title: Clinical microbiology

text: The clinical microbiology laboratory relies on traditional diagnostic methods such as culturing, Gram stains, and biochemical testing. Receipt of a high-quality specimen with an appropriate test order is integral to accurate testing. Recent technological advancements have led to decreased time to results and improved diagnostic accuracy. Examples of advancements discussed in this chapter include automation of bacterial culture processing and incubation, as well as introduction of mass spectrometry for the proteomic identification of microorganisms. In addition, molecular testing is increasingly common in the clinical laboratory. Commercially available multiplex molecular assays simultaneously test for a broad array of syndromic-related pathogens, providing rapid and sensitive diagnostic results. Molecular advancements have also transformed point-of-care (POC) microbiology testing, and molecular POC assays may largely supplant traditional rapid antigen testing in the future. Integration of new technologies with traditional testing methods has led to improved quality and value in the clinical microbiology laboratory.


Cautions about radiologic diagnosis of COVID-19 infection driven by artificial intelligence


title: AIDS, Avian flu, SARS, MERS, Ebola, Zika… what next?

text: Abstract Emerging infections have threatened humanity since times immemorial. The dramatic anthropogenic, behavioral and social changes that have affected humanity and the environment in the past century have accelerated the intrusion of novel pathogens into the global human population, sometimes with devastating consequences. The AIDS and influenza pandemics have claimed and will continue to claim millions of lives. The recent SARS and Ebola epidemics have threatened populations across borders. The emergence of MERS may well be warning signals of a nascent pandemic threat, while the potential for geographical spread of vector-borne diseases, such as Zika, but also Dengue and Chikungunya is unprecedented. Novel technologies and innovative approaches have multiplied to address and improve response preparedness towards the increasing yet unpredictable threat posed by emerging pathogens.


title: Adolescent psychiatric disorders during the COVID-19 pandemic and lockdown

text: The aim of this paper was to review the literature on adolescent psychiatric disorders related to the COVID-19 pandemic and lockdown. Stressful life events, extended home confinement, brutal grief, intrafamilial violence, overuse of the Internet and social media are factors that could influence the mental health of adolescents during this period. The COVID-19 pandemic could result in increased psychiatric disorders such as Post-Traumatic Stress, Depressive, and Anxiety Disorders, as well as grief-related symptoms. Adolescents with psychiatric disorders are at risk of a break or change in their care and management; they may experience increased symptoms. The COVID-19 pandemic and lockdown may have a negative impact on the mental health of adolescents, although there is still no data on the long term impact of this crisis. Adolescents’ individual, familial, and social vulnerability, as well as individual and familial coping abilities, are factors related to adolescent mental health in times of crisis. Adolescents are often vulnerable and require careful consideration by caregivers and healthcare system adaptations to allow for mental health support despite the lockdown. Research on adolescent psychiatric disorders in times of pandemics is necessary, as such a global situation could be prolonged or repeated.


docid: lrgimmhi

title: Confinement ou immunité collective: leçons tirés de 40 ans de pratique en hépatologie


title: 5.16 Infections in Pregnancy☆

text: Abstract Infections during pregnancy may affect a developing fetus. If left untreated, these infections can lead to the death of the mother, fetus, or neonate and other adverse sequelae. There are many factors that impact infection during pregnancy, such as the immune system changes during pregnancy, hormonal flux, stress, and the microbiome. We review some of the outcomes of infection during pregnancy, such as preterm birth, chorioamnionitis, meningitis, hydrocephaly, developmental delays, microcephaly, and sepsis. Transmission routes are discussed regarding how a pregnant woman may pass her infection to her fetus. This is followed by examples of infection during pregnancy: bacterial, viral, parasitic, and fungal infections. There are many known organisms that are capable of producing similar congenital defects during pregnancy; however, whether these infections share common mechanisms of action is yet to be determined. To protect the health of pregnant women and their offspring, additional research is needed to understand how these intrauterine infections adversely affect pregnancies and/or neonates in order to develop prevention strategies and treatments.


title: Helping Doctors Hasten COVID-19 Treatment: Towards a Rescue Framework for the Transfusion of Best Convalescent Plasma to the Most Critical Patients based on Biological Requirements via ML and Novel MCDM Methods

text: CONTEXT: People who have recently recovered from the threat of deteriorating coronavirus disease-2019 (COVID-19) have antibodies to the coronavirus circulating in their blood. Thus, the transfusion of these antibodies to deteriorating patients could theoretically help boost their immune system. Biologically, two challenges need to be surmounted to allow convalescent plasma (CP) transfusion to rescue the most severe COVID-19 patients. First, convalescent subjects must meet donor selection plasma criteria and comply with national health requirements and known standard routine procedures. Second, multi-criteria decision-making (MCDM) problems should be considered in the selection of the most suitable CP and the prioritisation of patients with COVID-19. OBJECTIVE: This paper presents a rescue framework for the transfusion of the best CP to the most critical patients with COVID-19 on the basis of biological requirements by using machine learning and novel MCDM methods. METHOD: The proposed framework is illustrated on the basis of two distinct and consecutive phases (i.e. testing and development). In testing, ABO compatibility is assessed after classifying donors into the four blood types, namely, A, B, AB and O, to indicate the suitability and safety of plasma for administration in order to refine the CP tested list repository. The development phase includes patient and donor sides. In the patient side, prioritisation is performed using a contracted patient decision matrix constructed between ‘serological/protein biomarkers and the ratio of the partial pressure of oxygen in arterial blood to fractional inspired oxygen criteria’ and ‘patient list based on novel MCDM method known as subjective and objective decision by opinion score method’. Then, the patients with the most urgent need are classified into the four blood types and matched with a tested CP list from the test phase in the donor side. Thereafter, the prioritisation of CP tested list is performed using the contracted CP decision matrix. RESULT: An intelligence-integrated concept is proposed to identify the most appropriate CP for corresponding prioritised patients with COVID-19 to help doctors hasten treatments. DISCUSSION: The proposed framework implies the benefits of providing effective care and prevention of the extremely rapidly spreading COVID-19 from affecting patients and the medical sector.


title: Facemask shortage and the novel coronavirus disease (COVID-19) outbreak: Reflections on public health measures

text: Abstract Background A novel coronavirus disease (COVID-19) outbreak due to the severe respiratory syndrome coronavirus (SARS-CoV-2) infection occurred in China in late December 2019. Facemask wearing with proper hand hygiene is considered an effective measure to prevent SARS-CoV-2 transmission, but facemask wearing has become a social concern due to the global facemask shortage. China is the major facemask producer in the world, contributing to 50% of global production. However, a universal facemask wearing policy would put an enormous burden on the facemask supply. Methods We performed a policy review concerning facemasks using government websites and mathematical modelling shortage analyses based on data obtained from the National Health Commission (NHC), the Ministry of Industry and Information Technology (MIIT), the Centre for Disease Control and Prevention (CDC), and General Administration of Customs (GAC) of the People's Republic of China. Three scenarios with respect to wearing facemasks were considered: (1) a universal facemask wearing policy implementation in all regions of mainland China; (2) a universal facemask wearing policy implementation only in the epicentre (Hubei province, China); and (3) no implementation of a universal facemask wearing policy. Findings Regardless of different universal facemask wearing policy scenarios, facemask shortage would occur but eventually end during our prediction period (from 20 Jan 2020 to 30 Jun 2020). The duration of the facemask shortage described in the scenarios of a country-wide universal facemask wearing policy, a universal facemask wearing policy in the epicentre, and no universal facemask wearing policy were 132, seven, and four days, respectively. During the prediction period, the largest daily facemask shortages were predicted to be 589·5, 49·3, and 37·5 million in each of the three scenarios, respectively. In any scenario, an N95 mask shortage was predicted to occur on 24 January 2020 with a daily facemask shortage of 2·2 million. Interpretation Implementing a universal facemask wearing policy in the whole of China could lead to severe facemask shortage. Without effective public communication, a universal facemask wearing policy could result in societal panic and subsequently, increase the nationwide and worldwide demand for facemasks. These increased demands could cause a facemask shortage for healthcare workers and reduce the effectiveness of outbreak control in the affected regions, eventually leading to a pandemic. To fight novel infectious disease outbreaks, such as COVID-19, governments should monitor domestic facemask supplies and give priority to healthcare workers. The risk of asymptomatic transmission and facemask shortages should be carefully evaluated before introducing a universal facemask wearing policy in high-risk regions. Public health measures aimed at improving hand hygiene and effective public communication should be considered along with the facemask policy.


title: Identification of a Pangolin Niche for a 2019-nCoV-like Coronavirus via an Extensive Meta-metagenomic Search

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 datasets are now available, with deep sequencing of samples from diverse biological niches. While any individual metagenomic dataset can be readily queried using web-based tools, meta-searches through all such datasets are less accessible. In this brief communication, we demonstrate such a meta-meta-genomic approach, examining close matches to the Wuhan coronavirus 2019-nCoV in all high-throughput sequencing datasets in the NCBI Sequence Read Archive accessible with the keyword “virome”. In addition to the homology to bat coronaviruses observed in descriptions of the 2019-nCoV sequence (F. Wu et al. 2020, Nature, doi.org/10.1038/s41586-020-2008-3; P. Zhou et al. 2020, Nature, doi.org/10.1038/s41586-020-2012-7), we note a strong homology to numerous sequence reads in a metavirome dataset generated from the lungs of deceased Pangolins reported by Liu et al. (Viruses 11:11, 2019, http://doi.org/10.3390/v11110979). Our observations are relevant to discussions of the derivation of 2019-nCoV and illustrate the utility and limitations of meta-metagenomic search tools in effective and rapid characterization of potentially significant nucleic acid sequences. Meta-metagenomic searches allow for high-speed, low-cost identification of potentially significant biological niches for sequences of interest.


title: Imaging analysis of human metapneumovirus-infected cells provides evidence for the involvement of F-actin and the raft-lipid microdomains in virus morphogenesis

text: BACKGOUND: Due to difficulties of culturing Human metapneumovirus (HMPV) much of the current understanding of HMPV replication can be inferred from other closely related viruses. The slow rates of virus replication prevent many biochemical analyses of HMPV particles. In this study imaging was used to examine the process of HMPV morphogenesis in individually infected LLC-MK2 cells, and to better characterise the sites of HMPV assembly. This strategy has circumvented the problems associated with slow replication rates and allowed us to characterise both the HMPV particles and the sites of HMPV morphogenesis. METHODS: HMPV-infected LLC-MK2 cells were stained with antibodies that recognised the HMPV fusion protein (F protein), attachment protein (G protein) and matrix protein (M protein), and fluorescent probes that detect GM1 within lipid-raft membranes (CTX-B-AF488) and F-actin (Phalloidin-FITC). The stained cells were examined by confocal microscopy, which allowed imaging of F-actin, GM1 and virus particles in HMPV-infected cells. Cells co-expressing recombinant HMPV G and F proteins formed virus-like particles and were co-stained with antibodies that recognise the recombinant G and F proteins and phalloidin-FITC and CTX-B-AF594, and the distribution of the G and F proteins, GM1 and F-actin determined. RESULTS: HMPV-infected cells stained with anti-F, anti-G or anti-M revealed a filamentous staining pattern, indicating that the HMPV particles have a filamentous morphology. Staining of HMPV-infected cells with anti-G and either phalloidin-FITC or CTX-B-AF488 exhibited extensive co-localisation of these cellular probes within the HMPV filaments. This suggested that lipid-raft membrane domains and F-actin structures are present at the site of the virus morphogenesis, and are subsequently incorporated into the HMPV filaments. Furthermore, the filamentous virus-like particles that form in cells expressing the G protein formed in cellular structures containing GM1 and F-actin, suggesting the G protein contains intrinsic targeting signals to the sites of virus assembly. CONCLUSIONS: These data suggest that HMPV matures as filamentous particles and that virus morphogenesis occurs within lipid-raft microdomains containing localized concentrations of F-actin. The similarity between HMPV morphogenesis and the closely related human respiratory syncytial virus suggests that involvement of F-actin and lipid-raft microdomains in virus morphogenesis may be a common feature of the Pneumovirinae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-014-0198-8) contains supplementary material, which is available to authorized users.


title: Drivers of MERS-CoV transmission: what do we know?

text: Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged in 2012 has since resulted in sporadic cases, intra-familial transmission and major outbreaks in healthcare settings. The clinical picture of MERS-CoV includes asymptomatic infections, mild or moderately symptomatic cases and fatal disease. Transmissions of MERS-CoV within healthcare settings are facilitated by overcrowding, poor compliance with basic infection control measures, unrecognized infections, the superspreaders phenomenon and poor triage systems. The actual contributing factors to the spread of MERS-CoV are yet to be systematically studied, but data to date suggest viral, host and environmental factors play a major role. Here, we summarize the known factors for the diverse transmission of MERS-CoV.


title: Predicting the international spread of Middle East respiratory syndrome (MERS)

text: BACKGROUND: The Middle East respiratory syndrome (MERS) associated coronavirus has been imported via travelers into multiple countries around the world. In order to support risk assessment practice, the present study aimed to devise a novel statistical model to quantify the country-level risk of experiencing an importation of MERS case. METHODS: We analyzed the arrival time of each reported MERS importation around the world, i.e., the date on which imported cases entered a specific country, which was modeled as a dependent variable in our analysis. We also used openly accessible data including the airline transportation network to parameterize a hazard-based risk prediction model. The hazard was assumed to follow an inverse function of the effective distance (i.e., the minimum effective length of a path from origin to destination), which was calculated from the airline transportation data, from Saudi Arabia to each country. Both country-specific religion and the incidence data of MERS in Saudi Arabia were used to improve our model prediction. RESULTS: Our estimates of the risk of MERS importation appeared to be right skewed, which facilitated the visual identification of countries at highest risk of MERS importations in the right tail of the distribution. The simplest model that relied solely on the effective distance yielded the best predictive performance (Area under the curve (AUC) = 0.943) with 100 % sensitivity and 79.6 % specificity. Out of the 30 countries estimated to be at highest risk of MERS case importation, 17 countries (56.7 %) have already reported at least one importation of MERS. Although model fit measured by Akaike Information Criterion (AIC) was improved by including country-specific religion (i.e. Muslim majority country), the predictive performance as measured by AUC was not improved after accounting for this covariate. CONCLUSIONS: Our relatively simple statistical model based on the effective distance derived from the airline transportation network data was found to help predicting the risk of importing MERS at the country level. The successful application of the effective distance model to predict MERS importations, particularly when computationally intensive large-scale transmission models may not be immediately applicable could have been benefited from the particularly low transmissibility of the MERS coronavirus.


title: Coronavirus drug, water warning and virus-research funding.

text: One of the world’s best hopes for treating COVID-19 — a compound called remdesivir — has been authorized as a therapy against the disease On 1 May, the US Food and Drug Administration (FDA) granted an ‘emergency-use authorization’ for clinicians to use the drug, which is administered intravenously, in hospitals for people with severe COVID-19


title: Evaluation of rapid assays for the detection of bovine coronavirus, rotavirus A and Cryptosporidium parvum in faecal samples of calves

text: Abstract Rapid immunochromatographic assays for detecting infections with bovine coronavirus (BCV), rotavirus A and Cryptosporidium parvum in calf faeces were evaluated using as gold standards a reverse transcriptase polymerase chain reaction (BCV and rotavirus) and a sedimentation-flotation technique (C. parvum). Rapid tests for the detection of BCV and rotavirus showed a high specificity (96.4% and 95.3%, respectively), but a relatively low sensitivity (60.0% and 71.9%, respectively). Sensitivity and specificity for detection of C. parvum were high (100% and 94.6%, respectively).


title: Face Mask Use and Control of Respiratory Virus Transmission in Households

text: Many countries are stockpiling face masks for use as a nonpharmaceutical intervention to control virus transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. Mask use adherence was self-reported. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. We found that adherence to mask use significantly reduced the risk for ILI-associated infection, but <50% of participants wore masks most of the time. We concluded that household use of face masks is associated with low adherence and is ineffective for controlling seasonal respiratory disease. However, during a severe pandemic when use of face masks might be greater, pandemic transmission in households could be reduced. Many countries are stockpiling face masks for use as nonpharmaceutical interventions to reduce viral transmission during an influenza pandemic. We conducted a prospective cluster-randomized trial comparing surgical masks, non–fit-tested P2 masks, and no masks in prevention of influenza-like illness (ILI) in households. During the 2006 and 2007 winter seasons, 286 exposed adults from 143 households who had been exposed to a child with clinical respiratory illness were recruited. Intent-to-treat analysis showed no significant difference in the relative risk of ILI in the mask use groups compared with the control group; however, <50% of those in the mask use groups reported wearing masks most of the time. Adherence to mask use was associated with a significantly reduced risk of ILI-associated infection. We concluded that household use of masks is associated with low adherence and is ineffective in controlling seasonal ILI. If adherence were greater, mask use might reduce transmission during a severe influenza pandemic.


title: Serviceberry, a berry fruit with growing interest of industry: Physicochemical and quali-quantitative health-related compound characterisation

text: Abstract Amelanchier canadensis (L.) Medik., commonly called serviceberry, is a potential functional food that is also used for its medicinal purposes. This work evaluated the potential of a cultivated serviceberry species as a functional food by characterising its physicochemical characteristics, antioxidant capacity, vitamin C, phenolics and other phytochemicals selected as health-promoting biomarkers, using high-performance liquid chromatography. The most important compound class identified was polyphenols (62.10%), followed by organic acids (22.63%), monoterpenes (7.95%), and vitamins (7.32%). Results showed that serviceberry fruits could be good sources of phenolic constituents, as catechins (343.46 ± 29.46 mg/100 gFW), anthocyanins (220.66 ± 17.43 mg/100 gFW), and tannins (209.29 ± 7.81 mg/100 gFW) (FW = fresh weight). These results highlight the potential role of A. canadensis fruits as a functional food. Further studies are needed to identify several genotypes for breeding to get suitable cultivars for fresh consumption and processing.


Building Viral Replication Organelles: Close Encounters of the Membrane Types


title: Traditional Chinese medicine in the Chinese health care system

text: Abstract Objectives This study examines the role and value of traditional Chinese medicine (TCM) in the current health care system in China. Methods Based on literature review and publicly available data in China. Results The study shows that TCM is well integrated in the Chinese health care system as one of the two mainstream medical practices. Also, the Chinese government is supportive of TCM development by increasing investment in TCM research and administration. However, there is downsizing of TCM utilization, a lack of TCM professionals with genuine TCM knowledge and skills, and limitations of and increasing public opinions on modernization and westernization. Conclusions TCM is still facing many challenges in playing critical roles in improving public health in China. These challenges can be explained from different perspectives. In addition to the unique characteristics of TCM, economic, cultural, and historical evolution in China may also be major determinants.


title: Three-dimensional domain swapping as a mechanism to lock the active conformation in a super-active octamer of SARS-CoV main protease

text: Proteolytic processing of viral polyproteins is indispensible for the lifecycle of coronaviruses. The main protease (M(pro)) of SARS-CoV is an attractive target for anti-SARS drug development as it is essential for the polyprotein processing. M(pro) is initially produced as part of viral polyproteins and it is matured by autocleavage. Here, we report that, with the addition of an N-terminal extension peptide, M(pro) can form a domain-swapped dimer. After complete removal of the extension peptide from the dimer, the mature M(pro) self-assembles into a novel super-active octamer (AO-M(pro)). The crystal structure of AO-M(pro) adopts a novel fold with four domain-swapped dimers packing into four active units with nearly identical conformation to that of the previously reported M(pro) active dimer, and 3D domain swapping serves as a mechanism to lock the active conformation due to entanglement of polypeptide chains. Compared with the previously well characterized form of M(pro), in equilibrium between inactive monomer and active dimer, the stable AO-M(pro) exhibits much higher proteolytic activity at low concentration. As all eight active sites are bound with inhibitors, the polyvalent nature of the interaction between AO-M(pro) and its polyprotein substrates with multiple cleavage sites, would make AO-M(pro) functionally much more superior than the M(pro) active dimer for polyprotein processing. Thus, during the initial period of SARS-CoV infection, this novel active form AOM(pro) should play a major role in cleaving polyproteins as the protein level is extremely low. The discovery of AOM(pro) provides new insights about the functional mechanism of M(pro) and its maturation process. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s13238-010-0044-8 and is accessible for authorized users.


title: IL-33 and ST2 as predictors of disease severity in children with viral acute lower respiratory infection

text: Abstract Background Mechanisms influencing severity of acute lower respiratory infection (ALRI) in children are not established. We aimed to assess the role of inflammatory markers and respiratory viruses in ALRI severity. Methods Concentrations of interleukin(IL)-33, soluble suppression of tumorigenicity (sST)2, IL-1ß, tumor necrosis factor α, IL-4, IL-6 and IL- 8 and types of respiratory viruses were evaluated in children at the first and fifth days after hospital admission. Disease severity was defined as need for mechanical ventilation. Results Seventy-nine children <5 years-old were included; 33(41.8%) received mechanical ventilation. No associations between virus type, viral load or co-detections and severity of disease were observed. Detection of IL-33 and sST2 in nasopharyngeal aspirates (NPA) on admission were associated with higher risk for mechanical ventilation (RR = 2.89 and RR = 4.57, respectively). IL-6 and IL-8 concentrations were higher on Day 5 in mechanically ventilated children. IL-6 NPA concentrations decreased from Day 1 to Day 5 in children who did not receive mechanical ventilation. Increase in sST2 NPA concentrations from Day 1 to Day 5 was associated with longer hospital length of stay (p < 0.01). Conclusions An exacerbated local activation of the IL-33/ST2 axis and persistently high sST2 concentrations over time were associated with severity of viral ALRI in children.


Spike Gene Determinants of Mouse Hepatitis Virus Host Range Expansion


title: Next-Generation Techniques for Discovering Human Monoclonal Antibodies

text: Monoclonal antibodies have found wide applications in the treatment of cancer, as well as of autoimmune, infectious, and other diseases. Several dozen new antibodies are currently undergoing different stages of clinical trials, and some of them will soon be added to the list of immunotherapeutic drugs. Most of these antibodies have been generated using hybridoma technology or a phage display. In recent years, new methods of obtaining human monoclonal antibodies have been actively developing. These methods rely on sequencing immunoglobulin genes from B lymphocytes, as well as on the creation of antibody-secreting stable B-cell lines. The term next-generation antibody-discovery platforms has already been established in the literature to refer to these approaches. Our review focuses on describing the results obtained by these methods.


title: Pneumopathie à métapneumovirus humain chez un adulte suspect de syndrome respiratoire aigu sévère (Sras)

text: Résumé Introduction Le métapneumovirus humain (hMPV) est un virus récemment identifié chez l’homme, responsable d’infections respiratoires parfois sévères que l’on observe surtout chez l’enfant. Observation Un patient âgé de 59 ans a été hospitalisé pour une atteinte respiratoire fébrile 3 jours après le retour d’un voyage en Chine effectué pendant l’épidémie de syndrome respiratoire aigu sévère (Sras). En dehors de la fièvre (>38 °C), étaient notées une toux sèche, des myalgies, des arthralgies, une opacité paracardiaque droite et une lymphopénie modérée. Les recherches virologiques conventionnelles étaient négatives. La recherche du nouveau coronavirus responsable du Sras était négative, mais la recherche de métapneumovirus humain (hMPV) était positive. Discussion Cette observation indique que le hMPV peut être responsable d’une atteinte respiratoire fébrile pouvant initialement évoquer un Sras chez un patient ayant séjourné en zone d’endémie. Conclusion La recherche de hMPV paraît indiquée dans les infections respiratoires aiguës de l’adulte. Summary Introduction Human metapneumovirus (hMPV) is a newly identified virus responsible for occasionally severe respiratory infections, mainly observed in children. Observation A 59-year old man was hospitalised for respiratory problmems and fever 3 days after his return from China during the epidemic of severe acute respiratory syndrome (SARS). Other than fever (> 38°C), the patient exhibited a dry cough, myalgias, arthralgias and mild lymphopenia and the chest radiography showed an opacity on the right lower lung. Conventional virological investigations remained negative. Detection of the novel SARS-associated coronavirus was negative but hMPV detection was positive. Discussion The present observation indicates that hMPV may cause respiratory symptoms mimicking initial manifestations of SARS in adults visiting epidemic countries. Conclusion hMPV testing has clinical utility in adult patients with acute respiratory tract infection.


COVID infection and sentinel lymph node procedure for melanoma: Management in a dermato‐oncology center in a high‐risk pandemic area


title: Verification and diagnostic evaluation of the RealStar(®) Middle East respiratory syndrome coronavirus (N gene) reverse transcription-PCR kit 1.0

text: AIM: We report the diagnostic evaluation of a confirmatory reverse transcription-PCR (RT-PCR) kit targeting the Middle East respiratory syndrome coronavirus (MERS-CoV) N gene. MATERIAL & METHODS: 33 patient samples from two collections sites in Riyadh, Saudi Arabia, which were pre-characterized via real-time RT-PCR targeting MERS-CoV orf1a and upE, and were tested using the MERS-CoV N gene, as a confirmatory assay. This diagnostic procedure follows a two-step diagnostics scheme, recommended by the WHO. RESULTS: 18/33 samples tested positive, 11/33 tested negative for MERS-CoV RNA and 2/33 showed uncertain results. CONCLUSION: The results suggest, that the RealStar(®) MERS-CoV (N gene) RT-PCR kit 1.0 can be considered a suitable and reliable confirmatory assay in combination with the RealStar MERS-CoV RT-PCR kit 1.0 according to the diagnostic scheme recommended by WHO.


title: The nonparametric maximum likelihood estimator for middle-censored data

text: Abstract In this note, we consider data subjected to middle censoring where the variable of interest becomes unobservable when it falls within an interval of censorship. We demonstrate that the nonparametric maximum likelihood estimator (NPMLE) of distribution function can be obtained by using Turnbull's (1976) EM algorithm or self-consistent estimating equation (Jammalamadaka and Mangalam, 2003) with an initial estimator which puts mass only on the innermost intervals. The consistency of the NPMLE can be established based on the asymptotic properties of self-consistent estimators (SCE) with mixed interval-censored data (Yu et al., 2000, 2001).


title: Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus

text: BACKGROUND: Severe Acute Respiratory Syndrome (SARS) emerged as a human disease in 2002 and detailed phylogenetic analysis and epidemiological studies have suggested that the SARS-Coronavirus (SARS-CoV) originated from animals. The Spike (S) glycoprotein has been identified as a major target of protective immunity and contains at least three regions that are targeted by neutralizing antibodies in the S1 and S2 domains. We previously characterized a panel of neutralizing human monoclonal antibodies (MAbs) but the majority of epitopes recognized by the MAbs remained unknown. METHODS: In this study we generated neutralization escape mutants and studied the effect of these neutralization escape mutations on human and animal receptor usage as well as in vitro and in vivo fitness. RESULTS: Distinct but partially overlapping sets of amino acids were identified that are critical to the binding of MAbs with differential neutralization profiles. We also identified possible interactions between the S1 and S2 domains of the SARS-CoV S glycoprotein. Finally, we showed that escape from neutralization usually attenuates SARS-CoV infection. CONCLUSIONS: These data provide a mechanism to overcome neutralization escape by using broadly cross reactive cocktails of cross-neutralizing MAbs that recognize residues within the receptor binding domain, critical for virus replication and virulence.


Recomendaciones Éticas Y Clínicas Para La Toma De Decisiones En El Entorno Residencial En Contexto De La Crisis De Covid-19


title: Arenaviridae exoribonuclease presents genomic RNA edition capacity

text: The Arenaviridae is a large family of viruses causing both acute and persistent infections and causing significant public health concerns in afflicted regions. A “trademark” of infection is the quick and efficient immuno-suppression mediated in part by a 3’-5’ RNA exonuclease domain (ExoN) of the Nucleoprotein (NP). Mopeia virus, the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We have recently reported the crystal structure of the Mopeia virus ExoN domain, which presents a conserved fold and active site. In the present study, we show that the ExoN activity rules out a direct link between ExoN activity and alteration of the host innate immunity. We found that the Arenavirus ExoN, however, is able to excise mis-incorporated bases present at the 3’-end of double stranded RNA. ExoN(-) arenaviruses cultured in cells dampened in innate immunity still replicated in spite of a significant reduction in the viral charge over several passages. The remaining ExoN(-) virus population showed an increased base substitution rate on a narrow nucleotide spectrum, linking the ExoN activity to genome editing. Since, the Arenavirus ExoN belongs to the same nuclease family as that of the nsp14 coronavirus ExoN ; which has been recently shown to promote viral RNA synthesis proofreading; we propose that Arenavirus ExoN is involved in a “limited RNA editing” mechanism mainly controlled by structural constraints and a low mutational/fitness ratio. Only Arenaviridae and Coronaviridae encode a 3’-5’ RNA exonuclease domain (ExoN) in their genome. This activity is either used to counteract the innate immunity response during viral infection or to ensure genome stability during replication. Mopeia virus (MOPV), the eastern African counterpart of Lassa virus, carries such ExoN domain, but does not suppress the host innate immunity. We studied MOPV ExoN activity both in vitro and in cellula to assess the role of ExoN MOPV and found that the Arenaviral ExoN is fully active on dsRNA, and is able like the one of Coronaviridae to excise a mismatched base. We measured genetic stability and found evidence of a limited spectrum of RNA synthesis proofreading mechanism, together with a strongly impacted viral replication. We propose that the Arenaviral ExoN is involved in a functional check of the conserved RNA structures of the viral genome.


title: Can Stem Cells Beat COVID-19: Advancing Stem Cells and Extracellular Vesicles Toward Mainstream Medicine for Lung Injuries Associated With SARS-CoV-2 Infections

text: A number of medicines are currently under investigation for the treatment of COVID-19 disease including anti-viral, anti-malarial, and anti-inflammatory agents. While these treatments can improve patient's recovery and survival, these therapeutic strategies do not lead to unequivocal restoration of the lung damage inflicted by this disease. Stem cell therapies and, more recently, their secreted extracellular vesicles (EVs), are emerging as new promising treatments, which could attenuate inflammation but also regenerate the lung damage caused by COVID-19. Stem cells exert their immunomodulatory, anti-oxidant, and reparative therapeutic effects likely through their EVs, and therefore, could be beneficial, alone or in combination with other therapeutic agents, in people with COVID-19. In this review article, we outline the mechanisms of cytokine storm and lung damage caused by SARS-CoV-2 virus leading to COVID-19 disease and how mesenchymal stem cells (MSCs) and their secreted EVs can be utilized to tackle this damage by harnessing their regenerative properties, which gives them potential enhanced clinical utility compared to other investigated pharmacological treatments. There are currently 17 clinical trials evaluating the therapeutic potential of MSCs for the treatment of COVID-19, the majority of which are administered intravenously with only one clinical trial testing MSC-derived exosomes via inhalation route. While we wait for the outcomes from these trials to be reported, here we emphasize opportunities and risks associated with these therapies, as well as delineate the major roadblocks to progressing these promising curative therapies toward mainstream treatment for COVID-19.


title: Infectious Bronchitis Virus Variants: Molecular Analysis and Pathogenicity Investigation

text: Infectious bronchitis virus (IBV) variants constantly emerge and pose economic threats to poultry farms worldwide. Numerous studies on the molecular and pathogenic characterization of IBV variants have been performed between 2007 and 2017, which we have reviewed herein. We noted that viral genetic mutations and recombination events commonly gave rise to distinct IBV genotypes, serotypes and pathotypes. In addition to characterizing the S1 genes, full viral genomic sequencing, comprehensive antigenicity, and pathogenicity studies on emerging variants have advanced our understanding of IBV infections, which is valuable for developing countermeasures against IBV field outbreaks. This review of IBV variants provides practical value for understanding their phylogenetic relationships and epidemiology from both regional and worldwide viewpoints.


title: CCR5 ameliorates Japanese encephalitis via dictating the equilibrium of regulatory CD4(+)Foxp3(+) T and IL-17(+)CD4(+) Th17 cells

text: BACKGROUND: CCR5 is a CC chemokine receptor involved in the migration of effector leukocytes including macrophages, NK, and T cells into inflamed tissues. Also, the role of CCR5 in CD4(+)Foxp3(+) regulatory T cell (Treg) homing has recently begun to grab attention. Japanese encephalitis (JE) is defined as severe neuroinflammation of the central nervous system (CNS) following infection with mosquito-borne flavivirus JE virus. However, the potential contribution of CCR5 to JE progression via mediating CD4(+)Foxp3(+) Treg homing has not been investigated. METHODS: Infected wild-type (Ccr5(+/+)) and CCR5-deficient (Ccr5(−/−)) mice were examined daily for mortality and clinical signs, and neuroinflammation in the CNS was evaluated by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, NK- and JEV-specific T cell responses were analyzed. Adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs was used to evaluate the role of Tregs in JE progression. RESULTS: CCR5 ablation exacerbated JE without altering viral burden in the extraneural and CNS tissues, as manifested by increased CNS infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Compared to Ccr5(+/+) mice, Ccr5(−/−) mice unexpectedly showed increased responses of IFN-γ(+)NK and CD8(+) T cells in the spleen, but not CD4(+) T cells. More interestingly, CCR5-ablation resulted in a skewed response to IL-17(+)CD4(+) Th17 cells and correspondingly reduced CD4(+)Foxp3(+) Tregs in the spleen and brain, which was closely associated with exacerbated JE. Our results also revealed that adoptive transfer of sorted CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice could ameliorate JE progression without apparently altering the viral burden and CNS infiltration of IL-17(+)CD4(+) Th17 cells, myeloid-derived Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. Instead, adoptive transfer of CCR5(+)CD4(+)Foxp3(+) Tregs into Ccr5(−/−) mice resulted in increased expression of anti-inflammatory cytokines (IL-10 and TGF-β) in the spleen and brain, and transferred CCR5(+) Tregs were found to produce IL-10. CONCLUSIONS: CCR5 regulates JE progression via governing timely and appropriate CNS infiltration of CD4(+)Foxp3(+) Tregs, thereby facilitating host survival. Therefore, this critical and extended role of CCR5 in JE raises possible safety concerns regarding the use of CCR5 antagonists in human immunodeficiency virus (HIV)-infected individuals who inhabit regions in which both HIV and flaviviruses, such as JEV and West Nile virus, are endemic.


title: Marked Up-Regulation of ACE2 in Hearts of Patients with Obstructive Hypertrophic Cardiomyopathy: Implications for SARS-CoV-2-Mediated COVID-19

text: Abstract Objective To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls. Patients and Methods RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and from 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All HCM patients were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time PCR (qRT-PCR) and Western blot. This study was started on January 1, 1999 and final analysis was completed on April 20, 2020. Results Overall, 22% of the transcriptome (8443 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4-6% of the transcriptome exhibiting differential expression between genotypic subgroups. qRT-PCR confirmed differential expression in 92% of tested transcripts. Notably, in the context of COVID-19, the transcript for ACE2, a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change 3.53, q-value=1.30x10-23), which was confirmed with qRT-PCR in triplicate (fold-change 3.78; p=5.22x10-4), and Western blot confirmed a >5-fold over-expression of ACE2 protein (fold-change 5.34, p=1.66x10-6). Conclusions Over 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM indicating perhaps the heart’s compensatory effort to mount an anti-hypertrophic, anti-fibrotic response. However, given that the SARS-CoV-2 uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart.


title: A comparison study of SARS‐CoV‐2 IgG antibody between male and female COVID‐19 patients: A possible reason underlying different outcome between sex

text: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in China at the end of 2019 has spread throughout the world and caused many thousands of deaths. The previous study reported a higher severe status rate and mortality rate in male patients in China. However, the reason underlying this difference has not been reported. The convalescent plasma containing a high level of SARS‐CoV‐2 immunoglobulin G (IgG) antibody has been used in clinical therapy and achieved good effects in China. In this study, to compare the differences of the SARS‐CoV‐2 IgG antibody between male and female patients, a total number of 331 patients confirmed SARS‐CoV‐2 infection were enrolled. The serum of these patients was collected during hospitalization and detected for the SARS‐CoV‐2 IgG antibody. Our data showed that the concentration of IgG antibody in mild, general, and recovering patients showed no difference between male and female patients. In severe status, compared with male patients, there were more female patients having a relatively high concentration of serum SARS‐CoV‐2 IgG antibody. In addition, the generation of IgG antibody in female patients was stronger than male patients in disease early phase. Our study identified a discrepancy in the SARS‐CoV‐2 IgG antibody level in male and female patients, which may be a potential cause leading to a different outcome of Coronavirus Disease 2019 between sex.


title: Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada

text: PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT(3) antagonists are recommended over dexamethasone.


docid: pxggjaby

title: Modern mRNA Proofreading and Repair: Clues that the Last Universal Common Ancestor Possessed an RNA Genome?

text: RNA repair has now been demonstrated to be a genuine biological process and appears to be present in all three domains of life. In this article, we consider what this might mean for the transition from an early RNA-dominated world to modern cells possessing genetically encoded proteins and DNA. There are significant gaps in our understanding of how the modern protein-DNA world could have evolved from a simpler system, and it is currently uncertain whether DNA genomes evolved once or twice. Against this backdrop, the discovery of RNA repair in modern cells is timely food for thought and brings us conceptually one step closer to understanding how RNA genomes were replaced by DNA genomes. We have examined the available literature on multisubunit RNA polymerase structure and function and conclude that a strong case can be made that the Last Universal Common Ancestor (LUCA) possessed a repair-competent RNA polymerase, which would have been capable of acting on an RNA genome. However, while this lends credibility to the proposal that the LUCA had an RNA genome, the alternative, that LUCA had a DNA genome, cannot be completely ruled out.


title: Case Investigations of Infectious Diseases Occurring in Workplaces, United States, 2006–2015

text: Workers in specific settings and activities are at increased risk for certain infectious diseases. When an infectious disease case occurs in a worker, investigators need to understand the mechanisms of disease propagation in the workplace. Few publications have explored these factors in the United States; a literature search yielded 66 investigations of infectious disease occurring in US workplaces during 2006–2015. Reported cases appear to be concentrated in specific industries and occupations, especially the healthcare industry, laboratory workers, animal workers, and public service workers. A hierarchy-of-controls approach can help determine how to implement effective preventive measures in workplaces. Consideration of occupational risk factors and control of occupational exposures will help prevent disease transmission in the workplace and protect workers’ health.


title: Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes

text: African horse sickness virus (AHSV), an orbivirus in the Reoviridae family with nine different serotypes, causes devastating disease in equids. The virion particle is composed of seven proteins organized in three concentric layers, an outer layer made of VP2 and VP5, a middle layer made of VP7, and inner layer made of VP3 that encloses a replicase complex of VP1, VP4, and VP6 and a genome of 10 double-stranded RNA segments. In this study, we sought to develop highly efficacious candidate vaccines against all AHSV serotypes, taking into account not only immunogenic and safety properties but also virus productivity and stability parameters, which are essential criteria for vaccine candidates. To achieve this goal, we first established a highly efficient reverse genetics (RG) system for AHSV serotype 1 (AHSV1) and, subsequently, a VP6-defective AHSV1 strain in combination with in trans complementation of VP6. This was then used to generate defective particles of all nine serotypes, which required the exchange of two to five RNA segments to achieve equivalent titers of particles. All reassortant-defective viruses could be amplified and propagated to high titers in cells complemented with VP6 but were totally incompetent in any other cells. Furthermore, these replication-incompetent AHSV particles were demonstrated to be highly protective against homologous virulent virus challenges in type I interferon receptor (IFNAR)-knockout mice. Thus, these defective viruses have the potential to be used for the development of safe and stable vaccine candidates. The RG system also provides a powerful tool for the study of the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis. IMPORTANCE African horse sickness virus is transmitted by biting midges and causes African horse sickness in equids, with mortality reaching up to 95% in naive horses. Therefore, the development of efficient vaccines is extremely important due to major economic losses in the equine industry. Through the establishment of a highly efficient RG system, replication-deficient viruses of all nine AHSV serotypes were generated. These defective viruses achieved high titers in a cell line complemented with VP6 but failed to propagate in wild-type mammalian or insect cells. Importantly, these candidate vaccine strains showed strong protective efficacy against AHSV infection in an IFNAR(−/−) mouse model.


title: Induction of type I interferon by RNA viruses: cellular receptors and their substrates

text: Virus recognition and induction of interferon (IFN) are critical components of the innate immune system. The Toll-like receptor (TLR) and RIG-I-like receptor families have been characterized as key players in RNA virus detection. Signaling cascades initiated by these receptors are crucial for establishment of an IFN signaling mediated antiviral state in infected and neighboring cells and containment of virus replication as well as initiation of the adaptive immune response. In this review, we focus on the diverse and overlapping functions of these receptors, their physiological importance, and respective viral inducers. We highlight the roles of TRL3, TLR7/8, retinoic acid inducible gene I, melanoma differentiation-associated gene 5, and the RNA molecules responsible for activating these viral sensors.


title: First case of drug‐induced liver injury associated with the use of tocilizumab in a patient with COVID‐19

text: BACKGROUND AND AIMS: Tocilizumab (TCZ; interleukine‐6 receptor antagonist) has been proposed to treat severe forms of Coronavirus disease‐19 (COVID‐19) because interleukine‐6 plays an important role in COVID‐19‐induced cytokine storm. Several clinical studies have shown very good effects of TCZ in patients with COVID‐19, with a few minor side effects reported. Only eight serious liver injuries caused by TCZ were reported before being used in the treatment of patients with COVID‐19. Considering the significantly increased use of TCZ for the treatment of COVID‐19, we would like to warn of its rare but possible serious hepatotoxicity, especially when used together with other hepatotoxic drugs. METHODS: We describe a patient with COVID‐19‐induced cytokine storm who developed drug‐induced liver injury associated with the use of TCZ. RESULTS: One day after TCZ administration, serum transaminase levels increased 40‐fold. Nevertheless, TCZ had a positive effect on clinical and laboratory parameters in cytokine storm, with transaminases values normalizing in 10 days. CONCLUSIONS: This is the first reported case of DILI caused by TCZ in a COVID‐19 patient. Intensive liver function monitoring is imperative in COVID‐19 patients, because of frequent polypharmacy with potentially hepatotoxic drugs.


title: Human Coronaviruses: A Review of Virus–Host Interactions

text: Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs.


title: Treatment efficacy analysis of traditional Chinese medicine for novel coronavirus pneumonia (COVID-19): an empirical study from Wuhan, Hubei Province, China

text: BACKGROUND: A novel coronavirus was identified in December, 2019 in Wuhan, China, and traditional Chinese medicine (TCM) played an active role in combating the novel coronavirus pneumonia (NCP) caused by this fast-spreading virus COVID-19. Thus, we aimed to explore TCM characteristics of clinical efficacy to NCP, as well as to optimize Qingfei Paidu decoction (QFPDD) and the recommended formulas to NCP by National Health Commission (NHC). METHODS: Chinese medical sciences theory and clinical application of TCM were analyzed. A total of 54 NCP patients were observed in a hospital from Wuhan, whose clinical characteristics and utilization of Chinese Medicines (CMs) were described. Paired t test was used to measure the change of patients’ hemogram during hospitalization period, indicating the effect of CMs. Multiple linear regression analysis was applied to explore the factors affecting the length of hospital stay. Network pharmacology analysis was applied to figure out the performance of NHC-recommended formulas of five disease stages at levels of compounds, targets and pathways. RESULT: The average length of hospital stay was 8.96 days. Patients over 45 stayed 9.79 days in hospital in average, longer than 7.64 days of patients under 45. Comparing the hemograms between admission and discharge of hospital, the number of leukocytes, neutrophil, lymphocyte and platelet increased, while the numbers of erythrocytes, hemoglobin concentration and hematocrit decreased. According to the standard coefficients of regression, the factor affecting the length of stay for the most was CMs in category of invigorating spleen and removing dampness (ISRD), followed by administrating CMs, male, and cough. Thirty-two CMs were screened after deleting duplication from QFPDD and NHC-recommended formulas. Compound quercetin, luteolin, kaempferol, acacetin etc., were all involved in the treatment of various disease stages on the compound level both in generality and individuality. CONCLUSION: TCM has a systemic theoretical understanding on the pathological evolution and a positive clinical efficacy on NCP. The CMs of ISRD improved patients’ recovery, suggesting the importance of regulating intestinal function and keeping microenvironmental balance in TCM treatment of NCP. The active compounds from QFPDD and NHC-recommended formulas contribute to recovery of varied disease progresses during TCM treating NCP.


title: COVID-19 and ENT Pediatric otolaryngology during the COVID-19 pandemic. Guidelines of the French Association of Pediatric Otorhinolaryngology (AFOP) and French Society of Otorhinolaryngology (SFORL)

text: ABSTRACT Objective: joint guidelines of the French Pediatric Otolaryngology Society (AFOP) and of the French Society of otorhinolaryngology – Head and neck Surgery (SFORL) on the management of paediatric otolaryngology patients in the context of the COVID-19 pandemic. Methods: A nation-wide workgroup drew guidelines based on clinical experience, national and local recommendations and scientific literature. Proposals may have to be updated on a day-to-day basis. Results: In children, incidence of symptomatic COVID-19 (1-5%) is low and of good prognosis. The indications for nasal flexible endoscopy should be drastically limited. If undertaken, full Personal Protective Equipment (PPE) including FFP2 masks are required, as well as use of a sheath. Saline nose wash done by caregivers other than parents at home should require PPE. Unless foreign body tracheobronchial aspiration is clinically obvious, CT-scan should be performed to confirm indication of endoscopy. Surgical indications should be limited to emergencies and to cases that cannot be delayed beyond 2 months (especially endonasal, endopharyngeal laryngo-tracheobronchial procedures). Postponement should ideally be a group decision and recorded as such in the medical file. Surgical techniques should be adapted to limit the risk of viral dissemination in the air, avoiding the use of drills, microdebriders, monopolar cautery or lasers. Continuous suction should be placed near the operating field. In case of confirmed Covid-19 cases, or suspected cases (or in some centres systematically), PPE with FFP2 mask should be worn by all staff members present in the operating room.


title: Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak

text: The novel COVID-19 outbreak has affected more than 200 countries and territories as of March 2020. Given that patients with cancer are generally more vulnerable to infections, systematic analysis of diverse cohorts of patients with cancer affected by COVID-19 is needed. We performed a multicenter study including 105 patients with cancer and 536 age-matched noncancer patients confirmed with COVID-19. Our results showed COVID-19 patients with cancer had higher risks in all severe outcomes. Patients with hematologic cancer, lung cancer, or with metastatic cancer (stage IV) had the highest frequency of severe events. Patients with nonmetastatic cancer experienced similar frequencies of severe conditions to those observed in patients without cancer. Patients who received surgery had higher risks of having severe events, whereas patients who underwent only radiotherapy did not demonstrate significant differences in severe events when compared with patients without cancer. These findings indicate that patients with cancer appear more vulnerable to SARS-CoV-2 outbreak. SIGNIFICANCE: Because this is the first large cohort study on this topic, our report will provide much-needed information that will benefit patients with cancer globally. As such, we believe it is extremely important that our study be disseminated widely to alert clinicians and patients. This article is highlighted in the In This Issue feature, p. 747


docid: kxerrurc

title: SARS, avian flu, bioterror: infection control awareness for the optometrist

text: The outbreak of severe acute respiratory syndrome (SARS) in 2003 alerted the world to the new face of pandemic disease: highly contagious and fatal infections for which no vaccines are available and current drugs are largely ineffective. As a practitioner providing primary care, the optometrist must be familiar with new and evolving infections present in today’s society. Though they may be viewed as extreme events, scenarios such as the re‐emergence of SARS, the affliction posed by the H5N1 strain of avian influenza and the threat of a bioterrorist attack have all been described. In the event that such events occur, there is the potential for the spread of some highly virulent, transmissible disease. This paper highlights these public health threats and discusses several areas that the optometrist may want to consider regarding infection control in an era in which a highly transmissible disease is being spread from person to person.


title: Inhibition of Zika Virus Replication by Silvestrol

text: The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5′-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.


title: Current Approaches for Diagnosis of Influenza Virus Infections in Humans

text: Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans.


title: Chapter 8 Big Data Applications in Health Sciences and Epidemiology

text: Abstract There is growing concern about our preparedness for controlling the spread of pandemics such as H1N1 Influenza. The dynamics of epidemic spread in large-scale populations are very complex. Further, human behavior, social contact networks, and pandemics are closely intertwined and evolve as the epidemic spread. Individuals’ changing behaviors in response to public policies and their evolving perception of how an infectious disease outbreak is unfolding can dramatically alter normal social interactions. Effective planning and response strategies must take these complicated interactions into account. Mathematical models are key to understanding the spread of epidemics. In this chapter, we discuss a recent approach of diffusion in network models for studying the complex dynamics of epidemics in large-scale populations. Analyzing these models leads to very challenging computational problems. Further, using these models for forecasting epidemic spread and developing public health policies leads to issues that are characteristic of big data applications. The chapter describes the state of the art in computational and big data epidemiology.


title: shRNA-triggered RNAi inhibits expression of NDV NP gene in chicken embryo fibroblast

text: RNA interference (RNAi) technology is a powerful tool for identifying gene functions. Chicken embryo fibroblast (CEF) is an ideal model for studying the interaction between avian viruses and their hosts. To establish a methodological platform for RNAi studies in CEF, three plasmid vectors expressing short hairpin RNAs (shRNAs) targeted against the Newcastle disease virus (NDV) NP gene were constructed. One of them, ndv1, was proven effective on blocking viral replication in CEF and chicken embryos. Four hours prior to infection with NDV, the CEF was transfected with the plasmids by Silent-fect. An unrelated shRNA sequence (HK) was used in mock transfection. The expression of a potent shRNA resulted in up to 2.3, 21.1 and 9.8 fold decreases in NP gene expression at 3, 6 and 9 h post infection in CEF, respectively. The ndv1 was able to completely inhibit the replication of the virus in CEF within 48 post infection. Furthermore, the pathological changes in CEF caused by NDV were delayed, and the degree of pathological changes was lighter compared with the mock transfection in the presence of ndv1. When the complex of shRNA-Silent-fect and NDV was co-injected into the allantoic cavity of 10-day-old embryonated eggs with 10(5) or 10(6) ELD(50) NDV, NDV replication was decreased by 94.14% and 62.15% after 17 h, respectively. These findings suggest that the newly synthesized NP protein is critical for NDV transcription and replication and provide a basis for identifying the functions of viral genes and screening for effective siRNAs against viruses in CEF and chicken embryo by RNAi.


title: Evaluation of Glass Wool Filters and Hollow-Fiber Ultrafiltration Concentration Methods for qPCR Detection of Human Adenoviruses and Polyomaviruses in River Water

text: Pathogenic human viruses cause over half of gastroenteritis cases associated with recreational water use worldwide. They are difficult to concentrate from environmental waters due to low numbers and small sizes. Rapid enumeration of viruses by quantitative polymerase chain reaction (qPCR) has the potential to improve water quality analysis and risk assessment. However, capturing and recovering these viruses from environmental water remain formidable barriers to routine use. Here, we compared the recovery efficiencies of human adenoviruses (HAdVs) and human polyomaviruses (HPyVs) from 10-L river water samples seeded with raw human wastewater (100 and 10 mL) using hollow-fiber ultrafiltration (HFUF) and glass wool filter (GWF) methods. The mean recovery efficiencies of HAdVs in river water samples through HFUF were 36 and 86 % for 100 and 10 mL of seeded human wastewater, respectively. In contrast, the estimated mean recovery efficiencies of HAdVs in river water samples through GWF were 1.3 and 3 % for 100 and 10 mL seeded raw human wastewater, respectively. Similar trends were also observed for HPyVs. Recovery efficiencies of HFUF method were significantly higher (P < 0.05) than GWF for both HAdVs and HPyVs. Our results clearly suggest that HFUF would be a preferred method for concentrating HAdVs and HPyVs from river water followed by subsequent detection and quantification with PCR/qPCR assays.


title: Folding and Quality Control of Glycoproteins

text: Folding of proteins is essential so that they can exert their functions. For proteins that transit the secretory pathway, folding occurs in the endoplasmic reticulum (ER) and various chaperone systems assist in acquiring their correct folding/subunit formation. N-glycosylation is one of the most conserved posttranslational modification for proteins, and in eukaryotes it occurs in the ER. Consequently, eukaryotic cells have developed various systems that utilize N-glycans to dictate and assist protein folding, or if they consistently fail to fold properly, to destroy proteins for quality control and the maintenance of homeostasis of proteins in the ER.


title: Is SARS‐CoV‐2 transfusion transmitted?

text: See article on page 1119–1122, in this issue


title: Covid‐19 health crisis and lockdown associated with high level of sleep complaints and hypnotic uptake at the population level

text: The Covid‐19 pandemic has disrupted the habits of billions of people around the world. Lockdown at home is mandatory, forcing many families, each member with their own sleep–wake habits, to spend 24 hr a day together, continuously. Sleep is crucial for maintaining immune systems and contributes deeply to physical and psychological health. To assess sleep problems and use of sleeping pills, we conducted a cross‐sectional study of a representative sample of the general population in France. The self‐reported sleep complaint items, which covered the previous 8 days, have been used in the 2017 French Health Barometer Survey, a cross‐sectional survey on various public health issues. After 2 weeks of confinement, 74% of the participants (1,005 subjects) reported trouble sleeping compared with a prevalence rate of 49% in the last general population survey. Women reported more sleeping problems than men, with greater frequency or severity: 31% vs. 16%. Unusually, young people (aged 18–34 years) reported sleep problems slightly more frequently than elderly people (79% vs. 72% among those aged 35 or older), with 60% of the younger group reporting that these problems increased with confinement (vs. 51% of their elders). Finally, 16% of participants reported they had taken sleeping pills during the last 12 months, and 41% of them reported using these drugs since the lockdown started. These results suggest that the COVID crisis is associated with severe sleep disorders among the French population, especially young people.


title: Cytokine storm and immunomodulatory therapy in COVID-19: role of chloroquine and anti-IL-6 monoclonal antibodies

text: • Discussion of the role of immunomodulatory agents to reduce the cytokine storm in severe cases of COVID-19. • Potential immunomodulatory agents currently used in the treatment of COVID-19 (chloroquine, hydroxychloroquine and tocilizumab) are discussed. • Other immunomodulatory agents with good safety profiles may be considered for use in combination with antiviral drugs for the treatment of severe or critical cases of COVID-19.


title: DETECTION OF NON-INFLUENZA VIRUSES IN ACUTE RESPIRATORY INFECTIONS IN CHILDREN UNDER FIVE-YEAR-OLD IN COTE D’IVOIRE (JANUARY – DECEMBER 2013)

text: BACKGROUND: Influenza sentinel surveillance in Cote d’Ivoire showed that 70% of Acute Respiratory Infections (ARI) cases remained without etiology. This work aims to describe the epidemiological, clinical, and virological pattern of ARI that tested negative for influenza virus, in children under five years old. MATERIALS AND METHODS: one thousand and fifty nine samples of patients presenting influenza Like Illness (ILI) or Severe Acute Respiratory Infections (SARI) symptoms were tested for other respiratory viruses using multiplex RT-PCR assays targeting 10 respiratory viruses. RESULTS: The following pathogens were detected as follows, hRV 31,92% (98/307), hRSV 24.4% (75/329), PIV 20.5% (63/307), HCoV 229E 12,05% (37/307), hMPV 6.2% (19/307), HCoVOC43 1.0% (3/307) and EnV 1.0% (3/307). Among the 1,059 specimens analyzed, 917 (86.6%) were ILI samples and 142 (23.4%) were SARI samples. The proportion of children infected with at least one virus was 29.8% (273/917) in ILI cases and 23.9% (34/142) in SARI cases. The most prevalent viruses, responsible for ILI cases were hRV with 35.89% (98/273) and hRSV in SARI cases with 41.2% (14/34) of cases. Among the 1,059 patients, only 22 (2.1%) children presented risk factors related to the severity of influenza virus infection. CONCLUSION: This study showed that respiratory viruses play an important role in the etiology of ARI in children. For a better understanding of the epidemiology of ARI and improved case management, it would be interesting in this context to expand the surveillance of influenza to other respiratory viruses.


docid: cqicfhdn

title: Specific Considerations for Sonographers When Performing Echocardiograms During the 2019 Novel Coronavirus Outbreak: Supplement to the American Society of Echocardiography Statement

text: Sonographers need to be familiar with and prepared to implement strategies for reducing the risk of exposure to and transmission of the COVID-19 virus. Strategies to employ can be grouped into three broad categories: (1) whom to scan, (2) where to scan, and (3) how to scan. Whom to scan addresses sonographer strategies for determining essential and emergent scan status. Where to scan addresses sonographer practice strategies for selecting equipment, use of rooms, portable examinations, and training personnel. How to scan addresses the topics of scanning techniques (tailored protocols, right-handed scanning, use of barrier devices) and equipment cleaning and disinfecting.


Visceral Leishmaniasis diagnosis: a rapid test is a must at the hospital bedside


title: A molecular epidemiological study of human parainfluenza virus type 3 at a tertiary university hospital during 2013–2015 in Catalonia, Spain

text: Abstract Human parainfluenza virus type 3 (HPIV-3) is one of the most common respiratory viruses particularly among young children and immunocompromised patients. The seasonality, prevalence and genetic diversity of HPIV-3 at a Spanish tertiary-hospital from 2013 to 2015 are reported. HPIV-3 infection was laboratory-confirmed in 102 patients (76%, under 5 years of age). Among <5 years-old patients, 9 (11.5%) were under any degree of immunosuppression, whereas this percentage was significantly higher (19; 79.2%) among patients older than 5 years. HPIV-3 was detected at varying levels, but mainly during spring and summer. All characterized HN/F sequences fell within C1b, C5 and in other two closely C3a-related groups. Furthermore, a new genetic lineage (C1c) was described. Genetic similarity and epidemiological data confirmed some nosocomial infections, highlighting the importance of the HPIV-3 surveillance, particularly in high-risk patients. This study provides valuable information on HPIV-3 diversity due to the scarce information in Europe.


title: Impaired glucose metabolism in patients with diabetes, prediabetes and obesity is associated with severe Covid‐19

text: BACKGROUND: Identification of risk factors of severe Covid‐19 is critical for improving therapies and understanding SARS‐CoV‐2 pathogenesis. METHODS: We analyzed 184 patients hospitalized for Covid‐19 in Livingston, New Jersey for clinical characteristics associated with severe disease. RESULTS: The majority of Covid‐19 patients had diabetes mellitus (DM) (62.0%), Pre‐DM (23.9%) with elevated FBG, or a BMI > 30 with normal HbA1C (4.3%). SARS‐CoV‐2 infection was associated with new and persistent hyperglycemia in 29 patients, including several with normal HbA1C levels. Forty‐four patients required intubation, which occurred significantly more often in patients with DM as compared to non‐diabetics. CONCLUSIONS: Severe Covid‐19 occurs in the presence of impaired glucose metabolism in patients, including those with DM, PreDM and obesity. Covid‐19 is asociated with elevated FBG and several patients presented with new onset DM or in DKA. The association of dysregulated glucose metabolism and severe Covid‐19 suggests that SARS‐CoV‐2 pathogenesis involves a novel interplay with glucose metabolism. Exploration of pathways by which SARS‐CoV‐2 interacts glucose metabolism is critical for understanding disease pathogenesis and developing therapies. This article is protected by copyright. All rights reserved.


title: Viral Infection in Adults Hospitalized With Community-Acquired Pneumonia Prevalence, Pathogens, and Presentation

text: Background The potential role of respiratory viruses in the natural history of community-acquired pneumonia (CAP) in adults has not been well described since the advent of nucleic amplification tests (NATs). Methods From 2004 to 2006, adults with CAP who were admitted to five hospitals were prospectively enrolled in the study, and clinical data, cultures, serology, and nasopharyngeal swabs were obtained. NATs from swabs were tested for influenza, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), rhinovirus, parainfluenza virus 1–4, coronaviruses (OC43, 229E, and NL63), and adenovirus. Results A total of 193 patients were included; the median age was 71 years, 51% of patients were male, and 47% of patients had severe CAP. Overall, 75 patients (39%) had a pathogen identified. Of these pathogens, 29 were viruses (15%), 38 were bacteria (20%), 8 were mixed (4%), and the rest were “unknown.” Influenza (n = 7), hMPV (n = 7), and RSV (n = 5) accounted for most viral infections; other infections included rhinovirus (n = 4), parainfluenza (n = 3), coronavirus (n = 4), and adenovirus (n = 2). Streptococcus pneumoniae was the most common bacterial infection (37%). Compared with bacterial infection, patients with viral infection were older (76 vs 64 years, respectively; p = 0.01), were more likely to have cardiac disease (66% vs 32%, respectively; p = 0.006), and were more frail (eg, 48% with limited ambulation vs 21% of bacterial infections; p = 0.02). There were few clinically meaningful differences in presentation and no differences in outcomes according to the presence or absence of viral infection. Conclusions Viral infections are common in adults with pneumonia. Easily transmissible viruses such as influenza, hMPV, and RSV were the most common, raising concerns about infection control. Routine testing for respiratory viruses may be warranted for adults who have been hospitalized with pneumonia.


title: Status and Challenges of Public Health Emergency Management in China Related to COVID-19

text: Objective: This study aimed at exploring the current development status and problems of health emergency management in China and provides a reference for improving, constructing, and implementing a public health emergency management system. Methods: Cases of major and severe public health emergencies in China were analyzed along with the relevant health emergency management literature from the last decade. Results: China's health emergency system gradually improved during the study period. Monitoring and early warning systems were significantly strengthened. Material reserves and transfer management systems were constantly improved. However, the operational efficiency of command and decision systems was low, versatile talent accounted for a relatively small proportion, and emergency fund investment was insufficient. Conclusion: Constructing a sound and scientific emergency management mechanism is a lengthy and challenging process. To establish an emergency management mode for public health emergencies that is appropriate for China, it is necessary to solve existing problems and learn from the models and experiences of developed foreign countries.


title: Author response to Letter to the Editor ‘Liver impairment associated with disease progression in COVID‐19 patients’

text: We chose the CAP patients hospitalized in our hospital last year as the control because there was no suitable healthy control group available now. And considering the diverse etiology of CAP, the liver impairment appeared in CAP patients maybe result from ischemia/hypoxia-reperfusion injury, systemic inflammatory response or drug use before hospitalization, besides the pathogen itself.


title: Smoking prevalence and COVID-19 in Europe

text: INTRODUCTION: This ecological study investigates the association between smoking prevalence and COVID-19 occurrence and mortality in 38 European nations as of 30(th) May 2020. METHODS: Data were collected from Our World in Data. Regression analysis was conducted to adjust for potential confounding factors such as economic activity (GDP), the rate of COVID-19 testing, and the stringency of COVID-19 control policies. RESULTS: There was a statistically significant negative association between smoking prevalence and the prevalence of COVID-19 across the 38 European nations after controlling for confounding factors (p = 0.001). A strong association was found between the prevalence of COVID-19 per million people and economic activity (p = 0.002) and the rate of COVID-19 testing (p = 0.0006). Nations with stricter policy enactment showed fewer COVID-19 cases per million people, but the association was not significant (p = 0.122). Delaying policy enactment was associated with a greater prevalence of COVID-19 (p = 0.0535). Evidence of a direct association between smoking prevalence and COVID-19 mortality was not found (p = 0.626). There was a strong positive association between COVID-19 mortality rate and the prevalence of COVID-19 cases (p < 0.0001) as well as the proportion of the population over 65 years of age (p = 0.0034) and a negative association with the rate of COVID-19 testing (p = 0.0023). CONCLUSIONS: We found a negative association between smoking prevalence and COVID-19 occurrence at the population level in 38 European countries. This association may not imply a true or causal relationship, and smoking is not advocated as a prevention or treatment of COVID-19.


title: Nonessential Research in the New Normal: The Impact of COVID-19

text: Nonessential Research in the New Normal: The Impact of Novel Coronavirus Disease (COVID-19).


Simultaneous detection of HSV-1, HSV-2 and VZV in clinical samples by multiplex polymerase chain reaction (MPCR)


title: Detection and analysis of nucleic acid in various biological samples of COVID-19 patients

text: Abstract COVID-19 (corona virus disease 2019) is a kind of acute severe pneumonia caused by 2019-nCoV (2019-nCoV) infection. Since December 2019, it has been found in Wuhan, Hubei Province, and then spread to the whole country. Some parts of the world also showed an outbreak trend [1–3]. Real-time fluorescence quantitative reverse transcriptase polymerase chain reaction (reverse transcriptase-polymerase chain reaction,RT-PCR) and viral gene sequencing are the gold standard for the diagnosis of COVID-19. At present, upper respiratory tract nasopharyngeal swabs are mostly used as nucleic acid detection samples in China, but the positive rate is low. However, there are few reports on clinical application of 2019-nCoV nucleic acid detection in other biological samples. Methods | The East Section of Renmin Hospital of Wuhan University is a designated COVID-19 hospital in Wuhan City, Hubei Province, China. This observation study included 132 patients diagnosed with COVID-19 in the infectious disease areas of the East Section of Renmin Hospital of Wuhan University from 2020.1.31 to 2020.2.29. COVID-19 diagnostic criteria: according to China's 《pneumonia diagnosis and treatment Program of novel coronavirus infection (trial version 7) 》, in accordance with the relevant epidemiological and clinical manifestations, nasopharyngeal swabs real-time fluorescence RT-PCR detection of 2019-nCoV nucleic acid positive, COVID-19 cases were divided into mild, ordinary, severe and severe [4]. The nasopharyngeal swabs of 132 cases of COVID-19 were positive for 2019-nCoV nucleic acid on admission, including 72 males and 60 females, with an average age of 66.7 ± 9.1 years, including 80 cases of common type, 44 cases of severe type and 8 cases of critical type. During the period of admission, under the condition of tertiary protection, nasopharyngeal swabs, sputum, blood, feces and anal swabs of COVID-19 cases were collected many times in the isolation ward for 2019-nCoV nucleic acid detection. All biological samples are sealed and transferred to the laboratory in strict accordance with the standard process. The RT-PCR test kits (BioGerm) were recommended by the Chinese Center for Disease Control and Prevention. The same technician and brand of test kit was used for all RT-PCR testing reported; both internal controls and negative controls were routinely performed with each batch of tests. Results | 132 the results of 2019-nCoV nucleic acid test of various biological samples during the treatment of confirmed COVID-19 cases are as follows: the positive rate of 2019-nCoV nucleic acid test of nasopharyngeal swab is 38.13% (180/472 times), the positive rate of 2019-nCoV nucleic acid test of sputum is 48.68% (148/304 times), the positive rate of blood 2019-nCoV nucleic acid test is 3.03% (4/132 times), and the positive rate of 2019-nCoV nucleic acid test of feces is 9.83% (24/244 times). The positive rate of 2019-nCoV nucleic acid detection in anal swabs is 10.00% (12/120 times). Discussion| In this study, it was found that the positive rate of 2019-nCoV nucleic acid in sputum of 132 patients with COVID-19 was higher than that of nasopharyngeal swabs, and viral nucleic acids were also detected in blood and digestive tract (fecal/anal swabs). Simple detection of nasopharyngeal swab 2019-nCoV nucleic acid detection positive rate is not high, multi-sample 2019-nCoV nucleic acid detection can improve the accuracy, reduce the false negative rate, better guide clinical treatment and evaluate the therapeutic effect.


title: Utility of homology models in the drug discovery process

text: Abstract Advances in bioinformatics and protein modeling algorithms, in addition to the enormous increase in experimental protein structure information, have aided in the generation of databases that comprise homology models of a significant portion of known genomic protein sequences. Currently, 3D structure information can be generated for up to 56% of all known proteins. However, there is considerable controversy concerning the real value of homology models for drug design. This review provides an overview of the latest developments in this area and includes selected examples of successful applications of the homology modeling technique to pharmaceutically relevant questions. In addition, the strengths and limitations of the application of homology models during all phases of the drug discovery process are discussed.


title: Comparing Rapid Scoring Systems in Mortality Prediction of Critically Ill Patients With Novel Coronavirus Disease

text: OBJECTIVES: Rapid and early severity‐of‐illness assessment appears to be important for critically ill patients with novel coronavirus disease (COVID‐19). This study aimed to evaluate the performance of the rapid scoring system on admission of these patients. METHODS: A total of 138 medical records of critically ill patients with COVID‐19 were included in the study. Demographic and clinical characteristics on admission used for calculating Modified Early Warning Score (MEWS) and Rapid Emergency Medicine Score (REMS) and outcomes (survival or death) were collected for each case and extracted for analysis. All patients were divided into two age subgroups (<65 years and ≥65 years). The receiver operating characteristic (ROC) curve analyses were performed for overall patients and both subgroups. RESULTS: The median [25th quartile, 75th quartile] of MEWS of survivors versus nonsurvivors were 1 [1, 2] and 2 [1, 3] and those of REMS were 5 [2, 6] and 7 [6, 10], respectively. In overall analysis, the area under the ROC curve for the REMS in predicting mortality was 0.833 (95% confidence interval [CI] = 0.737 to 0.928), higher than that of MEWS (0.677, 95% CI = 0.541 to 0.813). An optimal cutoff of REMS (≥6) had a sensitivity of 89.5%, a specificity of 69.8%, a positive predictive value of 39.5%, and a negative predictive value of 96.8%. In the analysis of subgroup of patients aged <65 years, the area under the ROC curve for the REMS in predicting mortality was 0.863 (95% CI = 0.743 to 0.941), higher than that of MEWS (0.603, 95% CI = 0.462 to 0.732). CONCLUSION: To our knowledge, this study was the first exploration on rapid scoring systems for critically ill patients with COVID‐19. The REMS could provide emergency clinicians with an effective adjunct risk stratification tool for critically ill patients with COVID‐19, especially for the patients aged <65 years. The effectiveness of REMS for screening these patients is attributed to its high negative predictive value.


title: Changes in epithelial secretory cells and potentiation of neurogenic inflammation in the trachea of rats with respiratory tract infections

text: In rats respiratory tract infections due to Sendai virus and coronavirus usually are transient, but they can have long-lasting consequences when accompanied by Mycoplasma pulmonis infections. Morphological alterations in the tracheal epithelium and a potentiation of the inflammatory response evoked by sensory nerve stimulation (“neurogenic inflammation”) are evident nine weeks after the infections begin, but the extent to which these changes are present at earlier times is not known. In the present study we characterized these abnormalities in the epithelium and determined the extent to which they are present 3 and 6 weeks after the infections begin. We also determined the magnitude of the potentiation of neurogenic inflammation at these times, whether the potentiation can be reversed by glucocorticoids, and whether a proliferation of blood vessels contributes to the abnormally large amount of plasma extravasation associated with this potentiation. To this end, we studied Long-Evans rats that acquired these viral and mycoplasmal infections from other rats. We found that the tracheal epithelium of the infected rats had ten times as many Alcian blue-PAS positive mucous cells as did that of pathogen-free rats; but it contained none of the serous cells typical of pathogen-free rats, so the total number of secretory cells was not increased. In addition, the epithelium of the infected rats had three times the number of ciliated cells and had only a third of the number of globule leukocytes. In response to an injection of capsaicin (150 μg/kg i.v.), the tracheas of the infected rats developed an abnormally large amount of extravasation of two tracers Evans blue dye and Monastral blue pigment, and had an abnormally large number of Monastral blue-labeled venules, particularly in regions of mucosa overlying the cartilaginous rings. This abnormally large amount of extravasation was blocked by dexamethasone (1 mg/day i.p. for 5 days). We conclude that M. pulmonis infections, exacerbated at the outset by viral infections, result within three weeks in the transformation of epithelial serous cells into mucous cells, the proliferation of ciliated cells, and the depletion of globule leukocytes. They also cause a proliferation of mediator-sensitive blood vessels in the airway mucosa, which is likely to contribute to the potentiation of neurogenic inflammation that accompanies these infections.


Economic Evaluations of Public Health Surveillance Systems: a Systematic Review


title: The Impact of COVID-19 on Plastic Surgery Residency Training

text: ABSTRACT: Nowadays didactic and surgical activities for residents in the surgery field are less and less due to an increasing burden of documentation and “non-educational work.” Considering the current lockdown due to the COVID-19 pandemic, it has never been so important to find different ways to allow residents to improve their knowledge. We asked all plastic and esthetic surgery residents in our country to fill out a questionnaire to investigate changes in their didactical activity and analyze problems about their professional growth in the last few months. From the results of such questionnaires, we found that most of the residents feel the decrease in surgical activities during this time is a detrimental factor for their training and that even if all the schools have changed their didactical activities no school has introduced the use of virtual simulators to compensate for the decrease in surgical practice. Actually, the majority of residents use webinars to keep updated, stating that such technologies are useful but not sufficient to analyze plastic surgery topics in depth during COVID-19 lockdown. Virtual interactive tools are well known in different clinical and surgical specialties, and they are considered as a valid support, but it seems that in plastic surgery they are not so used. According to the most recent studies about residents’ didactical program, we have investigated the potential of Anatomage Table in combination with Touch Surgery application as physical and mental aids to bypass the decreased number and kind of surgical interventions performed in this particular time. Anatomage is an academic user-friendly touch screen table; it is used by both medical students and residents to learn human anatomy and to master surgical anatomy. Touch Surgery is an application available on smartphones and tablets that gives the possibility to watch real and virtually designed surgical videos, accompanied by explanatory comments on the surgical phases; they are interactive and give the possibility to check what you have learned through tests administered after virtual classes. In our opinion, these tools represent reliable solutions to improve plastic residents’ training, mostly during the COVID-19 pandemic. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.


CUIDANDO DESDE LA DISTANCIA A TRAVÉS DE VUESTRAS MANOS: UNA REFLEXIÓN SOBRE LAS REDES PROFESIONALES-PERSONALES EN TIEMPOS DE COVID-19


title: Novel Coronavirus Polymerase and Nucleotidyl-Transferase Structures: Potential to Target New Outbreaks

text: [Image: see text] The pandemic outbreak of a new coronavirus (CoV), SARS-CoV-2, has captured the world’s attention, demonstrating that CoVs represent a continuous global threat. As this is a highly contagious virus, it is imperative to understand RNA-dependent-RNA-polymerase (RdRp), the key component in virus replication. Although the SARS-CoV-2 genome shares 80% sequence identity with severe acute respiratory syndrome SARS-CoV, their RdRps and nucleotidyl-transferases (NiRAN) share 98.1% and 93.2% identity, respectively. Sequence alignment of six coronaviruses demonstrated higher identity among their RdRps (60.9%–98.1%) and lower identity among their Spike proteins (27%–77%). Thus, a 3D structural model of RdRp, NiRAN, non-structural protein 7 (nsp7), and nsp8 of SARS-CoV-2 was generated by modeling starting from the SARS counterpart structures. Furthermore, we demonstrate the binding poses of three viral RdRp inhibitors (Galidesivir, Favipiravir, and Penciclovir), which were recently reported to have clinical significance for SARS-CoV-2. The network of interactions established by these drug molecules affirms their efficacy to inhibit viral RNA replication and provides an insight into their structure-based rational optimization for SARS-CoV-2 inhibition.


title: Medical Ethics: Serious Reportable Communicable Diseases

text: Abstract Serious reportable or notifiable diseases are discussed in the context of the International Health Regulations 2005 and its historical development. The relevance of these Regulations and the local legislative reporting requirements to forensic practitioners is outlined and an example of the local reporting requirements in Victoria, Australia is provided.


docid: wbhuafmp

title: Rapid Detection of the Severe Acute Respiratory Syndrome (SARS) Coronavirus by a Loop-Mediated Isothermal Amplification Assay