title: Tocilizumab, Adipokines and Severe Complications of COVID-19

text: Acute ischemic stroke (AIS) is a life-threatening complication of coronavirus disease 2019 (COVID-19) infection Increasing reports suggest an association between COVID-19 and AIS, although the underlying mechanism remains uncertain We performed a systematic review to characterize the clinical characteristics, neuroimaging findings, and outcomes of AIS in COVID-19 patients A literature search was performed in PubMed and Embase using a suitable keyword search strategy from 1st December 2019 to 29th May 2020 All studies reporting AIS occurrence in COVID-19 patients were included A total of 39 studies comprising 135 patients were studied The pooled incidence of AIS in COVID-19 patients from observational studies was 1 2% (54/4466) with a mean age of 63 4 ± 13 1 years The mean duration of AIS from COVID-19 symptoms onset was 10 ± 8 days, and the mean NIHSS score was 19 ± 8 Laboratory investigations revealed an elevated mean d-dimer (9 2 ± 14 8 mg/L) and fibrinogen (5 8 ± 2 0 g/L) Antiphospholipid antibodies were detected in a significant number of cases The majority of AIS neuroimaging patterns observed was large vessel thrombosis, embolism or stenosis (62 1%, 64/103), followed by multiple vascular territory (26 2%, 27/103) A high mortality rate was reported (38 0%, 49/129) We report the pooled incidence of AIS in COVID-19 patients to be 1 2%, with a high mortality rate Elevated d-dimer, fibrinogen and the presence of antiphospholipid antibodies appear to be prominent in COVID-19 patients with concomitant AIS, but further mechanistic studies are required to elucidate their role in pathogenesis


title: Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

text: Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.


title: Viral respiratory tract infections in young children with cystic fibrosis: a prospective full-year seasonal study

text: BACKGROUND: Viral respiratory tract infections are common during early childhood. How they impact cystic fibrosis lung disease history in young children is poorly known. The principal aim of our study was to determinate respiratory tract infections frequency in this cystic fibrosis young population. Secondary outcomes were nature of viral agents recovered and impact of such infections. METHODS: We conducted a prospective cohort study of 25 children affected by cystic fibrosis and aged less than 2 years. Nasal samplings were taken systematically monthly or bimonthly with additional samples taken during respiratory tract infections episodes. Ten pathogens were tested by a combination of five duplex RT-PCRs or PCRs: influenza A and B, respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus/enterovirus (RV/EV)), coronavirus (HKU1, NL63, 229E and OC43), parainfluenza virus (1–4), adenovirus and bocavirus (Respiratory Multi-Well System MWS r-gene®, BioMérieux, Marcy l’Étoile, France). Cycle thresholds (CTs) were reported for all positive samples and considered positive for values below 40. Quantitative variables were compared using a nonparametric statistical test (Wilcoxon signed rank for paired comparisons). Pearson’s correlation coefficient (r) was used to assess relationships between two variables. Statistical analyses were performed using SAS v9.4 (SAS Institute, Cary, NC, USA) or GraphPad Prism V6.00 (GraphPad Software, La Jolla, CA, USA). The significance level was set at 0.05. RESULTS: The mean age at inclusion was 9.6 ± 6.7 months. The patients had 3.4 ± 1.7 respiratory tract infections episodes per child per year. Forty-four respiratory tract infections (69%) were associated with virus: rhinovirus and enterovirus (RV/EV) were implied in 61% of them and respiratory syncytial virus (RSV) in 14%. Only one patient required hospitalization for lower respiratory tract infections. 86% of the patients were treated by antibiotics for a mean of 13.8 ± 6.2 days. RSV infections (n = 6) were usually of mild severity. CONCLUSIONS: Respiratory tract infections in young children with cystic fibrosis were of mild severity, rarely requiring hospitalization. Unsurprisingly, RV/EV were the most frequent agents. RSV-related morbidity seems low in this population. This raises the question of the usefulness of RSV preventive medication in this young population.


title: Epidemiological features and viral shedding in children with SARS‐CoV‐2 infection

text: BACKGROUND: A pandemic of SARS‐CoV‐2 infection broke out all over the world, however, epidemiological data and viral shedding in pediatric patients are limited. METHODS: We conducted a retrospective, multi‐center study, and followed up with all children from the families with SARS‐CoV‐2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS‐CoV‐2 RNA with RT‐PCR method, and epidemiological data between children and adults in the same families was compared. Effect of antiviral therapy was evaluated observationally and fecal viral excretion times among groups with different antiviral regiments were compared with Kaplan Meier plot. RESULTS: By February 29, 2020, 1298 cases from 883 families were confirmed with SARS‐CoV‐2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty‐three children had COVID‐19 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS‐CoV‐2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal‐viral‐excreting children. CONCLUSION: Children have lower susceptibility of SARS‐CoV‐2 infection, longer incubation and fecal viral excretion time. Positive results of fecal SARS‐CoV‐2 RNA detection were not used as indication for hospitalization or quarantine. This article is protected by copyright. All rights reserved.


title: Successful treatment of chronic myelomonocytic leukaemia with hydroxycarbamide in a patient presenting with acute hypoxic respiratory failure due to COVID‐19 pneumonia

text: On 30th March 2020, a 57‐year‐old male patient presented to the Emergency Department with a 6‐day history of cough, persistent fevers and worsening dyspnoea. His only known comorbidity was hypertension, managed with amlodipine and an angiotensin converting enzyme inhibitor. On admission, he was tachypnoeic and in severe hypoxic respiratory failure with dangerously low peripheral oxygen saturations (SpO(2)) 83% on 15L oxygen. Chest radiographic changes were consistent with COVID‐19 infection and demonstrated bilateral changes with diffuse airspace shadowing with more confluence in the lower zones (Figure 1A).


title: STEM: An Open Source Tool for Disease Modeling

text: The Spatiotemporal Epidemiologic Modeler (STEM) is an open source software project supported by the Eclipse Foundation and used by a global community of researchers and public health officials working to track and, when possible, control outbreaks of infectious disease in human and animal populations. STEM is not a model or a tool designed for a specific disease; it is a flexible, modular framework supporting exchange and integration of community models, reusable plug-in components, and denominator data, available to researchers worldwide at www.eclipse.org/stem. A review of multiple projects illustrates its capabilities. STEM has been used to study variations in transmission of seasonal influenza in Israel by strains; evaluate social distancing measures taken to curb the H1N1 epidemic in Mexico City; study measles outbreaks in part of London and inform local policy on immunization; and gain insights into H7N9 avian influenza transmission in China. A multistrain dengue fever model explored the roles of the mosquito vector, cross-strain immunity, and antibody response in the frequency of dengue outbreaks. STEM has also been used to study the impact of variations in climate on malaria incidence. During the Ebola epidemic, a weekly conference call supported the global modeling community; subsequent work modeled the impact of behavioral change and tested disease reintroduction via animal reservoirs. Work in Germany tracked salmonella in pork from farm to fork; and a recent doctoral dissertation used the air travel feature to compare the potential threats posed by weaponizing infectious diseases. Current projects include work in Great Britain to evaluate control strategies for parasitic disease in sheep, and in Germany and Hungary, to validate the model and inform policy decisions for African swine fever. STEM Version 4.0.0, released in early 2019, includes tools used in these projects and updates technical aspects of the framework to ease its use and re-use.


title: Combating Canine ‘Visiting Cards’: Public Hygiene and the Management of Dog Mess in Paris since the 1920s

text: This article examines the history of dog mess in Paris, from its ‘discovery’ in the late 1920s to the management regime of the early twenty-first century. Mayor Jacques Chirac’s anti-excrement campaigns in the 1980s are a particular focus. Situating the meaning and management of dog mess within histories of public hygiene and disgust, and mobilising insights from work on public hygiene, biopolitics and governmentality, this article shows how Chirac’s attempt to produce self-regulating and responsible dog owners through education failed to persuade them to overcome their disgust at their pets’ excrement. Fining alongside education proved a more effective management strategy. The history of dog mess in Paris highlights the biopolitical problems raised by animal excrement decades after the apogee of the public hygiene movement, and shows how human–animal partnerships expose the limits of governmentality approaches to public hygiene and neo-liberal urban governance.


title: Section 8 Multiple Choice Questions

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COVID‐19 transmission through host cell directed network of GPCR


title: Brome Mosaic Virus (Bromoviridae) ☆

text: Abstract Brome mosaic virus (BMV) is an isometric, non-enveloped, positive-strand RNA virus and a well-studied, representative member of the alphavirus-like super-family of human, animal, and plant viruses. BMV has been extensively studied as a model to examine some of the common features shared by all positive-strand RNA viruses. This article provides insights into virion assembly, encapsidation, gene expression, recombination, RNA replication, and virus-host interactions. These studies have not only advanced understanding of BMV, but have also revealed insights and principles extending to many other viruses and to general cellular biology.


title: Potential Therapeutic Targets and Promising Drugs for Combating SARS‐CoV‐2

text: As of April 9, 2020, a novel coronavirus (SARS‐CoV‐2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we have learned the genome structure, epidemiological and clinical characteristics and pathogenic mechanisms of SARS‐CoV‐2. Based on these discoveries, identifying potential targets involved in the processes of virus pathogenesis is urgently needed, and discovering or developing promising drugs based on potential targets is the most pressing need. Therefore, we summarize the potential therapeutic targets involved in virus pathogenesis and discuss the advancements, possibilities and significance of promising drugs based on these targets for treating SARS‐CoV‐2. This review will facilitate the identification of potential targets and provide promising clues for drug development that can be translated into clinical applications for combating SARS‐CoV‐2.


title: Review article: COVID‐19 and liver disease—what we know on 1st May 2020

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the causative pathogen of coronavirus disease 2019 (COVID‐19), became a global threat to human health. Liver impairment has been frequently reported as a common manifestation, although its clinical significance is still unclear, particularly in patients with underlying chronic liver disease (CLD). AIMS: To summarise the changes in liver function tests during SARS‐CoV‐2 infection and the impact of COVID‐19 in patients with underlying CLD. METHODS: A literature review using online database PubMed was done using the search terms “SARS‐CoV‐2”, “COVID‐19”, “liver”, “cirrhosis” and “liver transplantation”. RESULTS: COVID‐19 is frequently associated with different degrees of abnormal liver function tests, most notably transaminases, which are usually transitory and of mild degree. Available evidence suggests that liver injury may result from direct pathogenic effect by the virus, systemic inflammation or toxicity from commonly used drugs in this subset of patients. SARS‐CoV‐2 infection in children is associated with minimal or no increase in liver enzymes, thus the presence of abnormal liver function tests should trigger evaluation for underlying liver diseases. Although it seems that patients with CLD are not at greater risk for acquiring the infection, those with cirrhosis, hepatocellular carcinoma, non‐alcoholic fatty liver disease, autoimmune liver diseases or liver transplant may have a greater risk for severe COVID‐19. CONCLUSIONS: Abnormal liver function tests during the course of COVID‐19 are common, though clinically significant liver injury is rare. Further research is needed focusing on the effect of existing liver‐related comorbidities on treatment and outcome of COVID‐19.


title: Impact of COVID 19 lockdown on orthopaedic surgeons in India: A survey()

text: BACKGROUND: In the fight against COVID 19, the government of India announced a 3 weeks lockdown of the entire country of 1.3 billion people on 24(th) March 2020. METHODS: One week after the lockdown was announced, we conducted an anonymous online survey of the orthopaedic surgeons in India through social media platforms to assess the impact of the lockdown during COVID 19. The survey had a total of 13 questions with (3–5) options and was designed with an aim to understand the perception and the state of mind of the Orthopaedic surgeons in the lockdown situation. RESULTS: The survey was completed by 611 orthopaedic surgeons from 140 cities in India. There were 22.5% orthopaedic surgeons who said that they were definitely stressed out, and 40.5% who said they were mildly stressed out. As the age decreased, the percentage of orthopaedic surgeons feeling “definitely stressed out” increased. Disruption of life-work balance and uncertainties regarding return to work were other strongly associated factors with the “definitely stressed out” group. CONCLUSION: The psychological impact of the lockdown during COVID 19 on orthopaedic surgeons may become a potential concern that will require addressal through open discussion. LEVEL OF EVIDENCE: diagnostic level 4.


title: ECMO use in COVID-19: lessons from past respiratory virus outbreaks—a narrative review

text: The spread of coronavirus disease 2019 (COVID-19) continues to grow exponentially in most countries, posing an unprecedented burden on the healthcare sector and the world economy. Previous respiratory virus outbreaks, such as severe acute respiratory syndrome (SARS), pandemic H1N1 and Middle East respiratory syndrome (MERS), have provided significant insights into preparation and provision of intensive care support including extracorporeal membrane oxygenation (ECMO). Many patients have already been supported with ECMO during the current COVID-19 pandemic, and it is likely that many more may receive ECMO support, although, at this point, the role of ECMO in COVID-19-related cardiopulmonary failure is unclear. Here, we review the experience with the use of ECMO in the past respiratory virus outbreaks and discuss potential role for ECMO in COVID-19.


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title: COVID highlights another crisis: lack of Black physicians and scientists


title: Impact of Middle East Respiratory Syndrome coronavirus (MERS‐CoV) on pregnancy and perinatal outcome

text: BACKGROUND: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a viral respiratory disease. Most people infected with MERS-CoV develop severe acute respiratory illness. It was first reported in Saudi Arabia in 2012 and has since spread to several other countries. We report the clinical course of MERS-CoV infection in a pregnant woman who acquired the infection during the last trimester. CASE PRESENTATION: The patient is a 33-year-old female working as a critical care nurse. She was 32 weeks pregnant when she presented with respiratory symptoms after direct contact with a MERS-COV patient. Although the patient was in respiratory failure, necessitated mechanical ventilation, and intensive care (ICU) admission, a healthy infant was delivered. The mother recovered. To the best of our knowledge, this is the first reported case of a laboratory-confirmed Middle East Respiratory Syndrome Coronavirus in a pregnant woman. CONCLUSIONS: Middle East Respiratory Syndrome coronavirus (MERS-CoV) known to cause severe acute respiratory illness associated with a high risk of mortality Various factors may have contributed to the successful outcome of this patient such as young age, presentation during the last stages of pregnancy, and possible differences in immune response.


title: Allergy clinics in times of the SARS-CoV-2 pandemic: an integrated model

text: BACKGROUND: Almost the entire World is experiencing the Coronavirus-Disease-2019 (COVID-19) pandemic, responsible, at the end of May 2020, of more than five million people infected worldwide and about 350,000 deaths. In this context, a deep reorganization of allergy clinics, in order to ensure proper diagnosis and care despite of social distancing measures expose, is needed. MAIN TEXT: The reorganization of allergy clinics should include programmed checks for severe and poorly controlled patients, application of digital medicine service for mild-to-moderate disease in well-controlled ones, postponement of non urgent diagnostic work-ups and domiciliation of therapies, whenever possible. As far as therapies, allergen immunotherapy (AIT) should not be stopped and sublingual immunotherapy (SLIT) fits perfectly for this purpose, since a drug home-delivery service can be activated for the entire pandemic duration. Moreover, biologic agents for severe asthma, chronic spontaneous urticaria and atopic dermatitis should be particularly encouraged to achieve best control possible of severe disease in times of COVID-19 and, whenever possible, home-delivery and self-administration should be the preferred choice. CONCLUSION: During COVID-19 pandemic, allergists have the responsibility of balancing individual patients’ needs with public health issues, and innovative tools, such as telemedicine and digital medicine services, can be helpful to reduce the risk of viral spreading while delivering up-to-date personalized care.


title: Double Jeopardy Cardiomyopathy Requiring Heart Transplant: Hydroxychloroquine and Rheumatoid Arthritis

text: [Figure: see text]


title: SARS coronavirus induces apoptosis in Vero E6 Cells

text: Severe acute respiratory syndrome (SARS) is an emerging infectious disease. Its etiological agent has been convincingly identified as a new member of family Coronaviridae (SARS‐CoV). It causes serious damage to the respiratory system yet the mechanism is not clear. Infection‐induced apoptosis or necrosis is suspected but no direct evidence for this yet exists. To date, Vero E6 cells are the only cell line that could be used to replicate the virus with obvious CPE (cytopathic effect) in vitro. It is known for some viruses (including members of family Coronaviridae) that CPE can be caused either by virus‐induced apoptosis (active death) or cell necrosis (passive death). In this study, we examined the apoptosis in the SARS‐CoV infected Vero E6 cells. Indeed, the results do show that the CPE was induced by apoptosis rather than necrosis, shown by typical DNA fragmentation, through the existence of apoptotic bodies and swollen mitochondria. This observation has some implications for the SARS‐CoV pathogenicity: SARS‐CoV does induce apoptosis in cell cultures and might have the same effect in vivo, responsible for the severe damage of the respiratory system. J. Med. Virol. 73:323–331, 2004. © 2004 Wiley‐Liss, Inc.


Coronavirus and Chronic Lung Allograft Dysfunction: Hiding in Plain Sight?


title: Beryllium metallicum

text: Abstract Acute viral respiratory epidemic diseases are more and more frequent, sometimes causing serious complications. What homeopathic treatment, used in addition to conventional treatments, could be indicated? The study of the Materia Medica of Beryllium metallicum reveals many clinical signs common to the symptoms presented by patients with acute viral respiratory disease.


title: Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha

text: Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2–4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2–4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2–4) by fusing the variable region of mouse mAb 2–4 to the constant region of feline antibody. The chimeric mAb 2–4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2–4 and chimeric mAb 2–4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2–4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2–4 was reduced. In contrast, in cats treated with chimeric mAb 2–4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2–4-treated cats.


The Relationship Between Parenting Stress and School Closures due to the COVID‐19 Pandemic


title: Characterizing super-spreading in microblog: An epidemic-based information propagation model

text: Abstract As the microblogging services are becoming more prosperous in everyday life for users on Online Social Networks (OSNs), it is more favorable for hot topics and breaking news to gain more attraction very soon than ever before, which are so-called “super-spreading events”. In the information diffusion process of these super-spreading events, messages are passed on from one user to another and numerous individuals are influenced by a relatively small portion of users, a.k.a. super-spreaders. Acquiring an awareness of super-spreading phenomena and an understanding of patterns of wide-ranged information propagations benefits several social media data mining tasks, such as hot topic detection, predictions of information propagation, harmful information monitoring and intervention. Taking into account that super-spreading in both information diffusion and spread of a contagious disease are analogous, in this study, we build a parameterized model, the SAIR model, based on well-known epidemic models to characterize super-spreading phenomenon in tweet information propagation accompanied with super-spreaders. For the purpose of modeling information diffusion, empirical observations on a real-world Weibo dataset are statistically carried out. Both the steady-state analysis on the equilibrium and the validation on real-world Weibo dataset of the proposed model are conducted. The case study that validates the proposed model shows that the SAIR model is much more promising than the conventional SIR model in characterizing a super-spreading event of information propagation. In addition, numerical simulations are carried out and discussed to discover how sensitively the parameters affect the information propagation process.


title: Nitric oxide induced by Indian ginseng root extract inhibits Infectious Bursal Disease virus in chicken embryo fibroblasts in vitro

text: Infectious Bursal Disease is a severe viral disease of chicken responsible for serious economic losses to poultry farmers. The causative agent, Infectious Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian ginseng, Withania somnifera, inhibits Infectious Bursal Disease virus in vitro. Also, Withania somnifera root extract is known to induce nitric oxide production in vitro. Therefore, the present study was undertaken to determine if the inhibitory activity of Withania somnifera against Infectious Bursal Disease virus was based on the production of nitric oxide. We show that besides other mechanisms, the inhibition of Infectious Bursal Disease virus by Withania somnifera involves the production of nitric oxide. Our results also highlight the paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal Disease.


title: Clinical Characteristics and Reasons for Differences in Duration From Symptom Onset to Release From Quarantine Among Patients With COVID-19 in Liaocheng, China

text: Objective: This study aimed to identify additional characteristics and features of coronavirus disease (COVID-19) by assessing the clinical courses among COVID-19 patients in a region outside Hubei province. Methods: We analyzed retrospective data regarding general characteristics, epidemiologic history, underlying chronic diseases, clinical symptoms and complications, chest computed tomography findings, biochemical monitoring, disease severity, treatments, and outcomes among 37 adult patients with COVID-19. According to the duration from symptom onset to release from quarantine, the patients were divided into the ≤20 and >20-day groups, and the similarities and differences between them were compared. Results: Among the 37 patients, five had mild disease, 30 had moderate disease, one had severe disease, and one was critically ill. All of the patients were released from quarantine, and no mortality was observed. The average duration from symptom onset to release from quarantine was 20.2 ± 6.6 days. The average duration from symptom onset to hospitalization was 4.1 ± 3.7 days, and the patients were hospitalized for an average of 16.1 ± 6.2 days. The average age was 44.3 ± 1.67 years, and 78.4% of cases were caused by exposure to a patient with confirmed disease or the workplace of a patient with confirmed disease. The main symptoms were cough (67.6%), fever (62.2%), shortness of breath (32.4%), fatigue (24.3%), sore throat (21.6%), vomiting, and diarrhea (21.6%). White blood cell count was decreased in 27.0% of patients, and lymphocyte count was decreased in 62.2% of the patients, among whom 43.5% patients had counts of ≤0.6 × 10(9)/L. On admission, 86.5% of patients showed pneumonia in chest CT scans, including some asymptomatic patients, while 68.8% of patients showed bilateral infiltration. In the >20-day group, the average age was 49.9 ± 1.38 years, and the average duration from symptom onset to hospitalization was 5.5 ± 3.9 days. Compared with the ≤20-day group, patients in the >20-day group were older and the duration was longer (P < 0.05). All of the seven asymptomatic patients belonged to the ≤20-day group. When the 37 patients were released from quarantine, the white blood cell count of 16.2% of the patients was <4.0 × 10(9)/L, the lymphocyte count of 59.5% of the patients was <1.1 × 10(9)/L, and the absolute counts of white blood cells and lymphocytes were 5.02 ± 1.34 × 10(9)/L and 1.03 ± 0.34 × 10(9)/L, respectively, compared with those recorded on admission (P > 0.05). Conclusion: The majority of COVID-19 cases in the study area were mild and moderate, with good clinical outcomes. There were some special characteristics in the clinical course. The reasons for differences in the duration from symptom onset to release from quarantine were complex. There was no significant change in the number of granulocytes at the time of release from quarantine compared to that at the time of admission.


title: Chloroplast-Derived Vaccine Antigens and Biopharmaceuticals: Expression, Folding, Assembly and Functionality

text: Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance, and multi-gene expression in a single transformation event. Oral delivery is facilitated by hyperexpression of vaccine antigens against cholera, tetanus, anthrax, plague, or canine parvovirus (4%–31% of total soluble protein, TSP) in transgenic chloroplasts (leaves) or non-green plastids (carrots, tomato) as well as the availability of antibiotic free selectable markers or the ability to excise selectable marker genes. Hyperexpression of several therapeutic proteins, including human serum albumin (11.1% TSP), somatotropin (7% TSP), interferon-alpha (19% TSP), interferon-gamma (6% TSP), and antimicrobial peptide (21.5% TSP), facilitates efficient and economic purification. Also, the presence of chaperones and enzymes in chloroplasts facilitates assembly of complex multisubunit proteins and correct folding of human blood proteins with proper disulfide bonds. Functionality of chloroplast-derived vaccine antigens and therapeutic proteins has been demonstrated by several assays, including the macrophage lysis assay, GM1-ganglioside binding assay, protection of HeLA cells or human lung carcinoma cells against encephalomyocarditis virus, systemic immune response, protection against pathogen challenge, and growth or inhibition of cell cultures. Purification of human proinsulin has been achieved using novel purification strategies (inverse temperature transition property) that do not require expensive column chromatography techniques. Thus, transgenic chloroplasts are ideal bioreactors for production of functional human and animal therapeutic proteins in an environmentally friendly manner.


title: Prediction of Epidemic Peak and Infected Cases for COVID-19 Disease in Malaysia, 2020

text: The coronavirus COVID-19 has recently started to spread rapidly in Malaysia. The number of total infected cases has increased to 3662 on 05 April 2020, leading to the country being placed under lockdown. As the main public concern is whether the current situation will continue for the next few months, this study aims to predict the epidemic peak using the Susceptible–Exposed–Infectious–Recovered (SEIR) model, with incorporation of the mortality cases. The infection rate was estimated using the Genetic Algorithm (GA), while the Adaptive Neuro-Fuzzy Inference System (ANFIS) model was used to provide short-time forecasting of the number of infected cases. The results show that the estimated infection rate is 0.228 ± 0.013, while the basic reproductive number is 2.28 ± 0.13. The epidemic peak of COVID-19 in Malaysia could be reached on 26 July 2020, with an uncertain period of 30 days (12 July–11 August). Possible interventions by the government to reduce the infection rate by 25% over two or three months would delay the epidemic peak by 30 and 46 days, respectively. The forecasting results using the ANFIS model show a low Normalized Root Mean Square Error (NRMSE) of 0.041; a low Mean Absolute Percentage Error (MAPE) of 2.45%; and a high coefficient of determination (R(2)) of 0.9964. The results also show that an intervention has a great effect on delaying the epidemic peak and a longer intervention period would reduce the epidemic size at the peak. The study provides important information for public health providers and the government to control the COVID-19 epidemic.


title: Comparative venomics of Psyttalia lounsburyi and P. concolor, two olive fruit fly parasitoids: a hypothetical role for a GH1 β-glucosidase

text: Venom composition of parasitoid wasps attracts increasing interest – notably molecules ensuring parasitism success on arthropod pests – but its variation within and among taxa is not yet understood. We have identified here the main venom proteins of two braconid wasps, Psyttalia lounsburyi (two strains from South Africa and Kenya) and P. concolor, olive fruit fly parasitoids that differ in host range. Among the shared abundant proteins, we found a GH1 β-glucosidase and a family of leucine-rich repeat (LRR) proteins. Olive is extremely rich in glycoside compounds that are hydrolyzed by β-glucosidases into defensive toxic products in response to phytophagous insect attacks. Assuming that Psyttalia host larvae sequester ingested glycosides, the injected venom GH1 β-glucosidase could induce the release of toxic compounds, thus participating in parasitism success by weakening the host. Venom LRR proteins are similar to truncated Toll-like receptors and may possibly scavenge the host immunity. The abundance of one of these LRR proteins in the venom of only one of the two P. lounsburyi strains evidences intraspecific variation in venom composition. Altogether, venom intra- and inter-specific variation in Psyttalia spp. were much lower than previously reported in the Leptopilina genus (Figitidae), suggesting it might depend upon the parasitoid taxa.


title: Success of Big Infectious Disease Reimbursement Policy in China

text: Big infectious diseases do harm to the whole society, and it is highly crucial to control them on time. The major purpose of this article is to theoretically demonstrate that the Chinese government’s intervention in large-scale infectious diseases is successful and efficient. Two potential strategies were considered: strategy 1 was infectious disease without government intervention, and strategy 2 was infectious disease with government intervention. By evolution model, this article illustrates the efficiency of big infectious disease reimbursement policy in China. Without government reimbursement, this article finds that high expenditures accelerate the disease infection. The number of infected persons decreases under big infectious disease reimbursement policy in China. The higher the treatment costs, the more important the government intervention. Big infectious disease reimbursement policy in China can serve as an efficient example to cope with big infectious diseases.


title: N-Methylation as a Strategy for Enhancing the Affinity and Selectivity of RNA-binding Peptides: Application to the HIV-1 Frameshift-Stimulating RNA

text: [Image: see text] Human Immunodeficiency Virus (HIV) type 1 uses a −1 programmed ribosomal frameshift (−1 PRF) event to translate its enzymes from the same transcript used to encode the virus’ structural proteins. The frequency of this event is highly regulated, and significant deviation from the normal 5–10% frequency has been demonstrated to decrease viral infectivity. Frameshifting is primarily regulated by the Frameshift Stimulatory Signal RNA (FSS-RNA), a thermodynamically stable, highly conserved stem loop that has been proposed as a therapeutic target. We describe the design, synthesis, and testing of a series of N-methyl peptides able to bind the HIV-1 FSS RNA stem loop with low nanomolar affinity and high selectivity. Surface plasmon resonance (SPR) data indicates increased affinity is a reflection of a substantially enhanced on rate. Compounds readily penetrate cell membranes and inhibit HIV infectivity in a pseudotyped virus assay. Viral infectivity inhibition correlates with compound-dependent changes in the ratios of Gag and Gag-Pol in virus particles. As the first compounds with both single digit nanomolar affinities for the FSS RNA and an ability to inhibit HIV in cells, these studies support the use of N-methylation for enhancing the affinity, selectivity, and bioactivity of RNA-binding peptides.


Letter: does the IFNL4 gene discovery really provide a causal role for the IL28B haplotype blocks?


title: Not all world leaders use Twitter in response to the COVID-19 pandemic: impact of the way of Angela Merkel on psychological distress, behaviour and risk perception

text: At a time of growing governmental restrictions and ‘physical distancing’ in order to decelerate the spread of COVID-19, psychological challenges are increasing. Social media plays an important role in maintaining social contact as well as exerting political influence. World leaders use it not only to keep citizens informed but also to boost morale and manage people’s fears. However, some leaders do not follow this approach; an example is the German Chancellor. In a large online survey, we aimed to determine levels of COVID-19 fear, generalized anxiety, depression, safety behaviour, trust in government and risk perception in Germany. A total of 12 244 respondents participated during the period of restraint and the public shutdown in March 2020. Concurrent with the German Chancellor’s speech, a reduction of anxiety and depression was noticeable in the German population. It appears that, in addition to using social media platforms like Twitter, different—and sometimes more conservative—channels for providing information can also be effective.


title: Independent review of emergency economic stimulus measures: Global Financial Crisis and COVID‐19

text: Major government emergency interventions demand, and generally receive, independent scrutiny. This article looks back at reviews of the Australian government's economic stimulus measures introduced in the aftermath of the 2008 Global Financial Crisis (GFC), in anticipation of reviews of responses to the COVID‐19 emergency, noting similarities and differences between the two crises. We examine 10 independent reviews of the Australian government's response to the GFC with a particular focus on their nature and the context in which they occurred. As a result, we identify five themes: when and how often reviews are conducted; recognition of context; the need for clear program objectives; explicit design principles; and governance. We develop a typology of independent reviews that has three key and interrelated dimensions: purpose, timing, and reviewer. We observe that there was patchwork coverage of the GFC measures, with no single report providing a holistic assessment of what was achieved or lessons learnt. We contend that, notwithstanding differences between crises, the typology will aid understanding of the role, key issues, and contributions of reviews that have already been, or will be, commissioned into COVID‐19 and future emergency economic stimulus measures.


Effect of COVID-19 Pandemic and Lockdown on Children With Gastrointestinal Disorders


title: Gut-lung axis and dysbiosis in COVID-19

text: COVID-19, a novel infectious disease, caused by SARS-CoV-2, affected millions of people around the world with a high mortality rate. Although SARS-CoV-2 mainly causes lung infection, gastrointestinal symptoms described in COVID-19 patients and detection of the viral RNA in feces of infected patients drove attentions to a possible fecal-oral transmission route of SARS-CoV-2. However, not only the viral RNA but also the infectious viral particles are required for the viral infection and no proof has been demonstrated the transmission of the infectious virus particles via the fecal-oral route yet. Growing evidence indicates the crosstalk between gut microbiota and lung, that maintains host homeostasis and disease development with the association of immune system. This gut-lung interaction may influence the COVID-19 severity in patients with extrapulmonary conditions. Severity of COVID-19 has mostly associated with old ages and underlying medical conditions. Since the diversity in the gut microbiota decreases during aging, dysbiosis could be the reason for older adults being at high risk for severe illness from COVID-19. We believe that gut microbiota contributes to the course of COVID-19 due to its bidirectional relationship with immune system and lung. Dysbiosis in gut microbiota results in gut permeability leading to secondary infection and multiple organ failure. Conversely, disruption of the gut barrier integrity due to dysbiosis may lead to translocation of SARS-CoV-2 from the lung into the intestinal lumen via circulatory and lymphatic system. This review points out the role of dysbiosis of the gut microbiota involving in sepsis, on the severity of SARS-CoV-2 infection. Additionally, this review aims to clarify the ambiguity in fecal-oral transmission of SARS- CoV-2.


title: Measurement of abomasal conditions (pH, pressure and temperature) in healthy and diarrheic dairy calves using a wireless ambulatory capsule

text: Abstract This study investigated abomasal luminal parameters in healthy and diarrheic calves by using a wireless ambulatory capsule (WAC). The acetaminophen absorption test (APAT) was used to determine abomasal emptying rate. Four healthy and five diarrheic female Holstein-Friesian calves (age < 14 days) were included in the study. For APAT, calves were fed 2L of milk replacer containing 50mg acetaminophen/kg body weight, and blood samples were taken during a 12-h period afterward. Concomitantly, a WAC in the abomasum continuously measured luminal pH, pressure, and temperature. Five hours post suckling, intraluminal temperature was significantly higher in diarrheic calves than in healthy calves. Abomasal pH and pressure were not significantly different, but intraluminal pressure was always numerically lower in diarrheic calves. During APAT no significant differences in maximum acetaminophen concentrations (Cmax) and time to reach maximum acetaminophen concentration (Tmax) were observed. Nonlinear regression findings revealed a longer acetaminophen half-time (AAP t1/2) in diarrheic calves compared to healthy calves [564 ± 96min vs. 393 ± 84min, respectively; P = 0.04] and lower area under the concentration curve values (e.g., 60min postprandial AUC60 681 ± 244 (µg∙min)/mL vs. 1064 ± 23 (µg∙min)/mL, respectively; P = 0.04). In conclusion, abomasal luminal conditions were different between diarrheic and healthy calves. Significant differences in APAT reflected a delay in abomasal emptying in diarrheic calves. Impaired abomasal movement may induce enhanced bacterial fermentation processes as indicated by a higher abomasal temperature in diarrheic calves, which should be considered in management of their feeding.


Commentary: What happens after the lockdown?


title: Diagnosis of ventilator-associated pneumonia in critically ill adult patients—a systematic review and meta-analysis

text: The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06036-z) contains supplementary material, which is available to authorized users.


title: Isolation and characterization of adenoviruses infecting endangered golden snub-nosed monkeys (Rhinopithecus roxellana)

text: BACKGROUND: Adenoviruses are important pathogens with the potential for interspecies transmission between humans and non-human primates. Although many adenoviruses have been identified in monkeys, the knowledge of these viruses from the Colobinae members is quite limited. FINDINGS: We conducted a surveillance of viral infection in endangered golden snub-nosed monkeys (Rhinopithecus roxellana) in the subfamily Colobinae in China, and found that 5.1% of sampled individuals were positive for adenovirus. One of the adenoviruses (SAdV-WIV19) was successfully isolated and its full-length genome was sequenced. The full-length genome of WIV19 is 33,562 bp in size, has a G + C content of 56.2%, and encodes 35 putative genes. Sequence analysis revealed that this virus represents a novel species in the genus Mastadenovirus. Diverse cell lines, including those of human origin, were susceptible to WIV19. CONCLUSION: We report the first time the isolation and full-length genomic characterization of an adenovirus from the subfamily Colobinae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0648-6) contains supplementary material, which is available to authorized users.


Dispatches


title: Matrix metallopeptidase 9 as a host protein target of chloroquine and melatonin for immunoregulation in COVID-19: A network-based meta-analysis

text: AIMS: The molecular pathogenesis of COVID-19 is similar to other coronavirus (CoV) infections viz. severe acute respiratory syndrome (SARS) in human. Due to scarcity of the suitable treatment strategy, the present study was undertaken to explore host protein(s) targeted by potent repurposed drug(s) in COVID-19. MATERIALS AND METHODS: The differentially expressed genes (DEGs) were identified from microarray data repository of SARS-CoV patient blood. The repurposed drugs for COVID-19 were selected from available literature. Using DEGs and drugs, the protein-protein interaction (PPI) and chemo-protein interaction (CPI) networks were constructed and combined to develop an interactome model of PPI-CPI network. The top-ranked sub-network with its hub-bottleneck nodes were evaluated with their functional annotations. KEY FINDINGS: A total of 120 DEGs and 65 drugs were identified. The PPI-CPI network (118 nodes and 293 edges) exhibited a top-ranked sub-network (35 nodes and 174 connectivities) with 12 hub-bottleneck nodes having two drugs chloroquine and melatonin in association with 10 proteins corresponding to six upregulated and four downregulated genes. Two drugs interacted directly with the hub-bottleneck node i.e. matrix metallopeptidase 9 (MMP9), a host protein corresponding to its upregulated gene. MMP9 showed functional annotations associated with neutrophil mediated immunoinflammation. Moreover, literature survey revealed that angiotensin converting enzyme 2, a membrane receptor of SARS-CoV-2 virus, might have functional cooperativity with MMP9 and a possible interaction with both drugs. SIGNIFICANCE: The present study reveals that between chloroquine and melatonin, melatonin appears to be more promising repurposed drug against MMP9 for better immunocompromisation in COVID-19.


title: Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure

text: Summary Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.


title: Immunogenicity of transmissible gastroenteritis virus (TGEV) M gene delivered by attenuated Salmonella typhimurium in mice

text: Attenuated Salmonella typhimurium (S. typhimurium) was selected as a transgenic vehicle for the development of live mucosal vaccines against transmissible gastroenteritis virus (TGEV) based on the M gene. An approximate 1.0 kb DNA fragment, encoding for glycoprotein M, was amplified by RT-PCR and cloned into eukaryotic expression vector pVAX1. The recombinant plasmid pVAX-M was transformed by electroporation into attenuated S. typhimurium SL7207, and the expression and translation of the pVAX-M delivered by recombinant S. typhimurium SL7207 (pVAX-M) was detected both in vitro and in vivo. BALB/c mice were inoculated orally with SL7207 (pVAX-M) at different dosages to evaluate safety of the vaccines. The bacterium was safe to mice at a dosage of 2 × 10(9) CFU, almost eliminated from the spleen and liver at week 4 post-immunization and eventually cleared at week 6. Mice immunized with 1 × 10(9) CFU of SL7207 (pVAX-M) elicited specific anti-TGEV local mucosal and humoral responses including levels of IgA, IgG, IL-4, and IFN-γ as measured by indirect ELISA assay. Moreover, the control groups (pVAX group, PBS group) maintained at a normal level during week 4–8 post-immunization. The results indicated that attenuated S. typhimurium could be used as a delivery vector for oral immunization of TGEV M gene vaccine.


title: Virus entry paradigms

text: Viruses, despite being relatively simple in structure and composition, have evolved to exploit complex cellular processes for their replication in the host cell. After binding to their specific receptor on the cell surface, viruses (or viral genomes) have to enter cells to initiate a productive infection. Though the entry processes of many enveloped viruses is well understood, that of most non-enveloped viruses still remains unresolved. Recent studies have shown that compared to direct fusion at the plasma membrane, endocytosis is more often the preferred means of entry into the target cell. Receptor-mediated endocytic pathways such as the dynamin-dependent clathrin and caveolar pathways are well characterized as viral entry portals. However, many viruses are able to utilize multiple uptake pathways. Fluid phase uptake, though relatively non-specific in terms of its cargo, potentially aids viral infection by its ability to intersect with the endocytic pathway. In fact, many viruses despite using specialized pathways for entry are still able to generate productive infection via fluid phase uptake. Macropinocytosis, a major fluid uptake pathway found in epithelial cells and fibroblasts, is stimulated by growth factor receptors. Many viruses can induce these signaling cascades in cells leading to macropinocytosis. Though endocytic trafficking is utilized by both enveloped and non-enveloped viruses, key differences lie in the way membranes are traversed to deposit the viral genome at its site of replication. This review will discuss recent developments in the rapidly evolving field of viral entry.


title: An evaluation of emergency guidelines issued by the World Health Organization in response to four infectious disease outbreaks

text: BACKGROUND: The production of high-quality guidelines in response to public health emergencies poses challenges for the World Health Organization (WHO). The urgent need for guidance and the paucity of structured scientific data on emerging diseases hinder the formulation of evidence-informed recommendations using standard methods and procedures. OBJECTIVES: In the context of the response to recent public health emergencies, this project aimed to describe the information products produced by WHO and assess the quality and trustworthiness of a subset of these products classified as guidelines. METHODS: We selected four recent infectious disease emergencies: outbreaks of avian influenza A—H1N1 virus (2009) and H7N9 virus (2013), Middle East respiratory syndrome coronavirus (MERS-CoV) (2013), and Ebola virus disease (EVD) (2014 to 2016). We analyzed the development and publication processes and evaluated the quality of emergency guidelines using AGREE-II. RESULTS: We included 175 information products of which 87 were guidelines. These products demonstrated variable adherence to WHO publication requirements including the listing of external contributors, management of declarations of interest, and entry into WHO’s public database of publications. For guidelines, the methods for development were incompletely reported; WHO’s quality assurance process was rarely used; systematic or other evidence reviews were infrequently referenced; external peer review was not performed; and they scored poorly with AGREE II, particularly for rigour of development and editorial independence. CONCLUSIONS: Our study suggests that WHO guidelines produced in the context of a public health emergency can be improved upon, helping to assure the trustworthiness and utility of WHO information products in future emergencies.


title: Proposed Intranasal Route for Drug Administration in the Management of Central Nervous System Manifestations of COVID-19

text: [Image: see text] There is mounting evidence of the central nervous system manifestations associated with COVID-19, particularly in severe cases. Up to 25% of COVID-19 cases exhibit neurological manifestations associated with COVID-19. In view of the devastating nature of the disease due to severe acute respiratory syndrome coronavirus 2, here we debate intranasal drug delivery, in addition to intravenous delivery, as a therapeutic strategy in the management of COVID-19 cases with central nervous system involvement.


title: More effective strategies are required to strengthen public awareness of COVID-19: Evidence from Google Trends

text: BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has posed stress on the health and well-being of both Chinese people and the public worldwide. Global public interest in this new issue largely reflects people’s attention to COVID-19 and their willingness to take precautionary actions. This study aimed to examine global public awareness of COVID-19 using Google Trends. METHODS: Using Google Trends, we retrieved public query data for terms of “2019-nCoV + SARS-CoV-2 + novel coronavirus + new coronavirus + COVID-19 + Corona Virus Disease 2019” between the 31(st) December 2019 and the 24(th) February 2020 in six major English-speaking countries, including the USA, the UK, Canada, Ireland, Australia, and New Zealand. Dynamic series analysis demonstrates the overall change trend of relative search volume (RSV) for the topic on COVID-19. We compared the top-ranking related queries and sub-regions distribution of RSV about COVID-19 across different countries. The correlation between daily search volumes on the topic related to COVID-19 and the daily number of people infected with SARS-CoV-2 was analyzed. RESULTS: The overall search trend of RSV regarding COVID-19 increased during the early period of observing time and reached the first apex on 31(st) January 2020. A shorter response time and a longer duration of public attention to COVID-19 was observed in public from the USA, the UK, Australia, and Canada, than that in Ireland and New Zealand. A slightly positive correlation between daily RSV about COVID-19 and the daily number of confirmed cases was observed (P < 0.05). People across countries presented a various interest to the RSV on COVID-19, and public awareness of COVID-19 was different in various sub-regions within countries. CONCLUSIONS: The results suggest that public response time to COVID-19 was different across countries, and the overall duration of public attention was short. The current study reminds us that governments should strengthen the publicity of COVID-19 nationally, strengthen the public's vigilance and sensitivity to COVID-19, inform public the importance of protecting themselves with enough precautionary measures, and finally control the spread of COVID-19 globally.


title: Phenotypic characteristics of human type II alveolar epithelial cells suitable for antigen presentation to T lymphocytes

text: BACKGROUND: Type II alveolar epithelial cells (AECII) are well known for their role in the innate immune system. More recently, it was proposed that they could play a role in the antigen presentation to T lymphocytes but contradictory results have been published both concerning their surface expressed molecules and the T lymphocyte responses in mixed lymphocyte cultures. The use of either AECII cell line or fresh cells could explain the observed discrepancies. Thus, this study aimed at defining the most relevant model of accessory antigen presenting cells by carefully comparing the two models for their expression of surface molecules necessary for efficient antigen presentation. METHODS: We have compared by flow cytometry the surface expression of the major markers involved in the immunological synapse on the A549 cell line, the most popular model of type II alveolar epithelial cells, and freshly isolated cells. HLA-DR, CD80, CD86, ICOS-L, CD54, CD58 surface expression were studied in resting conditions as well as after IFN-γ/TNF-α treatment, two inflammatory cytokines, known to modulate some of these markers. RESULTS: The major difference found between the two cells types was the very low surface expression of HLA-DR on the A549 cell line compared to its constitutive expression on freshly isolated AECII. The surface expression of co-stimulatory molecules from the B7 family was very low for the CD86 (B7-2) and ICOS-L (B7-H2) and absent for CD80 (B7-1) on both freshly isolated cells and A549 cell line. Neither IFN-γ nor TNF-α could increase the expression of these classical co-stimulatory molecules. However CD54 (ICAM-1) and CD58 (LFA-3) adhesion molecules, known to be implicated in B7 independent co-stimulatory signals, were well expressed on the two cell types. CONCLUSIONS: Constitutive expression of MHC class I and II molecules as well as alternative co-stimulatory molecules by freshly isolated AECII render these cells a good model to study antigen presentation.


title: Public health education at China’s higher education institutions: a time-series analysis from 1998 to 2012

text: BACKGROUND: Although China’s modern education for public health was developing over the past 60 years, there is a lack of authoritative statistics and analyses on the nation’s development of education for public health at higher education institutions (HEIs). Few quantitative studies on this topic have been published in domestic and international peer-reviewed journals. To address this knowledge gap, we aimed to use national data to quantitatively analyse the scale, structure, and changes of public health education in China’s HEIs, and to compare the changes of public health education with those of other health science disciplines. METHODS: This study uses previously unreleased national data provided by the Ministry of Education of China that includes the number of health professional students by school and major. The data, which spans from 1998 to 2012, are descriptively analyzed. RESULTS: The number of HEIs for public health education per 100 million population increased from 7.2 in 1998 to 11.3 in 2012. The total enrolment, number of students, and number of graduates increased at rates of 7.3, 7.4, and 5.8% per year, respectively. The percentage of junior college students dropped drastically from 24.0 to 8.4% from 1998 to 2012. During that same period, the number of undergraduates, master and doctorate students increased. Undergraduates accounted for the majority of public health graduates (63.1%) in 2012, and master and doctorate students increased by 10.0 and 5.1 times, respectively, from 1998 to 2012. The relative percentage of public health enrollment, students, and graduates to all health education disciplines dropped from about 6.0% percent in 1998 to around 2% in 2012. CONCLUSIONS: The overall scale of public health education has clearly expanded, though at a slower pace than many other health science disciplines in China. The increase of public health graduates helped to address the previous shortage of public health professionals. Gradually adopting a modern model of education, public health education in China has undergone notable changes that may be informative to other developing countries though it still faces a complex situation in terms of graduates’ adherence to public health, student recruitment, teaching and training, program planning and reform.


Chapter 51 Respiratory Viral Vaccines


title: Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy

text: Immunosuppression is the predominant cause of mortality for sepsis due to failure to eradicate invading pathogens. Unfortunately, no effective and specific drugs capable of reversing immunosuppression are available for clinical use. Increasing evidence implicates vitamin D receptor (VDR) involved in sepsis-induced immunosuppression. Herein, artesunate (AS) was discovered to reverse sepsis-induced immunosuppression and its molecular mechanism is investigated. Effect of artesunate on sepsis-induced immunosuppression was investigated in mice and in vitro. VDR was predicted to be an interacted candidate of AS by bioinformatics predict, then identified using PCR and immunoblotting. VDR, ATG16L1 and NF-κB p65 were modified to investigate the alteration of AS’s effect on pro-inflammatory cytokines release, bacteria clearance and autophagy activities in sepsis-induced immunosuppression. AS significantly reduced the mortality of cecal ligation and puncture (CLP)-induced sepsis immunosuppression mice challenged with Pseudomonas Aeruginosa, and enhanced proinflammatory cytokines release and bacterial clearance to reverse sepsis-induced immunosuppression in vivo and in vitro. Mechanically, AS interacted with VDR thereby inhibited the nuclear translocation of VDR, then influencing ATG16L1 transcription and subsequent autophagy activity. In addition, AS inhibited physical interaction between VDR and NF-κB p65 in LPS tolerance macrophages, then promoted nuclear translocation of NF-κB p65, which activated the transcription of NF-κB p65 target genes such as pro-inflammatory cytokines. Our findings provide an evidence that AS interacted with VDR to reverse sepsis-induced immunosuppression in an autophagy and NF-κB dependent way, highlighting a novel approach for sepsis treatment and drug repurposing of AS in the future.


title: A review on versatile applications of transition metal complexes incorporating Schiff bases

text: Abstract Schiff bases and their complexes are versatile compounds synthesized from the condensation of an amino compound with carbonyl compounds and widely used for industrial purposes and also exhibit a broad range of biological activities including antifungal, antibacterial, antimalarial, antiproliferative, anti-inflammatory, antiviral, and antipyretic properties. Many Schiff base complexes show excellent catalytic activity in various reactions and in the presence of moisture. Over the past few years, there have been many reports on their applications in homogeneous and heterogeneous catalysis. The high thermal and moisture stabilities of many Schiff base complexes were useful attributes for their application as catalysts in reactions involving at high temperatures. The activity is usually increased by complexation therefore to understand the properties of both ligands and metal can lead to the synthesis of highly active compounds. The influence of certain metals on the biological activity of these compounds and their intrinsic chemical interest as multidentate ligands has prompted a considerable increase in the study of their coordination behaviour. Development of a new chemotherapeutic Schiff bases and their metal complexes is now attracting the attention of medicinal chemists. This review compiles examples of the most promising applied Schiff bases and their complexes in different areas.


title: Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents

text: Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.


title: Pichia pastoris: A highly successful expression system for optimal synthesis of heterologous proteins

text: One of the most important branches of genetic engineering is the expression of recombinant proteins using biological expression systems. Nowadays, different expression systems are used for the production of recombinant proteins including bacteria, yeasts, molds, mammals, plants, and insects. Yeast expression systems such as Saccharomyces cerevisiae (S. cerevisiae) and Pichia pastoris (P. pastoris) are more popular. P. pastoris expression system is one of the most popular and standard tools for the production of recombinant protein in molecular biology. Overall, the benefits of protein production by P. pastoris system include appropriate folding (in the endoplasmic reticulum) and secretion (by Kex2 as signal peptidase) of recombinant proteins to the external environment of the cell. Moreover, in the P. pastoris expression system due to its limited production of endogenous secretory proteins, the purification of recombinant protein is easy. It is also considered a unique host for the expression of subunit vaccines which could significantly affect the growing market of medical biotechnology. Although P. pastoris expression systems are impressive and easy to use with well‐defined process protocols, some degree of process optimization is required to achieve maximum production of the target proteins. Methanol and sorbitol concentration, Mut forms, temperature and incubation time have to be adjusted to obtain optimal conditions, which might vary among different strains and externally expressed protein. Eventually, optimal conditions for the production of a recombinant protein in P. pastoris expression system differ according to the target protein.


title: Growth enhancement of porcine epidemic diarrhea virus (PEDV) in Vero E6 cells expressing PEDV nucleocapsid protein

text: More recently emerging strains of porcine epidemic diarrhea virus (PEDV) cause severe diarrhea and especially high mortality rates in infected piglets, leading to substantial economic loss to worldwide swine industry. These outbreaks urgently call for updated and effective PEDV vaccines. Better understanding in PEDV biology and improvement in technological platforms for virus production can immensely assist and accelerate PEDV vaccine development. In this study, we explored the ability of PEDV nucleocapsid (N) protein in improving viral yields in cell culture systems. We demonstrated that PEDV N expression positively affected both recovery of PEDV from infectious clones and PEDV propagation in cell culture. Compared to Vero E6 cells, Vero E6 cells expressing PEDV N could accelerate growth of a slow-growing PEDV strain to higher peak titers by 12 hours or enhance the yield of a vaccine candidate strain by two orders of magnitude. Interestingly, PEDV N also slightly enhances replication of porcine reproductive and respiratory virus, a PEDV relative in the Nidovirales order. These results solidify the importance of N in PEDV recovery and propagation and suggest a potentially useful consideration in designing vaccine production platforms for PEDV or closely related pathogens.


How is COVID-19 going to affect education in neurosurgery? A step toward a new era of educational training


Coronavirus disease 2019 (COVID‐19) outbreak: Could pigs be vectors for human infections?


title: Longitudinal Change of SARS-Cov2 Antibodies in Patients with COVID-19

text: BACKGROUND: A novel coronavirus, SARS-CoV-2, has recently emerged and caused the rapid spread of COVID-19 worldwide. METHODS: We did a retrospective study and included COVID-19 patients admitted to Renmin Hospital of Wuhan University between February 1 and February 29, 2020. Antibody assay was conducted to detect COVID-19 envelope protein E and nucleocapsid protein N antigen. RESULTS: 112 patients were recruited with symptoms of fever, cough, fatigue, myalgia, and diarrhoea. All patients underwent antibody tests. Fifty-eight (51.79%) were positive for both IgM and IgG, 7 (6.25%) were negative for both antibodies, 1 (0.89%) was positive for only IgM, and 46 (41.07%) were positive for only IgG. IgM antibody appeared within a week post disease onset, and lasted for one month and gradually decreased, while IgG antibody was produced 10 days after infection, and lasted for a longer time. However, no significant difference in level of IgM and IgG antibody between positive and negative patients of nucleic acid test after treatment was found. CONCLUSIONS: Our results indicate that serological tests could be powerful approach for the early diagnosis of COVID-19.


title: A single T cell epitope drives the neutralizing anti-drug antibody response to natalizumab in multiple sclerosis patients

text: Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)(1,2), but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation(3,4). To understand the basis of the ADA response and the mechanism of ADA-mediated neutralization, we performed an in-depth analysis of the B and T cell responses in two patients. By characterizing a large panel of NZM-specific monoclonal antibodies, we found that, in both patients, the response was polyclonal and targeted different epitopes of the NZM idiotype. The neutralizing activity was acquired through somatic mutations and correlated with a slow dissociation rate, a finding that was supported by structural data. Interestingly, in both patients, the analysis of the CD4(+) T cell response, combined with mass spectrometry-based peptidomics, revealed a single immunodominant T cell epitope spanning the FR2-CDR2 region of the NZM light chain. Moreover, a CDR2-modified version of NZM was not recognized by T cells, while retaining binding to α4 integrins. Collectively, our integrated analysis identifies the basis of T-B collaboration that leads to ADA-mediated therapeutic resistance and delineates an approach to design novel deimmunized antibodies for autoimmune disease and cancer treatment.


SARS-CoV-2 in Romania - situation update and containment strategies.


title: A cluster of coxsackievirus A21 associated acute respiratory illness: the evidence of efficient transmission of CVA21

text: In March 2016, a cluster of unexplained respiratory illnesses was reported by the acute respiratory infections (ARI) surveillance system of Guangdong Province, China. Twenty-three high school students and one teacher from the four neighboring classes were admitted to a hospital. CVA21 was found in eight of fourteen patients. Phylogenetic analysis suggested that the CVA21 outbreak was most likely caused by transmission of the virus from person to person. This is the first report of an ARI outbreak caused by CVA21, which suggests that CVA21 has the potential to be transmitted efficiently from person to person and should be closely monitored by clinicians and public health agencies.


title: Chapter 10 Pathogenesis and the gastrointestinal tract of growing fish

text: Publisher Summary This chapter presents information on (1) adhesion of bacteria to mucosal surfaces, (2) protection against bacterial adhesion, (3) bacterial translocation, (4) invasion of host cells, (5) effect of diet in disease resistance, and (6) data obtained from endothermic animals, which may have relevance to pathogenesis of fish. A number of bacteria cause pathology in the gut of fish and this can be a route of systemic infection in many instances, comparable to that of invasive enteropathogens of mammals. To adhere successfully, colonize, and produce disease, the pathogen must overcome the host defence system. Adhesion of bacteria to surfaces such as epithelial cells involves different types of interaction, depending on the distance separating the bacteria from the surface. The indigenous intestinal flora is prevented from gaining access to other sites in the body by a single epithelial cell layer on the mucosa. The mechanisms that help the bacteria to translocate from the gut to appear in other organs are an important phenomenon in the pathogenesis of opportunistic infections by indigenous intestinal bacteria. Entry into host cells is a specialized strategy for survival and multiplication utilized by a number of pathogens that can exploit existing eukaryotic internalization pathways. Methods including the use of expressed markers such as green fluorescent protein and laser confocal microscopy will provide more definitive analysis of pathways of invasion by pathogens taken up via the gastrointestinal (GI) tract.


title: Development of a Screening and Isolation Protocol for Patients Presenting to the Emergency Department (ED) with Communicable Diseases

text: ISSUE: The 2003 outbreak of Severe Acute Respiratory Syndrome (SARS) underscored the importance of rapid recognition and isolation of patients with highly communicable diseases to prevent nosocominal spread to other patients, staff, and visitors. The SARS issue and a recent outbreak of measles in New York City (NYC) highlighted the need for EDs to have effective measures to rapidly triage and isolate patients with potentially communicable illnesses. PROJECT: A multidisciplinary team at a NYC hospital developed a screening and isolation protocol in collaboration with the NYC Department of Health and Mental Hygiene. Education and training was provided through classroom instruction using a train the trainer format. This training included a power point presentation along with interactive case scenarios. Pre and post tests, and a series of unannounced drills were used to evaluate the process. RESULTS: Ninety percent of registered nurses, 67% of emergency medical physicians, 82% of emergency service assistants, 63% of patient access workers and 73% of social workers in the ED were in-serviced. Patient access workers failed to follow the quick registration process for patients presenting with a cough. The triage nurse was able to isolate the patient based on symptoms and travel history, and knew the appropriate mask to be worn by the patient versus the medical staff. However, basic infection control including hand hygiene was not consistently practiced. Personal Protective Equipment was not readily available in the triage area. LESSONS LEARNED: Although a large proportion of the ED staff received training, breaches in basic infection control were observed. Consistency of educational in-service was difficult to assure using the train the trainer format. Increased involvement of Infection Control Professionals is needed to help translate education into practice, and to improve compliance with procedures.


docid: rixuuytu

title: Estrogen Mediates Innate and Adaptive Immune Alterations to Influenza Infection in Pregnant Mice

text: Pregnancy is a leading risk factor for severe complications during an influenza virus infection. Women infected during their second and third trimesters are at increased risk for severe cardiopulmonary complications, premature delivery, and death. Here, we establish a murine model of aerosolized influenza infection during pregnancy. We find significantly altered innate antiviral responses in pregnant mice, including decreased levels of IFN-β, IL-1α, and IFN-γ at early time points of infection. We also find reduced cytotoxic T cell activity and delayed viral clearance. We further demonstrate that pregnancy levels of the estrogen 17-β-estradiol are able to induce key anti-inflammatory phenotypes in immune responses to the virus independently of other hormones or pregnancy-related stressors. We conclude that elevated estrogen levels result in an attenuated anti-viral immune response, and that pregnancy-associated morbidities occur in the context of this anti-inflammatory phenotype.


title: Viral pathogens associated with acute lower respiratory tract infections in children younger than 5 years of age in Bulgaria

text: Acute lower respiratory infections (ALRIs) are a leading cause of morbidity and hospital admissions in children. This study aimed to determine the viral etiology of these infections in children aged < 5 years during three successive epidemic seasons in Bulgaria. Nasopharyngeal and throat specimens were collected from children with bronchiolitis and pneumonia during the 2015/2016, 2016/2017, and 2017/2018 seasons. The viral etiology was determined by individual real-time PCR assays against 11 respiratory viruses. Of the 515 children examined, 402 (78.1%) were positive for at least one virus. Co-infections with two and three viruses were found in 64 (15.9%) of the infected children. Respiratory syncytial virus (RSV) was the predominant pathogen (37.5%), followed by rhinoviruses (13.8%), metapneumovirus (9.1%), adenoviruses (7%), bocaviruses (7%), influenza A(H1N1)pdm09 (4.9%), A(H3N2) (4.3%), type B (4.1%), and parainfluenza viruses 1/2/3 (2.9%). RSV-B were more prevalent than RSV-A during the three seasons. At least one respiratory virus was identified in 82.6% and 70.1% of the children with bronchiolitis and pneumonia, respectively. Respiratory viruses, especially RSV, are principal pathogens of ALRIs in children aged < 5 years. Diagnostic testing for respiratory viruses using molecular methods may lead to the reduced use of antibiotics and may assist in measures to control infection.


title: Clinical Characteristics of 312 Hospitalized Older Patients with COVID-19 in Wuhan, China

text: OBJECTIVES: Much of the previous research on COVID-19 was based on all population. But substantial numbers of severe episodes occur in older patients. There is a lack of data about COVID-19 in older adults. The aims of this study were to analyze the clinical characteristics of older adult patients with COVID-19. METHODS: Retrospective study of older patients hospitalized with COVID-19 from February 1 st to March 31 st, 2020 was conducted in the Sino-French New City Branch of Tongjing Hospital in Wuhan, China. According to the degree of severity of COVID-19 during hospitalization, 312 older patients were divided into non-severe and severe cases. RESULTS: the mean age of the patients was 69.2 ± 7.3 years, and 47.4% of patients had exposure history. 77.2% of patients had a co-morbidity, with hypertension being the most common(57.1%), followed by diabetes(38.8%) and cardiovascular disease(29.8%). Multivariable regression showed increasing odds of severe COVID-19 associated with age(OR 1.59, 95%CI 1.13-2.08), SOFA score(OR 5.89, 95%CI 3.48-7.96), APACHEⅡ score(OR 3.13, 95%CI 1.85-5.62), platelet count＜125 × 10(9)/L(OR 2.36, 95%CI 1.03-4.14), d-dimer(OR 4.37, 95%CI 2.58-7.16), creatinine＞133 μmol/L(OR 1.85, 95%CI 1.12-3.04), interleukin-6(OR 4.32, 95%CI 2.07-7.13), and lung consolidation(OR 1.94, 95%CI 1.45-4.27) on admission. The most common complication was acute respiratory distress syndrome(35.6%), followed by acute cardiac injury(33.0%) and coagulation disorders(30.8%). 91.7% of patients were prescribed antiviral therapy, followed by immune globulin(52.9%) and systemic glucocorticoids(43.6%). 21.8% of patients received invasive ventilation, 1.92% for extracorporeal membrane oxygenation. The overall mortality was 6.73%, and mortality of severe patients was 17.1%, which was higher than non-severe patients(0.962%). CONCLUSIONS: Older patients with COVID-19 had much more co-morbidity, complications and mortality. More attention should be paid to older patients with COVID-19.


title: Prevalence of Enteropathogens in Suckling and Weaned Piglets with Diarrhoea in Southern Germany

text: Faecal samples from suckling (n=205) and weaned piglets (n=82) with diarrhoea from 24 farms in Southern Germany were examined for shedding of important metazoic parasitic, viral and bacterial pathogens using culture, microscopic and electronmicroscopic methods. Escherichia coli isolates were tested further for the enterotoxin genes est‐Ia and elt‐I by colony blot hybridization. Isospora suis was diagnosed in 26.9 % and Cryptosporidium parvum in 1.4 % of the piglets investigated. The proportion of coronavirus‐positive animals was 13.4 % and 4 % were positive for rotavirus. It was found that 17.6 % of the animals were infected with enterotoxigenic E. coli (ETEC; 10.1 % ETEC‐ST‐Ia and 8.6 % ETEC‐LT‐I, respectively). The occurrence of the pathogens was significantly associated with the age of the animals examined (P < 0.001). Isospora suis was predominantly isolated from suckling piglets (in the second and third week of life), while in weaned piglets (fourth week of life) rotavirus and ETEC were most prevalent. On 22 of the 24 piglet production farms examined at least one of the investigated pathogens was detected. Coronavirus was diagnosed in 66.7 %, I. suis in 62.5 %, rotavirus in 20.8 % and C. parvum in 8.3 % of the farms. These results underline the fact that despite the hygienic, technical and immune preventive efforts during the last years, enteropathogens are still common in German piglet production units.


title: Whole-lung Low Dose Irradiation for SARS-Cov2 Induced Pneumonia in the Geriatric Population: An Old Effective Treatment for a New Disease? Recommendation of the International Geriatric Radiotherapy Group

text: A cytokine storm induced by SARS-Cov2 may produce pneumonitis which may be fatal for older patients with underlying lung disease. Hyper-elevation of Interleukin1 (IL-1), Tumor necrosis factor-1alfa (TNF-1 alfa), and Interleukin 6 (IL-6) produced by inflammatory macrophage M1 may damage the lung alveoli leading to severe pneumonitis, decreased oxygenation, and potential death despite artificial ventilation. Older patients may not be suitable candidates for pharmaceutical intervention targeting IL-1/6 blockade or artificial ventilation. Low dose total lung (LDTL) irradiation at a single dose of 50 cGy may stop this cytokine cascade, thus preventing, and/or reversing normal organs damage. This therapy has been proven in the past to be effective against pneumonitis of diverse etiology and could be used to prevent death of older infected patients. Thus, LDRT radiotherapy may be a cost-effective treatment for this frail patient population whom radiation -induced malignancy is not a concern because of their advanced age. This hypothesis should be tested in future prospective trials.


title: SARS-CoV-2 Infections and Serologic Responses from a Sample of U.S. Navy Service Members — USS Theodore Roosevelt, April 2020

text: Compared with the volume of data on coronavirus disease 2019 (COVID-19) outbreaks among older adults, relatively few data are available concerning COVID-19 in younger, healthy persons in the United States (1,2). In late March 2020, the aircraft carrier USS Theodore Roosevelt arrived at port in Guam after numerous U.S. service members onboard developed COVID-19. In April, the U.S. Navy and CDC investigated this outbreak, and the demographic, epidemiologic, and laboratory findings among a convenience sample of 382 service members serving aboard the aircraft carrier are reported in this study. The outbreak was characterized by widespread transmission with relatively mild symptoms and asymptomatic infection among this sample of mostly young, healthy adults with close, congregate exposures. Service members who reported taking preventive measures had a lower infection rate than did those who did not report taking these measures (e.g., wearing a face covering, 55.8% versus 80.8%; avoiding common areas, 53.8% versus 67.5%; and observing social distancing, 54.7% versus 70.0%, respectively). The presence of neutralizing antibodies, which represent antibodies that inhibit SARS-CoV-2, among the majority (59.2%) of those with antibody responses is a promising indicator of at least short-term immunity. This report improves the understanding of COVID-19 in the U.S. military and among young adults in congregate settings and reinforces the importance of preventive measures to lower risk for infection in similar environments.


title: Protective Efficacy of VP1-Specific Neutralizing Antibody Associated with a Reduction of Viral Load and Pro-Inflammatory Cytokines in Human SCARB2-Transgenic Mice

text: Hand-foot-mouth diseases (HFMD) caused by enterovirus 71 (EV71) and coxsackievirus 16 (CVA16) in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16) as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype) or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype). This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.


docid: vonzrqji

title: Inhibition of infectious haematopoietic necrosis virus in cell cultures with peptide‐conjugated morpholino oligomers

text: Delivery of phosphorodiamidate morpholino oligomers (PMO) into fish cells in vitro and tissues in vivo was examined. Uptake was evaluated by fluorescence microscopy and flow cytometry after treating cultured cells or live rainbow trout with 3′ fluorescein‐tagged PMO. Arginine‐rich peptide conjugated to the 5′ end of the PMO markedly enhanced cellular uptake in culture by 8‐ to 20‐fold compared with non‐peptide‐conjugated PMO as determined by flow cytometry. Enhanced uptake of PMO conjugated to peptide was also observed in tissues of fish treated by immersion. The efficacy of PMO as inhibitors of infectious haematopoietic necrosis virus (IHNV) replication was determined in vitro. Peptide‐conjugated PMOs targeting sequences within the IHNV genomic RNA (negative polarity) or antigenomic RNA (positive polarity) significantly inhibited replication in a dose‐dependent and sequence‐specific manner. A PMO complementary to sequence near the 5′ end of IHNV genomic RNA was the most effective, diminishing titre by 97%, as measured by plaque assay and Western blot. These data demonstrate that replication of a negative‐stranded non‐segmented RNA virus can be inhibited by antisense compounds that target positive polarity viral RNA, or by a compound that targets negative polarity viral RNA.


title: Impact of human coronavirus infections in otherwise healthy children who attended an emergency department

text: This prospective clinical and virological study of 2,060 otherwise healthy children aged <15 years of age (1,112 males; mean age ± SD, 3.46 ± 3.30 years) who attended the Emergency Department of Milan University's Institute of Pediatrics because of an acute disease excluding trauma during the winter season 2003–2004 was designed to compare the prevalence and clinical importance of human coronaviruses (HCoVs) in children. Real‐time polymerase chain reaction (PCR) in nasopharyngeal aspirates revealed HCoV infection in 79 cases (3.8%): 33 HCoV‐229E (1.6%), 13 HCoV‐NL63 (0.6%), 11 HCoV‐OC43 (0.5%), none HCoV‐HKU1 genotype A, and 22 (1.1%) co‐detections of a HCoV and another respiratory virus. The HCoVs were identified mainly in children with upper respiratory tract infection; there was no significant difference in clinical presentation between single HCoV infections and HCoV co‐infections. Diagnostic methods were used in a limited number of patients, and the therapy prescribed and clinical outcomes were similar regardless of the viral strain. There were a few cases of other members of the households of HCoV‐positive children falling ill during the 5–7 days following enrollment. These findings suggest that HCoV‐229E and HCoV‐OC43 have a limited clinical and socioeconomic impact on otherwise healthy children and their household contacts, and the HCoV‐NL63 identified recently does not seem to be any different. The quantitative and qualitative role of HCoV‐HKU1 genotype A is apparently very marginal. J. Med. Virol. 78:1609–1615, 2006. © 2006 Wiley‐Liss, Inc.


title: Ignac Semmelweis—Father of Hand Hygiene

text: Hungarian obstetrician Ignac Semmelweis (1818–1865) was one of the earliest clinical investigators of modern medical science. In nineteenth century Europe, puerperal fever (childbed fever) was a major clinical and public health problem with very high maternal mortality. It was thought to be caused by miasma, epidemicity, or the Will of Providence. Apart from bloodletting, there was no cure for it. Semmelweis cared for the childbed fever women during their illness, and when they died, he did autopsies on them. Astute clinical observations and logical reasoning goaded Semmelweis to suspect the role of “unholy” hands of “holy” physicians in the transmission of puerperal fever. He enforced a hand-washing policy for physicians. Those with unwashed hands were disallowed into labor room. The hand-washing practice for 1 year led to unprecedented decrease in maternal mortality. It enabled Semmelweis to establish a strong, specific, temporal causal association between unclean hands and puerperal fever. Although not accepted during his lifetime, this causal hypothesis contributed significantly to the understanding of etiopathophysiology of not only puerperal fever but also many other communicable diseases. Clinical hand washing, since then, has prevented millions of deaths of humankind. In the present times too, his idea of hand hygiene plays a central role in COVID-19 pandemic management. Authors present a brief account of life and work of this maverick genius, who was born “too early in the darkness.” He is also called the “Father of infection control” and “Savior of mothers.”


title: Origin and Possible Genetic Recombination of the Middle East Respiratory Syndrome Coronavirus from the First Imported Case in China: Phylogenetics and Coalescence Analysis

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory tract infection with a high fatality rate in humans. Coronaviruses are capable of infecting multiple species and can evolve rapidly through recombination events. Here, we report the complete genomic sequence analysis of a MERS-CoV strain imported to China from South Korea. The imported virus, provisionally named ChinaGD01, belongs to group 3 in clade B in the whole-genome phylogenetic tree and also has a similar tree topology structure in the open reading frame 1a and -b (ORF1ab) gene segment but clusters with group 5 of clade B in the tree constructed using the S gene. Genetic recombination analysis and lineage-specific single-nucleotide polymorphism (SNP) comparison suggest that the imported virus is a recombinant comprising group 3 and group 5 elements. The time-resolved phylogenetic estimation indicates that the recombination event likely occurred in the second half of 2014. Genetic recombination events between group 3 and group 5 of clade B may have implications for the transmissibility of the virus.


title: Legitimacy building and e-commerce platform development in China: The experience of Alibaba

text: Abstract Although existing studies have connected the emergence and development of e-commerce with infrastructure, culture, and regulations, we approach technological and platform acceptance from the perspective of legitimacy building. In our study, legitimacy is categorized into market, relational, and social legitimacy, and the link between each type of legitimacy and acceptance is explored. We select the case of Alibaba and argue that Alibaba was especially competent in building legitimacy. Alibaba's continuous efforts to build legitimacy facilitated platform evolution despite its exposed weakness in intellectual property rights. These efforts rendered Alibaba as a de facto standard e-business model. This research suggests that any firm that wants market acceptance for its platform or e-commerce technology should focus more on building legitimacy among stakeholders than on anything else.


title: COVID-19 Pandemic: Impact on Psychiatric Care in the United States, a Review

text: Abstract The World Health Organization declared the coronavirus outbreak a pandemic on March 11, 2020. Infection by the SARS-CoV2 virus leads to the COVID-19 disease which can be fatal, especially in older patients with medical co-morbidities. The impact to the US healthcare system has been disruptive, and the way healthcare services are provided has changed drastically. Here, we present a compilation of the impact of the COVID-19 pandemic on psychiatric care in the US, in the various settings: outpatient, emergency room, inpatient units, consultation services, and the community. We further present effects seen on psychiatric physicians in the setting of new and constantly evolving protocols where adjustment and flexibility have become the norm, training of residents, leading a team of professionals with different expertise, conducting clinical research, and ethical considerations. The purpose of this paper is to provide examples of “how to” processes based on our current front-line experiences and research to practicing psychiatrists and mental health clinicians, inform practitioners about national guidelines affecting psychiatric care during the pandemic, and inform health care policy makers and health care systems about the challenges and continued needs of financial and administrative support for psychiatric physicians and mental health systems.


title: SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping

text: The current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host’s lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause ‘cytokine storm’ involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-α, IFN-γ, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung.