title: Original Article: Real time reverse transcription (RRT)‐polymerase chain reaction (PCR) methods for detection of pandemic (H1N1) 2009 influenza virus and European swine influenza A virus infections in pigs

text: Please cite this paper as: Slomka et al. (2010) Real time reverse transcription (RRT)‐polymerase chain reaction (PCR) methods for detection of pandemic (H1N1) 2009 influenza virus and European swine influenza A virus infections in pigs. Influenza and Other Respiratory Viruses 4(5), 277–293. Background There is a requirement to detect and differentiate pandemic (H1N1) 2009 (H1N1v) and established swine influenza A viruses (SIVs) by real time reverse transcription (RRT) PCR methods. Objectives First, modify an existing matrix (M) gene RRT PCR for sensitive generic detection of H1N1v and other European SIVs. Second, design an H1 RRT PCR to specifically detect H1N1v infections. Methods RRT PCR assays were used to test laboratory isolates of SIV (n = 51; 37 European and 14 North American), H1N1v (n = 5) and avian influenza virus (AIV; n = 43). Diagnostic sensitivity and specificity were calculated for swabs (n = 133) and tissues (n = 116) collected from field cases and pigs infected experimentally with SIVs and H1N1v. Results The “perfect match” M gene RRT PCR was the most sensitive variant of this test for detection of established European SIVs and H1N1v. H1 RRT PCR specifically detected H1N1v but not European SIVs. Validation with clinical specimens included comparison with virus isolation (VI) as a “gold standard”, while field infection with H1N1v in swine was independently confirmed by sequencing H1N1v amplified by conventional RT PCR. “Perfect match” M gene RRT PCR had 100% sensitivity and 95·2% specificity for swabs, 93·6% and 98·6% for tissues. H1 RRT PCR demonstrated sensitivity and specificity of 100% and 99·1%, respectively, for the swabs, and 100% and 100% for the tissues. Conclusions Two RRT PCRs for the purposes of (i) generic detection of SIV and H1N1v infection in European pigs, and for (ii) specific detection of H1N1v (pandemic influenza) infection were validated.


title: Massive cutback in orthopaedic healthcare services due to the COVID-19 pandemic

text: PURPOSE: Due to the lack of evidence, it was the aim of the study to investigate current possible cutbacks in orthopaedic healthcare due to the coronavirus disease 2019 pandemic (COVID-19). METHODS: An online survey was performed of orthopaedic surgeons in the German-speaking Arthroscopy Society (Gesellschaft für Arthroskopie und Gelenkchirurgie, AGA). The survey consisted of 20 questions concerning four topics: four questions addressed the origin and surgical experience of the participant, 12 questions dealt with potential cutbacks in orthopaedic healthcare and 4 questions addressed the influence of the pandemic on the particular surgeon. RESULTS: Of 4234 contacted orthopaedic surgeons, 1399 responded. Regarding arthroscopic procedures between 10 and 30% of the participants stated that these were still being performed—with actual percentages depending on the specific joint and procedure. Only 6.2% of the participants stated that elective total joint arthroplasty was still being performed at their centre. In addition, physical rehabilitation and surgeons’ postoperative follow-ups were severely affected. CONCLUSION: Orthopaedic healthcare services in Austria, Germany, and Switzerland are suffering a drastic cutback due to COVID-19. A drastic reduction in arthroscopic procedures like rotator cuff repair and cruciate ligament reconstruction and an almost total shutdown of elective total joint arthroplasty were reported. Long-term consequences cannot be predicted yet. The described disruption in orthopaedic healthcare services has to be viewed as historic. LEVEL OF EVIDENCE: V. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00167-020-06032-2) contains supplementary material, which is available to authorized users.


title: Camfil starts making CamProtect face masks in Sweden

text: Responding to the coronavirus pandemic, Camfil is manufacturing respiratory protection masks in Sweden that have been designed and developed at its laboratory in Trosa Tech Center.


Management of Telogen Effluvium During The Covid‐19 Emergency: Psychological Implications


title: Detection of Recently Discovered Human Polyomaviruses in a Longitudinal Kidney Transplant Cohort

text: A large number of human polyomaviruses have been discovered in the last 7 years. However, little is known about the clinical impact on vulnerable immunosuppressed patient populations. Blood, urine, and respiratory swabs collected from a prospective, longitudinal adult kidney transplant cohort (n = 167) generally pre‐operatively, at day 4, months 1, 3, and 6 posttransplant, and at BK viremic episodes within the first year were screened for 12 human polyomaviruses using real‐time polymerase chain reaction. Newly discovered polyomaviruses were most commonly detected in the respiratory tract, with persistent shedding seen for up to 6 months posttransplant. Merkel cell polyomavirus was the most common detection, but was not associated with clinical symptoms or subsequent development of skin cancer or other skin abnormalities. In contrast, KI polyomavirus was associated with respiratory disease in a subset of patients. Human polyomavirus 9, Malawi polyomavirus, and human polyomavirus 12 were not detected in any patient samples.


title: Meta-transcriptomics and the evolutionary biology of RNA viruses

text: Abstract Metagenomics is transforming the study of virus evolution, allowing the full assemblage of virus genomes within a host sample to be determined rapidly and cheaply. The genomic analysis of complete transcriptomes, so-called meta-transcriptomics, is providing a particularly rich source of data on the global diversity of RNA viruses and their evolutionary history. Herein we review some of the insights that meta-transcriptomics has provided on the fundamental patterns and processes of virus evolution, with a focus on the recent discovery of a multitude of novel invertebrate viruses. In particular, meta-transcriptomics shows that the RNA virus world is more fluid than previously realized, with relatively frequent changes in genome length and structure. As well as having a transformative impact on studies of virus evolution, meta-transcriptomics presents major new challenges for virus classification, with the greater sampling of host taxa now filling many of the gaps on virus phylogenies that were previously used to define taxonomic groups. Given that most viruses in the future will likely be characterized using metagenomics approaches, and that we have evidently only sampled a tiny fraction of the total virosphere, we suggest that proposals for virus classification pay careful attention to the wonders unearthed in this new age of virus discovery.


title: Synthesis, Spectroscopic Characterizations of Novel Norcantharimides, Their ADME Properties and Docking Studies Against COVID‐19 M(pr)°

text: A series of novel Norcantharimide derivatives were synthesized and their structures were characterized by FTIR, (1)H and (13)C NMR spectroscopy as well as elemental analyses. The absorption, distribution, metabolism and excretion (ADME) properties of the synthesized molecules were investigated. The results obtained in silico demonstrated that these molecules can be considered as orally active drug candidates due to their physicochemical properties. Also, docking studies demonstrated that all derivatives exhibit a good theoretical affinity with MolDock Score in between 124–138 against the main protease of Coronavirus Disease 2019 (COVID‐19 M(pr)°) that caused worldwide epidemics. We believe that newly synthesized norcantharimide derivatives can guide many future studies in organic synthesis, medicine and pharmaceutical applications.


title: Solving one of the pieces of the puzzle: COVID-19 and type 2 diabetes()

text: The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the 2 diseases.


title: Distribution of HLA allele frequencies in 82 Chinese individuals with coronavirus disease‐2019 (COVID‐19)

text: COVID‐19 is a respiratory disease caused by a novel coronavirus and is currently a global pandemic. HLA variation is associated with COVID‐19 because HLA plays a pivotal role in the immune response to pathogens. Here, 82 individuals with COVID‐19 were genotyped for HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, ‐DQA1, ‐DQB1, ‐DPA1, and ‐DPB1 loci using next‐generation sequencing (NGS). Frequencies of the HLA‐C*07:29, C*08:01G, B*15:27, B*40:06, DRB1*04:06, and DPB1*36:01 alleles were higher, while the frequencies of the DRB1*12:02 and DPB1*04:01 alleles were lower in COVID‐19 patients than in the control population, with uncorrected statistical significance. Only HLA‐C*07:29 and B*15:27 were significant when the corrected P‐value was considered. These data suggested that some HLA alleles may be associated with the occurrence of COVID‐19.


title: In silico investigations of possible routes of assembly of ORF 3a from SARS-CoV

text: ORF 3a of human severe acute respiratory syndrome corona virus (SARS-CoV) has been identified as a 274 amino acid membrane protein. When expressed in Xenopus oocytes the protein forms channels. Based on bioinformatics approaches the topology has been identified to include three transmembrane domains (TMDs). Since structural models from experiments are still lacking, computational methods can be challenged to generate such models. In this study, a ‘sequential approach’ for the assembly is proposed in which the individual TMDs are assembled one by one. This protocol is compared with a concerted protocol in which all TMDs are assembled simultaneously. The role of the loops between the TMDs during assembly of the monomers into a bundle is investigated. Molecular dynamics simulations for 20 ns are performed as a short equilibration to assess the bundle stability in a lipid environment. The results suggest that bundles are likely with the second TMD facing the putative pore. All the putative bundles show water molecules trapped within the lumen of the pore with only occasional events of complete crossing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-011-1092-6) contains supplementary material, which is available to authorized users.


title: Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages

text: Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels.


title: Coronaviren als Ursache respiratorischer Infektionen

text: BACKGROUND: There are six human pathogenic coronaviruses (CoV), which mainly cause infections of the respiratory system. In everyday clinical practice, it is helpful to know the relevance and characteristics of these pathogens. OBJECTIVE: To present the epidemiology, clinical picture and differences of human pathogenic CoV and to provide information on the diagnostics and treatment of patients suspected of having CoV infections. MATERIAL AND METHODS: Selective literature search, presentation of results and discussion of fundamental works and expert recommendations, including publications by the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC) and the Robert Koch Institute. RESULTS: The four endemic human CoVs (HCoV-NL63, HCoV-229E, HCoV-OC43 and HCoV-HKU1) mainly cause mild respiratory tract infections. In addition to these four endemic HCoV, the two epidemic CoV, severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV can cause severe pneumonia. The SARS-CoV has not been detected in humans in the last 15 years and MERS-CoV has been circulating mainly on the Arabian Peninsula since 2012; however, neither a specific treatment nor approved vaccines exist for any of the six human pathogenic CoVs. CONCLUSION: All six human CoVs can be diagnosed using RT-PCR on respiratory specimens but this is rarely necessary for the four endemic strains. In current clinical practice SARS-CoV has no importance as it has not been detected in humans for 15 years; however, a possible MERS-CoV infection should be taken into account in patients with typical symptoms and travel history to endemic regions. In this case, rapid diagnostic and general hygiene practices are important to prevent further transmission.


title: Institution of a Novel Process for N95 Respirator Disinfection with Vaporized Hydrogen Peroxide in the setting of the COVID-19 Pandemic at a Large Academic Medical Center

text: Abstract Personal protective equipment (PPE) has been an invaluable yet limited resource when it comes to protecting healthcare workers against infection during the COVID-19 pandemic. In the US, N95 respirator supply chains are severely strained and conservation strategies are needed. A multidisciplinary team at the Washington University School of Medicine, Barnes Jewish Hospital, and BJC Healthcare was formed to implement a program to disinfect N95 respirators. The process described extends the life of N95 respirators using vaporized hydrogen peroxide (VHP) disinfection and allows healthcare workers to retain their own N95 respirator across a large metropolitan health care system.


Oncology care in a lower middle‐income country during the COVID‐19 pandemic


Receptor Usage and the Pathogenesis in Acute and Chronic Virus Infections


title: MicroRNA transcriptome analysis of porcine vital organ responses to immunosuppressive porcine cytomegalovirus infection

text: BACKGROUND: Porcine cytomegalovirus (PCMV) is an immunosuppressive virus that mainly inhibits T-lymphocyte and macrophage immune functions; it has significantly damaged the farming industry. Although recent studies have shown that miRNAs play important roles in immune responses, the regulatory mechanisms of miRNAs during immunosuppressive virus infection remain unclear. METHODS: In this study, porcine small-RNA transcriptomes of PCMV-infected and uninfected vital organs were first characterised by high-throughput sequencing. miRDeep2 software was used to predict novel pig-encoded miRNAs. To verify the accuracy of the high-throughput sequencing results, stem-loop qRT-PCR was performed on 12 significantly DE miRNAs. The physical and functional interactions between the immune-related target genes of the DE miRNAs in PCMV-infected organs were analysed using the STRING database. RESULTS: In total, 306 annotated and 295 novel miRNAs were identified from PCMV-infected and uninfected porcine organs, respectively, through alignment with known Sus scrofa pre-miRNAs. Overall, 92, 107, 95, 77 and 111 miRNAs were significantly differentially expressed in lung, liver, spleen, kidney and thymus after PCMV infection, respectively. According to Gene Ontology enrichment analysis, target genes of the differentially expressed miRNAs associated with immune system processes, regulation of biological processes and metabolic processes were enriched in every sample. Integrated expression analysis of the differentially expressed miRNAs and their target mRNAs in PCMV-infected thymus showed that the significant differential expression of specific miRNAs under the pressure of PCMV infection in central immune organs interfered with the expression of genes involved in important immune-related signalling pathways, thus promoting the viral infection. CONCLUSIONS: This is the first comprehensive analysis of the responses of host small-RNA transcriptomes to PCMV infection in vital porcine organs. It provides new insights into the regulatory mechanisms of miRNAs during infection by immunosuppressive viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0922-x) contains supplementary material, which is available to authorized users.


title: Collaboration between infection control and occupational health in three continents: a success story with international impact

text: Globalization has been accompanied by the rapid spread of infectious diseases, and further strain on working conditions for health workers globally. Post-SARS, Canadian occupational health and infection control researchers got together to study how to better protect health workers, and found that training was indeed perceived as key to a positive safety culture. This led to developing information and communication technology (ICT) tools. The research conducted also showed the need for better workplace inspections, so a workplace audit tool was also developed to supplement worker questionnaires and the ICT. When invited to join Ecuadorean colleagues to promote occupational health and infection control, these tools were collectively adapted and improved, including face-to-face as well as on-line problem-based learning scenarios. The South African government then invited the team to work with local colleagues to improve occupational health and infection control, resulting in an improved web-based health information system to track incidents, exposures, and occupational injury and diseases. As the H1N1 pandemic struck, the online infection control course was adapted and translated into Spanish, as was a novel skill-building learning tool that permits health workers to practice selecting personal protective equipment. This tool was originally developed in collaboration with the countries from the Caribbean region and the Pan American Health Organization (PAHO). Research from these experiences led to strengthened focus on building capacity of health and safety committees, and new modules are thus being created, informed by that work. The products developed have been widely heralded as innovative and interactive, leading to their inclusion into “toolkits” used internationally. The tools used in Canada were substantially improved from the collaborative adaptation process for South and Central America and South Africa. This international collaboration between occupational health and infection control researchers led to the improvement of the research framework and development of tools, guidelines and information systems. Furthermore, the research and knowledge-transfer experience highlighted the value of partnership amongst Northern and Southern researchers in terms of sharing resources, experiences and knowledge.


title: Laboratory Detection of Respiratory Viruses by Automated Techniques

text: Advances in clinical virology for detecting respiratory viruses have been focused on nucleic acids amplification techniques, which have converted in the reference method for the diagnosis of acute respiratory infections of viral aetiology. Improvements of current commercial molecular assays to reduce hands-on-time rely on two strategies, a stepwise automation (semi-automation) and the complete automation of the whole procedure. Contributions to the former strategy have been the use of automated nucleic acids extractors, multiplex PCR, real-time PCR and/or DNA arrays for detection of amplicons. Commercial fully-automated molecular systems are now available for the detection of respiratory viruses. Some of them could convert in point-of-care methods substituting antigen tests for detection of respiratory syncytial virus and influenza A and B viruses. This article describes laboratory methods for detection of respiratory viruses. A cost-effective and rational diagnostic algorithm is proposed, considering technical aspects of the available assays, infrastructure possibilities of each laboratory and clinic-epidemiologic factors of the infection


SEVERE HUMAN RHINOVIRUS OUTBREAK ASSOCIATED WITH FATALITIES IN A LONG‐TERM CARE FACILITY IN ONTARIO, CANADA


title: Animal movements and the spread of infectious diseases

text: Domestic and wild animal population movements are important in the spread of disease. There are many recent examples of disease spread that have occurred as a result of intentional movements of livestock or wildlife. Understanding the volume of these movements and the risks associated with them is fundamental in elucidating the epidemiology of these diseases, some of which might entail zoonotic risks. The importance of the worldwide animal trade is reviewed and the role of the unregulated trade in animals is highlighted. A range of key examples are discussed in which animal movements have resulted in the introduction of pathogens to previously disease-free areas. Measures based on heightened surveillance are proposed that mitigate the risks of new pathogen introductions.


title: Preconditioning with high mobility group box 1 protein protects against myocardial ischemia–reperfusion injury

text: Abstract Objective To investigate whether preconditioning with high mobility group box 1 protein (HMGB1) could reduce myocardial ischemia–reperfusion (I/R) injury. Methods and results Infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were assessed. HMGB1 preconditioning reduced significantly the infarct size induced by I/R. The LDH, CK, TNF-α and IL-6 levels were significantly decreased by HMGB1 preconditioning compared to those in the I/R group. Conclusion The present study suggested that preconditioning with HMGB1 could induce HMGB1 tolerance and protect against myocardial I/R injury.


title: Education and the COVID-19 pandemic

text: The COVID-19 pandemic is a huge challenge to education systems. This Viewpoint offers guidance to teachers, institutional heads, and officials on addressing the crisis. What preparations should institutions make in the short time available and how do they address students’ needs by level and field of study? Reassuring students and parents is a vital element of institutional response. In ramping up capacity to teach remotely, schools and colleges should take advantage of asynchronous learning, which works best in digital formats. As well as the normal classroom subjects, teaching should include varied assignments and work that puts COVID-19 in a global and historical context. When constructing curricula, designing student assessment first helps teachers to focus. Finally, this Viewpoint suggests flexible ways to repair the damage to students’ learning trajectories once the pandemic is over and gives a list of resources.


title: Trends in the Mechanistic and Dynamic Modeling of Infectious Diseases

text: The dynamics of infectious disease epidemics are driven by interactions between individuals with differing disease status (e.g., susceptible, infected, immune). Mechanistic models that capture the dynamics of such “dependent happenings” are a fundamental tool of infectious disease epidemiology. Recent methodological advances combined with access to new data sources and computational power have resulted in an explosion in the use of dynamic models in the analysis of emerging and established infectious diseases. Increasing use of models to inform practical public health decision making has challenged the field to develop new methods to exploit available data and appropriately characterize the uncertainty in the results. Here, we discuss recent advances and areas of active research in the mechanistic and dynamic modeling of infectious disease. We highlight how a growing emphasis on data and inference, novel forecasting methods, and increasing access to “big data” are changing the field of infectious disease dynamics. We showcase the application of these methods in phylodynamic research, which combines mechanistic models with rich sources of molecular data to tie genetic data to population-level disease dynamics. As dynamics and mechanistic modeling methods mature and are increasingly tied to principled statistical approaches, the historic separation between the infectious disease dynamics and “traditional” epidemiologic methods is beginning to erode; this presents new opportunities for cross pollination between fields and novel applications.


title: SARS-CoV-2 et Cancer en France: les internes d’oncologie en première ligne. Témoignage des internes d’oncologie de deux clusters français, le Grand Est et l’Île de France

text: Résumé Un nouveau coronavirus, le SARS-CoV-2 est responsable de la première pandémie du XXIe siècle. Après la région de Wuhan, Hubei en Chine, premier cluster de ce virus, les pays européens, dont la France, sont actuellement les pays avec le plus de nouveaux cas de patients contaminés. Cette épidémie bouleverse l’organisation du corps médical et paramédical, notamment la prise en charge des patients de cancérologie, infectés ou non par le virus, tant elle mobilise de moyens de santé et nécessite en urgence une modification des pratiques médicales. Abstract À new coronavirus, named SARS-CoV-2, is responsible of the first pandemic in the 21st century. The outbreak of 2019 novel coronavirus disease (COVID19) first occurred in Wuhan, Hubei in China. European countries, and France, are now the main cluster, with thousands of new cases of COVID-19 patients. This epidemic requires such health care resources and an urgent modification of our medical procedures that it is about to upset profoundly the entire medical organization. In particular, the epidemic changes totally the management of patients in oncology, be they infected or not. We report hereby the testimonies of residents in oncology regarding modifications in health and patient care and the different organizations that are implemented in France, in two clusters of the infection, to cope with the virus. Residents, who are given higher autonomy, are especially concerned with the short- and long-term consequences of the situation for their patients.


Artificial Intelligence during a pandemic: The COVID‐19 example


Very low reporting rate of connective tissue diseases among coronavirus disease 2019 (Covid-19) patients and the renin-angiotensin system – an overlooked association?


title: Effects of trading networks on the risk of bovine tuberculosis incidents on cattle farms in Great Britain

text: Trading animals between farms and via markets can provide a conduit for spread of infections. By studying trading networks, we might better understand the dynamics of livestock diseases. We constructed ingoing contact chains of cattle farms in Great Britain that were linked by trading, to elucidate potential pathways for the transmission of infection and to evaluate their effect on the risk of a farm experiencing a bovine tuberculosis (bTB) incident. Our findings are consistent with variation in bTB risk associated with region, herd size, disease risk area and history of previous bTB incidents on the root farm and nearby farms. However, we also identified effects of both direct and indirect trading patterns, such that connections to more farms in the England High-Risk Area up to three movements away from the root farm increased the odds of a bTB incident, while connections with more farms in the England Low-Risk Area up to eight movements away decreased the odds. Relative to other risk factors for bTB, trading behaviours are arguably more amenable to change, and consideration of risks associated with indirect trading, as well direct trading, might therefore offer an additional approach to bTB control in Great Britain.


title: The laboratory’s role in combating COVID-19

text: Since Coronavirus Disease 2019 (COVID-19) first emerged in December 2019, the disease has rapidly evolved into a pandemic that threatens societies around the world. As soon as the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified and its genome sequence determined, a laboratory diagnosis based on nucleic acid amplification technologies was quickly established and has played essential roles in the confirmation of a clinical diagnosis. Serological testing for antibodies against SARS-CoV-2 is becoming available for complementary diagnosis, identification of convalescent plasma, and epidemiologic studies. Additional laboratory biochemical tests, including monitoring the change in blood cells, blood gas, coagulation, liver function, cardiac markers, and inflammatory responses such as cytokine levels in plasma, are also critical in combating COVID-19. Nevertheless, with overwhelming numbers of patients and potentially large numbers of asymptomatic cases, clinical laboratories encounter enormous challenges in diagnostic approaches that can rapidly and accurately identify infected persons. Strategies that can effectively detect disease progression in order to stratify patients for appropriate care, and that can thereby prevent exacerbation of the disease, are urgently needed. This review discusses the laboratory’s role and challenges in combating COVID-19.


Tweeting, tweeting


title: Host resilience to emerging coronaviruses

text: Recently, two coronaviruses, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, have emerged to cause unusually severe respiratory disease in humans. Currently, there is a lack of effective antiviral treatment options or vaccine available. Given the severity of these outbreaks, and the possibility of additional zoonotic coronaviruses emerging in the near future, the exploration of different treatment strategies is necessary. Disease resilience is the ability of a given host to tolerate an infection, and to return to a state of health. This review focuses on exploring various host resilience mechanisms that could be exploited for treatment of severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus and other respiratory viruses that cause acute lung injury and acute respiratory distress syndrome.


title: Interferon-Induced Transmembrane Protein 3 Inhibits Hantaan Virus Infection, and Its Single Nucleotide Polymorphism rs12252 Influences the Severity of Hemorrhagic Fever with Renal Syndrome

text: Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Previous studies have identified interferon-induced transmembrane proteins (IFITMs) as an interferon-stimulated gene family. However, the role of IFITMs in HTNV infection is unclear. In this study, we observed that IFITM3 single nucleotide polymorphisms (SNP) rs12252 C allele and CC genotype associated with the disease severity and HTNV load in the plasma of HFRS patients. In vitro experiments showed that the truncated protein produced by the rs12252 C allele exhibited an impaired anti-HTNV activity. We also proved that IFITM3 was able to inhibit HTNV infection in both HUVEC and A549 cells by overexpression and RNAi assays, likely via a mechanism of inhibiting virus entry demonstrated by binding and entry assay. Localization of IFITM3 in late endosomes was also observed. In addition, we demonstrated that the transcription of IFITM3 is negatively regulated by an lncRNA negative regulator of interferon response (NRIR). Taken together, we conclude that IFITM3, negatively regulated by NRIR, inhibits HTNV infection, and its SNP rs12252 correlates with the plasma HTNV load and the disease severity of patients with HFRS.


title: Knowledge of Latin American gastroenterologists and endoscopists regarding SARS-CoV-2 infection

text: Abstract Introduction After the World Health Organization declared the COVID-19 outbreak a pandemic, the number of patients with confirmed SARS-CoV-2 infection (COVID-19) has increased exponentially, and gastroenterologists and other specialists most likely will be involved in the care of those patients. Aim To evaluate the knowledge Latin American gastroenterologists and endoscopists (staff physicians and residents) have about the characteristics of COVID-19, as well as the prevention measures to be taken during endoscopic procedures. Materials and methods We conducted a cross-sectional study that included gastroenterologists and endoscopists from 9 Latin American countries. An electronic questionnaire was applied that was designed to evaluate the knowledge of symptoms, risk groups for severe disease, prevention measures, and the reprocessing of endoscopes utilized in patients with COVID-19. Results Information was obtained from 133 physicians. Ninety-five percent of them correctly identified the most frequent symptoms of the virus, and 60% identified the 3 risk groups for severe disease. Sixty-six percent of those surveyed did not consider it necessary to use standard precautions during endoscopic procedures, and 30% did not consider contact precautions necessary. Forty-eight percent of the participants surveyed were not familiar with the protocol for reprocessing the endoscopes utilized in patients with COVID-19. Conclusion The majority of the gastroenterologists and endoscopists surveyed were familiar with the signs and symptoms of COVID-19 and the populations at risk for complications. There was a lack of knowledge about prevention measures (during clinical care and endoscopic procedures) and the reprocessing of endoscopic equipment by 70% and 48%, respectively, of those surveyed. Dissemination and teaching strategies that increase the knowledge of specific biosafety measures must be carried out.


Renin-angiotensin-aldosterone system inhibitors impact on COVID-19 mortality: What’s next for ACE2?


title: Degenerate primer design to clone the human repertoire of immunoglobulin heavy chain variable regions

text: Amplifying the variable (Fv or V) regions of immunoglobulins (Ig) has become a challenge in cloning antibody genes for phage display, a technique used to study protein–protein, protein–peptide, and protein–DNA interactions using bacteriophages to connect proteins with the genetic information that encodes them. Key parameters affecting the amplification of full antibody repertoires includes the availability of primers that can amplify as many V genes as possible; however the strategy used to design these primers and programs used to make the necessary alignments have not been well studied and clearly detailed in the literature. Here, we present a set of primers computationally designed by iCODEHOP based on a database of human germline Ig sequences. We used reverse transcription polymerase chain reaction (RT-PCR) protocols that would recognize the V(H) genes from human peripheral blood mononuclear cells. We identified the most highly conserved region in framework 1 and framework 4 of the Ig cDNA, and designed a set of degenerated 5′ primers. The V(H) genes were successfully amplified by RT-PCR. This new primer has facilitated the creation of more diverse V(H) libraries than has been previously possible. Moreover, iCODEHOP improved the primer design efficiency and was found useful both for cloning unknown genes in gene families and for building V(H) gene libraries.


title: High prevalence of SARS-CoV-2 infection in repatriation flights to Greece from three European countries

text: Passengers on repatriation flights to Greece from the UK, Spain and Turkey were screened with oropharyngeal swabs on arrival for SARS-CoV-2 infection. Despite almost all passengers being asymptomatic, many tested positive (3.6% from UK, 6.3% from Spain and 6.3% from Turkey), indicating widespread transmission of SARS-CoV-2 in these countries.


title: Straw particle size in calf starters: Effects on digestive system development and rumen fermentation 1

text: Abstract Two trials were conducted to determine effects of straw particle size in calf starter on rumen fermentation and development in calves. Holstein calves (n=17 in trial 1; n=25 in trial 2) were housed in individual pens; bedding (wood shavings) was covered with landscape fabric to completely avoid consumption of bedding. Milk replacer was fed at 12% of birth body weight per day and water offered free choice. Calves were randomly assigned to 4 treatments differing in geometric mean particle length (Xgm) of straw comprising 5% of starter dry matter. Straw was provided within the pellet at manufacture (PS; 0.82mm Xgm) or mixed with the pellet at time of feeding at Xgm of 3.04 (SS), 7.10 (MS), or 12.7 (LS) mm. Calves (n=12; 3/treatment) in trial 1 were fitted with a rumen cannula by wk 2 of age. A fixed amount of starter that was adjusted with age and orts were fed through the cannula in cannulated calves. Calves were euthanized 6 wk after starter was offered (9 and 7 wk of age for trials 1 and 2, respectively). Rumen digesta pH linearly decreased with age, whereas volatile fatty acid concentration increased with age. Overall pH had a cubic trend with SS lower than that of PS and MS. Molar proportion of acetate decreased with age whereas propionate proportion increased. Overall molar proportions of volatile fatty acids were not affected by diet. Fecal Xgm was not different in spite of changes in diet particle size and rumen digesta of PS being greater than SS, MS, and LS at slaughter. Fecal pH and starch concentration were not affected by diet; however, pH decreased whereas starch content increased with age. Weight of stomach compartments, rumen papillae length and width, and rumen wall thickness did not differ between diets. Omasum weight as a percentage of body weight at harvest linearly decreased as straw particle size increased. Under the conditions of this study, modifying straw particle length in starter grain resulted in minimal rumen fermentation parameter changes and no changes in rumen development. Rumen pH and fermentation changes with age were likely effects of increasing starter intake.


title: Anti‐poliovirus activity of Baccharis dracunculifolia and propolis by cell viability determination and real‐time PCR

text: Aims: The aim of this work was to evaluate the antiviral activities of Baccharis dracunculifolia (extract and essential oil), propolis and some isolated compounds (caffeic and cinnamic acids) against poliovirus type 1 (PV1) replication in HEp‐2 cells. Method: Three different protocols (pre‐, simultaneous and post‐treatments) were used to verify the effect of addition time of the variables on PV1 replication by crystal violet method and relative viral RNA quantification by real‐time PCR for analysing in which step of virus replication the variables could interfere. Conclusions: Data revealed that the B. dracunculifolia showed the best antiviral activity percentage in the simultaneous treatment, as well as lower relative viral quantification by real‐time PCR. Variables might block partially the viral entry within cells, affect the steps of viral cycle replication into cells, or lead to RNA degradation before the virus entry into cells or after their release to the supernatant. Significance and Impact of the Study: Baccharis dracunculifolia is the most important botanical source of the south‐eastern Brazilian propolis, and its potential for the development of new phytotherapeutic medicines has been investigated. Propolis is commonly used for its antimicrobial and immunomodulatory activities. Nevertheless, B. dracunculifolia and propolis effects on PV1 have not been investigated yet.


title: Preparing for uncertainty during public health emergencies: What Canadian health leaders can do now to optimize future emergency response

text: It is clear that the risk for epidemics with high health and socio-economic impacts remains but there will be many unknowns at the start of future responses to these events. This article highlights principles and practices to assist health leaders in preparing for uncertainty, including integrating scalability to ensure response activities can be more easily adapted to suit evolving needs; assessing risk and capabilities to inform planning for appropriate response measures; and considering overall flexibility and adaptability of plans, systems, and resources. Ultimately, being prepared for “Disease X” is about applying the approaches that we have learned from previous events, using evidence-based practices to develop and strengthen foundational capacities, so that we are able to respond to the unanticipated in proportionate and appropriate ways.


title: Improving the large scale purification of the HIV microbicide, griffithsin

text: BACKGROUND: Griffithsin is a broad spectrum antiviral lectin that inhibits viral entry and maturation processes through binding clusters of oligomannose glycans on viral envelope glycoproteins. An efficient, scaleable manufacturing process for griffithsin active pharmaceutical ingredient (API) is essential for particularly cost-sensitive products such as griffithsin -based topical microbicides for HIV-1 prevention in resource poor settings. Our previously published purification method used ceramic filtration followed by two chromatography steps, resulting in a protein recovery of 30%. Our objective was to develop a scalable purification method for griffithsin expressed in Nicotiana benthamiana plants that would increase yield, reduce production costs, and simplify manufacturing techniques. Considering the future need to transfer griffithsin manufacturing technology to resource poor areas, we chose to focus modifying the purification process, paying particular attention to introducing simple, low-cost, and scalable procedures such as use of temperature, pH, ion concentration, and filtration to enhance product recovery. RESULTS: We achieved >99% pure griffithsin API by generating the initial green juice extract in pH 4 buffer, heating the extract to 55°C, incubating overnight with a bentonite MgCl(2) mixture, and final purification with Capto™ multimodal chromatography. Griffithsin extracted with this protocol maintains activity comparable to griffithsin purified by the previously published method and we are able to recover a substantially higher yield: 88 ± 5% of griffithsin from the initial extract. The method was scaled to produce gram quantities of griffithsin with high yields, low endotoxin levels, and low purification costs maintained. CONCLUSIONS: The methodology developed to purify griffithsin introduces and develops multiple tools for purification of recombinant proteins from plants at an industrial scale. These tools allow for robust cost-effective production and purification of griffithsin. The methodology can be readily scaled to the bench top or industry and process components can be used for purification of additional proteins based on biophysical characteristics.


Peripheral lymphocyte subset alterations in COVID‐19 patients


title: The Role of Genomics in the Identification, Prediction, and Prevention of Biological Threats

text: In all likelihood, it is only a matter of time before our public health system will face a major biological threat, whether intentionally dispersed or originating from a known or newly emerging infectious disease. It is necessary not only to increase our reactive “biodefense,” but also to be proactive and increase our preparedness. To achieve this goal, it is essential that the scientific and public health communities fully embrace the genomic revolution, and that novel bioinformatic and computing tools necessary to make great strides in our understanding of these novel and emerging threats be developed. Genomics has graduated from a specialized field of science to a research tool that soon will be routine in research laboratories and clinical settings. Because the technology is becoming more affordable, genomics can and should be used proactively to build our preparedness and responsiveness to biological threats. All pieces, including major continued funding, advances in next-generation sequencing technologies, bioinformatics infrastructures, and open access to data and metadata, are being set in place for genomics to play a central role in our public health system.


title: Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway

text: Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID) “hot spot” in a light chain CDR (complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in combination of chain-shuffling as well as hot-spot CDR mutagenesis, can be exploited to broaden neutralization activity, to improve anti-viral nAb therapies, and directly manipulate virus evolution.


The impact of diabetes on COVID‐19 infection


title: On respiratory droplets and face masks

text: Face mask filters—textile, surgical, or respiratory—are widely used in an effort to limit the spread of airborne viral infections. Our understanding of the droplet dynamics around a face mask filter, including the droplet containment and leakage from and passing through the cover, is incomplete. We present a fluid dynamics study of the transmission of respiratory droplets through and around a face mask filter. By employing multiphase computational fluid dynamics in a fully coupled Eulerian–Lagrangian framework, we investigate the droplet dynamics induced by a mild coughing incident and examine the fluid dynamics phenomena affecting the mask efficiency. The model takes into account turbulent dispersion forces, droplet phase-change, evaporation, and breakup in addition to the droplet–droplet and droplet–air interactions. The model mimics real events by using data, which closely resemble cough experiments. The study shows that the criteria employed for assessing the face mask performance must be modified to take into account the penetration dynamics of airborne droplet transmission, the fluid dynamics leakage around the filter, and reduction of efficiency during cough cycles. A new criterion for calculating more accurately the mask efficiency by taking into account the penetration dynamics is proposed. We show that the use of masks will reduce the airborne droplet transmission and will also protect the wearer from the droplets expelled from other subjects. However, many droplets still spread around and away from the cover, cumulatively, during cough cycles. Therefore, the use of a mask does not provide complete protection, and social distancing remains important during a pandemic. The implications of the reduced mask efficiency and respiratory droplet transmission away from the mask are even more critical for healthcare workers. The results of this study provide evidence of droplet transmission prevention by face masks, which can guide their use and further improvement.


Helmet Continuous Positive Airway Pressure and prone positioning: a proposal for an early management of COVID-19 patients.


title: Model Selection in Time Series Studies of Influenza-Associated Mortality

text: BACKGROUND: Poisson regression modeling has been widely used to estimate influenza-associated disease burden, as it has the advantage of adjusting for multiple seasonal confounders. However, few studies have discussed how to judge the adequacy of confounding adjustment. This study aims to compare the performance of commonly adopted model selection criteria in terms of providing a reliable and valid estimate for the health impact of influenza. METHODS: We assessed four model selection criteria: quasi Akaike information criterion (QAIC), quasi Bayesian information criterion (QBIC), partial autocorrelation functions of residuals (PACF), and generalized cross-validation (GCV), by separately applying them to select the Poisson model best fitted to the mortality datasets that were simulated under the different assumptions of seasonal confounding. The performance of these criteria was evaluated by the bias and root-mean-square error (RMSE) of estimates from the pre-determined coefficients of influenza proxy variable. These four criteria were subsequently applied to an empirical hospitalization dataset to confirm the findings of simulation study. RESULTS: GCV consistently provided smaller biases and RMSEs for the influenza coefficient estimates than QAIC, QBIC and PACF, under the different simulation scenarios. Sensitivity analysis of different pre-determined influenza coefficients, study periods and lag weeks showed that GCV consistently outperformed the other criteria. Similar results were found in applying these selection criteria to estimate influenza-associated hospitalization. CONCLUSIONS: GCV criterion is recommended for selection of Poisson models to estimate influenza-associated mortality and morbidity burden with proper adjustment for confounding. These findings shall help standardize the Poisson modeling approach for influenza disease burden studies.


Covid-19 and The Documented Failure of the American Illness Profit System — We Have to Stop Treating our Doctors, Nurses, Healthcare Workers, and Ourselves this Way


title: Virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms

text: The novel coronavirus SARS-CoV2, the causative agent of the pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide necessitated the discovery of new substances for anti-COVID-19 drug development. With the aid of bioinformatics and computational modelling, ninety seven antiviral secondary metabolites from fungi were docked onto five SARS-CoV2 enzymes involved in viral attachment, replication, post-translational modification, and host immunity evasion infection mechanisms followed by molecular dynamics simulation and in silico ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds. Thus, three fumiquinazoline alkaloids scedapin C (15), quinadoline B (19) and norquinadoline A (20), the polyketide isochaetochromin D1 (8), and the terpenoid 11a-dehydroxyisoterreulactone A (11) exhibited high binding affinities on the target proteins, papain-like protease (PLpro), chymotrypsin-like protease (3CLpro), RNA-directed RNA polymerase (RdRp), non-structural protein 15 (nsp15), and the spike binding domain to GRP78. Molecular dynamics simulation was performed to optimize the interaction and investigate the stability of the top-scoring ligands in complex with the five target proteins. All tested complexes were found to have dynamic stability. Of the five top-scoring metabolites, quinadoline B (19) was predicted to confer favorable ADMET values, high gastrointestinal absorptive probability and poor blood-brain barrier crossing capacities. Communicated by Ramaswamy H. Sarma


title: Identifying sources of tick blood meals using unidentified tandem mass spectral libraries

text: Rapid and reliable identification of the vertebrate species on which a disease vector previously parasitized is imperative to study ecological factors that affect pathogen distribution and can aid the development of public health programs. Here we describe a proteome profiling technique designed to identify the source of blood meals of hematophagous arthropods. This method employs direct spectral matching and thus does not require a priori knowledge of any genetic or protein sequence information. Using this technology, we detect remnants of blood in blacklegged ticks (Ixodes scapularis) and correctly determine the vertebrate species from which the blood was derived even six months after the tick had fed. This biological fingerprinting methodology is sensitive, fast, cost-effective, and can potentially be adapted for other biological and medical applications when existing genome-based methods are impractical or ineffective.


title: An Experimental Model for Myocarditis and Congestive Heart Failure after Rabbit Coronavirus Infection

text: In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2–5) and subacute (days 6–12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.


title: Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

text: The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a target of the antiviral drug, Remdesivir. Here we report the cryo-EM structure of the SARS-CoV-2 RdRp either in the apo form at 2.8 Å resolution or in complex with a 50-base template-primer RNA and Remdesivir at 2.5 Å resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp where Remdesivir is covalently incorporated into the primer strand at the first replicated base pair and terminates chain elongation. Our structures provide critical insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.


title: Neurosonology during the COVID‐19 pandemic (Editorial commentary from the chairs of the ultrasound panel of the EAN)

text: The COVID‐19 pandemic is seriously affecting the lives of billions of people around the world, especially in the healthcare systems.(1) Although the impact of pandemic on health services are mostly negative, there is still a chance to use this situation as an opportunity for positive changes. Neurosonological examination involves direct contact between the patient and the sonographer, often for several tens of minutes.


title: Vaginal delivery in SARS‐CoV‐2‐infected pregnant women in Northern Italy: a retrospective analysis

text: OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID‐19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID‐19‐confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS‐CoV‐2‐infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co‐morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID‐19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0–72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7–59.0) cases: in eight cases the indication was unrelated to COVID‐19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8–61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3–61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1–45.6) were admitted to a critical care unit. Two women with COVID‐19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS‐Cov‐2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS‐Cov‐2 transmission to the newborn.


title: Anticipation and response: pandemic influenza in Malawi, 2009

text: Background: In 2006, Malawi developed a national influenza plan to mitigate, prevent and manage the burden of infection should an outbreak occur. In 2009, it translated its contingency plan to respond to the unfolding influenza pandemic. However, little is known of how Malawi translated its national influenza plan into response actions, or the success of these responses. Objective: To investigate how Malawi translated its preparedness plan and so broaden our understanding of the outcomes of the responses. Methods: We draw on data from 22 in-depth interviews with government policymakers and people working at a policy level in various non-governmental organisations, conducted to assess the level of preparedness and the challenges of translating this. Results: Through a number of public health initiatives, authorities developed communication strategies, strengthened influenza surveillance activities and updated overall goals in pandemic training and education. However, without influenza drills, exercises and simulations to test the plan, activating the pandemic plan, including coordinating and deploying generic infection control measures, was problematic. Responses during the pandemic were at times ‘weak and clumsy’ and failed to mirror the activities and processes highlighted in the preparedness plan. Conclusions: Participants stressed that in order to achieve a coordinated and successful response to mitigate and prevent the further transmission of pandemic influenza, good preparation was critical. The key elements which they identified as relevant for a rapid response included effective communications, robust evidence-based decision-making, strong and reliable surveillance systems and flexible public health responses. To effectively articulate a viable trajectory of pandemic responses, the potential value of simulation exercises could be given more consideration as a mean of sustaining good levels of preparedness and responses against future pandemics. These all demand a well-structured planning for and response to pandemic influenza strategy developed by a functioning scientific and policy advisory committee.


title: PCAF interacts with XBP-1S and mediates XBP-1S-dependent transcription

text: X-box binding protein 1 (XBP-1) is a key regulator required for cellular unfolded protein response (UPR) and plasma cell differentiation. In addition, involvement of XBP-1 in host cell–virus interaction and transcriptional regulation of viruses, such as human T-lymphotropic virus type 1 (HTLV-1), has been revealed recently. Two XBP-1 isoforms, XBP-1U and XBP-1S, which share an identical N-terminal domain, are present in cells. XBP-1S is a transcription activator while XBP-1U is the inactive isoform. Although the transactivation domain of XBP-1S has been identified within the XBP-1S-specific C-terminus, molecular mechanism of the transcriptional activation by XBP-1S still remains unknown. Here we report the interaction between p300/CBP-associated factor (PCAF) and XBP-1S through the C-terminal domain of XBP-1S. No binding between XBP-1U and PCAF is detected. In a cell-based reporter assay, overexpression of PCAF further stimulates the XBP-1S-mediated cellular and HTLV-1 transcription while knockdown of PCAF exhibits the opposite effect. Expression of endogenous XBP-1S cellular target genes, such as BiP and CHOP, is significantly inhibited when PCAF is knocked down. Furthermore, PCAF is recruited to the promoters of XBP-1S target genes in vivo, in a XBP-1S-dependent manner. Collectively, our results demonstrate that PCAF mediates the XBP-1S-dependent transcription through the interaction with XBP-1S.


title: Assessing visible aerosol generation during vitrectomy in the era of Covid-19

text: OBJECTIVE: To assess visible aerosol generation during simulated vitrectomy surgery. METHODS: A model comprising a human cadaveric corneoscleral rim mounted on an artificial anterior chamber was used. Three-port 25 gauge vitrectomy simulated surgery was performed with any visible aerosol production recorded using high-speed 4K camera. The following were assessed: (1) vitrector at maximum cut rate in static and dynamic conditions inside the model, (2) vitrector at air–fluid interface in a physical model, (3) passive fluid–air exchange with a backflush hand piece, (4) valved cannulas under air, and (5) a defective valved cannula under air. RESULTS: No visible aerosol or droplets were identified when the vitrector was used within the model. In the physical model, no visible aerosol or droplets were seen when the vitrector was engaged at the air–fluid interface. Droplets were produced from the opening of backflush hand piece during passive fluid–air exchange. No visible aerosol was produced from the intact valved cannulas under air pressure, but droplets were seen at the beginning of fluid–air exchange when the valved cannula was defective. CONCLUSIONS: We found no evidence of visible aerosol generation during simulated vitrectomy surgery with competent valved cannulas. In the physical model, no visible aerosol was generated by the high-speed vitrector despite cutting at the air–fluid interface.


title: COVID‐19 is a challenge for dental education—A commentary

text: The COVID‐19, which appeared to originate in China in December 2019, has spread worldwide pandemically. In this commentary, authors described this new challenge for dental education using the recent literature and experience gained in the Italian University of Catanzaro.


title: Proteomics informed by transcriptomics for characterising differential cellular susceptibility to Nelson Bay orthoreovirus infection

text: BACKGROUND: Nelson Bay orthoreovirus (NBV) is a fusogenic bat borne virus with an unknown zoonotic potential. Previous studies have shown that NBV can infect and replicate in a wide variety of cell types derived from their natural host (bat), as well as from human, mouse and monkey. Within permissive cells, NBV induced significant cytopathic effects characterised by cell-cell fusion and syncytia formation. To understand the molecular events that underpin NBV infection we examined the host transcriptome and proteome response of two cell types, derived from bat (PaKiT03) and mouse (L929), to characterise differential cellular susceptibility to NBV. RESULTS: Despite significant differences in NBV replication and cytopathic effects in the L929 and PaKiT03 cells, the host response was remarkably similar in these cells. At both the transcriptome and proteome level, the host response was dominated by IFN production and signalling pathways. The majority of proteins up-regulated in L929 and PaKiT03 cells were also up-regulated at the mRNA (gene) level, and included many important IFN stimulated genes. Further functional experimentation demonstrated that stimulating IFN signalling prior to infection, significantly reduced NBV replication in PaKiT03 cells. Moreover, inhibiting IFN signalling (through specific siRNAs) increased NBV replication in L929 cells. In line with the significant cytopathic effects seen in PaKiT03 cells, we also observed a down-regulation of genes involved in cell-cell junctions, which may be related to the fusogenic effects of NBV. CONCLUSIONS: This study provides new multi-dimensional insights into the host response of mammalian cells to NBV infection. We show that IFN activity is capable of reducing NBV replication, although it is unlikely that this is solely responsible for the reduced replication of NBV in L929 cells. The molecular events that underpin the fusogenic cytopathic effects described here will prove valuable for identifying potential therapeutic targets against fusogenic orthoreovirus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3994-x) contains supplementary material, which is available to authorized users.


title: Comparing the economic effects of climate change and zooanthroponosis in Korea: Prerequisites for the creative economy?

text: Abstract Societies in the 21st century require more proactive management of risks in many areas owing to the complexities people have built into socioeconomic systems, ranging from science and technology, economics, and finance to education, entertainment, and tourism infrastructure. All these systems thrive on stability, which can easily be challenged by unexpected risks. This study compares zooanthroponosis and climate change-induced sea level rise through a cost–benefit analysis in Korea. Borrowing from other methodological approaches, this study shows that the cost–benefit estimation is consistent with the existing macroeconomic speculations, which assume potential loss of GDP due to the two risks. This paper also presents a policy alternative of creating research institutions specializing in the two risks from a cost–benefit perspective as a prerequisite for the "Creative Economy".


title: Viral Pathogen Detection by Metagenomics and Pan-Viral Group Polymerase Chain Reaction in Children With Pneumonia Lacking Identifiable Etiology

text: BACKGROUND. Community-acquired pneumonia (CAP) is a leading cause of pediatric hospitalization. Pathogen identification fails in approximately 20% of children but is critical for optimal treatment and prevention of hospital-acquired infections. We used two broad-spectrum detection strategies to identify pathogens in test-negative children with CAP and asymptomatic controls. METHODS. Nasopharyngeal/oropharyngeal (NP/OP) swabs from 70 children <5 years with CAP of unknown etiology and 90 asymptomatic controls were tested by next-generation sequencing (RNA-seq) and pan viral group (PVG) PCR for 19 viral families. Association of viruses with CAP was assessed by adjusted odds ratios (aOR) and 95% confidence intervals controlling for season and age group. RESULTS. RNA-seq/PVG PCR detected previously missed, putative pathogens in 34% of patients. Putative viral pathogens included human parainfluenza virus 4 (aOR 9.3, P = .12), human bocavirus (aOR 9.1, P < .01), Coxsackieviruses (aOR 5.1, P = .09), rhinovirus A (aOR 3.5, P = .34), and rhinovirus C (aOR 2.9, P = .57). RNA-seq was more sensitive for RNA viruses whereas PVG PCR detected more DNA viruses. CONCLUSIONS. RNA-seq and PVG PCR identified additional viruses, some known to be pathogenic, in NP/OP specimens from one-third of children hospitalized with CAP without a previously identified etiology. Both broad-range methods could be useful tools in future epidemiologic and diagnostic studies.


title: Guidelines: Anaesthesia in the context of COVID-19 pandemic

text: ABSTRACT Objectives: The world is currently facing an unprecedented healthcare crisis caused by COVID-19 pandemic. The objective of these guidelines is to produce a framework to facilitate the partial and gradual resumption of intervention activity in the context of the COVID-19 pandemic. Methods: The group has endeavoured to produce a minimum number of recommendations to highlight the strengths to be retained in the 7 predefined areas: (1) Protection of staff and patients; (2) Benefit/Risk and Patient Information; (3) Pre-operative assessment and decision on intervention; (4) Modalities of the pre-anaesthesia consultation; (5) Specificity of anaesthesia and analgesia; (6) Dedicated circuits and (7) Containment Exit Type of Interventions. Results: The SFAR Guideline panel provides 51 statements on anaesthesia management in the context of COVID-19 pandemic. After one round of discussion and various amendments, a strong agreement was reached for 100% of the recommendations and algorithms. Conclusion: We present suggestions for how the risk of transmission by and to anaesthetists can be minimised and how personal protective equipment policies relate to COVID-19 pandemic context


title: RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination

text: BACKGROUND: TRIM25 is a novel RNA-binding protein and a member of the Tripartite Motif (TRIM) family of E3 ubiquitin ligases, which plays a pivotal role in the innate immune response. However, there is scarce knowledge about its RNA-related roles in cell biology. Furthermore, its RNA-binding domain has not been characterized. RESULTS: Here, we reveal that the RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain, which we postulate to be a novel RNA-binding domain. Using CLIP-seq and SILAC-based co-immunoprecipitation assays, we uncover TRIM25’s endogenous RNA targets and protein binding partners. We demonstrate that TRIM25 controls the levels of Zinc Finger Antiviral Protein (ZAP). Finally, we show that the RNA-binding activity of TRIM25 is important for its ubiquitin ligase activity towards itself (autoubiquitination) and its physiologically relevant target ZAP. CONCLUSIONS: Our results suggest that many other proteins with the PRY/SPRY domain could have yet uncharacterized RNA-binding potential. Together, our data reveal new insights into the molecular roles and characteristics of RNA-binding E3 ubiquitin ligases and demonstrate that RNA could be an essential factor in their enzymatic activity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-017-0444-9) contains supplementary material, which is available to authorized users.


title: The effect of variant interference on de novo assembly for viral deep sequencing

text: BACKGROUND: Viruses have high mutation rates and generally exist as a mixture of variants in biological samples. Next-generation sequencing (NGS) approaches have surpassed Sanger for generating long viral sequences, yet how variants affect NGS de novo assembly remains largely unexplored. RESULTS: Our results from > 15,000 simulated experiments showed that presence of variants can turn an assembly of one genome into tens to thousands of contigs. This “variant interference” (VI) is highly consistent and reproducible by ten commonly-used de novo assemblers, and occurs over a range of genome length, read length, and GC content. The main driver of VI is pairwise identities between viral variants. These findings were further supported by in silico simulations, where selective removal of minor variant reads from clinical datasets allow the “rescue” of full viral genomes from fragmented contigs. CONCLUSIONS: These results call for careful interpretation of contigs and contig numbers from de novo assembly in viral deep sequencing.


title: Role of Clinical Endoscopy in Emphasizing Endoscope Disinfection

text: Based on the unexpected Middle East respiratory syndrome (MERS) outbreak in Korea, it was established that the virus can spread easily, MERS exposure in hospitals carries an extreme risk for infection as well as mortality, and the sharing of information was essential for infection control. Although the incidence of exogenous infections related to contaminated endoscopes is very low, the majority of published outbreaks have been caused by various shortcomings in reprocessing procedures, including insufficient training or awareness. Ever since the inauguration of "Clinical Endoscopy" as an English-language journal of the Korean Society of Gastrointestinal Endoscopy in 2011, it has published several articles on disinfection of the endoscope and its accessories. Many Science Citation Index journals have also emphasized high-level disinfection of the gastrointestinal endoscope. Many papers have been produced specifically, since the outbreak of carbapenem-resistant Enterobacteriaceae in 2013. The recent review papers concluded that quality control is the most important issue among all the aspects of procedural care, including the efficiency of the gastrointestinal endoscopy unit and reprocessing room. Thorough reprocessing of endoscopes using high-level disinfection and sterilization methods may be essential for reducing the risk of infection.


title: Isolation of a Chinook Salmon Bafinivirus (CSBV) in Imported Goldfish Carassius auratus L. in the United Kingdom and Evaluation of Its Virulence in Resident Fish Species

text: This is the first record of a fish nidovirus isolated from a consignment of goldfish at the United Kingdom (UK) border. The full-length viral genome was 25,985 nt, sharing a 97.9% nucleotide identity with the Chinook salmon bafinivirus (CSBV) NIDO with two deletions of 537 and 480 nt on the ORF Ia protein. To assess the potential impact on UK fish species, Atlantic salmon, common carp and goldfish were exposed to the virus via an intraperitoneal (IP) injection and bath challenge. Moribundity was recorded in only 8% of IP-injected goldfish. A high viral load, ≈10(7) of the CSBV PpIa gene, was measured in the kidney of moribund goldfish. Mild histopathological changes were observed in the kidneys of challenged carps. Ultrastructural observations in renal tubule epithelial cells of goldfish showed cylindrical tubes (≈15 nm in diameter) and tubular structures budding spherical virions (≈200 nm in diameter) with external spike-like structures. Negative staining showed both circular and bacilliform virions. Seroconversion was measured in common carp and goldfish but not in Atlantic salmon. This study reinforces the potential risk of novel and emerging pathogens being introduced to recipient countries via the international ornamental fish trade and the importance of regular full health screens at the border inspection posts to reduce this risk.


title: Facility-based surveillance for emerging infectious diseases; diagnostic practices in rural West African hospital settings: observations from Ghana

text: The aim of this study was to better understand the effectiveness of Integrated Disease Surveillance and Response (IDSR) facility-based surveillance in detecting newly emerging infectious diseases (EIDs) in rural West African settings. A six-month ethnographic study was undertaken in 2012 in the Techiman Municipality of the Brong-Ahafo Region of Ghana, aimed at documenting the trajectories of febrile illness cases of unknown origin occurring within four rural communities. Particular attention was paid to where these trajectories involved the use of formal healthcare facilities and the diagnostic practices that occurred there. Seventy-six participants were enrolled in the study, and 24 complete episodes of illness were documented. While participants routinely used hospital treatment when confronted with enduring or severe illness, the diagnostic process within clinical settings meant that an unusual diagnosis, such as an EID, was unlikely to be considered. Facility-based surveillance is unlikely to be effective in detecting EIDs due to a combination of clinical care practices and the time constraints associated with individual episodes of illness, particularly in the resource-limited settings of rural West Africa, where febrile illness due to malaria is common and specific diagnostic assays are largely unavailable. The success of the ‘One Health' approach to EIDs in West Africa is predicated on characterization of accurately diagnosed disease burdens. To this end, we must address inefficiencies in the dominant approaches to EID surveillance and the weaknesses of health systems in the region generally. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being'.


title: A Health System Response to COVID‐19 in Long‐Term Care and Post‐Acute Care: A Three‐Phase Approach

text: BACKGROUND: The Seattle, WA, area was ground zero for coronavirus disease 2019 (COVID‐19). Its initial emergence in a skilled nursing facility (SNF) not only highlighted the vulnerability of its patients and residents, but also the limited clinical support that led to national headlines. Furthermore, the coronavirus pandemic heightened the need for improved collaboration among healthcare organizations and local and state public health. METHODS: The University of Washington Medicine's (UWM's) Post‐Acute Care (PAC) Network developed and implemented a three‐phase approach within its pre‐existing network of SNFs to help slow the spread of the disease, support local area SNFs from becoming overwhelmed when inundated with COVID‐19 cases or persons under investigation, and help decrease the burden on area hospitals, clinics, and emergency medical services. RESULTS: Support of local area SNFs consisted of the following phases that were implemented at various times as COVID‐19 impacted each facility at different times. Initial Phase: This phase was designed to (1) optimize communication, (2) review infection control practices, and (3) create a centralized process to track and test the target population. Delayed Phase: The goals of the Delayed Phase were to slow the spread of the disease once it is present in the SNF by providing consistent education and reinforcing infection prevention and control practices to all staff. Surge Phase: This phase aimed to prepare facilities in response to an outbreak by deploying a "Drop Team" within 24 hours to the facility to expeditiously test patients and exposed employees, triage symptomatic patients, and coordinate care and supplies with local public health authorities. CONCLUSIONS: The COVID‐19 Three‐Phase Response Plan provides a standardized model of care that may be implemented by other health systems and SNFs to help prepare and respond to COVID‐19.


title: Clinical trials in the pandemic age: What is fit for purpose?

text: It is critical to ensure that COVID-19 studies provide clear and timely answers to the scientific questions that will guide us to scalable solutions for all global regions. Significant challenges in operationalizing trials include public policies for managing the pandemic, public health and clinical capacity, travel and migration, and availability of tests and infrastructure. These factors lead to spikes and troughs in patient count by location, disrupting the ability to predict when or if a trial will reach recruitment goals. The focus must also be on understanding how to provide equitable access to these interventions ensuring that interventions reach those who need them the most, be it patients in low resource settings or vulnerable groups. We introduce a website to be used by The Bill & Melinda Gates Foundation, Wellcome Trust, and other funders of the COVID Therapeutics Accelerator that accept proposals for future clinical research. The portal enables evaluations of clinical study applications that focus on study qualities most likely to lead to informative outcomes and completed studies.


Research, friendship, the joy of writing and the editorship of Journal of Nephrology


title: COVID-19 Serosurveillance May Facilitate Return-to-Work Decisions

text: Public health measures are needed to resolve the novel coronavirus disease (COVID-19) pandemic, although a looming economic fallout merits close attention. Early safe reintroduction of immune individuals into the workforce may be essential to protecting the economic welfare of communities. Reverse transcriptase–polymerase chain reaction testing, our primary diagnostic tool to date, has sensitivity and timing concerns, owing to sampling/handling errors, as well as a complex virus–host interaction. Reverse transcriptase–polymerase chain reaction assays do not establish immune status once the virus has been cleared. Targeted serosurveillance for the determination of individuals’ potential for transmissibility, particularly if paired with direct pathogen testing, may aid in “cleared for business” decision-making.


title: Detection of enteric pathogens in Turkey flocks affected with severe enteritis, in Brazil

text: Twenty-two flocks of turkeys affected by enteric problems, with ages between 10 and 104 days and located in the Southern region of Brazil, were surveyed for turkey by PCR for turkey astrovirus type 2 (TAstV-2), turkey coronavirus (TCoV), hemorrhagic enteritis virus (HEV), rotavirus, reovirus, Salmonella spp., and Lawsonia intracellularis (Li) infections. Eleven profiles of pathogen combination were observed. The most frequently encountered pathogen combinations were TCoV-Li, followed by TCoV-TAstV-2-Li, TCoV-TastV-2. Only TCoV was detected as the sole pathogen in three flocks. Eight and 19 flocks of the 22 were positive for TAstV-2 and TCoV, respectively. Six were positive for Salmonella spp. and L. intracellularis was detected in 12 turkey flocks. Reovirus and HEV were not detected in this survey. These results throw new light on the multiple etiology of enteritis in turkeys. The implications of these findings and their correlation with the clinical signs are comprehensively discussed, illustrating the complexity of the enteric diseases.


title: Neurological Complications during Treatment of Middle East Respiratory Syndrome

text: BACKGROUND AND PURPOSE: Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012. METHODS: We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described. RESULTS: Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2–3 weeks. CONCLUSIONS: Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.


To All Doctors: What You Can Do to Help as a Bunch of Older People Are About to Get Sick and Die


title: COVID‐19: A series of important recent clinical and laboratory reports in immunology and pathogenesis of SARS‐CoV‐2 infection and care of allergy patients

text: The “coronavirus disease 2019 (COVID‐19)” outbreak was first reported in December 2019 (China). Since then, this disease has rapidly spread across the globe and in March 2020 the World Health Organization (WHO) declared the COVID‐19 pandemic.(1) Since the outbreak was first announced, our journal has extensively focused on the clinical features, outcomes, diagnosis, immunology, and pathogenesis of COVID‐19 and its infectious agent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).


title: Cumulative biological source index volumes 1–30

text: Publisher Summary This chapter lists the important subjects on biological source that are discussed in the publication, such as Abies grandis Acanthodris nanaimoensis, Baccharis crispa, acanthosterol sulfates, Agelas dispar, Plasmodium falciparum, Podophyllum hexandrum, Quillaja saponaria, and Rauwolfia serpentina. The terms are mentioned along with the page numbers in which they are discussed in the publication.


Global health beyond geographical boundaries: reflections from global health education


title: Analysis of Ebola Virus Entry Into Macrophages

text: Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells.


title: Rethinking how we care for our patients in a time of social distancing

text: Online consultations


Evolution of Plastic Surgery Provision due to COVID-19 – The Role of the ‘Pandemic Pack’


title: Enterovirus 71 induces anti-viral stress granule-like structures in RD cells

text: Abstract Stress granules (SGs) are dynamic cytoplasmic granules formed in response to a variety of stresses, including viral infection. Several viruses can modulate the formation of SG with different effects, but the relationship between SG formation and EV71 infection is poorly understood. In this study, we report that EV71 inhibits canonical SGs formation in infected cells and induces the formation of novel RNA granules that were distinguished from canonical SGs in composition and morphology, which we termed ‘SG like structures’. Our results also demonstrated that EV71 triggered formation of SG-like structures is dependent on PKR and eIF2α phosphorylation and requires ongoing cellular mRNA synthesis. Finally, we found that SG-like structures are antiviral RNA granules that promote cellular apoptosis and suppress EV71 propagation. Taken together, our findings explain the formation mechanism of SG-like structures induced by EV71 and shed light on virus-host interaction and molecular mechanism underlying EV71 pathogenesis.


title: Presumed pulmonary COVID-19 infection detected incidentally on breast MR

text: COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A global pandemic was declared by the World Health Organisation on 11 March 2020. Approximately 30% of infected individuals are asymptomatic.(1) We present the case of a 68-year-old female who underwent outpatient breast magnetic resonance (MR) imaging for assessment of a right breast mass. The study demonstrated abnormal subpleural high T2 signal intensity change within in the partially visualised lungs, which showed enhancement following administration of contrast. Concern was raised that the pulmonary changes may represent COVID-19 infection. The patient was urgently contacted and denied any current symptoms but reported suffering mild upper respiratory tract symptoms two weeks earlier. An outpatient chest radiograph demonstrated changes consistent with COVID-19 infection and the patient was treated as COVID-19 positive and advised to self-isolate for seven days as per Public Health England guidance.(2) Due to increasing breathlessness the patient presented to our Emergency Department the next day and underwent a CT pulmonary angiogram which demonstrated segmental pulmonary emboli and subpleural consolidation in keeping with COVID-19 infection. This represents the first case of COVID-19 identified on breast MR imaging that the authors have seen and highlights the importance of prompt identification and flagging of incidental pulmonary findings to minimise further transmission of the virus in asymptomatic carriers.


title: Pandemics and food systems - towards a proactive food safety approach to disease prevention & management

text: Recent large-scale pandemics such as the covid19, H1N1, Swine flu, Ebola and the Nipah virus, which impacted human health and livelihoods, have come about due to inadequate food systems safeguards to detect, trace and eliminate threats arising from zoonotic diseases. Such diseases are transmitted to humans through their interaction with animals in the food value chain including through the consumption of bush meat. Climate change has also facilitated the emergence of new zoonotic diseases. The lack of adequately enforced food-safety standards in managed agricultural production systems creates the necessary conditions for diseases to mutate into highly contagious strains. The lack of food safety measures in handling, packaging and sales of food increases risks of cross-species contamination. Finally, increasing anti-microbial resistance, combined with rapid urbanization and global interconnectedness allows diseases to spread rapidly among humans. Thus, part of the reconstruction efforts, post covid19, should include prioritizing proactive investments in food safety. The key to stave off another such pandemic lies in integrating one-health knowledge on zoonotic diseases along with food safety measures along the food value chain. Refocusing policy priorities from disease control to prevention will improve international coordination efforts in pandemic prevention. Implementing such proactive actions will cost a very small fraction of the reconstruction budgets. However, the expected benefits of the food-safety approach will include preventing global economic losses due to pandemics.


title: Strategies to halt 2019 novel coronavirus (COVID‐19) spread for organ transplantation programs at the Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, China

text: During the coronavirus outbreak in China, our center performed 16 organ transplants (10 kidney, 4 liver and 2 lung transplants, from January 24 to March 11, 2020) harvested from deceased donors. Regarding the strategies to prevent infections of COVID‐19, we implemented specific measures for the donor and recipient management, as well as prevention of hospital‐acquired infections. All 16 organ recipients had a favorable outcome without COVID‐19 infection. Our approaches aiming to interrupt the spread of coronavirus within the transplantation wards were successful and allowed us to maintain the transplantation program for deceased liver, kidney and lung recipients.


Spinal cord disorders


title: The role of miR-29c/B7-H3/Th17 axis in children with Mycoplasma pneumoniae pneumonia

text: BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is one of the most common causes of community-acquired pneumonia in children. Recent studies demonstrated that the incidence of severe or fatal M. pneumoniae was gradually increasing, which may be related to the excessive inflammation. However, the exact pathogenesis of excessive inflammation in Mycoplasma pneumoniae pneumonia(MPP) is still unclear. This study aimed to reveal the role of miR-29c/B7-H3/Th17 axis in children with MPP. METHODS: Children hospitalized in Respiratory Department during Jan. 2014 to Dec. 2015 were enrolled. All children enrolled was confirmed with MP infection using real-time PCR and ELISA. Children were excluded if they were co-infected with other pathogens. A total of 52 children with MPP and 26 controls were enrolled. miR-29c expression in monocytes of children with MPP was determined by real-time PCR and soluble B7-H3 (sB7-H3) and IL-17 were determined by ELISA, and explore their clinical significance. miR-29c overexpression and silencing technology and luciferase reporter assay were performed to confirm whether B7-H3 is the direct target of miR-29c. The levels of transcription factor ROR-γt in CD4+ T cells and cytokine IL-17A in supernatant were detected after stimulated by different concentrations of B7-H3 fusion protein in vitro. RESULTS: Of all 52 children with MPP, the mean age of the children were 77 ± 33 months, and 23 cases were male accounting for 44.2%. Nineteen cases had pleural effusion accounting for 36.5%. Children with MPP had significantly lower level of miR-29c and higher level of sB7-H3 and IL-17 compared to controls (both P < 0.05). The level of miR-29c significantly increased during convalescent phase compared to that of acute phase while sB7-H3 and IL-17 significantly decreased during convalescent phase (both P < 0.05). There was a positive correlation between the level of sB7-H3 and IL-17 in children with MPP during acute-stage (r = 0.361,P = 0.009). Children with MPP combined with pleural effusion had significantly higher level of sB7-H3 compared to those without pleural effusion (9952.3 ± 3065.3 vs. 7449.7 ± 2231.5, pg/ml), and the levels of sB7-H3 was positively correlated with the number of days of fever. The level of miR-29c was negatively correlated with M. pneumoniae specific IgG, IgM level. High concentrations of B7-H3(15μg/ml) could enhance ROR-γt expression and increase IL-17A. Functional studies based on luciferase reporter assay and immunofluorescence staining suggested that B7-H3 is the direct target of miR-29c, and miR-29c silencing or overexpression could up- or down-regulate the expression of B7-H3 in THP-1 cells. CONCLUSIONS: The axis of miR-29c/B7-H3/Th17 plays a vital role in children with MPP through excessive inflammation. miR-29c and B7-H3 may be the new target for the prevention and treatment of MPP, and may be the novel and potential biomarkers for the assessment of prognosis.


title: Post-transcriptional gene regulation by RNA-binding proteins in vascular endothelial dysfunction

text: Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions, including impairment of the barrier functions, control of vascular tone, disturbance of proliferative and migratory capacity of endothelial cells, as well as control of leukocyte trafficking. Endothelial dysfunction is an early step in vascular inflammatory diseases such as atherosclerosis, diabetic vascular complications, sepsis-induced or severe virus infection-induced organ injuries. The expressions of inflammatory cytokines and vascular adhesion molecules induced by various stimuli, such as modified lipids, smoking, advanced glycation end products and bacteria toxin, significantly contribute to the development of endothelial dysfunction. The transcriptional regulation of inflammatory cytokines and vascular adhesion molecules has been well-studied. However, the regulation of those gene expressions at post-transcriptional level is emerging. RNA-binding proteins have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level in microRNA-dependent or independent manners. This review summarizes the latest insights into the roles of RNA-binding proteins in controlling vascular endothelial cell functions and their contribution to the pathogenesis of vascular inflammatory diseases.


How fragile we are