title: Bayesian Networks for Supply Chain Risk, Resilience and Ripple Effect Analysis: A Literature Review

text: In the broad sense, the Bayesian networks (BN) are probabilistic graphical models that possess unique methodical features to model dependencies in complex networks, such as forward and backward propagation (inference) of disruptions. BNs have transitioned from an emerging topic to a growing research area in supply chain (SC) resilience and risk analysis. As a result, there is an acute need to review existing literature to ascertain recent developments and uncover future areas of research. Despite the increasing number of publications on BNs in the domain of SC uncertainty, an extensive review on their application to SC risk and resilience is lacking. To address this gap, we analyzed research articles published in peer-reviewed academic journals from 2007 to 2019 using network analysis, visualization-based scientometric analysis, and clustering analysis. Through this study, we contribute to literature by discussing the challenges of current research, and, more importantly, identifying and proposing future research directions. The results of our survey show that further debate on the theory and application of BNs to SC resilience and risk management is a significant area of interest for both academics and practitioners. The applications of BNs, and their conjunction with machine learning algorithms to solve big data SC problems relating to uncertainty and risk, are also discussed.


title: The complex associations of climate variability with seasonal influenza A and B virus transmission in subtropical Shanghai, China

text: Abstract Most previous studies focused on the association between climate variables and seasonal influenza activity in tropical or temperate zones, little is known about the associations in different influenza types in subtropical China. The study aimed to explore the associations of multiple climate variables with influenza A (Flu-A) and B virus (Flu-B) transmissions in Shanghai, China. Weekly influenza virus and climate data (mean temperature (MeanT), diurnal temperature range (DTR), relative humidity (RH) and wind velocity (Wv)) were collected between June 2012 and December 2018. Generalized linear models (GLMs), distributed lag non-linear models (DLNMs) and regression tree models were developed to assess such associations. MeanT exerted the peaking risk of Flu-A at 1.4 °C (2-weeks’ cumulative relative risk (RR): 14.88, 95% confidence interval (CI): 8.67–23.31) and 25.8 °C (RR: 12.21, 95%CI: 6.64–19.83), Flu-B had the peak at 1.4 °C (RR: 26.44, 95%CI: 11.52–51.86). The highest RR of Flu-A was 23.05 (95%CI: 5.12–88.45) at DTR of 15.8 °C, that of Flu-B was 38.25 (95%CI: 15.82–87.61) at 3.2 °C. RH of 51.5% had the highest RR of Flu-A (9.98, 95%CI: 4.03–26.28) and Flu-B (4.63, 95%CI: 1.95–11.27). Wv of 3.5 m/s exerted the peaking RR of Flu-A (7.48, 95%CI: 2.73–30.04) and Flu-B (7.87, 95%CI: 5.53–11.91). DTR ≥ 12 °C and MeanT <22 °C were the key drivers for Flu-A and Flu-B, separately. The study found complex non-linear relationships between climate variability and different influenza types in Shanghai. We suggest the careful use of meteorological variables in influenza prediction in subtropical regions, considering such complex associations, which may facilitate government and health authorities to better minimize the impacts of seasonal influenza.


docid: tjvbduqh

title: Adapting a Hospital‐at‐Home Care Model to Respond to New York City's COVID‐19 Crisis


title: Development of an ELISA-array for simultaneous detection of five encephalitis viruses

text: Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), and eastern equine encephalitis virus (EEEV) can cause symptoms of encephalitis. Establishment of accurate and easy methods by which to detect these viruses is essential for the prevention and treatment of associated infectious diseases. Currently, there are still no multiple antigen detection methods available clinically. An ELISA-array, which detects multiple antigens, is easy to handle, and inexpensive, has enormous potential in pathogen detection. An ELISA-array method for the simultaneous detection of five encephalitis viruses was developed in this study. Seven monoclonal antibodies against five encephalitis-associated viruses were prepared and used for development of the ELISA-array. The ELISA-array assay is based on a "sandwich" ELISA format and consists of viral antibodies printed directly on 96-well microtiter plates, allowing for direct detection of 5 viruses. The developed ELISA-array proved to have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for clinical use.


title: Capturing rapidly evolving molecular medical microbiology Molecular Microbiology: Diagnostic Principles and Practice 3rd Edition 2016

text: Unknown


title: Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches

text: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel corona virus that causes corona virus disease 2019 (COVID-19). The COVID-19 rapidly spread across the nations with high mortality rate even as very little is known to contain the virus at present. In the current study, we report novel natural metabolites namely, ursolic acid, carvacrol and oleanolic acid as the potential inhibitors against main protease (M(pro)) of COVID-19 by using integrated molecular modeling approaches. From a combination of molecular docking and molecular dynamic (MD) simulations, we found three ligands bound to protease during 50 ns of MD simulations. Furthermore, the molecular mechanic/generalized/Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations showed that these chemical molecules have stable and favourable energies causing strong binding with binding site of M(pro) protein. All these three molecules, namely, ursolic acid, carvacrol and oleanolic acid, have passed the ADME (Absorption, Distribution, Metabolism, and Excretion) property as well as Lipinski’s rule of five. The study provides a basic foundation and suggests that the three phytochemicals, viz. ursolic acid, carvacrol and oleanolic acid could serve as potential inhibitors in regulating the M(pro) protein’s function and controlling viral replication. Communicated by Ramaswamy H. Sarma


title: The Effect of Having a Regular Doctor as a Primary Care Provider on Emergency Room Utilization in South Korea

text: BACKGROUND: Because primary care is the cornerstone of an effective health care system, many developed countries have striven to establish and strengthen their primary care systems. However, the primary care system in South Korea is not well established, and primary care research is still in its infancy. This study aimed to show the benefits of regular doctors as primary care providers in South Korea by analyzing the effect of regular doctor visits on emergency room (ER) visits. METHODS: We analyzed cross-sectional data on 11,293 adults aged 18 years and over collected from the 2013 Korea Health Panel Survey (beta version 1.0). We classified those participants with and without regular doctors into the treatment and control groups, respectively, and estimated the average treatment effect (ATE) of having a regular doctor on ER visits. We used counterfactual framework and propensity score analysis to adjust for unevenly distributed confounding covariates between treatments and control groups. RESULTS: The estimated conditional ATE of a regular doctor on ER visits was statistically insignificant in the general population (-0.4%; 95% confidence interval [CI], -2.0 to 1.2) and in the subgroup of patients with hypertension (-1.8%; 95% CI, -4.5 to 0.9). However, in patients with diabetes mellitus (DM), the estimated ATE was statistically significant (-5.0; 95% CI, -9.2 to -0.7). CONCLUSION: In the total study population, having a regular doctor did not result in a significant difference in ER visits. However, there was a decrease in ER visits in patients with DM in South Korea.


title: Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats

text: Old World frugivorous bats have been identified as natural hosts for emerging zoonotic viruses of significant public health concern, including henipaviruses (Nipah and Hendra virus), Ebola virus, and Marburg virus. Epidemiological studies of these viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaviruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4–271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7–299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0–289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76–80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related Henipavirus serological data collected from wild pteropid bats.


title: The genome segment B encoding the RNA-dependent RNA polymerase protein VP1 of very virulent infectious bursal disease virus (IBDV) is phylogenetically distinct from that of all other IBDV strains

text: A full-length cDNA clone of the segment B of the very virulent infectious bursal disease virus (IBDV) strain BD 3/99 was constructed and the full-length nucleotide sequence was established. The nucleotide sequence encoding VP1, an RNA-dependent RNA polymerase, of BD 3/99 was aligned with that of 17 other IBDV strains including six very virulent, three classical virulent, five classical attenuated, one antigenic variant and two serotype 2 strains. The VP1 genes of all very virulent strains were 97.5% to 99.8% identical. With the exception of an atypical Australian strain, 002-73, all of the classical virulent or attenuated and antigenic variant strains were also 97.5% to 100% identical. Serotype 2 strains showed only 4–6% divergence from serotype 1 classical virulent or attenuated strains; in contrast, however, the very virulent strains were 10.5% to 12.5% divergent from the classical virulent or attenuated strains as well as serotype 2 strains. Analysis of the deduced amino acid sequence of VP1 revealed 17 common, including 8 unique amino acid substitutions in the very virulent strains. In the phylogenetic tree the very virulent strains formed a distinct cluster and all other strains including classical virulent, attenuated and antigenic variant strains and even serotype 2 strains were grouped together. It to is suggested that the VP1 of very virulent IBDV is phylogenetically distinct from that of all other IBDV strains and probably originated from a hitherto unidentified source.


title: Rhinovirus replication and innate immunity in highly differentiated human airway epithelial cells

text: BACKGROUND: Human rhinovirus (HRV) infections are the primary cause of the common cold and are a major trigger for exacerbations of lower airway diseases, such as asthma and chronic obstructive pulmonary diseases. Although human bronchial epithelial cells (HBE) are the natural host for HRV infections, much of our understanding of how HRV replicates and induces host antiviral responses is based on studies using non-airway cell lines (e.g. HeLa cells). The current study examines the replication cycle of HRV, and host cell responses, in highly differentiated cultures of HBE. METHODS: Highly differentiated cultures of HBE were exposed to initial infectious doses ranging from 10(4) to 10(1) 50% tissue culture-infective dose (TCID(50)) of purified HRV-16, and responses were monitored up to 144 h after infection. Viral genomic RNA and negative strand RNA template levels were monitored, along with levels of type I and II interferons and selected antivirals. RESULTS: Regardless of initial infectious dose, relatively constant levels of both genomic and negative strand RNA are generated during replication, with negative strand copy numbers being10,000-fold lower than those of genomic strands. Infections were limited to a small percentage of ciliated cells and did not result in any overt signs of epithelial death. Importantly, regardless of infectious dose, HRV-16 infections were cleared by HBE in the absence of immune cells. Levels of type I and type III interferons (IFNs) varied with initial infectious dose, implying that factors other than levels of double-stranded RNA regulate IFN induction, but the time-course of HRV-16 clearance HBE was the same regardless of levels of IFNs produced. Patterns of antiviral viperin and ISG15 expression suggest they may be generated in an IFN-independent manner during HRV-16 infections. CONCLUSIONS: These data challenge a number of aspects of dogma generated from studies in HeLa cells and emphasize the importance of appropriate cell context when studying HRV infections.


title: Lung pathology of fatal severe acute respiratory syndrome

text: Summary Background Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear. Methods Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry. Findings All six patients had serological evidence of recent infection with SARS-CoV. Diffuse alveolar damage was common but not universal. Morphological changes identified were bronchial epithelial denudation, loss of cilia, and squamous metaplasia. Secondary bacterial pneumonia was present in one case. A giant-cell infiltrate was seen in four patients, with a pronounced increase in macrophages in the alveoli and the interstitium of the lung. Haemophagocytosis was present in two patients. The alveolar pneumocytes also showed cytomegaly with granular amphophilic cytoplasm. The patient for whom full autopsy was done had atrophy of the white pulp of the spleen. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus. Interpretation SARS is associated with epithelial-cell proliferation and an increase in macrophages in the lung. The presence of haemophagocytosis supports the contention that cytokine dysregulation may account, at least partly, for the severity of the clinical disease. The case definition of SARS should acknowledge the range of lung pathology associated with this disease. Published online May 16, 2003 http://image.thelancet.com/extras/03art4347web.pdf


title: Chapter 14 Family Astroviridae

text: Abstract Astroviruses are unsegmented, positive-sense RNA viruses with ~7–9kb genomes. The family name derives from astron, meaning star, in Greek. These small unenveloped viruses have spikes that project about 41nm from the surface of the capsid, giving them a star-like appearance. Human astroviruses cause gastroenteritis in children and adults. Symptoms include diarrhea, nausea, vomiting, fever, malaise, and abdominal pain; for the most part disease is self-limiting.


title: A review on Promising vaccine development progress for COVID-19 disease

text: Abstract The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) that causes corona virus disease 2019 (COVID-19) and its impact on in the world have made imperative progress to develop an effective and safe vaccine. Despite several measures undertaken, the spread of this virus is ongoing. So far, more than 1,560,000 cases and 1000,000 deaths occurred in the world. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS. However, currently, no approved vaccine exists for these coronavirus strains. Such Previous research efforts to develop a coronavirus vaccine in the years following the 2003 pandemic have opened the door for the scientist to design a new vaccine for the COVID-19. Both SARS-CoV and SARS-CoV-2 has a high degree of genetic similarity and bind to the same host cell ACE2 receptor. By using different vaccine development platforms including whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines several candidates displayed efficacy in vitro studies but few progressed to clinical trials. This review provides a brief introduction of the general features of SARS-CoV-2 and discusses the current progress of ongoing advances in designing vaccine development efforts to counter COVID-19.


Surgical oncology at the time of COVID‐19 outbreak


La médecine par l’épreuve1


COVID-19 y tratamiento guiado con tests de diagnóstico bioquímicos y moleculares para reducir el daño cardiaco y la cardiotoxicidad


title: A comparison of the susceptibility of three human gut tumour-derived differentiated epithelial cell lines, primary monkey kidney cells and human rhabdomyosarcoma cell line to 66-prototype strains of human enteroviruses

text: Abstract The growth of prototype strains of 31 serotypes of ECHO, 3 polio, 6 Coxsackie B, 24 Coxsackie A and enterovirus serotypes 70 and 71 were tested in parallel in primary monkey kidney cells (PMK), RD cells and three gut tumour-derived differentiated epithelial cell lines (HRT-18 HT-29 in SKCO-1). All 31 serotypes of ECHO viruses grew in HT-29, 27 and SKCO-1, 5 in HRT-18, 29 in PMK and 29 in RD. There was good growth of poliovirus serotypes in all five cell types. Coxsackie B viruses grew well in all the cell lines except RD. Fifteen of the Coxsackie A viruses grew in SKCO-1, 4 in HT-29, 3 in HRT-18 and 7 in RD. Enterovirus serotypes 70 and 71 grew only in RD cells after 3 serial passages. These results showed that 2 of the gut tumour-derived cell lines, HT-29 and SKCO-1 had a markedly wider susceptibility, with comparable or wider sensitivity, for enteroviruses, than PMK and RD. While their use for field isolation from clinical samples is not yet fully established HT-29 and SKCO-1 would appear to be ideal for a variety of laboratory manipulations of the majority of enteroviruses.


docid: opgtkmnb

title: Sleep During Times of Coronavirus: Early Chinese Experience


docid: hfzygxjj

title: De-O-Acetylation of mucin-derived sialic acids by recombinant NanS-p esterases of Escherichia coli O157:H7 strain EDL933

text: Abstract Enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain EDL933 encodes the single chromosomal 9-O-acetylesterase NanS, and several copies of prophage-encoded 9-O-acetylesterases (NanS-p). These enzymes have recently been shown to cleave 5-N-acetyl-9-O-acetyl neuraminic acid (Neu5,9Ac2) to yield de-O-acetylated Neu5Ac, the latter of which may serve as a carbon and/or nitrogen source. In the current study, we investigated the NanS- and NanS-p-mediated digestion of synthetic O-acetylated neuraminic acids and bovine submaxillary glands mucin (BSM)-derived O-acetylneuraminic acids by high-performance thin-layer chromatography (HPTLC) and nano electrospray ionization mass spectrometry (nanoESI MS). Initial HPTLC analyses showed the expected activity of NanS and NanS-p variants for Neu5,9Ac2. However, all tested enzymes were unable to de-O-acetylate 5-N-acetyl-4-O-acetylneuraminic acid (Neu5,4 Ac2) in our test system. The nanoESI MS analysis of neuraminic acids after treatment of BSM with NanS-p gave evidence that NanS-p variants of EHEC O157:H7 strain EDL933 cleave off O-acetyl groups from mono-, di-, and tri-O-acetylated Neu5Ac and N-glycolylneuraminic acid (Neu5Gc), regardless of the carbon positions C7, C8 or C9 of the acetate esters. This enzyme activity leads to neuraminidase-accessible Neu5Ac and Neu5Gc on mucin glycans. Moreover, we could demonstrate by HPTLC analyses that recombinant Bacteroides thetaiotaomicron sialidase (BTSA-His) was able to cleave Neu5Ac and Neu5,9Ac2 from BSM and that the combination of BTSA-His with both NanS-His and NanS-p-His derivatives enhanced the release of de-O-acetylated core Neu5Ac and Neu5Gc from mammalian mucin O-glycans. Growth experiments with EHEC wildtype strain EDL933, its nanS and nanS/nanS-p1a-p7 mutant and exogenous BTSA-His in BSM demonstrated that the presence of BTSA-His enhanced growth of EDL933 and the nanS deletion mutant but not the nanS/nanS-p1a-p7 mutant. Thus, we hypothesize that the expression of sialic acid O-acetylesterases with a broad specificity could be an advantage in competition with the gut microbiota for nutrients and facilitate EHEC colonization in the human large intestine.


title: Cytokine storms are primarily responsible for the rapid death of ducklings infected with duck hepatitis A virus type 1

text: Duck hepatitis A virus type 1 (DHAV-1) is one of the most harmful pathogens in the duck industry. The infection of adult ducks with DHAV-1 was previously shown to result in transient cytokine storms in their kidneys. To understand how DHAV-1 infection impacts the host liver, we conducted animal experiments with the virulent CH DHAV-1 strain and the attenuated CH60 commercial vaccine strain. Visual observation and standard hematoxylin and eosin staining were performed to detect pathological damage in the liver, and viral copy numbers and cytokine expression in the liver were evaluated by quantitative PCR. The CH strain (10(8.4) copies/mg) had higher viral titers than the CH60 strain (10(4.9) copies/mg) in the liver and caused ecchymotic hemorrhaging on the liver surface. Additionally, livers from ducklings inoculated with the CH strain were significantly infiltrated by numerous red blood cells, accompanied by severe cytokine storms, but similar signs were not observed in the livers of ducklings inoculated with the CH60 strain. In conclusion, the severe cytokine storm caused by the CH strain apparently induces hemorrhagic lesions in the liver, which might be a key factor in the rapid death of ducklings.


title: Contingency plans in a radiation oncology department amid the 2019-nCoV outbreak in Switzerland

text: Abstract The ongoing novel coronavirus (2019-nCoV) pandemic is expected to develop into an unprecedented stress test for health care systems worldwide. This brief report, written from a radiation oncology perspective during the developing outbreak of 2019-nCoV in Switzerland, highlights the challenges identified and measures taken in our department to mitigate risks and ensure continued operations during the outbreak.


title: Non-Invasive Sample Collection for Respiratory Virus Testing by Multiplex PCR

text: BACKGROUND: Identifying respiratory pathogens within populations is difficult because invasive sample collection, such as with nasopharyngeal aspirate (NPA), is generally required. PCR technology could allow for non-invasive sampling methods. OBJECTIVES: Evaluate the utility of non-invasive sample collection using anterior nare swabs and facial tissues for respiratory virus detection by multiplex PCR. STUDY DESIGN: Children aged 1 month – 17 years evaluated in a pediatric emergency department for respiratory symptoms had a swab, facial tissue, and NPA sample collected. All samples were tested for respiratory viruses by multiplex PCR. Viral detection rates were calculated for each collection method. Sensitivity and specificity of swabs and facial tissues were calculated using NPA as the gold standard. RESULTS: 285 samples from 95 children were evaluated (92 swab-NPA pairs, 91 facial tissue-NPA pairs). 91% of NPA, 82% of swab, and 77% of tissue samples were positive for ≥ 1 virus. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) were most common. Overall, swabs were positive for 74% of virus infections, and facial tissues were positive for 58%. Sensitivity ranged from 17–94% for swabs and 33–84% for tissues. Sensitivity was highest for RSV (94% swabs and 84% tissues). Specificity was ≥ 95% for all viruses except HRV for both collection methods. CONCLUSIONS: Sensitivity of anterior nare swabs and facial tissues in the detection of respiratory viruses by multiplex PCR varied by virus type. Given its simplicity and specificity, non-invasive sampling for PCR testing may be useful for conducting epidemiologic or surveillance studies in settings where invasive testing is impractical or not feasible.


title: Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development

text: Heterologous immunity (H.I.) is a consequence of an encounter with a specific antigen, which can alter the subsequent immune response to a different antigen. This can happen at the innate immune system level—often called trained immunity or innate immune memory—and/or at the adaptive immune system level involving T memory cells and antibodies. Viruses may also induce T cell-mediated H.I., which can confer protection or drive immunopathology against other virus subtypes, related or unrelated viruses, other pathogens, auto- or allo-antigens. It is important to understand the underlying mechanisms for the development of antiviral “universal” vaccines and broader T cell responses rather than just subtype-specific antibody responses as in the case of influenza. Furthermore, knowledge about determinants of vaccine-mediated H.I. may inform public health policies and provide suggestions for repurposing existing vaccines. Here, we introduce H.I. and provide an overview of evidence on virus- and antiviral vaccine-induced T cell-mediated cross-reactive responses. We also discuss the factors influencing final clinical outcome of virus-mediated H.I. as well as non-specific beneficial effects of live attenuated antiviral vaccines such as measles and vaccinia. Available epidemiological and mechanistic data have implications both for the development of new vaccines and for personalized vaccinology, which are presented. Finally, we formulate future research priorities and opportunities.


title: VIGOR extended to annotate genomes for additional 12 different viruses

text: A gene prediction program, VIGOR (Viral Genome ORF Reader), was developed at J. Craig Venter Institute in 2010 and has been successfully performing gene calling in coronavirus, influenza, rhinovirus and rotavirus for projects at the Genome Sequencing Center for Infectious Diseases. VIGOR uses sequence similarity search against custom protein databases to identify protein coding regions, start and stop codons and other gene features. Ribonucleicacid editing and other features are accurately identified based on sequence similarity and signature residues. VIGOR produces four output files: a gene prediction file, a complementary DNA file, an alignment file, and a gene feature table file. The gene feature table can be used to create GenBank submission. VIGOR takes a single input: viral genomic sequences in FASTA format. VIGOR has been extended to predict genes for 12 viruses: measles virus, mumps virus, rubella virus, respiratory syncytial virus, alphavirus and Venezuelan equine encephalitis virus, norovirus, metapneumovirus, yellow fever virus, Japanese encephalitis virus, parainfluenza virus and Sendai virus. VIGOR accurately detects the complex gene features like ribonucleicacid editing, stop codon leakage and ribosomal shunting. Precisely identifying the mat_peptide cleavage for some viruses is a built-in feature of VIGOR. The gene predictions for these viruses have been evaluated by testing from 27 to 240 genomes from GenBank.


title: How mobility habits influenced the spread of the COVID-19 pandemic: Results from the Italian case study

text: Abstract Starting from December 2019 the world has faced an unprecedented health crisis caused by the new Coronavirus (COVID-19) due to the SARS-CoV-2 pathogen. Within this topic, the aim of the paper was to quantify the effect of mobility habits in the spread of the Coronavirus in Italy through a multiple linear regression model. Estimation results showed that mobility habits represent one of the variables that explains the number of COVID-19 infections jointly with the number of tests/day and some environmental variables (i.e. PM pollution and temperature). Nevertheless, a proximity variable to the first outbreak was also significant, meaning that the areas close to the outbreak had a higher risk of contagion, especially in the initial stage of infection (time-decay phenomena). Furthermore, the number of daily new cases was related to the trips performed three weeks before. This threshold of 21 days could be considered as a sort of positivity detection time, meaning that the mobility restrictions quarantine commonly set at 14 days, defined only according to incubation-based epidemiological considerations, is underestimated (possible delays between contagion and detection) as a containment policy and may not always contribute to effectively slowing down the spread of virus worldwide. This result is original and, if confirmed in other studies, will lay the groundwork for more effective containment of COVID-19 in countries that are still in the health emergency, as well as for possible future returns of the virus.


title: Fundamentals of gastroenterology with self-assessment work book. Edition 4 By L. W. Powell and D. W. Piper. John Wright-PSG Inc., Littleton, Massachusetts, 1984

text: Unknown


title: Estimation of incubation period and serial interval of COVID-19: analysis of 178 cases and 131 transmission chains in Hubei province, China

text: A novel coronavirus disease, designated as COVID-19, has become a pandemic worldwide. This study aims to estimate the incubation period and serial interval of COVID-19. We collected contact tracing data in a municipality in Hubei province during a full outbreak period. The date of infection and infector–infectee pairs were inferred from the history of travel in Wuhan or exposed to confirmed cases. The incubation periods and serial intervals were estimated using parametric accelerated failure time models, accounting for interval censoring of the exposures. Our estimated median incubation period of COVID-19 is 5.4 days (bootstrapped 95% confidence interval (CI) 4.8–6.0), and the 2.5th and 97.5th percentiles are 1 and 15 days, respectively; while the estimated serial interval of COVID-19 falls within the range of −4 to 13 days with 95% confidence and has a median of 4.6 days (95% CI 3.7–5.5). Ninety-five per cent of symptomatic cases showed symptoms by 13.7 days (95% CI 12.5–14.9). The incubation periods and serial intervals were not significantly different between male and female, and among age groups. Our results suggest a considerable proportion of secondary transmission occurred prior to symptom onset. And the current practice of 14-day quarantine period in many regions is reasonable.


docid: ldlgmlju

title: Hospital infection past and present Graham AJ Ayliffe Mary P English

text: Unknown


title: Can we contain the COVID-19 outbreak with the same measures as for SARS?

text: Summary The severe acute respiratory syndrome (SARS) outbreak in 2003 resulted in more than 8000 cases and 800 deaths. SARS was eventually contained by means of syndromic surveillance, prompt isolation of patients, strict enforcement of quarantine of all contacts, and in some areas top-down enforcement of community quarantine. By interrupting all human-to-human transmission, SARS was effectively eradicated. By contrast, by Feb 28, 2020, within a matter of 2 months since the beginning of the outbreak of coronavirus disease 2019 (COVID-19), more than 82 000 confirmed cases of COVID-19 have been reported with more than 2800 deaths. Although there are striking similarities between SARS and COVID-19, the differences in the virus characteristics will ultimately determine whether the same measures for SARS will also be successful for COVID-19. COVID-19 differs from SARS in terms of infectious period, transmissibility, clinical severity, and extent of community spread. Even if traditional public health measures are not able to fully contain the outbreak of COVID-19, they will still be effective in reducing peak incidence and global deaths. Exportations to other countries need not result in rapid large-scale outbreaks, if countries have the political will to rapidly implement countermeasures.


title: Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine

text: Abstract Background Combinations of hydroxychloroquine (HCQ) and azithromycin have been promoted as treatments for COVID-19 based on small, uncontrolled clinical trials that have not assessed potential risks. Risks of treatment include QT segment prolongation, Torsades de Pointes (TdP), and death. This comparative pharmacovigilance analysis evaluated the risk of these events. Methods Data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) (>13 million total reports) were used. Queries extracted reports based on exposures of HCQ/chloroquine (CQ) alone, azithromycin alone, HCQ/CQ + azithromycin, amoxicillin alone, HCQ/CQ + amoxicillin alone. Amoxicillin served as a control. Events of interest included death and TdP/QT prolongation as well as accidents/injuries and depression as control events. Proportional Reporting Ratios (PRR) and 95% confidence intervals (CI) were calculated where a lower limit of the of 95% CI (Lower95CI) value of ≥2.0 is interpreted as a potential safety signal. Results Lower95CIs for HCQ/CQ alone showed no potential safety signals for TdP/QT prolongation, death, or any of the control events included. The PRRs and 95% CIs for TdP/QT prolongation was 1.43 (1.29–2.59) with HCQ/CQ use alone and 4.10 (3.80–4.42) for azithromycin alone. For the combined HCQ/CQ + azithromycin group, the PRR and 95% CI was 3.77 (1.80–7.87). For the control of amoxicillin, there were no safety signals when used alone or in combination with HCQ/CQ. Conclusions HCQ/CQ use was not associated with a safety signal in this analysis of FAERS data. However, azithromycin used alone was associated with TdP/QT prolongation events and should be used with caution.


title: Ferret models of viral pathogenesis

text: Abstract Emerging and well-known viral diseases remain one the most important global public health threats. A better understanding of their pathogenesis and mechanisms of transmission requires animal models that accurately reproduce these aspects of the disease. Here we review the role of ferrets as an animal model for the pathogenesis of different respiratory viruses with an emphasis on influenza and paramyxoviruses. We will describe the anatomic and physiologic characteristics that contribute to the natural susceptibility of ferrets to these viruses, and provide an overview of the approaches available to analyze their immune responses. Recent insights gained using this model will be highlighted, including the development of new prophylactic and therapeutic approaches. To provide decision criteria for the use of this animal model, its strengths and limitations will be discussed.


title: Global health diplomacy: An integrative review of the literature and implications for nursing

text: Abstract The increasing interconnectedness of the world and the factors that affect health lay the foundation for the evolving practice of global health diplomacy. There has been limited discussion in the nursing literature about the concept of global health diplomacy or the role of nurses in such initiatives. A discussion of this concept is presented here by the members of a Task Force on Global Health Diplomacy of the American Academy of Nursing Expert Panel on Global Nursing and Health (AAN EPGNH). The purpose of this article is to present an integrative review of literature on the concept of global health diplomacy and to identify implications of this emerging field for nursing education, practice, and research. The steps proposed by Whittemore and Knafl (2005) were adapted and applied to the integrative review of theoretical and descriptive articles about the concept of global health diplomacy. This review included an analysis of the historical background, definition, and challenges of global health diplomacy and suggestions about the preparation of global health diplomats. The article concludes with a discussion of implications for nursing practice, education, and research. The Task Force endorses the definition of global health diplomacy proposed by Adams, Novotny, and Leslie (2008) but recommends that further dialogue and research is necessary to identify opportunities and educational requirements for nurses to contribute to the emerging field of global health diplomacy.


title: Heterologous expression of Brucella abortus GroEL heat-shock protein in Lactococcus lactis

text: BACKGROUND: Brucella abortus is a facultative intracellular pathogen that mainly infects cattle and humans. Current vaccines rely on live attenuated strains of B. abortus, which can revert to their pathogenic status and thus are not totally safe for use in humans. Therefore, the development of mucosal live vaccines using the food-grade lactic acid bacterium, Lactococcus lactis, as an antigen delivery vector, is an attractive alternative and a safer vaccination strategy against B. abortus. Here, we report the construction of L. lactis strains genetically modified to produce B. abortus GroEL heat-shock protein, a candidate antigen, in two cellular locations, intracellular or secreted. RESULTS: Only the secreted form of GroEL was stably produced in L. lactis, suggesting a detrimental effect of GroEL protein when intracellularly produced in this bacterium. Only trace amounts of mature GroEL were detected in the supernatant fraction of induced lactococcal cultures, and the GroEL precursor remained stacked in the cell fraction. Attempts to raise the secretion yields were made, but even when GroEL was fused to a synthetic propeptide, secretion of this antigen was not improved. CONCLUSION: We found that L. lactis is able to produce, and to secrete, a stable form of GroEL into the extracellular medium. Despite the low secretion efficiency of GroEL, which suggest that this antigen interacts with the cell envelope of L. lactis, secretion seems to be the best way to achieve both production and protein yields, regardless of cellular location. The L. lactis strain secreting GroEL has potential for in vivo immunization.


title: Microwave-assisted tissue processing for same-day EM-diagnosis of potential bioterrorism and clinical samples

text: Abstract The purpose of this study was to explore the turnaround times, section and image quality of a number of more “difficult” specimens destined for rapid diagnostic electron microscopy (EM) after microwave-assisted processing. The results were assessed and compared with those of conventionally processed samples. A variety of infectious agents, some with a potential for bioterrorism, and liver biopsies serving as an example for routine histopathology samples were studied. The samples represented virus-producing cell cultures (such as SARS-coronavirus, West Nile virus, Orthopox virus), bacteria suspensions (cultures of Escherichia coli and genetically knockout apathogenic Bacillus anthracis), suspensions of parasites (malaria Plasmodium falciparum, Leishmania major, Microsporidia cuniculi, Caenorhabditis elegans), and whole Drosophila melanogaster flies infected with microsporidia. Fresh liver samples and infected flies were fixed in Karnovsky-fixative by microwaving (20min), all other samples were fixed in buffered glutaraldehyde or Karnovsky-fixative overnight or longer. Subsequently, all samples were divided to evaluate alternative processing protocols: one part of the sample was OsO4-postfixed, ethanol-dehydrated, Epon-infiltrated (overnight) in an automated tissue processor (LYNX, Leica), and polymerized at 60°C for 48h; in parallel the other part was microwave-assisted processed in the bench microwave device (REM, Milestone), including post-osmication and the resin block polymerization. The microwave-assisted processing protocol required at minimum 3h 20min: the respective epon resin blocks were uniformly polymerized allowing an easy sectioning of semi- and ultrathin sections. Sections collected on non-coated 200mesh grids were stable in the electron beam and showed an excellent preservation of the ultrastructure and high contrast, thus allowing an easy, unequivocal and rapid assessment of specimens. Compared with conventional routine methods, microwave technology facilitates a significant reduction in sample processing time from days to hours without any loss in ultrastructural details. Microwave-assisted processing could, therefore, be a substantial benefit for the routine electron microscopic diagnostic workload. Due to its speed and robust performance it could be applied wherever a rapid electron microscopy diagnosis is required, e.g., if bioterrorism or emerging agents are suspected. Combining microwave technology with digital image acquisition, the 1-day diagnosis based on ultrathin section electron microscopy will become possible, with crucial or interesting findings being consulted or shared worldwide with experts using modern telemicroscopy tools via Internet.


title: Co-expression vs. co-infection using baculovirus expression vectors in insect cell culture: Benefits and drawbacks

text: Abstract The baculovirus expression vector system (BEVS) is a versatile and powerful platform for protein expression in insect cells. With the ability to approach similar post-translational modifications as in mammalian cells, the BEVS offers a number of advantages including high levels of expression as well as an inherent safety during manufacture and of the final product. Many BEVS products include proteins and protein complexes that require expression from more than one gene. This review examines the expression strategies that have been used to this end and focuses on the distinguishing features between those that make use of single polycistronic baculovirus (co-expression) and those that use multiple monocistronic baculoviruses (co-infection). Three major areas in which researchers have been able to take advantage of co-expression/co-infection are addressed, including compound structure-function studies, insect cell functionality augmentation, and VLP production. The core of the review discusses the parameters of interest for co-infection and co-expression with time of infection (TOI) and multiplicity of infection (MOI) highlighted for the former and the choice of promoter for the latter. In addition, an overview of modeling approaches is presented, with a suggested trajectory for future exploration. The review concludes with an examination of the gaps that still remain in co-expression/co-infection knowledge and practice.


title: Recommendations for Triage, Prioritization and Treatment of Breast Cancer Patients During the COVID-19 Pandemic

text: Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated disease (COVID-19) outbreak seriously challenges globally all health care systems and professionals. Expert projections estimate that despite social distancing and lockdown being practiced, we have yet to feel the full impact of COVID-19. In this manuscript we provide guidance to prepare for the impact of COVID-19 pandemic on breast cancer patients and advise on how to triage, prioritize and organize diagnostic procedures, surgical, radiation and medical treatments.


COVID‐19 and programmatic assessment


docid: ltdhgtdl

title: Coronavirus Disease–Activated Emergency Scaling of Anesthesiology Responsibilities Intensive Care Unit

text: In response to the rapidly evolving Coronavirus Disease 2019 (COVID-19) pandemic and the potential need for physicians to provide critical care services, the American Society of Anesthesiologists (ASA) has collaborated with the Society of Critical Care Anesthesiologists (SOCCA), the Society of Critical Care Medicine (SCCM), and the Anesthesia Patient Safety Foundation (APSF) to develop the COVID-Activated Emergency Scaling of Anesthesiology Responsibilities (CAESAR) Intensive Care Unit (ICU) workgroup. CAESAR-ICU is designed and written for the practicing general anesthesiologist and should serve as a primer to enable an anesthesiologist to provide limited bedside critical care services.


title: Synthesis of a library of glycosylated flavonols

text: Abstract Flavonols are an important class of natural products isolated from plants. Some glycosylated flavonols showed very interesting biological activities. A library of flavonols has been made through Algar–Flynn–Oyamada reaction from 2′-hydroxyacetophenones and benzaldehydes. Glycosylation of these flavonols with various glycosyl donors affords a library of glycosylated flavonols. These compounds are potentially useful pharmacologically active compounds and will be studied for biological activities.


Electroconvulsive therapy practice during the COVID-19 pandemic


title: Late viral or bacterial respiratory infections in lung transplanted patients: impact on respiratory function

text: BACKGROUND: Respiratory infections are a major threat for lung recipients. We aimed to compare with a monocentric study the impact of late viral and bacterial respiratory infections on the graft function. METHODS: Patients, who survived 6 months or more following lung transplantation that took place between 2009 and 2014, were classified into three groups: a viral infection group (VIG) (without any respiratory bacteria), a bacterial infection group (BIG) (with or without any respiratory viruses), and a control group (CG) (no documented infection). Chronic lung allograft dysfunction (CLAD) and acute rejection were analysed 6 months after the inclusion in the study. RESULTS: Among 99 included lung recipients, 57 (58%) had at least one positive virological respiratory sample during the study period. Patients were classified as follows: 38 in the VIG, 25 in the BIG (among which 19 co-infections with a virus) and 36 in the CG. The BIG presented a higher initial deterioration in lung function (p = 0.05) than the VIG. But 6 months after the infection, only the VIG presented a median decrease of forced expiratory volume in 1 s; − 35 mL (IQR; − 340; + 80) in the VIG, + 140 mL (+ 60;+ 330) in the BIG and + 10 (− 84;+ 160) in the CG, p < 0.01. Acute rejection was more frequent in the VIG (n = 12 (32%)), than the BIG (n = 6 (24%)) and CG (n = 3 (8%)), p < 0.05, despite presenting no more CLAD (p = 0.21). CONCLUSIONS: Despite a less severe initial presentation, single viral respiratory infections seem to lead to a greater deterioration in lung function, and to more acute rejection, than bacterial infections.


title: COVID‐19 – neurologists stay aware!

text: In December 2019 an epidemic outbreak of a new virus disease in the Chinese area of Wuhan was reported. The new disease caused primarily symptoms of a respiratory tract infection with cough, shortness of breath, and viral pneumonia. The clinical spectrum showed mostly mild symptoms with some patients developing bilateral pneumonia needing partly intensive care treatment and causing death(1). It became apparent, that this new disease was highly contagious, and – intensive care ‐ patients numbers were rapidly rocketing, overwhelming the capacity of local health care facilities.


title: Association of mannose‐binding lectin gene polymorphisms with Kawasaki disease in the Japanese

text: Objective: Kawasaki disease (KD) is a systemic vasculitis in childhood; its etiology is unknown. The possibility that KD is an infectious disease has been discussed and investigated for decades, in light of the implication that infections are involved in the pathogenesis of KD. Young children rely on their innate immune system for protection against virus and micro‐organisms. Human mannose binding lectin (MBL) is a C‐type serum lectin synthesized by the liver as an acute phase protein and it plays an important role in the innate immune system. Here, we investigate the relationship between the MBL gene polymorphisms and the occurrence of KD in the Japanese population. Method: The frequencies of the genotypes, defined as mutations in codons 52, 54 and 57, and the functional promoter variants of the MBL were determined in 45 patients with KD. Results: The MBL codon‐54 polymorphism frequency of heterozygote (GGC/GAC) and promoter variants were significantly higher in the KD group than that in the control group (P < 0.05). Neither group showed codon 52 nor 57 polymorphisms. Conclusion: It is possible that mutations of the MBL gene might be related to the trigger of the pathogenesis of Kawasaki disease.


title: Medical Students Are Not Essential Workers: Examining Institutional Responsibility During the COVID-19 Pandemic

text: In light of the evolving COVID-19 pandemic, the Association of American Medical Colleges (AAMC) and Liaison Committee on Medical Education (LCME) released a joint statement in March 2020 recommending an immediate suspension of medical student participation in direct patient contact. As graduating medical students who will soon begin residency, the authors fully support this recommendation. Though paid health care workers, like residents, nurses, and environmental services staff, are essential to the management of COVID-19 patients, medical students are not. Students’ continued involvement in direct patient care will contribute to SARS-CoV-2 exposures and transmissions and will waste already limited personal protective equipment. By decreasing nonessential personnel in health care settings, including medical students, medical schools will contribute to national and global efforts to “flatten the curve.” The authors also assert that medical schools are responsible for ensuring medical student safety. Without the protections provided to paid health care workers, students are uniquely disadvantaged within the medical hierarchy; these inequalities must be addressed before medical students are safely reintegrated into clinical roles. Although graduating medical students and institutional leadership may worry that suspending clinical rotations might prevent students from completing graduation requirements, the authors argue the ethical obligation to “flatten the curve” supersedes usual teaching responsibilities. Therefore, the authors request further guidance from the LCME and AAMC regarding curricular exemptions/alternatives and adjusted graduation timelines. The pool of graduating medical students affected by this pause in direct patient contact represents a powerful reserve, which may soon need to be used as the COVID-19 pandemic continues to challenge the U.S. health care infrastructure.


title: Sequential circulation of canine adenoviruses 1 and 2 in captive wild carnivores, France

text: Abstract Scarce data are currently available about the ecology of canine adenoviruses (CAdVs) in wild carnivores. In this paper, the consecutive circulation of CAdV-1 and CAdV-2 in wild carnivores maintained in a French zoological park is reported. A fatal CAdV-1 infection was observed in a Eurasian wolf (Canis lupus lupus), which displayed gross lesions, histopathological changes and immunohistochemical findings suggestive of CAdV-1 infection. The virus was isolated on cell cultures and its genome was determined through next-generation sequencing, resulting genetically related to a recent Italian CAdV-1 strain detected in an Italian wolf. Subsequently, subclinical circulation of CAdV-2 was demonstrated by molecular methods in wild carnivores maintained in the same zoological park, some of which had been previously vaccinated with a CAdV-2 vaccine. Virus detection at a long distance from vaccination and by unvaccinated animals was suggestive of infection by a CAdV-2 field strain, although no data are available about the extent and duration of shedding of CAdV-2 modified-live virus in wild or domestic carnivores. The present paper provides new insights into the CAdV ecology in wildlife, although future studies are needed to fully understand the pathogenic potential of both CAdVs especially in endangered carnivore species.


title: A perspective on tropical sprue

text: A diagnosis of tropical sprue, an infrequent affliction of inhabitants and travelers in tropical regions, should be considered in patients with a compatible history, malabsorption, and chronic diarrhea. It can occur in either endemic or epidemic form and can be preceded by acute gastroenteritis. The cause of tropical sprue is still unknown, although most data support an infectious etiology. Therapeutic experience is greatest with folic acid and tetracycline. Most patients can be expected to recover with proper nutritional support, although relapses and slow responses occur.


title: Recombinant duck enteritis viruses expressing major structural proteins of the infectious bronchitis virus provide protection against infectious bronchitis in chickens

text: Abstract To design an alternative vaccine for control of infectious bronchitis in chickens, three recombinant duck enteritis viruses (rDEVs) expressing the N, S, or S1 protein of infectious bronchitis virus (IBV) were constructed using conventional homologous recombination methods, and were designated as rDEV-N, rDEV-S, and rDEV-S1, respectively. Chickens were divided into five vaccinated groups, which were each immunized with one of the rDEVs, covalent vaccination with rDEV-N & rDEV-S, or covalent vaccination with rDEV-N & rDEV-S1, and a control group. An antibody response against IBV was detectable and the ratio of CD4+/CD8+ T-lymphocytes decreased at 7 days post-vaccination in each vaccinated group, suggesting that humoral and cellular responses were elicited in each group as early as 7 days post-immunization. After challenge with a homologous virulent IBV strain at 21 days post-immunization, vaccinated groups showed significant differences in the percentage of birds with clinical signs, as compared to the control group (p < 0.01), as the two covalent-vaccination groups and the rDEV-S group provided better protection than the rDEV-N- or rDEV-S1-vaccinated group. There was less viral shedding in the rDEV-N & rDEV-S- (2/10) and rDEV-N & rDEV-S1- (2/10) vaccinated groups than the other three vaccinated groups. Based on the clinical signs, viral shedding, and mortality rates, rDEV-N & rDEV-S1 covalent vaccination conferred better protection than use of any of the single rDEVs.


The Ebola Epidemic Crystallizes the Potential of Passive Antibody Therapy for Infectious Diseases


docid: mapmeugl

title: Chapter 8 Improvement Healthcare Projects Meeting Healthcare and Technology Challenges

text: Abstract The complexity of the healthcare environment and the one related to the healthcare organization itself are some challenges of today’s healthcare, these challenges determine a relevant change in the way we understand health systems and determine approaches to improve the results of healthcare projects. In the same regard, the management of emerging technologies requires transformational changes to face effectively the trends in healthcare. The chapter introduces to Systems Engineering it involves thinking holistically and work with transdisciplinary teams to develop solutions.


title: Viral sensors: diversity in pathogen recognition

text: Summary: Innate sensors of viral infection detect viral products and initiate the signal cascades that lead to the antiviral response. Several proteins have been identified to play a role in this process, mostly members of the Toll‐like receptor and retinoic acid‐inducible gene I‐like receptor families. These receptors have been demonstrated to function in part by recognizing a diverse yet unique repertoire of nucleic acid substrates. Upon recognition of their ligands, these sensors activate distinct signaling pathways that lead to the secretion of type I interferon and inflammatory cytokines. It remains to be seen, however, if these sensors are redundant or whether each serves a unique function. In this work, we review the current knowledge of viral sensors, speculate on how they may function in vivo, and explore the potential reasons for their diversity.


title: Maternally-derived neutralizing antibodies reduce vaccine efficacy against porcine reproductive and respiratory syndrome virus infection

text: Abstract Modified live virus (MLV) vaccines are commonly used to reduce the impact of porcine reproductive and respiratory syndrome (PRRS) but limited efficacy is achieved in field conditions. Here, we evaluated the impact of maternally-derived neutralizing antibodies (MDNAs) on vaccine efficacy after PRRS virus (PRRSV) challenge. Piglets with low (A−) or high (A+) MDNA levels derived from a commercial pig herd were moved to experimental facilities to be vaccinated (V+) or not (V−) with a PRRSV-1 MLV vaccine at 3 weeks of age (woa). Because of unexpectedly low vaccine detection in A−V+ piglets post-vaccination (pv), all V+ piglets received a second vaccination at 4 woa. Five weeks (W5) pv, piglets were inoculated with a PRRSV-1 field strain to evaluate vaccine protection, and were mingled 24 h later with non-inoculated piglets of similar immune status to assess viral transmission. Vaccine strain was detected at W2 pv in 69% and 6% of A−V+ and A+V+ piglets, and at W5 pv in 50% and 25% of A−V+ and A+V+ piglets, respectively. At W5 pv, 94% of A−V+ and 44% of A+V+ piglets seroconverted, with a significant IFNg response induction in the A−V+ group only. After challenge, compared to the V− inoculated group, viremia was 100-fold lower at 10 days post-infection in A−V+ whereas viremia was not significantly reduced in A+V+ piglets. A lower transmission rate was estimated for the A−V+ group: 0.15 [0.07–0.29] versus 0.44 [0.18–1.76] and 0.32 [0.14–0.68] for the A+V+ and V− groups, respectively. Investigations about the low vaccine strain detection after the first vaccination suggested a relationship between IFNa levels and vaccine strain detection in A−V+ piglets. We showed that MDNAs impair vaccine efficacy against PRRSV both in inoculated and contact piglets, probably by reducing vaccine replication. IFNa may also interfere with PRRSV vaccination. These new data could help improving vaccination protocols.


title: COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome

text: Summary Zhou et al. (Nature) and Hoffmann et al. (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2. These results may explain proinflammatory cytokine release via the associated angiotestin II pathway and a possible therapeutic target via the IL-6-STAT3 axis.


Endothelin receptor antagonists for pulmonary arterial hypertension and COVID-19: friend or foe ?


title: Coronavirus Pandemic—Therapy and Vaccines

text: The current coronavirus COVID-19 pandemic, which originated in Wuhan, China, has raised significant social, psychological and economic concerns in addition to direct medical issues. The rapid spread of severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 to almost every country on the globe and the failure to contain the infections have contributed to fear and panic worldwide. The lack of available and efficient antiviral drugs or vaccines has further worsened the situation. For these reasons, it cannot be overstated that an accelerated effort for the development of novel drugs and vaccines is needed. In this context, novel approaches in both gene therapy and vaccine development are essential. Previous experience from SARS- and MERS-coronavirus vaccine and drug development projects have targeted glycoprotein epitopes, monoclonal antibodies, angiotensin receptor blockers and gene silencing technologies, which may be useful for COVID-19 too. Moreover, existing antivirals used for other types of viral infections have been considered as urgent action is necessary. This review aims at providing a background of coronavirus genetics and biology, examples of therapeutic and vaccine strategies taken and potential innovative novel approaches in progress.


title: Development of a vulnerability index for diagnosis with the novel coronavirus, COVID-19, in Washington State, USA

text: ●. In the United States, morbidity and mortality from COVID-19 infection varies substantially among populations and geographic regions; ●. Variation has been attributed to chronic disease burden, and certain sociodemographic factors; ●. We developed an index of COVID-19 vulnerability using a regression modeling approach with observed diagnosis at the Zipcode level in Washington State; ●. The resulting index can be used by policy makers for the targeting of public health and health care resources.


title: Retrospective Evaluation of Control Measures for Contacts of Patient with Marburg Hemorrhagic Fever

text: After an imported case of Marburg hemorrhagic fever was reported in 2008 in the Netherlands, control measures to prevent transmission were implemented. To evaluate consequences of these measures, we administered a structured questionnaire to 130 contacts classified as either having high-risk or low-risk exposure to body fluids of the case-patient; 77 (59.2%) of 130 contacts responded. A total of 67 (87.0%) of 77 respondents agreed that temperature monitoring and reporting was necessary, significantly more often among high-risk than low-risk contacts (p<0.001). Strict compliance with daily temperature monitoring decreased from 80.5% (62/77) during week 1 to 66.2% (51/77) during week 3. Contacts expressed concern about development of Marburg hemorrhagic fever (58.4%, 45/77) and infecting a family member (40.2%, 31/77). High-risk contacts had significantly higher scores on psychological impact scales (p<0.001) during and after the monitoring period. Public health authorities should specifically address consequences of control measures on the daily life of contacts.


title: Diseases associated with bovine viral diarrhea virus subtypes 1a and 2b in beef and dairy cattle in Uruguay

text: Bovine viral diarrhea virus (BVDV, Pestivirus) causes significant economic losses to the livestock industry worldwide. Although serological surveys show that BVDV exposure is widespread in cattle in Uruguay, BVDV-associated diseases are greatly underreported. The aim of this work is to describe the epidemiological, clinical, pathological, and virological findings from spontaneous outbreaks of BVDV-associated diseases in cattle in Uruguay. Diagnostic investigations were performed during 6 spontaneous disease outbreaks on beef and dairy cattle farms in the departments of Colonia, Rio Negro, and Soriano between November 2016 and April 2018. Carcasses of 8 naturally deceased cattle from these outbreaks were necropsied and subjected to histological examination and immunohistochemistry to detect BVDV antigen in the tissues. Reverse transcription real-time PCR and genomic sequencing were also performed to identify BVDV at the species and subtype levels. Other ancillary diagnostic tests, including bacterial cultures, were performed on a case-by-case basis to rule in/out differential diagnoses based on initial clinicopathological presumptive diagnoses. BVDV-associated conditions that were diagnosed in the 8 cases included mucosal disease, transient postnatal BVDV infections associated with digestive/septicemic salmonellosis by Salmonella serovar typhimurium, Histophilus somni bronchopneumonia, urinary tract coinfections with Escherichia coli and Streptococcus sp., enteric coinfection with coccidia, and transplacental fetal infections and abortions with Neospora caninum coinfection. BVDV-1a and BVDV-2b were each identified in four of the eight cases. We conclude that BVDV-1a and BVDV-2b contribute significantly to disease and mortality in cattle in Uruguay. Future research should estimate the economic impact of BVDV in the Uruguayan livestock sector. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42770-019-00170-7) contains supplementary material, which is available to authorized users.


title: Genetic stability of Schmallenberg virus in vivo during an epidemic, and in vitro, when passaged in the highly susceptible porcine SK-6 cell line

text: Abstract Schmallenberg virus (SBV), an arthropod-borne orthobunyavirus was first detected in 2011 in cattle suffering from diarrhea and fever. The most severe impact of an SBV infection is the induction of malformations in newborns and abortions. Between 2011 and 2013 SBV spread throughout Europe in an unprecedented epidemic wave. SBV contains a tripartite genome consisting of the three negative-sense RNA segments L, M, and S. The virus is usually isolated from clinical samples by inoculation of KC (insect) or BHK-21 (mammalian) cells. Several virus passages are required to allow adaptation of SBV to cells in vitro. In the present study, the porcine SK-6 cell line was used for isolation and passaging of SBV. SK-6 cells proved to be more sensitive to SBV infection and allowed to produce higher titers more rapidly as in BHK-21 cells after just one passage. No adaptation was required. In order to determine the in vivo genetic stability of SBV during an epidemic spread of the virus the nucleotide sequence of the genome from seven SBV field isolates collected in summer 2012 in Switzerland was determined and compared to other SBV sequences available in GenBank. A total of 101 mutations, mostly transitions randomly dispersed along the L and M segment were found when the Swiss isolates were compared to the first SBV isolated late 2011 in Germany. However, when these mutations were studied in detail, a previously described hypervariable region in the M segment was identified. The S segment was completely conserved among all sequenced SBV isolates. To assess the in vitro genetic stability of SBV, three isolates were passage 10 times in SK-6 cells and sequenced before and after passaging. Between two and five nt exchanges per genome were found. This low in vitro mutation rate further demonstrates the suitability of SK-6 cells for SBV propagation.


COVID-19: a look from the perspective of bioethics


title: Mycoplasma pneumoniaeassociated transverse myelitis presenting as asymmetric flaccid paralysis

text: Acute transverse myelitis is a rare spinal cord inflammatory disorder that manifests as sudden onset of motor, sensory, and autonomic dysfunctions. Here, we report a case of acute transverse myelitis in a 13- year-old boy secondary to Mycoplasma pneumoniae infection. He presented with left facial palsy and contralateral upper extremity weakness without sensory or autonomic changes. The patient was diagnosed with transverse myelitis based on his magnetic resonance imaging findings, although his presentation was mainly motor dysfunction, which is more consistent with acute flaccid paralysis.


title: Severe airport sanitarian control could slow down the spreading of COVID-19 pandemics in Brazil

text: BACKGROUND: We investigated a likely scenario of COVID-19 spreading in Brazil through the complex airport network of the country, for the 90 days after the first national occurrence of the disease. After the confirmation of the first imported cases, the lack of a proper airport entrance control resulted in the infection spreading in a manner directly proportional to the amount of flights reaching each city, following the first occurrence of the virus coming from abroad. METHODOLOGY: We developed a Susceptible-Infected-Recovered model divided in a metapopulation structure, where cities with airports were demes connected by the number of flights. Subsequently, we further explored the role of the Manaus airport for a rapid entrance of the pandemic into indigenous territories situated in remote places of the Amazon region. RESULTS: The expansion of the SARS-CoV-2 virus between cities was fast, directly proportional to the city closeness centrality within the Brazilian air transportation network. There was a clear pattern in the expansion of the pandemic, with a stiff exponential expansion of cases for all the cities. The more a city showed closeness centrality, the greater was its vulnerability to SARS-CoV-2. CONCLUSIONS: We discussed the weak pandemic control performance of Brazil in comparison with other tropical, developing countries, namely India and Nigeria. Finally, we proposed measures for containing virus spreading taking into consideration the scenario of high poverty.


title: A novel cell-based binding assay system reconstituting interaction between SARS-CoV S protein and its cellular receptor

text: Abstract Severe acute respiratory syndrome (SARS), a life-threatening disease, is caused by the newly identified virus SARS coronavirus (SARS-CoV). In order to study the spike (S) protein of this highly contagious virus, we established a clonal cell-line, CHO-SG, from the Chinese hamster ovary cells that stably expresses C-terminally EGFP-tagged SARS-CoV S protein (S-EGFP). The ectodomain of the S glycoprotein is localized on the surface of CHO-SG cells with N-acetyl-glucosamine-terminated carbohydrate structure. CHO-SG cells associated tightly with Vero E6 cells, a SARS-CoV receptor (ACE2) expressing cell-line, and the interaction remained stable under highly stringent condition (1M NaCl). This interaction could be blocked by either the serum from a SARS convalescent patient or a goat anti-ACE2 antibody, indicating that the interaction is specific. A binding epitope with lesser degree of glycosylation and native conformation was localized by using rabbit anti-sera raised against five denatured recombinant S protein fragments expressed in Escherichia coli. One of the sera obtained from the fragment encompassing amino acids 48-358 significantly blocked the interaction between CHO-SG and Vero E6 cells. The region is useful for studying neutralizing antibodies in future vaccine development. This paper describes an easy and safe cell-based assay suitable for studying the binding between SARS-CoV S protein and its receptor.


title: Successful cross-protective efficacy induced by heat-adapted live attenuated nephropathogenic infectious bronchitis virus derived from a natural recombinant strain

text: A natural recombinant nephropathogenic K40/09 strain of infectious bronchitis virus (IBV) was heat-adapted for possible future use as live attenuated vaccine. The K40/09 strain was selected during successive serial passages in specific-pathogen free (SPF) embryonated eggs at sub-optimal higher temperature (56 °C). Unlike the parental strain, the attenuated strain, designated K40/09 HP50, was found to be safe in 1-day-old SPF chicks, which showed neither mortality nor signs of morbidity, and rarely induced ciliostasis or histological changes in the trachea and kidney after intraocular and fine-spray administration. K40/09 HP50 provided almost complete protection against two distinct subgroups of a nephropathogenic strain (KM91-like and QX-like subgroup) and elicited the production of high titers of neutralizing antibody (neutralization index of 3.6). We conclude that the K40/09 HP50 vaccine virus is rapidly attenuated by heat adaptation and exhibits the desired level of attenuation, immunogenicity, and protective efficacy required for a live attenuated vaccine. These results indicate that the K40/09 vaccine could be helpful for the reduction of economic losses caused by recently emergent nephropathogenic IBV infection in many countries.


title: Learning Cytology in times of pandemic: an educational institutional experience with remote teaching

text: Abstracts Introduction As the coronavirus pandemic swept across national and state borders, institutions of higher learning, including cytology, began closing campuses and moving instructions on-line. We described a method of remotely teaching cytology in our institution, which includes utilizing the tele-cytology concept used in Rapid Onsite Evaluations (ROSE) and using remote conferencing/educational tools to conduct eCytology learning. This is a cost-effective way to transition a traditional in-classroom program into online teaching in cytology. It can also be implemented quickly. Methods In March 2020, our cytology program developed a method for teaching cytology remotely. The distance-learning teaching method included the use of remote conferencing (Zoom) and learning management platforms (Canvas) to present lectures and administer tests. Remote multi-head sessions were conducted by adapting the tele-cytology ROSE concept which attach a mobile device to the microscope to transmit live video to remote learners. Results When asked about their experiences with online learning, students responded positively to their experiences. All students indicate a willingness to attend classes remotely in the future, even when the traditional in-classroom learning option is available. Conclusion We present a method for educating students remotely through the use of existing technology that is affordable and could be implemented quickly by nearly all cytology education programs.


Urologic Oncology: News and Topics: Ethics of Urologic Care in the Time of COVID-19


title: The Impact of Internet Usage and Knowledge-Intensive Activities on Households’ Healthcare Expenditures

text: This paper examines the impact of the internet usage and knowledge intensive activities on households’ healthcare expenditures Similarly, the paper aims to recognize and understand, from a value-creation perspective, the correlation between: internet access of households (IA), individuals frequently using the internet (IU), individuals searching on internet for health-related information (HI), payments made by households for healthcare (PHH), expressed as euro per inhabitant and employment in knowledge-intensive activities (KIA). The approach utilized in the present study consists of two steps. First, a theoretical framework was conducted to determine the existing relationship between major variables. Next, the Vector Autoregressive (VAR) approach was applied in a case study at European level to prove the three hypothesis we consider. By analyzing the connection between the major variables, a positive and long- lasting impulse response function was revealed, followed by an ascending trend. This suggests that a self-multiplying effect is being generated; and it reasonable to assume that the more individuals use the Internet, the more electronic acquisitions occur. We can thus reasonably conclude that the improvement of the internet usage and knowledge intensive activities on households’ healthcare expenditures process is strongly dependent on people’s capability. Improving IU and KIA is the new reading key in the decision-making process in health system approach.


title: Smoking and SARS-CoV-2 Disease (COVID-19): Dangerous Liaisons or Confusing Relationships?

text: We read with great interest the article by Brake SJ and colleagues [...].


title: Covid-19 Sets off Mass Migration in India

text: Abstract The communication discusses Covid-19 triggered reverse migration in India. India has witnessed the second largest mass migration in its history after the Partition of India in 1947, where more than 14 million people were displaced and migrated to India and Pakistan respectively, depending on their religious faiths. The opinion describes the trend of migration and related effects on the migrants as well as the nation at large.


title: CHAPTER 7 CELL-SURFACE ANTIGENS

text: Publisher Summary The cell surface is covered with protein molecules that are held in the membrane by hydrophobic transmembrane segments or glycosyl–phosphatidylinositol (GPI) anchors. Antigens found on cell surfaces comprise not only those encoded by the cell itself but also the products of intracellular parasites. Soluble ligands may be bound to receptor structures on the cell membrane or lectin-like molecules bound to cell-surface carbohydrate structures. The molecules that form an integral part of the cell surface may be proteins, glycoproteins, or glycolipids. They subserve one of three major functions: adhesion, antigen recognition, or receptors for soluble mediators. However, many cell-surface molecules possess more than one function—for example, molecules involved in cell–cell or cell–extracellular matrix adhesion can also themselves be involved in signal transduction. The cell-surface antigens of leukocytes have been intensively studied because of ease of access to this cellular compartment.


title: A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2

text: Abstract In vitro infection of Vero E6 cells by SARS coronavirus (SARS-CoV) is blocked by hexapeptide Tyr-Lys-Tyr-Arg-Tyr-Leu. The peptide also inhibits proliferation of coronavirus NL63. On human cells both viruses utilize angiotensin-converting enzyme 2 (ACE2) as entry receptor. Blocking the viral entry is specific as alpha virus Sindbis shows no reduction in infectivity. Peptide 438YKYRYL443 is part of the receptor-binding domain (RBD) of the spike protein of SARS-CoV. Peptide libraries were screened by surface plasmon resonance (SPR) to identify RBD binding epitopes. 438YKYRYL443 carries the dominant binding epitope and binds to ACE2 with K D =46μM. The binding mode was further characterized by saturation transfer difference (STD) NMR spectroscopy and molecular dynamic simulations. Based on this information the peptide can be used as lead structure to design potential entry inhibitors against SARS-CoV and related viruses.


title: COVID-19 and the policy sciences: initial reactions and perspectives

text: The world is in the grip of a crisis that stands unprecedented in living memory. The COVID-19 pandemic is urgent, global in scale, and massive in impacts. Following Harold D. Lasswell’s goal for the policy sciences to offer insights into unfolding phenomena, this commentary draws on the lessons of the policy sciences literature to understand the dynamics related to COVID-19. We explore the ways in which scientific and technical expertise, emotions, and narratives influence policy decisions and shape relationships among citizens, organizations, and governments. We discuss varied processes of adaptation and change, including learning, surges in policy responses, alterations in networks (locally and globally), implementing policies across transboundary issues, and assessing policy success and failure. We conclude by identifying understudied aspects of the policy sciences that deserve attention in the pandemic’s aftermath.


title: Darunavir does not prevent SARS-CoV-2 infection in HIV patients

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title: Learning New Ways of Teaching and Assessment – The Impact of Covid‐19 on Undergraduate Dermatology Education

text: Covid‐19 has resulted in unprecedented global disruption. As this global pandemic persists with no end in sight, we must not ignore its impact on undergraduate medical education. Dermatology undergraduate exposure is variable, limited and often suboptimal. It has been shown that medical students and qualified doctors are not adequately confident in their ability to assess and manage skin conditions, and many feel that their undergraduate dermatology teaching was not satisfactory.


title: Isolation and identification of group A rotaviruses among neonatal diarrheic calves, Morocco

text: BACKGROUND: Group A rotaviruses (RVA) are the main cause of neonatal calve diarrhea (NCD) in Morocco. In this study, we isolated RVA strains from NCD clinical samples in order to support RVA disease control in Morocco. This isolation process constitutes a first step toward vaccine development. METHODS: Thirteen fecal samples were obtained from calves with a single episode of neonate calf diarrhea at three different dairies and two samples were collected from field during a severe NCD outbreak. Diagnosis of RVA infection was based on fecal immune-chromatographic rapid test and further evaluated for their hemagglutination (HA) activity. RVA isolation was carried out on MA104 cells after inoculates were treated with different concentrations of trypsin TPCK. All RVA isolates were confirmed by LSI VetMAX™ Triplex Ruminant Rotavirus & Coronavirus Real-Time PCR kit. G and P typing were determined by direct sequencing of the VP4 and VP7 amplicons. RESULTS: RVA isolation was achieved for nine clinical samples following one or two passages (60 %) and was properly depended on HA activity and trypsin treatment of inoculates. The first sign of CPE detected consisted of increased cell granularity, obscure cell boundaries, cell rounding, and eventual degeneration and detachment of cells. At lower TPCK concentration (3–10 μg/inoculum), no changes at the cellular level were observed, while cells activated with 25–30 μg of trypsin/inoculums, they degenerated and trypsin cytotoxicity was enhanced. Appreciable changes in cell’s morphology were detected with optimal trypsin concentration of 15–20 μg trypsin/inoculums. Data from qRT-PCR confirmed that unsuccessful cultivations have No-Ct, and all nine isolates have Ct values ranged between 12.17 and 24.69. Analysis sequencing revealed that field isolates were of G6 P[5] serotype and isolates from the dairy NCD samples were of G10 P[14] serotype. CONCLUSIONS: To our knowledge, this is the first study in Morocco which reports the circulation of G10P[14] in NCD on dairy farms and G6P[5] in the field. Our study constitutes a crucial and a necessary step allowing preventive and veterinary medicine to support RVA disease controls in the country.


title: Interaction of the Dengue Virus Fusion Peptide with Membranes Assessed by NMR: The Essential Role of the Envelope Protein Trp101 for Membrane Fusion

text: Summary Dengue virus (DV) infection depends on a step of membrane fusion, which occurs in the acidic environment of the endosome. This process is mediated by virus surface envelope glycoprotein, in which the loop between residues D98–G112 is considered to be crucial, acting as a fusion peptide. Here, we have characterized functionally and structurally the interaction between the DV fusion peptide and different model membranes by fluorescence and NMR. Its interaction was strongest in dodecylphosphocholine (DPC) micelles and anionic phosphatidylcholine/phosphatidylglycerol vesicles, the only vesicle that was fused by DV fusion peptide. The three-dimensional structure of DV fusion peptide bound to DPC micelles was solved by solution homonuclear NMR with an r.m.s.d. of 0.98 Å. The most striking result obtained from the solution structure was the hydrophobic triad formed by residues W101, L107, and F108, pointing toward the same direction, keeping the segment between G102 and G106 in a loop conformation. The interaction of DV fusion peptide with phosphatidylcholine/phosphatidylglycerol vesicles was also mapped by transfer-nuclear Overhauser enhancement (NOE) experiments, in which the majority of the NOE cross-peaks were from the hydrophobic triad, corroborating the DPC-bound structure. Substitution of the residue W101 by an alanine residue completely abolished membrane binding and, thus, fusion by the peptide and its NOE cross-peaks. In conclusion, the 15-residue DV fusion peptide has intrinsic ability to promote membrane fusion, most likely due to the hydrophobic interaction among the residues W101, L107, and F108, which maintains its loop in the correct spatial conformation.


title: Provision of obstetrics and gynaecology services during the COVID‐19 pandemic: a survey of junior doctors in the UK National Health Service

text: OBJECTIVE: The coronavirus disease 2019 (COVID‐19) pandemic is disrupting health services worldwide. We aimed to evaluate the provision of obstetrics and gynaecology services in the UK during the acute phase of the COVID‐19 pandemic. DESIGN: Interview‐based national survey. SETTING: Women's healthcare units in the National Health Service. POPULATION: Junior doctors in obstetrics and gynaecology. METHODS: Participants were interviewed by members of the UK Audit and Research in Obstetrics and Gynaecology trainees' collaborative between 28 March and 7 April 2020. We used a quantitative analysis for closed‐ended questions and a thematic framework analysis for open comments. RESULTS: We received responses from 148/155 units (95%), most of the participants were in years 3–7 of training (121/148, 82%). Most completed specific training drills for managing obstetric and gynaecological emergencies in women with COVID‐19 (89/148, 60.1%) and two‐person donning and doffing of Personal Protective Equipment (PPE) (96/148, 64.9%). The majority of surveyed units implemented COVID‐19‐specific protocols (130/148, 87.8%), offered adequate PPE (135/148, 91.2%) and operated dedicated COVID‐19 emergency theatres (105/148, 70.8%). Most units reduced face‐to‐face antenatal clinics (117/148, 79.1%) and suspended elective gynaecology services (131/148, 88.5%). The 2‐week referral pathway for oncological gynaecology was not affected in half of the units (76/148, 51.4%), but half reported a planned reduction in oncology surgery (82/148, 55.4%). CONCLUSION: The provision of obstetrics and gynaecology services in the UK during the acute phase of the COVID‐19 pandemic seems to be in line with current guidelines, but strategic planning is needed to restore routine gynaecology services and ensure safe access to maternity care in the long term. TWEETABLE ABSTRACT: Provision of obstetrics and gynaecology services during the acute phase of COVID‐19 is in line with current guidelines, strategic planning is needed to restore routine services and ensure safe access to care in the long term.


title: A Multi-Omics Study of Chicken Infected by Nephropathogenic Infectious Bronchitis Virus

text: Chicken gout resulting from nephropathogenic infectious bronchitis virus (NIBV) has become a serious kidney disease problem in chicken worldwide with alterations of the metabolic phenotypes in multiple metabolic pathways. To investigate the mechanisms in chicken responding to NIBV infection, we examined the global transcriptomic and metabolomic profiles of the chicken’s kidney using RNA-seq and GC–TOF/MS, respectively. Furthermore, we analyzed the alterations in cecal microorganism composition in chickens using 16S rRNA-seq. Integrated analysis of these three phenotypic datasets further managed to create correlations between the altered kidney transcriptomes and metabolome, and between kidney metabolome and gut microbiome. We found that 2868 genes and 160 metabolites were deferentially expressed or accumulated in the kidney during NIBV infection processes. These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. In addition, the comprehensive correlations between the kidney metabolome and cecal microbial community showed contributions of gut microbiota in the progression of NIBV-infection. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout.


The impacts of the COVID‐19 pandemic on medical students in Australia


Elective endotracheal intubation for urgent GI endoscopy among hospitalized patients with SARS-CoV-2


title: Metabolism of Epimedium-derived Flavonoid Glycosides in Intestinal Flora of Rabbits and Its Inhibition by Gluconolactone

text: Abstract Aim The metabolism of Epimedium-derived flavonoid glycosides (EF, with icariin as the main component) in rabbit intestinal flora and its inhibition by gluconolactone were investigated in this paper to help reveal the metabolic pathway of EF in rabbits and to identify the in vivo bioactive components of EF in the prevention of steroid-associated osteonecrosis. Methods EF were incubated at 37 °C anaerobically with rabbit intestinal flora, and then water-saturated ethyl acetate was used for sample extraction at different time points. Furthermore, gluconolactone was added at different concentrations (8, 12 and 16 mg·mL−1) to study its inhibition of the metabolism of EF in rabbit intestinal flora. The separation was performed on a ODS column by gradient elution with acetonitrile-water (including 0.1% formic acid respectively) as mobile phase at detection wavelength of 335 nm. Results EF were metabolized to icariside II in 2 h, and then to icaritin when incubated for 8 h; gluconolactone showed the inhibition of EF metabolism in rabbit intestinal flora in a concentration-dependent manner. Conclusion EF were found to be metabolized rapidly by hydrolysis of rabbit intestinal flora to produce icariside II and icaritin; and the total inhibition was achieved by gluconolactone at a concentration of 16 mg·mL−1.


title: Glycyrrhetinic acid alleviates hepatic inflammation injury in viral hepatitis disease via a HMGB1-TLR4 signaling pathway

text: Abstract Various human disorders are cured by the use of licorice, a key ingredient of herbal remedies. Glycyrrhizic acid (GL), a triterpenoid glycoside, is the aqueous extract from licorice root. Glycyrrhetinic acid (GA) has been reported to be a major bioactive hydrolysis product of GL and has been regarded as an anti-inflammatory agent for the treatment of a variety of inflammatory diseases, including hepatitis. However, the mechanism by which GA inhibits viral hepatic inflammatory injury is not completely understood. In this study, we found that, by consecutively treating mice with a traditional herbal recipe, licorice plays an important role in the detoxification of mice. We also employed a murine hepatitis virus (MHV) infection model to illustrate that GA treatment inhibited activation of hepatic inflammatory responses by blocking high-mobility group box 1 (HMGB1) cytokine activity. Furthermore, decreased HMGB1 levels and downstream signaling triggered by injection of a neutralizing HMGB1 antibody or TLR4 gene deficiency, also significantly protected against MHV-induced severe hepatic injury. Thus, our findings characterize GA as a hepatoprotective therapy agent in hepatic infectious disease not only by suppressing HMGB1 release and blocking HMGB1 cytokine activity, but also via an underlying viral-induced HMGB1-TLR4 immunological regulation axis that occurs during the cytokine storm. The present study provides a new therapy strategy for the treatment of acute viral hepatitis in the clinical setting.


title: Microarrays in infection and immunity

text: Over the past decade, microarrays have revolutionized the scientific world as dramatically as the internet has changed everyday life. From the initial applications of DNA microarrays to uncover gene expression patterns that are diagnostic and prognostic of cancer, understanding the interplay between immune responses and disease has been a prime application of this technology. More recent efforts have moved beyond genetic analysis to functional analysis of the molecules involved, including identification of immunodominant antigens and peptides as well as the role of post-translational glycosylation. Here, we focus on recent applications of microarray technology in understanding the detailed chemical biology of immune responses to disease in an effort to guide development of vaccines and other protective therapies.


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title: When Separation is not the Answer: Breastfeeding Mothers and Infants affected by COVID‐19

text: The World Health Organisation (WHO) has provided detailed guidance on the care of infants of women who are a person under investigation (PUI) or confirmed to have COVID‐19, which supports immediate postpartum mother‐infant contact and breastfeeding with appropriate respiratory precautions. Although many countries have followed WHO guidance, others have implemented infection prevention and control policies (IPC) that impose varying levels of postpartum separation and discourage or prohibit breastfeeding or provision of expressed breastmilk. These policies aim to protect infants from the potential harm of infection from their mothers, yet they may fail to fully account for the impact of separation. Global COVID‐19 data are suggestive of potentially lower susceptibility and a typically milder course of disease among children, although the potential for severe disease in infancy remains. Separation causes cumulative harms, including disrupting breastfeeding and limiting its protection against infectious disease, which has disproportionate impacts on vulnerable infants. Separation also presumes the replaceability of breastfeeding – a risk that is magnified in emergencies. Moreover, separation does not ensure lower viral exposure during hospitalizations and post‐discharge, and contributes to the burden on overwhelmed health systems. Finally, separation magnifies maternal health consequences of insufficient breastfeeding and compounds trauma in communities who have experienced long‐standing inequities and violence, including family separation. Taken together, separating PUI/confirmed SARS‐CoV‐2 positive mothers and their infants may lead to excess preventable illnesses and deaths among infants and women around the world. Health services must consider the short‐and‐long‐term impacts of separating mothers and infants in their policies.


title: Community Pharmacists in Taiwan at the Frontline Against the Novel Coronavirus Pandemic: Gatekeepers for the Rationing of Personal Protective Equipment

text: Compared with other countries, Taiwan has had relatively few cases during the COVID-19 pandemic. One of the many measures the government implemented was a system for rationing and distributing surgical masks to the public while prioritizing allocation of masks to health care workers. This essay describes the role of community pharmacists in implementing the system and distributing masks to the public.


title: Effect of handling and storage conditions and stabilizing agent on the recovery of viral RNA from oral fluid of pigs

text: There is an increasing interest in using oral fluid to determine herd health and documenting the circulation of viruses in commercial swine populations but little is known about the stability of viruses in oral fluid. Hepatitis E virus (HEV) is a zoonotic virus which is widespread in swine herds. Information on optimal handling methods such as heat treatments, freezing and RNA stabilization agents is needed to prevent or minimize degradation of viral RNA by degradative enzymes. The objectives of the study were to determine optimum handling conditions of the oral fluid before RNA extraction and to compare the performance of the RNeasy Protect Saliva Mini kit, which contains a stabilizing agent, with that of the QIAamp Viral RNA Mini kit, which does not contain a stabilizing agent. Preliminary studies with oral fluid inoculated with HEV indicated that a heat treatment of 60 °C for 15 min was detrimental to HEV RNA. HEV was recovered from 25/25 and 24/25 samples of oral fluid when samples were incubated for ≤24 h at 4 °C and 30 days at −20 °C, respectively, without a stabilizing agent and extracted with the QiaAMP kit. In contrast, HEV RNA was detected in 16/25 and 11/25 samples when samples were incubated with a stabilizing agent for 24 h at 37 °C and 30 days at −20 °C, respectively, and extracted with the RNeasy Protect Saliva kit. Moreover, the mean number of genome copies/ml of HEV recovered from oral fluid stored at −20 °C without the stabilizing agent was 2.9 log units higher than oral fluid stored at −20 °C in the presence of the stabilizing agent. The recovery of RNA from HEV, F-RNA coliphage MS2 and murine norovirus (MNV), which are surrogates for norovirus, was significantly greater when oral fluid was incubated for 24 h at 4 °C than when oral fluid was stabilized with RNAprotect Saliva Reagent for 24 h at 37 °C, where the relative differences between the two processes were 1.4, 1.8, and 2.7 log genome copies/ml for MS2, MNV, and HEV, respectively. The findings suggest that it is unnecessary to stabilize oral fluid from swine for the detection of viral RNA, provided the samples are stored at 4 °C or frozen at −20 °C, and that the RNeasy Protect Saliva Mini kit did not perform well for the detection of viral RNA.