirus replication are the need for cholesterol and phosphatidylinositol 4-phosphate (PI4P). In infected cells, type III phosphatidylinositol 4-kinases (PI4KIIIs) generate elevated levels of PI4P, which is then exchanged for cholesterol at replication organelles. For the enteroviruses, replication organelles form at Golgi membranes in a process that utilizes PI4KIIIβ. Other picornaviruses, for example the cardioviruses, are believed to initiate replication at the endoplasmic reticulum and subvert PI4KIIIα to generate PI4P. Here we investigated the role of PI4KIII in foot-and-mouth disease virus (FMDV) replication. Our results showed that, in contrast to the enteroviruses and the cardioviruses, FMDV replication does not require PI4KIII (PI4KIIIα and PI4KIIIβ), and PI4P levels do not increase in FMDV-infected cells and PI4P is not seen at replication organelles. These results point to a unique requirement towards lipids at the FMDV replication membranes.


title: The role of infections in the emergence of non-communicable diseases (NCDs): Compelling needs for novel strategies in the developing world

text: Summary The emergence of non-communicable diseases (NCDs) follows multiple aetiological pathways requiring recognition for effective control and prevention. Infections are proving to be conventional, emerging and re-emerging aetiological factors for many NCDs. This review explores the possible mechanisms by which infections induce NCDs citing examples of studies in Africa and elsewhere where NCDs and infections are proposed or confirmed to be causally linked and also discusses the implications and challenges of these observations for science and medicine. The need to re-evaluate and expand early community and individual preventive and control strategies that will lead to reduction and even elimination of NCDs especially in Africa and other developing countries where infections are prevalent is highlighted.


title: Emerging Molecular Assays for Detection and Characterization of Respiratory Viruses

text: This article describes several emerging molecular assays that have potential applications in the diagnosis and monitoring of respiratory viral infections. These techniques include direct nucleic acid detection by quantum dots, loop-mediated isothermal amplification, multiplex ligation-dependent probe amplification, amplification using arbitrary primers, target-enriched multiplexing amplification, pyrosequencing, padlock probes, solid and suspension microarrays, and mass spectrometry. Several of these systems already are commercially available to provide multiplex amplification and high-throughput detection and identification of a panel of respiratory viral pathogens. Further validation and implementation of such emerging molecular assays in routine clinical virology services will enhance the rapid diagnosis of respiratory viral infections and improve patient care.


title: Persistent viral shedding of SARS‐CoV‐2 in faeces – a rapid review

text: AIM: In addition to respiratory symptoms, COVID‐19 can present with gastrointestinal complaints suggesting possible faeco‐oral transmission. The primary aim of this review was to establish the incidence and timing of positive faecal samples for SARS‐CoV‐2 in patients with COVID‐19. METHODS: A systematic literature review identified studies describing COVID‐19 patients tested for faecal virus. Search terms for MEDLINE included ‘clinical’, ‘faeces’, ‘gastrointestinal secretions’, ‘stool’, ‘COVID‐19’, ‘SARS‐CoV‐2’ and ‘2019‐nCoV’. Additional searches were done in the American Journal of Gastroenterology, Gastroenterology, Gut, Lancet Gastroenterology and Hepatology, the World Health Organization Database, the Centre for Evidence‐Based Medicine, New England Journal of Medicine, social media and the National Institute for Health and Care Excellence, bioRxiv and medRxiv preprints. Data were extracted concerning the type of test, number and timing of positive samples, incidence of positive faecal tests after negative nasopharyngeal swabs and evidence of viable faecal virus or faeco‐oral transmission of the virus. RESULTS: Twenty‐six relevant articles were identified. Combining study results demonstrated that 53.9% of those tested for faecal RNA were positive. The duration of faecal viral shedding ranged from 1 to 33 days after a negative nasopharyngeal swab with one result remaining positive 47 days after onset of symptoms. There is insufficient evidence to suggest that COVID‐19 is transmitted via faecally shed virus. CONCLUSION: There is a high rate of positive polymerase chain reaction tests with persistence of SARS‐CoV‐2 in faecal samples of patients with COVID‐19. Further research is needed to confirm if this virus is viable and the degree of transmission through the faeco‐oral route. This may have important implications on isolation, recommended precautions and protective equipment for interventional procedures involving the gastrointestinal tract.


title: Do crocodilians get the flu? Looking for influenza A in captive crocodilians

text: It is well established that several wild aquatic bird species serve as reservoirs for the influenza A virus. It has also been shown that the influenza A virus can be transmitted to mammalian species such as tigers and domestic cats and dogs through ingestion of infected birds. Another group of animals that should also be considered as potential hosts for the influenza A virus are the crocodilians. Many crocodilian species share aquatic environments with wild birds that are known to harbor influenza viruses. In addition, many large crocodilians utilize birds as a significant food source. Given these factors in addition to the close taxonomic proximity of aves to the crocodilians, it is feasible to ask whether crocodilian species may also harbor the influenza A virus. Here we analyzed 37 captive crocodilians from two locations in Florida (plus 5 wild bird fecal‐samples from their habitat) to detect the presence of influenza A virus. Several sample types were examined. Real‐time RT‐PCR tests targeting the influenza A matrix gene were positive for four individual crocodilians—Alligator sinensis, Paleosuchus trigonatus, Caiman latirostris and Crocodylus niloticus. Of the seven serum samples tested with the avian influenza virus agar gel immunodiffusion assay, three showed a nonspecific reaction to the avian influenza virus antigen—A. sinensis, P. trigonatus and C. niloticus (C. latirostris was not tested). Viable virus could not be recovered from RT‐PCR‐positive samples, although this is consistent with previous attempts at viral isolation in embryonated chicken eggs with crocodilian viruses. J. Exp. Zool. 309A:571–580, 2008. © 2008 Wiley‐Liss, Inc.


Impact of COVID‐19 on clinical practice


Danger of Potential-Pandemic-Pathogen Research Enterprises


title: Long-Term Care Facilities: A Cornucopia of Viral Pathogens

text: OBJECTIVES: To determine the frequency and types of respiratory viruses circulating in Boston long-term care facilities (LTCFs) during a 3-year period. DESIGN: Observational. SETTING: Thirty-three Boston-area LTCFs over a 3-year period. PARTICIPANTS: Residents of long-term care who had previously participated in a trial of vitamin E supplementation and had paired serum samples available for viral analysis. MEASUREMENTS: Viral antibody titers to eight respiratory viruses (influenza A and B, respiratory syncytial virus (RSV), parainfluenza virus serotype three (PIV-3), PIV-2, human metapneumovirus (hMPV), and coronaviruses 229E and OC43) were measured using enzyme immunoassay at baseline and 53 weeks. Infection was defined as a more than quadrupling of viral titers. Clinical data on respiratory illnesses were collected throughout the study period. RESULTS: A total of 617 persons were enrolled in the trial. Of these, 382 (62%) had sera available for viral analysis. A total of 204 viral infections were documented in 157 subjects. Serological responses to all eight viruses were documented, with hMPV (12.8%) and coronavirus 229E (10.5%) being the most common and PIV-2 (2.4%) the least common. The occurrence of bronchitis (P = .007), pneumonia (P = .02), and any lower respiratory tract infection (P = .002) was significantly associated with having a viral diagnosis. CONCLUSION: A wide range of respiratory viruses cocirculates in LTCFs and contributes to respiratory illness morbidity in these populations.


title: Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation

text: BACKGROUND: Porcine parvovirus (PPV) infection primarily causes reproductive failure of pregnant swine and results in host cell death. Boars, as an important disseminator, shed PPV to sows via semen. PPV infects and numerously replicates in boar testicle, which results in damage of swine testicle in vivo. Reactive oxygen species (ROS), a mediator of cell apoptosis, play a crucial role in the mitochondria apoptotic pathway. However, whether PPV infection induces ST cells apoptosis and ROS accumulation is still unclear. METHODS: To determine the effects of PPV infection on the apoptosis, we detected morphological changes, DNA ladder, activities of caspases, and expression of PARP in PPV-infected ST cells. Moreover, aiming to investigate the effect of PPV infection on the mitochondrial apoptotic pathway and ROS accumulation, we detected the Δψm, apoptosis-related genes, and ROS. To investigate the role of ROS in the process of PPV-induced apoptosis, the ST cells were infected with PPV and treated with the ROS antioxidants. The ROS level was measured using Reactive Oxygen Species Assay Kit and the Δψm, expression level of Bcl-2, translocation of Bax, and redistribution of mitochondria cytochrome c were tested. RESULTS: In this study, we demonstrated that PPV infection could induce apoptosis that was characterized by morphological changes, DNA fragmentation and activation of caspases. Moreover, PPV infection suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, decreased the mitochondrial transmembrane potential, and triggered the release of cytochrome c, which caused the subsequent activation of caspase-9 and caspase-3 and initiation of apoptosis. However, during the process of PPV-induced apoptosis, the protein levels of Fas and FasL were not affected. Further studies showed that PPV infection caused ROS accumulation. Inhibition of ROS could reduce mitochondrial transmembrane potential and could significantly block ST cells apoptosis via suppressing Bax translocation, cytochrome c and caspase-3 activation. CONCLUSIONS: All these results suggest that PPV-induced ROS accumulation mediates apoptosis in ST cells, which provided theoretical basis for the molecular pathogenesis of PPV infection.


title: Incidence of anogenital warts in Liuzhou, south China: a comparison of data from a prospective study and from the national surveillance system

text: To determine the incidence of anogenital warts (AGWs) in the Chinese general population, we compared the data from a prospective study and from the National Notifiable Disease Report System (NNDRS). A cohort study including 2378 women and 2309 men aged 18–55 years old enrolled from Liuzhou, China, was conducted with three scheduled visits at 6-month intervals from May 2014 to March 2016. And, a questionnaire survey was performed to collect the diagnosis history of AGWs at the enrollment visit. The data on reported AGW cases of Liuzhou in the NNDRS from 2006 to 2015 were also analyzed. Overall, the incidence rates of AGWs in the prospective study, in the self-reported diagnosis during past 12 months and in the NNDRS were 1.26 per 1000 person-years (95% confidence interval (CI): 0.16–2.37), 2.35 (95% CI: 1.17–4.20) and 0.183 (95% CI: 0.178–0.187), respectively. Human papillomavirus 6 or 11 were found in all the AGW biopsy samples (10/10). The onset time of AGWs in women was earlier, and the cumulative risk increased more quickly at a young age along with each subsequent younger birth cohort (P<0.0001), whereas slight differences were observed in the different male birth cohorts (P=0.0785). The sexual behavior of individuals and their sexual partners had a strong relationship with self-reported AGWs. Our study indicates that the incidence of AGWs in China is as high as that in developed countries, and the data based on the national surveillance system seriously underestimate the real disease burden of AGWs.


title: Strengthening laboratory capacity for detection of respiratory viral pathogens through the Global Health Security Agenda (GHSA) framework

text: BACKGROUND: Endemic and emerging respiratory viruses are a threat to public health, and a robust public health laboratory system is essential to ensure global health security. OBJECTIVE: This program sought to expand molecular laboratory testing capacity to detect a broad range of respiratory pathogens in clinical respiratory specimens collected during disease surveillance and outbreak investigations. METHODS: As a part of the Global Health Security Agenda (GHSA), the United States Centers for Disease Control and Prevention utilised the equipment and training infrastructure already in place at the World Health Organization National Influenza Centers to expand testing capacity for respiratory viruses in laboratories in GHSA partner countries. This was done through the provision of quality assured reagents, including multiplex platforms and technical guidance for laboratory staff, as well as the assessment of laboratory testing accuracy. CONCLUSION: Early findings illustrated that GHSA laboratories have been able to expand testing capacity using specimens from routine surveillance, as well as from outbreak situations.


title: Descriptive epidemiology and characteristics of confirmed cases of Middle East respiratory syndrome coronavirus infection in the Makkah Region of Saudi Arabia, March to June 2014

text: BACKGROUND AND OBJECTIVES: Describe the epidemiology and characteristics of Middle East respiratory syndrome coronavirus (MERS-CoV), which are essential for control and treatment. METHODS: We conducted a retrospective review of all cases of MERS-CoV reported in four cities of the Makkah Region from March to June 2014. Exposure factors and comorbid conditions were analyzed using Epi Info. RESULTS: Analysis of the 261 cases revealed that the incidence peaked in mid-April 2014 and the fatality rate was 42%. Cough, fever, radiological evidence of pneumonia, and shortness of breath were identified as significant risk factors for a diagnosis of MER-CoV infection. Healthcare workers (HCWs) are at a higher risk of acquiring MERS-CoV than non-HCWs. Males in Jeddah are at higher risk due to greater outdoor exposure while females in Taif are at higher risk due to domestic caregiving. Filipino nurses are at highest risk among all HCWs. CONCLUSION: The findings indicate the need to screen all contacts of HCWs to improve MERS control and form public–private partnerships to investigate the true burden of MERS.


title: Mortality estimates among adult patients with severe acute respiratory infections from two sentinel hospitals in southern Arizona, United States, 2010–2014

text: BACKGROUND: From October 2010 through February 2016, Arizona conducted surveillance for severe acute respiratory infections (SARI) among adults hospitalized in the Arizona-Mexico border region. There are few accurate mortality estimates in SARI patients, particularly in adults ≥ 65 years old. The purpose of this study was to generate mortality estimates among SARI patients that include deaths occurring shortly after hospital discharge and identify risk factors for mortality. METHODS: Patients admitted to two sentinel hospitals between 2010 and 2014 who met the SARI case definition were enrolled. Demographic data were used to link SARI patients to Arizona death certificates. Mortality within 30 days after the date of admission was calculated and risk factors were identified using logistic regression models. RESULTS: Among 258 SARI patients, 47% were females, 51% were white, non-Hispanic and 39% were Hispanic. The median age was 63 years (range, 19 to 97 years) and 80% had one or more pre-existing health condition; 9% died in hospital. Mortality increased to 12% (30/258, 30% increase) when electronic vital records and a 30-day post-hospitalization time frame were used. Being age ≥ 65 years (OR = 4.0; 95% CI: 1.6–9.9) and having an intensive care unit admission (OR = 7.4; 95% CI: 3.0–17.9) were independently associated with mortality. CONCLUSION: The use of electronic vital records increased SARI-associated mortality estimates by 30%. These findings may help guide prevention and treatment measures, particularly in high-risk persons in this highly fluid border population.


title: Investigating a safe ventilation rate for the prevention of indoor SARS transmission: An attempt based on a simulation approach

text: This paper identifies the “safe ventilation rate” for eliminating airborne viral infection and preventing cross-infection of severe acute respiratory syndrome (SARS) in a hospital-based setting. We used simulation approaches to reproduce three actual cases where groups of hospital occupants reported to be either infected or not infected when SARS patients were hospitalized in nearby rooms. Simulations using both computational fluid dynamics (CFD) and multi-zone models were carried out to understand the dilution level of SARS virus-laden aerosols during these scenarios. We also conducted a series of measurements to validate the simulations. The ventilation rates (dilution level) for infection and non-infection were determined based on these scenarios. The safe ventilation rate for eliminating airborne viral infection is to dilute the air emitted from a SARS patient by 10000 times with clean air. Dilution at lower volumes, specifically 1000 times, is insufficient for protecting non-infected people from SARS exposure and the risk of infection is very high. This study provides a methodology for investigating the necessary ventilation rate from an engineering viewpoint.


title: Beatmung geriatrischer Patienten — ein ethisches Dilemma?: Corona-Pandemie 2020

text: Dieser Beitrag möchte einen Überblick darüber geben, wie und mit Hilfe welcher Kriterien eine medizinisch, ethisch und rechtlich vertretbare Entscheidung darüber getroffen werden kann, welche der betagten Patienten mit einer schweren COVID-19-Pneumonie mittels künstlicher Beatmung behandelt werden sollten und welche von einer solchen Therapie eher nicht profitieren würden.


title: TLR3 Signaling in Macrophages Is Indispensable for the Protective Immunity of Invariant Natural Killer T Cells against Enterovirus 71 Infection

text: Enterovirus 71 (EV71) is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. The mechanisms that determine the age-dependent susceptibility remain largely unclear. Here, we found that the paucity of invariant natural killer T (iNKT) cells together with immaturity of the immune system was related to the susceptibility of neonatal mice to EV71 infection. iNKT cells were crucial antiviral effector cells to protect young mice from EV71 infection before their adaptive immune systems were fully mature. EV71 infection led to activation of iNKT cells depending on signaling through TLR3 but not other TLRs. Surprisingly, iNKT cell activation during EV71 infection required TLR3 signaling in macrophages, but not in dendritic cells (DCs). Mechanistically, interleukin (IL)-12 and endogenous CD1d-restricted antigens were both required for full activation of iNKT cells. Furthermore, CD1d-deficiency led to dramatically increased viral loads in central nervous system and more severe disease in EV71-infected mice. Altogether, our results suggest that iNKT cells may be involved in controlling EV71 infection in children when their adaptive immune systems are not fully developed, and also imply that iNKT cells might be an intervention target for treating EV71-infected patients.


title: Differential induction of apoptosis in demyelinating and nondemyelinating infection by mouse hepatitis virus

text: The role of apoptosis in mouse hepatitis virus (MHV) infection is still controversial. To better assess the role of apoptosis in MHV infection, we used three different biologic phenotypes of MHV to examine their differential effect on the induction of apoptosis. MHV-A59 produces acute hepatitis, meningoencephalitis, and chronic demyelination. MHV-2 causes only acute hepatitis and meningitis, whereas Penn98-1 produces acute hepatitis and meningoencephalitis without demyelination. We detected TdT-mediated dUTP nick-end labeling (TUNEL) staining in the livers and meninges of MHV-A59-, MHV-2-, and Penn98-1-infected mice. TUNEL staining in brain parenchyma was only detected in MHV-A59- and Penn98-1-infected mice. We detected apoptosis by electron-microscopy in olfactory neurons during acute infection with MHV-A59. The kinetics and distribution of TUNEL staining correlated with the pathologic damage and colocalized with viral antigen in some cells. At 1 month, TUNEL staining was found exclusively in areas of demyelination in the spinal cord of MHV-A59-infected mice; however, it was not found in nondemyelinated mice infected with MHV-2 or Penn98-1, or in mock-infected mice. TUNEL-positive cells were identified as macrophage/microglial cells, some astrocytes, and some oligodendrocytes, by colabeling with cell-specific markers. The presence of TUNEL staining in oligodendrocytes suggests that apoptosis may play an important role in MHV-induced demyelination.


title: Social media and moral panics: Assessing the effects of technological change on societal reaction

text: Answering calls for deeper consideration of the relationship between moral panics and emergent media systems, this exploratory article assesses the effects of social media – web-based venues that enable and encourage the production and exchange of user-generated content. Contra claims of their empowering and deflationary consequences, it finds that, on balance, recent technological transformations unleash and intensify collective alarm. Whether generating fear about social change, sharpening social distance, or offering new opportunities for vilifying outsiders, distorting communications, manipulating public opinion, and mobilizing embittered individuals, digital platforms and communications constitute significant targets, facilitators, and instruments of panic production. The conceptual implications of these findings are considered.


title: Comment réaliser un prélèvement rhinopharyngé chez l’adulte et l’enfant en période de la pandémie de la maladie COVID-19

text: Abstract The nasopharyngeal swab is currently the main testing method used to diagnose COVID-19. The principle is to collect respiratory cells infected by the virus and to use the RT-PCR (Reverse Transcription - Polymerase Chain Reaction) technique to detect the RNA of the virus. The false negative rate is high, about 30%, which can mainly be explained by an incorrect execution of the technique may increase the false negative rate and decrease the test’s sensitivity. The aim of this note is to help healthcare providers to perform this test correctly in adults and children.


title: 12 Phytochemical and biological research of Polygoneae medicinal resources

text: Abstract This chapter synthesizes current knowledge on phytochemistry, bioactivity, molecular phylogeny, and omics of Polygoneae medicinal resources. Many species in the seven genera of Polygoneae are traditional and popular medicinal herbs. Anthraquinones and stilbenes are characteristic medicinal compounds of Polygoneae, while other useful constituents, such as alkaloids, glycosides, flavonoids, volatile oils, tannins, resins, coumarins, and lignans, have also been isolated from Polygoneae species. Among versatile bioactivities of Polygoneae compounds, their effects on the cardiovascular and nervous systems and their anti-inflammatory, antimicrobial, antiparasitic, insecticidal, anticancer, and antioxidant activities are highlighted. Interspecific hybridization and the following polyploidization play a major role in Polygoneae diversification. Nuclear ITS and chloroplast DNA sequences are retrieved to resolve the interspecific relationship and reassign some taxa to the appropriate genus. Omics study of Polygoneae is at the budding stage, which will revolutionize the sustainable utilization of Polygoneae medicinal resources.


title: Advice on Standardized Diagnosis and Treatment for Spinal Diseases during the Coronavirus Disease 2019 Pandemic

text: Coronavirus disease 2019 (COVID-19) outbreak started in December 2019 that caused difficulties for clinical work. Practical work experience in our spinal outpatient and emergency department during the COVID-19 pandemic is summarized in this article, with combined evidence-based medical evidence to explore a standardized process of diagnosis and treatment for spinal diseases. Outpatient reservation, continuous screening, triage, and isolation, first consultation accountability system, pandemic reporting system, and online revisit were strictly followed. We hope that our experience in prevention and control of COVID-19 can help spine surgeons globally in stopping the spread of COVID-19. Spine surgeons should collaborate with infection control specialists to avoid cross-infection in hospitals and optimize treatment.


title: Renin-angiotensin system at the heart of COVID-19 pandemic

text: Abstract Significant aspects of COVID-19 pandemic remain obscure. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system, whose expression dominates on lung alveolar epithelial cells, is the human cell receptor of SARS-CoV-2, the causative agent of COVID-19. We strongly encourage the concept that thorough considerations of receptor-ligand interactions should be kept at the heart of scientific debate on infection. In this idea, the whole renin-angiotensin system has to be evaluated. We hypothesize that factors related to ethnicity, environment, behaviors, associated illness, and medications involving this complex system are probably responsible for situations regarded as anomalous from both an epidemiological and a clinical point of view, but, taken together, such factors may explain most of the aspects of current outbreak. We decided to use the analogy of a play and speculate about the possible impact in this tragedy of 1) air pollution via the interference of nitrogen dioxide on ACE2 expression; 2) the dual role of nicotine; 3) the hypothetical involvement of ACE2 polymorphisms, the relationships of which with ethnic factors and susceptibility to cardiovascular disease seems intriguing; 4) the impact on the severity of infection of hypertension and related medications acting on the renin/angiotensin system, and, finally, 5) the possible helpful role of chloroquine, thanks to its capacity of modifying ACE2 affinity to the viral spike protein by altering glycosylation. This hypothesis paper is an urgent call for the development of research programs that aim at questioning whether the putative protagonists of this tragedy are real-life actors in COVID-19.


title: Différence de diagnostic des infections broncho-pulmonaires virales ou bactériennes chez l'enfant

text: Résumé Les bronchopneumopathies communautaires de l'enfant sont fréquentes et entraînent une morbidité importante. Elles peuvent se décomposer en bronchiolites, qui sont toutes d'origine virale, bronchites (ou trachéobronchites), qui sont aussi d'origine virale le plus souvent (80 %) et qui se surinfectent parfois, pneumopathies qui sont potentiellement graves et qui sont dues à une bactérie (60 %), un virus (40 %) ou aux deux (coïnfection : 20 %). L'impossibilité d'écarter un processus bactérien lors d'une pneumopathie implique la mise en route rapide d'une antibiothérapie probabiliste. Abstract Community-acquired bronchopneumonia is very common in children and responsible for a great morbidity. It can be revealed by bronchiolitis, due to viral infection, bronchitis (80% due to viruses), and pneumonia potentially much more severe due to bacteria (60%), viruses (40%) or both causes (20%). Being unable to exclude a bacterial origin in pneumonia leads physicians to prescribe systematically antibiotics.


title: A crude future? COVID-19s challenges for oil demand, supply and prices

text: Assessing prospects for future oil prices is an uncertain activity but, barring Middle East conflict creating severe supply issues, crude oil prices are expected to stage a recovery by third-quarter 2020 and modest further recovery in first-half 2021, with the range $40 to $60 per barrel for WTI and Brent. Despite such a recovery there will be many oil sectors incurring losses, from US shale oil and Canadian tar sands producers, to many standard crude oil exporters incurring problems with production equipment access and costs, or experiencing lack of competitiveness in key markets.


title: Synthetic Biology: Mapping the Scientific Landscape

text: This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves.


Identifying Behavioral Risk Intervention Points to Prevent Zoonotic Spillover at Animal Markets, Farms, and Abattoirs in Egypt


title: Acute Encephalitis

text: Acute encephalitis remains one of the contemporary challenges of critical care medicine. The diagnosis is difficult and sometimes unconfirmed, and encephalitis remains without clear evidence-based therapies or even therapeutic goals for the prevention of high neurologic sequelae. This article provides a framework for pediatric intensivists to guide the diagnosis and management of patients with suspected encephalitis. It provides an in-depth review of the most common causes of encephalitis in children. The article promotes early recognition, appropriate testing and empiric treatment, and management of the expected complications of acute encephalitis.


title: Potential effective treatment for COVID-19: systematic review and meta-analysis of the severe infectious disease with convalescent plasma therapy

text: Abstract Background Convalescent plasma (CP) has been used successfully to treat many types of infectious diseases, and it has shown initial effects in the treatment of the emerging 2019 coronavirus disease (COVID-19). However, its curative effect and feasibility have yet to be confirmed by formal evaluation and well-designed clinical trials. To explore the effectiveness of treatment and predict the potential effect of CP for COVID-19, studies of different types of infectious diseases treated with CP were included in this systematic review and meta-analysis. Methods Related studies were obtained from databases and screened based on the inclusion criteria. The data quality was assessed, and the data were extracted and pooled for analysis. Results We included 40 studies on CP treatment for infectious diseases We found that CP treatment could reduce the risk of mortality with a low incidence of adverse events, promote the production of antibodies, show the decline in viral load, and shorten the disease course. A meta-analysis of 15 controlled studies showed that there was a significantly lower mortality rate in the group treated with CP (pooled OR = 0.32, 95% CI: 0.19-0.52, P < 0.001, I2 = 54%) than in the control groups. Studies were mostly of low or very low quality with a moderate or high risk of bias. The sources of clinical and methodological heterogeneity were identified. The exclusion of heterogeneity indicated that the results were stable. Conclusions CP therapy has some curative effect and is well tolerated to treat infectious diseases. It is a potentially effective treatment for COVID-19.


title: Impact of Severe Acute Respiratory Syndrome (SARS) on Blood Services and Blood in Hong Kong in 2003

text: The current global pandemic of COVID‐19 due to the novel coronavirus SARS‐CoV‐2 is causing considerable loss of life and enormous social and economic disruption. Here, we describe the response of the blood service, the impact on blood donation and the effects on the blood supply in Hong Kong posed by the earlier SARS epidemic in 2002 and 2003. The infection, like SARS‐CoV‐2 was highly contagious through droplet transmission. In the 2003 SARS epidemic in Hong Kong, donor and staff safety was secured by using stringent infection control measures to protect both donors and staff from contacting the virus. All the donors were requested to wear face masks within the donation venue and use an alcohol‐based hand rinse. The donors' body temperature was checked before donation and staff's body temperatures were checked daily. The safety of the blood supply was secured by a donor deferral policy for 4 weeks following contact with a confirmed or suspected case of and a post‐donation call‐back system. Despite scheduling mobile donation sessions and a decrease in donors attending blood donor centers, the blood supply was maintained as there was a 12.8% reduction of the demand of blood and only a 16.9% reduction in the blood donation. Lessons learnt during the epidemic may help preparation for future epidemics and provide a basis for understanding the pathogenesis, laboratory diagnosis and role of coronaviruses in transfusion medicine. These are continuing problems as coronavirus epidemics may recur with future impact on blood collection and blood donation screening. This article is protected by copyright. All rights reserved.


title: Oxymetazoline modulates proinflammatory cytokines and the T‐cell stimulatory capacity of dendritic cells

text: Abstract: The nasal decongestant oxymetazoline (OMZ) is frequently used in the topical treatment of rhinitis/sinusitis. As proinflammatory cytokines play a critical role in the development and maintenance of local inflammation, the aim of this study was to investigate the influence of OMZ on immune cells in order to diminish the mucosal infiltration of the nose. Peripheral blood mononuclear cells (PBMC) from buffy coats of healthy volunteers were isolated and stimulated in the presence or absence of OMZ. In addition, monocyte‐derived dendritic cells (DC) were generated and different concentrations of OMZ were added. DC phenotype and their T‐cell stimulatory properties were analysed. The vasoactive substance OMZ showed a concentration dependent inhibitory effect on T‐cell activation as well as a dominant effect on T‐cell stimulatory properties of DC. Low concentrations of OMZ inhibited the proliferation of polyclonally activated T cells. In addition, secretion of proinflammatory mediators such as the cytokines interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF α), IL‐6 and IL‐8 were inhibited in the presence of physiological doses of OMZ. Interestingly, the addition of IL‐6 to DC‐T‐cell co‐culture was able to completely restore T‐cell proliferation. In conclusion, these findings indicate that the anti‐inflammatory properties of OMZ are partially mediated by the inhibition of proinflammatory cytokines as well as reduced T‐cell stimulatory capacity of DC resulting in a repressed stimulation of T cells. Therefore, the therapeutic benefit of OMZ can be explained in part by its immunomodulating effects in the topical treatment of nasal inflammation.


Please cite this paper as: Burns et al. (2011) Respiratory viruses in children with cystic fibrosis: viral detection and clinical findings. Influenza and Other Respiratory Viruses 6(3), 218–223. Background Viral detection from different respiratory sample types in children with cystic fibrosis (CF) is facilitated by available molecular methods, but optimum sampling strategies have not been identified. In addition, associations between viral detection and respiratory symptoms are not well described. Objectives Study goals were to compare molecular detection of viruses from concurrent upper airway and sputum samples in children with CF and to describe relative frequency of respiratory viral infections and identify potential clinical associations. Methods We conducted a 2‐year prospective surveillance study in 44 children with CF aged 6–18 years. Upper airway and sputum samples were collected quarterly and during pulmonary exacerbations and tested for respiratory syncytial virus (RSV), influenza viruses, parainfluenza viruses types 1–4, human metapneumovirus, coronaviruses, rhinoviruses, and adenoviruses. Physical exams and symptom surveys were used to identify respiratory signs and symptoms. Results Upper airway samples were collected at 359 visits; concordance of PCR‐based viral detection was examined in a subset of paired upper airway and sputum samples from 21 participants at 92 visits. Rhinovirus was the most commonly detected virus (23·1% overall), and rhinovirus detection was the same for both sample types (21·7% each). Sensitivity and specificity for the detection of rhinovirus in sputum relative to upper airway sampling were 70% and 91·7%, respectively. Respiratory symptoms associated with rhinovirus detection included increased cough, increased nasal congestion, increased sputum production, and wheezing. Conclusions A relatively high frequency of rhinovirus detection was observed by either upper airway or sputum samples, and clinical findings suggest a significant‐associated symptom burden.


title: An immunohistochemical investigation of porcine epidemic diarrhoea

text: Summary A sudden outbreak of epidemic diarrhoea of piglets occurred in Japan, the principal features being watery diarrhoea, dehydration and high mortality in newborn animals. The microscopical lesions were villous atrophy in the small intestine, the villous enterocytes being vacuolated and cuboidal in shape. The villus-crypt ratio was severely reduced, varying from 1:1 to 3:1. Transmission electron microscopy showed numerous coronaviruses within the cytoplasm of enterocytes and among microvilli. Specific antigens of porcine epidemic diarrhoea (PED) virus were detected in the cytoplasm of enterocytes by the streptavidin-biotin (SAB) technique. Infected cells, which were most abundant in the villous epithelia of the jejunum and ileum, were present in small numbers in the large intestine, the crypt epithelia, the lamina propria and Peyer's patches. The study suggests that the SAB technique is useful for the diagnosis of PED.


title: Increased severity of COVID‐19 in people with obesity: are we overlooking plausible biological mechanisms?

text: The relationship between obesity and more severe disease in patients with COVID‐19 is intriguing. Recent articles published in Obesity (1‐3) discuss the possible effects of increased proinflammatory cytokines and disturbances of lung function in people with obesity, but we believe that they overlook an important player in this scenario, which is endothelial dysfunction.


title: A comprehensive assessment of N-terminal signal peptides prediction methods

text: BACKGROUND: Amino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved off upon the passenger protein reaching its destination. The explosive growth in sequencing technologies has led to the deposition of vast numbers of protein sequences necessitating rapid functional annotation techniques, with subcellular localization being a key feature. Of the myriad software prediction tools developed to automate the task of assigning the SP cleavage site of these new sequences, we review here, the performance and reliability of commonly used SP prediction tools. RESULTS: The available signal peptide data has been manually curated and organized into three datasets representing eukaryotes, Gram-positive and Gram-negative bacteria. These datasets are used to evaluate thirteen prediction tools that are publicly available. SignalP (both the HMM and ANN versions) maintains consistency and achieves the best overall accuracy in all three benchmarking experiments, ranging from 0.872 to 0.914 although other prediction tools are narrowing the performance gap. CONCLUSION: The majority of the tools evaluated in this study encounter no difficulty in discriminating between secretory and non-secretory proteins. The challenge clearly remains with pinpointing the correct SP cleavage site. The composite scoring schemes employed by SignalP may help to explain its accuracy. Prediction task is divided into a number of separate steps, thus allowing each score to tackle a particular aspect of the prediction.