title: Neurogenic pulmonary edema following febrile status epilepticus in a 22-month-old infant with multiple respiratory virus co-detection: a case report

text: BACKGROUND: Neurogenic pulmonary edema is a rare but serious complication of febrile status epilepticus in children. Comprehensive screening for viral pathogens is seldomly performed in the work-up of febrile children. CASE PRESENTATION: A 22-month-old girl presented with her first episode of febrile status epilepticus, after which she developed acute pulmonary edema and respiratory failure. After the termination of seizure activity, the patient was intubated and managed on mechanical ventilation in the emergency room. The resolution of respiratory failure, as well as the neurological recovery, was achieved 9 h after admission, and the patient was discharged 6 days after admission without any complications. Molecular biological diagnostic methods identified the presence of human coronavirus HKU1, influenza C virus, and human parainfluenza virus 2 from the patient’s nasopharyngeal specimens. CONCLUSIONS: Neurogenic pulmonary edema following febrile status epilepticus was suspected to be the etiology of our patient’s acute pulmonary edema and respiratory failure. Timely seizure termination and rapid airway and respiratory intervention resulted in favorable outcomes of the patient. Molecular biological diagnostic methods identified three respiratory viruses; however, their relevance and association with clinical symptoms remain speculative.


title: COVID‐19 PANDEMIC AND SOCIAL DISTANCING IN PRISONS

text: In the context of the Covid‐19 pandemic, how can the early release of prisoners, requested by the World Health Organization, members of civil society and non‐governmental organizations, be considered a ‘humane’ decision? In this article, the author examines the Portuguese context, discussing the ways that the urgency and fear of contagion highlighted, once more, the inability of prisons to cope with the needs of both those they confine and those they intend to protect.


title: Chinese patent medicines for the treatment of the common cold: a systematic review of randomized clinical trials

text: BACKGROUND: Many Chinese patent medicines (CPMs) have been authorized by the Chinese State of Food and Drug Administration for the treatment of the common cold. A number of clinical trials have been conducted and published. However, there is no systematic review or meta-analysis on their efficacy and safety for the common cold to justify their clinical use. METHODS: We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites for published and unpublished randomized clinical trials (RCTs) of CPMs for the common cold till 31 March 2013. Revman 5.2 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). RESULTS: A total of five RCTs were identified. All of the RCTs were of high risk of bias with flawed study design and poor methodological quality. All RCTs included children aged between 6 months to 14 years. Results of individual trials showed that Shuanghuanglian oral liquid (RR 4.00; 95% CI: 2.26 to 7.08), and Xiaoer Resuqing oral liquid (RR 1.43; 95% CI: 1.15 to 1.77) had higher cure rates compared with antivirus drugs. Most of the trials did not report adverse events, and the safety of CPMs was still uncertain. CONCLUSIONS: Some CPMs showed a potential positive effect for the common cold on cure rate. However, due to the poor methodology quality and the defects in the clinical design of the included RCTs, such as the lack of placebo controlled trials, the inappropriate comparison intervention and outcome measurement, the confirmative conclusions on the beneficial effect of CPMs for the common cold could not be drawn.


title: Sinochem building first additives plant outside China

text: Chinese fine chemicals manufacturer Sinochem International Corp, the international arm of Beijing-based Sinochem Group, is building its first overseas polymer additives production facility in Thailand, according to reports in the domestic and international press. The company is investing about Yuan 290 million (c. US$41 million) in the plant, which will produce rubber antioxidants. The facility is already under construction, with a simplified, official ground-breaking ceremony taking place in early March in compliance with Thai and Chinese coronavirus restrictions.


title: Understanding the spatial diffusion process of severe acute respiratory syndrome in Beijing

text: Summary Objectives To measure the spatial contagion of severe acute respiratory syndrome (SARS) in Beijing and to test the different epidemic factors of the spread of SARS in different periods. Methods A join-count spatial statistic study was conducted and the given hypothetical processes of the spread of SARS in Beijing were tested using various definitions of ‘joins’. Results The spatial statistics showed that of the six diffusion processes, the highest negative autocorrelation occurred in the doctor-number model (M-5) and the lowest negative autocorrelation was found in the population-amount model (M-3). The results also showed that in the whole 29-day research period, about hour or more days experienced a significant degree of contagion. Conclusions Spatial analysis is helpful in understanding the spatial diffusion process of an epidemic. The geographical relationships were important during the early phase of the SARS epidemic in Beijing. The statistic based on the number of doctors was significant and more informative than that of the number of hospitals. It reveals that doctors were important in the spread of SARS in Beijing, and hospitals were not as important as doctors in the contagion period. People are the key to the spread of SARS, but the population density was more significant than the population size, although they were both important throughout the whole period.


title: Differences between asthmatics and nonasthmatics hospitalised with influenza A infection

text: Asthmatics hospitalised because of influenza A infection are less likely to require intensive care or die compared with nonasthmatics. The reasons for this are unknown. We performed a retrospective analysis of data on 1520 patients admitted to 75 UK hospitals with confirmed influenza A/H1N1 2009 infection. A multivariable model was used to investigate reasons for the association between asthma and severe outcomes (intensive care unit support or death). Asthmatics were less likely than nonasthmatics to have severe outcome (11.2% versus 19.8%, unadjusted OR 0.51, 95% CI 0.36–0.72) despite a greater proportion requiring oxygen on admission (36.4% versus 26%, unadjusted OR 1.63) and similar rates of pneumonia (17.1% versus 16.6%, unadjusted OR 1.04). The results of multivariable logistic regression suggest the association of asthma with outcome (adjusted OR 0.62, 95% CI 0.36–1.05; p=0.075) are explained by pre-admission inhaled corticosteroid use (adjusted OR 0.34, 95% CI 0.18–0.66) and earlier admission (≤4 days from symptom onset) (adjusted OR 0.60, 95% CI 0.38–0.94). In asthmatics, systemic corticosteroids were associated with a decreased likelihood of severe outcomes (adjusted OR 0.36, 95% CI 0.18–0.72). Corticosteroid use and earlier hospital admission explained the association of asthma with less severe outcomes in hospitalised patients.


title: Genetic manipulation of porcine deltacoronavirus reveals insights into NS6 and NS7 functions: a novel strategy for vaccine design

text: Porcine deltacoronavirus (PDCoV) is an emerging swine coronavirus that causes severe diarrhea, resulting in high mortality in neonatal piglets. Despite widespread outbreaks in many countries, no effective PDCoV vaccines are currently available. Here, we generated, for the first time, a full-length infectious cDNA clone of PDCoV. We further manipulated the infectious clone by replacing the NS6 gene with a green fluorescent protein (GFP) to generate rPDCoV-ΔNS6-GFP; likewise, rPDCoV-ΔNS7 was constructed by removing the ATG start codons of the NS7 gene. Growth kinetics studies suggest that rPDCoV-ΔNS7 could replicate similarly to that of the wild-type PDCoV, whereas rPDCoV-ΔNS6-GFP exhibited a substantial reduction of viral titer in vitro and in vivo. Piglets inoculated with rPDCoV-ΔNS7 or wild-type PDCoV showed similar diarrheic scores and pathological injury. In contrast, rPDCoV-ΔNS6-GFP-infected piglets did not show any clinical signs, indicating that the NS6 protein is an important virulence factor of PDCoV and that the NS6-deficient mutant virus might be a promising live-attenuated vaccine candidate. Taken together, the reverse genetics platform described here not only provides more insights into the role of PDCoV accessory proteins in viral replication and pathogenesis, but also allows the development of novel vaccines against PDCoV infection.


title: Antihelminthic niclosamide modulates dendritic cells activation and function

text: Abstract Dendritic cells (DCs) link the sensing of the environment by the innate immune system to the initiation of adaptive immune responses. Accordingly, DCs are considered to be a major target in the development of immunomodulating compounds. In this study, the effect of niclosamide, a Food and Drug Administration-approved antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated murine bone marrow-derived DCs was examined. Our experimental results show that niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS-activated DCs. In addition, niclosamide also affected the expression of MHC and costimulatory molecules and influenced the ability of the cells to take up antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T cell proliferation and IFN-γ production. Furthermore, intravenous injection of niclosamide also attenuated contact hypersensitivity (CHS) in mice during sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced activation of MAPK-ERK, JNK and NF-κB may contribute to the inhibitory effect of niclosamide on DC activation. Collectively, our findings suggest that niclosamide can manipulate the function of DCs. These results provide new insight into the immunopharmacological role of niclosamide and suggest that it may be useful for the treatment of chronic inflammatory disorders or DC-mediated autoimmune diseases.


docid: mycpozhk

title: Translation initiation of viral mRNAs

text: Viruses depend on cells for their replication but have evolved mechanisms to achieve this in an efficient and, in some instances, a cell‐type‐specific manner. The expression of viral proteins is frequently subject to translational control. The dominant target of such control is the initiation step of protein synthesis. Indeed, during the early stages of infection, viral mRNAs must compete with their host counterparts for the protein synthetic machinery, especially for the limited pool of eukaryotic translation initiation factors (eIFs) that mediate the recruitment of ribosomes to both viral and cellular mRNAs. To circumvent this competition viruses use diverse strategies so that ribosomes can be recruited selectively to viral mRNAs. In this review we focus on the initiation of protein synthesis and outline some of the strategies used by viruses to ensure efficient translation initiation of their mRNAs. Copyright © 2010 John Wiley & Sons, Ltd.


title: Neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF) produced by macrophages in cats infected with feline infectious peritonitis virus contribute to the pathogenesis of granulomatous lesions

text: Feline infectious peritonitis (FIP) is a feline coronavirus (FCoV)-induced fatal disease of domestic and wild cats. The infiltration of neutrophils into granulomatous lesions is unusual for a viral disease, but it is a typical finding of FIP. This study aimed to investigate the reason for the lesions containing neutrophils in cats with FIP. Neutrophils of cats with FIP were cultured, and changes in the cell survival rate were assessed. In addition, the presence or absence of neutrophil survival factors was investigated in specimens collected from cats with FIP. Furthermore, it was investigated whether macrophages, one of the target cells of FIPV infection, produce neutrophil survival factors (TNF-alpha, GM-CSF, and G-CSF). We showed that virus-infected macrophages overproduce neutrophil survival factors, and these factors act on neutrophils and up-regulate their survival. These observations suggest that sustained production of neutrophil survival factors by macrophages during FCoV infection is sufficient for neutrophil survival and contributes to development of granulomatous lesions.


title: Respiratory Syncityal Virus A and B: three bronchiolitis seasons in a third level hospital in Italy

text: BACKGROUND: Respiratory syncytial virus (RSV) is the main cause of hospitalization for bronchiolitis among infants. RSV is classified into two subtypes, A and B, whose predominance alternates during different epidemic seasons. The clinical impact of viral factors is controversial and many evidences suggest a critical role for the immune host response. Premature children are at the highest risk for severe RSV infection. The main aim of this study is to identify the different RSV subtypes circulating in the last three epidemic seasons and to evaluate whether any of them was associated with poor prognosis in term and preterm infants. METHODS: We performed a retrospective analysis of medical records for all patients aged less than one year which were hospitalized during the winter season between November 2015 and April 2018 with clinical diagnosis of bronchiolitis and nasopharyngeal aspirates positive for RSV. RESULTS: We enrolled 422 children, of which 50 were born preterm. During the analysis period, we observed a significant increase in the rates of oxygen supplementation and admission to intensive care unit. The evidence shows an alternating pattern in the prevalence of RSV subtypes among term born; in each epidemic season, the prevalent serotype is the cause of the majority of the cases requiring intensive care. Conversely, RSV-A is always prevalent in preterm children and caused most of the cases requiring intensive care. CONCLUSIONS: During the 3 seasons analyzed, we observed an alternating prevalence of RSV A and B. While there are no differences in severity between RSV A and B in term population, RSV-A is prevalent and causes most of the severe cases in the premature group. Furthermore, an increase in RSV-related oxygen therapy and PICU admission has been documented not only in the premature population. Considering the absence of appropriate therapeutic strategies, our work emphasizes the importance of implementing prophylaxis measures against RSV and highlights the urgent need to gain knowledge about immune response to the virus, also in premature children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13052-019-0704-0) contains supplementary material, which is available to authorized users.


Systems Biology and Biomarker Discovery


title: Evaluation of a multiplex PCR assay for detection of respiratory viruses and Mycoplasma pneumoniae in oropharyngeal swab samples from outpatients

text: BACKGROUND: Respiratory viruses, such as influenza viruses, initially infect the upper airways but can manifest as severe lower respiratory tract infections in high‐risk patients with significant morbidity and mortality. For syndromic diagnosis, several multiplex nucleic acid amplification tests have been developed for clinics, of which SureX 13 Respiratory Pathogen Multiplex Kit (ResP) can simultaneously detect 13 pathogens directly from airway secretion specimens. The organisms identified are influenza virus A, influenza virus A pdmH1N1 (2009), influenza virus A H3N2, influenza virus B, adenovirus, boca virus, rhinovirus, parainfluenza virus, coronavirus, respiratory syncytial virus, human metapneumovirus, Mycoplasma pneumoniae, and Chlamydia. METHODS: This study provides performance evaluation data of this assay by comparing with pathogen‐specific PCRs from oropharyngeal swab samples. RESULTS: Ten pathogens were detected in this assay, of which rhinovirus, adenovirus, and influenza virus A pdmH1N1 (2009) were the most common. The overall agreement between the ResP and the comparator tests was 93.8%. The ResP demonstrated 86.5% agreement for positive results and 97.8% agreement for negative results. CONCLUSION: The ResP assay demonstrated a highly concordant performance comparing with pathogen‐specific PCRs for detection of respiratory pathogens in oropharyngeal swabs from outpatients and could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.


title: Endocrine and metabolic aspects of the COVID-19 pandemic

text: COVID-19 infection has tremendously impacted our daily clinical practice as well as our social living organization. Virtually all organs and biological systems suffer from this new coronavirus infection, either because the virus targets directly specific tissues or because of indirect effects. Endocrine diseases are not an exception and some of endocrine organs are at risk of direct or indirect lesion by COVID-19. Although there is still no evidence of higher predisposition to contract the infection in patients with diabetes and/or obesity, the coexistence of these conditions contributes to a worse prognosis because both conditions confer an impaired immunologic system. Cytokines storm can be amplified by these two latter conditions thereby leading to multisystemic failure and death. Glycaemic control has been demonstrated to be crucial to avoiding long hospital stays, ICU requirement and also prevention of excessive mortality. Endocrine treatment modifications as a consequence of COVID-19 infection are required in a proactive manner, in order to avoid decompensation and eventual hospital admission. This is the case of diabetes and adrenal insufficiency in which prompt increase of insulin dosage and substitutive adrenal steroids through adoption of the sick day’s rules should be warranted, as well as easy contact with the health care provider through telematic different modalities. New possible endocrinological targets of COVID-19 have been recently described and warrant a full study in the next future.


title: Sofosbuvir as Repurposed Antiviral Drug Against COVID-19: Why Were we Convinced to Evaluate the Drug in a Registered/Approved Clinical Trial?

text: COVID-19 is a devastating global pandemic around the world. While the majority of infected cases appear mild, in some cases individuals present respiratory complications with possible serious lung damage. There are no specific treatments for COVID-19 as yet, though a number are under evaluation, including experimental antivirals. Sofosbuvir, the clinically approved anti-hepatitis C virus (HCV) drug, is also capable of suppressing other families of positive-strand RNA viruses; Flaviviridae and Togaviridae. Coronaviruses are a family of positive-strand RNA viruses with conserved polymerase, so SARS-CoV-2 RdRp is very likely to be effectively inhibited by sofosbuvir. More importantly, sofosbuvir is safe and well tolerated at 400 mg daily in a 24 week therapeutic regimen. Sofosbuvir active metabolite, however, shows an extremely high intracellular stability So, it is hypothesized that SARS-CoV-2 infection could also be susceptible to sofosbuvir and we were convinced to design and run a clinical trial to evaluate the effect of sofosbuvir 400 mg (in combination with velpatasvir 100 mg, as add-on treatment, in addition to standard of care) on the COVID-19. However, we believe that this manuscript/correspondence should be made available to the international scientific community as soon as possible, with the help of this esteemed journal.


title: Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein

text: Abstract The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by altering the S-adenosylmethionine (SAM) binding site in the conserved region VI of the large polymerase protein. To test this hypothesis, we established an efficient reverse genetics system for the rMV-Hu191 strain and generated two recombinant MV-Hu191 carrying mutations in the SAM binding site. These two mutants grew to high titer in Vero cells, were genetically stable, and were significantly more attenuated in vitro and in vivo compared to the parental rMV-Hu191 vaccine strain. Importantly, both MV-Hu191 mutants triggered a higher neutralizing antibody than rMV-Hu191 vaccine and provided complete protection against MV challenge. These results demonstrate its potential for an improved MV vaccine candidate.


title: Dissecting host cell death programs in the pathogenesis of influenza

text: Abstract Influenza A virus (IAV) is a pulmonary pathogen, responsible for significant yearly morbidity and mortality. Due to the absence of highly effective antiviral therapies and vaccine, as well as the constant threat of an emerging pandemic strain, there is considerable need to better understand the host–pathogen interactions and the factors that dictate a protective versus detrimental immune response to IAV. Even though evidence of IAV-induced cell death in human pulmonary epithelial and immune cells has been observed for almost a century, very little is known about the consequences of cell death on viral pathogenesis. Recent study indicates that both the type of cell death program and its kinetics have major implications on host defense and survival. In this review, we discuss advances in our understanding of cell death programs during influenza virus infection, in hopes of fostering new areas of investigation for targeted clinical intervention.


title: Polymorphism of 2′-5′-oligoadenylate synthetase (OAS) genes, associated with predisposition to severe forms of tick-borne encephalitis, in human populations of North Eurasia

text: 2′-5′-oligoadenylate synthetases are a family of interferon-induced enzymes playing an important role in antiviral defense in mammals. In the human genome, three genes encoding functional synthetases (OAS1, OAS2 and OAS3) form a cluster. Previously, we found that particular genotypes and/or alleles of five single nucleotide polymorphisms (SNPs) of OAS2 and OAS3 are associated with predisposition to severe forms of tick-borne encephalitis (TBE) in Russians. In the current study, we investigated the distribution of three of the above SNPs, OAS3 rs2285932 (C/T, Ile438Ile), OAS3 rs2072136 (G/A, Ser567Ser), and OAS2 rs15895 (G/A, Trp720Ter relative to p71 isoform), in seven populations of North Eurasia: Caucasians (Russians, Germans from Altai region), Central Asian Mongoloids (Altaians, Khakass, Tuvinians, and Shorians), and Arctic Mongoloids (Chukchi). Interpopulational differences in genotype, allele and haplotype frequencies and in linkage disequilibrium structure for these SNPs were detected. These frequencies correlated with the ethnicity of the populations and with their supposed differential exposure to the TBE virus. In particular, the lowest frequencies of G/G genotype for OAS3 SNP rs2072136 (which, according to our earlier results, is associated with predisposition to severe forms of TBE) were found in Altaians, Khakass, Tuvinians, and Shorians, who commonly contact with the TBE virus in their habitation regions. Thus, the data obtained suggest that the TBE virus might act as a selection factor for particular OAS variants in Central Asian Mongoloids.


title: AGA Clinical Practice Update on Management of Inflammatory Bowel Disease During the COVID-19 Pandemic: Expert Commentary

text: Description The purpose of this AGA Institute Clinical Practice Update is to rapidly review the emerging evidence and provide timely expert recommendations regarding the management of patients with inflammatory bowel disease during the COVID-19 pandemic. Methods This expert commentary was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely perspective on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology.


title: Anti-cancer therapy and clinical trial considerations for gynecologic oncology patients during the COVID-19 pandemic crisis

text: Abstract Objectives The COVID-19 pandemic has consumed considerable resources and has impacted the delivery of cancer care. Patients with cancer may have factors which place them at high risk for COVID 19 morbidity or mortality. Highly immunosuppressive chemotherapy regimens and possible exposure to COVID-19 during treatment may put patients at additional risk. The Society of Gynecologic Oncology convened an expert panel to address recommendations for best practices during this crisis to minimize risk to patients from deviations in cancer care and from COVID-19 morbidity. Methods An expert panel convened to develop initial consensus guidelines regarding anti-neoplastic therapy during the COVID-19 pandemic with respect to gynecologic cancer care and clinical trials. Results COVID-19 poses special risks to patients who are older, have medical co-morbidities, and cancer. In addition, this pandemic will likely strain resources, making delivery of cancer care or conduct of clinical trials unpredictable. Recommendations are to limit visits and contact with health care facilities by using telemedicine when appropriate, and choosing regimens which require less frequent visits and which are less immunosuppressive. Deviations will occur in clinical trials as a result of limited resources, and it is important to understand regulatory obligations to trial sponsors as well as to the IRB to ensure that clinical trial and patient safety oversight are maintained. Conclusions The ongoing crisis will strain resources needed to deliver cancer care. When alterations to the delivery of care are mandated, efforts should be taken to minimize risks and maximize safety while approximating standard practice.


title: No 225-Lignes directrices quant à la prise en charge des patientes en obstétrique chez lesquelles la présence du syndrome respiratoire aigu sévère (SRAS) est soupçonnée ou probable, et des nouveau-nés issus de ces patientes

text: Résumé Objectif Le présent document résume notre expérience limitée quant à la présence du SRAS pendant la grossesse et suggère des lignes directrices quant à sa prise en charge. Issues Les exposés de cas issus d’Asie laissent entendre que les issues maternelles et fœtales sont aggravées par la présence du SRAS pendant la grossesse. Résultats Des recherches ont été menées dans Medline afin d’en tirer les articles pertinents publiés en anglais entre 2000 et 2007. Des exposés de cas ont été analysés et nous avons sollicité l’opinion de spécialistes. Valeurs Les recommandations ont été formulées conformément aux lignes directrices élaborées par le Groupe d’étude canadien sur les soins de santé préventifs. Commanditaire La Société des obstétriciens et gynécologues du Canada. Recommandations 1. Tous les hôpitaux devraient mettre en œuvre des systèmes de prévention des infections, afin de s’assurer que des alertes au sujet des modifications que connaissent les facteurs de risque d’exposition au SRAS ou à d’autres maladies transmissibles potentiellement graves sont communiquées sans tarder aux unités cliniques, y compris l’unité de travail et d’accouchement (III-C). 2. En présence d’une éclosion de SRAS, toutes les patientes enceintes évaluées ou admises à l’hôpital devraient faire l’objet d’un dépistage des symptômes et des facteurs de risque du SRAS (III-C). 3. À leur arrivée au sein de l’unité de triage quant au travail, les patientes enceintes chez lesquelles la présence du SRAS est soupçonnée et probable devraient être placées dans une salle d’isolement dotée d’un système de ventilation à pression négative comptant au moins six renouvellements d’air à l’heure. Toutes les unités de travail et d’accouchement offrant des soins à des patientes chez lesquelles la présence du SRAS est soupçonnée et probable devraient disposer d’au moins une salle dans laquelle ces patientes peuvent connaître leur travail et leur accouchement en toute sûreté, et ce, malgré la nécessité d’assurer un isolement aérogène (III-C). 4. Dans la mesure du possible, le travail et l’accouchement (y compris l’accouchement opératoire ou la césarienne) devraient être pris en charge, dans une salle d’isolement désignée dotée d’un système de ventilation à pression négative, par du personnel désigné disposant d’une tenue de protection et d’une formation spécialisée en prévention des infections (III-C). 5. Tant l’anesthésie régionale que générale peuvent s’avérer adéquates pour l’accouchement des patientes atteintes du SRAS (III-C). 6. Les nouveau-nés issus de mères atteintes du SRAS devraient être isolés au sein d’une unité désignée jusqu’à ce que leur état ait été satisfaisant pendant 10 jours ou jusqu’à ce que la période d’isolement de la mère ait pris fin. La mère ne devrait pas allaiter pendant cette période (III-C). 7. Une équipe multidisciplinaire (comprenant des obstétriciens, des infirmières, des pédiatres, des spécialistes de la prévention des infections, des inhalothérapeutes et des anesthésiologistes) devrait être nommée au sein de chaque unité et être responsable de l’organisation et de la mise en œuvre des protocoles de prise en charge du SRAS de l’unité (III-C). 8. Le personnel offrant des soins aux patientes enceintes atteintes du SRAS ne devraient pas offrir leurs services aux autres patientes enceintes. Le personnel offrant des soins aux patientes enceintes atteintes du SRAS devraient activement faire l’objet d’une surveillance visant la fièvre et d’autres symptômes du SRAS. Ces personnes ne devraient pas travailler en présence de tout symptôme du SRAS se manifestant dans les 10 jours suivant une exposition à un patient atteint du SRAS (III-C). 9. Tous les professionnels des soins de santé, les résidents et les membres du personnel de soutien devraient bénéficier d’une formation sur la prise en charge et le confinement des infections afin de prévenir la propagation du virus du SRAS (III-A). 10. Les autorités sanitaires régionales, conjointement avec le personnel hospitalier, devraient envisager la désignation d’établissements ou d’unités de soins de santé particulières (y compris des centres de soins primaires, secondaires ou tertiaires) en ce qui concerne l’offre de soins aux patients atteints du SRAS ou de maladies semblables (III-A).


title: Astrovirus-like, coronavirus-like, and parvovirus-like particles detected in the diarrheal stools of beagle pups

text: Astrovirus-like, coronavirus-like, and parvovirus-like particles were detected through electron microscopic (EM) examination of loose and diarrheal stools from a litter of beagle pups. Banding patterns obtained from equilibrium centrifugations in CsCl supported the EM identification. Densities associated with the identified particles were: 1.34 g/ml for astrovirus, 1.39 g/ml for “full” parvovirus, and 1.24–1.26 g/ml for “typical” coronavirus. Convalescent sera from the pups aggregated these three particle types as observed by immunoelectron microscopy (IEM). Only coronavirus-like particles were later detected in formed stools from these same pups. Coronavirus and parvo-like viruses are recognized agents of canine viral enteritis, however, astrovirus has not been previously reported in dogs.


docid: alowbibu

title: Effect of COVID-19 on Hip and Knee Arthroplasty Surgical Volume in the United States

text: Abstract In an effort to help combat the COVID-19 pandemic and preserve essential healthcare resources, starting in mid-March 2020, surgeons have been instructed to only perform essential surgical procedures during this time. The vast majority of hip and knee arthroplasty surgery does not meet the definition of essential surgery. This study estimated the number of arthroplasty procedures that would be canceled due to these important restrictions. We estimated that approximately 30,000 primary and 3,000 revision hip and knee arthroplasty procedures will be canceled each week while COVID-19 restrictions regarding non-essential surgery are in place. This large number of canceled procedures will undoubtedly have a profound impact on patients and the healthcare system.


title: Three Amino Acid Changes in Avian Coronavirus Spike Protein Allow Binding to Kidney Tissue

text: Infectious bronchitis virus (IBV) infects ciliated epithelial cells in the chicken respiratory tract. While some IBV strains replicate locally, others can disseminate to various organs, including the kidney. Here, we elucidate the determinants for kidney tropism by studying interactions between the receptor-binding domain (RBD) of the viral attachment protein spike from two IBV strains with different tropisms. Recombinantly produced RBDs from the nephropathogenic IBV strain QX and from the nonnephropathogenic strain M41 bound to the epithelial cells of the trachea. In contrast, only QX-RBD binds more extensively to cells of the digestive tract, urogenital tract, and kidneys. While removal of sialic acids from tissues prevented binding of all proteins to all tissues, binding of QX-RBD to trachea and kidney could not be blocked by preincubation with synthetic alpha-2,3-linked sialic acids. The lack of binding of QX-RBD to a previously identified IBV-M41 receptor was confirmed by enzyme-linked immunosorbent assay (ELISA), demonstrating that tissue binding of QX-RBD is dependent on a different sialylated glycan receptor. Using chimeric RBD proteins, we discovered that the region encompassing amino acids 99 to 159 of QX-RBD was required to establish kidney binding. In particular, QX-RBD amino acids 110 to 112 (KIP) were sufficient to render IBV-M41 with the ability to bind to kidney, while the reciprocal mutations in IBV-QX abolished kidney binding completely. Structural analysis of both RBDs suggests that the receptor-binding site for QX is located at a different location on the spike than that of M41. IMPORTANCE Infectious bronchitis virus is the causative agent of infectious bronchitis in chickens. Upon infection of chicken flocks, the poultry industry faces substantial economic losses by diminished egg quality and increased morbidity and mortality of infected animals. While all IBV strains infect the chicken respiratory tract via the ciliated epithelial layer of the trachea, some strains can also replicate in the kidneys, dividing IBV into the following two pathotypes: nonnephropathogenic (example, IBV-M41) and nephropathogenic viruses (including IBV-QX). Here, we set out to identify the determinants for the extended nephropathogenic tropism of IBV-QX. Our data reveal that each pathotype makes use of a different sialylated glycan ligand, with binding sites on opposite sides of the attachment protein. This knowledge should facilitate the design of antivirals to prevent coronavirus infections in the field.


title: Fledertiere und andere Reservoirwirte der Filoviridae. Epidemiegefahr am afrikanischen Kontinent? – Eine deduktive Literaturanalyse

text: Ebola and Marburg virus, forming the Filoviridae family, cause hemorrhagic fever in countries of sub-Saharan Africa. These viral diseases are characterized by a sudden epidemic occurrence as well as a high lethality. Even though a reservoir host has not been approved yet, literature indicates the order of bats (Chiroptera) as a potential reservoir host. Significant references lead to a delineation of a hypothetical ecosystem of Filoviridae including Chiroptera. IgG-specific Ebola-Zaire antibodies were detected in Hammer-headed Bats (Hypsignathus monstrosus), Epauletted Fruit Bats (Epomops franqueti), and Little Collared Fruit Bats (Myonycteris torquata) during Ebola outbreaks between 2001 and 2005 in Gabon and the Republic of the Congo. The discovery of IgG-specific-Marburg virus antibodies and virus-specific ribonucleic acid in Egyptian Fruit Bats (Rousettus aegyptiacus) provided further indication for the exploration of the reservoir host. In 2007, the Marburg virus isolation could for the first time be accomplished directly from apparently healthy and naturally infected Egyptian Fruit Bats (Rousettus aegyptiacus) in Kitaka Mine (Uganda). Risk groups can be defined through chronological reprocessing and interpretation of existing epidemic-outbreaks on the African continent and the search for infection reasons of the index cases. The following risk factors for an infection with Ebola or Marburg virus must be put into consideration: Contact with and consumption of wild animal carcasses, sightseeing in caves as well as work in mines. The focus of this review is the demonstration of risk profiles and their exposure to Chiroptera and other potential reservoir hosts.


Reading for Pandemic: Viral Modernism by Elizabeth Outka, New York: Columbia University Press, 2020


DIFFERENTIAL DIAGNOSIS OF RESPIRATORY VIRUSES BY USING REAL TIME RT-PCR METHODOLOGY


title: A double antibody sandwich enzyme-linked immunosorbent assay for detection of soft-shelled turtle iridovirus antigens

text: Abstract A double antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) for detection of the soft-shelled turtle iridovirus (STIV) was developed using a specific monoclonal antibody (mAb) against STIV and anti-STIV rabbit serum. Using DAS-ELISA, the detection limit of STIV was found to be 103 PFU/ml. The positive rate of 15 STIV samples was 100%, while the positive rate of 100 other aquatic virus samples was 0%. These data show that DAS-ELISA is highly specific and sensitive for the detection of STIV. In clinical tests, 128 samples isolated from pond-reared turtles were subjected to DAS-ELISA and PCR. The overall agreement between the results obtained by DAS-ELISA and PCR was 98.4%. The results indicate that the DAS-ELISA method could be used for diagnosing diseases caused by STIV.


title: Chapter 4 Modeling Risks in Supply Chains

text: Abstract This chapter discusses ways to identify, categorize, and assess risks in supply chains. It pays particular attention to the often hidden risks that can lurk deep within global supply chains. Using case studies, the chapter shows how companies assess and prioritize supplier risks, and it explains the underlying factors that give rise to deep-chain risks. The sweep of examples in the chapter shows that companies can model the likelihood and impacts of a wide range of risks to their facilities, suppliers, and logistics infrastructure.


title: Detection of adenovirus, papillomavirus and parvovirus in Brazilian bats of the species Artibeus lituratus and Sturnira lilium

text: Bats play a significant role in maintaining their ecosystems through pollination, dispersal of seeds, and control of insect populations, but they are also known to host many microorganisms and have been described as natural reservoirs for viruses with zoonotic potential. The diversity of viruses in these animals remains largely unknown, however, because studies are limited by species, location, virus target, or sample type. Therefore, the aim of this study was to detect fragments of viral genomes in bat samples. We performed high-throughput sequencing analysis and specific PCR and RT-PCR on pools of anal and oropharyngeal swabs from Artibeus lituratus and Sturnira lilium collected in southern Brazil. As a result, a member of the family Adenoviridae related to human adenovirus C was detected in anal swabs from S. lilium. In addition, we detected a papillomavirus in an anal swab from A. lituratus. Our analyses also allowed the detection of adenoviruses and parvoviruses in oropharyngeal swabs collected from A. lituratus. These results increase our knowledge about viral diversity and illustrate the importance of conducting virus surveillance in bats.


title: Prophylactic use of a standardized botanical extract for the prevention of naturally occurring diarrhea in newborn Holstein calves

text: ABSTRACT The objectives of this study were to evaluate the prophylactic use of SB-300 (Jaguar Animal Health, San Francisco, CA), a standardized botanical extract isolated from the bark latex of Croton lechleri, on reducing fecal water losses and diarrhea events in Holstein bull calves individually housed under a restricted whole-milk feeding regimen (6 L/d) from 1 to 25 d of life. Fluid therapy administration due to dehydration, average weight gain, and the fecal microbiome were also evaluated. Bull calves used in this study were born from normal parturition, fed 4 L of pooled pasteurized colostrum by esophageal feeder, and moved to a research facility at Cornell University (Ithaca, NY). A double-blinded randomized clinical trial was designed to allocate a total of 40 newborn calves into 1 of 2 treatment groups: calves receiving (twice daily) a solution containing 500 mg of SB-300 added to the whole milk for the first 15 d of life (SB-300, n = 20) or a control group receiving sterile water added to whole milk for the same period (CTR, n = 20). Treatment solutions had a total volume of 10 mL per treatment. Data regarding fecal dry matter were collected to precisely measure water content in fecal samples and to define diarrhea events; the SB-300 group had significantly increased fecal dry matter during the study period. Additionally, significantly fewer events of diarrhea were observed for calves in the SB-300 group (16.9%) compared with calves in the CTR group (46.5%). Dehydration status was evaluated and treated accordingly; calves with moderate dehydration were offered oral electrolytes, and calves with severe dehydration were rescued with intravenous fluid therapy. Calves in the SB-300 group had fewer intravenous fluid therapies administered during the study period (1.6%) compared with the CTR group (3.1%). Overall fluid therapy administered (oral electrolytes plus intravenous fluids) was significantly higher for the CTR group (9.2%) compared with the SB-300 group (6.1%) during the study period. No differences in milk consumption, calf starter intake, or weight gain were observed between treatment groups. A single time increase in Bifidobacterium was observed on d 20 of life for the SB-300 group; otherwise, no differences in fecal microbiome profile were detected between treatment groups. These results suggest that 500 mg of SB-300 added to the milk for 15 d can reduce the incidence of diarrhea and reduce severe dehydration in milk-fed calves.


title: Das schwere akute Atemwegssyndrom (SARS)

text: Severe acute respiratory syndrome (SARS) is a viral disease, observed primarily in Southern China in November 2002, with variable flu-like symptoms and pneumonia, in approx. 5% leading to death from respiratory distress syndrome (RDS). The disease was spread over more than 30 states all over the globe by SARS-virus-infected travelers. WHO and CDC received first information about a new syndrome by the end of February 2003, after the first cases outside the Republic of China had been observed. A case in Hanoi, Vietnam, led to the first precise information about the new disease entity to WHO, by Dr. Carlo Urbani, a co-worker of WHO/Doctors without Borders, who had been called by local colleagues to assist in the management of a patient with an unknown severe disease by the end of February 2003. Dr. Urbani died from SARS, as did many other health care workers. In the meantime, more than 7,000 cases have been observed worldwide, predominantly in China and Hong Kong, but also in Taiwan, Canada, Singapore, and the USA, and many other countries, and more than 600 of these patients died from RDS. Since the beginning of March 2003, when WHO and CDC started their activities, in close collaboration with a group of international experts, including the Bernhard-Nocht-Institute in Hamburg and the Department of Virology in Frankfurt/Main, a previously impossible success in the disclosure of the disease was achieved. Within only 8 weeks of research it was possible to describe the infectious agent, a genetically modified coronavirus, including the genetic sequence, to establish specific diagnostic PCR methods and to find possible mechanisms for promising therapeutic approaches. In addition, intensifying classical quarantine and hospital hygiene measures, it was possible to limit SARS in many countries to sporadic cases, and to reduce the disease in countries such as Canada and Vietnam. This review article summarizes important information about many issues of SARS (May 15th, 2003).


title: Surveillance, response systems, and evidence updates on emerging zoonoses: the role of one health

text: Globally, emerging zoonotic diseases are increasing. Existing surveillance systems for zoonoses have substantial gaps, especially in developing countries, and the systems in place in the developed world require improvements. Resources and updates on evidence-based practice (EBP) for zoonoses are sparser in the veterinary literature as compared to the medical literature. Evidence updates for emerging zoonoses are either absent or rudimentary in both human and veterinary medicine. A ‘one-health’ concept, including a global signaling surveillance system for emerging zoonoses, will be essential for correct diagnoses, interventions, and public health strategies. An open access EBP platform supported by builders of EBP resources is urgently needed to counter emerging zoonoses.


title: NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap(4)A) and Down-Regulates Immune Response and Cancer Promotion Genes

text: Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap(4)A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap(4)A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap(4)A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity(®) Pathway Analysis (IPA(®)) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA(®) for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap(4)A and/or NUDT2 disruption include binding of Ap(4)A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap(4)A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap(4)A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis.


title: The impact of the Severe Acute Respiratory Syndrome on hotels: a case study of Hong Kong

text: Hotel business in Hong Kong has been badly affected by the outbreak of the Severe Acute Respiratory Syndrome (SARS) since March 2003. Medical reports suggest that a direct contact with the secretion or respiratory droplets from a patient through a short distance is very likely to be the possible way of transmitting the disease. World Health Organization (WHO), hence, has advised international travellers to avoid visiting several regions that have the most number of SARS cases, including Hong Kong. Since then, the number of hotel guests has largely dropped to a level that Hong Kong has never experienced before. As a totally new experience to the hotel industry in Hong Kong and elsewhere, hoteliers basically do not have enough knowledge to respond to epidemic crisis. In view of the lack of published articles in the hospitality literature that examine the issue, this paper investigates the impact of the SARS outbreak on the hotel industry in Hong Kong. In addition, this paper addresses the issue of SARS crisis management in risk identification, assessment and alleviation. The paper is expected to benefit the entire hotel industry from better understanding and planning to face the mysterious illness.


title: Relationships between antimicrobial use and antimicrobial resistance in Gram-negative bacteria causing nosocomial infections from 1991–2003 at a university hospital in Taiwan

text: Abstract This study was conducted to evaluate the relationship between antimicrobial resistance and antimicrobial use in a university hospital in Taiwan. Disk susceptibility data of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus spp., Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia and other non-fermentative Gram-negative bacilli causing nosocomial infections were evaluated. Data on annual patient-days and annual consumption (defined daily dose (DDD) per 1000 patient-days) of extended-spectrum cephalosporins (cefotaxime, ceftriaxone, ceftazidime, flumoxef, cefepime and cefpirome), β-lactam–β-lactamase inhibitor combinations (ticarcillin/clavulanic acid and piperacillin/tazobactam), carbapenems (imipenem and meropenem), aminoglycosides (amikacin, gentamicin and tobramycin), fluoroquinolones (ciprofloxacin (oral and injectable) and oral levofloxacin and moxifloxacin) from 1991 to 2003 were analysed. Increasing trends of incidences of several of these bacteria causing all nosocomial infections or nosocomial bloodstream infections were noted from 1991 to 2003. The annual patient-days of the hospital significantly increased, from 360210 in 1991 to 672676 in 2002 (linear regression analysis, P <0.05), but slightly decreased in 2003 (629168) owing to the severe acute respiratory syndrome epidemic in Taiwan. The rise in cefotaxime-resistant or ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa was significantly correlated with increased consumption of extended-spectrum cephalosporins, β-lactam–β-lactamase inhibitor combinations, carbapenems, fluoroquinolones and aminoglycosides (for ciprofloxacin-resistant E. coli and meropenem-resistant P. aeruginosa only) in the hospital (Pearson's correlation coefficient, r >0.72 (or <−0.72) and P-value<0.05). Increased ciprofloxacin-resistant K. pneumoniae and meropenem-resistant Acinetobacter spp. was significantly associated with the increased usage of extended-spectrum cephalosporins but not with the other four classes of antibiotics. This 13-year study in a hospital demonstrated significant changes in antimicrobial use, which may have affected antimicrobial resistance in certain Gram-negative bacteria at the hospital.


title: COVID‐19 and anatomy: Stimulus and initial response

text: The outbreak of COVID‐19, resulting from widespread transmission of the SARS‐CoV‐2 virus, represents one of the foremost current challenges to societies across the globe, with few areas of life remaining untouched. Here, we detail the immediate impact that COVID‐19 has had on the teaching and practice of anatomy, providing specific examples of the varied responses from several UK, Irish and German universities and medical schools. Alongside significant issues for, and suspension of, body donation programmes, the widespread closure of university campuses has led to challenges in delivering anatomy education via online methods, a particular problem for a practical, experience‐based subject such as anatomy. We discuss the short‐term consequences of COVID‐19 for body donation programmes and anatomical education, and highlight issues and challenges that will need to be addressed in the medium to long term in order to restore anatomy education and practice throughout the world.[Image: see text]


title: Evidence-based recommendations for gastrointestinal cancers during the COVID-19 pandemic by the Brazilian Gastrointestinal Tumours Group

text: PURPOSE: As of 2020, the world is facing the great challenge of the COVID-19 (Coronavirus disease 2019) pandemic, caused by the SARS-CoV-2 virus. While the overall mortality is low, the virus is highly virulent and may infect millions of people worldwide. This will consequently burden health systems, particularly by those individuals considered to be at high risk of severe complications from COVID-19. Such risk factors include advanced age, cardiovascular and pulmonary diseases, diabetes and cancer. However, few data on the outcomes of cancer patients infected by SARS CoV-2 exist. Therefore, there is a lack of guidance on how to manage cancer patients during the pandemic. We sought to propose specific recommendations about the management of patients with gastrointestinal malignancies. METHODS: The Brazilian Gastrointestinal Tumours Group board of directors and members sought up-to-date scientific literature on each tumour type and discussed all recommendations by virtual meetings to provide evidence-based—and sometimes, expert opinion—recommendation statements. Our objectives were to recommend evidence-based approaches to both treat and minimise the risk of COVID-19 for cancer patients, and simultaneously propose how to decrease the use of hospital resources at a time these resources need to be available to treat COVID-19 patients. RESULTS: Overall and tumour-specific recommendations were made by stage (including surgical, locoregional, radiotherapy, systemic treatments and follow-up strategies) for the most common gastrointestinal malignancies: esophagus, gastric, pancreas, bile duct, hepatocellular, colorectal, anal cancer and neuroendocrine tumours. CONCLUSIONS: Our recommendations emphasise the importance of treating cancer patients, using the best evidence available, while simultaneously taking into consideration the world-wide health resource hyperutilisation to treat non-cancer COVID-19 patients.


title: Adjusting to the new reality: Evaluation of early practice pattern adaptations to the COVID-19 pandemic

text: OBJECTIVE: We aim to define national practice patterns to assess current clinical practice, anticipated delays and areas of concern that potentially could lead to deviations from the normal standard of care. METHODS: Anonymous surveys were emailed to members of the Society of Gynecologic Oncology (SGO). The spread of COVID-19 and its impact on gynecologic oncology care in terms of alterations to normal treatment patterns and anticipated challenges were assessed. The Wilcoxon rank sum test was performed to determine risk factors for COVID-19 infection. RESULTS: We analyzed the responses of 331 gynecologic oncology providers. COVID-19 is present in 99.1% of surveyed communities with 99.7% reporting mitigation efforts in effect. The infection rate differs significantly between regions (p≪0.001) with the Northeast reporting the highest number of COVID-19 cases. Practice volume has dropped by 61.6% since the start of the pandemic with most cancellations being provider initiated. A majority of responders (52.8%) believed that ovarian cancer will be the most affected cancer by COVID-19. >94% of responders are proceeding with gynecologic cancer surgeries with exception of grade 1, endometrioid endometrial adenocarcinoma (36.3%). Surgical backlog (58.6%), delayed cancer diagnosis (43.2%) and re-establishing normal care with delayed patient (37.8%) were identified as the top 3 challenges after COVID-19 has abated. CONCLUSIONS: COVID-19 is widespread and has radically altered normal practice patterns. Despite COVID-19 related concerns, most gynecologic oncology care is proceeding. However, the steep decline in clinical volume shows there is a large group of patients who are not being diagnosed or are deferring care.


title: 2019 Novel Coronavirus (COVID-19) Pandemic: Built Environment Considerations To Reduce Transmission

text: With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county, and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE)-mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics. Author Video: An author video summary of this article is available.


title: Zambia’s National Cancer Centre response to the COVID-19 pandemic—an opportunity for improved care

text: The COVID-19 pandemic has overwhelmed health systems around the globe even in countries with strong economies. This is of particular concern for nations with weaker health systems. This article reports the response of a comprehensive cancer centre in a lower-middle income country to prevent COVID-19 transmission and how the implementation of pragmatic strategies have served as a springboard to improve cancer services beyond the COVID-19 pandemic. The strategies included establishment of a local taskforce, increased education and facilitation of good hygiene practices, staff training, patient triaging, improved patient scheduling, remote review of patients and establishing a virtual platform for meetings.


title: Chapter 12 The Virus–Host Interactome Knowing the Players to Understand the Game

text: Abstract While viruses encode a limited repertoire of factors, their influence on host proteins is substantial. Various high-throughput technologies have been employed to gain a global understanding of how viruses rewire cellular machinery to promote replication and evade immune responses. These approaches can elucidate the interplay that occurs between virus and host by identifying host factors that directly associate with viral proteins, determining what cellular factors impact the viral lifecycle and what viral countermeasures circumvent immune surveillance. This chapter will discuss system-level technologies that are used to identify host proteins, pathways, and biochemical complexes that govern viral pathogenesis. We will examine the information that can be gained from genome- and proteome-level analyses of host–pathogen interactions, the advantages and pitfalls of various methods and provide examples of significant breakthroughs that have been facilitated using OMICs-based technologies.


title: A microbial detection array (MDA) for viral and bacterial detection

text: BACKGROUND: Identifying the bacteria and viruses present in a complex sample is useful in disease diagnostics, product safety, environmental characterization, and research. Array-based methods have proven utility to detect in a single assay at a reasonable cost any microbe from the thousands that have been sequenced. METHODS: We designed a pan-Microbial Detection Array (MDA) to detect all known viruses (including phages), bacteria and plasmids and developed a novel statistical analysis method to identify mixtures of organisms from complex samples hybridized to the array. The array has broader coverage of bacterial and viral targets and is based on more recent sequence data and more probes per target than other microbial detection/discovery arrays in the literature. Family-specific probes were selected for all sequenced viral and bacterial complete genomes, segments, and plasmids. Probes were designed to tolerate some sequence variation to enable detection of divergent species with homology to sequenced organisms, and to have no significant matches to the human genome sequence. RESULTS: In blinded testing on spiked samples with single or multiple viruses, the MDA was able to correctly identify species or strains. In clinical fecal, serum, and respiratory samples, the MDA was able to detect and characterize multiple viruses, phage, and bacteria in a sample to the family and species level, as confirmed by PCR. CONCLUSIONS: The MDA can be used to identify the suite of viruses and bacteria present in complex samples.


Tracking the transmission and evolution of MERS-CoV


title: Enjeux de l’utilisation des psychotropes dans le cadre de la pandémie au SARS-Cov-2

text: Abstract French recommendations have been proposed for psychotropics use and possible adaptations during the SARS-CoV-2 epidemic. Between uncertainties linked to the lack of data and speculations about possible benefits of psychotropics against the coronavirus, we propose here elements allowing to base the pharmacotherapeutic decisions potentially useful in Covid+ patients with psychiatric disorders.


title: Children coronavirus dilemma

text: Other reasons rather then absence of prior immunity could play a crucial role in the children coronavirus dilemma


title: Divergent roles of β‐ and γ‐actin isoforms during spread of vaccinia virus

text: Actin is a major component of the cytoskeleton and is present as two isoforms in non‐muscle cells: β‐ and γ‐cytoplasmic actin. These isoforms are strikingly conserved, differing by only four N‐terminal amino acids. During spread from infected cells, vaccinia virus (VACV) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell‐to‐cell spread of infection. Here we show that virus‐tipped actin comets are composed of β‐ and γ‐actin. We employed isoform‐specific siRNA knockdown to examine the role of the two isoforms in VACV‐induced actin comets. Despite the high level of similarity between the actin isoforms, and their colocalization, VACV‐induced actin nucleation was dependent exclusively on β‐actin. Knockdown of β‐actin led to a reduction in the release of virus from infected cells, a phenotype dependent on virus‐induced Arp2/3 complex activity. We suggest that local concentrations of actin isoforms may regulate the activity of cellular actin nucleator complexes.


title: Extracellular superoxide dismutase, a molecular transducer of health benefits of exercise

text: Extracellular superoxide dismutase (EcSOD) is the only extracellular scavenger of superoxide anion (O(2)(.-)) with unique binding capacity to cell surface and extracellular matrix through its heparin-binding domain. Enhanced EcSOD activity prevents oxidative stress and damage, which are fundamental in a variety of disease pathologies. In this review we will discuss the findings in humans and animal studies supporting the benefits of EcSOD induced by exercise training in reducing oxidative stress in various tissues. In particularly, we will highlight the importance of skeletal muscle EcSOD, which is induced by endurance exercise and redistributed through the circulation to the peripheral tissues, as a molecular transducer of exercise training to confer protection against oxidative stress and damage in various disease conditions.


title: National Geriatric Network Rapidly Addresses Trainee Telehealth Needs in Response to COVID‐19

text: BACKGROUND/OBJECTIVES: COVID‐19 has pushed many geriatric healthcare providers to attempt video visits for the first time. While the Veterans Health Administration (VA) is a pioneer in telemedicine, rapid shifts to nearly exclusive use of telehealth for healthcare delivery and changes regarding trainee engagement in telehealth served as the impetus for rapidly assessing telehealth training needs. DESIGN/SETTING/PARTICIPANTS: Trainees (n=89) representing 12 disciplines affiliated with VA Geriatric Research Education and Clinical Centers (GRECCs) were surveyed regarding prior experience conducting video‐to‐home visits and training needs. RESULTS: Two‐thirds had received some telehealth training. However, the majority had never done a video‐to‐home visit and, regardless of telehealth experience, reported low confidence. Based on open‐ended questions exploring training needs, educational resources were rapidly developed and disseminated. Intervention: Within one week of the assessment, a nuts‐and‐bolts guide regarding remote access, technology requirements, video conferencing platforms, and managing emergencies was sent to the national network of GRECC Associate Directors for Education for dissemination among discipline‐specific training directors at their sites. Subsequently, this resource was submitted to the national VA COVID Strong Practices SharePoint site. Additionally, an interdisciplinary team of geriatric specialists with extensive video‐to‐home experience organized a national webinar, which peaked at just over 700 participants. “GRECC Connect,” a network of geriatric specialty teams funded to improve care access for rural older Veterans using telehealth, and Associated Health Training programs at each GRECC, facilitated rapid development and dissemination of both resources. CONCLUSION: We rapidly identified and responded to telehealth training needs of geriatrics trainees to optimize care for rural older adults as part of a rapid response to COVID‐19. While the webinar and nuts‐and‐bolts resources were developed within the VA context, they have demonstrated high demand and broader applicability. Results should continue to inform curriculum development efforts to address telehealth training gaps within and outside the VA. This article is protected by copyright. All rights reserved.


docid: lpxmmbpy

title: Respiratory syncytial virus contributes to more severe respiratory morbidity than influenza in children < 2 years during seasonal influenza peaks

text: PURPOSE: To compare the frequency and the severity of influenza and respiratory syncytial viruses (RSV) infections among children < 24 months hospitalized with respiratory symptoms. METHODS: Data from a prospective study conducted during the peak of five influenza seasons in the Province of Quebec, Canada were used. RESULTS: We detected higher frequency of RSV compared to influenza viruses (55.3% vs. 16.3%). Radiologically confirmed pneumonia was significantly more frequent in children with RSV (39%) than those with influenza (18%) and the clinical course was more severe in RSV than influenza-infected children, especially among infants < 3 months. CONCLUSION: Even during peak weeks of influenza season, we found a higher burden and severity of RSV compared with influenza virus disease in hospitalized children < 24 months.


title: 23 Acute Infections That Produce Upper Airway Obstruction

text: Abstract This chapter discusses the common and potentially serious infective causes of acute upper airway obstruction in children. The laryngeal anatomy of young children makes them particularly susceptible to upper airway obstruction, and during acute infections this is exacerbated by inflammation and edema of the airway mucosa. The most common cause of infective upper airway obstruction in children is viral laryngotracheobronchitis, or croup, which is usually a mild and self-limiting illness, but management with corticosteroids may still be necessary. Bacterial causes of upper airway obstruction have fortunately become rare since the introduction of the Haemophilus influenzae B (HiB) immunization, but a few cases of epiglottitis do still occur due to nonimmunization, vaccine failure, and infection with non-HiB organisms. These cases constitute a medical emergency due to the risk of rapid progression to complete airway obstruction. Other rare conditions are discussed including bacterial tracheitis, diphtheria, retropharyngeal, and peritonsillar abscesses. Key learning points in this chapter include the main discriminating factors of the various causes of infective upper airway obstruction, the importance of a calm and minimally distressing approach to the child presenting with stridor, and the need for early anesthetic team involvement in cases with a suspected bacterial etiology or signs of impending airway obstruction.


title: The effect of drought stress on the expression of key genes involved in the biosynthesis of triterpenoid saponins in liquorice (Glycyrrhiza glabra)

text: Abstract Glycyrrhiza glabra is an important medicinal plant throughout the world. Glycyrrhizin is a triterpenoid that is among the most important secondary metabolites produced by liquorice. Drought stress is proposed to enhance the levels of secondary metabolites. In this study, the effect of drought stress on the expression of important genes involved in the glycyrrhizin biosynthetic pathway was examined. Drought stress at the seedling stage was applied to 8-day-old plants using polyethylene glycol. Subsequently, the samples were collected 0, 4, 8 or 24h post-treatment. At the adult plant stage, 10-month-old plants were subjected to drought stress by discontinuing irrigation. Subsequently, samples were collected at 2, 16 and 28days after drought imposition (S2d, S16d and S28d, respectively). We performed semi-quantitative RT-PCR assays to evaluate the gene expression levels of sequalene synthase (SQS), β-amyrin synthase (bAS), lupeol synthase (LUS) and cycloartenol synthase (CAS) during stress. Finally, the glycyrrhizin content of stolons was determined via HPLC. The results revealed that due to osmotic stress, the gene expression levels of SQS and bAS were increased, whereas those of CAS were relatively unchanged at the seedling stage. At the adult plant stage, the expression levels of SQS and bAS were increased under drought stress conditions, whereas the gene expression level of CAS remained relatively constant. The glycyrrhizin content in stolons was increased only under severe drought stress conditions (S28d). Our results indicate that application of controlled drought stress up-regulates the expression of key genes involved in the biosynthesis of triterpenoid saponins and directly enhances the production of secondary metabolites, including glycyrrhizin, in liquorice plants.


title: Singleplex real-time RT-PCR for detection of influenza A virus and simultaneous differentiation of A/H1N1v and evaluation of the RealStar influenza kit

text: Abstract Background A novel influenza A virus, subtype A/H1N1v emerged in April 2009 and caused the first influenza pandemic of the 21st century. Reliable detection and differentiation from seasonal influenza viruses is mandatory for appropriate case management as well as public health. Objectives To develop and technically validate a novel one-step real-time RT-PCR assay which can be used for influenza A virus screening and subtyping of A/H1N1v in a singleplex fashion. To assess the clinical performance of a novel commercial influenza RT-PCR kit based on the in-house version. Study design A real-time RT-PCR assay targeting the matrix gene of influenza A viruses was developed and validated using in vitro transcribed RNA derived from influenza A/H1N1v, A/H1N1 and A/H3N2 virus as well as plaque-quantified influenza A/H1N1v, A/H1N1 and A/H3N2 virus samples. After validation of the in-house version the commercial RealStar kit was used to assess the clinical performance and specificity on a panel of influenza viruses including A/H1N1v, A/H1N1, swine A/H1N1, A/H3N2, avian A/H5N1 as well as patient specimens. Results The lower limit of detection of the in-house version was 2149, 1376 and 2994 RNA copies/ml for A/H1N1v, A/H1N1 and A/H3N2, respectively. The RealStar kit displayed 100% sensitivity and specificity and could reliably discriminate influenza A viruses from A/H1N1v. No cross reaction with swine A/H1N1 and A/H1N2 was observed with the RealStar A/H1N1v specific probe. Conclusion Both assays demonstrated high sensitivity and specificity and might assist in the diagnosis of suspected influenza cases.


docid: vhphlccl

title: Epidemiological characteristics of the first 53 laboratory-confirmed cases of COVID-19 epidemic in Hong Kong, 13 February 2020

text: BACKGROUND: COVID-19, caused by SARS-CoV-2, first appeared in China and subsequently developed into an ongoing epidemic. Understanding epidemiological factors characterising the transmission dynamics of this disease is of fundamental importance. AIMS: This study aimed to describe key epidemiological parameters of COVID-19 in Hong Kong. METHODS: We extracted data of confirmed COVID-19 cases and their close contacts from the publicly available information released by the Hong Kong Centre for Health Protection. We used doubly interval censored likelihood to estimate containment delay and serial interval, by fitting gamma, lognormal and Weibull distributions to respective empirical values using Bayesian framework with right truncation. A generalised linear regression model was employed to identify factors associated with containment delay. Secondary attack rate was also estimated. RESULTS: The empirical containment delay was 6.39 days; whereas after adjusting for right truncation with the best-fit Weibull distribution, it was 10.4 days (95% CrI: 7.15 to 19.81). Containment delay increased significantly over time. Local source of infection and number of doctor consultations before isolation were associated with longer containment delay. The empirical serial interval was 4.58–6.06 days; whereas the best-fit lognormal distribution to 26 certain-and-probable infector–infectee paired data gave an estimate of 4.77 days (95% CrI: 3.47 to 6.90) with right-truncation. The secondary attack rate among close contacts was 11.7%. CONCLUSION: With a considerable containment delay and short serial interval, contact-tracing effectiveness may not be optimised to halt the transmission with rapid generations replacement. Our study highlights the transmission risk of social interaction and pivotal role of physical distancing in suppressing the epidemic.


title: Reanimación y prevención de las infecciones nosocomiales

text: Los servicios de reanimación deben organizar de forma minuciosa la prevención de infecciones en sus enfermos, ya que éstos suelen estar inmunodeprimidos, están sometidos a múltiples procedimientos invasivos realizados por un personal sanitario variado, a menudo en situaciones de urgencia y a cualquier hora del día o de la noche. Las principales infecciones que hay que tratar de prevenir son las neumonías bacterianas adquiridas asociadas a ventilación mecánica (NAVM), las infecciones relacionadas con catéteres intravasculares y las infecciones urinarias asociadas al sondeo vesical. La incidencia de estas infecciones ha disminuido en la mayoría de los servicios que realizan un control cifrado, sobre todo gracias a la implantación de programas de mejora de la calidad. Las técnicas de prevención son múltiples y deben aplicarse simultáneamente. Incluyen medidas globales, como las modalidades de prevención de la transmisión cruzada (higiene de las manos, sobre todo) o de uso de antibióticos, concebidas para reducir la presión de selección de bacterias resistentes a éstos, así como medidas específicas relativas a la colocación y uso de cada uno de los dispositivos invasivos. Numerosas técnicas han demostrado su eficacia en estudios de buen nivel metodológico (higiene de las manos, apósitos para catéteres, etc.), mientras que otras siguen siendo objeto de controversias, por lo que las recomendaciones nacionales e internacionales se actualizan regularmente de acuerdo con los nuevos datos científicos. Estas medidas, implantadas de manera razonada en el marco de programas de mejora de la calidad, permiten obtener tasas muy bajas de infecciones relacionadas con el uso de catéteres vasculares y resultados menos satisfactorios con las NAVM, que justifican la necesidad de proseguir la investigación en este campo.


title: Efficient transport of Semliki Forest virus glycoproteins through a Golgi complex morphologically altered by Uukuniemi virus glycoproteins.

text: In infected BHK21 cells, the glycoproteins G1 and G2 of a temperature-sensitive mutant (ts12) of Uukuniemi virus (UUK) accumulate at 39 degrees C in the Golgi complex (GC) causing an expansion and vacuolization of this organelle. We have studied whether such an altered Golgi complex can carry out the glycosylation and transport to the plasma membrane (PM) of the Semliki Forest virus (SFV) glycoproteins in double-infected cells. Double-immunofluorescence staining showed that approximately 90% of the cells became infected with both viruses. Almost the same final yield of infectious SFV was obtained from double-infected cells as from cells infected with SFV alone. The rate of transport from the endoplasmic reticulum (ER) via the GC to the plasma membrane of the SFV glycoproteins was analysed by immunofluorescence, surface radioimmunoassay and pulse-chase labeling followed by immunoprecipitation, endoglycosidase H digestion and SDS-PAGE. The results showed that: the SFV glycoproteins were readily transported to the cell surface in double-infected cells, whereas the UUK glycoproteins were retained in the GC; the transport to the PM was retarded by approximately 20 min, due to a delay between the ER and the central Golgi; E1 of SFV appeared at the PM in a sialylated form. These results indicate that the morphologically altered GC had retained its functional integrity to glycosylate and transport plasma membrane glycoproteins.


title: Patterns of human social contact and contact with animals in Shanghai, China

text: East Asia is as a principal hotspot for emerging zoonotic infections. Understanding the likely pathways for their emergence and spread requires knowledge on human-human and human-animal contacts, but such studies are rare. We used self-completed and interviewer-completed contact diaries to quantify patterns of these contacts for 965 individuals in 2017/2018 in a high-income densely-populated area of China, Shanghai City. Interviewer-completed diaries recorded more social contacts (19.3 vs. 18.0) and longer social contact duration (35.0 vs. 29.1 hours) than self-reporting. Strong age-assortativity was observed in all age groups especially among young participants (aged 7–20) and middle aged participants (25–55 years). 17.7% of participants reported touching animals (15.3% (pets), 0.0% (poultry) and 0.1% (livestock)). Human-human contact was very frequent but contact with animals (especially poultry) was rare although associated with frequent human-human contact. Hence, this densely populated area is more likely to act as an accelerator for human-human spread but less likely to be at the source of a zoonosis outbreak. We also propose that telephone interview at the end of reporting day is a potential improvement of the design of future contact surveys.


title: Challenges of COVID‐19 pandemic for dermatology

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a new coronavirus responsible for the pandemic named coronavirus disease 2019 (COVID‐19). The disease causes SARS with a significant morbidity and mortality. We provide a review with a focus on COVID‐19 in dermatology. We discuss triage of suspected infectious patients, protection of medical doctors and nurses. We discuss the available data on cutaneous symptoms, although disease‐specific symptoms have yet not been observed. COVID‐19 is a challenge for the treatment of dermatologic patients, either with severe inflammatory disorders or with skin cancer. The consequences for systemic treatment are obvious but it will be most important to collect the clinical data for a better decision process. Last but not least, education in dermatology for students will not be temporarily possible in the classical settings. COVID‐19, although not a skin disease, by itself has an immense impact on dermatology.


title: Fear of nuclear power? Evidence from Fukushima nuclear accident and land markets in China

text: Abstract This paper examines whether the 2011 Fukushima Nuclear Accident (FNA) changed the Chinese public's attitude toward nuclear energy by studying transactions in land markets near nuclear power plants in China. Using a data set that matched the details of all nuclear reactors in China with information on land transactions around them before and after the FNA, we find that the accident had dynamic effects on land markets in China. Land prices within 40km of nuclear power plants dropped by about 18% one month after the nuclear accident. However, the impact of FNA decreased over the longer term, eventually becoming statistically insignificant. Also, the impacts of the disaster varied with plant characteristics such as operating status, construction year, and size.


title: SseG, a virulence protein that targets Salmonella to the Golgi network

text: Intracellular replication of the bacterial pathogen Salmonella enterica occurs in membrane-bound compartments called Salmonella-containing vacuoles (SCVs). Maturation of the SCV has been shown to occur by selective interactions with the endocytic pathway. We show here that after invasion of epithelial cells and migration to a perinuclear location, the majority of SCVs become surrounded by membranes of the Golgi network. This process is dependent on the Salmonella pathogenicity island 2 type III secretion system effector SseG. In infected cells, SseG was associated with the SCV and peripheral punctate structures. Only bacterial cells closely associated with the Golgi network were able to multiply; furthermore, mutation of sseG or disruption of the Golgi network inhibited intracellular bacterial growth. When expressed in epithelial cells, SseG co-localized extensively with markers of the trans-Golgi network. We identify a Golgi-targeting domain within SseG, and other regions of the protein that are required for localization of bacteria to the Golgi network. Therefore, replication of Salmonella in epithelial cells is dependent on simultaneous and selective interactions with both endocytic and secretory pathways.


title: Response to Ribeiro da Silva et al.,“Role of Nonstructural Proteins in the Pathogenesis of SARS‐CoV‐2

text: We are writing regarding the Letter entitled “Role of non‐structural Proteins in the Pathogenesis of SARSCoV‐2” from Ribeiro da Silva et al., published in Journal of Medical Virology(1). We welcome the discussion on published article, which could improve the science and clarify any controversial issues. This article is protected by copyright. All rights reserved.


title: Chicken egg yolk antibodies (IgY) as non-antibiotic production enhancers for use in swine production: a review

text: In recent years, the use of in-feed antibiotics for growth and disease prevention in livestock production has been under severe scrutiny. The use and misuse of in-feed antibiotics has led to problems with drug residues in animal products and increased bacterial resistance. Chicken egg yolk antibodies (IgY) have attracted considerable attention as an alternative to antibiotics to maintain swine health and performance. Oral administration of IgY possesses many advantages over mammalian IgG such as cost-effectiveness, convenience and high yield. This review presents an overview of the potential to use IgY immunotherapy for the prevention and treatment of swine diarrhea diseases and speculates on the future of IgY technology. Included are a review of the potential applications of IgY in the control of enteric infections of either bacterial or viral origin such as enterotoxigenic Escherichia coli, Salmonella spp., rotavirus, porcine transmissible gastroenteritis virus, and porcine epidemic diarrhea virus. Some potential obstacles to the adoption of IgY technology are also discussed.


docid: dwrazfli

title: The Fire This Time: The Stress of Racism, Inflammation and COVID-19


title: Thermal stability and inactivation of hepatitis C virus grown in cell culture

text: BACKGROUND: Hepatitis C virus (HCV) is a blood-borne flavivirus that infects many millions of people worldwide. Relatively little is known, however, concerning the stability of HCV and reliable procedures for inactivating this virus. METHODS: In the current study, the thermostability of cell culture-derived HCV (HCVcc, JFH-1 strain) under different environmental temperatures (37°C, room temperature, and 4°C) and the ability of heat, UVC light irradiation, and aldehyde and detergent treatments to inactivate HCVcc were evaluated. The infectious titers of treated viral samples were determined by focus-forming unit (FFU) assay using an indirect immunofluorescence assay for HCV NS3 in hepatoma Huh7-25-CD81 cells highly permissive for HCVcc infection. MTT cytotoxicity assay was performed to determine the concentrations of aldehydes or detergents at which they were no longer cytotoxic. RESULTS: HCVcc in culture medium was found to survive 37°C and room temperature (RT, 25 ± 2°C) for 2 and 16 days, respectively, while the virus was relatively stable at 4°C without drastic loss of infectivity for at least 6 weeks. HCVcc in culture medium was sensitive to heat and could be inactivated in 8 and 4 min when incubated at 60°C and 65°C, respectively. However, at 56°C, 40 min were required to eliminate HCVcc infectivity. Addition of normal human serum to HCVcc did not significantly alter viral stability at RT or its susceptibility to heat. UVC light irradiation (wavelength = 253.7 nm) with an intensity of 450 μW/cm(2 )efficiently inactivated HCVcc within 2 min. Exposures to formaldehyde, glutaraldehyde, ionic or nonionic detergents all destroyed HCVcc infectivity effectively, regardless of whether the treatments were conducted in the presence of cell culture medium or human serum. CONCLUSIONS: The results provide quantitative evidence for the potential use of a variety of approaches for inactivating HCV. The ability of HCVcc to survive ambient temperatures warrants precautions in handling and disposing of objects and materials that may have been contaminated with HCV.


title: Characterization and utility of monoclonal antibodies against spike protein of transmissible gastroenteritis virus

text: Aims: This work aims to characterize the utility of four newly generated monoclonal antibodies (mAbs) against transmissible gastroenteritis virus (TGEV). Methods and Results: Four monoclonal antibodies (mAbs) against the N‐terminal half of spike protein (S1 protein) of TGEV were identified. Affinity constant of these mAbs was analysed. These mAbs were capable of reacting with the TGEV S1 protein analysed by ELISA and Western blot. A competition assay between the different mAbs was performed to determine whether the different antibodies mapped in the same or a different antigenic region of the protein. Investigation on the neutralizing ability of these mAbs indicated that two of these mAbs completely neutralized TGEV at an appropriate concentration. These mAbs were able to detect the TGEV‐infected cells in immunofluorescence assays and Western blot. Moreover, they differentiated TGEV S protein from other control proteins. Conclusions: The generated four mAbs are very specific, and the established immunofluorescence assays, Western blot and discrimination ELISA are useful approaches for detecting of TGEV. Significance and Impact of the Study: It is a novel report regarding the use of the S1 protein of TGEV to generate specific mAbs. Their utility and the established immunoassays contribute to the surveillance of TGE coronavirus.


SARS Control and Psychological Effects of Quarantine, Toronto, Canada


title: ICAM-1 receptors and cold viruses

text: Abstract Human rhinoviruses (HRVs), the single most important etiologic agent of common colds, are small viruses composed of an icosahedral protein shell that encapsidates a single, positive RNA strand. Multiplication of HRVs occurs in the cytoplasm of the host cell. To produce infection, HRVs must first attach to specific cellular receptors embedded in the plasma membrane. Ninety percent of HRVs immunogenic variants use as receptor intercellular adhesion molecule-1 (ICAM-1), a cell surface glycoprotein that promotes intercellular signaling in processes derived from inflammation response. As HRV receptor, ICAM-1 positions the virus to within striking distance of the membrane, and then triggers a conformational change in the virus that ultimately results in delivery of the viral RNA genome into the cytoplasm, across a lipid bilayer. The interaction between ICAM-1 and HRVs has been analyzed by the combination of crystal structures of HRVs and ICAM-1 fragments with electron microscopy reconstructions of the complexes. The resulting molecular models are useful to address questions about receptor recognition, binding specificity, and mechanisms by which ICAM-1 induces virus uncoating.


title: A cutting-edge immunoinformatics approach for design of multi-epitope oral vaccine against dreadful human malaria

text: Abstract Human malaria is a pathogenic disease mainly caused by Plasmodium falciparum, which was responsible for about 405,000 deaths globally in the year 2018. To date, several vaccine candidates have been evaluated for prevention, which failed to produce optimal output at various preclinical/clinical stages. This study is based on designing of polypeptide vaccines (PVs) against human malaria that cover almost all stages of life cycle of Plasmodium and for the same 5 genome derived predicted antigenic proteins (GDPAP) have been used. For the development of a multi-immune inducer, 15 PVs were initially designed using T cell epitope ensemble which covered >99% human population as well as linear B cell epitopes with or without adjuvants. The immune simulation of PVs showed higher levels of T-cell and B-cell activities compared to positive and negative vaccine controls. Furthermore, in silico cloning of PVs and codon optimization followed by enhanced expression within Lactococcus lactis host system was also explored. Although, the study has sound theoretical and in silico findings, the in vitro/in vivo evaluation seems imperative to warrant the immunogenicity and safety of PVs towards management of P. falciparum infection in the future.


docid: xiyeceib

title: The Antibody Germline/Maturation Hypothesis, Elicitation of Broadly Neutralizing Antibodies Against HIV-1 and Cord Blood IgM Repertoires

text: We have previously observed that all known potent broadly neutralizing antibodies (bnAbs) against HIV-1 are highly divergent from their putative germline predecessors in contrast to bnAbs against viruses causing acute infections such as henipaviruses and SARS CoV, which are much less divergent from their germline counterparts. Consequently, we have hypothesized that germline antibodies may not bind to the HIV-1 envelope glycoprotein (Env) because they are so different compared to the highly somatically mutated HIV-1-specific bnAbs. We have further hypothesized that the immunogenicity of highly conserved epitopes on the HIV-1 envelope glycoproteins (Envs) may be reduced or eliminated by their very weak or absent interactions with germline antibodies and immune responses leading to the elicitation of bnAbs may not be initiated and/or sustained. Even if such responses are initiated, the maturation pathways are so extraordinarily complex that prolonged periods of time may be required for elicitation of bnAbs with defined unique sequences. We provided the initial evidence supporting this antibody germline/maturation hypothesis, which prompted a number of studies to design vaccine immunogens that could bind putative germline predecessors of known bnAbs and to explore complex B cell lineages. However, guiding the immune system through the exceptionally complex antibody maturation pathways to elicit known bnAbs remains a major challenge. Here, we discuss studies exploring the antibody germline/maturation hypothesis as related to elicitation of bnAbs against HIV-1 and present our recent data demonstrating the existence of germline-like precursors of VRC01 antibodies in a human cord blood IgM library.


title: Isolation and purification of clemastanin B and indigoticoside A from Radix Isatidis by high-speed counter-current chromatography

text: A preparative high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of ethyl acetate–n-butanol–water (2:7:9, v/v/v) was successfully performed to isolate and separate clemastanin B and indigoticoside A from the plant of Radix Isatidis, a traditional Chinese medicine. A total of 59.2 mg clemastanin B and 66.1 mg indigoticoside A with purities of 94.6% and 99.0% determined by high performance liquid chromatography (HPLC) were obtained in one-step elution from 250 mg crude extract, which contained clemastanin B 24.8% and indigoticoside A 28.4%, and the recoveries of clemastanin B and indigoticoside A were 90.3% and 92.2%, respectively. The chemical structure was identified by IR, MS, (1)H NMR and (13)C NMR.


title: Leading on the Edge of Insanity

text: Abstract COVID-19 has officially consumed every nurse leader's time and efforts. The purpose of this article is to share early learnings from the west coast of the United States, where the first U.S case was cared for. In this article, I describe the emerging principles allowing us to respond to an unprecedented crisis: Prevent, Protect, and Control. By the time this crisis is over, I do not doubt that we will have additional science and experience to support our frontline nurses and our nurse leaders. That said, I felt it was important to share our expertise in real-time for others to benefit from. I would also point out that writing about what you are feeling is cathartic—I encourage my colleagues to join me in writing about what you are experiencing.


title: Animal Health: Global Antibiotic Issues

text: Abstract Antibiotics are antimicrobial compounds that can inhibit and even destroy bacterial and fungal growth. Antibiotics are used in both human diseases to kill bacterial and fungal pathogens and in farm animals to reduce incidences of animal diseases as veterinary drugs, promote animal weight gain, and control the zoonotic pathogens in milk, egg, meat, and meat products. Use of antibiotics in agricultural farm animals may aid bacterial antibiotic resistance. Though it is still a debatable topic, a comprehensive understanding of using antibiotics in farm animal production and the replacement of these antibiotics with some natural products is under pressure.


title: Anti-Cytomegalovirus Activity of the Anthraquinone Atanyl Blue PRL

text: Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC(50) of 4.9 μM but was cytotoxic at concentrations only two-fold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238–265 μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC(50) of 6.3 μM, significantly below its 50% cytotoxic concentration of 216 μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to one h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24 h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC(50) of 4.5 and 9.3 μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development.