title: Development and Evaluation of Reverse Transcription Loop-Mediated Isothermal Amplification Assay for Rapid and Real-Time Detection of the Swine-Origin Influenza A H1N1 Virus

text: The recent emergence of the swine-origin influenza A H1N1 virus (S-OIV) poses a serious global health threat. Rapid detection and differentiation of S-OIV from seasonal influenza is crucial for patient management and control of the epidemics. A one-step, single-tube accelerated and quantitative S-OIV-specific H1 reverse transcription loop-mediated isothermal amplification (RTLAMP) assay for clinical diagnosis of S-OIV by targeting the H1 gene is reported in this article. A comparative evaluation of the H1-specific RTLAMP assay vis-à-vis the World Health Organization-approved real-time polymerase chain reaction (RTPCR), involving 239 acute-phase throat swab samples, demonstrated exceptionally higher sensitivity by picking up all of the 116 H1N1-positive cases and 36 additional positive cases among the negatives that were sequence-confirmed as S-OIV H1N1. None of the real-time RTPCR-positive samples were missed by the RTLAMP system. The comparative analysis revealed that S-OIV RTLAMP was up to tenfold more sensitive than the World Health Organization real-time RTPCR; it had a detection limit of 0.1 tissue culture infectious dosage of (50)/ml. One of the most attractive features of this isothermal gene amplification assay is that it seems to have an advantage in monitoring gene amplification by means of SYBR Green I dye-mediated naked-eye visualization within 30 minutes compared to 2 to 3 hours for a real-time reverse transcription polymerase chain reaction. This suggests that the RTLAMP assay is a valuable tool for rapid, real-time detection and quantification of S-OIV in acute-phase throat swab samples without requiring sophisticated equipment.


title: Attenuation of RNA viruses by redirecting their evolution in sequence space

text: RNA viruses pose serious threats to human health. Their success relies on their capacity to generate genetic variability and, consequently, on their adaptive potential. We describe a strategy to attenuate RNA viruses by altering their evolutionary potential. We rationally altered the genomes of Coxsackie B3 and influenza A viruses to redirect their evolutionary trajectories towards detrimental regions in sequence space. Specifically, viral genomes were engineered to harbour more serine and leucine codons with nonsense mutation targets: codons that could generate Stop mutations after a single nucleotide substitution. Indeed, these viruses generated more Stop mutations both in vitro and in vivo, accompanied by significant losses in viral fitness. In vivo, the viruses were attenuated, generated high levels of neutralizing antibodies and protected against lethal challenge. Our study demonstrates that cornering viruses in ‘risky’ areas of sequence space may be implemented as a broad-spectrum vaccine strategy against RNA viruses. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nmicrobiol.2017.88) contains supplementary material, which is available to authorized users.


title: Lack of serological evidence of Middle East respiratory syndrome coronavirus infection in virus exposed camel abattoir workers in Nigeria, 2016

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic threat of global public health concern and dromedary camels are the source of zoonotic infection. Although MERS-CoV is enzootic in dromedaries in Africa as well as the Middle East, zoonotic disease has not been reported in Africa. Methods: In an abattoir in Kano, Nigeria, we tested nasal swabs from camels and investigated 261 humans with repeated occupational exposure to camels, many of whom also reported drinking fresh camel milk (n = 138) or urine (n = 94) or using camel urine for medicinal purposes (n = 96). Results: Weekly MERS-CoV RNA detection in January–February 2016 ranged from 0–8.4% of camels sampled. None of the abattoir workers with exposure to camels had evidence of neutralising antibody to MERS-CoV. Conclusion: There is a need for more studies to investigate whether or not zoonotic transmission of MERS-CoV does take place in Africa.


title: COVID 19: a clue from innate immunity

text: The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death. Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important. Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.


title: Defense genes missing from the flight division

text: Abstract Birds have a smaller repertoire of immune genes than mammals. In our efforts to study antiviral responses to influenza in avian hosts, we have noted key genes that appear to be missing. As a result, we speculate that birds have impaired detection of viruses and intracellular pathogens. Birds are missing TLR8, a detector for single-stranded RNA. Chickens also lack RIG-I, the intracellular detector for single-stranded viral RNA. Riplet, an activator for RIG-I, is also missing in chickens. IRF3, the nuclear activator of interferon-beta in the RIG-I pathway is missing in birds. Downstream of interferon (IFN) signaling, some of the antiviral effectors are missing, including ISG15, and ISG54 and ISG56 (IFITs). Birds have only three antibody isotypes and IgD is missing. Ducks, but not chickens, make an unusual truncated IgY antibody that is missing the Fc fragment. Chickens have an expanded family of LILR leukocyte receptor genes, called CHIR genes, with hundreds of members, including several that encode IgY Fc receptors. Intriguingly, LILR homologues appear to be missing in ducks, including these IgY Fc receptors. The truncated IgY in ducks, and the duplicated IgY receptor genes in chickens may both have resulted from selective pressure by a pathogen on IgY FcR interactions. Birds have a minimal MHC, and the TAP transport and presentation of peptides on MHC class I is constrained, limiting function. Perhaps removing some constraint, ducks appear to lack tapasin, a chaperone involved in loading peptides on MHC class I. Finally, the absence of lymphotoxin-alpha and beta may account for the observed lack of lymph nodes in birds. As illustrated by these examples, the picture that emerges is some impairment of immune response to viruses in birds, either a cause or consequence of the host-pathogen arms race and long evolutionary relationship of birds and RNA viruses.


Shifting dermatology market strategies from cosmetics to moisturizers and sanitizers treatments in COVID‐19 era


Caring for children with neurological disorders in China during the COVID‐19 pandemic


title: Sizes of Long RNA Molecules Are Determined by the Branching Patterns of Their Secondary Structures

text: Long RNA molecules are at the core of gene regulation across all kingdoms of life, while also serving as genomes in RNA viruses. Few studies have addressed the basic physical properties of long single-stranded RNAs. Long RNAs with nonrepeating sequences usually adopt highly ramified secondary structures and are better described as branched polymers. To test whether a branched polymer model can estimate the overall sizes of large RNAs, we employed fluorescence correlation spectroscopy to examine the hydrodynamic radii of a broad spectrum of biologically important RNAs, ranging from viral genomes to long noncoding regulatory RNAs. The relative sizes of long RNAs measured at low ionic strength correspond well to those predicted by two theoretical approaches that treat the effective branching associated with secondary structure formation—one employing the Kramers theorem for calculating radii of gyration, and the other featuring the metric of maximum ladder distance. Upon addition of multivalent cations, most RNAs are found to be compacted as compared with their original, low ionic-strength sizes. These results suggest that sizes of long RNA molecules are determined by the branching pattern of their secondary structures. We also experimentally validate the proposed computational approaches for estimating hydrodynamic radii of single-stranded RNAs, which use generic RNA structure prediction tools and thus can be universally applied to a wide range of long RNAs.


title: A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses

text: Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories.


docid: jzrlywfe

title: A NS1-binding monoclonal antibody interacts with two residues that are highly conserved in seasonal as well as newly emerged influenza A virus

text: The non-structural protein 1 (NS1) of influenza A virus (IAV) is a multifunctional protein that antagonizes host antiviral responses, modulating virus pathogenesis. As such, it serves as a good target for research and diagnostic assay development. In this study, we have generated a novel monoclonal antibody (mAb) 19H9 and epitope mapping revealed that two residues, P85 and Y89, of NS1 are essential for interacting with this mAb. Furthermore, residues P85 and Y89 are found to be highly conserved across different IAV subtypes, namely seasonal H1N1 and H3N2, as well as the highly pathogenic H5N1 and H5N6 avian strains. Indeed, mAb 19H9 exhibits broad cross-reactivity with IAV strains of different subtypes. The binding of mAb 19H9 to residue Y89 was further confirmed by the abrogation of interaction between NS1 and p85β. Additionally, mAb 19H9 also detected NS1 proteins expressed in IAV-infected cells, showing NS1 intracellular localization in the cytoplasm and nucleolus. To our knowledge, mAb 19H9 is the first murine mAb to bind at the juxtaposition between the N-terminal RNA-binding domain and C-terminal effector domain of NS1. It could serve as a useful research tool for studying the conformational plasticity and dynamic changes in NS1.


title: The Boston Medical Center COVID-19 Procedure Team: Optimizing the Surgeon’s Role in Pandemic Care at a Safety Net Hospital

text: BACKGROUND: The COVID-19 pandemic has claimed many lives and strained the US health care system. At Boston Medical Center (BMC), a regional safety net hospital, the Department of Surgery created a dedicated, COVID-19 Procedure Team to ease the burden on other providers coping with the surge of infected patients. As restrictions on social distancing are lifted, health systems are bracing for additional surges in COVID-19 cases. Our objective is to quantify the volume and types of procedures performed, review outcomes, and highlight lessons for other institutions that may need to establish similar teams. STUDY DESIGN: Procedures were tracked prospectively along with patient demographics, immediate complications, and time from donning to doffing of the personal protective equipment (PPE). Retrospective chart review was conducted to obtain patient outcomes and delayed adverse events. We hypothesized that a dedicated, surgeon-led team would perform invasive bedside procedures expeditiously and with few complications. RESULTS: From March 30 to April 30, 2020, there were 1,196 COVID-19 admissions. The Procedure Team performed 272 procedures on 125 patients, including placement of 135 arterial catheters, 107 central venous catheters, 25 hemodialysis catheters, and 4 thoracostomy tubes. Specific to central venous access, the average procedural time was 47 minutes, and the rate of immediate complications was 1.5%, including 1 arterial cannulation and 1 pneumothorax. CONCLUSIONS: Procedural complication rate was less than rates reported in the literature. The team saved approximately 192 hours of work that could be re-directed to other patient care needs. In times of crisis, redeployment of surgeons (who arguably have the most procedural experience) into procedural teams is a practical approach to optimize outcomes and preserve resources.


title: Comparative Viral Sampling in the Sinonasal Passages; Different Viruses at Different Sites

text: Background: With the emergence of the microbiome as an important factor in health and disease in the respiratory tract standardised, validated techniques are required for its accurate characterisation. No standardised technique has been reported specifically for viral sampling in the sinonasal passages. Aim: To optimise viral sampling techniques from the sinonasal cavity. Methods: Sterile cytology brushes were used under endoscopic guidance to sample the sinonasal mucosa at time of endoscopic sinus surgery at both the middle and inferior meatuses (MM and IM). DNA and RNA were extracted from the samples and underwent PCR or RT-PCR testing, respectively, for a panel of 15 common upper respiratory tract viruses. Results: Twenty-four adult patients were recruited for this study. 18/24 (75%) patients were positive for virus in at least one site, while 8/24 (33%) were positive for virus at both sites. The mean number of viruses identified at the two sites were similar (0.875 ± 0.899 at the MM vs. 0.750 ± 1.032 at the IM). 6/24 (25%) of patients showed no virus at either site, while 3/24 (12.5%) demonstrated the same viral species at both sites. Conclusion: Although the number of viruses present at different sites with the nasal cavity are similar, discord exists in the viral species between sites. It is therefore recommended that both sites are sampled in the clinical and research setting better to characterise the viral species within the nasal cavity.


title: Inferior vena cava filter in a patient with COVID-19 pneumonia to prevent a massive pulmonary embolism.

text: COVID 19 predispose to deep vein thrombosis . We describe an early placement of inferior vena cava filter added to the therapeutic anticoagulation to prevent a massive pulmonary embolism.


title: Péritonite infectieuse féline

text: Résumé La péritonite infectieuse féline (PIF) est une maladie mortelle des félidés due à un coronavirus, qui touche surtout les jeunes animaux entre 6 mois et 2 ans. Cette maladie se traduit cliniquement par des symptômes divers dont le plus caractéristique est l'accumulation de liquide d'épanchement dans la cavité abdominale ou pleurale. Il existe en fait deux biotypes de coronavirus félins, l'un pathogène responsable de la PIF (FIPV) et l'autre non pathogène (FeCV), plus répandu dans la population féline. La forte homologie génétique entre les souches FeCV et FIPV suggère que les virus responsables de la PIF dérivent d'une mutation génétique des coronavirus non pathogènes FeCV. Cette parenté entre les deux biotypes pose un problème dans l'interprétation du diagnostic viral, car aucun test à l'heure actuelle ne permet de les distinguer. Cet article s'intéresse tout particulièrement aux aspects cliniques, diagnostiques, épidémiologiques et prophylactiques de la PIF. Abstract Feline infectious peritonitis is a fatal disease of felidae due to a feline coronavirus, occurring mainly in kittens between 6 months and 2 years. This disease manifests clinically in varied symptoms, the most characteristic being the accumulation of fluid in the abdominal or pleural cavity. In fact, there are two feline coronavirus biotypes, which include respectively the virulent strains that cause feline infectious peritonitis (FIPV) and the avirulent strains (FeCV) more common in feline population. The high genetic similarity between FeCV and FIPV strains suggests that FIPVs arise by mutation from avirulent coronavirus FeCVs. This link between the two biotypes makes viral laboratory diagnosis interpretation complex, as currently no diagnostic tool allows distinguishing them. This article presents recent information regarding aetiology, pathogenicity, clinical aspects, epidemiology, diagnosis and prophylaxis of this disease.


title: Clinical appearance and pathology of cattle persistently infected with bovine viral diarrhoea virus of different genetic subgroups

text: Abstract Bovine viral diarrhoea (BVD) is an economically important cattle disease with a world-wide distribution that is caused by BVD virus, a pestivirus of the flaviviridae family. BVD viruses are genetically highly variable. They are classified into two genetic species (BVDV-1 and -2) that are further divided into numerous subgroups, particularly for BVDV-1. The complexity of these viruses is also reflected in their interaction with the host animals. Infections are either transient or persistent and can cause a wide spectrum of clinical signs, from no or very mild disease to severe forms, reminiscent of viral haemorrhagic fevers. In this work, we have analysed the clinical signs and the pathology of BVD viral infections in a cattle population where different subgroups of BVDV-1 genotype viruses are endemic. In addition, we have examined potential virulence properties of BVDV-1 subgroups during persistent infection by comparing the viral subgroups present in clinical cases with those detected in persistently infected (PI) animals sampled for epidemiological criteria, irrespective of their health condition. Furthermore, the clinical and postmortem findings were compared with respect to genetic characteristics of the viruses isolated from these animals. Our results indicate that the BVDV positive animals fall roughly into two categories, depending on the primary organ affected and the age, with lung-centred pathology occurring mainly in young animals and mucosal pathology predominantly in older animals. Furthermore, we found a markedly higher proportion of representatives of the BVDV-1e subgroup in stillborn calves and aborted foetuses originating from epidemically unrelated cattle herds, suggesting that BVDV-1e may play a special role in prenatal and perinatal losses.


title: Antibody therapies for the treatment of COVID-19

text: An outbreak of COVID-19, the disease caused by infection of the coronavirus SARS-CoV-2, that began in December 2019 in Wuhan, China has caused more than 2,990,559 confirmed human infections and 207,446 deaths as of April 27, 2020 (Coronavirus COVID-19 Global Cases by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University). Scientists are working quickly on multiple aspects of the pandemic. Genetic analyses are conducted to reveal the source and evolution of SARS-CoV-2, providing knowledge that can be used to contain it and to avoid future outbreaks. Epidemiological studies which incorporates lessons learned from outbreaks of previous related viral diseases can guide development of public health measures effective to contain the current and future outbreaks. Basic virology studies reveal viral structure and function. Pathology studies inform development of strategies to interfere with infection. COVID-19 prevention and treatment strategies are being developed in preclinical and clinical studies. Antibody-based therapy is one viable treatment option. Here, we discuss some of the most active areas of developing strategies to treat COVID-19, focusing on approaches to generate neutralizing antibodies against SARS-CoV-2 for prophylactic and therapeutic treatment of COVID-19. SIGNIFICANCE: Development of SARS-CoV-2 neutralizing antibodies with the desired efficacy and safety profile is a critical part of the toolbox of therapies for the treatment of COVID-19. We discuss in this review the current state of discovery and development of such antibodies.


COVID‐19 in a UK neurology hospital


title: Simultaneous and automated detection of influenza A virus hemagglutinin H7 and H9 based on magnetism and size mediated microfluidic chip

text: Abstract Influenza viruses with multiple subtypes have highly virulent in humans, of which influenza hemagglutinin (HA) is the major viral surface antigen. Simultaneous and automated detection of multiple influenza HA are of great importance for early-stage diagnosis and operator protection. Herein, a magnetism and size mediated microfluidic platform was developed for point-of-care detection of multiple influenza HA. With multiplex microvalves and computer program control, the detection process showed high automation which had a great potential for avoiding the high-risk virus exposure to the operator. Taking advantage of magnetism and size mediated multiple physical fields, multiple influenza HA could be simultaneous separation and detection depended on different-size magnetic beads. Using high-luminance quantum dots as reporter, this assay achieved high sensitivity with a detection limit of 3.4 ng/mL for H7N9 HA and 4.5 ng/mL for H9N2 HA, and showed excellent specificity, anti-interference ability and good reproducibility. These results indicate that this method may propose new avenues for early detection of multiple influenza subtypes.


title: The macroeconomic impact of oil earnings uncertainty: New evidence from analyst forecasts

text: We develop measures of oil earnings uncertainty (OEU) using analyst forecasts drawn from a large firm-level dataset. OEU is related to future economic downturns, so some OEU measures may serve to forecast future downturns. An increase in OEU also has adverse effects on the US oil sector. The results are robust to conditioning on aggregate uncertainty. At the same time, OEU is related to increases in stock prices – unlike aggregate uncertainty, which has the opposite effect. OEU is thus an independent influence on both the oil industry and on economic aggregates.


title: Diarrhea

text: Diarrheal diseases continue to contribute significant morbidity and mortality to pediatric populations in developed and developing countries around the world. The prevalence of diarrheal illness across cultures is inversely proportional to the availability of public sanitation, clean water supply, and adequate medical care. As such, it is not surprising that the incidence of diarrheal disease is much higher in developing societies and can approach 10 episodes per child per year in children under 5 years of age. In these areas, aggregate mortality can reach 3–5 million deaths per year. In the US and other developed nations, both the incidence (1–2 episodes per year) and mortality (approximately 400–500 deaths annually) are considerably decreased. Nonetheless, the burdens placed on Western healthcare systems by pediatric diarrheal disease are considerable and approximately 20% of all pediatric ambulatory visits and 10% of all inpatient hospital admissions in children under 3 years of age are for the evaluation and treatment of these disorders and their complications.


title: Experts Consensus on Epidemic Prevention and Control in Radiotherapy Centers during the COVID-19 Outbreak: Experiences from Sichuan Province

text: After the outbreak of COVID-19, medical institutions in China and even around the world are facing unprecedented challenges. In order to minimize the adverse impact of this unexpected epidemic on patients who need radiotherapy, the expert group of our radiotherapy center immediately formulated comprehensive emergency plans and prevention and control measures, partitioned the work area, launched online staff training, and optimized the radiotherapy process after the outbreak, which provided a strong guarantee for the safe and orderly operation of our radiotherapy center and kept the infection rate to an extremely low level. We hope our experience could provide reference and suggestions for other medical institutions.


Response to Letter to the Editor: COVID-19: Current Knowledge and Best Practices for Orthopaedic Surgeons


title: The experience of treating patients with acute myocardial infarction under the COVID‐19 epidemic

text: Worldwide Coronavirus Disease 2019 (COVID‐19) epidemic makes the management of acute myocardial infarction (AMI) more complicated, effective treatment without further dissemination is thus quite challenging. Recently, we successfully treated three representative AMI cases, by sharing these detailed procedures, we summarized some important issues including patient screening, reperfusion strategy selecting, personnel/catheter lab protection principle, as well as operation tactics, which may lend precious experience on AMI treating during the ongoing COVID‐19 pandemic situation.


title: Travelers’ Actual and Subjective Knowledge about Risk for Ebola Virus Disease

text: To determine travelers’ actual and subjective knowledge about risk for Ebola virus disease, we surveyed travelers from France. Actual knowledge did not prevent irrational perceptions or promote safe behavior. Rather, readiness to adopt protective behavior depended on subjective knowledge and overconfidence in ability to self-protect.


title: Prevalence of feline herpesvirus 1, feline calicivirus and Chlamydophila felis in clinically normal cats at a Korean animal shelter

text: The prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), and Chlamydophila (C.) felis was studied in cats of an animal shelter in Korea. Total 78 cats without ocular and upper respiratory tract disease were examined. Specimens were obtained from ocular conjunctiva and oropharynx. Using multiplex polymerase chain reaction (PCR) and reverse transcription PCR, three pathogens were simultaneously detected. In examined 78 cats, 49 (63%) cats were positive for FHV-1. However, all specimens were negative for C. felis and FCV. In conclusion, many cats recovered from FHV-1 infection remain subclinical carriers in shelter environment.


title: Comparative sequence analyses of a new mammalian reovirus genome and the mammalian reovirus S1 genes from six new serotype 2 human isolates

text: We previously described isolation of a potentially new mammalian reovirus, designated BYD1, which can cause clinical symptoms similar to that of severe acute respiratory syndrome (SARS) in guinea pigs and macaques, from throat swabs of one SARS patient of Beijing, in 2003. For this study, we determined the genome sequences of BYD1 and the S1 gene sequences of other five mammalian reovirus isolates (BLD, JP, and BYL were isolated from different SARS patients during the outbreak, 302I and 302II were isolated from fecal specimens of two children of Beijing in 1982) to allow molecular comparison with other previously reported mammalian reoviruses (MRVs). Comparative analyses of the BYD1 genome with those of three prototype mammalian reovirus strains demonstrated that BYD1 is a novel reassortant virus, with its S1 gene segment coming from a previously unidentified serotype 2 isolate and other nine segments coming from ancestors of homologous T1L and T3D segments, which supports the hypothesis that mammalian reovirus gene segments reassort in nature. Further analyses of the S1 segments of the six isolates showed that all the isolates are novel serotype 2 MRVs based on their S1 gene sequences, which are markedly different from those of all previously reported, and the S1 genes of the four new isolates share more than 99% identity with each other, proving that they diverged from a common ancestor most recently, and the S1 genes of the four new isolates share about 65% identity with those of the two strains isolated in 1982.


title: Babesia vesperuginis, a neglected piroplasmid: new host and geographical records, and phylogenetic relations

text: BACKGROUND: Babesia spp. are hemoparasites which infect the red blood cells of a large variety of mammals. In bats, the only known species of the genus is Babesia vesperuginis. However, except a few old reports, the host range and geographical distribution of this bat parasite have been poorly studied. This study aimed to investigate the presence of piroplasms in tissues of bats collected in four different countries from eastern and central Europe: Austria, Czech Republic, Hungary and Romania. METHODS: A total of 461 bat carcasses (24 species) were collected between 2001 and 2016 from caves, mines and buildings. PCR was performed using specific primers targeting a portion of the 18S rDNA nuclear gene and cytochrome c oxidase subunit 1 mitochondrial gene, followed by sequencing. RESULTS: The results of this study show for the first time the presence of B. vesperuginis in bats in central and eastern Europe. The phylogenetic analysis of the 18S rDNA nuclear gene revealed no variability between the sequences and the phylogenetic analysis of the cox1 mitochondrial gene proved that B. vesperuginis could be divided into two subclades. CONCLUSION: Our study showed a broad geographical distribution of B. vesperuginis in European bats, reporting its presence in five new host species (M. cf. alcathoe, M. bechsteinii, M. myotis, Pi. nathusii and V. murinus) and three new countries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-017-2536-3) contains supplementary material, which is available to authorized users.


Severe fever with thrombocytopenia syndrome virus expands its borders


title: Foaming properties, wettability alteration and interfacial tension reduction by saponin extracted from soapnut (Sapindus Mukorossi) at room and reservoir conditions

text: In this study, a natural surfactant, saponin was isolated from soapnut (Sapindus Mukorossi). The extracted surfactant was characterized by Fourier-transform infrared spectroscopy (FTIR) analysis. The effectiveness of the isolated surfactant as EOR agent was evaluated from foam generation/stabilization properties, wettability alteration of the rock surfaces, as well as oil-water interfacial tension (IFT) reduction characteristics. The performance of the extracted saponin was compared with that of a commercial saponin and sodium dodecyl sulfate (SDS). The foaming properties of the saponin with carbon dioxide (CO(2)) was characterized using Teclis Foamscan instrument at room condition and 60 °C. The IFT and contact angles at room conditions and reservoir conditions were measured using KRŰSS Drop Shape Analyzer (DSA 25 and DSA 100) via pendant drop and sessile drop techniques respectively. The foamability of the saponin-stabilized foam was good at ambient condition and 60 °C. Moreover, the time taken for almost 100% liquid drainage was higher in saponin-stabilized foam than the SDS-stabilized foam. The optimum concentration for attaining maximum foam stability decreased from 0.4 wt% at room temperature to 0.1 wt% at 60 °C. Signifying that the quantity of the surfactant to be used in foam generation could reduce at high temperature. The isolated saponin exhibited relatively good interfacial activities individually and in synergistic interaction with silicon dioxide (SiO(2)) nanoparticles at reservoir conditions. Precisely, at 8 MPa and 80 °C, the crude-oil water IFT was reduced from 23.24 mN/m to 1.59 mN/m (about 93.2%) by 0.2 wt% saponin concentration. The IFT was further reduced to 0.87 mN/m (about 96.3%) by a mixed system of 0.5 wt% saponin and 0.05 wt% SiO(2) nanoparticles concentration. Increasing IFT with increasing temperature were observed at very high temperature due to phase separation resulting from clouding phenomenon. However, the clouding temperature increased with 0.1 wt% saponin concentration, and in presence of SiO(2) nanoparticles (0.05 wt% and 0.1 wt%). The study suggests that the extracted saponin could be considered as supplementary alternative to conventional EOR surfactants.


First do no harm—beware the risk of therapeutic plasma exchange in severe COVID-19


Pandemic influenza (H1N1) 2009 and infection control controversies: Working with ongoing change


title: Selective evolution of Toll-like receptors 3, 7, 8, and 9 in bats

text: Previous studies have shown that bats are reservoirs of a large number of viruses, many of which cause illness and mortality in humans and other animals. However, these bat-associated pathogens cause little, if any, clinicopathology in bats. This long-term adaptation should be reflected somewhat in the immune system. Toll-like receptors (TLRs) are the first line of immune defense against pathogens in vertebrates. Therefore, this study focuses on the selection of TLRs involved in virus recognition. The coding sequences of TLR3, TLR7, TLR8, and TLR9 were sequenced in ten bats. The selection pressure acting on each gene was also detected using branch- and site-specific methods. The results showed that the ancestor of bats and certain other bat sublineages evolved under positive selection for TLR7, TLR8, and TLR9. The highest proportion of positive selection occurred in TLR9, followed by TLR8 and TLR7. All of the positively selected sites were located in the leucine-rich repeat (LRR) domain, which implied their important roles in pathogen recognition. However, TLR3 evolved under negative selection. Our results are not in line with previous studies which identified more positively selected sites in TLR8 in mammalian species. In this study, the most positively selected sites were found in TLR9. This study encompassed more species that were considered natural reservoirs of viruses. The positive selection for TLR7, TLR8, and TLR9 might contribute to the adaptation of pathogen-host interaction in bats, especially in bat TLR9. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00251-016-0966-2) contains supplementary material, which is available to authorized users.


title: Two Conserved Residues Are Important for Inducing Highly Ordered Membrane Domains by the Transmembrane Domain of Influenza Hemagglutinin

text: The interaction with lipids of a synthetic peptide corresponding to the transmembrane domain of influenza hemagglutinin was investigated by means of electron spin resonance. A detailed analysis of the electron spin resonance spectra from spin-labeled phospholipids revealed that the major effect of the peptide on the dynamic membrane structure is to induce highly ordered membrane domains that are associated with electrostatic interactions between the peptide and negatively charged lipids. Two highly conserved residues in the peptide were identified as being important for the membrane ordering effect. Aggregation of large unilamellar vesicles induced by the peptide was also found to be correlated with the membrane ordering effect of the peptide, indicating that an increase in membrane ordering, i.e., membrane dehydration, is important for vesicle aggregation. The possibility that hydrophobic interaction between the highly ordered membrane domains plays a role in vesicle aggregation and viral fusion is discussed.


Doxycycline: From Ocular Rosacea to COVID-19 Anosmia. New Insight Into the Coronavirus Outbreak


docid: bcqxhvpa

title: Infecciones por virus de la gripe y virus respiratorios

text: Resumen Las infecciones respiratorias, en general, son infecciones benignas autolimitadas, pero en ocasiones pueden producir cuadros graves y ser una causa importante de mortalidad y morbilidad, especialmente en los grupos de población más vulnerables. La gripe aparece anualmente de forma epidémica, pudiendo ocasionar pandemias cada varios años, como las producidas por los tipos H1N1 o H3N2. La clínica fundamental es la sintomatología respiratoria asociada a fiebre, pudiendo presentar complicaciones como la neumonía. Para la confirmación diagnóstica se recomienda la obtención de exudado nasofaríngeo y la realización de RT-PCR, pudiéndose obtener resultados también para otros virus. El tratamiento en general es sintomático, reservándose para los casos más graves el tratamiento con inhibidores de la neuraminidasa. La mejor medida preventiva es la vacunación anual a la población de riesgo. Otros virus con especial relevancia son los coronavirus por sus posibles implicaciones pronósticas y en la edad infantil debe tenerse en cuenta el virus sincitial respiratorio y los parainfluenza. Abstract In general, respiratory infections are benign and self-limiting, but occasionally they can cause severe symptoms and become a major cause of mortality and morbidity, especially in the more vulnerable population groups. Flu epidemics occur annually, and there can be pandemics every few years, such as those caused by types H1N1 or H3N2. The main clinical manifestations are respiratory symptoms associated with fever, and complications such as pneumonia can arise. Nasopharyngeal swab and RT-PCR should be performed to confirm the diagnosis, which can yield results for other viruses as well. Treatment is generally symptomatic, reserving neuraminidase inhibitors for the more serious cases. The best preventive measure is annual vaccination of the population at risk. The coronavirus is also particularly relevant, due to its potential prognostic implications, and the respiratory syncytial virus and parainfluenza virus should be borne in mind in children.


docid: lurrrrbs

title: Surgical cancer care in the COVID-19 era: front line views and consensus

text: OBJECTIVE: to suggest a script for surgical oncology assistance in COVID-19 pandemic in Brazil METHOD: a narrative review and a "brainstorming" consensus were carried out after discussion with more than 350 Brazilian specialists and renowned surgeons from Portugal, France, Italy and United States of America RESULTS: consensus on testing for COVID-19: 1- All patients to be operated should be tested between 24 and 48 before the procedure;2- The team that has contact with sick or symptomatic patients should be tested;3 - Chest tomography was suggested to investigate pulmonary changes Consensus on protection of care teams: 1 - Use of surgical masks inside the hospitals Use of N95 masks for all professionals in the operating room;2 - Selection of cases for minimally invasive surgery and maximum pneumoperitoneal aspiration before removal of the surgical specimen;2 - Optimization of the number of people in teams, with a minimum number of professionals, reducing their occupational exposure, the consumption of protective equipment and the circulation of people in the hospital environment;3 - Isolation of contaminated patients Priority consensus: 1- Construction of service priorities;2 - Interdisciplinary discussion on minimally invasive or conventional pathways CONCLUSION: the Brazilian Society of Surgical Oncology (BSSO) suggests a script for coping with oncological treatment, remembering that the impoundment in the assistance of these cases, can configure a new wave of overload in health systems


title: Developing nucleic acid-based electrical detection systems

text: Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and requirements for an ideal detector suitable for nucleic acid analysis include high sensitivity and high specificity protocol that can be completed in a relatively short time offering at the same time low detection limit. Moreover, systems that can be miniaturized and automated present a significant advantage over conventional technology, especially if detection is needed in the field. Electrical system technology for nucleic acid-based detection is an enabling mode for making miniaturized to micro- and nanometer scale bio-monitoring devices via the fusion of modern micro- and nanofabrication technology and molecular biotechnology. The electrical biosensors that rely on the conversion of the Watson-Crick base-pair recognition event into a useful electrical signal are advancing rapidly, and recently are receiving much attention as a valuable tool for microbial pathogen detection. Pathogens may pose a serious threat to humans, animal and plants, thus their detection and analysis is a significant element of public health. Although different conventional methods for detection of pathogenic microorganisms and their toxins exist and are currently being applied, improvements of molecular-based detection methodologies have changed these traditional detection techniques and introduced a new era of rapid, miniaturized and automated electrical chip detection technologies into pathogen identification sector. In this review some developments and current directions in nucleic acid-based electrical detection are discussed.


title: Verification of Sensitivity and Specificity of Group A Rotavirus Detection in Piglets Faeces with Monoclonal Blocking ELISA Methods

text: Monoclonal antibodies to group A rotavirus Vp6 protein were prepared and used for verification of three blocking enzyme‐linked immunosorbent assay (ELISA) modifications to detect rotavirus A. Selected competitive blocking ELISA (CB‐ELISA) and electron microscopy (EM) were used for examination of 194 field faecal samples of piglets affected with diarrhoea. Rotavirus was detected in 43 samples (22.2%) by CB‐ELISA method, whereas in 26 (13.4%) samples by EM examination. However, of 26 samples positive by EM, rotavirus A was detected by CB‐ELISA in 19 (73.1%) samples; indicating the share of group A rotavirus in all cases of gastroenteritis caused by rotavirus. The sensitivity and specificity of the CB‐ELISA was verified both by inclusion of control samples containing transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhoea virus (PEDV) in each analysis and by comparative examination of samples with the commercial ELISA kit. The CB‐ELISA sensitivity was positively affected by examination of samples in the presence of chelating agent.


title: CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2 and are differentially expressed in lung and kidney epithelial and endothelial cells

text: The spike protein (S) of SARS-CoV-2 mediates entry into human cells by interacting with human angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). Here, we report identification of CD209L/L-SIGN and a related protein, CD209/DSIGN as alternative receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed a prominent expression of CD209L in the lung and kidney epithelial and endothelial cells of small and medium-sized vessels, whereas CD209 was detected only in a limited number of cell types. Biochemical assays revealed that ectopically expressed CD209L and CD209 bind to S-RBD and mediate SARS-CoV-2 S-pseudotyped virus entry. Furthermore, we demonstrate that human endothelial cells endogenously express CD209L and are permissive to SARS-CoV-2 infection. Soluble CD209L-Fc neutralized virus entry. Our observations show that CD209L and CD209 serve as alternative receptors for SARS-CoV-2 in disease-relevant cell types, including the vascular system. This may have implications for antiviral drug development.


title: Cord blood hemopoietic progenitor profiles predict acute respiratory symptoms in infancy

text: Atopy is characterized by eosinophilic inflammation associated with recruitment of eosinophil/basophil (Eo/B) progenitors. We have previously shown that Eo/B progenitor phenotypes are altered in cord blood (CB) in infants at high risk of atopy/asthma, and respond to maternal dietary intervention during pregnancy. As respiratory tract viral infections have been shown to induce wheeze in infancy, we investigated the relationship between CB progenitor function and phenotype and acute respiratory illness (ARI), specifically wheeze and fever. CB from 39 high‐risk infants was studied by flow cytometry for CD34(+) progenitor phenotype and by ex vivo Eo/B‐colony forming unit (CFU) responses to cytokine stimulation in relation to ARI in the first year of life. A consistent relationship was observed between increased numbers of granulocyte/macrophage (GM)‐colony‐stimulating factor (CSF)‐ and IL‐3‐responsive Eo/B‐CFU in CB and the frequency/characteristics of ARI during infancy. Comparable associations were found between ARI and CB IL‐3R(+) and GM‐CSFR(+)CD34(+) cell numbers. Conversely, a reciprocal decrease in the proportion of CB IL‐5R(+) cells was found in relation to the clinical outcomes. The elevation of IL‐3/GM‐CSF‐responsive Eo/B progenitors in high‐risk infants in relation to ARI outcomes suggests a mechanism for the increased severity of inflammatory responses in these subjects following viral infection.


title: Epigenetic Landscape during Coronavirus Infection

text: Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus–host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype. Epigenetic modifications, such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, function as important regulators that remodel host chromatin, altering host expression patterns and networks in a highly flexible manner. For most of the past two and a half decades, research has focused on the molecular mechanisms by which RNA viruses antagonize the signaling and sensing components that regulate induction of the host innate immune and antiviral defense programs upon infection. More recently, a growing body of evidence supports the hypothesis that viruses, even lytic RNA viruses that replicate in the cytoplasm, have developed intricate, highly evolved, and well-coordinated processes that are designed to regulate the host epigenome, and control host innate immune antiviral defense processes, thereby promoting robust virus replication and pathogenesis. In this article, we discuss the strategies that are used to evaluate the mechanisms by which viruses regulate the host epigenome, especially focusing on highly pathogenic respiratory RNA virus infections as a model. By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host’s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection.


title: Molecular signatures of epithelial oviduct cells of a laying hen (Gallus gallus domesticus) and quail (Coturnix japonica)

text: BACKGROUND: In this work we have determined molecular signatures of oviduct epithelial and progenitor cells. We have proposed a panel of selected marker genes, which correspond with the phenotype of oviduct cells of a laying hen (Gallus gallus domesticus) and quail (Coturnix japonica). We demonstrated differences in characteristics of those cells, in tissue and in vitro, with respect to different anatomical and functional parts of the oviduct (infundibulum (INF), distal magnum (DM, and proximal magnum (PM)). The following gene expression signatures were studied: (1) oviduct markers (estrogen receptor 1, ovalbumin, and SPINK7 - ovomucoid), (2) epithelial markers (keratin 5, keratin 14, and occludin) and (3) stem-like/progenitor markers (CD44 glycoprotein, LGR5, Musashi-1, and sex determining region Y-box 9, Nanog homebox, OCT4/cPOUV gene encoding transcription factor POU5F3). RESULTS: In chicken, the expression of oviduct markers increased toward the proximal oviduct. Epithelial markers keratin14 and occludin were high in distal oviduct and decreased toward the proximal magnum. In quail oviduct tissue, the gene expression pattern of oviduct/epithelial markers was similar to chicken. The markers of progenitors/stemness in hen oviduct (Musashi-1 and CD44 glycoprotein) had the highest relative expression in the infundibulum and decreased toward the proximal magnum. In quail, we found significant expression of four progenitor markers (LGR5 gene, SRY sex determining region Y-box 9, OCT4/cPOUV gene, and CD44 glycoprotein) that were largely present in the distal oviduct. After in vitro culture of oviduct cells, the gene expression pattern has changed. High secretive potential of magnum-derived cells diminished by using decreased abundance of mRNA. On the other hand, chicken oviduct cells originating from the infundibulum gained ability to express OVM and OVAL. Epithelial character of the cells was maintained in vitro. Among progenitor markers, both hen and quail cells expressed high level of SOX9, LGR5 and Musashi-1. CONCLUSION: Analysis of tissue material revealed gradual increase/decrease pattern in majority of the oviduct markers in both species. This pattern changed after the oviductal cells have been cultured in vitro. The results can provide molecular tools to validate the phenotype of in vitro biological models from reproductive tissue. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12861-018-0168-2) contains supplementary material, which is available to authorized users.


docid: qdxuyzki

title: Ignorance is not bliss


title: Descriptors of 2D-dynamic graphs as a classification tool of DNA sequences

text: A new tool of the classification of DNA sequences is introduced. The method is based on 2D-dynamic graphs and their descriptors. Using the descriptors created by centers of masses, moments of inertia, angles between the x axis and the principal axis of inertia of the 2D-dynamic graphs one can obtain classification diagrams in which similar sequences are clustered in separated areas.


title: Anchors Aweigh: Protein Traffic Mediated by Transmembrane Domains

text: The transmembrane domains (TMDs) of integral membrane proteins have emerged as major determinants of intracellular localization and transport in the secretory and endocytic pathways. Unlike sorting signals in the cytosolic domains, TMD sorting determinants are not conserved amino-acid sequences but physical properties such as length and hydrophilicity of the transmembrane span. The underlying sorting machinery is still poorly characterized but several mechanisms have been proposed, including TMD recognition by transmembrane sorting receptors and partitioning into membrane lipid domains. Here we review the nature of TMD sorting determinants and how they may dictate transmembrane protein localization and transport.


title: Modelling fatality curves of COVID-19 and the effectiveness of intervention strategies

text: The main objective of the present article is twofold: first, to model the fatality curves of the COVID-19 disease, as represented by the cumulative number of deaths as a function of time; and second, to use the corresponding mathematical model to study the effectiveness of possible intervention strategies. We applied the Richards growth model (RGM) to the COVID-19 fatality curves from several countries, where we used the data from the Johns Hopkins University database up to May 8, 2020. Countries selected for analysis with the RGM were China, France, Germany, Iran, Italy, South Korea, and Spain. The RGM was shown to describe very well the fatality curves of China, which is in a late stage of the COVID-19 outbreak, as well as of the other above countries, which supposedly are in the middle or towards the end of the outbreak at the time of this writing. We also analysed the case of Brazil, which is in an initial sub-exponential growth regime, and so we used the generalised growth model which is more appropriate for such cases. An analytic formula for the efficiency of intervention strategies within the context of the RGM is derived. Our findings show that there is only a narrow window of opportunity, after the onset of the epidemic, during which effective countermeasures can be taken. We applied our intervention model to the COVID-19 fatality curve of Italy of the outbreak to illustrate the effect of several possible interventions.


docid: xnfdjriz

title: Protective effects of vaccinations and endemic infections on COVID-19: A Hypothesis


title: Assessment of Immunoreactive Synthetic Peptides from the Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus

text: Background: The widespread threat of severe acute respiratory syndrome (SARS) to human life has spawned challenges to develop fast and accurate analytical methods for its early diagnosis and to create a safe antiviral vaccine for preventive use. Consequently, we thoroughly investigated the immunoreactivities with patient sera of a series of synthesized peptides from SARS-coronavirus structural proteins. Methods: We synthesized 41 peptides ranging in size from 16 to 25 amino acid residues of relatively high hydrophilicity. The immunoreactivities of the peptides with SARS patient sera were determined by ELISA. Results: Four epitopic sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N proteins, respectively, were detected by screening synthesized peptides. Notably, N371 and N385, located at the COOH terminus of the N protein, inhibited binding of antibodies to SARS-coronavirus lysate and bound to antibodies in >94% of samples from SARS study patients. N385 had the highest affinity for forming peptide-antibody complexes with SARS serum. Conclusions: Five peptides from SARS structural proteins, especially two from the COOH terminus of the N protein, appear to be highly immunogenic and may be useful for serologic assays. The identification of these antigenic peptides contributes to the understanding of the immunogenicity and persistence of SARS coronavirus.


title: Human‐enteric‐coronaviruslike particles (CVLP) with different epidemiological characteristics

text: One hundred fifty‐six diarrheic and 115 control stools collected throughout a year from nonhospitalized children were examined by electron microscopy in Haut‐Ogooué, Gabon; 65.2% of the controls and 38.5% of the diarrheics were found to contain coronaviruslike particles (CVLP). In both diarrheic and control groups the CVLP prevalences showed a seasonal variation whereas significant variation of prevalence with age was observed only in the controls. Thus, the CVLP in controls were significantly more abundant in children over 2 years old (76% vs 48%, P < .01) and more frequently observed during the months of rainy seasons (75% vs 54%, P < .02). On the other hand, the higher prevalence of CVLP in diarrheics over 2 years old was not significant (48% vs 36%, P = .20), whereas a significantly lower prevalence of CVLP during the months of rainy seasons was observed in this group (27% vs 50%, P < .01). Studies of the climatological factors in this equatorial climate showed a parallel cyclical variation of parameters representing rainfall, temperature, as well as relative humidity. We were not able to distinguish which of these factors was influencing more directly the prevalence of CVLP.


title: Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice

text: Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response in such animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8(+) T cell response and, to a lesser extent, a CD4(+) T cell response. These findings suggest that T-cell responses may be more important than serum IgG in the observed protection induced by rAd5N.


title: Equine Viral Arteritis

text: Equine viral arteritis is an infrequently encountered contagious viral disease of equids that has assumed increased veterinary medical and economic significance since the 1984 epidemic in Thoroughbreds in Kentucky. The most important consequences of infection are abortion in the mare and establishment of the carrier state in the stallion. Aspects of the pathogenesis, immunity, and epidemiology of equine arteritis virus are discussed in relation to current methods for the diagnosis, treatment, and control of this disease.


title: New directions for protease inhibitors directed drug discovery

text: Proteases play crucial roles in various biological processes, and their activities are essential for all living organisms—from viruses to humans. Since their functions are closely associated with many pathogenic mechanisms, their inhibitors or activators are important molecular targets for developing treatments for various diseases. Here, we describe drugs/drug candidates that target proteases, such as malarial plasmepsins, β‐secretase, virus proteases, and dipeptidyl peptidase‐4. Previously, we reported inhibitors of aspartic proteases, such as renin, human immunodeficiency virus type 1 protease, human T‐lymphotropic virus type I protease, plasmepsins, and β‐secretase, as drug candidates for hypertension, adult T‐cell leukaemia, human T‐lymphotropic virus type I‐associated myelopathy, malaria, and Alzheimer's disease. Our inhibitors are also described in this review article as examples of drugs that target proteases. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 563–579, 2016.


title: Expression of ACE2, the SARS-CoV-2 receptor, and TMPRSS2 in prostate epithelial cells

text: The COVID-19 pandemic has spread across more than 200 countries and resulted in over 170,000 deaths. For unclear reasons, higher mortality rates from COVID-19 have been reported in men compared to women. While the SARS-CoV-2 receptor ACE2 and serine protease TMPRSS2 have been detected in lung and other tissues, it is not clear what sex differences may exist. We analyzed a publicly-available normal human prostate single-cell RNA sequencing dataset and found TMPRSS2 and ACE2 co-expressing cells in epithelial cells, with a higher proportion in club and hillock cells. Then we investigated datasets of lung epithelial cells and also found club cells co-expressing TMPRSS2 and ACE2. A comparison of ACE2 expression in lung tissue between males and females showed higher expression in males and a larger proportion of ACE2+ cells in male type II pneumocytes, with preliminary evidence that type II pneumocytes of all lung epithelial cell types showed the highest expression of ACE2. These results raise the possibility that sex differences in ACE2 expression and the presence of double-positive cells in the prostate may contribute to the observed disparities of COVID-19.


"COVID-19, health rights of prison staff and the bridge between prison and public health in Africa "


title: Molecular Evidence of Influenza A Virus Circulation in African Dromedary Camels Imported to Saudi Arabia, 2017–2018

text: Little is known about influenza A viruses in dromedaries. Here, we detected influenza A viral RNA in 11 specimens (1.7 %) out of 665 nasal swabs collected from dromedaries between 2017 and 2018 in Saudi Arabia. Positive samples were detected only in imported camels from Sudan and Djibouti but not local ones. Partial genome sequencing indicates a close relationship to 2009–2019 human/swine influenza A H1N1 isolates from different countries, suggesting possible interspecies transmission. Taken together, dromedaries could represent a potentially unrecognized permissive host for these viruses, highlighting the need for enhanced surveillance in animals to aid implementation of one-health strategies.


title: Assessment of 10-nm Particle Number (PN) Portable Emissions Measurement Systems (PEMS) for Future Regulations

text: The particle number (PN) emissions of vehicles equipped with particulate filters are low. However, there are technologies that can have high PN levels, especially below the currently lower regulated particle size of 23 nm. Sub-23-nm particles are also considered at least as dangerous as the larger ultrafine particles. For this reason, the European Union (EU) is planning to regulate particles down to 10 nm. In this study we compared prototype portable emission measurement systems (PEMS) and reference laboratory systems measuring from 10 nm. The tests included cycles and constant speeds, using vehicles fuelled with diesel, gasoline or liquefied petroleum gas (LPG). The results showed that the PEMS were within ±40% of the reference systems connected to the tailpipe and the dilution tunnel. Based on the positive findings and the detection efficiencies of the prototype instruments, a proposal for the technical specifications for the future regulation was drafted.


title: The 2017 Oslo conference report on neglected tropical diseases and emerging/re-emerging infectious diseases – focus on populations underserved

text: BACKGROUND: In 2017, the Centre for Global Health (CGH) at the University of Oslo in collaboration with the Coalition for Epidemic Preparedness Innovations (CEPI) and the Norwegian Agency for Development Cooperation (Norad) held a meeting to discuss together with leading figures in disease control, research and development the issue of neglected tropical diseases and emerging/re-emerging infectious diseases. This commentary has taken up this discussion and the conclusions drawn at this meeting to make a case for the opportunity the Sustainable Development Goals (SDGs) provide in highlighting the interconnectedness of factors that are relevant in the successful fight against neglected tropical diseases (NTDs) and emerging infectious diseases (EIDS). MAIN BODY: Despite NTDs being endemic and EIDS being epidemic, in order to prevent both disease groups effectively, it is important to appreciate that they share essential health determining factors, namely: neglect, poverty, a lack of access to clean water and sanitation facilities and an absence of or severely limited provision of healthcare as well as in many cases a zoonotic nature. Instead of looking to “simple disease management” for the answer, the SDGs help to understand the interplay of multiple priority areas and thereby help to promote a more holistic approach to addressing these two disease groups. CONCLUSIONS: Their commonalities mean that the Global Health community should leverage opportunities and efforts in the prevention and elimination of both NTDs and EIDs. Doing so using a One Health approach is considered to offer a “public health best-buy”. Concrete solutions are proposed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40249-019-0550-8) contains supplementary material, which is available to authorized users.


title: An Extensive Meta-Metagenomic Search Identifies SARS-CoV-2-Homologous Sequences in Pangolin Lung Viromes

text: In numerous instances, tracking the biological significance of a nucleic acid sequence can be augmented through the identification of environmental niches in which the sequence of interest is present. Many metagenomic data sets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic data set can be readily queried using web-based tools, meta-searches through all such data sets are less accessible. In this brief communication, we demonstrate such a meta-metagenomic approach, examining close matches to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in all high-throughput sequencing data sets in the NCBI Sequence Read Archive accessible with the “virome” keyword. In addition to the homology to bat coronaviruses observed in descriptions of the SARS-CoV-2 sequence (F. Wu, S. Zhao, B. Yu, Y. M. Chen, et al., Nature 579:265–269, 2020, https://doi.org/10.1038/s41586-020-2008-3; P. Zhou, X. L. Yang, X. G. Wang, B. Hu, et al., Nature 579:270–273, 2020, https://doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in metavirome data sets generated from the lungs of deceased pangolins reported by Liu et al. (P. Liu, W. Chen, and J. P. Chen, Viruses 11:979, 2019, https://doi.org/10.3390/v11110979). While analysis of these reads indicates the presence of a similar viral sequence in pangolin lung, the similarity is not sufficient to either confirm or rule out a role for pangolins as an intermediate host in the recent emergence of SARS-CoV-2. In addition to the implications for SARS-CoV-2 emergence, this study illustrates the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences. IMPORTANCE Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.


title: Development and validation of a monoclonal antibody-based competitive ELISA for detection of antibodies against porcine epidemic diarrhoea virus (PEDV)

text: Abstract Porcine epidemic diarrhoea virus (PEDV), belongs to the genus Alphacoronavirus in the family Coronaviridae and causes severe diarrhoea, vomiting, dehydration and high mortality in seronegative newborn piglets. Thus, a precise and rapid diagnosis of PEDV infection is important for the application of control measures to limit viral dissemination. In this investigation, a monoclonal antibodies (MAbs)-based competitive enzyme-linked immunosorbent assay (ELISA) for detecting antibodies against PEDV was developed and validated. The diagnostic performance of the test was evaluated by receiver operating characteristic (ROC) analysis using a panel of 829 known sera collected from different commercial pig farms, with or without a history of PED presence and from experimentally infected pigs. The competitive ELISA showed excellent diagnostic performance and discriminatory power with high sensitivity (Se) and specificity (Sp) values (Se = 96.5%, 95% IC 94.1–98.1; Sp = 98.2%, 95% IC 96.3–99.3). Moreover, this competitive ELISA method has other properties, such as high feasibility of testing sera without pre-treatment and automatic and instrument-mediated revealing, that makes it appropriate for large-scale screenings of affected pig farms in endemic regions or for monitoring plans in PEDV-free areas.


docid: ykmmtmsn

title: Therapeutic uncertainties in people with cardiometabolic diseases and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or COVID‐19)

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or COVID‐19) has been declared a pandemic by the World Health Organization and sent all countries scrambling to review emergency healthcare provisions. There is global evidence of each nation struggling to effectively manage the number of people being diagnosed with the virus. These are testing times which have not been experienced in recent generations and there are a number of insecurities regarding the management of people with COVID‐19 and cardiometabolic diseases. This review highlights the current concerns related to COVID‐19 and provides advice in terms of the therapeutic uncertainty and potential adverse harms associated with therapy when managing people, particularly those with cardiometabolic diseases, who have contracted or are at increased risk of contracting COVID‐19.


title: Detection of ubiquitin–proteasome enzymatic activities in cells: Application of activity-based probes to inhibitor development

text: Abstract Background: Synthetic probes that mimic natural substrates can enable the detection of enzymatic activities in a cellular environment. One area where such activity-based probes have been applied is the ubiquitin–proteasome pathway, which is emerging as an important therapeutic target. A family of reagents has been developed that specifically label deubiquitylating enzymes (DUBs) and facilitate characterization of their inhibitors. Scope of review: Here we focus on the application of probes for intracellular DUBs, a group of specific proteases involved in the ubiquitin proteasome system. In particular, the functional characterization of the active subunits of this family of proteases that specifically recognize ubiquitin and ubiquitin-like proteins will be discussed. In addition we present the potential and design of activity-based probes targeting kinases and phosphatases to study phosphorylation. Major conclusions: Synthetic molecular probes have increased our understanding of the functional role of DUBs in living cells. In addition to the detection of enzymatic activities of known members, activity-based probes have contributed to a number of functional assignments of previously uncharacterized enzymes. This method enables cellular validation of the specificity of small molecule DUB inhibitors. General significance: Molecular probes combined with mass spectrometry-based proteomics and cellular assays represent a powerful approach for discovery and functional validation, a concept that can be expanded to other enzyme classes. This addresses a need for more informative cell-based assays that are required to accelerate the drug development process. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.


title: Household Transmission of SARS-CoV-2, Zhuhai, China, 2020

text: BACKGROUND: To illustrate the extent of transmission, identify affecting risk factors and estimate epidemiological modeling parameters of SARS-CoV-2 in household setting. METHODS: We enrolled 35 confirmed index cases and their 148 household contacts, January 2020–February 2020, in Zhuhai, China. All participants were interviewed and asked to complete questionnaires. Household contacts were then prospectively followed active symptom monitoring through the 21-day period and nasopharyngeal and/or oropharyngeal swabs were collected at 3-7 days intervals. Epidemiological, demographic and clinical data (when available) were collected. RESULTS: Assuming that all these secondary cases were infected by their index cases, the second infection rate (SIR) in household context is 32.4% (95% confidence interval [CI] 22.4%-44.4%), with 10.4% of secondary cases being asymptomatic. Multivariate analysis showed that household contacts with underlying medical conditions, a history of direct exposure to Wuhan and its surrounding areas, and shared vehicle with an index patient were associated with higher susceptibility. Household members without protective measures after illness onset of the index patient seem to increase the risk for SARS-CoV-2 infection. The median incubation period and serial interval within household were estimated to be 4.3 days (95% CI; 3.4 to 5.3 days) and 5.1 days (95% CI; 4.3 to 6.2 days), respectively. CONCLUSION: Early isolation of patients with COVID-19 and prioritizing rapid contact investigation, followed by active symptom monitoring and periodic laboratory evaluation, should be initiated immediately after confirming patients to address the underlying determinants driving the continuing pandemic.


title: Epidemiological evidence for association between higher influenza vaccine uptake in the elderly and lower COVID‐19 deaths in Italy

text: The Italian COVID-19 epidemic may finally be slowing, although the virus has spread from the North in Lombardy throughout the rest of the country. While there have been more than 233,000 confirmed cases, and a mortality rate estimated around 14%, Italy will now navigate an exit from lockdown with continued testing, monitoring, and contact tracing of any new infections. This article is protected by copyright. All rights reserved.


title: A Comparison of the Clinical and Epidemiological Characteristics of Adult Patients with Laboratory-Confirmed Influenza A or B during the 2011–2012 Influenza Season in Korea: A Multi-Center Study

text: BACKGROUND: During the 2011/2012 winter influenza season in the Republic of Korea, influenza A (H3N2) was the predominant virus in the first peak period of influenza activity during the second half of January 2012. On the other hand, influenza B was the predominant virus in the second peak period of influenza activity during the second half of March 2012. The objectives of this study were to compare the clinical and epidemiological characteristics of patients with laboratory-confirmed influenza A or influenza B. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed data from 2,129 adult patients with influenza-like illnesses who visited the emergency rooms of seven university hospitals in Korea from October 2011 to May 2012. Of 850 patients with laboratory-confirmed influenza, 656 (77.2%) had influenza A (H3N2), and 194 (22.8%) influenza B. Age, and the frequencies of cardiovascular disorders, diabetes, hypertension were significantly higher in patients with influenza A (H3N2) (P<0.05). The frequencies of leukopenia or thrombocytopenia in patients with influenza B at initial presentation were statistically higher than those in patients with influenza A (H3N2) (P<0.05). The rate of hospitalization, and length of hospital stay were statistically higher in patients with influenza A (H3N2) (P<0.05), and of the 79 hospitalized patients, the frequency of diabetes, hypertension, cases having at least one of the comorbid conditions, and the proportion of elderly were significantly higher in patients with influenza A (H3N2) (P<0.05). CONCLUSIONS: The proportion of males to females and elderly population were significantly higher for influenza A (H3N2) patients group compared with influenza B group. Hypertension, diabetes, chronic lung diseases, cardiovascular disorders, and neuromuscular diseases were independently associated with hospitalization due to influenza. Physicians should assess and treat the underlying comorbid conditions as well as influenza viral infections for the appropriate management of patients with influenza.


title: Environmental and non-infectious factors in the aetiology of pharyngitis (sore throat)

text: OBJECTIVES: The aim of this review is to examine the causes, pathophysiology and experimental models of non-infectious pharyngitis (sore throat). INTRODUCTION: The causes of sore throat can be infectious (viruses, bacteria, and fungi) or non-infectious, although the relative proportion of each is not well documented. METHODS: A PubMed database search was performed for studies of non-infectious sore throat. RESULTS AND CONCLUSIONS: Non-infectious causes of sore throat include: physico-chemical factors, such as smoking, snoring, shouting, tracheal intubation, medications, or concomitant illness; and environmental factors including indoor and outdoor air pollutants, temperature and humidity, and hazardous or occupational irritants. The pathophysiology underlying non-infectious sore throat is largely uncharacterised, although neurogenic inflammation looks to be a promising candidate. It is likely that there will be individual disposition factors or the coincidence of more than one irritant with possible—up to now unknown—interactions between them. Therefore, experimental models with defined conditions and objective endpoints are needed. A new model using cold dry air to directly induce pharyngeal irritation in humans, with pharyngeal lavage to measure biomarkers, may provide a useful tool for the study of mechanisms and treatment of non-infectious sore throat.


title: IFITM1 expression is crucial to gammaherpesvirus infection, in vivo

text: The oncogenic gammaherpesviruses, Epstein–Barr virus (EBV) and Kaposi’s sarcoma herpesvirus (KSHV), are etiologically associated with a variety of human cancers, including Burkitt’s lymphoma (BL), Hodgkin lymphoma (HL), Kaposi’s sarcoma (KS), and primary effusion lymphoma (PEL). Recently, we demonstrated KSHV infection of B- and endothelial cells to significantly upregulate the expression of interferon induced transmembrane protein 1 (IFITM1) which in turn enhances virus entry. This is an extension of the above study. In here, we determined EBV infection of cells to trigger IFITM1 expression, in vitro. Silencing IFITM1 expression using siRNA specifically lowered gammaherpesvirus infection of cells at a post binding stage of entry. A natural model system to explore the effect of IFITM1 on gammaherpesvirus infection in vivo is infection of BALB/c mice with murine gammaherpesvirus 68 (MHV-68). Priming mice with siRNA specific to IFITM1 significantly lowered MHV-68 titers in the lung specimens compared to priming with (NS)siRNA or PBS. MHV-68 titers were monitored by plaque assay and qPCR. Taken together, for the first time, this study provides insight into the critical role of IFITM1 to promoting in vivo gammaherpesvirus infections.


docid: qejocjyh

title: Digital tools against COVID-19: taxonomy, ethical challenges, and navigation aid

text: Data collection and processing via digital public health technologies are being promoted worldwide by governments and private companies as strategic remedies for mitigating the COVID-19 pandemic and loosening lockdown measures. However, the ethical and legal boundaries of deploying digital tools for disease surveillance and control purposes are unclear, and a rapidly evolving debate has emerged globally around the promises and risks of mobilising digital tools for public health. To help scientists and policy makers to navigate technological and ethical uncertainty, we present a typology of the primary digital public health applications that are in use. These include proximity and contact tracing, symptom monitoring, quarantine control, and flow modelling. For each, we discuss context-specific risks, cross-sectional issues, and ethical concerns. Finally, recognising the need for practical guidance, we propose a navigation aid for policy makers and other decision makers for the ethical development and use of digital public health tools.


title: Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model

text: Advances in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) have led to improved progression-free survival of many patients; however the therapies are toxic, rarely achieve durable long-term complete responses and are not curative. Herein we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site. The local antibody delivery led to marked immune checkpoint blockade. Tumor growth diminished 5 times and tumor weight reduced 50–80% when compared with the anti-CAIX CAR T cells alone in a humanized mice model of ccRCC. The expression of PD-L1 and Ki67 in the tumors decreased and an increase in granzyme B levels was found in CAR T cells. The anti-PD-L1 IgG1 isotype, which is capable of mediating ADCC, was also able to recruit human NK cells to the tumor site in vivo. These armed second-generation CAR T cells empowered to secrete human anti-PD-L1 antibodies in the ccRCC milieu to combat T cell exhaustion is an innovation in this field that should provide renewed potential for CAR T cell immunotherapy of solid tumors where limited efficacy is currently seen.


docid: bqdsfgdc

title: Estimando el número de casos de COVID-19 mediante una herramienta web: resultados de la primera semana del proyecto "Covid-19 Trends" en Euskadi

text: Resumen Objetivo: En Euskadi, dos casos de COVID-19 fueron diagnosticados el 28 de febrero de 2020. El 14 de marzo el Gobierno español estableció el estado de alarma. La única información acerca del número de casos de Covid-19 eran los confirmados por RT-PCR. Lanzamos una herramienta de vigilancia basada en la web para estimar el número mínimo de casos sintomáticos de Covid-19 y generar información útil para la toma de decisiones en salud pública. Material y métodos: Implementamos un cuestionario web anónimo y lo difundimos a través de redes sociales. Recopilamos información epidemiológica sobre variables de “tiempo” (fecha de inicio de los síntomas), “lugar” (código postal) y “persona” (género, edad). Comparamos los casos positivos detectados mediante RT-PCR con los casos estimados según la definición de caso del Ministerio de Sanidad Consumo y Bienestar Social. Calculamos la tasa de respuesta al cuestionario y la incidencia acumulada a 14 días. Resultados: Entre el 19 y 26 de marzo de 2020, el cuestionario fue contestado por 128.182 personas (5,5% de la población vasca).De ellas 27.599 cumplieron la definición de caso. Los casos estimados fueron seis veces más que los RT-PCR positivos para COVID-19. La incidencia acumulada a 14 días fue de 463,3 por 100.000 habitantes comparada con la de los casos positivos por RT-PCR que fue de 139,6 por 100.000 habitantes. Conclusiones: Esta herramienta mostró su utilidad para estimar el mínimo número de casos sintomáticos en Euskadi lo cual podría apoyar aciones de salud pública. Summary Objective: In the Basque Country, two cases of COVID-19 were diagnosed on February 28 2020. On March 14, the Spanish Government established a state of alarm. Only cases confirmed by molecular biology (reverse-transcriptase polymerase chain reaction [RT-PCR]) were known. We launched a web-based surveillance tool to estimate the number of symptomatic cases of COVID-19 to contribute to Public Health decision-making. Material and methods: We implemented an anonymous web questionnaire and disseminated it through online social media social. We collected epidemiological information about "time" (date of onset of symptoms), "place" (zip code), and "person" (gender, age). We compared cases detected by RT-PCR with the estimated cases, according to the case definition of the Ministry of Health. We calculated the questionnaire response rate and the cumulative incidence at 14 days. Results: Between March 19 and 26, 128,009 people answered the questionnaire (5.5% of the Basque population). Of these, 26,375 met the case definition (symptom prevalence of 21.4%). The estimated cases were almost six times more than COVID-19 positive RT-PCR. The estimated 14-day cumulative incidence was 578.3 per 100,000 population compared to RT-PCR positive cases, which was 139.6 per 100,000 population. Conclusions: This tool was useful in estimating the minimum number of symptomatic cases in the Basque Country, which could support Public Health actions.


title: A Structural View of the Inactivation of the SARS Coronavirus Main Proteinase by Benzotriazole Esters

text: Summary The main proteinase (Mpro) of the severe acute respiratory syndrome (SARS) coronavirus is a principal target for the design of anticoronaviral compounds. Benzotriazole esters have been reported as potent nonpeptidic inhibitors of the enzyme, but their exact mechanism of action remains unclear. Here we present crystal structures of SARS-CoV Mpro, the active-site cysteine of which has been acylated by benzotriazole esters that act as suicide inhibitors. In one of the structures, the thioester product has been hydrolyzed and benzoic acid is observed to bind to the hydrophobic S2 pocket. This structure also features the enzyme with a shortened N-terminal segment (“amputated N finger”). The results further the understanding of the important role of the N finger for catalysis as well as the design of benzotriazole inhibitors with improved specificity.


title: Elevation of blood glucose level predicts worse outcomes in hospitalized patients with COVID-19: a retrospective cohort study

text: INTRODUCTION: With intense deficiency of medical resources during COVID-19 pandemic, risk stratification is of strategic importance. Blood glucose level is an important risk factor for the prognosis of infection and critically ill patients. We aimed to investigate the prognostic value of blood glucose level in patients with COVID-19. RESEARCH DESIGN AND METHODS: We collected clinical and survival information of 2041 consecutive hospitalized patients with COVID-19 from two medical centers in Wuhan. Patients without available blood glucose level were excluded. We performed multivariable Cox regression to calculate HRs of blood glucose-associated indexes for the risk of progression to critical cases/mortality among non-critical cases, as well as in-hospital mortality in critical cases. Sensitivity analysis were conducted in patient without diabetes. RESULTS: Elevation of admission blood glucose level was an independent risk factor for progression to critical cases/death among non-critical cases (HR=1.30, 95% CI 1.03 to 1.63, p=0.026). Elevation of initial blood glucose level of critical diagnosis was an independent risk factor for in-hospital mortality in critical cases (HR=1.84, 95% CI 1.14 to 2.98, p=0.013). Higher median glucose level during hospital stay or after critical diagnosis (≥6.1 mmol/L) was independently associated with increased risks of progression to critical cases/death among non-critical cases, as well as in-hospital mortality in critical cases. Above results were consistent in the sensitivity analysis in patients without diabetes. CONCLUSIONS: Elevation of blood glucose level predicted worse outcomes in hospitalized patients with COVID-19. Our findings may provide a simple and practical way to risk stratify COVID-19 inpatients for hierarchical management, particularly where medical resources are in severe shortage during the pandemic.


Characteristics and Outcomes of 21 Critically Ill Patients with COVID-19 in Washington State Arentz M, Yim E, Klaff L, et al. JAMA. Published online March 19, 2020. doi:10.1001/jama.2020.4326.


title: Challenges and Opportunities for the Biotechnology Research Community During the Coronavirus Pandemic

text: Abstract The COVID-19 pandemic has presented some significant challenges to the scientific community. However, this conundrum has also offered new opportunities for the pursuit of new scientific activities, and in particular for the field of biotechnology.


Preventing COVID-19-induced pneumonia with anticytokine therapy


title: China's online parrot trade: Generation length and body mass determine sales volume via price

text: Abstract The wildlife trade threatens global biodiversity and animal welfare, where parrots are among the taxa most frequently traded, supplying exotic pets and captive breeders worldwide. Using phylogenetic path analysis, we examine how biological factors interact with price to influence online protected parrot trade volumes in China, using transactions recorded for 46 species (n = 5,862 individuals). Trade was greatest in smaller, faster breeding species that commanded a lower price. This price effect followed the economic law of demand, with Relatively Inelastic Demand (−0.758), outweighing indicators of ‘quality’ such as body coloration, and conservation status. We identify two areas of concern: those larger, slower-breeding, rarer species, even though sold at lower numbers, may be at conservation risk if harvested from the wild. In contrast, the sheer numbers (over 90% of the individuals were under median generation length, body mass and/or price) and ready availability of smaller and more common species comprises a substantial overall animal welfare issue, given that the capture, importation, or captive breeding of many parrot species in China is illegal and thus unregulated. Our investigation highlights the importance of properly understanding the internal relations among drivers of wildlife trade to inform appropriate management.


A case of intrafamilial Human Parechovirus type 3 infections resulting in sepsis-like illness in a neonate but hand, foot and mouth disease in an elder sibling


title: 2.18 Promiscuous Ligands

text: Computational and experimental high-throughput screening are frequently used to discover new leads for drug design. Although novel ligands have been identified by these methods, it has become clear that screening hit lists are plagued by false positives. These nuisance compounds are ultimately found to be developmental dead-ends and are abandoned, often after considerable effort has been invested in them. Much work over the last decade has been devoted to exploring the origins of false-positive screening hits, and ligand promiscuity has emerged as one such cause. Well-known mechanisms of promiscuity include reactive species and privileged substructures. More recently, it has been found that some nonspecific screening hits form aggregates of 30–1000nm in diameter. It has been proposed that these aggregate particles are responsible for the promiscuous behavior of many false positives and that aggregate-forming compounds may be widespread among screening hits. This chapter will review the known mechanisms of ligand promiscuity with an emphasis on the recently described model of aggregation. Experimental and computational methods for identifying promiscuous compounds will be described, and some outstanding questions in the field will be considered.


Covid-19 in Brazil


title: Impact of lockdown on learning status of undergraduate and postgraduate students during COVID-19 pandemic in West Bengal, India

text: To assess the impact of lockdown amidst COVID-19 on undergraduate and postgraduate learners of various colleges and universities of West Bengal. An online survey was conducted from 1 May to 8 May 2020 to collect the information. A structural questionnaire link using ‘Google form’ was sent to students’ through WhatsApp and E-mail. A total of 232 students provided complete information regarding the survey. The simple percentage distribution was used to assess the learning status of the study participants. During the lockdown period, around 70% of learners were involved in e-learning. Most of the learners were used android mobile for attending e-learning. Students have been facing various problems related to depression anxiety, poor internet connectivity, and unfavorable study environment at home. Students from remote areas and marginalized sections mainly face enormous challenges for the study during this pandemic. This study suggests targeted interventions to create a positive space for study among students from the vulnerable section of society. Strategies are urgently needed to build a resilient education system in the state that will ensure to develop the skill for employability and the productivity of the young minds.


title: Post-Translational Protein Deimination Signatures in Serum and Serum-Extracellular Vesicles of Bos taurus Reveal Immune, Anti-Pathogenic, Anti-Viral, Metabolic and Cancer-Related Pathways for Deimination

text: The bovine immune system is known for its unusual traits relating to immunoglobulin and antiviral responses. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that cause post-translational deimination, contributing to protein moonlighting in health and disease. PADs also regulate extracellular vesicle (EV) release, forming a critical part of cellular communication. As PAD-mediated mechanisms in bovine immunology and physiology remain to be investigated, this study profiled deimination signatures in serum and serum-EVs in Bos taurus. Bos EVs were poly-dispersed in a 70–500 nm size range and showed differences in deiminated protein cargo, compared with whole sera. Key immune, metabolic and gene regulatory proteins were identified to be post-translationally deiminated with some overlapping hits in sera and EVs (e.g., immunoglobulins), while some were unique to either serum or serum-EVs (e.g., histones). Protein–protein interaction network analysis of deiminated proteins revealed KEGG pathways common for serum and serum-EVs, including complement and coagulation cascades, viral infection (enveloped viruses), viral myocarditis, bacterial and parasitic infections, autoimmune disease, immunodeficiency intestinal IgA production, B-cell receptor signalling, natural killer cell mediated cytotoxicity, platelet activation and hematopoiesis, alongside metabolic pathways including ferroptosis, vitamin digestion and absorption, cholesterol metabolism and mineral absorption. KEGG pathways specific to EVs related to HIF-1 signalling, oestrogen signalling and biosynthesis of amino acids. KEGG pathways specific for serum only, related to Epstein–Barr virus infection, transcription mis-regulation in cancer, bladder cancer, Rap1 signalling pathway, calcium signalling pathway and ECM-receptor interaction. This indicates differences in physiological and pathological pathways for deiminated proteins in serum-EVs, compared with serum. Our findings may shed light on pathways underlying a number of pathological and anti-pathogenic (viral, bacterial, parasitic) pathways, with putative translatable value to human pathologies, zoonotic diseases and development of therapies for infections, including anti-viral therapies.


title: Chapter 5 Role of risk analysis and risk communication in food safety management

text: Abstract Concept of “risk analysis” in food safety management needs to be understood to assess, manage, and communicate risks for proper implementation of food safety policies, food laws, and standards, in a country. Science-based approaches, which are an integral part of risk analysis to improve modern food safety systems, are intimately linked to processes such as good quality practices. Risk analysis strengthens the ability of traditional food safety systems to meet current challenges. Risk analysis is just one part of an effective food safety system. Other components of food safety system like food safety policies, food legislation, food inspection, laboratory analysis, epidemiological surveillance of food-borne diseases, monitoring systems for chemical and microbiological contamination in foods, and information, education and communication, also need to be improved continuously. “Food safety controls” are now being replaced by “risk-based controls” in all stages of food production.


Virology: Molecular biology of the coronaviruses


title: Genomic RNA sequence of feline coronavirus strain FCoV C1Je

text: This paper reports the first genomic RNA sequence of a field strain feline coronavirus (FCoV). Viral RNA was isolated at post mortem from the jejunum and liver of a cat with feline infectious peritonitis (FIP). A consensus sequence of the jejunum-derived genomic RNA (FCoV C1Je) was determined from overlapping cDNA fragments produced by reverse transcriptase polymerase chain reaction (RT-PCR) amplification. RT-PCR products were sequenced by a reiterative sequencing strategy and the genomic RNA termini were determined using a rapid amplification of cDNA ends PCR strategy. The FCoV C1Je genome was found to be 29,255 nucleotides in length, excluding the poly(A) tail. Comparison of the FCoV C1Je genomic RNA sequence with that of the laboratory strain FCoV FIP virus (FIPV) 79-1146 showed that both viruses have a similar genome organisation and predictions made for the open reading frames and cis-acting elements of the FIPV 79-1146 genome hold true for FCoV C1Je. In addition, the sequence of the 3′-proximal third of the liver derived genomic RNA (FCoV C1Li), which encompasses the structural and accessory protein genes of the virus, was also determined. Comparisons of the enteric (jejunum) and non-enteric (liver) derived viral RNA sequences revealed 100% nucleotide identity, a finding that questions the well accepted ‘internal mutation theory’ of FIPV pathogenicity.