title: White-nose syndrome is associated with increased replication of a naturally persisting coronaviruses in bats

text: Spillover of viruses from bats to other animals may be associated with increased contact between them, as well as increased shedding of viruses by bats. Here, we tested the prediction that little brown bats (Myotis lucifugus) co-infected with the M. lucifugus coronavirus (Myl-CoV) and with Pseudogymnoascus destructans (Pd), the fungus that causes bat white-nose syndrome (WNS), exhibit different disease severity, viral shedding and molecular responses than bats infected with only Myl-CoV or only P. destructans. We took advantage of the natural persistence of Myl-CoV in bats that were experimentally inoculated with P. destructans in a previous study. Here, we show that the intestines of virus-infected bats that were also infected with fungus contained on average 60-fold more viral RNA than bats with virus alone. Increased viral RNA in the intestines correlated with the severity of fungus-related pathology. Additionally, the intestines of bats infected with fungus exhibited different expression of mitogen-activated protein kinase pathway and cytokine related transcripts, irrespective of viral presence. Levels of coronavirus antibodies were also higher in fungal-infected bats. Our results suggest that the systemic effects of WNS may down-regulate anti-viral responses in bats persistently infected with M. lucifugus coronavirus and increase the potential of virus shedding.


title: Novel Coronavirus, Old Partisanship: COVID-19 Attitudes and Behaviours in the United States and Canada

text: The novel coronavirus reached the United States and Canada almost at the same time. The first reported American case was January 20, 2020, and in Canada it was January 15, 2020 (Canada, 2020; Holshue et al., 2020). Yet, the response to this crisis has been different in the two countries. In the US, President Donald Trump, prominent Republicans, and conservative media initially dismissed the dangers of COVID-19 (Stecula, 2020). The pandemic became politicized from the early days, and even though Trump and Republicans have walked back many of their initial claims, there continue to be media reports of partisan differences in public opinion shaped by that early response. At the same time, the response in Canada has been mostly characterized by across-the-board partisan consensus among political elites (Merkley et al., 2020).


title: Chiral zirconium quantum dots: A new class of nanocrystals for optical detection of coronavirus

text: A synthetic way of chiral zirconium quantum dots (Zr QDs) was presented for the first time using L(+)-ascorbic acid acts as a surface as well as chiral ligands. Different spectroscopic and microscopic analysis was performed for thorough characterization of Zr QDs. As-synthesized QDs exhibited fluorescence and circular dichroism properties, and the peaks were located at 412 nm and 352 nm, respectively. MTT assay was performed to test the cytotoxicity of the synthesized Zr QDs against rat brain glioma C6 cells. Synthesized QDs was further conjugated with anti-infectious bronchitis virus (IBV) antibodies of coronavirus to form an immunolink at the presence of the target analyte and anti-IBV antibody-conjugated magneto-plasmonic nanoparticles (MPNPs). The fluorescence properties of immuno-conjugated QD–MP NPs nanohybrids through separation by an external magnetic field enabled biosensing of coronavirus with a limit of detection of 79.15 EID/50 μL.


title: Zoonoses☆

text: Abstract Zoonoses are the ‘diseases and infections that are naturally transmitted between vertebrate animals and man,’ as defined in 1951 by the World Health Organization (WHO) Expert Committee on Zoonoses. The word zoonosis (plural zoonoses) is the combination of two Greek words (zoon, animals and noson, disease), and was coined at the end of the nineteenth century by Rudolph Virchow to designate human diseases caused by animals. Nevertheless, the term should also include vertebrate animal diseases caused by exposure to humans, such as measles in non-human primates, which is of major concern in any major primate center. The term ‘zoonosis’ is also considered to be shorter and more convenient than ‘anthropozoonosis’ (animals to humans) and ‘zooanthroponosis’ (humans to animals), which are based on the prevailing direction of transmission between humans and other vertebrates.


Multicenter analysis of clinical characteristics and outcome of COVID-19 patients with liver injury


title: Induction of insert-specific immune response in mice by hamster polyomavirus VP1 derived virus-like particles carrying LCMV GP33 CTL epitope

text: Abstract Hamster polyomavirus (HaPyV) major capsid protein VP1 based chimeric virus-like particles (VLPs) carrying model GP33 CTL epitope derived from Lymphocytic choriomeningitis virus (LCMV) were generated in yeast and examined for their capability to induce CTL response in mice. Chimeric VP1-GP33 VLPs were effectively processed in antigen presenting cells in vitro and in vivo and induced antigen-specific CD8+ T cell proliferation. Mice immunized only once with VP1-GP33 VLPs without adjuvant developed an effective GP33-specific memory T cell response: 70% were fully and 30% partially protected from LCMV infection. Moreover, aggressive growth of tumors expressing GP33 was significantly delayed in these mice in vivo. Therefore, HaPyV VP1-derived VLP harboring CTL epitopes are attractive vaccine candidates for the induction of insert-specific CTL immune response.


docid: lprvsgsx

title: « Crown protection » ou velléités protectrices du Corona Covid-19 et ses rencontres improbables

text: Résumé Notre premier cas illustre la possibilité de nos patients de relativiser la gravité de la pandémie et de son impact et le deuxième cas soutient cette hypothèse. Les modalités de traitement psychotrope sont très importantes dans des cas spécifiques de pathologie et cela peut apporter des éléments nouveaux dans le domaine psychiatrique et dans le domaine immunitaire au sujet de la protection antibiothérapique pré- et post-opératoire. Rencontre improbable avec une maladie qui conduit à un épisode de folie et la prise en charge psychologique après un épisode sévère de Covid-19. L’accompagnement psychologique est bouleversé par cette maladie, comme le reste. La clinique revient à son sens d’origine : au lit du malade pour comprendre cette nouvelle maladie et ses effets protecteurs et/ou révélateurs. Rencontre à la fois avec une forme grave de cette nouvelle maladie et l’expression psychopathologique au sein des unités des soins intensifs et de post-réanimation. L’écoute singulière et psychanalytique permet au patient de comprendre le processus de construction de son épisode d’apparence délirant, comme la construction onirique. Adaptation et création d’une clinique nécessitant d’être au plus proche du malade pour permettre la restructuration psychique ayant été désorganisation en lien avec la maladie mais également avec l’environnement hospitalier et familial, fortement impactés par l’angoisse. Abstract The title of our paper could be receipted (intellectually receipted) like a paradox or like choking item. In real life of our hospital activity is not at all true because in both clinical situations the symptomatology of infectious disease was protected about a long psychotic or pseudo psychotic episode. The most important for the psychiatric stabilization was strictly observance and repetition of consultations who created a secure feel, necessarily for construction after psychodramatic real story Covid-19. Our clinical case shows the possibility of our patients to relativize the gravity of the pandemic and his impact. The modalities of psychotropic treatment are very important in this specific pathologic case and our presentation could give us new ideas in psychiatry and immunology about protection by ay antibiotherapy in pre- and post-operatory. Unlikely encounter with a disease that leads to an episode of madness and psychological care after a severe episode of Covid-19. Psychological support is upset by this disease, like the rest. The clinic returns to its original meaning: at the patient's bed to understand this new disease and its protective and / or revealing effects. Clinical presentation of an unlikely encounter in the context of the Covid-19 epidemic. Encounter with both a severe form of this new disease and psychopathological expression in intensive care and post-reanimation units. Psychological support in a patient suffering from a delusional episode and identity disorders related to Covid-19. Psychological support is disrupted by this disease, as is the rest. The clinic returns to its original meaning: in the patient's bed to understand this new disease and its protective and/or revealing effects.The singular and psychoanalytic listening allows the patient to understand the process of constructing his episode of delusional appearance, like dreamlike construction. Adaptation and creation of a clinic requiring to be as close as possible to the patient to allow the psychological restructuring having been disorganized in connection with the disease but also with the hospital and family environment, strongly impacted by anxiety.


title: Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice

text: Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine–phosphate–guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design.


The role of (18)F-FDG PET for COVID-19 infection: myth versus reality


docid: mrltpnyw

title: Chapter Three Recent Advances in the Discovery of Deubiquitinating Enzyme Inhibitors

text: Abstract This review examines the small molecules described over the past decade as inhibitors of any of the approximately 100 human deubiquitinating enzymes (DUBs). Structures from patent publications as well as from the primary literature are included. Inhibitors of two viral DUBs are also described since these proteases share structural similarity with one of the human DUB sub-families. The structure, function and disease associations of certain DUBs are presented. The evolution of the screening assays used to identify and characterise new inhibitors is discussed. Several emerging trends in the series are highlighted and the ‘drug-likeness’ of the various inhibitors is analysed. Large pharmaceutical company collaborations have drawn attention to this field, and these recent advances are discussed in the context of the wider range of therapeutically important DUB targets.


Letter to the Editor: Our Response to COVID-19 as Endocrinologists and Diabetologists


Important considerations regarding the future management of Coronavirus (COVID-19)


title: Computational Analysis of Virus–Host Interactomes

text: High-throughput methods for screening of physical and functional interactions now provide the means to study virus–host interactions on a genome scale. The limited coverage of these methods and the large size and uncertain quality of the identified interaction sets, however, require sophisticated computational approaches to obtain novel insights and hypotheses on virus infection processes from these interactions. Here, we describe the central steps of bioinformatics methods applied most commonly for this task and highlight important aspects that need to be considered and potential pitfalls that should be avoided.


title: Picornavirus RNA polyadenylation by 3D(pol), the viral RNA-dependent RNA polymerase

text: Poly(A) tails are functionally important features of all picornavirus RNA genomes. Some viruses have genomes with relatively short poly(A) tails (encephalomyocarditis virus) whereas others have genomes with longer poly(A) tails (polioviruses and rhinoviruses). Here we review the polyadenylation of picornavirus RNA as it relates to the structure and function of 3D(pol). Poliovirus 3D(pol) uses template-dependent reiterative transcription mechanisms as it replicates the poly(A) tails of viral RNA (Steil et al., 2010). These mechanisms are analogous to those involved in the polyadenylation of vesicular stomatitis virus and influenza virus mRNAs. 3D(pol) residues intimately associated with viral RNA templates and products regulate the size of poly(A) tails in viral RNA (Kempf et al., 2013). Consistent with their ancient evolutionary origins, picornavirus 3D(pol) and telomerase reverse transcriptase (TERT) share structural and functional features. Structurally, both 3D(pol) and TERT assume a “right-hand” conformation with thumb, palm and fingers domains encircling templates and products. Functionally, both 3D(pol) and TERT use template-dependent reiterative transcription mechanisms to synthesize repetitive sequences: poly(A) tails in the case of picornavirus RNA genomes and DNA telomeres in the case of eukaryotic chromosomes. Thus, picornaviruses and their eukaryotic hosts (humans & animals) maintain the 3’ ends of their respective genomes via evolutionarily related mechanisms.


title: Chronology of COVID-19 Cases on the Diamond Princess Cruise Ship and Ethical Considerations: A Report From Japan

text: The Diamond Princess cruise ship has been anchored at the Yokohama port in Japan since February 3, 2020. A total of 691 cases of the coronavirus disease 2019 (COVID-19) infection had been confirmed as of February 23. The government initially assumed that the infection was not spreading aboard and therefore indicated that any persons who either tested negative for the virus or were asymptomatic should immediately disembark. However, on February 5, the government set a 14-day health observation period because of the severity of the infection. Passengers confirmed to be free from infection began disembarking on Day 15 (February 19) of the quarantine. The effectiveness and validity of infection control, justification for the timing of inspections, and even the nature of COVID-19 itself now are all in question. The ethical considerations related to cruise ship infection control include the reasonable justification for isolation, the psychological fragility and quality of life of the isolated passengers and crew members, the procedural justice inherent in a forced quarantine, and the optimization of control measures. The international coordination framework and the global ramifications of such outbreaks should be reevaluated by the international community. Denying a ship’s entry based on local politics is incompatible with global justice. Events such as these require an international response and global regulations that seek to reduce disparities.


Presence of Neutralizing Antibody against the 229E Strain of Coronavirus in the Sera of Residents of Sendai


Precision medicine in COVID-19: IL-1β a potential target


title: You are my death: the shattered temporalities of zombie time

text: This essay considers the relationship between the experience of life shortening chronic illness and the current COVID-19 crisis. Martin O’Brien uses his experience of living with cystic fibrosis to interrogate the temporal experience of living within a global pandemic. He returns to his concept of zombie time, the temporal experience of living longer than expected, in order to understand the presence of death as a way of life. The essay uses some of O’Brien’s own art practices, and an analysis of his own sick, coughing body in order to think through what it means to live with cystic fibrosis during a pandemic, which mimics much of its features. O’Brien argues that we are currently occupying a widespread zombie time, which frames other people as carriers of death, and that we must find ways of being together in order to survive.


title: Major swine viral diseases: an Asian perspective after the African swine fever introduction

text: Asia is a major pig producer of the world, and at present, African swine fever virus (ASFV) continues to significantly impact the Asian pig industry. Since more than 50% of the world’s pig population is in Asia, ASFV outbreaks in Asia will affect the global pig industry. Prior to the introduction of ASF, several outbreaks of major swine viruses occurred in Asia over the last two decades, including porcine reproductive and respiratory syndrome virus (PRRSV), porcine epidemic diarrhea virus (PEDV) and foot and mouth disease virus (FMDV). The rapid spreading of those viruses throughout Asia involve many factors such as the various pig production systems and supply chains ranging from back-yard to intensive industrial farms, animal movement and animal product trading within and among countries, and consumer behaviors. ASF has notoriously been known as a human-driven disease. Travelers and international trading are the major ASFV-carriers for the transboundary transmission and introduction to naïve countries. Globalization puts the entire pig industry at risk for ASF and other infectious diseases arising from Asian countries. Disease control strategies for the various pig production systems in Asia are challenging. In order to ensure future food security in the region and to prevent the deleterious consequences of ASF and other major viral disease outbreaks, disease control strategies and production systems must be improved and modernized.


title: Emerging Concepts of Data Integration in Pathogen Phylodynamics

text: Phylodynamics has become an increasingly popular statistical framework to extract evolutionary and epidemiological information from pathogen genomes. By harnessing such information, epidemiologists aim to shed light on the spatio-temporal patterns of spread and to test hypotheses about the underlying interaction of evolutionary and ecological dynamics in pathogen populations. Although the field has witnessed a rich development of statistical inference tools with increasing levels of sophistication, these tools initially focused on sequences as their sole primary data source. Integrating various sources of information, however, promises to deliver more precise insights in infectious diseases and to increase opportunities for statistical hypothesis testing. Here, we review how the emerging concept of data integration is stimulating new advances in Bayesian evolutionary inference methodology which formalize a marriage of statistical thinking and evolutionary biology. These approaches include connecting sequence to trait evolution, such as for host, phenotypic and geographic sampling information, but also the incorporation of covariates of evolutionary and epidemic processes in the reconstruction procedures. We highlight how a full Bayesian approach to covariate modeling and testing can generate further insights into sequence evolution, trait evolution, and population dynamics in pathogen populations. Specific examples demonstrate how such approaches can be used to test the impact of host on rabies and HIV evolutionary rates, to identify the drivers of influenza dispersal as well as the determinants of rabies cross-species transmissions, and to quantify the evolutionary dynamics of influenza antigenicity. Finally, we briefly discuss how data integration is now also permeating through the inference of transmission dynamics, leading to novel insights into tree-generative processes and detailed reconstructions of transmission trees. [Bayesian inference; birth–death models; coalescent models; continuous trait evolution; covariates; data integration; discrete trait evolution; pathogen phylodynamics.


title: Viral nanoparticles for drug delivery, imaging, immunotherapy, and theranostic applications

text: Viral nanoparticles (VNPs) encompass a diverse array of naturally occurring nanomaterials derived from plant viruses, bacteriophages, and mammalian viruses. The application and development of VNPs and their genome-free versions, the virus-like particles (VLPs), for nanomedicine is a rapidly growing. VLPs can encapsulate a wide range of active ingredients as well as be genetically or chemically conjugated to targeting ligands to achieve tissue specificity. VLPs are manufactured through scalable fermentation or molecular farming, and the materials are biocompatible and biodegradable. These properties have led to a wide range of applications, including cancer therapies, immunotherapies, vaccines, antimicrobial therapies, cardiovascular therapies, gene therapies, as well as imaging and theranostics. The use of VLPs as drug delivery agents is evolving, and sufficient research must continuously be undertaken to translate these therapies to the clinic. This review highlights some of the novel research efforts currently underway in the VNP drug delivery field in achieving this greater goal.


title: Prevalence of stress, anxiety, depression among the general population during the COVID-19 pandemic: a systematic review and meta-analysis

text: BACKGROUND: The COVID-19 pandemic has had a significant impact on public mental health. Therefore, monitoring and oversight of the population mental health during crises such as a panedmic is an immediate priority. The aim of this study is to analyze the existing research works and findings in relation to the prevalence of stress, anxiety and depression in the general population during the COVID-19 pandemic. METHOD: In this systematic review and meta-analysis, articles that have focused on stress and anxiety prevalence among the general population during the COVID-19 pandemic were searched in the Science Direct, Embase, Scopus, PubMed, Web of Science (ISI) and Google Scholar databases, without a lower time limit and until May 2020. In order to perform a meta-analysis of the collected studies, the random effects model was used, and the heterogeneity of studies was investigated using the I(2) index. Moreover. data analysis was conducted using the Comprehensive Meta-Analysis (CMA) software. RESULTS: The prevalence of stress in 5 studies with a total sample size of 9074 is obtained as 29.6% (95% confidence limit: 24.3–35.4), the prevalence of anxiety in 17 studies with a sample size of 63,439 as 31.9% (95% confidence interval: 27.5–36.7), and the prevalence of depression in 14 studies with a sample size of 44,531 people as 33.7% (95% confidence interval: 27.5–40.6). CONCLUSION: COVID-19 not only causes physical health concerns but also results in a number of psychological disorders. The spread of the new coronavirus can impact the mental health of people in different communities. Thus, it is essential to preserve the mental health of individuals and to develop psychological interventions that can improve the mental health of vulnerable groups during the COVID-19 pandemic.


docid: zddwajzg

title: Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance

text: Abstract Viruses still represent a significant threat to human and animal health worldwide. In the fight against viral infections, high-purity viral stocks are needed for manufacture of safer vaccines. It is also a priority to ensure the viral safety of biopharmaceuticals such as blood products. Chromatography techniques are widely implemented at both academic and industrial levels in the purification of viral particles, whole viruses and virus-like particles, and to remove viral contaminants from biopharmaceutical products. This paper focuses on polysaccharide adsorbents, particulate resins and membrane adsorbers, used in virus purification/removal chromatography processes. Different chromatographic modes are surveyed, with particular attention on ion exchange and affinity/pseudo-affinity adsorbents among which commercially available agarose-based resins (Sepharose®) and cellulose-based membrane adsorbers (Sartobind®) occupy a dominant position. Mainly built on the development of new ligands coupled to conventional agarose/cellulose matrices, the development perspectives of polysaccharide-based chromatography media in this antiviral area are stressed in a conclusive part.


title: Interferon-gamma response of PBMC indicates productive pseudorabies virus (PRV) infection in swine

text: Abstract In Chinese Meishan/German Landrace cross-bred swine F2 generation interferon gamma (IFN-γ) production by peripheral blood mononuclear cells (PBMC) was determined directly ex vivo at different time points after survival of a virulent pseudorabies virus (PRV) infection. This reactivity was compared with the reactivity of naïve PBMC. Significant IFN-γ production was determined in ELISA and ELISPOT only after in vitro PBMC re-stimulation with PRV and not with the closely related bovine herpesvirus BHV-1. The PRV-specific IFN-γ secretion from re-stimulated PBMC showed high levels 6 days after infection, before the presence of serum antibodies, and it persisted at a high level over a 3 months period. The response of a group of eight piglets infected intranasally with PRV varied. Only two animals showed the expected typical fever response. PRV specific IFN-γ production by PBMC clearly indicated that infection had occurred. Early significant IFN-γ production by primed PBMC turned out to be a reliable and specific ex vivo marker for cellular response against productive PRV infection in swine before antibody formation.


title: Identification and expressional analysis of two cathepsins from half-smooth tongue sole (Cynoglossus semilaevis)

text: Abstract Cathepsins are a family of lysosomal proteases that play an important role in protein degradation, antigen presentation, apoptosis, and inflammation. Cathepsins are divided into three groups, i.e., cysteine protease, serine protease, and aspartic protease. Cathepsin D and cathepsin L, which are aspartic protease and cysteine protease respectively, have been identified in a number of teleosts; however, the immunological relevance of fish cathepsins is largely unknown. In this study, we cloned and analyzed the expression profiles of a cathepsin D (CsCatD) and a cathepsin L (CsCatL) homologs from half-smooth tongue sole (Cynoglossus semilaevis). CsCatD is composed of 396 amino acid residues and shares 67.6–88.4% overall sequence identities with fish and human cathepsin D. Structurally CsCatD possesses an aspartic endopeptidase domain, which contains two conserved aspartic acid residues that form the catalytic site. CsCatL is 336 residues in length and shares 64.7–90.2% overall sequence identities with fish and human cathepsin L. CsCatL has an N-terminal cathepsin propeptide inhibitor domain followed by a Papain family cysteine protease domain, the latter containing four conserved catalytic residues: Gln-133, Cys-139, His-279, and Asn-303. Recombinant CsCatL purified from Escherichia coli exhibited apparent protease activity. Quantitative real time RT-PCR analysis detected constitutive expression of CsCatD and CsCatL in multiple tissues, with the lowest level found in heart and the highest level found in liver. Experimental challenge of tongue sole with the bacterial pathogen Vibrio anguillarum and megalocytivirus caused significant inductions of both CsCatD and CsCatL expression in kidney and spleen in time-dependent manners. Immunization of the fish with a subunit vaccine also enhanced CsCatD and CsCatL expression in the first week post-vaccination. These results suggest involvement of CsCatD and CsCatL in host immune reactions to bacterial and viral infections and in the process of antigen-induced immune response.


title: Humanitarian Access to Unapproved Interventions in Public Health Emergencies of International Concern

text: Jerome Singh considers how regulatory mechanisms can allow access to experimental interventions in humanitarian emergencies such as the Ebola epidemic.


title: Age-dependent variation in innate immune responses to porcine epidemic diarrhea virus infection in suckling versus weaned pigs

text: Abstract Porcine epidemic diarrhea (PED) is an enteric coronaviral infection that causes severe morbidity and mortality in suckling pigs, but less severe disease in older pigs. Consequently, it causes significant economic losses to the pork industry. There are limited studies on the innate immune responses to PED virus (PEDV) in pigs. The aims of our study were to investigate differences in innate immune responses to PEDV infection in suckling and weaned pigs and to examine if disease severity coincides with reduced innate immune responses. Weaned 26-day-old pigs (n =20) and 9-day-old nursing pigs (n =20) were assigned to PEDV inoculated or uninoculated control groups. The pigs were observed daily for clinical signs, virus shedding and were euthanized at post-inoculation days (PIDs) 1 and 5 to assay immune responses. Blood samples were collected at PIDs 1, 3 and 5. The natural killer (NK) cell frequencies, NK cell activities (lysis of target K562 tumor cells in vitro), CD3+CD4+ T cell and CD3+CD8+ T cell frequencies were measured in blood and ileum at PIDs 1 and 5. The PEDV infected suckling pigs showed severe diarrhea and vomiting at PID 1, whereas the PEDV infected weaned pigs showed milder clinical signs starting at PID 3. PEDV infected suckling pigs had significantly higher diarrhea scores, earlier fecal PEDV RNA shedding and significantly higher viremia (viral RNA in serum) compared to weaned pigs. There was no mortality in either infected suckling or infected weaned pigs. The control pigs not inoculated with PEDV did not show any clinical signs and no detectable fecal or serum PEDV RNA. Strikingly, PEDV infected suckling pigs had significantly lower NK cell frequencies, undetectable NK cell activity and lower IFNγ producing NK cells in blood and ileum compared to PEDV infected weaned pigs. Pro-inflammatory cytokine profiles of PEDV infected suckling pigs differed from those of PEDV infected weaned pigs and coincided with onset of fecal PEDV RNA shedding and serum PEDV RNA titers. The infected suckling pigs have higher and earlier increases in serum IFNα, but lower serum IL-8 and TNFα levels compared to infected weaned pigs. CD3+CD4+ T cell frequencies were significantly higher in ileum of suckling pigs than in weaned pigs, whereas there was no difference in CD3+CD8+ T cell frequencies. In conclusion, the observations of impaired lytic activity and IFN-γ production by NK cells in suckling pigs coincided with the increased severity of PEDV infection in the suckling pigs compared with the weaned pigs.


title: Evaluation of sialic acid and acute-phase proteins (haptoglobin and serum amyloids A) in healthy and avian infection bronchitis virus-infected chicks

text: Forty-five 24-day-old Cobb chicks infected with infectious bronchitis virus (IBV) and ten healthy 24-day-old Cobb chicks without any clinical signs of IBV as control group were selected for the study. All of the diseased chicks showed some or all of the clinical signs of infectious bronchitis including gasping, coughing and nasal discharge, wet eyes, swollen sinuses, reduction of food consumption and weight gain. Diagnosis of IBV was based on clinical signs and ELISA test. Blood samples were taken from the wing vein into two tubes: one containing ethylenediaminetetraacetic acid (EDTA) and one without EDTA. Haptoglobin (Hp), serum amyloid A (SAA), total sialic acid (TSA), lipid-bound sialic acid (LBSA) and protein-bound sialic acid (PBSA) concentrations were measured. All of the study variables were significantly higher in diseased birds compared with control group. Results showed that there were significant positive correlations between TSA, LBSA and PBSA in both groups. No correlation was observed between Hp and SAA with any other parameters; however, there was significant negative correlation between Hp and SAA in the control group. Results for receiver operating characteristic analysis showed that area under the curve (AUC) for TSA, LBSA, PBSA, Hp and SAA were 0.93, 0.98, 0.90, 0.90 and 0.80, respectively. According to AUC, LBSA was the most sensitive factor to change in the diseased birds. It can be concluded that in naturally occurring IBV infection, significant increases in TSA, LBSA, PBSA, Hp and SAA concentrations are expected and among study variables, LBSA had the most obvious change so it may be considered as the most sensitive parameter.


title: Nucleoside hydrolase DNA vaccine against canine visceral leishmaniasis

text: Abstract The Nucleoside Hydrolase (NH36) is the main marker of the FML complex of Leishmania donovani, antigen of the licensed Leishmune® vaccine for prophylaxis of canine visceral leishmaniasis. As a DNA vaccine in mice, it induces a TH1 immune response. We vaccinated mongrel dogs with the VR1012NH36 vaccine for prophylaxis and immunotherapy against a high dose Leishmania chagasi infection (7 x 108 infective amastigotes). The untreated controls developed more symptoms, higher parasite/lymphocyte ratio, smaller DTH reactions, lower proportions of NH36-specific CD4+ cells and sustained NH36-specific CD8+ cell counts than dogs of the prophylaxis group. In the immunotherapy treated group, enlarged DTH reactions, enhanced CD4+ and sustained CD8+ lymphocyte proportions were also detected, however, without reduction of symptoms or parasite/lymphocyte ratio, indicating that the vaccine was sufficiently potent to prevent but not to control the disease. Both treatments determined higher survival rates. Anti-FML antibodies increased in vaccinated and control dogs while anti-NH36 antibodies were only increased in vaccinees (p= 0.000). The parasite load of an untreated survivor control dog (638.05 parasites) felt outside the IC95% of that of vaccinated dogs (32.02, IC95% 9.45–64.59) suggesting that both vaccination treatments succeeded in reducing the Leishmania infective burden. Accordingly, an untreated control dog showed lower levels of IFN γ-β, IL-2, IL4 but not IL-10 β actin-relative quantification. We conclude that the VR1012-NH36 vaccine induces strong prophylactic protection and a milder immunotherapeutic effect against a high dose canine experimental infection with Leishmania chagasi.


title: Profile of resistance to IVIG treatment in patients with Kawasaki disease and concomitant infection

text: INTRODUCTION: Kawasaki disease (KD) can be associated with concomitant viral or bacterial infections. Children with persistent or recurrent fever 36 hours after the end of intravenous immunoglobulin (IVIG) are considered to be resistant to treatment and are at increased risk for coronary complications. Although concomitant infection does not affect coronary outcome, it is unknown how it influences the response to IVIG treatment. METHODOLOGY: Retrospective cohort study between 2008 and 2016 in a tertiary pediatric university hospital, including 154 children, of which 59 (38%) had concomitant infection. RESULTS: Children with concomitant infection were more likely to have fever 48 hours after initial IVIG treatment (36% vs 20%, p = 0.05) and to be treated with a second dose (33% vs 18%, p = 0.04). Children with infection had higher C-reactive protein at the time of diagnosis (148 vs 112 mg/L, p = 0.04), and 48 hours after IVIG administration (111 vs 59 mg/L, p = 0.003). Nevertheless, there was no statistically significant difference in the prevalence of coronary complications (Z-score > 2.5) between children with and without concomitant infection (36% vs 39%, p = 0.68). CONCLUSION: Children with KD and concomitant infection are more likely to have persistent fever and elevated inflammatory markers after treatment. This association increases the likelihood of receiving a second dose of IVIG but not the risk of coronary complication. Accordingly, prospective studies to distinguish true IVIG resistance from infection induced persistent fever is warranted.


docid: walbutor

title: Growth and trade in the United States and the world economy: Overview

text: Abstract After the slow recovery from the 2008–2009 global financial crisis, the world economy faced slower growth than in the previous decade and even the prospect of a new global financial crisis. This paper starts by examining the reasons for the slow economic recovery and growth in the after the 2008–2009 global financial crisis and "great recession". Then, it examines the reasons the United States grew faster than other advanced countries (especially Europe and Japan), the slowing growth of emerging market economies (and even economic crisis in some of them), and whether the world is now (February 2020) sliding toward a new global financial crisis and recession.


title: Complete Genome Characterization of Chinese Porcine Deltacoronavirus Strain CHN/Tianjin/2016

text: As we all know, porcine deltacoronavirus was first detected in Hong Kong, China. Here, we report the complete genome sequence of the Chinese porcine deltacoronavirus strain CHN/Tianjin/2016, which was collected and amplified from clinical fecal samples in March of 2016.


title: Impact of molecular point‐of‐care testing on clinical management and in‐hospital costs of patients suspected of influenza or RSV infection: a modeling study

text: BACKGROUND: At hospital admission, patients suspected of infection with influenza or respiratory syncytial virus (RSV) are placed in isolation, pending the outcome of diagnostics. In a significant number, isolated care proves unnecessary. We investigated the potential impact of molecular point‐of‐care (POC) diagnostics on patient management and in‐hospital costs. METHOD: Prospective collection of data on resource utilization within the hospital from consecutive patients 18 years or older presenting at our university medical center with symptoms of respiratory tract infection from December 2016 to April 2017. A cost analysis was conducted using Markov modeling comparing the actual course of events (on the basis of routine diagnostic tests) with two hypothetical scenarios: when POC would impact time to diagnosis only (scenario 1) or on discharge from the hospital, too (scenario 2). RESULTS: A total of 283 patients were included, of whom 217 (76.7%) were admitted. Influenza and RSV were detected in 31% and 7% of the patients, respectively. Fifty‐four percent of patients tested negative, of which 79% were kept in isolated care waiting for test results, with a median duration of 24 hours. Median length of stay was 6.0 days. Mean total in‐hospital costs per patient were € 5243. Introducing POC would lower mean costs per patient to € 4904 (scenario 1) and € 4206 (scenario 2). At the hospital level, this would result in a total cost reduction of € 95 937 to € 293 471 in a single influenza season. CONCLUSIONS: Introducing POC testing for patients presenting with symptoms of viral respiratory tract infection can reduce time‐to‐diagnosis, hospital stay and, thereby, in‐hospital costs.


title: A decade and a half of protein intrinsic disorder: Biology still waits for physics

text: The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically “freeze” while their “pictures are taken.” However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs.


docid: tqzmlpjw

title: The 13th European Colorectal Congress (#ECCStGallen), 1–5 December 2019, St Gallen, Switzerland: Congress Report


Ethical issues when planning mental health services after COVID-19 outbreak


Infecciones víricas. Clasificación. Infecciones por virus herpes


title: Synthesis, proteolytic processing and complex formation of N-terminally nested precursor proteins of the Rift Valley fever virus glycoproteins

text: Abstract The genomic M RNA segment of Rift Valley fever virus is transcribed to produce a single mRNA with multiple translation initiation sites. The products of translation are an N-terminal nested series of polyproteins. These polyproteins enter the secretory system of the host cell and are proteolytically processed to yield the mature virion glycoproteins, Gn and Gc, and two non-structural glycoproteins. By means of pulse-chase immune precipitation experiments we identify the Gn and Gc precursor molecules and also show that signal peptidase cleavage is required for mature Gn and Gc production. We also demonstrate that a hydrophobic domain at the N-terminus of Gn acts as a signal peptide only in the context of the polyprotein precursors that initiate at the second, fourth or fifth AUGs. In addition, we document that formation of Gn/Gc heteromeric complexes occur rapidly (<5 min) and can occur prior to signal peptidase processing of Gn, suggesting that this complex forms in the endoplasmic reticulum. Interestingly, Gc can form a complex with a glycoprotein that has been considered nonstructural, a discovery that has implications for both the topology and potential packaging of this glycoprotein.


title: Mitigating disruptions, and scalability of radiation oncology physics work during the COVID‐19 pandemic

text: PURPOSE: The COVID‐19 pandemic has led to disorder in work and livelihood of a majority of the modern world. In this work, we review its major impacts on procedures and workflow of clinical physics tasks, and suggest alternate pathways to avoid major disruption or discontinuity of physics tasks in the context of small, medium, and large radiation oncology clinics. We also evaluate scalability of medical physics under the stress of “social distancing”. METHODS: Three models of facilities characterized by the number of clinical physicists, daily patient throughput, and equipment were identified for this purpose. For identical objectives of continuity of clinical operations, with constraints such as social distancing and unavailability of staff due to system strain, however with the possibility of remote operations, the performance of these models was investigated. General clinical tasks requiring on‐site personnel presence or otherwise were evaluated to determine the scalability of the three models at this point in the course of disease spread within their surroundings. RESULTS: The clinical physics tasks within three models could be divided into two categories. The former, which requires individual presence, include safety‐sensitive radiation delivery, high dose per fraction treatments, brachytherapy procedures, fulfilling state and nuclear regulatory commission's requirements, etc. The latter, which can be handled through remote means, include dose planning, physics plan review and supervision of quality assurance, general troubleshooting, etc. CONCLUSION: At the current level of disease in the United States, all three models have sustained major system stress in continuing reduced operation. However, the small clinic model may not perform if either the current level of infections is maintained for long or staff becomes unavailable due to health issues. With abundance, and diversity of innovative resources, medium and large clinic models can sustain further for physics‐related radiotherapy services.


title: A research agenda for aging in China in the 21st century

text: China is encountering formidable healthcare challenges brought about by the problem of aging. By 2050, there will be 400 million Chinese citizens aged 65+, 150 million of whom will be 80+. The undesirable consequences of the one-child policy, rural-to-urban migration, and expansion of the population of ‘empty nest ’ elders are eroding the traditional family care of the elders, further exacerbating the burden borne by the current public healthcare system. The challenges of geriatric care demand prompt attention by proposing strategies for improvement in several key areas. Major diseases of the elderly that need more attention include chronic non-communicable diseases and mental health disorders. We suggest the establishment of a home care-dominated geriatric care system, and a proactive role for researchers on aging in reforming geriatric care through policy dialogs. We propose ideas for preparation of the impending aging burden and the creation of a nurturing environment conducive to healthy aging in China.


title: Doing more tests: Next challenge for Covid 19 in India

text: In response to Coronavirus 19 pandemic, countries are struggling to contain its spread and save precious human lives. Like others, India is also trying to enhance testing capacity to identify every case and break the chain of transmission. Due to several constrains like geographic distribution of the laboratories, social stigma, prevailing lockdown, people are not being able to seek medical help every time they need. In addition, the states are not doing laboratory tests in similar frequency. In future, doing extensive tests would emerge as a major strategy for stopping the progression of the pandemic.


title: Early respiratory viral infections in infants with cystic fibrosis

text: Abstract Background Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. Methods Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. Results Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0–10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. Conclusions Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF.


title: Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

text: A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved. Therefore, therapeutic agents that protect the CNS are warranted. In both animal models as well as human patients with MS, T cell entry into the CNS is generally considered the initiating inflammatory event. In order to assess if a drug protects the CNS, any potential effects on immune cell infiltration or proliferation in the periphery must be ruled out. This protocol describes how to determine whether CNS protection observed after drug intervention is a consequence of attenuating CNS-infiltrating immune cells or blocking death of CNS cells during inflammatory insults. The ability to examine MS treatments that are protective to the CNS during inflammatory insults is highly critical for the advancement of therapeutic strategies since current treatments reduce, but do not completely eliminate, relapses (i.e., immune cell infiltration), leaving the CNS vulnerable to degeneration.


title: Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

text: Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.


Response to Letter to the Editor: “Trends in Endocrinology Fellowship Recruitment: Reasons for Concern and Possible Interventions”


title: Successful Treatment of Preterm Labor in Association with Acute COVID-19 Infection

text: Novel coronavirus disease 2019 (COVID-19) infection occurring during pregnancy is associated with an increased risk of preterm delivery. This case report describes successful treatment of preterm labor during acute COVID-19 infection. Standard treatment for preterm labor may allow patients with acute COVID-19 infection to recover without the need for preterm delivery. Key Points: Acute COVID-19 infection is associated with a high rate of preterm delivery. Standard treatment for preterm labor such as intravenous magnesium sulfate, antepartum steroid therapy and antibiotic prophylaxis for group B streptococcus infection were effective in this patient. In the absence of maternal or fetal compromise, acute COVID-19 infection is not an indication for early elective delivery.


title: Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies

text: Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections. Research efforts to develop antiviral agents against coronavirus demonstrated the main protease (Mpro) protein may represent effective drug target. X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166, Cys141, and His41 residues involved in protein dimerization and its catalytic function. We performed in silico screening of compounds from Curcuma longa L. (Zingiberaceae family) against Mpro protein inhibition. Employing a combination of molecular docking, scoring functions, and molecular dynamics simulations, 267 compounds were screened by docking on Mpro crystallographic structure. Docking score and interaction profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C1 (1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and C2 (4Z,6E)‐1,5‐dihydroxy‐1,7‐bis(4‐hydroxyphenyl)hepta‐4,6‐dien‐3‐one as lead agents. Compound C1 and C2 showed minimum binding score (–9.08 and –8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (≈ −5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalytic core of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus. Communicated by Ramaswamy H. Sarma


docid: qinnjcgs

title: Comparison of a commercially available oral nutritional supplement and intravenous fluid therapy for dehydration in dairy calves

text: ABSTRACT Calf scours is a primary cause of morbidity and mortality in the dairy industry. Effective treatments are needed to minimize death, maximize welfare, and maintain growth and productivity. The objective of this trial was to compare the efficacy of a commercially available nutritional supplement (Diaque, Boehringer-Ingelheim Vetmedica Inc., St. Joseph, MO) and i.v. lactated Ringer's solution (LRS) in rehydrating, preventing acidemia, and correcting electrolyte imbalances in an experimental model for calf scours. Twenty-four colostrum-fed suckling dairy calves were used in a modified crossover design. An osmotic diarrhea was induced by orally feeding commercial milk replacer modified with high level of sucrose to create a hypertonic milk solution, and administering oral hydrochlorothiazide and spironolactone for 48 h. The intention was to create a challenge sufficient to result in moderately dehydrated, standing calves without producing severe depression or loss of suckle. The efficacy of i.v. fluid therapy and a commercial nutritional supplement were subsequently compared for reversing the effects of the diarrheal disease. Treatment A consisted of administering the nutritional supplement according to label directions (100 g in 1.9 L of warm water, 3 times a day), and treatment B consisted of i.v. LRS (2 L, once a day). Clinical signs and laboratory results were obtained once daily by a blinded observer. The induction method was effective in creating the desired effect, as demonstrated by weight loss and subjective health and hydration scores. Both treatment groups experienced increases in body weight, base excess, and bicarbonate, and decreases in total protein and packed cell volume following treatment. Both i.v. LRS and Diaque are effective methods to correct hypovolemia and control derangements in acid-base status in calves with diarrhea and dehydration.


title: Clinical progression of patients with COVID-19 in Shanghai, China

text: Summary Background Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. Methods In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. Results Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2–7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12–20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8–11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10–12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. Conclusions The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.


title: Combination of thrombolytic and immunosuppressive therapy for coronavirus disease 2019: A case report

text: In a proportion of patients Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes a multi-systematic syndrome characterized by hyperinflammation, Acute Respiratory Distress Syndrome (ARDS) and hypercoagulability. A 68-year-old man with Coronavirus Disease 2019 (COVID-19) presented in our Intensive Care Unit (ICU) with respiratory failure, Cytokine Release Syndrome (CRS) and skin ischemia – microthrombosis. Specific coagulation and inflammatory markers (D-dimer, ferritin and C-reactive protein) along with the clinical picture triggered the trial of recombinant tissue plasminogen activator (rt-PA) and Tocilizumab. This was followed by resolution of skin ischemia and CRS while respiratory parameters improved. No major complications associated with rt-PA or Tocilizumab occurred. Combination of rt-PA with targeted anti-inflammatory treatment could be a new therapeutic option for patients with COVID-19, ARDS, hyperinflammation and increased blood viscosity.


title: Regulation of RIG-I-like receptor signaling by host and viral proteins

text: Abstract Vertebrate innate immunity is characterized by an effective immune surveillance apparatus, evolved to sense foreign structures, such as proteins or nucleic acids of invading microbes. RIG-I-like receptors (RLRs) are key sensors of viral RNA species in the host cell cytoplasm. Activation of RLRs in response to viral RNA triggers an antiviral defense program through the production of hundreds of antiviral effector proteins including cytokines, chemokines, and host restriction factors that directly interfere with distinct steps in the virus life cycle. To avoid premature or abnormal antiviral and proinflammatory responses, which could have harmful consequences for the host, the signaling activities of RLRs and their common adaptor molecule, MAVS, are delicately controlled by cell-intrinsic regulatory mechanisms. Furthermore, viruses have evolved multiple strategies to modulate RLR-MAVS signal transduction to escape from immune surveillance. Here, we summarize recent progress in our understanding of the regulation of RLR signaling through host factors and viral antagonistic proteins.


title: Financial implications of fourth industrial revolution: Can bitcoin improve prospects of energy investment?

text: Bitcoin and the blockchain technology on which it is based are the key drivers behind the accelerated pace of Fourth Industrial Revolution in the domain of Finance. The offshoots of this technology however are not limited and are rapidly spreading in other domains such as oil market. This paper investigates the causality or influences that both markets, Bitcoin price (BP) and oil price (OP) have on each other by applying the bootstrap Granger causal relationship tests considering full as well as sub-samples. Our analysis reveals that shocks originated in OP and transmitted towards BP can be both positive or negative. The positive impact indicates that Bitcoin can be viewed as an asset helpful in avoiding the risks of the high OP, which also indicates that Bitcoin and oil are in the same boat, however, the negative effects cannot support this view. The negative influence of OP on BP can be explained by the burst of the Bitcoin bubble which has weakened its hedging ability. In turn, there is also a negative influence or reverse causality running from BP to OP, highlighting that the demand for oil by investors can be threatened by the increasing BP. Keeping in view the more integrated and complexed financial dynamics which are the results of Fourth Industrial Revolution, investors can benefit from this interrelationship to diversify the risks and optimize their investment by building a more balanced portfolio. Also, governments could promote and protect the healthy development of the Bitcoin and energy market by preventing the Bitcoin bubbles and understanding the reasons of oil price volatility.


title: Taming wildlife disease: bridging the gap between science and management

text: 1. Parasites and pathogens of wildlife can threaten biodiversity, infect humans and domestic animals, and cause significant economic losses, providing incentives to manage wildlife diseases. Recent insights from disease ecology have helped transform our understanding of infectious disease dynamics and yielded new strategies to better manage wildlife diseases. Simultaneously, wildlife disease management (WDM) presents opportunities for large‐scale empirical tests of disease ecology theory in diverse natural systems. 2. To assess whether the potential complementarity between WDM and disease ecology theory has been realized, we evaluate the extent to which specific concepts in disease ecology theory have been explicitly applied in peer‐reviewed WDM literature. 3. While only half of WDM articles published in the past decade incorporated disease ecology theory, theory has been incorporated with increasing frequency over the past 40 years. Contrary to expectations, articles authored by academics were no more likely to apply disease ecology theory, but articles that explain unsuccessful management often do so in terms of theory. 4. Some theoretical concepts such as density‐dependent transmission have been commonly applied, whereas emerging concepts such as pathogen evolutionary responses to management, biodiversity–disease relationships and within‐host parasite interactions have not yet been fully integrated as management considerations. 5. Synthesis and applications. Theory‐based disease management can meet the needs of both academics and managers by testing disease ecology theory and improving disease interventions. Theoretical concepts that have received limited attention to date in wildlife disease management could provide a basis for improving management and advancing disease ecology in the future.


Raoult, social distancing and the rebelious French ‐ A reflection on COVID‐19 treatments online debates


title: Commentary on Ferguson, et al., “Impact of Non-pharmaceutical Interventions (NPIs) to Reduce COVID-19 Mortality and Healthcare Demand”

text: A recent manuscript (Ferguson et al. in Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand, Imperial College COVID-19 Response Team, London, 2020. https://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf) from Imperial College modelers examining ways to mitigate and control the spread of COVID-19 has attracted much attention. In this paper, we will discuss a coarse taxonomy of models and explore the context and significance of the Imperial College and other models in contributing to the analysis of COVID-19.


title: Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle

text: Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.


title: Xenosurveillance: A Novel Mosquito-Based Approach for Examining the Human-Pathogen Landscape

text: BACKGROUND: Globally, regions at the highest risk for emerging infectious diseases are often the ones with the fewest resources. As a result, implementing sustainable infectious disease surveillance systems in these regions is challenging. The cost of these programs and difficulties associated with collecting, storing and transporting relevant samples have hindered them in the regions where they are most needed. Therefore, we tested the sensitivity and feasibility of a novel surveillance technique called xenosurveillance. This approach utilizes the host feeding preferences and behaviors of Anopheles gambiae, which are highly anthropophilic and rest indoors after feeding, to sample viruses in human beings. We hypothesized that mosquito bloodmeals could be used to detect vertebrate viral pathogens within realistic field collection timeframes and clinically relevant concentrations. METHODOLOGY/PRINCIPAL FINDINGS: To validate this approach, we examined variables influencing virus detection such as the duration between mosquito blood feeding and mosquito processing, the pathogen nucleic acid stability in the mosquito gut and the pathogen load present in the host’s blood at the time of bloodmeal ingestion using our laboratory model. Our findings revealed that viral nucleic acids, at clinically relevant concentrations, could be detected from engorged mosquitoes for up to 24 hours post feeding by qRT-PCR. Subsequently, we tested this approach in the field by examining blood from engorged mosquitoes from two field sites in Liberia. Using next-generation sequencing and PCR we were able to detect the genetic signatures of multiple viral pathogens including Epstein-Barr virus and canine distemper virus. CONCLUSIONS/SIGNIFICANCE: Together, these data demonstrate the feasibility of xenosurveillance and in doing so validated a simple and non-invasive surveillance tool that could be used to complement current biosurveillance efforts.


title: The Hepatitis E virus intraviral interactome

text: Hepatitis E virus (HEV) is an emerging virus causing epidemic acute hepatitis in developing countries as well as sporadic cases in industrialized countries. The life cycle of HEV is still poorly understood and the lack of efficient cell culture systems and animal models are the principal limitations for a detailed study of the viral replication cycle. Here we exhaustively examine all possible intraviral protein-protein interactions (PPIs) of HEV by systematic Yeast two-hybrid (Y2H) and LuMPIS screens, providing a basis for studying the function of these proteins in the viral replication cycle. Key PPIs correlate with the already published HEV 3D structure. Furthermore, we report 20 novel PPIs including the homodimerization of the RNA dependent RNA polymerase (RdRp), the self-interaction of the papain like protease, and ORF3 interactions with the papain-like protease and putative replicase components: RdRp, methylase and helicase. Furthermore, we determined the dissociation constant (K(d)) of ORF3 interactions with the viral helicase, papain-like protease and methylase, which suggest a regulatory function for ORF3 in orchestrating the formation of the replicase complex. These interactions may represent new targets for antiviral drugs.


title: Chitosan elicitation of Isatis tinctoria L. hairy root cultures for enhancing flavonoid productivity and gene expression and related antioxidant activity

text: Abstract Elicitation for phytochemical enhancement via cost-effective elicitors can overcome the limitation of commercial application faced by plant cell and organ culture technology. Chitosan is a natural, low-cost, and nontoxic elicitor that can trigger plant defense responses with the concomitant enhancement in phytochemical biosynthesis. In this work, the elicitation of Isatis tinctoria L. hairy root cultures by chitosan was conducted to enhance the production of pharmacologically active flavonoids. In comparison with control (2.31 ± 0.29 mg/g DW), a 7.08-fold enhancement of total flavonoids (16.35 ± 0.88 mg/g DW) was achieved in 24 day-old I. tinctoria hairy root cultures elicited by 150 mg/L chitosan for 36 h. Interestingly, the multiple hydroxyl-substituted ﬂavonoids (rutin, quercetin, isorhamnetin, and isoliquiritigenin) were noticed to increase significantly in chitosan-elicited I. tinctoria hairy root cultures. Moreover, the transcription of associated genes involved in flavonoid biosynthesis pathway was significantly up-regulated underlying chitosan elicitation, among which chalcone synthase and flavonoid 3′-hydroxylase might play an important role in flavonoid enhancement. Additionally, extracts from chitosan-elicited I. tinctoria hairy root cultures exhibited higher antioxidant activities with lower IC50 values as compared with control. Overall, a cost-effective strategy via the simple chitosan elicitation is provided here to enhance the production of high-added value flavonoids in I. tinctoria hairy root cultures, which paves the way toward the successful commercialization of this in vitro culture system in the future.


Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS‐CoV‐2


title: Emerging diseases, zoonoses and vaccines to control them

text: Vaccination, when available, is undoubtedly the most cost-effective means of preventing and controlling, and even eradicating, infectious diseases. In recent years vaccination has also been used for other purposes in animal health, production and welfare, e.g. immunocastration. Vaccination of animals serves many different purposes, such as controlling animal infections and infestations, thus improving animal health and welfare; controlling anthropozoonoses and food poisoning in humans, thereby protecting public health; solving problems associated with antibiotic and anthelmintic resistance; helping to leave food-producing animals free of chemical residues; protecting the environment and biodiversity and ensuring animal farming sustainability. The problem is nevertheless more complex when facing emerging or re-emerging infections particularly zoonotic ones.


title: Detection rate and clinical impact of respiratory viruses in children with Kawasaki disease

text: PURPOSE: The purpose of this prospective case-control study was to survey the detection rate of respiratory viruses in children with Kawasaki disease (KD) by using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR), and to investigate the clinical implications of the prevalence of respiratory viruses during the acute phase of KD. METHODS: RT-PCR assays were carried out to screen for the presence of respiratory syncytial virus A and B, adenovirus, rhinovirus, parainfluenza viruses 1 to 4, influenza virus A and B, metapneumovirus, bocavirus, coronavirus OC43/229E and NL63, and enterovirus in nasopharyngeal secretions of 55 KD patients and 78 control subjects. RESULTS: Virus detection rates in KD patients and control subjects were 32.7% and 30.8%, respectively (P=0.811). However, there was no significant association between the presence of any of the 15 viruses and the incidence of KD. Comparisons between the 18 patients with positive RT-PCR results and the other 37 KD patients revealed no significant differences in terms of clinical findings (including the prevalence of incomplete presentation of the disease) and coronary artery diameter. CONCLUSION: A positive RT-PCR for currently epidemic respiratory viruses should not be used as an evidence against the diagnosis of KD. These viruses were not associated with the incomplete presentation of KD and coronary artery dilatation.


title: ORBiT: Oak Ridge biosurveillance toolkit for public health dynamics

text: BACKGROUND: The digitization of health-related information through electronic health records (EHR) and electronic healthcare reimbursement claims and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing effective biosurveillance tools. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build systems that can track, monitor and report such events in a timely manner. Further, it is also important to identify susceptible geographic regions and populations where emerging diseases may have a significant impact. METHODS: In this paper, we present an overview of Oak Ridge Biosurveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various biosurveillance-related tasks. RESULTS: We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using claims data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the claims data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as "bridge regions" contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. CONCLUSIONS: These quantitative insights show how the claims data combined with novel analytical techniques can provide important information to decision makers when an epidemic spreads throughout the country. Taken together ORBiT provides a scalable and extensible platform for public health surveillance.


title: Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses

text: Abstract Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734™) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524™), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.


Protecting the Homeless During The COVID-19 Pandemic


title: Utilization of deceased donors during a pandemic: An argument against using SARS‐CoV‐2 positive donors

text: SARS‐CoV‐2 has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained healthcare resources and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplantation continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of COVID‐19 positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID‐19 positive donors. The factors we consider include: 1) the risk of blood transmission SARS‐CoV‐2, 2) involvement of donor organs, 3) lack of effective therapies, 4) exposure of healthcare and recovery teams, 5) disease transmission and propagation, and 6) hospital resource utilization. While we acknowledge that transplantation fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients, but also to the community and to healthcare workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID‐19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplantation societies.


title: Reducing SARS‐CoV‐2 transmission in the UK: A behavioural science approach to identifying options for increasing adherence to social distancing and shielding vulnerable people

text: PURPOSE: To describe and discuss a systematic method for producing a very rapid response (3 days) to a UK government policy question in the context of reducing SARS‐CoV‐2 transmission. METHODS: A group of behavioural and social scientists advising the UK government on COVID‐19 contributed to the analysis and writing of advice through the Government Office for Science. The question was as follows: What are the options for increasing adherence to social distancing (staying at home except for essential journeys and work) and shielding vulnerable people (keeping them at home and away from others)? This was prior to social distancing legislation being implemented. The first two authors produced a draft, based on analysis of the current government guidance and the application of the Behaviour Change Wheel (BCW) framework to identify and evaluate the options. RESULTS: For promoting social distancing, 10 options were identified for improving adherence. They covered improvements in ways of achieving the BCW intervention types of education, persuasion, incentivization, and coercion. For promoting shielding of vulnerable people, four options were identified covering the BCW intervention types of incentivization, coercion, and enablement. CONCLUSIONS: Responding to policymakers very rapidly as has been necessary during the COVID‐19 pandemic can be facilitated by using a framework to structure the thinking and reporting of multidisciplinary academics and policymakers.


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title: Potentiating health and the crisis of the immune system: integrative approaches to prevention and healing of modern diseases


title: Improving rheumatic fever surveillance in New Zealand: results of a surveillance sector review

text: BACKGROUND: The New Zealand (NZ) Government has made a strong commitment to reduce the incidence of rheumatic fever (RF) by two thirds, to 1.4 cases per 100,000, by mid-2017. We reviewed the NZ RF surveillance sector, aiming to identify potential improvements which would support optimal RF control and prevention activities. METHODS: This review used a recently developed surveillance sector review method. Interviews with 36 key informants were used to describe the sector, assess it and identify its gaps. Priorities for improvement and implementation strategies were determined following discussion with these key informants, with policy advisors and within the research team. RESULTS: Key improvements identified included the need for a comprehensive RF surveillance strategy, integrated reporting and an online national RF register. At a managerial level this review provided evidence for system change and built support for this across the surveillance sector. CONCLUSIONS: The surveillance sector review approach can be added to the small set of tools currently available for developing and evaluating surveillance systems. This new approach is likely to prove useful as we confront the challenges of combating new emerging infectious diseases, responding to global environmental changes, and reducing health inequalities.


title: Lung ultrasonography in COVID‐19: a gamechanger in the Stroke Unit?

text: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) is rapidly spreading worldwide, and the WHO declared its pandemic nature on 11(th) March 2020(1). The outbreak has hit Europe and, as of April 19, 2020, Italy has the third largest number of confirmed cases, namely a total of 175,925 cases and 23,227 deaths according to the John Hopkins University (2). This is the largest health and economic emergency of our country since the post‐war period, and many hospitals are now dedicated exclusively to COVID‐19 assistance. Our University Hub Stroke Unit of Cattinara Hospital is in the northeaster Italian region of Friuli Venezia Giulia which enlisted 2,731 cases and 222 deaths at the time of writing(3).


title: Coronavirus infections and immune responses

text: Coronaviruses (CoVs) are by far the largest group of known positive‐sense RNA viruses having an extensive range of natural hosts. In the past few decades, newly evolved Coronaviruses have posed a global threat to public health. The immune response is essential to control and eliminate CoV infections, however, maladjusted immune responses may result in immunopathology and impaired pulmonary gas exchange. Gaining a deeper understanding of the interaction between Coronaviruses and the innate immune systems of the hosts may shed light on the development and persistence of inflammation in the lungs and hopefully can reduce the risk of lung inflammation caused by CoVs. In this review, we provide an update on CoV infections and relevant diseases, particularly the host defense against CoV‐induced inflammation of lung tissue, as well as the role of the innate immune system in the pathogenesis and clinical treatment.


Virtual dermatopathology: A potential educational tool during COVID‐19 pandemic


Prevention and Treatment of Skin Damage Caused by Personal Protective Equipment: Experience of the First-Line Clinicians Treating 2019-nCoV Infection


title: Solid phase synthesis and biological evaluation of probestin as an angiogenesis inhibitor

text: Probestin is a potent aminopeptidase N (APN) inhibitor originally isolated from the bacterial culture broth. Here, we report probestin synthesis by solid phase peptide synthesis (SPPS) method and evaluated its activity to inhibit angiogenesis using a chicken embryo chorioallantoic membrane (CAM) assay and a CAM tumor xenograft model. Results from these studies demonstrate that probestin inhibits the angiogenic activity and tumor growth.


title: Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014

text: Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.


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title: Ramping Up the Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from the Canadian Society of Cardiac Surgeons

text: Abstract The coronavirus disease 2019 (COVID-19) has had a profound global impact. Its rapid transmissibility has forced whole countries to adopt strict measures to contain its spread. As part of necessary pandemic planning, the majority of Canadian cardiac surgical programs have prioritized and delayed elective procedures in an effort to reduce the burden on the health care system and to mobilize resources in the event of a pandemic surge. While the number of COVID-19 cases continue to increase worldwide, new cases have begun to decline in many jurisdictions. This “flattening of the curve” has inevitably prompted discussions around re-opening of the economy, relaxing some public health restrictions and resuming non-urgent health care delivery.


title: The Role of Complement in Transfusion-Related Acute Lung Injury

text: Abstract Transfusion-related acute lung injury (TRALI) is a life-threatening complication of acute respiratory distress occurring within 6 hours of blood transfusion. TRALI is one of the leading causes of transfusion-related fatalities and specific therapies are unavailable. Neutrophils are recognized as the major pathogenic cells, whereas T regulatory cells and dendritic cells appear to be important for protection against TRALI. The pathogenesis, however, is complex and incompletely understood. It is frequently postulated that the complement system plays an important role in the TRALI pathogenesis. In this article, we assess the evidence regarding the involvement of complement in TRALI from both human and animal studies. We hypothesize about the potential connection between the complement system and neutrophils in TRALI. Additionally, we draw parallels between TRALI and other acute pulmonary disorders of acute lung injury and acute respiratory distress syndrome regarding the involvement of complement. We conclude that, even though a role for complement in the TRALI pathogenesis seems plausible, studies investigating the role of complement in TRALI are remarkably limited in number and also present conflicting findings. Different types of TRALI animal models, diverse experimental conditions, and the composition of the gastrointestinal microbiota may perhaps all be factors which contribute to these discrepancies. More systematic studies are warranted to shed light on the contribution of the complement cascade in TRALI. The underlying clinical condition of the patient, which influences the susceptibility to TRALI, as well as the transfusion factor (antibody-mediated vs non–antibody-mediated), will be important to take into consideration when researching the contribution of complement. This should significantly increase our understanding of the role of complement in TRALI and may potentially result in promising new treatment strategies.


title: Host endomembrane recruitment for plant RNA virus replication

text: Although there is a significant amount of literature that deals with the identification of plant viral proteins involved in membrane remodeling and vesicle production in infected cells, there are very few investigations that report on the impact that infection has on the overall architecture and dynamics of the early secretory endomembranes. Recent investigations have shown that for some viruses the endoplasmic reticulum, Golgi bodies and other organelles are heavily recruited into virus-induced perinuclear structures. These structures are not isolated organelles and are dynamically connected to the bulk of non-modified endomembranes. They also have a functional link with peripheral motile vesicles involved in virus intracellular movement. The full molecular events that consubstantiate with this endomembrane recruitment in virus-induced structures remain to be elucidated but viral genome replication and virion assembly are probably taking place within these structures.


title: Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of Randomized Controlled Trials

text: Background: The coronavirus disease 2019 (COVID-19) pandemic has caused a worldwide outbreak of respiratory illness. This review aims to evaluate the effectiveness and adverse events of herbal medicines for the treatment of COVID-19. Methods: Twelve databases were searched through 12 May 2020. Randomized controlled trials (RCTs) and quasi-RCTs assessing the effects of herbal medicines for the treatment of COVID-19 were eligible. The study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias tool was used for the assessment of the risk of bias in all included RCTs. Mean differences (MDs), risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, and the effect sizes of the studies were pooled. Results: Seven RCTs with a total of 855 patients were included. All included trials compared the combined therapy of herbal medicine with Western medicine to Western medicine alone. The combined therapy significantly improved the total effective rate (RR 1.23, 95% CI 1.13 to 1.34, p < 0.001), cough symptom disappearance rate (RR 1.45, 95% CI 1.12 to 1.89, p = 0.005), and sputum production symptom disappearance rate (RR 1.73, 95% CI 1.19 to 2.50, p = 0.004). Beneficial effects of the combined therapy were also seen in TCM syndrome score of cough (MD −1.18, 95% CI −1.34 to −1.03, p < 0.001), fever (MD −0.62, 95% CI −0.79 to −0.45, p < 0.001), dry and sore throat (MD −0.83, 95% CI −1.45 to −0.20, p = 0.009), and fatigue (MD −0.60, 95% CI −1.04 to −0.17, p = 0.007). The overall risk of bias of the included studies was unclear. No serious adverse events were reported. Conclusion: Significant effects of the combined therapy of herbal medicine with Western medicine were found, and revealed the potential role of herbal medicine in treating COVID-19. More high-quality RCTs are needed to further validate the effectiveness and adverse events of herbal medicine in the treatment of COVID-19.


title: Innate immune restriction and antagonism of viral RNA lacking 2׳-O methylation

text: Abstract N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m7GpppN; cap 1, m7GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.


title: Neurological dysfunction in three dogs and one cat following attenuation of intrahepatic portosystemic shunts

text: Neurological dysfunction is an uncommon complication following extrahepatic portosystemic shunt ligation. Three dogs and one cat are described that developed neurological signs within 21 to 42 hours of attenuation of intrahepatic portosystemic shunts. None of these cases had biochemical evidence of hepatic encephalopathy postoperatively. Two dogs died during management of status epilepticus following aspiration of food. One dog died six months postoperatively. The cat had persistent neurological dysfunction at discharge, but was alive and had recovered most of its neurological function at the time of writing, 37 months after surgery. This report demonstrates the potential for animals with intrahepatic portosystemic shunts to develop postoperative neurological signs and highlights the difficulty of managing such cases. Two dogs had both intrahepatic and extrahepatic portosystemic shunts. Large intestinal malrotation (partial situs inversus) may have been linked to the development of a portosystemic shunt in the remaining dog.


title: Ecosystem-centric business continuity planning (eco-centric BCP): A post COVID19 new normal

text: Abstract This article views the COVID-19 pandemic as an opportunity leading to a significant reduction in pollution levels, clean waters in rivers, improved visibility, and other tangible benefit to humanity and the environment. In Post-COVID scenario, to restore the margins and regain the lost production, industries are likely to increase their production leading to a quantum jump in the pollution levels. Having precedence of such a scenario in 2008–09, this article looks at what are the possible avenues to engage the city government and business houses through an a new normal ECO-BCP concept for long term sustainability. All economic stimulus needs to be tied down with the stringent reduction in the emission norms. The Ten Principles for the Eco-centric BCP guide the reopening of MSMEs after lockdown period called to check the spread of the COVID-19 pandemic. The Eco-centric BCP model will help the MSMEs to adopt the new-normal business strategies to align with the country-specific commitments to SDGs, SFDRR and Paris declaration.