title: 21-Day Lockdown in India Dramatically Reduced Air Pollution Indices in Lucknow and New Delhi, India

text: In December 2019, the outbreak of viral disease labeled as Novel Coronavirus started in Wuhan, China, which later came to be known as Covid-19. The disease has spread in almost every part of the world and has been declared a global pandemic in March 2020 by World Health Organization (WHO). The corona virus outbreak has emerged as one of the deadliest pandemics of all time in human history. The ongoing pandemic of COVID-19 has forced several countries of the world to observe complete lockdown forcing people to live in their homes. India also faced the phase of total lockdown for 21 days (in first phase) to avoid the spread of coronavirus to the maximum possible extent. This lockdown impacted the pollution levels of environment and improved air and water quality in the short span owing to very less human activities. The present work scientifically analyzed the available data for primary air pollutants (PM(2.5), NO(2), SO(2) and CO) from two major Indian cities, Lucknow and New Delhi. The analysis was based on air quality data for before lockdown and after lockdown (first phase of 21 days) periods of 21 days each. The results showed significant decline in the studied air pollution indices and demonstrated improvement of air quality in both the cities. The major impact was seen in the levels of PM(2.5), NO(2) and CO. The levels of SO(2) showed less significant decline during the lockdown period. The results are presented with future perspectives to mitigate air pollution in near future by adopting the short and periodical lockdown as a tool. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00128-020-02895-w) contains supplementary material, which is available to authorized users.


“I’m going to die in the street”: Haitian lives in the pandemic


title: Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles

text: Abstract Acid-degradable cationic nanoparticles encapsulating a model antigen (i.e., ovalbumin) were prepared by inverse microemulsion polymerization with acid-cleavable acetal cross-linkers. Incubation of these degradable nanoparticles with dendritic cells derived from bone marrow (BMDCs) resulted in the enhanced presentation of ovalbumin-derived peptides, as quantified by B3Z cells, a CD8+ T cell hybridoma. The cationic nature of the particles contributed to the increased surface endocytosis (or phagocytosis) observed with BMDCs, which is the first barrier to overcome for successful antigen delivery. The acid sensitivity of the particles served to direct more ovalbumin antigens to be processed into the appropriately trimmed peptide fragments and presented via the major histocompatibility complex (MHC) class I pathway following hydrolysis within the acidic lysosomes. It was also shown that adjuvant molecules such as unmethylated CpG oligonucleotides (CpG ODN) and anti-interleukin-10 oligonucleotides (AS10 ODN) could be co-delivered with the protein antigen for maximized cellular immune response.


title: Expression of a selenomethionyl derivative and preliminary crystallographic studies of human cystatin C

text: Human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of papain‐like mammalian proteases, has been produced in its full‐length form by recombinant techniques and crystallized in two polymorphic forms: cubic and tetragonal. A selenomethionyl derivative of the protein, obtained by Escherichia coli expression and with complete Met→Se‐Met substitution confirmed by mass spectrometry, amino‐acid analysis and X‐ray absorption spectra, was crystallized in the cubic form. A truncated variant of the protein, lacking ten N‐terminal residues, has also been crystallized. The crystals of this variant are tetragonal and, like the two polymorphs of the full‐length protein, contain multiple copies of the molecule in the asymmetric unit, suggesting oligomerization of the protein.


title: Initial Test of Emergency Procedure Performance in Temporary Negative Pressure Isolation by Using Simulation Technologies

text: STUDY OBJECTIVE: The potential of infectious disease spread in diseases such as tuberculosis, infectious disease epidemic such as avian flu and the threat of terrorism with agents capable of airborne transmission have focused attention on the need for increased surge capacity for patient isolation. Total negative pressure isolation using portable bioisolation tents may provide a solution. The study assesses the ability of health care workers to perform emergency procedures in this environment. METHODS: Physician performance in completing predetermined critical actions in 5 emergency care scenarios inside and outside of a bioisolation tent (“setting”) was studied in an advanced medical simulation laboratory. By design, no pretraining of subjects about total negative pressure isolation use occurred. Impact of setting on time to completion of predetermined critical actions was the primary outcome measured. Secondary variables studied included impact of study groups, scenarios, and run order (inside or outside of the tent first). Subjective assessments were obtained through questionnaires. RESULTS: Four teams of 3 physicians completed 5 emergency patient care scenarios during 2 4-hour sessions. Mean time to completion of critical actions was for tent/no tent 298 seconds/284 seconds (P=.69, one way ANOVA), respectively. Mean time to completion for first versus second performance of a scenario in the crossover design was 338 versus 243 (P=.01). The mean score for self-assessed performance did not differ according to setting. CONCLUSION: The ability of physicians naive to the total negative pressure isolation environment to perform emergency medical critical actions was not significantly degraded by a simulated bioisolation tent patient care environment.


Commentary: Coronary Artery Bypass Grafting in COVID-19 Patients: Darkness Cannot Drive Out Darkness


title: Incidence of viral infection detected by PCR and real‐time PCR in childhood community‐acquired pneumonia: A meta‐analysis

text: Several studies examining the incidence of viral infection in childhood community‐acquired pneumonia (CAP) utilizing polymerase chain reaction (PCR) or real‐time PCR methods have been reported. We systematically searched Pubmed and Embase for studies reporting the incidence of respiratory viral infection in childhood CAP. The pooled incidences of viral infection were calculated with a random‐effects model. Sources of heterogeneity were explored by subgroup analysis and a univariant metaregression analysis. We included 21 eligible reports in our study. We found significant heterogeneity on the incidence of viral infection in childhood CAP. The random effects pooled incidence was 57.4% (95% confidence interval (CI): 50.8–64.1). The pooled incidence of mixed infection was 29.3% (95%CI: 23.0–35.6) with considerable heterogeneity. The pooled incidence of mixed infection was 29.3% (95%CI: 23.0–35.6). Rhinovirus, respiratory syncytial virus (RSV) and bocavirus were found to be the three most common viruses in childhood CAP. We also demonstrated that respiratory viruses were detected in 76.1% of patients aged ≤1 year, 63.1% of patients aged 2–5 years and 27.9% of patients aged ≥ 6 years. We conclude that respiratory viruses are widely detected in paediatric patients with CAP by PCR or real‐time PCR methods. More than half of viral infections are probably concurrent with bacterial infections. Rhinovirus, RSV and bocavirus are the three most frequent viruses identified in childhood CAP; the incidence of viral infection decreased with age.


title: Membrane Protein of Human Coronavirus NL63 Is Responsible for Interaction with the Adhesion Receptor

text: Human coronavirus NL63 (HCoV-NL63) is a common respiratory virus that causes moderately severe infections. We have previously shown that the virus uses heparan sulfate proteoglycans (HSPGs) as the initial attachment factors, facilitating viral entry into the cell. In the present study, we show that the membrane protein (M) of HCoV-NL63 mediates this attachment. Using viruslike particles lacking the spike (S) protein, we demonstrate that binding to the cell is not S protein dependent. Furthermore, we mapped the M protein site responsible for the interaction with HSPG and confirmed its relevance using a viable virus. Importantly, in silico analysis of the region responsible for HSPG binding in different clinical isolates and the Amsterdam I strain did not exhibit any signs of cell culture adaptation. IMPORTANCE It is generally accepted that the coronaviral S protein is responsible for viral interaction with a cellular receptor. Here we show that the M protein is also an important player during early stages of HCoV-NL63 infection and that the concerted action of the two proteins (M and S) is a prerequisite for effective infection. We believe that this study broadens the understanding of HCoV-NL63 biology and may also alter the way in which we perceive the first steps of cell infection with the virus. The data presented here may also be important for future research into vaccine or drug development.


title: Chapter 1 Discovery and Classification

text: Abstract The virus was first described 120 years ago as a filterable, transmissible agent that causes disease in plants and animals. A virus is a “submicroscopic and intracellular parasite” that can propagate only inside a living cell. The obligatory nature of a virus brought a debate on whether it is living or nonliving. Virology, as a discipline that studies the diverse aspects of viral infection of host cells and its consequence, became established during the early 20th century. Viruses are found in almost all living organisms on earth, ranging from bacteria, fungi, and amoeba, to plants and animals. Viruses are classified into seven groups, according to genomic features. This molecular classification, also called the “Baltimore classification,” allows us to predict precisely the mode of viral genome replication.


title: Otolaryngology in the Time of Corona: Assessing Operative Impact and Risk During the COVID-19 Crisis

text: OBJECTIVE: Limited research exists on the coronavirus disease 2019 (COVID-19) pandemic pertaining to otolaryngology–head and neck surgery (OHNS). The present study seeks to understand the response of OHNS workflows in the context of policy changes and to contribute to developing preparatory guidelines for perioperative management in OHNS. STUDY DESIGN: Retrospective cohort study. SETTING: Pediatric and general adult academic medical centers and a Comprehensive Cancer Center (CCC). SUBJECTS AND METHODS: OHNS cases from March 18 to April 8, 2020—the 3 weeks immediately following the Ohio state-mandated suspension of all elective surgery on March 18, 2020—were compared with a 2019 control data set. RESULTS: During this time, OHNS at the general adult and pediatric medical centers and CCC experienced 87.8%, 77.1%, and 32% decreases in surgical procedures as compared with 2019, respectively. Aerosol-generating procedures accounted for 86.8% of general adult cases, 92.4% of pediatric cases, and 62.0% of CCC cases. Preoperative COVID-19 testing occurred in 7.1% of general adult, 9% of pediatric, and 6.9% of CCC cases. The majority of procedures were tiers 3a and 3b per the Centers for Medicare & Medicaid Services. Aerosol-protective personal protective equipment (PPE) was worn in 28.6% of general adult, 90% of pediatric, and 15.5% of CCC cases. CONCLUSION: For OHNS, the majority of essential surgical cases remained high-risk aerosol-generating procedures. Preoperative COVID-19 testing and intraoperative PPE usage were initially inconsistent; systemwide guidelines were developed rapidly but lagged behind recommendations of the OHNS department and its academy. OHNS best practice standards are needed for preoperative COVID-19 status screening and PPE usage as we begin national reopening.


title: Development of qPCR platform with probes for quantifying prevalent and biomedically relevant human gut microbial taxa

text: Abstract Nowadays the advent of innovative high-throughput sequencing allows obtaining high-quality microbiome profiling. However, PCR-based tests are still considered the “golden standard” for many clinical applications. Here, we designed a qPCR-based platform with fluorescent-labeled oligonucleotide probes for assessing human gut microbiome composition. The system allows conducting qualitative and semiquantitative analysis for 12 prokaryotic taxa that are prevalent in the human gut and associated with diseases, diet, age and other factors. The platform was validated by comparing microbiome profile data obtained with two different methods - the platform and high-throughput 16S rRNA sequencing - across 42 stool samples. The test can form the basis for precise and cost-efficient microbiome assay for large-scale surveys including clinical trials with interventions related to diet and disease risks.


title: Drug Delivery–mediated Control of RNA Immunostimulation

text: RNA interference (RNAi) has generated significant interest as a strategy to suppress viral infection, but in some cases antiviral activity of unmodified short-interfering RNA (siRNA) has been attributed to activation of innate immune responses. We hypothesized that immunostimulation by unmodified siRNA could mediate both RNAi as well as innate immune stimulation depending on the mode of drug delivery. We investigated the potential of immunostimulatory RNAs (isRNAs) to suppress influenza A virus in vivo in the mouse lung. Lipidoid 98N12-5(1) formulated with unmodified siRNA targeting the influenza nucleoprotein gene exhibited antiviral activity. Formulations were optimized to increase antiviral activity, but the antiviral activity of lipidoid-delivered siRNA did not depend on sequence homology to the influenza genome as siRNA directed against unrelated targets also suppressed influenza replication in vivo. This activity was primarily attributed to enhancement of innate immune stimulation by lipidoid-mediated delivery, which indicates increased toll-like receptor (TLR) activation by siRNA. Certain chemical modifications to the siRNA backbone, which block TLR7/8 activation but retain in vitro RNAi activity, prevented siRNA-mediated antiviral activity despite enhanced lipidoid-mediated delivery. Here, we demonstrate that innate immune activation caused by unmodified siRNA can have therapeutically relevant effects, and that these non-RNAi effects can be controlled through chemical modifications and drug delivery.


title: The FilmArray® respiratory panel: an automated, broadly multiplexed molecular test for the rapid and accurate detection of respiratory pathogens

text: The FilmArray Respiratory Panel (RP) (BioFire(™) Diagnostics, Inc., Salt Lake City, UT, USA) is the first multiplex molecular panel cleared by the US FDA for the detection of both bacterial and viral respiratory pathogens in nasopharygeal swabs. The FilmArray RP targets 20 pathogens including 17 viruses and subtypes and three bacteria, and is performed with minimal sample manipulation. The FilmArray RP has a fully automated sample-to-answer workflow with a turn-around-time of approximately 1 h. The reported sensitivity and specificity of the assay ranges from 80 to 100 and 100%, respectively, with the sensitivity for the adenovirus as low as 46%. A new version of the FilmArray RP assay (version 1.7) with improved sensitivity for the adenovirus was released in 2013. The performance characteristics and simplified workflow have allowed its implementation in a wide range of laboratories. The FilmArray RP has changed the diagnostic landscape and will have a significant impact on the care of patients with respiratory tract infection.


title: Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway

text: BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0665-9) contains supplementary material, which is available to authorized users.


title: Attempted immunisation of cats against feline infectious peritonitis using canine coronavirus

text: Specific pathogen free kittens were vaccinated with an unattenuated field isolate of canine coronavirus (ccv) either by aerosol or subcutaneously, and received boosting vaccinations four weeks later. Aerosolisation elicited a homologous virus-neutralising (vn) antibody response that increased steadily over a four-week period and levelled off one to two weeks after revaccination. The initial aerosolised dose produced an asymptomatic infection with excretion of ccv from the oropharynx up to eight days after vaccination; virus shedding was not detected, however, after the second inoculation. Cats vaccinated subcutaneously developed low vn antibody titres after the first ccv dose and experienced a strong anamnestic response after the second dose. Neutralising antibody titres then levelled off one to two weeks after revaccination at mean values somewhat lower than in cats vaccinated by aerosol. ccv was not isolated from the oropharynx after either subcutaneous dose. Four weeks after ccv boosting inoculations, vaccinated cats and sham-vaccinated control cats were divided into three subgroups and challenged by aerosol with the virulent ucd1 strain of feline infectious peritonitis virus (fipv ucd1) at three different dosage levels. Five of six cats (including sham-vaccinated controls) given the lowest challenge dose showed no signs of disease, while all other cats developed lesions typical of feline infectious peritonitis (fip). The five surviving cats developed fip after subsequent challenge with a fivefold higher dose of fipv. Thus heterotypic vaccination of cats with ccv did not provide effective protection against fipv challenge.


title: Modeling tourism: A fully identified VECM approach

text: Abstract System-based cointegration methods have become popular tools for economic analysis and forecasting. However, the identification of structural relationships is often problematic. Using a theory-directed sequential reduction method suggested by Hall, Henry and Greenslade [Hall, S. G., Henry, S., & Greenslade, J. (2002). On the identification of cointegrated systems in small samples: A modelling strategy with an application to UK wages and prices. Journal of Economic Dynamics and Control, 26, 1517–1537], we estimate a vector error correction model of Hawaii tourism, where both demand and supply-side influences are important. We identify reasonable long-run equilibrium relationships, and Diebold–Mariano tests for forecast accuracy demonstrate satisfactory forecasting performance.


title: Sequence Analysis and Structural Prediction of the Severe Acute Respiratory Syndrome Coronavirus nsp5

text: The non-structural proteins (nsp or replicase proteins) of coronaviruses are relatively conserved and can be effective targets for drugs. Few studies have been conducted into the function of the severe acute respiratory syndrome coronavirus (SARS-CoV) nsp5. In this study, bioinformatics methods were employed to predict the secondary structure and construct 3-D models of the SARS-CoV GD strain nsp5. Sequencing and sequential comparison was performed to analyze the mutation trend of the polymerase nsp5 gene during the epidemic process using a nucleotide-nucleotide basic local alignment search tool (BLASTN) and a protein-protein basic local alignment search tool (BLASTP). The results indicated that the nsp5 gene was steady during the epidemic process and the protein was homologous with other coronavirus nsp5 proteins. The protein encoded by the nsp5 gene was expressed in COS-7 cells and analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This study provided the foundation for further exploration of the protein's biological function, and contributed to the search for anti-SARS-CoV drugs.


title: Effects of prebiotic dietary fibers and probiotics on human health: With special focus on recent advancement in their encapsulated formulations

text: BACKGROUND: Dietary fibers (DFs) are known as potential formulations in human health due to their beneficial effects in control of life-threatening chronic diseases including cardiovascular disease (CVD), diabetes mellitus, obesity and cancer. In recent decades scientists around the globe have shown tremendous interest to evaluate the interplay between DFs and gastrointestinal (GIT) microbiota. Evidences from various epidemiological and clinical trials have revealed that DFs modulate formation and metabolic activities of the microbial communities residing in the human GIT which in turn play significant roles in maintaining health and well-being. Furthermore, interestingly, a rapidly growing literature indicates success of DFs being prebiotics in immunomodulation, namely the stimulation of innate, cellular and humoral immune response, which could also be linked with their significant roles in modulation of the probiotics (live beneficial microorganisms). SCOPE AND APPROACH: The main focus of the current review is to expressively highlight the importance of DFs being prebiotics in human health in association with their influence on gut microbiota. Now in order to significantly achieve the promising health benefits from these prebiotics, it is aimed to develop novel formulations to enhance and scale up their efficacy. Therefore, finally, herein unlike previously published articles, we highlighted different kinds of prebiotic and probiotic formulations which are being regarded as hot research topics among the scientific community now a days. CONCLUSION: The information in this article will specifically provide a platform for the development of novel functional foods the demands for which has risen drastically in recent years.


title: Enhanced tumor necrosis factor alpha in coronavirus but not in paracetamol‐induced acute hepatic necrosis in mice

text: Abstract: Previous reports have demonstrated that tumor necrosis factor alpha (TNF‐α) plays an important role in the pathogenesis of fulminant hepatic necrosis. The purpose of this experimental study was to measure TNF‐α blood activity in paracetamol‐induced liver necrosis and in coronavirus (MHV3)‐induced fulminant hepatitis in mice. No elevation of TNF‐α activity was found in hepatic failure complicating paracetamol poisoning. In contrast, TNF‐α activity significantly increased in response to MHV3, reaching 16.3 ± 5.5 U/ml from 24 h post infection (P>0.01). This augmentation was observed even though the virus was not detectable in the liver. Serum alanine aminotransferase levels were low and no histological lesion was observed. In conclusion, our study further supports the implication of TNF‐α in virus‐induced hepatitis failure and confirms that paracetamol poisoning does not cause increased TNF‐α activity in the circulation.


title: Chapter 2.10 Lab-on-a-Chip, Micro- and Nanoscale Immunoassay Systems, and Microarrays

text: This chapter provides a comprehensive review of miniaturized immunoassays. The economic considerations and user needs are discussed. There is a comprehensive analysis of the fundamentals of miniaturization, explaining how the relative effects of forces like surface tension and gravity change as devices and fluidics are reduced in size. These effects can be harnessed to manage flow and other kinetic elements, using forces such as capillary flow. Other means of fluid actuation and movement are described. There is a review of the types of device available, including a systematic look at the key elements of an immunoassay: antibodies, capture/solid phase, calibration, and signal generation and detection, which are covered in further detail. Methods used for microfluidic flow control are described. Analytes for which microfluidic devices have been reported are listed. There is a comprehensive list of commercial microfluidic immunodiagnostic systems, with sources of further information. The final part of the chapter covers microarrays and the detection methods associated with them. This part includes tables of label-free detection methods and commercial microarray systems, The outlook for microarrays in clinical diagnosis is considered.


title: Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions

text: Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.


title: Non-viral siRNA delivery to the lung

text: Abstract SiRNAs exert their biological effect by guiding the degradation of their cognate mRNA sequence, thereby shutting down the corresponding protein production (gene silencing by RNA interference or RNAi). Due to this property, siRNAs are emerging as promising therapeutic agents for the treatment of inherited and acquired diseases, as well as research tools for the elucidation of gene function in both health and disease. Because of their lethality and prevalence, lung diseases have attracted particular attention as targets of siRNA-mediated cures. In addition, lung is accessible to therapeutic agents via multiple routes, e.g., through the nose and the mouth, thus obviating the need for targeting and making it an appealing target for RNAi-based therapeutic strategies. The clinical success of siRNA-mediated interventions critically depends upon the safety and efficacy of the delivery methods and agents. Delivery of siRNAs relevant to lung diseases has been attempted through multiple routes and using various carriers in animal models. This review focuses on the recent progress in non-viral delivery of siRNAs for the treatment of lung diseases, particularly infectious diseases. The rapid progress will put siRNA-based therapeutics on fast track to the clinic.


title: Evaluation of inactivation methods for severe acute respiratory syndrome coronavirus in noncellular blood products

text: BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS‐CoV) has been detected in the blood of infected individuals, which may have the potential to contaminate donated blood and plasma‐derived products in the event of a future outbreak. Effective methods for inactivating the SARS‐CoV in protein solutions are described in this report. STUDY DESIGN AND METHODS: Heat, ultraviolet (UV) irradiation, octanoic acid, and solvent/detergent (S/D) methods were tested individually for their ability to inactivate SARS‐CoV in protein solutions appropriately mimicking blood‐derived products. Treated samples were tested for inactivation in a tissue culture growth assay. RESULTS: Viral inactivation by heat treatment at 60°C required 15 to 30 minutes to inactivate the SARS‐CoV. UVC efficiently inactivated SARS‐CoV in 40 minutes, whereas UVA required the addition of psoralen to enhance inactivation of the virus. The presence of bovine serum albumin limited the ability of UVC and UVA to inactivate SARS‐CoV and octanoic acid treatment does not reduce the infectivity of SARS‐CoV–spiked protein solutions. S/D treatment required 2, 4, and up to 24 hours for Triton X‐100, Tween 80, and sodium cholate inactivation, respectively. CONCLUSION: Heat, UVC irradiation, and S/D treatments effectively inactivate SARS‐CoV, whereas octanoic acid treatment is insufficient for inactivation of the virus.


title: NIAID resources for developing new therapies for severe viral infections

text: Abstract Severe viral infections, including hemorrhagic fever and encephalitis, occur throughout the world, but are most prevalent in developing areas that are most vulnerable to infectious diseases. Some of these can also infect related species as illustrated by the threatened extinction of gorillas by Ebola infection in west and central Africa. There are no safe and effective treatments available for these serious infections. In addition to the logistical difficulties inherent in developing a drug for infections that are sporadic and occur mainly in the third world, there is the overwhelming barrier of no hope for return on investment to encourage the pharmaceutical industry to address these unmet medical needs. Therefore, the National Institute of Allergy and infectious Disease (NIAID) has developed and supported a variety of programs and resources to provide assistance and lower the barrier for those who undertake these difficult challenges. The primary programs relevant to the development of therapies for severe viral infections are described and three case studies illustrate how they have been used. In addition, contact information for accessing these resources is supplied.


title: Aerosol Filtration Efficiency of Common Fabrics Used in Respiratory Cloth Masks

text: [Image: see text] The emergence of a pandemic affecting the respiratory system can result in a significant demand for face masks. This includes the use of cloth masks by large sections of the public, as can be seen during the current global spread of COVID-19. However, there is limited knowledge available on the performance of various commonly available fabrics used in cloth masks. Importantly, there is a need to evaluate filtration efficiencies as a function of aerosol particulate sizes in the 10 nm to 10 μm range, which is particularly relevant for respiratory virus transmission. We have carried out these studies for several common fabrics including cotton, silk, chiffon, flannel, various synthetics, and their combinations. Although the filtration efficiencies for various fabrics when a single layer was used ranged from 5 to 80% and 5 to 95% for particle sizes of <300 nm and >300 nm, respectively, the efficiencies improved when multiple layers were used and when using a specific combination of different fabrics. Filtration efficiencies of the hybrids (such as cotton–silk, cotton–chiffon, cotton–flannel) was >80% (for particles <300 nm) and >90% (for particles >300 nm). We speculate that the enhanced performance of the hybrids is likely due to the combined effect of mechanical and electrostatic-based filtration. Cotton, the most widely used material for cloth masks performs better at higher weave densities (i.e., thread count) and can make a significant difference in filtration efficiencies. Our studies also imply that gaps (as caused by an improper fit of the mask) can result in over a 60% decrease in the filtration efficiency, implying the need for future cloth mask design studies to take into account issues of “fit” and leakage, while allowing the exhaled air to vent efficiently. Overall, we find that combinations of various commonly available fabrics used in cloth masks can potentially provide significant protection against the transmission of aerosol particles.


title: The Impact of Prior Information on Estimates of Disease Transmissibility Using Bayesian Tools

text: The basic reproductive number (R₀) and the distribution of the serial interval (SI) are often used to quantify transmission during an infectious disease outbreak. In this paper, we present estimates of R₀ and SI from the 2003 SARS outbreak in Hong Kong and Singapore, and the 2009 pandemic influenza A(H1N1) outbreak in South Africa using methods that expand upon an existing Bayesian framework. This expanded framework allows for the incorporation of additional information, such as contact tracing or household data, through prior distributions. The results for the R₀ and the SI from the influenza outbreak in South Africa were similar regardless of the prior information ([Image: see text] = 1.36–1.46, [Image: see text] = 2.0–2.7, [Image: see text] = mean of the SI). The estimates of R₀ and μ for the SARS outbreak ranged from 2.0–4.4 and 7.4–11.3, respectively, and were shown to vary depending on the use of contact tracing data. The impact of the contact tracing data was likely due to the small number of SARS cases relative to the size of the contact tracing sample.


title: Rhinovirus et infections respiratoires aiguës de l’enfant hospitalisé. Étude rétrospective de 1998 à 2000

text: Résumé Objectifs. – Les rhinovirus sont les principaux agents du rhume, mais la fréquence et la gravité de leurs autres atteintes sont mal connues. Le but de ce travail est d’étudier l’expression clinique et la gravité potentielle des infections à rhinovirus de l’enfant hospitalisé. Méthodes. – De septembre 1998 à octobre 2000, nous avons étudié rétrospectivement une cohorte hospitalière de 211 enfants infectés par un rhinovirus, celui-ci étant recherché par culture ou RT-PCR. Résultats. – Chez les enfants infectés par un rhinovirus, 60 cas (28,4 %) d’atteintes ORL, 81 cas (38,4 %) de bronchiolites, 25 cas (11,9 %) de pneumopathies et 12 cas (4,7 %) de crises d’asthme aiguës ont été identifiés. Parmi les signes cliniques on relève 32 % de râles sibilants, 37 % de râles bronchiques et 29 % de signes de détresse respiratoire ; 40 % des radiographies pulmonaires sont anormales. Huit enfants ont été transférés en réanimation et deux sont décédés. Vingt-cinq enfants (11,8 %) avaient une infection à rhinovirus d’origine nosocomiale. Dans 19 cas le rhinovirus (9 %) était associé à un autre virus : 3 VRS, 2 virus influenza, 8 virus para-influenza, 2 adénovirus, 4 entérovirus ; 19 enfants (9 %) présentent une surinfection bactérienne. L’identification virologique des 211 cas d’infections à rhinovirus a été faite par isolement en culture dans 112 cas (53 %) et lorsque celui-ci était négatif par RT-PCR dans 99 cas (47 %). Conclusion. – En éliminant les cas de co-infections virales et bactériennes, les tableaux cliniques des infections à rhinovirus isolées de l’enfant sont dans notre étude les suivants : 25,6 % d’infections ORL, 25,6 % de bronchiolites ou bronchites, 6,2 % de pneumopathies et 5,7 % de crises d’asthme. Le diagnostic virologique est beaucoup amélioré par les outils moléculaires. Abstract Objectives. – Rhinoviruses are the most common aetiological agents of colds, but the frequency and the severity of other locations of the infection are not well known. This study describes the clinical aspects and the severity of rhinovirus infections in hospitalised children. Methods. – Isolation in culture and a RT-PCR were performed for the detection of rhinovirus in nasal aspirates from hospitalised children from September 1998 to October 2000. A group of 211 children found to be positive for rhinovirus was studied. Results. – Rhinovirus-infected children suffered from the following clinical syndromes: 60 (28.4%) upper airway infections, 81 (38.4%) bronchiolitis, 25 (11.9%) pneumonias and 12 (4.7%) acute attacks of asthma. Clinical symptoms were wheezing (32%), ronchi (37%) and 29% of children presented with acute distress respiratory syndrome; 40% of the available chest X-Ray were abnormal. Eight children were hospitalised in the intensive care unit and two children died. Twenty-five children (10.9%) had a nosocomial infection; a dual infection was observed in 19 cases (9%) with the following viruses: RSV (3), influenza (2) parainfluenza (8), adenovirus (2), enterovirus (4); 19 (9%) children had a secondary bacterial infection. Rhinoviruses were detected in nasal aspirates in 112 cases (53%) according to the culture and in the rhinovirus culture-negative samples in 99 cases (47%) according to the RT-PCR assay. Conclusion. – After eliminating cases of bacterial or viral dual infections, the clinical aspects of rhinovirus infections in children are the following: upper respiratory tract infections (25.6%), bronchiolitis ou bronchitis (25.6%), pneumonia (6.2%), acute attack of asthma (5.7%). The virological diagnosis according to culture is mainly improved by molecular techniques.


title: Ferritin: An Inflammatory Player Keeping Iron at the Core of Pathogen-Host Interactions

text: Iron is an essential element for virtually all cell types due to its role in energy metabolism, nucleic acid synthesis and cell proliferation. Nevertheless, if free, iron induces cellular and organ damage through the formation of free radicals. Thus, iron levels must be firmly controlled. During infection, both host and microbe need to access iron and avoid its toxicity. Alterations in serum and cellular iron have been reported as important markers of pathology. In this regard, ferritin, first discovered as an iron storage protein, has emerged as a biomarker not only in iron-related disorders but also in inflammatory diseases, or diseases in which inflammation has a central role such as cancer, neurodegeneration or infection. The basic research on ferritin identification and functions, as well as its role in diseases with an inflammatory component and its potential as a target in host-directed therapies, are the main considerations of this review.


title: Equine Inflammatory Markers in the Twenty-First Century A Focus on Serum Amyloid A

text: Serum amyloid A (SAA) is a marker of inflammation and infection in the horse that can be assessed in the field, with rapid and marked changes seen following initiation of an inflammatory stimulus. This quality of SAA also makes its clinical use challenging, because even small inflammatory conditions can cause large changes in SAA levels. Review of the current literature provides guidelines for responses of SAA to various conditions, which can be applied to specific clinical cases. The practitioner is encouraged to use SAA in conjunction with physical examination and other diagnostic modalities to guide treatment and monitor case progression.


title: Recurrent Corneal Perforation and Acute Calcareous Corneal Degeneration in Chronic Graft-Versus-Host Disease

text: Keratoconjunctivitis sicca (KCS) is a common complication of graft-versus-host disease (GVHD), and may lead to corneal epithelial defect and melting. In contrast, recurrent corneal calcareous degeneration and perforation is rare. A 46-year-old woman developed chronic GVHD after bone marrow transplantation for aplastic anemia. Severe KCS with corneal melting and calcium deposits were noted in the left eye. Penetrating keratoplasty was performed because of corneal perforation, but poor re-epithelialization and calcium deposition recurred. Lamellar keratectomy and amniotic membrane transplantation (AMT) were performed, but acute calcareous degeneration developed with subsequent recurrence of corneal perforation. After regraft, AMT and tarsorrhaphy, the corneal graft remained clear for 3 months. However, breakdown of the corneal epithelium occurred 3 weeks after spontaneous separation of tarsorrhaphy. Six months later, corneal perforation recurred again along with exacerbation of GVHD. Regraft was performed, but the patient refused tarsorrhaphy and AMT. Poor re-epithelialization persisted after regraft. Corneal melting with impending corneal perforation ensued. Further corneal surgery was refused and the patient chose to undergo evisceration. This case demonstrates that the ocular complications of GVHD may be severe enough to lead to corneal perforation and calcareous degeneration that is recalcitrant to medical and surgical treatment.


title: Therapeutic Plasma Exchange in Adults with Severe COVID-19 Infection

text: OBJECTIVES: To evaluate the therapeutic use of plasma exchange in COVID-19 patients compared to controls. METHODS: Case series of critically ill adult men and non-pregnant women, ≥18 years of age, with laboratory confirmed COVID-19, was conducted at the Royal Hospital, Oman, from April 17(th) to May 11(th), 2020. Therapeutic plasma exchange (TPE) was performed on patients admitted to intensive care unit (ICU) with confirmed or imminent acute respiratory distress syndrome (ARDS) or severe pneumonia. Analysis was performed using univariate statistics. RESULTS: A total of 31 COVID-19 patients were included with an overall mean age of 51 ± 15 years (range: 27-76 years), 90% (n = 28) were males, and 35% (n = 11) of the patients had TPE as a mode of treatment. The TPE group was associated with higher extubation rates than the non-TPE cohort (73% versus 20%; p = 0.018). Additionally, patients on TPE had a lower 14 days (0 versus 35%; p = 0.033) and 28 days (0 versus 35%; p = 0.033) all-cause mortality compared to patients not on TPE. However, all-cause mortality was only marginally lower in the TPE group compared to the non-TPE group (9.1% versus 45%; p = 0.055; power = 66%). Laboratory and ventilatory parameters also improved with the TPE. CONCLUSIONS: The use of TPE in severe COVID-19 patients has been associated with improved outcomes, however, randomized controlled clinical trials are warranted to draw final conclusive findings.


docid: aotrkajb

title: A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study

text: Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3′ end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals.


title: The effects of border control and quarantine measures on the spread of COVID-19

text: The rapid expansion of coronavirus disease 2019 (COVID-19) has been observed in many parts of the world. Many newly reported cases of COVID-19 during early outbreak phases have been associated with travel history from an epidemic region (identified as imported cases). For those cases without travel history, the risk of wider spreads through community contact is even higher. However, most population models assume a homogeneous infected population without considering that the imported and secondary cases contracted by the imported cases can pose different risks to community spread. We have developed an “easy-to-use” mathematical framework extending from a meta-population model embedding city-to-city connections to stratify the dynamics of transmission waves caused by imported, secondary, and others from an outbreak source region when control measures are considered. Using the cumulative number of the secondary cases, we are able to determine the probability of community spread. Using the top 10 visiting cities from Wuhan in China as an example, we first demonstrated that the arrival time and the dynamics of the outbreaks at these cities can be successfully predicted under the reproduction number R(0) = 2.92 and incubation period τ = 5.2 days. Next, we showed that although control measures can gain extra 32.5 and 44.0 days in arrival time through an intensive border control measure and a shorter time to quarantine under a low R(0) (1.4), if the R(0) is higher (2.92), only 10 extra days can be gained for each of the same measures. This suggests the importance of lowering the incidence at source regions together with infectious disease control measures in susceptible regions. The study allows us to assess the effects of border control and quarantine measures on the emergence and global spread of COVID-19 in a fully connected world using the dynamics of the secondary cases.


title: Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells

text: BACKGROUND: Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells. METHODS: We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro. RESULTS: We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus. CONCLUSION: The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease.


title: Chapter 26 Health Benefits of Traditional Culinary and Medicinal Mediterranean Plants

text: Publisher Summary This chapter focuses on the health benefits of traditional culinary and medicinal plants of the Mediterranean region. The Mediterranean diet is mentioned to be rich in fruits and vegetables, monounsaturated fatty acids and olive oil and the diet has a negative association with incidence of metabolic syndrome that contributes to an increased risk for cardiovascular disease. Mediterranean plants are believed to prevent or cure a wide range of ailments based on their bioactive components that can exert anti-oxidant, anti-inflammatory, anti-carcinogenic or anti-diabetic activities. A table is presented that gives a list of Mediterranean plants and their health benefits as well as brief accounts of the medicinal use of the plants and includes rosemary, licorice, chamomile and olive oil among others. The consumption of olive oil has a strong correlation with reduced hypertension, cancers of the prostate, breast and colon. It highlights the mechanism of action of the bioactive components and the molecular targets derived from these plants.


title: One Health and Emerging Infectious Diseases: Clinical Perspectives

text: To date, there has been little articulation of specific One Health clinical activities for veterinary and human health care providers regarding emerging infectious diseases, yet they could play a critical role. Under current clinical paradigms, both human and animal health professionals routinely diagnose and treat zoonotic infectious diseases in their patients, but tend to work in parallel with little cross-professional communication or coordination of care. For this to evolve toward a One Health model, both types of clinicians need to see how individual cases can be “sentinel events” indicating environmental risk for disease emergence, and develop mechanisms of rapid communication about these risks. Human and animal clinicians also need to take a more proactive and preventive approach to zoonotic diseases that includes the occupational health of animal workers in farms, laboratories, veterinary clinics, and other settings, as well as the recognition of increased risk among immunocompromised individuals in contact with animals. This requires training in One Health clinical competencies including the ability to diagnose and treat zoonotic diseases, implement preventive care interventions for individual patients, provide occupational health services for animal workers, recognize sentinel cases, report cases to public heath and clinical colleagues, and assess and help to intervene with environmental factors driving infectious disease risk in humans and animals. To provide an evidence base for such competency training, there is a need for development and testing of innovative protocols for One Health clinical collaborations.


title: Diagnostics in a digital age: an opportunity to strengthen health systems and improve health outcomes

text: Diagnostics play a critical role in clinical decision making, and in disease control and prevention. Rapid point-of-care (POC) tests for infectious diseases can improve access to diagnosis and patient management, but the quality of these tests vary, quality of testing is often not assured and there are few mechanisms to capture test results for surveillance when the testing is so decentralised. A new generation of POC molecular tests that are highly sensitive and specific, robust and easy to use are now available for deployment in low resource settings. Decentralisation of testing outside of the laboratory can put tremendous stress on the healthcare system and presents challenges for training and quality assurance. A feature of many of these POC molecular devices is that they are equipped with data transmission capacities. In a digital age, it is possible to link data from diagnostic laboratories and POC test readers and devices to provide data on testing coverage, disease trends and timely information for early warning of infectious disease outbreaks to inform design or optimisation of disease control and elimination programmes. Data connectivity also allows control programmes to monitor the quality of tests and testing, and optimise supply chain management; thus, increasing the efficiency of healthcare systems and improving patient outcomes.


title: A new Sephadex™-based method for removing microbicidal and cytotoxic residues when testing antiseptics against viruses: Experiments with a human coronavirus as a model

text: Abstract The relative lack of efficient methods for evaluating antiseptic antiviral activity, together with weaknesses in the existing European Standard (i.e. NF EN 14476+A1), underlines the need to seek a new method which could allow a more precise evaluation of the antiseptic antiviral activity of chemical agents. This protocol is based on an original gel-based filtration method, using “in-house” G-25 and G-10 Sephadex™ columns. This method allows the neutralization of both the activity and the cytotoxicity of a large range of molecules, according to their molecular size, in only 1min. The viral model used was the human coronavirus (HCoV) 229E chosen for (i) its increasing medical interest, (ii) its potential resistance and (iii) its representing enveloped viruses mentioned in the European Standard. First, the protocol was validated and it was demonstrated that it was fully operational for evaluating antiviral antiseptic potentiality and useful to screen potentially antiseptic molecules. Second, chlorhexidine (CHX) and hexamidine (HXM) were assessed for their potential anti-HCoV 229E antiseptic activities. It was demonstrated clearly that (i) HXM had no activity on the HCoV 229E and (ii) CHX showed a moderate anti-HCoV 229E activity but insufficient to be antiseptic.


title: Nicotinic acetylcholine receptors regulate clustering, fusion and acidification of the rat brain synaptic vesicles

text: The brain nicotinic acetylcholine receptors (nAChRs) expressed in pre-synaptic nerve terminals regulate neurotransmitter release. However, there is no evidence for the expression of nAChRs in synaptic vesicles, which deliver neurotransmitter to synaptic cleft. The aim of this paper was to investigate the presence of nAChRs in synaptic vesicles purified from the rat brain and to study their possible involvement in vesicles life cycle. According to dynamic light scattering analysis, the antibody against extracellular domain (1-208) of α7 nAChR subunit inhibited synaptic vesicles clustering. Sandwich ELISA with nAChR subunit-specific antibodies demonstrated the presence of α4β2, α7 and α7β2nAChR subtypes in synaptic vesicles and showed that α7 and β2 nAChR subunits are co-localized with synaptic vesicle glycoprotein 2A (SV2A). Pre-incubation with either α7-selective agonist PNU282987 or nicotine did not affect synaptic vesicles clustering but delayed their Ca(2+)-dependent fusion with the plasma membranes. In contrast, nicotine but not PNU282987 stimulated acidification of isolated synaptic vesicles, indicating that α4β2 but not α7-containing nAChRs are involved in regulation of proton influx and neurotransmitter refilling. Treatment of rats with levetiracetam, a specific modulator of SV2A, increased the content of α7 nAChRs in synaptic vesicles accompanied by increased clustering but decreased Ca(2+)-dependent fusion. These data for the first time demonstrate the presence of nAChRs in synaptic vesicles and suggest an active involvement of cholinergic regulation in neurotransmitter release. Synaptic vesicles may be an additional target of nicotine inhaled upon smoking and of α7-specific drugs widely discussed as anti-inflammatory and pro-cognitive tools.


title: Dimeric structure of pseudokinase RNase L bound to 2-5A reveals a basis for interferon induced antiviral activity

text: RNase L is an ankyrin repeat domain containing dual endoribonuclease-pseudokinase that is activated by unusual 2′,5′-oligoadenylate (2-5A) second messengers and which impedes viral infections in higher vertebrates. Despite its importance in interferon regulated antiviral innate immunity, relatively little is known about its precise mechanism of action. Here, we present a functional characterization of 2.5 Å and 3.25 Å X-ray crystal and small angle x-ray scattering structures of RNase L bound to a natural 2-5A activator with and without ADP or the non-hydrolysable ATP mimetic AMP-PNP. These studies reveal how recognition of 2-5A through interactions with the ankyrin repeat domain and the pseudokinase domain together with nucleotide binding, impose a rigid intertwined dimer configuration that is essential for RNase catalytic and anti-viral functions. The involvement of the pseudokinase domain of RNase L in 2-5A sensing, nucleotide binding, dimerization, and ribonuclease functions highlights the evolutionary adaptability of the eukaryotic protein kinase fold.


title: DVT incidence and risk factors in critically ill patients with COVID-19

text: Few data are available on the incidence of deep vein thrombosis (DVT) in critically ill COVID-19 with thrombosis prophylaxis. This study retrospectively included 88 patients in the ICU with critically ill COVID-19 at Jinyintan Hospital in Wuhan, China. All patients underwent compression ultrasonography for identifying DVT. Firth logistic regression was used to examine the association of DVT with sex, age, hypoalbuminemia, D-dimer, and SOFA score. The median (interquartile range [IQR]) age and SOFA score of 88 patients were 63 (55–71) years old and 5 (4–6), respectively. Despite all patients receiving guideline-recommended low-molecular-weight heparin (LMWH) thromboprophylaxis, the incidence of DVT was 46% (95% CI 35–56%). Proximal DVT was recognized in 9% (95% CI 3–15%) of the patients, while 46% (95% CI 35–56%) of patients had distal DVT. All of the proximal DVT combined with distal DVT. Risk factors of DVT extension occurred in all distal DVT patients. As Padua score ≥ 4 or IMPROVE score ≥ 2, 53% and 46% of patients had DVT, respectively. Mortality was higher in patients with acute DVT (30%) compared with non-DVT (17%), but did not reach statistical significance. Hypoalbuminemia (odds ratio [OR], 0.17; 95% CI 0.06–0.05, P = 0.001), higher SOFA score (OR per IQR, 2.07; 95% CI 1.38–3.39, P = 0.001), and elevated D-dimer (OR per IQR, 1.04; 95% CI 1.03–1.84, P = 0.029) were significant DVT risk factors in multivariable analyses. High incidence of DVT was identified in patients with critically ill COVID-19, despite the use of guideline-recommended pharmacologic thromboprophylaxis. The presence of hypoalbuminemia, higher SOFA score, and elevated D-dimer were significantly independent risk factors of DVT. More effective VTE prevention and management strategies may need to be addressed.


docid: toglzyci

title: Cryo-electron Microscopy Analysis of Structurally Heterogeneous Macromolecular Complexes

text: Cryo-electron microscopy (cryo-EM) has for a long time been a technique of choice for determining structure of large and flexible macromolecular complexes that were difficult to study by other experimental techniques such as X-ray crystallography or nuclear magnetic resonance. However, a fast development of instruments and software for cryo-EM in the last decade has allowed that a large range of complexes can be studied by cryo-EM, and that their structures can be obtained at near-atomic resolution, including the structures of small complexes (e.g., membrane proteins) whose size was earlier an obstacle to cryo-EM. Image analysis to identify multiple coexisting structures in the same specimen (multiconformation reconstruction) is now routinely done both to solve structures at near-atomic resolution and to study conformational dynamics. Methods for multiconformation reconstruction and latest examples of their applications are the focus of this review.


title: Medication treatment for opioid use disorder in expectant mothers (MOMs): Design considerations for a pragmatic randomized trial comparing extended-release and daily buprenorphine formulations

text: Abstract Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6–30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population.


title: A Spotlight on Viruses—Application of Click Chemistry to Visualize Virus-Cell Interactions

text: The replication of a virus within its host cell involves numerous interactions between viral and cellular factors, which have to be tightly controlled in space and time. The intricate interplay between viral exploitation of cellular pathways and the intrinsic host defense mechanisms is difficult to unravel by traditional bulk approaches. In recent years, novel fluorescence microscopy techniques and single virus tracking have transformed the investigation of dynamic virus-host interactions. A prerequisite for the application of these imaging-based methods is the attachment of a fluorescent label to the structure of interest. However, their small size, limited coding capacity and multifunctional proteins render viruses particularly challenging targets for fluorescent labeling approaches. Click chemistry in conjunction with genetic code expansion provides virologists with a novel toolbox for site-specific, minimally invasive labeling of virion components, whose potential has just recently begun to be exploited. Here, we summarize recent achievements, current developments and future challenges for the labeling of viral nucleic acids, proteins, glycoproteins or lipids using click chemistry in order to study dynamic processes in virus-cell interactions.


title: Myocardial localization of coronavirus in COVID‐19 cardiogenic shock

text: We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a 69‐year‐old patient with flu‐like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low‐grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.


title: Role of Transportation in Spread of Porcine Epidemic Diarrhea Virus Infection, United States

text: After porcine epidemic diarrhea virus (PEDV) was detected in the United States in 2013, we tested environmental samples from trailers in which pigs had been transported. PEDV was found in 5.2% of trailers not contaminated at arrival, , suggesting that the transport process is a source of transmission if adequate hygiene measures are not implemented.


title: Evaluation of the Serologic Cross-Reactivity between Transmissible Gastroenteritis Coronavirus and Porcine Respiratory Coronavirus Using Commercial Blocking Enzyme-Linked Immunosorbent Assay Kits

text: This study compared the performances of three commercial transmissible gastroenteritis virus/porcine respiratory coronavirus (TGEV/PRCV) blocking enzyme-linked immunosorbent assays (ELISAs) using serum samples (n = 528) collected over a 49-day observation period from pigs inoculated with TGEV strain Purdue (n = 12), TGEV strain Miller (n = 12), PRCV (n = 12), or with virus-free culture medium (n = 12). ELISA results were evaluated both with “suspect” results interpreted as positive and then as negative. All commercial kits showed excellent diagnostic specificity (99 to 100%) when testing samples from pigs inoculated with virus-free culture medium. However, analyses revealed differences between the kits in diagnostic sensitivity (percent TGEV- or PRCV-seropositive pigs), and all kits showed significant (P < 0.05) cross-reactivity between TGEV and PRCV serum antibodies, particularly during early stages of the infections. Serologic cross-reactivity between TGEV and PRCV seemed to be TGEV strain dependent, with a higher percentage of PRCV-false-positive results for pigs inoculated with TGEV Purdue than for TGEV Miller. Moreover, the overall proportion of false positives was higher when suspect results were interpreted as positive, regardless of the ELISA kit evaluated. IMPORTANCE Current measures to prevent TGEV from entering a naive herd include quarantine and testing for TGEV-seronegative animals. However, TGEV serology is complicated due to the cross-reactivity with PRCV, which circulates subclinically in most swine herds worldwide. Conventional serological tests cannot distinguish between TGEV and PRCV antibodies; however, blocking ELISAs using antigen containing a large deletion in the amino terminus of the PRCV S protein permit differentiation of PRCV and TGEV antibodies. Several commercial TGEV/PRCV blocking ELISAs are available, but performance comparisons have not been reported in recent research. This study demonstrates that the serologic cross-reactivity between TGEV and PRCV affects the accuracy of commercial blocking ELISAs. Individual test results must be interpreted with caution, particularly in the event of suspect results. Therefore, commercial TGEV/PRCV blocking ELISAs should only be applied on a herd basis.


title: The effect of physical activity on cognition relative to APOE genotype (PAAD-2): study protocol for a phase II randomized control trial

text: BACKGROUND: By 2050, the prevalence of Alzheimer’s disease (AD) in the United States is predicted to reach 13.8 million. Despite worldwide research efforts, a cure for AD has not been identified. Thus, it is critical to identify preventive strategies that can reduce the risk of or delay the onset of AD. Physical activity (PA) has potential in this regard. This randomized clinical trial aims to (a) test the causal relationship between PA and AD-associated cognitive function for persons with a family history of AD (FH+), (b) determine the moderating role of apolipoprotein epsilon 4 (APOE4) carrier status on cognition, and (c) assess cerebral structure, cerebral function, and putative biomarkers as mediators of the effects of PA on cognition. METHODS: We are recruiting cognitively normal, middle aged (40–65 years) sedentary adults with FH+. Participants are randomly assigned to a 12-month PA intervention for 3 days/week or to a control group maintaining their normal lifestyle. Saliva samples are taken at pre-test to determine APOE genotype. At pre-, mid-, and post-tests, participants complete a series of cognitive tests to assess information-processing speed, verbal and visual episodic memory, constructional praxis, mnemonic discrimination, and higher-order executive functions. At pre- and post-tests, brain imaging and blood biomarkers are assessed. DISCUSSION: We hypothesize that 1) the PA group will demonstrate improved cognition compared with controls; 2) PA-derived cognitive changes will be moderated by APOE4 status; and 3) PA-induced changes in neural and blood biomarkers will contribute to cognitive changes and differ as a function of APOE4 status. Our results may provide important insights into the potential of PA to preserve neurocognitive function in people with a heightened risk of AD due to FH+ and as moderated by APOE4 status. By using sophisticated analytic techniques to assess APOE as a moderator and neurobiological mechanisms as mediators across trajectories of cognitive change in response to PA, we will advance our understanding of the potential of PA in protecting against AD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03876314. Registered March 15, 2019.


title: Efficacy and safety of Anluohuaxian in the treatment of patients with severe Coronavirus disease 2019- a multicenter, open label, randomized controlled study: a structured summary of a study protocol for a randomised controlled trial

text: OBJECTIVES: Patients with severe COVID-19 often suffer from significant pulmonary fibrosis. Although the pathogenesis of pulmonary fibrosis has not been fully explained, the signal pathways and cytokines involved are very similar to hepatic fibrosis. This has been successfully treated with the Anluohuaxian Pill, a proprietary Chinese medicine composed of a variety of Chinese herbal medicines. The aim of this study is to evaluate the efficacy and safety of Anluohuaxian in the treatment of pulmonary fibrosis in patients with severe COVID-19. TRIAL DESIGN: This is a prospective, multicenter, open, randomized controlled trial. The distribution ratio was 2:1, 500 cases in the experimental group and 250 cases in the control group. PARTICIPANTS: Minimum Age: 18 Years Maximum Age: 80 Years Sex: All Gender Based: No Accepts Healthy Volunteers: No 1. Confirmed COVID-19, and the nucleic acid test of respiratory specimens such as sputum or nasopharyngeal swabs is negative twice after the treatment (sampling interval is at least 24 hours); 2. Negative nucleic acid test of respiratory specimens such as sputum or nasopharyngeal swabs during screening visits; 3. High-resolution CT of the lung (HRCT) indicates pulmonary fibrosis (thickness of lobular septum, honeycomb-like changes, with or without bronchial / pleural distraction); 4. Voluntarily participate in research and sign informed consent. 1. Combined with severe heart, lung (diagnosed with interstitial lung disease, bronchial asthma, chronic obstructive pulmonary disease, etc.), liver and kidney disease or with endocrine, rheumatic, neurologic, malignant and other systemic diseases; 2. Have been diagnosed with connective tissue disease; 3. Pregnant or lactating women; 4. History of mental disorders, substance abuse or dependence; 5. Have used other anti-pulmonary fibrosis drugs in the past 14 days, such as nintedanib, pirfenidone, penicillamine, colchicine, tumor necrosis factor alpha blocker, imatinib, glucocorticoid hormones, morphomycodyl esters, azathioprine, cyclophosphamide, interferon-γ, and traditional Chinese medicine; 6. Researchers consider it inappropriate to participate in research; 7. Participating in other clinical research. This mutli-centre RCT will be undertaken in 9 trial centres: The Second People's Hospital of Fuyang, Ezhou Central Hospital, Huoshenshan Hospital of Wuhan, Jinyintan Hospital of Wuhan, Tongji Hospital of Huazhong University of Science and Technology, West Hospital Union Hospital Huazhong University of Science and Technology, Wuhan Pulmonary Hospital, Zhongnan Hospital of Wuhan University, Wenzhou Medical University Affiliated First Hospital. INTERVENTION AND COMPARATOR: The research drug is Anluohuaxian Pill, which is provided by Senlong Pharmaceutical Co., Ltd. The basic therapeutic drugs for COVID-19 involved in the study include antiviral drugs. Brands can be selected according to the treatment routines of each research center to facilitate the improvement of treatment compliance. MAIN OUTCOMES: 1. Changes in high-resolution computer tomography of the lung. Changes in ground-glass shadows, interstitial or air nodules found on high-resolution computer tomography : 2. Change in 6-minute walking distance; [Time Frame: 3 months] RANDOMISATION: In this study, the central randomization system (IWRS, an interactive network response system based on network) is used to randomise the groups. The subjects who met the entry criteria were randomly divided into the experimental group and the control group according to the proportion of 2:1. In this study, the block randomized grouping method is used, and the block length is 6. The random grouping program is set up by statistical and computer professionals in the randomization process. BLINDING (MASKING): This is an open label trial. Trial participants, investigators, care givers, outcome assessors, and date analysts are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 750 patients are expected to be enrolled and the cases are allocated according to the ratio of 2 (Anluohuaxian combined with regular treatment group):1 (regular treatment group). TRIAL STATUS: Protocol version number 3.0, 10th April 2020. The recruitment has not yet started. Actual Study Start Date: April 1, 2020 Estimated Primary Completion Date: June 1, 2020 Estimated Study Completion Date: December 1, 2020 TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04334265. Registered on 3 April 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


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title: La pandémie du Covid-19: surdosage médiatique, craintes et bientôt antonomase? Une pandémie exposant deux


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title: Purification of Coronavirus Virions for Cryo-EM and Proteomic Analysis

text: Purification of intact enveloped virus particles can be useful as a first step in understanding the structure and function of both viral and host proteins that are incorporated into the virion. Purified preparations of virions can be used to address these questions using techniques such as mass spectrometry proteomics. Recent studies on the proteome of coronavirus virions have shown that in addition to the structural proteins, accessory and non-structural virus proteins and a wide variety of host cell proteins associate with virus particles. To further study the presence of virion proteins, high-quality sample preparation is crucial to ensure reproducible analysis by the wide variety of methods available for proteomic analysis.


COVID-19 Pandemic – Let’s not forget surfaces


title: Anticancer activity studies of novel metal complexes of ligands derived from polycyclic aromatic compound via greener route

text: Abstract Methoxy and tert-butyl substituted carboxamide, carboxylic acid and hydrazone Schiff base groups have been assembled into our newly designed fluorenone based ligands and prepared coordination compounds of some first row transition metals and characterized thoroughly with spectroscopic (1H and 13C NMR, IR, GC–MS, UV–Vis), analytical, TGA and molar conductance measurements. The stoichiometry of all the metal complexes is found to be 1: 2 (M: L2) with the general formula, [M(L)2], where L is a singly deprotonated ligand and the geometry of all the metal complexes is found to be octahedral. Ligands and their metal complexes successfully cleaved the pBR322 plasmid DNA and in case of anticancer activity against MCF–7 (human breast adenocarcinoma) cell line, the synthesized compounds found to exhibit excellent activity with prominent apoptotic effect which is characterized by cell shrinkage, cell breakage and turgidity and results were compared with the standard drug cisplatin. Very significant anticancer activity was observed for compounds L1H, Cu(L1)2, Cu(L2)2, Ni(L1)2 and Ni(L2)2 with IC50 value of <10 μgmL−1. Molecular docking studies were performed to assess the bonding mode of synthesized compounds. In case of antioxidant activity study, the compounds L1H, Ni(L1)2, Cu(L1)2, Cu(L2)2 and Ni(L2)2 exhibited significant scavenging activity with good percentage when compared with remaining tested compounds.


docid: zkvjbdlf

title: Medical conspiracy theories: cognitive science and implications for ethics

text: Although recent trends in politics and media make it appear that conspiracy theories are on the rise, in fact they have always been present, probably because they are sustained by natural dispositions of the human brain. This is also the case with medical conspiracy theories. This article reviews some of the most notorious health-related conspiracy theories. It then approaches the reasons why people believe these theories, using concepts from cognitive science. On the basis of that knowledge, the article makes normative proposals for public health officials and health workers as a whole, to deal with conspiracy theories, in order to preserve some of the fundamental principles of medical ethics.


title: SARS in Singapore—challenges of a global health threat to local institutions

text: SARS (Severe Acute Respiratory Syndrome) has been declared by WHO (World Health Organisation) as a global health threat. Within a period of four to five months in 2003, the disease infected some 8,000 people in more than 25 countries and left 774 dead. The many studies that have been done on the spread of SARS in Asia as well as countries as far flung as Germany and Canada have focused on the global dimension of the infectious disease as well as the speed of its spread upon emergence in southern China and then Hong Kong. Less attention has been paid to its spatial distribution at the national and local scales. This discussion focuses on the spread of SARS at the national and local spatial scales. In the process, the study presents the management of a hazard, in this case, an emerging infectious disease by national health care institutions such as the hospitals that ultimately proved to have been wholly unprepared for coping with at least the health aspects of the outcome of a globalised national agenda for growth and economic progress.


title: Effectiveness of Family-Based Behavior Change Interventions on Obesity-Related Behavior Change in Children: A Realist Synthesis

text: Effective treatment interventions for childhood obesity involve parents, are multicomponent and use behavior change strategies, but more information is needed on the mechanisms influencing behavioral outcomes and the type of parental involvement that is efficacious in behavioral treatment interventions with school-age children. This review aimed to understand key characteristics of programs that contribute to dietary and physical activity behavioral outcomes, and through which key mechanisms. This was a systematic review with narrative synthesis following PRISMA guidelines and realist analysis using RAMESES guidelines to explain outcome patterns and influence of parental involvement. Overall, the findings contribute to understanding the complex relationship between family barriers to behavior change, strategies employed in treatment interventions and behavioral outcomes. Implications for enhancing future policy and practice include involving parents in goal setting, motivational counselling, role modeling, and restructuring the physical environment to promote mutual empowerment of both parents and children, shared value and whole-family ownership in which intrinsic motivation and self-efficacy are implicit. These characteristics were associated with positive dietary and physical activity behavior change in children and may be useful considerations for the design and implementation of future theory-based treatment interventions to encourage habitual healthy diet and physical activity to reduce childhood obesity.


Initial rapid and proactive response for the COVID-19 outbreak — Taiwan's experience


title: Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection

text: Abstract SARS-CoV-2 infection is mild in the majority of individuals, but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed ‘trained immunity’, by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections, through epigenetic, transcriptional and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole microorganism vaccines may represent an important tool for reducing susceptibility and severity to SARS-CoV-2.


title: Interventional oncology at the time of COVID-19 pandemic: problems and solutions

text: Abstract The COVID-19 pandemic has deeply impacted the activity of interventional oncology in hospitals and cancer centers. In this review based on official recommendations of different international societies, but also on local solutions found in different expert large-volume centers, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology. A literature review of potential solutions in a context of scarce anesthesiologic resources, limited staff and limited access to hospital beds are proposed and discussed based on the literature data.


title: An international multicentre study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise

text: BACKGROUND: The outbreak of Covid-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multi-center study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the Quadripartite Equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium- sized liver transplant centers from twelve countries across four continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a “sickest-first” approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - Recipient Outcome, Donor/Graft Safety, Waiting List Mortality and Healthcare Resources for seven countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of Quadripartite Equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems to allow greater global solidarity and transparency in these austere times.


title: Pathogenicity of neutralization escape mutants of mouse hepatitis virus : correlation with T- and B-cell depletions

text: Summary Viral pathogenicity is a result of an imbalance between viral replication and the host's immune defences. When the virus is lymphotropic, understanding the pathogenic process of the viral disease becomes complicated because virus/lymphocyte interactions can alter the cell's integrity and subsequently induce immunodeficiency. The immune system plays an important role in the outcome of acute disease induced by the mouse hepatitis virus type 3 (MHV3). The use of attenuated escape mutants provides a tool to study the role of viral properties involved in its pathogenicity. We selected MHV3 mutants by virtue of their resistance to neutralization by monoclonal antibodies (mAb), in order to study their pathogenic properties. We reported that two MHV3 escape mutants were attenuated in their pathogenic properties according to inoculation site and with regard to survival time and ability to deplete T- and B-cell subpopulations in the spleen, thymus and bone marrow of susceptible Balb/c mice. The highly attenuated CL12 mutant could not induce depletion in T or B cells following intraperitoneal (i.p.) or intranasal (i.n.) inoculations, at three days postinfection. The less attenuated 51.6 mutant, however, maintained the ability to deplete T and B cells following i.p. inoculation, as described with the pathogenic MHV3. In contrast, no depletion of T cells following i.n. inoculation was induced with this mutant, although B lineage cells decreased. The use of such mutants enabled us to examine the role of each compartment of the immune system, since the highly attenuated CL12 mutant induced no immunodeficiency, as defined by immune cell depletion, whereas the less attenuated 51.6 mutant maintained its ability to decrease only the B-cell compartment after i.n. inoculation. Results are discussed with regard to the virus/lymphocyte interactions during the pathogenic process.


title: A positive perspective during COVID-19 related to groundwater crisis

text: The months from March to June refer as water crisis months in many places of India, because in these months of summer generally, Indian people face shortage of water. In the summer season, groundwater level decreases due to high temperature and increased evaporation of water in most of the places. This present discussion is focused on one positive aspect during the COVID-19 pandemic, which is related to rainfall during this summer in India. It has been observed that the rainfall in India in the months of March to May (as of now, on May 18, 2020) is high as compared to previous years and it might increase the groundwater level and people of India would not face a water crisis during this summer.


title: Characterization of murine hepatitis virus (JHM) RNA from rats with experimental encephalomyelitis

text: Abstract When Wistar Furth rats are inoculated intracerebrally with the murine hepatitis virus JHM they often develop a demyelinating disease with resulting hind leg paralysis. Using an RNA transfer procedure and hybridization kinetic analysis, the virus-specific RNA in these rats was characterized. The pattern of JHM-specific RNA varied with individual infections of Wistar Furth rats. However, two species of JHM-specific RNA, the nucleocapsid and a 2.1–2.4 × 106-Da RNA species were generally present. A general decrease in JHM-specific RNA in brains' and spinal cord samples taken later than 20 days postinoculation was observed; however, JHM-specific RNA persisted in the spinal cord longer than in the brain of these rats.


title: Exploring the coronavirus epidemic using the new WashU Virus Genome Browser

text: Since its debut in mid-December, 2019, the novel coronavirus (2019-nCoV) has rapidly spread from its origin in Wuhan, China, to several countries across the globe, leading to a global health crisis. As of February 7, 2020, 44 strains of the virus have been sequenced and uploaded to NCBI’s GenBank [1], providing insight into the virus’s evolutionary history and pathogenesis. Here, we present the WashU Virus Genome Browser, a web-based portal for viewing virus genomic data. The browser is home to 16 complete 2019-nCoV genome sequences, together with hundreds of related viral sequences including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus. In addition, the browser features unique customizability, supporting user-provided upload of novel viral sequences in various formats. Sequences can be viewed in both a track-based representation as well as a phylogenetic tree-based view, allowing the user to easily compare sequence features across multiple strains. The WashU Virus Genome Browser inherited many features and track types from the WashU Epigenome Browser, and additionally incorporated a new type of SNV track to address the specific needs of viral research. Our Virus Browser portal can be accessed at https://virusgateway.wustl.edu, and documentation is available at https://virusgateway.readthedocs.io/.


title: Disaster Nursing: A Retrospective Review

text: This article presents a review of the literature related to disaster preparedness and nursing. A definition of disaster as set forth by the American Red Cross is provided. Eight themes, including (1) defining disaster, (2) nursing during and after disaster, (3) nursing education in disaster preparedness, (4) military nurse preparedness, (5) postdisaster stress, (6) ethical issues and intent to respond, (7) policy, and (8) hospital emergency policy, were derived from the review and are explored in this article. Although a plethora of disaster-related literature exists, the voice of the nurses who worked during these disasters is missing. Areas of proposed research illuminated by current research are suggested.


title: Masks and thermometers: Paramount measures to stop the rapid spread of SARS-CoV-2 in the United States

text: Abstract In the United States, there is currently an exponential growth for the COVID-19 cases. The US president’s coronavirus guidelines for Americans “30 Days to Slow The Spread” are necessary. To effectively curb the rapid spread of SARS-CoV-2, two more control measures masks and thermometers are strongly suggested to be included in the Guidelines.


title: H7N9 influenza and its impact on pregnancy

text: Abstract This short article specifically focuses on the new emerging H7N9 influenza which has just been observed since early 2013. As a new disease, it is lack for the knowledge on the new H7N9 influenza. Here, the author will discuss on the impact of emerging H7N9 influenza on pregnancy.


title: World Competitive Contests (WCC) algorithm: A novel intelligent optimization algorithm for biological and non-biological problems

text: Abstract Since different sciences face lots of problems which cannot be solved in reasonable time order, we need new methods and algorithms for getting acceptable answers in proper time order. In the present study, a novel intelligent optimization algorithm, known as WCC (World Competitive Contests), has been proposed and applied to find the transcriptional factor binding sites (TFBS) and eight benchmark functions discovery processes. We recognize the need to introduce an intelligent optimization algorithm because the TFBS discovery is a biological and an NP-Hard problem. Although there are some intelligent algorithms for the purpose of solving the above-mentioned problems, an optimization algorithm with good and acceptable performance, which is based on the real parameters, is essential. Like the other optimization algorithms, the proposed algorithm starts with the first population of teams. After teams are put into different groups, they will begin competing against their rival teams. The highly qualified teams will ascend to the elimination stage and will play each other in the next rounds. The other teams will wait for a new season to start. In this paper, we’re going to implement our proposed algorithm and compare it with five famous optimization algorithms from the perspective of the following: the obtained results, stability, convergence, standard deviation and elapsed time, which are applied to the real and randomly created datasets with different motif sizes. According to our obtained results, in many cases, the WCC׳s performance is better than the other algorithms’.


title: Surface glycoprotein of Borna disease virus mediates virus spread from cell to cell

text: Borna disease virus (BDV) is a non‐segmented negative‐stranded RNA virus that maintains a strictly neurotropic and persistent infection in affected end hosts. The primary target cells for BDV infection are brain cells, e.g. neurons and astrocytes. The exact mechanism of how infection is propagated between these cells and especially the role of the viral glycoprotein (GP) for cell–cell transmission, however, are still incompletely understood. Here, we use different cell culture systems, including rat primary astrocytes and mixed cultures of rat brain cells, to show that BDV primarily spreads through cell–cell contacts. We employ a highly stable and efficient peptidomimetic inhibitor to inhibit the furin‐mediated processing of GP and demonstrate that cleaved and fusion‐active GP is strictly necessary for the cell‐to‐cell spread of BDV. Together, our quantitative observations clarify the role of Borna disease virus‐glycoprotein for viral dissemination and highlight the regulation of GP expression as a potential mechanism to limit viral spread and maintain persistence. These findings furthermore indicate that targeting host cell proteases might be a promising approach to inhibit viral GP activation and spread of infection.


ENDOSCOPIC FINDINGS IN PATIENTS INFECTED WITH 2019 NOVEL CORONAVIRUS IN LOMBARDY, ITALY


title: An insect cell derived respiratory syncytial virus (RSV) F nanoparticle vaccine induces antigenic site II antibodies and protects against RSV challenge in cotton rats by active and passive immunization

text: Abstract Post-infectious immunity to respiratory syncytial virus (RSV) infection results in limited protection as evidenced by the high rate of infant hospitalization in the face of high titer, maternally derived RSV-specific antibodies. By contrast, RSV fusion (F) glycoprotein antigenic site II humanized monoclonal antibodies, palivizumab and motavizumab, have been shown to reduce RSV-related hospitalization in infants. Immunogenicity and efficacy studies were conducted in cotton rats comparing a recombinant RSV F nanoparticle vaccine with palivizumab and controlled with live RSV virus intranasal immunization and, formalin inactivated RSV vaccine. Active immunization with RSV F nanoparticle vaccine containing an alum adjuvant induced serum levels of palivizumab competing antibody (PCA) greater than passive administration of 15mg/kg palivizumab (human prophylactic dose) in cotton rats and neutralized RSV-A and RSV-B viruses. Immunization prevented detectable RSV replication in the lungs and, unlike passive administration of palivizumab, in the nasal passage of challenged cotton rats. Histology of lung tissues following RSV challenge showed no enhanced disease in the vaccinated groups in contrast to formalin inactivated ‘Lot 100’ vaccine. Passive intramuscular administration of RSV F vaccine-induced immune sera one day prior to challenge of cotton rats reduced viral titers by 2 or more log10 virus per gram of lung and nasal tissue and at doses less than palivizumab. A recombinant RSV F nanoparticle vaccine protected lower and upper respiratory tract against both RSV A and B strain infection and induced polyclonal palivizumab competing antibodies similar to but potentially more broadly protective against RSV than palivizumab.


Pancreatitis aguda en paciente con infección por COVID-19


title: Infection Density and Epidemic Size of COVID-19 in China outside the Hubei province

text: The novel coronavirus (COVID-19) has spread to almost all countries in the world, claiming more than 160,000 lives and sickening more than 2,400,000 people by April 21, 2020. There has been research showing that on average, each infected person spreads the infection to more than two persons. Therefore the majority of the population is at risk of infection if no intervention measures were undertaken. The true size of the COVID-19 epidemic remains unknown, as a significant proportion of infected individuals only exhibit mild symptoms or are even asymptomatic. A timely assessment of the evolving epidemic size is crucial for resource allocation and triage decisions. In this article, we modify the back-calculation algorithm to obtain a lower bound estimate of the number of COVID-19 infected persons in China outside the Hubei province. We estimate the infection density among infected and show that the drastic control measures enforced throughout China following the lockdown of Wuhan City effectively slowed down the spread of the disease in two weeks. Our findings from China are expected to provide guidelines and enlightenment for surveillance and control activities of COVID-19 in other countries around the world.