title: The nucleotide sequence of the peplomer gene of porcine transmissible gastroenteritis virus (TGEV): comparison with the sequence of the peplomer protein of feline infectious peritonitis virus (FIPV)

text: Abstract The amino acid sequence of the peplomer protein of transmissible gastroenteritis virus (TGEV) has been derived from the cloned cDNA sequence. The gene encodes a protein of 1447 amino acids with a molecular weight of 159 574. Comparison with the primary structure of the peplomer protein of feline infectious peritonitis virus (FIPV) (de Groot et al., 1987b) revealed one domain, from amino acids 1 to 274, in which the nucleotide homology was 39%, whereas in the second domain (from residues 275 to 1447) the homology was 93%.


title: Attenuation of SARS coronavirus by a short hairpin RNA expression plasmid targeting RNA-dependent RNA polymerase

text: Abstract Severe acute respiratory syndrome (SARS) is a highly contagious and sometimes a lethal disease, which spread over five continents in 2002–2003. Laboratory analysis showed that the etiologic agent for SARS is a new type of coronavirus. Currently, there is no specific treatment for this disease. RNA interference (RNAi) is a recently discovered antiviral mechanism in plant and animal cells that induces a specific degradation of double-stranded RNA. Here, we provide evidences that RNAi targeting at coronavirus RNA-dependent RNA polymerase (RDRP) using short hairpin RNA (shRNA) expression plasmids can specifically inhibit expression of extraneous coronavirus RDRP in 293 and HeLa cells. Moreover, this construct significantly reduced the plaque formation of SARS coronaviruses in Vero-E6 cells. The data may suggest a new approach for treatment of SARS patients.


Powerless in the ICU: Perspectives from Intensive Care Units in the Face of COVID-19.


title: Middle East Respiratory Syndrome-Corona Virus (MERS-CoV) associated stress among medical students at a university teaching hospital in Saudi Arabia

text: Abstract Background and objectives Middle East Respiratory Syndrome Corona Virus (MERS-CoV) outbreak in 2014 was associated with high public anxiety in the affected countries. Media speculations may have increased this psychological distress. The healthcare community was the most distressed because they were at the highest risk of infection. This study is the first to explore MERS-CoV epidemic impact on medical students’ perception and determinants of their psychological distress during this outbreak. Methods We randomly selected and surveyed 200 students from the College of Medicine at King Saud University, Riyadh, Saudi Arabia. A predesigned questionnaire was answered by participants, and the collected data were statistically analyzed. Results One hundred and seventy-four (87%) responded. Female students had a significantly higher mean stress level than males (P < 0.001). Participants had a mean GAD score of 2.7 ± 3.1 and a median of 2. Perceived sufficiency of information score was the highest mean and median (17.4 ± 4.2 and 18 respectively). College and hospital announcements were the most common source of information (25.4%). One hundred and thirty-four (77%) reported minimal anxiety, thirty-two (18.4%) reported mild anxiety, 8 (4.6%) reported moderate anxiety, and none of them reported severe anxiety (score >14). The stress level (as reported on 1–10 scale) shows significant correlation with Generalized Anxiety Disorder (GAD-7) score. We found in this study that significant predictors in our model, in terms of more significant to the least, were: an increased self-report on hygienic habits, self-reported social avoidance, the generalized anxiety score and finally being female gander while other variables including numbers of resources access, agreeing with public fear and knowledge score on MERS-CoV all were found to be non-significant. However, the number of accessed resources, as per students, has borderline significant correlation with higher self-reported anxiety from MERS-CoV. Conclusions Medical students’ psychological needs during the MERS-CoV outbreak should be addressed appropriately. Our results highlight the need to establish psychological support programs for medical students during an infectious disease outbreak.


title: Demand for Health Information on COVID-19 among Vietnamese

text: Due to the rapid spread of coronavirus, Vietnam introduced its first national partial lockdown on April 1st, 2020. The public relied on online sources, whether through official websites or phone-based applications, to acquire up-to-date health information, provide accurate instructions, and limit misinformation. This study aims to provide insight regarding the current level of awareness of the pandemic, and to identify associated factors in Vietnamese participants to recommend necessary interventions. A cross-sectional study was conducted using a web-based survey during the first week of the lockdown period. There were 341 observations collected using a snowball sampling technique. A Tobit multivariable regression model was used to identify factors associated with the demand for each category of health information. The most requested information was the latest updated news on the epidemic, followed by information about disease symptoms and updated news on the outbreak. The prevalence of diverse socioeconomic, demographic, and ethnic factors in Vietnam requires consideration of the specific health information needs of unique groups. Identifying group-specific demands would be helpful to provide proper information to fulfill each population group’s needs.


title: Comparable humoral response after two doses of adjuvanted influenza A/H1N1pdm2009 vaccine or natural infection in allogeneic stem cell transplant recipients

text: BACKGROUND: The present study evaluated immunogenicity and tolerance of two-dose influenza A/H1N1pdm09 vaccination in allogeneic hematopoietic stem cell transplantation (HSCT) recipients, and compared the vaccine-induced humoral response to that triggered by natural infection in another group of HSCT patients. METHODS: Adult allogeneic HSCT recipients vaccinated with two doses of influenza A/H1N1pdm09 vaccine, separated by 3 weeks, and patients with proven influenza A/H1N1pdm09 infection were included. Antibody responses were measured by hemagglutination-inhibition assay 1) on days 0, 21, 42 and 6 months after the first vaccine injection in vaccinated patients and 2) before pandemic and after influenza A/H1N1pdm09 infection, in patients presented natural infection. RESULTS: At baseline, 3% of 59 recipients of adjuvanted vaccine and 0% of 20 infected patients were seroprotected (antibody titer ≥ 1/40). Seroprotection rate observed 42 days after vaccination was not different from that observed after natural infection (66% and 60% respectively, p = 0.78). In vaccinated patients, seroprotection rate increased significantly from 54% to 66% between day 21 and 42 (p = 0.015). Moreover, after 6 months, seroprotection rate in 21 vaccinated patients was similar to that observed in 10 infected patients evaluated at least 76 days after infection (D76–217) (60% and 81% respectively, p = 0.2). In multivariate analysis, no immunosuppressive treatment or chronic graft-versus-host disease (GVHD) and longer time between transplantation and vaccination/infection were associated with a stronger humoral response. The adjuvanted vaccine was safe with low rate of GVHD worsening. CONCLUSION: In HSCT recipients, two doses of influenza A/H1N1pdm09 adjuvanted vaccine were safe and induced a humoral response comparable to that triggered by natural infection in these patients.


docid: xubsqetp

title: COVID-19: Four Paediatric Cases in Malaysia

text: Abstract Objective This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia Background COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. Cases In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. Discussion There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.


The importance of IL-6 blockade beyond the COVID-19 pandemic: consideration for cancer care


title: Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

text: Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.


title: Stress hormones bring birds, pathogens and mosquitoes together

text: Do stress hormones such as corticosterone enhance bird susceptibility to mosquitoes in ways that enhance rates of coinfection? Does this then enhance pathogen emergence?


title: ESMO management and treatment adapted recommendations in the COVID-19 era: colorectal cancer

text: COVID-19 pandemic challenges health system capacities in many countries. National healthcare services have to manage unexpected shortage of healthcare resources that have to be reallocated according to the principles of fair and ethical prioritisation, in order to maintain the highest levels of care to all patients, ensure the safety of patients and healthcare workers and save as many lives as possible. Beyond that, cancer care services have to pursue restructuring, following the same evidence-based dispositions. In this article, we propose guidance to the management of colorectal cancer during the pandemic, prioritised according to a three-tiered framework, based on expert clinical judgement and magnitude of benefit expected from specific interventions. Since the availability of resources for diagnostic procedures, surgery and postoperative care, systemic therapy and radiotherapy may differ, authors did separate prioritisation analyses. The impact of postponing or abrogating cancer interventions on outcomes according to a high, medium or low priority scale, is outlined and discussed. The implementation of healthcare services using telemedicine is explored: it reveals itself as functional and effective for limiting patients’ need to travel to centres and thereby has the potential to reduce diffusion of severe acute respiratory syndrome coronavirus 2. Colorectal cancer demands a considerable amount of medical resources. Therefore, the redefinition of its diagnostic and therapeutic algorithms with a rigorous method is crucial in order to ensure the highest quality of continuum of care in the broader context of the pandemic and the challenged healthcare systems.


title: The Politics of Disease Epidemics: a Comparative Analysis of the SARS, Zika, and Ebola Outbreaks

text: Over the past few decades, disease outbreaks have become increasingly frequent and widespread. The epicenters of these outbreaks have differed, and could be linked to different economic contexts. Arguably, the responses to these outbreaks have been “political” and inherently burdensome to marginalized populations. Key lessons can be learned from exploring the narratives about the different epidemics in varying income settings. Based on a review of the published medical, social, and political literature, which was accessed using four electronic databases—PubMed, Sociological Abstracts, Scholars Portal, and Web of Science, the overall objective of this paper discuss scholars’ narratives on the “politics” of Ebola in a low-income setting, Zika virus in a middle-income setting, and SARS in a high-income setting. Various themes of the politics of epidemics were prominent in the literature. The narratives demonstrated the influence of power in whose narratives and what narratives are presented in the literature. While marginalized populations were reported to have borne the brunt of all disease outbreaks in the different contexts, the prevalence of their narratives within the reviewed literature was limited. Regardless of income setting, there is a need to give voice to the most marginalized communities during an epidemic. The experiences and narratives of those most vulnerable to an epidemic—specifically poor communities—need to be represented in the literature. This could contribute to mitigating some of the negative impact of the politics in epidemics.


Transforming Schools into Pre-designed Alternative Care Sites as Part of Preparedness Plan for Pandemic H5N1 Influenza


title: A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles

text: Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell’s viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell’s viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1’s endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell’s viper are not susceptible to infection because EBOV cannot bind to viper NPC1. This resistance to infection can be mapped to a single amino acid residue in viper NPC1 that renders it unable to bind to EBOV GP. The newly solved structure of EBOV GP bound to NPC1 confirms our findings, revealing that this residue dips into the GP receptor-binding pocket and is therefore critical to the binding interface. Consequently, this otherwise well-conserved residue in vertebrate species influences the ability of reptilian NPC1 proteins to bind to EBOV GP, thereby affecting viral host range in reptilian cells.


title: Intravenous Hypertonic Saline Solution (7.5%) and Oral Electrolytes to Treat of Calves with Noninfectious Diarrhea and Metabolic Acidosis

text: OBJECTIVE: The aim of this study was to compare the efficacy of treating osmotic diarrhea and dehydration in calves with hypertonic saline solution (HSS) IV, isotonic electrolyte solution (IES) PO, and a combination of these 2 solutions (HSS + IES). EXPERIMENTAL DESIGN: Eighteen male calves 8–30 days of age were used to evaluate the efficacy of 3 methods of fluid therapy after induction of osmotic diarrhea and dehydration. The diarrhea and dehydration were induced by administration of saccharose, spironolactone, and hydrochlorothiazide for 48 hours. The animals were randomly divided into 3 experimental groups: Group 1: 7.2% hypertonic saline solution‐HSS (5 mL/kg IV); Group 2: oral isotonic electrolyte solution IES (60 mL/kg PO); or Group 3: HSS+IES. Clinical signs and laboratory finding observed 48 hours post‐induction (Time 0) included diarrhea, dehydration, lethargy, and metabolic acidosis. RESULTS: Calves treated with HSS + IES experienced decreases in hematocrit, total protein concentration, albumin concentration, urea nitrogen concentration, and plasma volume as well as increases in blood pH, blood bicarbonate concentration, and central venous pressure between 1 and 3 hours post‐treatment. These findings also were observed in animals treated with IES, however, at a slower rate than in the HSS + IES‐treated animals. Animals treated with HSS continued to display signs of dehydration, lethargy, and metabolic acidosis 24 hours post‐treatment. CONCLUSION: Treatment with a combination of HSS and IES produced rapid and sustainable correction of hypovolemia and metabolic acidosis in calves with noninfections diarrhea and dehydration.


Earth Day Reflections: Hope Amid the Pandemic


title: The potential impact of vulnerability and coping capacity on the pandemic control of COVID-19

text: • The European commission has developed an index for risk management named INFORM; • Two dimensions (vulnerability and lack of coping capacity) are relevant to COVID-19; • We examined if these dimensions were associated with COVID-19 pandemic control; • Higher vulnerability and poorer coping capacity were associated with poorer control; • Modifying these two dimensions might potentially mitigate COVID-19 pandemic control.


title: Biosensors and rapid diagnostic tests on the frontier between analytical and clinical chemistry for biomolecular diagnosis of dengue disease: A review

text: Abstract The past decades have witnessed enormous technological improvements towards the development of simple, cost-effective and accurate rapid diagnostic tests for detection and identification of infectious pathogens. Among them is dengue virus, the etiologic agent of the mosquito-borne dengue disease, one of the most important emerging infectious pathologies of nowadays. Dengue fever may cause potentially deadly hemorrhagic symptoms and is endemic in the tropical and sub-tropical world, being also a serious threat to temperate countries in the developed world. Effective diagnostics for dengue should be able to discriminate among the four antigenically related dengue serotypes and fulfill the requirements for successful decentralized (point-of-care) testing in the harsh environmental conditions found in most tropical regions. The accurate identification of circulating serotypes is crucial for the successful implementation of vector control programs based on reliable epidemiological predictions. This paper briefly summarizes the limitations of the main conventional techniques for biomolecular diagnosis of dengue disease and critically reviews some of the most relevant biosensors and rapid diagnostic tests developed, implemented and reported so far for point-of-care testing of dengue infections. The invaluable contributions of microfluidics and nanotechnology encompass the whole paper, while evaluation concerns of rapid diagnostic tests and foreseen technological improvements in this field are also overviewed for the diagnosis of dengue and other infectious and tropical diseases as well.


title: Changes in liver transplant center practice in response to COVID‐19: Unmasking dramatic center‐level variability

text: The COVID‐19 pandemic, caused by the SARS‐CoV‐2 virus, has been devastating to health care delivery in many parts of the US and has had a significant impact on organ transplantation. With shelter‐in‐place orders, outpatient clinics transitioned to telemedicine, and the threat of hospitals being overrun with COVID‐19 patients, liver transplant programs have been faced with the challenge of balancing patient and staff safety while operating in a resource limited environment.


Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods Eight hundred and ninety‐three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results Coinfections were identified in 103 (18%) of 566 virus‐positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV‐1, multiple virus illnesses had a significantly lower viral load (log(10) copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu‐A, PIV‐3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.


title: Enhanced Design of PPE Based on Electrostatic Principle to Eliminate Viruses (SARS-CoV-2)

text: The ongoing global pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in the crucial stage. The vaccine is still at the developing stage. Currently, the only way to check the spreading of this virus is self-isolation. It is reported that a good number of health workers are infected while treating patients suffering from COVID 19. Therefore, an effort is made to develop a system that can enhance safety and check unwanted viruses. Although the complete specification of the SARS-CoV-2 is yet to be evaluated, the present work considers the characteristic of SARS-CoV-1, which closely relates to that of SARS-CoV-2. The proteins are one of the most important structural and functional molecules of the virus; therefore, few properties of a protein are considered. In this work, we propose a sanitization procedure of the personal protective equipment (PPE), such as gloves and masks, before and after the use, by employing high voltage charge generator (30 kV) from a very low DC source of 5 V to eliminate the virus from the surface of PPE. The positive output is connected to a metallic surface coated with carbon nanotubes (CNT) or a metallic surface ablated using lithography to achieve desired nano-grooves of 200 nm. At the tip of these nano-grooves, a very high electric field is generated which readily ionises the air in the vicinity of the tip. The high electric field alters the induced dipole of the protein of the virus, causing permanent damage in terms of electroporation. Further positive salt ions diffuse into the protein of the viruses, causing it inactive and disintegrate.


title: Emerging infectious diseases and outbreaks: implications for women’s reproductive health and rights in resource-poor settings

text: This century is witnessing dramatic changes in the health needs of the world’s populations. The double burden of infectious and chronic diseases constitutes major causes of morbidity and mortality. Over the last two decades, there has been a rise in infectious diseases, including the severe acute respiratory syndrome virus (SARS), the H1N1 pandemic influenza, the Ebolavirus and the Covid-19 virus. These diseases have rapidly spread across the world and have reminded us of the unprecedented connectivity that defines our modern civilization. Though some countries have made substantial progress toward improving global surveillance for emerging infectious diseases (EIDs), the vast majority of Low-and Middle-income Countries (LMICs) with fragile health systems and various system-related bottlenecks remain vulnerable to outbreaks and, as such, experience dramatic social and economic consequences when they are reported. Lessons learned from past outbreaks suggest that gender inequalities are common across a range of health issues relating to Sexual and Reproductive Health and Rights (SRHR), with women being particularly disadvantaged, partially due to the burden placed on them. Though these countries are striving to improve their health systems and be more inclusive to this vulnerable group, the national/ global outbreaks have burdened the overall system and thus paralyzed normal services dedicated to the delivery of Sexual and Reproductive Health (SRH) services. In this paper, we discuss the global commitments to SRH, the impact of the EIDs on the LMICs, the failure in the delivery of SRH services, and the strategies for successful implementation of recovery plans that must address the specific and differentiated needs of women and girls in resource-poor settings.


Berufspolitik BvDU


title: Epidemiological analysis of the early 38 fatalities in Hubei, China, of the coronavirus disease 2019

text: BACKGROUND: Since the emergence of coronavirus disease 2019 (COVID-19) in Hubei province of China by the end of 2019, it has burned its way across the globe, resulting in a still fast-growing death toll that far exceeded those from severe acute respiratory syndrome (SARS) in less than two months. As there is a paucity of evidence on which population is more likely to progress into severe conditions among cases, we looked into the first cluster of death cases, aiming to add to current evidence and reduce panic among the population. METHODS: We prospectively collected the demographic and clinical data of the first 38 fatalities whose information was made public by the Health Commission of Hubei province and the official Weibo account of China Central Television news center, starting from 9 January through 24 January 2020. The death cases were described from four aspects (gender and age characteristics, underlying diseases, the time course of death, symptoms at the incipience of illness and hospital admission). RESULTS: Among the 38 fatalities, 71.05% were male, and 28.95% were female, with the median age of 70 years (interquartile range (IQR) = 65-81). Persons aged 66-75 made up the largest share. Twenty-five cases had a history of chronic diseases. The median time between the first symptoms and death was 12.50 days (IQR = 10.00-16.25), while the median time between the admission and death was 8.50 (IQR = 5.00-12.00) days. In persons aged over 56 years, the time between the first symptoms and death decreased with age, and so did the time between the admission and death, though the latter increased again in persons aged over 85 years. The major first symptoms included fever (52.63%), cough (31.58%), dyspnea (23.68%), myalgia and fatigue (15.79%). CONCLUSIONS: Among the death cases, persons with underlying diseases and aged over 65 made up the majority. The time between the first symptoms and death decreased with the advanced age. In all the age groups, males dominated the fatalities.


docid: ifptdqqf

title: LETTER TO THE EDITOR: Labor and Delivery Guidance for COVID-19


title: A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8

text: Ebola virus (EBOV) is a single-stranded negative-sense RNA virus belonging to the Filoviridae family. The leader and trailer non-coding regions of the EBOV genome likely regulate its transcription, replication, and progeny genome packaging. We investigated the cis-acting RNA signals involved in RNA–RNA and RNA–protein interactions that regulate replication of eGFP-encoding EBOV minigenomic RNA and identified heat shock cognate protein family A (HSC70) member 8 (HSPA8) as an EBOV trailer-interacting host protein. Mutational analysis of the trailer HSPA8 binding motif revealed that this interaction is essential for EBOV minigenome replication. Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. Results of minigenome assays and an EBOV reverse genetic system rescue support a role for both the panhandle domain and HSPA8 motif 1 in virus replication.


SARS-CoV, MERS-CoV and now the 2019-novel CoV: Have we investigated enough about coronaviruses? – A bibliometric analysis


title: Proteasome inhibition reduces avian reovirus replication and apoptosis induction in cultured cells

text: Abstract The interplay between avian reovirus (ARV) replication and apoptosis and proteasome pathway was studied in cultured cells. It is shown that inhibition of the proteasome did not affect viral entry and host cell translation but had influence on ARV replication and ARV-induced apoptosis. Evidence is provided to demonstrate that ubiquitin-proteasome blocked ARV replication at an early step in viral life cycle. However, viral transcription and protein translation were also reduced markedly after addition of proteasome inhibitor MG132. Treatment of BHK-21 cells with the MG132 markedly decreased virus titer as well as prevented virus-induced apoptosis. The expression of ARV proteins σC, σA, and σNS was also reduced markedly, suggesting that suppression of virus replication is due to down-regulation of these ARV proteins by ubiquitin-proteasome system. MG132 was also shown to suppress ARV σC-induced phosphrylation of p53 on serine 46, caspase 3 activities, and DNA fragmentation leading to complete inhibition of ARV-induced apoptosis.


title: Animal-based national surveillance for zoonotic disease: Quality, limitations, and implications of a model system for monitoring rabies

text: Abstract Surveillance for zoonotic diseases among wildlife is a research and public health challenge. The inherent limitations posed by the requisite human–animal interactions are often undefined and underappreciated. The national surveillance system for animal rabies in the United States was examined as a model system; reporting of animal rabies is legally mandated, each case of rabies is laboratory confirmed, and data have been consistently collected for more than 50 years. Factors influencing the monthly counts of animal rabies tests reported during 1992–2001 were assessed by univariate and multivariable regression methods. The suitability of passively collected surveillance data for determining the presence or absence of the raccoon-associated variant of rabies within states and within individual counties was assessed by determining critical threshold values from the regression analyses. The size of the human population and total expenditures within a county accounted for 72% and 67%, respectively, of the variance in testing. The annual median number of rabies tests performed was seven for counties without rabies, 22 for counties with non-raccoon rabies, and 34 for counties with raccoon rabies. Active surveillance may be required in locales with sparse human populations when a high degree of confidence in the status of rabies is required.


title: eHealth in kidney care

text: eHealth is gaining momentum in nephrology, although evidence for its efficacy remains unclear and challenges to its widespread adoption persist. Successful integration of eHealth into kidney care will require patient engagement to develop effective interventions and issues such as data validity, regulation, oversight and adequate infrastructure to be addressed.


title: What face mask for what use in the context of COVID-19 pandemic? The French guidelines

text: Summary In the context of the COVID-19 pandemic, wearing a face mask has become usual and ubiquitous, in both hospitals and community. However, the general public is consuming surgical or filtering face piece (FFP) masks irrespective of their specificity, leading to global supply shortage for the most exposed persons, which are healthcare workers. This underlines the urgent need to clarify the indications of the different categories of mask, in order to rationalize their use. The study herein specifies the French position for the rational use of respiratory protective equipment for healthcare workers.


docid: jrssbsbx

title: Identification of influenza A nucleoprotein as an antiviral target

text: Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains(1,2,3,4,5). Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly(6,7,8,9), creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC(50)) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nbt.1638) contains supplementary material, which is available to authorized users.


title: Well-controlled vs Poorly-controlled Diabetes in Patients with COVID-19: Are There Any Differences in Outcomes and Imaging Findings?

text: AIMS: Herein, we aimed to compare the clinical outcomes and imaging findings between COVID-19 patients with well-controlled diabetes and those with poorly-controlled diabetes. METHODS: In this retrospective single-center study, 117 patients with coexistent COVID-19 and type 2 diabetes mellitus were included. Patients were divided into two groups based on HbA1c values. The chest computed tomography (CT) score was defined by the summation of individual scores from 5 lung lobes: scores of 0, 1, 2, 3, 4 and 5 were respectively assigned for each lobe if pulmonary involvement was 0%, less than 5%, 5%-25%, 26%-49%, 50%-75%, or more than 75% of each region. Clinical data and laboratory parameters were also collected from patients’ medical records. RESULTS: Among all patients with diabetes, 93 (79.5%) patients had poor-controlled diabetes and 24 (20.5%) had well-controlled diabetes; 66 (56.4%) patients were male and the median age was 66 years (IQR, 55-75 years). The chest CT severity scores were not significantly different between patients with well-controlled diabetes and those with poorly-controlled diabetes (p=0.33). Also, the mortality and recovery rates were similar between the two groups (p=0.54 and p=0.85, respectively). CONCLUSION: Based on the results, clinical outcomes and chest CT severity scores are similar between patients with well-controlled and poorly-controlled diabetes among the Iranian population with COVID-19.


docid: kgoczioe

title: Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs

text: Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.


title: Purification and Electron Cryomicroscopy of Coronavirus Particles

text: Intact, enveloped coronavirus particles vary widely in size and contour, and are thus refractory to study by traditional structural means such as X-ray crystallography. Electron microscopy (EM) overcomes some problems associated with particle variability and has been an important tool for investigating coronavirus ultrastructure. However, EM sample preparation requires that the specimen be dried onto a carbon support film before imaging, collapsing internal particle structure in the case of coronaviruses. Moreover, conventional EM achieves image contrast by immersing the specimen briefly in heavy-metal-containing stain, which reveals some features while obscuring others. Electron cryomicroscopy (cryo-EM) instead employs a porous support film, to which the specimen is adsorbed and flash-frozen. Specimens preserved in vitreous ice over holes in the support film can then be imaged without additional staining. Cryo-EM, coupled with single-particle image analysis techniques, makes it possible to examine the size, structure and arrangement of coronavirus structural components in fully hydrated, native virions. Two virus purification procedures are described.


title: FilmArray® respiratory panel performance in respiratory samples from neonatal care units

text: Abstract FilmArray Respiratory Panel (RP) (Idaho Technology, Inc., Salt Lake City, UT, USA) performance was retrospectively evaluated in respiratory samples collected from neonates in 2 reference neonatology units. Using the FilmArray RP assay, 121/152 (79.6%) samples were positive for at least 1 respiratory virus, while 31/152 (20.4%) were negative. FilmArray RP results were concordant in 68/72 (94.4%) respiratory samples tested with laboratory-developed real-time PCR assays, while in 4/72 (5.6%) samples, the FilmArray RP assay detected an additional virus (2 human rhinovirus/enterovirus and 2 bocavirus). In addition, FilmArray RP results for 70 of 80 (87.5%) respiratory samples tested were concordant with the Seegene Seeplex RV15® detection assay (Seegene, Inc., Seoul, South Korea), while 10/80 (12.5%) were discordant. The advantages of the FilmArray RP are the rapid detection of respiratory viruses (1 hour), the wide number of pathogens detectable in a single assay, and the reduced hands-on time.


title: Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system

text: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.


title: Human coronavirus NL-63 infection in a Brazilian patient suspected of H1N1 2009 influenza infection: Description of a fatal case

text: Abstract Human coronaviruses (HCoVs) cause upper respiratory tract and occasionally lower respiratory tract diseases. The recently described human coronavirus NL63 has not been well investigated among Brazilian patients. We reported the clinical course of an HCoV-NL63 infection in a hospitalised patient suspected of H1N1 2009 infection during the second pandemic wave of influenza activity. A 46-year-old female, health care worker with diabetes and presenting with influenza-like illness (ILI) was admitted to the hospital. During 9 days of influenza-like symptoms, the patient had diabetes decompensation, haemorrhagic pneumonia, rhabdomyolysis, respiratory and renal failure, pericarditis, and brain edema and died. HCoV-NL63 may be a causative agent of previously unexplained respiratory illnesses.


title: Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain

text: This study presents data from a prospective study of adult patients with community-acquired pneumonia (CAP). Of 493 patients included in the study, 223 (45.2%) were aged ≥ 65 years, and 265 (53.7%) had one or more underlying diseases, mostly chronic obstructive pulmonary disease, diabetes mellitus or dementia. In total, 281 microorganisms were identified in 250 (50.7%) patients, with two or more pathogens detected in 28 (5.7%) cases. Microbial diagnosis varied according to age, severity, co-morbidity and site-of-care, but there was much overlap among groups. Streptococcus pneumoniae was the single most prevalent organism in outpatients, patients admitted to hospital, and patients who died, either as a single pathogen or combined with another organism. Infections caused by ‘atypical’ pathogens were seen across all groups, including the elderly and patients with co-morbidities. Mortality varied according to the pneumonia severity index (PSI) of the pneumonia patient outcomes research team. Shock (OR 34.48), an age of > 65 years (OR 25) and altered mental status (OR 9.92) were factors associated independently with 30-day mortality. Key findings from this study were the advanced age of the population with CAP, and the high prevalence of dementia as an underlying disease. The study also revealed that microbiological diagnosis of CAP remains problematic. Although certain epidemiological features may help to predict the microbial aetiology, the overlap among groups reduces the usefulness of this information in guiding therapeutic decisions. Greater effort should be made to improve identification methods for microbial pathogens causing CAP.


Ebola: between mathematics and reality


title: Combining Procalcitonin and Rapid Multiplex Respiratory Virus Testing for Antibiotic Stewardship in Older Adult Patients With Severe Acute Respiratory Infection

text: Abstract Objectives Virus infection is underevaluated in older adults with severe acute respiratory infections (SARIs). We aimed to evaluate the clinical impact of combining point-of-care molecular viral test and serum procalcitonin (PCT) level for antibiotic stewardship in the emergency department (ED). Design A prospective twin-center cohort study was conducted between January 2017 and March 2018. Setting and Participants Older adult patients who presented to the ED with SARIs received a rapid molecular test for 17 respiratory viruses and a PCT test. Measures To evaluate the clinical impact, we compared the outcomes of SARI patients between the experimental cohort and a propensity score–matched historical cohort. The primary outcome was the proportion of antibiotics discontinuation or de-escalation in the ED. The secondary outcomes included duration of intravenous antibiotics, length of hospital stay, and mortality. Results A total of 676 patients were included, of which 169 patients were in the experimental group and 507 patients were in the control group. More than one-fourth (27.9%) of the patients in the experimental group tested positive for virus. Compared with controls, the experimental group had a significantly higher proportion of antibiotics discontinuation or de-escalation in the ED (26.0% vs 16.1%, P = .007), neuraminidase inhibitor uses (8.9% vs 0.6%, P < .001), and shorter duration of intravenous antibiotics (10.0 vs 14.5 days, P < .001). Conclusions and Implications Combining rapid viral surveillance and PCT test is a useful strategy for early detection of potential viral epidemics and antibiotic stewardship. Clustered viral respiratory infections in a nursing home is common. Patients transferred from nursing homes to ED may benefit from this approach.


How to safeguard children’s mental health during emergencies


title: IL-12 and Viral Infections

text: Abstract Interleukin-12 activates natural killer cells and promotes the differentiation of Th1 CD4+ cells; it is a critical factor in viral immunity. IL-12 is secreted by antigen presenting cells including dendritic cells, macrophages and astrocytes, both in tissues and in secondary lymphoid organs. Experimental studies have shown that administration of the cytokine rapidly activates both innate and specific immune responses; this results in enhanced host cellular responses and generally, promotes clearance of virus and host recovery from infection. The observations of many laboratories, studying viral immunity to both RNA and DNA based pathogens, are summarized.


title: Detection of enteroviruses and parechoviruses by a multiplex real-time RT-PCR assay

text: Abstract Detection of all enteroviruses while excluding cross-detection of rhinoviruses is challenging because of sequence similarities in the commonly used conserved targets for molecular assays. In addition, simultaneous detection and differentiation of enteroviruses and parechoviruses would be beneficial because of a similar clinical picture presented by these viruses. A sensitive and specific real-time RT-PCR protocol that can address these clinical needs would be valuable to molecular diagnostic laboratories. Here we report a multiplex nucleic acid based assay using hydrolysis probes targeting the 5′ non-translated region for the detection and differentiation of enteroviruses and parechoviruses without cross-detection of rhinoviruses. This assay has been shown to detect enteroviruses belonging to the different species in a variety of specimen types without detecting the different species of rhinoviruses. Laboratory validation shows the assay to be sensitive, specific, reproducible, easy to set up and uses generic cycling conditions. This assay can be implemented for diagnostic testing of patient samples in a high throughput fashion.


title: World Health Assembly Agendas and trends of international health issues for the last 43 years: Analysis of World Health Assembly Agendas between 1970 and 2012

text: Abstract Objective To analyse the trends and characteristics of international health issues through agenda items of the World Health Assembly (WHA) from 1970 to 2012. Methods Agendas in Committees A/B of the WHA were classified as Administrative or Technical and Health Matters. Agenda items of Health Matters were sorted into five categories by the WHO reform in the 65th WHA. The agenda items in each category and sub-category were counted. Results There were 1647 agenda items including 423 Health Matters, which were sorted into five categories: communicable diseases (107, 25.3%), health systems (81, 19.1%), noncommunicable diseases (59, 13.9%), preparedness surveillance and response (58, 13.7%), and health through the life course (36, 8.5%). Among the sub-categories, HIV/AIDS, noncommunicable diseases in general, health for all, millennium development goals, influenza, and international health regulations, were discussed frequently and appeared associated with the public health milestones, but maternal and child health were discussed three times. The number of the agenda items differed for each Director-General's term of office. Conclusions The WHA agendas cover a variety of items, but not always reflect international health issues in terms of disease burden. The Member States of WHO should take their responsive roles in proposing more balanced agenda items.


title: Current applications and future trends of molecular diagnostics in clinical bacteriology

text: Molecular diagnostics of infectious diseases, in particular, nucleic-acid-based methods, are the fastest growing field in clinical laboratory diagnostics. These applications are stepwise replacing or complementing culture-based, biochemical, and immunological assays in microbiology laboratories. The first-generation nucleic acid assays were monoparametric such as conventional tests, determining only a single parameter. Improvements and new approaches in technology now open the possibility for the development of multiparameter assays using microarrays, multiplex nucleic acid amplification techniques, or mass spectrometry, while the introduction of closed-tube systems has resulted in rapid microbial diagnostics with a subsequently reduced contamination risk. Whereas the first assays were focused on the detection and identification of microbial pathogens, these new technologies paved the way for the parallel determination of multiple antibiotic resistance determinants or to perform microbial epidemiology and surveillance on a genetic level.


title: Implications of altered replication fidelity on the evolution and pathogenesis of coronaviruses

text: RNA virus evolution results from viral replication fidelity and mutational robustness in combination with selection. Recent studies have confirmed the impact of increased fidelity on RNA virus replication and pathogenesis; however, the impact of decreased fidelity is less defined. Coronaviruses have the largest RNA genomes, and encode an exoribonuclease activity that is required for high-fidelity replication. Genetically stable exoribonuclease mutants will allow direct testing of viral mutational tolerance to RNA mutagens and other selective pressures. Recent studies support the hypothesis that coronavirus replication fidelity may result from a multi-protein complex, suggesting multiple pathways to disrupt or alter virus fidelity and diversity, and attenuate pathogenesis.


title: COVID‐19 under spotlight: A close look at the origin, transmission, diagnosis, and treatment of the 2019‐nCoV disease

text: Months after the outbreak of a new flu‐like disease in China, the entire world is now in a state of caution. The subsequent less‐anticipated propagation of the novel coronavirus disease, formally known as COVID‐19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS‐CoV‐2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID‐19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.


Self‐reported olfactory loss in COVID‐19: is it really a favorable prognostic factor?


title: All India Ophthalmological Society – Indian Journal of Ophthalmology consensus statement on preferred practices during the COVID-19 pandemic

text: The COVID-19 pandemic has taken tragic proportions and has disrupted lives globally. In the wake of governmental lockdowns, ophthalmologists need practical and actionable guidelines based on advisories from national health departments on how to conduct their duties during nationwide lockdowns and after these are lifted. In this paper, we present a preferred practice pattern (PPP) based on consensus discussions between leading ophthalmologists and health care professionals in India including representatives from major governmental and private institutions as well as the All India Ophthalmological Society leadership. In this document, the expert panel clearly defines the range of activities for Indian ophthalmologists during the ongoing lockdown phase and precautions to be taken once the lockdown is lifted. Guidelines for triage, governmental guidelines for use of personal protective equipment from ophthalmologists' point of view, precautions to be taken in the OPD and operating room as well as care of various ophthalmic equipment have been described in detail. These guidelines will be applicable to all practice settings including tertiary institutions, corporate and group practices and individual eye clinics and should help Indian ophthalmologists in performing their professional responsibilities without being foci of disease transmission.


title: Steroid responsiveness and wheezing phenotypes

text: Summary Oral corticosteroids are the cornerstone of management of acute moderate or severe asthma whilst preventive inhaled corticosteroids are the mainstay of the preventive management of children with asthma. Yet, variation in the magnitude of response to corticosteroids has been observed. There is increasing evidence that preschool-aged children with viral-induced asthma may display a certain degree of corticosteroid resistance, requiring higher doses of corticosteroids to overcome it. The identification of determinants of responsiveness is complicated by design issues, including heterogeneous populations of children with asthma and bronchiolitis or of children with viral-induced and multi-trigger asthma phenotypes in published trials. Potential key determinants of responsiveness may include age, trigger, phenotype, tobacco smoke exposure and genotype. The mechanistic pathway for corticoresistance may originate from a gene-environment interaction, leading to non-eosinophilic airway inflammation. The clinician should carefully confirm the diagnosis of asthma and ascertain the phenotype to select appropriate phenotype-specific therapy.


docid: duwhazer

title: Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model

text: Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1β, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/β, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1β, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/β, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner.


title: Cultural shift towards sustainability in the construction industry of Hong Kong

text: Abstract Sustainable development is forward-looking; it is a continuous mission for future developments of human society. A genuinely sustainable society is one that initiates developments in sustainable ways. The development of a genuinely sustainable society is supported by its citizens who think and act according to a recognized code of conduct - the sustainable culture. Similar to other forms of culture, sustainable culture of a society is not static, but changes over time. The changes found in a sustainable culture are reflections of the status of sustainability in a society and these changes should be measured from time to time. The resulting measurement gives very important information for decision-makers, in the government and in the private sector, to examine the magnitude of changes that have taken place in a given period of time. The results will also enable them to review and adjust policies in order to better accommodate changes according to the trends of society. This paper provides a method – the T-model, to investigate and measure the extent of change of sustainable culture through two extensive surveys among participants of the construction industry of Hong Kong. The change in sustainable culture is reflected by the change in attitude and practice among construction participants, this can be found in their performance in project development, design and construction operations. The data of these changes are collected and converted to numerical scores. The T-model synthesized these scores and revealed the change of sustainable culture within the specific study time frame.


title: Enteric adenoviruses

text: In 1978, the World Health Organisation initiated a programme for global prevention and control of childhood diarrhoeas. As a result, the relative importance of various pathogens in the aetiology of diarrhoea in many parts of the world has been recognised. Rotavirus, which ranks as the most prevalent viral pathogen in childhood diarrhoea may be closer to control as many vaccines are in sight. This has been made possible due to a decade of intense research since its discovery. E Ad, which probably ranks as the second most important viral pathogen has not received much attention. As has been discussed, much information has to be gathered about this virus, before W.H.O's. goal of controlling childhood diarrhoea is realised.


title: Adjustments in the Use of Intravesical Instillations of Bacillus Calmette-Guérin for High-risk Non–muscle-invasive Bladder Cancer During the COVID-19 Pandemic

text: Non–muscle-invasive bladder cancer patients with COVID-19 are more likely to develop acute respiratory distress syndrome. Thus, several adjustments to the use of intravesical instillations of bacillus Calmette-Guérin should be made during the current pandemic to limit the risk of contamination.


Pädiatrie aktuell – Forschung kurz notiert


title: Development of a one-step RT-PCR assay for detection of pancoronaviruses (α-, β-, γ-, and δ-coronaviruses) using newly designed degenerate primers for porcine and avian `fecal samples

text: Abstract Coronaviruses (CoVs) are critical human and animal pathogens because of their potential to cause severe epidemics of respiratory or enteric diseases. In pigs, the newly emerged porcine deltacoronavirus (PDCoV) and re-emerged porcine epidemic diarrhea virus (PEDV) reported in the US and Asia, as well as the discovery of novel CoVs in wild bats or birds, has necessitated development of improved detection and control measures for these CoVs. Because the previous pancoronavirus (panCoV) RT-PCR established in our laboratory in 2007–2011 did not detect deltacoronaviruses (δ-CoVs) in swine fecal and serum samples, our goal was to develop a new panCoV RT-PCR assay to detect known human and animal CoVs, including δ-CoVs. In this study, we designed a new primer set to amplify a 668 bp-region within the RNA-dependent RNA polymerase (RdRP) gene that encodes the most conserved protein domain of α-, β-, γ-, and δ-CoVs. We established a one-step panCoV RT-PCR assay and standardized the assay conditions. The newly established panCoV RT-PCR assay was demonstrated to have a high sensitivity and specificity. Using a panel of 60 swine biological samples (feces, intestinal contents, and sera) characterized by PEDV, PDCoV and transmissible gastroenteritis virus-specific RT-PCR assays, we demonstrated that sensitivity and specificity of the newly established panCoV RT-PCR assay were 100%. 400 avian fecal (RNA) samples were further tested simultaneously for CoV by the new panCoV RT-PCR and a one-step RT-PCR assay with the δ-CoV nucleocapsid-specific universal primers. Four of 400 avian samples were positive for CoV, three of which were positive for δ-CoV by the conventional RT-PCR. PanCoV RT-PCR fragments for 3 of the 4 CoVs were sequenced. Phylogenetic analysis revealed the presence of one γ-CoV and two δ-CoV in the sequenced samples. The newly designed panCoV RT-PCR assay should be useful for the detection of currently known CoVs in animal biological samples.


title: The clinical impact of pneumocystis and viral PCR testing on bronchoalveolar lavage in immunosuppressed patients

text: Abstract Introduction Pulmonary infiltrates in immunosuppressed patients are common. Yields from bronchoscopy with bronchoalveolar lavage (BAL) has been reported to be between 31 and 65%. The clinical impact of pneumocystis and viral Polymerase chain reaction (PCR) testing on BAL has not been extensively evaluated in a mixed immunosuppressed patient population. Methods We performed a retrospective chart review of immunosuppressed adults with pulmonary infiltrates who underwent BAL at the University of Rochester Medical Center. Only one BAL per patient was included. We compared the rate of positive PCR testing to conventional testing. We then investigated factors associated with positive PCR testing. Finally, we assessed for changes in antimicrobial therapy after bronchoscopy. Results Three hundred and fifty-nine patients underwent BAL with 249 patients having pneumocystis PCR testing and 142 having viral PCR testing. Pneumocystis identification occurred in 43 patients and viral species identification occurred in 56 patients. PCR testing increased pneumocystis identification compared to microscopy, 14% vs. 5%, p = 0.01, and viral identification compared to culture, 25% vs. 6%, p = 0.0001. Of the patients with positive pneumocystis PCR testing 49% had antibiotics stopped, 66% were started on anti-pneumocystis therapy, and only 6% did not receive treatment. There was no difference in the number of patients with antibiotics stopped based on viral PCR testing results. Discussion PCR testing increases BAL yield in immunosuppressed patients compared to conventional testing. Pneumocystis identified by PCR only may cause a self-limited infection and may not require antimicrobial therapy. PCR testing should be included in the evaluation of pulmonary infiltrates in immunosuppressed patients.


title: Crisis management and recovery: how restaurants in Hong Kong responded to SARS

text: Abstract The 2003 Severe Acute Respiratory Syndrome (SARS) outbreak constitutes an example of the many crises that a restaurant may encounter. This article reviews a typology of crises, examines the crisis response of restaurants in Hong Kong, illustrates how local restaurants deal with this unprecedented situation and develop strategies for management and recovery. The lessons and experience gained from dealing with the SARS crisis serve as references for restaurants in other destinations when they face similar crises in future.


title: Chapter 9 Recovery from Infection

text: This chapter addresses the factors involved in recovery from infection. Antibody and cellular responses (CMI) are considered. The mechanisms by which antibodies neutralise viruses/prevent infection are described, as is the involvement of antibody in bacterial and protozoal diseases. The role of CMI in recovery from specific bacterial, protozoal and viral infections is considered. The mechanisms of cell killing by cytotoxic T-cells is described and the role of NK cells and macrophages in pathogen clearance is discussed, as is the role of inflammation. Mechanisms by which the complement system acts and its role in vivo is discussed, as is the interferon response. Recovery from S. typhimurium is used to illustrate the multimechanistic nature of recovery. The role of temperature in recovery and pathogen factors that induce fever are considered. Tissue repair mechanisms are discussed, as is finally resistance to infection.


Response letter: handling of COVID-19 positive patients during the pandemic


Viral respiratory infections in BMT - A common cold is not just a cold in transplant recipients


title: Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review

text: For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral circulation and thus on the cerebral perfusion. Early studies suggested that ketamine could increase the intracranial pressure thus lowering the cerebral perfusion and hence reduce the oxygen supply to the injured brain. However, more recent studies are less conclusive and might even indicate that patients with acute brain injury could benefit from ketamine sedation. This systematic review summarizes the evidence regarding the use of ketamine in patients suffering from traumatic brain injury. Databases were searched for studies using ketamine in acute brain injury. Outcomes of interest were mortality, intracranial pressure, cerebral perfusion pressure, blood pressure, heart rate, spreading depolarizations, and neurological function. In total 11 studies were included. The overall level of evidence concerning the use of ketamine in brain injury is low. Only two studies found a small increase in intracranial pressure, while two small studies found decreased levels of intracranial pressure following ketamine administration. We found no evidence of harm during ketamine use in patients suffering from acute brain injury.


2020 - The Year that Needed the Nurse: Considerations for Critical Care Nursing Research and Practice Emerging in the Midst of COVID-19


title: Propagation analysis and prediction of the COVID-19

text: Based on the official data modeling, this paper studies the transmission process of the Corona Virus Disease 2019 (COVID-19). The error between the model and the official data curve is quite small. At the same time, it realized forward prediction and backward inference of the epidemic situation, and the relevant analysis help relevant countries to make decisions.


title: Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys

text: The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.


WHO's Director-General candidates: visions and priorities


title: Phospholipid vesicles containing bovine heart mitochondrial cytochrome c oxidase exhibit proton translocating activity in the presence of gramicidin

text: Abstract Phospholipid vesicles containing bovine heart mitochondrial cytochrome c oxidase (COV) were characterized for electron transfer and proton translocating activities in the presence of the mobile potassium ionophore, valinomycin, and the channel-forming ionophore, gramicidin, in order to determine if the ionophores modify the functional properties of the enzyme. In agreement with previous work, incubation of COV with valinomycin resulted in a perturbation of the absorbance spectrum of oxidized heme aa 3 in the Soret region (430 nm); gramicidin had no effect on the heme aa 3 absorbance spectrum. Different concentrations of the two ionophores were required for maximum respiratory control ratios in COV; 40- to 70-fold higher concentrations of valinomycin were required to completely uncouple electron transfer activity when compared to gramidicin. The proton translocating activity of COV incubated with each ionophore gave a similar apparent proton translocated to electron transferred stoichiometry ( H+ e− ratio) of 0.66 ± 0.10. However, COV treated with low concentrations of gramicidin (0.14 mg/g phospholipid) exhibited 1.5- to 2.5-fold higher rates of alkalinization of the extravesicular media after the initial proton translocation reaction than did COV treated with valinomycin, suggesting that gramicidin allows more rapid equilibration of protons across the phospholipid bilayer during the proton translocation assay. Moreover, at higher concentrations of gramicidin (1.4 mg/g phospholipid), the observed H+ e− ratio decreased to 0.280 ± 0.020, while the rate of alkalinization increased an additional 2-fold, suggesting that at higher concentrations, gramicidin acts as a proton ionophore. These results support the hypothesis that cytochrome c oxidase is a redox-linked proton pump that operates at similar efficiencies in the presence of either ionophore. Low concentrations of gramicidin dissipate the membrane potential in COV most likely by a channel mechanism that is different from the carrier mechanism of valinomycin, yet does not make the phospholipid bilayer freely permeable to protons.


title: Immunological aspects of the efficiency of protectotype vaccination strategy against chicken infectious bronchitis

text: BACKGROUND: One of the most commonly applied protectotype vaccination protocol against infectious bronchitis (IB) in broiler chickens in the EU is simultaneous or alternate use of Ma5 and 4/91 vaccine strains. After IB vaccination and infection, systemic and upper respiratory tract (URT), humoral and cell-mediated immunity (CMI), are stimulated. The level of this stimulation correlates with the level of protection against IB. RESULTS: We’ve investigated the development of URT and systemic, cell-mediated and humoral immunity in commercial broiler chickens vaccinated with Ma5 and/or 4/91 strains at hatch day. We’ve demonstrated that the group vaccinated with Ma5 and 4/91 strain simultaneously developed the most desirable immunity which reflects the level of CD8(+) T cells stimulation in spleen and Harderian gland, as well as the level of IgA and IgY in URT washings and serum and their cross-reactivity with 7 IBV strains. CONCLUSIONS: Although we did not demonstrate directly why Ma5 + 4/91 protocol is so efficient it seems that it combines the benefits of monovalent vaccination with either Ma5 or 4/91 and while Ma5 seems to stimulate CMI more efficiently, the 4/91 strain generates a wider spectrum of immune system cross-reactivity and higher URT IgA production.


title: Relationships between cold-temperature indices and all causes and cardiopulmonary morbidity and mortality in a subtropical island

text: Abstract This study aimed to identify optimal cold-temperature indices that are associated with the elevated risks of mortality from, and outpatient visits for all causes and cardiopulmonary diseases during the cold seasons (November to April) from 2000 to 2008 in Northern, Central and Southern Taiwan. Eight cold-temperature indices, average, maximum, and minimum temperatures, and the temperature humidity index, wind chill index, apparent temperature, effective temperature (ET), and net effective temperature and their standardized Z scores were applied to distributed lag non-linear models. Index-specific cumulative 26-day (lag 0–25) mortality risk, cumulative 8-day (lag 0–7) outpatient visit risk, and their 95% confidence intervals were estimated at 1 and 2 standardized deviations below the median temperature, comparing with the Z score of the lowest risks for mortality and outpatient visits. The average temperature was adequate to evaluate the mortality risk from all causes and circulatory diseases. Excess all-cause mortality increased for 17–24% when average temperature was at Z=−1, and for 27–41% at Z=−2 among study areas. The cold-temperature indices were inconsistent in estimating risk of outpatient visits. Average temperature and THI were appropriate indices for measuring risk for all-cause outpatient visits. Relative risk of all-cause outpatient visits increased slightly by 2–7% when average temperature was at Z=−1, but no significant risk at Z=−2. Minimum temperature estimated the strongest risk associated with outpatient visits of respiratory diseases. In conclusion, the relationships between cold temperatures and health varied among study areas, types of health event, and the cold-temperature indices applied. Mortality from all causes and circulatory diseases and outpatient visits of respiratory diseases has a strong association with cold temperatures in the subtropical island, Taiwan.


title: Electron Microscopy in Discovery of Novel and Emerging Viruses from the Collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)

text: Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and for some viruses, by the ultrastructural cytopathic effects and/or specific structures forming in the host cell during their replication. Ultrastructural characteristics are usually sufficient for the identification of a virus to the family level. In this review, we summarize 25 years of experience in identification of novel viruses from the collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA).


title: The spleen morphophysiology of fruit bats

text: Spleen is one of the important lymphoid organs with wide variations of morphological and physiological functions according to species. Morphology and function of the spleen in bats, which are hosts to several viral strains without exhibiting clinical symptoms, remain to be fully elucidated. This study aims to examine the spleen morphology of fruit bats associated with their physiological functions. Spleen histological observations were performed in three fruit bats species: Cynopterus titthaecheilus (n = 9), Rousettus leschenaultii (n = 3) and Pteropus vampyrus (n = 3). The spleens of these fruit bats were surrounded by a thin capsule. Red pulp consisted of splenic cord and wide vascular space filled with blood. Ellipsoids in all three studied species were found numerously and adjacent to one another forming macrophages aggregates. White pulp consisted of periarteriolar lymphoid sheaths (PALS), lymphoid follicles and marginal zone. The lymphoid follicle contained a germinal centre and a tingible body macrophage that might reflect an active immune system. The marginal zone was prominent and well developed. This study reports some differences in spleen structure of fruit bats compared to other bat species previously reported and discusses possible physiological implications of the spleen based on its morphology.


title: Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

text: Abstract Porcine epidemic diarrhea virus (PEDV) invades porcine intestinal epithelial cells (IECs) and causes diarrhea and dehydration in pigs. In the present study, we showed a suppression of PEDV infection in porcine jejunum intestinal epithelial cells (IPEC-J2) by an increase in autophagy. Autophagy was activated by rapamycin at a dose that does not affect cell viability and tight junction permeability. The induction of autophagy was examined by LC3I/LC3II conversion. To confirm the autophagic-flux (entire autophagy pathway), autophagolysosomes were examined by an immunofluorescence assay. Pre-treatment with rapamycin significantly restricted not only a 1 h infection but also a longer infection (24 h) with PEDV, while this effect disappeared when autophagy was blocked. Co-localization of PEDV and autophagosomes suggests that PEDV could be a target of autophagy. Moreover, alleviation of PEDV-induced cell death in IPEC-J2 cells pretreated with rapamycin demonstrates a protective effect of rapamycin against PEDV-induced epithelial cell death. Collectively, the present study suggests an early prevention against PEDV infection in IPEC-J2 cells via autophagy that might be an effective strategy for the restriction of PEDV, and opens up the possibility of the use of rapamycin in vivo as an effective prophylactic and prevention treatment.


Riesgo de reactivación de la hepatitis B asociado al tratamiento con corticoides frente a SARS-CoV-2 (COVID-19)


title: Induction of interleukin-8 by Naegleria fowleri lysates requires activation of extracellular signal-regulated kinase in human astroglial cells

text: Naegleria fowleri is a pathogenic free-living amoeba which causes primary amoebic meningoencephalitis in humans and experimental animals. To investigate the mechanisms of such inflammatory diseases, potential chemokine gene activation in human astroglial cells was investigated following treatment with N. fowleri lysates. We demonstrated that N. fowleri are potent inducers for the expression of interleukin-8 (IL-8) genes in human astroglial cells which was preceded by activation of extracellular signal-regulated kinase (ERK). In addition, N. fowleri lysates induces the DNA binding activity of activator protein-1 (AP-1), an important transcription factor for IL-8 induction. The specific mitogen-activated protein kinase kinase/ERK inhibitor, U0126, blocks N. fowleri-mediated AP-1 activation and subsequent IL-8 induction. N. fowleri-induced IL-8 expression requires activation of ERK in human astroglial cells. These findings indicate that treatment of N. fowleri on human astroglial cells leads to the activation of AP-1 and subsequent expression of IL-8 which are dependent on ERK activation. These results may help understand the N. fowleri-mediated upregulation of chemokine and cytokine expression in the astroglial cells.


title: Patterns of influenza B circulation in Brazil and its relevance to seasonal vaccine composition

text: Abstract Data on the burden of disease and circulation patterns of influenza B lineages for Brazil are limited. This review aims to describe the pattern of influenza B occurrence in Brazil to have a better understanding of its epidemiology and its relevance when considering seasonal influenza vaccine composition. A review of the data including analysis of international and local surveillance data as well as information from online search of databases using Medical Subject Headings terms in conjunction with screening of abstracts from scientific events was performed. Based on international epidemiologic surveillance data, moderate levels of influenza B disease (19%; 2006–2014) were observed. Of these nine years, it was possible to compare data from three years (2007, 2008 and 2013) which have information on the circulating influenza B lineage. Co-circulation of influenza B lineages was observed in all these three influenza seasons, of which, during one season, a high degree of mismatch between the vaccine lineage and the predominant circulating lineage (91.4% [2013]) was observed. Local surveillance data reveal a distinct and dynamic distribution of respiratory viruses over the years. Data from published literature and abstracts show that influenza B is a significant cause of disease with an unpredictable circulation pattern and showing trends indicating reemergence of the B/Victoria lineage. The abstracts report notable levels of co-circulation of both influenza B lineages (2000–2013). Mismatch between the Southern hemisphere vaccine and the most prevalent circulating viruses in Brazil were observed in five influenza seasons. The evidence on co-circulation of two influenza B lineages and mismatched seasons in Brazil indicates the benefit of quadrivalent influenza vaccines in conferring broader seasonal influenza protection. Additionally, improving influenza surveillance platforms in Brazil is important for monitoring disease trends and the impact of introducing seasonal influenza vaccination.


title: ALTERED THEOPHYLLINE PHARMACOKINETICS DURING ACUTE RESPIRATORY VIRAL ILLNESS

text: Abstract The plasma half-life of theophylline was determined during and 1 month after serologically confirmed upper-respiratory-tract viral illness in six children with chronic asthma. In this group the plasma-theophylline half-life (mean=419·8 min) was significantly longer during the acute stage of their illness than 1 month later (mean 249·9 min). There was no appreciable change in half-life in 4 patients who were febrile but in whom seroconversion did not occur. These preliminary results suggest that certain upper-respiratory-tract viral infections may affect theophylline metabolism.


title: The correlation between viral clearance and biochemical outcomes of 94 COVID-19 infected discharged patients

text: OBJECTIVE: This study aims to evaluate the correlation between viral clearance and blood biochemical index of 94 discharged patients with COVID-19 infection in Shenzhen Third People’s Hospital, enrolled from Jan 5 to Feb 13, 2020. METHODS: The clinical and laboratory findings were extracted from the electronic medical records of the patients. The data were analysed and reviewed by a trained team of physicians. Information on clinical signs and symptoms, medical treatment, virus clearance, and laboratory parameters including interleukin 6 (IL-6) and C-reactive protein were collected. RESULTS: COVID-19 mRNA clearance ratio was identified significantly correlated with the decline of serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, COVID-19 mRNA clearance time was positively correlated with the length of hospital stay in patients treated with either IFN-α + lopinavir/ritonavir or IFN-α + lopinavir/ritonavir + ribavirin. CONCLUSIONS: Therapeutic regimens of IFN-α + lopinavir/ritonavir and IFN-α + lopinavir/ritonavir + ribavirin might be beneficial for treatment of COVID-19. Serum LDH or CK decline may predict a favorable response to treatment of COVID-19 infection.


title: Testing for Respiratory Viruses in Adults With Severe Lower Respiratory Infection

text: Viral pathogens are a common cause of severe lower respiratory tract infection in adults. Our ability to rapidly and accurately identify viral infections has dramatically improved as slow culture-based techniques have been largely replaced by multiplex high-throughput systems. Given these advances, reevaluation of the role of respiratory viral testing in adults presenting with lower respiratory tract infection is important. This article reviews the potential benefits of testing, provides an overview of the most commonly used diagnostic techniques, and considers whether current evidence supports routine testing.


title: Complete title: Codon bias analysis may be insufficient for identifying host(s) of a novel virus

text: A novel kind of coronavirus has infected more than 1, 600, 000 people, claimed over 100, 000 lives, and spread to 212 countries and territories since December 2019.(1) The virus has been named SARS‐CoV‐2 (provisionally termed 2019‐nCoV before(2)), and the pneumonia caused by it is COVID‐19. Though many scientists and researchers are trying to identify the animals harboring SARS‐CoV‐2, the intermediate host remains under the veil. This article is protected by copyright. All rights reserved.


Care for patients with rheumatic diseases during COVID‐19 pandemic: A position statement from APLAR


title: Evaluation of humoral immune status in porcine epidemic diarrhea virus (PEDV) infected sows under field conditions

text: Porcine epidemic diarrhea virus (PEDV) is an economically devastating enteric disease in the swine industry. The virus infects pigs of all ages, but it cause severe clinical disease in neonatal suckling pigs with up to 100% mortality. Currently, available vaccines are not completely effective and feedback methods utilizing PEDV infected material has variable success in preventing reinfection. Comprehensive information on the levels and duration of effector/memory IgA and IgG antibody secreting B cell response in the intestines and lymphoid organs of PEDV-infected sows, and their association with specific antibody levels in clinical samples such as plasma, oral fluid, and feces is important. Therefore, our goal in this study was to quantify PEDV specific IgA and IgG B cell responses in sows at approximately 1 and 6 months post-infection in commercial swine herds, including parity one and higher sows. Our data indicated that evaluation of both PEDV specific IgA and IgG antibody levels in the plasma and oral fluid (but not feces) samples is beneficial in disease diagnosis. PEDV specific B cell response in the intestine and spleen of infected sows decline by 6 months, and this associates with specific antibody levels in the plasma and oral fluid samples; but the virus neutralization titers in plasma remains high beyond 6 months post-infection. In conclusion, in sows infected with PEDV the presence of effector/memory B cell response and strong virus neutralization titers in plasma up to 6 months post-infection, suggests their potential to protect sows from reinfection and provide maternal immunity to neonates, but challenge studies are required to confirm such responses.


title: Expression of the protective antigen for PEDV in transgenic duckweed, Lemna minor

text: Duckweeds are small, floating aquatic plants with a number of useful characteristics, including edibility, fast-growing, and a clonal proliferation. Duckweed is also fed to animals as a diet complement because of its high nutritional value. Porcine epidemic diarrhea virus (PEDV) is a major causative agent of fatal diarrhea in piglets and is a serious problem in the hog-raising industry. In this study, we assessed the feasibility of producing a protective antigen for the PEDV spike protein 1 using duckweed, Lemna minor. Stably transformed Lemna were obtained by co-cultivation with A. tumefaciens EHA105 harboring the PEDV spike protein gene. Transgene integration and expression of the PEDV spike protein 1 gene were confirmed by genomic PCR and RT-PCR and western blot analysis of transgenic Lemna, respectively. This is the first report of the expression of a vaccine antigen against an animal infectious disease in duckweed.


title: The Infectious Bronchitis Virus Coronavirus Envelope Protein Alters Golgi pH to Protect Spike Protein and Promote Release of Infectious Virus

text: Coronaviruses (CoVs) are important human pathogens with significant zoonotic potential. Progress has been made toward identifying potential vaccine candidates for highly pathogenic human CoVs, including use of attenuated viruses that lack the CoV envelope (E) protein or express E mutants. However, no approved vaccines or anti-viral therapeutics exist. CoVs assemble by budding into the lumen of the early Golgi prior to exocytosis. The small CoV E protein plays roles in assembly, virion release, and pathogenesis. CoV E has a single hydrophobic domain (HD), is targeted to Golgi membranes, and has cation channel activity in vitro. The E protein from the avian infectious bronchitis virus (IBV) has dramatic effects on the secretory system, which requires residues in the HD. Mutation of the HD of IBV E during infection results in impaired growth kinetics, impaired release of infectious virions, accumulation of IBV S protein on the plasma membrane when compared IBV WT infected cells, and aberrant cleavage of IBV S on the surface of virions. We previously reported the formation of two distinct oligomeric pools of IBV E in transfected and infected cells. Disruption of the secretory pathway by IBV E correlates with a form that is likely monomeric, suggesting that the effects on the secretory pathway are independent of E ion channel activity. Here, we present evidence suggesting that the monomeric form of IBV E correlates with a rise in the pH of the Golgi lumen. We demonstrate that infection with IBV induces neutralization of Golgi luminal pH, promoting a model in which IBV E alters the secretory pathway through interaction with host cells factors, protecting IBV spike protein (S) from premature cleavage and leading to the efficient release of infectious virus from the cells.


title: Clustering analysis of countries using the COVID-19 cases dataset

text: There is a worldwide effort of the research community to explore the medical, economic and sociologic impact of the COVID-19 pandemic. Many different disciplines try to find solutions and drive strategies to a great variety of different very crucial problems. The present study presents a novel analysis which results to clustering countries with respect to active cases, active cases per population and active cases per population and per area based on Johns Hopkins epidemiological data. The presented cluster results could be useful to a variety of different policy makers, such as physicians and managers of the health sector, economy/finance experts, politicians and even to sociologists. In addition, our work suggests a new specially designed clustering algorithm adapted to the request for comparison of the various COVID time-series of different countries.


title: Influenza‐like illnesses caused by a cluster of imported Italian COVID‐19

text: The ongoing pandemic of 2019 corona‐virus disease (COVID‐19) is caused by an emerging family of SARS‐CoV‐2, threatening human health worldwide. Here we report a cluster of Italian COVID‐19 imported to Lishui City, China. Of all the eight patients, 7 consistently display cough, a representative sign of influenza‐like illness (ILI), and the remaining one is a cryptic case. This further our understanding a full spectrum of COVID‐19 repertoire. This article is protected by copyright. All rights reserved.


title: Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians

text: BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12871-016-0198-x) contains supplementary material, which is available to authorized users.


title: RNA-mediated translation regulation in viral genomes: computational advances in the recognition of sequences and structures

text: RNA structures are widely distributed across all life forms. The global conformation of these structures is defined by a variety of constituent structural units such as helices, hairpin loops, kissing-loop motifs and pseudoknots, which often behave in a modular way. Their ubiquitous distribution is associated with a variety of functions in biological processes. The location of these structures in the genomes of RNA viruses is often coordinated with specific processes in the viral life cycle, where the presence of the structure acts as a checkpoint for deciding the eventual fate of the process. These structures have been found to adopt complex conformations and exert their effects by interacting with ribosomes, multiple host translation factors and small RNA molecules like miRNA. A number of such RNA structures have also been shown to regulate translation in viruses at the level of initiation, elongation or termination. The role of various computational studies in the preliminary identification of such sequences and/or structures and subsequent functional analysis has not been fully appreciated. This review aims to summarize the processes in which viral RNA structures have been found to play an active role in translational regulation, their global conformational features and the bioinformatics/computational tools available for the identification and prediction of these structures.