title: Chapter 11 New Technologies for Monitoring Marine Mammal Health

text: Abstract Omics technologies have been developed in recent decades and applied to different subjects, although the greatest advancements have been achieved in human biology and disease. Genome sequencing and the exploration of its coding and noncoding regions are rapidly yielding meaningful answers to diverse questions, relating genome information to protein activity to environmental changes. In the past, marine mammal genetic and transcriptional studies have been restricted due to the lack of reference genomes. But the advance of high-throughput sequencing is revolutionizing the life sciences technologies. As long-lived organisms, at the top of the food chain, marine mammals play an important role in marine ecosystems and while their protected status is in favor of conservation of the species, it also complicates the researcher's approach to traditional measurements of health. Omics data generated by high-throughput technologies will represent an important key for improving the scientific basis for understanding both marine mammal and environment health.


title: Quality Improvement Through the Introduction of Interdisciplinary Geriatric Hemodialysis Rehabilitation Care

text: Background Provision of rehabilitation with the aim of restoring personal independence in elderly hemodialysis patients faces several challenges. Design Quality improvement report. Setting & Participants First 3 years of experience of an inpatient geriatric hemodialysis rehabilitation program in Toronto. Patients with new-onset disability from prolonged illness or an acute event rendering them incapable of living independently. Quality Improvement Plan Provision of in-patient rehabilitation with on-site dialysis; a simplified referral system; preferential admission of elderly dialysis patients; short daily dialysis sessions; integrated multidisciplinary care by experts in rehabilitation, geriatric medicine, and nephrology; and reciprocal continued medical education among staff. Measures Outcome measures were percentage of patients discharged home, score on the Functional Independence Measure, and attainment of rehabilitation goals. Results In the first 36 months, 164 dialysis patients aged 74.5 ± 7.8 years were admitted. On admission, patients had a mean Charlson comorbidity score of 7.8 ± 2.5, 98% had difficulty walking, and 84% required help with bed-to-chair transfers. After a median of 48.5 days, 111 patients (69%) were discharged home; 15 patients (9%), to an assisted-living setting; 20 patients (12%), to a long-term care facility; and 18 patients (11%), to other facilities for acute or palliative care. Of those completing therapy, 82% met some or all of their rehabilitation goals. Limitations The program relied on the leadership and drive of key personnel. Discharge disposition as an outcome can be affected by many factors, and definition of attainment of rehabilitation goals is arbitrary. Conclusion The introduction of an integrated dialysis rehabilitation service can help older dialysis patients with new-onset functional decline return to their home. Am J Kidney Dis 00:00-00


Where do we go from here? A child rights-based response to COVID-19


Letter to the editor regarding “lack of supporting data make the risks of a clinical trial of radiation therapy as a treatment for COVID-19 pneumonia unacceptable”


Ethical and Legal Challenges During the COVID‐19 Pandemic – Are We Thinking About Rural Hospitals?


title: Emerging Antiviral Strategies to Interfere with Influenza Virus Entry

text: Influenza A and B viruses are highly contagious respiratory pathogens with a considerable medical and socioeconomical burden and known pandemic potential. Current influenza vaccines require annual updating and provide only partial protection in some risk groups. Due to the global spread of viruses with resistance to the M2 proton channel inhibitor amantadine or the neuraminidase inhibitor oseltamivir, novel antiviral agents with an original mode of action are urgently needed. We here focus on emerging options to interfere with the influenza virus entry process, which consists of the following steps: attachment of the viral hemagglutinin to the sialylated host cell receptors, endocytosis, M2‐mediated uncoating, low pH‐induced membrane fusion, and, finally, import of the viral ribonucleoprotein into the nucleus. We review the current functional and structural insights in the viral and cellular components of this entry process, and the diverse antiviral strategies that are being explored. This encompasses small molecule inhibitors as well as macromolecules such as therapeutic antibodies. There is optimism that at least some of these innovative concepts to block influenza virus entry will proceed from the proof of concept to a more advanced stage. Special attention is therefore given to the challenging issues of influenza virus (sub)type‐dependent activity or potential drug resistance.


title: China's limited push model of FOI legislation

text: Abstract China has adopted a push model of Freedom of Information (FOI) legislation that emphasizes proactive disclosure of government information. This differs from a pull model that stresses citizen-initiated access or reactive disclosure. The push model of FOI legislation, which has reduced the importance of access requests in China, grew out of its local causes. However, the degree of push or proactive disclosure under China's current FOI Regulations is undermined by several factors, including a limited access mechanism, broad and vague exemptions, and the omission of the maximum disclosure principle.


Caught by NETs


title: Needlestick injuries: a density-equalizing mapping and socioeconomic analysis of the global research

text: BACKGROUND: Needlestick injuries have caused a deleterious effect on the physical and mental health of millions of health-care workers over the past decades, being responsible for occupational infections with viruses such as HIV or hepatis C. Despite this heavy burden of disease, no concise studies have been published on the global research landscape so far. METHODS: We used the New Quality and Quantity Indices in Science platform to analyze global NSI research (n = 2987 articles) over the past 115 years using the Web of Science and parameters such as global versus country-specific research activities, semi-qualitative issues, and socioeconomic figures. RESULTS: Density-equalizing mapping showed that although a total of n = 106 countries participated in NSI research, large parts of Africa and South America were almost invisible regarding global participation in NSI research. Average citation rate (cr) analysis indicated a high rate for Switzerland (cr = 25.1), Italy (cr = 23.5), and Japan (cr = 19.2). Socioeconomic analysis revealed that the UK had the highest quotient Q(GDP) of 0.13 NSI-specific publications per bill. US-$ gross domestic product (GDP), followed by South Africa (Q(GDP) = 0.12). Temporal analysis of HIV versus hepatitis research indicated that NSI-HIV research culminated in the early 1990s, whereas NSI-hepatitis research increased over the observed period from the 1980s until the last decade. CONCLUSION: Albeit NSI research activity is generally increasing, the growth is asymmetrical from a global viewpoint. International strategies should be followed that put a focus on NSI in non-industrialized areas of the world. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00420-020-01547-0) contains supplementary material, which is available to authorized users.


title: Clinical practice guideline: Approach to childhood asthma in the era of COVID-19: The official statement endorsed by the Saudi Pediatric Pulmonology Association (SPPA)

text: Abstract Coronaviruses are a large family of viruses that can infect humans, which may result in mild symptoms similar to those of the common cold. COVID-19 is most recent subtype similar or even worse than the two previous pandemic strains which were the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). The first cases of COVID-19 emerged in December 2019. Since then, the virus causing the disease has infected more than four million around the globe and led to death of hundreds of thousands of people. We think addressing the management of asthma in the era of this pandemic is important for the several reasons: high prevalence of asthma in Saudi Arabia, further, majorities were uncontrolled disease. The statement will provide special instructions and answers to common questions of physicians dealing with asthmatic children during this pandemic.


title: The usefulness of case reports in managing emerging infectious disease

text: Emerging infectious diseases are an important problem in medicine. Case reports usually document episodes in the early emerging phase or in a small outbreak. Although the case report is considered weak evidence in medical literature, it is usually the first report when there is a new emerging infectious disease. There is no doubt that case reports can provide useful information for further case series, reviews and studies. This editorial focuses on the usefulness of the case report on emerging infectious disease to the medical society. Publication in this area is highly welcomed by the journal and can serve as a future point of reference.


title: Molecular Typing and Epidemiology Profiles of Human Adenovirus Infection among Paediatric Patients with Severe Acute Respiratory Infection in China

text: BACKGROUND: Human adenoviruses (HAdVs) have been recognised as pathogens that cause a broad spectrum of diseases. The studies on HAdV infection among children with severe acute respiratory infection (SARI) are limited. OBJECTIVE: To investigate the prevalence, epidemiology, and genotype of HAdV among children with SARI in China. STUDY DESIGN: Nasopharyngeal aspirates (NPAs) or induced sputum (IS) was collected from hospitalised children with SARIs in Beijing (representing Northern China; n = 259) and Zhejiang Province (representing Eastern China; n = 293) from 2007 to 2010. The prevalence of HAdV was screened by polymerase chain reaction (PCR), followed by sequence typing of PCR fragments that targeted the second half of the hexon gene. In addition, co-infection with other human respiratory viruses, related epidemiological profiles and clinical presentations were investigated. RESULTS AND CONCLUSIONS: In total, 76 (13.8%) of 552 SARI patients were positive for HAdV, and the infection rates of HAdV in Northern and Eastern China were 20.1% (n = 52) and 8.2% (n = 24), respectively. HAdV co-infection with other respiratory viruses was frequent (infection rates: Northern China, 90.4%; Eastern China, 70.8%). The peak seasons for HAdV-B infection was winter and spring. Additionally, members of multiple species (Human mastadenovirus B, C, D and E) were circulating among paediatric patients with SARI, of which HAdV-B (34/52; 65.4%) and HAdV-C (20/24, 83.3%) were the most predominant in Northern and Eastern China, respectively. These findings provide a benchmark for future epidemiology and prevention strategies for HAdV.


title: Infections virales et asthme

text: Summary Rhinovirus, parainfluenza, influenza, adenovirus and respiratory syncytial virus respiratory tract infections are frequent causes of asthmatic exacerbations, especially in children. All these viru3es can induce bronchial inflammation which, by adding to the allergic inflammation specific to asthma, can worsen the obstruction and bronchial hyperreactivity of asthmatic patients. Respiratory viral infections can also amplify the bronchial allergic reaction induced by inhalation of an allergen and facilitate the development of asthma or an atopic state. Some viruses can induce the synthesis of specific IgE and an immunological response favouring the TH2 lymphocyte phenotype, promoting allergy. Asthma and atopy predispose to viral infections of the affected organ, possibly via local allergic inflammation (expression of ICAM1, desquamation of the mucosa, mucostasis, etc.) and/or anti-inflammatory effects of histamine


title: Immortalization of Human B Cells: Analysis of B Cell Repertoire and Production of Human Monoclonal Antibodies

text: One of the major challenges in human B cell immunology field has been the objective to establish stable monoclonal cells lines that express the B cell receptor (BCR) on their cell surface and secrete antibodies. Such a system is extremely attractive not only for studying various aspect of BCR signaling but also for the generation of human monoclonal antibody and the analysis of the human B cell repertoire. This chapter describes an efficient method to immortalize and clone human B cells by Epstein–Barr Virus (EBV) transformation.


title: Detection of KI polyomavirus and WU polyomavirus DNA by real‐time polymerase chain reaction in nasopharyngeal swabs and in normal lung and lung adenocarcinoma tissues

text: Polyomaviruses KI (KIPyV) and WU (WUPyV) were detected from 7 (3.0%) and 38 (16.4%) of 232 children with respiratory tract infections by real‐time PCR. The rates of infection by KIPyV and WUPyV alone were 3 of 7 (42.9%) and 20 of 38 (52.6%), respectively. In the other samples, various viruses (human respiratory syncytial virus, human metapneumovirus, human rhinovirus, parainfluenza virus 1 and human bocavirus) were detected simultaneously. One case was positive for KIPyV, WUPyV and hMPV. There was no obvious difference in clinical symptoms between KIPyV‐positive and WUPyV‐positive patients with or without coinfection. KIPyV was detected in one of 30 specimens of lung tissue (3.3%). Neither of the viruses was detected in 30 samples of lung adenocarcinoma tissue.


Covid-19: Airborne transmission is being underestimated, warn experts.


title: Etiological analysis and predictive diagnostic model building of community-acquired pneumonia in adult outpatients in Beijing, China

text: BACKGROUND: Etiological epidemiology and diagnosis are important issues in adult community-acquired pneumonia (CAP), and identifying pathogens based on patient clinical features is especially a challenge. CAP-associated main pathogens in adults include viruses as well as bacteria. However, large-scale epidemiological investigations of adult viral CAP in China are still lacking. In this study, we analyzed the etiology of adult CAP in Beijing, China and constructed diagnostic models based on combinations of patient clinical factors. METHODS: A multicenter cohort was established with 500 adult CAP outpatients enrolled in Beijing between November 2010 to October 2011. Multiplex and quantitative real-time fluorescence PCR were used to detect 15 respiratory viruses and mycoplasma pneumoniae, respectively. Bacteria were detected with culture and enzyme immunoassay of the Streptococcus pneumoniae urinary antigen. Univariate analysis, multivariate analysis, discriminatory analysis and Receiver Operating Characteristic (ROC) curves were used to build predictive models for etiological diagnosis of adult CAP. RESULTS: Pathogens were detected in 54.2% (271/500) of study patients. Viruses accounted for 36.4% (182/500), mycoplasma pneumoniae for 18.0% (90/500) and bacteria for 14.4% (72/500) of the cases. In 182 of the patients with viruses, 219 virus strains were detected, including 166 single and 53 mixed viral infections. Influenza A virus represented the greatest proportion with 42.0% (92/219) and 9.1% (20/219) in single and mixed viral infections, respectively. Factors selected for the predictive etiological diagnostic model of viral CAP included cough, dyspnea, absence of chest pain and white blood cell count (4.0-10.0) × 10(9)/L, and those of mycoplasma pneumoniae CAP were being younger than 45 years old and the absence of a coexisting disease. However, these models showed low accuracy levels for etiological diagnosis (areas under ROC curve for virus and mycoplasma pneumoniae were both 0.61, P < 0.05). CONCLUSIONS: Greater consideration should be given to viral and mycoplasma pneumoniae infections in adult CAP outpatients. While predictive etiological diagnostic models of viral and mycoplasma pneumoniae based on combinations of demographic and clinical factors may provide indications of etiology, diagnostic confirmation of CAP remains dependent on laboratory pathogen test results.


Schistosomiasis control: experiences and lessons from China


title: Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is now pandemic with nearly three million cases reported to date. Although the majority of COVID-19 patients experience only mild or moderate symptoms, a subset will progress to severe disease with pneumonia and acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Emerging results indicate a dysregulated immune response characterized by runaway inflammation, including cytokine release syndrome (CRS), as the major driver of pathology in severe COVID-19. With no treatments currently approved for COVID-19, therapeutics to prevent or treat the excessive inflammation in severe disease caused by SARS-CoV-2 infection are urgently needed. Here, in 10 terminally-ill, critical COVID-19 patients we report profound elevation of plasma IL-6 and CCL5 (RANTES), decreased CD8+ T cell levels, and SARS-CoV-2 plasma viremia. Following compassionate care treatment with the CCR5 blocking antibody leronlimab, we observed complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. Consistent with reduction of plasma IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes. These results demonstrate a novel approach to resolving unchecked inflammation, restoring immunologic deficiencies, and reducing SARS-CoV-2 plasma viral load via disruption of the CCL5-CCR5 axis, and support randomized clinical trials to assess clinical efficacy of leronlimab-mediated inhibition of CCR5 for COVID-19.


title: Monitoring of risk perceptions and correlates of precautionary behaviour related to human avian influenza during 2006 - 2007 in the Netherlands: results of seven consecutive surveys

text: BACKGROUND: Avian influenza (AI) is a public health challenge because of ongoing spread and pandemic potential. Non-pharmaceutical measures are important to prevent the spread of AI and to contain a pandemic. The effectiveness of such measures is largely dependent on the behaviour of the population. Risk perception is a central element in changing behaviour. This study aimed to investigate perceived vulnerability, severity and precautionary behaviour related to AI in the Netherlands during seven consecutive surveys in 2006 - 2007 as well as possible trends in risk perception and self-reported precautionary behaviours. METHODS: Seven web-based surveys were conducted including 3,840 respondents over a one-year period. Time trends were analyzed with linear regression analyses. Multivariate analysis was used to study determinants of precautionary behaviour. RESULTS: While infection with AI was considered a very severe health problem with mean score of 4.57 (scale 1 - 5); perceived vulnerability was much lower, with a mean score of 1.69. While perceived severity remained high, perceived vulnerability decreased slightly during a one-year period covering part of 2006 and 2007. Almost half of the respondents (46%) reported taking one or more preventive measures, with 36% reporting to have stayed away from (wild) birds or poultry. In multivariate logistic regression analysis the following factors were significantly associated with taking preventive measures: time of the survey, higher age, lower level of education, non-Dutch ethnicity, vaccinated against influenza, higher perceived severity, higher perceived vulnerability, higher self efficacy, lower level of knowledge, more information about AI, and thinking more about AI. Self efficacy was a stronger predictor of precautionary behaviour for those who never or seldom think about AI (OR 2.3, 95% CI 1.9 - 2.7), compared to those who think about AI more often (OR 1.5, 95% CI 1.2 - 1.9). CONCLUSIONS: The fact that perceived severity of AI appears to be high and remains so over time offers a good point of departure for more specific risk communications to promote precautionary actions. Such communications should aim at improving knowledge about the disease and preventive actions, and focus on perceived personal vulnerability and self efficacy in taking preventive measures.


title: Modeling the formation of social conventions from embodied real-time interactions

text: What is the role of real-time control and learning in the formation of social conventions? To answer this question, we propose a computational model that matches human behavioral data in a social decision-making game that was analyzed both in discrete-time and continuous-time setups. Furthermore, unlike previous approaches, our model takes into account the role of sensorimotor control loops in embodied decision-making scenarios. For this purpose, we introduce the Control-based Reinforcement Learning (CRL) model. CRL is grounded in the Distributed Adaptive Control (DAC) theory of mind and brain, where low-level sensorimotor control is modulated through perceptual and behavioral learning in a layered structure. CRL follows these principles by implementing a feedback control loop handling the agent’s reactive behaviors (pre-wired reflexes), along with an Adaptive Layer that uses reinforcement learning to maximize long-term reward. We test our model in a multi-agent game-theoretic task in which coordination must be achieved to find an optimal solution. We show that CRL is able to reach human-level performance on standard game-theoretic metrics such as efficiency in acquiring rewards and fairness in reward distribution.


title: Screening of Natural Extracts for Inhibitors against Japanese Encephalitis Virus Infection

text: The mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide that is associated with high morbidity and mortality. Currently, there are no effective drugs approved for the treatment of JEV infection. Drug-repurposing screening is an alternative approach to discover potential antiviral agents. In this study, high-content screening (HCS) of a natural extracts library was performed, and two hit FDA-approved Na(+)/K(+)-ATPase inhibitors, ouabain and digoxin, were identified as having robust efficiency against JEV infection with the selectivity indexes over 1,000. The results indicated that ouabain and digoxin blocked the JEV infection at the replication stage by targeting the Na(+)/K(+)-ATPase. Furthermore, it was proven that ouabain significantly reduced the morbidity and mortality caused by JEV in a BALB/c mouse model. This work demonstrated that Na(+)/K(+)-ATPase could serve as the target of treatment of JEV infection, and ouabain has the potential to be developed as an effective anti-JEV drug.


title: Modulation of the Immune Response to Respiratory Viruses by Vitamin D

text: Background: Vitamin D deficiency has been shown to be independently associated with increased risk of viral acute respiratory infection (ARI) in a number of observational studies, and meta-analysis of clinical trials of vitamin D supplementation for prevention of ARI has demonstrated protective effects. Several cellular studies have investigated the effects of vitamin D metabolites on immune responses to respiratory viruses, but syntheses of these reports are lacking. Scope: In this article, we review the literature reporting results of in vitro experiments investigating immunomodulatory actions of vitamin D metabolites in human respiratory epithelial cells infected with respiratory viruses. Key findings: Vitamin D metabolites do not consistently influence replication or clearance of rhinovirus, respiratory syncytial virus (RSV) or influenza A virus in human respiratory epithelial cell culture, although they do modulate expression and secretion of type 1 interferon, chemokines including CXCL8 and CXCL10 and pro-inflammatory cytokines, such as TNF and IL-6. Future research: More studies are needed to clarify the effects of vitamin D metabolites on respiratory virus-induced expression of cell surface markers mediating viral entry and bacterial adhesion to respiratory epithelial cells.


title: Immobilization Techniques for Aptamers on Gold Electrodes for the Electrochemical Detection of Proteins: A Review

text: The development of reliable biosensing platforms plays a key role in the detection of proteins in clinically and environmentally derived samples for diagnostics, as well as for process monitoring in biotechnological productions. For this purpose, the biosensor has to be stable and reproducible, and highly sensitive to detect potentially extremely low concentrations and prevent the nonspecific binding of interfering compounds. In this review, we present an overview of recently published (2017–2019) immobilization techniques for aptamers on gold electrodes for the electrochemical detection of proteins. These include the direct immobilization of thiolated aptamers and the utilization of short linkers, streptavidin/biotin interaction, as well as DNA nanostructures and reduced graphene oxide as immobilization platforms. Applied strategies for signal amplification and the prevention of biofouling are additionally discussed, as they play a crucial role in the design of biosensors. While a wide variety of amplification strategies are already available, future investigations should aim to establish suitable antifouling strategies that are compatible with electrochemical measurements. The focus of our review lies on the detailed discussion of the underlying principles and the presentation of utilized chemical protocols in order to provide the reader with promising ideas and profound knowledge of the subject, as well as an update on recent discoveries and achievements.


title: Porcine epidemic diarrhea virus virus-like particles produced in insect cells induce specific immune responses in mice

text: Porcine epidemic diarrhea virus (PEDV), which causes 80–100% mortality in neonatal piglets, is one of the most devastating viral diseases affecting swine worldwide. To date, the lack of effective vaccines and drugs is the main problem preventing control of the global spread of PEDV. In this study, we produced PEDV virus-like particles (VLPs) composed of S, M, and E proteins with a baculovirus expression system and tested them via indirect immunofluorescence assay (IFA)and Western blot analysis. Electron microscopy showed that the morphological structure of the PEDV VLPs was similar to that of the protovirus. Microneutralization assays and ELISpot analysis demonstrated that PEDV VLPs induced highly specific antibody responses and Th2-mediated humoral immunity. As a result, the PEDV VLPs displayed excellent immunogenicity in mice. Therefore, a VLP-based vaccine has the potential to prevent PEDV infection.


title: COVID-19 IN 7 MULTIPLE SCLEROSIS PATIENTS IN TREATMENT WITH ANTI-CD20 THERAPIES

text: BACKGROUND AND AIM: In December 2019, the first cases of SARS-CoV-2 infection were detected in Wuhan. Within two months, it had begun to spread around the world in what became an unprecedented pandemic. Patients with Multiple Sclerosis (MS) in a state of immunosuppression may be considered at risk for complications in the COVID-19 pandemic, although there is increasing evidence postulating a possible protective role of selective immunosuppression. One group of such immunosuppressants used in MS comprises the anti-CD20 monoclonal antibodies (mAbs) ocrelizumab and rituximab. Anti-CD20 mAbs bind to the surface of B cells, causing their depletion. We describe our experience in seven cases of patients with multiple sclerosis who have been affected by SARS-COV-2 (with a clinical/serological diagnosis or PCR diagnosis) and who were being treated with anti-CD20+ monoclonal antibodies. MATERIAL AND METHODS: We review the development of patients during infection as well as the resolution of their clinical picture. We also analyze the serology status against SARS-CoV-2 after resolution of the infection. RESULTS: Although the severity of the clinical pictures was variable, patients' development was good. Not all patients, however, developed antibodies against SARS-CoV-2. CONCLUSIONS: Patients treated with anti-CD20+ have adequate resolution of COVID-19 despite the fact that the presence of antibodies against SARS-CoV-2 was not detected in all cases. It is possible that the presence of humoral immunity is not always necessary fora good clinical course of SARS-CoV-2 infection.


title: Confirmed Invasive Pulmonary Aspergillosis and COVID-19: the value of postmortem findings to support antemortem management

text: We present postmortem evidence of invasive pulmonary aspergillosis (IPA) in a patient with severe COVID-19. Autopsies of COVID-19 confirmed cases were performed. The patient died despite antimicrobials, mechanical ventilation, and vasopressor support. Histopathology and peripheral blood galactomannan antigen testing confirmed IPA. Aspergillus penicillioides infection was confirmed by nucleotide sequencing and BLAST analysis. Further reports are needed to assess the occurrence and frequency of IPA in SARS-CoV-2 infections, and how they interact clinically.


The unfolded protein response in virus infections


title: Synthesis of symmetrical and unsymmetrical 3,3-di(indolyl)indolin-2-ones under controlled catalysis of ionic liquids

text: Abstract Three ionic liquids, [BMIM][BF4] doped with 60mol% of LiCl ([BMIM][BF4]–LiCl), N,N,N,N-tetramethylguanidinium trifluoroacetate (TMGT), and N,N,N,N-tetramethylguanidinium triflate (TMGTf) were found useful as catalyst solvents for controlled 3-indolylation of isatins. Our investigation revealed that the reaction between isatin and indoles in [BMIM][BF4]–LiCl or TMGTf media stops at the step of addition of the two components providing 3-indolyl-3-hydroxyindolin-2-ones while the ionic liquid TMGT runs the reaction further through accompanying Friedel–Crafts substitution to afford symmetrical 3,3-di(indol-3-yl)indolin-2-ones. To take advantage of the difference between the effects of these ionic liquids on the reaction progress, we planned a two-step protocol for the efficient synthesis of unsymmetrical 3,3-di(indol-3-yl)indolin-2-ones.


title: What we know so far about Coronavirus Disease 2019 in children: A meta‐analysis of 551 laboratory‐confirmed cases

text: AIM: To summarize what we know so far about coronavirus disease (COVID‐19) in children. METHOD: We searched PubMed, Scientific Electronic Library Online, and Latin American and Caribbean Center on Health Sciences Information from 1 January 2020 to 4 May 2020. We selected randomized trials, observational studies, case series or case reports, and research letters of children ages birth to 18 years with laboratory‐confirmed COVID‐19. We conducted random‐effects meta‐analyses to calculate the weighted mean prevalence and 95% confidence interval (CI) or the weighted average means and 95% CI. RESULT: Forty‐six articles reporting 551 cases of COVID‐19 in children (aged 1 day‐17.5 years) were included. Eighty‐seven percent (95% CI: 77%‐95%) of patients had household exposure to COVID‐19. The most common symptoms and signs were fever (53%, 95% CI: 45%‐61%), cough (39%, 95% CI: 30%‐47%), and sore throat/pharyngeal erythema (14%, 95% CI: 4%‐28%); however, 18% (95% CI: 11%‐27%) of cases were asymptomatic. The most common radiographic and computed tomography (CT) findings were patchy consolidations (33%, 95% CI: 23%‐43%) and ground glass opacities (28%, 95% CI: 18%‐39%), but 36% (95% CI: 28%‐45%) of patients had normal CT images. Antiviral agents were given to 74% of patients (95% CI: 52%‐92%). Six patients, all with major underlying medical conditions, needed invasive mechanical ventilation, and one of them died. CONCLUSION: Previously healthy children with COVID‐19 have mild symptoms. The diagnosis is generally suspected from history of household exposure to COVID‐19 case. Children with COVID‐19 and major underlying condition are more likely to have severe/critical disease and poor prognosis, even death.


title: Mechanism of Dayuanyin in the treatment of coronavirus disease 2019 based on network pharmacology and molecular docking

text: BACKGROUND: At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. METHODS: First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein–protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. RESULTS: First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine–cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. CONCLUSIONS: DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.


title: Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome

text: Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1)-mediated DNA episomal genome replication and persistence are essential for the viral pathogenesis. Cyclophilin A (CYPA) is upregulated in EBV-associated nasopharyngeal carcinoma (NPC) with unknown roles. In the present approach, cytosolic CYPA was found to be bound with EBNA1 into the nucleus. The amino acid 376-459 of the EBNA1 domain was important for the binding. CYPA depletion attenuated and ectopic CYPA expression improved EBNA1 expression in EBV-positive cells. The loss of viral copy number was also accelerated by CYPA consumption in daughter cells during culture passages. Mechanistically, CYPA mediated the connection of EBNA1 with oriP (origin of EBV DNA replication) and subsequent oriP transcription, which is a key step for the initiation of EBV genome replication. Moreover, CYPA overexpression markedly antagonized the connection of EBNA1 to Ubiquitin-specific protease 7 (USP7), which is a strong host barrier with a role of inhibiting EBV genome replication. The PPIase activity of CYPA was required for the promotion of oriP transcription and antagonism with USP7. The results revealed a strategy that EBV recruited a host factor to counteract the host defense, thus facilitating its own latent genome replication. This study provides a new insight into EBV pathogenesis and potential virus-targeted therapeutics in EBV-associated NPC, in which CYPA is upregulated at all stages.


title: Mesenchymal Stem Cell Therapy for COVID-19: Present or Future

text: “COVID-19” is the word that certainly isn’t forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient’s immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.


title: Detection and Isolation of Exotic Newcastle Disease Virus from Field-Collected Flies

text: Flies were collected by sweep net from the vicinity of two small groups of "backyard" poultry (10–20 chickens per group) that had been identified as infected with exotic Newcastle disease virus (family Paramyxoviridae, genus avulavirus, ENDV) in Los Angeles County, CA, during the 2002–2003 END outbreak. Collected flies were subdivided into pools and homogenized in brain-heart infusion broth with antibiotics. The separated supernatant was tested for the presence of ENDV by inoculation into embryonated chicken eggs. Exotic Newcastle disease virus was isolated from pools of Phaenicia cuprina (Wiedemann), Fannia canicularis (L.), and Musca domestica L., and it was identified by hemagglutination inhibition with Newcastle disease virus antiserum. Viral concentration in positive pools was low (<1 egg infectious dose(50) per fly). Isolated virus demonstrated identical monoclonal antibody binding profiles as well as 99% sequence homology in the 635-bp fusion gene sequence compared with ENDV recovered from infected commercial egg layer poultry during the 2002 outbreak.


title: The C Type Lectins DC-SIGN and L-SIGN: Receptors for Viral Glycoproteins

text: DC-SIGN and L-SIGN are C-type lectins that recognize carbohydrate structures present on viral glycoproteins and function as attachment factors for several enveloped viruses. DC-SIGN and L-SIGN enhance viral entry and facilitate infection of cells that express the cognate entry receptor (cis-infection). They are also able to capture viruses and transfer viral infections to other target cells (trans-infection). In this chapter, we will give an overview of protocols used to produce soluble viral glycoproteins at high levels and to study the molecular basis of viruses/DC-SIGN and L-SIGN binding and internalization. We will also describe techniques to investigate the molecular mechanisms by which DC-SIGN or L-SIGN spread viral infections.


Equine influenza and air transport


The Novel Coronavirus Outbreak: What We Know and What We Don’t


title: Emerging Manufacturers engagements in the COVID -19 vaccine research, development and supply

text: The World Health Organization declared the COVID-19 disease as a pandemic requiring a rapid response. Through online search, direct communication with network members and an internal survey, engagements of developing countries’ vaccine manufacturers’ network members in the research and development of COVID-19 vaccines and their capacities in the manufacturing, fill-finish and distribution of vaccines were assessed. Currently, 19 network members engaged in research and development of COVID-19 vaccines, using six principal technology platforms. In addition, an internal survey showed that the number of vaccines supplied collectively by 37 members, in 2018-19, was about 3.5 billion doses annually. Almost a third of network members having vaccines prequalified by the World Health Organization comply with international regulations and mechanisms to distribute vaccines across borders. The use of existing manufacturing, fill-finish and distribution capabilities can support an efficient roll-out of vaccines against COVID-19, while maintaining supply security of existing vaccines for on-going immunization programmes.


title: Rethinking Smallpox

text: The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.


Professional Educational Opportunities


title: Perioperative Considerations in Urgent Surgical Care of Suspected and Confirmed Coronavirus Disease 2019 Orthopaedic Patients: Operating Room Protocols and Recommendations in the Current Coronavirus Disease 2019 Pandemic

text: By April 7, 2020, severe acute respiratory syndrome coronavirus 2 was responsible for 1,383,436 confirmed cases of Coronavirus disease 2019 (COVID-19), involving 209 countries around the world; 378,881 cases have been confirmed in the United States. During this pandemic, the urgent surgical requirements will not stop. As an example, the most recent Centers of Disease Control and Prevention reports estimate that there are 2.8 million trauma patients hospitalized in the United States. These data illustrate an increase in the likelihood of encountering urgent surgical patients with either clinically suspected or confirmed COVID-19 in the near future. Preparation for a pandemic involves considering the different levels in the hierarchy of controls and the different phases of the pandemic. Apart from the fact that this pandemic certainly involves many important health, economic, and community ramifications, it also requires several initiatives to mandate what measures are most appropriate to prepare for mitigating the occupational risks. This article provides evidence-based recommendations and measures for the appropriate personal protective equipment for different clinical and surgical activities in various settings. To reduce the occupational risk in treating suspected or confirmed COVID-19 urgent orthopaedic patients, recommended precautions and preventive actions (triage area, ED consultation room, induction room, operating room, and recovery room) are reviewed.


title: Automating the Classification of Complexity of Medical Decision-Making in Patient-Provider Messaging in a Patient Portal

text: BACKGROUND: Patient portals are consumer health applications that allow patients to view their health information. Portals facilitate the interactions between patients and their caregivers by offering secure messaging. Patients communicate different needs through portal messages. Medical needs contain requests for delivery of care (e.g. reporting new symptoms). Automating the classification of medical decision complexity in portal messages has not been investigated. MATERIALS AND METHODS: We trained two multiclass classifiers, multinomial Naïve Bayes and random forest on 500 message threads, to quantify and label the complexity of decision-making into four classes: no decision, straightforward, low, and moderate. We compared the performance of the models to using only the number of medical terms without training a machine learning model. RESULTS: Our analysis demonstrated that machine learning models have better performance than the model that did not use machine learning. Moreover, machine learning models could quantify the complexity of decision-making that the messages contained with 0.59, 0.45, and 0.58 for macro, micro, and weighted precision and 0.63,0.41, and 0.63 for macro, micro, and weighted recall. CONCLUSIONS: This study is one of the first to attempt to classify patient portal messages by whether they involve medical decision-making and the complexity of that decision-making. Machine learning classifiers trained on message content resulted in better message thread classification than classifiers that employed medical terms in the messages alone.


title: Integration of the Gene Ontology into an object-oriented architecture

text: BACKGROUND: To standardize gene product descriptions, a formal vocabulary defined as the Gene Ontology (GO) has been developed. GO terms have been categorized into biological processes, molecular functions, and cellular components. However, there is no single representation that integrates all the terms into one cohesive model. Furthermore, GO definitions have little information explaining the underlying architecture that forms these terms, such as the dynamic and static events occurring in a process. In contrast, object-oriented models have been developed to show dynamic and static events. A portion of the TGF-beta signaling pathway, which is involved in numerous cellular events including cancer, differentiation and development, was used to demonstrate the feasibility of integrating the Gene Ontology into an object-oriented model. RESULTS: Using object-oriented models we have captured the static and dynamic events that occur during a representative GO process, "transforming growth factor-beta (TGF-beta) receptor complex assembly" (GO:0007181). CONCLUSION: We demonstrate that the utility of GO terms can be enhanced by object-oriented technology, and that the GO terms can be integrated into an object-oriented model by serving as a basis for the generation of object functions and attributes.


title: Identifying strategies to improve access to credible and relevant information for public health professionals: a qualitative study

text: BACKGROUND: Movement towards evidence-based practices in many fields suggests that public health (PH) challenges may be better addressed if credible information about health risks and effective PH practices is readily available. However, research has shown that many PH information needs are unmet. In addition to reviewing relevant literature, this study performed a comprehensive review of existing information resources and collected data from two representative PH groups, focusing on identifying current practices, expressed information needs, and ideal systems for information access. METHODS: Nineteen individual interviews were conducted among employees of two domains in a state health department – communicable disease control and community health promotion. Subsequent focus groups gathered additional data on preferences for methods of information access and delivery as well as information format and content. Qualitative methods were used to identify themes in the interview and focus group transcripts. RESULTS: Informants expressed similar needs for improved information access including single portal access with a good search engine; automatic notification regarding newly available information; access to best practice information in many areas of interest that extend beyond biomedical subject matter; improved access to grey literature as well as to more systematic reviews, summaries, and full-text articles; better methods for indexing, filtering, and searching for information; and effective ways to archive information accessed. Informants expressed a preference for improving systems with which they were already familiar such as PubMed and listservs rather than introducing new systems of information organization and delivery. A hypothetical ideal model for information organization and delivery was developed based on informants' stated information needs and preferred means of delivery. Features of the model were endorsed by the subjects who reviewed it. CONCLUSION: Many critical information needs of PH practitioners are not being met efficiently or at all. We propose a dual strategy of: 1) promoting incremental improvements in existing information delivery systems based on the expressed preferences of the PH users of the systems and 2) the concurrent development and rigorous evaluation of new models of information organization and delivery that draw on successful resources already operating to deliver information to clinical medical practitioners.


title: Acuted Disseminated Encephalomyelitis

text: Acute disseminated encephalomyelitis (ADEM) is a disorder of the central nervous system (CNS) characterized by an acute event, typically with encephalopathy, in which diffuse CNS involvement occurs. It may follow an infectious event and occurs more commonly in young children. Pulse steroid treatment is frequently used to treat ADEM. Although ADEM is typically described as a benign condition, with children generally recovering motor function and resolution of lesions on magnetic resonance imaging (MRI), residual cognitive deficits may occur. This chapter aims to review the clinical features, typical presentation, differential diagnosis, treatment and prognosis of ADEM.


title: Small-Molecule Antiviral β-d-N(4)-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance

text: Coronaviruses (CoVs) have emerged from animal reservoirs to cause severe and lethal disease in humans, but there are currently no FDA-approved antivirals to treat the infections. One class of antiviral compounds, nucleoside analogues, mimics naturally occurring nucleosides to inhibit viral replication. While these compounds have been successful therapeutics for several viral infections, mutagenic nucleoside analogues, such as ribavirin and 5-fluorouracil, have been ineffective at inhibiting CoVs. This has been attributed to the proofreading activity of the viral 3′-5′ exoribonuclease (ExoN). β-d-N(4)-Hydroxycytidine (NHC) (EIDD-1931; Emory Institute for Drug Development) has recently been reported to inhibit multiple viruses. Here, we demonstrate that NHC inhibits both murine hepatitis virus (MHV) (50% effective concentration [EC(50)] = 0.17 μM) and Middle East respiratory syndrome CoV (MERS-CoV) (EC(50) = 0.56 μM) with minimal cytotoxicity. NHC inhibited MHV lacking ExoN proofreading activity similarly to wild-type (WT) MHV, suggesting an ability to evade or overcome ExoN activity. NHC inhibited MHV only when added early during infection, decreased viral specific infectivity, and increased the number and proportion of G:A and C:U transition mutations present after a single infection. Low-level NHC resistance was difficult to achieve and was associated with multiple transition mutations across the genome in both MHV and MERS-CoV. These results point to a virus-mutagenic mechanism of NHC inhibition in CoVs and indicate a high genetic barrier to NHC resistance. Together, the data support further development of NHC for treatment of CoVs and suggest a novel mechanism of NHC interaction with the CoV replication complex that may shed light on critical aspects of replication. IMPORTANCE The emergence of coronaviruses (CoVs) into human populations from animal reservoirs has demonstrated their epidemic capability, pandemic potential, and ability to cause severe disease. However, no antivirals have been approved to treat these infections. Here, we demonstrate the potent antiviral activity of a broad-spectrum ribonucleoside analogue, β-d-N(4)-hydroxycytidine (NHC), against two divergent CoVs. Viral proofreading activity does not markedly impact sensitivity to NHC inhibition, suggesting a novel interaction between a nucleoside analogue inhibitor and the CoV replicase. Further, passage in the presence of NHC generates only low-level resistance, likely due to the accumulation of multiple potentially deleterious transition mutations. Together, these data support a mutagenic mechanism of inhibition by NHC and further support the development of NHC for treatment of CoV infections.


title: Initial Steps in Mammalian Autophagosome Biogenesis

text: During the last decade, autophagy has been pointed out as a central process in cellular homeostasis with the consequent implication in most cellular settings and human diseases pathology. At present, there is significant data available about molecular mechanisms that regulate autophagy. Nevertheless, autophagy pathway itself and its importance in different cellular aspects are still not completely clear. In this article, we are focused in four main aspects: (a) Induction of Autophagy: Autophagy is an evolutionarily conserved mechanism induced by nutrient starvation or lack of growth factors. In higher eukaryotes, autophagy is a cell response to stress which starts as a consequence of organelle damage, such as oxidative species and other stress conditions. (b) Initiation of Autophagy; The two major actors in this signaling process are mTOR and AMPK. These multitasking protein complexes are capable to summarize the whole environmental, nutritional, and energetic status of the cell and promote the autophagy induction by means of the ULK1-Complex, that is the first member in the autophagy initiation. (c) ULK1-Complex: This is a highly regulated complex responsible for the initiation of autophagosome formation. We review the post-transductional modifications of this complex, considering the targets of ULK1. (d)The mechanisms involved in autophagosome formation. In this section we discuss the main events that lead to the initial structures in autophagy. The BECN1-Complex with PI3K activity and the proper recognition of PI3P are one of these. Also, the transmembrane proteins, such as VMP1 and ATG9, are critically involved. The membrane origin and the cellular localization of autophagosome biogenesis will be also considered. Hence, in this article we present an overview of the current knowledge of the molecular mechanisms involved in the initial steps of mammalian cell autophagosome biogenesis.


COVID-19 y la esperanza de la inmunidad


title: Cutaneous Dengue Virus Inoculation Triggers Strong B Cell Reactions but Contrastingly Poor T Cell Responses

text: Dengue is a global health problem without current specific treatment nor safe vaccines available. While severe dengue is related to pre-existing non-neutralizing dengue virus (DENV) antibodies, the role of T cells in protection or pathology is unclear. Using cutaneous DENV infection in immunocompetent mice we previously showed the generation of PNA+ germinal centers (GCs), now we assessed the activation and proliferation of B and T cells in draining lymph nodes (DLNs). We found a drastic remodelling of DLN compartments from 7 to 14 days post-infection (dpi) with greatly enlarged B cell follicles, occupying almost half of the DLN area compared to ~24% in naïve conditions. Enormous clusters of proliferating (Ki-67+) cells inside B follicles were found 14 dpi, representing ~33% of B cells in DLNs but only ~2% in non-infected mice. Inside GCs, we noticed an important recruitment of tingle body macrophages removing apoptotic cells. In contrast, the percentage of paracortex area and total T cells decreased by 14–16 dpi, compared to controls. Scattered randomly distributed Ki-67+ T cells were found, similar to non-infected mice. CD69 expression by CD4+ and CD8+ T cells was minor, while it was remarkable in B cells, representing 1764.7% of change from basal levels 3 dpi. The apparent lack of T cell responses cannot be attributed to apoptosis since no significant differences were observed compared to non-infected mice. This study shows massive B cell activation and proliferation in DLNs upon DENV infection. In contrast, we found very poor, almost absent CD4+ and CD8+ T cell responses.


At the center of the COVID‐19 pandemic: Lessons learned for otolaryngology‐head and neck surgery in China


COVID ‐19 and the gastroenterologist


title: A contextual behavioral approach for responding to moral dilemmas in the age of COVID-19()()

text: Prior pandemics and current news stories suggest that a “second pandemic” of potentially devastating mental health consequences will follow the COVID-19 pandemic. Given the changing contextual demands associated with the pandemic for many people, the mental health consequences of COVID-19 are likely to include exposure to a range of moral dilemmas. Such dilemmas may set the stage for the development of moral distress and moral injury in a broad range of contexts from the ER to the grocery store. In the current paper we offer an approach to responding to moral dilemmas presented by COVID-19. We propose a contextual behavioral model of moral injury that is relevant to those experiencing moral pain associated with the COVID-19 pandemic. Based on this model, we offer two different approaches to intervening on COVID-19-related moral dilemmas. First, we propose the use of Acceptance and Commitment Therapy for Moral Injury (ACT-MI) among individuals suffering from moral injury. Second, to intervene on moral dilemmas at the level of the group, we propose the use of the Prosocial intervention. We offer case examples describing ACT-MI and Prosocial to highlight how these interventions might be applied to moral-dilemma-related concerns during the COVID-19 pandemic and discuss implications for future research.


title: Coronaviruses and the human airway: a universal system for virus-host interaction studies

text: Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition.


title: Acute otitis media and respiratory viruses

text: The present study was performed to elucidate the clinical outcome, and etiology of acute otitis media (AOM) in children based on virologic and bacteriologic tests. The study group consisted of 120 children aged 6 to 144 months with AOM. Middle ear fluid (MEF) was tested for viral pathogens by reverse transcriptase polymerase chain reaction (RT-PCR) and for bacteria by gram-staining and culture. Clinical response was assessed on day 2 to 4, 11 to 13, 26 to 28. Respiratory viruses were isolated in 39 patients (32.5%). Respiratory syncytial virus (RSV) (46.5%) was the most common virus identified in MEF samples, followed by human rhinovirus (HRV) (25.6%), human coronavirus (HCV) (11.6%), influenza (IV) type A (9.3%), adenovirus type sub type A (AV) (4%), and parainfluenza (PIV) type -3 (2%) by RT-PCR. In total 69 bacterial species were isolated from 65 (54.8%) of 120 patients. Streptococcus pneumoniae (S. pneumoniae) was the most frequently isolated bacteria. Viral RNA was detected in 31 (56.3%) of 55 bacteria-negative specimens and in 8 (12.3%) of 65 bacteria-positive MEF samples. No significant differences were found between children representing viral infection alone, combined viral and bacterial infection, bacterial infection alone, and neither viral nor bacterial infection, regarding clinical cure, relapse and reinfection rates. A significantly higher rate of secretory otitis media (SOM) was observed in alone or combined RSV infection with S. pneumonia or Haemophilus influenzae (H. influenzae) than in other viruses infection. Conclusion. This study provides information about etiologic agents and diagnosis of AOM in Turkish children. The findings highlight the importance of common respiratory viruses and bacterial pathogens, particularly RSV, HRV, S. pneumoniae and H. influenzae, in predisposing to and causing AOM in children.


Is Vitamin D One of the Key Elements in COVID-19 Days?


title: Genomic and protein structure modelling analysis depicts the origin and infectivity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China

text: Detailed genomic and structure-based analysis of a new coronavirus, namely 2019-nCoV, showed that the new virus is a new type of bat coronavirus and is genetically fairly distant from the human SARS coronavirus. Structure analysis of the spike (S) protein of this new virus showed that its S protein only binds weakly to the ACE2 receptor on human cells whereas the human SARS coronavirus exhibits strongly affinity to the ACE receptor. These findings suggest that the new virus does not readily transmit between humans and should theoretically not able to cause very serious human infection. These data are important to guide design of infection control policy and inform the public on the nature of threat imposed by 2019-nCov when results of direct laboratory tests on this virus are not expected to be available in the near future.


title: A Porcine Epidemic Diarrhea Virus Outbreak in One Geographic Region of the United States: Descriptive Epidemiology and Investigation of the Possibility of Airborne Virus Spread

text: This study describes a spring 2013 outbreak of porcine epidemic diarrhea virus (PEDv), using data from 222 swine sites in 14 counties area in 4 contiguous states in the United States. During the outbreak, the premises-level incidence of PEDv was 40.5 percent (90/222 sites). One of the three companies from which data were collected had a lower incidence (19.5 percent) than the other two companies (41.1 and 47.2 percent). Sow sites had the highest incidence of PEDv during the outbreak (80.0 percent). Spatial analysis showed that PEDv was clustered rather than randomly distributed, which suggested that sites near a positive site had increased risk of acquiring PEDv infection. Meteorological data were used to investigate the hypothesis that PEDv was spread by air. If airborne dissemination played a role in this outbreak, we would expect the direction of disease spread to correlate with the predominant wind direction. Two methods were used to determine the direction of disease spread—linear direction mean analysis in ArcGIS and the direction test in ClusterSeer. The former method indicated PEDv spread was south to slightly southwest, and the latter indicated spread was to the southeast. The predominant wind direction during the month of the outbreak was toward the south, with some southeast and southwest winds; the strongest wind gusts were toward the southwest. These findings support the hypothesis that PEDv was spread by air. The results, however, should be interpreted cautiously because we did not have information on direct and indirect contacts between sites, such as movement of trucks, feed, pigs or people. These types of contacts should be evaluated before pathogen spread is attributed to airborne mechanisms. Although this study did not provide a definitive assessment of airborne spread of PEDv, we believe the findings justify additional research to investigate this potential mechanism of transmission.


title: Obesity is Associated with Severe Forms of COVID‐19

text: We have read with great interest the Brief Cutting Edge Report from Simonnet et al. which reports a high prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) requiring invasive mechanical ventilation. In the context of unprecedented health crisis due to the coronavirus disease 2019 (COVID-19) outbreak, these results are of a great importance and may have major implications in public health strategy especially in western countries affected by a high prevalence of obesity.


title: Feeding associated neonatal necrotizing enterocolitis (Primary NEC) is an inflammatory bowel disease

text: Abstract Neonatal necrotizing enterocolitis which develops after feeding preterm infants is characterized by severe intestinal inflammation and profound systemic metabolic acidosis. The fermentation of undigested dietary carbohydrate by colonic flora yields gases (CO2 and H2) and short chain organic acids. These organic acids can disrupt the intestinal mucosa and initiate inflammation driven predominantly by resident mast cells and by granulocytes which are recruited from blood. A systemic acidosis ensues derived from intestinal acids, not classic lactic acidosis produced from anaerobic metabolism. The systemic acidosis further compromises inflamed bowel leading to bowel necrosis.


title: A primer on COVID‐19 Mathematical Models

text: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or COVID‐19) disease has led to a wide‐spread global pandemic (1). COVID‐19 symptoms and mortality are disproportionately more severe in people with obesity and obesity related comorbidities (2, 3). This is of concern for the United States, where ~42% have obesity and of these, 85% have type 2 diabetes.


title: High quality protein microarray using in situ protein purification

text: BACKGROUND: In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC). This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. RESULTS: Two slide surfaces were examined, chelated Cu(2+ )slides suspended on a polyethylene glycol (PEG) coating and chelated Ni(2+ )slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu(2+ )slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST) composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents protein solubility and denaturation problems caused by buffer exchange steps and freeze-thaw cycles, which are associated with resin-based purification, intermittent protein storage and deposition on microarrays. CONCLUSION: An optimized platform for in situ protein purification on microarray slides using His-tagged recombinant proteins is a desirable tool for the screening of novel protein functions and protein-protein interactions. In the context of immunoproteomics, such protein microarrays are complimentary to approaches using non-recombinant methods to discover and characterize bacterial antigens.


title: Knowledge and attitudes of Ebola among the general public of Trinidad and Tobago during the 2014-15 West Africa outbreak

text: Objective Health system resilience and resilience of a country include the capacity of health personnel, institutions, and populations to prepare for and effectively respond to crises. This study investigates the knowledge and attitudes of the public concerning Ebola Virus Disease in Trinidad and Tobago. Design and Methods A cross sectional study whereby respondents (n = 920) were sampled from public places. Data were collected via interviewer administered questionnaires. Data were analysed using SPSS version 23. Results The response rate was 67.6 % (622/920). The main age category of responders was the 20 to 30 year age category (40.5%); responders were mostly female (58.0 %). Regarding knowledge, there were significant differences among occupational categories (F = 2.811, df1 = 6, df2 = 571, p-value = 0.011). Tukey’s HSD post hoc test revealed that the mean knowledge scores for professional and sales occupations differed significantly (p-value = 0.003). There was a significant association between being afraid to go for treatment and age (p-value = 0.001). Significant associations were also found between occupational grouping and education attainment with opinion about the preparedness of private medical facilities, likelihood to shun family members with Ebola, being afraid to go for treatment and preference for traditional medicine (p-value <0.05). Conclusion This study highlights opportunities for community engagement to enhance health system resilience during outbreaks which would maximise national and global health security.


Spreading from Hot Foci of COVID-19 to another Country: Observation from Thailand on Disease Importation by Foreigner


Sars Coronavirus Vaccine Development


title: Does ‘Fear of COVID-19’ trigger future career anxiety? An empirical investigation considering depression from COVID-19 as a mediator

text: BACKGROUND: Due to the outbreak of COVID-19, the mental health of the people all around the world is severely disrupted. AIM: The purpose of this study is to identify whether ‘Fear of COVID-19’ impacted on future workforces’ career anxiety at the first place and whether depression from COVID-19 has any indirect effect on ‘Fear of COVID-19’ and future workforces’ career anxiety. METHOD: Based on three different scales related to ‘Fear of COVID-19’, depression and career anxiety, a structured questionnaire was developed and the survey data was collected for this study. RESULTS: The empirical result of the study reveals that, due to the outbreak of COVID-19 fear, the future workforce is getting anxious about their future career. Again, depression from COVID-19, caused by ‘Fear of COVID-19’, as a mediator, has a significant indirect impact on the relationship between ‘Fear of COVID-19’ and future career anxiety, resulting in a full mediation. This means, due to the outbreak of ‘Fear of COVID-19’ people are becoming depressed and anxious about their future career which is creating a long-term negative effect on human psychology. CONCLUSION: These research findings will be a major tool for the policymakers, as well as the human resource planning professionals, to sketch plans after COVID-19 pandemic. This study is a novel work combining the concepts of fear and depression with career anxiety in a pandemic situation like COVID-19, and also assists future researchers in many folds.


title: Risk factors for febrile respiratory illness and mono-viral infections in a semi-closed military environment: a case-control study

text: BACKGROUND: Febrile respiratory illness (FRI) results in substantial burden in semi-closed environments. Tackling risk factors may reduce transmission and infection. However, risk factors involved in one setting may not be generalizable in all settings due to differences in climate, residential environment, population genetic and cultural backgrounds. This study aims to identify risk factors of FRI and mono-viral infections in a tropical military environment. METHODS: From year 2009 to 2012, military personnel with temperature ≥37.5 °C, cough and/or sore throat, and personnel with no fever or no respiratory symptoms were recruited as cases and controls, respectively. Subjects provided nasal wash specimens and answered a standardized questionnaire. Resplex assays were used to determine the viral etiologies. Descriptive, univariate and multivariate analyses of the variables were performed using appropriate descriptive tests and logistic regression modelling, respectively, with R program. RESULTS: A total of 7,743 FRI cases and 1,247 non-FRI study controls were recruited. Increasing age [adjusted odds ratio (AOR) = 1.03; 95 % confidence interval (CI) = 1.01-1.05], recruit camp (AOR = 4.67; 95 % CI = 3.99-5.46) and smoker (AOR = 1.31; 95 % CI = 1.13-1.52) were independent risk factors of FRI. Malay ethnicity was positively associated with influenza A(H1N1)pdm09 (AOR = 1.50; 95 % CI = 1.04-2.15) and coxsackie/echovirus (AOR = 1.67; 95 % CI = 1.19-2.36) mono-infection. Significant contact risk factors were stay-out personnel with ill household member (AOR = 4.96; 95 % CI = 3.39-7.24), and stay-in personnel with ill bunkmate and household member (AOR = 3.55; 95 % CI = 2.57-4.91). Staying in camp with none ill in bunk and at home was a protective factor against FRI (AOR = 0.80; 95 % CI = 0.64-0.99). These contact risk factors were similarly observed for the five most common viruses detected, namely adenovirus, rhinoviruses, influenza A and B, and coxsackie/echovirus. CONCLUSION: Increasing age, smoker, recruit-camp, stay-out personnel with ill household members and stay-in personnel with ill bunkmates were independent risk factors of FRI in a semi-closed military environment. Early identification and isolation of ill personnel from their bunk may be effective to prevent and reduce transmission and disease burden.


Neurological dysfunction in coronavirus disease-19 (COVID-19)


title: Saudi Arabia, pharmacists and COVID-19 pandemic

text: The latest outbreak of Covid-19 pandemic has placed a significant effect on health care system around the world. This article discusses the role of pharmacists in Saudi Arabia during the current Covid-19 pandemic. Pharmacists are an important part of everyday healthcare in Saudi Arabia. Pharmacists helped to protect the public from Covid-19 pandemic disease by participating in various initiatives including health education and promotion, medication dispensing, medication reconciliation, medication and patient counselling, training for self-management in current outbreak and emergency preparedness. Full utilization of skills of pharmacists boosted the safety response of Saudi Arabia to Covid-19 pandemic.


title: Conseils de bonnes pratiques: consultation d’ORL en contexte épidémique COVID-19

text: Résumé Ces conseils de bonnes pratiques sur la consultation en ORL en contexte épidémique COVID-19 ont été rédigés car l’examen et les soins ORL sont dans certaines situations à risque de contamination par le virus SARS-CoV-2. Ainsi, les spécialistes ORL comptent parmi les professionnels les plus exposés à cette infection. En contexte épidémique, dans la mesure où un patient asymptomatique peut être infectant, il est proposé de respecter les mêmes précautions que le patient soit atteint, suspect ou sans évidence clinique d’infection COVID-19. En fonction des données scientifiques à disposition, les examens et actes exposant potentiellement à des projections/aérosolisations de produits biologiques d’origine humaine sont considérés comme à risque de contamination du personnel. Pour les soins ORL sans exposition à de telles projections / aérosolisations, le professionnel porte une tenue à manches longues, un masque chirurgical et des gants à usage unique en cas de contact avec les muqueuses. Pour les soins ORL exposant à ces projections / aérosolisations, leur réalisation nécessite des précautions additionnelles dites complémentaires de type « contact », « gouttelettes » et « air » et « gouttelettes »: appareil de protection respiratoire de type FFP2, protection oculaire, gants à usage unique systématiques, charlotte, surblouse à manches longues.


title: Emerging infections – implications for dental care

text: Over the last 20 years the majority of emerging infections which have spread rapidly across the globe have been respiratory infections that are spread via droplets, a trend which is likely to continue. Aerosol spray generation in the dental surgery has the potential to spread such infections to staff or other patients. Although the diseases may differ, some common approaches can reduce the risk of transmission. Dental professionals should be aware of areas affected by emerging infections, the incubation period and the recent travel history of patients. Elective dental care for those returning from areas affected by emerging infections should be delayed until the incubation period for the infection is over.


Pragmatic recommendations for intubating critically ill patients with suspected COVID‐19


title: Impact of the Coronavirus (COVID-19) pandemic on surgical practice - Part 1 (Review Article)

text: The Coronavirus (COVID-19) pandemic has resulted in over 2.3 million confirmed cases and over 160,000 deaths. The impact of COVID-19 on surgical practice is widespread ranging from workforce and staffing issues, procedural prioritisation, viral transmission risk intraoperatively, changes to perioperative practice and ways of working alongside the impact on surgical education and training. Whilst there has been a growing literature base describing the early clinical course of COVID-19 and on aspects of critical care related to treating these patients, there has been a dearth of evidence on how this pandemic will affect surgical practice. This paper seeks to review the current evidence and offers recommendations for changes to surgical practice to minimise the effect of the COVID-19 pandemic.


title: Microvascular Disease Confers Additional Risk to COVID-19 Infection

text: The majority of fatalities thus far in the COVID-19 pandemic have been attributed to pneumonia. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin “COVID-19 Clinical Guidance for the CV Care Team”, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79 years; 14.8% ≥80 years), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a biological reason for the higher mortality risk in these populations that is apparent. We further present a set of pathophysiological reasons for the heightened danger that could lead to therapies for enhanced management and prevention. MVD And COVID Abstract The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-Cov2) results in COVID-19 which can lead to severe illness and death. The majority of fatalities thus far in the pandemic have been attributed to pneumonia. The overall mortality risk reported as of March 28, 2020 varies from 2.3% in China, 2.7% in Iran, and 0.5% in South Korea. As expected, the fatality rate reported in China is higher in people with chronic pulmonary disease (6.3%) and those who have cancer (5.6%). According to the American College of Cardiology Clinical Bulletin “COVID-19 Clinical Guidance for the CV Care Team”, there is a significantly higher fatality rate in people who are elderly (8.0% 70-79; 14.8% ≥80), diabetic (7.3%), hypertensive (6.0%), or have known cardiovascular disease (CVD) (10.5%). We propose a reason for the higher mortality risk in these populations that is not apparent. We further present a set of pathophysiological reasons for the heightened danger could lead to therapies for enhanced management and prevention.


title: The outbreak pattern of SARS cases in China as revealed by a mathematical model

text: Abstract Since it first appeared in China's Guangdong Province, Severe Acute Respiratory Syndrome (SARS) has caused serious damages to many parts of the world, especially Asia. Little is known about its epidemiology. We developed a modified discrete SIR model including susceptible individuals, non-hospitalized SARS persons; hospitalized patients, cured hospital patients, and those who have died due to SARS infection. Here, we demonstrate the effective reproduction number is determined by infection rates and infectious period of hospitalized and non-hospitalized SARS patients. Both infection rate and the effective reproductive number of the SARS virus are significantly negatively correlated with the total number of cumulative cases, indicating that the control measures implemented in China are effective, and the outbreak pattern of accumulative SARS cases in China is a logistic growth curve. We estimate the basic reproduction number R 0 of SARS virus is 2.87 in mainland of China, very close to the estimations in Singapore and Hong Kong.


title: Molecular identification of Cryptosporidium isolates from ill exotic pet animals in Japan including a new subtype in Cryptosporidium fayeri

text: Abstract Cryptosporidium is an obligate intracellular parasite which can cause fatal diarrheal disease in exotic animals. Sugar gliders (Petaurus breviceps), hedgehogs (Atelerix albiventris), chinchillas (Chinchilla lanigera), and common leopard geckos (Eublepharis macularius) are popular exotic animals commonly sold in pet shops in Japan. We herein investigated the species and subtypes of Cryptosporidium in these animals. Cryptosporidium fayeri was detected in a sugar glider in a Japanese animal hospital. Sequence analyses of the 60-kDa glycoprotein (gp60) gene revealed that C. fayeri belonged to subtype family IVh (IVhA13G2T1), which was proposed to be a new subtype. This is the first study to report C. fayeri infection in a sugar glider. In other animals, the Cryptosporidium horse genotype, C. ubiquitum, and C. varanii were detected in two four-toed hedgehogs (A. albiventris), a chinchilla (C. lanigera), and common leopard gecko (E. macularius), respectively. The gp60 subtypes identified were VIbA13 of the horse genotype and XIId of C. ubiquitum. The present results revealed that potentially zoonotic Cryptosporidium is widespread in exotic animals in Japan.


title: Genomic signal processing for DNA sequence clustering

text: Genomic signal processing (GSP) methods which convert DNA data to numerical values have recently been proposed, which would offer the opportunity of employing existing digital signal processing methods for genomic data. One of the most used methods for exploring data is cluster analysis which refers to the unsupervised classification of patterns in data. In this paper, we propose a novel approach for performing cluster analysis of DNA sequences that is based on the use of GSP methods and the K-means algorithm. We also propose a visualization method that facilitates the easy inspection and analysis of the results and possible hidden behaviors. Our results support the feasibility of employing the proposed method to find and easily visualize interesting features of sets of DNA data.


title: Mouse Hepatitis Virus 3 Binding to Macrophages Correlates with Resistance to Experimental Infection

text: Mouse hepatitis virus 3 (MHV3) infection of A/J and BALB/c mice has been used as a model of resistance/susceptibility. A/J mice recover from a mild disease after 4–6 days of infection and the BALB/c mice develop an acute hepatitis and die after 3–4 days of infection. In view of studying the MHV3 binding to cells or cell extracts, we performed an enzyme‐linked immunosorbent assay‐like virus‐binding assay, preparing microplates with L929 cells, A/J or BALB/c mouse macrophages and also with proteins extracted from these cells. Higher MHV3 bindings were observed to proteins of BALB/c macrophages than to the A/J ones. The interferon‐γ (IFN‐γ) activation led to a reduction of MHV3 binding only to proteins of resistant A/J mouse macrophages. Our experiments contribute to the hypothesis that IFN‐γ activation of macrophages plays an important role against MHV3 infection by downregulating the expression of viral receptors.


title: A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses

text: Bats provide important ecosystem services as pollinators, seed dispersers, and/or insect controllers, but they have also been found harboring different viruses with zoonotic potential. Virome studies in bats distributed in Asia, Africa, Europe, and North America have increased dramatically over the past decade, whereas information on viruses infecting South American species is scarce. We explored the virome of Tadarida brasiliensis, an insectivorous New World bat species inhabiting a maternity colony in Rosario (Argentina), by a metagenomic approach. The analysis of five pooled oral/anal swab samples indicated the presence of 43 different taxonomic viral families infecting a wide range of hosts. By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. TbraPV1 is the first papillomavirus type identified in this host and the prototype of a novel genus. TbGkyV1 is the first genomovirus reported in New World bats and constitutes a new species within the genus Gemykibivirus. Our findings extend the knowledge about oral/anal viromes of a South American bat species and contribute to understand the evolution and genetic diversity of the novel characterized viruses.


title: The molecular epidemiology of respiratory viruses associated with asthma attacks: A single-center observational study in Japan

text: Few reports have described the significance of viral respiratory infections (VRIs) in exacerbation of asthma in adult patients. The aim of this study was to elucidate the profiles of VRIs in adult patients with asthma along with their molecular epidemiology. A cross-sectional observational study was conducted at Kyorin University Hospital from August 2012 to May 2015. To identify respiratory pathogens in inpatients and outpatients suffering from asthma attacks, RT-PCR/sequencing/phylogenetic analysis methods were applied alongside conventional microbiological methods. Phylogenetic and pairwise distance analyses of 10 viruses were performed. A total of 106 asthma attack patients enrolled in this study in both inpatient (n = 49) and outpatient (n = 57) settings. The total 106 respiratory samples were obtained from nasopharyngeal swab (n = 68) or sputum (n = 38). Among these, patients with virus alone (n = 39), virus and bacterial (n = 5), and bacterial alone (n = 5) were identified. The ratio of virus-positive patients in inpatient or outpatient to the total cases were 31.1% (n = 33) and 10.4% (n = 11), respectively. The frequency of virus-positive patients was significantly higher in inpatients (75.3%, n = 33) than in outpatients (19.3%, n = 11). Major VRIs included human rhinovirus (HRV) (n = 24), human metapneumovirus (hMPV) (n = 9), influenza virus (Inf-V) (n = 8), and respiratory syncytial virus (RSV) (n = 3) infections with seasonal variations. HRV-A and HRV-C were the most commonly detected viruses, with wide genetic divergence on phylogenetic analysis. Asthmatic exacerbations in adults are highly associated with VRIs such as HRV-A or HRV-C, hMPV, RSV, and Inf-V infections with seasonal variations and genetic divergence, but similar frequencies of VRIs occurred in asthma attack patients throughout the seasons.


title: Caution regarding potential changes in AVR practices during the COVID‐19 pandemic

text: To improve resource allocation in face of the COVID‐19 pandemic, hospitals around the country are restricting the performance of elective surgery to preserve ventilators, operating rooms, ICU beds and protect anesthesiologists. For patients with severe aortic stenosis, efforts to bring treatment to symptomatic patients amid this pandemic might lead to favored use of catheter based management using minimalist techniques that do not require these elements. In this context, some patients with well tested surgical indications for valve replacement may be treated by catheter‐based methods. It is important that outcomes for these cases are followed closely both at respective sites and in national registries. As we recover from this pandemic, surgical cases should once again be driven by multi‐disciplinary discussion and clinical trial data, and not a mentality of crisis management.


title: A review of equine sepsis

text: Sepsis is defined as an exaggerated, systemic inflammatory response to infection and is a common condition in horses. Systemic inflammatory response syndrome (SIRS) associated with bacterial infection is a hallmark of sepsis. Sepsis in neonatal foals is a common sequela of failure of passive transfer and, in addition to development of SIRS, may be characterised by bacteraemia, pneumonia, enterocolitis, omphalophlebitis, meningoencephalitis or arthritis. Sepsis in mature horses is most commonly observed secondary to gastrointestinal lesions that result in disrupted mucosa and bacterial translocation into circulation (endotoxaemia). Pleuropneumonia and metritis may also cause sepsis in mature horses. Diagnosis of sepsis is based on SIRS criteria as well as suspected or confirmed infection. Due to the relatively low sensitivity of microbial culture and the subjectivity of sepsis scoring, many sepsis biomarkers are being studied for their usefulness in diagnosis and prognostication of sepsis in horses. Treatment of sepsis requires an intensive care approach that includes antimicrobial drug administration, fluid resuscitation and pressure support, and treatment for inflammation, endotoxaemia and coagulopathy. Early recognition of sepsis and prompt antimicrobial drug treatment are critical for a successful outcome. Multiple organ dysfunction syndrome may occur in severe cases of sepsis, with common manifestations including laminitis and coagulopathies. Although prognosis for septic mature horses depends highly on the primary disease process, the overall survival rate in septic neonatal foals ranges from 26 to 86%, with most studies indicating a survival rate of 45–60%.


Prone positioning in high-flow nasal cannula for COVID-19 patients with severe hypoxemia: a pilot study


title: The role of CCR1 and therapeutic effects of anti‐CCL3 antibody in herpes simplex virus‐induced Behçet's disease mouse model

text: Behçet's disease (BD) is a chronic systemic inflammatory disease with unclear etiopathogenesis. Although gene variants of CC chemokine receptor type 1 (CCR1) have been reported, the protein expression of CCR1 in patients with BD remains unclear. The objective of this study was to analyze the frequencies of CCR1(+) cells in a herpes simplex virus‐induced mouse model of BD. The frequencies of CCR1(+) cells on the surface and in the cytoplasm of peripheral blood mononuclear cells and lymph nodes were analyzed by flow cytometry. The CCR1(+) cells were significantly down‐regulated in BD mice compared with the normal control and symptom‐free control mice. Colchicine and pentoxifylline treatment improved the symptoms of BD and increased the frequencies of CCR1(+) cells in BD mice. Treatment with chemokine CC motif ligand 3 (CCL3), a ligand of CCR1, caused BD symptoms to deteriorate in 10 of 16 BD mice (62·5%) via down‐regulation of CCR1(+) cells. Anti‐CCL3 antibody treatment ameliorated BD symptoms in 10 of 20 mice (50%) and significantly decreased the disease severity score compared with CCL3‐treated BD mice (P = 0·01) via up‐regulation of CCR1(+) cell frequencies. In patients with BD, plasma levels of CCL3 in an active state were significantly higher than in healthy control individuals (P = 0·02). These results show that the up‐regulation of CCR1(+) cells was related to the control of systemic inflammation of BD in mouse models.


title: New intriguing possibility for prevention of coronavirus pneumonitis: Natural purified polyphenols

text: COVID-19 is an infectious disease characterized by several important systemic problems such as severe pneumonia. One of mechanisms responsible of these systemic problems is the release of pro-inflammatory cytokines, such as interleukin (IL)-1beta and IL-6(Conti et al., 2020). The binding of virus to TRL (Toll Like Receptor) can determine the release of pro-IL-1beta with successive activation and production of active mature IL-1beta, responsible of lung inflammation, fever and fibrosis(Conti et al., 2020). The interstitial pneumonia is linked to an over-production of IL-6. Based on this principle, several researchers started the use of an anti-arthritis drug, tocilizumab, for its anti-IL-6 action.


title: The effects of SNS communication: How expressing and receiving information predict MERS-preventive behavioral intentions in South Korea

text: Abstract Individuals use social network sites (SNSs) as an effective tool for communicating relevant information with others during the outbreak of infectious diseases. However, little is known about the underlying mechanism through which communicative behaviors influence preventive behaviors. Thus, in the context of Middle East respiratory syndrome (MERS) in South Korea, this study investigated how two communicative behaviors (message expression and reception) in SNSs affected the communicators’ intentions to engage in MERS-preventive behaviors. Using data collected from a nationally representative panel survey of 1000 Korean adults aged 19 or older, we examined a theoretical expression and reception effects model. Results support the presence of effects from expressing and receiving MERS-related information via SNSs and their underlying mechanism during South Korea’s MERS outbreak. Public health officials and communication professionals should actively use SNS communication in coping with public health crisis caused by emerging infectious diseases.


title: 2-Substituted benzoxazinone analogues as anti-human coronavirus (anti-HCoV) and ICAM-1 expression inhibition agents

text: Abstract A series of 2-substituted benzoxazinones were synthesized and subjected to anti-human coronavirus and ICAM-1 expression inhibition assays. Among them, compounds 1, 3, 4, 5, 6, and 7 exhibited significant anti-HCoV activities, and the IC50 value of these compounds are 6.08, 5.06, 6.83, 1.92, 7.59, and 5.79μg/mL, respectively. Furthermore, compounds 1 and 6 showed significant inhibitory effect on ICAM-1 expression, the ED50 values of 1 and 6 are 1.00 and 0.50μg/mL, respectively.


title: 4.06 Safe Sanitation in Low Economic Development Areas

text: This chapter presents the advances in sanitation for developing countries as well as the needs in terms of goals, standards, technology, and policy. To understand why a special chapter for low-income areas is needed, it describes the main types of pollutants, their origins, and treatment options. As part of the text and to face the requirements for poor rural and urban areas and water-scarce regions, basic sanitation, wastewater treatment, and water reuse alternatives are described with emphasis on their constraints and limitations for developing countries. Some aspects concerning the development of policies, costs, and funding to fulfill the Millennium Development Goals are also included. The importance of developing innovative solutions that can be sustainable, affordable, and progressively implemented is discussed.