title: Anticomplementary principles of a Chinese multiherb remedy for the treatment and prevention of SARS

text: Abstract Aim of the study To elucidate the anticomplementary principles of a Chinese multiherb remedy used for the treatment and prevention of SARS, which contains five ingredients of Herba Houttuyniae, Flos Chrysanthemi Indici, Herba Artemisiae Scopariae, Herba Eupatorii and Fructus Tsaoko. Materials and methods The anticomplementary activity was evaluated from hemolytic assays through the classical pathway (CP) and the alternative pathway (AP) of complement system in vitro. Compounds were isolated using bioactivity-guided fractionation and tested in vitro for their complement-inhibiting properties on the CP and AP. HPLC-DAD-ESI-MS was used to assign the isolated compounds in the five ingredient herbs. Results 15 compounds, including chlorogenic acid (1), rutin (2), hyperoside (3), p-hydroxyacephenone (4), scopoletin (5), quercitrin (6) (3R,4R,6S)-3,6-dihydroxy-1-menthene (7), acaciin (8), scoparone (9), luteolin (10), quercetin (11), apigenin (12), acacetin (13), aristolactam (14), and apigenin-7,4′-dimethyl ether (15) were isolated and identified. Nine flavonoids (2, 3, 6, 8, 10–13, 15) were found to show inhibitory effects towards the CP and AP of complement system, luteolin (10) was the most potent with the CH50 and AP50 values of 0.19 and 0.17mM. The bioactive flavonoids were mainly derived from Herba Houttuyniae, Flos Chrysanthemi Indici and Herba Artemisiae Scopariae. Conclusions A Chinese multiherb remedy used for the treatment and prevention of SARS has robust inhibitory effect on complement system through the CP and AP, and its anticomplementary activity could be attributed to the flavonoids present in some ingredient herbs. Luteolin could be a potential anticomplementary agent.


title: Multitask learning for host–pathogen protein interactions

text: Motivation: An important aspect of infectious disease research involves understanding the differences and commonalities in the infection mechanisms underlying various diseases. Systems biology-based approaches study infectious diseases by analyzing the interactions between the host species and the pathogen organisms. This work aims to combine the knowledge from experimental studies of host–pathogen interactions in several diseases to build stronger predictive models. Our approach is based on a formalism from machine learning called ‘multitask learning’, which considers the problem of building models across tasks that are related to each other. A ‘task’ in our scenario is the set of host–pathogen protein interactions involved in one disease. To integrate interactions from several tasks (i.e. diseases), our method exploits the similarity in the infection process across the diseases. In particular, we use the biological hypothesis that similar pathogens target the same critical biological processes in the host, in defining a common structure across the tasks. Results: Our current work on host–pathogen protein interaction prediction focuses on human as the host, and four bacterial species as pathogens. The multitask learning technique we develop uses a task-based regularization approach. We find that the resulting optimization problem is a difference of convex (DC) functions. To optimize, we implement a Convex–Concave procedure-based algorithm. We compare our integrative approach to baseline methods that build models on a single host–pathogen protein interaction dataset. Our results show that our approach outperforms the baselines on the training data. We further analyze the protein interaction predictions generated by the models, and find some interesting insights. Availability: The predictions and code are available at: http://www.cs.cmu.edu/∼mkshirsa/ismb2013_paper320.html Contact: j.klein-seetharaman@warwick.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.


docid: ctdadbbc

title: Effects of the COVID-19 lockdown on human sleep and rest-activity rhythms

text: Blume et al. studied the effects of the COVID-19 lockdown on the mismatch between social and biological sleep-wake timing as well as sleep. Increased flexibility of social schedules reduced the mismatch while sleep quality was reduced, possibly due to increased burden. These adverse effects may be alleviated by daylight exposure and physical exercising.


title: Pathogenicity of a GI-22 genotype infectious bronchitis virus isolated in China and protection against it afforded by GI-19 vaccine

text: Abstract Avian infectious bronchitis (IB) is a globally circulating bird disease caused by infectious bronchitis virus (IBV). In China, the most prevalent IBV genotype is GI-19/QX-like because the protective efficiency of the classical IBV vaccine is low, and new GI-19 vaccines are under development. In 2018, a GI-22 genotype strain CK/CH/LGD/2018 (abbreviated ‘LGD’) was isolated in northern China, which caused 10%–30% morality in H120-vaccinated chickens. A phylogenetic analysis showed that this new isolate displays novel features compared with other earlier-isolated reference strains. To monitor the epidemic trend of IBV in China, the pathogenicity of LGD was first evaluated in 1-day-old specific-pathogen-free chickens. LGD induced classical IBV damage in the trachea and kidney, whereas it also infected and damaged the bursa of Fabricius, an important immune organ of chickens. The efficacy of our earlier-developed GI-19 vaccine, strain SZ200, against LGD was also evaluated in this study. The GI-19 genotype vaccine provided sufficient protection against the new GI-22 genotype strain, and may be a promising candidate vaccine with which to control both wild GI-19 and GI-22 strains in the future.


title: Ball Python Nidovirus: a Candidate Etiologic Agent for Severe Respiratory Disease in Python regius

text: A severe, sometimes fatal respiratory disease has been observed in captive ball pythons (Python regius) since the late 1990s. In order to better understand this disease and its etiology, we collected case and control samples and performed pathological and diagnostic analyses. Electron micrographs revealed filamentous virus-like particles in lung epithelial cells of sick animals. Diagnostic testing for known pathogens did not identify an etiologic agent, so unbiased metagenomic sequencing was performed. Abundant nidovirus-like sequences were identified in cases and were used to assemble the genome of a previously unknown virus in the order Nidovirales. The nidoviruses, which were not previously known to infect nonavian reptiles, are a diverse order that includes important human and veterinary pathogens. The presence of the viral RNA was confirmed in all diseased animals (n = 8) but was not detected in healthy pythons or other snakes (n = 57). Viral RNA levels were generally highest in the lung and other respiratory tract tissues. The 33.5-kb viral genome is the largest RNA genome yet described and shares canonical characteristics with other nidovirus genomes, although several features distinguish this from related viruses. This virus, which we named ball python nidovirus (BPNV), will likely establish a new genus in Torovirinae subfamily. The identification of a novel nidovirus in reptiles contributes to our understanding of the biology and evolution of related viruses, and its association with lung disease in pythons is a promising step toward elucidating an etiology for this long-standing veterinary disease.


Focus on the Crosstalk Between COVID-19 and Urogenital Systems


title: A comparative sequence analysis to revise the current taxonomy of the family Coronaviridae

text: The Coronaviridae family, comprising the Coronavirus and Torovirus genera, is part of the Nidovirales order that also includes two other families, Arteriviridae and Roniviridae. Based on genetic and serological relationships, groups 1, 2 and 3 were previously recognized in the Coronavirus genus. In this report we present results of comparative sequence analysis of the spike (S), envelope (E), membrane (M), and nucleoprotein (N) structural proteins, and the two most conserved replicase domains, putative RNA-dependent RNA polymerase (RdRp) and RNA helicase (HEL), aimed at a revision of the Coronaviridae taxonomy. The results of pairwise comparisons involving structural and replicase proteins of the Coronavirus genus were consistent and produced percentages of sequence identities that were distributed in discontinuous clusters. Inter-group pairwise scores formed a single cluster in the lowest percentile. No homologs of the N and E proteins have been found outside coronaviruses, and the only (very) distant homologs of S and M proteins were identified in toroviruses. Intragroup sequence conservation was higher, although for some pairs, especially those from the most diverse group 1, scores were close or even overlapped with those from the intergroup comparisons. Phylogenetic analysis of six proteins using a neighbor-joining algorithm confirmed three coronavirus groups. Comparative sequence analysis of RdRp and HEL domains were extended to include arterivirus and ronivirus homologs. The pairwise scores between sequences of the genera Coronavirus and Torovirus (22–25% and 21–25%) were found to be very close to or overlapped with the value ranges (12 to 22% and 17 to 25%) obtained for interfamily pairwise comparisons, but were much smaller than values derived from pairwise comparisons within the Coronavirus genus (63–71% and 59–67%). Phylogenetic analysis confirmed toroviruses and coronaviruses to be separated by a large distance that is comparable to those between established nidovirus families. Based on comparison of these scores with those derived from analysis of separate ranks of several multi-genera virus families, like the Picornaviridae, a revision of the Coronaviridae taxonomy is proposed. We suggest the Coronavirus and Torovirus genera to be re-defined as two subfamilies within the Coronavirdae or two families within Nidovirales, and the current three informal coronavirus groups to be converted into three genera within the Coronaviridae.


SARS-CoV-2 detection with CRISPR diagnostics


title: The Emergence of Risk Communication Networks and the Development of Citizen Health-Related Behaviors during the COVID-19 Pandemic: Social Selection and Contagion Processes

text: Amid the novel coronavirus pandemic, a variety of public health strategies have been implemented by governments worldwide. However, the fact that strict government mandates focus on physical distancing does not mean that social connectedness for voluntary risk communication among citizens should be sacrificed. Furthermore, we lack an understanding of citizens’ behaviors regarding the voluntary adoption of public health measures and the control of mental wellbeing in the age of physical distancing. Key variables in the response to the global pandemic are the emergence of risk deliberation networks, voluntary compliance with government guidelines, and the restoration of citizens’ subjective health. However, little is known about how citizens’ health-related behaviors coevolve with social connections for sharing information and discussing urgent pandemic issues. The findings show that selection and social influence mechanisms coexist by affecting each citizen’s health-related behaviors and community-led risk discourses in the face of the urgent health crisis.


title: NMR evidence for oligosaccharide release from the dendritic‐cell specific intercellular adhesion molecule 3‐grabbing non‐integrin‐related (CLEC4M) carbohydrate recognition domain at low pH

text: Dendritic cell‐specific intercellular adhesion molecule 3‐grabbing non‐integrin‐related (DC‐SIGNR), also known as liver/lymph node‐specific intercellular adhesion molecule 3‐grabbing non‐integrin, CLEC4M, CD209L, and CD299, is a Ca(2+)‐dependent lectin that has been implicated in increasing the infection rates of several viruses, including HIV, but the physiological role of DC‐SIGNR in healthy cells is currently not known with certainty. A close homologue of DC‐SIGNR, dendritic‐cell specific intercellular adhesion molecule 3‐grabbing non‐integrin, has been shown to act as a recycling endocytic receptor, which binds pathogens at the cell's surface and then releases them in the low pH environment of endosomal compartments. However, it is currently under debate in the literature as to whether DC‐SIGNR plays a similar role. In this work, we used NMR to explore whether the DC‐SIGNR carbohydrate recognition domain (CRD) shows any pH dependence in its ability to bind carbohydrates and Ca(2+). We found clear evidence of reduced or abolished CRD‐binding affinities for three different glycans at low pH (4.2) as compared to neutral pH (6.8). We also report the assignment of the DC‐SIGNR CRD in the apo form, and use these new results to characterize the degree of structural rearrangement upon binding (or release) of Ca(2+). Finally, we report a differential effect of pH on the affinities of glycans containing mannose exclusively versus glycans containing GlcNAc moieties. Our results lead us to propose that the DC‐SIGNR CRD rapidly and reversibly releases glycan ligands and Ca(2+) at reduced pH (behaviour that would be expected for an endocytic receptor), and that the binding of mannose‐containing oligosaccharides is more strongly affected by pH than the binding of GlcNAc‐containing oligosaccharides.


title: Complete Genome Sequence of a Very Virulent Porcine Epidemic Diarrhea Virus Strain, CH/GDGZ/2012, Isolated in Southern China

text: The classical symptoms of porcine epidemic diarrhea (PED) are acute diarrhea and dehydration. The isolated porcine epidemic diarrhea virus (PEDV) CH/GDGZ/2012 strain was obtained from the feces of diseased pigs in 2012 in southern China. We report the complete genome sequence of strain CH/GDGZ/2012, which might be useful for better understanding the molecular characteristics of this virus.


title: Identification of protein functions using a machine-learning approach based on sequence-derived properties

text: BACKGROUND: Predicting the function of an unknown protein is an essential goal in bioinformatics. Sequence similarity-based approaches are widely used for function prediction; however, they are often inadequate in the absence of similar sequences or when the sequence similarity among known protein sequences is statistically weak. This study aimed to develop an accurate prediction method for identifying protein function, irrespective of sequence and structural similarities. RESULTS: A highly accurate prediction method capable of identifying protein function, based solely on protein sequence properties, is described. This method analyses and identifies specific features of the protein sequence that are highly correlated with certain protein functions and determines the combination of protein sequence features that best characterises protein function. Thirty-three features that represent subtle differences in local regions and full regions of the protein sequences were introduced. On the basis of 484 features extracted solely from the protein sequence, models were built to predict the functions of 11 different proteins from a broad range of cellular components, molecular functions, and biological processes. The accuracy of protein function prediction using random forests with feature selection ranged from 94.23% to 100%. The local sequence information was found to have a broad range of applicability in predicting protein function. CONCLUSION: We present an accurate prediction method using a machine-learning approach based solely on protein sequence properties. The primary contribution of this paper is to propose new PNPRD features representing global and/or local differences in sequences, based on positively and/or negatively charged residues, to assist in predicting protein function. In addition, we identified a compact and useful feature subset for predicting the function of various proteins. Our results indicate that sequence-based classifiers can provide good results among a broad range of proteins, that the proposed features are useful in predicting several functions, and that the combination of our and traditional features may support the creation of a discriminative feature set for specific protein functions.


title: Comprehensive analysis of synonymous codon usage patterns in orf3 gene of porcine epidemic diarrhea virus in China

text: Abstract The ORF3 protein of porcine epidemic diarrhea virus (PEDV) is found to function as an ion channel which influences virus virulence and production. Taking consideration of the importance of PEDV orf3 gene, we have performed comprehensive analysis to investigate its synonymous codon usage patterns. In this study, the results of base composition analysis showed A/T rich and G/C poor in PEDV orf3 genes, and the most abundant base was nucleotide T. The relative synonymous codon usage value in each codon revealed that codon usage bias existed. The mean ENC value of each gene was 48.75, indicating a low codon usage bias, as well as a relatively instable change in PEDV orf3 genes. The general correlation analysis between base composition and codon usage bias indicated that mutational bias has an impact on the PEDV codon usage bias. Neutral analysis suggested that natural selection pressure takes a more important influence than mutational bias in shaping codon usage bias. Moreover, other factors including hydrophobicity and aromaticity have been also found to influence the codon usage variation among the PEDV orf3 genes. This study not only represents the most systematic analysis of codon usage patterns in PEDV orf3 genes, but also provides a basic shaping mechanism of the codon usage bias.


title: Novel coronavirus SARS-CoV-2 and COVID-19. Practice recommendations for obstetric anaesthesia: what we have learned thus far

text: • Pregnancy does not seem to be associated with more severe COVID-19 infections. • Risk of antenatal vertical transmission of COVID-19 is low. • Epidural analgesia should be considered, provided platelet counts are not low. • Droplet precautions are indicated for all women with suspected COVID-19. • Airborne precautions recommended for general anaesthesia or higher risk thereof.


title: Commensal bacteria as a novel delivery system for subunit vaccines directed against agents of bioterrorism

text: Abstract Following the anthrax attacks of 2001 and the recent SARS outbreak, concerns about emerging and re-emerging infectious diseases have catalyzed a renewed interest in developing new vaccination strategies that provide rapid and flexible response options to future threats. Because the probability of encountering one of these exotic agents is unknown, it is essential that new vaccine formulations employ methods that provide effective protection and extremely good safety profiles if they are to be used by either military or civilian populations. One approach, which potentially satisfies these criteria, is the use of live recombinant Gram-positive commensal bacteria as expression vectors. This review provides an overview of the system, its advantages and limitations, and details an example of how Gram-positive commensal bacteria are being developed as a fifth generation vaccine against a Class A biowarfare pathogen, namely smallpox.


title: What’s new in the renin-angiotensin system?: Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus

text: Cellular entry of enveloped viruses is often dependent on attachment proteins expressed on the host cell surface. Viral envelope proteins bind these receptors, and, in an incompletely understood process, facilitate fusion of the cellular and viral membranes so as to introduce the viral core into the cytoplasm. Only a small fraction of viral receptors have been identified so far. Recently, a novel coronavirus was identified as the etiological agent of severe acute respiratory syndrome (SARS). The fusion protein gene of SARS coronavirus (SARS-CoV) was cloned and characterized, and shortly thereafter, angiotensin-converting enzyme 2 (ACE2) was shown to be its functional receptor. Identification of ACE2 as a receptor for SARS-CoV will likely contribute to the development of antivirals and vaccines. It may also contribute to the development of additional animal models for studying SARS pathogenesis, and could help identify the animal reservoir of SARS-CoV.


Addressing excessive pricing concerns in time of the COVID-19 pandemic—a view from South Africa


title: Full-length genome sequencing analysis of avian infectious bronchitis virus isolate associated with nephropathogenic infection

text: Abstract Infectious bronchitis virus (IBV) produces infectious bronchitis (IB) disease in poultry worldwide. In spite of proper vaccinations against the IBV, new IBV strains are continually emerging worldwide. In this study, a new highly virulent nephropathogenic IBV strain named CK/CH/XDC-2/2013 was identified from a vaccinated flock with clinical signs of IB in the Jiangsu province of China. The full-length genome sequence of the isolate was 27,714 nucleotides long, and the genome was organized similarly to classical IBV strains. Minimum divergence, phylogenetic analysis, and distance matrix of the genome showed that the CK/CH/XDC-2/2013 isolate had the highest similarity to the IBV BJ strain. The spike glycoprotein (S) gene had the greatest similarity to the nephropathogenic BJ strain and showed an 8 amino acid insertion (YSNGNSDV) at 73 to 80 sites and 3 amino acid deletion at sites 126 to 128 compared to the IBV vaccine strains. A recombination analysis of the S gene showed that the new isolate evolved from the IBV BJ strain and the KM91 vaccine strain. An animal challenge experiment showed a mortality of 60 to 80% in early-age chickens by different inoculation routes. Pathological examinations of the kidneys revealed inflammation, distention with uric acid deposits, and tubular degeneration. It indicated that the CK/CH/XDC-2/2013 isolate has robust kidney tissue tropism, and new nephropathogenic IBV strains are continuously evolving in China.


title: Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase

text: SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3’-fluoro-3’-deoxythymidine triphosphate, 3’-azido-3’-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results offer a strong molecular basis for these nucleotide analogues to be evaluated as potential therapeutics for COVID-19.


title: Gemcitabine, a broad-spectrum antiviral drug, suppresses enterovirus infections through innate immunity induced by the inhibition of pyrimidine biosynthesis and nucleotide depletion

text: Gemcitabine, an anti-cancer chemotherapy drug, has additionally shown the antiviral activity against a broad range of viruses and we also have previously reported its synergistic antiviral activity with ribavirin against enteroviruses. As a cytidine analog, gemcitabine has been reported to have an inhibitory activity on the pyrimidine biosynthesis. In addition, a few inhibitors of the pyrimidine biosynthesis have shown to induce the innate immunity in a yet-to-be-determined manner and inhibit the virus infection. Thus, we also investigated whether the anti-enteroviral activity of gemcitabine is mediated by innate immunity, induction of which is related with the inhibition of the pyrimidine synthesis. In this study, we found that the addition of exogenous cytidine, uridine and uridine mono-phosphate (UMP) effectively reversed the antiviral activity of gemcitabine in enterovirus-infected as well as enteroviral replicon-harboring cells, demonstrating gemcitabine’s targeting of the salvage pathway. Moreover, the expression of several interferon (IFN)-stimulated genes (ISGs) was significantly induced by the treatment of gemcitabine, which was also suppressed by the co-treatment with cytidine. These results suggest that the antiviral activity of gemcitabine involves ISGs induced by the inhibition of the pyrimidine biosynthesis.


title: Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages

text: Background: Information about the clinical characteristics and mortality of patients with coronavirus disease 2019 at different ages is limited. Results: The older group had more patients with dyspnea and fewer patients with fever and muscle pain. Older patients had more underlying diseases, secondary infection, myocardial injury, renal dysfunction, coagulation dysfunction, and immune dysfunction on admission. More older patients received immunoglobulin therapy and mechanical ventilation. The proportions of patients with multiple organ injuries, critically ill patients and death increased significantly with age. The older groups had higher cumulative death risk than the younger group. Hypertension, cerebrovascular disease, comorbidities, acute cardiac injury, shock and complications are independent predictors of death. Conclusions: The symptoms of the elderly patients were more atypical, with more comorbidities, secondary infection, organ injuries, immune dysfunction and a higher risk of critical illness. Older age was an important risk factor for mortality. Methods: 1000 patients diagnosed with coronavirus disease 2019 from January 1, 2020 to February 14, 2020 were enrolled. According to age, patients were divided into group 1 (<60 years old), group 2 (60-74 years old) and group 3 (≥75 years old). The clinical symptoms, first laboratory results, CT findings, organ injuries, disease severity and mortality were analyzed.


title: Detection of Severe Acute Respiratory Syndrome (SARS) Coronavirus Nucleocapsid Protein Using AlGaN/GaN High Electron Mobility Transistors

text: AlGaN/GaN high electron mobility transistors (HEMTs) were used to detect the SARS coronavirus (SARS-CoV) nucleocapsid protein interaction without fluorescent labeling. The detection limit in our system was approximately 0.003 nM of protein sample. Our result showed that this technique was more competitive than isotope-labeling EMSA. We demonstrated AlGaN/GaN was highly potential in constructing a semiconductor-based-sensor binding assay to extract the dissociation constants of nucleic acid-protein interaction.


title: Rheostat positions: A new classification of protein positions relevant to pharmacogenomics

text: To achieve the full potential of pharmacogenomics, one must accurately predict the functional outcomes that arise from amino acid substitutions in proteins. Classically, researchers have focused on understanding the consequences of individual substitutions. However, literature surveys have shown that most substitutions were created at evolutionarily conserved positions. Awareness of this bias leads to a shift in perspective, from considering the outcomes of individual substitutions to understanding the roles of individual protein positions. Conserved positions tend to act as “toggle” switches, with most substitutions abolishing function. However, nonconserved positions have been found equally capable of affecting protein function. Indeed, many nonconserved positions act like functional dimmer switches (“rheostat” positions): this is revealed when multiple substitutions are made at a single position. Each substitution has a different functional outcome; the set of substitutions spans a range of outcomes. Finally, some nonconserved positions appear neutral, capable of accommodating all amino acid types without modifying function. This paper reviews the currently-known properties of rheostat positions, with examples shown for pyruvate kinase, organic anion transporting polypeptide 1B1, the beta-lactamase inhibitory protein, and angiotensin-converting enzyme 2. Outcomes observed for rheostat positions have implications for the rational design of drug analogs and allosteric drugs. Furthermore, this new framework—comprising three types of protein positions—provides a new approach to interpreting disease and population-based databases of amino acid changes. In conclusion, although a full understanding of substitution outcomes at rheostat positions poses a challenge, utilization of this new frame of reference will further advance the application of pharmacogenomics.


title: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

text: Abstract Background Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. Patients and methods French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.


title: Factors Influencing the Emergence of New (and “Old”) Diseases

text: Since its introduction in 1992, the paradigm that views the emergence of new human infections as a product of man-made ‘factors of emergence’ has been widely adopted. However, only some of these factors have been studied in depth. This article reviews three factors that have been characterized scientifically: changes in land use, travel and trade, and microbial adaptation and change. The introduction of new factors by the Institute of Medicine has created overlapping of domains for research. To adequately define the operation of man-made factors will require careful multidisciplinary research, and the development and testing of metrics to describe factors that operate alone and with other factors in the emergence of new infections.


title: The Assessment of the HSR Impacts on Spanish Tourism: An Approach Based on Multivariate Panel Data Analysis

text: Abstract Literature review shows that little research has done so far to estimate how tourism indicators are affected by new High Speed Rail (HSR) lines. In 2012, a multivariate panel analysis developed by Chen and Haynes was applied to the Chinese regions to quantify the HSR impact on tourism output. The Chinese experience confirmed that, during the period 1999-2010, emerging high speed rail services did have significant positive impacts on boosting tourism in China. Since them, no similar empirical tool has ever been tested in Europe. The aim of this paper is to analyze and validate the suitability of this tool to assess empirically the effects of HSR on Spanish tourism during the period 1999-2014, and to enhance the abovementioned model with a tourism database. With more than 20 years’ HSR experience, and operating the longest HSR network in Europe (2,900 km), Spain offers a good scenario for this model application because Spanish tourism sector represents 10.2% of its gross domestic product (GDP). Results clearly show that there is a direct linkage between the evolution of certain Spanish tourism outputs and the construction of the HSR network. However, authorś recommendations include future new research on some variables limitations like the type of tourism output considered or the consideration of alternative explanatory indicators.


title: Les nouveaux traitements de la stéatohépatite non-alcoolique

text: Résumé La stéatohépatite non-alcoolique (NASH) est une maladie du foie responsable de complications et de mortalité de cause hépatique (fibrose, cirrhose, hépatocarcinome) et extra-hépatique (insulinorésistance, maladies cardiovasculaires). Actuellement, il n’existe pas de traitement approuvé dans cette indication. Toutefois, une perte de poids de 5 à 10% du poids initial permet d’améliorer l’histologie hépatique. Cet objectif est cependant soit difficile à atteindre chez tous les patients soit peu efficace ou pas indiqué en cas de diagnostic de la maladie à un stade de cirrhose irréversible. Différents médicaments à notre disposition dans le contexte dysmétabolique sont présentés (statines, metformine,…) avec leur impact sur la maladie hépatique. Récemment, de nombreux traitements à l’étude ont donné des résultats modestes mais encourageants. Plusieurs composés testés en phase 2 sont expliqués dans cet article dont les agonistes FXR et TGR5, agonistes PPARα/δ/γ, le FGF21 recombinant, l’analogue du FGF19, l’agoniste du récepteur thyroïdien β1, les agonistes GLP-1, les inhibiteurs de la lipogenèse, l’antagoniste CCR2/5… Les résultats les plus avancés concernent l’évaluation intermédiaire de l’étude de phase 3 de l’acide obéticholique (agoniste FXR) qui a notamment confirmé une régression de la fibrose hépatique avec ce traitement. Quatre autres composés sont actuellement également testés en phase 3. L’article fait également le point sur le bénéfice potentiel d’une combinaison de traitements. D’autres pistes thérapeutiques comme la chirurgie de l’obésité, la modulation du microbiote et l’endoscopie bariatrique sont exposés. Abstract Non-alcoholic steatohepatitis (NASH) is a liver disease responsible for complications and mortality from hepatic (fibrosis, cirrhosis, hepatocellular carcinoma) and extrahepatic (insulin resistance, cardiovascular diseases) causes. Currently, there is no approved treatment for this indication. However, a weight loss of 5 to 10% of the initial body weight is able to improve liver histology. However, it is difficult to achieve in all patients or ineffective / not indicated if the disease is diagnosed at an irreversible cirrhosis stage. Different drugs available in the dysmetabolic context are presented (statins, metformin, etc.) with their impact on liver disease. Recently, numerous agents have shown modest but positive results. Several compounds tested in phase 2 trials are explained in this article including FXR or TGR5 agonists, PPARα/δ/γ agonists, recombinant FGF21, FGF19 analog, thyroid receptor agonist β1, GLP-1 agonists, inhibitors of lipogenesis, CCR2/5 antagonist… The most advanced results concern the interim analysis of the phase 3 study on obeticholic acid (FXR agonist) which notably confirmed a regression of hepatic fibrosis with this treatment. Four other compounds are also currently tested in phase 3 trials. The multi-mechanistic strategy of a combination therapy is also discussed. Other therapeutic approaches such as obesity surgery, microbiota modulation and bariatric endoscopy are exposed.


title: Coronavirus-Induced Membrane Fusion Requires the Cysteine-Rich Domain in the Spike Protein

text: Abstract The spike glycoprotein of mouse hepatitis virus strain A59 mediates the early events leading to infection of cells, including fusion of the viral and cellular membranes. The spike is a type I membrane glycoprotein that possesses a conserved transmembrane anchor and an unusual cysteine-rich (cys) domain that bridges the putative junction of the anchor and the cytoplasmic tail. In this study, we examined the role of these carboxyl-terminal domains in spike-mediated membrane fusion. We show that the cytoplasmic tail is not required for fusion but has the capacity to enhance membrane fusion activity. Chimeric spike protein mutants containing substitutions of the entire transmembrane anchor and cys domain with the herpes simplex virus type 1 glycoprotein D (gD-1) anchor demonstrated that fusion activity requires the presence of the A59 membrane-spanning domain and the portion of the cys domain that lies upstream of the cytoplasmic tail. The cys domain is a required element since its deletion from the wild-type spike protein abrogates fusion activity. However, addition of the cys domain to fusion-defective chimeric proteins was unable to restore fusion activity. Thus, the cys domain is necessary but is not sufficient to complement the gD-1 anchor and allow for membrane fusion. Site-specific mutations of conserved cysteine residues in the cys domain markedly reduce membrane fusion, which further supports the conclusion that this region is crucial for spike function. The results indicate that the carboxyl-terminus of the spike transmembrane anchor contains at least two distinct domains, both of which are necessary for full membrane fusion.


title: DFT studies on vibrational and electronic spectra, HOMO–LUMO, MEP, HOMA, NBO and molecular docking analysis of benzyl-3-N-(2,4,5-trimethoxyphenylmethylene)hydrazinecarbodithioate

text: Benzyl-3-N-(2,4,5-trimethoxyphenylmethylene)hydrazinecarbodithioate (compound 1) is a bidentate and nitrogen-sulfur containing Schiff base, which has been synthesized by the condensation reaction of S-benzylndithiocarbazate and 2,4,5-trimethoxybenzaldehyde. The theoretical calculations of the mentioned compound have been carried out using the more popular density functional theory method, Becke-3-Parameter-Lee-Yang-Parr (B3LYP) in 6-31G+(d,p) basis set. The computational results of the compound were compared with the obtained experimental value. Moreover, the highest occupied molecular orbital, the lowest unoccupied molecular orbital, molecular electrostatic potential, chemical reactivity parameters and natural bond orbital of the optimized structure have been evaluated at the same level of theory. Furthermore, the UV–Vis spectrum of the compound has been carried out for the better understanding of electronic absorption spectra with the help of the time-dependent density functional theory at room temperature. Besides, the molecular docking simulation of the mentioned molecule with target protein was also investigated. In addition, in silico studies were performed to predict absorption, distribution, metabolism, excretion and toxicity profiles of the designed compound. The results indicated that the theoretical data have well correlated with the observed values. The narrow frontier orbital gap indicated that the eventual charge transfer interaction occurs within the studied molecule and showed high chemical reactivity. The global reactivity values showed that the compound is soft molecule, electrophilic species and has strong binding ability with biomolecules. The molecular electrostatic potential structure indicated that the negative and positive potential sites are around electronegative atoms and hydrogen atoms of studied compound, respectively. The natural bond orbital data revealed that the compound contains 97.42% Lewis and 2.58% non-Lewis structure. The intra and inter-molecular charge transfers process occur within the studied compound. The studied compound showed more binding energy (−6.0 kcal/mol) with target protein than hydroxychloroquine (−5.6 kcal/mol). The absorption, distribution, metabolism, excretion and toxicity investigation predicted that the compound has good drug like character.


title: Activity screening and structure–activity relationship of the hit compounds targeting APN/CD13

text: Aminopeptidase N (APN) plays an important role in tumor progression, which participates in the progress such as proliferation, attachment, angiogenesis, and tumor invasion. All of this makes APN as a good chemical therapeutic anti‐tumor target. In this study, a series of chemically synthesized APN inhibitors were tested for the anti‐tumor activities, and three most effective compounds were chosen according to the MTT assay. Then, the enzyme inhibitory, anti‐tumor, specificity, angiogenesis, and invasion were determined to evaluate the activity of these three compounds. All compounds can markedly inhibit the enzyme activity of APN, angiogenesis of endothelial cells, and the invasion of ES‐2 cells. And it had little effect on the viability of K562 which express low level of APN. This data indicated that the tested compounds were APN hit compounds. We also did kinetic assay to determine the inhibition constant and constructed a three‐dimensional quantitative structure–activity relationship model to analyze the structure–activity relationship to direct the further design of novel APN inhibitors as anti‐tumor agents. These data demonstrate that the tested compounds can be developed as novel candidates of anticancer agent.


title: Epidemiology of acute febrile illness in Latin America

text: Abstract Background The causes of acute febrile illness (AFI) in Latin America are diverse and their complexity increases as the proportion of fever due to malaria decreases, as malaria control measures and new pathogens emerge in the region. In this context, it is important to shed light on the gaps in the epidemiological characteristics and the geographic range for many AFI aetiologies. Objectives To review studies on community-acquired fever aetiology other than malaria in Latin America, and to highlight knowledge gaps and challenges needing further investigation. Sources PubMed from 2012 to April 2018. Content We found 17 eligible studies describing 13 539 patients. The median number of pathogens tested per individual was 3.5 (range 2–17). A causative pathogen could be determined for 6661 (49.2%) individuals. The most frequently reported pathogen during the study periods was dengue virus (DENV) (14 studies), followed by chikungunya virus (nine studies) and Zika virus (seven studies). Among the studies reporting concurrent infections, 296 individuals (2.2%) were found to have co-infections. In-hospital mortality was reported in eight (47%) studies, ranging between 0% and 18%. Implications DENV fever is the febrile illness most frequently reported, reflecting its importance, while chikungunya and zika viruses present increasing trends since their emergence in the region. Studies with systematic and harmonized approaches for detection of multiple pathogens are needed and would probably reveal a higher burden of neglected pathogens such as Rickettsia spp. and arenaviruses. The lack of point-of-care tests and harmonized approach limits the care provided by health professionals and the efficacy of surveillance for AFI in the region.


title: Strategies for mitigating an influenza pandemic

text: Development of strategies for mitigating the severity of a new influenza pandemic is now a top global public health priority. Influenza prevention and containment strategies can be considered under the broad categories of antiviral, vaccine and non-pharmaceutical (case isolation, household quarantine, school or workplace closure, restrictions on travel) measures(1). Mathematical models are powerful tools for exploring this complex landscape of intervention strategies and quantifying the potential costs and benefits of different options(2,3,4,5). Here we use a large-scale epidemic simulation(6) to examine intervention options should initial containment(6,7) of a novel influenza outbreak fail, using Great Britain and the United States as examples. We find that border restrictions and/or internal travel restrictions are unlikely to delay spread by more than 2–3 weeks unless more than 99% effective. School closure during the peak of a pandemic can reduce peak attack rates by up to 40%, but has little impact on overall attack rates, whereas case isolation or household quarantine could have a significant impact, if feasible. Treatment of clinical cases can reduce transmission, but only if antivirals are given within a day of symptoms starting. Given enough drugs for 50% of the population, household-based prophylaxis coupled with reactive school closure could reduce clinical attack rates by 40–50%. More widespread prophylaxis would be even more logistically challenging but might reduce attack rates by over 75%. Vaccine stockpiled in advance of a pandemic could significantly reduce attack rates even if of low efficacy. Estimates of policy effectiveness will change if the characteristics of a future pandemic strain differ substantially from those seen in past pandemics. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature04795) contains supplementary material, which is available to authorized users.


title: Biological roles of glycans

text: Simple and complex carbohydrates (glycans) have long been known to play major metabolic, structural and physical roles in biological systems. Targeted microbial binding to host glycans has also been studied for decades. But such biological roles can only explain some of the remarkable complexity and organismal diversity of glycans in nature. Reviewing the subject about two decades ago, one could find very few clear-cut instances of glycan-recognition-specific biological roles of glycans that were of intrinsic value to the organism expressing them. In striking contrast there is now a profusion of examples, such that this updated review cannot be comprehensive. Instead, a historical overview is presented, broad principles outlined and a few examples cited, representing diverse types of roles, mediated by various glycan classes, in different evolutionary lineages. What remains unchanged is the fact that while all theories regarding biological roles of glycans are supported by compelling evidence, exceptions to each can be found. In retrospect, this is not surprising. Complex and diverse glycans appear to be ubiquitous to all cells in nature, and essential to all life forms. Thus, >3 billion years of evolution consistently generated organisms that use these molecules for many key biological roles, even while sometimes coopting them for minor functions. In this respect, glycans are no different from other major macromolecular building blocks of life (nucleic acids, proteins and lipids), simply more rapidly evolving and complex. It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences.


Avian influenza remains a challenge to China in the post-SARS era


title: Regulation, competition and network evolution in aviation

text: Abstract Our focus is the evolution of business strategies and network structure decisions in the commercial passenger aviation industry. The paper reviews the growth of hub-and-spoke networks as the dominant business model following deregulation in the latter part of the 20th century, followed by the emergence of value-based airlines as a global phenomenon at the end of the century. The paper highlights the link between airline business strategies and network structures, and examines the resulting competition between divergent network structure business models. In this context we discuss issues of market structure stability and the role played by competition policy.


title: COVID-19 UK Lockdown Forecasts and R(0)

text: Introduction: The first reported UK case of COVID-19 occurred on 30 January 2020. A lockdown from 24 March was partially relaxed on 10 May. One model to forecast disease spread depends on clinical parameters and transmission rates. Output includes the basic reproduction number R(0) and the log growth rate r in the exponential phase. Methods: Office for National Statistics data on deaths in England and Wales is used to estimate r. A likelihood for the transmission parameters is defined from a gaussian density for r using the mean and standard error of the estimate. Parameter samples from the Metropolis-Hastings algorithm lead to an estimate and credible interval for R(0) and forecasts for cases and deaths. Results: The UK initial log growth rate is r = 0.254 with s.e. 0.004. R(0) = 6.94 with 95% CI (6.52, 7.39). In a 12 week lockdown from 24 March with transmission parameters reduced throughout to 5% of their previous values, peaks of around 90,000 severely and 25,000 critically ill patients, and 44,000 cumulative deaths are expected by 16 June. With transmission rising from 5% in mid-April to reach 30%, 50,000 deaths and 475,000 active cases are expected in mid-June. Had such a lockdown begun on 17 March, around 30,000 (28,000, 32,000) fewer cumulative deaths would be expected by 9 June. Discussion: The R(0) estimate is compatible with some international estimates but over twice the value quoted by the UK government. An earlier lockdown could have saved many thousands of lives.


title: A data-driven model for influenza transmission incorporating media effects

text: Numerous studies have attempted to model the effect of mass media on the transmission of diseases such as influenza; however, quantitative data on media engagement has until recently been difficult to obtain. With the recent explosion of ‘big data’ coming from online social media and the like, large volumes of data on a population’s engagement with mass media during an epidemic are becoming available to researchers. In this study, we combine an online dataset comprising millions of shared messages relating to influenza with traditional surveillance data on flu activity to suggest a functional form for the relationship between the two. Using this data, we present a simple deterministic model for influenza dynamics incorporating media effects, and show that such a model helps explain the dynamics of historical influenza outbreaks. Furthermore, through model selection we show that the proposed media function fits historical data better than other media functions proposed in earlier studies.


docid: rmoroqrv

title: Does culture matter social distancing under the COVID-19 pandemic?

text: This paper is the first to examine the role of the cultural dimension in practising social distancing across the world. By drawing the data from the Google COVID-19 community mobility reports and the Hofstede cultural factors for 58 countries over the period from 16 February to 29 March 2020, we find that countries with higher ‘Uncertainty Avoidance Index’ predict the lower proportion of people gathering in public such as retail and recreation, grocery and pharmacy, parks, transit stations, workplaces. However, we do not find any predictive factor in having a relationship with the percentage of citizens staying in their residential areas. Our results are robust by adding the control variable as the wealth status, GDP per capita. Hence, this paper suggests some effective communications to contain the COVID-19 pandemic by emphasizing the role of uncertainties.


title: The neonatal anti-viral response fails to control measles virus spread in neurons despite interferon-gamma expression and a Th1-like cytokine profile

text: Abstract Neonates are highly susceptible to viral infections in the periphery, potentially due to deviant cytokine responses. Here, we investigated the role of interferon-gamma (IFNγ), a key anti-viral in the neonatal brain. We found that (i) IFNγ, which is critical for viral control and survival in adults, delays mortality in neonates, (ii) IFNγ limits infiltration of macrophages, neutrophils, and T cells in the neonatal brain, (iii) neonates and adults differentially express pathogen recognition receptors and Type I interferons in response to the infection, (iv) both neonates and adults express IFNγ and other Th1-related factors, but expression of many cytokines/chemokines and IFNγ-responsive genes is age-dependent, and (v) administration of IFNγ extends survival and reduces CD4 T cell infiltration in the neonatal brain. Our findings suggest age-dependent expression of cytokine/chemokine profiles in the brain and distinct dynamic interplays between lymphocyte populations and cytokines/chemokines in MV-infected neonates.


title: Rotavirus diarrhea in bovines and other domestic animals

text: Rotavirus diarrhea is the major cause of death of millions of children in developing countries besides causing economically significant malady in neonates of many domestic animals. In neonates, the infection is non-viremic, have very short incubation period, and manifests profuse diarrhea and severe dehydration. Concurrent infection with secondary pathogens may augment the disease severity. Diarrhea occurs due to virus-mediated destruction of absorption efficient enterocytes, activation of enteric nervous system, or due to a rotavirus enterotoxin. Diagnosis of the infection relies on conventional techniques like isolation in MA 104 cell lines, electron microscopy, electro-pherotyping, and various serological tests. Presently, diagnosis and molecular typing is performed using serotype specific RT-PCR, sequencing or genomic hybridization techniques. As the rotaviruses are known to exhibit extreme genetic diversity and outplay disinfection procedures, eradication of the pathogen is often difficult. Hence, for prevention, good management practices coupled with vaccination of dam for protecting young ones, has to be practiced. Recently, new generation prophylactic strategies including DNA vaccines, subunit vaccines, virus-like particles (VLPs) and edible vaccines have been found to induce sufficient levels of passive immunity. Aside to the infection in animals, zoonotic significance of the animal rotaviruses has to be further unearthed. In this review, efforts have been made to highlight the importance and prevalence of the disease in bovines, its pathogenesis along with preventive measures, salient features of rotaviruses and their inter-species transmission abilities, zoonotic implications, and a concise account of the infection in various domestic animals and poultry.


COVID-19 et psychiatrie infanto-juvénile


title: Asthma in Children and Adolescents: A Comprehensive Approach to Diagnosis and Management

text: Asthma is a chronic disease that has a significant impact on quality of life and is particularly important in children and adolescents, in part due to the higher incidence of allergies in children. The incidence of asthma has increased dramatically during this time period, with the highest increases in the urban areas of developed countries. It seems that the incidence in developing countries may follow this trend as well. While our knowledge of the pathophysiology of asthma and the available of newer, safer medication have both improved, the mortality of the disease has undergone an overall increase in the past 30 years. Asthma treatment goals in children include decreasing mortality and improving quality of life. Specific treatment goals include but are not limited to decreasing inflammation, improving lung function, decreasing clinical symptoms, reducing hospital stays and emergency department visits, reducing work or school absences, and reducing the need for rescue medications. Non-pharmacological management strategies include allergen avoidance, environmental evaluation for allergens and irritants, patient education, allergy testing, regular monitoring of lung function, and the use of asthma management plans, asthma control tests, peak flow meters, and asthma diaries. Achieving asthma treatment goals reduces direct and indirect costs of asthma and is economically cost-effective. Treatment in children presents unique challenges in diagnosis and management. Challenges in diagnosis include consideration of other diseases such as viral respiratory illnesses or vocal cord dysfunction. Challenges in management include evaluation of the child’s ability to use inhalers and peak flow meters and the management of exercise-induced asthma.


title: Contribution of Mutation and RNA Recombination to the Evolution of a Plant Pathogenic RNA

text: The nucleotide sequence of 17 variants of the satellite RNA of cucumber mosaic virus (CMV-satRNA) isolated from field-infected tomato plants in the springs of 1989, 1990, and 1991 was determined. The sequence of each of the 17 satRNAs was unique and was between 334 and 340 nucleotides in length; 57 positions were polymorphic. There was much genetic divergence, ranging from 0.006 to 0.141 nucleotide substitutions per site for pairwise comparisons, and averaging 0.074 for any pair. When the polymorphic positions were analyzed relative to a secondary structure model proposed for CMV-satRNAs, it was found that there were significantly different numbers of changes in base-paired and non–base-paired positions, and that mutations that did not disrupt base pairing were preferred at the putatively paired sites. This supports the concept that the need to maintain a functional structure may limit genetic divergence of CMV-satRNA. Phylogenetic analyses showed that the 17 CMV-satRNA variants clustered into two subgroups, I and II, and evolutionary lines proceeding by the sequential accumulation of mutations were apparent. Three satRNA variants were outliers for these two phylogenetic groups. They were shown to be recombinants of subgroup I and II satRNAs by calculating phylogenies for different molecular regions and by using Sawyer's test for gene conversion. At least two recombination events were required to produce these three recombinant satRNAs. Thus, recombinants were found to be frequent (∼17%) in natural populations of CMV-satRNA, and recombination may make an important contribution to the generation of new variants. To our knowledge this is the first report of data allowing the frequency of recombinant isolates in natural populations of an RNA replicon to be estimated.


title: Separation and isolation methods for analysis of the active principles of Sho-saiko-to (SST) oriental medicine

text: Abstract Sho-saiko-to (SST) was introduced into Japan as an oriental classical medicine from China approximately 1500 years ago, and it is currently the most representative Kampo medicine (traditional Japanese medicine). SST is manufactured in Japan as an ethical drug on a modern industrial scale in which the quality of ingredients is standardized with Good Manufacturing Practices (GMP) regulation. SST is widely used for the treatment of chronic hepatitis. Experimental and clinical studies including multi-center, placebo-controlled, double-blind studies have demonstrated the various pharmacological effects of SST. SST is prepared from the hot water extraction of seven raw materials, therefore many kinds of constituents are included. Three-dimensional (3D) HPLC analysis is useful for obtaining many kinds of constituents, especially low molecular ultraviolet (UV) quenching compounds, contained in SST as well as its fractions. Fingerprint pattern provided by 3D HPLC analysis makes possible to identify the overall-viewing of SST. Databases of UV spectra of the components of medicinal herbs obtained by reversed-phase (RP) HPLC using a photodiode array (PDA) and fingerprint patterns of crude drugs made by 3D HPLC analysis facilitate the identification, analysis and quality of herbal drugs. Studies using both PDA HPLC and an amino acid analysis with a fluorometric detector have found that SST contains fifteen major low molecular compounds (i.e. baicalin, wogonin-7-O-glucuronide, liquiritin, their three aglycons, liquiritin apioside, glycyrrhizin, saikosaponin b1, saikosaponin b2, ginsenoside Rg1, ginsenoside Rb1, (6)-gingerol, (6)-shogaol and arginine). These compounds have various pharmacological actions, and are assumed to be responsible, at least partly, for the pharmacological effects of SST. Although there have only been a few investigations on high molecular compounds with pharmacological actions contained in SST, several kinds of polysaccharides have been isolated from constituent herbs of SST. This review paper summarizes analytical methods of separation, isolation and identification of compounds with biological activities from SST, which is a mixture drug of medicinal herbs. Accordingly, this paper would not focus on methods of separation, isolation and analysis of particular compounds from each constituent herb of SST.


title: An Internet of Things Assisted Drone Based Approach to Reduce Rapid Spread of Covid-19

text: Abstract With the quick spread of pandemic disease, many individuals have lost their lives across different parts of the world. So, the need for a novel approach or model to overcome the problem becomes a necessity. In this paper, a mechanism is proposed called DBCMS (Drone Based Covid-19 Medical Service) for the safety of medical employees who are prone to Covid-19 infection. The proposed mechanism can effectively improve the treatment process of Covid-19 patients. Drones are nowadays commonly used in the field of medical emergency situations. The proposed model in this paper uses drone service to reduce the risk of infection to the doctors or other medical staff, thereby preventing the disease spread. This paper further assumes that the primary step is to isolate people at their home instead of admitting them to the hospitals, also called a situation of lockdown or curfew. Thus, in this way, the spread can be significantly reduced across the globe if DBCMS approach is implemented at cluster level.


title: Respiratory Syncytial Virus Seasonality, Beijing, China, 2007–2015

text: During July 2007–June 2015, we enrolled 4,225 hospitalized children with pneumonia in a study to determine the seasonality of respiratory syncytial virus (RSV) infection in Beijing, China. We defined season as the period during which >10% of total PCRs performed each week were RSV positive. We identified 8 distinctive RSV seasons. On average, the season onset occurred at week 41 (mid-October) and lasted 33 weeks, through week 20 of the next year (mid-May); 97% of all RSV-positive cases occurred during the season. RSV seasons occurred 3–5 weeks earlier and lasted ≈6 weeks longer in RSV subgroup A–dominant years than in RSV subgroup B–dominant years. Our analysis indicates that monitoring such RSV subgroup shifts might provide better estimates for the onset of RSV transmission. PCR-based tests could be a flexible or complementary way of determining RSV seasonality in locations where RSV surveillance is less well-established, such as local hospitals throughout China.


title: Protecting healthcare workers from SARS-CoV-2 infection: practical indications

text: The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID-19), has airborne transmission via droplets. The rate of transmission is quite high, higher than common influenza. Healthcare workers are at high risk of contracting the infection particularly when applying respiratory devices such as oxygen cannulas or noninvasive ventilation. The aim of this article is to provide evidence-based recommendations for the correct use of “respiratory devices” in the COVID-19 emergency and protect healthcare workers from contracting the SARS-CoV-2 infection.


title: How to carry out and interpret EEG recordings in COVID-19 patients in ICU?

text: Abstract There are questions and challenges regarding neurologic complications in COVID-19 patients. EEG is a safe and efficient tool for the evaluation of brain function, even in the context of COVID-19. However, EEG technologists should not be put in danger if obtaining an EEG does not significantly advance diagnosis or change management in the patient. Not every neurologic problem stems from a primary brain injury: confusion, impaired consciousness that evolves to stupor and coma, and headaches are frequent in hypercapnic/hypoxic encephalopathies. In patients with chronic pulmonary disorders, acute symptomatic seizures have been reported in acute respiratory failure in 6%. The clinician should be aware of the various EEG patterns in hypercapnic/hypoxic and anoxic (post-cardiac arrest syndrome) encephalopathies as well as encephalitides. In this emerging pandemic of infectious disease, single-use subdermal EEG needle electrodes may be used in comatose patients. Full EEG montages using the 10-20 system, including a derivation for ECG, are strongly recommended so as to cover relevant temporal lobe regions. We recommend noting whether the patient is undergoing or has been placed prone, as well as noting the body and head position during the EEG recording (supine versus prone) to avoid overinterpretation of respiratory, head movement, electrode, muscle or other artifacts. There is slight elevation of intracranial pressure in the prone position. In non-comatose patients, the hyperventilation procedure should be avoided. At present, non-specific EEG findings and abnormalities should not be considered as being specific for COVID-19 related encephalopathy.


docid: nmjtvpzl

title: Clinical and epidemiological predictors of transmission in Severe Acute Respiratory Syndrome (SARS)

text: BACKGROUND: Only a minority of probable SARS cases caused transmission. We assess if any epidemiological or clinical factors in SARS index patients were associated with increased probability of transmission. METHODS: We used epidemiological and clinical data on probable SARS patients admitted to Tan Tock Seng Hospital. Using a case-control approach, index patients who had probable SARS who subsequently transmitted the disease to at least one other patient were analysed as "cases" against patients with no transmission as "controls", using multivariate logistic regression analysis. RESULTS: 98 index patients were available for analysis (22 with transmission, 76 with no transmission). Covariates positively associated with transmission in univariate analysis at p < 0.05 included delay to isolation (Day 7 of illness or later), admission to a non-isolation facility, pre-existing chronic respiratory disease and immunosuppressive disease, need for oxygen, shortness of breath, vomiting, and higher lactate dehydrogenase levels and higher neutrophil counts. In the multivariate analysis, only three factors were significant: delay to isolation, admission to a non-isolation facility and higher lactate dehydrogenase levels of >650 IU/L (OR 6.4, 23.8 and 4.7 respectively). CONCLUSION: Clinical and epidemiological factors can help us to explain why transmission was observed in some instances but not in others.


title: TEMPORARY REMOVAL: Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB

text: The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, β-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution. In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics.


title: Identification of a druggable binding pocket in the spike protein reveals a key site for existing drugs potentially capable of combating Covid-19 infectivity

text: BACKGROUND: Following the recent outbreak of the new coronavirus pandemic (Covid-19), the rapid determination of the structure of the homo-trimeric spike glycoprotein has prompted the study reported here. The aims were to identify potential “druggable” binding pockets in the protein and, if located, to virtual screen pharmaceutical agents currently in use for predicted affinity to these pockets which might be useful to restrict, reduce, or inhibit the infectivity of the virion. RESULTS: Our analyses of this structure have revealed a key potentially druggable pocket where it might be viable to bind pharmaceutical agents to inhibit its ability to infect human cells. This pocket is found at the inter-chain interface that exists between two domains prior to the virion binding to human Angiotensin Converting Enzyme 2 (ACE2) protein. One of these domains is the highly mobile receptor binding domain, which must move into position to interact with ACE2, which is an essential feature for viral entry to the host cell. Virtual screening with a library of purchasable drug molecules has identified pharmaceuticals currently in use as prescription and over the counter medications that, in silico, readily bind into this pocket. CONCLUSIONS: This study highlights possible drugs already in use as pharmaceuticals that may act as agents to interfere with the movements of the domains within this protein essential for the infectivity processes and hence might slow, or even halt, the infection of host cells by this new coronavirus. As these are existing pharmaceuticals already approved for use in humans, this knowledge could accelerate their roll-out, through repurposing, for affected individuals and help guide the efforts of other researchers in finding effective treatments for the disease.


title: The Cell Cycle and Virus Infection

text: A number of different viruses interact with the cell cycle in order to subvert host-cell function and increase the efficiency of virus replication; examples can be found from DNA, retro, and RNA viruses. The majority of studies have been conducted on DNA and retroviruses whose primary site of replication is the nucleus, but increasingly a number of researchers are demonstrating that RNA viruses, whose primary site of replication is normally the cytoplasm, also interfere with the cell cycle. Viral interference with the cell cycle can have a myriad of different effects to improve virus infection, for example to promote replication of viral DNA genomes, or to delay the cell cycle to allow sufficient time for RNA virus assembly. Although cell cycle control is fairly well characterized in terms of checkpoints and control molecules (e.g., cyclins), in recent years several researchers have demonstrated that the nucleolus is also involved in cell cycle control. The nucleolus and associated subnuclear structures can sequester cell cycle regulatory complexes, and nucleolar proteins also have a direct and indirect effect on the cycling cell. Viruses also interact with the nucleolus. In order to study the interactions between a virus and the cell cycle and vice versa we have developed and adapted a number of different approaches and strategies. These include determinations of virus yield and measurements of virus replication to flow cytometry and confocal analysis of the host cell. Increasingly we have found that proteomic approaches allow the rapid analysis of a whole plethora of cell cycle proteins that may be affected by virus infection.


title: A review on MnZn ferrites: Synthesis, characterization and applications

text: Abstract Researchers are taking great interest in the synthesis and characterization of MnZn ferrites due to their wide range of applications in many areas. MnZn ferrites are a class of soft magnetic materials that have very good electrical, magnetic and optical properties. The properties of MnZn ferrites include high value of resistivity, permeability, permittivity, saturation magnetization, low power losses and coercivity. The above mentioned advantageous features of MnZn ferrites make them suitable for the use in various applications. In biomedical field these ferrites are used for cancer treatment and MRI. MnZn ferrites are also used in electronic applications for making transformers, transducers and inductors. These ferrites are also used in magnetic fluids, sensors and biosensors. MnZn ferrite is highly useful material for several electrical and electronic applications. It finds applications in almost every household appliances like mobile charger, LED bulb, TV, refrigerator, juicer mixer, washing machine, iron, microwave oven, mobile, laptop, desktop, printer and so on. Therefore, the present review focuses on different techniques for synthesis of MnZn ferrites in literature, their characterization tools, effect of doping on the properties of MnZn ferrite and finally we will discuss about their applications.


title: Gene Variations in Cis-Acting Elements between the Taiwan and Prototype Strains of Porcine Epidemic Diarrhea Virus Alter Viral Gene Expression

text: In 2013, the outbreak of porcine epidemic diarrhea (PED) in Taiwan caused serious economic losses. In this study, we examined whether the variations of the cis-acting elements between the porcine epidemic diarrhea virus (PEDV) Taiwan (TW) strain and the prototype strain CV777 alter gene expression. For this aim, we analyzed the variations of the cis-acting elements in the 5′ and 3′ untranslated regions (UTRs) between the PEDV TW, CV777, and other reference strains. We also determined the previously unidentified transcription regulatory sequence (TRS), a sequence motif required for coronavirus transcription, and found that a nucleotide deletion in the TW strain, in comparison with CV777 strain, immediately downstream of the leader core sequence alters the identity between the leader TRS and the body TRS. Functional analyses using coronavirus defective interfering (DI) RNA revealed that such variations in cis-acting elements for the TW strain compared with the CV777 strain have an influence on the efficiency of gene expression. The current data show for the first time the evolution of PEDV in terms of cis-acting elements and their effects on gene expression, and thus may contribute to our understanding of recent PED outbreaks worldwide.


title: The history of the plague and the research on the causative agent Yersinia pestis

text: Abstract The plague is an infectious bacterial disease having a high fatality rate without treatment. It has occurred in three huge pandemics since the 6th century with millions of deaths and numerous smaller epidemics and sporadic cases. Referring to specific clinical symptoms of pulmonary plague the disease became known as the Black Death. This pandemic probably originated in central Asia and began spreading westward along major trade routes. Upon the arrival in the eastern Mediterranean the disease quickly spread especially by sea traffic to Italy, Greece and France and later throughout Europe by land. Until the 18th century many European cities were frequently affected by other great plague epidemics. The worldwide spread of the third pandemic began when the plague reached Hong Kong and Canton in the year 1894. The gram-negative coccobacillus now designated as Yersinia pestis has been discovered as the causative agent of plague in this Hong Kong outbreak. In the following years the role of rats and fleas and their detailed role in the transmission of plague has been discovered and experimentally verified. Today the plague is still endemic in many countries of the world.


Quest for outsmarting fate: Bulgaria and the COVID‐19 crisis


title: Tracking and visualization of space-time activities for a micro-scale flu transmission study

text: BACKGROUND: Infectious diseases pose increasing threats to public health with increasing population density and more and more sophisticated social networks. While efforts continue in studying the large scale dissemination of contagious diseases, individual-based activity and behaviour study benefits not only disease transmission modelling but also the control, containment, and prevention decision making at the local scale. The potential for using tracking technologies to capture detailed space-time trajectories and model individual behaviour is increasing rapidly, as technological advances enable the manufacture of small, lightweight, highly sensitive, and affordable receivers and the routine use of location-aware devices has become widespread (e.g., smart cellular phones). The use of low-cost tracking devices in medical research has also been proved effective by more and more studies. This study describes the use of tracking devices to collect data of space-time trajectories and the spatiotemporal processing of such data to facilitate micro-scale flu transmission study. We also reports preliminary findings on activity patterns related to chances of influenza infection in a pilot study. METHODS: Specifically, this study employed A-GPS tracking devices to collect data on a university campus. Spatiotemporal processing was conducted for data cleaning and segmentation. Processed data was validated with traditional activity diaries. The A-GPS data set was then used for visual explorations including density surface visualization and connection analysis to examine space-time activity patterns in relation to chances of influenza infection. RESULTS: When compared to diary data, the segmented tracking data demonstrated to be an effective alternative and showed greater accuracies in time as well as the details of routes taken by participants. A comparison of space-time activity patterns between participants who caught seasonal influenza and those who did not revealed interesting patterns. CONCLUSIONS: This study proved that tracking technology an effective technique for obtaining data for micro-scale influenza transmission research. The findings revealed micro-scale transmission hotspots on a university campus and provided insights for local control and prevention strategies.


title: Personalized Risk–Benefit Ratio Adaptation of Breast Cancer Care at the Epicenter of COVID‐19 Outbreak

text: Northern Italy has been one of the European regions reporting the highest number of COVID‐19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID‐19‐positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID‐19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer‐related outcome. In this article, we attempt to estimate the individual risk–benefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID‐19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. IMPLICATIONS FOR PRACTICE: Managing patients with breast cancer during the COVID‐19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID‐19‐related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients’ and health workers’ psychological distress.


title: Bovine coronavirus hemagglutinin protein

text: Abstract Treatment of purified bovine coronavirus (Mebus strain) with pronase destroyed the integrity of virion surface glycoproteins gp140, gp120, gp100, reduced the amount of gp26 and destroyed the hemagglutinating activity of the virus. Bromelain, on the other hand, destroyed the integrity of gp120, gp100 and gp26 but failed to remove gp140 and failed to destroy viral hemagglutinating activity. These experiments suggest that gp140 is the virion hemagglutinin. Immunoblotting studies using monospecific antiserum demonstrate that gp140 is a disulfide-linked dimeric structure reducible to monomers of 65 kDa.


title: Virus associated immune and pharmacologic mechanisms in disorders of respiratory and cutaneous atopy

text: Abstract Anaphylaxis represents non-atopic immediate hypersensitivity, whereas manifestations of atopic immediate hypersensitivity include bronchial asthma, hay fever, allergic rhinitis, chronic urticaria, and atopic dermatitis. In spite similar antigen exposure, only a minority of the population shown some form of atopic disease. Atopic disease with its spontaneous pattern of familial occurrence cannot be induced at will. The exact pathogenesis of atopy is yet to be elucidated. Two theories prevail: 1) atopy is a primary disorder of the immune system with sequelae in the various effector tissues; and 2) a concept of atopy as a primary autonomic imbalance, essentially beta adrenergic in character, with sequelae in effector cells, including those engaged in the production of antibodies. The autonomic imbalance is perceived as caused not by some disorder of the autonomic nervous system itself but by a defector functioning of its effector cells. These two concepts are not mutually exclusive. The IgE antibody, which mediates allergic reactions, is essentially identical with atopic reagin in various animal species. The beta adrenergic theory regards atopic disorders (i.e., perennial and seasonal allergic rhinitis, bronchial asthma, and atopic dermatitis) not as immunologic diseases but as unique patterns of altered reactivities to a broad spectrum of immunologic, psychic, infectious, chemical and physical stimuli. The antigen-antibody interaction is given the same role as that of a broad category of nonspecific stimuli that function only to trigger the same defective homeostatic mechanism in the various effector cells involved in immediate hypersensitivities. Current evidence favors the possibility that there are inherited and/or acquired multiple abnormalities in the receptor—adenylate cyclase—cyclic AMP system of all effector cells that are critical in the organization of immune reactivities. Atopic abnormality may be 1) acquired by functional receptor regulatory shifts caused by hormonal changes, infection (viral, bacterial, etc), allergic tissue injury or other event; 2) genetically determined; or 3) caused by autoimmune disease. One, two or all three of these effector mechanisms may be operative in a particular disease. There is an important relationship between asthma and viral respiratory infection. A history of childhood viral respiratory illness is a risk factor for the development of chronic obstructive airway syndromes in later life. Asthmatic attacks occurred only when the infection produced fever, malaise, cough or coryza. The dominant role of fever in these episodes immediately suggests the profound involvement of adrenergic effector mechanisms. The presence of autoantibodies to beta-adrenoceptors in patients correlated well with a reduced beta—and an increased alpha-adrenergic responsiveness. Virus infections can elicit autoantibody formation. In patients with atopic dermatitis an increased susceptibility and abnormal host response to viral infections in general. Defective cytotoxic T cells, abnormally functioning macrophages and natural killer cells, a reduced production of IFNα in children, and of IFNγ in atopic patients with food allergy has recently been demonstrated. Lymphocytic cyclic AMP-phosphodiesterase, that destroys cyclic AMP, is increased in atopic dermatitis and in allergic respiratory disease of adults, and this increased activity correlated closely with histamine release from basophils. Peripheral blood leukocytes and lymphocytes in atopic dermatitis have frequently demonstrated impaired beta adrenergic reactivity. Allergic tissue injury may be initiated by antigen-specific IgE antibodies that combine with Fcε receptors on various cell types and trigger mediator release upon encounter with the antigen. Various noxious agents that are capable of triggering asthma are capable of releasing inflammatory mediators from the same target cells. Accounting only for those pharmacologic mediators where the cell-type has been identified, the spectrum of mediator-storing, synthesizing, or transporting cells includes neutrophil leucocytes, basophilic leucocytes eosinophilic leucocytes; mast cells, “chromaffin-positive” mast cells, enterochromaffin cells, chromaffin cells; platelets, neurosecretory cells and nerve cells that potentially produce all amine-mediators as well as prostaglandins and kinins.


EPIDEMIOLOGY OF PARKINSON'S DISEASE


title: Rapid development and evaluation of a live-attenuated QX-like infectious bronchitis virus vaccine

text: Infectious bronchitis (IB) is an acute, highly contagious disease, which causes economic losses to the poultry industry worldwide. To control the disease, biosecurity and vaccination are required. In the current research, we rapidly attenuated a QX-like IBV field strain ZYY-2014 using passage in embryos at limiting dilution and tested the safety and efficacy of the attenuated Chinese QX-like IBV strain ZYYR-2014 in 1-day-old specific-pathogen-free (SPF) chickens through spray route. Our result revealed that the attenuated strain presented a decreased pathogenicity in 1-day-old chickens. The strain ZYY-2014 inoculated birds presented typical IBV clinical signs with a mortality of 43%, while the attenuated strain ZYYR-2014 inoculated birds remained healthy. The strain ZYYR-2014 also presented stronger antibody responses and lower viral loads in tracheas, lungs and kidneys. When vaccinated through spray route into 1-day-old SPF chickens, our data suggest a potential of the attenuated ZYYR-2014 strain as a vaccine candidate applied in hatchery, which can contribute in preventing the QX-like IBV infections. Furthermore, attenuation by passage at limiting dilution could be applied for rapid vaccine development against emerging strains.


title: Cybercrime in America amid COVID-19: the Initial Results from a Natural Experiment

text: The COVID-19 pandemic has radically altered life, killing hundreds of thousands of people and leading many countries to issue “stay-at-home” orders to contain the virus’s spread. Based on insights from routine activity theory (Cohen & Felson 1979), it is likely that COVID-19 will influence victimization rates as people alter their routines and spend more time at home and less time in public. Yet, the pandemic may affect victimization differently depending on the type of crime as street crimes appear to be decreasing while domestic crimes may be increasing. We consider a third type of crime: cybercrime. Treating the pandemic as a natural experiment, we investigate how the pandemic has affected rates of cybervictimization. We compare pre-pandemic rates of victimization with post-pandemic rates of victimization using datasets designed to track cybercrime. After considering how the pandemic may alter routines and affect cybervictimization, we find that the pandemic has not radically altered cyberroutines nor changed cybervictimization rates. However, a model using routine activity theory to predict cybervictimization offers clear support for the theory’s efficacy both before and after the pandemic. We conclude by considering plausible explanations for our findings.


title: Digital privacy in mental healthcare: current issues and recommendations for technology use

text: Mental healthcare providers increasingly use technology for psychotherapy services. This progress enables professionals to communicate, store information, and rely on digital software and hardware. Emails, text messaging, telepsychology/telemental health therapy, electronic medical records, cloud-based storage, apps/applications, and assessments are now available within the provision of services. Of those mentioned, some are directly utilized for psychotherapy while others indirectly aid providers. Whereas professionals previously wrote notes locally, technology has empowered providers to work more efficiently with third-party services and solutions. However, the implementation of these advancements in mental healthcare involves consequences to digital privacy and might increase clients’ risk of unintended breaches of confidentiality. This manuscript reviews common technologies, considers the vulnerabilities therein, and proposes suggestions to strengthen privacy.


COVID-19 Epidemic and Enhancing China’s National Biosecurity System


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title: Being a front-line dentist during the Covid-19 pandemic: a literature review

text: Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.


title: Evaluation of green tea extract as a safe personal hygiene against viral infections

text: BACKGROUND: Viral infections often pose tremendous public health concerns as well as economic burdens. Despite the availability of vaccines or antiviral drugs, personal hygiene is considered as effective means as the first-hand measure against viral infections. The green tea catechins, in particular, epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity. In this study, we evaluated the green tea extract as a safe personal hygiene against viral infections. RESULTS: Using the influenza virus A/Puerto Rico/8/34 (H1N1) as a model, we examined the duration of the viral inactivating activity of green tea extract (GTE) under prolonged storage at various temperature conditions. Even after the storage for 56 days at different temperatures, 0.1% GTE completely inactivated 10(6) PFU of the virus (6 log(10) reduction), and 0.01% and 0.05% GTE resulted in 2 log(10) reduction of the viral titers. When supplemented with 2% citric acid, 0.1% sodium benzoate, and 0.2% ascorbic acid as anti-oxidant, the inactivating activity of GTE was temporarily compromised during earlier times of storage. However, the antiviral activity of the GTE was steadily recovered up to similar levels with those of the same concentrations of GTE without the supplements, effectively prolonging the duration of the virucidal function over extended period. Cryo-EM and DLS analyses showed a slight increase in the overall size of virus particles by GTE treatment. The results suggest that the virucidal activity of GTE is mediated by oxidative crosslinking of catechins to the viral proteins and the change of physical properties of viral membranes. CONCLUSIONS: The durability of antiviral effects of GTE was examined as solution type and powder types over extended periods at various temperature conditions using human influenza A/H1N1 virus. GTE with supplements demonstrated potent viral inactivating activity, resulting in greater than 4 log(10) reduction of viral titers even after storage for up to two months at a wide range of temperatures. These data suggest that GTE-based antiviral agents could be formulated as a safe and environmentally friendly personal hygiene against viral infections.


Expansion by self antigen is necessary for the induction of experimental autoimmune encephalomyelitis by T cells primed with a cross-reactive environmental antigen


title: Cancer and COVID-19 — potentially deleterious effects of delaying radiotherapy

text: Radiotherapy can be safely delivered during the coronavirus disease 2019 (COVID-19) pandemic, often through use of hypofractionated regimens, which minimize the number of visits to treatment centres while also avoiding potentially detrimental delays in the delivery of cancer care.


title: Evidence for Human Norovirus Infection of Dogs in the United Kingdom

text: Human noroviruses (HuNoVs) are a major cause of viral gastroenteritis, with an estimated 3 million cases per year in the United Kingdom. HuNoVs have recently been isolated from pet dogs in Europe (M. Summa, C.-H. von Bonsdorff, and L. Maunula, J Clin Virol 53:244–247, 2012, http://dx.doi.org/10.1016/j.jcv.2011.12.014), raising concerns about potential zoonotic infections. With 31% of United Kingdom households owning a dog, this could prove to be an important transmission route. To examine this risk, canine tissues were studied for their ability to bind to HuNoV in vitro. In addition, canine stool samples were analyzed for the presence of viral nucleic acid, and canine serum samples were tested for the presence of anti-HuNoV antibodies. The results showed that seven different genotypes of HuNoV virus-like particles (VLPs) can bind to canine gastrointestinal tissue, suggesting that infection is at least theoretically possible. Although HuNoV RNA was not identified in stool samples from 248 dogs, serological evidence of previous exposure to HuNoV was obtained in 43/325 canine serum samples. Remarkably, canine seroprevalence for different HuNoV genotypes mirrored the seroprevalence in the human population. Though entry and replication within cells have not been demonstrated, the canine serological data indicate that dogs produce an immune response to HuNoV, implying productive infection. In conclusion, this study reveals zoonotic implications for HuNoV, and to elucidate the significance of this finding, further epidemiological and molecular investigations will be essential.


title: A Randomized Study of Immune Plasma for the Treatment of Severe Influenza

text: BACKGROUND: Influenza causes significant morbidity and mortality despite currently available treatments. Anecdotal reports suggest plasma with high antibody titers towards influenza may be of benefit in the treatment of severe influenza. METHODS: We conducted a randomized, open-label, multicenter phase 2 trial at 29 academic medical centers in the United States to assess the safety and efficacy of anti-influenza plasma with hemagglutination inhibition (HAI) antibody titers of ≥ 1:80 to the infecting strain. Hospitalized children and adults (including pregnant women) with severe influenza A or B (defined as hypoxia or tachypnea) were randomly assigned to receive either 2 units (or pediatric equivalent) of anti-influenza plasma plus standard care (P+S), versus standard care alone (S), and were followed for 28 days. The primary endpoint was time to normalization of patients’ respiratory status (respiratory rate of ≤ 20 for adults or age defined thresholds of 20–38 for children), and a room air saturation of oxygen ≥ 93%. ClinicalTrials.gov Identifier: NCT01052480 FINDINGS: Between January 13, 2011 and March 2, 2015, 113 participants were screened, and 98 were randomized. Of the participants with confirmed influenza, 28 of 42 (67%) of P+S participants normalized their respiratory status by Day 28, as compared to 24 of 45 (53%) of S participants (p=0·069). The estimated hazard ratio comparing P+S to S was 1·71 (95% CI: 0·96 to 3·06). Six participants died, 1 (2%) and 5 (10%) from the P+S and S arms respectively (p=0·093). P+S participants had non-significant reductions in days in hospital (median 6 vs. 11 days, p=0·13) and days on mechanical ventilation (median 0 vs. 3 days, p=0·14), and significantly improved clinical status at Day 7 (p=0·020). Fewer P+S participants experienced SAEs compared to S recipients (20% vs. 38%, p= 0·041), the most frequent of which were acute respiratory distress syndrome (1 [2%] vs 2 [4%]) and stroke (1 [2%] vs 2 [4%]). INTERPRETATION: Results from this Phase II randomized trial of immune plasma for the treatment of severe influenza provides support for a possible benefit of immunotherapy across the primary and secondary endpoints. A Phase III randomized trial is now underway to further evaluate this intervention.