title: Comparison of the Panther Fusion and Allplex assays for the detection of respiratory viruses in clinical samples

text: Respiratory viral infections are the most frequent clinical syndrome affecting both children and adults, and early detection is fundamental to avoid infection-related risks and reduce the healthcare costs incurred by unnecessary antibiotic treatments. In this study, performance characteristics of two commercial methods, the Panther Fusion® assay (Hologic Inc., San Diego, CA, USA) were compared to Allplex(™) respiratory panels (Seegene, Seoul, South Korea) for the detection of influenza A (Flu A), influenza B (Flu B), respiratory syncytial virus (RSV), parainfluenza virus (PIV), human metapneumovirus (hMPV), rhinovirus (RV) and adenovirus (AdV) targets. A total of 865 specimens collected prospectively and retrospectively were included, and discordant results were further examined using another commercial product, R-GENE(™) respiratory kits (bioMérieux, Marcy l’Etoile, France). There was high agreement between both methods, with 98.6% concordance and a kappa (k) value of 0.9 (95% CI: 0.89–0.92). A specific analysis of both methods for each viral agent demonstrated comparable sensitivity and specificity, both ranging from 0.83 to 1 with good predictive values for the prospective part of the study. Good agreement between both methods was also found for the κ values obtained (ranging from 97.55% to 98.9%), with the lowest for hMPV (k = 0.83, 95% CI: 0.75–0.91) and RV (k = 0.73, 95% CI: 0.65–0.81). Amplification efficiency, measured according to the value of the cycle threshold (C(t)) obtained in each of the amplifications in both tests, was significantly better with Panther Fusion for Flu A, Flu B, hMPV and RV. Regarding discordant results, R-GENE showed higher agreement with Panther Fusion-positive specimens (negative for Allplex; n = 28/71, 34.9%) than with Allplex-positive samples (negative for Panther Fusion; n = 7/49, 14.3%). In summary, Panther Fusion proved to be a more efficient fully-automated methodology, requiring shorter hands-on and turnaround times than Allplex.


MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract


title: PLP2 of Mouse Hepatitis Virus A59 (MHV-A59) Targets TBK1 to Negatively Regulate Cellular Type I Interferon Signaling Pathway

text: BACKGROUND: Coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) have evolved strategies to disable the innate immune system for productive replication and spread of infection. We have previously shown that papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, encodes a deubiquitinase (DUB) and inactivates IFN regulatory factor 3 (IRF3) thereby the type I interferon (IFN) response. PRINCIPAL FINDINGS: Here we provide further evidence that PLP2 may also target TANK-binding kinase-1 (TBK1), the upstream kinase of IRF3 in the IFN signaling pathway. Overexpression experiments showed that PLP2 deubiquitinated TBK1 and reduced its kinase activity, hence inhibited IFN-β reporter activity. Albeit promiscuous in deubiquitinating cellular proteins, PLP2 inactivated TBK1 and IFN-β response in TNF receptor associated factor 3 (TRAF3) deficient cells, suggesting that targeting TBK1 would be sufficient for PLP2 to inhibit IRF3 activation. This notion was further supported by in vitro kinase assays, in which prior treatment of TBK1 with PLP2 inhibited its kinase activity to phosphorylate IRF3. Intriguing enough, results of PLP2 overexpression system and MHV-A59 infection system proved that PLP2 formed an inactive complex with TBK1 and IRF3 in the cytoplasm and the presence of PLP2 stabilized the hypo-phosphorylated IRF3-TBK1 complex in a dose-dependent manner. CONCLUSIONS: These results suggest that PLP2 not only inactivates TBK1, but also prevents IRF3 nuclear translocation hence inhibits IFN transcription activation. Identification of the conserved DUB activity of PLP2 in suppression of IFN signaling would provide a useful clue to the development of therapeutics against coronaviruses infection.


title: Prediction of numbers of the accumulative confirmed patients (NACP) and the plateau phase of 2019-nCoV in China

text: In the present study, I propose a novel fitting method to describe the outbreak of 2019-nCoV in China. The fitted data were selected carefully from the non-Hubei part and Hubei Province of China respectively. For the non-Hubei part, the time period of data collection corresponds from the beginning of the policy of isolation to present day. But for Hubei Province, the subjects of Wuhan City and Hubei Province were included from the time of admission to the Huoshenshan Hospital to present day in order to ensure that all or the majority of the confirmed and suspected patients were collected for diagnosis and treatment. The employed basic functions for fitting are the hyperbolic tangent functions [Formula: see text] since in these cases the 2019-nCoV is just an epidemic. Subsequently, the 2019-nCoV will initially expand rapidly and tend to disappear. Therefore, the numbers of the accumulative confirmed patients in different cities, provinces and geographical regions will initially increase rapidly and subsequently stabilize to a plateau phase. The selection of the basic functions for fitting is crucial. In the present study, I found that the hyperbolic tangent functions [Formula: see text] could satisfy the aforementioned properties. By this novel method, I can obtain two significant results. They base on the conditions that the rigorous isolation policy is executed continually. Initially, I can predict the numbers very accurately of the cumulative confirmed patients in different cities, provinces and parts in China, notably, in Wuhan City with the smallest relative error estimated to [Formula: see text] , in Hubei Province with the smallest relative error estimated to [Formula: see text] and in the non-Hubei part of China with the smallest relative error of [Formula: see text] 0.195% in the short-term period of infection. In addition, perhaps I can predict the times when the plateau phases will occur respectively in different regions in the long-term period of infection. Generally for the non-Hubei part of China, the plateau phase of the outbreak of the 2019-nCoV will be expected this March or at the end of this February. In the non-Hubei region of China it is expected that the epidemic will cease on the 30th of March 2020 and following this date no new confirmed patient will be expected. The predictions of the time of Inflection Points and maximum NACP for some important regions may be also obtained. A specific plan for the prevention measures of the 2019-nCoV outbreak must be implemented. This will involve the present returning to work and resuming production in China. Based on the presented results, I suggest that the rigorous isolation policy by the government should be executed regularly during daily life and work duties. Moreover, as many as possible the confirmed and suspected cases should be collected to diagnose or treat.


docid: slnncoag

title: Incidence of Deep Vein Thrombosis among non‐ICU Patients Hospitalized for COVID‐19 Despite Pharmacological Thromboprophylaxis

text: BACKGROUND: A remarkably high incidence of VTE has been reported among critically ill patients with COVID‐19 assisted in the Intensive Care Unit (ICU). However, VTE burden among non‐ICU patients hospitalized for COVID‐19 that receive guideline‐recommended thromboprophylaxis is unknown. OBJECTIVES: To determine the incidence of VTE among non‐ICU patients hospitalized for COVID‐19 that receive pharmacological thromboprophylaxis. METHODS: We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non‐ICU patients hospitalized for COVID‐19, independently of the presence of signs or symptoms of DVT. All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux. RESULTS: The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6±13.5 years and a mean Padua Prediction Score of 5.1±1.6. Seventy‐two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden. In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% CI 4.98–18.82). Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI ‐0.87–5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23–5.77). Significant differences between subjects with and without DVT were D‐dimer >3,000 µg/L (P<0.05), current or previous cancer (P<0.05), and need of high flow nasal oxygen therapy and/or non‐invasive ventilation (P<0.01). CONCLUSIONS: DVT may occur among non‐ICU patients hospitalized for COVID‐19, despite guideline‐recommended thromboprophylaxis.


title: A Three-Stemmed mRNA Pseudoknot in the SARS Coronavirus Frameshift Signal

text: A wide range of RNA viruses use programmed −1 ribosomal frameshifting for the production of viral fusion proteins. Inspection of the overlap regions between ORF1a and ORF1b of the SARS-CoV genome revealed that, similar to all coronaviruses, a programmed −1 ribosomal frameshift could be used by the virus to produce a fusion protein. Computational analyses of the frameshift signal predicted the presence of an mRNA pseudoknot containing three double-stranded RNA stem structures rather than two. Phylogenetic analyses showed the conservation of potential three-stemmed pseudoknots in the frameshift signals of all other coronaviruses in the GenBank database. Though the presence of the three-stemmed structure is supported by nuclease mapping and two-dimensional nuclear magnetic resonance studies, our findings suggest that interactions between the stem structures may result in local distortions in the A-form RNA. These distortions are particularly evident in the vicinity of predicted A-bulges in stems 2 and 3. In vitro and in vivo frameshifting assays showed that the SARS-CoV frameshift signal is functionally similar to other viral frameshift signals: it promotes efficient frameshifting in all of the standard assay systems, and it is sensitive to a drug and a genetic mutation that are known to affect frameshifting efficiency of a yeast virus. Mutagenesis studies reveal that both the specific sequences and structures of stems 2 and 3 are important for efficient frameshifting. We have identified a new RNA structural motif that is capable of promoting efficient programmed ribosomal frameshifting. The high degree of conservation of three-stemmed mRNA pseudoknot structures among the coronaviruses suggests that this presents a novel target for antiviral therapeutics.


title: Testing the hypothesis of a recombinant origin of the SARS-associated coronavirus

text: The origin of severe acute respiratory syndrome-associated corona-virus (SARS-CoV) is still a matter of speculation, although more than one year has passed since the onset of the SARS outbreak. In this study, we implemented a 3-step strategy to test the intriguing hypothesis that SARS-CoV might have been derived from a recombinant virus. First, we blasted the whole SARS-CoV genome against a virus database to search viruses of interest. Second, we employed 7 recombination detection techniques well documented in successfully detecting recombination events to explore the presence of recombination in SARS-CoV genome. Finally, we conducted phylogenetic analyses to further explore whether recombination has indeed occurred in the course of coronaviruses history predating the emergence of SARS-CoV. Surprisingly, we found that 7 putative recombination regions, located in Replicase 1ab and Spike protein, exist between SARS-CoV and other 6 coronaviruses: porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), bovine coronavirus (BCoV), human coronavirus 229E (HCoV), murine hepatitis virus (MHV), and avian infectious bronchitis virus (IBV). Thus, our analyses substantiate the presence of recombination events in history that led to the SARS-CoV genome. Like the other coronaviruses used in the analysis, SARS-CoV is also a mosaic structure.


title: First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in China in December, 2019. In January, 2020, state, local, and federal public health agencies investigated the first case of COVID-19 in Illinois, USA. METHODS: Patients with confirmed COVID-19 were defined as those with a positive SARS-CoV-2 test. Contacts were people with exposure to a patient with COVID-19 on or after the patient's symptom onset date. Contacts underwent active symptom monitoring for 14 days following their last exposure. Contacts who developed fever, cough, or shortness of breath became persons under investigation and were tested for SARS-CoV-2. A convenience sample of 32 asymptomatic health-care personnel contacts were also tested. FINDINGS: Patient 1—a woman in her 60s—returned from China in mid-January, 2020. One week later, she was hospitalised with pneumonia and tested positive for SARS-CoV-2. Her husband (Patient 2) did not travel but had frequent close contact with his wife. He was admitted 8 days later and tested positive for SARS-CoV-2. Overall, 372 contacts of both cases were identified; 347 underwent active symptom monitoring, including 152 community contacts and 195 health-care personnel. Of monitored contacts, 43 became persons under investigation, in addition to Patient 2. These 43 persons under investigation and all 32 asymptomatic health-care personnel tested negative for SARS-CoV-2. INTERPRETATION: Person-to-person transmission of SARS-CoV-2 occurred between two people with prolonged, unprotected exposure while Patient 1 was symptomatic. Despite active symptom monitoring and testing of symptomatic and some asymptomatic contacts, no further transmission was detected. FUNDING: None.


Caution about early intubation and mechanical ventilation in COVID-19


Quality control assessment for the PCR diagnosis of TBEV infections


title: The Sentinel System as the Main Influenza Surveillance Tool

text: Poland has implemented the influenza surveillance system called Sentinel as of 2004. The system consists of both epidemiological and virological surveillance. It is an important tool for monitoring the situation in the entire country, coordinated by the National Influenza Center situated at the National Institute of Public Health-National Institute of Hygiene (NIPH-NIH) in Warsaw, Poland. In the 2015/2016 epidemic season, more than 1600 samples were tested in the Sentinel System, of which 38.6% were positive. The samples were evaluated in seven age-groups: 0–4, 5–9, 10–14, 15–25, 26–44, 45–64, and over 65 years of age. Significant differences were reported in the number of confirmed cases of infection caused by influenza and influenza-like viruses, depending on the age-group. The highest number of confirmed cases of infections was reported for the age range of 26–44 years, accounting for 30% of the total. In each age-group, the presence of infection caused by influenza-like viruses, collectively accounting for only 3.8% of all positive tests, was also confirmed. Weekly reports generated by the Sentinel System enable to determine and control a current influenza activity in the country, which is of essential importance in case of the emergence of a new strain with a pandemic potential.


title: Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination

text: BACKGROUND: There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer. METHODS: In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. RESULTS: We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore, treatment with CRT/E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition, treatment with imiquimod led to increased number of NK1.1+ cells and F4/80+ cells in the tumor microenvironment. Macrophages and NK1.1+ cells were found to play an important role in the antitumor effects mediated by treatment with CRT/E7 DNA in combination with imiquimod. CONCLUSIONS: Thus, our data suggests that the combination of therapeutic HPV DNA vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA vaccination. The current study has significant implications for future clinical translation.


title: Microbial Neuraminidase Induces a Moderate and Transient Myelin Vacuolation Independent of Complement System Activation

text: AIMS: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. METHODS: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles. Neuronal death in the affected axonal tracts was assessed by Fluoro-Jade B and anti-caspase-3 staining. To evaluate the role of the complement, membrane attack complex (MAC) deposition on damaged bundles was analyzed using anti-C5b9. Rats ICV injected with the anaphylatoxin C5a were studied for myelin damage. In addition, NA-induced vacuolation was studied in rats with different degrees of complement inhibition: normal rats treated with anti-C5-blocking antibody and C6-deficient rats. RESULTS: The stria medullaris, the optic chiasm, and the fimbria were the most consistently damaged axonal tracts. Vacuolation peaked 7 days after NA injection and reverted by day 15. Olig2+ cell number in the damaged tracts was unaltered, and neurodegeneration associated with myelin alterations was not detected. MAC was absent on damaged axonal tracts, as revealed by C5b9 immunostaining. Rats ICV injected with the anaphylatoxin C5a displayed no myelin injury. When the complement system was experimentally or constitutively inhibited, NA-induced myelin vacuolation was similar to that observed in normal rats. CONCLUSION: Microbial NA induces a moderate and transient myelin vacuolation that is not caused either by neuroinflammation or complement system activation.


title: Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection

text: BACKGROUND: Middle East Respiratory Syndrome (MERS) is a disease of the lower respiratory tract and is characterized by high mortality. It is caused by a beta coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been reported from Saudi Arabia. AIM: We investigated the human leukocyte antigen (HLA) Class II alleles in patients with severe MERS who were admitted in our Intensive Care Unit. METHODS: A total of 23 Saudi patients with severe MERS-CoV infection were typed for HLA class II, results were compared with those of 161 healthy controls. RESULTS: Two HLA class II alleles were associated with the disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome. CONCLUSIONS: Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be associated with susceptibility to MERS.


title: Chloroquine cardiac effects and toxicity.A short update.

text: There is currently an increased interest in using the antimalarials chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as COVID-19. However, risks of cardiotoxic effects tend to limit their use. The effects of these drugs on the electrical and mechanical activities of the heart, as well as on the remodeling of the cardiac tissue are presented, and the underlying molecular and cellular mechanisms discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions, resulting from their inhibition of ion channels, including voltage-dependent Na(+) and Ca(2+) channels, background and voltage-dependent K(+) channels, and pacemaker channels. The drugs also exert a vagolytic effect, due at least in part to a muscarinic receptor antagonist action. They also interfere with the normal autophagy flux, an effect which could aggravate ischemia/reperfusion injury or post-infarct remodeling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.


title: Prediction of conserved long-range RNA-RNA interactions in full viral genomes

text: Motivation: Long-range RNA-RNA interactions (LRIs) play an important role in viral replication, however, only a few of these interactions are known and only for a small number of viral species. Up to now, it has been impossible to screen a full viral genome for LRIs experimentally or in silico. Most known LRIs are cross-reacting structures (pseudoknots) undetectable by most bioinformatical tools. Results: We present LRIscan, a tool for the LRI prediction in full viral genomes based on a multiple genome alignment. We confirmed 14 out of 16 experimentally known and evolutionary conserved LRIs in genome alignments of HCV, Tombusviruses, Flaviviruses and HIV-1. We provide several promising new interactions, which include compensatory mutations and are highly conserved in all considered viral sequences. Furthermore, we provide reactivity plots highlighting the hot spots of predicted LRIs. Availability and Implementation: Source code and binaries of LRIscan freely available for download at http://www.rna.uni-jena.de/en/supplements/lriscan/, implemented in Ruby/C ++ and supported on Linux and Windows. Contact: manja@uni-jena.de Supplementary information: Supplementary data are available at Bioinformatics online.


title: Chapter 17 Paramyxoviridae

text: Publisher Summary Members of the family Paramyxoviridae cause most devastating diseases of animals and humans. In particular, the viruses causing rinderpest, canine distemper, Newcastle disease, measles, and mumps have arguably caused more morbidity and mortality than any other single group of related viruses in history. The impact of these diseases has been dramatically reduced through the use of vaccines in both humans and animals, in combination with depopulation and restrictions on animal movements for diseases such as rinderpest and Newcastle disease. The history of the paramyxoviruses is replete with incorrect reports that complicate their taxonomic classification and confuses assessment of their true ability to cause interspecies infections. The nomenclature of viruses within the family Paramyxoviridae is confusing and fraught with inconsistencies, as individual viruses have variously been named according to their species of origin, geographic sites of discovery, antigenic relationships, or given names related to the diseases that they produce in affected animals or humans. Paramyxovirus virions are pleomorphic, 150–350 nm in diameter. Virions are enveloped, covered with large glycoprotein spikes, and contain a “herringbone-shaped” helically symmetrical nucleocapsid, approximately 1 μm in length and 18 nm (Paramyxovirinae) or 13–14 nm (Pneumovirinae) in diameter. Paramyxoviruses usually cause lytic infection in cell cultures, but adaptation of the virus is usually necessary to achieve high-titer yields of virus.


Mayo Clinic Strategies for COVID-19 Community Engagement With Vulnerable Populations


title: Neutrophil-to-Lymphocyte Ratio and Outcomes in Louisiana Covid-19 Patients

text: BACKGROUND: Due to the rapidly escalating number of cases and the low baseline of overall health in Louisiana, we sought to determine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in hospitalized COVID patients in 2 major metropolitan areas with the highest prevalence of cases and exceedingly high rates of obesity and other comorbid conditions. We hypothesized that elevated NLR would be a prognostic indicator of mortality. METHODS: This was a review of a prospective registry of adult (18+ years) hospitalized SARS-CoV-2 patients from to two large urban safety net hospitals in Louisiana. Blood cell counts at days 2 and 5 were used to obtain NLR. Receiver operating characteristic (ROC) curve analysis assessed predictive capacity of NLR on mortality. Kaplan-Meier (KM) survival analysis and Cox regression models examined the effect of NLR on survival. RESULTS: The study population of 125 patients was majority African American (88.6%) and female (54.8%) with a mean age and BMI of 58.7 years and 34.2. Most (96.0%) had comorbidities of which hypertension (72.0%), obesity (66.7%), and diabetes (40.0%) were the most common. Mortality was 18.4%. NLR > 4.94 on day 1 predicted intubation (P = 0.02). NLR above established cutoff values on hospital days 2 and 5 each significantly predicted mortality (P < 0.001 and P = 0.002, respectively). CONCLUSIONS: NLR is a prognostic factor for endotracheal intubation upon hospital admission and independent predictor for risk of mortality in SARS-CoV-2 patients on subsequent hospital days. Clinical research efforts should examine effects of strategies such as arginase inhibition alone and/or inhaled nitric oxide to ameliorate the effects of elevated NLR.


Anakinra for patients with COVID-19 – Authors' reply


title: Will the COVID-19 Epidemic Reshape Cardiology?

text: The emergence of the novel coronavirus infection (COVID-19) began a series of unparalleled changes in health care systems worldwide. In the United States, the rapid evolution of the epidemic poses unprecedented challenges to hospitals, medical staff, training programs, policy makers, and professional societies(1). For cardiology, COVID-19 brings substantial changes to the way we conceptualize and practice medicine. As others have observed, the abrupt change of our routines and priorities offers us the opportunity for reinvention; in this space, we can critically examine several facets of our profession. In this perspective, we discuss key questions resonating in the cardiology community in the midst of the epidemic. The discussion is structured around three domains: clinical practice, education and training, and professional values. We describe the immediate ramifications and potential long-term impact of COVID-19 on each domain.


title: ‘All In’: a pragmatic framework for COVID‐19 testing and action on a global scale

text: Current demand for SARS‐CoV‐2 testing is straining material resource and labor capacity around the globe. As a result, the public health and clinical community are hindered in their ability to monitor and contain the spread of COVID‐19. Despite broad consensus that more testing is needed, pragmatic guidance toward realizing this objective has been limited. This paper addresses this limitation by proposing a novel and geographically agnostic framework (the 4Ps framework) to guide multidisciplinary, scalable, resource‐efficient, and achievable efforts toward enhanced testing capacity. The 4Ps (Prioritize, Propagate, Partition, and Provide) are described in terms of specific opportunities to enhance the volume, diversity, characterization, and implementation of SARS‐CoV‐2 testing to benefit public health. Coordinated deployment of the strategic and tactical recommendations described in this framework has the potential to rapidly expand available testing capacity, improve public health decision‐making in response to the COVID‐19 pandemic, and/or to be applied in future emergent disease outbreaks.


title: Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4

text: Abstract Coronaviruses replicate their genomes in association with rearranged cellular membranes. The coronavirus nonstructural integral membrane proteins (nsps) 3, 4 and 6, are key players in the formation of the rearranged membranes. Previously, we demonstrated that nsp3 and nsp4 interact and that their co-expression results in the relocalization of these proteins from the endoplasmic reticulum (ER) into discrete perinuclear foci. We now show that these foci correspond to areas of rearranged ER-derived membranes, which display increased membrane curvature. These structures, which were able to recruit other nsps, were only detected when nsp3 and nsp4 were derived from the same coronavirus species. We propose, based on the analysis of a large number of nsp3 and nsp4 mutants, that interaction between the large luminal loops of these proteins drives the formation of membrane rearrangements, onto which the coronavirus replication–transcription complexes assemble in infected cells.


title: Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group

text: Summary Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.


title: Genomic characterization and phylogenetic analysis of SARS‐COV‐2 in Italy

text: This report describes the isolation, molecular characterization, and phylogenetic analysis of the first three complete genomes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from three patients involved in the first outbreak of COVID‐19 in Lombardy, Italy. Early molecular epidemiological tracing suggests that SARS‐CoV‐2 was present in Italy weeks before the first reported cases of infection.


title: Pseudotyping exosomes for enhanced protein delivery in mammalian cells

text: Exosomes are cell-derived nanovesicles that hold promise as living vehicles for intracellular delivery of therapeutics to mammalian cells. This potential, however, is undermined by the lack of effective methods to load exosomes with therapeutic proteins and to facilitate their uptake by target cells. Here, we demonstrate how a vesicular stomatitis virus glycoprotein (VSVG) can both load protein cargo onto exosomes and increase their delivery ability via a pseudotyping mechanism. By fusing a set of fluorescent and luminescent reporters with VSVG, we show the successful targeting and incorporation of VSVG fusions into exosomes by gene transfection and fluorescence tracking. We subsequently validate our system by live cell imaging of VSVG and its participation in endosomes/exosomes that are ultimately released from transfected HEK293 cells. We show that VSVG pseudotyping of exosomes does not affect the size or distributions of the exosomes, and both the full-length VSVG and the VSVG without the ectodomain are shown to integrate into the exosomal membrane, suggesting that the ectodomain is not required for protein loading. Finally, exosomes pseudotyped with full-length VSVG are internalized by multiple-recipient cell types to a greater degree compared to exosomes loaded with VSVG without the ectodomain, confirming a role of the ectodomain in cell tropism. In summary, our work introduces a new genetically encoded pseudotyping platform to load and enhance the intracellular delivery of therapeutic proteins via exosome-based vehicles to target cells.


title: A proposed role for the SARS‐CoV‐2 nucleocapsid protein in the formation and regulation of biomolecular condensates

text: To date, the recently discovered SARS‐CoV‐2 virus has afflicted >6.9 million people worldwide and disrupted the global economy. Development of effective vaccines or treatments for SARS‐CoV‐2 infection will be aided by a molecular‐level understanding of SARS‐CoV‐2 proteins and their interactions with host cell proteins. The SARS‐CoV‐2 nucleocapsid (N) protein is highly homologous to the N protein of SARS‐CoV, which is essential for viral RNA replication and packaging into new virions. Emerging models indicate that nucleocapsid proteins of other viruses can form biomolecular condensates to spatiotemporally regulate N protein localization and function. Our bioinformatic analyses, in combination with pre‐existing experimental evidence, suggest that the SARS‐CoV‐2 N protein is capable of forming or regulating biomolecular condensates in vivo by interaction with RNA and key host cell proteins. We discuss multiple models, whereby the N protein of SARS‐CoV‐2 may harness this activity to regulate viral life cycle and host cell response to viral infection.


title: Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) infection

text: Abstract The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV), the pathogenic agent of Covid-19, represent a serious health problem worldwide. Respiratory viral infections are, in general, associated with cytokine production, inflammation, cell death, and other pathophysiological processes, which could be link with a redox imbalance or oxidative stress. These phenomena are substantially increased during aging. Actually, severity and mortality risk of SARS-CoV-2 infection or Covid-19 disease have been associated with the age. The aim of the present work was to contribute with the understanding of the possible link between oxidative stress and the pathogenesis, severity and mortality risk in patients affected by SARS-CoV infection.


title: Development of a Conventional RT-PCR Assay for Rapid Detection of Porcine Deltacoronavirus with the Same Detection Limit as a SYBR Green-Based Real-Time RT-PCR Assay

text: Porcine deltacoronavirus (PDCoV) is a newly discovered coronavirus, which belongs to the family Coronaviridae. It causes watery diarrhea, vomiting, and dehydration in newborn piglets. A sensitive RT-PCR method is urgently required to detect PDCoV infection. In this study, we developed and evaluated a conventional RT-PCR assay and a SYBR green-based real-time RT-PCR assay that targeted the PDCoV n gene. Both assays are specific and have the same limit of detection at 2 × 10(1) copies of RNA molecules per reaction. Eighty-four clinical samples were subjected to both conventional RT-PCR and real-time RT-PCR, and the same positive rate (41.7%) was achieved, which was much higher than the positive rate (26.2%) using a previously described one-step RT-PCR technique. In summary, a conventional RT-PCR technique was successfully established for the detection of PDCoV with the same detection limit as a SYBR green-based real-time RT-PCR assay.


title: In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus

text: Abstract Objective In this study we execute a rational screen to identify Chinese medical herbs that are commonly used in treating viral respiratory infections and also contain compounds that might directly inhibit 2019 novel coronavirus (2019-nCoV), an ongoing novel coronavirus that causes pneumonia. Methods There were two main steps in the screening process. In the first step we conducted a literature search for natural compounds that had been biologically confirmed as against sever acute respiratory syndrome coronavirus or Middle East respiratory syndrome coronavirus. Resulting compounds were cross-checked for listing in the Traditional Chinese Medicine Systems Pharmacology Database. Compounds meeting both requirements were subjected to absorption, distribution, metabolism and excretion (ADME) evaluation to verify that oral administration would be effective. Next, a docking analysis was used to test whether the compound had the potential for direct 2019-nCoV protein interaction. In the second step we searched Chinese herbal databases to identify plants containing the selected compounds. Plants containing 2 or more of the compounds identified in our screen were then checked against the catalogue for classic herbal usage. Finally, network pharmacology analysis was used to predict the general in vivo effects of each selected herb. Results Of the natural compounds screened, 13 that exist in traditional Chinese medicines were also found to have potential anti-2019-nCoV activity. Further, 125 Chinese herbs were found to contain 2 or more of these 13 compounds. Of these 125 herbs, 26 are classically catalogued as treating viral respiratory infections. Network pharmacology analysis predicted that the general in vivo roles of these 26 herbal plants were related to regulating viral infection, immune/inflammation reactions and hypoxia response. Conclusion Chinese herbal treatments classically used for treating viral respiratory infection might contain direct anti-2019-nCoV compounds.


title: Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease

text: Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) diagnostic submission from Kansas identified contigs with approximately 90% nucleotide similarity to BRAV2 and BRBV. A combination of de novo and templated assemblies using reference genomes yielded near complete BRAV2 and BRBV genomes. The near complete genome of bovine rhinitis A virus 1 (BRAV1) was also determined from a historical isolate to enable further molecular epidemiological studies. A 5’-nuclease reverse transcription PCR assay targeting the 3D polymerase gene was designed and used to screen 204 archived BRD clinical specimens. Thirteen (6.4%) were positive. Metagenomic sequencing of six positive samples identified mixed BRAV1/BRAV2, BRAV1/BRBV and BRAV2/BRBV infections for five samples. One sample showed infection only with BRAV1. Seroprevalence studies using a cell culture adapted BRBV found immunofluorescence assay-reactive antibodies were common in the herds analyzed. Altogether, these results demonstrate that BRV infections are common in cattle with respiratory disease and that BRAV1, BRAV2 and BRBV co-circulate in U.S. cattle and have high similarity to viruses isolated more than 30 years ago from diverse locations.


title: Detection and analysis of clinical features of patients with different COVID‐19 types

text: OBJECTIVE: This study was designed to investigate the change of various indexes in patients with different types of coronavirus disease 2019 (COVID‐19). METHODS: 75 COVID‐19 patients were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, and they were classified into moderate, severe and critically severe types according to the disease severity. The basic information, blood routine, pneumonia‐related blood indexes, immune‐related indexes along with liver, kidney and myocardial indexes in patients with different types were analyzed. RESULTS: The analysis of immune‐related indexes showed that the proportions of critically severe patients with abnormal IL‐2 and IL‐4 were higher than those of severe and moderate patients. In addition, the proportion of patients with abnormal total cholesterol increased as the severity of disease increased, and the proportion in critically severe patients was significantly higher than that in moderate patients. CONCLUSIONS: The patients with a more severe COVID‐19 are older and more likely to have a history of hypertension. With the progression of COVID‐19, the abnormal proportion of total white blood cell, neutrophils, lymphocytes, IL‐2, IL‐4 and total cholesterol increased. The change of these indexes in patients with different COVID‐19 types could provide reference for the disease severity identification and diagnosis of COVID‐19. In addition, the change in the total cholesterol level suggested that COVID‐19 would induce some liver function damage in patients. This article is protected by copyright. All rights reserved.


Elective surgeries during the COVID‐19 outbreak


title: An astrovirus frameshift signal induces ribosomal frameshifting in vitro

text: Expression of the astrovirus RNA-dependent RNA polymerase has been hypothesized to be regulated by (− 1) ribosomal frameshifting. Sequence analysis of the 70 nucleotide region between open reading frames 1a and 1b indicates the presence of a shifty heptamer consensus sequence and downstream sequences that may be needed for ribosomal frameshifting. We constructed four astrovirus cassettes that spanned this region and inserted each into the rhesus rotavirus VP4 gene. The constructs were expressed in an in vitro system, and products were immunoprecipitated by rotavirus amino and carboxy terminal-specific monoclonal antibodies. Ribosomal frameshifting, at an efficiency of 6–7%, was demonstrated in all constructs containing the shifty heptamer and stem-loop. Deletion of the downstream sequence potentially involved in pseudoknot formation did not affect frameshifting efficiency. However, deletion of the shifty heptamer resulted in no detectable frameshift activity.


docid: cyetlmgt

title: Jumping species—a mechanism for coronavirus persistence and survival

text: Zoonotic transmission of novel viruses represents a significant threat to global public health and is fueled by globalization, the loss of natural habitats, and exposure to new hosts. For coronaviruses (CoVs), broad diversity exists within bat populations and uniquely positions them to seed future emergence events. In this review, we explore the host and viral dynamics that shape these CoV populations for survival, amplification, and possible emergence in novel hosts.


title: Appropriate arrangement of cancer treatment after COVID-19 epidemic peaks in China

text: PURPOSE: COVID-19 is causing a lot of problems in health services around the world, especially in medical institutions receiving cancer patients. On March 12, China’s National Health Commission announced that the peak of the COVID-19 epidemic has passed in China. Thus, a proper arrangement of medication, surgery and radiotherapy for patients with cancer is of vital importance after the epidemic peak. METHODS: A range of measures have been implemented in our center. Specific patients take priority for chemotherapy treatment. The amount of semi-elective and elective surgeries could be gradually increased beyond urgent and emergency surgery. The hypofractionated radiotherapy is recommended in the right circumstances. RESULTS: On March 13, our center announced that more than 5000 visits of chemotherapy and radiotherapy are arranged in our outpatient clinics and none of our patients and staffs have been diagnosed with COVID-19 as of March 28, 2020. CONCLUSION: The rational arrangement we make now may be helpful to the future restoration of cancer treatments in other countries.


title: The evolving structure of the Southeast Asian air transport network through the lens of complex networks, 1979–2012

text: Abstract This paper presents a novel approach to investigating and understanding the evolving structure of the Southeast Asian air transport network (SAAN) over the period 1979–2012. Our approach captures the main topological and spatial changes from a complex network perspective. We find that the SAAN combines a relatively stable topological structure with a changing multilayered geographical structure. Statistical analysis indicates that the SAAN is a scale-free network with an increasing number of hub cities and has been characterized by small-world properties since 1996. Furthermore, the SAAN exhibits a recently intensified disassortative mixing pattern, suggesting an increasing dependence of small cities on hub-and-spoke configuration for better accessibility. A decomposition analysis is used to disaggregate the SAAN into a hierarchical core-bridge-periphery structure. The core layer consists of capital cities, the most economic vibrant secondary cities, and tourist destinations. This core layer is also densely interconnected with its center of gravity moving towards the north. The periphery layer, comprised of cities in remote areas, sustains a low significance with declining internal connectivity despite a rising number of cities being connected. The bridge layer lies in between both extremes, and is characterized by a high volatility over time. The connections and passengers between different layers increase, especially those between core and bridge after 1996. In our discussion, we trace these changes back to a series of socio-economic and politico-institutional dynamics in Southeast Asia.


title: The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker

text: The efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. Several O,O-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and cytostatic activity against murine leukaemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Acyclonucleotide 22e exhibited activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC(50) = 17 μM) and feline herpes virus (EC(50) = 24 μM) in CRFK cell cultures, while compounds 20k, 21k, 22k and 23k preferentially inhibited proliferation of human T-lymphocyte CEM cells at IC(50) in the 2.8–12 μM range.


docid: fdqhnmwn

title: Electoral incentives to combat mosquito-borne illnesses: Experimental evidence from Brazil()

text: Mosquito-borne illnesses present significant health challenges to the developing world. If citizens are informed about their government’s efforts to combat these diseases, will they reward incumbents who have performed well and punish those who have done poorly at this task? Electoral sanctioning requires that combatting disease be a sufficiently salient concern, which, in turn, is likely to depend upon subjective perceptions of the risks posed by particular illnesses. Epidemics typically prompt stronger risk perceptions than endemic diseases, but where both types circulate jointly, the more familiar endemic disease may determine public reactions. The salience of health threats also varies among individuals; those with a self-interest in prevention or a personal connection to the effects of mosquito-borne illnesses may react more strongly. This study presents the results of a face-to-face survey experiment in Pernambuco, Brazil, informing subjects about their mayor’s use of federal funds to combat mosquito-borne illnesses such as dengue (an endemic disease) and Zika and chikungunya (both epidemics). We examine the effect of this information on intended vote for the mayor’s reelection. For the full sample, the treatment has no significant effect. However, we find a large and significant punishment effect among voters who know someone affected by microcephaly or the Zika virus. Drawing on survey and focus group evidence, we argue that most voters fail to act upon our treatment information because mosquito control is a low-salience concern primarily associated with endemic rather than epidemic diseases. Our study constitutes the first experimental evidence as to whether informing citizens about government public health efforts affects voting behavior. Our results suggests that, where similar epidemic and endemic diseases circulate together, informational campaigns aiming to induce electoral accountability should also seek to boost the salience of the information by educating the public about the difference between familiar and newer threats.


title: Bartonella-associated inflammatory cardiomyopathy in a dog

text: Abstract A 6-year-old, male, mongrel dog was presented for acute onset of dyspnea and cough. At admission, the dog was cachectic and severely depressed. The electrocardiogram showed a sinus rhythm conducted with left bundle truncular branch block and interrupted by frequent multiform ventricular ectopic beats organized in allorhythmias. Thoracic radiographs revealed a marked cardiomegaly with perihilar edema, whereas transthoracic echocardiography revealed a dilated cardiomyopathy with segmental dyskinesis. Furosemide, enalapril, pimobendan, and mexiletine were prescribed, and a Holter was scheduled after resolution of congestive heart failure. Three days later, the dog died suddenly during sleep. Histopathology revealed diffuse myocyte hypertrophy with multifocal hemorrhages, alternating to areas of severe replacement fibrosis and lymphoplasmocytic infiltrates. Immunohystochemistry stains were strongly positive for T-lymphocyte infiltration (CD3) and weakly positive for B-lymphocytes (CD79). Polymerase chain reaction was positive for Bartonella spp. Based on these results, a post-mortem diagnosis of bacterial inflammatory cardiomyopathy was made.


title: Developing and Using Therapeutics for Emerging Infections

text: This issue of Clinical Pharmacology & Therapeutics focuses on emerging infections. The outbreaks of the vaccine‐preventable diseases (e.g., measles) and the emerging pathogens (e.g., Ebola) show us how small the world has become. These outbreaks also show the pressing need for effective public education and development of novel therapies. This issue covers various aspects of relevant therapeutic topics ranging from preclinical models, pharmacokinetics, pharmacodynamics, pharmacogenomics, and clinical trial results, to education efforts in this area. Pharmacokinetic/dynamic modeling had an appreciable role in reducing the morbidity and mortality associated with human immunodeficiency virus and hepatitis C virus, recent emerging infections. However, these gains could be lessened by poor adherence to therapies, which has contributed to the development of multidrug‐resistant tuberculosis. We must not forget lessons from previous infections, or they may reemerge.


title: Development and application of a multiplex PCR method for the simultaneous detection and differentiation of feline panleukopenia virus, feline bocavirus, and feline astrovirus

text: A multiplex polymerase chain reaction (mPCR) assay was developed to detect and distinguish feline panleukopenia virus (FPV), feline bocavirus (FBoV) and feline astrovirus (FeAstV). Three pairs of primers were designed based on conserved regions in the genomic sequences of the three viruses and were used to specifically amplify targeted fragments of 237 bp from the VP2 gene of FPV, 465 bp from the NP1 gene of FBoV and 645 bp from the RdRp gene of FeAstV. The results showed that this mPCR assay was effective, because it could detect at least 2.25-4.04 × 10(4) copies of genomic DNA of the three viruses per μl, was highly specific, and had a good broad-spectrum ability to detect different genotypes of the targeted viruses. A total of 197 faecal samples that had been screened previously for FeAstV and FBoV were collected from domestic cats in northeast China and were tested for the three viruses using the newly developed mPCR assay. The total positive rate for these three viruses was 59.89% (118/197). From these samples, DNA from FPV, FBoV and FeAstV was detected in 73, 51 and 46 faecal samples, respectively. The mPCR testing results agreed with the routine PCR results with a coincidence rate of 100%. The results of this study show that this mPCR assay can simultaneously detect and differentiate FPV, FBoV and FeAstV and can be used as an easy, specific and efficient detection tool for clinical diagnosis and epidemiological investigation of these three viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04394-8) contains supplementary material, which is available to authorized users.


title: Gel-Filtration Chromatography

text: Gel-filtration chromatography is a versatile method that permits the effective separation of biological molecules in high yield. This article describes the basis of the method, the selection of suitable operating conditions, and contrasts typical matrix types. Applications of the technique are described, with references to the scientific literature.


title: Epidemiological and genetic analysis of severe acute respiratory syndrome

text: Summary The severe acute respiratory syndrome (SARS) epidemics in 2002–2003 showed how quickly a novel infectious disease can spread both within communities and internationally. We have reviewed the epidemiological and genetic analyses that have been published both during and since these epidemics, and show how quickly data were collected and analyses undertaken. Key factors that determine the speed and scale of transmission of an infectious disease were estimated using statistical and mathematical modelling approaches, and phylogenetic analyses provided insights into the origin and evolution of the SARS-associated coronavirus. The SARS literature continues to grow, and it is hoped that international collaboration in the analysis of epidemiological and contact-network databases will provide further insights into the spread of this newly emergent infectious disease.


title: Resistance to synthetic blood penetration of National Institute for Occupational Safety and Health-approved N95 filtering facepiece respirators and surgical N95 respirators

text: BACKGROUND: Surgical N95 filtering facepiece respirators (FFRs), certified by the National Institute for Occupational Safety and Health (NIOSH) as a respirator and cleared by the Food and Drug Administration (FDA) as a surgical mask, are often used to protect from the inhalation of infectious aerosols and from splashes/sprays of body fluids in health care facilities. A shortage of respirators can be expected during a pandemic. The availability of surgical N95 FFRs can potentially be increased by incorporating FDA clearance requirements in the NIOSH respirator approval process. METHODS: Fluid resistance of NIOSH-approved N95 FFRs, and FDA-cleared surgical N95 FFRs and surgical masks was tested using the ASTM F1862 method at 450 and 635 cm/sec velocities and compared with the results from a third-party independent laboratory. Blood penetration through different layers of filter media of masks were also analyzed visually. RESULTS: Four N95 FFR models showed no test failures at both velocities. The penetration results obtained in the NIOSH laboratory were comparable to those from the third-party independent laboratory. The number of respirator samples failing the test increased with increasing test velocity. CONCLUSIONS: The results indicate that several NIOSH-approved N95 FFR models would likely pass FD clearance requirements for resistance to synthetic blood penetration.


docid: ptcenlnx

title: Recommandations de la Société Française de Médecine du Travail (SFMT) : Avis relatif à l’affectation, dans le contexte de l’épidémie SARS-CoV-2 (Covid-19), des professionnels exerçant en milieu de soins et travailleurs assimilés, présentant un asthme. 7 avril 2020


docid: masvhhte

title: Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects

text: Thrombomodulin (TM) is a 557-amino acid protein with a broad cell and tissue distribution consistent with its wide-ranging physiological roles. When expressed on the lumenal surface of vascular endothelial cells in both large vessels and capillaries, its primary function is to mediate endothelial thromboresistance. The complete integral membrane-bound protein form displays five distinct functional domains, although shorter soluble (functional) variants comprising the extracellular domains have also been reported in fluids such as serum and urine. TM-mediated binding of thrombin is known to enhance the specificity of the latter serine protease toward both protein C and thrombin activatable fibrinolysis inhibitor (TAFI), increasing their proteolytic activation rate by almost three orders of magnitude with concomitant anticoagulant, antifibrinolytic, and anti-inflammatory benefits to the vascular wall. Recent years have seen an abundance of research into the cellular mechanisms governing endothelial TM production, processing, and regulation (including flow-mediated mechanoregulation)—from transcriptional and posttranscriptional (miRNA) regulation of TM gene expression, to posttranslational processing and release of the expressed protein—facilitating greater exploitation of its therapeutic potential. The goal of the present paper is to comprehensively review the endothelial/TM system from these regulatory perspectives and draw some fresh conclusions. This paper will conclude with a timely examination of the current status of TM's growing therapeutic appeal, from novel strategies to improve the clinical efficacy of recombinant TM analogs for resolution of vascular disorders such as disseminated intravascular coagulation (DIC), to an examination of the complex pleiotropic relationship between statin treatment and TM expression.


title: Global Coronavirus Pandemic (SARS CoV‐2): Past, Present, And Future Of Pediatric Dermatology

text: Two months have passed since the World Health Organization (WHO) declared the pandemic of the Coronavirus Disease 19 (COVID‐19), caused by the SARS CoV‐2 virus, on March 11, 2020. Medical and healthcare workers have continued to be on the frontline to defeat this disease, however, continual changes are being made to their working habits which are proving to be difficult. Although the skin is not the main target of the SARS CoV‐2 infection, it is strongly involved both directly and indirectly, in many aspects of dermatological disease management, and particularly in pediatric dermatology. In this manuscript, our goal was to provide a “up‐to‐date” account on this topic, through analysis of current literature and sharing our experiences during this pandemic. This article is protected by copyright. All rights reserved.


title: Molecular Imaging of Influenza and Other Emerging Respiratory Viral Infections

text: Research on the pathogenesis and therapy of influenza and other emerging respiratory viral infections would be aided by methods that directly visualize pathophysiologic processes in patients and laboratory animals. At present, imaging of diseases, such as swine-origin H1N1 influenza, is largely restricted to chest radiograph and computed tomography (CT), which can detect pulmonary structural changes in severely ill patients but are more limited in characterizing the early stages of illness, differentiating inflammation from infection or tracking immune responses. In contrast, imaging modalities, such as positron emission tomography, single photon emission CT, magnetic resonance imaging, and bioluminescence imaging, which have become useful tools for investigating the pathogenesis of a range of disease processes, could be used to advance in vivo studies of respiratory viral infections in patients and animals. Molecular techniques might also be used to identify novel biomarkers of disease progression and to evaluate new therapies.


title: Trends and Patterns of Burden of Disease and Injuries in Korea Using Disability-Adjusted Life Years

text: BACKGROUND: It is extremely important to objectively take a view of population health to provide useful information to decision makers, health-sector leaders, researchers, and informed citizens. This study aims to examine the burden of disease in Korea as of 2015, and to study how the burden of disease changes with the passage of time. METHODS: We used results from the Korean National Burden of Disease and Injuries Study 2015 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive disability-adjusted life years (DALYs) by gender and age groups from 2007 to 2015. DALYs were calculated as the sum of the years of life lost (YLLs) and the years lived with disability (YLDs). RESULTS: In 2015, the burden of disease for Korean people was calculated at 29,476 DALYs per 100,000 population. DALYs caused by low back pain were the highest, followed by diabetes mellitus and chronic obstructive pulmonary disease. The burden of disease showed a consistently increasing trend from 2007 to 2015. Although YLLs have been on the decrease since 2011, the increase in YLDs has contributed to the overall rise in DALYs. The DALYs per 100,000 population in 2015 increased by 28.1% compared to 2007. CONCLUSION: As for the diseases for which the burden of disease is substantially increasing, it is needed to establish appropriate policies in a timely manner. The results of this study are expected to be the basis for prioritizing public health and health care policies in Korea.


Avril 2020 au GHR de Mulhouse entre SMUR et Réanimation: Au cœur de la pandémie COVID-19


title: The rise of molecular simulations in fragment-based drug design (FBDD): an overview

text: Fragment-based drug discovery (FBDD) is an innovative approach, progressively more applied in the academic and industrial context, to enhance hit identification for previously considered undruggable biological targets. In particular, FBDD discovers low-molecular-weight (LMW) ligands (<300 Da) able to bind to therapeutically relevant macromolecules in an affinity range from the micromolar (μM) to millimolar (mM). X-ray crystallography (XRC) and nuclear magnetic resonance (NMR) spectroscopy are commonly the methods of choice to obtain 3D information about the bound ligand–protein complex, but this can occasionally be problematic, mainly for early, low-affinity fragments. The recent development of computational fragment-based approaches provides a further strategy for improving the identification of fragment hits. In this review, we summarize the state of the art of molecular dynamics simulations approaches used in FBDD, and discuss limitations and future perspectives for these approaches.


title: Detection of pathogens in water: from phylochips to qPCR to pyrosequencing

text: Waterborne pathogens pose a significant threat to human health and a proper assessment of microbial water quality is important for decision making regarding water infrastructure and treatment investments and eventually to provide early warning of disease, particularly given increasing global disasters associated with severe public health risks. Microbial water quality monitoring has undergone tremendous transition in recent years, with novel molecular tools beginning to offer rapid, high-throughput, sensitive and specific detection of a wide spectrum of microbial pathogens that challenge traditional culture-based techniques. High-density microarrays, quantitative real-time PCR (qPCR) and pyrosequencing which are considered to be breakthrough technologies borne out of the ‘molecular revolution’ are at present emerging rapidly as tools of pathogen detection and discovery. Future challenges lie in integrating these molecular tools with concentration techniques and bioinformatics platforms for unbiased guide of pathogen surveillance in water and developing standardized protocols.


title: Clinical signs, reproduction of attaching/effacing lesions, and enterocyte invasion after oral inoculation of an O118 enterohaemorrhagic Escherichia coli in neonatal calves

text: Abstract Attaching and effacing (AE) lesions are produced among others by enteropathogenic Escherichia coli and enterohaemorrhagic E. coli (EHEC), which differs from the former by the production of cytotoxins active on various cell cultures, the verocytotoxins, or shigacytotoxins. EHEC are associated with diarrhoea and dysentery in humans and in ruminants, mainly calves from two to eight weeks of age. Clinical signs and/or lesions have been reproduced experimentally with EHEC strains belonging to serotypes O5:K4/Nm, O26:K-:H11, O111:Nm, and O157:H7 which are isolated from cattle and/or humans. The purpose of this work was to develop an experimental model of infection in newborn calves with a bovine EHEC strain isolated from a calf which of died of diarrhoea, and belonging to the O118:H16 serotype, which is also common to both cattle and humans. The bovine O118:H16 EHEC strain was able to colonize the gut of three newborn calves, and to induce diarrhoea twenty-four hours after challenge and to produce AE lesions in the small and/or large intestines. AE lesions were detected microscopically and ultrastructurally in the small intestine of one calf and in the whole intestinal track of two calves. Internalization of bacteria and also of pedestal-bacteria complex inside of the enterocyte was observed in two of the three calves. The significance of this stage is unknown but may be related to the invasion of the calf by the bacteria. The challenge strain was isolated from the mesenteric lymph nodes of the same two calves but not from other organs or from heart blood. No blood was observed in the faeces of any of the three calves, nor were any lesions in the internal organs, which may have been related to the production of a verotoxin whose role is still unknown in cattle.


docid: kcklocnc

title: The COVID-19 pandemic: implications for the head and neck anesthesiologist

text: As the COVID-19 pandemic has unfolded, there has been growing recognition of risks to the anesthesia and surgical teams that require careful consideration to ensure optimal patient care. Airway management and other head and neck procedures risk exposure to mucosal surfaces, secretions, droplets, and aerosols that may harbor the SARS-CoV-2 virus. This review provides guidance on optimal practice approaches for performing patient evaluation and management of head and neck procedures with the shared goal of providing safe and effective patient care while minimizing the risk of viral transmission. METHODS: The scientific literature was evaluated, focusing on strategies to reduce risk to health care workers involved in airway management and head and neck surgery. The search strategy involved curating consensus statements and guidelines relating to COVID-19 or prior coronavirus outbreaks in relation to aerosol-generating procedures (AGPs) and other high-risk procedures, with the search restricted to the scope of head and neck anesthesia. A multidisciplinary team analyzed the findings, using iterative virtual communications through video conference, telephone, email, and shared online documents until consensus was achieved, loosely adapted from the Delphi technique. Items without consensus were so indicated or removed from the manuscript. RESULTS: Health care worker infection and deaths during the COVID-19 pandemic and prior outbreaks mandate robust standards for infection control. Most head and neck anesthesiology procedures generate aerosols, and algorithms may be modified to mitigate risks. Examples include preoxygenation before induction of anesthesia, rapid sequence induction, closing circuits expeditiously, and consideration of apneic technique for surgical entry of airway. Rescue measures are also modified, with supraglottic airways elevated in the difficult airway algorithm to minimize the need for bag mask ventilation. Personal protective equipment for AGPs include fit-tested N95 mask (or purified air positive respirator), gloves, goggles, and gown for patients with known or suspected COVID-19. Meticulous donning and doffing technique, minimizing personnel and room traffic, diligent hand hygiene, and social distancing all can decrease risks. Perioperative management approaches may differ from commonly employed patterns including avoidance of techniques such as jet ventilation, high-flow nasal oxygen and instead utilizing techniques with a closed ventilatory circuit and secured endotracheal tube, minimizing open suctioning, and preventing aerosolization at emergence. Recommendations are made for the following head and neck procedures and considerations: primary airway management; high-flow nasal oxygen delivery; jet ventilation for laryngotracheal surgery; awake intubation; transnasal skull base surgery; tracheostomy; and use of personal protective equipment. COVID-19 testing may facilitate decision making, but it is currently often unavailable and urgency of surgical treatment must be considered. CONCLUSIONS: During pandemics, head and neck anesthesia and surgical teams have a duty to not only provide high quality patient care but also to ensure the safety of the health care team. Several specific perioperative approaches are recommended that have some variance from commonly employed practices, focusing on the reduction of AGP to minimize the risk of infection from patients with known or suspected COVID-19 infection.


title: Selective Inhibition of USP7

text: The deubiquitinating enzyme USP7 is an emerging oncology and antiviral target. Reverdy et al., in this issue of Chemistry & Biology, disclose the first small-molecule inhibitor selective for USP7, which recapitulates its knockdown in cancer cells and hence demonstrates the therapeutic feasibility of USP7 inhibitors.


RAT Coronavirus Infection of Primary RAT Alveolar Epithelial Cells


docid: rdmaaowm

title: Joint detection of tumor markers with imaging ellipsometry biosensor

text: Tumor marker detection contributes to the early diagnosis of cancers. However, due to the lack of detection specificity, its results cannot act as a direct evidence to confirm cancer occurrence in clinic. Joint detection of tumor markers may improve the detection specificity. As a trial for clinical diagnosis of hepatocellular carcinoma, α-fetoprotein, α-l-fucosidase and ferritin have been combined and detected with a label-free, phase sensitive and high throughput imaging ellipsometry biosensor (IEB). Eighty-two sera have been quantitatively detected with IEB and the results are in agreement with the clinical standard approaches. Evaluated by receiver operating characteristic analysis, the specificity of joint detection improves remarkably with IEB for hepatocellular carcinoma. It can be foreseen that the joint detection of tumor markers with IEB has a potential for clinical cancer diagnosis.


title: Understanding Knowledge and Behaviors Related to CoViD–19 Epidemic in Italian Undergraduate Students: The EPICO Study

text: Background: On February 2020, the novel coronavirus (2019−nCoV) epidemic began in Italy. In order to contain the spread of the virus, the Italian government adopted emergency measures nationwide, including closure of schools and universities, workplaces and subsequently lockdown. This survey was carried out among Italian undergraduates to explore their level of knowledge about the epidemic and the behaviors they adopted during the lockdown. Methods: An electronic questionnaire was administered to the students attending three Italian universities. Results: A good level of knowledge about the epidemic and its control was registered in the sample, mainly among students attending life sciences degree courses. The majority of the students did not modify their diet and smoking habits, while a great part of the sample reported a decrease in physical activity (PA). Conclusions: Students from life sciences courses showed a higher awareness regarding the infection and the control measures. The lockdown caused an important reduction of PA. Preventive interventions should transform the restrictive measures also as an opportunity to improve lifestyle.


Laparoscopic versus open surgery: aerosols and their implications for surgery during the COVID-19 pandemic


title: Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review

text: BACKGROUND: Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak control. Experiences from previous epidemics have identified multiple challenges to undertaking timely clinical research responses. This scoping review is a systematic appraisal of political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges to clinical research responses to emergency epidemics and solutions identified to address these. METHODS: A scoping review. We searched six databases (MEDLINE, Embase, Global Health, PsycINFO, Scopus and Epistemonikos) for articles published from 2008 to July 2018. We included publications reporting PEARLES challenges to clinical research responses to emerging epidemics and pandemics and solutions identified to address these. Two reviewers screened articles for inclusion, extracted and analysed the data. RESULTS: Of 2678 articles screened, 76 were included. Most presented data relating to the 2014–2016 Ebola virus outbreak or the H1N1 outbreak in 2009. The articles related to clinical research responses in Africa (n = 37), Europe (n = 8), North America (n = 5), Latin America and the Caribbean (n = 3) and Asia (n = 1) and/or globally (n = 22). A wide range of solutions to PEARLES challenges was presented, including a need to strengthen global collaborations and coordination at all levels and develop pre-approved protocols and equitable frameworks, protocols and standards for emergencies. Clinical trial networks and expedited funding and approvals were some solutions implemented. National ownership and community engagement from the outset were a key enabler for delivery. Despite the wide range of recommended solutions, none had been formally evaluated. CONCLUSIONS: To strengthen global preparedness and response to the COVID-19 pandemic and future epidemics, identified solutions for rapid clinical research deployment, delivery, and dissemination must be implemented. Improvements are urgently needed to strengthen collaborations, funding mechanisms, global and national research capacity and capability, targeting regions vulnerable to epidemics and pandemics. Solutions need to be flexible to allow timely adaptations to context, and research led by governments of affected regions. Research communities globally need to evaluate their activities and incorporate lessons learnt to refine and rehearse collaborative outbreak response plans in between epidemics.


docid: rnkawxrq

title: Healthcare workers' attitudes to working during pandemic influenza: a qualitative study

text: BACKGROUND: Healthcare workers (HCWs) will play a key role in any response to pandemic influenza, and the UK healthcare system's ability to cope during an influenza pandemic will depend, to a large extent, on the number of HCWs who are able and willing to work through the crisis. UK emergency planning will be improved if planners have a better understanding of the reasons UK HCWs may have for their absenteeism, and what might motivate them to work during an influenza pandemic. This paper reports the results of a qualitative study that explored UK HCWs' views (n = 64) about working during an influenza pandemic, in order to identify factors that might influence their willingness and ability to work and to identify potential sources of any perceived duty on HCWs to work. METHODS: A qualitative study, using focus groups (n = 9) and interviews (n = 5). RESULTS: HCWs across a range of roles and grades tended to feel motivated by a sense of obligation to work through an influenza pandemic. A number of significant barriers that may prevent them from doing so were also identified. Perceived barriers to the ability to work included being ill oneself, transport difficulties, and childcare responsibilities. Perceived barriers to the willingness to work included: prioritising the wellbeing of family members; a lack of trust in, and goodwill towards, the NHS; a lack of information about the risks and what is expected of them during the crisis; fear of litigation; and the feeling that employers do not take the needs of staff seriously. Barriers to ability and barriers to willingness, however, are difficult to separate out. CONCLUSION: Although our participants tended to feel a general obligation to work during an influenza pandemic, there are barriers to working, which, if generalisable, may significantly reduce the NHS workforce during a pandemic. The barriers identified are both barriers to willingness and to ability. This suggests that pandemic planning needs to take into account the possibility that staff may be absent for reasons beyond those currently anticipated in UK planning documents. In particular, staff who are physically able to attend work may nonetheless be unwilling to do so. Although there are some barriers that cannot be mitigated by employers (such as illness, transport infrastructure etc.), there are a number of remedial steps that can be taken to lesson the impact of others (providing accommodation, building reciprocity, provision of information and guidance etc). We suggest that barriers to working lie along an ability/willingness continuum, and that absenteeism may be reduced by taking steps to prevent barriers to willingness becoming perceived barriers to ability.


title: Attitudes, practices and information needs regarding novel influenza A (H7N9) among employees of food production and operation in Guangzhou, Southern China: a cross-sectional study

text: BACKGROUND: As of 30 May 2013, 132 human infections with avian influenza A (H7N9) had been reported in 10 Chinese cities. On 17 May 2013, because a chicken infection with H7 subtype avian influenza virus was detected in Guanzhou, Guangzhou became the 11th city to conduct emergency response operations. The goal of this study was to identify attitudes, practices and information needs among employees of food production and operation in Guangzhou. METHODS: A cross-sectional survey of face-to-face interviews was used during 17–24 June 2013. All adults seeking health examination in Guangzhou Center for Disease Control and Prevention who had lived in Guangzhou for at least 3 months, were engaged in food production and operation, and agreed to participate were interviewed. RESULTS: Of 1,450 participants, 69.72% worried about being infected with the A/H7N9 and 74.41% stated that they had searched for information about A/H7N9. The internet (76.92%), television (67.56%), and newspapers (56.26%) were the main methods of obtaining information; the use of these methods differed significantly by various demographic variables (P < 0.05). More than one-fifth of participants complained that the information was not timely enough (20.28%) and was intentionally concealed by the government (20.76%). Nearly one-third (32.35%) did not believe that the government could control the A/H7N9 epidemic. Most participants (80.76%) reported washing hands more frequently than before, while over one-third (37.17%) stated no longer buying poultry. A total of 84.00% indicated a willingness to receive an A/H7N9 vaccine, and the primary reason for not being willing was concern about safety (58.19%). A history of influenza vaccination and worry about being infected with the A/H7N9 were significantly associated with intention to receive an A/H7N9 vaccine (P < 0.05). CONCLUSIONS: Our findings provide insight into the attitudes and practices of employees of food production and operation 3 months after the first human A/H7N9 case reported in China, and 1 month after infected chickens were identified in Guangzhou. Distrust in the health department should be addressed, and more effort should be made to improve compliance of proper preventive measures to reduce panic among the public. The information needs should be taken into account in the next step of health education.


title: Societal Learning in Epidemics: Intervention Effectiveness during the 2003 SARS Outbreak in Singapore

text: BACKGROUND: Rapid response to outbreaks of emerging infectious diseases is impeded by uncertain diagnoses and delayed communication. Understanding the effect of inefficient response is a potentially important contribution of epidemic theory. To develop this understanding we studied societal learning during emerging outbreaks wherein patient removal accelerates as information is gathered and disseminated. METHODS AND FINDINGS: We developed an extension of a standard outbreak model, the simple stochastic epidemic, which accounts for societal learning. We obtained expressions for the expected outbreak size and the distribution of epidemic duration. We found that rapid learning noticeably affects the final outbreak size even when learning exhibits diminishing returns (relaxation). As an example, we estimated the learning rate for the 2003 outbreak of severe acute respiratory syndrome (SARS) in Singapore. Evidence for relaxation during the first eight weeks of the outbreak was inconclusive. We estimated that if societal learning had occurred at half the actual rate, the expected final size of the outbreak would have reached nearly 800 cases, more than three times the observed number of infections. By contrast, the expected outbreak size for societal learning twice as effective was 116 cases. CONCLUSION: These results show that the rate of societal learning can greatly affect the final size of disease outbreaks, justifying investment in early warning systems and attentiveness to disease outbreak by both government authorities and the public. We submit that the burden of emerging infections, including the risk of a global pandemic, could be efficiently reduced by improving procedures for rapid detection of outbreaks, alerting public health officials, and aggressively educating the public at the start of an outbreak.


title: Update of the ERS international Adult Respiratory Medicine syllabus for postgraduate training

text: First published in 2006, the first European core syllabus in Adult Respiratory Medicine was developed with the intention of harmonising education and training throughout Europe. Internationally recognised by the European Union of Medical Specialists and identified as the first document of its kind in respiratory medicine, it has provided a comprehensive guide for both local and national institutions in the development of adult respiratory training programmes. Like all fields in education, respiratory medicine is an ever-changing area and as such, respective syllabi, curricula and training programmes must adapt and diversify in line with the evolution of core medical concepts. Given the proven importance of the Adult Respiratory Medicine syllabus from both a national and international standpoint, it is of equal importance that said syllabus remains abreast of emerging trends so as to sustain the synchronisation of respiratory medicine in Europe. In order to develop an updated programme, a comprehensive review process of the current syllabus is a necessary endeavour and a step that the European Respiratory Society (ERS) has undertaken through the process of a needs assessment.


Modified tracheal extubation for patients with COVID–19


Mitteilungen des BV Geriatrie


title: Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus

text: Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like disease but typically only with mild symptoms. Humans are the main reservoir of the virus, but it also infects pigs and dogs. Very recently, influenza C-like viruses were isolated from pigs and cattle that differ from classical influenza C virus and might constitute a new influenza virus genus. Influenza C virus is unique since it contains only one spike protein, the hemagglutinin-esterase-fusion glycoprotein HEF that possesses receptor binding, receptor destroying and membrane fusion activities, thus combining the functions of Hemagglutinin (HA) and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the epidemiology and pathology of the virus and the morphology of virus particles and their genome. The main focus is on the structure of the HEF protein as well as on its co- and post-translational modification, such as N-glycosylation, disulfide bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits. Finally, we describe the functions of HEF: receptor binding, esterase activity and membrane fusion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13238-015-0193-x) contains supplementary material, which is available to authorized users.


Mayo Clinic Strategies for COVID-19 Revisiting the Safety of Health Care Workers


title: Environmental investigation of respiratory pathogens during the Hajj 2016 and 2018

text: Abstract Background Respiratory tract infections are common in the context of the Hajj pilgrimage and respiratory pathogens can be transmitted via contact with contaminated surfaces. We sampled surfaces during the Hajj to detect the presence of respiratory bacteria and viruses. Methods Frequently touched surfaces at Mecca, Mina, Arafat and Medina were sampled. The common respiratory pathogens were tested by qPCR. Results 70/142 (49.3%) environmental samples collected were positive for at least one respiratory pathogen. Among the positive samples, Klebsiella pneumoniae was the bacterium most frequently tested positive (57.1%), followed by Streptococcus pneumoniae (12.9%), Staphylococcus aureus (10.0%) and Haemophilus influenzae (7.1%). 32.9% positive samples tested positive for rhinovirus and 1.4% for coronavirus. Surfaces with the highest rates of positive samples were kitchen tables (100%), water fountain faucet (73.3%) and edge of water coolers lid (84.6%). Samples collected in Mina were the most frequently contaminated with 68.8% being positive for at least one pathogen and 18.8% positive for a combination of multiple pathogens. Conclusion These preliminary results indicate that respiratory pathogens are common in environmental surfaces from areas frequented by Hajj pilgrims. Further larger-scale studies are needed to better assess the possible role of environmental respiratory pathogens in respiratory infections in Hajj pilgrims.


title: Novel Pharmacotherapies for Recurrent Pericarditis: Current Options in 2020

text: ABSTRACT: Recent advances have shown impressive results by anti-interleukin 1 (IL-1) agents in refractory idiopathic recurrent pericarditis. PURPOSE OF REVIEW: We critically discuss the current state of the art of therapy of relapsing pericarditis, with a focus on new pharmacological approaches and on specific clinical settings such as pregnancy, pediatric patients, and secondary forms of relapsing pericarditis. RECENT FINDINGS: Antagonism of the IL-1 is highly effective in idiopathic recurrent pericarditis with autoinflammatory features. Currently, available anti-IL-1 agents are anakinra and canakinumab. Rilonacept is another IL-1 antagonist, currently studied in the phase-3 clinical trial RHAPSODY. Available data suggest similar efficacy and safety profiles of these three agents, although only anakinra has been tested in randomized clinical trials. These agents have slightly different pharmacological properties, being canakinumab a specific IL-1ß antagonist while anakinra and rilonacept are unselective IL-1α and IL-1ß blockers. To date, there is no evidence that specificity against IL-1ß affects safety and efficacy in patients with relapsing pericarditis, although it has been proposed that unspecific blockage might be useful in severe disease. SUMMARY: Anakinra is the first anti-IL-1 agent with well-documented efficacy and safety in adult and pediatric patients with idiopathic relapsing pericarditis. Other anti-IL-1 agents are currently under study. Future research should clarify the optimal duration of therapy and tapering schedule of treatment with these agents. Moreover, biomarkers would be required to understand which patients will benefit from early administration of IL-1 blockers due to refractoriness to conventional therapy and which others will suffer from recurrences during the tapering of these agents. Lastly, future studies should focus on the subjects with the autoimmune or the pauci-inflammatory phenotype of idiopathic refractory pericarditis.


title: Immune responses and protective effects against Japanese encephalitis induced by a DNA vaccine encoding the prM/E proteins of the attenuated SA14-14-2 strain

text: Japanese encephalitis virus (JEV) is the causal pathogen of Japanese encephalitis (JE), which has become a severe public health problem and is one of the most rapidly spreading mosquito-borne diseases worldwide. Currently, there is no specific treatment for JEV. A vaccine would be an effective measure for reducing morbidity and mortality. Although the live attenuated vaccine SA14-14-2 has been approved in some countries, it is still necessary to develop safer, more effective, and less costly vaccines. In this study, a DNA vaccine candidate, pV-SA14ME, expressing the prM/E proteins of SA14-14-2 was inoculated into BALB/c mice via intramuscular electroporation, and the immunogenicity and degree of protection were evaluated. We found that administration of 50 μg pV-SA14ME via electroporation via three immunizations could induce persistent humoral and cellular immune responses and effectively protect mice against lethal JEV challenge. This study provides a basis for the subsequent promotion and use of the vaccine and lays the foundation for its further use in swine and humans.


docid: uvigylgi

title: EV‐D68 infection in children with asthma exacerbation and pneumonia in Mexico City during 2014 autumn

text: BACKGROUND: Human enterovirus D68 (EV‐D68) recently caused an increase in mild‐to‐severe pediatric respiratory cases in North America and some European countries. Even though few of these children presented with acute paralytic disease, direct causal relationship cannot yet be assumed. OBJECTIVES: The purposes of this report were to describe the clinical findings of an outbreak of EV‐D68 infection in Mexico City and identify the genetic relationship with previously reported strains. PATIENTS/METHODS: Between September and December 2014, 126 nasopharyngeal samples (NPS) of hospitalized children <15 years of age with ARI were tested for the presence of respiratory viruses using a multiplex RT‐qPCR and EV‐D68‐specific RT‐qPCR. Clinical, epidemiological, and demographic data were collected and associated with symptomatology and viral infections. Phylogenetic analyses were performed using VP1 region. RESULTS: Enterovirus/rhinovirus infection was detected in 40 patients (31·7%), of which 24 patients were EV‐D68‐positive. EV‐D68 infection prevailed over September and October 2014 and was associated with neutrophilia and lymphopenia, and patients were more likely to develop hypoxemia. Phylogenetic analyses showed that Mexican EV‐D68 belongs to the new B1 clade. CONCLUSIONS: This is the first EV‐D68 outbreak described in Mexico and occurred few weeks after the United States reported similar infections. Although EV‐D68 belongs to new B1 clade, no neurological affection was observed.


title: Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study

text: Abstract Background Different degrees of disorders are reported in respiratory function, physical function and psychological function in patients with corona virus disease 2019 (COVID-19), especially in elderly patients. With the experience of improved and discharged COVID-19 patients, timely respiratory rehabilitation intervention may improve prognosis, maximize functional preservation and improve quality of life (QoL), but there lacks of studies worldwide exploring the outcome of this intervention. Objective To investigate the effects of 6-week respiratory rehabilitation training on respiratory function, QoL, mobility and psychological function in elderly patients with COVID-19. Methods This paper reported the findings of an observational, prospective, quasi-experimental study, which totally recruited 72 participants, of which 36 patients underwent respiratory rehabilitation and the rest without any rehabilitation intervention. The following outcomes were measured: pulmonary function tests including plethysmography and diffusing lung capacity for carbon monoxide (DLCO), functional tests (6-min walk distance test), Quality of life (QoL) assessments (SF-36 scores), activities of daily living (Functional Independence Measure, FIM scores), and mental status tests (SAS anxiety and SDS depression scores). Results After 6 weeks of respiratory rehabilitation in the intervention group, there disclosed significant differences in FEV1(L), FVC(L), FEV1/FVC%, DLCO% and 6-min walk test. The SF-36 scores, in 8 dimensions, were statistically significant within the intervention group and between the two groups. SAS and SDS scores in the intervention group decreased after the intervention, but only anxiety had significant statistical significance within and between the two groups. Conclusions Six-week respiratory rehabilitation can improve respiratory function, QoL and anxiety of elderly patients with COVID-19, but it has little significant improvement on depression in the elderly.


title: The psychosocial implications of COVID-19 for a neurology program in a pandemic epicenter

text: OBJECTIVE: We discuss the psychosocial implications of the COVID-19 pandemic as self-reported by housestaff and faculty in the NYU Langone Health Department of Neurology, and summarize how our program is responding to these ongoing challenges. METHODS: During the period of May 1–4, 2020, we administered an anonymous electronic survey to all neurology faculty and housestaff to assess the potential psychosocial impacts of COVID-19. The survey also addressed how our institution and department are responding to these challenges. This report outlines the psychosocial concerns of neurology faculty and housestaff and the multifaceted support services that our department and institution are offering in response. Faculty and housestaff cohorts were compared with regard to frequencies of binary responses (yes/ no) using the Fisher's exact test. RESULTS: Among 130 total survey respondents (91/191 faculty [48%] and 37/62 housestaff [60%]), substantial proportions of both groups self-reported having increased fear (79%), anxiety (83%) and depression (38%) during the COVID-19 pandemic. These proportions were not significantly different between the faculty and housestaff groups. Most respondents reported that the institution had provided adequate counseling and support services (91%) and that the department had rendered adequate emotional support (92%). Participants offered helpful suggestions regarding additional resources that would be helpful during the COVID-19 pandemic. CONCLUSION: COVID-19 has affected the lives and minds of faculty and housestaff in our neurology department at the epicenter of the pandemic. Efforts to support these providers during this evolving crisis are imperative for promoting the resilience necessary to care for our patients and colleagues.


title: An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus

text: A new SARS animal model was established by inoculating SARS coronavirus (SARS‐CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5–60 after virus inoculation. All eight animals showed a transient fever 2–3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS‐CoV‐specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS‐CoV RNA could be detected in pharyngeal swab samples using nested RT‐PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS‐CoV‐related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


title: Home testing is no quick fix

text: UK prime minister Boris Johnson says antibody tests for covid-19 are a game changer, but they may not do much in the short term, argues Michael Le Page